Browsing by Author "Li, Qian"

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    Bayesian Order Constrained Adaptive (BOCA) Design for Phase II Clinical Trials Evaluating Subgroup-Specific Treatment Effect
    (Sage, 2023) Shan, Mu; Guo, Beibei; Liu, Hao; Li, Qian; Zang, Yong; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    The "one-size-fits-all'' paradigm is inappropriate for phase II clinical trials evaluating biotherapies, which are often expected to have substantial heterogeneous treatment effects among different subgroups defined by biomarker. For these biotherapies, the objective of phase II clinical trials is often to evaluate subgroup-specific treatment effects. In this article, we propose a simple yet efficient Bayesian adaptive phase II biomarker-guided design, referred to as the Bayesian-order constrained adaptive design, to detect the subgroup-specific treatment effects of biotherapies. The Bayesian order constrained adaptive design combines the features of the enrichment design and sequential design. It starts with a "all-comers" stage, and subsequently switches to an enrichment stage for either the marker-positive subgroup or marker-negative subgroup, depending on the interim analysis results. The go/no go enrichment criteria are determined by two posterior probabilities utilizing the inherent ordering constraint between two subgroups. We also extend the Bayesian-order constrained adaptive design to handle the missing biomarker situation. We conducted comprehensive computer simulation studies to investigate the operating characteristics of the Bayesian order constrained adaptive design, and compared it with other existing and conventional designs. The results shown that the Bayesian order constrained adaptive design yielded the best overall performance in detecting the subgroup-specific treatment effects by jointly considering the efficiency and cost-effectiveness of the trials. The software for simulation and trial implementation are available for free download.
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    Meta-Analysis: Contrast-Enhanced Ultrasound Versus Conventional Ultrasound for Differentiation of Benign and Malignant Breast Lesions
    (Elsevier, 2018-05) Li, Qian; Hu, Min; Chen, Zhikui; Li, Changtian; Zhang, Xi; Song, Yiqing; Xiang, Feixiang; Epidemiology, School of Public Health
    This meta-analysis aimed to compare the diagnostic performance of contrast-enhanced ultrasound (CEUS), conventional ultrasound (US) combined with CEUS (US + CEUS) and US for distinguishing breast lesions. From thorough literature research, studies that compared the diagnostic performance of CEUS versus US or US + CEUS versus US, using pathology results as the gold standard, were included. A total of 10 studies were included, of which 9 compared the diagnostic performance of CEUS and US, and 5 studies compared US + CEUS and US. In those comparing CEUS versus US, the pooled sensitivity was 0.93 (95% CI: 0.91–0.95) versus 0.87 (95% CI: 0.85–0.90) and pooled specificity was 0.86 (95% CI: 0.84–0.88) versus 0.72 (95% CI: 0.69–0.75). In studies comparing US + CEUS versus US, the pooled sensitivity was 0.94 (95% CI: 0.92–0.96) versus 0.87 (95% CI: 0.84–0.90) and pooled specificity was 0.86 (95% CI: 0.82–0.89) versus 0.80 (95% CI: 0.76–0.84). In terms of diagnosing breast malignancy, areas under the curve of the summary receiver operating characteristic (of both CEUS (p = 0.003) and US + CEUS (p = 0.000) were statistically higher than that of US. Both CEUS alone and US + CEUS had better diagnostic performance than US in differentiation of breast lesions, and US + CEUS also had low negative likelihood ratio.
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    Molybdopterin biosynthesis pathway contributes to the regulation of SaeRS two-component system by ClpP in Staphylococcus aureus
    (Taylor & Francis, 2022) Zhao, Na; Wang, Yanan; Liu, Junlan; Yang, Ziyu; Jian, Ying; Wang, Hua; Ahmed, Mahmoud; Li, Min; Bae, Taeok; Li, Qian; Biology, School of Science
    In Staphylococcus aureus, the SaeRS two-component system is essential for the bacterium's hemolytic activity and virulence. The Newman strain of S. aureus contains a variant of SaeS sensor kinase, SaeS L18P. Previously, we showed that, in the strain Newman, SaeS L18P is degraded by the membrane-bound protease FtsH. Intriguingly, the knockout mutation of clpP, encoding the cytoplasmic protease ClpP, greatly reduces the expression of SaeS L18P. Here, we report that, in the strain Newman, the positive regulatory role of ClpP on the SaeS L18P expression is due to its destabilizing effect on FtsH and degradation of MoeA, a molybdopterin biosynthesis protein. Although the transcription of ftsH was not affected by ClpP, the expression level of FtsH was increased in the clpP mutant. The destabilizing effect appears to be indirect because ClpXP did not directly degrade FtsH in an in vitro assay. Through transposon mutagenesis, we found out that the moeA gene, encoding the molybdopterin biosynthesis protein A, suppresses the hemolytic activity of S. aureus along with the transcription and expression of SaeS L18P. In a proteolysis assay, ClpXP directly degraded MoeA, demonstrating that MoeA is a substrate of the protease. In a murine bloodstream infection model, the moeA mutant displayed reduced virulence and lower survival compared with the WT strain. Based on these results, we concluded that ClpP positively controls the expression of SaeS L18P in an FtsH and MoeA-dependent manner, and the physiological role of MoeA outweighs its suppressive effect on the SaeRS TCS during infection.