The Human Cell Atlas (HCA) is a global partnership "to create comprehensive reference maps of all human cells-the fundamental units of life - as a basis for both understanding human health and diagnosing, monitoring, and treating disease." ( https://www.humancellatlas.
View Article and Find Full Text PDFSpatial omics technologies decipher functional components of complex organs at cellular and subcellular resolutions. We introduce Spatial Graph Fourier Transform (SpaGFT) and apply graph signal processing to a wide range of spatial omics profiling platforms to generate their interpretable representations. This representation supports spatially variable gene identification and improves gene expression imputation, outperforming existing tools in analyzing human and mouse spatial transcriptomics data.
View Article and Find Full Text PDFAchieving fluid homeostasis and the management of fluid and electrolyte complications are constants in the treatment of seriously ill children worldwide. Consensus on the most appropriate fluid strategy for unwell children has been difficult to achieve and has evolved over the last two decades, most notably in high-income countries where adverse events relating to poor fluid management were identified more readily, and official robust inquiries were possible. However, this has not been the situation in many low-income settings where fluids that are prohibited from use in high-income countries may be all that are available, local guidelines and processes to recognise adverse events are not developed, and there has been limited training on safe fluid management for front-line healthcare workers.
View Article and Find Full Text PDFSingle-cell datasets often lack individual cell labels, making it challenging to identify cells associated with disease. To address this, we introduce Mixture Modeling for Multiple Instance Learning (MMIL), an expectation maximization method that enables the training and calibration of cell-level classifiers using patient-level labels. Our approach can be used to train e.
View Article and Find Full Text PDFAI is rapidly becoming part of many aspects of daily life, with an impact that reaches all fields of research. We asked investigators to share their thoughts on how AI is changing immunology research, what is necessary to move forward, the potential and the pitfalls, and what will remain unchanged as the field journeys into a new era.
View Article and Find Full Text PDFCell population delineation and identification is an essential step in single-cell and spatial-omics studies. Spatial-omics technologies can simultaneously measure information from three complementary domains related to this task: expression levels of a panel of molecular biomarkers at single-cell resolution, relative positions of cells, and images of tissue sections, but existing computational methods for performing this task on single-cell spatial-omics datasets often relinquish information from one or more domains. The additional reliance on the availability of "atlas" training or reference datasets limits cell type discovery to well-defined but limited cell population labels, thus posing major challenges for using these methods in practice.
View Article and Find Full Text PDFObjectives: The inJectable Antiretroviral feasiBility Study (JABS) aimed to evaluate the implementation of long-acting regimens in a 'real world' Australian setting, with inclusion of participants with complex medical needs, social vulnerability and/or historical non-adherence.
Methods: JABS was a 12-month, single-centre, single-arm, open-label phase IV study of long-acting cabotegravir 600 mg plus rilpivirine 900 mg administered intramuscularly every 2 months to adults with treated HIV-1 infection. The primary endpoint was the proportion of attendances and administration of injections within a 14-day dosing window over 12 months, out of the total prescribed doses.
Cancer progression is a complex process involving interactions that unfold across molecular, cellular, and tissue scales. These multiscale interactions have been difficult to measure and to simulate. Here, we integrated CODEX multiplexed tissue imaging with multiscale modeling software to model key action points that influence the outcome of T cell therapies with cancer.
View Article and Find Full Text PDFMetal hydroborates and their derivatives have been receiving attention as potential solid-state ion conductors for battery applications owing to their impressive electrochemical and mechanical characteristics. However, to date only a fraction of these compounds has been investigated as solid-state electrolytes. Here, MBHNH (M = Li and Na) hydroborates are synthesized and investigated as electrolyte materials for all-solid-state batteries.
View Article and Find Full Text PDFThe utility of spatial omics in leveraging cellular interactions in normal and diseased states for precision medicine is hampered by a lack of strategies for matching disease states with spatial heterogeneity-guided cellular annotations. Here we use a spatial context-dependent approach that matches spatial pattern detection to cell annotation. Using this approach in existing datasets from ulcerative colitis patient colonic biopsies, we identified architectural complexities and associated difficult-to-detect rare cell types in ulcerative colitis germinal-center B cell follicles.
View Article and Find Full Text PDFTumor-associated macrophages are transcriptionally heterogeneous, but the spatial distribution and cell interactions that shape macrophage tissue roles remain poorly characterized. Here, we spatially resolve five distinct human macrophage populations in normal and malignant human breast and colon tissue and reveal their cellular associations. This spatial map reveals that distinct macrophage populations reside in spatially segregated micro-environmental niches with conserved cellular compositions that are repeated across healthy and diseased tissue.
View Article and Find Full Text PDFUnderstanding the atomic-scale mechanisms that govern the structure of interfaces is critical across materials systems but particularly so for two-dimensional (2D) moiré materials. Here, we image, atom-by-atom, the thermally induced structural evolution of twisted bilayer transition metal dichalcogenides using in situ transmission electron microscopy. We observe low-temperature, local conversion of moiré superlattice into nanoscale aligned domains.
View Article and Find Full Text PDFAutism spectrum disorder (ASD) and schizophrenia (SZ) are neuropsychiatric disorders that overlap in symptoms associated with social-cognitive impairment. Alterations of the cingulate cortex, subcortical, medial-temporal, and orbitofrontal structures are frequently reported in both disorders. In this study, we examined white-matter connectivity between these structures in adults with ASD and SZ patients compared with their respective neurotypical controls and indirectly with each other, using probabilistic and local DTI tractography.
View Article and Find Full Text PDFThe intricate and dynamic interactions between the host immune system and its microbiome constituents undergo dynamic shifts in response to perturbations to the intestinal tissue environment. Our ability to study these events on the systems level is significantly limited by approaches capable of generating simultaneous insights from both host and microbial communities. Here, we introduce Microbiome Cartography (MicroCart), a framework for simultaneous probing of host features and its microbiome across multiple spatial modalities.
View Article and Find Full Text PDFSpatial omics technologies are capable of deciphering detailed components of complex organs or tissue in cellular and subcellular resolution. A robust, interpretable, and unbiased representation method for spatial omics is necessary to illuminate novel investigations into biological functions, whereas a mathematical theory deficiency still exists. We present SpaGFT (Spatial Graph Fourier Transform), which provides a unique analytical feature representation of spatial omics data and elucidates molecular signatures linked to critical biological processes within tissues and cells.
View Article and Find Full Text PDFAppendiceal intussusception is a rare condition with an unknown incidence of clinical presentation, and an estimated incidence of 0.01% is based on a histological study only. It presents a diagnostic challenge with lack of standardized management strategies, and its description in literature is limited to case reports and series.
View Article and Find Full Text PDFThe redirection of T cells has emerged as an attractive therapeutic principle in B cell non-Hodgkin lymphoma (B-NHL). However, a detailed characterization of lymphoma-infiltrating T cells across B-NHL entities is missing. Here we present an in-depth T cell reference map of nodal B-NHL, based on cellular indexing of transcriptomes and epitopes, T cell receptor sequencing, flow cytometry and multiplexed immunofluorescence applied to 101 lymph nodes from patients with diffuse large B cell, mantle cell, follicular or marginal zone lymphoma, and from healthy controls.
View Article and Find Full Text PDFHighly multiplexed protein imaging is emerging as a potent technique for analyzing protein distribution within cells and tissues in their native context. However, existing cell annotation methods utilizing high-plex spatial proteomics data are resource intensive and necessitate iterative expert input, thereby constraining their scalability and practicality for extensive datasets. We introduce MAPS (Machine learning for Analysis of Proteomics in Spatial biology), a machine learning approach facilitating rapid and precise cell type identification with human-level accuracy from spatial proteomics data.
View Article and Find Full Text PDFCancer progression is a complex process involving interactions that unfold across molecular, cellular, and tissue scales. These multiscale interactions have been difficult to measure and to simulate. Here we integrated CODEX multiplexed tissue imaging with multiscale modeling software, to model key action points that influence the outcome of T cell therapies with cancer.
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