Computer-aided detection or decision support systems aim to improve breast cancer screening programs by helping radiologists to evaluate digital mammography (DM) exams. Commonly such methods proceed in two steps: Selection of candidate regions for malignancy, and later classification as either malignant or not. In this study, we present a candidate detection method based on deep learning to automatically detect and additionally segment soft tissue lesions in DM. A database of DM exams (mostly bilateral and two views) was collected from our institutional archive. In total, 7196 DM exams (28294 DM images) acquired with systems from three different vendors (General Electric, Siemens, Hologic) were collected, of which 2883 contained malignant lesions verified with histopathology. Data was randomly split on an exam level into training (50%), validation (10%) and testing (40%) of deep neural network with u-net architecture. The u-net classifies the image but also provides lesion segmentation. Free receiver operating characteristic (FROC) analysis was used to evaluate the model, on an image and on an exam level. On an image level, a maximum sensitivity of 0.94 at 7.93 false positives (FP) per image was achieved. Similarly, per exam a maximum sensitivity of 0.98 at 7.81 FP per image was achieved. In conclusion, the method could be used as a candidate selection model with high accuracy and with the additional information of lesion segmentation.

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Objective To uncover the microRNA (miRNA) interactome of the osteoarthritis (OA) pathophysiological process in the cartilage.
Methods We performed RNA sequencing in 130 samples (n=35 and n=30 pairs for messenger RNA (mRNA) and miRNA, respectively) on macroscopically preserved and lesioned OA cartilage from the same patient and performed differential expression (DE) analysis of miRNA and mRNAs. To build an OA-specific miRNA interactome, a prioritisation scheme was applied based on inverse Pearson’s correlations and inverse DE of miRNAs and mRNAs. Subsequently, these were filtered by those present in predicted (TargetScan/microT-CDS) and/or experimentally validated (miRTarBase/TarBase) public databases. Pathway enrichment analysis was applied to elucidate OA-related pathways likely mediated by miRNA regulatory mechanisms.
Results We found 142 miRNAs and 2387 mRNAs to be differentially expressed between lesioned and preserved OA articular cartilage. After applying prioritisation towards likely miRNA-mRNA targets, a regulatory network of 62 miRNAs targeting 238 mRNAs was created. Subsequent pathway enrichment analysis of these mRNAs (or genes) elucidated that genes within the ‘nervous system development’ are likely mediated by miRNA regulatory mechanisms (familywise error=8.4×10−5). Herein NTF3 encodes neurotrophin-3, which controls survival and differentiation of neurons and which is closely related to the nerve growth factor.
Conclusions By an integrated approach of miRNA and mRNA sequencing data of OA cartilage, an OA miRNA interactome and related pathways were elucidated. Our functional data demonstrated interacting levels at which miRNA affects expression of genes in the cartilage and exemplified the complexity of functionally validating a network of genes that may be targeted by multiple miRNAs.@en