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Essential Tremor (ET) is characterized by action tremor often associated with resting tremor (rET). Although previous studies have identified widespread brain white matter (WM) alterations in ET patients, differences between ET and rET have been less explored. In this study we employed differential tractography to investigate WM microstructural alterations in these tremor disorders. We conducted a Diffusion Tensor Imaging (DTI) study on age- and sex-matched cohorts: 25 healthy controls (HC), 30 ET, and 30 rET patients. Differential tractography using DSI Studio was employed to pairwise compare fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) among cohorts. ET and rET patients compared to HC exhibited similar widespread MD increase especially in basal ganglia and brainstem projections. WM changes were more pronounced in the left cerebral hemisphere and cerebellum (crus I and II) in ET, while in rET patients WM alterations were prevalent in right cerebral hemisphere and cerebellum crus I. Small FA decrease was found in rET but not in ET patients. ET patients showed changes in the left non-decussating dentato-rubro-thalamic tract (ndDRTT), whereas rET patients showed changes in both left ndDRTT and right decussating DRTT. In conclusion, our findings confirmed the DRTT involvement in essential tremor and demonstrated that ET and rET exhibited similar microstructural WM changes in the brain, with different hemispheric involvement-greater on the left side in ET and on the right side in rET-suggesting that these tremor disorders may be distinct subtypes of the same disease.
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http://dx.doi.org/10.1016/j.nicl.2025.103734 | DOI Listing |
Head Neck Pathol
September 2025
Department of Laboratory Medicine and Pathology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Myoepithelial carcinoma (MECA) is a malignant neoplasm composed exclusively of myoepithelial cells and accounts for less than 1% of all salivary gland tumors. Its diagnosis is often challenging due to histologic overlaps with benign lesions and its variable morphologic presentation. Although molecular profiling has emerged as a valuable tool in salivary gland tumor classification, the genetic landscape of MECA remains incompletely defined.
View Article and Find Full Text PDFJ Med Chem
September 2025
Applied Pharmaceutical Science, Inc., Building 10-1, No.2, Jingyuan North Street, BDA, Beijing 100176, China.
This study reports the discovery and preclinical activity of APS03118, a novel selective RET inhibitor featuring a novel tricyclic pyrazolo[3',4':3,4]pyrazolo[1,5-]pyridine hinge-binding scaffold designed to overcome acquired resistance to first-generation selective RET inhibitors (SRIs). By enhancing hydrogen bonding with conserved hinge residues (Glu805, Ala807), APS03118 potently inhibits wild-type RET and diverse resistance mutations, including solvent-front (G810R/S/C), gatekeeper (V804M/L/E), roof (L730I/M), and hinge (Y806C/N/H) variants. In preclinical models, APS03118 induced complete tumor regression in KIF5B-RET and CCDC6-RET V804 M patient-derived xenografts (PDXs) and significantly prolonged survival in an intracranial CCDC6-RET metastasis model.
View Article and Find Full Text PDFCurr Cancer Drug Targets
September 2025
Department of Critical Care Medicine, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, 358 Datong Road, Pudong New District, Shanghai 200137, China.
Introduction: The incidence of brain metastases in patients diagnosed with ad-vanced lung cancer is high, drawing significant attention to the risk factors associated with this progression.
Methods: A total of 252 advanced non-small cell lung cancer (NSCLC) patients with brain metastases were enrolled in this study between July 2018 and December 2023 from our hos-pital. Additionally, driver genes, including EGFR, ALK, ROS1, KRAS, and RET, were doc-umented.
Bioorg Chem
September 2025
Department of Pharmacy, Personalized Drug Research and Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. Electronic address:
RET tyrosine kinase, a key regulator of cellular signaling, is abnormally activated due to mutations or fusions in various cancers, making it an important therapeutic target. Traditional multi-kinase inhibitors (MKIs, such as cabozantinib and vandetanib) exhibit significant side effects due to non-selective inhibition of targets like VEGFR, and also suffer from resistance associated with RET mutations (e.g.
View Article and Find Full Text PDFJ Am Soc Cytopathol
July 2025
Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
Introduction: Molecular testing on thyroid fine needle aspirations with indeterminate cytology is integral to patient management. The aim of this study was to investigate the risk of malignancy in nodules diagnosed as Bethesda category IV, follicular neoplasm (FN), with and without cytologic atypia.
Methods: A total of 186 thyroid fine needle aspirations classified as Bethesda category IV (FN) were identified, and were categorized as FN with cytologic atypia or without cytologic atypia.