Multivariate Dynamic Mediation Analysis under a Reinforcement Learning Framework

Mediation analysis is an important analytic tool commonly used in a broad range of scientific applications. In this article, we study the problem of mediation analysis when there are multivariate and conditionally dependent mediators, and when the variables are observed over multiple time points. The problem is challenging, because the effect of a mediator involves not only the path from the treatment to this mediator itself at the current time point, but also all possible paths pointed to this mediator from its upstream mediators, as well as the carryover effects from all previous time points. We propose a novel multivariate dynamic mediation analysis approach. Drawing inspiration from the Markov decision process model that is frequently employed in reinforcement learning, we introduce a Markov mediation process paired with a system of time-varying linear structural equation models to formulate the problem. We then formally define the individual mediation effect, built upon the idea of simultaneous interventions and intervention calculus. We next derive the closed-form expression and propose an iterative estimation procedure under the Markov mediation process model. We study both the asymptotic property and the empirical performance of the proposed estimator, and further illustrate our method with a mobile health application

Molecular profile reveals immune-associated markers of medulloblastoma for different subtypes

Medulloblastoma, a common pediatric malignant tumor, has been recognized to have four molecular subgroups [wingless (WNT), sonic hedgehog (SHH), group 3, group 4], which are defined by the characteristic gene transcriptomic and DNA methylomic profiles, and has distinct clinical features within each subgroup. The tumor immune microenvironment is integral in tumor initiation and progression and might be associated with therapeutic responses. However, to date, the immune infiltrative landscape of medulloblastoma has not yet been elucidated. Thus, we proposed MethylCIBERSORT to estimate the degree of immune cell infiltration and weighted correlation network analysis (WGCNA) to find modules of highly correlated genes. Synthesizing the hub genes in the protein–protein interaction (PPI) network and modules of the co-expression network, we identify three candidate biomarkers [GRB2-associated-binding protein 1 (GAB1), Abelson 1 (ABL1), and CXC motif chemokine receptor type 4 (CXCR4)] via the molecular profiles of medulloblastoma. Given this, we investigated the correlation between these three immune hub genes and immune checkpoint blockade response and the potential of drug prediction further. In addition, this study demonstrated a higher presence of endothelial cells and infiltrating immune cells in Group 3 tumor bulk. The above results will be conducive to better comprehending the immune-related pathogenesis and treatment of medulloblastoma

Pharmacological effects and mechanisms of YiYiFuZi powder in chronic heart disease revealed by metabolomics and network pharmacology

Introduction: YiYiFuZi powder (YYFZ) is a classical formula in Chinese medicine, which is commonly used clinically for the treatment of Chronic Heart Disease (CHD), but it’s pharmacological effects and mechanism of action are currently unclear.Methods: An adriamycin-induced CHD model rat was established to evaluate the pharmacological effects of YYFZ on CHD by the results of inflammatory factor level, histopathology and echocardiography. Metabolomic studies were performed on rat plasma using UPLC-Q-TOF/MS to screen biomarkers and enrich metabolic pathways; network pharmacology analysis was also performed to obtain the potential targets and pathways of YYFZ for the treatment of CHD.Results: The results showed that YYFZ significantly reduced the levels of TNF-α and BNP in the serum of rats, alleviated the disorder of cardiomyocyte arrangement and inflammatory cell infiltration, and improved the cardiac function of rats with CHD. The metabolomic analysis identified a total of 19 metabolites, related to amino acid metabolism, fatty acid metabolism, and other metabolic pathways. Network pharmacology showed that YYFZ acts through PI3K/Akt signaling pathway, MAPK signaling pathway and Ras signaling pathway.Discussion: YYFZ treatment of CHD modulates blood metabolic pattern and several protein phosphorylation cascades but importance specific changes for therapeutic effect require further studies

Predictors of everyday functional impairment in older patients with schizophrenia: A cross-sectional study

ObjectiveThis study investigates the prevalence of everyday functional impairment among older adults with schizophrenia and builds a predictive model of functional decline.MethodsA total of 113 hospitalized older patients enrolled in this study. Functional impairment is defined according to the Functional Activities Questionnaire (FAQ). Patients who scored <9 could function independently daily, while those who scored ≥9 had problems in everyday functional activities. Data collected include sociodemographic characteristics, depressive symptoms, social support, and physical comorbidities, which were classified according to the eight anatomical systems of the human body.ResultsThe sample comprised 75% female participants with a mean age of 63.74 ± 7.42 years old. A total of 33.6% had a functional impairment, while cognitive impairment was present in 63.7%. Independent participants had better urinary system and respiratory system health (P < 0.05). After adjusting for the potential confounders of age, disease course, physical comorbidities, psychiatric symptoms, the ability to independently carry out daily activities, and cognitive function, we found that impaired everyday function is associated with poor cognition, depressive symptoms, first admission, psychiatric symptoms (especially positive symptoms), ADL, and respiratory and urinary system diseases.ConclusionEveryday functional capacity is predicted by disease course, admission time, cognition, depressive symptoms, severity of psychosis, ability to carry out daily activities, and respiratory and urinary system health status. Urinary system diseases contribute significantly to the prediction of impaired function. Future studies should focus on health status, drug use, and everyday functional recovery in older patients with schizophrenia

Evidence Based Management of Acute Heart Failure in the Era of COVID-19 Pandemic

Abstract This editorial is to highlight current issues of heart failure management during COVID-19 pandemic