Abstract. We present initial prototype and preliminary experimental demonstration of a new class of microsurgical instruments that incorporate common path optical coherence tomography (CP-OCT) capabilities. These instruments may be used freehand or with robotic assistance. We describe a prototype 25 gauge microsurgical pick incorporating a single 125 μm diameter optical fiber interfaced to a Fourier Domain CP-OCT system developed in our laboratory. For initial experimentation, we have interfaced this instrument with an extremely precise, cooperatively controlled robot. We describe the tool, system design, and demonstration of three control methods on simple phantom models: 1) enforcement of safety constraints preventing unintentional collisions of the instrument with the retinal surface; 2) the ability to scan the probe across a surface while maintaining a constant distance offset; and 3) the ability to place the pick over a subsurface target identified in a scan and then penetrate the surface to hit the target.
CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) plays a crucial role in the stability of the programmed death-ligand 1 (PD-L1). However, there has been no previous study of CMTM6 in non-small cell lung cancer (NSCLC) and its association with PD-L1 has not been confirmed. The aim of this study was to investigate the expression of CMTM6 and PD-L1 and to confirm their predictive roles for anti-PD-1 therapy in non-small cell lung cancer. CMTM6 and PD-L1 immunohistochemical expressions were evaluated in 35 advanced, treatment-refractory NSCLC patients who received PD-1 inhibitor therapy. The correlation between CMTM6 and PD-L1 expression was also determined based on immunohistochemistry and RNA-sequencing data obtained from The Cancer Genome Atlas (TCGA) database. CMTM6 expression was positively correlated with PD-L1 expression in immunohistochemical data (Pearson's r = 0.342 and p = .044). A positive correlation was also identified in the mRNA expression data. Using receiver operating characteristic curves, the levels of CMTM6 and PD-L1 expression which provided the best distinguishing point between responder versus non-responder to PD-1 inhibitors were 70 and 75 H-scores, respectively. The patients in the PD-1 inhibitor responder group had higher CMTM6 expressions in univariate logistic regression analysis (odds ratio (OR) = 5.333, p = .037). However, PD-L1 expression was not associated with response to PD-1 inhibitor (p = .288). In multivariate analysis, CMTM6 was also found to be an independent predictor of the response to PD-1 inhibitors (OR = 6.226, p = .032). CMTM6 expression can be a promising predictor useful for therapeutic decision-making regarding PD-1 inhibitors.
A single-arm interferometer based optical coherence tomography (OCT) system known as common-path OCT (CPOCT) is rapidly progressing towards practical application. Due in part to the simplicity and robustness of its design, Fourier Domain CPOCT (FD-CP-OCT) offers advantages in many endoscopic sensing and imaging applications. FD-CP-OCT uses simple, interchangeable fiber optic probes that are easily integrated into small and delicate surgical tools. The system is capable of providing not only high resolution imaging but also optical sensing. Here, we report progress towards practical application of FD-CP-OCT in the setting of delicate microsurgical procedures such as intraocular retinal surgery. To meet the challenges presented by the microsurgical requirements of these procedures, we have developed and initiated the validation of applicable fiber optic probes. By integrating these probes into our developing imaging system, we have obtained high resolution OCT images and have also completed a demonstration of their potential sensing capabilities. Specifically, we utilize multiple SLEDs to demonstrate sub 3-micron axial resolution in water; we propose a technique to quantitatively evaluate the spatial distribution of oxygen saturation levels in tissue; and we present evidence supportive of the technology’s surface sensing and tool guidance potential by demonstrating topological and motion compensation capabilities.
A new nonribosomal peptide, nyuzenamide C (1), was discovered from riverine sediment-derived Streptomyces sp. DM14. Comprehensive analysis of the spectroscopic data of nyuzenamide C (1) revealed that 1 has a bicyclic backbone composed of six common amino acid residues (Asn, Leu, Pro, Gly, Val, and Thr) and four nonproteinogenic amino acid units, including hydroxyglycine, β-hydroxyphenylalanine, p-hydroxyphenylglycine, and 3,β-dihydroxytyrosine, along with 1,2-epoxypropyl cinnamic acid. The absolute configuration of 1 was proposed by Jbased configuration analysis, the advanced Marfey's method, quantum mechanics-based DP4 calculations, and bioinformatic analysis of its nonribosomal peptide synthetase biosynthetic gene cluster. Nyuzenamide C (1) displayed antiangiogenic activity in human umbilical vein endothelial cells and induced quinone reductase in murine Hepa-1c1c7 cells.
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