Targeting N-Myc in neuroblastoma with selective Aurora kinase A degraders.

The N-Myc transcription factor, encoded by MYCN, is a mechanistically validated, yet challenging, target for neuroblastoma (NB) therapy development. In normal neuronal progenitors, N-Myc undergoes rapid degradation, while, in MYCN-amplified NB cells, Aurora kinase A (Aurora-A) binds to and stabilizes N-Myc, resulting in elevated protein levels. Here, we demonstrate that targeted protein degradation of Aurora-A decreases N-Myc levels.

Structural Insights into the Assembly and Regulation of 2'- RNA Methylation by SARS-CoV-2 nsp16/nsp10.

2'- -ribose methylation of the first transcribed base (adenine or A in SARS-CoV-2) of viral RNA mimics the host RNAs and subverts the innate immune response. How nsp16, with its obligate partner nsp10, assembles on the 5'-end of SARS-CoV-2 mRNA to methylate the A has not been fully understood. We present a ∼ 2.

Mammalian ZAP and KHNYN independently restrict CpG-enriched avian viruses.

Unlabelled: Zoonotic viruses are an omnipresent threat to global health. Influenza A virus (IAV) transmits between birds, livestock, and humans. Proviral host factors involved in the cross-species interface are well known.

Optimum diagnostic pathway and pathologic confirmation rate of early stage lung cancer: Results from the VIOLET randomised controlled trial.

Background: Pathologic confirmation of lung cancer influences treatment selection for suspected early-stage lung cancer. High pre-treatment tissue confirmation rates are recommended. We sought to define management and outcomes of patients undergoing surgery for primary lung cancer in a UK multi-centre clinical trial.

Impact and cost-effectiveness of scaling up HCV testing and treatment strategies for achieving HCV elimination among people who inject drugs in England: a mathematical modelling study.

Background: England aims to reach the World Health Organization (WHO) elimination target of decreasing HCV incidence among people who inject drugs (PWID) to <2 per 100 person-years (/100pyrs) by 2030. We assessed what testing and treatment strategies will achieve this target and whether they are cost-effective.

Methods: A dynamic deterministic HCV transmission model among PWID was developed for four England regions, utilising data on the scale-up of HCV treatment among PWID in prisons, drug treatment centres (DTC, where opioid agonist therapy is provided), and any other setting (e.