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12 pages, 1905 KB  
Article
Analysis of HA5 Hemagglutinins from Influenza A Viruses for Mass-Charge Patterns to Understand Antigenic Drift Related to Immune Escape
by Wenhao Zhang, Xinran Wu, Rui Zhu, Xinyi Pan, Shancheng Yu, Jie Wang, Jun Steed Huang and Wandong Zhang
Viruses 2026, 18(9), 1025; https://doi.org/10.3390/v18091025 - 15 Sep 2026
Abstract
Influenza A viruses remain a persistent global health threat due to their ability to mutate and evade host immune defences, a process largely driven by changes in hemagglutinin (HA). HA is a glycoprotein present on the surface of influenza virions and plays a [...] Read more.
Influenza A viruses remain a persistent global health threat due to their ability to mutate and evade host immune defences, a process largely driven by changes in hemagglutinin (HA). HA is a glycoprotein present on the surface of influenza virions and plays a critical role in viral entry into host cells by binding to cellular receptors. In this study, 23 HA5 protein sequences from various influenza viral strains collected from wild birds, seagulls, ducks, geese, and chickens, as well as from humans in mainland China during the period from 2023 to 2024, were analyzed for mass-charge patterns by our predictive modelling algorithm to understand the nonlinear trend of viral evolution, particularly regarding their antigenic drift and immune escape potential. Two critical regions in HA5 proteins were identified and analyzed. The first region is a “mutable zone” (the negative gravity centre identified by mass-charge pattern analysis), which frequently accumulates multiple mutations. This leads to antigenic drift and instability, enabling the virus to evade pre-existing herd immunity. Analyzing and monitoring mass-charge changes may help predict the evolutionary trend of the viruses and the emergence of future variants in these regions where the viruses were collected, thereby informing the design and development of vaccines for the viruses analyzed and related strains. The second region is a “stable core” (positive gravity centre), a highly conserved region essential for viral function. Due to its conservation across strains, it may represent a promising target for developing universal vaccines and broad-spectrum antibodies capable of conferring protection against multiple variants simultaneously for the viruses analyzed and related strains. In summary, our analyses, with a predictive modelling algorithm for mass-charge patterns of HA5 protein sequences, provide a novel metric for viral evolution and evaluating the immune evasion potential, and offer a strategic framework for designing vaccines against the viruses analyzed and related strains. Full article
(This article belongs to the Special Issue Influenza Viruses in Wildlife 2026)
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21 pages, 953 KB  
Article
Historical Evolution of Unrelated Donor (URD) Recruitment of the Murcia Region Registry and Conditioning Social Events: Assessment of Quality, Effective URD Improvement, and Molecular HLA Characterization by NGS
by Manuel Muro-Pérez, María Rosa Moya-Quiles, Carmen Botella, José Antonio Galián, Marina Fernández-González, Rosana González-López, María José Alegría, Alicia Hita, Helios Martínez-Banaclocha, Javier Muro, Isabel Legaz and Manuel Muro
Int. J. Mol. Sci. 2026, 27(18), 8218; https://doi.org/10.3390/ijms27188218 - 15 Sep 2026
Abstract
The Murcia Region unrelated donor (URD) registry was established in 1992 as part of the Spanish Bone Marrow Donor Registry (REDMO). This study aimed to comprehensively characterize the long-term evolution of URD recruitment, human leukocyte antigen (HLA) genetic diversity, allele and haplotype frequencies, [...] Read more.
The Murcia Region unrelated donor (URD) registry was established in 1992 as part of the Spanish Bone Marrow Donor Registry (REDMO). This study aimed to comprehensively characterize the long-term evolution of URD recruitment, human leukocyte antigen (HLA) genetic diversity, allele and haplotype frequencies, and the spectrum of novel HLA alleles detected over the 34 years from 1992 to 2025. Recruitment trends, URD demographic characteristics, HLA allele and haplotype frequencies, and newly detected HLA alleles were analyzed retrospectively. HLA typing was performed using serological methods (1992–1996); PCR-SSO, PCR-SSP, and PCR-SSO Luminex (1997–2018); sequence-based typing (SBT, 2018–2021); and next-generation sequencing (NGS, 2021–2025). NGS was used to analyze a subset of 650 URDs to determine high-resolution HLA allele frequencies, Hardy–Weinberg equilibrium, expected heterozygosity, and extended HLA haplotypes. Newly detected HLA alleles were further characterized by the affected HLA locus and the localization of sequence variants within exons, introns, and the 3′-untranslated region (3′UTR). Between 1992 and 2025, 33.271 URDs were recruited, of whom 27.107 remained active in REDMO at the time of analysis. URD recruitment increased substantially following the implementation of the Spanish National Bone Marrow Plan in 2012 and reached a historical high in 2017. Additional recruitment peaks were associated with major regional public awareness campaigns. High-resolution HLA analysis of the NGS cohort demonstrated extensive immunogenetic diversity across all analyzed HLA loci, with a mean expected heterozygosity of 0.914. Ten frequent extended HLA haplotypes were identified, the most prevalent being HLA-A*29:02-C*16:01-B*44:03-DRB1*07:01-DQB1*02:02. Thirty-nine novel HLA alleles were characterized, exhibiting heterogeneous distributions among HLA loci and across coding and non-coding genomic regions. Exonic variants were predominantly detected in HLA-C, whereas intronic variants were mainly observed in HLA-C, HLA-DQB1, and HLA-A. This study integrates 34 years of URD recruitment with high-resolution immunogenetic characterization of the Murcia Region URD registry, providing new insights into the evolution of donor recruitment, HLA diversity, and the discovery of novel HLA alleles. The implementation of NGS enabled precise molecular characterization of HLA diversity and substantially expanded the detection and characterization of novel HLA alleles. Together, these findings provide a robust immunogenetic framework for the Murcia URD population, supporting donor recruitment strategies, optimization of URD searches, registry management, and future research in population genetics and hematopoietic stem cell transplantation. Full article
(This article belongs to the Special Issue Next Generation Sequencing in Human Diseases)
21 pages, 2322 KB  
Article
Light Regime and Exposure Duration Shape Essential Oil and Biochemical Responses in Rosemary (Salvia rosmarinus Spenn.)
by Mahdi Bikdeloo, Hamid Reza Roosta, Mohammad Javad Kalbali and Nazim S. Gruda
Horticulturae 2026, 12(9), 1164; https://doi.org/10.3390/horticulturae12091164 - 15 Sep 2026
Abstract
The spectral composition and duration of light exposure can influence plant growth, secondary metabolism, and essential oil composition in medicinal and aromatic plants. Here, we evaluated the effects of lighting regime and exposure duration on the biochemical traits and essential oil composition of [...] Read more.
The spectral composition and duration of light exposure can influence plant growth, secondary metabolism, and essential oil composition in medicinal and aromatic plants. Here, we evaluated the effects of lighting regime and exposure duration on the biochemical traits and essential oil composition of rosemary (Salvia rosmarinus Spenn.) under controlled conditions. Plants were exposed to white, blue, red, red/blue LED, or natural sunlight for 2, 3, or 4 weeks. The artificial light treatments were maintained at 200 ± 10 μmol m−2 s−1 PPFD, whereas the sunlight treatment was not PPFD-matched and therefore served as a greenhouse reference rather than a spectrum-matched control. Four biological replicates were used for each treatment. Chlorophyll, carotenoids, soluble sugars, total phenolics and flavonoids, DPPH radical scavenging activity, and essential oil composition were assessed. Essential oils were analyzed by gas chromatography–mass spectrometry (GC-MS). Lighting regime and exposure duration significantly affected several biochemical traits, whereas total phenolic content was not significantly affected by lighting regime. Red/blue LED treatment was associated with the highest mean values of total chlorophyll, carotenoids, total flavonoids, soluble sugars, and DPPH radical scavenging activity, although statistical significance varied among traits. Approximately 37 volatile compounds were identified across the treatments. The major constituents included α-pinene, 1,8-cineole, camphor, verbenone, borneol, bornyl acetate, and camphene and their relative abundances varied among lighting regimes and exposure durations. Principal component analysis (PCA) described differences in multivariate essential oil profiles among treatment combinations, while correlation analysis revealed associations among the relative abundances of volatile constituents. The highest essential oil yield was obtained under blue light at week 2 (1.53 ± 0.02% dry weight), whereas red/blue lighting at week 3 was associated with favorable responses in several biochemical traits. Thus, no single lighting regime and exposure duration was optimal for all measured traits. These findings indicate that lighting regime and exposure duration may be useful factors for modulating specific biochemical and essential oil characteristics of rosemary under controlled environment conditions. Full article
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15 pages, 1231 KB  
Article
Antibiotic Escalation Following Rapid Multiplex PCR Pneumonia Panel Testing in Intensive Care Patients with Severe Pneumonia: A Retrospective Cohort Study
by Soo Kyun Jung, Keum Ju Choi and Eun Jin Kim
Antibiotics 2026, 15(9), 903; https://doi.org/10.3390/antibiotics15090903 - 14 Sep 2026
Abstract
Background/Objectives: Severe community-acquired pneumonia (CAP) can be fatal and requires the rapid and appropriate administration of antibiotics. Rapid multiplex PCR pneumonia panels are widely used tools for antimicrobial de-escalation and stewardship; however, their role in driving antibiotic escalation in severe pneumonia requiring intensive [...] Read more.
Background/Objectives: Severe community-acquired pneumonia (CAP) can be fatal and requires the rapid and appropriate administration of antibiotics. Rapid multiplex PCR pneumonia panels are widely used tools for antimicrobial de-escalation and stewardship; however, their role in driving antibiotic escalation in severe pneumonia requiring intensive care is less well characterized. Methods: We retrospectively analyzed 288 adults with severe CAP who were admitted to the intensive care unit (ICU) of a tertiary hospital and underwent lower-respiratory BioFire FilmArray Pneumonia Panel (BFPP) testing between April 2023 and September 2024. The primary outcome was antibiotic escalation, defined as addition of an agent or a change to broader-spectrum therapy after the BFPP result, and its associated factors. Secondary outcomes were in-hospital mortality, hospital and ICU length of stay (LOS), and ventilator duration according to the antibiotic escalation. Results: Patients were elderly (median 72 years old; 60.8% male) and critically ill (median SOFA 8; median APACHE-II 19; shock 49.0%; mechanical ventilation 56.9%). The panel was positive in 66.3% of cases, and results were obtained with a median turnaround time of 2 h versus 67 h for sputum culture. After the panel, antibiotics were escalated in 34.0% of cases, de-escalated in 2.8%, discontinued in 0.7%, and unchanged in 62.5%. Escalation was independently associated with resistance gene detection (adjusted odds ratio [aOR] 3.15, 95% CI 1.71–5.82), panel positivity (aOR 1.97, 95% CI 1.02–3.80), and SOFA score (aOR 1.10 per point, 95% CI 1.01–1.19). Thirty-day mortality, in-hospital mortality, hospital LOS, ICU LOS, and ventilator duration did not differ between escalation and non-escalation groups. Conclusions: In severe CAP requiring intensive care and managed with a comparatively narrow initial empirical regimen, panel testing was predominantly followed by antibiotic escalation rather than de-escalation, particularly when resistance genes were detected. No statistically measurable difference in clinical outcomes was observed, but the study was not powered to exclude any clinically meaningful benefit or harm of escalation. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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33 pages, 45594 KB  
Article
Integrated Multisource Radar and Geophysical Data for Depth-Resolved Structural Analysis and Mineral Prospectivity: DEM, NISAR, BIOMASS, and Aeromagnetic Data
by Hala F. Ali, Changcheng Wang, Faris A. Abanumay and Sobhi M. Ghoneim
Minerals 2026, 16(9), 939; https://doi.org/10.3390/min16090939 - 14 Sep 2026
Abstract
This study introduces a multisource, multiscale approach to delineate structural lineaments and assess mineralization controls in Wadi El-Markh, Central Eastern Desert, Egypt. Four datasets (ALOS PALSAR DEM, NISAR L-band SAR, BIOMASS P-band SAR, and aeromagnetic data) were processed using tailored workflows to extract [...] Read more.
This study introduces a multisource, multiscale approach to delineate structural lineaments and assess mineralization controls in Wadi El-Markh, Central Eastern Desert, Egypt. Four datasets (ALOS PALSAR DEM, NISAR L-band SAR, BIOMASS P-band SAR, and aeromagnetic data) were processed using tailored workflows to extract lineaments at complementary depths, from the surface to deep crustal levels. The AP-DEM workflow employed multi-azimuth hill-shading and directional Prewitt filtering. NISAR data were speckle-denoised before directional filtering of the HH and HV polarizations. BIOMASS data underwent polarimetric decomposition followed by directional filtering. Aeromagnetic data were reduced to the pole, analyzed using power-spectrum for depth estimation and regional–residual separation, and then processed using a CET grid-analysis workflow for lineaments extraction and generation of a Contact Occurrence Density (COD) map. Directional analysis revealed sensor-dependent biases: NISAR HH favored an E-W trend, whereas HV yielded a more isotropic distribution; BIOMASS surface scattering highlighted E-W and N-S trends, whereas volume scattering emphasized NW-SE and NE-SW trends. Aeromagnetic data identified both shallow- and deep-seated structures, with a dominant NW-SE trend. GIS-based fuzzy overlay produced a consensus structural complexity map. Validation against 15 known mining sites showed spatial coincidence rates ranging from 60% (AP-DEM and NISAR HH) to 86.7% (BIOMASS volume scattering and fuzzy overlay) for mining sites falling within high-structural-complexity zones. The results establish a reliable framework for identifying structurally controlled mineralization targets in arid terrains. Full article
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25 pages, 1910 KB  
Article
Association Between Toe Walking and Repetitive Behaviors in Children with Autism Spectrum Disorder: A Cross-Sectional Phenotypic Analysis
by Martina Gnazzo, Giuditta Bargiacchi, Beatrice Gallai, Giulia Spoto, Gabriella Di Rosa, Valentina Baldini, Lucia Parisi, Agata Maltese, Michele Roccella, Eva Germanò, Maria Esposito and Marco Carotenuto
Medicina 2026, 62(9), 1764; https://doi.org/10.3390/medicina62091764 - 13 Sep 2026
Abstract
Background and Objectives: Toe walking (TW) is frequently observed in children with Autism Spectrum Disorder (ASD), yet its clinical significance remains incompletely understood. While previous studies have linked TW to ASD severity and multisystem involvement, its relationship with the behavioral phenotype of [...] Read more.
Background and Objectives: Toe walking (TW) is frequently observed in children with Autism Spectrum Disorder (ASD), yet its clinical significance remains incompletely understood. While previous studies have linked TW to ASD severity and multisystem involvement, its relationship with the behavioral phenotype of repetitive behaviors has not been systematically explored. Materials and Methods: This study analyzed a cohort of 289 children with ASD who underwent comprehensive clinical assessment, including motor evaluation, sleep assessment using the Sleep Disturbance Scale for Children (SDSC), feeding behavior using the Brief Autism Mealtime Behavior Inventory (BAMBI), and detailed behavioral characterization through the Repetitive Behavior Scale-Revised (RBS-R) at the item level. Statistical analyses included non-parametric group comparisons, Spearman correlation analyses, and multivariable regression models. Results: TW was observed in 27.3% of participants. Children with TW showed significantly higher scores in stereotyped behaviors (7.71 ± 2.09 vs. 4.26 ± 2.06, r = 0.756, pFDR < 0.001), ritualistic/sameness behaviors (11.78 ± 3.21 vs. 7.05 ± 3.03, r = 0.709, pFDR < 0.001), and total RBS-R scores (25.52 ± 4.51 vs. 15.88 ± 4.64, r = 0.867, pFDR < 0.001). Correlation analyses revealed a strong association between TW and stereotyped behaviors (ρ = 0.588, p < 0.001) and a moderate association with ritualistic/sameness behaviors (ρ = 0.549, p < 0.001). RBS-R total scores were also correlated with sleep disturbances (ρ = 0.532, p < 0.001). In the multivariate linear model, TW was associated with an adjusted mean increase of 7.77 points in the RBS-R Total Score (B = 7.771, 95% CI 6.603–8.939, p < 0.001, β = 0.551). In the multivariate logistic model, the combined Ritualistic/Sameness behavior domain independently predicted the presence of TW (OR = 1.549, 95% CI 1.366–1.757, p < 0.001). Conclusions: In children with ASD, TW was associated with specific domains of repetitive behavior, particularly stereotyped and ritualistic/sameness patterns. These cross-sectional findings suggest a phenotypic association between motor and behavioral features, without establishing specificity, causality, or a shared underlying mechanism. This multidimensional perspective may support future studies investigating the clinical and biological correlates of TW in ASD. Full article
(This article belongs to the Section Pediatrics)
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18 pages, 8234 KB  
Article
Symmetric Chaotic Behavior in 4D Variable-Order Fractional Systems Under Liouville–Caputo Operators
by Mohamed Elbadri, Nidal E. Taha, Walid Hdidi, Hamdy M. Barakat and Mohamed A. Abdoon
Symmetry 2026, 18(9), 1525; https://doi.org/10.3390/sym18091525 - 11 Sep 2026
Viewed by 71
Abstract
In this paper, a novel four-dimensional variable-order fractional chaotic system is presented through the use of the Liouville–Caputo variable-order fractional derivative to represent the time-varying memory properties of nonlinear dynamical behaviors. Special attention will be paid to the chaotic behavior of the proposed [...] Read more.
In this paper, a novel four-dimensional variable-order fractional chaotic system is presented through the use of the Liouville–Caputo variable-order fractional derivative to represent the time-varying memory properties of nonlinear dynamical behaviors. Special attention will be paid to the chaotic behavior of the proposed system and their chaotic attractors depending on different memory effects. For calculation of the solutions of such systems, a numerical approach for the variable-order fractional systems is used, and three memory functions of the variable order are considered to investigate their effect on the behavior of the system. The obtained behavior will be analyzed by means of time responses, phase portraits, bifurcation diagrams, the spectrum of the Lyapunov exponents, and the Kaplan–Yorke fractal dimension. From the numerical simulations, it is shown that different fractional orders lead to completely different dynamical regimes and the appearance of symmetric chaotic attractors with different geometrical and topological structures while the physical parameters of the system are kept the same. These results highlight the important role of time-varying memory in controlling and generating chaotic structures in fractional-order nonlinear systems. Full article
(This article belongs to the Special Issue Symmetries in Differential Equations and Application—3rd Edition)
31 pages, 5062 KB  
Review
Research Progress on Bidirectional Regulation of the Microbiota–Gut–Brain Axis in Autism Spectrum Disorder Based on the Immune–Metabolic–Endocrine Interactive Network
by Weiao Kong, Haoke Qiu, Yuhang Jiang, Huanhuan Ge, Wanyi Wu, Lefan Huang, Lisheng Chu and Lijun Ge
Biomolecules 2026, 16(9), 1321; https://doi.org/10.3390/biom16091321 - 11 Sep 2026
Viewed by 77
Abstract
Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder characterized by core features of social communication deficits and high prevalence of gastrointestinal comorbidities. With its continuously rising global prevalence, current therapeutic modalities remain unable to target and ameliorate the core symptoms of [...] Read more.
Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder characterized by core features of social communication deficits and high prevalence of gastrointestinal comorbidities. With its continuously rising global prevalence, current therapeutic modalities remain unable to target and ameliorate the core symptoms of ASD. The microbiota–gut–brain axis (MGBA), a critical pathway mediating crosstalk between the gut microbiota and the brain, has been extensively documented to be deeply involved in the pathological progression of ASD in recent years. However, prior studies have predominantly focused on the unidirectional regulation of the brain by gut microbiota, lacking an integrated account of the bidirectional regulation across immune, metabolic, and endocrine systems. Centered on the immune–metabolic–endocrine interactive network, this review systematically delineates the bidirectional regulatory mechanisms of the MGBA in ASD by integrating recent evidence from microbiota sequencing, animal models, and clinical intervention studies, with the aim of clarifying the bidirectional causal controversy between intestinal microecological disturbance and ASD behavioral abnormalities. This review proposes that in children with ASD, decreased abundance of beneficial intestinal bacteria and disrupted metabolic profiles of short-chain fatty acids synergistically impair intestinal barrier integrity, triggering peripheral chronic inflammation that further drives excessive microglial activation-mediated central neuroinflammation. Subsequently, disturbances in the homeostasis of multiple neurotransmitters including 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), histamine, and dopamine occur via the vagus nerve and hypothalamic–pituitary–adrenal (HPA) axis, ultimately driving ASD behavioral abnormalities. Conversely, chronic stress and behavioral characteristics associated with ASD reshape the intestinal microecology through neuroendocrine pathways, forming a vicious cycle of “microbiota dysbiosis—immune inflammation—HPA axis hyperactivity—further intestinal microecological imbalance”. This review summarizes the therapeutic efficacy and translational bottlenecks of three types of microecological interventions: fecal microbiota transplantation (FMT), probiotics, and ketogenic diet, and analyzes the current limitations in the field, including pronounced population heterogeneity, unclear cross-talk mechanisms among multiple pathways, and the scarcity of large-sample clinical evidence. Collectively, this review preliminarily elucidates the complete multi-system interactive framework of MGBA regulation in ASD, providing theoretical support for mechanistic research and gut-targeted individualized interventions for ASD. Full article
(This article belongs to the Special Issue Microbiome–Gut–Brain Axis in Neurodevelopmental Disorders)
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12 pages, 1208 KB  
Brief Report
Targeted 3.34-Million CpG Site Sequencing Reveals Preliminary Cord Blood Epigenetic Alterations of Autism Spectrum Disorder: A Pilot Study Highlighting the PCDHA1PCDHA8 Cluster
by Marina Armas-González, Nieves Luisa González-González, Enrique González-Dávila, Olivia Orribo-Morales, José Ramón Castro-Conde, Candelaria González-Campos, Carlos Flores, José Miguel Lorenzo-Salazar, Rafaela González-Montelongo, Adrián Muñoz-Barrera, Erika Padrón-Pérez, Laura Tascón-Padrón and María Núñez Catalán
Int. J. Mol. Sci. 2026, 27(18), 8038; https://doi.org/10.3390/ijms27188038 - 9 Sep 2026
Viewed by 135
Abstract
Rising reported Autism Spectrum Disorder (ASD) prevalence underscores the need to explore early perinatal biological markers. To conduct an exploratory pilot investigation of cord blood DNA methylation patterns as potential early epigenetic candidate loci associated with ASD in infants born to mothers with [...] Read more.
Rising reported Autism Spectrum Disorder (ASD) prevalence underscores the need to explore early perinatal biological markers. To conduct an exploratory pilot investigation of cord blood DNA methylation patterns as potential early epigenetic candidate loci associated with ASD in infants born to mothers with obesity and gestational diabetes. This prospective pilot study analyzed 14 mother-infant pairs comprising infants born to mothers with obesity and gestational diabetes later diagnosed with ASD (n = 2); healthy infants born to mothers with obesity and diabetes (IODM, n = 6); and healthy controls (IHM, n = 6). Targeted methyl-capture sequencing (covering 3.34 million CpG sites) identified differentially methylated region (DMR)-associated genes. Neurodevelopment was evaluated at 24–26 months using Bayley-III scales. ASD infants showed lower Bayley-III scores across all domains. In this small cohort (n = 2 ASD cases), we identified 249 DMR-associated genes common to both ASD vs. IHM and ASD vs. IODM comparisons, representing preliminary candidate loci. Enrichment analysis identified homophilic cell–cell adhesion as the most significant pathway (fold enrichment = 8.28; FDR = 6.31 × 10−6), driven by the PCDH1PCDHA8 cluster, alongside morphogenesis in neuron differentiation (fold enrichment = 3.45; FDR = 2.08 × 10−2). Although prospective validation in larger independent cohorts is required, these pilot results suggest that cord blood PCDHA1PCDHA8 cluster methylation alterations represent preliminary candidate loci for hypothesis generation and future biomarker evaluation, regardless of maternal metabolic status. Full article
(This article belongs to the Special Issue Advances in Epigenetics of Mental Disorders)
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23 pages, 699 KB  
Review
Metacognition and Self-Disturbances in Schizophrenia: Implications for Psychological and Neurocognitive Therapy
by Natasza Orlov, Izabela Sarzyńska, Jolanta Góral-Półrola, Patrycja Leśnicka, Oliwia Bartkowska, Szymon Stańczyk, Ewa Siwiec, Artur Ziółkowski and Marta Kopańska
Brain Sci. 2026, 16(9), 956; https://doi.org/10.3390/brainsci16090956 - 9 Sep 2026
Viewed by 215
Abstract
Background/Objectives: Schizophrenia is a complex psychiatric disorder characterized by positive, negative, and cognitive symptoms, as well as disturbances of the self and metacognitive dysfunction. Increasing evidence suggests that these dimensions contribute substantially to psychosocial functioning and recovery, yet they are often investigated [...] Read more.
Background/Objectives: Schizophrenia is a complex psychiatric disorder characterized by positive, negative, and cognitive symptoms, as well as disturbances of the self and metacognitive dysfunction. Increasing evidence suggests that these dimensions contribute substantially to psychosocial functioning and recovery, yet they are often investigated separately. This narrative review aims to integrate current knowledge on self-disturbances and metacognition in schizophrenia and discuss their relevance for contemporary therapeutic approaches. This review proposes an integrative conceptual framework positioning disturbances of the minimal self and metacognitive dysfunction as complementary dimensions that may contribute to schizophrenia psychopathology and may have relevance for recovery-oriented interventions. Methods: A narrative review of the peer-reviewed literature was conducted. Classical theoretical papers, recent empirical studies, systematic reviews, and meta-analyses addressing self-disturbances, metacognition, and therapeutic interventions in schizophrenia spectrum disorders were analyzed. Results: Current evidence indicates that disturbances of the minimal self and metacognitive dysfunction may represent complementary and interacting dimensions of schizophrenia psychopathology. Self-disturbances affect the subjective sense of identity, agency, and self-presence, whereas metacognitive deficits impair the integration of information about oneself and others into coherent mental representations. These impairments are associated with poorer psychosocial functioning, reduced quality of life, and limited recovery. Interventions targeting metacognitive functioning, including Metacognitive Reflection and Insight Therapy, Metacognitive Training, and cognitive remediation, have shown promising effects on functional outcomes and recovery. Conclusions: Integrating phenomenological concepts of self-disturbance with contemporary metacognitive models may provide a broader understanding of schizophrenia than symptom-based approaches alone. In clinical practice, instruments such as the Examination of Anomalous Self-Experience (EASE) and Metacognition Assessment Scale–Abbreviated (MAS-A) may complement standard assessment by providing information about anomalous self-experiences, insight, and psychosocial functioning. However, the additional diagnostic value of combining these assessments with established clinical procedures has not yet been clearly demonstrated. They should therefore be regarded as supplementary tools that may inform clinical formulation and individualized, recovery-oriented treatment planning rather than as standalone diagnostic measures. Full article
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17 pages, 1071 KB  
Article
Compartment-Specific Immune, Endothelial, and Fibrotic Programs in Diabetic Retinopathy: An Integrative Multi-Cohort Transcriptomic Study
by Ece Celik, Buket Yilmaz Bulbul, Burak Andac and Mehmet Celik
Biology 2026, 15(18), 1581; https://doi.org/10.3390/biology15181581 - 9 Sep 2026
Viewed by 173
Abstract
Proliferative diabetic retinopathy (PDR) is molecularly heterogeneous, but it is unclear whether immune-rich and endothelial-rich transcriptional patterns recur across retinal compartments. We integrated five public human transcriptomic datasets and analyzed PhysioNet CDED separately as the exploratory clinical context. GSE307925 served as the discovery [...] Read more.
Proliferative diabetic retinopathy (PDR) is molecularly heterogeneous, but it is unclear whether immune-rich and endothelial-rich transcriptional patterns recur across retinal compartments. We integrated five public human transcriptomic datasets and analyzed PhysioNet CDED separately as the exploratory clinical context. GSE307925 served as the discovery cohort; GSE245561 and GSE165784 provided independent single-cell cross-cohort evaluation; GSE94019 provided CD31-enriched endothelial evaluation; and GSE160306 provided whole-retina disease-spectrum contextualization. In GSE307925, CD31-low and CD31-high samples separated strongly (PC1 61.5%; exact permutation p = 0.0013), with separation retained in all 12 leave-one-out analyses and under TMM normalization. In the two single-cell cohorts, the discovery-derived CD31-low signature localized to myeloid cells and the CD31-high signature to endothelial cells in all nine PDR donors (exact sign-test p = 0.00195 for each); the fibrotic/ECM-remodeling core localized to stromal/pericyte cells in all nine donors. In GSE94019, the fibrotic/ECM-remodeling program was increased in PDR (p = 0.0028; q = 0.0084) and remained associated with PDR after adjustment for an independent pericyte-lineage score (β = 1.473, 95% CI 0.758–2.189; p < 0.001). In GSE160306, the discovery-derived CD31-low program showed a nominal association with advanced DR/DME (β = 0.306, 95% CI 0.026–0.585; p = 0.032; q = 0.085). These findings support compartment-dependent molecular enrichment rather than fixed binary patient subtypes. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Retina Development and Degeneration)
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30 pages, 41013 KB  
Article
A Robust Sequential Acoustic Sensing Framework for Shallow-Water Meteorological Monitoring in IoUT
by Xuefeng Liu, Rui Tang, Qindong Sun and Sichen Zou
IoT 2026, 7(3), 76; https://doi.org/10.3390/iot7030076 - 8 Sep 2026
Viewed by 114
Abstract
Passive acoustic monitoring of ocean surface wind speed and rainfall faces severe degradation in shallow waters due to multipath propagation and non-meteorological noise interference. To address these challenges within the Internet of Underwater Things (IoUT), this study proposes a sequential acoustic sensing framework [...] Read more.
Passive acoustic monitoring of ocean surface wind speed and rainfall faces severe degradation in shallow waters due to multipath propagation and non-meteorological noise interference. To address these challenges within the Internet of Underwater Things (IoUT), this study proposes a sequential acoustic sensing framework for vertical linear array (VLA) nodes to enhance meteorological inversion accuracy. First, an incoherent averaging method is introduced to mitigate acoustic field fluctuations by accumulating vertical spatial information across the sensing channels. Second, the Correlation Matrix of Energy Spectrum (CMES) and the higher-order bispectrum are analyzed to decouple cross-frequency characteristics and identify the dominant frequency bands of the acoustic sources. On this basis, a Principal Component Analysis (PCA)-assisted bispectral entropy method is implemented after spectral reconstruction, enabling accurate environmental scenario classification and interference suppression at the sensor level. Experimental validation using ambient noise data recorded by an IoUT VLA node in the South China Sea demonstrates that the proposed framework effectively stabilizes the acoustic field, reducing continuous spectrum fluctuations by 7–8 dB. Consequently, the applicability and robustness of empirical wind speed inversion models are significantly improved, providing a resilient and high-fidelity sensing solution for interference-prone shallow sea IoUT applications. Full article
(This article belongs to the Special Issue Internet of Underwater Things (IoUT))
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22 pages, 1175 KB  
Article
Allostatic and Circadian Drives in Patients with Bipolar Disorder in Depressive Episodes or with Post-Traumatic Stress Disorder Versus Healthy Controls: Neuroendocrine Comparison Through Cortisol and 6-Sulfatoxymelatonin Overnight Urine Excretion
by Valerio Dell’Oste, Matteo Gambini, Virginia Pedrinelli, Berenice Rimoldi, Lionella Palego, Gino Giannaccini, Laura Betti and Claudia Carmassi
Int. J. Mol. Sci. 2026, 27(18), 7993; https://doi.org/10.3390/ijms27187993 - 8 Sep 2026
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Abstract
Neuroendocrine and circadian dysfunctions are thought to underlie bipolar disorder (BD) and could be implemented as markers of complex symptom conditions, including the presence of Post-Traumatic Stress Disorder (PTSD) comorbidity. The primary objective of this study was to investigate neuroendocrine profiles in different [...] Read more.
Neuroendocrine and circadian dysfunctions are thought to underlie bipolar disorder (BD) and could be implemented as markers of complex symptom conditions, including the presence of Post-Traumatic Stress Disorder (PTSD) comorbidity. The primary objective of this study was to investigate neuroendocrine profiles in different BD phenotypes through the measure of nocturnal urinary levels of Cortisol (stress-response factor) and 6-sulfatoxymelatonin (aMT6s; light/dark signal) in euthymic BD patients diagnosed with PTSD (PTSD group) or with major depressive episodes without trauma symptoms (DEP group). Both groups were compared against healthy controls (CTL). Nighttime urinary levels of aMT6s and Cortisol were analyzed by competitive ELISA, with ensuing values normalized for specific gravity. The Cortisol-to-aMT6s ratio (Cort/aMT6s) was calculated as an exploratory proxy for the homeostatic balance between HPA-mediated catabolic/coping activities and Melatonin-related reparative functions. Clinical severity and psychosocial activities were assessed by using mood HAM-D, YMRS, trauma IES-R and functioning WSAS scales. Results revealed distinct biological patterns: PTSD subjects showed increased nocturnal Cortisol compared to DEP and CTL groups, whereas DEP patients exhibited lower aMT6s levels and an elevated Cort/aMT6s ratio. Cortisol and aMT6s correlated positively in PTSD, while the ratio correlated positively with Cortisol solely in controls. Clinically, Cortisol correlated positively with IES-R and functional impairment (WSAS), whereas aMT6s correlated negatively with HAM-D and YMRS scores. Present findings suggest a possible neuroendocrine divergence in BD patients with depression versus PTSD: nocturnal Melatonin deficiency may be associated with depression, while HPA-axis hyperactivity and altered crosstalk between the two systems may characterize PTSD comorbidity, with the Cort/aMT6s ratio as a potential index of impaired daily functioning. These results could be promising for the use of biomarkers linked to allostatic and circadian responses within the BD spectrum. Full article
(This article belongs to the Special Issue Molecular Biomarkers in Mood Disorders)
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16 pages, 5458 KB  
Article
Response Characteristics of Karst Water Level to Precipitation and Hydrological Circulation Patterns in the Jinan Spring Basin, Northern China
by Dalu Yu, Huan Qi, Qingyu Xu, Caiping Hu, Guomeng Guan, Yan Li and Liting Xing
Water 2026, 18(18), 2224; https://doi.org/10.3390/w18182224 - 8 Sep 2026
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Abstract
Karst groundwater systems are characterized by highly heterogeneous flow networks, resulting in complex responses of groundwater levels to precipitation variability. The Jinan Spring Basin, one of the most representative karst spring systems in northern China, has experienced substantial changes in spring discharge due [...] Read more.
Karst groundwater systems are characterized by highly heterogeneous flow networks, resulting in complex responses of groundwater levels to precipitation variability. The Jinan Spring Basin, one of the most representative karst spring systems in northern China, has experienced substantial changes in spring discharge due to variations in precipitation, groundwater exploitation, and hydrogeological conditions. However, the temporal scales at which precipitation signals control groundwater-level fluctuations and the mechanisms governing their transmission within the karst aquifer remain poorly understood. In this study, daily precipitation data from 30 meteorological stations and groundwater-level records at Baotu Spring during 2016–2018 were analyzed using global wavelet spectrum (GWS) and wavelet transform coherence (WTC) approaches. The dominant precipitation cycles, scale-dependent precipitation–groundwater relationships, and phase-derived groundwater response lags were quantified to reveal the hydrological response characteristics of the Jinan karst system. Three prominent precipitation periods were identified at 17.37, 29.22, and 330.57 days. Groundwater responses presented clear temporal-scale dependence, with short-period signals showing rapid but localized responses, while intermediate and long-period signals demonstrated stronger and more persistent coherence. The percentage of significant coherence area (PASC) increased from 23.50% at the 0–17.37 day scale to 64.28% at the 29.22–330.57 day scale, indicating that accumulated precipitation rather than individual rainfall events exerts the dominant control on groundwater-level variations. The spatial distribution of response lags revealed that rapid responses (17.37 days) mainly occurred in the southern recharge areas, reflecting preferential recharge through well-developed karst conduits. Intermediate responses (29.22 days) showed a progressive increase in lag time from south to north, indicating the influence of regional groundwater flow and aquifer storage. Long-period responses (330.57 days) were locally enhanced near major faults, suggesting structural controls on deeper groundwater circulation. This study reveals that precipitation signals in the Jinan Spring Basin are transmitted through multiple groundwater circulation pathways with distinct temporal characteristics. The identified multi-scale response patterns provide new insights into the internal structure and hydrological functioning of karst aquifers and offer scientific support for sustainable management of spring water resources. Full article
(This article belongs to the Special Issue Advances in Hydrochemistry and Hydrogeology)
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15 pages, 9224 KB  
Article
Global Research Trends in Pediatric Lower Urinary Tract Dysfunction: A Bibliometric Analysis (1945–2026)
by Emine Baran
Healthcare 2026, 14(17), 2883; https://doi.org/10.3390/healthcare14172883 - 7 Sep 2026
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Abstract
Background/Objectives: Pediatric lower urinary tract symptoms and bladder–bowel dysfunction are common and clinically related problems recognized within the ICCS framework, but no bibliometric study has previously mapped this broad field comprehensively. This study aimed to map the global structure, thematic evolution, and emerging [...] Read more.
Background/Objectives: Pediatric lower urinary tract symptoms and bladder–bowel dysfunction are common and clinically related problems recognized within the ICCS framework, but no bibliometric study has previously mapped this broad field comprehensively. This study aimed to map the global structure, thematic evolution, and emerging research trends in pediatric lower urinary tract dysfunction using bibliometric methods. Methods: A total of 3004 publications published between 1945 and May 2026 and retrieved from the Web of Science Core Collection were analyzed. Keyword co-occurrence networks, country co-authorship networks, and document citation networks were constructed using VOSviewer (version 1.6.20)). Results: Annual publication counts first exceeded 100 in 2013 and remained largely at or above this level thereafter, peaking at 135 in 2020, with a subsequent plateau. The USA (26.1%), Turkiye (10.5%), and the United Kingdom (6.5%) were the most productive countries. Harvard University led institutional output (n = 131). Keyword network analysis identified 15 clusters, the most coherent of which centered on enuresis pathophysiology/pharmacology, overactive bladder treatment, sleep medicine, and core urinary and bowel symptoms. Overlay visualization identified artificial intelligence (~2024), telemedicine (~2022), and autism spectrum disorder (~2021) as the most recent emerging research themes. Conclusions: This is the first bibliometric analysis to map global pediatric lower urinary tract dysfunction research across the broader field. Artificial intelligence, telemedicine, and autism spectrum disorder emerged as the most recent research themes, while substantial geographic gaps remained in sub-Saharan Africa and South Asia. Full article
(This article belongs to the Section Women’s and Children’s Health)
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