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  • 2025

    Metastatic castration‐resistant prostate cancer (mCRPC) is a heterogeneous disease. Several studies have identified transcriptional subtypes of mCRPC, but comprehensive analysis of prognostic gene expression pathways has been limited. Therefore, we aggregated a cohort of 1012 mCRPC tissue samples from 769 patients and investigated the association of gene expression‐based pathways with clinical outcomes and intrapatient and intratumor heterogeneity. Survival data were obtained for 272 patients. Pathway‐level enrichment was evaluated using gene set variation analysis. scRNA‐seq datasets from mCRPC tissue biopsies and circulating tumor cells were used to investigate heterogeneity of adverse pathways. We identified five pathway clusters: (a) Immune response/WNT/TGF‐beta signaling, (b) AR signaling/luminal signatures, (c) mTOR signaling and glycolysis, (d) cell proliferation, and (e) neuroendocrine differentiation. Proliferation, AR signaling loss, and glycolysis/mTOR signaling were independently prognostic. Adverse prognostic pathway scores decreased on treatment with AR signaling inhibitors, but not at progression, suggesting failure to permanently target these pathways. scRNA‐seq datasets from mCRPC tissue biopsies and circulating tumor cells were used to investigate heterogeneity of adverse pathways. Our results suggest loss of AR signaling, high proliferation, and a glycolytic phenotype as adverse prognostic pathways in mCRPC that could be used in conjunction with clinical factors to prognosticate for treatment decisions.
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  • 2025

    Abstract Understanding helium (He) plasma-induced tungsten (W) surface modifications, and the effect of irradiation defects on He plasma-induced W surface modifications under a real divertor environment are important for the operation of fusion reactors. In this study, two iron (Fe) ions pre-irradiated W samples with dislocation loops and voids, and two unirradiated W samples were exposed to He plasma at a divertor leg position of the Large Helical Device (LHD). The gross erosion rate are 1.0×1020 atoms m-2 s-1, 1.0×1020 atoms m-2 s-1, 9.3×1019 atoms m-2 s-1, 7.4×1019 atoms m-2 s-1 for W9, W10, W11, W12, respectively. The surface of each sample after the exposure was different at the strike point and the two regions on either side of the strike point, the scrape-off layer (SOL) region and the private region. The typical He plasma-induced structures at the SOL region were stripe structure, sawtooth structure, and no undulating structure, which are collectively called He-structures in the present study. At the strike point, the typical He plasma-induced structure was dense W protrusions. At the private flux region, the typical He plasma-induced structures are semi-formed He-structures. The formations of these structures were depended on the grain orientation. And pinholes were observed on these structures. No significant difference in the He plasma-induced structures was found between the pre-irradiated W and the unirradiated W. The formations of no undulating structure and stripe structure were discussed based on the observed semi-formed He-structures.
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  • 2025

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