Purpose: To identify MRI-based radiomics as prognostic factors in patients with advanced nasopharyngeal carcinoma (NPC).Experimental Design: One-hundred and eighteen patients (training cohort: n ¼ 88; validation cohort: n ¼ 30) with advanced NPC were enrolled. A total of 970 radiomics features were extracted from T2-weighted (T2-w) and contrast-enhanced T1-weighted (CET1-w) MRI. Least absolute shrinkage and selection operator (LASSO) regression was applied to select features for progression-free survival (PFS) nomograms. Nomogram discrimination and calibration were evaluated. Associations between radiomics features and clinical data were investigated using heatmaps.Results: The radiomics signatures were significantly associated with PFS. A radiomics signature derived from joint CET1-w and T2-w images showed better prognostic performance than signatures derived from CET1-w or T2-w images alone. One radiomics nomogram combined a radiomics signature from joint CET1-w and T2-w images with the TNM staging system. This nomogram showed a significant improvement over the TNM staging system in terms of evaluating PFS in the training cohort (C-index, 0.761 vs. 0.514; P < 2.68 Â 10 À9 ). Another radiomics nomogram integrated the radiomics signature with all clinical data, and thereby outperformed a nomogram based on clinical data alone (C-index, 0.776 vs. 0.649; P < 1.60 Â 10 À7 ). Calibration curves showed good agreement. Findings were confirmed in the validation cohort. Heatmaps revealed associations between radiomics features and tumor stages. Conclusions: Multiparametric MRI-based radiomics nomograms provided improved prognostic ability in advanced NPC. These results provide an illustrative example of precision medicine and may affect treatment strategies.

Supporting information placeholder ABSTRACT:We measure electronic conductance through single conjugated molecules bonded to Au metal electrodes with direct Au-C covalent bonds using the scanning tunneling microscope based break-junction technique. We start with molecules terminated with trimethyltin end groups that cleave off in situ resulting in formation of a direct covalent sigma bond between the carbon backbone and the gold metal electrodes. The molecular carbon backbone used in this study consist of a conjugated system that has one terminal methylene group on each end, which bonds to the electrodes, achieving large electronic coupling of the electrodes to the system. The junctions formed with the prototypical example of 1,4-dimethylenebenzene show a conductance approaching one conductance quantum (G 0 = 2e 2 /h). Junctions formed with methylene terminated oligophenyls with two to four phenyl units show a hundred-fold increase in conductance compared with junctions formed with amine-linked oligophenyls. The conduction mechanism for these longer oligophenyls is tunneling as they exhibit an exponential dependence of conductance with oligomer length. In addition, density functional theory based calculations for the Au-xylylene-Au junction show nearresonant transmission with a cross-over to tunneling for the longer oligomers.

FAM134B/RETREG1 is a selective ER-phagy receptor that regulates the size and shape of the endoplasmic reticulum. The structure of its reticulon-homology domain (RHD), an element shared with other ER-shaping proteins, and the mechanism of membrane shaping remain poorly understood. Using molecular modeling and molecular dynamics (MD) simulations, we assemble a structural model for the RHD of FAM134B. Through MD simulations of FAM134B in flat and curved membranes, we relate the dynamic RHD structure with its two wedge-shaped transmembrane helical hairpins and two amphipathic helices to FAM134B functions in membrane-curvature induction and curvature-mediated protein sorting. FAM134B clustering, as expected to occur in autophagic puncta, amplifies the membrane-shaping effects. Electron microscopy of in vitro liposome remodeling experiments support the membrane remodeling functions of the different RHD structural elements. Disruption of the RHD structure affects selective autophagy flux and leads to disease states.

We report the simultaneous measurement of conductance and thermopower of highly conducting single-molecule junctions using a scanning tunneling microscope-based break-junction setup. We start with molecular backbones (alkanes and oligophenyls) terminated with trimethyltin end groups that cleave off in situ to create junctions where terminal carbons are covalently bonded to the Au electrodes. We apply a thermal gradient across these junctions and measure their conductance and thermopower. Because of the electronic properties of the highly conducting Au-C links, the thermoelectric properties and power factor are very high. Our results show that the molecular thermopower increases nonlinearly with the molecular length while conductance decreases exponentially with increasing molecular length. Density functional theory calculations show that a gateway state representing the Au-C covalent bond plays a key role in the conductance. With this as input, we analyze a series of simplified models and show that a tight-binding model that explicitly includes the gateway states and the molecular backbone states accurately captures the experimentally measured conductance and thermopower trends.