Estimating individualized treatment rules by optimizing the adjusted probability of a longer survival.

Individualized treatment rules inform tailored treatment decisions based on the patient's information, where the goal is to optimize clinical benefit for the population. When the clinical outcome of interest is survival time, most of current approaches typically aim to maximize the expected time of survival. We propose a new criterion for constructing Individualized treatment rules that optimize the clinical benefit with survival outcomes, termed as the adjusted probability of a longer survival. This objective captures the likelihood of living longer with being on treatment, compared to the alternative, which provides an alternative and often straightforward interpretation to communicate with clinicians and patients. We view it as an alternative to the survival analysis standard of the hazard ratio and the increasingly used restricted mean survival time. We develop a new method to construct the optimal Individualized treatment rule by maximizing a nonparametric estimator of the adjusted probability of a longer survival for a decision rule. Simulation studies demonstrate the reliability of the proposed method across a range of different scenarios. We further perform data analysis using data collected from a randomized Phase III clinical trial (SWOG S0819).

Identification of Nanog as a novel inhibitor of Rad51.

To develop inhibitors targeting DNA damage repair pathways is important to improve the effectiveness of chemo- and radiotherapy for cancer patients. Rad51 mediates homologous recombination (HR) repair of DNA damages. It is widely overexpressed in human cancers and overwhelms chemo- and radiotherapy-generated DNA damages through enhancing HR repair signaling, preventing damage-caused cancer cell death. Therefore, to identify inhibitors of Rad51 is important to achieve effective treatment of cancers. Transcription factor Nanog is a core regulator of embryonic stem (ES) cells for its indispensable role in stemness maintenance. In this study, we identified Nanog as a novel inhibitor of Rad51. It interacts with Rad51 and inhibits Rad51-mediated HR repair of DNA damage through its C/CD2 domain. Moreover, Rad51 inhibition can be achieved by nanoscale material- or cell-penetrating peptide (CPP)-mediated direct delivery of Nanog-C/CD2 peptides into somatic cancer cells. Furthermore, we revealed that Nanog suppresses the binding of Rad51 to single-stranded DNAs to stall the HR repair signaling. This study provides explanation for the high γH2AX level in unperturbed ES cells and early embryos, and suggests Nanog-C/CD2 as a promising drug candidate applied to Rad51-related basic research and therapeutic application studies.

Comparison of contrast-enhanced ultrasonography with virtual touch tissue quantification in the evaluation of focal liver lesions.

PURPOSE: To evaluate the diagnostic efficacy of virtual touch tissue quantification (VTQ) and contrast-enhanced ultrasonography (CEUS), separately and in combination, in diagnosing malignant focal liver lesions (FLLs). METHODS: Forty-six patients with 55 FLLs (28 benign and 27 malignant) underwent both VTQ and CEUS. The diagnostic values of VTQ and CEUS, alone and in combination, were compared. RESULTS: The diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of CEUS were 92.6% (25/27), 96.4% (27/28), 94.5% (52/55), 96.2% (25/26), and 93.1% (27/29), respectively. The diagnostic sensitivity, specificity, accuracy, PPV, and NPV of VTQ with a cutoff of 2.22 m/s were 51.9% (14/27), 85.7% (24/28), 69.1% (38/55), 77.8% (14/18), and 64.9% (24/37), respectively. The diagnostic sensitivity, specificity, accuracy, PPV, and NPV of VTQ and CEUS combined were 96.3% (26/27), 82.1% (23/28), 89.1% (49/55), 83.9% (26/31), and 95.8% (23/24), respectively. Comparing the accuracies of the three methods, the diagnostic values of CEUS and of the combination of CEUS with VTQ were significantly higher than those of VTQ alone (p ≤ 0.01). There was no significant difference between the combination of CEUS with VTQ and CEUS (p = 0.49). CONCLUSIONS: CEUS is superior to VTQ in diagnosing malignant FLLs. Adding VTQ to CEUS did not improve the diagnosis of FLLs. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:347-353, 2016.

[Time-resolved FTIR study of amorphous process of nylon 6 with calcium chloride].

The influence of calcium chloride on the crystallinity of nylon 6 was studied by means of time-resolved FTIR, WADX and DSC. The results show that the crystallinity of nylon 6 decreased with the increase of CaCl2, and finally nylon 6 changed from crystal phase to amorphous phase. Because hydrogen bond is the main reason that nylon has three-dimensional ordered structure and forms crystalline phase, we further studied the changes of wave number of NH, amide I and amide II related to hydrogen bond in CaCl2/PA6 complexes by time-resolved FTIR. These studies indicate that in the chloroethanol solution of nylon 6 and calcium chloride, complex bonds between calcium cation and oxygen atom of carbonyl group gradually form, and calcium cations are inserted into the molecular chains of nylon 6, which weaken the hydrogen bonds between the molecular chains of nylon 6 and damage the three-dimensional ordered structure of nylon 6, so the crystallinity of nylon 6 decreases and nylon 6 changes from crystalline to amorphous phase.