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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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The exercise pressor reflex is a feedback mechanism engaged upon stimulation of mechano- and metabosensitive skeletal muscle afferents. Activation of these afferents elicits a reflex increase in heart rate, blood pressure, and ventilation in an intensity-dependent manner. Consequently, the exercise pressor reflex has been postulated to be one of the principal mediators of the cardiorespiratory responses to exercise. In this updated review, we will discuss classical and recent advancements in our understating of the exercise pressor reflex function in both human and animal models. Particular attention will be paid to the afferent mechanisms and pathways involved during its activation, its effects on different target organs, its potential role in the abnormal cardiovascular response to exercise in diseased states, and the impact of age and biological sex on these responses. Finally, we will highlight some unanswered questions in the literature that may inspire future investigations in the field.

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Among the chief limitations in achieving early detection and control of animal‐origin influenza of pandemic potential in high‐risk livestock populations is the existing lag time between sample collection and diagnostic result. Advances in molecular diagnostics are permitting deployment of affordable, rapid, highly sensitive, and specific point‐of‐capture assays, providing opportunities for targeted surveillance driving containment strategies with potentially compelling returns on investment. Interrupting disease transmission at source holds promise of disrupting cycles of animal‐origin influenza incursion to endemicity and limiting impact on animal production, food security, and public health. Adoption of new point‐of‐capture diagnostics should be undertaken in the context of promoting robust veterinary services systems and parallel support for operationalizing pre‐authorized plans and communication strategies that will ensure that the full potential of these new platforms is realized.  相似文献   
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