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1.
Georg Prokop Benedikt Wiestler Daniel Hieber Fynn Withake Karoline Mayer Jens Gempt Claire Delbridge Friederike Schmidt-Graf Nicole Pfarr Bruno Märkl Jürgen Schlegel Friederike Liesche-Starnecker 《International journal of cancer. Journal international du cancer》2023,153(9):1658-1670
Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered. 相似文献
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Jasmine Poonian Nicola Walsham Thomas Kilner Elizabeth Bradbury Kristen Brooks Emma West 《Emergency medicine Australasia : EMA》2020,32(4):700-702
Emergency Medicine staff in Australia and New Zealand are at the forefront of the healthcare response to COVID‐19. This article describes a well‐being plan for ED staff that has been devised to mitigate against the negative psychological impact of the COVID‐19 pandemic. 相似文献
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Zaida Araujo Sietze Brandes Elena Pinelli María A. Bochichio Andrea Palacios Albina Wide Bruno Rivas-Santiago Juan Carlos Jiménez 《Revista do Instituto de Medicina Tropical de S?o Paulo》2015,57(1):47-55
The present study aimed at measuring seropositivities for infection by
Ascaris suum and Toxocara canis using the
excretory/secretory (E/S) antigens from Ascaris suum (AES) and
Toxocara canis (TES) within an indigenous population. In
addition, quantification of cytokine expressions in peripheral blood cells was
determined. A total of 50 Warao indigenous were included; of which 43 were adults and
seven children. In adults, 44.1% were seropositive for both parasites; whereas
children had only seropositivity to one or the other helminth. For ascariosis, the
percentage of AES seropositivity in adults and children was high; 23.3% and 57.1%,
respectively. While that for toxocariosis, the percentage of TES seropositivity in
adults and children was low; 9.3% and 14.3%, respectively. The percentage of
seronegativity was comparable for AES and TES antigens in adults (27.9%) and children
(28.6%). When positive sera were analyzed by Western blotting technique using AES
antigens; three bands of 97.2, 193.6 and 200.2 kDas were mostly recognized. When the
TES antigens were used, nine major bands were mostly identified; 47.4, 52.2, 84.9,
98.2, 119.1, 131.3, 175.6, 184.4 and 193.6 kDas. Stool examinations showed that
Blastocystis hominis, Hymenolepis nana and
Entamoeba coli were the most commonly observed intestinal
parasites. Quantification of cytokines IFN-γ, IL-2, IL-6, TGF-β, TNF-α, IL-10 and
IL-4 expressions showed that there was only a significant increased expression of
IL-4 in indigenous with TES seropositivity (p < 0.002).
Ascaris and Toxocara seropositivity was
prevalent among Warao indigenous. 相似文献
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