https://www.selleckchem.com/products/nsc697923.html This article proposes four new principles for logical biomarker cut-point selection methods to adhere to subgroup sensibility, sensitivity, specificity, and target monotonicity. At every cut-point value, our method gives confidence intervals not only for the efficacy at that cut-point value, but also efficacies in the marker-positive and marker-negative subgroups defined by that cut-point. These confidence intervals are given simultaneously for all possible cut-point values. Using Alzheimer's disease (AD) and type 2 diabetes (T2DM) as examples, we show our method achieves the four principles. Our method strongly controls familywise type I error rate (FWER) across both levels of multiplicity the multiplicity of having marker-positive and marker-negative subgroups at each cut-point, and the multiplicity of searching through infinitely many cut-points. This is in contrast to other available methods. The confidence level of our simultaneous confidence intervals is in fact exact (not conservative). An application (app) is available, which implements the method we propose.Dedifferentiation of tubular epithelial cells is involved in both regeneration and fibrosis following acute kidney injury (AKI). Prostaglandin E2 receptor 4 (EP4 ) antagonist can inhibit the dedifferentiation of renal tubular cells. The present study investigated whether the time of blockage of EP4 receptors, using grapiprant, could affect the tubular regeneration or interstitial fibrosis in AKI. Cisplatin was used to induce AKI in 72 C57BL/6 adult female mice. Animals were assigned to four groups; control, cisplatin-treated, cisplatin-treated with early grapiprant intervention and cisplatin-treated with late grapiprant intervention. AKI was assessed by kidney function tests and histopathology. Fibrosis was evaluated by Masson's trichrome and alpha smooth muscle actin (α-SMA) expression. Markers of dedifferentiation, CD133, and epithelial to mesenchymal