Fewer than 50% of metastatic deficient mismatch repair (dMMR) colorectal cancer (CRC) patients respond to immune checkpoint inhibition (ICI). Identifying and expanding this patient population remains a pressing clinical need. Here, we report that an interferon-high immunophenotype locally enriched in cytotoxic lymphocytes and antigen-presenting macrophages is required for response.
View Article and Find Full Text PDFDespite the great relevance of the neurosteroid allopregnanolone and related isomers to various health conditions, quantification typically involves immunoassay, which suffers from serious issues with cross-reactivity of closely related molecules. This article describes the development and partial validation of a liquid chromatography coupled with tandem mass spectrometry assay for the simultaneous quantification of allopregnanolone, pregnanolone, isopregnanolone, epi-allopregnanolone, and testosterone in the human serum of healthy males and females aged 5-85 years. 1-amino-4-methylpiperazine (AMP) was used as a derivatisation reagent to enhance the ionisation signal.
View Article and Find Full Text PDFBenzotriazoles (BZTs) and benzothiazoles (BTs) are high-production-volume chemicals utilized in many different commercial products and industrial processes, such as metal corrosion inhibitors, vulcanization accelerators, plastic-associated UV stabilizers, and pharmaceutical precursors. This study assessed age, gender, and temporal trends of BZTs and BTs in deidentified surplus pathology urine samples, pooled and stratified by age, gender, and sample collection year from a general Australian population (168 pools representing 16,800 individuals). Tolyltriazole (TTri), 5,6-dimethyl-1H-benzotriazole (DMBZT), 1,3-benzothiazole (BTH), 2-hydroxybenzothiazole (2-OH-BTH), and 2-aminobenzothiazole (2-amino-BTH) were detected in >50% of the pools.
View Article and Find Full Text PDFThe growing scale and dimensionality of multiplexed imaging require reproducible and comprehensive yet user-friendly computational pipelines. TRACERx-PHLEX performs deep learning-based cell segmentation (deep-imcyto), automated cell-type annotation (TYPEx) and interpretable spatial analysis (Spatial-PHLEX) as three independent but interoperable modules. PHLEX generates single-cell identities, cell densities within tissue compartments, marker positivity calls and spatial metrics such as cellular barrier scores, along with summary graphs and spatial visualisations.
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