Background: Temporomandibular disorders (TMD) show substantial clinical and genetic overlap with anxiety, yet it remains unclear whether TMD risk reflects shared anxiety-related liability or distinct anxiety-independent genetic mechanisms. Disentangling these components is essential for understanding TMD heterogeneity beyond symptom-based classifications. Methods: We applied GWAS-by-subtraction using genome-wide summary statistics for TMD (20,799 cases and 479,549 controls; FinnGen Release 12) and anxiety disorders (74,973 cases and 400,243 controls), partitioning TMD heritability into two orthogonal latent components: an anxiety-dependent factor (F _Anxiety ) and an anxiety-independent factor (F _Non-Anxiety ). To delineate the mechanisms underlying each component, we integrated fine-mapping, transcriptome- and proteome-wide association analyses, genetic colocalization, brain imaging–genetics, and single-cell RNA sequencing from human embryonic temporomandibular joint tissue. Results: Anxiety showed significant genetic correlation with TMD (rg = 0.4417, p = 1.98 × 10 ^{− 1 9} ) and accounted for 19.50% of TMD heritable variance. F _Anxiety yielded multiple genome-wide significant loci ( CNTNAP5 , PCLO , PRSS16 , BTN1A1 , RAB27B ), whereas F _Non-Anxiety produced a single independent signal near GPNMB , demonstrating sharply divergent genetic architectures. Multi-omic integration identified RAB27B as a driver of the anxiety-related pathway, implicating synaptic vesicle trafficking and neuroimmune regulation, while GPNMB and KLHL7 supported anxiety-independent pathways involving musculoskeletal remodeling and peripheral inflammation. BrainXcan analyses showed that F _Anxiety predominantly affected limbic and external capsule microstructure, whereas F _Non-Anxiety mapped to thalamic–sensorimotor white matter networks. Single-cell mapping further revealed distinct enrichment patterns of RAB27B , KLHL7 , and GPNMB across TMJ cell types. Conclusion: These findings demonstrate that TMD genetic liability comprises separable anxiety-related and anxiety-independent dimensions with distinct molecular, neurostructural, and cellular signatures. Rather than defining clinical subtypes, these latent components represent associative dimensions of genetic risk at the population level. This integrative framework clarifies the genetic architecture underlying TMD heterogeneity and provides a foundation for future studies integrating individual-level phenotyping to assess clinical relevance and causal mechanisms.

Oral disorders are among the most prevalent diseases globally, yet their burden in Southeast Asia remains poorly characterized. Understanding regional patterns is critical for health planning and prevention. We analysed data from the Global Burden of Disease 2021 study to assess the prevalence, incidence, and disability-adjusted life years of oral disorders across the 10 Association of Southeast Asian Nations (ASEAN) member states from 1990 to 2021. Indicators were age-standardized and analysed by sex, age, country, and socio-demographic index. Oral disorders accounted for nearly half of all-cause prevalence and around 1% of total disease burden in 2021. From 1990 to 2021, prevalent cases rose by over 50% and incident cases by more than 30%, while age-standardized rates showed slight declines. Population growth and ageing were the primary drivers of these increases. Caries of permanent teeth contributed the largest share, followed by periodontal disease and edentulism. Higher socio-demographic index correlated with lower overall burden but a higher proportion of periodontal disease. These findings indicate that oral health remains a major source of morbidity across ASEAN despite modest epidemiologic improvement. Demographic pressures continue to offset gains from prevention and care. Expanding prevention and primary oral healthcare - including sugar reduction, fluoridation, and sealant or varnish programs - could substantially reduce disability and unmet need. Routine regional surveillance using harmonized indicators is essential to guide equitable policy and investment within the post-2025 ASEAN health agenda.

Polycaprolactone (PCL) is a biodegradable polymer widely used in bone tissue engineering; however, its regenerative performance in cranial defect models remains incompletely characterized. This systematic review and meta-analysis evaluated the effect of PCL scaffolds on bone regeneration in preclinical cranial defect models. PubMed, Embase, Web of Science, and Scopus were systematically searched, and eligible animal studies were selected according to predefined criteria. A total of 37 studies were included in the systematic review. Data on scaffold characteristics, animal models, and osteogenic outcomes were extracted, followed by random-effects meta-analysis and meta-regression to investigate potential sources of heterogeneity. PCL-based scaffolds significantly enhanced bone regeneration at one and two months post-surgery, with pooled mean differences of 1.68 (95% CI: 0.34–3.03; p = 0.01) and 5.60 (95% CI: 3.48–7.72; p < 0.00001), respectively. The treatment effect was greatest at two months but decreased at three months and was no longer statistically significant (MD = 2.22, 95% CI: −1.36–5.80; p = 0.22). Extreme between-study heterogeneity was observed across the time-point analyses, limiting the consistency and generalizability of the pooled estimates. Meta-regression identified animal species as a significant moderator at one month, accounting for 28.8% of the estimated heterogeneity, whereas follow-up duration and defect size were not significant moderators. Overall, PCL-based scaffolds demonstrate a beneficial but potentially time-dependent effect on bone regeneration, while their long-term regenerative performance remains uncertain.

Background: Interstitial brachytherapy is an effective and organ-preserving radiotherapeutic modality for pediatric and adolescent patients with head and neck tumors, offering favorable outcomes with minimal impact on surrounding normal tissues. However, the long-term effects of brachytherapy on dental development in young patients remain underexplored, despite clinical observations of tooth anomalies in tumor survivors. This study aimed to provide longitudinal outcomes of tooth developmental anomalies in pediatric and adolescent tumor survivors who underwent head and neck interstitial brachytherapy and to investigate the relevant factors. Methods: The longitudinal panoramic radiographs of the patients at different ages before brachytherapy and during follow-up were evaluated. A modified Demirjian staging technique was used to allocate a developmental stage for each tooth, and the defect index classification criteria were applied to describe the severity of tooth damage. Logistic regression analysis was performed to identify factors associated with long-term dental abnormalities. Results: A total of 210 developing permanent teeth from seven patients were included and evaluated. There were 31 teeth (14.76%) that exhibited developmental anomalies. The incidence and severity of tooth developmental abnormalities after brachytherapy were jointly determined by the radiation dose received by a given tooth and its developmental stage at the time of treatment. Multivariable analysis indicated that D _2cc had the largest effect size (OR 1.029, 95% CI 1.017–1.042) and the most significant statistical association ( P = 0.002). When D _2cc was 0–10 Gy, the incidence of tooth developmental abnormalities was 1.90%; and when D _2cc >100 Gy, the incidence reached 85.7%. The maxillary region with implanted radioactive seeds had a significantly higher risk of dental abnormalities compared to other regions. Conclusion: This study suggests that interstitial brachytherapy may contribute to dental developmental alterations in pediatric and adolescent patients, with severity potentially influenced by radiation dose and tooth developmental stage. D _2cc appeared to be the most informative dose-volume parameter, with lower risks observed at < 10 Gy and higher risks at > 100 Gy. Although limited by sample size and retrospective design, these findings underscore the importance of considering developing dentition when planning individualized radiotherapy for young patients.