Search Results (2,872)

Cibotium barometz (L.) J.Sm., a medicinal fern, relies on three interconnected processes for in vitro propagation: spore germination, ordered gametophyte development, and successful initiation and early establishment of the sporophyte generation. However, during aseptic subculture, gametophytes frequently deviate from this developmental trajectory. The predominant abnormalities include filamentous arrest, thick fan-shaped blades, and irregular spatulate blades, all of which were associated with reduced archegonial maturation and subsequent sporophyte establishment. In this study, developmental time-course observation, paraffin-section histology, and medium-regulation experiments were integrated to establish a diagnosis–recovery–initiation framework for Cibotium barometz gametophytes. Spore germination and gametophyte development were divided into eight practical checkpoints: spore imbibition, spore-wall rupture, rhizoid emergence, rhizoid elongation, filamentous prothallus, lamellar prothallus, cordate gametophyte, and sporophyte formation. The ontogeny of archegonia was delineated into six histological stages, ranging from the initial-cell stage to the pre-fertilization stage. Based on an integrative assessment of population appearance, individual morphology, and anatomical sections, abnormal gametophytes were classified into three diagnostic categories. Filamentous arrest manifested as wool-like or thread-like growth patterns, featuring persistent chain-like cellular organization and failure to develop a two-dimensional blade. Thick fan-shaped blades showed pronounced enlargement and thickening; section images revealed narrow, densely packed cells, accumulation of storage compounds, and localized wall thickening, a pattern consistent with, but not sufficient to demonstrate, a preferential shift toward vegetative proliferation. Irregular spatulate blades were narrow and asymmetric and showed morphological and histological features suggestive of disrupted tissue polarity. Although archegonial initial cells or primordium-like structures were intermittently detected, they infrequently advanced to mature archegonia. Medium treatment significantly affected arrest rate, hypertrophy rate, sporophyte initiation, and mean young-sporophyte height (p < 0.001). Murashige and Skoog (MS) medium supplemented with IAA, 6-BA, and activated carbon was associated with the highest arrest rate, whereas full-strength MS medium was associated with the most pronounced hypertrophy. Among hormone-free subculture treatments, 1/2 MS + activated carbon gave the highest sporophyte initiation rate (71.45% ± 9.16%); the same formula also performed well in primary hormone-free cultures (70.54% ± 9.07%). Correlation analysis showed a strong positive association between sporophyte initiation rate and mean young-sporophyte height (r = 0.935, p < 0.001), while arrest and hypertrophy were negatively associated with sporophyte initiation. These results support evaluating in vitro propagation using quantified developmental outcomes—arrest rate, hypertrophy rate, sporophyte initiation rate, and mean young-sporophyte height—rather than biomass alone. Under the tested conditions, hormone-free 1/2 MS + activated carbon was associated with the most favorable recovery outcomes; the underlying mechanisms require validation by quantitative histology, gene-expression analysis, endogenous-hormone profiling, and direct measurement of compounds adsorbed by activated carbon. Full article

Science, Technology, Engineering, Arts, and Mathematics (STEAM) education has been increasingly recognized for its potential to promote early childhood development, while inclusion has become a fundamental principle of early childhood education. However, research and practice on STEAM in reverse inclusive activities remain limited. This study aimed to explore whether STEAM in reverse inclusive activities in preschools works and how it works. Participants included 6 children with special education needs and 22 typically developing children aged 4–6 years from a public preschool in China. The Assessment, Evaluation, and Programming System Chinese version was used to assess children’s early childhood development in daily routines and during STEAM in reverse inclusive activities. The findings indicated that STEAM in reverse inclusive activities in preschool was effective, with both typically developing children and children with special educational needs demonstrating developmental gains. Children’s early development within the activities was facilitated by the integration of art, embodied learning, effective peer interaction, and flexible teacher support responsive to children’s inquiry problems. Overall, this study provided initial evidence regarding the implementation and effectiveness of STEAM in reverse inclusive activities and offered practical implications for promoting early childhood development. Full article

Background/Objectives: Dental age estimation is important in clinical and forensic practice, particularly when skeletal indicators are unavailable or compromised. Machine-learning models often achieve lower regression errors than conventional dental methods; however, whether this translates into better classification performance at legally relevant age thresholds remains unclear. This study compared the Demirjian and Willems methods with several machine learning models for overall accuracy and threshold-specific performance at the jurisdiction-specific ages of 12 and 15 years. Methods: A total of 1384 panoramic radiographs from individuals aged 8.00–15.99 years were retrospectively evaluated. The developmental stages of the seven left mandibular permanent teeth and sex were used as model inputs. Linear Regression, Decision Tree, Random Forest, Support Vector Regression, Multilayer Perceptron, Gradient Boosting, and XGBoost were trained using cross-validation and evaluated on an internal holdout set. Performance was assessed using regression errors, age-group-specific bias, sensitivity, specificity, balanced accuracy, and likelihood ratios. Results: Machine-learning models generally produced lower errors than conventional methods. In the holdout set, the lowest mean absolute error was 0.512 years for Support Vector Regression and Gradient Boosting, followed by 0.519 years for XGBoost, compared with 0.649 and 0.654 years for the Willems and Demirjian methods. However, lower regression error did not consistently improve threshold-specific performance. At 12 years, machine learning models increased sensitivity but reduced specificity and positive likelihood ratios relative to Willems. At 15 years, Linear Regression and Random Forest produced no positive predictions, whereas the better-performing models showed results similar to Willems. Conclusions: Lower regression error does not necessarily indicate better forensic threshold-specific classification performance. Dental age-estimation models should therefore be validated using threshold-specific likelihood ratios, classification metrics, and age-group-specific bias in addition to overall prediction errors. Full article

Background: Brain MRI in patients with autism spectrum disorder (ASD) is generally considered when additional neurologic, developmental, or syndromic concerns warrant structural evaluation. In the study practice, ASD alone was not used as the reason to obtain MRI. We examined documented MRI use and broad result coding while explicitly separating selection for imaging from abnormal-result status. Methods: This retrospective specialty-practice cohort included 1884 patients with ASD. The primary outcome was the proportion of documented MRI examinations coded abnormal. Secondary analyses examined associations of age, sex, seizure history, EEG status, and genetic test status with abnormal versus normal MRI coding and with documented MRI utilization. MRI categories and the pediatric restriction were exploratory and sensitivity analyses. Results: An MRI result was recorded for 704 patients (37.4%; 95% CI 35.2–39.6); 322 were coded abnormal (45.7%; 95% CI 42.0–49.5). The abnormal-result models had low in-sample discrimination (AUC 0.528 and 0.553), and adjusted confidence intervals for all measured variables included 1.00; these results do not demonstrate equivalence between clinical groups. Seizure history was associated with documented imaging in the full cohort (aOR 2.47, 95% CI 1.94–3.14), and abnormal EEG was associated in the exploratory complete-case utilization model (aOR 2.83, 95% CI 1.93–4.14). Conclusions: Broad MRI abnormalities were frequent among patients selected for imaging because of additional clinical concerns, but a broad abnormal code is not equivalent to clinically actionable yield. The routinely captured variables available in this dataset were insufficient to distinguish abnormal from normal MRI coding. These findings favor individualized MRI decisions based on the clinical question prompting imaging and motivate future studies with richer neurologic and developmental phenotyping. Full article

Background: Pathogenic variants in SLC6A1, which encodes the γ-aminobutyric acid (GABA) transporter GAT-1, cause developmental and epileptic encephalopathies (DEEs) through reduced GABA uptake, impaired transporter trafficking, and functional haploinsufficiency. 4-phenylbutyrate (PBA) is a clinically available small molecule with chemical-chaperone and histone-deacetylase-inhibitor activities that can rescue misfolded GABAergic proteins, but variant-level rescue data are needed to guide precision treatment. Methods: We report a novel de novo missense mutation p.Ala305Val in GAT-1 encoding SLC6A1, in a patient with myoclonic-atonic epilepsy and a developmental and epileptic encephalopathy phenotype. Ala305Val was compared with the residue-matched comparator p.Ala305Thr (Ala305Thr). Variant effects were evaluated by (i) protein-structure prediction across nine stability-prediction algorithms using the cryo-EM-derived human GAT-1 template (PDB 7Y7W); (ii) 3H-GABA uptake assays in HEK293T cells and in human iPSC-derived astrocytes and cortical neurons; (iii) live-cell confocal microscopy of ER colocalization; (iv) pharmacologic rescue with PBA, TUDCA and salubrinal (v) and GAT-1 cDNA gene-augmentation, alone and in combination with PBA. Results: AI-based stability predictors uniformly indicated destabilization of GAT-1 p.Ala305Val and GAT-1 p.Ala305Thr. GAT-1 p.Ala305Val reduced 3H GABA uptake across HEK293Ts, astrocytes, and neurons. The mutant transporter accumulated within the endoplasmic reticulum (ER), with ER colocalization rising from approximately 30% in wildtype to ~80% in GAT-1 p.Ala305Val; PBA reduced ER retention to approximately ~40% and restored total GAT-1 fluorescence toward wildtype levels. Pharmacochaperones (PBA, TUDCA) restored GABA uptake for the mutant transporters. Wildtype GAT-1 gene augmentation improved GABA uptake in the heterozygous condition but combined PBA plus wildtype allele augmentation produced rescue greater than either intervention alone in the available dose-response ranges. Conclusions: GAT-1 p.Ala305Val is a trafficking-impaired, loss-of-function variant whose dysfunction is amenable to two convergent therapeutic axes: pharmacologic correction of folding and trafficking, and augmentation of functional transporter expression. These findings support a two-pronged precision-medicine framework for SLC6A1-related DEEs in which PBA increased the transporter function augmented by genetic approaches. Full article

Background/Objectives: Embryo donation/adoption separates the recipient environment from the genetic origin of the embryo and provides a clinical model for studying offspring sex distribution after assisted reproduction. We evaluated whether recipient body mass index (BMI) was associated with sex distribution among live-birth events after frozen embryo transfer involving embryo donation/adoption. Methods: This retrospective cohort study included frozen embryo transfer cycles involving embryo donation/adoption performed between January 2018 and December 2024 at a tertiary fertility center. All embryos were generated by intracytoplasmic sperm injection, cultured to the day-5 blastocyst stage, transferred singly, and not subjected to preimplantation genetic testing. The analytical cohort comprised 104 independent live-birth transfer events representing 104 unique recipients and 104 unique embryo–donor couples. Recipient BMI was evaluated across quartiles and in an exploratory adjusted logistic regression model including female embryo donor BMI and age, endometrial thickness, serum progesterone concentration, and top-quality embryo status. Results: The cohort included 51 male and 53 female live-birth events. Recipient BMI was higher in female than male live-birth events (25.6 ± 4.3 versus 23.5 ± 4.2 kg/m²; p = 0.007). In a descriptive quartile analysis, male live-birth event proportions were 69.2% in the lowest BMI quartile and 34.6% in the highest quartile, with corresponding female proportions of 30.8% and 65.4% (p for trend = 0.007). In the primary adjusted model, higher recipient BMI was associated with lower odds of a male live-birth event (adjusted OR 0.88 per 1 kg/m²; 95% CI 0.80–0.98; p = 0.017). Conclusions: Recipient BMI was associated with sex distribution among live-birth events after embryo donation/adoption. The observed pattern is compatible with a recipient-side post-fertilization association but does not establish a selection mechanism, causality, or the developmental stage at which the association arose. Full article

Colonias are historically underserved communities along the Texas–Mexico border facing infrastructure deficiencies, socioeconomic vulnerability, and environmental hazards. This study examines parcel-level development conditions across 66,160 properties in Cameron, Hidalgo, Starr, and Willacy Counties, Texas. Property appraisal records, colonia boundaries and 2014 classifications, and geographic information system analyses were integrated to evaluate property values, platting, public service district coverage, floodplain exposure, and reconstructed building patterns from 1990 to 2025. These indicators represent physical and economic conditions associated with resilience rather than a comprehensive measure of community resilience. Results reveal variation among counties and 2014 baseline classification categories. Communities classified as Green exhibited higher property values, greater district coverage, and more established development, whereas those classified as Red showed lower values and greater developmental disadvantages. Reconstructed building inventories more than doubled in Hidalgo and Cameron Counties and increased in Starr County, although survivorship bias and missing year-built data limit interpretation of growth rates. Many colonia properties remain within mapped floodplains, particularly in Hidalgo County. Because the analysis is descriptive, these patterns cannot be causally attributed to specific policies. This study provides a replicable parcel-level framework for evaluating development disparities and floodplain exposure to inform equitable infrastructure investment and planning in underserved border communities. Full article

Several phytophagous thrips can act as facultative predators within arthropod food webs, and this trophic flexibility may shape pest population dynamics when thrips co-occur with spider mites or conspecific competitors on shared host plants. Here we examined intraguild predation among three economically important thrips species, Frankliniella occidentalis, Thrips palmi, and Megalurothrips usitatus, and the two-spotted spider mite Tetranychus urticae, which frequently cooccur on vegetable crops. Predation assays showed that all three thrips species consumed T. urticae, but predation varied markedly with predator species, predator stage, and prey stage. Mite eggs were the most vulnerable prey stage with F. occidentalis showing high egg predation across developmental stages, while T. palmi and M. usitatus showed lower and more variable predation. Predation on active mite stages was generally weaker. Intraguild interactions among the three thrips species were limited in active-stage assays, but larval M. usitatus significantly reduced the survival of F. occidentalis eggs. Removing host plant material increased predation on T. urticae eggs, especially for F. occidentalis and T. palmi. In 20-day mixed-rearing assays, co-rearing with thrips significantly reduced active T. urticae abundance, whereas pairwise thrips co-rearing produced no clear suppression of thrips population abundance. Species-specific qPCR confirmed prey DNA in a subset of predators after feeding assays, supporting the direct trophic interactions detected in the behavioral experiments. These findings highlight the need to treat thrips not only as herbivores but also as context-dependent omnivores when evaluating pest interactions and integrated pest management strategies. Full article

Background: Primitive reflex (PR) assessments based on the Institute for Neuro-Physiological Psychology (INPP) framework are increasingly used in developmental and athletic populations. However, the reproducibility of these observer-based assessments remains insufficiently documented. This study investigated the intra- and inter-rater reliability of subjective PR assessments and examined the potential influence of evaluator expertise in elite youth football athletes. Methods: Sixty-nine male youth football players from an elite academy (age: 18 ± 2 years) participated in this study. PR assessments included the Moro reflex, asymmetrical tonic neck reflex, symmetrical tonic neck reflex, and tonic labyrinthine reflex, evaluated using standardized INPP procedures (0–4 ordinal scoring scale). Intra-rater reliability was assessed by an experienced examiner across three testing sessions performed over six months. Inter-rater reliability was evaluated using standardized video recordings independently scored by two novice raters. Relative reliability was assessed using intraclass correlation coefficients (ICCs) with corresponding 95% confidence intervals (95% CIs), while absolute reliability was quantified using the standard error of measurement (SEM) and the minimal detectable change at the 95% confidence level (MDC95). Results: Good to excellent intra-rater relative reliability (ICC = 0.86–0.98; 95% CI = [0.81–0.99]) was observed, with SEM values of 0.1–0.6 and MDC95 values of 0.3–1.7 points. Moderate to excellent video-based inter-rater reliability was found (ICC = 0.69–0.99; 95% CI [0.56–0.99]), with SEM values of 0.1–0.7 and MDC95 values of 0.3–2.0 points. Pairwise comparisons among raters showed moderate to excellent relative reliability (ICC = 0.57–0.99; 95% CI [0.35–0.99]), with SEM values of 0.1–0.5 and MDC95 values of 0.2–1.3 points. Conclusions: Subjective PR assessments performed using the INPP framework demonstrated good to excellent intra-rater relative reliability and moderate to excellent video-based inter-rater relative reliability, together with generally low absolute measurement error in elite youth football athletes. These findings provide preliminary psychometric support for the use of standardized PR assessments in research and applied sport settings. Full article

Variation in gaze behavior due to age is currently a considerable challenge in building reliable eye-tracking systems for Autism Spectrum Disorder (ASD) diagnosis. However, existing strategies often focus on static gaze representation or dataset-based information, which can lead to limited generalization of findings depending on developmental groups and heterogeneous recording conditions. In this paper, we present a temporal transformer-based system for ASD classification using eye-tracking sequences. This allows you to model gaze behavior as a structured temporal process in the context of contextual attention, as well as employing entropy-based modeling for various distributions of variability over time and temporal consistency constraints to capture sequential gaze dynamics related to ASD behavioral patterns. The framework was evaluated using public eye-tracking corpus containing temporally ordered gaze recordings from ASD and TD participants across age groups. Five sequential experiments on baseline classification, class-balancing analysis, cross-age evaluation, ablation analysis, and cross-dataset transfer learning were performed to conduct experiment-based evaluations. Model performed 0.91 in in-domain Area Under the Receiver Operating Characteristic Curve (AUC) and 0.81 in F1-score on the primary eye-tracking dataset. In the cross-dataset assessment stage, the framework presented a relatively stable performance, with an AUC of 0.85 and an average F1-score of 0.74, irrespective of differences in participant distributions and recording conditions. Ablation analysis also revealed that entropy regularization and temporal consistency mechanisms played a significant role in model stability and classification performance. The ablation analysis provides additional insight into the contribution of the proposed framework components beyond the overall classification performance. Removing the entropy-based regularization reduced the model’s ability to represent variability in gaze allocation, whereas removing the temporal-consistency regularization resulted in less stable sequence representations during learning. These observations indicate that the proposed components complement the transformer-based sequence encoder by improving representation stability and preserving diagnostically relevant temporal information. Rather than acting as independent classifiers, the regularization mechanisms serve as supporting constraints that enhance the quality and robustness of the learned temporal representations. The results indicate that temporally structured gaze modeling is more robust, interpretable, and general in comparison to static gaze representations. In summary, the presented framework can represent a scalable and developmentally appropriate approach to gaze-based ASD classification and support the implementation of trusted neurodevelopmental screening systems. Full article

Passiflora edulis seed oil (PESO) is a rich source of lipophilic bioactive compounds with potential to modulate oxidative stress and free glucose levels. This preclinical study aimed to evaluate the toxicological profile, antioxidant and glucose-modulating effects of PESO using hyperglycemic Danio rerio embryos (AB strain). PESO was chemically characterized by GC-FID/GC-MS after derivatization to fatty acid methyl esters. In animal studies, the median lethal concentration (LC₅₀) of PESO at 96 h post-exposure (hpe) was determined using concentrations ranging from 12.5 to 400 μg/mL, and sublethal concentrations corresponding to 1/10 and 1/20 of the LC₅₀ were selected for further investigations, including survival rate up to 144 hpe, continuous and pulsatile hyperglycemia assays (total free glucose was quantified in washed embryo or larval homogenates using an Accu-Chek Active^® glucometer) (Roche Diabetes Care GmbH, Mannheim, Germany), total reactive oxygen species (ROS) production, and antioxidant gene expression at 96 hpe. Data were analyzed by nonlinear regression or analysis of variance followed by appropriate post hoc tests, with significance set at p ≤ 0.05. Chemical characterization identified linoleic acid (C18:2) as the predominant fatty acid. PESO exhibited an LC₅₀ of 191.1 µg/mL. PESO at 9.5 and 19.1 µg/mL achieved embryonic survival above 85% and reduced total free glucose values in washed embryo or larval homogenates under pulsatile and continuous hyperglycemic conditions (p ≤ 0.05), although less effective than insulin (0.1 U/mL). PESO attenuated ROS production by 2% (w/v) glucose (p ≤ 0.05). PESO treatment was associated with distinct concentration-related expression profiles among the selected antioxidant-related genes: sod1 and cat expression increased at both concentrations, sod2, gpx1a, and gsr increased at 19.1 µg/mL, and nfe2l2a increased at 9.5 µg/mL (p ≤ 0.05). At the selected sublethal concentrations, PESO showed low embryotoxicity and was associated with reduced total free glucose values, partial attenuation of ROS accumulation, and changes in selected antioxidant-related transcripts in embryos exposed to hyperglycemic conditions. Full article

Background: Juvenile-onset Huntington disease (JoHD) is a rare form of Huntington disease characterized by symptom onset at or before 20 years of age. Early manifestations are often non-choreic and may be attributed to developmental, psychiatric, movement, metabolic, or epileptic disorders. We described three molecularly confirmed cases and examined early manifestations, diagnostic pathways, and epilepsy. Methods: We conducted a retrospective case series and a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 systematic review of PubMed, Scopus, and Web of Science Core Collection through 5 July 2026. The strict patient-level synthesis required attributable onset at or before 20 years, patient-specific molecular confirmation of a pathogenic HTT repeat expansion, and extractable clinical data. Complementary aggregate or linked reports using closely aligned JoHD criteria were retained for context but excluded from patient-level calculations. Results: The cases included childhood-onset JoHD with drug-resistant epilepsy, adolescent-onset JoHD with progressive motor-cognitive decline and epilepsy in a known Huntington disease pedigree, and childhood-onset JoHD without available family history, in whom status epilepticus prompted renewed diagnostic evaluation. Ninety-three reports were included; of these, 81 contributed 228 unique patients and 12 provided complementary data. Early manifestations were heterogeneous and broadly consistent with previously described childhood-onset JoHD phenotypes. Diagnostic delay was extractable in 180/228 patients; among 172 with point estimates, the median was 4.0 years. Definite epilepsy was reported in 60/145 patients with ascertainable seizure status and was descriptively more frequent in childhood-onset (<10 years) than adolescent-onset (10–20 years) JoHD (49/84 [58.3%] vs. 11/57 [19.3%]). Conclusions: JoHD should be considered in children and adolescents with progressive multisystem neurological involvement, particularly when epilepsy occurs with developmental regression, gait or speech deterioration, pyramidal or extrapyramidal signs, basal-ganglia abnormalities, or a compatible family history. Full article

Fruit ripening is accompanied by extensive reprogramming of secondary metabolism, which determines the antioxidant value of medicine-food homologous fruits. Ziziphus jujuba Mill. cv. ‘Junzao’ (Junzao) is a high-quality cultivar rich in bioactive compounds, yet its stage-dependent metabolite accumulation and the corresponding antioxidant capacity remain poorly resolved. In this study, widely targeted metabolomics was combined with the quantification of total phenolic (TPC), total flavonoid (TFC), and total triterpenoid (TTC) contents and with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) radical-scavenging assays to profile Junzao fruits at five developmental stages. A total of 2388 secondary metabolites were identified, with flavonoids and terpenoids representing the major classes. TPC and TFC were highest at the immature YG (young-fruit) stage, whereas TTC peaked at the BS (white-ripe) stage; all three decreased during subsequent ripening, consistent with the stronger DPPH and ABTS radical-scavenging activities observed in early-stage fruits. Multivariate analyses revealed distinct metabolic profiles among developmental stages, and 2111 differentially accumulated metabolites (DAMs) were identified. K-means clustering resolved nine temporal accumulation patterns, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicated dynamic regulation of flavonoid biosynthesis, phenylpropanoid metabolism, and triterpenoid-related pathways. Spearman correlation analyses further identified ten metabolites, comprising six flavonoids, three triterpenes, and one phenolic acid, that were strongly associated with antioxidant capacity (|r| ≥ 0.5, p < 0.05), highlighting their potential as biomarkers for quality evaluation. Overall, immature Junzao fruits exhibited superior antioxidant capacity, supporting their promise as functional-food ingredients and providing a basis for stage-specific harvesting and utilization. Full article

Background: Fetal programming, conceptualized within the Developmental Origins of Health and Disease framework, describes how intrauterine exposures may shape long-term offspring physiology and disease susceptibility. Metformin is increasingly used during pregnancy for gestational diabetes mellitus, type 2 diabetes mellitus, and selected cases of polycystic ovary syndrome. Its developmental interpretation is complex because the drug improves the maternal metabolic environment but also crosses the placenta and directly exposes the fetus. Methods: This focused narrative review used iterative, targeted searches of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar to identify pharmacological, placental, mechanistic, clinical, guideline-based, and offspring follow-up evidence. The literature search covered publications available through 31 May 2026. The manuscript was subsequently revised during the editorial submission and peer-review process, and the evidence synthesis was re-evaluated against this final literature cut-off date. Earlier landmark studies were retained where necessary for historical, pharmacological, or methodological context. Results: Metformin reduces hepatic glucose production and maternal insulin resistance and may limit gestational weight gain, insulin requirements, neonatal hypoglycemia, and excessive fetal growth in selected pregnancies. Placental transfer creates biological plausibility for direct effects on AMPK, mitochondrial, mTOR, nutrient-sensing, and epigenetic pathways. Long-term studies are broadly reassuring regarding neurodevelopment and major metabolic disease, but findings on growth trajectory, adiposity, and small-for-gestational-age risk remain heterogeneous and indication-dependent. Conclusions: Metformin should be interpreted neither as uniformly beneficial nor as developmentally neutral. Its use should be individualized according to maternal phenotype, indication, glycemic benefit, placental function, fetal growth, dose, timing, and the limitations of long-term offspring evidence. Full article

Background/Objectives: Regular participation in physical activity is essential for maintaining health and well-being and plays a key role in disease prevention and quality of life, both in the general population and among people with disabilities, who represent approximately 16% of the global population. Martial arts-based physical activity programs incorporating safe-falling techniques may contribute to improving physical fitness, reducing fall-related injuries, and supporting adherence to the World Health Organization physical activity recommendations. This systematic review primarily aimed to identify martial arts-based fall-training programs, particularly judo-based interventions, and examine their effects on health and well-being in individuals with intellectual disability. As a secondary objective, evidence from other populations and martial arts disciplines was considered to identify relevant fall-training protocols and transferability. Methods: The research question was formulated using the PEO framework. Eligibility criteria included: people with intellectual and developmental disabilities or special educational needs; exposure to exercise programs involving martial arts, combat sports, or judo; and outcomes related to safe falling, falls, balance, motor skills, and physical condition. A systematic literature search was conducted between December 2025 and April 2026 on the Web of Science Core Collection, Scopus, PubMed, and SPORTDiscus in accordance with PRISMA guidelines. Results: From a total of 658 records identified, 27 studies met the inclusion criteria, encompassing 1892 participants with various disabilities, including intellectual disability, autism spectrum disorder, visual impairment, and deafness. The interventions involved different martial arts modalities, such as judo, taekwondo, karate, tai chi, and capoeira. Overall, the available evidence suggests beneficial effects on physical fitness, motor abilities, balance, psychosocial outcomes, and safe-falling skills across different populations; however, substantial clinical and methodological heterogeneity was observed among the included studies. Conclusions: No studies investigating structured martial arts-based fall-training programs in individuals with intellectual disability were identified. Although evidence from other populations is promising, it remains heterogeneous. Further high-quality studies are needed to evaluate these interventions in individuals with intellectual disabilities. Full article