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Commun Biol
January 2025
University of Twente, Enschede, The Netherlands.
Deep learning classification models based on Convolutional Neural Networks (CNNs) are increasingly used in population genetic inference for detecting signatures of natural selection. Prevailing detection methods treat the design of the classifier as a discrete phase, assuming that high classification accuracy is the sole prerequisite for precise detection. This frequently steers method development toward classification-driven optimizations that can inadvertently impede detection.
View Article and Find Full Text PDFJ Hepatobiliary Pancreat Sci
January 2025
Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.
In Japan, 5 years have passed since the initiation of precision cancer medicine, and recent data accumulation in familial pancreatic cancer (FPC) and hereditary pancreatic cancer is outstanding. Multigene germline panel tests (MGPTs) have revealed that 7%-18% of patients with pancreatic cancer (PC) harbor pathogenic germline variants (PGVs), almost equal to the levels of breast, ovarian, endometrial, and colorectal cancers, with a higher incidence in FPC (14%-26%). The majority of PGVs seen in PC patients are clinically actionable and associated with homologous recombination (HR) pathways (6%-10%, particularly BRCA1/2 in 5%-6%), and the clinical guidelines recommend or propose genetic testing for all PC patients.
View Article and Find Full Text PDFSci Transl Med
January 2025
College of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou 310058, China.
Macrophages play a central role in antitumor immunity, making them an attractive target for gene therapy strategies. However, macrophages are difficult to transfect because of nucleic acid sensors that can trigger the degradation of foreign plasmid DNA. Here, we developed a macrophage-specific editing (MAGE) system by which compact plasmid DNA encoding a CasRx editor can be delivered to macrophages by a poly(β-amino ester) (PBAE) carrier to bypass the DNA sensor and enable RNA editing in vitro and in vivo.
View Article and Find Full Text PDFGenes Chromosomes Cancer
January 2025
Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, University of Gothenburg, Gothenburg, Sweden.
Pleomorphic adenoma (PA) is the most common salivary gland tumor. PAs are characterized by chromosomal rearrangements of 8q12 and 12q14-15, leading to gene fusions involving the PLAG1 and HMGA2 oncogenes. Here, we performed the first comprehensive study of the transcriptomic and gene fusion landscape of 38 cytogenetically characterized PAs.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
Conjugation plays a major role in dissemination of antimicrobial resistance genes. Following transfer of IncF-like plasmids, recipients become refractory to a second wave of conjugation with the same plasmid via entry (TraS) and surface (TraT) exclusion mechanisms. Here, we show that TraT from the pKpQIL and F plasmids (TraT and TraT) exhibits plasmid surface exclusion specificity.
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