Molecular characterisation of pancreatic ductal adenocarcinoma with NTRK fusions and review of the literature

AimsThe majority of pancreatic ductal adenocarcinomas (PDACs) harbour oncogenic mutations in KRAS with variants in TP53, CDKN2A and SMAD4 also prevalent. The presence of oncogenic fusions including NTRK fusions are rare but important to identify. Here we ascertain the prevalence of NTRK fusions and document their genomic characteristics in a large series of PDAC.MethodsWhole genome sequencing and RNAseq were performed on a series of patients with resected or locally advanced/metastatic PDAC collected between 2008 and 2020 at a single institution. A subset of specimens underwent immunohistochemistry (IHC) analysis. Clinical and molecular characterisation and IHC sensitivity and specificity were evaluated.Results400 patients were included (resected n=167; locally advanced/metastatic n=233). Three patients were identified as harbouring an NTRK fusion, two EML4-NTRK3 (KRAS-WT) and a single novel KANK1-NTRK3 fusion. The latter occurring in the presence of a subclonal KRAS mutation. Typical PDAC drivers were present including mutations in TP53 and CDKN2A. Substitution base signatures and tumour mutational burden were similar to typical PDAC. The prevalence of NTRK fusions was 0.8% (3/400), while in KRAS wild-type tumours, it was 6.25% (2/32). DNA prediction alone documented six false-positive cases. RNA analysis correctly identified the in-frame fusion transcripts. IHC analysis was negative in the KANK1-NTRK3 fusion but positive in a EML4-NTRK3 case, highlighting lower sensitivity of IHC.ConclusionNTRK fusions are rare; however, with emerging therapeutic options targeting these fusions, detection is vital. Reflex testing for KRAS mutations and subsequent RNA-based screening could help identify these cases in PDAC.

Multi-Dimensional Automatic Detection of Scanning Radar Images of Marine Targets Based on Radar PPInet

Traditional radar target detection algorithms are mostly based on statistical theory. They have weak generalization capabilities for complex sea clutter environments and diverse target characteristics, and their detection performance would be significantly reduced. In this paper, the range-azimuth-frame information obtained by scanning radar is converted into plain position indicator (PPI) images, and a novel Radar-PPInet is proposed and used for marine target detection. The model includes CSPDarknet53, SPP, PANet, power non-maximum suppression (P-NMS), and multi-frame fusion section. The prediction frame coordinates, target category, and corresponding confidence are directly given through the feature extraction network. The network structure strengthens the receptive field and attention distribution structure, and further improves the efficiency of network training. P-NMS can effectively improve the problem of missed detection of multi-targets. Moreover, the false alarms caused by strong sea clutter are reduced by the multi-frame fusion, which is also a benefit for weak target detection. The verification using the X-band navigation radar PPI image dataset shows that compared with the traditional cell-average constant false alarm rate detector (CA-CFAR) and the two-stage Faster R-CNN algorithm, the proposed method significantly improved the detection probability by 15% and 10% under certain false alarm probability conditions, which is more suitable for various environment and target characteristics. Moreover, the computational burden is discussed showing that the Radar-PPInet detection model is significantly lower than the Faster R-CNN in terms of parameters and calculations.

Instance-Aware Coherent Video Style Transfer for Chinese Ink Wash Painting

Recent researches have made remarkable achievements in fast video style transfer based on western paintings. However, due to the inherent different drawing techniques and aesthetic expressions of Chinese ink wash painting, existing methods either achieve poor temporal consistency or fail to transfer the key freehand brushstroke characteristics of Chinese ink wash painting. In this paper, we present a novel video style transfer framework for Chinese ink wash paintings. The two key ideas are a multi-frame fusion for temporal coherence and an instance-aware style transfer. The frame reordering and stylization based on reference frame fusion are proposed to improve temporal consistency. Meanwhile, the proposed method is able to adaptively leave the white spaces in the background and to select proper scales to extract features and depict the foreground subject by leveraging instance segmentation. Experimental results demonstrate the superiority of the proposed method over state-of-the-art style transfer methods in terms of both temporal coherence and visual quality. Our project website is available at https://oblivioussy.github.io/InkVideo/.

Recurrent chromosomal translocations in sarcomas create a mega-complex that mislocalizes NuA4/TIP60 to Polycomb target loci

Chromosomal translocations frequently promote carcinogenesis by producing gain-of-function fusion proteins. Recent studies have identified highly recurrent chromosomal translocations in patients with Endometrial Stromal Sarcomas (ESS) and Ossifying FibroMyxoid Tumors (OFMT) leading to an in-frame fusion of PHF1 (PCL1) to six different subunits of the NuA4/TIP60 complex. While NuA4/TIP60 is a co-activator that acetylates chromatin and loads the H2A.Z histone variant, PHF1 is part of the Polycomb repressive complex 2 (PRC2) linked to transcriptional repression of key developmental genes through methylation of histone H3 on lysine 27. In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation. The chimeric protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 activities and leads to mislocalization of chromatin marks in the genome. These are linked to aberrant gene expression, in particular over an entire topologically-associated domain including part of the HOXD cluster. Furthermore, we show that JAZF1, implicated with PRC2 components in the most frequent translocations in ESS, is a potent transcription activator that physically associates with NuA4/TIP60. Altogether, these results indicate that most chromosomal translocations linked to these sarcomas employ the same molecular oncogenic mechanism through a physical merge of NuA4/TIP60 and PRC2 complexes leading to mislocalization of histone marks and aberrant polycomb target gene expression.