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BackgroundImage segmentation is a fundamental technique that allows researchers to process images from various sources into individual components for certain applications, such as visual or numerical evaluations. Image segmentation is beneficial when studying medical images for healthcare purposes. However, existing semantic image segmentation models like the U-net are computationally intensive. This work aimed to develop less complicated models that could still accurately segment images.MethodologyRule-based and linear layer neural network models were developed in Mathematica and trained on mouse vertebrae micro-computed tomography scans. These models were tasked with segmenting the cortical shell from the whole bone image. A U-net model was also set up for comparison.ResultsIt was found that the linear layer neural network had comparable accuracy to the U-net model in segmenting the mice vertebrae scans.ConclusionsThis work provides two separate models that allow for automated segmentation of mouse vertebral scans, which could be potentially valuable in applications such as pre-processing the murine vertebral scans for further evaluations of the effect of drug treatment on bone micro-architecture.

Global health remains threatened by spillovers of zoonotic SARS-like betacoronaviruses (sarbecoviruses) that could be mitigated by a pan-sarbecovirus vaccine . We described elicitation of potently neutralizing and cross-reactive anti-sarbecovirus antibodies by mosaic-8 nanoparticles (NPs) displaying eight different sarbecovirus spike receptor-binding domains (RBDs) as 60 copies of eight individual RBDs (mosaic-8 RBD-NPs) or 30 copies of two \"quartets,\" each presenting four tandemly-arranged RBDs (dual quartet RBD-NPs). To facilitate manufacture of a broadly protective mosaic-8 vaccine, we generated membrane-bound RBD quartets that can be genetically encoded and delivered via mRNA: dual quartet RBD-mRNA and dual quartet RBD-EABR-mRNA, which utilizes ESCRT- and ALIX-binding region (EABR) technology that promotes immunogen presentation on cell surfaces and circulating enveloped virus-like particles (eVLPs) . Immunization with mRNA immunogens elicited equivalent or improved binding breadths, neutralization potencies, T cell responses, and targeting of conserved RBD epitopes across sarbecoviruses, demonstrating successful conversion of protein-based mosaic-8 RBD vaccines to mRNA formats. Systems serology showed that the mRNA vaccines elicited balanced IgG subclass responses with increased Fcγ receptor-binding IgGs, consistent with potentially superior Fc effector functions. A new technique, Systems Serology-Polyclonal Epitope Mapping (SySPEM), revealed distinct IgG-subclass-specific epitope targeting signatures across mRNA and protein-based vaccine modalities. These results demonstrate successful conversion of mosaic-8 RBD-NPs to mRNA or EABR-mRNA vaccines that provide easy manufacturing and enhanced protection from future pandemic sarbecovirus outbreaks.

Effective pan-sarbecovirus vaccines could prevent future zoonotic spillovers of SARS-like betacoronaviruses. We previously developed protein-based mosaic-8 nanoparticles displaying eight diverse sarbecovirus RBDs, either individually (mosaic-8 RBD-NPs) or as two “quartets” of four tandemly-arranged RBDs (dual-quartet RBD-NPs), which elicited broadly cross-reactive antibodies but require multi-component manufacturing. Here, we address scalability challenges by extending the mosaic-8 concept to mRNA by encoding membrane-bound RBD quartets as dual-quartet RBD-mRNA and dual-quartet RBD-EABR-mRNA, the latter leveraging ESCRT- and ALIX-binding region (EABR) technology for immunogen display on cell surfaces and secreted virus-like particles. Compared with protein-based mosaic-8 immunogens, mRNA-encoded mosaic-8 vaccines induced equivalent or enhanced antibody breadth, neutralization potencies, T-cell responses, and targeting of conserved RBD epitopes. In addition, mRNA-encoded mosaic-8 vaccines elicited more balanced IgG subclass profiles and increased Fcγ receptor–binding IgGs, consistent with potentially superior Fc effector functions. These findings demonstrate successful translation of mosaic-8 RBD-NPs into mRNA/EABR-mRNA vaccines, enabling scalable manufacturing and improving protection against future sarbecovirus outbreaks. Finally, our newly developed technique, Systems Serology–Polyclonal Epitope Mapping (SySPEM), revealed distinct IgG-subclass-specific epitope signatures across mRNA, EABR-mRNA, and protein vaccines, demonstrating that the mode of antigen display can shape epitope recognition. We translated a pan-sarbecovirus RBD vaccine from protein nanoparticles to scalable mRNA and EABR-mRNA platforms encoding RBD quartets. Compared with protein-based immunogens, mRNA-based vaccines matched or improved antibody breadth, T-cell responses, Fc functionality, and conserved epitope targeting. A newly-developed Systems Serology–Polyclonal Epitope Mapping (SySPEM) technique revealed that antigen presentation modality shapes IgG subclass–specific epitope recognition.