We determined whether a large, multi-analyte panel of circulating biomarkers can improve detection of early-stage pancreatic ductal adenocarcinoma (PDAC). We defined a biologically relevant subspace of blood analytes based on previous identification in premalignant lesions or early-stage PDAC and evaluated each in pilot studies. The 31 analytes that met minimum diagnostic accuracy were measured in serum of 837 subjects (461 healthy, 194 benign pancreatic disease, 182 early stage PDAC). We used machine learning to develop classification algorithms using the relationship between subjects based on their changes across the predictors. Model performance was subsequently evaluated in an independent validation data set from 186 additional subjects.
The data set includes individual images of mouse cochleae, both scanning electron micrographs and fluorescent micrographs, used to generate aggregated data described in Pecha PP, Almishaal AA, Mathur PD, et al. Role of Free Radical Formation in Murine Cytomegalovirus–Induced Hearing Loss. Otolaryngology–Head and Neck Surgery. 2020;162(5):709-717. doi:10.1177/0194599820901485 and Objectives
The goal of the study was to determine whether reactive oxygen species (ROS) mediates cytomegalovirus (CMV)–induced labyrinthitis.
Murine model of CMV infection.
Subjects and Methods
Nrf2 knockout mice were inoculated with murine CMV. Auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) were then performed on these and uninfected controls. BALB/c mice were inoculated with murine CMV to determine whether a marker for ROS production, dihydroethidium (DHE), is expressed 7 days after inoculation. Finally, 2 antioxidants—D-methionine and ACE-Mg (vitamins A, C, and E with magnesium)—were administered 1 hour before and after infection in inoculated mice for 14 days. Temporal bones were harvested at postnatal day 10 for DHE detection. ABR and DPOAE testing was done at postnatal day 30. Scanning electron microscopy was also performed at postnatal day 30 to evaluate outer hair cell integrity.
Nrf2-infected mice had worse hearing than uninfected mice (P < .001). A statistically significant increase in DHE fluorescence was detected in BALB/c-infected mice as compared with uninfected mice 7 days after inoculation. D-methionine- and ACE-Mg-treated mice demonstrated an attenuation of the DHE fluorescence and a significant improvement in ABR and DPOAE thresholds when compared with untreated infected controls (P < .0001). Scanning electron microscopy demonstrated less outer hair cell loss in the treated versus untreated infected controls.
These results demonstrate for the first time that excessive ROS mediates CMV-induced hearing loss in a mouse model.