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19 pages, 2264 KiB  
Article
Extramedullary Plasmacytomas of the Nasal Cavity: Case-Based Perspectives into Optimizing the Diagnostic Differentiation from Inflammatory Polyps
by Carmen Aurelia Mogoantă, Codruț Sarafoleanu, Andrei Osman, Irina Enache, Shirley Tarabichi, Constantin-Ioan Busuioc, Ilona Mihaela Liliac, Dan Iovanescu and Ionuţ Tănase
Medicina 2025, 61(8), 1406; https://doi.org/10.3390/medicina61081406 (registering DOI) - 1 Aug 2025
Abstract
Background and Objectives: Extramedullary plasmacytoma (EMP) is a rare monoclonal B-cell neoplasm that typically affects the head and neck region, with a predilection for the sinonasal tract. Clinical presentation is often nonspecific, leading to delayed diagnosis. This study aims to improve our [...] Read more.
Background and Objectives: Extramedullary plasmacytoma (EMP) is a rare monoclonal B-cell neoplasm that typically affects the head and neck region, with a predilection for the sinonasal tract. Clinical presentation is often nonspecific, leading to delayed diagnosis. This study aims to improve our understanding of sinonasal EMP by reviewing the recent literature and presenting a case series from our clinical experience. Materials and Methods: A systematic review of published cases of sinonasal EMP from 2000 to 2023 was conducted using the PubMed database, yielding 28 eligible cases. Additionally, we retrospectively analyzed three patients diagnosed and treated at our institutions. Inclusion criteria included histologically and immunohistochemically confirmed EMP without evidence of systemic multiple myeloma. Data on demographics, tumor location, symptoms, treatment, and outcomes were collected and analyzed descriptively. Results: Sinonasal EMP most commonly presented with unilateral nasal obstruction and epistaxis. Tumors were primarily located in the nasal cavity and paranasal sinuses, often extending beyond a single anatomical site. In the literature cohort, the most frequent treatment was combined surgery and radiotherapy (35.71%), followed by radiotherapy alone (17.86%). Recurrence was reported in 10.71% of cases, and 7.14% of patients died due to disease progression. All three patients in our case series underwent surgical excision; two received postoperative radiotherapy. No recurrences or progression to multiple myeloma were observed during follow-up (12–24 months). Conclusions: Sinonasal EMP is a rare but radiosensitive tumor with a favorable prognosis when treated with surgery and/or radiotherapy. Early diagnosis, histopathological confirmation, and exclusion of systemic disease are essential. Multidisciplinary management and long-term follow-up are critical due to the risk of recurrence and transformation into multiple myeloma. Full article
(This article belongs to the Special Issue Optimizing Outcomes in Head and Neck Surgery)
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21 pages, 6893 KiB  
Article
Nose-Wheel Steering Control via Digital Twin and Multi-Disciplinary Co-Simulation
by Wenjie Chen, Luxi Zhang, Zhizhong Tong and Leilei Liu
Machines 2025, 13(8), 677; https://doi.org/10.3390/machines13080677 (registering DOI) - 1 Aug 2025
Viewed by 91
Abstract
The aircraft nose-wheel steering system serves as a critical component for ensuring ground taxiing safety and maneuvering efficiency. However, its dynamic control stability faces significant challenges under complex operational conditions. Existing research predominantly focuses on single-discipline modeling, with insufficient in-depth analysis of the [...] Read more.
The aircraft nose-wheel steering system serves as a critical component for ensuring ground taxiing safety and maneuvering efficiency. However, its dynamic control stability faces significant challenges under complex operational conditions. Existing research predominantly focuses on single-discipline modeling, with insufficient in-depth analysis of the coupling effects between hydraulic system dynamics and mechanical dynamics. Traditional PID controllers exhibit limitations in scenarios involving nonlinear time-varying conditions caused by normal load fluctuations of the landing gear buffer strut during high-speed landing phases, including increased control overshoot and inadequate adaptability to abrupt load variations. These issues severely compromise the stability of high-speed deviation correction and overall aircraft safety. To address these challenges, this study constructs a digital twin model based on real aircraft data and innovatively implements multidisciplinary co-simulation via Simcenter 3D, AMESim 2021.1, and MATLAB R2020a. A fuzzy adaptive PID controller is specifically designed to achieve adaptive adjustment of control parameters. Comparative analysis through co-simulation demonstrates that the proposed mechanical–electrical–hydraulic collaborative control strategy significantly reduces response delay, effectively minimizes control overshoot, and decreases hydraulic pressure-fluctuation amplitude by over 85.2%. This work provides a novel methodology for optimizing steering stability under nonlinear interference scenarios, offering substantial engineering applicability and promotion value. Full article
(This article belongs to the Section Robotics, Mechatronics and Intelligent Machines)
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18 pages, 10032 KiB  
Article
Design and Efficiency Analysis of High Maneuvering Underwater Gliders for Kuroshio Observation
by Zhihao Tian, Bing He, Heng Zhang, Cunzhe Zhang, Tongrui Zhang and Runfeng Zhang
Oceans 2025, 6(3), 48; https://doi.org/10.3390/oceans6030048 (registering DOI) - 1 Aug 2025
Viewed by 42
Abstract
The Kuroshio Current’s flow velocity imposes exacting requirements on underwater vehicle propulsive systems. Ecological preservation necessitates low-noise propeller designs to mitigate operational disturbances. As technological evolution advances toward greater intelligence and system integration, intelligent unmanned systems are positioning themselves as a critical frontier [...] Read more.
The Kuroshio Current’s flow velocity imposes exacting requirements on underwater vehicle propulsive systems. Ecological preservation necessitates low-noise propeller designs to mitigate operational disturbances. As technological evolution advances toward greater intelligence and system integration, intelligent unmanned systems are positioning themselves as a critical frontier in marine innovation. In recent years, the global research community has increased its efforts towards the development of high-maneuverability underwater vehicles. However, propeller design optimization ignores the key balance between acoustic performance and hydrodynamic efficiency, as well as the appropriate speed threshold for blade rotation. In order to solve this problem, the propeller design of the NACA 65A010 airfoil is optimized by using OpenProp v3.3.4 and XFlow 2022 software, aiming at innovating the propulsion system of shallow water agile submersibles. The study presents an integrated design framework combining lattice Boltzmann method (LBM) simulations synergized with fully Lagrangian-LES modeling, implementing rotational speed thresholds to detect cavitation inception, followed by advanced acoustic propagation analysis. Through rigorous comparative assessment of hydrodynamic metrics, we establish an optimization protocol for propeller selection tailored to littoral zone operational demands. Studies have shown that increasing the number of propeller blades can reduce the single-blade load and delay cavitation, but too many blades will aggravate the complexity of the flow field, resulting in reduced efficiency and noise rebound. It is concluded that the propeller with five blades, a diameter of 234 mm, and a speed of 500 RPM exhibits the best performance. Under these conditions, the water efficiency is 69.01%, and the noise is the lowest, which basically realizes the balance between hydrodynamic efficiency and acoustic performance. This paradigm-shifting research carries substantial implications for next-generation marine vehicles, particularly in optimizing operational stealth and energy efficiency through intelligent propulsion architecture. Full article
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29 pages, 1505 KiB  
Review
Biological Macromolecule-Based Dressings for Combat Wounds: From Collagen to Growth Factors—A Review
by Wojciech Kamysz and Patrycja Kleczkowska
Med. Sci. 2025, 13(3), 106; https://doi.org/10.3390/medsci13030106 (registering DOI) - 1 Aug 2025
Viewed by 53
Abstract
Wound care in military and combat environments poses distinct challenges that set it apart from conventional medical practice in civilian settings. The nature of injuries sustained on the battlefield—often complex, contaminated, and involving extensive tissue damage—combined with limited access to immediate medical intervention, [...] Read more.
Wound care in military and combat environments poses distinct challenges that set it apart from conventional medical practice in civilian settings. The nature of injuries sustained on the battlefield—often complex, contaminated, and involving extensive tissue damage—combined with limited access to immediate medical intervention, significantly increases the risk of infection, delayed healing, and adverse outcomes. Traditional wound dressings frequently prove inadequate under such extreme conditions, as they have not been designed to address the specific physiological and logistical constraints present during armed conflicts. This review provides a comprehensive overview of recent progress in the development of advanced wound dressings tailored for use in military scenarios. Special attention has been given to multifunctional dressings that go beyond basic wound coverage by incorporating biologically active macromolecules such as collagen, chitosan, thrombin, alginate, therapeutic peptides, and growth factors. These compounds contribute to properties including moisture balance control, exudate absorption, microbial entrapment, and protection against secondary infection. This review highlights the critical role of advanced wound dressings in improving medical outcomes for injured military personnel. The potential of these technologies to reduce complications, enhance healing rates, and ultimately save lives underscores their growing importance in modern battlefield medicine. Full article
(This article belongs to the Collection Advances in Skin Wound Healing)
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32 pages, 3202 KiB  
Article
An Integrated Framework for Urban Water Infrastructure Planning and Management: A Case Study for Gauteng Province, South Africa
by Khathutshelo Godfrey Maumela, Tebello Ntsiki Don Mathaba and Mahalieo Kao
Water 2025, 17(15), 2290; https://doi.org/10.3390/w17152290 (registering DOI) - 1 Aug 2025
Viewed by 47
Abstract
Effective water infrastructure planning and management is key to sustainable water supply globally. This research assesses water infrastructure planning and management in Gauteng, South Africa, amid growing challenges from rapid urbanisation, high water demand, climate change, and resource scarcity. These challenges threaten the [...] Read more.
Effective water infrastructure planning and management is key to sustainable water supply globally. This research assesses water infrastructure planning and management in Gauteng, South Africa, amid growing challenges from rapid urbanisation, high water demand, climate change, and resource scarcity. These challenges threaten the achievement of Sustainable Development Goals 6 and 11; hence, an integrated approach is required for water sustainability. The study responds to a gap in the literature, which often treats planning and management separately, by adopting an integrated, multi-institutional approach across the water value chain. A mixed-methods triangulation strategy was employed for data collection whereby surveys provided quantitative data, while two sets of structured interviews were conducted: the first round to determine causal relationships among the critical success factors and the second round to validate the proposed framework. The findings reveal a misalignment between infrastructure planning and implementation, contributing to infrastructure backlogs and a short- to medium-term focus. Infrastructure management is further constrained by inadequate system redundancy, leading to ineffective maintenance. External factors such as delayed adoption of 4IR technologies, lack of climate resilient strategies, and fragmented institutional coordination exacerbate these issues. Using Decision-Making Trial and Evaluation Laboratory (DEMATEL) analysis, the study identified Strategic Alignment and a Value-Driven Approach as the most influential critical success factors in water asset management. The research concludes by proposing an integrated water infrastructure and planning framework that supports sustainable water supply. Full article
(This article belongs to the Section Urban Water Management)
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27 pages, 1832 KiB  
Review
Breaking the Traffic Code: How MaaS Is Shaping Sustainable Mobility Ecosystems
by Tanweer Alam
Future Transp. 2025, 5(3), 94; https://doi.org/10.3390/futuretransp5030094 (registering DOI) - 1 Aug 2025
Viewed by 68
Abstract
Urban areas are facing increasing traffic congestion, pollution, and infrastructure strain. Traditional urban transportation systems are often fragmented. They require users to plan, pay, and travel across multiple disconnected services. Mobility-as-a-Service (MaaS) integrates these services into a single digital platform, simplifying access and [...] Read more.
Urban areas are facing increasing traffic congestion, pollution, and infrastructure strain. Traditional urban transportation systems are often fragmented. They require users to plan, pay, and travel across multiple disconnected services. Mobility-as-a-Service (MaaS) integrates these services into a single digital platform, simplifying access and improving the user experience. This review critically examines the role of MaaS in fostering sustainable mobility ecosystems. MaaS aims to enhance user-friendliness, service variety, and sustainability by adopting a customer-centric approach to transportation. The findings reveal that successful MaaS systems consistently align with multimodal transport infrastructure, equitable access policies, and strong public-private partnerships. MaaS enhances the management of routes and traffic, effectively mitigating delays and congestion while concurrently reducing energy consumption and fuel usage. In this study, the authors examine MaaS as a new mobility paradigm for a sustainable transportation system in smart cities, observing the challenges and opportunities associated with its implementation. To assess the environmental impact, a sustainability index is calculated based on the use of different modes of transportation. Significant findings indicate that MaaS systems are proliferating in both quantity and complexity, increasingly integrating capabilities such as real-time multimodal planning, dynamic pricing, and personalized user profiles. Full article
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26 pages, 3012 KiB  
Perspective
The Palisades Fire of Los Angeles: Lessons to Be Learned
by Vytenis Babrauskas
Fire 2025, 8(8), 303; https://doi.org/10.3390/fire8080303 (registering DOI) - 31 Jul 2025
Viewed by 84
Abstract
In 1961, Los Angeles experienced the disastrous Bel Air fire, which swept through an affluent neighborhood situated in a hilly, WUI (wildland–urban interface) location. In January 2025, the city was devastated again by a nearly-simultaneous series of wildfires, the most severe of which [...] Read more.
In 1961, Los Angeles experienced the disastrous Bel Air fire, which swept through an affluent neighborhood situated in a hilly, WUI (wildland–urban interface) location. In January 2025, the city was devastated again by a nearly-simultaneous series of wildfires, the most severe of which took place close to the 1961 fire location. Disastrous WUI fires are, unfortunately, an anticipatable occurrence in many U.S. cities. A number of issues identified earlier remained the same. Some were largely solved, while other new ones have emerged. The paper examines the Palisades Fire of January, 2025 in this context. In the intervening decades, the population of the city grew substantially. But firefighting resources did not keep pace. Very likely, the single-most-important factor in causing the 2025 disasters is that the Los Angeles Fire Department operational vehicle count shrank to 1/5 of what it was in 1961 (per capita). This is likely why critical delays were experienced in the initial attack on the Palisades Fire, leading to a runaway conflagration. Two other crucial issues were the management of vegetation and the adequacy of water supplies. On both these issues, the Palisades Fire revealed serious problems. A problem which arose after 1961 involves the unintended consequences of environmental legislation. Communities will continue to be devastated by wildfires unless adequate vegetation management is accomplished. Yet, environmental regulations are focused on maintaining the status quo, often making vegetation management difficult or ineffective. House survival during a wildfire is strongly affected by whether good vegetation management practices and good building practices (“ignition-resistant” construction features) have been implemented. The latter have not been mandatory for housing built prior to 2008, and the vast majority of houses in the area predated such building code requirements. California has also suffered from a highly counterproductive stance on insurance regulation. This has resulted in some residents not having property insurance, due to the inhospitable operating conditions for insurance firms in the state. Because of the historical precedent, the details in this paper focus on the Palisades Fire; however, many of the lessons learned apply to managing fires in all WUI areas. Policy recommendations are offered, which could help to reduce the potential for future conflagrations. Full article
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34 pages, 2049 KiB  
Article
Tailoring a Three-Layer Track Model to Delay Instability and Minimize Critical Velocity Effects at Very High Velocities
by Zuzana Dimitrovová
Infrastructures 2025, 10(8), 200; https://doi.org/10.3390/infrastructures10080200 - 31 Jul 2025
Viewed by 63
Abstract
The aim of this paper is to tailor the geometry and material parameters of a three-layer railway track model to achieve favorable properties for the circulation of high-speed trains at very high velocities. The three layers imply that the model should have three [...] Read more.
The aim of this paper is to tailor the geometry and material parameters of a three-layer railway track model to achieve favorable properties for the circulation of high-speed trains at very high velocities. The three layers imply that the model should have three critical velocities for resonance. However, in many cases, some of these values are missing and must be replaced by pseudo-critical values. Since no resonance occurs at pseudo-critical velocities, even in the absence of damping, deflections never reach infinity. By using optimization techniques, it is possible to adjust the model’s parameters, so that the increase in vibrations remains minimal and does not pose a real danger. In this way, circulation velocities could be extended beyond the critical value, thereby increasing the network capacity and, consequently, improving the competitiveness of rail transport compared to other modes of transportation, thus contributing to decarbonization. The presented results are preliminary and require further analysis and validation. Several optimization techniques are implemented, leading to the establishment of designs that already have rather high pseudo-critical velocities. Further research will show how these theoretical findings can be utilized in practice.  Full article
13 pages, 1001 KiB  
Review
Old and New Definitions of Acute Respiratory Distress Syndrome (ARDS): An Overview of Practical Considerations and Clinical Implications
by Cesare Biuzzi, Elena Modica, Noemi De Filippis, Daria Pizzirani, Benedetta Galgani, Agnese Di Chiaro, Daniele Marianello, Federico Franchi, Fabio Silvio Taccone and Sabino Scolletta
Diagnostics 2025, 15(15), 1930; https://doi.org/10.3390/diagnostics15151930 - 31 Jul 2025
Viewed by 186
Abstract
Lower respiratory tract infections remain a leading cause of morbidity and mortality among Intensive Care Unit patients, with severe cases often progressing to acute respiratory distress syndrome (ARDS). This life-threatening syndrome results from alveolar–capillary membrane injury, causing refractory hypoxemia and respiratory failure. Early [...] Read more.
Lower respiratory tract infections remain a leading cause of morbidity and mortality among Intensive Care Unit patients, with severe cases often progressing to acute respiratory distress syndrome (ARDS). This life-threatening syndrome results from alveolar–capillary membrane injury, causing refractory hypoxemia and respiratory failure. Early detection and management are critical to treat the underlying cause, provide protective lung ventilation, and, eventually, improve patient outcomes. The 2012 Berlin definition standardized ARDS diagnosis but excluded patients on non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) modalities, which are increasingly used, especially after the COVID-19 pandemic. By excluding these patients, diagnostic delays can occur, risking the progression of lung injury despite ongoing support. Indeed, sustained, vigorous respiratory efforts under non-invasive modalities carry significant potential for patient self-inflicted lung injury (P-SILI), underscoring the need to broaden diagnostic criteria to encompass these increasingly common therapies. Recent proposals expand ARDS criteria to include NIV and HFNCs, lung ultrasound, and the SpO2/FiO2 ratio adaptations designed to improve diagnosis in resource-limited settings lacking arterial blood gases or advanced imaging. However, broader criteria risk overdiagnosis and create challenges in distinguishing ARDS from other causes of acute hypoxemic failure. Furthermore, inter-observer variability in imaging interpretation and inconsistencies in oxygenation assessment, particularly when relying on non-invasive measurements, may compromise diagnostic reliability. To overcome these limitations, a more nuanced diagnostic framework is needed—one that incorporates individualized therapeutic strategies, emphasizes lung-protective ventilation, and integrates advanced physiological or biomarker-based indicators like IL-6, IL-8, and IFN-γ, which are associated with worse outcomes. Such an approach has the potential to improve patient stratification, enable more targeted interventions, and ultimately support the design and conduct of more effective interventional studies. Full article
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12 pages, 3098 KiB  
Article
Microbial Lipopolysaccharide Regulates Host Development Through Insulin/IGF-1 Signaling
by Lijuan Teng and Jingyan Zhang
Int. J. Mol. Sci. 2025, 26(15), 7399; https://doi.org/10.3390/ijms26157399 (registering DOI) - 31 Jul 2025
Viewed by 181
Abstract
Lipopolysaccharide (LPS), the defining outer membrane component of Gram-negative bacteria, is a potent immunostimulant recognized by Toll-like receptor 4 (TLR4). While extensively studied for its roles in immune activation and barrier disruption, the potential function of LPS as a developmental cue remains largely [...] Read more.
Lipopolysaccharide (LPS), the defining outer membrane component of Gram-negative bacteria, is a potent immunostimulant recognized by Toll-like receptor 4 (TLR4). While extensively studied for its roles in immune activation and barrier disruption, the potential function of LPS as a developmental cue remains largely unexplored. By leveraging Caenorhabditis elegans and its genetic and gnotobiotic advantages, we screened a panel of Escherichia coli LPS biosynthesis mutants. This screen revealed that the loss of outer core glycosylation in the ∆rfaG mutant causes significant developmental delay independent of bacterial metabolism. Animals exhibited developmental delay that was rescued by exogenous LPS or amino acid supplementation, implicating that LPS triggers nutrient-sensing signaling. Mechanistically, this developmental arrest was mediated by the host FOXO transcription factor DAF-16, which is the key effector of insulin/IGF-1 signaling (IIS). Our findings uncover an unprecedented role for microbial LPS as a critical regulator of host development, mediated through conserved host IIS pathways, fundamentally expanding our understanding of host–microbe crosstalk. Full article
(This article belongs to the Special Issue C. elegans as a Disease Model: Molecular Perspectives: 2nd Edition)
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12 pages, 1159 KiB  
Review
Neuroinflammation in Radiation Maculopathy: A Pathophysiologic and Imaging Perspective
by Giulia Midena, Raffaele Parrozzani, Marisa Bruno, Elisabetta Pilotto and Edoardo Midena
Cancers 2025, 17(15), 2528; https://doi.org/10.3390/cancers17152528 - 31 Jul 2025
Viewed by 172
Abstract
Background: Radiation maculopathy (RM) is a delayed, sight-threatening complication of ocular radiotherapy. Traditionally regarded as a pure microvascular disease, emerging evidence points to the central role played by retinal neuroinflammation, driven by microglial activation and cytokine dysregulation affecting both the retina and the [...] Read more.
Background: Radiation maculopathy (RM) is a delayed, sight-threatening complication of ocular radiotherapy. Traditionally regarded as a pure microvascular disease, emerging evidence points to the central role played by retinal neuroinflammation, driven by microglial activation and cytokine dysregulation affecting both the retina and the choroid. Hyperreflective retinal foci, neuroinflammatory in origin (I-HRF), visualized through advanced imaging modalities such as spectral domain optical coherence tomography (OCT), have been identified as early and critical biomarkers of both preclinical and clinical retinal neuroinflammation. Materials and Methods: This review synthesizes findings from experimental and clinical studies to explore the pathophysiology of neuroinflammation and the associated imaging parameters in RM. Results: The integration of experimental and clinical evidence specifically underscores the significance of I-HRF as an early indicator of neuroinflammation in RM. OCT enables the identification and quantification of these biomarkers, which are linked to microglial activation and cytokine dysregulation. Conclusions: The pathophysiology of RM has evolved from a predominantly vascular condition to one strongly secondary to neuroinflammatory mechanisms involving the retina and choroid. In particular, I-HRF, as early biomarkers, offers the potential for preclinical diagnosis and therapeutic intervention, paving the way for improved management of this sight-threatening complication. Full article
(This article belongs to the Special Issue Advances in Choroidal Melanoma: From Treatment to Prognosis)
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24 pages, 2070 KiB  
Article
Reinforcement Learning-Based Finite-Time Sliding-Mode Control in a Human-in-the-Loop Framework for Pediatric Gait Exoskeleton
by Matthew Wong Sang and Jyotindra Narayan
Machines 2025, 13(8), 668; https://doi.org/10.3390/machines13080668 - 30 Jul 2025
Viewed by 183
Abstract
Rehabilitation devices such as actuated lower-limb exoskeletons can provide essential mobility assistance for pediatric patients with gait impairments. Enhancing their control systems under conditions of user variability and dynamic disturbances remains a significant challenge, particularly in active-assist modes. This study presents a human-in-the-loop [...] Read more.
Rehabilitation devices such as actuated lower-limb exoskeletons can provide essential mobility assistance for pediatric patients with gait impairments. Enhancing their control systems under conditions of user variability and dynamic disturbances remains a significant challenge, particularly in active-assist modes. This study presents a human-in-the-loop control architecture for a pediatric lower-limb exoskeleton, combining outer-loop admittance control with robust inner-loop trajectory tracking via a non-singular terminal sliding-mode (NSTSM) controller. Designed for active-assist gait rehabilitation in children aged 8–12 years, the exoskeleton dynamically responds to user interaction forces while ensuring finite-time convergence under system uncertainties. To enhance adaptability, we augment the inner-loop control with a twin delayed deep deterministic policy gradient (TD3) reinforcement learning framework. The actor–critic RL agent tunes NSTSM gains in real-time, enabling personalized model-free adaptation to subject-specific gait dynamics and external disturbances. The numerical simulations show improved trajectory tracking, with RMSE reductions of 27.82% (hip) and 5.43% (knee), and IAE improvements of 40.85% and 10.20%, respectively, over the baseline NSTSM controller. The proposed approach also reduced the peak interaction torques across all the joints, suggesting more compliant and comfortable assistance for users. While minor degradation is observed at the ankle joint, the TD3-NSTSM controller demonstrates improved responsiveness and stability, particularly in high-load joints. This research contributes to advancing pediatric gait rehabilitation using RL-enhanced control, offering improved mobility support and adaptive rehabilitation outcomes. Full article
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28 pages, 3082 KiB  
Article
Genetic Insights and Diagnostic Challenges in Highly Attenuated Lysosomal Storage Disorders
by Elena Urizar, Eamon P. McCarron, Chaitanya Gadepalli, Andrew Bentley, Peter Woolfson, Siying Lin, Christos Iosifidis, Andrew C. Browning, John Bassett, Udara D. Senarathne, Neluwa-Liyanage R. Indika, Heather J. Church, James A. Cooper, Jorge Menendez Lorenzo, Maria Elena Farrugia, Simon A. Jones, Graeme C. Black and Karolina M. Stepien
Genes 2025, 16(8), 915; https://doi.org/10.3390/genes16080915 (registering DOI) - 30 Jul 2025
Viewed by 464
Abstract
Background: Lysosomal storage diseases (LSDs) are a genetically and clinically heterogeneous group of inborn errors of metabolism caused by variants in genes encoding lysosomal hydrolases, membrane proteins, activator proteins, or transporters. These disease-causing variants lead to enzymatic deficiencies and the progressive accumulation of [...] Read more.
Background: Lysosomal storage diseases (LSDs) are a genetically and clinically heterogeneous group of inborn errors of metabolism caused by variants in genes encoding lysosomal hydrolases, membrane proteins, activator proteins, or transporters. These disease-causing variants lead to enzymatic deficiencies and the progressive accumulation of undegraded substrates within lysosomes, disrupting cellular function across multiple organ systems. While classical phenotypes typically manifest in infancy or early childhood with severe multisystem involvement, a combination of advances in molecular diagnostics [particularly next-generation sequencing (NGS)] and improved understanding of disease heterogeneity have enabled the identification of attenuated forms characterised by residual enzyme activity and later-onset presentations. These milder phenotypes often evade early recognition due to nonspecific or isolated symptoms, resulting in significant diagnostic delays and missed therapeutic opportunities. Objectives/Methods: This study characterises the clinical, biochemical, and molecular profiles of 10 adult patients diagnosed with LSDs, all representing attenuated forms, and discusses them alongside a narrative review. Results: Enzyme activity, molecular data, and phenotypic assessments are described to explore genotype–phenotype correlations and identify diagnostic challenges. Conclusions: These findings highlight the variable expressivity and organ involvement of attenuated LSDs and reinforce the importance of maintaining clinical suspicion in adults presenting with unexplained cardiovascular, neurological, ophthalmological, or musculoskeletal findings. Enhanced recognition of atypical presentations is critical to facilitate earlier diagnosis, guide management, and enable cascade testing for at-risk family members. Full article
(This article belongs to the Special Issue Molecular Basis and Genetics of Intellectual Disability)
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15 pages, 747 KiB  
Article
Comparative Analysis of LLMs in Dry Eye Syndrome Healthcare Information
by Gloria Wu, Hrishi Paliath-Pathiyal, Obaid Khan and Margaret C. Wang
Diagnostics 2025, 15(15), 1913; https://doi.org/10.3390/diagnostics15151913 - 30 Jul 2025
Viewed by 188
Abstract
Background/Objective: Dry eye syndrome affects 16 million Americans with USD 52 billion in annual healthcare costs. With large language models (LLMs) increasingly used for healthcare information, understanding their performance in delivering equitable dry eye guidance across diverse populations is critical. This study aims [...] Read more.
Background/Objective: Dry eye syndrome affects 16 million Americans with USD 52 billion in annual healthcare costs. With large language models (LLMs) increasingly used for healthcare information, understanding their performance in delivering equitable dry eye guidance across diverse populations is critical. This study aims to evaluate and compare five major LLMs (Grok, ChatGPT, Gemini, Claude.ai, and Meta AI) regarding dry eye syndrome information delivery across different demographic groups. Methods: LLMs were queried using standardized prompts simulating a 62-year-old patient with dry eye symptoms across four demographic categories (White, Black, East Asian, and Hispanic males and females). Responses were analyzed for word count, readability, cultural sensitivity scores (0–3 scale), keyword coverage, and response times. Results: Significant variations existed across LLMs. Word counts ranged from 32 to 346 words, with Gemini being the most comprehensive (653.8 ± 96.2 words) and Claude.ai being the most concise (207.6 ± 10.8 words). Cultural sensitivity scores revealed Grok demonstrated highest awareness for minority populations (scoring 3 for Black and Hispanic demographics), while Meta AI showed minimal cultural tailoring (0.5 ± 0.5). All models recommended specialist consultation, but medical term coverage varied significantly. Response times ranged from 7.41 s (Meta AI) to 25.32 s (Gemini). Conclusions: While all LLMs provided appropriate referral recommendations, substantial disparities exist in cultural sensitivity, content depth, and information delivery across demographic groups. No LLM consistently addressed the full spectrum of dry eye causes across all demographics. These findings underscore the importance for physician oversight and standardization in AI-generated healthcare information to ensure equitable access and prevent care delays. Full article
(This article belongs to the Special Issue Artificial Intelligence Application in Cornea and External Diseases)
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21 pages, 1971 KiB  
Review
Etiology of Delayed Lactogenesis in Obesity
by Gema Gomez-Casado, Natalia Saldaña-Garcia, Ernesto Gonzalez-Mesa and Almudena Ortega-Gomez
Biomedicines 2025, 13(8), 1848; https://doi.org/10.3390/biomedicines13081848 - 30 Jul 2025
Viewed by 222
Abstract
Obesity is a multifactorial condition that influences metabolic, endocrine, inflammatory, circadian, and behavioral systems. These disruptions can adversely affect the initiation of lactogenesis II—the critical process marking the onset of copious milk secretion following childbirth. In mothers with obesity, prolonged inflammation within the [...] Read more.
Obesity is a multifactorial condition that influences metabolic, endocrine, inflammatory, circadian, and behavioral systems. These disruptions can adversely affect the initiation of lactogenesis II—the critical process marking the onset of copious milk secretion following childbirth. In mothers with obesity, prolonged inflammation within the mammary gland, a blunted hormonal response (notably of prolactin), altered progesterone and estrogen dynamics, high leptin levels, and misaligned circadian rhythms contribute significantly to delayed lactogenesis. In addition, mechanical difficulties and psychological factors further hinder effective breastfeeding. This report synthesizes evidence from human epidemiological studies and animal models that elucidate the diverse mechanisms linking maternal obesity to delayed lactogenesis. We review the role of obesity-associated inflammatory mediators in impairing mammary tissue remodeling, the endocrine aberrations that impair lactogenic signaling, the consequences of circadian disruption on hormonal rhythmicity, and the behavioral influences that challenge effective breastfeeding. Finally, we discuss the clinical implications of these findings and propose future research directions targeting endocrine modulation, anti-inflammatory therapy, circadian interventions, and enhanced lactation support strategies for mothers with obesity. Full article
(This article belongs to the Special Issue Molecular Research in Obesity, 2nd Edition)
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