Publications

Empowering Educators to Build AI Chatbots in Health Professions Education: Tutorial on a No-Code Design Workflow

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AI is entering clinical practice faster than health professions curricula can teach it, leaving many educators eager to use AI-based teaching tools but unsure of how to build them. Generative AI chatbots—configured as simulated patients, clinical coaches, or formative assessment partners—offer scalable, interactive practice without any programming, yet most educators lack a structured method for designing and deploying them well. This tutorial provides that method: a practical, platform-agnostic workflow for building no-code AI chatbots using widely available large language model platforms. The workflow is organized in five sequential sections that follow the arc of a design project: (1) defining the educational purpose, learner group, and persona; (2) configuring behavior through the system prompt, graduated information disclosure, and structured feedback; (3) refining the learner experience through communication-style calibration, voice interaction, and curated knowledge documents; (4) adding realism and testing, including AI avatar generation and rigorous pilot-testing; and (5) embedding the tool within the curriculum and governing its use ethically. Each section pairs concrete, copy-ready design steps with the reasoning behind them, drawing on the technological pedagogical content knowledge framework and on established learning mechanisms—deliberate practice, self-regulated learning, formative feedback, and simulation-based learning—so that design choices are pedagogically grounded rather than merely technical. Throughout, 2 locally developed initiatives, the Virtual Integrated Patient and the Depression Avatars project, serve as illustrative implementation examples that motivated specific design decisions. These are presented as feasibility and acceptability experiences, not as evidence of educational effectiveness. The tutorial also addresses when a chatbot is not the right tool, the principal risks (hallucination, automation bias, data privacy exposure, and bias in generated personas), and a practical governance checklist for safe deployment. Although the examples are clinical, the workflow is discipline-agnostic and transferable across higher education. No-code AI chatbots are a feasible, accessible way for educators to build interactive learning tools; rigorous, multi-institutional evaluation using validated instruments remains the essential next step.

Full Article: https://mededu.jmir.org/2026/1/e103399

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Cannabidiol induces apoptosis and autophagy via STAT3 and NF-κB inhibition and synergistically enhances paclitaxel efficacy in non-small cell lung cancer

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Abstract

Background

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, driven in part by persistent activation of pro-survival pathways such as STAT3 and NF-κB.

Aim

Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has emerged as a potential anti-cancer agent; however, its mechanisms in NSCLC remain incompletely defined. In particular, CBD has not been systematically investigated for its ability to simultaneously suppress both constitutive and inducible STAT3/NF-κB activation, while coordinating apoptosis and autophagy in NSCLC. Furthermore, its role as a chemosensitizer in combination with paclitaxel remains to be validated in vivo.

Methods

Human NSCLC cell lines (A549, PC9, and H1299) were treated with cannabidiol (CBD), alone or in combination with paclitaxel. Apoptosis and autophagy were evaluated via caspase-3/7 activity, Western blotting, and immunocytochemistry. The effects of CBD on STAT3 and NF-κB signaling were assessed using EMSA, luciferase reporter assays, and nuclear translocation analysis. Anti-tumor efficacy was further validated in a xenograft mouse model.

Results

Here, we demonstrate that CBD reduced cell viability in NSCLC cells (A549 and PC9), while showing less cytotoxicity in normal lung fibroblasts. Mechanistically, CBD induced apoptosis and autophagy and suppressed STAT3 and NF-κB activation at the levels of phosphorylation, nuclear localization, and transcriptional activity. These effects were also observed in inducible signaling models using IL-6–stimulated H1299 cells. Importantly, CBD enhanced the efficacy of paclitaxel, a commonly used chemotherapeutic agent, by synergistically inducing apoptosis and autophagy and further suppressing STAT3/NF-κB signaling. In a xenograft mouse model, CBD treatment significantly reduced tumor growth without affecting body weight, and combination therapy with paclitaxel led to the most pronounced tumor suppression. Tumor tissue analyses confirmed that CBD downregulated phosphorylated STAT3 and p65, reduced proliferation marker Ki-67, and increased expression of cleaved PARP, LC3 II, and other cell death-associated proteins.

Conclusion

Our findings provide preclinical evidence that CBD exerts potent anti-tumor activity in NSCLC by coordinating inhibition of oncogenic signaling and activation of programmed cell death pathways. To our knowledge, this study provides evidence that CBD concurrently inhibits STAT3 and NF-κB signaling, affecting both constitutive and inducible activation in NSCLC, and enhances paclitaxel efficacy in vivo, thereby establishing a novel mechanistic and translational basis for its therapeutic potential. These results support the therapeutic effect of CBD as a potential adjuvant in lung cancer treatment.

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Baseline characteristics of the SINgapore GERiatric Intervention Study to Reduce Cognitive Decline and Physical Frailty (SINGER) multidomain dementia prevention randomized controlled trial and insights from the recruitment process

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Abstract

INTRODUCTION

The SINgapore GERiatric Intervention Study to Reduce Cognitive Decline and Physical Frailty (SINGER) is the first large Southeast Asian randomized controlled trial of multidomain lifestyle interventions in older adults at increased dementia risk.

METHODS

Baseline assessments included sociodemographic, cognitive, lifestyle, and clinical risk factors. Recruitment strategies and adaptations to coronavirus disease 2019 (COVID-19) restrictions and operational challenges were documented.

RESULTS

A total of 3841 individuals were pre-screened, with 1218 randomized 1:1 to a Structured Lifestyle Intervention or a Self-Guided Intervention (606 each; three exclusions per arm). Participants had a mean age of 68.7 years and a mean of 12.5 years of education; 96.4% were Chinese. High rates of inactivity, limited cognitive engagement, and suboptimal diet were observed.

DISCUSSION

Despite pandemic disruptions, SINGER achieved its recruitment target through adaptive strategies, enrolling a cohort with significant scope for dementia risk reduction and positioned to test the effectiveness of multidomain lifestyle interventions.

Full Article: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.71313

Baseline characteristics of the SINgapore GERiatric Intervention Study to Reduce Cognitive Decline and Physical Frailty (SINGER) multidomain dementia prevention randomized controlled trial and insights from the recruitment process Read More »

Metabolic Regulation of Immune Responses: Molecular Mechanisms, Diseases, and Therapeutic Targets

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ABSTRACT

Cancer-associated metabolic reprogramming profoundly reshapes the tumor microenvironment (TME), emerging as a central driver of immune evasion and therapeutic resistance. Increasing evidence indicates that metabolic enzymes function not only as bioenergetic regulators but also as active modulators of immune signaling, immune cell fate, and immune checkpoint expression. To elucidate these complex immunometabolic networks, this review utilizes fructose-1,6-bisphosphatase 1 (FBP1)—a key gluconeogenic enzyme—as a paradigmatic metabolic gatekeeper to illustrate how metabolic dysregulation drives tumor progression. By examining both the canonical metabolic effects and noncanonical signaling mechanisms of such enzymes, we synthesize recent advances demonstrating how metabolic rewiring promotes glycolytic reprogramming, immune suppression, and resistance to immunotherapy. Specifically, we explore broad mechanisms of immune evasion, including STAT3–PD-L1 regulation, modulation of innate immune surveillance, T cell exhaustion, and remodeling of stromal and fibrotic tumor niches. Furthermore, we discuss emerging therapeutic strategies targeting these immunometabolic pathways, encompassing small-molecule modulators, vitamin- and gene-based interventions, nanotechnology-enabled delivery systems, and metabolism-informed combination immunotherapy. Finally, we highlight key challenges, including metabolic heterogeneity and context-dependent enzyme function, emphasizing the need for biomarker-guided precision strategies to translate fundamental immunometabolic insights into durable and safe cancer therapies.

Full Article: https://onlinelibrary.wiley.com/doi/10.1002/mco2.70801

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Next-Generation Risk Assessment for cosmetic ingredients: a critical evaluation of published case studies

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ABSTRACT

The replacement of animal testing in cosmetic safety evaluation remains an urgent scientific and regulatory imperative. Next Generation Risk Assessment (NGRA) offers a human-centric, exposure-led, hypothesis-based framework that integrates new approach methodologies (NAMs), including (1) in silico modeling and 2) mechanistically informed in vitro assays, and in chemico methods, to characterize potential human health hazards under realistic exposure conditions. The aim of this review was to critically evaluate current state of NGRA in cosmetic safety by analyzing 9 published case studies with 7 chemicals across various endpoints such as systemic toxicity, skin sensitization, reproductive and developmental toxicity, and organ-specific effects. This analysis encompassed key NGRA components including physiologically based kinetic (PBK) modeling, adverse outcome pathways (AOPs), integrated approaches to testing and assessment (IATA), threshold of toxicological concern (TTC), and defined approaches for skin sensitization. Data demonstrated that NGRA successfully identified safe concentrations for cosmetic ingredients with margins of safety above regulatory thresholds. There are currently no apparent validated NGRA frameworks for systemic toxicity endpoints where significant gaps remain for complex toxicological endpoints, even though defined approaches for skin sensitization and eye irritation have gained regulatory acceptance. Future advancement still requires integration of metabolically competent models, artificial intelligence-driven prediction tools, micro-physiological systems using multi-organs, and standardized frameworks for interpreting NAM-derived points of departure. This review provides by examining successful applications and limitations, a roadmap for strengthening NGRA as a robust, efficient, and ethically grounded approach to human health risk assessment.

Full Article: https://www.tandfonline.com/doi/full/10.1080/10937404.2026.2702958

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Spermidine alleviates sepsis-induced cardiomyopathy by improving mitochondrial quality and quantity via a Metallothionein 1–dependent antioxidant pathway

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Abstract

Background

Sepsis-induced cardiomyopathy (SICM) is characterized by mitochondrial dysfunction, impaired mitophagic flux, and overwhelming oxidative stress. Spermidine (SPD), a natural polyamine known to enhance autophagy and preserve cardiac function in aging and metabolic disorders, has not been systematically evaluated in the context of septic cardiomyopathy.

Purpose

To determine the therapeutic potential and mechanistic basis of SPD in septic cardiac dysfunction.

Methods

Network pharmacology, RNA sequencing, a cecal ligation and puncture (CLP) mouse model, and multiple cellular assays were integrated to assess the protective actions of SPD. Mitochondrial function, mitophagy flux, and oxidative stress were evaluated using transmission electron microscopy (TEM), immunohistochemistry (IHC), Western blotting, structured illumination microscopy (SIM), mitochondrial membrane potential assays, oxygen consumption rate (OCR) analysis, and mitochondrial DNA (mtDNA) quantification. Transcriptomic clustering and pathway enrichment identified molecular targets, which were validated through siRNA-mediated gene silencing.

Results

SPD markedly attenuated SICM in vivo and in vitro by improving both mitochondrial quantity and quality. It restored sepsis-impaired mitophagy by upregulating LC3B and ATG7, promoting autophagosome maturation, and enhancing cellular ubiquitination. Transcriptomic profiling highlighted metallothionein-1 (MT1) as a key node in metal-ion response pathways. SPD activated the NRF2–MT1–SOD2 antioxidant axis, reduced mitochondrial reactive oxygen species (mtROS) under lipopolysaccharide (LPS) stimulation, and reversed sepsis-induced suppression of SOD2. MT1 knockdown abolished SPD-mediated SOD2 stabilization and mtROS clearance, confirming its essential role in SPD’s cardioprotective effects.

Conclusion

SPD mitigates SICM by orchestrating the restoration of mitochondrial quality control, normalization of mitophagic flux, and stabilization of cellular redox homeostasis. These findings support SPD as a promising therapeutic candidate for septic cardiomyopathy.
Full Article: https://www.sciencedirect.com/science/article/abs/pii/S0944711326004083?via%3Dihub

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White Matter Hyperintensities Moderate the Association Between Diabetes and Non-AD Brain Atrophy

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OBJECTIVE

White matter hyperintensities (WMHs) moderate the association between diabetes and cognition, but the underlying mechanisms remain unknown. This study investigated the interaction effect between diabetes and WMHs on brain atrophy, the resulting atrophy patterns, and whether brain atrophy mediates the effect of diabetes on cognition.

RESEARCH DESIGN AND METHODS

This study included individuals without dementia from two independent memory clinic–based cohorts: Harmonization (primary analysis, n = 112 case subjects with diabetes, n = 284 control subjects) and Alzheimer’s Disease Neuroimaging Initiative (ADNI) (secondary analysis, n = 64 case subjects with diabetes, n = 600 control subjects). Participants underwent longitudinal brain MRI and cognitive assessments, along with plasma pTau181 measurement as a marker of Alzheimer disease (AD). WMHs and brain atrophy were quantified, with Schwarz signature, McEvoy signature, and hippocampal volume used as AD-specific atrophy measures.

RESULTS

Diabetes was not associated with brain atrophy cross-sectionally or longitudinally. Instead, an interactive effect between diabetes and WMHs on brain atrophy was observed. In Harmonization, this interaction was significant in cross-sectional analyses, affecting cortical gray matter and the frontal lobe. No interactive effect was found for AD-specific atrophy, and the observed interactive effect remained significant after adjusting for plasma pTau181. Cortical gray matter mediated the effect of diabetes on cognition at higher WMHs burden. These results were replicated in ADNI, where diabetes and WMHs interacted to accelerate brain atrophy over time.

CONCLUSIONS

Our study demonstrated diabetes and WMHs synergistically contribute to brain atrophy independent of AD, suggesting diabetes-associated cognitive impairment is primarily driven by cerebrovascular disease rather than Alzheimer pathology.

Full Article: https://diabetesjournals.org/care/article/49/6/946/163685/White-Matter-Hyperintensities-Moderate-the

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From symbiosis to immunity: the evolutionary revival of mitochondrial defense programs in inflammatory diseases

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Abstract

Mitochondria, descendants of ancestral α-proteobacteria, embody a dual identity that unites metabolic symbiosis with immune regulation. While evolution has transformed their form and function, mitochondria still preserve a tripartite heritage, an outer membrane resembling the host, an inner membrane of bacterial origin, and a matrix enriched with prokaryotic remnants such as unmethylated mitochondrial DNA (mtDNA), N-formyl peptides, and cardiolipin. Under physiological conditions, this architecture supports efficient energy generation while maintaining immunological silence. However, during infection, hypoxia, or systemic inflammation, this endosymbiotic equilibrium collapses, reawakening innate immune programs encoded in their bacterial ancestry. This review introduces the framework of Mitochondrial Endosymbiotic Dysregulation (MED) to describe the progressive transition of mitochondria from metabolic collaborators to immune activators under inflammatory stress. The MED model delineates three sequential stages: MED-I (Adaptive Remodeling), where mitochondria dynamically reorganize to preserve homeostasis, exhibiting characteristic structures such as mitochondrial flagella-like acquisition and retrieval extension (mitoFLARE) and mito-donut; MED-II (Functional Collapse), characterized by the failure of mitochondrial communication and the emergence of defensive structures such as mito-matryoshka; and MED-III (Structural Disintegration), marked by membrane rupture, release of mitochondrial damage-associated molecular patterns (DAMPs), and amplification of innate immune cascades. Rather than viewing mitochondrial dysfunction as a passive byproduct of injury, the MED paradigm reframes it as a reactivation of ancient bacterial defense programs, coupling bioenergetic failure to immune amplification. Thus, by integrating evolutionary, structural, and immunometabolic perspectives, this review discusses how mitochondrial remodeling under inflammatory stress contributes to diseases such as sepsis, autoimmune disorders, and neuroinflammation, and explores emerging therapeutic strategies aimed at restoring mitochondrial–host symbiosis.

Full Article: https://link.springer.com/article/10.1186/s12964-026-02736-z

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The exposome of brain aging across 34 countries

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Abstract

The physical and social exposome affects human aging, and brain clocks may track its effects. However, most studies neglect multidomain exposures (physical, social and political) across diverse settings globally and their associations with brain aging. In this study, we characterized the associations between 73 country-level physical and social exposomal factors and multimodal brain age in 18,701 participants from 34 countries (healthy individuals and those with Alzheimer’s disease, frontotemporal lobar degeneration or mild cognitive impairment). Exposome effects were assessed using generalized additive models and meta-analytic frameworks. Aggregated exposome models explained up to 15.5-fold more variance than individual exposures (delta Akaike information criterion (ΔAIC): 2,034–3,127). Physical exposome was primarily associated with accelerated structural brain aging (limbic, subcortical and cerebellar regions), whereas social exposome was more strongly associated with functional brain aging (frontotemporal and limbic networks). Exposome burden accounted for 3.3−9.1-fold higher risk of accelerated aging, exceeding effects of clinical diagnoses. Findings were out-of-sample validated in cross-sectional and longitudinal designs, remained consistent across clinical subgroups and persisted after adjustment for demographics, age correction bias, cognition, scanner type and data quality. The exposome accelerates brain aging in health and disease, underscoring the need to address physical, social and political inequities.

Full Article: https://www.nature.com/articles/s41591-026-04302-z

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Kavain for health promotion and disease mitigation: Pharmacological promise and therapeutic perspectives

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Abstract

Background

Chronic diseases remain a predominant cause of mortality worldwide despite existing therapies, which often have side effects and high costs. Natural compounds, such as kavain from Piper methysticum, have attracted attention for their therapeutic potential and safety, showing diverse biological activities useful in treating various health conditions.

Purpose

This study aimed to assess the potential role of kavain in the prevention and treatment of chronic diseases, with a particular focus on its anti-inflammatory, anxiolytic, antithrombotic, neuroprotective, and anticancer properties.

Method

A comprehensive literature search on kavain was conducted using PubMed, Scopus, Science direct and Web of Science databases, considering both preclinical and clinical studies. The term “kavain” was used, and all titles, abstracts, and keywords were screened for relevant information.

Results

Findings from various experimental models suggest that kavain exhibits significant biological and pharmacological activities across various pathological conditions, including inflammation, anxiety, neurological disorders, cardiovascular diseases, and cancer. Pharmacokinetic studies reveal its rapid absorption, moderate oral bioavailability, and efficient systemic clearance. Mechanistically, kavain regulates various molecular pathways including nuclear factor-κB and mitogen-activated protein kinase signaling, modulation of γ-aminobutyric acid type A receptor activity, and inhibition of osteoclastogenesis. Toxicity studies indicate that kavain is well-tolerated at physiologically relevant concentrations. Clinical reports show its anxiolytic potential with favorable safety profile.

Conclusion

Kavain has demonstrated considerable therapeutic potential in the prevention and management of various chronic diseases, with relatively few adverse effects. Consequently, further clinical investigations will be beneficial to validate its efficacy and safety in human populations.
Full Article: https://www.sciencedirect.com/science/article/abs/pii/S0944711326002540?via%3Dihub

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