No abstract

Existing cell-free DNA (cfDNA) methods lack the sensitivity needed for detecting minimal residual disease (MRD) following therapy. We developed a test for tracking hundreds of patient-specific mutations to detect MRD with a 1,000-fold lower error rate than conventional sequencing. Experimental Design: We compared the sensitivity of our approach to digital droplet PCR (ddPCR) in a dilution series, then retrospectively identified two cohorts of patients who had undergone prospective plasma sampling and clinical data collection: 16 patients with ERþ/HER2À metastatic breast cancer (MBC) sampled within 6 months following metastatic diagnosis and 142 patients with stage 0 to III breast cancer who received curative-intent treatment with most sampled at surgery and 1 year postoperative. We performed whole-exome sequencing of tumors and designed individualized MRD tests, which we applied to serial cfDNA samples. Results: Our approach was 100-fold more sensitive than ddPCR when tracking 488 mutations, but most patients had fewer identifiable tumor mutations to track in cfDNA (median ¼ 57; range ¼ 2-346). Clinical sensitivity was 81% (n ¼ 13/16) in newly diagnosed MBC, 23% (n ¼ 7/30) at postoperative and 19% (n ¼ 6/32) at 1 year in early-stage disease, and highest in patients with the most tumor mutations available to track. MRD detection at 1 year was strongly associated with distant recurrence [HR ¼ 20.8; 95% confidence interval, 7.3-58.9]. Median lead time from first positive sample to recurrence was 18.9 months (range ¼ 3.4-39.2 months). Conclusions: Tracking large numbers of individualized tumor mutations in cfDNA can improve MRD detection, but its sensitivity is driven by the number of tumor mutations available to track.

We report a hydrothermal reaction to make t-selenium nanotubes, in the absence of a surfactant or polymer to direct nanoparticle growth, and without externally added forces (such as ultrasonic). A series of electron microscopy characterization results suggest that the growth of t-selenium nanotubes is governed by a nucleation−dissolution−recrystallization growth mechanism. In this mechanism, t-selenium nanoparticles were initially formed in the hydrothermal system, then the t-selenium nanoparticles started to dissolve into the solution and grow onto large nanoparticles of selenium, and spherelike microparticles were obtained. The spherelike microparticles then gradually dissolved to generate selenium atoms in the solution; these selenium atoms were renewedly transferred onto the surfaces of the spherelike microparticles and were recrystallized. Along with the dissolution−recrystallization process, the spherelike microparticles gradually evolved into novel groovelike nanostructures. The nanogrooves could grow along the circumferential direction and the tuber axis direction until all spherelike microparticles had been completely consumed, eventually growing into t-selenium nanotubes. Studies found that this growth mechanism is strongly affected by temperature and concentrations of NaOH. By adjusting temperature and concentrations of NaOH, t-selenium nanotubes, nanowires, microrods, porous microtubes, and polyhedrons can be synthesized, respectively.

This paper reports well-aligned arrays of CuO nanoplatelets synthesized through a hydrothermal route without template's assistance. The surface of well-aligned arrays of CuO nanoplatelets looks like a wall. These nanoplatelets, possessing four clear edges, are 50-80 nm in thickness, 150-250 nm in width, and 0.8-1.5 microm in length. Electron microscopic detection shows that the nanoplatelet grows along the [010] direction. The Ostwald ripening mechanism has been used to describe the growth of CuO nanoplatelets. In addition, the optic and electrochemical properties of as-obtained products have been discussed. And the arrays of CuO nanoplatelets exhibit the blue shift in UV-visible spectra, a slow capacity fading rate, and a relatively high Coulombic efficiency in charge-discharge process.