Persister cell phenotypes contribute to poor patient outcomes after neoadjuvant chemotherapy in PDAC

Neoadjuvant chemotherapy can improve the survival of individuals with borderline and unresectable pancreatic ductal adenocarcinoma; however, heterogeneous responses to chemotherapy remain a significant clinical challenge. Here, we performed RNA sequencing (n = 97) and multiplexed immunofluorescence (n = 122) on chemo-naive and postchemotherapy (post-CTX) resected patient samples (chemoradiotherapy excluded) to define the impact of neoadjuvant chemotherapy. Transcriptome analysis combined with high-resolution mapping of whole-tissue sections identified GATA6 (classical), KRT17 (basal-like) and cytochrome P450 3A (CYP3A) coexpressing cells that were preferentially enriched in post-CTX resected samples. The persistence of GATA6hi and KRT17hi cells post-CTX was significantly associated with poor survival after mFOLFIRINOX (mFFX), but not gemcitabine (GEM), treatment. Analysis of organoid models derived from chemo-naive and post-CTX samples demonstrated that CYP3A expression is a predictor of chemotherapy response and that CYP3A-expressing drug detoxification pathways can metabolize the prodrug irinotecan, a constituent of mFFX. These findings identify CYP3A-expressing drug-tolerant cell phenotypes in residual disease that may ultimately inform adjuvant treatment selection

Guest Editorial

Peer Reviewe

Guest Editorial

Peer Reviewe

Machine learning meets communication networks:current trends and future challenges

Abstract The growing network density and unprecedented increase in network traffic, caused by the massively expanding number of connected devices and online services, require intelligent network operations. Machine Learning (ML) has been applied in this regard in different types of networks and networking technologies to meet the requirements of future communicating devices and services. In this article, we provide a detailed account of current research on the application of ML in communication networks and shed light on future research challenges. Research on the application of ML in communication networks is described in: i) the three layers, i.e., physical, access, and network layers; and ii) novel computing and networking concepts such as Multi-access Edge Computing (MEC), Software Defined Networking (SDN), Network Functions Virtualization (NFV), and a brief overview of ML-based network security. Important future research challenges are identified and presented to help stir further research in key areas in this direction

The sweet spot: defining virus-sialic acid interactions

Viral infections are initiated by attachment of the virus to host cell surface receptors, including sialic acid-containing glycans. It is now possible to rapidly identify specific glycan receptors using glycan array screening, to define atomic-level structures of virus-glycan complexes and to alter the glycan-binding site to determine the function of glycan engagement in viral disease. This Review highlights general principles of virus-glycan interactions and provides specific examples of sialic acid binding by viruses with stalk-like attachment proteins, including influenza virus, reovirus, adenovirus and rotavirus. Understanding virus-glycan interactions is essential to combating viral infections and designing improved viral vectors for therapeutic applications