Search Results (9,925)

(1) Background: The characteristics of rare diseases (RDs) vary considerably—not only between different disease types but also between individual patients with the same condition. In the Roma community, we analyzed the most frequent rare genetic disorders related to the founder effect. (2) Methods: This retrospective study, conducted between January 2019 and January 2025 at the Clinical Genetics and Metabolics Outpatient Clinic in Košice, included 61 patients aged from infancy to 25 years diagnosed with hypomyelinating leukodystrophy 14, pontocerebellar hypoplasia type 1B, neuronal ceroid lipofuscinosis 7, or TMEM70 deficiency. (3) Results: This study includes the largest known cohort of patients with hypomyelinating leukodystrophy 14 caused by the UFM1 c.-273_-271delTCA mutation, predominantly affecting males (n = 17). The disorder is severe, with most patients dying before one year of age, and is characterized by inspiratory stridor, axial hypotonia, spastic quadriparesis, pseudobulbar signs, and microcephaly. In a separate group with pontocerebellar hypoplasia type 1B, six Roma patients (three males, three females) shared the same EXOSC3 mutation. Diagnosis occurred at an average age of 8.8 months, and most children did not survive beyond three years. Common features included microcephaly, severe hypotonia, and spastic quadriplegia. Thirteen children from eight families were diagnosed with neuronal ceroid lipofuscinosis 7, all carrying the same MFSD8 mutation. Symptoms typically began with psychomotor regression between ages 3 and 4, along with intellectual disability and seizures, which were more frequent in males. The mean age at diagnosis was 4.5 years, and eight children died before age nine. Finally, 25 patients with TMEM70 deficiency associated with Roma ancestry were identified, predominantly females, with a mean age of 9.95 years and the oldest patient aged 25. Four children died due to severe metabolic crises. Common findings included intellectual disability, global hypotonia, hypertrophic cardiomyopathy, epilepsy, and failure to thrive. (4) Conclusions: Most rare diseases are genetic and carry high morbidity and mortality, with no targeted therapies currently available. Their increased prevalence in the Roma population reflects founder effects and high consanguinity. Prenatal and newborn screening, along with voluntary carrier testing for couples, is essential for proactive health management. Full article

To address the issues of unbalanced residual energy caused by heterogeneous initial robot states and dynamic environmental disturbances, this paper proposes a dynamic task allocation and rescheduling strategy considering energy balance. A Multiple Traveling Salesman Problem (MTSP) mathematical model that incorporates energy constraints and load balancing is established. Furthermore, an Improved Genetic Algorithm (IGA) based on K-Means initialization and adaptive mutation strategies is proposed. By introducing an energy-aware operator, the algorithm achieves energy consumption balance within the robot swarm while optimizing the total path length. In addition, an event-triggered dynamic rescheduling mechanism is designed. When sudden robot failures or task updates are detected, a Local Greedy Insertion (LGI) strategy is activated to achieve rapid task takeover and reallocation. Experimental results show that the proposed IGA consistently reduces the system’s state of charge (SoC) range to less than 1%, significantly outperforming baseline algorithms. It strikes an excellent balance between solution accuracy and computational time overhead. Finally, by simulating sudden new tasks and robot failure scenarios, the effectiveness of the dynamic rescheduling mechanism is verified, ensuring the timeliness and high robustness of the system. Full article

Potato early blight (EB), caused by Alternaria, is an economically devastating fungal disease affecting global potato production. Using a hybrid population derived from distantly related varieties, we combined resistance evaluation, histological analysis, Bulked Segregant Analysis sequencing, RNA sequencing and molecular dynamics simulation, which successfully identified key candidate resistance genes. Genetic mapping localized three major resistance-associated regions on chromosome 8 spanning positions 25.07–29.20 Mb, 38.05–38.80 Mb, and 39.40–40.78 Mb. Through candidate gene analysis, we identified CND41, encoding an aspartic protease, as the prime candidate. This gene exhibited significantly higher basal expression levels and stronger pathogen-induced upregulation in resistant genotypes. Molecular dynamics simulations further identified six crucial non-synonymous mutations in the TAXI-N domain that likely contribute to enhanced resistance by destabilizing the susceptibility-associated protein conformation. Transient overexpression of CND41 provided functional evidence supporting its likely involvement in early blight resistance (EBR). These findings contribute valuable genetic resources and a strong candidate gene for molecular breeding toward EBR potato varieties. Full article

To accomplish underwater search missions of the target with stochastic motion, path planning is required prior to autonomous underwater vehicle (AUV) operations. Genetic algorithms (GAs) are a classical approach for target search path planning; however, when applied to moving underwater targets, they often rely on oversimplified motion models and lack flexible mutation direction control, resulting in suboptimal search paths and reduced detection performance. To address these limitations, this paper proposes a GA-based path planning method incorporating a target-position-controlled mutation strategy. First, a Markov process combined with a grid-based approach is used to model stochastic target motion and derive the spatial probability distribution of target positions. Second, based on the target distribution grid, the influence of random fluctuations on sonar signals is simulated to construct a probabilistic detection model. Finally, the target distribution and detection probability model are integrated into the proposed GA to generate an optimal AUV search path. Simulation results show that the proposed method effectively improves path planning for moving targets under stochastic conditions, increasing the target cumulative detection probability from 0.33 to 0.48. Full article

Generalized Arterial Calcification of Infancy (GACI) is a rare autosomal recessive disorder characterized by pathological calcium deposition in large and medium-sized arteries, leading to severe cardiovascular complications such as hypertension, heart failure, and stroke. The mortality rate is approximately 50% within the first six months of life if untreated. The disease is primarily caused by mutations in the ENPP1 or ABCC6 genes, resulting in a deficiency of inorganic pyrophosphate (PPi), a key inhibitor of arterial calcification. This review provides a comprehensive overview of the pathophysiology, genetic basis, and clinical features of GACI. In addition, we summarize current and emerging therapeutic strategies, including enzyme replacement therapy with recombinant ENPP1 (INZ-701), critically discussing available preclinical and early clinical evidence, as well as current limitations. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic disorder shaped by genetic variants and network-level interactions beyond obesity and insulin resistance. This study aimed to define the genetic and proteomic architecture of MASLD by integrating GWAS and plasma proteomic profiling from the UK Biobank. Genome-wide association analyses were conducted under additive and dominant models, with functional annotations performed using SIFT, PolyPhen-2, PROVEAN, REVEL, CADD, MutationTaster, and conservation metrics (GERP++, phyloP, phastCons, and B-statistic). Differential protein expression was assessed using the Olink^® platform, and STRING was applied for protein–protein interaction analysis. MASLD patients showed male predominance and significant differences in hepatic (AST, ALT, GGT, PDFF), metabolic (glucose, triglycerides, TyG index), and inflammatory markers (CRP, neutrophils, NLR, CAR). GWAS confirmed PNPLA3 (rs738409, I148M) and TM6SF2 (rs58542926, E167K) as major risk variants, while SAMM50 and NCAN showed weaker but conserved associations. Proteomics revealed downregulation of IGFBP2, IGFBP1, PON3, CKB, and APOF and upregulation of CPM, IGSF9, GUSB, ACY1, AFM, LEP, and GSTA1/3. PPI analysis identified ADIPOQ, LEP, FGF21, and ADH1B as central hubs in metabolic and inflammatory regulation. MASLD should be regarded as a network disease involving lipid metabolism, insulin/IGF signaling, mitochondrial function, and ECM–inflammatory pathways. These findings highlight PNPLA3 and TM6SF2 as major genetic drivers, while SAMM50, NCAN, and peripheral proteins contribute regulatory roles, suggesting novel biomarkers and therapeutic targets. Full article

Senecavirus A (SVA) has rapidly emerged as a globally distributed swine pathogen, with clinical signs mimicking vesicular diseases such as Foot-and-Mouth Disease, posing challenges for timely detection and control. Here, we analyzed 329 complete SVA genomes spanning multiple continents to provide a comprehensive view of its evolutionary dynamics, recombination patterns, haplotype diversity, and global dissemination. Phylogenetic analyses revealed two major lineages: Lineage 1, consisting mainly of early strains from the United States before 2007, and Lineage 2, which emerged post-2007 and subsequently spread across the Americas and East Asia. Recombination was confined to Lineage 2 and concentrated in nonstructural regions, particularly 2C, highlighting intra-lineage genetic exchange as a driver of recent diversification. Haplotype analysis of the 3AB gene identified 170 distinct haplotypes, revealing a star-like network structure consistent with rapid population expansion from a central ancestral variant, while secondary branches reflect ongoing regional diversification. Despite this high genetic variation, genome-wide dN/dS ratios remained below one, and purifying selection was strongest in the N-terminal domains of structural and nonstructural proteins, indicating functional constraints that maintain viral fitness. Time-scaled phylogenetic reconstruction and Bayesian Skyline analysis revealed rapid lineage diversification and a marked increase in effective population size in the early 2010s. Phylogeographic inference further identified repeated introductions from the Americas into East Asia, likely facilitated by swine trade and other anthropogenic factors. Collectively, SVA evolution is driven by frequent mutation and intra-lineage recombination yet constrained by pervasive purifying selection, generating extensive genetic diversity while maintaining functional integrity, with implications for genomic surveillance and targeted control. Full article

Background: Codon usage bias (CUB), which is shaped by mutation pressure, natural selection, and genetic drift, provides valuable insights into phylogenetic relationships and molecular evolution. This study investigated the patterns and determinants of mitochondrial genome codon usage in two Enicurus species (Enicurus scouleri and Enicurus schistaceus) and provided a foundation for understanding codon optimisation mechanisms and genetic relationships within this avian genus. Methods: Complete mitochondrial genome sequences were retrieved from GenBank, and ten protein-coding sequences were selected for CUB analysis. Evolutionary relationships across the studied species were investigated using phylogenetic trees and relative synonymous codon usage (RSCU) clustering diagrams. Results: GC1, GC2, and GC3 contents were below 50% in both species, with the third-position nucleotides exhibiting A3s > C3s > T3s > G3s composition. The average effective number of codons (ENC) value was >35, indicating a weak bias for codon usage. CUB reflects the combined effects of natural selection and mutational pressure, with the former exerting a stronger influence. Four shared optimal codons were identified with a strong bias towards A/C-ending triplets. Subsequent phylogenetic analysis validated the close kinship of the two Enicurus species, although RSCU-based clustering yielded results that diverged from the phylogenetic relationships. Conclusions: Comprehensive mechanistic analysis revealed natural selection as the dominant force shaping mitochondrial CUB in Enicurus species. The findings offered valuable insights for future research on the reproductive biology, environmental adaptation, and conservation of Enicurus birds while providing new perspectives on the molecular evolution and systematic development of Muscicapidae. Full article

Cutaneous T-cell lymphoma (CTCL), primarily mycosis fungoides (MF) and Sézary syndrome (SS), has long been characterized as a neoplasm of mature memory T cells, based on monoclonal T-cell receptor (TCR) rearrangements and tissue-resident memory (TRM)/central memory (TCM) T-cell phenotypes. This review synthesizes converging population-genetic, multi-omic, and single-cell evidence to argue that this characterization is incomplete and that a progenitor-based model better accounts for the full spectrum of disease biology. We present evidence that initiating mutations arise in hematopoietic stem or early lymphoid progenitor survive thymic selection, and diversify after TCR assembly, resulting in branched evolution across both blood and skin. In SS, paired analyses reveal > 200 shared variants between CD34⁺ progenitors and Sézary cells, as well as signal-joint T-cell receptor excision circle (sjTREC) positivity, providing direct progenitor-level evidence. In MF, convergent signals, multiple malignant clonotypes per lesion, greater blood–skin than skin–skin clonotype overlap, and compartment-specific CNV subclones, implicate hematogenous seeding and reseeding. Population-scale lymphoid clonal hematopoiesis and lymphoid-pattern mosaic chromosomal alterations define a compatible antecedent state. Spatial single-cell atlases and trajectory analyses map site-conditioned programs in skin, including Th2-skewed cytokines, microbial responses, and UV signatures, that select and expand subclones and explain inter- and intra-patient heterogeneity. This framework reconciles mature immunophenotypes with upstream initiation and clarifies why compartment-focused therapies often reshape rather than eradicate disease. It yields testable predictions and actionable implications: trials should pair multicompartment cytoreduction with strategies that attenuate progenitor-derived reservoirs, restore immune balance, and repair skin barrier dysfunction. A progenitor-initiated, niche-adapted model provides a coherent scaffold for more durable control in CTCL. Full article

This study investigates the problem of profit maximization in a retrial queueing-inventory system. Customers who arrive at the system when there is no stock enter a retrial orbit and are treated as retrial demands. We consider two strategies for inventory replenishment: the base stock policy and the (s, S) policy. For each strategy, we first formulate the fundamental equations needed to determine the rate matrix and the steady-state probabilities. Then, we compute the system’s performance metrics and profit function. Moreover, by leveraging particle swarm optimization (PSO) and genetic algorithm (GA), we introduce an improved hybrid optimization algorithm, Improved Hybrid Particle Swarm optimization (IHPSO), to solve the profit maximization problem. This algorithm initially uses PSO, followed by GA crossover and mutation to improve performance. In comparison to the canonical PSO algorithm (CPSO), our algorithm exhibits superior global search capabilities. Finally, we conduct a numerical analysis on the optimal decision variables and the corresponding profits utilizing the IHPSO algorithm and present several interesting findings. Full article

Background: Influenza A(H3N2) viruses remain a major public health concern due to their rapid antigenic evolution and association with severe disease, particularly among high-risk populations. During the 2025–2026 influenza season, a marked epidemiological shift was observed in Europe, with the emergence and predominance of the A(H3N2) subclade K (J.2.4.1). Objectives: This narrative review aims to provide an integrated overview of the epidemiology, evolutionary dynamics, and public health implications of subclade K, with a particular focus on its impact on vaccine effectiveness, in comparison with the 2024–2025 influenza season. Methods: A non-systematic literature review was conducted using major scientific databases and official public health sources, including WHO and ECDC reports. Recent surveillance data, genomic analyses, and epidemiological updates were included. Given the rapidly evolving evidence base, selected preprint studies were also considered and interpreted with caution. Results: The 2025–2026 influenza season in Europe was characterized by a relative genetic convergence, with subclade K accounting for the majority of A(H3N2) sequences. This variant demonstrated a clear selective advantage and was associated with an earlier and more intense epidemic peak. Molecular analyses indicate the accumulation of multiple mutations in the hemagglutinin protein, particularly within key antigenic sites, contributing to immune escape. These evolutionary changes have important implications for vaccine effectiveness, with current estimates suggesting moderate protection against infection but preserved effectiveness against severe outcomes. Antigenic mismatch, manufacturing constraints, and host-related factors further contribute to reduced vaccine performance. Conclusions: The emergence and rapid spread of subclade K highlight the dynamic nature of influenza virus evolution and its impact on public health. Continuous genomic surveillance and timely vaccine updates remain essential. Despite suboptimal effectiveness against infection, influenza vaccination continues to provide significant protection against severe disease and should remain a cornerstone of prevention strategies. Full article

The rise in antimicrobial resistance represents a significant challenge to global health. The reason partially lies in an inappropriate use of conventional antibiotics and the subsequent rapid spread of multidrug-resistant pathogen strains. This emergency requires an urgent search for conceptually new antimicrobial agents. A viable alternative to conventional antibiotics is antimicrobial peptides (AMPs), which are ribosomally synthesized molecules with considerable potential as next-generation anti-infectious therapeutics. Previously, we have reported on the β-hairpin peptide Ap9, an analog of abarenicin from the marine polychaeta Abarenicola pacifica, with potent activity against key Gram-negative pathogens. Here, it is shown that Ap9 acts in a manner resembling polymyxin B, namely via interaction with lipopolysaccharide (LPS), and retains its activity against polymyxin-resistant isolates without observed cross-resistance, and causes insignificant damage in cytoplasmic membrane at bactericidal concentrations. NMR spectroscopy reveals that LPS binding induces a conformational rearrangement of Ap9, its dimer formation, and local structural remodeling of the peptide region (residues 8–12) into 3₁₀-helix. Bacterial resistance to Ap9 was found to be relatively low with a reduced susceptibility associated with infrequent genetic alterations, such as the mutation in lptD or the deletion in mlaA. Furthermore, Ap9 demonstrates a favorable tolerability, a wider therapeutic window than that of polymyxin B, and a sufficiently long half-life through the systemic use, as well as in vivo efficacy in murine models of Gram-negative infections, including sepsis caused by the mcr-1-harboring Escherichia coli strain. The obtained results point to Ap9 as a promising candidate for further preclinical studies aimed at development of an alternative to polymyxins. Full article

Modern cattle comprise two major evolutionary lineages: intensively selected commercial breeds and locally adapted native populations. To investigate their genomic divergence, we performed a comparative population genomic analysis by integrating whole-genome resequencing (WGS) data from multiple representative native breeds and major European commercial breeds. Population genetic analyses showed clear phylogenetic separation between the two groups, with distinct patterns of genetic diversity. Chinese native cattle exhibited generally higher nucleotide diversity (π), lower inbreeding levels, and geographically structured admixed ancestry. Comparative analyses of selection signatures identified 886 candidate selected genes in European commercial breeds, which were primarily enriched in pathways related to production traits, including protein turnover, reproductive regulation, lipid metabolism, and neuro-regulation. In contrast, 50 candidate selected genes in Chinese native cattle were significantly enriched in nervous system functions, particularly ligand-gated ion channel activity and chloride transport (e.g., GRID2, GLRA2/4, GABRD), suggesting neural/ionic regulation may contribute to local adaptation alongside other polygenic mechanisms. Additionally, the two groups also differed in patterns of deleterious mutation load. These findings indicate partially distinct evolutionary trajectories between “production-optimized” and “environment-adapted” cattle and highlight the value of conserving the genetic diversity and adaptive alleles of Chinese native cattle. Full article

Background/Objectives: Bainbridge–Ropers syndrome (BRPS) is a rare neurodevelopmental disorder caused by truncating and splicing pathogenic variants in the additional sex combs-like 3 (ASXL3) gene. It is primarily characterized by neurodevelopmental delay and craniofacial dysmorphism. Most reported cases involve de novo mutations in the ASXL3 gene, whereas inherited mutations have been rarely described. The present report aims to describe the clinical and molecular presentation of a familial case of BRPS and to highlight the potential role of parental mosaicism. Methods: We describe the clinical and molecular presentation of a 12-year-old boy and his 20-month-old half-brother, both affected by Bainbridge–Ropers syndrome. Trio-exome sequencing (ES) was performed in the family to identify variants in the ASXL3 gene, and targeted Sanger sequencing was also performed for segregation analysis. Results: Genetic analysis identified a previously unreported heterozygous frameshift variant in the ASXL3 gene (c.1648_1649del; p.Met550Aspfs*5) shared by both siblings. The variant was inherited from their clinically unaffected mother, who carries the mutation in the mosaic state with a variant allele fraction of approximately 15% in peripheral blood DNA. Conclusions: This observation highlights parental mosaicism as a potential mechanism underlying the familial recurrence of BRPS and emphasizes the importance of considering mosaic variants during the genetic evaluation and counseling of affected families. Full article

To address the lack of traversable region awareness in conventional path planning algorithms for obstacle-crossing robots, an adaptive path planning method is proposed. First, a traversal-aware environment model is constructed by introducing graded traversable regions with associated physical traversal costs. To effectively navigate this complex model, a hybrid Ant Colony Optimization (ACO) framework integrating Jump Point Search (JPS) and the Genetic Algorithm (GA) is developed. Specifically, a JPS-inspired pruning strategy is incorporated into the state transition process to significantly reduce redundant node expansion. Crucially, genetic operators—namely crossover and mutation—are embedded within the main ACO iterative loop to dynamically sustain population diversity and effectively mitigate stagnation in local optima. Correspondingly, the pheromone initialization, state transition mechanisms, and update rules are redesigned to incorporate the robot’s obstacle traversal capabilities. The framework is further complemented by path optimization operations that reduce unnecessary turning points. Extensive simulation experiments demonstrate that the proposed method outperforms conventional ACO-based and classical path planning algorithms. In particular, it achieves an average reduction of 11.1% in path length and 65.5% in the number of waypoints, while ensuring effective coordination with the robot’s physical traversal capabilities. These results validate the superior search efficiency, robustness, and practical applicability of the proposed approach. Full article