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Search Results (249)

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19 pages, 1956 KB  
Article
Geohash-Based High-Definition Map Provisioning System Using Smart RSU
by Wangyu Park, Jimin Lee and Changjoo Moon
Sensors 2025, 25(17), 5509; https://doi.org/10.3390/s25175509 - 4 Sep 2025
Abstract
High-definition (HD) maps are essential for safe and reliable autonomous driving, but their growing size and the need for real-time updates pose significant challenges for in-vehicle storage and communication efficiency. This study proposes a lightweight and scalable HD map provisioning system based on [...] Read more.
High-definition (HD) maps are essential for safe and reliable autonomous driving, but their growing size and the need for real-time updates pose significant challenges for in-vehicle storage and communication efficiency. This study proposes a lightweight and scalable HD map provisioning system based on Geohash spatial indexing and Smart Roadside Units (Smart RSUs). The system divides HD map data into Geohash-based spatial blocks and enables vehicles to request only the map segments corresponding to their current location, reducing storage burden and communication load. To validate the system’s effectiveness, we constructed a simulation environment where multiple vehicle clients simultaneously request map data from a Smart RSU. Experimental results showed that the proposed Geohash-based approach achieved an average response time (RTT) of 1244.82 ms—approximately 296.3% faster than the conventional GPS-based spatial query method—and improved database query performance by 1072.6%. Additionally, we demonstrate the system’s scalability by adjusting Geohash levels according to road density, using finer blocks in urban areas and coarser blocks in rural areas. The hierarchical nature of Geohash also enables consistent integration of blocks with different resolutions. These results confirm that the proposed method provides an efficient and real-time HD map delivery framework suitable for dynamic and dense traffic environments. Full article
(This article belongs to the Section Sensor Networks)
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27 pages, 1482 KB  
Article
Less Is Fair: Reducing RTT Unfairness Through Buffer Sizing
by Agnieszka Piotrowska
Sensors 2025, 25(17), 5374; https://doi.org/10.3390/s25175374 - 1 Sep 2025
Viewed by 175
Abstract
Sharing bottleneck bandwidth among TCP flows with diverse round-trip times (RTTs) remains a persistent challenge. This study investigates RTT unfairness and evaluates the behavior of two widely deployed congestion control algorithms, TCP Cubic and TCP BBR, under a variety of scenarios. The main [...] Read more.
Sharing bottleneck bandwidth among TCP flows with diverse round-trip times (RTTs) remains a persistent challenge. This study investigates RTT unfairness and evaluates the behavior of two widely deployed congestion control algorithms, TCP Cubic and TCP BBR, under a variety of scenarios. The main objective is to better understand the underlying causes of RTT-based throughput disparity and to identify network configurations that promote fair bandwidth sharing. Using the Mininet emulation platform, extensive experiments were conducted to examine the effects of buffer size, sender distribution, and delay asymmetry on transmission performance metrics. The results show that while TCP BBR achieves high utilization with minimal buffering, its fairness depends on the interaction between RTT and buffer size. On the other hand, TCP Cubic achieves better fairness when moderate buffer sizes are provisioned and bandwidth imbalance is driven mostly by RTT ratio. These findings suggest that careful buffer sizing can reduce RTT unfairness and highlight the broader impact of queuing strategies on network performance. Full article
(This article belongs to the Section Communications)
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29 pages, 5025 KB  
Article
A Two-Stage T-Norm–Choquet–OWA Resource Aggregator for Multi-UAV Cooperation: Theoretical Proof and Validation
by Linchao Zhang, Jun Peng, Lei Hang and Zhongyang Cheng
Drones 2025, 9(9), 597; https://doi.org/10.3390/drones9090597 - 25 Aug 2025
Viewed by 344
Abstract
Multi-UAV cooperative missions demand millisecond-level coordination across three key resource dimensions—battery energy, wireless bandwidth, and onboard computing power—where traditional Min or linearly weighted schedulers struggle to balance safety with efficiency. We propose a prediction-enhanced two-stage T-norm–Choquet–OWA resource aggregator. First, an LSTM-EMA model forecasts [...] Read more.
Multi-UAV cooperative missions demand millisecond-level coordination across three key resource dimensions—battery energy, wireless bandwidth, and onboard computing power—where traditional Min or linearly weighted schedulers struggle to balance safety with efficiency. We propose a prediction-enhanced two-stage T-norm–Choquet–OWA resource aggregator. First, an LSTM-EMA model forecasts resource trajectories 3 s ahead; next, a first-stage T-norm (min) pinpoints the bottleneck resource, and a second-stage Choquet–OWA, driven by an adaptive interaction measure ϕ, elastically compensates according to instantaneous power usage, achieving a “bottleneck-first, efficiency-recovery” coordination strategy. Theoretical analysis establishes monotonicity, tight bounds, bottleneck prioritization, and Lyapunov stability, with node-level complexity of only O(1). In joint simulations involving 360 UAVs, the method holds the average round-trip time (RTT) at 55 ms, cutting latency by 5%, 10%, 15%, and 20% relative to Min, DRL-PPO, single-layer OWA, and WSM, respectively. Jitter remains within 11 ms, the packet-loss rate stays below 0.03%, and residual battery increases by about 12% over the best heuristic baseline. These results confirm the low-latency, high-stability benefits of the prediction-based peak-shaving plus two-stage fuzzy aggregation approach for large-scale UAV swarms. Full article
(This article belongs to the Section Drone Communications)
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29 pages, 919 KB  
Article
DDoS Defense Strategy Based on Blockchain and Unsupervised Learning Techniques in SDN
by Shengmin Peng, Jialin Tian, Xiangyu Zheng, Shuwu Chen and Zhaogang Shu
Future Internet 2025, 17(8), 367; https://doi.org/10.3390/fi17080367 - 13 Aug 2025
Viewed by 475
Abstract
With the rapid development of technologies such as cloud computing, big data, and the Internet of Things (IoT), Software-Defined Networking (SDN) is emerging as a new network architecture for the modern Internet. SDN separates the control plane from the data plane, allowing a [...] Read more.
With the rapid development of technologies such as cloud computing, big data, and the Internet of Things (IoT), Software-Defined Networking (SDN) is emerging as a new network architecture for the modern Internet. SDN separates the control plane from the data plane, allowing a central controller, the SDN controller, to quickly direct the routing devices within the topology to forward data packets, thus providing flexible traffic management for communication between information sources. However, traditional Distributed Denial of Service (DDoS) attacks still significantly impact SDN systems. This paper proposes a novel dual-layer strategy capable of detecting and mitigating DDoS attacks in an SDN network environment. The first layer of the strategy enhances security by using blockchain technology to replace the SDN flow table storage container in the northbound interface of the SDN controller. Smart contracts are then used to process the stored flow table information. We employ the time window algorithm and the token bucket algorithm to construct the first layer strategy to defend against obvious DDoS attacks. To detect and mitigate less obvious DDoS attacks, we design a second-layer strategy that uses a composite data feature correlation coefficient calculation method and the Isolation Forest algorithm from unsupervised learning techniques to perform binary classification, thereby identifying abnormal traffic. We conduct experimental validation using the publicly available DDoS dataset CIC-DDoS2019. The results show that using this strategy in the SDN network reduces the average deviation of round-trip time (RTT) by approximately 38.86% compared with the original SDN network without this strategy. Furthermore, the accuracy of DDoS attack detection reaches 97.66% and an F1 score of 92.2%. Compared with other similar methods, under comparable detection accuracy, the deployment of our strategy in small-scale SDN network topologies provides faster detection speeds for DDoS attacks and exhibits less fluctuation in detection time. This indicates that implementing this strategy can effectively identify DDoS attacks without affecting the stability of data transmission in the SDN network environment. Full article
(This article belongs to the Special Issue DDoS Attack Detection for Cyber–Physical Systems)
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23 pages, 5644 KB  
Article
Exploring the Performance of Transparent 5G NTN Architectures Based on Operational Mega-Constellations
by Oscar Baselga, Anna Calveras and Joan Adrià Ruiz-de-Azua
Network 2025, 5(3), 25; https://doi.org/10.3390/network5030025 - 18 Jul 2025
Viewed by 656
Abstract
The evolution of 3GPP non-terrestrial networks (NTNs) is enabling new avenues for broadband connectivity via satellite, especially within the scope of 5G. The parallel rise in satellite mega-constellations has further fueled efforts toward ubiquitous global Internet access. This convergence has fostered collaboration between [...] Read more.
The evolution of 3GPP non-terrestrial networks (NTNs) is enabling new avenues for broadband connectivity via satellite, especially within the scope of 5G. The parallel rise in satellite mega-constellations has further fueled efforts toward ubiquitous global Internet access. This convergence has fostered collaboration between mobile network operators and satellite providers, allowing the former to leverage mature space infrastructure and the latter to integrate with terrestrial mobile standards. However, integrating these technologies presents significant architectural challenges. This study investigates 5G NTN architectures using satellite mega-constellations, focusing on transparent architectures where Starlink is employed to relay the backhaul, midhaul, and new radio (NR) links. The performance of these architectures is assessed through a testbed utilizing OpenAirInterface (OAI) and Open5GS, which collects key user-experience metrics such as round-trip time (RTT) and jitter when pinging the User Plane Function (UPF) in the 5G core (5GC). Results show that backhaul and midhaul relays maintain delays of 50–60 ms, while NR relays incur delays exceeding one second due to traffic overload introduced by the RFSimulator tool, which is indispensable to transmit the NR signal over Starlink. These findings suggest that while transparent architectures provide valuable insights and utility, regenerative architectures are essential for addressing current time issues and fully realizing the capabilities of space-based broadband services. Full article
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30 pages, 891 KB  
Review
Communication Abilities, Assessment Procedures, and Intervention Approaches in Rett Syndrome: A Narrative Review
by Louiza Voniati, Angelos Papadopoulos, Nafsika Ziavra and Dionysios Tafiadis
Brain Sci. 2025, 15(7), 753; https://doi.org/10.3390/brainsci15070753 - 15 Jul 2025
Viewed by 496
Abstract
Background/Objectives: Rett syndrome (RTT) is a rare neurodevelopmental disorder that affects movement and communication skills primarily in females. This study aimed to synthesize the research from the last two decades regarding the verbal and nonverbal communication abilities, assessment procedures, and intervention approaches for [...] Read more.
Background/Objectives: Rett syndrome (RTT) is a rare neurodevelopmental disorder that affects movement and communication skills primarily in females. This study aimed to synthesize the research from the last two decades regarding the verbal and nonverbal communication abilities, assessment procedures, and intervention approaches for individuals with RTT. Methods: A structured literature search was conducted using the Embase, Scopus, and PubMed databases. Fifty-seven studies were selected and analyzed based on inclusion criteria. The data were categorized into four domains (verbal communication skills, nonverbal communication skills, assessment procedures, and intervention approaches). Results: The findings indicated a wide variety of communicative behaviors across the RTT population, including prelinguistic signals, regression in verbal output, and preserved nonverbal communicative intent. Moreover, the results highlighted the importance of tailored assessments (Inventory of Potential Communicative Acts, eye tracking tools, and Augmentative and Alternative Communication) to facilitate functional communication. The individualized intervention approaches were found to be the most effective in improving communicative participation. Conclusions: The current review provides an overview of the current evidence with an emphasis on the need for personalized and evidence-based clinical practices. Additionally, it provided guidance for professionals, clinicians, and researchers seeking to improve the quality of life for individuals with RTT. Full article
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17 pages, 5189 KB  
Article
YOLO-Extreme: Obstacle Detection for Visually Impaired Navigation Under Foggy Weather
by Wei Wang, Bin Jing, Xiaoru Yu, Wei Zhang, Shengyu Wang, Ziqi Tang and Liping Yang
Sensors 2025, 25(14), 4338; https://doi.org/10.3390/s25144338 - 11 Jul 2025
Viewed by 944
Abstract
Visually impaired individuals face significant challenges in navigating safely and independently, particularly under adverse weather conditions such as fog. To address this issue, we propose YOLO-Extreme, an enhanced object detection framework based on YOLOv12, specifically designed for robust navigation assistance in foggy environments. [...] Read more.
Visually impaired individuals face significant challenges in navigating safely and independently, particularly under adverse weather conditions such as fog. To address this issue, we propose YOLO-Extreme, an enhanced object detection framework based on YOLOv12, specifically designed for robust navigation assistance in foggy environments. The proposed architecture incorporates three novel modules: the Dual-Branch Bottleneck Block (DBB) for capturing both local spatial and global semantic features, the Multi-Dimensional Collaborative Attention Module (MCAM) for joint spatial-channel attention modeling to enhance salient obstacle features and reduce background interference in foggy conditions, and the Channel-Selective Fusion Block (CSFB) for robust multi-scale feature integration. Comprehensive experiments conducted on the Real-world Task-driven Traffic Scene (RTTS) foggy dataset demonstrate that YOLO-Extreme achieves state-of-the-art detection accuracy and maintains high inference speed, outperforming existing dehazing-and-detect and mainstream object detection methods. To further verify the generalization capability of the proposed framework, we also performed cross-dataset experiments on the Foggy Cityscapes dataset, where YOLO-Extreme consistently demonstrated superior detection performance across diverse foggy urban scenes. The proposed framework significantly improves the reliability and safety of assistive navigation for visually impaired individuals under challenging weather conditions, offering practical value for real-world deployment. Full article
(This article belongs to the Section Navigation and Positioning)
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32 pages, 2945 KB  
Article
SelfLoc: Robust Self-Supervised Indoor Localization with IEEE 802.11az Wi-Fi for Smart Environments
by Hamada Rizk and Ahmed Elmogy
Electronics 2025, 14(13), 2675; https://doi.org/10.3390/electronics14132675 - 2 Jul 2025
Viewed by 1060
Abstract
Accurate and scalable indoor localization is a key enabler of intelligent automation in smart environments and industrial systems. In this paper, we present SelfLoc, a self-supervised indoor localization system that combines IEEE 802.11az Round Trip Time (RTT) and Received Signal Strength Indicator [...] Read more.
Accurate and scalable indoor localization is a key enabler of intelligent automation in smart environments and industrial systems. In this paper, we present SelfLoc, a self-supervised indoor localization system that combines IEEE 802.11az Round Trip Time (RTT) and Received Signal Strength Indicator (RSSI) data to achieve fine-grained positioning using commodity Wi-Fi infrastructure. Unlike conventional methods that depend heavily on labeled data, SelfLoc adopts a contrastive learning framework to extract spatially discriminative and temporally consistent representations from unlabeled wireless measurements. The system integrates a dual-contrastive strategy: temporal contrasting captures sequential signal dynamics essential for tracking mobile agents, while contextual contrasting promotes spatial separability by ensuring that signal representations from distinct locations remain well-differentiated, even under similar signal conditions or environmental symmetry. To this end, we design signal-specific augmentation techniques for the physical properties of RTT and RSSI, enabling the model to generalize across environments. SelfLoc also adapts effectively to new deployment scenarios with minimal labeled data, making it suitable for dynamic and collaborative industrial applications. We validate the effectiveness of SelfLoc through experiments conducted in two realistic indoor testbeds using commercial Android devices and seven Wi-Fi access points. The results demonstrate that SelfLoc achieves high localization precision, with a median error of only 0.55 m, and surpasses state-of-the-art baselines by at least 63.3% with limited supervision. These findings affirm the potential of SelfLoc to support spatial intelligence and collaborative automation, aligning with the goals of Industry 4.0 and Society 5.0, where seamless human–machine interactions and intelligent infrastructure are key enablers of next-generation smart environments. Full article
(This article belongs to the Special Issue Collaborative Intelligent Automation System for Smart Industry)
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25 pages, 2065 KB  
Article
Lower-Latency Screen Updates over QUIC with Forward Error Correction
by Nooshin Eghbal and Paul Lu
Future Internet 2025, 17(7), 297; https://doi.org/10.3390/fi17070297 - 30 Jun 2025
Viewed by 470
Abstract
There are workloads that do not need the total data ordering enforced by the Transmission Control Protocol (TCP). For example, Virtual Network Computing (VNC) has a sequence of pixel-based updates in which the order of rectangles can be relaxed. However, VNC runs over [...] Read more.
There are workloads that do not need the total data ordering enforced by the Transmission Control Protocol (TCP). For example, Virtual Network Computing (VNC) has a sequence of pixel-based updates in which the order of rectangles can be relaxed. However, VNC runs over the TCP and can have higher latency due to unnecessary blocking to ensure total ordering. By using Quick UDP Internet Connections (QUIC) as the underlying protocol, we are able to implement a partial order delivery approach, which can be combined with Forward Error Correction (FEC) to reduce data latency. Our earlier work on consistency fences provides a mechanism and semantic foundation for partial ordering. Our new evaluation on the Emulab testbed, with two different synthetic workloads for streaming and non-streaming updates, shows that our partial order and FEC strategy can reduce the blocking time and inter-delivery time of rectangles compared to total delivery. For one workload, partially ordered data with FEC can reduce the 99-percentile message-blocking time to 0.4 ms versus 230 ms with totally ordered data. That workload was with 0.5% packet loss, 100 ms Round-Trip Time (RTT), and 100 Mbps bandwidth. We study the impact of varying the packet-loss rate, RTT, bandwidth, and CCA and demonstrate that partial order and FEC latency improvements grow as we increase packet loss and RTT, especially with the emerging Bottleneck Bandwidth and Round-Trip propagation time (BBR) congestion control algorithm. Full article
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18 pages, 503 KB  
Review
Sleep Disorders in Children with Rett Syndrome
by Christopher Harner, Thomas A. Gaffey, Shannon S. Sullivan, Manisha Witmans, Lourdes M. DelRosso and Mary Anne Tablizo
Children 2025, 12(7), 869; https://doi.org/10.3390/children12070869 - 30 Jun 2025
Viewed by 567
Abstract
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder marked by neurological regression, autonomic dysfunction, seizures, and significant sleep and breathing abnormalities. About 80% of affected individuals, especially young children, experience sleep disturbances such as insomnia, sleep-disordered breathing, nocturnal vocalizations, bruxism, and seizures. Breathing [...] Read more.
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder marked by neurological regression, autonomic dysfunction, seizures, and significant sleep and breathing abnormalities. About 80% of affected individuals, especially young children, experience sleep disturbances such as insomnia, sleep-disordered breathing, nocturnal vocalizations, bruxism, and seizures. Breathing irregularities during sleep—like apnea, alternating hyperventilation, and hypoventilation—are common, with both obstructive and central sleep apnea identified through polysomnography. This review focuses on the prevalent sleep disorders in children with Rett syndrome and highlights current recommendations for the management of sleep disorders. Full article
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23 pages, 678 KB  
Article
Unified Probabilistic and Similarity-Based Position Estimation from Radio Observations
by Max Werner, Markus Bullmann, Toni Fetzer and Frank Deinzer
Sensors 2025, 25(13), 4092; https://doi.org/10.3390/s25134092 - 30 Jun 2025
Viewed by 331
Abstract
We propose a modeling approach for position estimation based on the observed radio propagation in an environment. The approach is purely similarity-based and therefore free of explicit physical assumptions. What distinguishes it from classical related methods are probabilistic position estimates. Instead of just [...] Read more.
We propose a modeling approach for position estimation based on the observed radio propagation in an environment. The approach is purely similarity-based and therefore free of explicit physical assumptions. What distinguishes it from classical related methods are probabilistic position estimates. Instead of just providing a point estimate for a given signal sequence, our model returns the distribution of possible positions as continuous probability density function, which allows for appropriate integration into recursive state estimation systems. The estimation procedure starts by using a kernel to compare incoming data with reference recordings from known positions. Based on the obtained similarities, weights are assigned to the reference positions. An arbitrarily chosen density estimation method is then applied given this assignment. Thus, a continuous representation of the distribution of possible positions in the environment is provided. We apply the solution in a Particle Filter (PF) system for smartphone-based indoor localization. The approach is tested both with radio signal strength (RSS) measurements (Wi-Fi and Bluetooth Low Energy RSSI) and round-trip time (RTT) measurements, given by Wi-Fi Fine Timing Measurement. Compared to distance-based models, which are dedicated to the specific physical properties of each measurement type, our similarity-based model achieved overall higher accuracy at tracking pedestrians under realistic conditions. Since it does not explicitly consider the physics of radio propagation, the proposed model has also been shown to work flexibly with either RSS or RTT observations. Full article
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25 pages, 5708 KB  
Article
AEA-YOLO: Adaptive Enhancement Algorithm for Challenging Environment Object Detection
by Abdulrahman Kariri and Khaled Elleithy
AI 2025, 6(7), 132; https://doi.org/10.3390/ai6070132 - 20 Jun 2025
Viewed by 1177
Abstract
Despite deep learning-based object detection techniques showing promising results, identifying items from low-quality images under unfavorable weather settings remains challenging because of balancing demands and overlooking useful latent information. On the other hand, YOLO is being developed for real-time object detection, addressing limitations [...] Read more.
Despite deep learning-based object detection techniques showing promising results, identifying items from low-quality images under unfavorable weather settings remains challenging because of balancing demands and overlooking useful latent information. On the other hand, YOLO is being developed for real-time object detection, addressing limitations of current models, which struggle with low accuracy and high resource requirements. To address these issues, we provide an Adaptive Enhancement Algorithm YOLO (AEA-YOLO) framework that allows for an enhancement in each image for improved detection capabilities. A lightweight Parameter Prediction Network (PPN) containing only six thousand parameters predicts scene-adaptive coefficients for a differentiable Image Enhancement Module (IEM), and the enhanced image is then processed by a standard YOLO detector, called the Detection Network (DN). Adaptively processing images in both favorable and unfavorable weather conditions is possible with our suggested method. Extremely encouraging experimental results compared with existing models show that our suggested approach achieves 7% and more than 12% in mean average precision (mAP) on the PASCAL VOC Foggy artificially degraded and the Real-world Task-driven Testing Set (RTTS) datasets. Moreover, our approach achieves good results compared with other state-of-the-art and adaptive domain models of object detection in normal and challenging environments. Full article
(This article belongs to the Section AI Systems: Theory and Applications)
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18 pages, 1981 KB  
Article
Overcoming Challenges in Learning Prerequisites for Adaptive Functioning: Tele-Rehabilitation for Young Girls with Rett Syndrome
by Rosa Angela Fabio, Samantha Giannatiempo and Michela Perina
J. Pers. Med. 2025, 15(6), 250; https://doi.org/10.3390/jpm15060250 - 14 Jun 2025
Cited by 1 | Viewed by 595
Abstract
Background/Objectives: Rett Syndrome (RTT) is a rare neurodevelopmental disorder that affects girls and is characterized by severe motor and cognitive impairments, the loss of purposeful hand use, and communication difficulties. Children with RTT, especially those aged 5 to 9 years, often struggle [...] Read more.
Background/Objectives: Rett Syndrome (RTT) is a rare neurodevelopmental disorder that affects girls and is characterized by severe motor and cognitive impairments, the loss of purposeful hand use, and communication difficulties. Children with RTT, especially those aged 5 to 9 years, often struggle to develop the foundational skills necessary for adaptive functioning, such as eye contact, object tracking, functional gestures, turn-taking, and basic communication. These abilities are essential for cognitive, social, and motor development and contribute to greater autonomy in daily life. This study aimed to explore the feasibility of a structured telerehabilitation program and to provide preliminary observations of its potential utility for young girls with RTT, addressing the presumed challenge of engaging this population in video-based interactive training. Methods: The intervention consisted of 30 remotely delivered sessions (each lasting 90 min), with assessments at baseline (A), after 5 weeks (B1), and after 10 weeks (B2). Quantitative outcome measures focused on changes in eye contact, object tracking, functional gestures, social engagement, and responsiveness to visual stimulus. Results: The findings indicate that the program was feasible and well-tolerated. Improvements were observed across all measured domains, and participants showed high levels of engagement and participation throughout the intervention. While these results are preliminary, they suggest that interactive digital formats may be promising for supporting foundational learning processes in children with RTT. Conclusions: This study provides initial evidence that telerehabilitation is a feasible approach for engaging young girls with RTT and supporting adaptive skill development. These findings may inform future research and the design of controlled studies to evaluate the efficacy of technology-assisted interventions in this population. Full article
(This article belongs to the Special Issue Ehealth, Telemedicine, and AI in the Precision Medicine Era)
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18 pages, 1666 KB  
Review
Molecular Insights into Neurological Regression with a Focus on Rett Syndrome—A Narrative Review
by Jatinder Singh and Paramala Santosh
Int. J. Mol. Sci. 2025, 26(11), 5361; https://doi.org/10.3390/ijms26115361 - 3 Jun 2025
Viewed by 1094
Abstract
Rett syndrome (RTT) is a multisystem neurological disorder. Pathogenic changes in the MECP2 gene that codes for methyl-CpG-binding protein 2 (MeCP2) in RTT lead to a loss of previously established motor and cognitive skills. Unravelling the mechanisms of neurological regression in RTT is [...] Read more.
Rett syndrome (RTT) is a multisystem neurological disorder. Pathogenic changes in the MECP2 gene that codes for methyl-CpG-binding protein 2 (MeCP2) in RTT lead to a loss of previously established motor and cognitive skills. Unravelling the mechanisms of neurological regression in RTT is complex, due to multiple components of the neural epigenome being affected. Most evidence has primarily focused on deciphering the complexity of transcriptional machinery at the molecular level. Little attention has been paid to how epigenetic changes across the neural epigenome in RTT lead to neurological regression. In this narrative review, we examine how pathogenic changes in MECP2 can disrupt the balance of the RTT neural epigenome and lead to neurological regression. Environmental and genetic factors can disturb the balance of the neural epigenome in RTT, modifying the onset of neurological regression. Methylation changes across the RTT neural epigenome and the consequent genotoxic stress cause neurons to regress into a senescent state. These changes influence the brain as it matures and lead to the emergence of specific symptoms at different developmental periods. Future work could focus on epidrugs or epi-editing approaches that may theoretically help to restore the epigenetic imbalance and thereby minimise the impact of genotoxic stress on the RTT neural epigenome. Full article
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26 pages, 9830 KB  
Article
Neuronal Plasticity-Dependent Paradigm and Young Plasma Treatment Prevent Synaptic and Motor Deficit in a Rett Syndrome Mouse Model
by Sofía Espinoza, Camila Navia, Rodrigo F. Torres, Nuria Llontop, Verónica Valladares, Cristina Silva, Ariel Vivero, Exequiel Novoa-Padilla, Jessica Soto-Covasich, Jessica Mella, Ricardo Kouro, Sharin Valdivia, Marco Pérez-Bustamante, Patricia Ojeda-Provoste, Nancy Pineda, Sonja Buvinic, Dasfne Lee-Liu, Juan Pablo Henríquez and Bredford Kerr
Biomolecules 2025, 15(5), 748; https://doi.org/10.3390/biom15050748 - 21 May 2025
Viewed by 889
Abstract
Classical Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the MECP2 gene, resulting in a devastating phenotype associated with a lack of gene expression control. Mouse models lacking Mecp2 expression with an RTT-like phenotype have been developed to advance therapeutic [...] Read more.
Classical Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the MECP2 gene, resulting in a devastating phenotype associated with a lack of gene expression control. Mouse models lacking Mecp2 expression with an RTT-like phenotype have been developed to advance therapeutic alternatives. Environmental enrichment (EE) attenuates RTT symptoms in patients and mouse models. However, the mechanisms underlying the effects of EE on RTT have not been fully elucidated. We housed male hemizygous Mecp2-null (Mecp2-/y) and wild-type mice in specially conditioned cages to enhance sensory, cognitive, social, and motor stimulation. EE attenuated the progression of the RTT phenotype by preserving neuronal cytoarchitecture and neural plasticity markers. Furthermore, EE ameliorated defects in neuromuscular junction organization and restored the motor deficit of Mecp2-/y mice. Treatment with plasma from young WT mice was used to assess whether the increased activity could modify plasma components, mimicking the benefits of EE in Mecp2-/y. Plasma treatment attenuated the RTT phenotype by improving neurological markers, suggesting that peripheral signals of mice with normal motor function have the potential to reactivate dormant neurodevelopment in RTT mice. These findings demonstrate how EE and treatment with young plasma ameliorate RTT-like phenotype in mice, opening new therapeutical approaches for RTT patients. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis for Rare Genetic Diseases)
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