Publications by authors named "Bethany Hunter"
High-dimensional tissue profiling of immune cell responses in chronic lung allograft dysfunction.
J Heart Lung Transplant
November 2024
Article Synopsis
- The study investigates the immune mechanisms behind chronic lung allograft dysfunction (CLAD), which hampers long-term survival after lung transplants, using advanced tissue imaging techniques.
- Researchers analyzed lung tissue from 23 transplant recipients, identifying differences in immune cell populations associated with CLAD versus non-CLAD conditions.
- Key findings show that specific immune cells, like cytotoxic T cells and γδ T cells, expand in CLAD, highlighting unique characteristics in different CLAD phenotypes and offering new insights into how fibrosis progresses in these conditions.*
Background: Lung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliteration in cellularity estimates. We used an imaging mass cytometry (IMC) analysis with an airspace correction step to more accurately identify the cellular immune response that underpins the heterogeneity of severe COVID-19 lung disease.
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- The study addresses challenges in analyzing imaging mass cytometry (IMC) data, particularly issues with accurate single-cell segmentation and visualization, which can lead to misidentification of cell types and states.
- Researchers developed the OPTIMAL framework to systematically evaluate various methods for cell segmentation, data transformation, and clustering on a human tonsil tissue sample stained with 27 antibodies over multiple batches.
- Key findings include improved single-cell segmentation using a probability map, optimal data transformation with an arcsinh cofactor of 1, and the effectiveness of the PacMap dimensionality reduction technique combined with FLOWSOM clustering for better cell type identification.
Diffuse alveolar damage (DAD) is the histological expression of acute respiratory distress syndrome and characterises lung pathology due to infection with SARS-CoV-2, and other respiratory pathogens of clinical significance. DAD reflects a time-dependent immunopathological process, progressing from an early/exudative stage through to an organising/fibrotic stage, yet within an individual these different stages of DAD may coexist. Understanding the progression of DAD is central to the development of new therapeutics to limit progressive lung damage.
View Article and Find Full Text PDFT cells play key protective but also pathogenic roles in COVID-19. We studied the expression of long non-coding RNAs (lncRNAs) in COVID-19 T-cell transcriptomes by integrating previously published single-cell RNA sequencing datasets. The long intergenic non-coding RNA MALAT1 was the most highly transcribed lncRNA in T cells, with Th1 cells demonstrating the lowest and CD8+ resident memory cells the highest MALAT1 expression, amongst CD4+ and CD8+ T-cells populations, respectively.
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- This study focuses on improving the understanding of glioblastoma (GBM) tumors by developing a tool to analyze immune and cancer cell types within tumor samples using bulk RNA sequencing data.
- Researchers created a specific single immune cell reference for GBM and combined it with existing cancer cell data to develop effective deconvolution tools for characterizing the cellular makeup of tumors.
- The tool, named GBMdeconvoluteR, proved to be the most accurate method for quantifying cell types in GBM, revealing insights into the relationship between cancer cells and immune cells, particularly in patients with poorer prognoses.
Background: examination of lung and heart tissue has been vital to developing an understanding of COVID-19 pathophysiology; however studies to date have almost uniformly used tissue obtained from hospital-based deaths where individuals have been exposed to major medical and pharmacological interventions.
Methods: In this study we investigated patterns of lung and heart injury from 46 community-based, pre-hospital COVID-19-attributable deaths who underwent autopsy.
Results: The cohort comprised 22 females and 24 males, median age 64 years (range 19-91) at time of death with illness duration range 0-23 days.
Background: Pancreas and islet transplantation outcomes are negatively impacted by injury to the endocrine cells from acute stress during donor death, organ procurement, processing, and transplant procedures. Here, we report a novel electron microscopy scoring system, the Newcastle Pancreas Endocrine Stress Score (NPESS).
Methods: NPESS was adapted and expanded from our previously validated method for scoring pancreatic exocrine acinar cells, yielding a 4-point scale (0-3) classifying ultrastructural pathology in endocrine cell nuclei, mitochondria, endoplasmic reticulum, cytoplasmic vacuolization, and secretory granule depletion, with a maximum additive score of 15.