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https://www.selleckchem.com/pharmacological_epigenetics.html The detected regularities point to a compound self-organization processes in fault zones and suggest that the final stage of earthquake preparation can be revealed in analyzing the scaling characteristics of seismic-acoustic data.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Cancer of unknown primary (CUP) is an enigmatic disease entity encompassing heterogeneous malignancies without a detectable primary tumour, despite a thorough diagnostic workup. A minority of patients with CUP (15-20%) can be assigned a putative primary tissue of origin according to clinical and histopathological findings and typically have a more favourable prognosis with the use of corresponding tumour type-specific therapies. Thus, the majority of patients with CUP have disease that cannot be assigned to a culprit primary tumour, are treated with empirical chemotherapy and have a poor prognosis. In the molecular era, the use of (epi)genomic or transcriptomic CUP classifiers and DNA or RNA sequencing offers two, sometimes overlapping, therapeutic strategies tumour type-specific therapy and biomarker-guided therapy. Published data reveal that the accuracy of site-of-origin predictions made using CUP classifiers ranges between 54% and 98% when compared with the assignment made according to the recommended clinicopathological criteria. These advances have led to promising results in non-randomized prospective studies evaluating the efficacy of tumour type-specific therapy; however, the favourable outcomes were not confirmed in randomized controlled studies comparing this approach with standard empirical chemotherapy. Currently, the evidence supporting the use of biomarker-guided therapies is limited to case reports and small case series. In this Review, we discuss the clinical management of CUP in the era of precision medicine. We focus on the advances in understanding the biology o
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