Search Results (783)

The “Neuroimaging and Pathology Biomarkers in Parkinson’s Disease” course held on 12–13 September 2025 in Milan, Italy, convened an international faculty to review state-of-the-art biomarkers spanning neurotransmitter dysfunction, protein pathology and clinical translation. Here, we synthesize the four themed sessions and highlights convergent messages for diagnosis, stratification and trial design. The first session focused on neuroimaging markers of neurotransmitter dysfunction, highlighting how positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) provided complementary insights into dopaminergic, noradrenergic, cholinergic and serotonergic dysfunction. The second session addressed in vivo imaging of protein pathology, presenting recent advances in PET ligands targeting α-synuclein, progress in four-repeat tau imaging for progressive supranuclear palsy and corticobasal syndromes, and the prognostic relevance of amyloid imaging in the context of mixed pathologies. Imaging of neuroinflammation captures inflammatory processes in vivo and helps study pathophysiological effects. The third session bridged pathology and disease mechanisms, covering the biology of α-synuclein and emerging therapeutic strategies, the clinical potential of seed amplification assays and skin biopsy, the impact of co-pathologies on disease expression, and the “brain-first” versus “body-first” model of pathological spread. Finally, the fourth session addressed disease progression and clinical translation, focusing on imaging predictors of phenoconversion from prodromal to clinically overt stages of synucleinopathies, concepts of neural reserve and compensation, imaging correlates of cognitive impairment, and MRI approaches for atypical parkinsonism. Biomarker-informed pharmacological, infusion-based, and surgical strategies, including network-guided and adaptive deep brain stimulation, were discussed as examples of how multimodal biomarkers may inform personalized management. Across all sessions, the need for harmonization, longitudinal validation, and pathology-confirmed outcome measures was consistently emphasized as essential for advancing biomarker qualification in multicentre research and clinical practice. Full article

This study focuses on investigating the adaptive sliding mode control (SMC) problem for connected vehicles with input delays and unknown time-varying control coefficients. As a result of wear and tear of mechanical components, throttle response lags, and the internal data processing time of the controller, input delays widely exist in vehicle actuators. Since input delays may lead to instability of the vehicle platoon, an improved integral compensation mechanism (ICM) with the adjustment factor for input delays is developed to improve the platoon’s robustness. As the actuator efficiency, drive mechanism, and load of the vehicle may change during operation, the control coefficients of vehicle dynamics are usually unknown and time-varying. A novel adaptive updating mechanism utilizing a radial basis function neural network (RBFNN) is designed to deal with the unknown time-varying control coefficients, thereby improving the vehicle platoon’s tracking performance. By integrating the improved ICM and the RBFNN-based adaptive updating mechanism (RBFNN−AUM), an innovative distributed adaptive control scheme using sliding mode techniques is proposed to guarantee that the convergence of state errors to a predefined region and accomplish the vehicle platoon’s control objectives. Comparative numerical results confirm the effectiveness and superiority of the developed control strategy over existing method. Full article

Brain disorders remain a major global health challenge, highlighting the urgent need for innovative therapeutic strategies and efficient drug-delivery approaches. Among alternative routes, intranasal administration has garnered significant interest over recent decades, not only for its systemic delivery but also for its unique ability to bypass the bloodstream and the blood–brain barrier via the Nose-to-Brain (NtB) pathway. While numerous reviews have explored the opportunities and challenges of this route, industrial considerations—critical for successful clinical implementation and commercial development—remain insufficiently addressed. This review provides a comprehensive and critical assessment of the NtB pathway from a drug development and chemistry, manufacturing, and controls perspective, addressing key constraints in pre-clinical–clinical extrapolation, formulation design, device selection, dose feasibility, chronic safety, and regulatory requirements. We also discuss recent advances in neuronal targeting mechanisms, also with a focus on the role of trigeminal nerves. Dodecyl creatine ester (DCE), a highly unstable in plasma creatine prodrug developed by Ceres Brain Therapeutics, is presented as an illustrative case study. Delivered as a nasal spray, DCE enables direct neuronal delivery, exemplifying the potential of the NtB pathway for disorders characterized by neuronal energy deficiency, including creatine transporter deficiency and mitochondrial dysfunction. Overall, the NtB pathway—or, more precisely, the “Nose-to-Neurons” pathway—offers distinct advantages for unstable molecules and metabolic supplementation, particularly in neuron-centric diseases. Its successful implementation will depend on rational molecule design, optimized nasal formulations, appropriate devices, and early integration of industrial constraints to ensure feasibility, scalability, and safety for long-term treatment. Full article

Morphological variability on Mediterranean embayed sandy beaches is largely driven by wave storms and episodic sediment inputs from local streams during intense rainfall. While storm impacts are well documented, the combined influence of stream discharge, wave forcing and morphological response remains poorly understood. This study examines these interactions at Castell beach, one of the few non-urbanised, stream-fed embayed beaches on the northwestern Mediterranean, during two high-energy storms with heavy rainfall: December 2019 and January 2020 (Storm Gloria). Morphological changes in the subaerial and submerged beach, and stream dynamics were assessed using repeated RTK–GNSS surveys, orthophotos and echo-sounder bathymetry. Results show the stream mouth shifted along the beach (east, central or west) during heavy rainfall episodes depending on wave direction and pre-existing topography, tending toward more wave-sheltered zones. The storms induced contrasting responses: the first caused slight subaerial accretion, whereas Storm Gloria produced subaerial erosion and nearshore sediment deposition from both beach and stream sources. This material was subsequently reworked and reincorporated into the subaerial beach under calmer conditions, with full recovery by February 2022. These findings highlight the role of stream–wave interactions in sediment dynamics and the capacity of highly protected embayed beaches to adapt to extreme events. Full article

To address the low trajectory tracking accuracy and limited robustness of conventional reinforcement learning algorithms under complex marine environments involving wind, wave, and current disturbances, this study proposes a proximal policy optimization (PPO) algorithm incorporating an intrinsic curiosity mechanism to solve the unmanned surface vehicle (USV) trajectory tracking control problem. The proposed approach is developed on the basis of a three-degree-of-freedom (3-DOF) USV model and formulated within a Markov decision process (MDP) framework, where a multidimensional state space and a continuous action space are defined, and a multi-objective composite reward function is designed. By incorporating a pure pursuit guidance algorithm, the complexity of engineering implementation is reduced. Furthermore, an improved PPO algorithm integrated with an intrinsic curiosity mechanism is adopted as the trajectory tracking controller, in which the exploration incentives provided by the intrinsic curiosity module (ICM) guide the agent to explore the state space efficiently and converge rapidly to an optimal control policy. The final experimental results indicate that, compared with the conventional PPO algorithm, the improved PPO–ICM controller achieves a reduction of 54.2% in average lateral error and 47.1% in average heading error under simple trajectory conditions. Under the complex trajectory condition, the average lateral error and average heading error are reduced by 91.8% and 41.9%, respectively. These results effectively demonstrate that the proposed PPO–ICM algorithm attains high tracking accuracy and strong generalization capability across different trajectory scenarios, and can provide a valuable reference for the application of intelligent control algorithms in the USV domain. Full article

The high incidence of anthropogenic impacts in the Mediterranean basin raises concerns on the health and quality of commercial fish species. This study aims to evaluate the health status of the European hake, Merluccius merluccius, from three areas of the Catalan coast (NW Mediterranean Sea) with different anthropogenic impacts (i.e., chemical pollution, litter, …) and assess if hake could serve as a sentinel species. We measured biomarkers of chemical exposure including B-esterases, antioxidant enzymes (GST, GR, GPx, CAT), biotransformation markers (EROD), lipid peroxidation, and macro-parasite assemblages. Hake showed, generally, a good health status across all areas with homogeneous patterns for most parameters. Tissue-specific differences included elevated gonadal cholinesterases and higher brain and hepatic carboxylesterase activities in the south, and increased hepatic EROD but lower lipid peroxidation in the central Barcelona area. Parasite assemblages were dominated by Digenea, Cestoda, and Nematoda, with higher cestode prevalence in both central and south zones. In summary, despite a greater prevalence of environmental pollution in the central region, there was a homogeneous pattern in hake health indicators throughout the three studied fishing zones. These results establish a baseline for hake health in Mediterranean waters and suggest that the species’ high mobility and wide depth range may limit its utility to detect local-scale pollution impacts, though it may serve as a regional-scale bioindicator. Full article

The accuracy and timeliness of precipitation inputs have significant impact on flood forecasting. Upstream Minjiang River Basin is characterized by complex terrain and highly variable climatic conditions, posing a significant challenge for runoff forecasting. This study proposes a combined forecasting approach integrating numerical weather prediction (NWP) models with hydrodynamic models to enhance flood process simulation. The most appropriate initial field data for the Weather Research and Forecasting Model (WRF) exist in time and space resolution. Compared with the measured series, the characteristics of precipitation forecasting are summarized from practical and scientific perspectives. InfoWorks ICM is then used to implement runoff generation calculations and flooding processes. The results indicate that the WRF model effectively simulates the spatial distribution and peak timing of precipitation in the upper Minjiang River. The model systematically underestimates both peak rainfall intensity and cumulative precipitation compared to observations. Initial field data with 0.25° spatial resolution and 3 h temporal intervals demonstrate good performance and the 10–14 h forecast period exhibits superior predictive capability in numerical simulations. Updates to elevation and land use conditions yield increased cumulative rainfall estimates, though simulated peaks remain lower than measured values. The runoff results could indicate peak flow but rely on the precipitation inputs. Full article

This study evaluated the applicability of the dual drainage model, Hyper Connected–Solution for Urban Flood (HC-SURF), for real-time urban flood forecasting. The model was applied to the extreme rainfall event of August 2022 in the Sillim and Daerim drainage basins in Seoul. Its accuracy and computational efficiency were quantitatively compared with those of two widely used commercial models, the Personal Computer Storm Water Management Model (PC-SWMM) and InfoWorks Integrated Catchment Modelling (ICM). Accuracy was assessed by measuring spatial agreement with observed inundation trace maps using binary indicators, including the Critical Success Index (CSI), Probability of Detection (POD), and False Alarm Ratio (FAR). Computational efficiency was evaluated by comparing simulation times under identical conditions. In terms of accuracy against observations, HC-SURF achieved CSI values ranging from 0.26 to 0.45, with POD values from 0.37 to 0.81 and FAR values from 0.49 to 0.53 across the two basins. In inter-model comparisons, the model showed high hydraulic consistency, demonstrating CSI values between 0.72 and 0.88, POD between 0.82 and 0.99, and FAR between 0.08 and 0.15. In terms of computational efficiency, HC-SURF reduced calculation times by approximately 9% and 44% compared with InfoWorks ICM and PC-SWMM, respectively, for a 48 h simulation. The model also completed a 6 h rainfall simulation in approximately 8 min, meeting the lead time requirements for rapid urban flood forecasting. Overall, these findings show that HC-SURF effectively balances simulation accuracy with computational efficiency, demonstrating its suitability for real-time urban flood forecasting. Full article

The injection compression molding using dynamic mold control (ICM-DT) represents a promising technological approach to the manufacturing of highly filled, modified thermoplastic components with tight geometric tolerances. While the numerical prediction of flow states is, to date, predominantly based on the Cross–WLF modeling of viscoelastic characteristics of the melt, new material-related developments necessitate the assessment of process- and material-related boundaries. The present paper employs a highly filled graphite–polypropylene system, exhibiting a graphite mass fraction of 80%, for the quantitative comparison of Cross–WLF predictions and experimentally derived flow states. Based on coupled counter pressure-chamber high-pressure capillary rheometry (CPC-HCR) and counterpressurized viscometry (CPV) alongside the ICM-DT of thin-walled specimens, pressure-induced crystallization was identified to induce significant deviations from Cross–WLF predictions. Cross–WLF modeling strongly overestimates the processability of the applied graphite–polypropylene system under both injection molding (IM) and ICM regimes. We therefore observe a predominant influence of pressure-induced crystallization mechanisms in dynamic mold temperature process domains, in which the pressure-induced, crystallization-related exponential viscosity increase cannot be adequately modeled through both pressure-dependent and pressure-agnostic Cross–WLF models. The numerical approximation of flow states under dynamic mold temperature regimes hence necessitates the consideration of solidification-induced, self-intensifying pressure excursions. Full article

Legionella pneumophila, a waterborne pathogen naturally present in freshwater and capable of colonizing artificial water systems, is responsible for Legionnaires’ disease (LD), a severe form of pneumonia transmitted through inhalation of contaminated aerosols. Virulence of Legionella strains is affected by the plasticity of their genome, shaped by horizontal gene transfer and recombination events. Thus, contaminated water systems can host diverse Legionella populations with a distinct virulence potential. Here, we compare the genomic diversity of Legionella pneumophila strains isolated in water systems of academic buildings, together with their cytotoxicity and intracellular replication in THP-1-like macrophages. A six-year environmental surveillance revealed Legionella pneumophila contamination in 20 out of the 50 monitored sites, identifying five serogroups (sg) and 13 Sequence Types (STs). Phylogenetic investigations based on core genome multilocus sequence typing (cgMLST) and comparative genomics of representative isolates of each ST showed a broad diversity and a heterogeneous virulence repertoire, especially within the Dot/Icm and Lvh secretion systems. Following macrophage infection, a strain-dependent cytotoxicity and intracellular replication was observed, underlying significant pathogenic diversity within the same species and stage-dependent infection dynamics. Together, these results showed strain-specific genetic and phenotypic virulence traits to be considered during risk assessment in environmental surveillance. Full article

In response to escalating urban waterlogging crises exacerbated by global warming and accelerated urbanization, an innovative waterlogging risk assessment framework was advanced in this study to bolster urban resilience and promote sustainable urban development. Current methodologies often suffer from subjective bias in weight assignments for evaluation indicators. To overcome this limitation, the projection pursuit (PP) technique was integrated with a real-coded accelerated genetic algorithm (RAGA) to derive objective indicator weights. Focusing on the built-up area of Xiushan County in Chongqing, the InfoWorks ICM was employed to develop a 1D-2D coupled hydrodynamic model for simulating the dynamic spatiotemporal evolution of waterlogging events. Based on three dimensions namely hazard, sensitivity, and vulnerability, an urban waterlogging risk assessment model was developed and ArcGIS was utilized to precisely generate risk distribution maps under rainfall scenarios with return periods of 20 years and 100 years. Additionally, to enhance flood mitigation capabilities in identified high-risk zones, this study proposed implementing stormwater storage tank systems. Simulation results demonstrated that these measures achieve a 50.88% reduction in overflow volumes in critical areas, effectively lowering peak waterlogging depth from 0.74 m to 0.53 m. Key findings revealed that high-risk areas exhibit significant spatial clustering in low-elevation districts characterized by high population density and economic development intensity, where extreme rainfall events amplify water accumulation vulnerabilities, highlighting the importance of sustainable land use planning and climate adaptation strategies. The proposed assessment methodology not only enables objective quantification of urban waterlogging risks but also facilitates evidence-based formulation of targeted mitigation strategies, facilitating the goals of urban sustainability and long-term environmental resilience. Full article

Colorectal cancer (CRC) classification has progressed from consensus molecular subtypes (CMS) to epithelial–intrinsic consensus molecular subtypes (iCMS) and the layered intrinsic subtype-MSI-fibrosis (IMF) system that combines intrinsic state, MSI status, and fibrosis. This article reviews biological underpinnings of iCMS/IMF, their relationships to tumor-microenvironment crosstalk, and how single-cell and spatial transcriptomics refine therapeutic stratification by resolving tumor microenvironment heterogeneity and its impact on fibrosis. Prognostic and therapeutic implications are covered, including PD-1 blockade in MSI-high (MSI-H), MAPK-directed therapy in BRAF-mutant disease, and EGFR targeting in selected RAS wild-type (WT) left-sided tumors, and we suggest decision points specifically informed by the activity of the fibrosis axis. A step-by-step procedure is presented for the analysis of bulk and single-cell RNA and formalin-fixed, paraffin-embedded (FFPE) resources, along with open-source tools and reporting standards to make iCMS/IMF calling reproducible in clinics and trials. Future outlooks are outlined with near-term biomarker–drug hypotheses for microsatellite-stable (MSS)-iCMS3 and high fibrosis tumors and key gaps to close for clinical translation. This review outlines a roadmap for precision medicine in colorectal cancer by leveraging the iCMS/IMF framework to integrate pathology and digital pathology, molecular diagnostics, and therapy mapping with FAP-targeted imaging and therapy. Full article

The multifunctional role of forests in supplying renewable biomaterials and delivering ecosystem services (ESs) is often overlooked in standard life cycle assessment (LCA) methodologies, despite its relevance for sustainable construction. This study developed the BioCons Impact Compensation Model (ICM), which integrates ES into life cycle inventory (LCI) databases and quantifies proprietary BioCons Mitigation Indicators, capturing additional environmental information, ensuring transparency, and preventing greenwashing. Using structural Scots pine in Spain as a case study, the GWP_-luluc-roots indicator was found to be 226.84 kg CO_2-eq/FU, representing 36% of the biogenic carbon (616.45 kg CO_2-eq/FU), highlighting the contribution of root-derived carbon to long-term soil carbon storage. The BioCons Mitigation Indicators demonstrate that mitigation generally exceeds environmental impacts, except for HTP-nc-inorganics, with surplus ES available as biocredits to offset emissions in other life cycle stages. Integrating these indicators into environmental product declarations (EPDs) provides a transparent and accurate view of environmental performance. The results validate the hypothesis that forest bio-based construction products (FBCPs) act as carriers of ESs embedded in derived products, supporting more comprehensive and robust sustainability assessments. Full article

Passion fruit (Passiflora edulis f. flavicarpa), commonly known as yellow passion fruit, is widely grown across tropical and subtropical regions worldwide, with Brazil as one of the top producers. Mexico also produces a significant amount of this variety, mainly for juices, jams, or flavoring in desserts. Since this fruit is highly perishable with a short shelf life, it needs to be consumed or used quickly. Although different preservation methods have been suggested, no structural analyses of the peel have been performed to improve these processes. This study aimed to analyze the structural and chemical properties of the peel’s cuticular matrix to better understand water loss. CPMAS ¹³C NMR analysis revealed a matrix containing polysaccharides, a small amount of aliphatics, and a notable group of aromatic signals that may indicate lignin presence. This was supported by alkaline hydrolysis, which achieved only 30% hydrolysis. Soluble compounds identified included hexoses, palmitic acid, stearic acid, and derivatives of ferulic and caffeic acids, the latter being parts of lignin monomers. MCL and SEM analyses showed features similar to cutans, including pores along the structures. The BET surface area measurement indicated that the insoluble cuticular material (ICM) has a significant specific surface area. The lignin in the yellow passion fruit peel gives the shell toughness, which, along with its pores, may contribute to dehydration and a short shelf life. Full article

Reaction time (RT) is a key measure of neuromuscular and cognitive performance, but most existing methods rely on laboratory equipment or focus on localized actions such as finger taps or foot lifts, limiting their relevance for whole-body movements. In this work, we present a portable inertial measurement unit (IMU)-based system specifically designed to measure RT during sprint starts. The device integrates a triaxial accelerometer (ICM-20948, ±16 g) and an ESP32 microcontroller, which generates an auditory stimulus, acquires acceleration data at 1 kHz, and computes movement onset in real time. A fixed acceleration threshold, determined from calibration against a high-speed camera reference, was used to detect the first voluntary movement. Both desktop and smartphone applications were implemented to control the system, provide feedback, and store test data. Validation experiments showed good agreement with the high-speed camera used as a reference (R² = 0.9391), with a mean bias of –1.35 ms and 95% limits of agreement within ±25 ms. The proposed system combines high temporal resolution, portability, and straightforward deployment, enabling reliable assessment of whole-body RT in realistic sports and research environments. Full article