Composite large margin classifiers with latent subclasses for heterogeneous biomedical data

Chen, Guanhua,Liu, Yufeng,Shen, Dinggang,Kosorok, Michael R. Wiley Subscription Services, Inc., A Wiley Company 2016 Statistical analysis and data mining Vol.9 No.2

<P>High‐dimensional classification problems are prevalent in a wide range of modern scientific applications. Despite a large number of candidate classification techniques available to use, practitioners often face a dilemma of choosing between linear and general nonlinear classifiers. Specifically, simple linear classifiers have good interpretability, but may have limitations in handling data with complex structures. In contrast, general nonlinear classifiers are more flexible, but may lose interpretability and have higher tendency for overfitting. In this paper, we consider data with potential latent subgroups in the classes of interest. We propose a new method, namely the composite large margin (CLM) classifier, to address the issue of classification with latent subclasses. The CLM aims to find three linear functions simultaneously: one linear function to split the data into two parts, with each part being classified by a different linear classifier. Our method has comparable prediction accuracy to a general nonlinear classifier, and it maintains the interpretability of traditional linear classifiers. We demonstrate the competitive performance of the CLM through comparisons with several existing linear and nonlinear classifiers by Monte Carlo experiments. Analysis of the Alzheimer's disease classification problem using CLM not only provides a lower classification error in discriminating cases and controls, but also identifies subclasses in controls that are more likely to develop the disease in the future.</P>

Mesenchymal stem cell-derived extracellular vesicles protect against abdominal aortic aneurysm formation by inhibiting NET-induced ferroptosis

Chen Liang,Liu Yuting,Wang Zheyu,Zhang Leiyang,Xu Yi,Li Yinan,Zhang Lan,Wang Guiming,Yang Shuofei,Xue Guanhua 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Neutrophil extracellular traps (NETs) play an important role in abdominal aortic aneurysm (AAA) formation; however, the underlying molecular mechanisms remain unclear. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) may exert therapeutic effects on AAA through their immunomodulatory and regenerative abilities. This study aimed to examine the role and mechanism of MSC-EVs in regulating the development of NET-mediated AAA. Excessive release of NETs was observed in patients with AAA, and the levels of NET components were associated with the clinical outcomes of the patients. Datasets from the Gene Expression Omnibus database were analyzed and revealed that the PI3K/AKT pathway and ferroptosis were strongly associated with NETosis during AAA formation. Further experiments verified that NETs promoted AAA formation by inducing ferroptosis in smooth muscle cells (SMCs) by inhibiting the PI3K/AKT pathway. The PI3K agonist 740 Y-P, the ferroptosis inhibitor ferrostatin-1, and Padi4 deficiency significantly prevented AAA formation. MSC-EVs attenuated AAA formation by reducing NET release in an angiotensin II-induced AAA mouse model. In vitro experiments revealed that MSC-EVs reduced the release of NETs by shifting NETosis to apoptosis. Our study indicates an important role for NET-induced SMC ferroptosis in AAA formation and provides several potential targets for AAA treatment

Identity-based Deniable Authenticated Encryption for E-voting Systems

( Chunhua Jin ),( Guanhua Chen ),( Jianyang Zhao ),( Shangbing Gao ),( Changhui Yu ) 한국인터넷정보학회 2019 KSII Transactions on Internet and Information Syst Vol.13 No.6

Deniable authentication (DA) is a protocol in which a receiver can generate an authenticator that is probabilistically indistinguishable from a sender. DA can be applied in many scenarios that require user privacy protection. To enhance the security of DA, in this paper, we construct a new deniable authenticated encryption (DAE) scheme that realizes deniable authentication and confidentiality in a logical single step. Compared with existing approaches, our approach provides proof of security and is efficient in terms of performance analysis. Our scheme is in an identity-based environment; thus, it avoids the public key certificate-based public key infrastructure (PKI). Moreover, we provide an example that shows that our protocol is applicable for e-voting systems.

CT-Based Leiden Score Outperforms Confirm Score in Predicting Major Adverse Cardiovascular Events for Diabetic Patients with Suspected Coronary Artery Disease

Liu Zinuan,Ding Yipu,Dou Guanhua,Wang Xi,Shan Dongkai,He Bai,Jing Jing,Chen Yundai,Yang Junjie 대한영상의학회 2022 Korean Journal of Radiology Vol.23 No.10

Objective: Evidence supports the efficacy of coronary computed tomography angiography (CCTA)-based risk scores in cardiovascular risk stratification of patients with suspected coronary artery disease (CAD). We aimed to compare two CCTAbased risk score algorithms, Leiden and Confirm scores, in patients with diabetes mellitus (DM) and suspected CAD. Materials and Methods: This single-center prospective cohort study consecutively included 1241 DM patients (54.1% male, 60.2 ± 10.4 years) referred for CCTA for suspected CAD in 2015–2017. Leiden and Confirm scores were calculated and stratified as < 5 (reference), 5–20, and > 20 for Leiden and < 14.3 (reference), 14.3–19.5, and > 19.5 for Confirm. Major adverse cardiovascular events (MACE) were defined as the composite outcomes of cardiovascular death, nonfatal myocardial infarction (MI), stroke, and unstable angina requiring hospitalization. The Cox model and Kaplan–Meier method were used to evaluate the effect size of the risk scores on MACE. The area under the curve (AUC) at the median follow-up time was also compared between score algorithms. Results: During a median follow-up of 31 months (interquartile range, 27.6–37.3 months), 131 of MACE were recorded, including 17 cardiovascular deaths, 28 nonfatal MIs, 64 unstable anginas requiring hospitalization, and 22 strokes. An incremental incidence of MACE was observed in both Leiden and Confirm scores, with an increase in the scores (log-rank p < 0.001). In the multivariable analysis, compared with Leiden score < 5, the hazard ratios for Leiden scores of 5–20 and > 20 were 2.37 (95% confidence interval [CI]: 1.53–3.69; p < 0.001) and 4.39 (95% CI: 2.40–8.01; p < 0.001), respectively, while the Confirm score did not demonstrate a statistically significant association with the risk of MACE. The Leiden score showed a greater AUC of 0.840 compared to 0.777 for the Confirm score (p < 0.001). Conclusion: CCTA-based risk score algorithms could be used as reliable cardiovascular risk predictors in patients with DM and suspected CAD, among which the Leiden score outperformed the Confirm score in predicting MACE.

Arylazolyl(azinyl)thioacetanilide. Part 9#: Synthesis and Biological Investigation of Thiazolylthioacetamides Derivatives as a Novel Class of Potential Antiviral Agents

Peng Zhan,Xinyong Liu,Liu Wang,Hong Liu,Xuwang Chen,Xiao Li,Xin Jiang,Qiangqiang Zhang,Christophe Pannecouque,Lieve Naesens,Erik De Clercq,Ailin Liu,Guanhua Du 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.6

In continuation of our endeavor to develop new, potent, selective and less toxic antiviral agents, a novel series of 2-(2-amino/chloro-4-(2,4-dibromophenyl) thiazol-5-ylthio)acetamide derivatives was synthesized via an expeditious route and evaluated for their anti-HIV activities against wild-type virus and clinically relevant mutant strains, and for their anti-influenza virus activities against influenza A (H1N1 and H3N2) and influenza B in cellular assays. The selected active compounds were also assayed for their enzymic inhibitory activities. The results showed that some 2-chloro substituted thiazolylthioacetamide derivatives possessed potent activity against wild type HIV-1 and several key mutant strains (E138K, K103N, L100I) of HIV-1 in MT-4 cells with EC50 values in micromolar range. Two 2-amino substituted thiazole derivatives 8a7 and 8a8 displayed significant potency against influenza A/H1N1 in MDCK cells with EC50 values much lower than that of oseltamivir carboxylate, ribavirin, amantadine and rimantadine. Though the mechanism of actions is still unclear, these novel thiazolylthioacetamides might serve as original leads for further pharmacological investigations as potential therapeutic agents against HIV-1 or influenza virus.

Conductively coupled flexible silicon electronic systems for chronic neural electrophysiology

Li, Jinghua,Song, Enming,Chiang, Chia-Han,Yu, Ki Jun,Koo, Jahyun,Du, Haina,Zhong, Yishan,Hill, Mackenna,Wang, Charles,Zhang, Jize,Chen, Yisong,Tian, Limei,Zhong, Yiding,Fang, Guanhua,Viventi, Jonathan National Academy of Sciences 2018 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.115 No.41

<P>Materials and structures that enable long-term, intimate coupling of flexible electronic devices to biological systems are critically important to the development of advanced biomedical implants for biological research and for clinical medicine. By comparison with simple interfaces based on arrays of passive electrodes, the active electronics in such systems provide powerful and sometimes essential levels of functionality; they also demand long-lived, perfect biofluid barriers to prevent corrosive degradation of the active materials and electrical damage to the adjacent tissues. Recent reports describe strategies that enable relevant capabilities in flexible electronic systems, but only for capacitively coupled interfaces. Here, we introduce schemes that exploit patterns of highly doped silicon nanomembranes chemically bonded to thin, thermally grown layers of SiO2 as leakage-free, chronically stable, conductively coupled interfaces. The results can naturally support high-performance, flexible silicon electronic systems capable of amplified sensing and active matrix multiplexing in biopotential recording and in stimulation via Faradaic charge injection. Systematic in vitro studies highlight key considerations in the materials science and the electrical designs for high-fidelity, chronic operation. The results provide a versatile route to biointegrated forms of flexible electronics that can incorporate the most advanced silicon device technologies with broad applications in electrical interfaces to the brain and to other organ systems.</P>