Abstract: Plastic pollution has generated a novel anthropogenic habitat, the plastisphere, where microorganisms colonize and establish complex biofilms on the surfaces of synthetic polymers. Although considerable progress has been made in describing plastisphere microbial diversity, the ecological mechanisms linking community assembly, microbial communication, and polymer biodegradation remain poorly understood, particularly in saline ecosystems. Here, we review current knowledge on plastisphere formation in marine, estuarine, hypersaline, and other saline environments, emphasizing the ecological roles of quorum sensing (QS), halotolerant fungi, and microbial interactions in regulating biofilm development and microplastic degradation. We discuss how environmental factors characteristic of saline habitats, including osmotic stress, ultraviolet radiation, nutrient limitation, and high ionic strength, shape plastisphere succession and influence microbial physiology. Particular attention is given to halotolerant fungi, whose oxidative and hydrolytic enzymes—including laccases, peroxidases, cutinases, esterases, and lipases—complement bacterial metabolism during polymer transformation. We further examine recent evidence demonstrating that QS coordinates microbial attachment, extracellular polymeric substance production, biofilm maturation, extracellular enzyme secretion, and metabolic cooperation, thereby linking microbial communication with biodegradation efficiency. Based on current evidence, we propose an integrative ecological framework in which abiotic weathering, environmental filtering, quorum sensing, bacterial–fungal interactions, and extracellular enzymatic pathways constitute successive and interconnected processes governing plastisphere functioning in saline ecosystems. Finally, we identify major knowledge gaps and highlight future research priorities, including the integration of multi-omics approaches, synthetic microbial consortia, systems biology, and artificial intelligence for the discovery of novel plastic-degrading enzymes. By integrating microbial ecology, fungal biology, chemical communication, and environmental biotechnology, this review provides a systems-level perspective on the plastisphere and establishes a conceptual framework for understanding and enhancing microplastic biodegradation under saline conditions.

Abstract: Background/Objectives: The main neurodegenerative diseases (NDs) - Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) - represent a growing global health burden with no available disease-modifying therapies. Curcumin, a polyphenol from Curcuma longa, is a promising candidate owing to its pleiotropic antioxidant, anti-inflammatory, and neuroprotective profile, but its oral bioavailability (<1%) and blood-brain barrier (BBB) penetration (<0.1%) severely limit its clinical application. The objective of this work was to critically examine the therapeutic potential of curcumin in NDs, focusing on advanced drug delivery systems (DDS) designed to overcome its pharmacokinetic barriers. Methods: Narrative, non-systematic review of PubMed/MEDLINE, Scopus, and Web of Science, structured around five areas: molecular mechanisms, pharmacokinetic barriers, evolution of DDS, disease-specific applications, and translational limitations. Results: Curcumin exhibits neuroprotective activity in preclinical models of the four NDs analysed, acting on six interconnected mechanisms and the gut-brain axis. Four generations of DDS have been developed, from phytosomes and clinically used lipid dispersions (Meriva®, BCM-95®, Longvida®, Theracurmin®) to fourth-generation systems (biomimetic nanoparticles, MOFs, microneedles, 3D scaffolds, hydrogels, carbon dots) that substantially increase bioavailability in preclinical studies. Combination strategies, such as curcumin with resveratrol and dutasteride, show preliminary clinical signals in ALS. However, clinical translation remains limited: over 80% of positive animal findings have not been replicated in humans, formulation characterization is frequently incomplete, and most trials lack CNS-exposure biomarkers. Conclusions: DDS are essential to unlock curcumin’s therapeutic potential in neurology, but its clinical translation requires phase II/III trials with well-characterized formulations, cerebrospinal fluid exposure biomarkers, and adaptive designs.

Abstract: Minimal genome design, reducing a system to its smallest functional part set, is a core synthetic-biology strategy. Bacteriophages are attractive but underused chassis, yet wild-type phages are difficult to engineer. We present a comparative genomics-guided framework for synthetic minimal phage genome design, demonstrated on Streptococcus mutans, the primary agent of dental caries. Three S. mutans phages (M102AD, φAPCM01, SMHBZ8) were compared by synteny analysis, and their 123 proteins an-notated with InterProScan, EggNOG-mapper and HHpred. Conserved essential genes were selected by HHpred score, assembled as standardized transcriptional units, codon-optimized for E. coli K-12, and cloned in silico into the broad-host-range vector pBBR1MCS-2. Multi-host codon adaptation index (CAI) analysis assessed chassis flexibility. As a result, seventeen genes were assembled into a 15,792 bp synthetic insert; the final 20,948 bp construct raised mean CAI from 38.7% to 46.9% and cut rare-codon usage to 0.7%. Prokka confirmed 21 intact coding sequences, and CAI analysis predicted strong expression in Klebsiella pneumoniae (60.7%) and Pseudomonas aeruginosa (53.1%). This framework yields a validated, broad-host-range synthetic multi-gene phage-expression construct ready for experimental testing. One part (calcium-binding protein, CAI 34.4%) remains under-optimized, and Gibson Assembly, not restriction cloning, is recommended. The design logic is transferable to other phage-host systems.

Abstract: Cover crops (CCs) are widely used to improve soil function, support water regulation, and moderate vine vigor. This study evaluated alternative vineyard floor management strategies designed to improve ecosystem services while minimizing excessive competition with grapevines under semiarid Mediterranean conditions. A long-term, three-season field experiment was conducted in Bekoa, Israel, using 4 treatments: standard-management control, selective herbicide promoting annual winter grasses, interrow tall fescue (Festuca arundinacea-TF), and full-TF ground cover. Unlike conventional perennial CCs, the selective herbicide treatment promoted naturally occurring winter grasses that completed their life cycle before the dry summer period, thereby limiting prolonged competition with grapevines. Vine water status, vegetative-growth, yield components, and wine-quality parameters were monitored. Grass-based treatments progressively reduced vegetative growth and induced moderate vine water stress, as reflected by lower leaf area index and more negative stem water-potential. Yield declined over the three growing seasons due to reductions in cluster number, with the strongest effects observed in perennial turfgrass. In contrast, the selective herbicide treatment consistently produced intermediate physiological and agronomic responses. In the third season, wines from the perennial turfgrass treatments exhibited greater color intensity, particularly under full-cover TF, while hue was not significantly affected. Overall, CC-based vineyard floor management affected vine performance and wine quality, but the response depended on cover-type and duration of use. The selective promotion of naturally occurring winter grasses through targeted herbicide application represents a practical vineyard floor management strategy that retains many of the benefits associated with vineyard floor vegetation while minimizing excessive summer water competition under Mediterranean conditions.

Abstract: Purpose: To summarize current evidence on the incidence, magnitude, and possible predictors of rebound after cessation of myopia control treatments and to identify strategies that may help minimize rebound in practice. Methods: In this systematic review, we aimed to evaluate potential rebound effects following the cessation of optical, pharmacological, and low-level light therapy interventions used for myopia control. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search was conducted, and 1027 articles published up to November 2025 were identified through the following databases: PubMed, Web of Science, Scopus, and ClinicalTrials.gov. Three investigators independently performed the selection process according to these inclusion and exclusion criteria. Results: In most studies, axial length (AL) and spherical equivalent refraction (SER) values were higher in cessation groups than in groups that continued myopia control treatment. HAL/DIMS spectacles for myopia control interventions showed weak to moderate rebound effects after treatment cessation, with a mean rebound of 0.09 ± 0.17 mm (0.06 to 0.11) in AL and −0.16 ± 0.43 D (-0.18 to -0.13) in SER. Multifocal contact lenses generally showed weak or no rebound after treatment cessation, whereas Ortho-K lenses were more frequently associated with moderate to strong rebound effects, suggesting a mean rebound of 0.05 ± 0.61 mm (-0.43 to 0.62) in AL and 0.05 ± 0.60 D (-0.22 to 0.41) in SER. Similarly, the mean rebound effect in the atropine intervention was concentration-dependent and was 0.14 ± 0.19 mm (-0.02 to 0.35) in AL and -0.23 ± 0.47 D (-0.87 to 0.43) in SER. LLLT intervention showed moderate to strong rebound effects with the mean rebound effect of 0.23 ± 0.26 mm (0.15 to 0.30) in AL and -0.48 ± 0.37 D (-0.71 to -0.25) in SER. Overall, the treatment continuation subgroup showed a mean axial length (AL) change of 0.15 ± 0.16 mm (range: −0.09 to 0.46) and a mean spherical equivalent refraction (SER) change of −0.25 ± 0.41 D (range: −0.67 to 0.38). In contrast, the treatment cessation subgroup demonstrated a mean AL change of 0.25 ± 0.26 mm (0.00 to 0.58) and a mean SER change of −0.55 ± 0.44 D (-1.15 to -0.01). Conclusion: Various myopia control interventions produce rebound effects of differing magnitude in different parameters, including AL, SE, and choroidal thickness. Spectacle lenses and contact lenses showed the lowest rebound, whereas high-dose atropine and LLLT were associated with the greatest rebound, highlighting the dose-dependent nature of this phenomenon.

Abstract: Background/Objectives: Rotavirus vaccination reduces severe childhood gastroenteritis, but real-world effectiveness may vary across settings and calendar periods. We estimated the effectiveness of documented complete rotavirus vaccination against laboratory-confirmed rotavirus gastroenteritis and rotavirus-associated hospitalization among children younger than 5 years in Türkiye. Methods: This retrospective test-negative study included children aged 0–59 months who underwent stool rotavirus testing for clinically evaluated acute gastroenteritis at a tertiary hospital between January 2015 and June 2026. Tests occurring within 14 days in the same child were combined into one episode. Cases were rotavirus-positive episodes and controls were rotavirus-negative episodes. Complete vaccination was defined by an institutional record showing completion of the full schedule before the index test. Cluster-robust logistic regression adjusted for age group, sex, treatment setting, calendar year, and test month. Vaccine effectiveness (VE) was calculated as (1−adjusted odds ratio)×100%. Results: The analysis included 2,788 episodes among 2,242 children: 534 rotavirus-positive cases and 2,254 test-negative controls. Complete vaccination was documented in 81 cases (15.2%) and 539 controls (23.9%). Crude VE was 43.1% (95% confidence interval [CI], 26.2%–56.1%). Adjusted VE against laboratory-confirmed rotavirus gastroenteritis was 52.8% (95% CI, 37.6%–64.3%; P<0.001). Among hospitalized episodes, adjusted VE was 57.8% (95% CI, 33.5%–73.2%; P<0.001). Estimates were stable when vaccination completion was required at least 14 days before testing, when only the first episode per child was retained, and with 7- or 30-day episode definitions. Effectiveness varied markedly by calendar period: 15.3% (95% CI, −28.7% to 44.3%) in 2015–2019 and 77.7% (95% CI, 62.3%–86.8%) in 2022–2026. Conclusions: Documented complete rotavirus vaccination was associated with substantially lower odds of laboratory-confirmed rotavirus gastroenteritis and rotavirus-associated hospitalization. The marked period-specific variation indicates that the pooled estimate should be interpreted with attention to changes in epidemiology, testing, healthcare utilization, and residual confounding across the COVID-19 era.

Abstract: People often recognize spoken words more accurately and more quickly than written words. From the perspective of active inference under the free-energy principle, the present study develops a formal account of this speaking-over-writing advantage in production-modality retrieval. We modeled retrieval under spoken and written production-modality states, together with the selection of an early or late response policy according to its expected sensory consequences. University students spoke or wrote words presented on a computer screen and later judged the modality in which each word had been produced. Responses were followed by explicit visual feedback indicating whether each judgment was correct or incorrect, thereby providing an observable sensory consequence of the recognition response. Response times were implemented as early and late policies within a partially observable Markov decision process (POMDP). The model included modality-specific likelihood parameters linking response timing to feedback outcomes. Spoken words were identified more quickly and accurately than written words, and early responding was more strongly associated with correct feedback under the speaking state than under the writing state. Bayesian model selection favored the POMDP over a simpler linear model estimated using Variational Laplace, indicating that the POMDP provided a better balance of fit and complexity. These findings show how production modality, response timing, and expected sensory consequences can be represented within a common generative framework. The framework provides a basis for future extensions that model uncertainty about production modality, preserve continuous response timing, incorporate learning across trials, and compare active-inference accounts with alternative models of recognition memory.

Abstract: Grid-based density clustering methods—FlowGrid, FLOPTICS, and grid-accelerated DBSCAN and OPTICS—partition a d-dimensional feature space into an m^d array of bins and group the non-empty bins by density reachability. They leave a symmetry unexploited: relabelling and reflecting the feature axes permutes the bins while preserving density. We formalise this as an action of the hyperoctahedral group B_d = C₂ \( \wr \) S_d of order 2^dd! on bin-occupancy functions. We prove that the action preserves the Chebyshev bin-adjacency underlying grid reachability (Theorem 1); that grid density clustering is B_d-equivariant (Theorem 2); that configurations up to symmetry are counted by a Burnside average over B_d (Theorem 3), with an explicit parity-split closed form for the octahedral case at every resolution, which we have not found recorded elsewhere (Theorem 4 and Corollary 2); and that a canonical-form algorithm computes a unique representative per orbit in O (2^dd! m^d) time (Theorem 5). We are explicit about scope: a generic dataset has a trivial stabiliser, so there is no per-run gain; the benefit is canonical indexing, deduplication of symmetry-closed libraries, and caching when the same measurement recurs under a different axis convention. The group specialises to the D₄ and O_h symmetries of the DR Code. Symmetry enters twice: as the group acting on the grid, and as the line between symmetric instances and the generic asymmetric ones. All theorems and enumeration formulae are confirmed computationally.

Abstract: Halo-gravity traction (HGT) is widely used as a preoperative treatment for severe pediatric spinal deformities by gradually applying traction forces through a cranial fixation system. While the clinical effectiveness of HGT has been extensively documented, the uncertainty associated with the structural performance and operational reliability of mobile HGT systems has received comparatively little attention. This study presents a coupled clinical–structural uncertainty quantification framework for the evaluation of a mobile halo-gravity traction wheelchair. Reduced-order structural and clinical response models are combined with Monte Carlo simulation, Latin Hypercube Sampling, bounded beta-distributed input variables, Polynomial Chaos Expansion, and Sobol sensitivity analysis to propagate uncertainty from patient, operational, and design parameters to structural response metrics. The framework evaluates structural integrity, stability, halo-pin loading, traction delivery, factors of safety, and representative clinical response measures. The probabilistic analysis demonstrates that the proposed design maintains substantial structural safety margins throughout the investigated uncertainty space, with no sampled realization producing a governing factor of safety below unity. The proposed framework provides an efficient methodology for uncertainty-informed design and evaluation of pediatric halo-gravity traction systems.

Abstract: Pollution of coastal territories by marine litter is a pressing issue not only for large cities but also for remote and uninhabited regions such as the Arctic. At the same time, the scale of pollution is growing annually, while existing environmental monitoring methods remain labour-intensive. For the first time, an assessment of the volume and composition of marine litter was conducted for Arctic coastlines using high-resolution airphotos. The method is based on training the YOLOv8 (2023) convolutional neural network in the OBB configuration to recognise plastic, metal, fishing nets, wood, and other types of marine litter in images. Based on a comparative analysis, it was established that machine learning methods combined with remote sensing data represent a new high-precision tool for environmental monitoring, which can significantly contribute to reducing the anthropogenic pressure on the ecosystems of Arctic territories.

Abstract: Background: Multi-omics approaches provide a comprehensive framework for resolving the molecular heterogeneity of cancer by integrating transcriptomic, proteomic, genomic, epigenetic, immunological, and cellular information. WASHC2C, a scaffold component of the WASH regulatory complex, participates in actin remodeling, endosomal trafficking, and receptor recycling; however, its molecular and clinical relevance across human cancers remains insufficiently characterized. Methods: We conducted an integrated pan-cancer multi-omics analysis of WASHC2C using TCGA, GTEx, CPTAC, the Human Protein Atlas, and complementary public resources. Transcriptomic and proteomic expression, clinicopathological characteristics, survival outcomes, somatic mutations, copy-number alterations, DNA methylation, genomic-instability features, pathway activity, immune-cell infiltration, immunoregulatory gene expression, immunotherapy-associated datasets, and single-cell functional states were systematically evaluated. Results: WASHC2C displayed marked cancer-type-specific dysregulation. Its expression was increased in LIHC and PRAD but reduced in several malignancies, including COAD, BRCA, LUAD, LUSC, and HNSC. Clinical associations were similarly context-dependent: higher WASHC2C expression was associated with favorable survival outcomes in LUAD and BLCA but adverse outcomes in LIHC. Copy-number alterations were positively correlated with WASHC2C mRNA abundance across most evaluated cancers, whereas somatic mutation and DNA-methylation patterns were heterogeneous. Immune analyses demonstrated tumor-specific associations with CD8+ and CD4+ T cells, B cells, macrophages, natural killer cells, and cancer-associated fibroblasts. WASHC2C expression was also correlated with chemokines, immune-checkpoint molecules, and antigen-presentation genes, although the direction and magnitude differed among cancer types. Immunotherapy-associated datasets showed differences among responders, non-responders, and baseline samples in selected cohorts, without a consistent pan-cancer response pattern. At single-cell resolution, WASHC2C was associated with metastasis, epithelial–mesenchymal transition, hypoxia, inflammation, invasion, and quiescence. Conclusions: Integrated multi-omics profiling identifies WASHC2C as a context-dependent molecule associated with tumor behavior, genomic regulation, microenvironmental composition, and immunotherapy-related features. These findings provide a multidimensional framework for future mechanistic and prospective validation of WASHC2C across diverse human malignancies.

Abstract: Lumbar spinal stenosis (LSS) is a major cause of pain and disability, yet its pathophysiology remains incompletely understood. Although spinal decompression is the standard surgical treatment for LSS with disabling pain or with progressive neurological symptoms, clinical outcomes are often suboptimal, with reoperation required in 5-23% of cases. While degenerative changes of the vertebral canal have been extensively investigated, the potential contribution of the thoracolumbar fascia (TLF) has never been explored at the molecular level. We hypothesized that the TLF undergoes extracellular matrix remodeling and inflammatory changes in LSS. Thoracolumbar fascia biopsies were collected from 14 patients undergoing spinal surgery (7 with LSS and 7 controls with traumatic vertebral fractures). Total collagen content was quantified by hydroxyproline assay, collagen subtypes (I, III, VI and XII) by Western blotting, and inflammatory remodeling by ELISA quantification of TNF-α and MMP-2. LSS patients showed significantly higher hydroxyproline content (p = 0.026), indicating increased collagen deposition and fascial fibrosis, together with elevated MMP-2 levels (p = 0.038), supporting the presence of active chronic extracellular matrix remodeling. TNF-α levels did not differ significantly between groups, although marked inter-individual variability was observed. Collagen subtype expression showed distinct trends but no significant differences. These findings provide the first molecular evidence of fibrotic remodeling and altered extracellular matrix turnover in the TLF of LSS patients, supporting its role as an active contributor to disease pathophysiology and a potential diagnostic biomarker and therapeutic target.

Abstract: Introduction: The S0–S3 workflow arose from a recurring teaching question: how to help students and authors transform PRISMA selection into a work process that is understandable, traceable, and connected to the final writing of the article. This article reconstructs the conceptual development of the model based on previous methodological literature and experience gained while supervising final bachelor's and master's degree projects undertaken by students of Medicine, Dentistry, Nursing and Speech Therapy.Methods: A methodological and conceptual overview was conducted, informed by the PCC framework and reported in accordance with PRISMA-ScR. Guidelines, manuals, methodological articles and documents on reproducibility, traceability, risk of bias, certainty of evidence, automation and artificial intelligence were examined. The initial corpus comprised 38 references; 16 were considered essential and underwent full-text assessment, and 9 were included in the final synthesis.Results: The research culminated in a teaching and operational architecture comprising a preliminary phase and four stations: S0, identification; S1, screening; S2, eligibility; and S3, inclusion and synthesis. The workflow enables students to relate each selection stage to the PRISMA flow, document which references advance or are excluded, and determine which sources correspond to the Introduction, Methods, Results, Discussion and Conclusions of the final project in IMRDC format.Conclusions: The S0–S3 workflow is the result of conceptual research supported by methodological literature and teaching experience. It does not replace PRISMA or IMRDC; rather, it converts the selection flow into a documented work sequence and facilitates the transfer of selected evidence to the academic manuscript. The workflow requires prospective evaluation across different academic programmes, teams, and review types.

Abstract: Marine cage aquaculture contributes to nutrient enrichment of the surrounding waters, with ammonium (NH_4⁺) being the predominant ionized form of inorganic nitrogen (N) released. Elevated NH_4⁺ concentrations in marine waters may promote excessive phytoplankton growth, which may subsequently affect the ecological status of the surrounding ecosystem under certain environmental conditions. This study aims to investigate the potential of Sentinel-2 MSI imagery for estimating NH_4⁺ in an oligotrophic semi-enclosed cove where marine cage aquaculture operates. Firstly, the relationship between in situ NH_4⁺ and chlorophyll a (chl a) measurements was evaluated, both on a seasonal basis and across all seasons, to determine whether chl a could serve as a proxy for NH_4⁺ estimation. Given the weak correlation observed, the feasibility of direct NH_4⁺ retrieval was further evaluated. A band-selection procedure was applied to retain Sentinel-2 MSI spectral bands with the highest correlation with NH_4⁺ while minimizing multicollinearity arises from spectral “overlap” among bands. To evaluate the effectiveness of the proposed band-selection procedure in improving the generalization ability of three machine learning (ML) models, the complete set of Sentinel-2 MSI spectral bands at 10 and 20 m spatial resolutions was also used. The obtained RMSE and MAE values (0.29 and 0.22 μM, respectively) for the Random Forest–Bayesian Optimization with Tree-structured Parzen Estimator (RF-BO-TPE) and Support Vector Regression–Bayesian Optimization with Tree-structured Parzen Estimator (SVR-BO-TPE) models in the testing dataset, using the selected spectral bands (B03, B04, B05 and B08), indicated reasonable agreement with the actual NH₄⁺ concentrations (Range: 0.00-1.46 μΜ, SD = ±0.20 μM). Furthermore, the observed robustness against overfitting (ΔR² = 0.07, OR_RMSE = 1.10–1.11, and OR_MAE = 1.01–1.02) suggests that the developed models could provide useful NH₄⁺ estimates. These findings highlight the potential of Sentinel-2 MSI for NH₄⁺ estimation in oligotrophic coastal waters affected by cage aquaculture.

Abstract: Purpose of Review: Heart failure affects over 64 million people worldwide, yet diagnosis remains challenging, with nearly two-thirds of cases estimated to remain undiagnosed overall. This review synthesises current evidence on multimodal artificial intelligence (AI) for heart failure detection, covering fusion strategies, explainability, and implementation challenges. Recent Findings: Unimodal AI achieves good-to-excellent discrimination from routine clinical measurements, 12-lead electrocardiograms, and chest X-rays, while echocardiography and cardiac magnetic resonance enable measurement automation and phenotyping. However, subgroup performance and external validation remain limited. Multimodal AI combining ECG, echocardiography, radiography, and electronic health records improves discrimination and phenotyping compared to single-modality models, with the largest gains observed from foundation models pretrained on large imaging and waveform corpora. Summary: Multimodal AI could capture the multidimensional complexity of heart failure, but prospective validation, calibration, and generalisability remain critical gaps. Multicentre trials with standardised endpoints, co-designed interfaces, and regulatory frameworks are priorities for deployment-centric algorithms.

Abstract: This study numerically investigates the analogy between laser shock (LS) and projec-tile-based hypervelocity impact (HVI) for composite and hybrid spacecraft shielding materials and proposes a methodology for determining the equivalent LS parameters corresponding to a given HVI event. Numerical HVI models were developed in LS-DYNA and validated against published experimental data for two shielding con-figurations: (a) a CFRP bumper and (b) an Al/CFRP/Al/CFRP/Al hybrid shield, with emphasis on crater formation and damage morphology. An LS model was subse-quently calibrated through iterative adjustment of the pressure amplitude and pulse duration to reproduce the damage induced by HVI. The ablation-pressure scaling laws of Grün, Dautray, Pirri, and Phipps were then inverted to estimate the laser intensity and energy required for experimental implementation. Excellent agreement between the HVI and LS responses was achieved in terms of crater morphology, hole size, de-lamination, and damaged area. The predicted laser intensities (498–1424 GW/cm²) and energies (42–1049 J) fall within the validated range of the Grün and Phipps scaling laws and the capabilities of existing laser facilities, demonstrating that the proposed HVI–LS analogy is both physically consistent and experimentally feasible.

Abstract: The numerical simulation of incompressible viscous flows remains a central pillar of modern computational fluid dynamics (CFD). Over the past decades, a wide spectrum of numerical methodologies has been developed, reflecting fundamentally different mathematical formulations and discretization philosophies. Among these, domain-based approaches—including finite difference (FDM), finite volume (FVM), and finite element (FEM) methods—have emerged as versatile and general-purpose frameworks, while boundary element methods (BEM) provide efficient alternatives for selected classes of problems governed by linear physics, particularly in unbounded domains. Meshfree and particle-based methods constitute an alternative paradigm for problems involving large deformation, moving interfaces, free surfaces, and fragmentation. This review provides a unified comparison of FDM, FVM, FEM, BEM, and meshfree approaches, emphasizing their mathematical foundations, treatment of nonlinear operators, stability, consistency, convergence, computational characteristics, and compatibility with turbulence modeling. Particular attention is given to the interaction between discretization and Reynolds-averaged Navier– Stokes(RANS), large-eddy simulation (LES), direct numerical simulation (DNS), and hybrid RANS–LES methodologies, including detached-eddy simulation (DES), delayed detached-eddy simulation (DDES), improved delayed detached-eddy simulation (IDDES), and stress-blended eddy simulation (SBES). Recent developments in highorder discretization, immersed-boundary and hybrid formulations, meshfree methods, and artificial-intelligence-assisted CFD are also discussed. The review demonstrates that no numerical method is universally optimal; rather, methodological suitability is governed by the interplay among flow physics, Reynolds number, geometry, boundary conditions, and computational requirements.

Abstract: Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is a major global pathogen with increasing resistance to conventional antibiotics. LL-37 and its derivative peptides have shown promising in vivo antibacterial activity. This study evaluated whether these peptides improve bacterial clearance, wound healing, and survival compared with controls in animal models of MRSA infection. Methods: The literature search was last updated on 21 April 2026. A systematic search of PubMed, Scopus, and Embase was conducted to identify preclinical studies assessing the antibacterial activity of LL-37 and its derivatives in MRSA animal infection models. Guided by PRISMA, 1,014 unique records were screened after removing 368 duplicates; 23 studies met the inclusion criteria, and 16 were included in the qualitative synthesis. Four studies (one comprising three independent experiments) provided sufficient data for meta-analysis. Extracted variables included sample size, bacterial counts (mean ± SD), and intervention/control details. Standardized mean differences (Hedges' g) were calculated using a random-effects model, and study quality was assessed using SYRCLE's risk-of-bias tool. Results: The meta-analysis of bacterial clearance pooled data from six independent experimental results (n = 44 animals). LL-37 and its derivatives achieved markedly greater bacterial eradication than controls, yielding a pooled standardized mean difference (SMD) of -7.86 (95% CI: -9.40 to -6.33; P < 0.001). All studies favoured LL-37, with no confidence intervals crossing zero. Heterogeneity was negligible (I² = 0%, τ² < 0.0001, P = 0.645), and the prediction interval (-9.74 to -5.99) indicated consistently large effects across similar experimental contexts. For wound healing (binary outcome), pooled analysis showed that LL-37 significantly increased complete wound closure rates compared with controls, with a pooled risk ratio (RR) of 1.25 (95% CI: 1.16-1.36). The pooled proportion of healed wounds was 89.3% in the LL-37 groups versus 70.0% in controls, indicating a clinically relevant improvement. Conclusions: LL-37 and its derivative peptides demonstrate robust antibacterial activity and significantly enhance wound healing in MRSA-infected animal models. The large and consistent effects observed across studies support their advancement toward translational research and early-phase clinical trials for potential human therapeutic use.

Abstract: European regions aim to achieve climate neutrality. This requires the improvement of the carbon efficiency of their energy systems despite the substantial differences in climate conditions and economic structure. This study investigates whether carbon intensity converges across European NUTS-2 regions and examines the role of climate-driven energy demand and spatial interactions in the regional energy transition. Specifically, we use panel data from the period 2000–2024 and investigate the conditional β-convergence based on two-way fixed effects and spatial panel models. The results reveal significant convergence, persistent spatial dependence and slower adjustment in regions with initially high carbon intensity. Climate-driven energy demand, labor market conditions and industrial structure significantly affect the convergence process. These findings highlight the importance of place-based energy transition policies that account for regional heterogeneity and spatial spillovers to accelerate decarbonization.

Abstract: HIV-associated neurocognitive disorders (HAND) involve persistent central nervous system (CNS) viral reservoirs in microglia, driving chronic neuroinflammation, synaptic dysfunction, and neuronal injury. Thus, scalable, human-relevant multicellular CNS models are needed to elucidate neuroHIV pathogenesis and ART neurotoxicity. Here, we establish and characterize a fully human iPSC-derived (hiPSC) CNS tri-culture platform comprising isogenic neurons, astrocytes, and microglia that remains viable and functionally active for up to 32 days in vitro. Using a microglia-tropic fluorescent HIV reporter virus, GFP-HIV-AD8, we demonstrate selective infection of microglia with no detectable neuronal infection, consistent with human neuroHIV. HIV replication was quantified over 14 days post-infection and effectively suppressed by the first-generation integrase strand transfer inhibitor (INSTI)-containing regimen elvitegravir/tenofovir disoproxil fumarate/emtricitabine (EVG/TDF/FTC), and the second-generation INSTI-containing regimens dolutegravir/tenofovir disoproxil fumarate/emtricitabine (DTG/TDF/FTC) and bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC), at clinically achievable concentrations. HIV infection reduced microglial viability by approximately 70%, partially rescued by low-dose ART but worsened by high-dose DTG-containing regimens, suggesting concentration-dependent toxicity. In uninfected cultures, DTG induced microglial morphological changes consistent with a reactive or dysfunctional state. Calcium imaging revealed ART-specific neuronal effects: EVG/TDF/FTC reduced neuronal activity, whereas BIC/TAF/FTC enhanced it. In HIV-infected cultures, DTG shortened neuronal spike duration, suggesting HIV–ART interactions on synaptic physiology. Overall, second-generation INSTIs, particularly BIC/TAF/FTC, showed the most favorable CNS safety profile. Together, these findings establish a scalable iPSC-derived CNS tri-culture model for neuroHIV research, ART efficacy testing, and neurotoxicity assessment.