Patterns, timing and predictors of recurrence following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: an international multicentre retrospective cohort study.

Background: Most patients undergoing pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) develop recurrence. No previous studies have investigated predictors of local-only recurrence following PD for PDAC. Our study aimed to determine timing, pattern and predictors of any-site and local-only recurrence following PD for PDAC.

A High-Throughput Screening Pipeline to Identify Methyltransferase and Exonuclease Inhibitors of SARS-CoV-2 NSP14.

SARS-CoV-2 infections led to a worldwide pandemic in 2020. As of 2024, therapeutics against SARS-CoV-2 have continued to be desirable. NSP14 is a dual-function methyltransferase (MTase) and exonuclease (ExoN) with key roles in SARS-CoV-2 genome propagation and host immune system evasion.

Discovery of BBO-8520, a first-in-class direct and covalent dual inhibitor of GTP-bound (ON) and GDP-bound (OFF) KRASG12C.

Approved inhibitors of KRASG12C prevent oncogenic activation by sequestering the inactive, GDP-bound (OFF) form rather than directly binding and inhibiting the active, GTP-bound (ON) form. This approach provides no direct target coverage of the active protein. Expectedly, adaptive resistance to KRASG12C (OFF)-only inhibitors is observed in association with increased expression and activity of KRASG12C(ON).

TRAMP assembly alters the conformation and RNA binding of Mtr4 and Trf4-Air2.

The TRAMP complex contains two enzymatic activities essential for RNA processing upstream of the nuclear exosome. Within TRAMP, RNA is 3' polyadenylated by a sub-complex of Trf4/5 and Air1/2 and unwound 3' to 5' by Mtr4, a DExH helicase. The molecular mechanisms of TRAMP assembly and RNA shuffling between the two TRAMP catalytic sites are poorly understood.