BACKGROUND The inverse relationship between vitreous humour (VH) glucose and lactate, classically used in the Traub formula, is widely applied in post-mortem biochemistry. METHODS We analysed 127 VH samples from external examinations and forensic autopsies performed in a hospital forensic setting (PMI 4-187 h; 58 septic and 69 non-septic deaths). Glucose was available in 78 cases, lactic acid in all 127. Cases were stratified by PMI window, septic status and storage condition. Spearman correlations and non-parametric comparisons were applied. RESULTS Within the first 24 h post-mortem, glucose and lactic acid showed significant opposite correlations with PMI. Glucose reached a low-value floor of approximately 2 mg/dl by 25-48 h, after which no meaningful PMI-related decrease was observed. Lactic acid showed a different trajectory: septic and non-septic cases had similar baseline levels at ≤10 h, but diverged thereafter, with continued increase in septic cases through 25-48 h. This divergence emerged after glucose depletion, suggesting glucose-independent lactate accumulation. Glucose-lactate coupling was absent in septic cases and weak in non-septic cases. CONCLUSIONS VH glucose and lactic acid showed limited evidence of direct stoichiometric coupling in this hospital cohort. Glucose reflected PMI mainly within the first 24 h, whereas its interpretative value declined after reaching a post-mortem floor. Lactic acid showed a sepsis-associated post-mortem amplification not explained by glucose availability alone, possibly reflecting autolytic processes. These findings do not invalidate the Traub formula in its original diagnostic context, but caution against its uncritical application in heterogeneous forensic cohorts.

Summary Background WHO's Global Oral Health Action Plan (GOHAP) targets include a 10% relative reduction in the combined prevalence of main oral conditions by 2030. The first GOHAP evaluation was planned for 2023, with subsequent evaluations scheduled for 2026 and 2030. The aim of this systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 was to evaluate global and regional progress (2019–23) towards this target and related complementary indicators. Methods Using modelled estimates from epidemiological surveys and registries in 204 countries and territories, we estimated the age-standardised prevalence of untreated caries in deciduous and permanent teeth, severe periodontitis, edentulism, other oral disorders and orofacial clefts, and the age-standardised incidence of lip and oral cavity cancer. Progress towards GOHAP targets was measured by comparing the percentage change from 2019 to 2023 in the above indicators against the stated GOHAP target of a 10% relative reduction. Findings Globally, the age-standardised prevalence of main oral conditions declined (−1·55% [95% uncertainty interval −2·32 to −0·82]) between 2019 and 2023, but global cases increased by 3·07% (2·32 to 3·75), from 3·62 billion (3·35 to 3·95) to 3·73 billion (3·45 to 4·06). Among complementary indicators, reductions in age-standardised prevalence were observed for untreated caries in permanent teeth (−1·99% [−2·49 to −1·40]) whereas the age-standardised incidence of lip and oral cavity cancer increased (8·35% [0·13 to 16·32]), as did the age-standardised prevalence of orofacial clefts (2·25% [0·77 to 3·83]). Progress was heterogeneous across GBD super-regions, with south Asia having the largest reductions in the age-standardised prevalence of main oral conditions (−3·34% [−4·95 to −1·80]) and untreated caries in deciduous teeth (−9·09% [−17·62 to −0·08]). Sub-Saharan Africa showed the largest increase in prevalent cases of main oral conditions (9·51% [8·09–10·94]) and age-standardised incidence of lip and oral cavity cancer (14·86% [1·19–32·45]). The high-income super-region had an increase in the age-standardised prevalence of main oral conditions (1·24% [0·56–1·96]) and untreated caries in deciduous teeth (9·21% [6·60–11·89]). Interpretation Our modelled estimates of global trends in the prevalence of oral conditions from 2019 to 2023 suggest that early progress is modest and, at the current pace, insufficient to meet the 2030 GOHAP targets. Accelerated, equity-focused prevention and integration of essential oral health-care services within primary care and universal health coverage are needed, alongside strengthened oral cancer control and congenital anomaly care. Funding The Gates Foundation.

AIM To evaluate and compare the effects of topically applied diclofenac, ketoprofen, and piroxicam on key inflammatory mediators, including interleukin-17 (IL-17), prostaglandin E2 (PGE2), and signal transducer and activator of transcription 3 (STAT3), in a rat model of collagen-induced arthritis (CIA). METHODS Thirty male Wistar rats were assigned to five groups: three experimental groups receiving topical diclofenac, ketoprofen, or piroxicam, respectively, a positive control group receiving a placebo patch, and a negative control group without collagen injection. CIA was induced using bovine type II collagen and incomplete Freund's adjuvant, with arthritis severity assessed through macroscopic scoring. NSAID patches were applied to the right hind paw for 6 hours daily over 5 days. Immunological parameters were quantified via enzyme-linked immunosorbent assay (ELISA). Statistical analysis included ANOVA, Kruskal-Wallis, and mixed-effects models to evaluate drug effects over time. RESULTS A significant difference was observed in tissue PGE₂ levels (F(4,25) = 4.235; p=0.009; η² = 0.404), with diclofenac showing significantly lower values compared to the negative control and ketoprofen groups, while no significant differences were found for IL-17 or STAT3. CONCLUSION Topical NSAIDs demonstrated selective anti-inflammatory effects, primarily through significant suppression of tissue PGE₂, confirming effective local COX pathway inhibition. The absence of significant changes in IL-17 and STAT3 suggests that short-term topical therapy mainly targets prostaglandin-mediated inflammation rather than upstream cytokine or transcriptional pathways involved in rheumatoid arthritis pathogenesis, warranting further investigation into their long-term therapeutic benefits.

BACKGROUND Despite a general improvement in the HIV burden over the past two decades, gendered social determinants including intimate partner violence (IPV) continue to affect women's vulnerability to HIV, which could be further exacerbated as resources dwindle over the coming years. Our study aimed to quantify recent trends in the HIV burden, the magnitude of the HIV burden associated with IPV, and the potential impact of declining financial support globally. METHODS Using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework, we estimated annual HIV incidence, prevalence, and mortality for 204 countries and territories from 1990 to 2023, disaggregated by age and sex. Input data included national HIV programme reports, population-based serosurveys, clinical and vital registration data, and systematically reviewed literature. Countries and territories were grouped according to the availability and completeness of HIV prevalence and mortality data, with tailored modelling approaches applied for each group. To characterise the potential contributions of IPV to the HIV burden, time series estimates of IPV prevalence by location and effect size estimates were combined to generate population attributable fractions of the HIV burden. To forecast future trends and assess the potential impact of reductions in development assistance for health, we used a non-parametric stochastic frontier approach to estimate how funding levels could affect antiretroviral therapy (ART) coverage. Adjustments in future ART coverage were integrated into our forecasts, altering projected rates of HIV-related incidence and mortality. We compared scenarios with and without funding cuts, quantifying the potential epidemiological effects of reduced ART availability by sex. FINDINGS Between 2003 and 2023, the annual number of new HIV infections declined globally, from 2·85 million (95% uncertainty interval [UI] 2·76-2·96) to 2·06 million (1·88-2·29). Meanwhile, HIV-related deaths decreased from a peak of 1·71 million (1·61-1·83) in 2004 to 0·83 million (0·73-0·96) in 2023. The number of people living with HIV rose from 26·3 million (25·5-27·3) in 2003 to 42·4 million (40·3-44·4) in 2023, reflecting improved survival associated with ART expansion. Although females continued to have higher prevalence of HIV than males in 2023 (23·4 million [22·2-24·6] vs 19·1 million [17·6-20·5]), the gap in incidence between females and males has substantially declined. Regionally, sub-Saharan Africa had the greatest declines in both incidence (64·3%; 58·0-68·6) and mortality (74·6%; 70·4-78·5) between 2003 and 2023, while central Europe, eastern Europe, and central Asia recorded the highest increases in incidence rates (232·1%; 146·5-299·1) and mortality rates (37·8%; 31·2-45·5) during this period. IPV was associated with an estimated 10·7% (1·6-20·4) of HIV-related deaths among females aged 15 years and older globally in 2023, corresponding to 40 700 (6400-80 600) deaths, with the highest population attributable fractions observed in Oceania (17·4%; 2·8-33·1), central sub-Saharan Africa (14·2%; 2·1-29·4), and eastern sub-Saharan Africa (13·2%; 2·0-25·3). Forecasts indicate that funding reductions could decrease ART coverage by 8·1% globally between 2025 and 2030, resulting in approximately 1·6 million new HIV infections among females and 1·3 million new HIV infections among males, alongside 790 600 and 670 600 HIV-related deaths, respectively. These impacts are primarily concentrated in sub-Saharan Africa. INTERPRETATION Despite two decades of substantial progress, the global HIV response remains highly sensitive to gendered social determinants and funding stability. The potential contribution of IPV to HIV-related mortality among women underscores the need for integrated interventions that address violence prevention and post-violence care alongside HIV treatment. The projected effects of funding cuts-millions of additional infections and deaths-highlight the fragility of the gains achieved and the urgent need to protect HIV financing. Achieving and sustaining the UNAIDS 2030 targets will require renewed investment, gender-responsive programming, and resilient health systems capable of providing equitable access to care. FUNDING Gates Foundation and the US National Institute of Allergy and Infectious Diseases.

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C-related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C-attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C-attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

Background/Objectives: DNA-based identification of degraded human remains represents a major challenge in forensic science, particularly in cases involving burned, fragmented, or commingled bodies. Advances in forensic genetics have expanded the analytical capabilities for such samples; however, the effectiveness of different approaches and their integration within Disaster Victim Identification (DVI) workflows remain heterogeneous. This systematic review aims to critically evaluate current evidence on DNA-based identification of degraded remains, focusing on methodological strategies, emerging genomic technologies, and DVI applications, while integrating laboratory evidence and operational forensic practice into a structured analytical framework. Methods: A systematic literature search was conducted in Scopus and Web of Science from database inception to 5 June 2026, following PRISMA 2020 guidelines. Eligible studies included original research addressing DNA analysis of degraded, thermally altered, or highly compromised human remains in forensic or DVI contexts. After a multistep screening process involving title/abstract and full-text evaluation, 37 studies were included. Data were extracted and organized into three thematic categories: (i) core DNA analysis, (ii) advanced molecular technologies, and (iii) DVI case applications. Results: The findings demonstrate that DNA recovery from degraded remains is influenced by thermal exposure, tissue type, and sampling strategy. Teeth and dense cortical bone consistently provide higher DNA yield. While autosomal STR profiling remains the primary analytical approach, its limitations in highly degraded samples are mitigated through the complementary use of mitochondrial DNA (mtDNA), Y-chromosome STRs (Y-STRs), and SNP markers, together with advanced sequencing technologies such as massively parallel sequencing (MPS). Emerging technologies, including rapid DNA systems and predictive models based on macroscopic indicators, significantly enhance efficiency and success rates. DVI studies report identification rates exceeding 90–95% when multidisciplinary and structured workflows are applied. The evidence further supports a flexible triage-based analytical strategy, in which marker selection is guided by tissue preservation and degradation level. Conclusions: DNA-based identification of degraded human remains has evolved into an adaptive, multi-level forensic process. Successful outcomes rely on the integration of optimized sampling, hierarchical genetic analysis, and coordinated DVI strategies. The findings support a triage-based framework that links tissue selection, degradation assessment, and analytical methodology to maximize identification success. Future developments should focus on predictive models, advanced genomic tools, and standardized workflows to further improve identification in challenging forensic scenarios.

OBJECTIVE To assess whether transfer-learning models applied to panoramic radiographs (PANs) can classify individuals at the threshold of legal majority (≥18 years). MATERIALS AND METHODS Vision Transformer (ViT) and EfficientNetV2 models were trained on PANs from Bosnian and Lebanese individuals aged 14-24.99 years (n = 1764), considering pooled and sex-specific datasets with and without augmentation. Binary classification, multiclass classification, and regression models were trained and evaluated. Model performance on an internal test set derived from the same sample was summarized using accuracy, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (ROC AUC). For regression and multiclass models, legal majority classification was additionally assessed by thresholding predicted ages or age categories at 18 years. External validation employed an independent Brazilian dataset (n = 1579; 14-24.99 years). Formal statistical comparison between internal and external performance employed two-proportion z-tests for accuracy and DeLong's test for ROC AUC. RESULTS On the internal test set, the best-performing binary classification model, EfficientNetV2 with augmentation on the pooled dataset, achieved an accuracy of 0.90, sensitivity of 0.92, specificity of 0.86, F1 score of 0.91, and ROC AUC of 0.93. Using the same pooled, augmented configuration, thresholded regression predictions achieved accuracies of 0.85 for EfficientNetV2 and 0.83 for ViT, whereas thresholded multiclass predictions achieved accuracies of 0.84 and 0.73, respectively. Compared with direct binary classification, these thresholded outputs showed no clear advantage, and multiclass models generally showed higher specificity but lower sensitivity. This same pattern was retained when thresholded models were evaluated on the external validation set, with thresholded regression remaining comparatively stable and thresholded multiclass performance declining more markedly, especially for ViT. Visualization maps (gradient-weighted class activation mapping [Grad-CAM] and occlusion sensitivity) confirmed attention to relevant dental structures. On external validation, the same binary EfficientNetV2 configuration achieved an accuracy of 0.81, sensitivity of 0.90, specificity of 0.61, F1 score of 0.87, and ROC AUC of 0.85. Sex-specific models performed similarly, showing no clear advantage over pooled training. Statistical testing confirmed significant AUC degradation on external validation for both models (EfficientNetV2: p = 0.004; ViT: p < 0.001), while the accuracy drop was significant only for ViT (p = 0.035). CONCLUSIONS This study demonstrated that transfer learning with EfficientNetV2 and Vision Transformer can distinguish minors from adults using PANs with high internal performance and acceptable external generalization. Direct binary classification provided the most robust approach for legal age assessment in the present dataset. The findings support the forensic potential of these models, while also indicating the need for further work to improve robustness and real-world applicability.

Sex estimation is a fundamental component of biological profiling in forensic anthropology, particularly when skeletal remains are incomplete or fragmented. This study aimed to evaluate sex estimation of the cranial base using geometric morphometrics and to assess the predictive value of cranial base morphology for sex estimation. The study included 211 adult skulls (139 male, 72 female) from the Bosnian population. Each skull was digitized to generate 3D models, and 27 anatomical landmarks were recorded. Landmark coordinates were standardized using Generalized Procrustes Analysis, Principal Component Analysis, Discriminant Function Analysis with permutation testing, and regression of shape on centroid size. Statistically significant sex estimation was observed at both the form (shape and size) and shape levels. Classification accuracy based on cranial base form reached 92.81% for males and 86.11% for females. Shape-based classification, after removal of size effects, also showed high accuracy (90.65% for males and 81.94% for females). Regression analysis indicated that size contributed significantly but modestly to shape variation. The cranial base exhibits stable sexually dimorphic patterns and may represent a reliable anatomical region for sex estimation. These findings contribute to population-specific standards for the Bosnia and Herzegovina population and support the forensic applicability of 3D geometric morphometric approaches.

Summary Background Road injuries are a leading cause of mortality and morbidity worldwide. Years of international efforts have aimed to strengthen policy engagement, including the 2020 UN General Assembly's proclamation of the Second Decade of Action for Road Safety (2021–30), targeting a 50% reduction in road traffic deaths and serious injuries by 2030. The aim of this study is to provide estimates to monitor progress and identify intervention gaps. Methods As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2023, we estimated incidence, mortality, and morbidity of road injuries for 204 countries and territories from 1990 to 2023. Four road injury types and 47 nature-of-injury categories were examined. Morbidity and mortality data from clinical records, vital registration, and police reports were harmonised using meta-analytic techniques to ensure consistency and correct for systematic bias. Incidence was modelled with the meta-regression tool Disease Modelling-Meta-Regression version 2.1 and cause-specific mortality with the Cause of Death Ensemble model, both incorporating location-specific covariates to support interpolation. Years of life lived with disability (YLDs) were estimated from the prevalence and severity of the nature of road injury, and years of life lost (YLLs) from the number of cause-specific deaths multiplied by the standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were the sum of YLLs and YLDs. All metrics were calculated with 95% uncertainty intervals (UIs). Findings In 2023, there were 50·9 million (95% UI 46·1–56·1) road injury incident cases, 1·34 million (1·04–1·58) deaths, and 75·3 million (59·8–89·2) DALYs globally. Road injuries were the leading global cause of death among males aged 10–39 years. Between 1990 and 2023, age-standardised incidence decreased by 38·3% (95% UI 36·9–39·7) and mortality decreased by 32·3% (6·1–49·0), but progress varied widely by World Bank income group. Mortality in low-income countries (43·8 [95% UI 31·7–56·0] deaths per 100 000 population) was approximately six times higher than in high-income countries (7·5 [7·1–7·9] deaths per 100 000), despite the high-income countries showing the highest age-standardised incidence rates (858·1 [95% UI 781·9–947·1] cases per 100 000). In the past decade, many countries achieved notable reductions in road injuries, but others, including Ghana and the USA, saw increases. More severe injuries tended to occur in low-income and middle-income countries. Interpretation Although global incidence, mortality, and DALY rates from road injuries have declined, progress remains uneven, with pronounced disparities across income groups reflecting systemic inadequacies in infrastructure, vehicle standards, enforcement, and post-crash care. Strengthening emergency response, improving road design, enforcing safety measures, and adapting policies to the evolving demographics remain essential. Funding Gates Foundation.