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

Immersed in our narratives: a study of the effectiveness of cobrand anthropomorphism

Anthropomorphism strategies have been widely applied in brand marketing activities such as advertising, service communication, and word-of-mouth, and have become an important marketing strategy for many brands. However, prior research has focused on single-brand contexts, leaving the effects and mechanisms of co-brand anthropomorphism underexplored. Drawing on anthropomorphism theory and narrative transportation theory, this study constructs a model to examine how co-brand anthropomorphism influences consumers’ evaluations and intentions toward co-branded products. Three experimental studies were conducted. The studies show that: Compared to non-anthropomorphism, anthropomorphism significantly enhances consumers’ evaluations and purchase intentions for co-branded products, with narrative transportation mediating this effect. The type of co-branding appeal moderates the results: anthropomorphism is effective for abstract appeals but not for specific appeals. The findings offer practical insights for brands to leverage anthropomorphism in co-branding campaigns, improving ad persuasion effectiveness

Services aimed at achieving desirable clinical outcomes in patients with chronic kidney disease and diabetes mellitus: A narrative review

There is a large number of patients with chronic kidney disease (CKD), diabetes mellitus (DM), and hypertension (HT) but whether the targets on blood pressure (BP) control in patients with DM and/or CKD are met is not clear. This narrative review therefore investigated evidence on services aimed at achieving desirable clinical results in patients with CKD and DM, and HT in Australia. Literature pertaining to pathology diagnosis and management of these patients as well as the complexities in management were considered. This involved evidence from PubMed-listed articles published between 1993 and 2016 including original research studies, focusing on randomised controlled trials and prospective studies where possible, systematic and other review articles, meta- analyses, expert consensus documents and specialist society guidelines, such as those from the National Heart Foundation of Australia, American Diabetes Association, the Department of Health, The Royal College of Pathologists of Australasia, and The Australasian College of Emergency Medicine. Based on the literature reviewed, it is yet unknown as to how effective programs, such as diabetes inpatient services, endocrine out-patient services, and cardiac rehabilitation services, are at achieving guideline recommendations. It is also not clear how or whether clinicians are encumbered by complexities in their efforts of adhering to DM, HT, and glucose control recommendations, and the potential reasons for clinical inertia. Future studies are needed to ascertain the extent to which required BP and glucose control in patients is achieved, and whether clinical inertia is a barrier

Decoding immune low-response states in ovarian cancer: insights from single-cell and spatial transcriptomics for precision immunotherapy

Ovarian cancer represents a typically immune “cold” tumor, where obvious immunosuppression, spatial T-cell exclusion, and cellular dysfunction collectively limit immunotherapy effectiveness. Especially in high-grade serous ovarian carcinoma (HGSOC), the immune low-response state is driven by complex interactions among tumor-associated macrophages (TAMs), suppressive stromal networks, and the T-cell compartment (regulatory T cells, Tregs, and exhausted effector T cells). Emerging multi-omics technologies—particularly single-cell RNA sequencing and spatial transcriptomics—have showed the heterogeneity and spatial immune organization underlying this suppressed state. Here, we integrate these datasets to describe TAM phenotypes and spatial niches, T-cell exhaustion, Tregs accumulation, NK-cell dysfunction, and stromal barriers that enforce exclusion. We then derive phenotype-guided combination strategies to remodel the tumor microenvironment and improve responsiveness to immune checkpoint blockade. This synthesis provides a concise, multi-dimensional framework for precision immunotherapy and for overcoming resistance in immune-low ovarian cancers

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

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

Evaluating the effectiveness of integrated traditional Chinese and Western treatment based on symptom grading: a study protocol for a multi-center, randomized controlled trial of patients with depressive disorder

BackgroundApproximately one-third of depressed individuals receive treatment globally. The application rate of traditional Chinese medicine (TCM) for treating depression globally remains relatively low. The proposed study presents a pilot trial to evaluate the effectiveness of interventions at different levels in improving depression status in community populations.MethodsA randomized controlled trial will be conducted in two communities in Guangdong, China, with a follow-up period of 12 weeks. Participants will be randomly allocated to control or intervention groups. Participants in the control group will be assigned to routine care, while participants in the intervention group will receive TCM intervention measures. The participants in the intervention group will receive integrated traditional Chinese and Western treatment according to the symptom grading of depression severity. Primary outcome measurements include the Patient Health Questionnaire (PHQ-9), the Hamilton Depression Rating Scale (HAMD-17), and the Self-Rating Depression Scale (SDS). Secondary outcome measurements include the Athens Insomnia Scale (AIS), the Epworth Sleepiness Scale (ESS), the Multiple Mental Health Literacy Scale (MMHL), the Short-Form 12 (SF-12), and the Treatment Emergent Symptom Scale (TESS). The data will be collected at baseline (T1), 2 weeks after intervention (T2), 4 weeks after intervention (T3), 8 weeks after intervention (T4), and 12 weeks after intervention (T5).DiscussionThis study will provide an experimental basis for the effectiveness of hierarchical integrated traditional Chinese and Western medicine (ITCWM) in improving the condition of patients with different degrees of depression. At the end of the study, it is expected for the experimental group to have an improvement in depressive symptoms and sleep quality and an enhancement in mental health awareness.Clinical trial registrationhttp://www.chictr.org.cn, identifier ChiCTR2300075169

Factors influencing the level of insight and treatment attitude: a cross-sectional study of 141 elderly patients of major depression in Guangzhou, China

ObjectiveTo explore the insight, treatment attitude, and related influencing factors of hospitalized elderly patients suffering from major depression.MethodsA total of 141 hospitalized elderly patients with depression were selected as the research objects. Insight was evaluated by the total score of the Insight and Treatment Attitude questionnaire (ITAQ). The data collected included sociodemographic characteristics, psychiatric symptoms, delirium status, social functioning, social support, suicide risk, and cognitive function.ResultsThe sample included 74.5% of female patients, and the mean age was 67.53 (sd=7.19) years. The influencing factors of inpatients with depression included alcohol consumption, length of hospitalization, admission types, and the main caregivers (P<0.05). The various factors were further analyzed by linear regression, revealing that the insight and treatment attitude of elderly depressed hospitalized patients were mainly related to the Mini-Mental State Examination (MMSE) (β= 0.225, 95% CI 0.055–0.395, P=0.01), dependent on a caregiver (β=-5.810, 95% CI -8.086~-3.535, P<0.001), the type of admission (involuntary admission) (β=-3.365, 95% CI -5.448~-1.283, P=0.002), Functional Activities Questionnaire (FAQ) (β=-0.156, 95% CI -0.303~-0.010, P=0.037), and length of stay (≤28 days) (β=2.272, 95% CI 0.055~-4.489, P=0.045).ConclusionThe level of insight was affected by cognitive function, involuntary admission, dependent on a caregiver, social function and length of stay. Future studies should focus on cognitive function recovery, observation of admission mode, and self-care ability in elderly patients with depression

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