12 results on '"Zhao, Sihai"'
Search Results
2. Nonparametric empirical Bayes biomarker imputation and estimation.
- Author
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Barbehenn, Alton and Zhao, Sihai Dave
- Abstract
Biomarkers are often measured in bulk to diagnose patients, monitor patient conditions, and research novel drug pathways. The measurement of these biomarkers often suffers from detection limits that result in missing and untrustworthy measurements. Frequently, missing biomarkers are imputed so that down‐stream analysis can be conducted with modern statistical methods that cannot normally handle data subject to informative censoring. This work develops an empirical Bayes g$$ g $$‐modeling method for imputing and denoising biomarker measurements. We establish superior estimation properties compared to popular methods in simulations and with real data, providing the useful biomarker measurement estimations for down‐stream analysis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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3. Kernel Cox partially linear regression: Building predictive models for cancer patients' survival.
- Author
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Rong, Yaohua, Zhao, Sihai Dave, Zheng, Xia, and Li, Yi
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PREDICTION models , *PROPORTIONAL hazards models , *CANCER patients , *MULTIPLE myeloma - Abstract
Wide heterogeneity exists in cancer patients' survival, ranging from a few months to several decades. To accurately predict clinical outcomes, it is vital to build an accurate predictive model that relates the patients' molecular profiles with the patients' survival. With complex relationships between survival and high‐dimensional molecular predictors, it is challenging to conduct nonparametric modeling and irrelevant predictors removing simultaneously. In this article, we build a kernel Cox proportional hazards semi‐parametric model and propose a novel regularized garrotized kernel machine (RegGKM) method to fit the model. We use the kernel machine method to describe the complex relationship between survival and predictors, while automatically removing irrelevant parametric and nonparametric predictors through a LASSO penalty. An efficient high‐dimensional algorithm is developed for the proposed method. Comparison with other competing methods in simulation shows that the proposed method always has better predictive accuracy. We apply this method to analyze a multiple myeloma dataset and predict the patients' death burden based on their gene expressions. Our results can help classify patients into groups with different death risks, facilitating treatment for better clinical outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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4. Hepatic transcriptome signatures in mice and humans with nonalcoholic fatty liver disease.
- Author
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Ding, Yiming, Dai, Xulei, Bao, Miaoye, Xing, Yuanming, Liu, Junhui, Zhao, Sihai, Liu, Enqi, Yuan, Zuyi, and Bai, Liang
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- 2023
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5. Estimation of the proportion of treatment effect explained by a high‐dimensional surrogate.
- Author
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Zhou, Ruixuan Rachel, Zhao, Sihai Dave, and Parast, Layla
- Subjects
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BIOMARKERS , *TREATMENT effectiveness , *FAT , *GENE expression , *SAMPLE size (Statistics) - Abstract
Clinical studies examining the effectiveness of a treatment with respect to some primary outcome often require long‐term follow‐up of patients and/or costly or burdensome measurements of the primary outcome of interest. Identifying a surrogate marker for the primary outcome of interest may allow one to evaluate a treatment effect with less follow‐up time, less cost, or less burden. While much clinical and statistical work has focused on identifying and validating surrogate markers, available approaches tend to focus on settings in which only a single surrogate marker is of interest. Limited work has been done to accommodate the high‐dimensional surrogate marker setting where the number of potential surrogates is greater than the sample size. In this article, we develop methods to estimate the proportion of treatment effect explained by high‐dimensional surrogates. We study the asymptotic properties of our proposed estimator, propose inference procedures, and examine finite sample performance via a simulation study. We illustrate our proposed methods using data from a randomized study comparing a novel whey‐based oral nutrition supplement with a standard supplement with respect to change in body fat percentage over 12 weeks, where the surrogate markers of interest are gene expression probesets. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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6. Fat‐1 expression alleviates atherosclerosis in transgenic rabbits.
- Author
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Zhang, Chenyang, Wang, Xiaojing, Sun, Suping, Fu, Yu, Wu, Yi, Zhao, Sihai, Fan, Xinzhong, and Liu, Enqi
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OMEGA-6 fatty acids ,FATTY acid desaturase ,FATTY acid analysis ,OMEGA-3 fatty acids ,HDL cholesterol ,HIGH density lipoproteins ,ERECTOR spinae muscles - Abstract
Atherosclerosis is the main cause of cardiovascular diseases. The Fat‐1 gene can express the n‐3 fatty acid desaturase, which converts n‐6 polyunsaturated fatty acids (PUFA) to n‐3 PUFAs. The role of n‐3 PUFAs in atherosclerosis is widely debated. This study explored the effect of n‐3 PUFAs on atherosclerosis in rabbits. In this study, atherosclerosis was induced in Fat‐1 transgenic rabbits and their littermate (WT) rabbits by feeding a high‐cholesterol diet containing 0.3% cholesterol and 3% soybean oil for 16 weeks. Plasma lipid, fatty acid and pathological analyses of atherosclerotic lesions were conducted. Fatty acid composition in the liver and muscle showed that n‐3 PUFAs increased and n‐6 PUFAs decreased in the Fat‐1 group. Plasma high‐density lipoprotein cholesterol (HDL‐C) levels were significantly increased in the Fat‐1 group, and the atherosclerotic lesion area of the aortic arch in Fat‐1 transgenic rabbits was significantly reduced. Histological analysis showed that smooth muscle cells (SMCs) in atherosclerotic lesions decreased significantly. In conclusion, n‐3 PUFAs improve atherosclerosis in Fat‐1 transgenic rabbits, and this process may depend on the increase in plasma HDL‐C and the decrease in the amount of SMCs in atherosclerotic plaques. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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7. Kunming mouse strain is less susceptible to elastase‐induced abdominal aortic aneurysms.
- Author
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Liu, Haole, Tian, Kangli, Xia, Congcong, Wei, Panpan, Xu, Boyu, Fu, Weilai, Li, Yankui, Li, Yafeng, Bai, Liang, Wang, Rong, Wang, Weirong, Xu, Baohui, Liu, Enqi, and Zhao, Sihai
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- 2022
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8. Diagnostic and prognostic capabilities of a biomarker and EMR‐based machine learning algorithm for sepsis.
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Taneja, Ishan, Damhorst, Gregory L., Lopez‐Espina, Carlos, Zhao, Sihai Dave, Zhu, Ruoqing, Khan, Shah, White, Karen, Kumar, James, Vincent, Andrew, Yeh, Leon, Majdizadeh, Shirin, Weir, William, Isbell, Scott, Skinner, James, Devanand, Manubolo, Azharuddin, Syed, Meenakshisundaram, Rajamurugan, Upadhyay, Riddhi, Syed, Anwaruddin, and Bauman, Thomas
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SEPTIC shock ,MACHINE learning ,SEPSIS ,NEONATAL sepsis ,BIOMARKERS ,LENGTH of stay in hospitals ,ELECTRONIC health records ,ADULTS - Abstract
Sepsis is a major cause of mortality among hospitalized patients worldwide. Shorter time to administration of broad‐spectrum antibiotics is associated with improved outcomes, but early recognition of sepsis remains a major challenge. In a two‐center cohort study with prospective sample collection from 1400 adult patients in emergency departments suspected of sepsis, we sought to determine the diagnostic and prognostic capabilities of a machine‐learning algorithm based on clinical data and a set of uncommonly measured biomarkers. Specifically, we demonstrate that a machine‐learning model developed using this dataset outputs a score with not only diagnostic capability but also prognostic power with respect to hospital length of stay (LOS), 30‐day mortality, and 3‐day inpatient re‐admission both in our entire testing cohort and various subpopulations. The area under the receiver operating curve (AUROC) for diagnosis of sepsis was 0.83. Predicted risk scores for patients with septic shock were higher compared with patients with sepsis but without shock (p < 0.0001). Scores for patients with infection and organ dysfunction were higher compared with those without either condition (p < 0.0001). Stratification based on predicted scores of the patients into low, medium, and high‐risk groups showed significant differences in LOS (p < 0.0001), 30‐day mortality (p < 0.0001), and 30‐day inpatient readmission (p < 0.0001). In conclusion, a machine‐learning algorithm based on electronic medical record (EMR) data and three nonroutinely measured biomarkers demonstrated good diagnostic and prognostic capability at the time of initial blood culture. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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9. miR‐145 inhibits the proliferation and migration of vascular smooth muscle cells by regulating autophagy.
- Author
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Wang, Weirong, Chen, Lifang, Shang, Chenxu, Jin, Zhen, Yao, Feng, Bai, Liang, Wang, Rong, Zhao, Sihai, and Liu, Enqi
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VASCULAR smooth muscle ,MUSCLE cells ,TRANSMISSION electron microscopes ,CAROTID artery ,WESTERN immunoblotting - Abstract
miR‐145, the most abundant miRNA in the vascular smooth muscle cells (VSMCs), regulates VSMC function in intimal hyperplasia. It has been reported that autophagy participates in the regulation of proliferation and migration of VSMCs. However, the effect of miR‐145 on autophagy and related mechanism in the proliferation and migration of VSMCs remains unclear. Therefore, we aimed to determine the effect of miR‐145 on autophagy and the mechanism in VSMCs. Cell autophagy was determined by transmission electron microscope, mRFP‐GFP‐LC3 assay and Western blotting. A recombinant lentivirus containing miR‐145 was used to construct VSMCs with miR‐145 overexpression. We found that miR‐145 expression was decreased, and autophagy was increased in the carotid arteries of C57BL/6J mice with intimal hyperplasia and TGF‐β1‐stimulated VSMCs. Furthermore, miR‐145 overexpression inhibited cell autophagy, whereas miR‐145 inhibition promoted autophagy in TGF‐β1‐stimulated VSMCs. Meanwhile, miR‐145 inhibited the proliferation and migration of VSMCs. More importantly, our study showed that autophagy inhibition augmented the inhibitory effect of miR‐145 on the proliferation and migration of VSMCs. In addition, we found that the sirtuins are not direct targets of miR‐145 in the proliferation and migration of VSMCs. These results suggest that miR‐145 inhibits the proliferation and migration of VSMCs by suppressing the activation of autophagy. [ABSTRACT FROM AUTHOR]
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- 2020
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10. Cross‐species systems analysis of evolutionary toolkits of neurogenomic response to social challenge.
- Author
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Saul, Michael C., Blatti, Charles, Yang, Wei, Bukhari, Syed A., Shpigler, Hagai Y., Troy, Joseph M., Seward, Christopher H., Sloofman, Laura, Chandrasekaran, Sriram, Bell, Alison M., Stubbs, Lisa, Robinson, Gene E., Zhao, Sihai D., and Sinha, Saurabh
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TRANSCRIPTOMES ,STICKLEBACKS ,GENE expression in fishes ,TRANSCRIPTION factors ,NEURAL transmission ,SYSTEM analysis - Abstract
Social challenges like territorial intrusions evoke behavioral responses in widely diverging species. Recent work has showed that evolutionary "toolkits"—genes and modules with lineage‐specific variations but deep conservation of function—participate in the behavioral response to social challenge. Here, we develop a multispecies computational‐experimental approach to characterize such a toolkit at a systems level. Brain transcriptomic responses to social challenge was probed via RNA‐seq profiling in three diverged species—honey bees, mice and three‐spined stickleback fish—following a common methodology, allowing fair comparisons across species. Data were collected from multiple brain regions and multiple time points after social challenge exposure, achieving anatomical and temporal resolution substantially greater than previous work. We developed statistically rigorous analyses equipped to find homologous functional groups among these species at the levels of individual genes, functional and coexpressed gene modules, and transcription factor subnetworks. We identified six orthogroups involved in response to social challenge, including groups represented by mouse genes Npas4 and Nr4a1, as well as common modulation of systems such as transcriptional regulators, ion channels, G‐protein‐coupled receptors and synaptic proteins. We also identified conserved coexpression modules enriched for mitochondrial fatty acid metabolism and heat shock that constitute the shared neurogenomic response. Our analysis suggests a toolkit wherein nuclear receptors, interacting with chaperones, induce transcriptional changes in mitochondrial activity, neural cytoarchitecture and synaptic transmission after social challenge. It shows systems‐level mechanisms that have been repeatedly co‐opted during evolution of analogous behaviors, thus advancing the genetic toolkit concept beyond individual genes. Across distantly related species, social challenge modulates nuclear receptor signal transduction‐related molecules. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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11. Treatment With Small Molecule Inhibitors of Advanced Glycation End-Products Formation and Advanced Glycation End-Products-Mediated Collagen Cross-Linking Promotes Experimental Aortic Aneurysm Progression in Diabetic Mice.
- Author
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Li Y, Zheng X, Guo J, Samura M, Ge Y, Zhao S, Li G, Chen X, Shoji T, Ikezoe T, Miyata M, Xu B, and Dalman RL
- Subjects
- Mice, Male, Animals, Swine, Aorta, Abdominal pathology, Glycation End Products, Advanced metabolism, Maillard Reaction, Streptozocin metabolism, Mice, Inbred C57BL, Disease Models, Animal, Collagen metabolism, Diabetes Mellitus, Experimental metabolism, Aortic Aneurysm, Abdominal chemically induced, Aortic Aneurysm, Abdominal prevention & control, Aortic Aneurysm, Abdominal metabolism
- Abstract
Background Although diabetes attenuates abdominal aortic aneurysms (AAAs), the mechanisms by which diabetes suppresses AAAs remain incompletely understood. Accumulation of advanced glycation end- (AGEs) reduces extracellular matrix (ECM) degradation in diabetes. Because ECM degradation is critical for AAA pathogenesis, we investigated whether AGEs mediate experimental AAA suppression in diabetes by blocking AGE formation or disrupting AGE-ECM cross-linking using small molecule inhibitors. Methods and Results Male C57BL/6J mice were treated with streptozotocin and intra-aortic elastase infusion to induce diabetes and experimental AAAs, respectively. Aminoguanidine (AGE formation inhibitor, 200 mg/kg), alagebrium (AGE-ECM cross-linking disrupter, 20 mg/kg), or vehicle was administered daily to mice from the last day following streptozotocin injection. AAAs were assessed via serial aortic diameter measurements, histopathology, and in vitro medial elastolysis assays. Treatment with aminoguanidine, not alagebrium, diminished AGEs in diabetic AAAs. Treatment with both inhibitors enhanced aortic enlargement in diabetic mice as compared with vehicle treatment. Neither enhanced AAA enlargement in nondiabetic mice. AAA enhancement in diabetic mice by aminoguanidine or alagebrium treatment promoted elastin degradation, smooth muscle cell depletion, mural macrophage accumulation, and neoangiogenesis without affecting matrix metalloproteinases, C-C motif chemokine ligand 2, or serum glucose concentration. Additionally, treatment with both inhibitors reversed suppression of diabetic aortic medial elastolysis by porcine pancreatic elastase in vitro. Conclusions Inhibiting AGE formation or AGE-ECM cross-linking enhances experimental AAAs in diabetes. These findings support the hypothesis that AGEs attenuate experimental AAAs in diabetes. These findings underscore the potential translational value of enhanced ECM cross-linking as an inhibitory strategy for early AAA disease.
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- 2023
- Full Text
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12. Recombinant Interleukin-19 Suppresses the Formation and Progression of Experimental Abdominal Aortic Aneurysms.
- Author
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Tanaka H, Xu B, Xuan H, Ge Y, Wang Y, Li Y, Wang W, Guo J, Zhao S, Glover KJ, Zheng X, Liu S, Inuzuka K, Fujimura N, Furusho Y, Ikezoe T, Shoji T, Wang L, Fu W, Huang J, Unno N, and Dalman RL
- Subjects
- Animals, Cytokines, Disease Models, Animal, Male, Matrix Metalloproteinase 2, Mice, Mice, Inbred C57BL, Pancreatic Elastase, Recombinant Proteins therapeutic use, Aortic Aneurysm, Abdominal chemically induced, Aortic Aneurysm, Abdominal genetics, Aortic Aneurysm, Abdominal prevention & control, Interleukins therapeutic use
- Abstract
Background Interleukin-19 is an immunosuppressive cytokine produced by immune and nonimmune cells, but its role in abdominal aortic aneurysm (AAA) pathogenesis is not known. This study aimed to investigate interleukin-19 expression in, and influences on, the formation and progression of experimental AAAs. Methods and Results Human specimens were obtained at aneurysm repair surgery or from transplant donors. Experimental AAAs were created in 10- to 12-week-old male mice via intra-aortic elastase infusion. Influence and potential mechanisms of interleukin-19 treatment on AAAs were assessed via ultrasonography, histopathology, flow cytometry, and gene expression profiling. Immunohistochemistry revealed augmented interleukin-19 expression in both human and experimental AAAs. In mice, interleukin-19 treatment before AAA initiation via elastase infusion suppressed aneurysm formation and progression, with attenuation of medial elastin degradation, smooth-muscle depletion, leukocyte infiltration, neoangiogenesis, and matrix metalloproteinase 2 and 9 expression. Initiation of interleukin-19 treatment after AAA creation limited further aneurysmal degeneration. In additional experiments, interleukin-19 treatment inhibited murine macrophage recruitment following intraperitoneal thioglycolate injection. In classically or alternatively activated macrophages in vitro, interleukin-19 downregulated mRNA expression of inducible nitric oxide synthase, chemokine C-C motif ligand 2, and metalloproteinases 2 and 9 without apparent effect on cytokine-expressing helper or cytotoxic T-cell differentiation, nor regulatory T cellularity, in the aneurysmal aorta or spleen of interleukin-19-treated mice. Interleukin-19 also suppressed AAAs created via angiotensin II infusion in hyperlipidemic mice. Conclusions Based on human evidence and experimental modeling observations, interleukin-19 may influence the development and progression of AAAs.
- Published
- 2021
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