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In this research paper, an adaptive sliding controller designed to enhance seismic response mitigation in structural systems with prescribed performance is presented. The performance function converts the error to a converging error within a predefined neighborhood. Furthermore, the adaptive algorithm is also designed to ensure the controller operates effectively under uncertain system parameters. The serial–parallel estimation model was adopted for parameter vector and error model. The Lyapunov function is chosen to ensure the convergence stability of the control strategy. Through comprehensive theoretical analysis and simulation studies, the efficiency of the performance function has been simulated for a one-degree-of-freedom structure. Simulation results demonstrated the effectiveness of the control algorithm in reducing the seismic response. more...

Despite suppressive antiretroviral therapy (ART), HIV-1 persists in latent reservoirs that seed new HIV infections if ART is interrupted, necessitating lifelong therapy for people with HIV. Activation of latent HIV during ART could improve recognition and elimination of infected cells by the immune system. Protein kinase C (PKC) isozymes increase HIV transcription and hence are potential latency reversal agents. However, the clinical utility of PKCs for this application is limited due to toxicity, which is poorly understood. Our studies showed that PKC activation with multiple classes of agonists leads to widespread platelet activation, consistent with disseminated intravascular coagulation, at concentrations that were similar to those required for T-cell activation. Differential expression analysis indicated that PKC-ε and PKC-η isoforms are expressed at high levels in human CD4+ T cells but not in platelets. Using structure-based drug design, we developed a novel PKC agonist, C-233, with increased selectivity for PKC-ε. C-233 increased both supernatant HIV RNA and p24 expression ex vivo after treatment of CD4+ T cells from ART-suppressed people with HIV. C-233 was 5-fold more potent for T-cell activation relative to platelet activation. Our studies support the use of structure-based drug design to create selective novel PKC agonists for the safe activation of HIV reservoirs and improved tolerability. Author summary: Elimination of the HIV-1 reservoir is a key step in a therapeutic strategy leading to HIV drug-free remission and/or cure. Activation of latent HIV could improve recognition and eventual clearance of persistent HIV by the immune system. Protein kinase C (PKC) agonists are highly effective at activating latent HIV expression but are limited by safety concerns and an insufficient understanding of the mechanism of their adverse effects. In this study, we show that the currently available PKC agonists cause widespread platelet activation, leading to a severe syndrome that closely resembles disseminated intravascular coagulation. However, agonists with increased PKC-ε selectivity had improved in vivo tolerability relative to the other agonists. Using structure-based drug design, we developed a molecule, C-233, which has increased selectivity for PKC-ε, reduced platelet toxicity, and strongly activates latent HIV RNA and viral protein expression. This novel strategy for improving PKC agonist safety may help advance this class of compounds as part of a therapeutic strategy leading to HIV drug-free remission and/or cure. [ABSTRACT FROM AUTHOR] more...

The prevalence and predictors of mortality following an ischemic stroke or intracerebral hemorrhage have not been well established among patients in Vietnam. 2885 consecutive diagnosed patients with ischemic stroke and intracerebral hemorrhage at ten stroke centres across Vietnam were involved in this prospective study. Posthoc analyses were performed in 2209 subjects (age was 65.4 ± 13.7 years, with 61.4% being male) to explore the clinical characteristics and prognostic factors associated with 90-day mortality following treatment. An explainable machine learning model using extreme gradient boosting and SHapley Additive exPlanations revealed the correlation between original clinical research and advanced machine learning methods in stroke care. In the 90 days following treatment, the mortality rate for ischemic stroke was 8.2%, while for intracerebral hemorrhage, it was higher at 20.5%. Atrial fibrillation was an elevated risk of 90-day mortality in the ischemic stroke patient (OR 3.09; 95% CI 1.90–5.02, p<0.001). Among patients with intracerebral hemorrhage, there was no statistical significance in those with hypertension compared to their counterparts without hypertension (OR 0.65, 95% CI 0.41–1.03, p > 0.05). The baseline NIHSS score was a significant predictor of 90-day mortality in both patient groups. The machine learning model can predict a 0.91 accuracy prediction of death rate after 90 days. Age and NIHSS score were in the top high risks with other features, such as consciousness, heart rate, and white blood cells. Stroke severity, as measured by the NIHSS, was identified as a predictor of mortality at discharge and the 90-day mark in both patient groups. [ABSTRACT FROM AUTHOR] more...

Arenavirus-based vectors are being investigated as therapeutic vaccine candidates with the potential to elicit robust CD8 T-cell responses. We compared the immunogenicity of replicating (artPICV and artLCMV) and non-replicating (rPICV and rLCMV) arenavirus-based vectors expressing simian immunodeficiency virus (SIV) Gag and Envelope (Env) immunogens in treatment-naïve non-human primates. Heterologous regimens with non-replicating and replicating vectors elicited more robust SIV IFN-γ responses than a homologous regimen, and replicating vectors elicited significantly higher cellular immunogenicity than non-replicating vectors. The heterologous regimen elicited high anti-Env antibody titers when administered intravenously, with replicating vectors inducing significantly higher titers than non-replicating vectors. Intramuscular immunization resulted in more durable antibody responses than intravenous immunization for both vector platforms, with no difference between the replicating and non-replicating vectors. Overall, both replicating and non-replicating arenavirus vectors generated robust T- and B-cell-mediated immunity to SIV antigens in treatment-naïve non-human primates, supporting further evaluation of these vectors in a clinical setting for HIV therapy. [ABSTRACT FROM AUTHOR] more...

Background: Delayed hospital arrival lowers the proportion of patients with stroke receiving recanalization therapy and results in poor outcomes. This study investigated the factors associated with pre-hospital delays in hospital arrival after stroke onset in the Thanh Hoa Province, Vietnam., Methods: Clinical data were collected from stroke patients within seven days of symptom onset who were prospectively registered in this study. Patients and their relatives were interviewed using a structured questionnaire about patient social demographics, address, post-stroke support actions, and stroke awareness. Pre-hospital delay in hospital arrival was dichotomized into ≤ 4.5 hours and > 4.5 hours, and multivariable logistic regression analysis was used to investigate factors associated with the delay., Result: Of the 328 participants analyzed, 181 (55.4%) arrived at the hospital 4.5 hours after the symptom onset. The patients' and relatives' awareness of stroke was poor, with 298 (91.4%) who had never heard about signs of stroke onset, facial drooping, arm weakness, speech difficulties, and time to call emergency service (FAST). Pre-hospital delays were longer for patients living >10 km away from a healthcare facility and those with secondary or lower education levels, with odds ratios of 2.07 and 1.99, respectively. Seeking care at a district or private hospital as the first point of healthcare or non-use of emergency medical services did not show significant associations with odds ratio and 95% CI of 1.57 (0.93-2.65)., Discussion: The study revealed that most patients with stroke did not arrive at the hospital in time for recanalization therapy. Moreover, the low stroke awareness among patients and their relatives is concerning. Further research is needed to investigate the reasons for pre-hospital delays and develop targeted interventions to improve stroke awareness and reduce these delays., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Ethics Committees of Thanh Hoa General Hospital and School of Health Innovation, Kanagawa University of Human Services issued approval 2022-16-008. As the result of (Ordinary Review/Expedited Review) by the Research Ethics Committee of the Graduate School of Health Innovation on the above research, which was submitted to us for our review as of September 2, 2022, we herewith report to you that the decision has been made as follows; 1. Review Result: Approved (Report of Review Result No. SHI‐20) 2. Reasons for the result: The research is ethically sound. 3. Comments, etc. to the applicant: None in particular. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Truong et al.) more...