Methylated SEPT9 showed relatively low sensitivity in detecting early stage colorectal cancer (CRC) and advanced adenomas (AA) in plasma. Combination of multiple biomarkers was an effective strategy to improve sensitivity in early stage cancer diagnosis and screening. A new qPCR‐based assay combining the detection of methylated SEPT9 and SDC2 (ColoDefense test) was used. Methylation statuses of SEPT9 and SDC2 were examined in 40 sets of cancer tissues and paired adjacent tissues, 10 adenomatous polyps and 3 hyperplastic polyps (HP). Then evaluated with 384 plasma samples, including 117 CRC patients, 23 AA patients, 78 small polyps patients, and 166 normal individuals. The limit of detection of ColoDefense was about 25 pg per reaction. Both SEPT9 and SDC2 were shown by ColoDefense to be heavily methylated in CRC tissues when compared to paired paracancerous tissues and HP (P < .01). The sensitivities for detecting AA and stage I CRC by plasma SEPT9 methylation alone were 12.1% and 65.0%, and those by plasma SDC2 methylation alone were 43.5% and 55.0%. In comparison, the sensitivities to detect AA and stage I CRC by ColoDefense improved to 47.8% and 80.0%. The overall sensitivity of ColoDefense in detecting CRC was 88.9% (95% CI: 81.4%‐93.7%) with a specificity of 92.8% (95% CI: 87.4%‐96.0%). Detection of the combinatorial biomarker of methylated SEPT9 and/or SDC2 is a powerful, convenient and highly effective strategy for early CRC screening with high sensitivity and specificity.
Langmuir circulations (LCs) generated by the interaction between wind-driven currents and surface waves can engulf the whole water column in neutrally stratified shallow water and interact with the turbulence in the bottom boundary layer. In this study, we perform a mechanistic study using wall-resolved large-eddy simulations (LES) based on the Craik–Leibovich equations to investigate the effects of LCs on turbulence statistics in the bottom half of shallow water. The highest Reynolds number considered in this paper, $Re_{\unicode[STIX]{x1D70F}}=1000$, is larger than the values considered in wall-resolved LES studies of shallow-water Langmuir turbulence reported in literature. The logarithmic layer is diagnosed based on a plateau region in the profile of a diagnostic function. It is found that the logarithmic layer disrupted at $Re_{\unicode[STIX]{x1D70F}}=395$ reappears at $Re_{\unicode[STIX]{x1D70F}}=1000$, but the von Kármán constant is slightly different from the traditional value $0.41$. To study the effects of LCs on turbulence statistics, LCs are extracted using streamwise averaging. The velocity fluctuations $u_{i}^{\prime }$ are decomposed into a LC-coherent part $u_{i}^{L}$ and a residual turbulence part $u_{i}^{T}$. It is found that the profiles of LC-coherent Reynolds shear stress $-\langle u^{L}v^{L}\rangle$ obtained at various Reynolds numbers are close to each other in the water-column coordinate $y/h$, with $h$ being the half-water depth. As the Reynolds number (or, by definition, the ratio between the outer and inner length scales) increases, the influence of LCs on the near-bottom momentum transfer is reduced, which is responsible for the reappearance of the logarithmic layer. At all of the Reynolds numbers under investigation, the peaks of $\langle u^{L}u^{L}\rangle$ are collocated in the water-column coordinate $y/h$, while those of $\langle u^{T}u^{T}\rangle$ are collocated in the inner-scale coordinate $y/(\unicode[STIX]{x1D708}/u_{\unicode[STIX]{x1D70F}})$. Due to the increase in the distance between the peaks of $\langle u^{L}u^{L}\rangle$ and $\langle u^{T}u^{T}\rangle$ with the Reynolds number, the profile of $\langle u^{\prime }u^{\prime }\rangle$ forms a bimodal shape at $Re_{\unicode[STIX]{x1D70F}}=700$ and $1000$.
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