Generalizable biomarker prediction from cancer pathology slides with self-supervised deep learning: A retrospective multi-centric study

Deep learning (DL) can predict microsatellite instability (MSI) from routine histopathology slides of colorectal cancer (CRC). However, it is unclear whether DL can also predict other biomarkers with high performance and whether DL predictions generalize to external patient populations. Here, we acquire CRC tissue samples from two large multi-centric studies. We systematically compare six different state-of-the-art DL architectures to predict biomarkers from pathology slides, including MSI and mutations in BRAF, KRAS, NRAS, and PIK3CA. Using a large external validation cohort to provide a realistic evaluation setting, we show that models using self-supervised, attention-based multiple-instance learning consistently outperform previous approaches while offering explainable visualizations of the indicative regions and morphologies. While the prediction of MSI and BRAF mutations reaches a clinical-grade performance, mutation prediction of PIK3CA, KRAS, and NRAS was clinically insufficient

The role of mitochondria in SAMS

In this chapter we summarize the evidence for a central role of mitochondrial dysfunction in statin-associated muscle symptoms. Statin-related mitochondrial dysfunction can manifest itself in skeletal muscle by inducing a plethora of architectural and biochemical adaptations. Structural changes seen in biopsy specimens, including red ragged fibers, cytochrome oxidase-negative myofibers, and lipid-loaded vacuoles, are signs of mitochondrial respiratory chain dysfunction. Disturbances in mitochondrial energy metabolism are shown through increased lactate/pyruvate ratios, disruption of beta-oxidation, a decrease in mitochondrial DNA, and disturbances in electron transport chain complex activities. Apoptosis of myofibers may occur as a result of mitochondrial-mediated apoptosis and the formation of reactive oxygen species. Furthermore the role of coenzyme Q10 deficiency and disturbances in calcium homeostasis in relation to statin-induced mitochondrial dysfunction will be discussed