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18 pages, 704 KB  
Systematic Review
The Effectiveness of Life Skills-Based School Violence Prevention Programs in Secondary Education: A Systematic Review and Meta-Analysis
by Konstantina Trimmi, Theodoros Fouskas, Vasiliki Yotsidi, Tonia Vassilakou, Aikaterini Papatheochari, Vana Gkora and Kyriakoula Merakou
Children 2026, 13(9), 1128; https://doi.org/10.3390/children13091128 (registering DOI) - 23 Aug 2026
Abstract
Background: School violence is a major public health concern, with bullying alone affecting up to 50% of adolescents worldwide. Life skills-based programs have been proposed as a promising preventive approach, yet evidence for their effectiveness in secondary education remains limited. This systematic [...] Read more.
Background: School violence is a major public health concern, with bullying alone affecting up to 50% of adolescents worldwide. Life skills-based programs have been proposed as a promising preventive approach, yet evidence for their effectiveness in secondary education remains limited. This systematic review and meta-analysis aims to synthesize the existing evidence on the effectiveness of life skills-based violence prevention programs among adolescents aged 12–18. Methods: A systematic literature search was conducted across five databases (PubMed, Scopus, ERIC, CINAHL, and PsycInfo) in accordance with PRISMA 2020 guidelines (INPLASY202650168). Interventional studies published between 2005 and 2025 that targeted secondary school students were eligible. Risk of bias was assessed using the Cochrane RoB2 (for RCTs/cRCTs) and ROBINS-I tools. A three-level random-effects meta-analytic model with Robust Variance Estimation was employed to pool Hedges’ g effect sizes. Results: Nineteen studies met the eligibility criteria, with 18 contributing 56 effect sizes to the meta-analysis. The pooled effect size was statistically significant (g = −0.2652, 95% CI [−0.4879, −0.0425], p = 0.0196), indicating an overall small reduction in violent behaviors. However, a high degree of variation in effects was observed across studies (Q(55) = 2263.58, p < 0.001; I2 = 99.23%). None of the examined moderators—including outcome type, study design, and risk-of-bias tier—significantly explained this heterogeneity. The sensitivity analysis, excluding one highly influential study, yielded a smaller pooled effect (g = −0.1422, 95% CI [−0.2246, −0.00598]) while maintaining high heterogeneity (I2 = 92.82%). Conclusions: Although life skills-based programs demonstrate a statistically significant overall average effect in reducing school violence among adolescents, this finding must be interpreted with extreme caution given the high degree of variation in effect sizes across contexts and the fact that prediction intervals span across zero. Because moderator analyses revealed no significant differences across intervention types, study designs, or outcome categories, no specific program type can be identified as consistently more effective. Future primary research must prioritize prospectively registered trials with multi-informant assessments to establish true intervention effectiveness. Full article
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21 pages, 3930 KB  
Review
Beyond Pathogens: Modulating the Commensal Microbiota to Reshape Immunity for Respiratory Disease Intervention
by Yang Yang, Jinglei Cui, Xinyue Dong, Yunhan Huang, Jiayao An, Tianyi Cui, Xiangqin Ou, Tao Liu, Xiumei Gao, Han Zhang and Xin Zhao
Pathogens 2026, 15(9), 883; https://doi.org/10.3390/pathogens15090883 (registering DOI) - 23 Aug 2026
Abstract
The respiratory tract microbiota has been recognized as a niche with complex and diverse microbial communities, the composition and function of which in the state of health and disease have become increasingly clear. Relevant literature on respiratory tract microbiota and immune and respiratory [...] Read more.
The respiratory tract microbiota has been recognized as a niche with complex and diverse microbial communities, the composition and function of which in the state of health and disease have become increasingly clear. Relevant literature on respiratory tract microbiota and immune and respiratory disease published in PubMed, SpringerLink and Web of Science up to June 2026 was narratively reviewed. This review aims to elucidate the interactions between the commensal microbiota of the respiratory tract and the host immune system and reveal how these interactions evolve from homeostasis to disease pathogenesis. We also analyze how dysbiosis can promote chronic airway inflammation by changing microbial metabolites, destroying the integrity of epithelial barrier, and activating abnormal immune and inflammatory pathways, thus playing a key driving role in chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis (CF), bronchiectasis and other diseases. Additionally, the potential and challenges of current treatment strategies based on microbiota regulation, such as herbal medicines and probiotics, in the prevention and treatment of respiratory diseases are discussed. This review provides a new perspective for revealing the etiology of respiratory diseases and lays a solid theoretical foundation for the development of microbial intervention therapy. Full article
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23 pages, 11636 KB  
Review
From FGFR3 Hyperactivation to Disease-Modifying Therapy in Pediatric Achondroplasia: Molecular Mechanisms, Clinical Evidence, and Emerging Treatments
by Rebecca Cristiana Șerban, Andreea Mitut-Veliscu, Alexandra Dumitra, Liana Marica, Cristina Popescu, Andrei Costache, Șerban Teona, Anca-Lelia Riza, Rodica Dirnu, Renata-Maria Varut and Ioana Streață
Children 2026, 13(8), 1121; https://doi.org/10.3390/children13081121 - 21 Aug 2026
Abstract
Background/Objectives: Achondroplasia is the most common genetic skeletal dysplasia associated with disproportionate short stature and is primarily caused by gain-of-function variants in the fibroblast growth factor receptor 3 (FGFR3) gene. Constitutive FGFR3 activation disrupts growth plate homeostasis and endochondral ossification through complex alterations [...] Read more.
Background/Objectives: Achondroplasia is the most common genetic skeletal dysplasia associated with disproportionate short stature and is primarily caused by gain-of-function variants in the fibroblast growth factor receptor 3 (FGFR3) gene. Constitutive FGFR3 activation disrupts growth plate homeostasis and endochondral ossification through complex alterations in chondrocyte proliferation, differentiation, hypertrophy, extracellular matrix organization, and intracellular signaling. The increasing understanding of these mechanisms has enabled the transition from exclusively supportive management toward disease-modifying and precision-based therapeutic strategies. This narrative review aimed to critically synthesize current evidence on the genetic basis, molecular pathogenesis, growth plate abnormalities, and current and emerging targeted therapies in achondroplasia. Methods: A narrative literature review was conducted using PubMed/MEDLINE, Scopus, and Web of Science Core Collection, with Google Scholar used as a supplementary source, together with manual screening of the reference lists of relevant original studies, clinical trials, reviews, consensus documents, and clinical guidelines. The principal literature search covered publications from January 2010 to March 2026, while selected seminal primary studies published before 2010 were included when necessary to document the original identification of pathogenic FGFR3 variants and foundational mechanisms of FGFR3-mediated growth plate regulation. Particular emphasis was placed on FGFR3 variants, receptor activation mechanisms, growth plate dysfunction, intracellular signaling pathways, vosoritide, C-type natriuretic peptide-based therapies, FGFR3 inhibitors, ligand–receptor blockade, drug repurposing, Wnt/β-catenin modulation, and gene-based therapeutic approaches. Results: Achondroplasia is characterized by marked molecular homogeneity, with the recurrent p.Gly380Arg substitution accounting for most cases. Mutant FGFR3 displays sustained activity through partial ligand independence, enhanced receptor dimerization and kinase activation, increased receptor stability, and reduced degradation. Excessive signaling through MAPK/ERK, STAT, PI3K/AKT, IHH/PTHrP, and related pathways impairs chondrocyte proliferation and hypertrophic differentiation, alters extracellular matrix turnover, disrupts primary cilium function, and reduces longitudinal bone growth. Vosoritide provides clinical proof that pharmacological modulation of FGFR3-related signaling can improve growth velocity. Additional therapeutic strategies under clinical or preclinical investigation include long-acting CNP analogues, selective FGFR inhibitors, decoy receptors, RNA aptamers, repurposed drugs, Wnt/DKK1 pathway modulation, and gene- or enhancer-targeted interventions. Conclusions: Achondroplasia is increasingly understood as a disorder of dysregulated growth plate signaling rather than solely a condition of reduced stature. Although vosoritide has established the feasibility of disease-modifying treatment, substantial uncertainty remains regarding final adult height, skeletal proportionality, cranio-spinal development, orthopedic outcomes, and long-term safety. Future progress will depend on mechanistically informed therapeutic combinations, improved biomarkers, advanced cellular and animal models, and long-term clinical and real-world evidence. Full article
(This article belongs to the Special Issue Advances in Pediatric Genetic Disorders)
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20 pages, 803 KB  
Review
Pregnancy After Breast Cancer: A Narrative Review of Oncologic Safety, Obstetric and Neonatal Outcomes, and Reproductive Survivorship
by Vahideh MoghaddamHosseini and Afshin Zand
Cancers 2026, 18(16), 2715; https://doi.org/10.3390/cancers18162715 - 21 Aug 2026
Abstract
Background: Survival after early breast cancer has improved to the point where reproductive health is no longer a peripheral concern in young survivors but a routine one. This review synthesizes current evidence on oncologic safety, obstetric and neonatal outcomes, fertility preservation, breastfeeding, and [...] Read more.
Background: Survival after early breast cancer has improved to the point where reproductive health is no longer a peripheral concern in young survivors but a routine one. This review synthesizes current evidence on oncologic safety, obstetric and neonatal outcomes, fertility preservation, breastfeeding, and psychosocial survivorship to develop a counseling framework that clinicians can apply in practice. Methods: This narrative review was informed by a structured literature search of PubMed/MEDLINE, Embase, and the Cochrane Library covering studies published from January 2000 to July 2026, with greater analytic weight given to studies published from 2010 onward to ensure the synthesis reflects contemporary treatment standards. Relevant evidence was identified and narratively synthesized according to the clinical and reproductive aspects of pregnancy after breast cancer. No formal risk-of-bias assessment or quantitative synthesis was undertaken. Results: On the currently available evidence, pregnancy after breast cancer is not associated with an increased risk of recurrence. This holds in hormone receptor-positive disease and in BRCA1/2 carriers, and it is supported prospectively by the POSITIVE trial, whose preplanned update at a median follow-up of 71 months found a five-year incidence of breast cancer-free interval events of 12.3% against 13.2% in matched external controls. Obstetric and neonatal risks are higher than in the general obstetric population, although the pooled effect sizes are small to moderate: odds ratios are approximately 1.14 for cesarean delivery, 1.45 for preterm birth, 1.50 for low birth weight, and 1.16 for small-for-gestational-age birth. The excess concentrates in pregnancies conceived within the first one to two years after diagnosis and attenuates thereafter. Fertility preservation techniques appear both effective and oncologically safe. Fertility-related distress, by contrast, is common and does not reliably resolve once treatment ends. Conclusions: Oncologic risk alone is not a reason to advise against pregnancy after breast cancer. Early oncofertility referral, multidisciplinary planning, and risk-adapted obstetric surveillance remain the priorities. Because the evidence base is predominantly observational, these conclusions describe what the current data show rather than establishing safety definitively. Full article
23 pages, 1653 KB  
Review
The Clinical Value of NT-proBNP, sST2, and Galectin-3 in the Management of Heart Failure: From Diagnosis to Dynamic Monitoring: A Narrative Review
by Diana Andreea Fărcaș, Monica Tarcea, Maria Cristina Tătar, Anda Cerghizan, Călin Crăciun, Hajnal Finta, Florina Gliga and Claudia Bănescu
Int. J. Mol. Sci. 2026, 27(16), 7480; https://doi.org/10.3390/ijms27167480 - 21 Aug 2026
Abstract
Heart failure management remains a critical clinical challenge. While modern neurohormonal therapies have significantly improved survival, standard clinical assessments often fail to capture the full complexity of underlying structural disease progression. To comprehensively synthesize the established literature regarding the biological and prognostic roles [...] Read more.
Heart failure management remains a critical clinical challenge. While modern neurohormonal therapies have significantly improved survival, standard clinical assessments often fail to capture the full complexity of underlying structural disease progression. To comprehensively synthesize the established literature regarding the biological and prognostic roles of NT-proBNP, soluble ST2 (sST2), and Galectin-3 (Gal-3) and, subsequently, to propose a hypothesis-generating multimarker framework for HF risk stratification. A narrative review of the literature (2006–2026) was conducted across PubMed, Scopus, and Google Scholar. The synthesis focused on the clinical utility, phenotypic specificities, and methodological limitations of evaluating NT-proBNP, sST2, and Gal-3 concentrations. Evidence from the literature confirms that while NT-proBNP remains the gold standard for acute hemodynamic assessment. sST2 and Gal-3 provide complementary insights into active biomechanical strain and interstitial fibrotic remodeling; however, prospective randomized clinical trials demonstrating that sST2- or Gal-3-guided management improves clinical outcomes remain lacking. Based on these established findings, we propose an investigational four-step multimarker framework spanning from acute diagnosis to dynamic outpatient monitoring. This framework hypothesizes that integrating these pathways can better identify high-risk phenotypes that remain undetected by natriuretic peptides alone. The synergistic application of NT-proBNP, sST2, and Gal-3 offers a deeper pathophysiological evaluation of HF. However, our proposed biomarker-guided framework represents a set of testable research hypotheses. It requires prospective randomized validation before integration into routine clinical protocols for therapeutic titration. Full article
(This article belongs to the Special Issue Neurohormones in Cardiac Fibrosis and Heart Failure)
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17 pages, 485 KB  
Review
Pharmacotherapy for Obstructive Sleep Apnea: From Pathophysiology to Emerging Treatments
by Ruobing Zhou, Ge Yin, Yun Zhu and Yu Sun
J. Clin. Med. 2026, 15(16), 6473; https://doi.org/10.3390/jcm15166473 - 21 Aug 2026
Abstract
Background/Objectives: Obstructive sleep apnea (OSA) is a highly prevalent sleep-related breathing disorder caused by recurrent upper-airway collapse during sleep, leading to intermittent hypoxia, sleep fragmentation, and excessive daytime sleepiness. Although continuous positive airway pressure (CPAP) remains the first-line therapy, long-term adherence is [...] Read more.
Background/Objectives: Obstructive sleep apnea (OSA) is a highly prevalent sleep-related breathing disorder caused by recurrent upper-airway collapse during sleep, leading to intermittent hypoxia, sleep fragmentation, and excessive daytime sleepiness. Although continuous positive airway pressure (CPAP) remains the first-line therapy, long-term adherence is often suboptimal, underscoring the need for more tolerable and flexible treatment options. This review aims to summarize the pathophysiological rationale for pharmacotherapy in OSA and to discuss recent developments in drug-based interventions. Methods: We conducted a narrative review of the literature on pharmacological interventions for OSA, with a systematic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov up to 4 August 2026. We included randomised controlled trials, observational studies, meta-analyses, and mechanistic human or animal studies that reported relevant sleep and respiratory outcomes, and graded evidence according to the principles of GRADE framework. Results: Several drug classes have shown promise: agents that increase upper-airway dilator muscle activity, respiratory stabilizers that reduce loop gain, medications that raise the arousal threshold, topical anti-inflammatory drugs for mucosal edema, and systemic metabolic modulators such as glucagon-like peptide-1 receptor agonists and dual incretin receptor agonists. Emerging strategies, including gene therapy directed at the hypoglossal motor system, are also under investigation at the preclinical stage. Moreover, combining pharmacotherapy with CPAP or other devices can produce synergistic benefits, enabling lower device pressures and enhanced patient comfort. Conclusions: Pharmacotherapy for OSA is progressively moving from exploratory research towards targeted, phenotype-driven personalized treatment. Future studies should focus on robust patient phenotyping, multi-mechanistic combination regimens, and long-term clinical outcome evaluations to facilitate the integration of drug-based therapies into routine OSA management, particularly in specific subgroups such as those with COMISA. Full article
(This article belongs to the Section Pharmacology)
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14 pages, 700 KB  
Review
Effect of COVID-19 on Retinal and Choroidal Microvasculature in the Pediatric Population: A Literature Review
by Evita Evangelia Christou, Jane L. Ashworth, Noha M. Soliman, Peter Kiraly and Tariq Aslam
Medicina 2026, 62(8), 1603; https://doi.org/10.3390/medicina62081603 - 21 Aug 2026
Viewed by 41
Abstract
Backgroundand Objectives: Retinal microcirculation may serve as a surrogate marker of systemic vascular status and can be non-invasively assessed using optical coherence tomography angiography (OCTA). Emerging evidence suggests that retinal and choroidal microvascular alterations may occur following coronavirus disease 2019 (COVID-19) [...] Read more.
Backgroundand Objectives: Retinal microcirculation may serve as a surrogate marker of systemic vascular status and can be non-invasively assessed using optical coherence tomography angiography (OCTA). Emerging evidence suggests that retinal and choroidal microvascular alterations may occur following coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C), potentially reflecting systemic vascular and inflammatory processes. This review summarizes the current evidence regarding retinal and choroidal microvascular changes detected by OCTA in pediatric patients with COVID-19 and MIS-C. Materials and Methods: A structured literature search of the National Center for Biotechnology Information (NCBI) PubMed database was conducted from inception until April 2026. Original English-language studies evaluating retinal and choroidal microcirculation using OCTA in pediatric patients with COVID-19 or MIS-C were identified and reviewed. Results: Available studies suggest variable retinal and choroidal microvascular alterations following COVID-19 and MIS-C, including changes in vessel density, perfusion, and foveal avascular zone parameters. Several investigations reported reduced vessel density, particularly within the deep capillary plexus, whereas others demonstrated increased peripapillary vascular parameters or no significant differences during the observation period. Differences in patient characteristics, disease severity, timing of imaging, OCTA protocols, and study design likely contribute to the heterogeneity of the reported findings. Conclusions: OCTA represents a promising research tool for investigating retinal and choroidal microvascular alterations associated with pediatric COVID-19 and MIS-C. However, the available evidence remains limited by small observational studies, methodological heterogeneity and inconsistent findings. Larger prospective longitudinal studies using standardized imaging protocols are needed to determine the clinical significance and reproducibility of OCTA-derived parameters and to establish whether they may have potential as biomarkers of ocular or systemic vascular involvement. Full article
(This article belongs to the Special Issue Vitreoretinal Diseases: From Pathophysiology to Therapeutics)
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24 pages, 1657 KB  
Review
Integrating Sleep, Eating, Bowel Habits, and Physical Activity in Children and Adolescents: A Conceptual Review of the Four Kai Framework
by Jun Kohyama
Children 2026, 13(8), 1115; https://doi.org/10.3390/children13081115 - 20 Aug 2026
Viewed by 65
Abstract
Background/Objectives: Recent pediatric sleep research has increasingly adopted an integrated lifestyle perspective, examining sleep together with diet, physical activity, sedentary behavior, and family environments. However, bowel habits remain comparatively underrepresented despite their potential importance for child health. This conceptual narrative review revisits the [...] Read more.
Background/Objectives: Recent pediatric sleep research has increasingly adopted an integrated lifestyle perspective, examining sleep together with diet, physical activity, sedentary behavior, and family environments. However, bowel habits remain comparatively underrepresented despite their potential importance for child health. This conceptual narrative review revisits the Four Kai framework, which brings together sleep, eating, bowel habits, and physical activity as four fundamental daily physiological behaviors and explores their potential relationships with adaptive pleasure, self-regulation, and daytime functioning. Methods: This conceptual narrative review incorporated a descriptive PubMed literature-mapping exercise conducted on 16 July 2026. The search covered publications from January through June of each year from 2022 to 2026 and focused on studies in which sleep was a principal research topic together with terms related to diet, bowel function, physical activity, and lifestyle. Publications clearly outside pediatric or adolescent populations were excluded. Titles and abstracts were reviewed, with full texts consulted when necessary, and eligible studies were classified thematically according to their principal research objective. This exercise was intended to provide descriptive context for the conceptual review and was not conducted as a systematic or scoping review. Results: The descriptive mapping and narrative synthesis indicate that pediatric sleep research frequently examines sleep in relation to diet, physical activity, sedentary behavior, family environments, and other lifestyle factors, whereas everyday bowel habits remain comparatively underrepresented. The reviewed literature supports multiple individual and pairwise associations among sleep, eating, physical activity, bowel function, and daytime functioning but does not establish that these four behaviors operate as a single integrated physiological system. Direct empirical evidence for a pathway linking the Four Kai through adaptive pleasure and positive self-regulation to daytime functioning is currently lacking. Conclusions: The Four Kai framework is best regarded as a hypothesis-generating conceptual framework rather than an established biological or causal model. Its potential value lies in bringing sleep, eating, bowel habits, and physical activity into a common perspective and generating testable questions about their possible functional integration. Future longitudinal and intervention studies should evaluate these behaviors together with adaptive pleasure, self-regulation, and daytime functioning to determine which proposed relationships can be empirically supported. Full article
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46 pages, 19374 KB  
Review
The Invasive Margin of Glioblastoma as a Molecular Ecosystem: Spatial Heterogeneity, Tumor–Host Interactions, and Therapeutic Opportunities
by Nikodem Kuczyński, Dawid Larysz, Dorota Uchman-Rzeżnik, Gunawan Irianto and Dawid Pilewski
Int. J. Mol. Sci. 2026, 27(16), 7449; https://doi.org/10.3390/ijms27167449 - 20 Aug 2026
Viewed by 103
Abstract
Glioblastoma (GBM) recurs predominantly from infiltrative disease that persists beyond the contrast-enhancing tumor (CET). This structured narrative review aims to define the invasive margin and peritumoral brain zone (PBZ) as a spatially organized molecular ecosystem, summarize the approaches used to interrogate this compartment, [...] Read more.
Glioblastoma (GBM) recurs predominantly from infiltrative disease that persists beyond the contrast-enhancing tumor (CET). This structured narrative review aims to define the invasive margin and peritumoral brain zone (PBZ) as a spatially organized molecular ecosystem, summarize the approaches used to interrogate this compartment, and evaluate how malignant-cell plasticity, host niches, and treatment-induced remodeling contribute to minimal residual disease and recurrence. A structured literature search of PubMed/MEDLINE, Scopus, and Web of Science identified the clinical, translational, preclinical, and review literature available through July 2026; evidence was synthesized qualitatively, with priority given to human tissue studies and single-cell or spatially resolved analyses. Across studies, the margin differs from both tumor core and normal brain and contains heterogeneous malignant states interacting with neural, vascular, immune, hypoxic, and extracellular-matrix-supported niches. Surgery, radiotherapy, and systemic treatment further reshape these interactions through inflammation, vascular injury, senescence, hypoxia, and fibrosis. The main translational challenge is therefore not simply to control the CET, but to identify biologically high-risk non-enhancing tissue and demonstrate that therapy reaches and modifies it. We propose three priorities: image-registered characterization of residual compartments, regional measurement of drug exposure and target engagement, and integration of local margin control with distributed and niche-directed treatment. Prospective validation is required before spatial PBZ biomarkers can guide routine care. Full article
(This article belongs to the Special Issue Molecular Insights into Glioblastoma Pathogenesis and Therapeutics)
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33 pages, 1373 KB  
Review
Dietary Aluminium Exposure and Human Health: Sources, Bioavailability, Toxicokinetics, and Health Risk Assessment
by Łukasz Kogut, Czesław Puchalski, Julia Jastrzębska and Grzegorz Zaguła
Nutrients 2026, 18(16), 2719; https://doi.org/10.3390/nu18162719 - 20 Aug 2026
Viewed by 133
Abstract
Background/Objectives: Aluminium is a widespread environmental element and food contaminant to which the general population is continuously exposed, primarily through diet and drinking water. Although gastrointestinal absorption is generally low, bioavailability varies according to chemical form, food matrix, and interactions with dietary [...] Read more.
Background/Objectives: Aluminium is a widespread environmental element and food contaminant to which the general population is continuously exposed, primarily through diet and drinking water. Although gastrointestinal absorption is generally low, bioavailability varies according to chemical form, food matrix, and interactions with dietary components. Prolonged exposure can nevertheless result in gradual tissue accumulation. This review summarises current evidence on dietary aluminium exposure, factors influencing its bioavailability, toxicokinetics, biological effects, gut microbiota interactions, and population-level health risk. Methods: A comprehensive narrative literature review was conducted using publications retrieved from PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Original research articles, review papers, and reports issued by international organisations were critically evaluated with particular emphasis on dietary sources, drinking water, food additives, food contact materials, gastrointestinal absorption, toxicokinetics, biological mechanisms, gut microbiota, and health risk assessment. Results: Food represents the principal source of aluminium exposure in the general population, while drinking water usually contributes a smaller but continuous fraction of total oral intake. Dietary exposure varies substantially between populations and is influenced by food composition, processing practices, the use of aluminium-containing additives, and migration from food contact materials. Aluminium bioavailability is modified by chemical speciation and dietary constituents, including citrate, phosphates, silicates, phytates, polyphenols, and essential minerals. Despite limited absorption, prolonged exposure can lead to gradual aluminium accumulation, particularly in bone tissue and the central nervous system. Proposed biological mechanisms include oxidative stress, mitochondrial dysfunction, disruption of mineral homeostasis, and inflammatory signalling. Emerging evidence also indicates that aluminium may alter the gut microbiota, impair intestinal barrier integrity, and influence the gut–brain axis. Population exposure assessments show considerable regional variation, with some groups approaching or exceeding established tolerable weekly intake values. Conclusions: Dietary aluminium exposure represents a relevant issue in nutritional toxicology and food safety. Although current evidence does not establish that typical dietary exposure directly causes chronic disease, long-term exposure, differences in bioavailability, and the possibility of elevated intake in selected population groups justify continued monitoring and further prospective human studies. Future research should integrate dietary intake, aluminium speciation, nutritional status, biomarkers of internal exposure, and long-term health outcomes to improve risk assessment and support effective exposure-reduction strategies. Full article
(This article belongs to the Section Micronutrients and Human Health)
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15 pages, 267 KB  
Review
Cardiopulmonary Failure in Hantavirus Disease: Mechanisms, Recognition, and ECMO-Based Management
by Deng Siang Lee and Aboubakr Hasan
Viruses 2026, 18(8), 915; https://doi.org/10.3390/v18080915 - 20 Aug 2026
Viewed by 188
Abstract
Background: Hantavirus pulmonary syndrome (HPS), also designated hantavirus cardiopulmonary syndrome, is caused by New World hantaviruses, principally Sin Nombre virus in North America and Andes virus in South America. The syndrome is characterized by rapidly progressive noncardiogenic pulmonary edema and myocardial depression, with [...] Read more.
Background: Hantavirus pulmonary syndrome (HPS), also designated hantavirus cardiopulmonary syndrome, is caused by New World hantaviruses, principally Sin Nombre virus in North America and Andes virus in South America. The syndrome is characterized by rapidly progressive noncardiogenic pulmonary edema and myocardial depression, with case fatality rates of 25% to 40%. A 2026 outbreak aboard an expedition cruise ship in the South Atlantic, comprising 13 cases and three deaths, confirmed that Andes virus can be transmitted between humans in a confined setting remote from the rodent reservoir. Methods: Virological, pathophysiological, clinical, and therapeutic aspects of HPS were reviewed, with particular emphasis on cardiopulmonary mechanisms. Sources were identified through PubMed, Scopus, and Google Scholar, with priority given to original research articles, clinical series, and controlled trials published through 2025. Literature published in English and Spanish was included. Results: Pathogenic hantaviruses enter endothelial cells and platelets via αvβ3 integrins, disrupting the VEGF-VEGFR2 signaling axis and rendering endothelial cells hypersensitive to physiological VEGF concentrations. Expansion of CD8+ T cells and activated macrophages releases TNF-alpha, IFN-gamma, and nitric oxide, amplifying microvascular permeability and contributing to myocardial depression. Autopsy studies demonstrate direct hantaviral myocarditis with viral antigen in cardiac endothelium and interstitial macrophages. Transpulmonary thermodilution confirms simultaneous hypovolemia, reduced global ejection fraction, and elevated extravascular lung water. Because the incubation period is long and the cardiopulmonary phase is substantially immune-mediated, seroconversion precedes rather than follows clinical deterioration, which preserves the diagnostic utility of IgM serology in a disease that can kill within 48 h. VA-ECMO initiated at the first signs of cardiopulmonary decompensation has reported survival rates approaching 80% in selected experienced centers. No antiviral has demonstrated efficacy in controlled trials during the cardiopulmonary phase, and no licensed vaccine exists. Conclusions: HPS produces a mixed shock state through increased microvascular permeability, T cell-mediated immunopathology, and direct myocarditis. Management follows a stepwise algorithm: suspected HPS triggers immediate complete blood count with peripheral blood smear and concurrent hantavirus IgM serology and RT-PCR, followed by ICU admission, conservative fluid resuscitation guided by transpulmonary thermodilution, and early contact with an ECMO-capable center at the first sign of rising lactate, falling cardiac index, refractory shock, arrhythmia, or rapid oxygenation failure. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
21 pages, 1936 KB  
Review
Image Quality as an Important Confounder in Quantitative OCT Angiography: A Review with Quantitative Synthesis
by Lilla István, Cecilia Czakó, Róbert Debreczeni, Péter Sótonyi, András Horváth, Nóra Szentmáry, Zoltán Zsolt Nagy and Illés Kovács
Med. Sci. 2026, 14(4), 498; https://doi.org/10.3390/medsci14040498 - 20 Aug 2026
Viewed by 159
Abstract
Background: Optical coherence tomography angiography (OCTA) provides quantitative metrics of the retinal microvasculature, most prominently vessel density (VD), that are increasingly used as biomarkers in ocular, systemic, and cerebrovascular disease. Because OCTA relies on the detection of flow-related motion contrast, image quality has [...] Read more.
Background: Optical coherence tomography angiography (OCTA) provides quantitative metrics of the retinal microvasculature, most prominently vessel density (VD), that are increasingly used as biomarkers in ocular, systemic, and cerebrovascular disease. Because OCTA relies on the detection of flow-related motion contrast, image quality has emerged as a pervasive determinant of these metrics, yet its effect has been reported in fragmentary and non-comparable ways across the literature. Methods: We identified OCTA studies indexed in PubMed that examined the relationship between image quality and quantitative OCTA parameters, and we summarised their methods and findings across the macular, foveal avascular zone, and peripapillary regions and across vascular layers. We integrated directly comparable per-unit scan-quality effects using random-effects meta-analysis and separately synthesized direct cross-sectional Pearson correlations between manufacturer-reported image quality and macular vessel-density outcomes from independent healthy cohorts. Results: Higher image quality was associated with higher measured vessel density in every contributing dataset. On the Optovue scan-quality (SQ, 0–10) scale, superficial macular VD increased by 3.46% (95% CI 1.85–5.07) per SQ unit in controlled signal-attenuation experiments and by covariate-adjusted observational estimates ranging from 0.90% to 2.16% per SQ unit; a combined order-of-magnitude estimate across both estimator types was 1.64% (95% CI 1.15–2.12). Peripapillary estimates were heterogeneous and derived from only two independent cohorts; they were therefore summarised descriptively rather than pooled. Across three independent externally authored healthy cohorts reporting direct cross-sectional Pearson correlations, higher image quality was strongly associated with higher macular vessel-density outcomes (random-effects pooled r = 0.64, 95% CI 0.50–0.75; I2 = 49%). Conclusions: Image quality is an important, directional confounder of VD-based OCTA metrics whose magnitude can rival the biological or physiological signal of interest. Platform-appropriate standardisation, transparent reporting, and consideration of image quality in acquisition and analysis are therefore important for the valid interpretation of vessel-density measurements, particularly in functional and longitudinal studies. Full article
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12 pages, 552 KB  
Systematic Review
Ultrasound-Based Biofeedback for Pelvic Floor Rehabilitation: A Systematic Review of Randomized Controlled Trials
by César Garrido-Fernández, Eva Lantarón-Caeiro, Isabel Escobio-Prieto and Pablo Hernandez-Lucas
J. Clin. Med. 2026, 15(16), 6422; https://doi.org/10.3390/jcm15166422 - 19 Aug 2026
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Abstract
Pelvic floor dysfunctions are highly prevalent and can substantially impair quality of life. Physiotherapy is considered a first-line conservative treatment, and the integration of technologies such as ultrasound may enhance outcomes through visual biofeedback. Objectives: To evaluate the effectiveness of ultrasound as [...] Read more.
Pelvic floor dysfunctions are highly prevalent and can substantially impair quality of life. Physiotherapy is considered a first-line conservative treatment, and the integration of technologies such as ultrasound may enhance outcomes through visual biofeedback. Objectives: To evaluate the effectiveness of ultrasound as a biofeedback tool in physiotherapeutic interventions for pelvic floor dysfunctions across different populations. Methods: A systematic review was conducted following PRISMA guidelines and registered in PROSPERO (CRD420261278982). The literature search was conducted between February and March 2025 in PubMed, Web of Science, Scopus, Medline, and PEDro. Randomized controlled trials using ultrasound as biofeedback in physiotherapy interventions were included. Methodological quality was assessed using the PEDro scale, and risk of bias was evaluated with the RoB 2 tool. Results: Two randomized controlled trials involving 75 women were included. One study investigated older women with urinary incontinence, whereas the other included postpartum women with pregnancy-related pelvic girdle pain. In Galea et al., transabdominal ultrasound biofeedback was not superior to conventional feedback based on vaginal palpation for urinary leakage, incontinence frequency, or quality of life, although the ultrasound group showed a significant within-group reduction in leakage episodes. In Kuo et al., ultrasound-guided biofeedback combined with pelvic floor and stabilization exercises reduced pain and disability compared with education alone and improved walking performance, but it was not consistently superior to exercise without biofeedback and did not significantly improve pelvic floor muscle contractility. The small number of studies, heterogeneity of populations and interventions, and low to very low certainty of the evidence limited the strength of the findings. Conclusions: Ultrasound-based biofeedback may be a useful adjunct to pelvic floor physiotherapy, particularly for facilitating correct muscle contraction and supporting motor learning. However, the available evidence does not demonstrate a consistent additional clinical benefit over conventional feedback or exercise alone. These findings should therefore be interpreted cautiously. Further high-quality randomized controlled trials with larger samples, standardized protocols, and longer follow-up are required. Full article
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26 pages, 19028 KB  
Systematic Review
Applications of Artificial Intelligence in the Health Sector: A PRISMA-Based Systematic Review
by Zakir Hossen Shaikh, Sarita Yadav, Bibhu Prasad Sahoo, Jay Shankar Sharma and Abdelrhman Meero
Healthcare 2026, 14(16), 2604; https://doi.org/10.3390/healthcare14162604 - 19 Aug 2026
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Abstract
Background: The health sector is getting transformed with the usage of AI, be it diagnosis, treatment planning, disease prediction, and or health system management. Research in this field has picked up in the last few years, which was made possible with the emergence [...] Read more.
Background: The health sector is getting transformed with the usage of AI, be it diagnosis, treatment planning, disease prediction, and or health system management. Research in this field has picked up in the last few years, which was made possible with the emergence of machine learning, natural language processing and the increasing number of e-health records. Objectives: The study aims to investigate the current trends in the implementation of artificial intelligence (AI) applications in medical settings by investigating the global scientific output/landscape on this theme, such as the annual publication trends, country-wise contributions, and publishing patterns. Methods: The current study is based on systematic review by combining bibliometric analysis and cluster analysis using VOSviewer version 1.6.20, R software version 4.5.0, and Biblioshiny (Bibliometrix package in R) along with preferred reporting items for systematic reviews and meta analyses (PRISMA), 2020 which provides transparency and rigorous visualization to examine the articles published in English on the use of AI in healthcare, after the onset of COVID-19 till date i.e., from 2020 to 2026 on the Scopus database. Results: Using the relevant search string, 5940 documents were identified between 2020 and 2026, 1434 were included for analysis after screening and relevant filters. The publications have increased remarkably after 2020 on this theme and more than half of the publications have their roots in the discipline of Medicine. The USA, China, and the United Kingdom have contributed the most to the volume of research. Natural language processing and diagnosis are the emerging themes. The Journal of Medical Internet Research, BMC Medical Informatics and Decision Making, Computers in Biology and Medicine, IEEE Journal of Biomedical and Health Informatics, Frontiers in Public Health, and Digital Health are some of the most influential sources in the field. Li J and Liu X are among the authors with remarkable local impact. Conclusions: The work aims to assist investigators, health care professionals, and policymakers to learn about modern trends and focus on critical areas of future research and collaboration in AI-enhanced health care. The limitation of the study is that it considered only the Scopus database but it has opened up opportunities for researchers for analysis using other databases such as Dimensions, Lens, and PubMed. Also, this review is considering the publication record since the onset of COVID-19 but a comparative analysis of pre and post-pandemic studies can also be conducted to get a holistic view of drastic collaboration of research in this field. Discussions: The findings suggest that the role of artificial intelligence in health care has paramount over recent years, with other supporting technologies but a technologically hesitant population as well as low acceptance of AI due to ethical issues, cannot be ignored for ensuring efficiency in the health sector. Full article
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13 pages, 1240 KB  
Article
CLCuMuV-Induced Autophagy Restricts Viral Accumulation in the MED Cryptic Species of Bemisia tabaci
by Yanbo Jia, Qingxing Shi, Jie Chen, Guojun Qi and Ting Chen
Insects 2026, 17(8), 862; https://doi.org/10.3390/insects17080862 - 19 Aug 2026
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Abstract
Autophagy is a conserved cellular degradation pathway that plays important roles in insect–virus interactions. In the MED cryptic species of Bemisia tabaci, cotton leaf curl Multan virus (CLCuMuV) can persist upon acquisition, yet this vector fails to transmit the virus. However, whether [...] Read more.
Autophagy is a conserved cellular degradation pathway that plays important roles in insect–virus interactions. In the MED cryptic species of Bemisia tabaci, cotton leaf curl Multan virus (CLCuMuV) can persist upon acquisition, yet this vector fails to transmit the virus. However, whether autophagy contributes to this antiviral response in MED whiteflies remains unknown. In this study, we show that CLCuMuV acquisition activates autophagy in MED whiteflies, as evidenced by increased LC3-I to LC3-II conversion, enhanced LC3-positive puncta formation in the gut, and dynamic transcriptional regulation of multiple autophagy-related genes. Functional investigations using RNAi-mediated silencing of Atg3 and Atg9, two essential autophagy genes, revealed that their knockdown elevated viral DNA accumulation by 1.4-fold at 48 h post-acquisition. Consistently, pharmacological blockade of autophagic flux with bafilomycin A1 led to a 1.0-, 2.2-, and 1.0-fold increase in viral loads across 24, 48, and 72 h post-acquisition, respectively, whereas treatment with rapamycin, an autophagy inducer, decreased viral DNA accumulation by 46.4% and 33.3% relative to control levels at 24 and 48 h post-acquisition, respectively. Together, these loss- and gain-of-function experiments demonstrate that autophagy functions as a host restriction mechanism that limits CLCuMuV persistence in MED whiteflies, providing molecular insights into the immune competence of this non-vector species. Full article
(This article belongs to the Special Issue New Insights into Molecular Mechanism of Insect–Virus Interaction)
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