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At least 19 records

Replacing non-biomedical concepts improves embedding of biomedical concepts

Embeddings are semantically meaningful representations of words in a vector space, commonly used to enhance downstream machine learning applications. Traditional biomedical embedding techniques often replace all synonymous words representing biological or medical concepts with a unique token, ensuring consistent representation and improving embedding quality. However, the potential impact of replacing non-biomedical concept synonyms has received less attention. Embedding approaches often employ concept replacement to replace concepts that span multiple words, such as non-small-cell lung carcinoma, with a single concept identifier (e.g., D002289). Also, all synonyms of each concept are merged into the same identifier. Here, we additionally leveraged WordNet to identify and replace sets of non-biomedical synonyms with their most common representatives. This combined approach aimed to reduce embedding noise from non-biomedical terms while preserving the integrity of biomedical concept representations. We applied this method to 1,055 biomedical concept sets representing molecular signatures or medical categories and assessed the mean pairwise distance of embeddings with and without non-biomedical synonym replacement. A smaller mean pairwise distance was interpreted as greater intra-cluster coherence and higher embedding quality. Embeddings were generated using the Word2Vec algorithm applied to a corpus of 10 million PubMed abstracts. Our results demonstrate that the addition of non-biomedical synonym replacement reduced the mean intra-cluster distance by an average of 8%, suggesting that this complementary approach enhances embedding quality. Future work will assess its applicability to other embedding techniques and downstream tasks. Python code implementing this method is provided under an open-source license.

algorithms↗

Advances in targeted proteomics and applications to biomedical research

Targeted proteomics technique has emerged as a powerful protein quantification tool in systems biology, biomedical research, and increasing for clinical applications. The most widely used targeted proteomics approach, selected reaction monitoring (SRM), also known as multiple reaction monitoring (MRM), can be used for quantification of cellular signaling networks and preclinical verification of candidate protein biomarkers. As an extension to our previous review on advances in SRM sensitivity (Shi et al., Proteomics , 12, 1074–1092, 2012) herein we review recent advances in the method and technology for further enhancing SRM sensitivity (from 2012 to present), and highlighting its broad biomedical applications in human bodily fluids, tissue and cell lines. Furthermore, we also review two recently introduced targeted proteomics approaches, parallel reaction monitoring (PRM) and data‐independent acquisition (DIA) with targeted data extraction on fast scanning high‐resolution accurate‐mass (HR/AM) instruments. Such HR/AM targeted quantification with monitoring all target product ions addresses SRM limitations effectively in specificity and multiplexing; whereas when compared to SRM, PRM and DIA are still in the infancy with a limited number of applications. Thus, for HR/AM targeted quantification we focus our discussion on method development, data processing and analysis, and its advantages and limitations in targeted proteomics. Finally, general perspectives on the potential of achieving both high sensitivity and high sample throughput for large‐scale quantification of hundreds of target proteins are discussed.

Shi, Tujin↗

Computational exploration of biomedical HfNbTaTiZr and Hf 0.5 Nb 0.5 Ta 0.5 Ti 1.5 Zr refractory high-entropy alloys

Refractory high entropy alloys (RHEAs) have been proven to be a potential candidate in the biomedical field due to their balanced mechanical properties and biocompatible composition. Recent experimental findings show that RHEAs like HfNbTaTiZr and Hf 0.5 Nb 0.5 Ta 0.5 Ti 1.5 Zr have good mechanical properties such as high polarization and wear resistance than others which establish them as potential materials for biomedical application. In this work, we performed first-principles density functional theory calculations on the mechanical and thermal properties of HfNbTaTiZr and Hf 0.5 Nb 0.5 Ta 0.5 Ti 1.5 Zr. The predicted lattice constant, density, Young's modulus, and Vickers hardness are consistent with the available experimental report, which verifies the accuracy of the applied model. The thermal coefficient of linear expansion of both RHEAs has been investigated by utilizing the Debye theory. The present methods could be applied to study other future RHEAs on exploration of their physical properties.

36 MATERIALS SCIENCE↗

BioADAPT-MRC: adversarial learning-based domain adaptation improves biomedical machine reading comprehension task

ABSTRACT Motivation Biomedical machine reading comprehension (biomedical-MRC) aims to comprehend complex biomedical narratives and assist healthcare professionals in retrieving information from them. The high performance of modern neural network-based MRC systems depends on high-quality, large-scale, human-annotated training datasets. In the biomedical domain, a crucial challenge in creating such datasets is the requirement for domain knowledge, inducing the scarcity of labeled data and the need for transfer learning from the labeled general-purpose (source) domain to the biomedical (target) domain. However, there is a discrepancy in marginal distributions between the general-purpose and biomedical domains due to the variances in topics. Therefore, direct-transferring of learned representations from a model trained on a general-purpose domain to the biomedical domain can hurt the model’s performance. Results We present an adversarial learning-based domain adaptation framework for the biomedical machine reading comprehension task (BioADAPT-MRC), a neural network-based method to address the discrepancies in the marginal distributions between the general and biomedical domain datasets. BioADAPT-MRC relaxes the need for generating pseudo labels for training a well-performing biomedical-MRC model. We extensively evaluate the performance of BioADAPT-MRC by comparing it with the best existing methods on three widely used benchmark biomedical-MRC datasets—BioASQ-7b, BioASQ-8b and BioASQ-9b. Our results suggest that without using any synthetic or human-annotated data from the biomedical domain, BioADAPT-MRC can achieve state-of-the-art performance on these datasets. Availability and implementation BioADAPT-MRC is freely available as an open-source project at https://github.com/mmahbub/BioADAPT-MRC. Supplementary information Supplementary data are available at Bioinformatics online.

60 APPLIED LIFE SCIENCES↗

A Review on Iron Oxide Nanoparticles and Their Biomedical Applications

The iron oxide nanoparticles have a great attraction in biomedical applications due to their non-toxic role in the biological systems. The iron oxide nanoparticles have both magnetic behaviour and semiconductor property which lead to multifunctional biomedical applications. The iron oxide nanoparticles used in biomedical fields such as antibacterial, antifungal and anticancer were reviewed. The uses of hematite (α-Fe{sub 2}O{sub 3}), maghemite (γ-Fe{sub 2}O{sub 3}) and magnetite (Fe{sub 3}O{sub 4}) nanoparticles, for an inhibition time in biological activities, are listed in this work. Also, this review explains the use of iron oxide nanoparticles in the biomedical fields with particular attention to the application of hematite and superparamagnetic iron oxide nanoparticles. In this review, analysis reveals that the role of iron oxide in biological activity is good due to its biocompatibility, biodegradability, ease of synthesis and different magnetic behaviours. The change of properties of iron oxide nanoparticles such as particle size, morphology, surface, agglomeration and electronic properties has specific impact in biomedical application. The review mainly focused in and discussed about antibacterial, anticancer, bone marrow and cell labelling activities. From this review work, the iron oxide nanoparticle may be specialised in particular bacterial and cancer treatments. Also discussed are the iron oxide nanoparticle-specific biomedical applications like human placenta, insulin and retinal locus treatments.

60 APPLIED LIFE SCIENCES↗

Pathophysiologic mechanisms of biomedical nanomaterials

Nanomaterials (NMs) have been widespread used in biomedical fields, daily consuming, and even food industry. It is crucial to understand the safety and biomedical efficacy of NMs. In this review, we summarized the recent progress about the physiological and pathological effects of NMs from several levels: protein-nano interface, NM-subcellular structures, and cell–cell interaction. We focused on the detailed information of nano-bio interaction, especially about protein adsorption, intracellular trafficking, biological barriers, and signaling pathways as well as the associated mechanism mediated by nanomaterials. We also introduced related analytical methods that are meaningful and helpful for biomedical effect studies in the future. We believe that knowledge about pathophysiologic effects of NMs is not only significant for rational design of medical NMs but also helps predict their safety and further improve their applications in the future. - Highlights: • Rapid protein adsorption onto nanomaterials that affects biomedical effects • Nanomaterials and their interaction with biological membrane, intracellular trafficking and specific cellular effects • Nanomaterials and their interaction with biological barriers • The signaling pathways mediated by nanomaterials and related biomedical effects • Novel techniques for studying translocation and biomedical effects of NMs.

60 APPLIED LIFE SCIENCES↗

Biolink Model: A universal schema for knowledge graphs in clinical, biomedical, and translational science

Abstract Within clinical, biomedical, and translational science, an increasing number of projects are adopting graphs for knowledge representation. Graph‐based data models elucidate the interconnectedness among core biomedical concepts, enable data structures to be easily updated, and support intuitive queries, visualizations, and inference algorithms. However, knowledge discovery across these “knowledge graphs” (KGs) has remained difficult. Data set heterogeneity and complexity; the proliferation of ad hoc data formats; poor compliance with guidelines on findability, accessibility, interoperability, and reusability; and, in particular, the lack of a universally accepted, open‐access model for standardization across biomedical KGs has left the task of reconciling data sources to downstream consumers. Biolink Model is an open‐source data model that can be used to formalize the relationships between data structures in translational science. It incorporates object‐oriented classification and graph‐oriented features. The core of the model is a set of hierarchical, interconnected classes (or categories) and relationships between them (or predicates) representing biomedical entities such as gene, disease, chemical, anatomic structure, and phenotype. The model provides class and edge attributes and associations that guide how entities should relate to one another. Here, we highlight the need for a standardized data model for KGs, describe Biolink Model, and compare it with other models. We demonstrate the utility of Biolink Model in various initiatives, including the Biomedical Data Translator Consortium and the Monarch Initiative, and show how it has supported easier integration and interoperability of biomedical KGs, bringing together knowledge from multiple sources and helping to realize the goals of translational science.

60 APPLIED LIFE SCIENCES↗

Applicability Analysis of Validation Evidence for Biomedical Computational Models

Computational modeling has the potential to revolutionize medicine the way it transformed engineering. However, despite decades of work, there has only been limited progress to successfully translate modeling research to patient care. One major difficulty which often occurs with biomedical computational models is an inability to perform validation in a setting that closely resembles how the model will be used. For example, for a biomedical model that makes in vivo clinically relevant predictions, direct validation of predictions may be impossible for ethical, technological, or financial reasons. Unavoidable limitations inherent to the validation process lead to challenges in evaluating the credibility of biomedical model predictions. Therefore, when evaluating biomedical models, it is critical to rigorously assess applicability, that is, the relevance of the computational model, and its validation evidence to the proposed context of use (COU). However, there are no well-established methods for assessing applicability. In this paper, we present a novel framework for performing applicability analysis and demonstrate its use with a medical device computational model. The framework provides a systematic, step-by-step method for breaking down the broad question of applicability into a series of focused questions, which may be addressed using supporting evidence and subject matter expertise. The framework can be used for model justification, model assessment, and validation planning. While motivated by biomedical models, it is relevant to a broad range of disciplines and underlying physics. Finally, the proposed applicability framework could help overcome some of the barriers inherent to validation of, and aid clinical implementation of, biomedical models.

97 MATHEMATICS AND COMPUTING↗

Resource for the Development of Biomedical Accelerator Mass Spectrometry (AMS)

The NIH Research Resource for Biomedical AMS was originally funded at Lawrence Livermore National Laboratory in 1999 to develop and apply the technology of accelerator mass spectrometry (AMS) in broad- based biomedical research. The Resource’s niche is to fill needs for ultra high sensitivity quantitation when isotope-labeled agents are used. The Research Resource’s Technology Research and Development (TR&D) efforts will focus on the needs of the biomedical research community in the context of seven Driving Biomedical Projects (DBPs) that will drive the Center’s technical capabilities through three core TR&Ds. We will expand our present capabilities by developing a fully integrated HPLC AMS to increase our capabilities for metabolic measurements, we will develop methods to understand cellular processes and we will develop and validate methods for the application of AMS in human studies, which is a growing area of demand by collaborators and service users. In addition, we will continue to support new and ongoing collaborative and service projects that require the capabilities of the Resource. The Center will continue to train researchers in the use of the AMS capabilities being developed, and the results of all efforts will be widely disseminated to advance progress in biomedical research. Towards these goals, our specific aims are to:1.) Increase the value and information content of AMS measurements by combining molecular speciation with quantitation of defined macromolecular isolates. Specifically, develop and validate methods for macromolecule labeling, characterization and quantitation.2.) Develop and validate methods and strategies to enable AMS to become more broadly used in human studies. Specifically, demonstrate robust methods for conducting pharmacokinetic/pharmacodynamics studies in humans and model systems.3.) Increase the accessibility of AMS to the Biomedical research community and the throughput of AMS through direct coupling to separatory instruments.4.) Provide high throughput 14C BioAMS analysis for collaborative and service clients.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Resource for the Development of Biomedical Accelerator Mass Spectrometry (AMS) Final Report

The NIH Research Resource for Biomedical AMS was originally funded at Lawrence Livermore National Laboratory in 1999 to develop and apply the technology of accelerator mass spectrometry (AMS) in broad- based biomedical research. The Resource’s niche is to fill needs for ultra high sensitivity quantitation when isotope-labeled agents are used. The Research Resource’s Technology Research and Development (TR&D) efforts will focus on the needs of the biomedical research community in the context of seven Driving Biomedical Projects (DBPs) that will drive the Center’s technical capabilities through three core TR&Ds. We will expand our present capabilities by developing a fully integrated HPLC AMS to increase our capabilities for metabolic measurements, we will develop methods to understand cellular processes and we will develop and validate methods for the application of AMS in human studies, which is a growing area of demand by collaborators and service users. In addition, we will continue to support new and ongoing collaborative and service projects that require the capabilities of the Resource. The Center will continue to train researchers in the use of the AMS capabilities being developed, and the results of all efforts will be widely disseminated to advance progress in biomedical research. Towards these goals, our specific aims are to:1.) Increase the value and information content of AMS measurements by combining molecular speciation with quantitation of defined macromolecular isolates. Specifically, develop and validate methods for macromolecule labeling, characterization and quantitation.2.) Develop and validate methods and strategies to enable AMS to become more broadly used in human studies. Specifically, demonstrate robust methods for conducting pharmacokinetic/pharmacodynamics studies in humans and model systems.3.) Increase the accessibility of AMS to the Biomedical research community and the throughput of AMS through direct coupling to separatory instruments.4.) Provide high throughput 14C BioAMS analysis for collaborative and service clients.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

KEBLM: Knowledge-Enhanced Biomedical Language Models

Pretrained language models (PLMs) have demonstrated strong performance on many natural language processing (NLP) tasks. Despite their great success, these PLMs are typically pretrained only on unstructured free texts without leveraging existing structured knowledge bases that are readily available for many domains, especially scientific domains. As a result, these PLMs may not achieve satisfactory performance on knowledge-intensive tasks such as biomedical NLP. Comprehending a complex biomedical document without domain-specific knowledge is challenging, even for humans. Inspired by this observation, we propose a general framework for incorporating various types of domain knowledge from multiple sources into biomedical PLMs. We encode domain knowledge using lightweight adapter modules, bottleneck feed-forward networks that are inserted into different locations of a backbone PLM. For each knowledge source of interest, we pretrain an adapter module to capture the knowledge in a self-supervised way. We design a wide range of self-supervised objectives to accommodate diverse types of knowledge, ranging from entity relations to description sentences. Once a set of pretrained adapters is available, we employ fusion layers to combine the knowledge encoded within these adapters for downstream tasks. Each fusion layer is a parameterized mixer of the available trained adapters that can identify and activate the most useful adapters for a given input. Our method diverges from prior work by including a knowledge consolidation phase, during which we teach the fusion layers to effectively combine knowledge from both the original PLM and newly-acquired external knowledge using a large collection of unannotated texts. After the consolidation phase, the complete knowledge-enhanced model can be fine-tuned for any downstream task of interest to achieve optimal performance. Extensive experiments on many biomedical NLP datasets show that our proposed framework consistently improves the performance of the underlying PLMs on various downstream tasks such as natural language inference, question answering, and entity linking. These results demonstrate the benefits of using multiple sources of external knowledge to enhance PLMs and the effectiveness of the framework for incorporating knowledge into PLMs. Finally, while primarily focused on the biomedical domain in this work, our framework is highly adaptable and can be easily applied to other domains, such as the bioenergy sector.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗

K-RET: knowledgeable biomedical relation extraction system

Abstract Motivation Relation extraction (RE) is a crucial process to deal with the amount of text published daily, e.g. to find missing associations in a database. RE is a text mining task for which the state-of-the-art approaches use bidirectional encoders, namely, BERT. However, state-of-the-art performance may be limited by the lack of efficient external knowledge injection approaches, with a larger impact in the biomedical area given the widespread usage and high quality of biomedical ontologies. This knowledge can propel these systems forward by aiding them in predicting more explainable biomedical associations. With this in mind, we developed K-RET, a novel, knowledgeable biomedical RE system that, for the first time, injects knowledge by handling different types of associations, multiple sources and where to apply it, and multi-token entities. Results We tested K-RET on three independent and open-access corpora (DDI, BC5CDR, and PGR) using four biomedical ontologies handling different entities. K-RET improved state-of-the-art results by 2.68% on average, with the DDI Corpus yielding the most significant boost in performance, from 79.30% to 87.19% in F-measure, representing a P-value of 2.91×10−12. Availability and implementation https://github.com/lasigeBioTM/K-RET.

Sousa, Diana F. (ORCID:0000000305979273)↗

Announcing the Biomedical Data Translator: Initial Public Release

ABSTRACT The growing availability of biomedical data offers vast potential to improve human health, but the complexity and lack of integration of these datasets often limit their utility. To address this, the Biomedical Data Translator Consortium has developed an open‐source knowledge graph–based system—Translator—designed to integrate, harmonize, and make inferences over diverse biomedical data sources. We announce here Translator's initial public release and provide an overview of its architecture, standards, user interface, and core features. Translator employs a scalable, federated, knowledge graph framework for the integration of clinical, genomic, pharmacological, and other biomedical knowledge sources, enabling query retrieval, inference, and hypothesis generation. Translator's user interface is designed to support the exploration of knowledge relationships and the generation of insights, without requiring deep technical expertise and gradually revealing more detailed evidence, provenance, and confidence information, as needed by a given user. To demonstrate Translator's application and impact, we highlight features of the user interface in the context of three real‐world use cases: suggesting potential therapeutics for patients with rare disease; explaining the mechanism of action of a pipeline drug; and screening and validating drug candidates in a model organism. We discuss strengths and limitations of reasoning within a largely federated system and the need for rich concept modeling and deep provenance tracking. Finally, we outline future directions for enhancing Translator's functionality and expanding its data sources. Translator represents a significant step forward in making complex biomedical knowledge more accessible and actionable, aiming to accelerate translational research and improve patient care.

Research & Experimental Medicine↗

Knowledge Beacons: Web services for data harvesting of distributed biomedical knowledge

The continually expanding distributed global compendium of biomedical knowledge is diffuse, heterogeneous and huge, posing a serious challenge for biomedical researchers in knowledge harvesting: accessing, compiling, integrating and interpreting data, information and knowledge. In order to accelerate research towards effective medical treatments and optimizing health, it is critical that efficient and automated tools for identifying key research concepts and their experimentally discovered interrelationships are developed. As an activity within the feasibility phase of a project called “Translator” (https://ncats.nih.gov/translator) funded by the National Center for Advancing Translational Sciences (NCATS) to develop a biomedical science knowledge management platform, we designed a Representational State Transfer (REST) web services Application Programming Interface (API) specification, which we call a Knowledge Beacon. Knowledge Beacons provide a standardized basic API for the discovery of concepts, their relationships and associated supporting evidence from distributed online repositories of biomedical knowledge. This specification also enforces the annotation of knowledge concepts and statements to the NCATS endorsed the Biolink Model data model and semantic encoding standards (https://biolink.github.io/biolink-model/). Implementation of this API on top of diverse knowledge sources potentially enables their uniform integration behind client software which will facilitate research access and integration of biomedical knowledge.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗

Cellulose-MOFs hybrid materials: Chemistry and mechanism of applications in biomedical - A review

Rising costs and performance limits of modern biomedical materials motivate the search for advanced, biocompatible alternatives. Cellulose-based metal-organic frameworks (cellulose-MOFs) emerge as distinctive hybrids combining renewable polymer chemistry with tunable porous architectures, enabling uncommon structure–function relationships. Their large surface area, controllable pore size, adaptable functional groups, and efficient host–guest interactions underpin diverse biomedical functions. Till now, no comprehensive, application-focused review has systematically summarized cellulose-MOFs synthesis for biomedical applications. This review critically analyzes cellulose-MOFs, emphasizing mechanistic links between chemistry, synthesis routes, interfacial interactions, and biomedical performance, rather than cataloging applications alone. Antibacterial action, targeted drug delivery, and sensing/biosensing are discussed through comparative insights. The article identifies unresolved challenges and proposes future research pathways to rationally design next-generation cellulose-MOFs systems, guiding researchers and clinicians alike.

Biomedical↗

Progress toward a universal biomedical data translator

Clinical, biomedical, and translational science has reached an inflection point in the breadth and diversity of available data and the potential impact of such data to improve human health and well-being. However, the data are often siloed, disorganized, and not broadly accessible due to discipline-specific differences in terminology and representation. To address these challenges, the Biomedical Data Translator Consortium has developed and tested a pilot knowledge graph-based “Translator” system capable of integrating existing biomedical data sets and “translating” those data into insights intended to augment human reasoning and accelerate translational science. Having demonstrated feasibility of the Translator system, the Translator program has since moved into development, and the Translator Consortium has made significant progress in the research, design, and implementation of an operational system. Herein, we describe the current system’s architecture, performance, and quality of results. We apply Translator to several real-world use cases developed in collaboration with subject-matter experts. Finally, we discuss the scientific and technical features of Translator and compare those features to other state-of-the-art, biomedical graph-based question-answering systems.

60 APPLIED LIFE SCIENCES↗