Search Results (152)

Tooth agenesis is a common developmental anomaly of the human dentition, ranging from hypodontia to oligodontia, yet its marked phenotypic variability remains insufficiently explained. This review synthesizes developmental and molecular evidence on epithelial–mesenchymal interactions during early odontogenesis and proposes a signaling-threshold framework for human tooth agenesis. We focus on the coordinated roles of Wnt/β-catenin, bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and Sonic hedgehog (SHH) pathways and on recurrent disease-associated genes, including MSX1, PAX9, WNT10A, and AXIN2, as quantitative modulators of pathway activity rather than binary determinants of tooth identity. Within this framework, successful tooth initiation may depend on whether integrated signaling output exceeds a field-specific activation threshold within spatially graded developmental regions of the dental arch. Differences in signaling amplitude, duration, and transcriptional responsiveness may therefore account for distal tooth susceptibility, variable penetrance, arch asymmetry, and the broad clinical spectrum from mild hypodontia to severe oligodontia. By integrating molecular genetics with developmental field theory, this model provides a testable systems-level explanation for selective tooth absence and highlights priority directions for future functional and genotype–phenotype studies. Full article

Extremity vascular malformations in children and adolescents are congenital vascular developmental abnormalities that often present to pediatric orthopedic surgeons with pain, swelling, restricted motion, contracture, gait disturbance, limb asymmetry, and growth-related deformity rather than with an obvious vascular phenotype. The orthopedic importance of these lesions lies less in surface appearance than in their potential to affect muscle balance, joint integrity, osseous development, and peri-procedural safety. This review translates contemporary vascular anomaly classification and multidisciplinary management pathways into a practical orthopedic framework for diagnosis, referral, and longitudinal limb management. The most useful first step is to distinguish low-flow from high-flow lesions and then define lesion depth, periarticular or osseous involvement, coagulopathy risk, and syndromic overgrowth phenotype. Ultrasound is usually the first-line imaging modality for flow characterization, whereas magnetic resonance imaging is the cornerstone for defining extent and planning treatment. Plain radiographs remain highly relevant for identifying phleboliths, osseous remodeling, arthropathy, contracture-related deformity, and limb-length discrepancy. Venous malformations generally warrant pathway-based coagulation assessment, especially D-dimer and fibrinogen, because localized intravascular coagulopathy has direct implications for intervention and surgery. Arteriovenous malformations are best managed within specialist multidisciplinary teams. Fibro-adipose vascular anomaly and syndromic overgrowth phenotypes warrant particular attention because they frequently drive pain, contracture, and progressive limb imbalance. Outcome assessment in this field should extend beyond lesion size and incorporate pain, function, quality of life, and growth-related consequences. For pediatric orthopedic surgeons, management should move from late deformity correction toward early classification, early referral, longitudinal surveillance of joint and growth-related complications, and careful integration of local, surgical, and systemic therapies. Full article

(1) Background: Asymmetry in strength, movement, and neuromuscular control is common in youth sports, yet its role in anterior cruciate ligament (ACL) injury risk in pediatric athletes remains underexamined. (2) Methods: This narrative review synthesized studies that examined lower-limb asymmetry, biomechanics, ACL injury or reconstruction (ACLR), and rehabilitation in participants younger than 18 years, supplemented by key mechanistic and methodological work. (3) Results: Evidence indicates that asymmetry is multifactorial and sometimes functional, arising from limb dominance, sport-specific loading, growth-related morphological change, and neuromuscular variability. However, asymmetry becomes concerning when it coincides with high-risk landing or cutting mechanics, growth-related coordination deficits, or incomplete recovery after ACL reconstruction. Persistent strength and loading asymmetries are linked to secondary ACL injury and early structural joint changes, whereas neuromuscular training and technique-modification programs can improve symmetry and reduce high-risk mechanics. Major gaps include the absence of pediatric-specific asymmetry norms, limited longitudinal and sex-specific data, and heterogeneous measurement approaches. (4) Conclusions: Clarifying when asymmetry is adaptive versus maladaptive, and integrating this knowledge into screening, rehabilitation, and return-to-sport decision-making, will be essential for optimizing performance and promoting lifelong knee health in pediatric athletes. Full article

This study examines the Xinjiang Uygur Autonomous Region as a critical case study, constructing comprehensive evaluation frameworks for both ecological environment and tourism economy. We calculate the integrated development levels of both systems from 2010 to 2024, employing entropy weighting to derive composite development indices, Coupling Coordination Degree modeling to quantify the intensity and quality of system interactions, Relative Development Degree modeling to characterize coordination typologies and developmental asymmetries, and Grey Relational Analysis to identify key driving factors. Our findings reveal that although the coupling coordination of Xinjiang’s tourism–ecological system has transitioned from “mild imbalance” to “marginal coordination”, the system exhibits pronounced vulnerability and persistent “tourism-lag” dynamics. To effectively leverage the current “strategic window” of ecological surplus, we propose a multi-dimensional transformation pathway: (1) enhancing digital resilience through intelligent monitoring systems to mitigate external mobility shocks; (2) optimizing spatial connectivity via a “fast transit, slow travel” infrastructural paradigm; (3) institutionalizing micro-scale ecological governance to position oasis cities as sustainable “ecological gateways”; and (4) catalyzing deep cultural-tourism integration, shifting from scale-driven sightseeing to value-driven Silk Road heritage experiences. These pathways furnish a clear blueprint for Xinjiang to achieve high-quality, sustainable regional tourism development while maintaining its strategic positioning as a northwestern ecological security barrier. Full article

Hemispheric specialization is a widespread feature of vertebrate nervous systems, but the minimal conditions under which bilateral systems differentiate, acquire polarity, and retain asymmetric states remain unclear. Here, we examined these issues using a minimal evolutionary model with two initially equivalent processing channels. Each channel evolved a spatial integration width while receiving the same input, and fitness rewarded the magnitude of a bilateral mismatch-separation signal rather than explicit anomaly localization. Under exact developmental symmetry, 40 lineages evolved robust left–right differences in integration width without significant directional fixation (median |Δa| = 2.511; 22 right-wider, 18 left-wider). Weak developmental gain asymmetry biased polarity selection in a graded manner, shifting outcomes toward right-wider or left-wider solutions depending on bias direction. Forced-symmetry, shared-parameter, and single-channel controls showed that high performance depended on allowing differentiated bilateral processing. After biased solutions were reseeded under restored symmetry, differentiation was retained and amplified (median |Δa| > 6.6), consistent with history-dependent persistence within the sampled fitness landscape. Structured backgrounds increased differentiation magnitude but imposed greater decision-time costs. These results distinguish differentiation, polarity bias, and persistence as separable components of minimal hemispheric specialization. Full article

Chirality is a pervasive and functionally critical feature of biological macromolecules, yet its distributed and emergent forms remain poorly quantified in complex systems such as membrane proteins. We present Chirobiophore, a novel paradigm for capturing biochirality across scales—from atomic geometries to global structural asymmetries. Unlike traditional stereochemical metrics, Chirobiophore employs a multidimensional model-independent vector comprising Local Tetrahedral Asymmetry (LTA), Helical Path Curvature (HPC), Asymmetric Environment Score (AES), Directional Density Profile (DDP), Leaflet Asymmetry Index (LAI), and Orientation Twist Score (OTS). This framework enables coordinate-invariant comparisons of structurally diverse proteins in a continuous chirality space. We demonstrate its application to canonical, GPCR, and topologically complex membrane proteins, revealing distinct chirality signatures and functional clustering. Furthermore, we map Chirobiophore descriptors to tissue-level asymmetry indices, providing a bridge between molecular structure and morphogenetic patterning. Chirobiophore offers a unified, extensible platform for structural biology, synthetic design, and developmental modeling of chirality. Full article

Background/Objectives: Craniofacial malformations such as orofacial clefts affect ~1 in 700 births; 40–60% lack clear genetic etiology, and many exhibit asymmetry and variable expressivity unexplained by classical Sonic Hedgehog (SHH) morphogen gradient models. We investigated whether integrated molecular modules linking morphogen signaling with metabolic stress responses may better account for craniofacial developmental outcomes. Methods: Sequential UniProt gene set integration identified 186 candidate craniofacial regulators. STRING network analysis revealed modular architecture. Molecular docking profiled 17 compounds against SMO, CK1δ, PINK1, and TIE2 (control). Pathway reconstruction integrated the SHH–CK1δ–HIF1A–HEY1–PINK1 axis with in-silico-predicted CK1δ phosphorylation sites on SMO (S615, T593, S751), HIF1A (Ser247), and GLI1/2/3 transcription factors. A developmental decision tree mapped affinity profiles to node-specific phenotype hypotheses. Results: CK1δ and PINK1 emerged as candidate nodes coupling morphogen signaling with mitochondrial quality control. Cross-docking showed preferential binding to developmental kinases (CK1δ: −8.34 kcal/mol; PINK1: −8.80 kcal/mol) versus TIE2 control (−6.76 kcal/mol; p < 0.001). Pathway reconstruction suggested that CK1δ-mediated Ser247 phosphorylation of HIF1A disrupts ARNT dimerization, redirecting HIF1A toward ARNT-independent HEY1 induction and consequent PINK1 suppression. Based on computed profiles, node-specific associations were proposed as computational hypotheses: SMO perturbation → midline defects; CK1δ → facial asymmetry/clefting; PINK1 → mandibular hypoplasia. Multi-target compounds (e.g., purmorphamine, taladegib) generated composite phenotype predictions consistent with clinical complexity. Conclusions: This strictly in silico study identifies candidate integrated morphogenic modules whose multi-node perturbation may underlie anatomically specific craniofacial malformation patterns. Node–phenotype associations are prioritized computational hypotheses requiring experimental validation; if confirmed, the framework could inform developmental toxicity assessment, therapeutic design, and reclassification of idiopathic craniofacial anomalies. Full article

Background/Objectives: To evaluate margin reflex distance-1 (MRD-1), inter-eyelid symmetry, functional visual parameters, and cosmetic outcomes following Müller Muscle–Conjunctival Resection (MMCR) in selected pediatric patients with mild-to-moderate blepharoptosis, good levator function, and a positive 2.5% phenylephrine test. Methods: This retrospective observational study included pediatric patients (<18 years) who underwent MMCR between 2018 and 2023. Surgical indications were based on functional or developmental criteria, including visual axis obstruction, abnormal head posture, significant eyelid asymmetry, or psychosocial concerns, rather than eyelid height alone. Preoperative and postoperative examinations at 1 week, and at 1, 3, and 6 months, included best-corrected visual acuity (BCVA), MRD-1, eyelid symmetry, levator function, lagophthalmos, and ocular surface findings. Outcomes were analyzed separately for unilateral and bilateral cases. Statistical analyses were performed using non parametric tests, with p < 0.05 considered statistically significant. Results: Fifty patients (55 eyes; mean age 13.16 ± 4.04 years) were included. Mean preoperative MRD-1 increased significantly from 1.83 ± 0.89 mm to 2.97 ± 0.83 mm at 6 months (p < 0.001). Postoperative MRD-1 at 6 months showed a significant correlation with the phenylephrine response. In unilateral cases, excellent or satisfactory postoperative symmetry was achieved in 83.6% of eyes. Bilateral cases demonstrated comparable MRD-1 elevation with satisfactory contour and high patient/parent satisfaction. Transient lagophthalmos improved over time. No overcorrection, exposure keratopathy, or significant ocular surface complications were observed. Revision surgery was required in 8.9% of unilateral cases. Conclusions: MMCR is a safe and effective option for appropriately selected pediatric patients, providing predictable eyelid elevation, good symmetry, and low complication rates when functional indications are present. Full article

Background: The early detection of autism spectrum disorder (ASD) is imperative for enhancing long-term developmental outcomes. Nevertheless, conventional screening methods depend on time-consuming, expert-driven behavioral assessments and are characterized by limited scalability. Automated video-based analysis provides a noninvasive and objective approach for the extraction of behavioral biomarkers from naturalistic recordings. Methods: A modular multimodal framework was developed that integrates motion-based video analysis and facial feature extraction for the purpose of ASD versus typically developing (TD) classification. The system is capable of processing RGB videos, skeleton/stickman representations, and motion trajectory streams. A comprehensive set of kinematic features was extracted, encompassing joint trajectories, velocity and acceleration profiles, posture variability, movement smoothness, and bilateral asymmetry. The repetitive stereotypical behaviors exhibited by the subjects were characterized using frequency-domain analysis via FFT within the 0.3–7.0 Hz band. Facial expression features derived from normalized face crops and landmark-based morphological descriptors were integrated as complementary modalities. The feature-level fusion process was executed subsequent to z-score normalization, and the classification procedure was conducted using a Random Forest model with stratified 5-fold cross validation. The implementation of GPU acceleration was instrumental in facilitating near real-time inference. Results: The motion-based ComplexVideos pipeline demonstrated a cross-validated accuracy of 94.2 ± 2.1% with an area under the ROC curve (AUC) of 0.93. Skeleton-based KinectStickman inputs demonstrated moderate performance, with an accuracy range of 60–80%. In contrast, facial-only models exhibited an accuracy of approximately 60%. The integration of multiple modalities through feature fusion has been demonstrated to enhance the robustness of classification algorithms and mitigate the occurrence of false negative outcomes, thereby surpassing the performance of single-modality models. The mean inference time remained below one second per video frame under standard operating conditions. Conclusions: The experimental results demonstrate that the integration of multimodal cues, including motion and facial features, facilitates the development of effective and efficient video-based screening methods for autism spectrum disorder (ASD). The proposed framework is designed to offer a scalable, extensible, and computationally efficient solution that can support early screening in clinical and remote assessment settings. Full article

Background: Congenital scoliosis (CS) associated with multiple vertebral anomalies (MVAs) represents a biologically dynamic deformity in which cumulative segmental asymmetry, residual growth potential, and mechanobiological modulation interact to drive progression. Unlike isolated congenital lesions, MVAs exhibit growth-dependent and configuration-specific behavior, complicating risk stratification and timing of intervention. Despite extensive literature on congenital deformities, an integrated growth-oriented decision framework for this subgroup remains lacking. Methods: This narrative review synthesizes embryological, biomechanical, and clinical evidence related to vertebral growth potential, anomaly configuration, progression patterns, and age-dependent treatment strategies in CS with MVAs. A structured literature search of major databases was performed, and findings were analyzed thematically to propose a biologically grounded growth-based decision framework. Results: Across the literature, three interdependent determinants of progression consistently emerge: anomaly configuration, residual segmental growth capacity, and mechanobiological amplification during growth. High-risk configurations—particularly mixed formation–segmentation defects and fully segmented hemivertebrae with contralateral growth arrest—demonstrate rapid and often non-linear progression. Thoracic involvement further modifies clinical urgency due to its impact on pulmonary development. Integration of developmental biology and mechanobiological principles supports a structured, growth-informed approach to surveillance and intervention timing. Conclusions: MVAs should be conceptualized as dynamic growth systems rather than static structural defects. A shift from angle-driven to growth-informed decision-making may enhance early identification of high-risk patterns while minimizing unnecessary premature fusion in lower-risk cases. Adoption of a structured growth-based framework provides a biologically coherent foundation for individualized management and long-term optimization of spinal and thoracic development. Full article

Background: Physical functional capacity plays a critical role in sports performance and changes markedly from adolescence to adulthood. This study aimed to compare the physical functional characteristics between adolescent and collegiate soccer athletes. Methods: Fifty elite male soccer athletes (30 adolescents, 20 college students) were assessed for joint range of motion, muscle flexibility, dynamic balance, and trunk functional capacity. Results: Adolescent athletes achieved significantly greater general joint laxity score than collegiate athletes (p = 0.01), with significantly greater hip range of motion across all planes (abduction, internal rotation, and external rotation; all p < 0.01). College athletes had significantly lower SLR degree (left: p < 0.01, right: p < 0.05) but significantly greater degrees on passive Ely’s test (p < 0.01) than adolescent athletes. Collegiate athletes delivered significantly superior dynamic balance performance in the Y-balance test, particularly in the posterolateral and posteromedial directions (all p < 0.05). Unexpectedly, trunk functional capacity was significantly lower in collegiate athletes compared with adolescents (p < 0.01). Limb asymmetry was observed in both groups: collegiate athletes showed asymmetry only in the anterior reach direction of the Y-balance test (p = 0.018), whereas adolescents exhibited asymmetry across multiple joints (ankle, hip, hamstrings, and quadriceps; all p < 0.05) and in the posterolateral direction of the Y-balance test (p < 0.01). Conclusions: Adolescent athletes demonstrated significantly superior joint range of motion and lower limb flexibility, whereas collegiate players exhibited better balance performance, indicating distinct functional profiles between the two cohorts, which may be associated with differences in training experience and developmental stages. Full article

Background and Objectives: This study investigated whether crossover neuromuscular fatigue following unilateral handgrip exercise exhibits directional asymmetry, testing whether dominant-limb fatigue produces greater contralateral performance decrements than non-dominant-limb fatigue in adults and pre-peak-height-velocity children. Materials and Methods: Thirty-three healthy, right-handed males (16 adults: 22.5 ± 1.6 years; 17 pre-peak-height-velocity boys: 11.2 ± 0.8 years, maturity offset −2.2 ± 0.4 years) completed three counterbalanced experimental sessions (48–72 h apart): dominant-arm fatigue, non-dominant-arm fatigue, and control. The fatigue protocol consisted of 20 consecutive 6 s maximal voluntary isometric handgrip contractions. Primary outcomes were percentage changes in maximal voluntary isometric contraction of the contralateral limb across handgrip, elbow flexor, and elbow extensor muscle groups. Results: The experimental condition explained approximately 64% of crossover variance in adults (η_p² = 0.650, ηG² = 0.421) and children (η_p² = 0.638, ηG² = 0.448; both p < 0.001). Dominant-limb fatigue elicited substantially greater contralateral decrements than non-dominant-limb fatigue in adults (−11.00% vs. −3.92%, dz = −1.07) and children (−12.71% vs. −3.08%, dz = −1.33), representing 2.5- to 3.5-fold greater transfer efficiency (both p < 0.001). Age-group comparisons revealed no differences in crossover susceptibility (p = 0.627, η_p² = 0.008), with equivalence testing confirming developmental invariance. Crossover effects extended to heterologous proximal muscles without magnitude differences (p > 0.13). Conclusions: Crossover fatigue (contralateral performance decrement following unilateral exercise) exhibited directional asymmetry, with dominant-limb protocols eliciting 2.5- to 3.5-fold greater contralateral decrements. This pattern aligns with asymmetric transcallosal inhibitory projections demonstrated in prior transcranial magnetic stimulation studies, though direct neurophysiological confirmation was not obtained. Functional equivalence between pre-peak-height-velocity children and adults indicates that interhemispheric transfer mechanisms achieve operational maturity before peak height velocity. Extension to heterologous muscles implicates supraspinal mechanisms. The findings establish normative parameters for clinical populations with compromised transcallosal integrity. Full article

This study explores the reasons why, despite ambitious national strategies, the deployment of renewable energy in Arab countries has persistently lagged behind global trends. It investigates the drivers of this disparity by analyzing the impact of fiscal capacity, energy market size, and energy dependence on renewable energy development. To control for country heterogeneity, this paper divides Arab countries into three groups based on their degree of energy dependence: energy-importing countries, energy-exporting countries, and energy trade reversal countries. Using a panel dataset of 17 Arab countries from 1990 to 2022, this study employs a dynamic common correlated effects (DCCE) estimator, which uniquely accounts for cross-sectional dependence and distinguishes between short-run dynamics and long-run equilibrium. The results reveal three key findings. First, in energy-importing and energy trade reversal countries, improvements in government fiscal balance significantly promote renewable energy development. Second, higher energy consumption exerts a persistent negative effect on renewable energy development, suggesting that demand expansion reinforces carbon lock-in rather than facilitating transition. Third, energy dependence exhibits a temporal asymmetry: it hinders renewable deployment in the short run, but becomes a strong positive driver in the long run, reflecting a shift from immediate supply security to strategic energy security. However, for energy-exporting countries, those drivers are statistically insignificant, highlighting strong path dependence. These findings partly validate the “developmental state”, “carbon lock-in”, and “energy security” theories within the Arab context. The study concludes that fiscal buffers and the pursuit of energy security facilitate the deployment of renewable energy in specific country contexts, while growth in energy consumption reinforces carbon lock-in. These findings contribute to SDG 7 and SDG 13, with particular relevance to Arab countries grappling with the dual challenges of economic diversification and the climate commitments outlined in the Paris Agreement. Full article

Background: Ankylosis of the temporomandibular joint (TMJ) is a rare developmental disorder that involves fibrous or bony fusion within the joint. It is a severe structural and functional disorder. Typically, the phenotype manifests as joint immobilization and results in facial deformity and trismus. To date, ankylosis is rarely diagnosed as congenital and its occurrence mechanism has not been thoroughly understood. We observed a female patient who as a newborn showed slight facial asymmetry and impaired mandibular retraction. In addition, non-uniform occlusal fissures were noted; the lower part of the left earlobe was slightly smaller than the right earlobe. The aim of the work was the identification of pathogenic variants in the genome related to ankylosis. Ankylosis has no known causative gene yet; thus, Whole Exome Sequencing (WES) was performed. Materials and Methods: We observed a female patient with facial asymmetry and impaired mandibular retraction from birth. No phenotypic abnormalities were noted on the head or elsewhere on the body. A diagnostic computed tomography (CT) scan of the head performed at five months of age led to the diagnosis of congenital zygomatic-coronoid ankylosis. Genomic DNA samples were subjected to WES. Library preparation was carried out using the Twist Library Preparation EF Kit 2.0, followed by target enrichment with the Twist Exome 2.0 Plus Comprehensive Exome. Sequencing reads were aligned to the human reference genome (GRCh38), and variant calling was performed using standard bioinformatics workflows. Variants were subsequently filtered, annotated, and interpreted using VariantStudio. Assessment of variant pathogenicity was primarily based on comparisons with public databases, including ClinVar and VarSome, and was supported by in silico prediction tools such as SIFT and PolyPhen-2. Results: In genes responsible for disorders of the I and II pharyngeal arches, three pathogenic variants were identified: in the genes TCOF1 and POLR1B, responsible for the development of Treacher Collins syndrome (TCS), and one in the DHODH gene, responsible for Miller syndrome. Additionally, in genes that have not been linked so far with rare facial disorders, 42 variants were identified, of which 8 are listed as pathogenic. We present the first described patient with congenital ankylosis, who, although showing no phenotypic features of these syndromes, has identified pathogenic variants in genes responsible for craniofacial dysostosis. Conclusions: Variants in TCOF1, POLR1B and DHODH may represent candidate genetic factors associated with susceptibility to ankylosis. WES analysis is an appropriate method in the case of patients with congenital diseases with unknown genetic origin. In this study we provide a comprehensive list of all identified pathogenic variants. This might be useful for scientists searching for the genetic background of skeletal system issues, one of which could be bone and fibrous tissue remodeling. Full article

Objectives: The Pulmonary Auscultatory Triangle (PAT) is a bilateral region on the back delimited by the trapezius, latissimus dorsi, and scapula. Beyond its relevance for pulmonary auscultation, PAT also represents an important anatomical window for posterior thoracic approaches. While its anatomy has been extensively described in adults, data on its developmental morphology during fetal life remain scarce. This original morphometric study aimed to characterize the morphometry and morphology of the PAT in human fetuses and to evaluate differences according to sex, side, and gestational age. Methods: A total of 80 PATs from 40 human fetuses (20 male and 20 female) were examined. Using ImageJ software 1.54k, we measured margin lengths (inferior trapezius, medial scapular, and superior latissimus), area, and perimeter. Morphological classification was performed based on internal angles. Associations with sex, side, and gestational age were statistically assessed. Results: The mean gestational age was 28.6 weeks. PAT had a mean area of 103.2 mm² and a mean perimeter of 49.1 mm. Mean margin lengths were 20.1 mm for the trapezius, 12.4 mm for the scapular margin, and 16.6 mm for the latissimus dorsi. Three morphologies were observed: acute (42.5%), obtuse (25.0%), and rectangular (32.5%). A significant asymmetry in shape distribution was found between sides (p = 0.034). Weak but statistically significant positive correlations with gestational age were found for perimeter and for the trapezius and latissimus dorsi margins, indicating progressive enlargement with fetal growth. Conclusions: This study provides the first detailed morphometric and morphological description of the PAT in human fetuses. The findings establish a developmental anatomical baseline for the posterior thoracic wall and highlight growth-related changes and side-related variability. Full article