Mahidol University's Institutional Repository
คลังสารสนเทศสถาบันของมหาวิทยาลัยมหิดล
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Recent Submissions
CREB5 regulates stem cell-like transcriptional programs to enhance tumor progression in prostate cancer
(2026-01-01) Makovec A.; Phoenix J.T.; Bergom H.E.; Boytim E.; Gustafson A.P.; Deacon A.; Tape S.; Ali A.; Ludwig M.; Pitzen S.P.; Moline D.; Richter C.; Longie H.; Su M.C.; Jena S.; Likasitwatanakul P.; Drake J.M.; Huang R.S.; Hahn W.C.; Rennhack J.P.; Dehm S.M.; Kregel S.; Antonarakis E.S.; Hwang J.; Makovec A.; Mahidol University
Prostate gland cells can be transcriptionally and morphologically characterized as basal and luminal. About 30–40% of advanced prostate cancers (PC) harbor basal-like transcription programs. In castration-resistant PC (CRPC), studies indicate that basal and stem cell-like (SCL) tumors are major resistance mechanisms to androgen receptor (AR)-targeted therapies. SCL tumors have reduced AR activity and increased stem-cell activity that promotes tumor formation, which contributes to poor clinical outcomes. We determined that CREB5 is a key regulator of basal and SCL transcriptional programs and tumor-forming phenotypes in PC. Through in silico modeling of PC transcriptomes and several pre-defined PC signaling programs, CREB5 expression was best associated with basal-like gene signatures and SCL-associated genes in primary PC and CRPCs (n = 493 and 208). This included associations with FOSL1 and other AP-1 transcription factors. We further found that CREB5 interacted with AP-1 proteins and bound to the regulatory elements of AP-1 genes, suggesting a mechanistic role in regulating the activity of AP-1 genes. In AR-positive cells, CREB5 overexpression promoted cell colony growth with tumorigenic properties and increased tumor size in vivo. These findings implicate CREB5 as a driver of the transcriptional programs underlying AR-independent basal and SCL CRPC subtypes, and this activity is detectable in primary PC.
Epigenetic signatures and genetic variants associated with muscle strength in postmenopausal women: potential bone muscle cross talk via BMP1 mechanisms
(2026-03-01) da Silva Rodrigues G.; Noronha N.Y.; Benjamim J.; Sobrinho A.C.d.S.; Sousa Neto I.V.d.; Sae-Lee C.; Chitta P.; Kawamura T.; Barbosa F.; Nonino C.B.; Watanabe L.M.; Bueno C.R.; da Silva Rodrigues G.; Mahidol University
Muscle strength decline is a hallmark of aging and contributes to frailty and bone deterioration, yet the genomic and epigenomic mechanisms predicting functional strength remain unclear. We applied a multiomics approach to identify genetic and epigenetic signatures of muscle strength variability in postmenopausal women. A total of 141 women aged 50-70 yr underwent functional tests, biochemical analysis, anthropometry, blood pressure assessment, and dual-energy X-ray absorptiometry. Participants were classified into higher- and lower-strength groups based on validated upper and lower limb tests. Genome-wide genotyping was performed with the Illumina Global Screening Array, and DNA methylation was measured using the Illumina EPIC 850 K array. A polygenic risk score (PRS) was generated in a training cohort (n = 100) and validated in an independent group (n = 41). Epigenetic scores (EpiScores) were calculated using MethylDetectR, and four fitness-related epigenetic clocks (DNAmGrip, DNAmGait, DNAmVO2max, and DNAmFitAge) were derived with the methylclock package. Twelve single-nucleotide polymorphisms (SNPs) were associated with strength phenotypes, and the PRS predicted group classification with 51.2% accuracy. Epigenetic analysis revealed 12 differentially methylated regions, including higher bone morphogenetic protein 1 (BMP1) EpiScore levels in women with greater strength. Functional enrichment indicated pathways related to bone remodeling and vascular regulation. In the lower strength group, BMP1 EpiScore correlated inversely with femoral neck T-score (r = -0.66, P = 0.037). A meta-analysis of public muscle transcriptomes showed that resistance training increases BMP1 expression. These findings highlight molecular mechanisms linking genetic and epigenetic variation to musculoskeletal aging and functional decline in postmenopausal women.NEW & NOTEWORTHY This study integrates genome-wide genotyping, DNA methylation, and transcriptomic validation to reveal genetic and epigenetic determinants of muscle strength in postmenopausal women. We identify novel SNPs, a predictive polygenic risk score, and higher BMP1 epigenetic scores linked to greater muscle strength and bone remodeling pathways. These multiomics insights provide potential biomarkers for musculoskeletal aging and targets for strategies to preserve strength and skeletal health in older women.
Distribution disparities among medical specialists in Thailand: an equity analysis of the national health workforce database (2015-2024)
(2026-03-19) Sitthirat P.; Suppawittaya P.; Yoadsanit S.; Osotthanakorn P.; Srithamrongsawat S.; Suriyawongpaisal P.; Kaewkamjonchai P.; Tangcharoensathien V.; Sitthirat P.; Mahidol University
OBJECTIVES: Ensuring equity in medical specialist distribution is essential for achieving universal health coverage (UHC). This study explored the changes in the availability and distribution of medical specialists in Thailand from 2015 to 2024 and assessed the equity impacts on workforce. DESIGN: A retrospective longitudinal analysis of national administrative workforce data. SETTING: Public and private hospitals across Thailand, covering 1471 facilities in 77 provinces. PRIMARY OUTCOME AND EXPLANATORY VARIABLES: The primary outcomes were specialist-to-population ratios and geographical equity measured using the Gini coefficient (G), where values closer to 0 indicate greater equity. Explanatory variables included specialty type, geographical region and the timing of major workforce policies, including mandatory service and specialty-specific legislative interventions. RESULTS: Between 2015 and 2024, the GPs and specialists in Thailand expanded significantly, with improvements in both density and distribution. The Gini coefficient for GPs showed the largest equity improvement (G=0.42 in 2015 and G=0.22 in 2024), reflecting the impact of mandatory service programme and rural recruitment programmes. Among specialists, emergency and family medicine have shown rapid growth and significant reductions in distribution inequity, reflecting the success of legislative policies. Sustainability of workforce policies was challenged by the 'leaking stock' phenomenon due to attraction of career opportunities and economic drives. CONCLUSION: Workforce targeted interventions have led to improvements in the availability and equitable distribution of GPs and medical specialists over the past decade. Further policy, such as retention incentives and assisted technology, is needed to achieve equitable distribution across all specialties, particularly in low-density fields. Thailand's experience offers the lessons for other low- and middle-income countries as the evidence-based and equity-focused workforce policies for UHC advancement.
Enhancing Technology Acceptance Through Drone-Based STEM Activities: A TPCK Framework Approach
(2026-01-01) Kitrungloadjanaporn P.; Triampo D.; Nuttavut N.; Triampo W.; Kitrungloadjanaporn P.; Mahidol University
Drone-based Science, Technology, Engineering, and Mathematics (STEM) learning offers a practical means of connecting theory with real-world applications, enhancing student engagement meaningfully. This study investigates its impact on students’ technology acceptance using the Technology Acceptance Model (TAM) and examines differences by gender and school type in Thailand. Three modules were developed through the Technological Pedagogical Content Knowledge (TPCK) framework, covering drone fundamentals, operational skills, and applications such as agricultural survey or natural disaster management. A mixed-methods approach involved pre-and post-questionnaires from 130 high school students across different school types. Findings show significant improvement in all TAM areas—usefulness, ease of use, attitude, and intention—following the intervention, with minimal differences between genders and school backgrounds. The results demonstrate that drone-based STEM not only strengthens technology acceptance but also broadens access to engaging technology-enhanced education. These insights emphasize the value of integrating drone-based activities into future STEM curricula for both educators and policymakers.
A mixed-methods investigation of uncertainty-driven inquiry learning on motivation, cognitive flexibility, and academic resilience among Chinese teachers: Understanding through control-value theory
(2026-01-01) Ma Z.; Ma Z.; Mahidol University
This study investigated the effects of an uncertainty-driven inquiry learning intervention on high school teachers’ motivation, cognitive flexibility, and academic resilience, drawing on Pekrun’s (2006) Control-Value Theory. A mixed-methods, quasi-experimental pretest-posttest design was adopted. Ninety high school teachers were assigned to an experimental group (n = 45) that worked on open-ended inquiry tasks characterized by moderate ambiguity and guided scaffolding, or a control group (n = 45) that completed more structured tasks. Quantitative data were obtained through the Academic Motivation Scale, Cognitive Flexibility Scale, and Academic Resilience Scale, while qualitative insights were elicited through focus group discussions focusing on perceived control, task value, emotional responses, and strategy use. The quantitative findings indicated significantly greater gains for the experimental group across motivation, cognitive flexibility, and academic resilience relative to the control group. The qualitative analysis pointed to four themes: heightened perceptions of autonomy and control, strong task value appraisals, a mix of positive and challenging emotions, and active use of cognitive and self-regulated learning strategies when dealing with ambiguity. These findings suggest that purposeful integration of structured uncertainty in teacher education may strengthen key adaptive competencies and align with central propositions of Control-Value Theory.