Publications

Socioeconomic status (SES) and admission in medical school: A scoping review

Publications /

Purpose

Historically, medical students have predominantly come from affluent backgrounds, prompting discussions about the need for greater socioeconomic diversity in physician representation. This diversity is crucial for meeting the healthcare workforce’s needs and serving varied communities. Over the past decade, medical schools have introduced initiatives to expand access, including new admission tools and process improvements aimed at fostering inclusivity. However, there is not yet an integrated analysis in the literature examining how SES impacts admission disparities and what efforts have been made to alleviate such disparities.

Method

To address this gap, we conducted a systematic search across major databases, including PubMed, Scopus, Medline, APA PsycINFO, and EconLit. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension (PRISMA) guidelines, thirty-seven studies published from 2013 to 2024 were identified. Descriptive and thematic analyses were used to explore the data.

Results

Thirty-three studies emanated from Western contexts, with only four exploring Asian medical school admissions practices. Over half of the articles employed quantitative methodologies. Thematic analysis revealed the nuanced impacts of various admission tools on selecting applicants from diverse SES backgrounds. Capital barriers emerged as the predominant mechanism through which SES influences admission outcomes. To tackle these issues, most medical schools have adopted two pivotal measures: diversifying admission tools and expanding institutional support and admission policies. These measures are implemented at various stages – pre-, during-, and post-admission process.

Conclusions

This scoping review is the first extensive investigation into the interplay between SES and admission disparities in medical schools. It emphasises considering applicants’ SES while maintaining high academic standards and promoting diversity among future medical professionals. Medical schools have explored various approaches to address SES disparities, but careful implementation across different contexts to avoid the risk of discrimination is essential, especially to ensure higher SES applicants are not inadvertently disadvantaged.

Full Article: https://www.tandfonline.com/doi/full/10.1080/0142159X.2026.2672674

 

Socioeconomic status (SES) and admission in medical school: A scoping review Read More »

Resensitizing drug-resistant cancers by co-targeting apoptosis and mitochondrial stress pathway

Publications /

Abstract

Therapeutic resistance is a major barrier to durable cancer control in contemporary oncology practice. Despite extensive studies on individual cell death pathways and mitochondrial stress responses, a comprehensive framework describing how mitochondrial organization contributes to the coordination of multiple regulated cell death programs and therapeutic resistance remains insufficiently defined. This review examines resistance as malignant cells evade regulated cell death and adapt to mitochondrial stress. Mitochondria are framed as integrative hubs that link bioenergetics, redox regulation, metabolic flexibility, and stress signaling to apoptotic competence. It also describes how apoptosis connects with other death programs through mitochondrial compartmentalization. Signals from the matrix, inner membrane, and cristae, intermembrane space, and outer membrane influence ferroptosis, necroptosis, mitochondrial permeability transition-driven necrosis, and immunogenic cell death. Stress-response pathways are highlighted as interfaces between mitochondrial dysfunction and fate decisions, including the OMA1-DELE1-heme-regulated inhibitor kinase axis that activates the integrated stress response and ATF4-dependent transcription. Translationally, the review proposes a co-targeting framework that pairs apoptosis-directed therapies, especially BH3 mimetics, with interventions that destabilize mitochondrial homeostasis or tune stress signaling. Examples include electron transport chain inhibitors, integrated stress response modulators, and compartment-targeted strategies that alter cristae remodeling, calcium flux, or cardiolipin oxidation.

Resensitizing drug-resistant cancers by co-targeting apoptosis and mitochondrial stress pathway Read More »

Modelling the regulatory toxicology system to promote the effective use of new approach methodologies: a system thinking approach

Publications /

Abstract

The term “New Approach Methodologies” (NAMs) comprises a plethora of approaches with the potential for testing the safety, efficacy, and biological effects of chemicals, pharmaceuticals, and other substances without relying exclusively on traditional animal testing methodologies. While it is debateable whether “new” is the appropriate terminology – some NAMs have been around for several decades, while others have been developed recently – many scholars have observed that the effective uptake of NAMs in regulatory toxicology remains a challenge. The interdisciplinary CHANGE project applies a systems thinking approach to this challenge by modelling the behaviour of the regulatory toxicology system shaped by system-level factors and their interconnections. This article reports findings from two three-day workshops held in Oslo in summer 2024 (Workshop 1 “Explore”) and 2025 (Workshop 2 “Reflect”) with experienced practitioners from regulatory agencies, industry, civil society organisations and academia. Through structured collaborative activities, including small- and large-group discussions, modelling exercises and reflection activities, considerable qualitative data was gathered. Most sessions were recorded, transcribed, and analysed using a multi-step thematic analysis explicitly guided by systems thinking principles, enabling the identification of systemic structures and feedback mechanisms and their visualization in the form of a systems model. Insights from Workshop 1 “Explore” were revisited and stress-tested in Workshop 2 “Reflect”, deepening the robustness of the resulting systems model. This systems model shows structural, economic, social, cultural and technical factors that are interlinked through reinforcing and balancing feedback loops that promote or inhibit the effective use of NAMs. The systems model shows potential leverage points for system change, for instance enhancing the stability and reliability of the supply chain or ensuring that actors in the regulatory toxicology system have both educational and institutional support to effectively change established practices.

Modelling the regulatory toxicology system to promote the effective use of new approach methodologies: a system thinking approach Read More »

Circadian and behavioral timing in MASLD: a systematic review of human observational studies

Publications /

Summary

Background

Circadian disruption may affect metabolism through altered timing of sleep, activity, light exposure, hormonal rhythms, and food intake. However, its relationship with metabolic dysfunction-associated steatotic liver disease (MASLD), including fibrosis and cirrhosis remains unclear. To evaluate associations between circadian and behavioural timing exposures and MASLD in observational studies.

Methods

PubMed, Embase, and Scopus were searched from inception to 14 July 2026. Eligible studies examined naturally occurring timing-related exposures in adults and reported steatosis, fibrosis, cirrhosis, or quantitative liver-fat outcomes. Findings were synthesized narratively because heterogeneity precluded pooling. Risk of bias was assessed using AXIS or the Newcastle–Ottawa Scale, and certainty using an adapted domain-level GRADE approach (PROSPERO Registration number: CRD420261381636).

Findings

Twenty-four independent MASLD-related evidence sources were included in the primary synthesis; two additional mixed-aetiology cirrhosis studies were considered contextually. Shift work showed the most consistent associations and most longitudinal evidence. Chronotype was generally associated with disease occurrence but inconsistently with advanced outcomes: intermediate or late chronotype was associated with fibrosis in one clinical cohort, whereas morning chronotype was not independently associated with incident cirrhosis in a prospective cohort. Later sleep timing was associated with prevalent MASLD and, in one NHANES analysis, fibrosis. Evidence for objective rest-activity rhythms, light exposure, meal timing, and melatonin phase remained limited or heterogeneous. Mixed-aetiology cirrhosis studies suggested that advanced liver disease may itself disrupt circadian physiology.

Interpretation

Circadian and behavioural timing exposures showed trends associated with MASLD-related outcomes, with the most consistent evidence for shift work. Residual confounding, cross-sectional designs, self-reported exposures, heterogeneous outcomes, and reverse causality preclude causal conclusions. Prospective studies using objective circadian phenotyping and standardized fibrosis outcomes are needed.
Full Article: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00440-2/fulltext

Circadian and behavioral timing in MASLD: a systematic review of human observational studies Read More »

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

Publications /

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

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

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

Publications /

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.

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

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

Publications /

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

Publications /

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

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

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

Publications /

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

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

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

Publications /

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

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

Donate Today
Book Equipment & Facilities
Donate Today
Book Equipment & Facilities
Scroll to Top