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Targeted Next-Generation Sequencing in Succinate Dehydrogenase-Deficient GI Stromal Tumor Identifies Actionable Alterations in the PI3K/mTOR Pathway.
JCO Precis Oncol
January 2025
Sarcoma Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Purpose: Less than 5% of GI stromal tumors (GISTs) are driven by the loss of the succinate dehydrogenase (SDH) complex, resulting in a pervasive DNA hypermethylation pattern that leads to unique clinical features. Advanced SDH-deficient GISTs are usually treated with the same therapies targeting KIT and PDGFRA receptors as those used in metastatic GIST. However, these treatments display less activity in the absence of alternative therapeutic options.
View Article and Find Full Text PDFDrug Delivery in PROSE Device as Alternative to Frequent Drop Administration in Severe Ocular Surface Disease.
Eye Contact Lens
December 2024
Department of Ophthalmology, Massachusetts Eye & Ear, Harvard University, Boston, MA.
The design of the prosthetic replacement of the ocular surface ecosystem (PROSE) device allows it to serve as a novel drug delivery system. In this article, we describe the off-label administration of amphotericin B and cenegermin by instillation in the PROSE device reservoir for the treatment of Candida keratitis in the setting of a persistent epithelial defect.
View Article and Find Full Text PDFSoliton and rogue wave excitations in the Chen-Lee-Liu derivative nonlinear Schrödinger equation with two complex PT-symmetric potentials.
Chaos
January 2025
School of Mathematics and Statistics, Jiangsu Normal University, Xuzhou 221116, China.
We demonstrate that fundamental nonlinear localized modes can exist in the Chen-Lee-Liu equation modified by several parity-time (PT) symmetric complex potentials. The explicit formula of analytical solitons is derived from the physically interesting Scarf-II potential, and families of spatial solitons in internal modes are numerically captured under the optical lattice potential. By the spectral analysis of linear stability, we observe that these bright solitons can remain stable across a broad scope of potential parameters, despite the breaking of the corresponding linear PT-symmetric phases.
View Article and Find Full Text PDFModifications to rhesus macaque TCR constant regions improve TCR cell surface expression.
PLoS One
January 2025
AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
T cell immunotherapy success is dependent on effective levels of antigen receptor expressed at the surface of engineered cells. Efforts to optimize surface expression in T cell receptor (TCR)-based therapeutic approaches include optimization of cellular engineering methods and coding sequences, and reducing the likelihood of exogenous TCR α and β chains mispairing with the endogenous TCR chains. Approaches to promote correct human TCR chain pairing include constant region mutations to create an additional disulfide bond between the two chains, full murinization of the constant region of the TCR α and β sequences, and a minimal set of murine mutations to the TCR α and β constant regions.
View Article and Find Full Text PDFBackground: Understanding the relationship between genetic variations and brain imaging phenotypes is an important issue in Alzheimer's disease (AD) research. As an alternative to GWAS univariate analyses, canonical correlation analysis (CCA) and its deep learning extension (DCCA) are widely used to identify associations between multiple genetic variants such as SNPs and multiple imaging traits such as brain ROIs from PET/MRI. However, with the recent availability of numerous genetic variants from genotyping and whole genome sequencing data for AD, these approaches often suffer from severe overfitting when dealing with 'fat' genetics data, e.
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