Search Results (42,024)

Epidermolysis Bullosa (EB) comprises a group of inherited blistering disorders caused by pathogenic variants in genes essential for skin and mucosal integrity. Nonsense mutations, which generate premature termination codons (PTCs), result in reduced or absent protein expression and contribute to severe disease phenotypes in EB. Readthrough therapies, which may continue translation past PTCs to restore full-length functional proteins, have emerged as promising approaches. This review summarizes findings from preclinical studies investigating readthrough therapies in EB models, clinical studies demonstrating efficacy in EB patients, and emerging readthrough agents with potential application to EB. Preclinical and clinical studies with gentamicin have demonstrated restored type VII collagen and laminin-332 expression, leading to measurable clinical improvements. Parallel development of novel compounds—including aminoglycoside analogs (e.g., ELX-02), translation termination factor degraders (e.g., CC-90009, SRI-41315, SJ6986), tRNA post-transcriptional inhibitors (e.g., 2,6-diaminopurine, NV848), and nucleoside analogs (e.g., clitocine)—has expanded the therapeutic pipeline. Although challenges remain regarding toxicity, codon specificity, and variable protein restoration thresholds, continued advances in molecular targeting and combination therapies offer the potential to establish readthrough therapies as localized or systemic treatments addressing both cutaneous and extracutaneous disease manifestations in EB. Full article

Epileptic seizure prediction remains a critical challenge in neuroscience and healthcare, with profound implications for enhancing patient safety and quality of life. In this paper, we introduce a novel seizure prediction method that leverages electroencephalogram (EEG) data, combining discrete wavelet transform (DWT)-based time–frequency analysis, advanced feature extraction, and deep learning using Fourier neural networks (FNNs). The proposed approach extracts essential features from EEG signals—including entropy, power, frequency, and amplitude—to effectively capture the brain’s complex and nonstationary dynamics. We measure the method based on the broadly used CHB-MIT EEG dataset, ensuring direct comparability with prior research. Experimental results demonstrate that our DWT-FS-FNN model achieves a prediction accuracy of 98.96 with a zero false positive rate, outperforming several state-of-the-art methods. These findings underscore the potential of integrating advanced signal processing and deep learning methods for reliable, real-time seizure prediction. Future work will focus on optimizing the model for real-world clinical deployment and expanding it to incorporate multimodal physiological data, further enhancing its applicability in clinical practice. Full article

This paper presents a procedural method aimed at protecting maritime critical infrastructure, which is essential for the functioning of developed nations. A novel approach, developed by the authors, is introduced—focusing on the behavioral analysis of vessels to enable early identification of suspicious maritime activity and to prevent damage or destruction to key infrastructure elements. An integrated system is proposed, combining real-time electronic surveillance with continuous access to and analysis of data from both national and international databases. Drawing inspiration from medical sciences, a screening-based methodology has been developed. Data on vessels collected from various sources are processed according to the criteria adopted by the authors, using a multi-criteria decision analysis (MCDA) approach. MCDA is a decision-support method that considers multiple criteria simultaneously. It allows for the comparison and evaluation of different options, even when they are difficult to compare directly. This characteristic is used to select high-risk vessels for further monitoring. An initial classification of a vessel as suspicious does not constitute proof of criminal activity but rather serves as a trigger for further coordinated actions. Data on vessels is collected from the AIS (automatic identification system) and platforms that store vessel history. The AIS is a powerful tool that processes parameters such as a ship’s speed and course. This article presents sample results from surveillance and pre-selection analyses using the AIS, followed by a multi-criteria assessment of the behavior of vessels identified through this process. The results are presented both graphically and numerically. The authors conducted several scenarios, analyzing different groups of vessels. Based on this analysis, recommendations were developed for the interpretation of the findings. Full article

Anthracnose, a significant disease of aloe with characteristics of contact transmission, poses a considerable threat to the economic viability of aloe cultivation. To address the challenges of accurately detecting and classifying crop diseases in complex environments, this study proposes an enhanced algorithm, YOLOv11-seg-DEDB, based on the improved YOLOv11-seg model. This approach integrates multi-scale feature enhancement and a dynamic attention mechanism, aiming to achieve precise segmentation of aloe anthracnose lesions and effective disease level discrimination in complex scenarios. Specifically, a novel Disease Enhance attention mechanism is introduced, combining spatial attention and max pooling to improve the accuracy of lesion segmentation. Additionally, the DCNv2 is incorporated into the network neck to enhance the model’s ability to extract multi-scale features from targets in challenging environments. Furthermore, the Bidirectional Feature Pyramid Network structure, which includes an additional p2 detection head, replaces the original PANet network. A more lightweight detection head structure is designed, utilizing grouped convolutions and structural simplifications to reduce both the parameter count and computational load, thereby enhancing the model’s inference capability, particularly for small lesions. Experiments were conducted using a self-collected dataset of aloe anthracnose infected leaves. The results demonstrate that, compared to the original model, the improved YOLOv11-seg-DEDB model improves segmentation accuracy and mAP@50 for infected lesions by 5.3% and 3.4%, respectively. Moreover, the model size is reduced from 6.0 MB to 4.6 MB, and the number of parameters is decreased by 27.9%. YOLOv11-seg-DEDB outperforms other mainstream segmentation models, providing a more accurate solution for aloe disease segmentation and grading, thereby offering farmers and professionals more reliable disease detection outcomes. Full article

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy characterized by complex interactions within the tumor microenvironment (TME) that facilitate immune evasion and tumor progression. The TME consists of diverse cellular components, including cancer-associated fibroblasts, immune and endothelial cells, and extracellular matrix elements, that collectively modulate tumor growth, metastasis, and resistance to therapy. Immune evasion in HNSCC is orchestrated through multiple mechanisms, including the suppression of cytotoxic T lymphocytes, recruitment of immunosuppressive cells, such as regulatory T and myeloid-derived suppressor cells, and upregulation of immune checkpoint molecules (e.g., PD-1/PD-L1 and CTLA-4). Natural killer (NK) cells, which play a crucial role in anti-tumor immunity, are often dysfunctional within the HNSCC TME due to inhibitory signaling and metabolic constraints. Additionally, endothelial cells contribute to tumor angiogenesis and immune suppression, further exacerbating disease progression. Recent advancements in immunotherapy, particularly immune checkpoint inhibitors and NK cell-based strategies, have shown promise in restoring anti-tumor immunity. Moreover, TP53 mutations, frequently observed in HNSCC, influence tumor behavior and therapeutic responses, highlighting the need for personalized treatment approaches. This review provides a comprehensive analysis of the molecular and cellular mechanisms governing immune evasion in HNSCC with a focus on novel therapeutic strategies aimed at improving patient outcomes. Full article

Using Photoplethysmogram (PPG) signals for identity recognition has been proven effective in biometric authentication. However, in real-world applications, PPG signals are prone to interference from noise, physical activity, diseases, and other factors, making it challenging to ensure accurate user recognition and verification in complex environments. To address these issues, this paper proposes an improved MSF-SE ResNet50 (Multi-Scale Feature Squeeze-and-Excitation ResNet50) model based on 2D PPG signals. Unlike most existing methods that directly process one-dimensional PPG signals, this paper adopts a novel approach based on two-dimensional PPG signal processing. By applying Continuous Wavelet Transform (CWT), the preprocessed one-dimensional PPG signal is transformed into a two-dimensional time-frequency map, which not only preserves the time-frequency characteristics of the signal but also provides richer spatial information. During the feature extraction process, the SENet module is first introduced to enhance the ability to extract distinctive features. Next, a novel Lightweight Multi-Scale Feature Fusion (LMSFF) module is proposed, which addresses the limitation of single-scale feature extraction in existing methods by employing parallel multi-scale convolutional operations. Finally, cross-stage feature fusion is implemented, overcoming the limitations of traditional feature fusion methods. These techniques work synergistically to improve the model’s performance. On the BIDMC dataset, the MSF-SE ResNet50 model achieved accuracy, precision, recall, and F1 scores of 98.41%, 98.19%, 98.27%, and 98.23%, respectively. Compared to existing state-of-the-art methods, the proposed model demonstrates significant improvements across all evaluation metrics, highlighting its significance in terms of network architecture and performance. Full article

Rolling bearings are prone to failure, meaning that research on intelligent fault diagnosis is crucial in relation to this key transmission component in rotating machinery. The application of deep learning (DL) has significantly advanced the development of intelligent fault diagnosis. This paper proposes a novel method for rolling bearing fault diagnosis based on the fractional constant Q non-stationary Gabor transform (FCO-NSGT) and VMamba-Conv. Firstly, a rolling bearing fault experimental platform is established and the vibration signals of rolling bearings under various working conditions are collected using an acceleration sensor. Secondly, a kurtosis-to-entropy ratio (KER) method and the rotational kernel function of the fractional Fourier transform (FRFT) are proposed and applied to the original CO-NSGT to overcome the limitations of the original CO-NSGT, such as the unsatisfactory time–frequency representation due to manual parameter setting and the energy dispersion problem of frequency-modulated signals that vary with time. A lightweight fault diagnosis model, VMamba-Conv, is proposed, which is a restructured version of VMamba. It integrates an efficient selective scanning mechanism, a state space model, and a convolutional network based on SimAX into a dual-branch architecture and uses inverted residual blocks to achieve a lightweight design while maintaining strong feature extraction capabilities. Finally, the time–frequency graph is inputted into VMamba-Conv to diagnose rolling bearing faults. This approach reduces the number of parameters, as well as the computational complexity, while ensuring high accuracy and excellent noise resistance. The results show that the proposed method has excellent fault diagnosis capabilities, with an average accuracy of 99.81%. By comparing the Adjusted Rand Index, Normalized Mutual Information, F1 Score, and accuracy, it is concluded that the proposed method outperforms other comparison methods, demonstrating its effectiveness and superiority. Full article

Underwater image enhancement is crucial for fields like marine exploration, underwater photography, and environmental monitoring, as underwater images often suffer from reduced visibility, color distortion, and contrast loss due to light absorption and scattering. Despite recent progress, existing methods struggle to generalize across diverse underwater conditions, such as varying turbidity levels and lighting. This paper proposes a novel hybrid UNet–Transformer architecture based on MaxViT blocks, which effectively combines local feature extraction with global contextual modeling to address challenges including low contrast, color distortion, and detail degradation. Extensive experiments on two benchmark datasets, UIEB and EUVP, demonstrate the superior performance of our method. On UIEB, our model achieves a PSNR of 22.91, SSIM of 0.9020, and CCF of 37.93—surpassing prior methods such as URSCT-SESR and PhISH-Net. On EUVP, it attains a PSNR of 26.12 and PCQI of 1.1203, outperforming several state-of-the-art baselines in both visual fidelity and perceptual quality. These results validate the effectiveness and robustness of our approach under complex underwater degradation, offering a reliable solution for real-world underwater image enhancement tasks. Full article

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

“The Internet of Things” is a relatively new idea that refers to objects that can connect to the Internet and exchange data. The Internet of Things (IoT) enables novel interactions between objects and people by interconnecting billions of devices. While there are many IoT-related products, challenges pertaining to their effective implementation, particularly the lack of knowledge and confidence about security, must be addressed. To provide IoT-based enterprises with a platform for efficiency and sustainability, this study aims to identify the critical elements that influence the growth of a successful company integrated with an IoT system. This study proposes a decision support tool that evaluates the influential features of IoT using the Pythagorean Fuzzy and Interval Grey approaches within the Analytical Hierarchy Process (AHP). This study demonstrates that security, value, and connectivity are more critical than telepresence and intelligence indicators. When both strategies are used, market demand and information privacy become significant indicators. Applying the Pythagorean Fuzzy approach enables the identification of sensor networks, authorization, market demand, and data management in terms of importance. The application of the Interval Grey approach underscores the importance of data management, particularly in sensor networks. The indicators that were finally ranked are compared to obtain a good coefficient of agreement. These findings offer practical insights for promoting sustainability in enterprise operations by optimizing IoT infrastructure and decision-making processes. Full article

The advancement of artificial intelligence (AI), deep learning, and radiomics has introduced novel methodologies for the detection, classification, prognosis, and treatment evaluation of pancreatic ductal adenocarcinoma (PDAC). As the integration of AI into medical imaging continues to evolve, its potential to enhance early detection, refine diagnostic precision, and optimize treatment strategies becomes increasingly evident. However, despite significant progress, various challenges remain, particularly in terms of clinical applicability, generalizability, interpretability, and integration into routine practice. Understanding the current state of research is crucial for identifying gaps in the literature and exploring opportunities for future advancements. This literature review aims to provide a comprehensive overview of the existing studies on AI applications in PDAC, with a focus on disease detection, classification, survival prediction, treatment response assessment, and radiogenomics. By analyzing the methodologies, findings, and limitations of these studies, we aim to highlight the strengths of AI-driven approaches while addressing critical gaps that hinder their clinical translation. Furthermore, this review aims to discuss future directions in the field, emphasizing the need for multi-institutional collaborations, explainable AI models, and the integration of multi-modal data to advance the role of AI in personalized medicine for PDAC. Full article

A novel efficient method to evaluate time-periodic flows is applied to turbomachinery configurations in this paper (PSpTM). The technique reduces the overall computational cost of unsteady CFD calculations relative to conventional implicit approaches. The method is based on a pseudo-spectral definition of the time derivative rearranged in a time-marching fashion. The key advantage of this novel formulation compared with classical harmonic methods is that it requires minor modifications in the CFD solver structure. The method was implemented into an existing unstructured edge-based, second-order, compressible RANS solver. To benchmark the method, a well-established implicit time scheme based on a second-order backward implicit approach (BDF2) is used. Sample unsteady turbomachinery configurations are used to determine the accuracy and efficiency of the method. The accuracy of the solution is highly linked to the number of harmonics prescribed for the solution. An adequate level of accuracy was obtained while retaining a reduced number of harmonics, with approximately twice the number of harmonics of the unsteady perturbation. Notable savings in computational cost were observed when the PSpTM method was used with speed-up factors of between 2 and 10 with respect to the BDF2, depending on the case. However, the PSpTM method exhibits a poor periodic convergence rate, leaving room for further improvements in efficiency. However, even in its current form and with the current understanding, the method has a remarkable performance. Full article

Background: Endometriosis is a chronic inflammatory condition affecting 10–15% of women of reproductive age. Genome-wide association studies (GWASs) have accounted for only a fraction of its high heritability, indicating the need for alternative approaches to identify rare genetic variants contributing to its etiology. To this end, we performed whole-exome sequencing (WES) in a multi-affected family. Methods: A multigenerational family was studied, comprising three sisters, their mother, grandmother, and a daughter, all diagnosed with endometriosis. WES was conducted on the three sisters and their mother. We used the enGenome-Evai and Varelect software to perform our analysis, which mainly focused on rare, missense, frameshift, and stop variants. Results: Bioinformatic analysis identified 36 co-segregating rare variants. Six missense variants in genes associated with cancer growth were prioritized. The top candidates were c.3319G>A (p.Gly1107Arg) in the LAMB4 gene and c.1414G>A (p.Gly472Arg) in the EGFL6 gene. Variants in NAV3, ADAMTS18, SLIT1, and MLH1 may also contribute to disease onset through a synergistic and additive model. Conclusions: We identified novel candidate genes for endometriosis in a multigenerational affected family, supporting a polygenic model of the disease. Our study is an exploratory family-based WES study, and replication and functional studies are warranted to confirm these preliminary findings. Full article

Botrytis cinerea is a highly versatile pathogenic fungus, causing significant damage across a wide range of plant species. A central focus of this review is the recent advances made through proteomics, an advanced molecular tool, in understanding the mechanisms of B. cinerea infection. Recent advances in mass spectrometry-based proteomics—including LC-MS/MS, iTRAQ, MALDI-TOF, and surface shaving—have enabled the in-depth characterization of B. cinerea subproteomes such as the secretome, surfactome, phosphoproteome, and extracellular vesicles, revealing condition-specific pathogenic mechanisms. Notably, in under a decade, the proportion of predicted proteins experimentally identified has increased from 10% to 52%, reflecting the rapid progress in proteomic capabilities. We explore how proteomic studies have significantly enhanced our knowledge of the fungus secretome and the role of extracellular vesicles (EVs), which play key roles in pathogenesis, by identifying secreted proteins—such as pH-responsive elements—that may serve as biomarkers and therapeutic targets. These technologies have also uncovered fine regulatory mechanisms across multiple levels of the fungal proteome, including post-translational modifications (PTMs), the phosphomembranome, and the surfactome, providing a more integrated view of its infection strategy. Moreover, proteomic approaches have contributed to a better understanding of host–pathogen interactions, including aspects of the plant’s defensive responses. Furthermore, this review discusses how proteomic data have helped to identify metabolic pathways affected by novel, more environmentally friendly antifungal compounds. A further update on the advances achieved in the field of proteomics discovery for the organism under consideration is provided in this paper, along with a perspective on emerging tools and future developments expected to accelerate research and improve targeted intervention strategies. Full article

Background: Disruptions in freight transportation—such as service delays, infrastructure failures, and labor strikes—pose significant challenges to the reliability and efficiency of intermodal networks. To address these challenges, this study introduces Adaptive Intermodal Transportation (AIT), a resilient and flexible planning framework that enhances Synchromodal Freight Transport (SFT) by integrating real-time disruption management. Methods: Building on recent advances, we propose two novel strategies: (1) Reassign with Delay Buffer, which enables dynamic rerouting of shipments within a user-defined delay tolerance, and (2) (De)Consolidation, which allows splitting or merging of shipments across services depending on available capacity. These strategies are incorporated into a re-planning module that complements a baseline optimization model and a continuous disruption-monitoring system. Numerical experiments conducted on a Great Lakes-based case study evaluate the performance of the proposed strategies against a benchmark approach. Results: Results show that under moderate and high-disruption conditions, the proposed strategies reduce delay and disruption-incurred costs while increasing the percentage of matched shipments. The Reassign with Delay Buffer strategy offers controlled flexibility, while (De)Consolidation improves resource utilization in constrained environments. Conclusions: Overall, the AIT framework demonstrates strong potential for improving operational resilience in intermodal freight systems by enabling adaptive, disruption-aware planning decisions. Full article