Biomedical Research Community Research Articles

Super-resolution radial fluctuations microscopy for optimal resolution and fidelity.

Fluorescence fluctuation super-resolution microscopy (FF-SRM) has emerged as a promising method for the fast, low-cost, and uncomplicated imaging of biological specimens beyond the diffraction limit. Among FF-SRM techniques, super-resolution radial fluctuation (SRRF) microscopy is a popular technique but is prone to artifacts, resulting in low fidelity, especially under conditions of high-density fluorophores. In this Letter, we developed a novel, to the best of our knowledge, combinatory computational super-resolution microscopy method, namely VeSRRF, that demonstrated superior performance in SRRF microscopy. VeSRRF combined intensity and gradient variance reweighted radial fluctuations (VRRF) and enhanced-SRRF (eSRRF) algorithms, leveraging the enhanced resolution achieved through intensity and gradient variance analysis in VRRF and the improved fidelity obtained from the radial gradient convergence transform in eSRRF. Our method was validated using microtubules in mammalian cells as a standard biological model system. Our results demonstrated that VeSRRF consistently achieved the highest resolution and exceptional fidelity compared to those obtained from other algorithms in both single-molecule localization microscopy (SMLM) and FF-SRM. Moreover, we developed the VeSRRF software package that is freely available on the open-source ImageJ/Fiji software platform to facilitate the use of VeSRRF in the broader community of biomedical researchers. VeSRRF is an exemplary method in which complementary microscopy techniques are integrated holistically, creating superior imaging performance and capabilities.

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Peptide Science publishes peer‐reviewed papers covering all aspects of peptide synthesis, materials, structure and bioactivity. The journal includes both experimental and theoretical studies and serves the interdisciplinary biochemical, biomaterials, biophysical and biomedical research communities. image

Development of a piezo stack – Laser doppler vibrometer sensing approach for characterizing shear wave dispersion and local viscoelastic property distributions

Laser Doppler vibrometry and wavefield analysis have recently shown great potential for nondestructive evaluation, structural health monitoring, and studying wave physics. However, there are limited studies on these approaches for viscoelastic soft materials, especially, very few studies on the laser Doppler vibrometer (LDV)-based acquisition of time–space wavefields of dispersive shear waves in viscoelastic materials and the analysis of these wavefields for characterizing shear wave dispersion and evaluating local viscoelastic property distributions. Therefore, this research focuses on developing a piezo stack-LDV system and shear wave time–space wavefield analysis methods for enabling the functions of characterizing the shear wave dispersion and the distributions of local viscoelastic material properties. Our system leverages a piezo stack to generate shear waves in viscoelastic materials and an LDV to acquire time–space wavefields. We introduced space-frequency-wavenumber analysis and least square regression-based dispersion comparison to analyze shear wave time–space wavefields and offer functions including extracting shear wave dispersion relations from wavefields and characterizing the spatial distributions of local wavenumbers and viscoelastic properties (e.g., shear elasticity and viscosity). Proof-of-concept experiments were performed using a synthetic gelatin phantom. The results show that our system can successfully generate shear waves and acquire time–space wavefields. They also prove that our wavefield analysis methods can reveal the shear wave dispersion relation and show the spatial distributions of local wavenumbers and viscoelastic properties. We expect this research to benefit engineering and biomedical research communities and inspire researchers interested in developing shear wave-based technologies for characterizing viscoelastic materials.

Gold-nanoparticle-embedded membrane (GEM) for highly sensitive multiplexed sandwich immunoassays

For early disease diagnostics, highly sensitive biosensing methods are required to detect disease-related biomolecules in biofluids at low concentrations. Further, for complex diseases such as cancer, multiplexed detection is required to simultaneously measure multiple analytes in a single assay. Current technologies either lack sensitivity, multiplexing capabilities, or require complicated micro/nano-fabrication processes and specialized instrumentation, limiting their broader use in the biomedical research community as well as in clinical diagnostic applications. In this work, we have developed a gold-nanoparticle-embedded membrane (GEM) platform that consists of 3D nitrocellulose membranes preloaded with gold nanoparticles in microliter compartments for highly sensitive, multiplexed metal enhanced fluorescence (MEF)-based detection. After the development of the compartmentalized GEM and the optimization of size, shape, and concentration of the gold nanoparticles to achieve optimal MEF, we demonstrated its application for scalable multiplexed sandwich immunoassays in a microarray format for the quantification of three cancer-related proteins in blood plasma. In PBS buffer solution, the limit of detection for GM-CSF, TNF-α, and EGFR were improved by 287-folds, 949-folds, and 9.8-folds, respectively, when using the GEM compared to conventional ELISA. When spiked in pooled human plasma, low pg/mL sensitivity was also achieved for each protein, demonstrating its application for complex samples. Long-term storage was demonstrated for potential distribution of the GEM for wide availability among the biomedical and clinical community, facilitating technology dissemination. This technology offers simple, highly sensitive, and multiplexed detection capabilities with low reagent and sample consumption, suitable for accurate and early disease diagnostics.

Abstract 3542: The Chemical Probes Portal: An essential resource providing expert advice on chemical tools for cancer research

Abstract Background: The Chemical Probes Portal (Portal) serves as a vital resource in the realm of cancer research and biomedical science generally - offering expert guidance on high-quality chemical tools, usually protein inhibitors, crucial for studying physiological and pathological processes and validating therapeutic targets. Researchers often grapple with selecting suitable chemical probes, inadvertently utilizing tools ill-suited for their purpose, and not following best practice, thereby contaminating the scientific literature and wasting valuable time and resources. To address this challenge, the Portal (https://www.chemicalprobes.org) was established as a non-profit, independent online platform, meticulously curating, annotating, and scoring the quality of chemical probes and providing associated information and advice. Results: The Portal stands apart as the sole expert-curated public resource evaluating the quality and utility of small-molecule chemical tool compounds for use in cancer research and wider biomedical research. More than 250 experts, comprising scientific leaders in chemical biology, medicinal chemistry, pharmacology, and related fields, contribute their experience and insights to assess featured chemical probes. Since 2021, a progressively updated and enhanced version of the Portal has been operational, housing over 1000 compounds targeting 500+ proteins across diverse families, now including PROTACs and molecular glues. We also flag 254 ‘Unsuitables’, which are compounds that should not be used to interrogate a specific protein target. Additionally, the Portal now offers informative pages, providing advice delineating guidelines for selecting well-validated compounds, including those suitable for rodent studies, necessitating specific pharmacokinetic and pharmacodynamic properties. Best practice use requires employing high-quality chemical probes from more than one distinct chemical class that target the same protein, incorporating an inactive control compound, and following the recommended concentration range - all aimed at mitigating off-target risks. Conclusion: The enhanced Chemical Probes Portal provides a vital platform for researchers to navigate and evaluate chemical probes, easily and effectively. It employs a rigorous expert review to ensure the quality of the probes listed. The resource not only aids high-quality probe selection but also provides advice through an Information Centre, offering guidelines, FAQs, and additional information on probe criteria and use. The continuous expansion and outreach efforts aim to make the Portal an indispensable tool for cancer researchers and the broader biomedical research community. Researchers are encouraged to participate in the Portal's development and contribute to the robustness of chemical probe use in scientific endeavors. Citation Format: Domenico Sanfelice, Albert Antolin, Alisa Crisp, Yi Chen, Paul Brennan, Susanne Müller, Bissan Al-Lazikani, Aled Edwards, Paul Workman. The Chemical Probes Portal: An essential resource providing expert advice on chemical tools for cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3542.

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Peptide Science publishes peer‐reviewed papers covering all aspects of peptide synthesis, materials, structure and bioactivity. The journal includes both experimental and theoretical studies and serves the interdisciplinary biochemical, biomaterials, biophysical and biomedical research communities. image

Exploring pathways toward open-hardware ecosystems to safeguard genetic resources for biomedical research communities using aquatic model species.

Development of reliable germplasm repositories is critical for preservation of genetic resources of aquatic species, which are widely utilized to support biomedical innovation by providing a foundational source for naturally occurring variation and development of new variants through genetic manipulations. A significant barrier in repository development is the lack of cryopreservation capability and reproducibility across the research community, posing great risks of losing advances developed from billions of dollars of research investment. The emergence of open scientific hardware has fueled a new movement across biomedical research communities. With the increasing accessibility of consumer-level fabrication technologies, such asthree-dimensional printers, open hardware devices can be custom designed, and design files distributed to community members for enhancing rigor, reproducibility, and standardization. The overall goal of this review is to explore pathways to create open-hardware ecosystems among the communities using aquatic model resources for biomedical research. To gain feedback and insights from community members, an interactive workshop focusing on open-hardware applications in germplasm repository development was held at the 2022 Aquatic Models for Human Disease Conference, Woods Hole, Massachusetts. This work integrates conceptual strategies with practical insights derived from workshop interactions using examples of germplasm repository development. These insights can be generalized for establishment of open-hardware ecosystems for a broad biomedical research community. The specific objectives were to: (1) introduce an open-hardware ecosystem concept to support biomedical research; (2) explore pathways toward open-hardware ecosystems through four major areas, and (3) identify opportunities and future directions.

ExEmPLAR (Extracting, Exploring, and Embedding Pathways Leading to Actionable Research): a user-friendly interface for knowledge graph mining.

Knowledge graphs are being increasingly used in biomedical research to link large amounts of heterogenous data and facilitate reasoning across diverse knowledge sources. Wider adoption and exploration of knowledge graphs in the biomedical research community is limited by requirements to understand the underlying graph structure in terms of entity types and relationships, represented as nodes and edges, respectively, and learn specialized query languages for graph mining and exploration. We have developed a user-friendly interface dubbed ExEmPLAR (Extracting, Exploring, and Embedding Pathways Leading to Actionable Research) to aid reasoning over biomedical knowledge graphs and assist with data-driven research and hypothesis generation. We explain the key functionalities of ExEmPLAR and demonstrate its use with a case study considering the relationship of Trypanosoma cruzi, the etiological agent of Chagas disease, to frequently associated cardiovascular conditions. ExEmPLAR is freely accessible at https://www.exemplar.mml.unc.edu/. For code and instructions for the using the application, see: https://github.com/beasleyjonm/AOP-COP-Path-Extractor.

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Peptide Science publishes peer‐reviewed papers covering all aspects of peptide synthesis, materials, structure and bioactivity. The journal includes both experimental and theoretical studies and serves the interdisciplinary biochemical, biomaterials, biophysical and biomedical research communities. image

Pyrazolopyridine-based kinase inhibitors for anti-cancer targeted therapy.

The need for effective cancer treatments continues to be a challenge for the biomedical research community. In this case, the advent of targeted therapy has significantly improved therapeutic outcomes. Drug discovery and development efforts targeting kinases have resulted in the approval of several small-molecule anti-cancer drugs based on ATP-mimicking heterocyclic cores. Pyrazolopyridines are a group of privileged heterocyclic cores in kinase drug discovery, which are present in several inhibitors that have been developed against various cancers. Notably, selpercatinib, glumetinib, camonsertib and olverembatinib have either received approval or are in late-phase clinical studies. This review presents the success stories employing pyrazolopyridine scaffolds as hinge-binding cores to address various challenges in kinase-targeted drug discovery research.

Ten quick tips for fuzzy logic modeling of biomedical systems.

Fuzzy logic is useful tool to describe and represent biological or medical scenarios, where often states and outcomes are not only completely true or completely false, but rather partially true or partially false. Despite its usefulness and spread, fuzzy logic modeling might easily be done in the wrong way, especially by beginners and unexperienced researchers, who might overlook some important aspects or might make common mistakes. Malpractices and pitfalls, in turn, can lead to wrong or overoptimistic, inflated results, with negative consequences to the biomedical research community trying to comprehend a particular phenomenon, or even to patients suffering from the investigated disease. To avoid common mistakes, we present here a list of quick tips for fuzzy logic modeling any biomedical scenario: some guidelines which should be taken into account by any fuzzy logic practitioner, including experts. We believe our best practices can have a strong impact in the scientific community, allowing researchers who follow them to obtain better, more reliable results and outcomes in biomedical contexts.

Modeling of cryopreservation pathway operation at an aquatic biomedical stock center for zebrafish

Aquatic biomedical model organisms play a substantial role in advancing our understanding of human health, however, comparably little work has been directed towards developing dependable, high-throughput storage programs for valuable genetic resources. The Zebrafish International Resource Center (ZIRC) has developed a standardized cryopreservation pathway and stored thousands of genetic lines in their repository for use by the biomedical research community. This has yet to be replicated in other facilities, and an overall repository-level pathway has never been analyzed for aquatic species. To encourage repository development for other biomedical models and to improve the ZIRC storage process and system, this study used discrete-event simulation modeling to systematically analyze the cryopreservation pathway for efficiency, and to identify improvements. The models reflected “real-world” working conditions and were used to simulate key outputs, such as production capacity over time (throughput) and steps in the process that limit production (bottlenecks). With these models, recommendations were identified to eliminate waiting times and increase efficiency. These included following proper husbandry protocols because male quality significantly affected production time, and the use of part-time operators to assist with steps that had longer Waiting Times (i.e., time samples spent in a queue) to increase production capacity. Simulation process modeling is a powerful tool that can improve the operations of existing repositories. It can also support repository development at other biomedical stock centers, and at other facilities devoted to aquatic species such as research, conservation, and aquaculture production hatcheries.

Superporous soy protein isolate matrices as superabsorbent dressings for successful management of highly exuding wounds: In vitro and in vivo characterization

Soy protein isolate (SPI) has received widespread attention of the biomedical research community primarily due to its good biocompatibility, biodegradability, high availability and low cost. Herein, glutaraldehyde cross-linked microporous sponge-like SPI scaffolds were prepared using the cryogelation technique for tissue engineering applications. The prepared SPI scaffolds possess an interconnected porous structure with approximately 90% porosity and an average pore size in the range of 45–92 μm. The morphology, porosity, swelling capacity and degradation rate of the cryogels were found to be dependent on the concentration of polymer to crosslinking agent. All cryogels were found to be elastic and able to maintain physical integrity even after being compressed to one—fifth of their original length during cyclic compression analysis. These cryogels showed excellent mechanical properties, immediate water-triggered shape restoration and absorption speed. Furthermore, cryogels outperformed cotton and gauze in terms of blood clotting and blood cell adherence. The in vitro and in vivo studies demonstrated the potency of SPI scaffolds for skin tissue engineering applications. Our findings showed that crosslinking with glutaraldehyde had no detrimental effects on cell viability. In addition, an in vivo wound healing study in rats validated them as good potential wound dressing materials.

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Peptide Science publishes peer‐reviewed papers covering all aspects of peptide synthesis, materials, structure and bioactivity. The journal includes both experimental and theoretical studies and serves the interdisciplinary biochemical, biomaterials, biophysical and biomedical research communities. image

Bridge-building between communities: Imagining the future of biomedical autism research

A paradigm shift in research culture is required to ease perceived tensions between autistic people and the biomedical research community. As a group of autistic and non-autistic scientists and stakeholders, we contend that through participatory research, we can reject a deficit-based conceptualization of autism while building a shared vision for a neurodiversity-affirmative biomedical research paradigm.

Pharmaco-proteogenomic characterization of liver cancer organoids for precision oncology.

Organoid models have the potential to recapitulate the biological and pharmacotypic features of parental tumors. Nevertheless, integrative pharmaco-proteogenomics analysis for drug response features and biomarker investigation for precision therapy of patients with liver cancer are still lacking. We established a patient-derived liver cancer organoid biobank (LICOB) that comprehensively represents the histological and molecular characteristics of various liver cancer types as determined by multiomics profiling, including genomic, epigenomic, transcriptomic, and proteomic analysis. Proteogenomic profiling of LICOB identified proliferative and metabolic organoid subtypes linked to patient prognosis. High-throughput drug screening revealed distinct response patterns of each subtype that were associated with specific multiomics signatures. Through integrative analyses of LICOB pharmaco-proteogenomics data, we identified the molecular features associated with drug responses and predicted potential drug combinations for personalized patient treatment. The synergistic inhibition effect of mTOR inhibitor temsirolimus and the multitargeted tyrosine kinase inhibitor lenvatinib was validated in organoids and patient-derived xenografts models. We also provide a user-friendly web portal to help serve the biomedical research community. Our study is a rich resource for investigation of liver cancer biology and pharmacological dependencies and may help enable functional precision medicine.

NIDM-Terms: community-based terminology management for improved neuroimaging dataset descriptions and query.

The biomedical research community is motivated to share and reuse data from studies and projects by funding agencies and publishers. Effectively combining and reusing neuroimaging data from publicly available datasets, requires the capability to query across datasets in order to identify cohorts that match both neuroimaging and clinical/behavioral data criteria. Critical barriers to operationalizing such queries include, in part, the broad use of undefined study variables with limited or no annotations that make it difficult to understand the data available without significant interaction with the original authors. Using the Brain Imaging Data Structure (BIDS) to organize neuroimaging data has made querying across studies for specific image types possible at scale. However, in BIDS, beyond file naming and tightly controlled imaging directory structures, there are very few constraints on ancillary variable naming/meaning or experiment-specific metadata. In this work, we present NIDM-Terms, a set of user-friendly terminology management tools and associated software to better manage individual lab terminologies and help with annotating BIDS datasets. Using these tools to annotate BIDS data with a Neuroimaging Data Model (NIDM) semantic web representation, enables queries across datasets to identify cohorts with specific neuroimaging and clinical/behavioral measurements. This manuscript describes the overall informatics structures and demonstrates the use of tools to annotate BIDS datasets to perform integrated cross-cohort queries.

Origins of US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training.

The US Government Principles for the use of animals in research are a landmark statement of ethical values and guidance for the biomedical research community. However, when The Principles were introduced, a context was not provided for their source or foundation. The US Government Principles were formulated with input from the Council of Europe, World Health Organization, and US Interagency Research Animal Committee. The Principles continue to provide an ethical foundation for the biomedical research community.

Compartmentalized Linker Array: A Scalable and Transferrable Microarray Format for Multiplexed Immunoassays.

Microarrays have been widely used for multiplexed bioassays. Fabrication of a conventional microarray typically requires a complex microarray spotter, using which nanoliter bioreagent (e.g., antibody and cells) droplets are delivered onto a glass slide. However, arraying a delicate bioreagent in nanoliter volumes could cause the loss of bioactivity and needs a complex microarray spotter. Further, mixing of different bioreagents in a multiplexed assay leads to cross-reactions, producing false positive signals that impair assay reproducibility and scalability. In this work, we propose a new microarray format, named "compartmentalized linker array (CLA)", that consists of pre-prepared storable microarrays of chemical linkers in microliter compartments. CLA can be used for binding and patterning bioreagents into microarrays by simply pipetting and incubating bioreagent solutions in compartments. Using commonly used aminosilane linker-based antibody microarray, we developed CLA and demonstrated its application for a multiplexed sandwich immunoassay measuring three cancer-related proteins. A "two-phase" blocking system was established for de-activating background regions on glass where no linker molecules are present. Storage conditions of the CLA chip were explored and demonstrated for long-term storage. In a multiplexed immunoassay, low pg/mL sensitivity was achieved for all the three proteins, comparable to those of conventional assays. Moreover, CLA can be potentially used for other applications beyond protein assays, making microarray technology transferrable and widely available for the biological and biomedical research community.

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BiopolymersVolume 114, Issue 6 e23504 COVER IMAGEFree Access Cover Image First published: 20 June 2023 https://doi.org/10.1002/bip.23504AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Graphical Abstract Biopolymers celebrates its 60th anniversary! The journal was established in 1963 by Professor Murray Goodman as a founding editor and serves the interdisciplinary biochemical, biophysical, biomaterials and biomedical research communities. Volume114, Issue6June 2023e23504 RelatedInformation