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22 pages, 2333 KB  
Review
Reframing Rehabilitation Retention in Long-Term Conditions: A Theory-Informed Mini-Review of Psychological Adaptation and Engagement
by Mohammad Khoshraftar, Zahra Karimi, Lyudmila S. Yermukhanova, Nurbakyt Ardak and Alireza Afshar
Healthcare 2026, 14(17), 2697; https://doi.org/10.3390/healthcare14172697 (registering DOI) - 24 Aug 2026
Abstract
Rehabilitation in long-term conditions requires not only clinical capacity but also sustained patient engagement, yet retention is commonly reduced to crude completion metrics. This theory-informed conceptual mini-review used a purposive, non-systematic synthesis of literature identified from the authors’ existing knowledge base, targeted PubMed/MEDLINE [...] Read more.
Rehabilitation in long-term conditions requires not only clinical capacity but also sustained patient engagement, yet retention is commonly reduced to crude completion metrics. This theory-informed conceptual mini-review used a purposive, non-systematic synthesis of literature identified from the authors’ existing knowledge base, targeted PubMed/MEDLINE searches last updated on 9 August 2026, and backward reference checking; the final article cites 76 sources. Retention is reframed as six related phases comprising referral and eligibility, uptake or initiation, early attendance, ongoing attendance or dose, completion or planned discharge, and post-program maintenance, while time to dropout is treated as a longitudinal metric. Across these phases, disengagement may reflect interactions among clinical severity, symptom interpretation, illness beliefs, distress, motivational climate, therapeutic relationships, social context, and structural access. Four author-generated hypotheses concern psychological flexibility and acceptance, illness coherence and rehabilitation self-efficacy, autonomy-supportive care and therapeutic alliance, and social support and peer belonging. Direct evidence is concentrated in selected rehabilitation settings, whereas several stage-specific and cross-condition pathways remain theoretical extrapolations. Rehabilitation resilience is therefore proposed as a provisional interaction between patient adaptive resources and responsive care systems, not as a validated trait or a synonym for observable retention. Structural barriers may prevent participation directly, and discontinuation may be appropriate when treatment is unsafe, ineffective, burdensome, or inconsistent with informed patient goals. The framework is intended to guide prospective, condition-specific testing rather than imply causal validation or scientific consensus. Full article
(This article belongs to the Special Issue Healthcare Resilience and Patient Adherence in Rehabilitation)
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13 pages, 232 KB  
Article
Study of Microbial Contamination of Mobile Phones of Dental and Medical Students and Its Potential Epidemiological Implications for Microbial Transmission
by Veselina Kondeva, Velina Stoeva, Yordan Kalchev and Rumyana Stoyanova
Life 2026, 16(9), 1394; https://doi.org/10.3390/life16091394 (registering DOI) - 24 Aug 2026
Abstract
Background: Mobile phones are widely used by healthcare students during clinical training and may act as potential reservoirs for pathogenic microorganisms. Objectives: This study aimed to investigate and evaluate the role of mobile phones as epidemiological factors in the transmission of microorganisms in [...] Read more.
Background: Mobile phones are widely used by healthcare students during clinical training and may act as potential reservoirs for pathogenic microorganisms. Objectives: This study aimed to investigate and evaluate the role of mobile phones as epidemiological factors in the transmission of microorganisms in medical and dental practice. Methods: A cross-sectional epidemiological and microbiological study was conducted between September 2025 and April 2026. A total of 125 mobile phones belonging to fourth-year dental students and fifth-year medical students were examined. Samples were collected from the entire phone surface and cultured on blood agar, eosin–methylene blue agar, and Candida chromogenic agar. Participants also completed a structured questionnaire assessing demographic characteristics, clinical experience, hand hygiene practices, and mobile phone use and cleaning habits. Results: No microbial growth was detected in 52.8% of samples on blood agar, while 44.8% showed growth below 105 CFU of coagulase-negative staphylococci and 2.4% showed growth ≥105 CFU. Minimal growth was detected on eosin–methylene blue agar (0.8%). Fungal contamination was identified in 2.4% of samples, exclusively among students who reported touching their phones with contaminated gloves. Statistically significant associations were observed between microbiological growth and students’ specialty, duration of clinical experience, and contact with mobile phones while wearing contaminated gloves (p < 0.05). Conclusions: Touching mobile phones with contaminated gloves was significantly associated with microbial growth. These findings emphasize the need for targeted infection control education and stricter guidelines regarding mobile device use during clinical training. Full article
(This article belongs to the Section Epidemiology)
17 pages, 3682 KB  
Article
Dietary Sea Buckthorn Polysaccharide Supplementation Enhances Antioxidant Capacity, Modulates Inflammatory Cytokines, and Alters the Serum Metabolome in Tumbler Pigeons
by Hui Chen, Qiming Zheng, Haiying Li, Chen Ma, Xiaobin Li, Xinsheng Guo and Kunyu Liao
Animals 2026, 16(17), 2652; https://doi.org/10.3390/ani16172652 (registering DOI) - 24 Aug 2026
Abstract
Sea buckthorn polysaccharide (SP) has antioxidant and anti-inflammatory activities, but its effects in tumbler pigeons remain unclear. Eighty-four male tumbler pigeons were assigned to four treatments receiving diets containing 0, 100, 200, or 400 mg/kg effective SP for 60 days, with seven replicate [...] Read more.
Sea buckthorn polysaccharide (SP) has antioxidant and anti-inflammatory activities, but its effects in tumbler pigeons remain unclear. Eighty-four male tumbler pigeons were assigned to four treatments receiving diets containing 0, 100, 200, or 400 mg/kg effective SP for 60 days, with seven replicate cages per treatment. SP supplementation enhanced serum antioxidant capacity and modulated inflammatory cytokine profiles, with the most pronounced overall responses observed at 200 mg/kg. The SP200 and SP400 groups also had lower serum lactate, total cholesterol, and triglyceride concentrations than the control group, whereas most blood gas, electrolyte, and acid–base variables were unaffected. Because SP200 produced the strongest antioxidant and cytokine responses, the CON and SP200 groups were selected for untargeted serum metabolomics. This analysis identified 68 and 79 differential metabolites in positive- and negative-ion modes, respectively. KEGG enrichment analysis ranked purine metabolism, phenylalanine metabolism, primary bile acid biosynthesis, and the citrate cycle among the leading pathways; however, none remained significant after Benjamini–Hochberg correction. Exploratory Spearman analysis revealed associations between selected metabolites and phenotypic indicators. Taken together, these findings indicate that 200 mg/kg SP may be an effective dietary supplementation level for improving antioxidant and inflammatory status in tumbler pigeons, while the associated metabolomic changes warrant further targeted validation. Full article
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22 pages, 3025 KB  
Article
Beyond Coupling-Coordination Scores: Relative Digital-Transport Alignment and Urban Environmental Services in China
by Xiangzhang Zhao, Sujun Shao and Yu Zhang
Sustainability 2026, 18(17), 8655; https://doi.org/10.3390/su18178655 (registering DOI) - 24 Aug 2026
Abstract
Coupling-coordination degree (CCD) indices are often interpreted as evidence that urban systems are developing in a mutually supportive manner. The standard formula, however, combines similarity between subsystem scores with their average level. This article evaluates those two components against the following external outcome: [...] Read more.
Coupling-coordination degree (CCD) indices are often interpreted as evidence that urban systems are developing in a mutually supportive manner. The standard formula, however, combines similarity between subsystem scores with their average level. This article evaluates those two components against the following external outcome: municipal environmental services. A city panel for China in 2002–2024 combines broadband and mobile adoption, urban road provision, licensed internet data-center records, and seven indicators of water, gas, drainage, sewage, waste, and urban greening. The preferred sample contains 6094 observations for 275 cities in 28 provinces. We estimate city fixed-effect models with province-by-year fixed effects and report province-clustered, two-way-clustered, and 9999-repetition wild-cluster-bootstrap inference. In the baseline rank-based construction, a one-standard-deviation increase in relative digital-transport alignment is associated with a 0.046-standard-deviation increase in the environmental-service index (wild-bootstrap p = 0.042), whereas the portfolio-level coefficient is 0.191 (p < 0.001). The alignment estimate is concentrated in water and gas access and is not robust to complete-component outcomes, PCA or entropy weighting, logarithmic standardization, road density, or lags beyond one year. Portfolio level remains positive across these tests, although lead and reverse-direction estimates preclude causal interpretation. The findings show why infrastructure scale, relative configuration, and realized service outcomes should be monitored separately. For SDGs 9 and 11, city governments should target documented service bottlenecks and operating capacity rather than maximize a composite coordination score. Full article
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19 pages, 6620 KB  
Article
Altered Excitation–Inhibition Balance and mGluR1/5-Driven Plasticity in the Motor Cortical Surface in a Rat Model of Parkinson’s Disease
by Hongseong Shin, Yoon Ji Kwon, Hyunjung Hwang, Taewoo Ko, Eun Bi Choi, Yang Tae Kim, Yu Mi Han, Jae Geun Kim, Qiang Zhou, Sungchil Yang and Sunggu Yang
Int. J. Mol. Sci. 2026, 27(17), 7564; https://doi.org/10.3390/ijms27177564 (registering DOI) - 24 Aug 2026
Abstract
Parkinson’s disease (PD) is characterized by progressive dopaminergic degeneration and maladaptive motor cortical plasticity. However, the cellular pathways underlying cortical surface activity in the primary motor cortex (M1) remain unclear, despite serving as a potential target for electrotherapy. We investigated the excitatory–inhibitory (E-I) [...] Read more.
Parkinson’s disease (PD) is characterized by progressive dopaminergic degeneration and maladaptive motor cortical plasticity. However, the cellular pathways underlying cortical surface activity in the primary motor cortex (M1) remain unclear, despite serving as a potential target for electrotherapy. We investigated the excitatory–inhibitory (E-I) balance and synaptic plasticity of superficial M1 circuits in a unilateral 6-hydroxydopamine (6-OHDA)-induced rat model of PD. Using extracellular local field potential and whole-cell patch recordings from the contralateral and ipsilateral M1 hemispheres of hemi-parkinsonian rats, we observed a significantly elevated field excitatory postsynaptic potential (fEPSP) input–output function but unchanged intrinsic neuronal excitability in the M1 superficial layer. An altered relative contribution between alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and N-methyl-D-aspartate receptor (NMDAR)-mediated transmission was reflected by a significantly increased AMPA/NMDA ratio. Markedly reduced inhibitory synaptic tone was also evidenced by the decreased amplitude and frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), supporting an E-I imbalance favoring excitation in PD. Furthermore, group I metabotropic glutamate receptor (mGluR1/5)-dependent long-term depression (LTD) was abolished in the ipsilateral PD hemisphere, whereas NMDAR-dependent LTD remained intact. In summary, dopamine depletion appears to enhance network excitation and disrupt mGluR1/5-mediated control of M1 surface circuitry. Our findings identify altered cortical surface mGluR-dependent plasticity in the hemi-parkinsonian model; however, the relationship between these electrophysiological alterations and individual motor outcomes remains to be determined. Full article
(This article belongs to the Section Molecular Neurobiology)
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21 pages, 11784 KB  
Article
Feedforward Unsteady Lift Hysteresis Compensation of Variable Camber Wing Based on Prandtl–Ishlinskii Model
by Xiaoming Wang, Junyue Chen, Hao Wang, Xinhan Hu and Wenya Zhou
Mathematics 2026, 14(17), 3043; https://doi.org/10.3390/math14173043 (registering DOI) - 24 Aug 2026
Abstract
The maneuvering flight of future aircraft which employ morphing variable camber wings (VCWs) requires rapid and accurate aerodynamic regulation. However, the dynamic lift responses during fast morphing deflection exhibit unsteady hysteresis effects, hindering shape and flight control performance. This study proposes a novel [...] Read more.
The maneuvering flight of future aircraft which employ morphing variable camber wings (VCWs) requires rapid and accurate aerodynamic regulation. However, the dynamic lift responses during fast morphing deflection exhibit unsteady hysteresis effects, hindering shape and flight control performance. This study proposes a novel modeling and feedforward compensation algorithm based on the Prandtl–Ishlinskii (PI) model to identify and mitigate such unsteady hysteresis effects from a control perspective. First, unsteady lift responses of a two-dimensional trailing-edge VCW under periodic and non-periodic morphing motions are analyzed, and the influences of morphing trajectories on lift characteristics are investigated. The results reveal that the maximum lift decreases significantly as the morphing frequency increases. Under point-to-point non-periodic morphing conditions, pronounced hysteretic lift responses are observed and are strongly influenced by the morphing trajectories. A forward model mapping “morphing trajectory-lift response” is developed using PI hysteresis operators and log(t)-creep operators, identified using time-domain data from two-dimensional computational fluid dynamics (CFD) calculations. From this, an inverse model of the “expected lift response-compensated morphing trajectory” is derived using a hysteresis compensation function. Simulations indicate that periodic lift hysteresis is effectively compensated, yielding a quasi-steady linear relationship. For fast terminal morphing, compensated trajectories enable lift to reach targets rapidly, smoothly, and stably without lag. Robustness is validated for varying lift targets and terminal times. This work offers new insights into fast morphing-wing and high-maneuverability control of future smart aircraft. Full article
(This article belongs to the Special Issue Advances in Flight Dynamics Modeling and Control)
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22 pages, 5016 KB  
Article
Impact of Physico-Chemical Heterogeneity on the Reactive Transport Processes of Chromium (VI) in the Porous Medium
by Shuping Yi, Yi Liu, Pizhu Huang, Yi Deng and Zhiren Tian
Hydrology 2026, 13(9), 229; https://doi.org/10.3390/hydrology13090229 (registering DOI) - 24 Aug 2026
Abstract
The reactive transport of hexavalent chromium (Cr(VI)) in anthropogenically disturbed sites (e.g., mine waste rock dumps, chromium salt industrial sites) is critically influenced by physico-chemical heterogeneity, yet the interplay between physical and chemical heterogeneities remains poorly understood. This study employed a series of [...] Read more.
The reactive transport of hexavalent chromium (Cr(VI)) in anthropogenically disturbed sites (e.g., mine waste rock dumps, chromium salt industrial sites) is critically influenced by physico-chemical heterogeneity, yet the interplay between physical and chemical heterogeneities remains poorly understood. This study employed a series of experiments and numerical modeling to investigate the transport of Cr(VI), focusing on the implications of physical heterogeneity—represented by preferential flow paths—and chemical heterogeneity—characterized by reductive mineral lenses. Key findings indicate that physical heterogeneity accelerates Cr(VI) breakthrough by 1.4 to 2.1 pore volumes (PV) relative to homogeneous columns. The presence of pyrite lenses delays breakthrough by 0.6–1.2 PV under neutral pH and 1.6–2.0 PV under acidic pH. At a flow rate of 3.0 m/day, the apparent sorption capacity decreases by ~62.5% compared to 0.3 m/day, indicating that physical advection largely suppresses chemical retention under high-flux conditions. The above results demonstrate that physical heterogeneity governs flow paths and advection rates, whereas chemical heterogeneity impedes transport through heterogeneous adsorption and reduction in Cr(VI) to Cr(III) along these pathways. Furthermore, the presence of preferential paths leads to greater spatial variability, which subsequently influences the interaction dynamics between Cr(VI) and reactive minerals in the aqueous environment. The dominance shifts between physical/chemical controls based on flow rates and pH. At higher flow rates, the influence of physical heterogeneity becomes more pronounced, diminishing chemical reactions due to insufficient residence time of Cr(VI). Conversely, a lower pH environment enhances pyrite dissolution, which decouples the dependency on physical heterogeneity by promoting homogeneous reactions. Further evidence was obtained through X-ray photoelectron spectroscopy (XPS) analysis. The experimental observations are complemented by TOUGHREACT-based reactive transport simulations, which further reveal that the apparent dominance shifts arise from competing timescales between advection and surface reaction. The insights gained from the study emphasize the necessity of integrating both physical and chemical spatial variability in risk assessments, transport modeling, and designing targeted remediation strategies. Full article
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20 pages, 22108 KB  
Article
Aerosol Optical Depth Retrieval from MODIS Using a Physically Informed Machine Learning Framework
by Tianchen Liang, Linqing Zou, Qiaoning He and Lin Sun
Remote Sens. 2026, 18(17), 2862; https://doi.org/10.3390/rs18172862 (registering DOI) - 24 Aug 2026
Abstract
Retrieving aerosol optical depth (AOD) over land remains challenging because the relatively weak aerosol signal in top-of-atmosphere (TOA) observations must be separated from strong and spatially heterogeneous surface reflectance. Here, we develop a physically informed random forest framework for global 1 km land [...] Read more.
Retrieving aerosol optical depth (AOD) over land remains challenging because the relatively weak aerosol signal in top-of-atmosphere (TOA) observations must be separated from strong and spatially heterogeneous surface reflectance. Here, we develop a physically informed random forest framework for global 1 km land AOD retrieval from MODIS. The framework integrates multispectral TOA reflectance, surface properties, observation geometry, meteorological conditions, topography, and physically informed aerosol–surface features. Long-term Aerosol Robotic Network (AERONET) observations from 2001 to 2017 were collocated with MODIS and ancillary datasets for model development and evaluation. Two physically informed features were introduced to improve retrieval robustness across diverse aerosol and surface conditions, including minimum AOD derived from long-term AERONET observations and time-series clear-sky reflectance (TSCR) in the blue, red, and shortwave-infrared bands derived using the 6S radiative-transfer model. Independent retrieval evaluation for 2013–2014 showed good agreement with AERONET observations, with R = 0.81, MAE = 0.063, RMSE = 0.096, and 74.93% of matched samples falling within the MODIS land expected-error envelope, although increasing underestimation was observed at high aerosol loading (AOD > 1). The proposed retrievals also showed better agreement with AERONET than the MOD04 Dark Target and Deep Blue products. These results demonstrate the value of incorporating physically interpretable aerosol-background and surface-reflectance information into data-driven retrievals for AOD over land surfaces. Full article
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23 pages, 10288 KB  
Article
Real-World Antidepressant Prescribing Patterns and Comparative Safety Outcomes of Commonly Prescribed Antidepressants in Patients with Depressive Disorder: A Multicenter OMOP-CDM Study
by Jungha Min, Sueun Shin, Sohyeon Park, Jeongha Yun, Kaylnn Park and Sandy Jeong Rhie
Pharmaceuticals 2026, 19(9), 1332; https://doi.org/10.3390/ph19091332 - 24 Aug 2026
Abstract
Background/Objectives: Real-world antidepressant use for depressive disorder varies across clinical settings. This study aimed to characterize prescribing pathways and evaluate the comparative safety of frequently prescribed antidepressants in a large multicenter cohort with newly diagnosed depressive disorder. Methods: We conducted a [...] Read more.
Background/Objectives: Real-world antidepressant use for depressive disorder varies across clinical settings. This study aimed to characterize prescribing pathways and evaluate the comparative safety of frequently prescribed antidepressants in a large multicenter cohort with newly diagnosed depressive disorder. Methods: We conducted a retrospective multicenter observational study using electronic health record data standardized to the OMOP Common Data Model (1999–2026) in adults initiating antidepressants. Prescribing patterns among 13,381 patients were visualized using sunburst plots and Sankey diagrams. Comparative safety, escitalopram vs. sertraline and trazodone, was evaluated across 18 hospitals (n = 44,542) for nine clinical safety outcomes using propensity score-matched Cox proportional hazards models and empirically calibrated random-effects meta-analysis. Results: Selective serotonin reuptake inhibitors, particularly escitalopram (21.4%, n = 2868), were the preferred antidepressant. Common adjunctive medications included trazodone (14.6%, n = 794) and quetiapine (14.0%, n = 761), though utilization varied across hospitals. No clear differences were detected for most safety outcomes between cohorts. However, empirically calibrated QTc prolongation risk was significantly increased with sertraline relative to escitalopram (HR 1.75, 95% CI 1.10–2.78), a signal requiring further confirmation. Conclusions: This study demonstrates substantial institutional variation exists in real-world antidepressant treatment pathways and combination strategies. While comparative safety profiles were broadly comparable across evaluated outcomes, the isolated QTc prolongation signal for sertraline warrants targeted external confirmation. Furthermore, trazodone and escitalopram cohorts should not be regarded as clinically interchangeable first-line options, supporting individualized, evidence-based antidepressant selection in routine clinical practice. Full article
(This article belongs to the Section Pharmacology)
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23 pages, 2290 KB  
Review
The Role of Monoclonal Antibody Targeted Therapy (Panitumumab) in the Treatment of Metastatic Colorectal Cancer—A Narrative Review of Current Evidence and Emerging Therapeutic Strategies
by Lidia Kwiatkowska and Małgorzata Szczuko
Int. J. Mol. Sci. 2026, 27(17), 7559; https://doi.org/10.3390/ijms27177559 (registering DOI) - 24 Aug 2026
Abstract
Metastatic colorectal cancer (mCRC) remains one of the leading causes of cancer deaths worldwide. Mutations of the RAS and BRAF genes and the location of the primary tumor determine the choice of systemic therapy. Panitumumab—a fully human anti-EGFR monoclonal antibody—is well-established in the [...] Read more.
Metastatic colorectal cancer (mCRC) remains one of the leading causes of cancer deaths worldwide. Mutations of the RAS and BRAF genes and the location of the primary tumor determine the choice of systemic therapy. Panitumumab—a fully human anti-EGFR monoclonal antibody—is well-established in the treatment of patients with wild-type RAS and BRAF and left-sided tumor localization. The aim of this review is to summarize the role and potential of targeted therapies for colorectal cancer with monoclonal antibodies such as panitumumab or cetuximab, to provide current evidence on the position of panitumumab in the treatment of mCRC, and to discuss biomarkers and qualification strategies for targeted therapy, including the role of ctDNA in disease monitoring and rechallenge. The work is based on a narrative review of literature from the PubMed, Scopus, Web of Science and Google Scholar databases, including publications available until May 2026. The efficacy of panitumumab was confirmed in phase III studies: first-line (PRIME: prolongation of OS by 5.6 months) and second-line treatment. A key condition for eligibility is complete RAS and BRAF genotyping, assessment of MSI/dMMR status, HER2 amplification, and tumor location. ctDNA analysis enables monitoring of tumor clonal evolution and qualification for rechallenge—the CHRONOS study showed 30% objective responses with liquid biopsy-based selection. Associations with BRAF/MEK and KRAS G12C inhibitors and modulation of the immune microenvironment via the CCL5/CCR5 axis remain promising directions. Panitumumab occupies an important position in the treatment of patients with mCRC, but increasingly precise molecular stratification and dynamic monitoring of disease with ctDNA are becoming the basis for the effective and rational use of the drug. Unlike reviews that selectively focus on individual aspects of anti-EGFR therapy, the following work integrates all aspects: from molecular biology and biomarkers used to qualify patients to clinical data on panitumumab and new strategies in the fight against mCRC. Further development of next-generation sequencing methods and standardization of ctDNA panels will be crucial for the widespread deployment of targeted therapies in everyday clinical practice. The role of panitumumab is well established in appropriately selected patients with RAS wild-type, particularly left-sided, metastatic colorectal cancer (mCRC). Combining panitumumab with immune checkpoint inhibitors warrants further investigation, particularly in patients with MSS/pMMR mCRC. The observed activity of panitumumab in combination with nivolumab and ipilimumab provides a rationale for further clinical evaluation and monitoring. Full article
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20 pages, 2441 KB  
Article
Discharge Simulation Evaluations of ISIMIP3a Global Hydrological Models in the Yangtze River Basin
by Wei Qi, Libin Lu, Yanpeng Cai and Qian Tan
Water 2026, 18(17), 2076; https://doi.org/10.3390/w18172076 - 24 Aug 2026
Abstract
Global hydrological models (GHMs) are essential for assessing water resources and flood risk, yet systematic evaluations of ISIMIP3a models remain limited. We evaluated eight standard ISIMIP3a GHM configurations against observed discharge at four principal Yangtze mainstem gauges using a multi-metric framework covering daily [...] Read more.
Global hydrological models (GHMs) are essential for assessing water resources and flood risk, yet systematic evaluations of ISIMIP3a models remain limited. We evaluated eight standard ISIMIP3a GHM configurations against observed discharge at four principal Yangtze mainstem gauges using a multi-metric framework covering daily and monthly discharge, the seasonal cycle (defined as the mean annual cycle of monthly discharge), flow percentiles, and annual peak discharge. Metric-based model performance generally increased from daily to monthly and seasonal-cycle scales, partly reflecting the smoothing of short-term errors through temporal aggregation, whereas annual peak discharge remained more difficult to reproduce. WaterGAP2-2e achieved the strongest overall performance across the daily, monthly, and seasonal-cycle evaluations. However, this result was not fully independent of its inherited global discharge calibration, because three evaluation gauges (Yichang, Hankou, and Datong) spatially coincide with gauges in its calibration-station dataset. WaterGAP2-2e also systematically overestimated peak flows, with peak-flow Relative Bias (RBpeak) reaching 30.14%. Among the remaining configurations, WEB-DHM-SG showed the strongest overall performance and a relatively small station-averaged absolute peak-flow bias (|RBpeak| = 15.52%). However, this advantage did not extend to low-flow conditions. H08 and ORCHIDEE-MICT showed the weakest overall performance, with negative NSE values down to −3.61 and peak-flow biases reaching −99.10%, whereas MIROC-INTEG-LAND, CWatM, HydroPy, and JULES-W2-DDM30 showed intermediate performance. Overall, model suitability depended on temporal scale and flow regime, and apparent rankings should be interpreted in light of inherited calibration and configuration differences. These results provide a diagnostic basis for model selection and targeted improvement in regional discharge simulation and peak-flow-related applications. Full article
(This article belongs to the Special Issue Development and Application of Global Hydrological Models)
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31 pages, 1509 KB  
Review
The Next Frontiers in Stroke Prevention: Optimizing Left Atrial Appendage Closure in Atrial Fibrillation: Current Devices, Imaging-Guided Strategies, and Emerging Approaches
by Zain Al-Abdeen Mohammed Qassim, Mohamedanas Mohamedfaruk Patni, Biji Thomas George, Subhranshu Sekhar Kar, Rajani Dube, Reema Mohammed Saeed Al Shaibani, Ghina Hasan Yassin, Yara Mamoun Theyabat, Ibrahim Alabid and Malak Mohammed Qassim
J. Clin. Med. 2026, 15(17), 6526; https://doi.org/10.3390/jcm15176526 (registering DOI) - 24 Aug 2026
Abstract
Background/Objectives: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with ischemic stroke, systemic thromboembolism, heart failure, and mortality. Although oral anticoagulation (OAC) remains the cornerstone of stroke prevention, long-term therapy may be limited by bleeding risk, contraindications, [...] Read more.
Background/Objectives: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with ischemic stroke, systemic thromboembolism, heart failure, and mortality. Although oral anticoagulation (OAC) remains the cornerstone of stroke prevention, long-term therapy may be limited by bleeding risk, contraindications, intolerance, nonadherence, or thromboembolic events despite treatment. Left atrial appendage closure (LAAC) has therefore emerged as a non-pharmacological alternative for selected patients with nonvalvular AF. This review aimed to synthesize current evidence on LAAC, focusing on comparative efficacy versus OAC, device evolution, imaging-guided strategies, antithrombotic management, procedural optimization, unresolved challenges, and emerging technologies. Methods: This state-of-the-art narrative review was informed by targeted, non-systematic searches of PubMed and Scopus for publications from January 2009 to June 2026. Evidence was selected purposively to represent clinically relevant guidelines, randomized trials, registries, comparative observational studies, systematic reviews, meta-analyses, imaging studies, device-comparison studies, and reports of emerging technologies. The selected evidence was synthesized narratively; no exhaustive screening process, PRISMA flow diagram, formal risk-of-bias assessment, or quantitative synthesis was performed. Results: Randomized evidence was context dependent. OPTION supported LAAC as an alternative to oral anticoagulation in selected anticoagulation-eligible patients undergoing atrial fibrillation ablation. CHAMPION-AF established noninferiority of Watchman FLX to non–vitamin K antagonist oral anticoagulants for its composite efficacy endpoint in a predominantly moderate-risk, anticoagulation-eligible population and demonstrated less non-procedural bleeding, although ischemic stroke occurred numerically more often after LAAC. In contrast, CLOSURE-AF did not establish noninferiority of LAAC to physician-directed medical therapy in an older population at high risks of both stroke and bleeding. These findings indicate that the comparative value of LAAC depends strongly on patient selection, comparator therapy, endpoint composition, procedural risk, and trial design. Observational, registry, and emerging evidence was considered supportive or hypothesis-generating rather than equivalent to randomized evidence. OPTION enrolled only patients undergoing or recently undergoing AF ablation who were suitable for anticoagulation. CHAMPION-AF included 3000 anticoagulation-eligible patients but had relatively low baseline bleeding risk, while CLOSURE-AF studied 912 substantially older, higher-risk patients and did not meet its noninferiority criterion. Conclusions: LAAC has evolved into a precision-guided intervention integrating patient risk, left atrial appendage anatomy, device choice, imaging, antithrombotic therapy, and structured surveillance. Further studies are needed to optimize patient selection, standardize post-procedural therapy, and clarify its long-term role compared with contemporary direct oral anticoagulant therapy. Full article
(This article belongs to the Special Issue Advances in Cardiac Surgery: Techniques, Outcomes, and Innovations)
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15 pages, 2359 KB  
Article
Functional Characterization of Putative Novel MicroRNA-1133 in the Antioxidant Effects of Metformin in Hyperglycemia-Induced Endothelial Cells
by Nur Syakirah Othman, Amilia Aminuddin, Adila A. Hamid, Shahidee Zainal Abidin, Saiful Effendi Syafruddin, Mohd Faizal Ahmad, Farah Hanan Fathihah Jaffar, Nur Athirah Othman Basri and Azizah Ugusman
Int. J. Mol. Sci. 2026, 27(17), 7556; https://doi.org/10.3390/ijms27177556 (registering DOI) - 24 Aug 2026
Abstract
Diabetes mellitus induces endothelial dysfunction and oxidative stress, contributing to the development of vascular complications. Although metformin exerts well-established vasculoprotective and antioxidant effects, the molecular mechanisms underlying these actions remain incompletely understood. Novel miR-1133 was previously identified as a metformin-responsive putative microRNA (miRNA), [...] Read more.
Diabetes mellitus induces endothelial dysfunction and oxidative stress, contributing to the development of vascular complications. Although metformin exerts well-established vasculoprotective and antioxidant effects, the molecular mechanisms underlying these actions remain incompletely understood. Novel miR-1133 was previously identified as a metformin-responsive putative microRNA (miRNA), and bioinformatic analysis identified PIK3CA as a biologically plausible candidate target for further investigation. This study investigated the functional significance of novel miR-1133 in the antioxidant effects of metformin in hyperglycemia-induced human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to normal glucose (5.5 mmol/L), hyperglycemia (33.3 mmol/L), or hyperglycemia supplemented with metformin (10 μM) for 24 h. Metformin-treated hyperglycemic HUVECs were subsequently transfected with a novel miR-1133 mimic during continued hyperglycemic and metformin exposure. PIK3CA expression and oxidative stress markers, including reactive oxygen species (ROS), superoxide dismutase (SOD), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), were evaluated. Hyperglycemia increased novel miR-1133 expression, whereas metformin reduced its expression. Metformin treatment was associated with increased PIK3CA mRNA and protein expression, reduced ROS and 8-OHdG levels, and increased SOD expression and activity. Novel miR-1133 mimic transfection was associated with reduced PIK3CA expression, increased ROS and 8-OHdG levels, and decreased SOD expression and activity compared with the corresponding transfection control. Collectively, these findings demonstrate that metformin attenuates oxidative stress in hyperglycemia-induced endothelial cells and overall provide the first functional characterization of novel miR-1133. The reciprocal changes in PIK3CA expression and oxidative stress observed following novel miR-1133 mimic transfection suggest that novel miR-1133 may represent a candidate mediator of the endothelial antioxidant responses associated with metformin. Further studies are required to validate the direct interaction between novel miR-1133 and PIK3CA and to elucidate the underlying molecular mechanisms. Full article
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14 pages, 1335 KB  
Article
Docosahexaenoic Acid (DHA) Deficiency in Breast Milk: A Cross-Sectional Study of Lactating Women in Serbia, Montenegro, and North Macedonia
by Tena Niseteo, Ana Ilić, Nevena Cupara, Dijana Đurović, Maja Dimitrovska, Lidija Poček, Marina Pop Lazarova and Jelena Martić
Nutrients 2026, 18(17), 2761; https://doi.org/10.3390/nu18172761 (registering DOI) - 24 Aug 2026
Abstract
Background/Objectives: Docosahexaenoic acid (DHA) is an essential component of breast milk for infant neurocognitive and visual development. Because DHA depends largely on dietary intake, women with low seafood consumption are at increased risk of inadequate DHA contents in breast milk. This study [...] Read more.
Background/Objectives: Docosahexaenoic acid (DHA) is an essential component of breast milk for infant neurocognitive and visual development. Because DHA depends largely on dietary intake, women with low seafood consumption are at increased risk of inadequate DHA contents in breast milk. This study aims to quantify the DHA content in breast milk and assess how recommended dietary supplementation during lactation affects these contents among lactating women in three Balkan countries. Methods: This cross-sectional multicenter study included 128 lactating women (18–35 years). Dietary intake of DHA was assessed using a modified Food Frequency Questionnaire. DHA in breast milk was measured by gas chromatography following standard protocols. Both the FFQ and breast milk samples were collected at two time points: 20–40 (visit 1—V1) and 80–100 days (visit2—V2) postpartum. Results: In lactating women, seafood intake was low (Visit 1: 37.5 (0.0–93.8) g/week), meeting about 28% of the recommended amount, with some variation between countries. Consequently, the mean dietary n-3 PUFA and DHA intake for the total sample was less than 50% and 5% of the recommended daily allowance, respectively. Correlation analysis indicates that DHA content in breast milk is related to dietary DHA intake (Visit 1: r = 0.258, p = 0.001; Visit 2: r = 0.238, p = 0.012). DHA contents failed to reach the 0.3% clinical threshold for optimal neurodevelopment, with average levels ranging from 0.149 to 0.165%. Furthermore, no significant differences were observed between supplemented and unsupplemented women at either time point, highlighting a persistent regional deficit regardless of supplementation status. Conclusions: Lactating women in the Balkan region have a low dietary intake of n-3 PUFA and DHA, which is reflected in the breast milk lipid profile, regardless of standard supplementation. These findings highlight the need for a targeted nutritional strategy both via nutrition and supplementation to improve DHA intake in lactating women, but more importantly in infants. Full article
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14 pages, 548 KB  
Article
Pharmacokinetics of Isavuconazole in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation (ECMO) Support: A Prospective Exploratory Observational Study
by Alba Escolà-Rodríguez, Elena Sandoval, Jorge Moisés, Adrián Téllez Santoyo, Albert Carramiñana, Jaime I. Sainz de Medrano, Cristina Espinosa, Carlos Roca, Marta Hernández Meneses, Sabina Herrera, Mercè Brunet Serra, Pedro Castro, Dolors Soy Muner and Carla Bastida
Pharmaceutics 2026, 18(9), 1049; https://doi.org/10.3390/pharmaceutics18091049 - 24 Aug 2026
Abstract
Background: Isavuconazole, a broad-spectrum triazole antifungal, exhibits high lipophilicity and extensive plasma protein binding, properties that may predispose it to sequestration within extracorporeal membrane oxygenation (ECMO) circuits. This study aimed to characterize the pharmacokinetics (PK) of isavuconazole and to evaluate drug sequestration within [...] Read more.
Background: Isavuconazole, a broad-spectrum triazole antifungal, exhibits high lipophilicity and extensive plasma protein binding, properties that may predispose it to sequestration within extracorporeal membrane oxygenation (ECMO) circuits. This study aimed to characterize the pharmacokinetics (PK) of isavuconazole and to evaluate drug sequestration within the ECMO circuit in critically ill patients receiving ECMO support. Methods: We conducted a prospective, exploratory, single-center observational study including critically ill patients receiving ECMO (veno-venous (VV) or veno-arterial (VA)) and treated with intravenous isavuconazole. Serial blood samples were collected simultaneously from the patient’s arterial line and from pre- and post-membrane oxygenator sampling sites. Non-compartmental analysis was performed on arterial line samples to estimate PK measures, and concentration differences across sampling sites were analyzed to estimate circuit-related drug loss. PK/pharmacodynamic (PD) target attainment was assessed using established efficacy thresholds (AUC0–24/MIC ≥ 25 and Cmin > 2 mg/L). Results: A total of 41 plasma samples from 3 critically ill patients (2 VV-ECMO, 1 VA-ECMO) were included in the analysis. Limited, component-specific isavuconazole loss was observed in tubing and connectors (6.62% ± 20.8%, p = 0.294) and across the entire ECMO circuit (7.74% ± 20.2%, p = 0.211). Likewise, no relevant concentration difference was detected across the membrane oxygenator (0.849% ± 6.15%, p = 0.642). Interindividual variability was observed across PK parameters, particularly in measures of elimination and distribution. All patients achieved predefined PK/PD efficacy targets, with mean Cmin and AUC0–24/MIC of 3.07 ± 0.261 mg/L and 85.3 ± 4.03, respectively, and none exceeded the established toxicity threshold. Conclusions: Preliminary results showed variable concentration differences across ECMO sampling sites, with no consistent pattern of isavuconazole loss across the ECMO circuit under the conditions evaluated. All patients achieved predefined PK/PD efficacy targets using currently recommended dosing regimens; however, interindividual PK variability was observed, supporting the potential value of therapeutic drug monitoring (TDM) to guide individualized dosing decisions in this population. Larger population PK studies are warranted to further characterize determinants of isavuconazole exposure during ECMO support and refine evidence-based dosing strategies. Full article
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