Search Results (923)

Background: Neurodevelopmental disorders span a wide spectrum of deficits, often with a known or suspected genetic basis. While some genetic determinants may indicate treatment with selective compounds, more often both the molecular cause of the disorder and the mechanism of action for the therapeutic compound are more ambiguously matched. Due to the polypharmacological nature of most neuroactive compounds, measuring gene expression changes following drug perturbation could be an effective strategy to gain insight into shared therapeutic action downstream of diversity in receptor interaction. High-throughput drug discovery platforms have effectively measured changes in gene expression following drug perturbation in cell cultures, but unfortunately, these platforms often lack specificity for neuroactive compounds, fail to capture the developmental influence of cell–cell interactions, and do not accurately model drug metabolism in an intact system. Methods: In this study, we present a high-throughput, low-cost and cell-type-specific approach for capturing transcriptional changes in neural cell populations following neuroactive compound exposure through the combined use of transgenic zebrafish, cell sorting, and bulk RNA-seq. Results: Our system captures unique transcriptional profiles between neuronal and non-neuronal cell populations and demonstrates specific drug responsiveness within our neuronal cell population. We assessed two known positive allosteric modulators (PAMs) of γ-Aminobutyric acid sub-type A receptors (GABA_AR), ivermectin and propofol, as a case study to explore shared pathway and gene expression changes following drug exposure; these chemically distinct agents share a mechanistic signature that dampens the neuronal hyperexcitability characteristic of a broad spectrum of neurodevelopmental disorders. Two shared downregulated genes reflect a core expression module for modulating GABAergic tone: SRC proto-oncogene, non-receptor tyrosine kinase (SRC), and Glutamate decarboxylase 2 (GAD2). Conclusions: We provide this methodology and analysis as a framework for exploring shared changes in gene expression following neuroactive compound exposure in vivo, leading to a more complete and nuanced understanding of therapeutic effects on neurons that can aid in drug repurposing efforts for neurodevelopmental disorders. Full article

Objectives: To access the effects of febrile seizures from coexisting neurodevelopmental conditions that are commonly associated with autism spectrum disorder. We examined whether febrile seizures are independently associated with ASD after considering neurodevelopmental comorbidities and seizure-related clinical characteristics. Methods: We conducted a nationwide population-based matched cohort study using Taiwan’s National Health Insurance Research Database. The study included 948 children with FS and 3804 age- and sex-matched controls without FS. Participants were followed longitudinally for incident ASD. Associations were evaluated using Cox proportional hazards models with additional analyses restricted to the FS cohort. Neurodevelopmental comorbidities assessed included attention-deficit/hyperactivity disorder (ADHD), epilepsy, and Tourette syndrome/tic disorder. Results: Among 4752 children followed for more than 10 years, 43 (0.9%) developed ASD. FS were not independently associated with ASD in adjusted Cox regression models. In contrast, ADHD, epilepsy, and Tourette syndrome/tic disorder were strongly and consistently associated with ASD across analytic models. Conclusions: Febrile seizures were not independently associated with autism spectrum disorder. Instead, ASD risk was largely explained by coexisting neurodevelopmental comorbidities, consistent with a shared neurodevelopmental susceptibility framework. These findings suggest that developmental surveillance should prioritize children with neurodevelopmental disorders rather than those with febrile seizures alone. Full article

Background: Vascular compression syndromes are increasingly recognized as underdiagnosed contributors to morbidity in patients exhibiting dysautonomia. Underlying vascular compression syndromes affecting the head and neck, abdomen, pelvis, and lower extremities may influence venous return, neurohormonal signaling, and autonomic regulation. There is considerable clinical overlap among these syndromes, as well as between hypermobility spectrum disorders (HSD) and dysautonomia, indicating possible shared or interacting pathophysiological mechanisms. Purpose/Aims: This hypothesis-generating narrative review synthesizes current evidence linking vascular compression syndromes with dysautonomia, highlights potential mechanistic pathways, identifies patterns of syndromic overlap, and emphasizes the importance of systematic evaluation in affected patient populations. Key Findings: Evidence from retrospective studies, case series, and clinical observations indicates that vascular compression syndromes may be prevalent among patients with dysautonomia, particularly postural orthostatic tachycardia syndrome (POTS) and HSD, yet are often unrecognized. Proposed mechanisms based on limited data include impaired venous capacitance and preload reserve, increased intracranial pressure, altered renin–aldosterone and cortisol signaling, underlying autoimmune and systemic diseases, and sympathetic ganglion irritation. Several compression syndromes show symptom overlap and frequent co-occurrence, especially in patients with connective tissue disorders. Emerging data suggest that targeted interventions, such as surgical decompression or venous stenting, may improve orthostatic intolerance and quality-of-life measures in selected patients, though high-quality prospective data remain limited. Conclusions: Vascular compression syndromes may be an important yet underappreciated contributor to dysautonomia. Increased clinical awareness and systematic screening may reduce diagnostic delays and morbidity in this underserved population. Prospective studies are needed to clarify prevalence, establish causal relationships, and determine the impact of targeted treatments on autonomic outcomes. Full article

With the goal of maximizing opportunities for inclusivity for students with autism spectrum disorder (ASD), this systematic narrative review, which allows for more interpretive inferences, investigates the use of magic-based interventions to determine if the skills needed for learning and performing magic tricks have commonality with skills needed to improve social skills deficits, as described in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) (i.e., deficits in social–emotional reciprocity, nonverbal communication used for social interaction, and developing, maintaining, and understanding relationships). The main purpose of this article is to highlight empirical studies that explore how using magic tricks with students with ASD might be beneficial in social skills development, particularly social–emotional reciprocity. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and using predetermined inclusion and exclusion criteria, a systematic narrative review was conducted. This resulted in a total of 129 articles reviewed and discussed using an integrative narrative synthesis approach. The findings reveal elements in common in both learning and performing magic tricks and skills needed to improve social skills, including nonverbal communication skills used for social interactions. Skills gained when learning and performing magic tricks also share overlapping elements needed to create and maintain friendships. Conceptually, findings suggest that learning and performing magic tricks provide a natural setting to practice skills needed to successfully attain social–emotional reciprocity, which could, theoretically, increase inclusion opportunities for students with ASD. Therefore, educators may consider including magic tricks in the classroom setting as a strategy to improve social skills deficits of students with ASD. Full article

Objectives: Autism Spectrum Disorder (ASD) and psychotic disorders have long been considered separate diagnostic entities, yet increasing evidence highlights shared neurodevelopmental mechanisms and symptom overlap. Psychotic-like experiences have been frequently reported in individuals with ASD, while subthreshold autistic traits (ATs) in first-degree relatives may also confer vulnerability to psychotic symptoms. This cross-sectional study aimed to compare psychotic spectrum manifestations among adults with ASD, their first-degree relatives (BAP), and controls (HCs), to explore associations between psychotic and ATs, and to evaluate whether psychotic symptoms predict diagnostic group membership. Methods: 22 adults with ASD, 22 BAP, and 24 HCs were evaluated with the Psychotic Spectrum–Self Report (PSY-SR) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). Results: ASD participants scored significantly higher on the PSY-SR. BAP individuals showed higher PSY-SR total scores compared to HCs, though less severe than in ASD. All PSY-SR domains positively correlated with all AdAS Spectrum domains, with few exceptions. Multinomial regressions showed that higher PSY-SR total scores significantly predicted ASD and BAP membership, and that the PSY-SR Paranoid domain score specifically predicted inclusion in both groups in relation to HCs. Conclusions: Psychotic spectrum symptoms are elevated not only in individuals with ASD but also among first-degree relatives, supporting a continuum linking autistic and psychotic vulnerabilities. The strong association between paranoid symptoms and ATs highlights a dimension of potential clinical relevance for early identification and assessment. These findings reinforce shared neurodevelopmental pathways between the autism and psychosis spectra and underscore the importance of dimensional approaches across diagnostic categories. Full article

Background/Objectives: Atypical fibroxanthoma (AFX) and cutaneous undifferentiated pleomorphic sarcoma (cUPS)/pleomorphic dermal sarcoma (PDS) are related dermal neoplasms of uncertain histogenesis that occupy opposite ends of a shared clinical and histopathologic spectrum, with AFX displaying typically low-grade behavior and PDS representing its more aggressive counterpart. The recent literature has confirmed that AFX and PDS also overlap at the molecular and genomic levels; however, little is known about their gene-expression profiles. Methods: We performed gene-expression profiling using RNA sequencing with a Pan-Cancer RNA Panel on a small series of AFX and PDS samples. Results: Unsupervised cluster analysis showed a clear separation between the two groups. We confirmed a TP53 UV-radiation signature in both. However, while AFX and PDS share common DNA mutation profiles in our cohort, RNA sequencing reveals distinct gene-expression signatures that may aid in differentiating these related tumors. In particular, the MAPK pathway, cell adhesion, DNA repair, EMT-like signatures and inflammatory responses play key roles in distinguishing the two groups, at least in our limited cohort, consistent with their differing biological behavior. Differences in the expression of receptor tyrosine kinases were also observed. Conclusions: Gene-expression profiling have the potential to be a valuable tool for distinguishing AFX from PDS, clarifying their positions at opposite ends of a spectrum and providing deeper insight into the biology of these neoplasms. Full article

Background: Novel therapeutic compounds with strong efficacy and low resistance potential are urgently needed to combat life-threatening infections caused by antibiotic-resistant ESKAPEE pathogens. These pathogens contribute globally to a large share of bloodstream, respiratory, urinary, and wound infections, and often have levels of high antimicrobial resistance. This review examined the antimicrobial efficacy of different plant essential oils (EOs) against Gram-negative ESKAPEE pathogens and their cytotoxic effects and calculated selectivity indices in cancer and normal cell lines. Methods: This review was developed using studies retrieved from PubMed, Scopus, and Web of Science, covering publications between 2013 and 2024 using the search terms: “essential oils”, “plant extracts”, “safety”, “cytotoxicity”, “cell lines”, “human”, “in-vitro”, antimicrobial”, “antibacterial” and “antibiotic” with Boolean operators (“AND”, “OR”, “NOT”). Only studies that reported both antimicrobial inhibitory concentrations and concentrations causing toxicity to mammalian cells were included in the final review. These data were then used to calculate the selectivity indices of the EOs (toxic concentration/antimicrobial inhibitory concentration) to give an initial assessment of safety. Results: Ocimum basilicum EOs had strong antibacterial effects against the Gram-negative ESKAPEE pathogens Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, with minimum inhibitory concentrations (MICs) as low as 1 μg/mL and high selectivity indices of >80.4. Likewise, Satureja nabateorum EOs had potent antibacterial activity, with a low MIC of 0.1 μg/mL against K. pneumoniae, 2.3 μg/mL against E. coli, and 12.5 μg/mL against P. aeruginosa, along with a very high selectivity index (>100). Other EOs such as those from Eucalyptus spp., Thymus spp., Mentha spp., Cinnamomum spp., Artemisia spp., and Aquilaria crassna also had broad-spectrum antibacterial potential and minimal toxicity toward mammalian cells, making them promising candidates for safe and effective antimicrobial agents in clinical and industrial applications. However, several EOs had selectivity indices of <10, indicating that at their MIC they would also be potentially highly cytotoxic. EOs tended to show increased toxicity to cells derived from cancers. Conclusions and recommendations: Certain EOs are highly active against Gram-negative ESKAPEE pathogens. They are also toxic to cancer-derived mammalian cells. Additional studies using normal cell lines and clinical trials are warranted to further validate their safety and therapeutic potential. Full article

Terms are specialized words and expressions used in particular disciplines, cultures, or fields. They usually carry precise meanings and aim to describe referents accurately and clearly. Due to differences in culture, history, and other factors across countries, the development of indigenous Chinese linguistic terms plays a vital role in bridging cultural gaps and promoting the dissemination of Chinese culture. These terms not only explain specific words in Chinese and describe unique linguistic phenomena, but also embody the core concepts and academic traditions of Chinese linguistics, thereby contributing to the global spread and development of Chinese civilization. In order to achieve cross-linguistic dissemination of indigenous terms, we construct a linguistically informed bilingual corpus encompassing a broad spectrum of linguistic subfields, together with novel methods for the automatic extraction and cross-linguistic alignment of terminologies. The resulting corpus contains over 22,000 aligned sentence pairs across nine linguistic domains, providing a robust foundation for bilingual term mining. Building upon this resource, we further propose a multi-channel graph neural network (MCGNN) that jointly models semantic, syntactic, sequential, and co-occurrence relations, thereby enabling multi-perspective reasoning and achieving more accurate bilingual term extraction and alignment. Experimental results demonstrate that our approach substantially improves the accuracy and consistency of bilingual term extraction, alleviates the resource scarcity in the linguistic domain, and provides a solid foundation for future research and applications in cross-linguistic knowledge sharing and academic communication. Full article

Hot springs, hot-water bathing, and saunas are widely practiced forms of acute heat exposure and are often perceived as health-promoting. However, emergency clinicians frequently encounter patients in whom these exposures precipitate syncope, hypotension, drowning/aspiration, heat-related illness, and renal or electrolyte disturbances. This narrative review integrates these modalities within a unified “acute heat exposure” framework and summarizes pathophysiology and clinical implications from an emergency medicine perspective. We searched PubMed/MEDLINE from inception to January 2026 using controlled vocabulary and free-text terms related to heat stress, thermoregulation, hot-water immersion, sauna exposure, and acute clinical outcomes; evidence was synthesized qualitatively. Across modalities, acute heat exposure induces shared physiological responses—peripheral vasodilation, relative hypovolemia, circulatory stress, and internal heat storage—that can trigger diverse emergency presentations. We classify acute heat exposure–related illness into four domains: (1) cardiovascular events, including syncope, hypotension, and arrhythmic/ischemic complications in vulnerable individuals; (2) the heat-illness spectrum from exhaustion to heat stroke with organ dysfunction; (3) renal and electrolyte disturbances related to dehydration and hypoperfusion; and (4) neurological and traumatic complications, including falls, drowning, and aspiration. This framework may support risk stratification, evaluation, management, and prevention after hot spring, hot bath, or sauna use. Full article

Diabetes mellitus is increasingly recognized as a biologically heterogeneous disorder that extends beyond traditional phenotype-based classifications. Advances in human genetics have revealed that monogenic and polygenic forms of diabetes are not discrete entities, but rather represent points along a continuum of genetic architectures that converge on shared molecular pathways governing pancreatic β-cell identity, function, and survival. Rare monogenic forms, including maturity-onset diabetes of the young and neonatal diabetes, arise from highly penetrant single-gene defects that directly impair transcriptional regulation, glucose sensing, insulin biosynthesis, or stimulus–secretion coupling. Although individually uncommon, these disorders provide high-resolution models of β-cell dysfunction and have demonstrated the clinical value of genotype-guided diagnosis and therapy. At the opposite end of the spectrum, type 1 and type 2 diabetes result from complex interactions between multiple genetic variants and environmental factors, with genome-wide association studies highlighting a central role for genetically determined β-cell vulnerability alongside immune-mediated and metabolic stress pathways. Importantly, intermediate phenotypes such as latent autoimmune diabetes in adults further illustrate the overlap between autoimmune and metabolic mechanisms, challenging rigid diagnostic boundaries. This review synthesizes current evidence on the genetic architecture of diabetes across monogenic and polygenic forms, emphasizing convergent molecular mechanisms and their translational implications. By integrating insights from rare genetic disorders with findings from large-scale population studies, we propose a continuum-based framework that supports a shift from phenotype-driven labels toward a mechanistic, biology-informed approach to diabetes classification, risk stratification, and personalized care. Full article

Background: Goldenhar syndrome (oculo–auriculo–vertebral spectrum, OAVS) is a rare congenital disorder characterized by craniofacial malformations, systemic anomalies, and significant phenotypic variability. Although it is the second most common craniofacial malformation after a cleft palate, the genetic etiology of Goldenhar syndrome remains largely unexplored. This study aimed to identify genetic variants contributing to Goldenhar syndrome in a Lebanese family with three affected individuals, using whole-exome sequencing and complementary genomic approaches. Methods: Whole-exome sequencing was performed on the nuclear family to identify variants associated with the syndrome. Complementary DNA methylation and gene ontology analyses were conducted to explore epigenetic modifications. Results: A missense shared variant in the MID1 between the affected individuals [NP_000372.1): p. Ile593Phe] gene was observed in the family, while current ACMG evidence was insufficient to establish causality. Additional variants were identified, including a de novo mutation in FBXW11 and a rare frameshift alteration in NDUFAF8, with limited segregation, implicating these genes in associated phenotypes such as craniofacial anomalies and cardiac defects. DNA methylation analysis revealed hypomethylation at CpG sites within the ZC3H3 gene, suggesting an epigenetic contribution to disease variability. Conclusions: Our findings underscore the genetic and epigenetic complexity of Goldenhar syndrome, providing new insights into its molecular etiology and highlighting the challenges of variant interpretation in familial cases of rare congenital disorders. Full article

Tetracyclines are broad-spectrum bacteriostatic agents with well-established antimicrobial efficacy and a shared core chemical structure, differentiated by distinct functional substitutions across generations. Beyond their antibacterial action, tetracyclines also exhibit pleiotropic biological effects, including modulation of bone metabolism. Nevertheless, the selection of agents and dosing for local bone applications remains largely empirical. Therefore, this study compares the tissue-level osteogenic potential of four tetracyclines from distinct generations using a translational ex vivo embryonic chick femur model. Organotypic femur cultures were maintained for 11 days and exposed to tetracycline (TC), doxycycline (DC), minocycline (MC), or sarecycline (SC), at 1 and 10 µg/mL, concentrations corresponding to clinically relevant local and systemic exposures. Osteogenic outcomes included microcomputed tomography, histological analyses, and quantitative gene expression. At 1 µg/mL, tetracyclines promoted osteogenic effects, increasing collagen deposition by approximately 30%, enhancing matrix maturation by 100%, stimulating tissue mineralization by 20–50%, and upregulating osteogenic marker expression, with TC exhibiting weaker activity. At 10 µg/mL, osteogenic stimulation was notably reduced across all groups. This study provides the first tissue-level, head-to-head comparison of four tetracyclines and their effects on bone biology. The findings indicate that tetracycline-induced osteogenic activity is both agent-specific and concentration-dependent, underscoring the importance of using lower doses to maximize osteogenic responses and supporting the preferential use of DC, MC, and SC in bone regeneration and adjunctive therapeutic applications. Full article

Background/Objectives: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder classically associated with emphysema and COPD. However, emerging evidence indicates that its clinical spectrum extends to airway-predominant diseases such as bronchiectasis and asthma, where protease–antiprotease imbalance and neutrophilic inflammation may drive tissue injury. This narrative review aims to synthesize current evidence on the relationship between AATD and airway diseases beyond emphysema, focusing on epidemiological patterns, underlying mechanisms, diagnostic strategies, and therapeutic implications. Methods: A narrative synthesis of the literature was performed, integrating data from registries, with observational and translational studies addressing the prevalence, pathobiology, and therapeutic implications of AATD in bronchiectasis, asthma, and severe asthma. Epidemiologic and mechanistic insights were analyzed to identify overlapping pathways and evidence gaps. Results: Evidence supports a non-negligible prevalence of bronchiectasis and asthma among AATD individuals, particularly in severe or heterozygous genotypes. Neutrophil elastase overactivity, impaired mucociliary clearance, and chronic neutrophilic inflammation emerge as shared mechanisms promoting bronchial remodeling and airflow limitation. In asthma, AATD appears linked to T2-low, steroid-resistant phenotypes and persistent obstruction, whereas in severe asthma cohorts, up to 20% may carry non-PiMM SERPINA 1 variants. No randomized trials have evaluated augmentation therapy and standardized screening algorithms are lacking. Conclusions: AATD represents a systemic disorder with clinically relevant airway manifestations beyond COPD and emphysema. Targeted testing should be considered in patients with idiopathic bronchiectasis or severe asthma. Future genotype-stratified, prospective studies are required to clarify causality, define biomarkers of disease activity, and evaluate the potential role of anti-protease-based therapeutic strategies. Full article

Autoimmune ocular surface diseases represent a complex group of disorders in which systemic immune dysregulation triggers chronic inflammation, epithelial dysfunction, and progressive tissue fibrosis. Systemic lupus erythematosus, primary Sjögren’s syndrome, and ocular cicatricial pemphigoid are the principal entities linking systemic autoimmunity to ocular surface pathology. These conditions share convergent mechanisms—including dysregulated cytokine signaling (IFN-I, IL-6, and IL-17), complement activation, and epithelial–mesenchymal transition—culminating in tear film instability and visual impairment. Recent advances in molecular immunology and omics profiling have elucidated disease-specific pathways and identified actionable therapeutic targets. Conventional immunosuppressants such as corticosteroids and cyclosporine remain fundamental, yet emerging biologics targeting BAFF, IFNAR, and JAK/STAT signaling—alongside regenerative strategies employing mesenchymal and induced pluripotent stem cells—are transforming disease management. Parallel innovations in amniotic membrane transplantation, keratoprosthesis, and bioengineered corneal scaffolds integrate structural reconstruction with immune modulation. Furthermore, the convergence of multi-omics analytics, artificial intelligence-assisted diagnostics, and microbiome-based immunomodulation heralds a new era of precision ophthalmology. This review synthesizes current molecular insights, clinical observations, and translational advances that collectively redefine autoimmune ocular surface diseases—from chronic inflammatory disorders into a targetable, regenerative, and potentially reversible spectrum of conditions. Full article

Terahertz (THz) sub-millimeter wave imaging offers unique capabilities for stand-off biometrics through concealment, yet it suffers from severe sparsity, low resolution, and high noise. To address these limitations, we introduce a novel unified Multi-Task Learning (MTL) network centered on a custom shared U-Net-like THz data encoder. This network is designed to simultaneously solve three distinct critical tasks on concealed THz facial data, given a limited dataset of approximately 1400 THz facial images of 20 different identities. The tasks include concealed face verification, facial posture classification, and a generative reconstruction of unconcealed faces from concealed ones. While providing highly successful MTL results as a standalone solution on the very challenging dataset, we further studied the expansion of this architecture via a cross-modal teacher-student approach. During training, a privileged visible-spectrum teacher fuses limited visible features with THz data to guide the THz-only student. This distillation process yields a student network that relies solely on THz inputs at inference. The cross-modal trained student achieves better latent space in terms of inter-class separability compared to the single-modality baseline, but with reduced intra-class compactness, while maintaining a similar success in the task performances. Both THz-only and distilled models preserve high unconcealed face generative fidelity. Full article