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17 pages, 2767 KB  
Article
A Novel Whole-Body Wearable Technology for Motor Assessment in Multiple Sclerosis: Feasibility and Usability Pilot Study
by Jessica Podda, Erica Grange, Claudia Latella, Andrea Tacchino, Enrico Valli, Ludovica Danovaro, Gianluca Milani, Marco Forleo, Antonella Tatarelli, Davide Gorbani, Alex Coppola, Ludovico Pedullà, Giampaolo Brichetto and Daniele Pucci
Sensors 2025, 25(19), 6214; https://doi.org/10.3390/s25196214 - 7 Oct 2025
Abstract
(1) Background: Technological advancements provide new opportunities to objectively assess motor deficits in people with Multiple Sclerosis (PwMS). This pilot study aimed to evaluate the performance and usability of iFeel, a novel wearable system which integrates inertial sensors, instrumented shoes, and an AI-based [...] Read more.
(1) Background: Technological advancements provide new opportunities to objectively assess motor deficits in people with Multiple Sclerosis (PwMS). This pilot study aimed to evaluate the performance and usability of iFeel, a novel wearable system which integrates inertial sensors, instrumented shoes, and an AI-based algorithm. (2) Methods: Sixteen adult PwMS (Expanded Disability Status Scale—EDSS ≤ 6) performed motor tests (Timed 25-Foot Walk—T25FW; Timed Up and Go—TUG) both with and without the iFeel suit. Patient-reported outcomes (PROs) were also collected to assess perceived fatigue, dual-task impact, and walking difficulties. System Usability Scale (SUS) and ad hoc questionnaires have been further administered to test usability. (3) Results: No significant differences were found between the clinician and system-based scores for both T25FW (p = 0.383) and TUG (p = 0.447). Reliability analyses showed good agreement for T25FW (Intraclass Correlation Coefficient—ICC = 0.83) and excellent agreement for TUG (ICC = 0.92). Sensor-derived measures correlated strongly with PROs on fatigue, dual-task interference, and mobility. Usability was rated high (SUS: 78.6 ± 16.1), with participants reporting minimal discomfort and positive perceptions of iFeel usefulness for rehabilitation, health monitoring, and daily activities. (4) Conclusions: This pilot study provides preliminary yet promising evidence on the feasibility, usability, and perceived usefulness of the iFeel technology for motor assessment in PwMS. The findings support its further development and potential integration into clinical practice, particularly for remote or continuous motor monitoring. Full article
(This article belongs to the Special Issue Sensor-Based Rehabilitation in Neurological Diseases)
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22 pages, 5706 KB  
Article
Impact of Annealing Treatment on the Potential Stability of SUS316L and Its Possibility for Realizing a Quasi-Reference Electrode
by Kyosuke Sawada, Shinji Okazaki, Tatsuki Inaba and Motohiro Sakuma
Chemosensors 2025, 13(10), 356; https://doi.org/10.3390/chemosensors13100356 - 1 Oct 2025
Viewed by 237
Abstract
This work demonstrates the use of SUS316L stainless steel as a new material for the fabrication of quasi-reference electrodes (QREs) intended to replace conventional reference electrodes (REs) in electrochemical sensors. The present study examined the potentials generated by SUS316L specimens annealed in air [...] Read more.
This work demonstrates the use of SUS316L stainless steel as a new material for the fabrication of quasi-reference electrodes (QREs) intended to replace conventional reference electrodes (REs) in electrochemical sensors. The present study examined the potentials generated by SUS316L specimens annealed in air at 400 °C and above for 1 h or more. Annealing above 500 °C increased the proportion of Cr in surface oxide films, hence reducing the stability of the potential. Samples annealed at 400 °C for 5 h produced the most stable electrode potential, which was attributed to a higher concentration of Fe in the oxide layer. The potential of such specimens increased by only 28.3 mV between test durations of 24 and 168 h, and potential data acquired at 30 s intervals had a standard deviation of less than 2 µV. Applying a surface treatment prior to immersion in the simulated tap water evidently stabilized the electrode potential, as a consequence of the formation of an inner oxide layer together with an outer layer consisting primarily of iron oxides. Full article
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36 pages, 2054 KB  
Article
Evaluating Learning Success, Engagement, and Usability of Moalemy: An Arabic Rule-Based Chatbot
by Dalal Al Faia and Khalid Alomar
Future Internet 2025, 17(10), 449; https://doi.org/10.3390/fi17100449 - 30 Sep 2025
Viewed by 125
Abstract
A rule-based chatbot is a type of chatbot that responds by matching users’ queries with pre-defined rules. In e-learning, chatbots can enhance the learning experience by assisting teachers in delivering learning materials pleasantly. This research introduces Moalemy, an Arabic rule-based chatbot designed to [...] Read more.
A rule-based chatbot is a type of chatbot that responds by matching users’ queries with pre-defined rules. In e-learning, chatbots can enhance the learning experience by assisting teachers in delivering learning materials pleasantly. This research introduces Moalemy, an Arabic rule-based chatbot designed to provide a personalized learning experience by tailoring educational content to each learner’s prior knowledge. This empirical study evaluates learning outcomes, user engagement, and system usability using both subjective and objective metrics. It compares the effectiveness of a proposed Arabic rule-based chatbot with adaptive personalization to that of a static, non-personalized chatbot. The comparison was conducted across three levels of task difficulty (easy, medium, and hard) using a 2 × 3 within-subject experimental design with 34 participants. Descriptive statistics revealed higher mean values of usability and engagement in the adaptive method. Although the analysis revealed no significant variations in learning outcomes and SUS scores, it showed statistically significant differences in user satisfaction in favor of the adaptive method, p = 0.003. Analyses showed no significant differences between the two learning methods in terms of effectiveness, efficiency, and engagement. Across difficulty levels, the adaptive method outperforms the static method in terms of efficiency and effectiveness at the medium level, and in engagement at the easy level. Full article
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9 pages, 1031 KB  
Article
Tracking Inflammation in CAR-T Therapy: The Emerging Role of Serum Amyloid A (SAA)
by Ilaria Pansini, Eugenio Galli, Alessandro Corrente, Marcello Viscovo, Silvia Baroni, Nicola Piccirillo, Patrizia Chiusolo, Federica Sorà and Simona Sica
Cancers 2025, 17(19), 3184; https://doi.org/10.3390/cancers17193184 - 30 Sep 2025
Viewed by 177
Abstract
Background: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of relapsed/refractory large B-cell lymphoma (LBCL), but its administration is often complicated by cytokine release syndrome (CRS). Interleukin-6 (IL-6) is widely used to monitor CRS, though its clinical value diminishes after tocilizumab [...] Read more.
Background: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of relapsed/refractory large B-cell lymphoma (LBCL), but its administration is often complicated by cytokine release syndrome (CRS). Interleukin-6 (IL-6) is widely used to monitor CRS, though its clinical value diminishes after tocilizumab administration. We aimed to evaluate serum amyloid A (SAA), a dynamic acute-phase reactant, as a treatment-independent biomarker of inflammation and toxicity in CAR-T recipients. Methods: This retrospective study included 43 adults with LBCL treated with axicabtagene ciloleucel. SAA and other inflammatory markers were assessed from lymphodepletion through day +11 post-infusion. CRS and ICANS were graded per ASTCT criteria. Statistical analyses included Mann–Whitney U tests, Spearman’s correlation, and ROC curve analysis to evaluate predictive performance. Results: SAA levels peaked at day +4 and normalized by day +11, displaying wave-like kinetics. Levels were significantly higher in patients with any-grade CRS at early timepoints but showed no association with ICANS. SAA correlated strongly with CRP, suPAR, sST2, fibrinogen, ferritin, procalcitonin, and IL-6. Compared to IL-6, SAA was more predictive of CRS at day +2 and +4, and unaffected by tocilizumab. Baseline SAA also correlated with the mEASIX score, suggesting linkage to endothelial stress. Non-responders at 3-month PET had higher baseline SAA than responders (196.0 vs. 17.7 mg/L, p = 0.036), with ROC analysis yielding an AUC of 0.74 and an optimal threshold of 79.8 mg/L. Conclusions: SAA is a robust and dynamic marker of systemic inflammation, with potential utility in both toxicity monitoring and response prediction in the CAR-T setting. Its independence from IL-6 modulation positions it as a promising biomarker for future integration into clinical algorithms. Full article
(This article belongs to the Special Issue Advances in Targets for CAR T Therapy in Hematologic Malignancies)
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27 pages, 12688 KB  
Article
Near-Field Pressure Signature of New-Concept Supersonic Aircraft Obtained Using Open-Source Approach
by Antimo Glorioso, Francesco Petrosino, Mattia Barbarino and Giuseppe Pezzella
Sci 2025, 7(3), 127; https://doi.org/10.3390/sci7030127 - 9 Sep 2025
Viewed by 490
Abstract
This study investigates the numerical prediction of the sonic boom phenomenon in supersonic aircraft by evaluating the near-field pressure signatures of three different aeroshapes. Two computational fluid dynamics (CFD) solvers, the open-source SU2 Multiphysics code and ANSYS Fluent, were employed to assess their [...] Read more.
This study investigates the numerical prediction of the sonic boom phenomenon in supersonic aircraft by evaluating the near-field pressure signatures of three different aeroshapes. Two computational fluid dynamics (CFD) solvers, the open-source SU2 Multiphysics code and ANSYS Fluent, were employed to assess their effectiveness in modeling the aerodynamic flow field. A preliminary validation of numerical methods was conducted against numerical data available from the Sonic Boom Prediction Workshops (SBPW) organized by NASA, ensuring simulation reliability. Particular attention is paid to the topology of the mesh grid, exploring hybrid approaches that combine structured and unstructured grids to optimize the accuracy of pressure wave transmission. In addition, different numerical schemes were analyzed to determine the best practices for sonic boom simulations. The proposed methodology was finally applied to three supersonic aircraft developed within the European project MORE&LESS, demonstrating the capability of the model to estimate shock wave generation, evaluate the aeroacoustic performance of different supersonic aeroshapes from Mach 2 to Mach 5, and provide predictions to support ground-level noise assessment. The findings of this study contribute to the definition of a comprehensive workflow for sonic boom evaluation, providing a reliable methodology for exploring future supersonic aircraft designs. Full article
(This article belongs to the Section Computer Sciences, Mathematics and AI)
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14 pages, 791 KB  
Article
Assessment of Cardiorenal Involvement in Systemic Sclerosis Patients
by Chiara Pellicano, Giancarlo D’Ippolito, Annalisa Villa, Ottavio Martellucci, Umberto Basile, Valeria Carnazzo, Valerio Basile, Edoardo Rosato, Mariapaola Marino and Antonietta Gigante
Biomolecules 2025, 15(9), 1297; https://doi.org/10.3390/biom15091297 - 9 Sep 2025
Viewed by 464
Abstract
Systemic sclerosis (SSc) is an autoimmune disease associated with a high burden of morbidity and mortality due to organ complications. Pulmonary arterial hypertension (PAH) and cardiac involvement, characterized by chronic right ventricular (RV) pressure overload with consequent RV dysfunction and ultimately right heart [...] Read more.
Systemic sclerosis (SSc) is an autoimmune disease associated with a high burden of morbidity and mortality due to organ complications. Pulmonary arterial hypertension (PAH) and cardiac involvement, characterized by chronic right ventricular (RV) pressure overload with consequent RV dysfunction and ultimately right heart failure (HF), are among these. A common comorbidity in SSc is chronic kidney disease (CKD). CKD is often present at the time of PAH diagnosis or a decline in renal function may occur during the course of the disease. CKD is strongly and independently associated with mortality in patients with PAH and HF. The cardiovascular and renal systems are closely interconnected, and disruption of this balance may result in cardiorenal syndrome (CRS). Type 2 CRS refers to CKD as a consequence of chronic HF. In clinical practice, non-specific markers such as troponin, B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), and serum creatinine aid in CRS diagnosis. More specific biomarkers, including cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), galectin-3, and soluble urokinase plasminogen activator receptor (suPAR), have shown value for diagnosis and prognosis in CRS. This study aimed to evaluate comprehensively heart/kidney damage markers related to CRS in SSc patients compared with healthy controls (HC) and to examine their association with renal and cardiac ultrasound parameters. SSc patients showed significantly higher CRS markers than HC (p < 0.001). SSc patients with clinically diagnosed CRS had significantly elevated galectin-3, suPAR, sNGAL, and uNGAL levels (p < 0.05) than SSc patients without CRS. Positive correlations were found between renal resistive index (RRI) and NT-proBNP (r = 0.335, p < 0.05), and between RRI and suPAR (r = 0.331, p < 0.05). NT-proBNP, suPAR, galectin-3, sNGAL, and uNGAL emerge as promising biomarkers for the early detection of cardiac and renal involvement in SSc patients. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Cardiorenal Syndrome)
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14 pages, 970 KB  
Article
NeuroSkin®: AI-Driven Wearable Functional Electrical Stimulation for Post-Stroke Gait Recovery—A Multicenter Feasibility Study
by Amine Metani, Lana Popović-Maneski, Perrine Seguin and Julie Di Marco
Sensors 2025, 25(18), 5614; https://doi.org/10.3390/s25185614 - 9 Sep 2025
Viewed by 1153
Abstract
(1) Background: Functional Electrical Stimulation (FES) is a recognized method for post-stroke gait rehabilitation but remains underutilized due to workflow complexity and the need for manual configuration. NeuroSkin®, a wearable FES system integrating AI-driven stimulation and sensor-based gait monitoring, was developed [...] Read more.
(1) Background: Functional Electrical Stimulation (FES) is a recognized method for post-stroke gait rehabilitation but remains underutilized due to workflow complexity and the need for manual configuration. NeuroSkin®, a wearable FES system integrating AI-driven stimulation and sensor-based gait monitoring, was developed to streamline clinical use by automating phase-specific, multi-muscle stimulation. (2) Methods: This retrospective multicenter feasibility study evaluated the integration of NeuroSkin® into routine inpatient rehabilitation. Fifteen subacute stroke patients across seven centers underwent 10 to 20 FES-assisted gait training sessions. Standardized assessments (10MWT, 6MWT, TUG, NFAC) were performed pre- and post-intervention. Therapists completed the System Usability Scale (SUS) questionnaire. (3) Results: All outcomes showed statistically significant improvement: walking speed and endurance increased by 70% and 171% respectively, TUG time decreased by 39%, and ambulation level improved by three NFAC categories. No adverse events were reported, and usability was rated as excellent (mean SUS score: 84.6). (4) Conclusions: NeuroSkin® was safely and effectively implemented in diverse clinical settings, demonstrating strong usability and promising functional benefits. These findings support the need for prospective controlled trials to confirm its clinical efficacy and broader applicability in stroke rehabilitation. Full article
(This article belongs to the Special Issue Sensors and Wearables for Rehabilitation)
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21 pages, 9666 KB  
Article
Spatial Polarisation of Extreme Temperature Responses and Its Future Persistence in Guangxi, China: A Multiscale Analysis over 1940–2023
by Siyi Hu and Xiangling Tang
Atmosphere 2025, 16(9), 1046; https://doi.org/10.3390/atmos16091046 - 3 Sep 2025
Viewed by 494
Abstract
To explore the spatiotemporal evolution of extreme temperature events in Guangxi (1940–2023), reveal regional response mechanisms, and assess future trends of persistence under climate warming, a multi-scale analysis was conducted using ERA5 reanalysis data. Methodologies included RH tests for homogeneity correction, collaborative kriging [...] Read more.
To explore the spatiotemporal evolution of extreme temperature events in Guangxi (1940–2023), reveal regional response mechanisms, and assess future trends of persistence under climate warming, a multi-scale analysis was conducted using ERA5 reanalysis data. Methodologies included RH tests for homogeneity correction, collaborative kriging for data optimisation, Mann–Kendall tests for trend and abrupt change detection, Morlet wavelet analysis for cyclic pattern identification, Exploratory Spatio-Temporal Data Analysis (ESTDA) for spatial heterogeneity quantification, and Rescaled Range (R/S) analysis to calculate Hurst indices for future persistence assessment. Results showed the following: (1) The ERA5 dataset exhibited high applicability in Guangxi (R = 0.9989, RMSE = 1.9492 °C), supporting robust evidence of continuous warming—warm indices (e.g., SU25, TX90p) increased significantly (SU25 at 0.2044 d/10a), while cold indices (e.g., TN10p, FD0) declined (TN10p at −0.0519 d/10a); abrupt changes of cold indices were concentrated in 1942–1950, with warm indices accelerating post-2000 and TXx exhibited the highest warming rate (0.23 °C/decade). (2) Extreme temperature indices displayed a primary 19–21-year oscillation cycle (dominant in warm indices) and a secondary 13-year cycle (prominent in cold indices). (3) Spatial heterogeneity featured northwest–southeast cold–heat inversion, coastal–inland intensity gradients, and latitudinal zonation of extreme indices; ESTDA revealed intensified polarisation, with warm indices clustering in low-latitude regions (e.g., Baise) and cold indices declining homogeneously in mountainous areas (e.g., Guilin), indicating an irreversible transition to a warming steady state. (4) R/S analysis indicated all indices had Hurst indices of 0.65–0.92, reflecting persistent future trends consistent with historical evolution, with warm indices (e.g., TNn, SU25) showing stronger persistence (H > 0.85). This work clarifies the spatial polarisation mechanism and future persistence of extreme temperature dynamics in Guangxi, providing a multi-scale scientific basis for disaster early warning and adaptation planning in climate-sensitive karst-monsoon regions. Full article
(This article belongs to the Section Meteorology)
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16 pages, 369 KB  
Article
Fairness-Based User Scheduling and Performance Optimization in Energy Harvesting Cognitive Network
by Neetu Ahirwal, N. Jayanthi and Anup Kumar Mandpura
Electronics 2025, 14(17), 3459; https://doi.org/10.3390/electronics14173459 - 29 Aug 2025
Viewed by 442
Abstract
In this work we consider a cognitive radio network with a energy harvesting relay that facilitates coexistence between primary users and multiple secondary users (SU) and a secondary destination. We analyze the outage performance of this cognitive radio network that employs a decode-and-forward [...] Read more.
In this work we consider a cognitive radio network with a energy harvesting relay that facilitates coexistence between primary users and multiple secondary users (SU) and a secondary destination. We analyze the outage performance of this cognitive radio network that employs a decode-and-forward (DF) relay and harvests energy from the secondary user’s transmitted signal. Cumulative distribution function-based user scheduling is performed for equitable allocation of channels to each SU. We consider block Rayleigh fading channels and derive novel closed-form expressions for the outage probability and system throughput. Monte Carlo simulations are conducted to verify the accuracy of the outage expression. We also develop the expression for the outage probability at a high interference threshold and utilize it to examine the impact of the power splitting factor (α) on overall performance. Our results demonstrate that through using an optimum power splitting factor the outage performance can be enhanced by nearly 2 dB. Full article
(This article belongs to the Section Microwave and Wireless Communications)
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10 pages, 705 KB  
Article
Introducing Holographic Surgical Navigation in Pediatric Wilms’ Tumor Patients: A Feasibility Study During Total Nephrectomy
by Nick T. de Groot, Jasper M. van der Zee, Guus M. J. Bökkerink, Annemieke S. Littooij, Caroline C. C. Hulsker, Cecilia E. J. Terwisscha van Scheltinga, Cornelis P. van de Ven, Ruud C. Wortel, Aart J. Klijn, Marc H. W. A. Wijnen, Matthijs Fitski and Alida F. W. van der Steeg
Bioengineering 2025, 12(8), 896; https://doi.org/10.3390/bioengineering12080896 - 21 Aug 2025
Viewed by 640
Abstract
Wilms’ tumor is a common pediatric renal malignancy. In selected cases, nephron-sparing surgery (NSS) may be employed as part of the surgical approach. To prevent positive margins, optimal understanding of the tumor–kidney edge is essential. Augmented reality (AR) enables intraoperative visualization of patient-specific [...] Read more.
Wilms’ tumor is a common pediatric renal malignancy. In selected cases, nephron-sparing surgery (NSS) may be employed as part of the surgical approach. To prevent positive margins, optimal understanding of the tumor–kidney edge is essential. Augmented reality (AR) enables intraoperative visualization of patient-specific three-dimensional (3D) holograms. In this study, we aim to validate the clinical feasibility of a holographic landmark-based registration system in pediatric patients planned for a total nephrectomy (TN), to ensure that the holographic visualization will not influence surgical decision making. In a single-center prospective study, ten pediatric patients undergoing TN were included. Patient-specific 3D holograms were created from preoperative MRI, and intraoperatively landmark-based registration was performed using the HoloLens 2. Clinical feasibility was conducted using accuracy measurements, the System Usability Scale (SUS), and a self-developed questionnaire. Three out of ten patients had a successful registration with a median measured accuracy of 7.0 mm (Interquartile Range (IQR) 6–13.5) and a median SUS score of 75 (IQR 65–77.5). Surgeons reported improved depth perception and anatomical understanding. However, in seven out of ten patients, registration failed due to multiple reasons. The most important factors were large tumor volumes obstructing landmark placement and insufficient spatial distributions of the landmarks, causing rotational misalignment. Although AR showed potential in improving the depth perception and relation in anatomical structures, the landmark-based registration with the HoloLens 2 was currently deemed insufficient for clinical implementation in pediatric abdominal surgery. Full article
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13 pages, 788 KB  
Article
Treatment Disparities, Heterogeneities, and Barriers to Access for Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: A National Survey from Brazil
by Heloisa Resende, Vinícius de Q. Aguiar, Nataline F. de A. Santos, João Vitor Siqueira Jardim and André Ornelas
Curr. Oncol. 2025, 32(8), 471; https://doi.org/10.3390/curroncol32080471 - 19 Aug 2025
Viewed by 648
Abstract
Breast cancer (BC) is the most common malignancy among Brazilian women, with a high percentage of the cases diagnosed at advanced or metastatic stages (mBC). In Brazil, where 75% of the population depends on the resource-limited public health system (SUS), mBC poses significant [...] Read more.
Breast cancer (BC) is the most common malignancy among Brazilian women, with a high percentage of the cases diagnosed at advanced or metastatic stages (mBC). In Brazil, where 75% of the population depends on the resource-limited public health system (SUS), mBC poses significant treatment challenges and disparities. To characterize this scenario, we conducted an online survey assessing treatment strategies available for HER2-negative, hormone receptor (HR)-positive mBC across public and private health systems. The 48-question survey addressed topics such as waiting time (WT) from oncology unit entry to treatment initiation, availability of oncologic medications, and access to palliative and multidisciplinary care teams. Between 2 August 2022 and 30 September 2022, a total of 180 oncologists were invited, and 150 met the inclusion criteria. The median WT for surgery was 60 days in the SUS versus 30 days in the private sector (p < 0.0001), and for chemotherapy, 30 days in the SUS versus 15 days privately (p < 0.0001). Endocrine therapy was the preferred first-line treatment in the SUS (83.3%), while fulvestrant was available to only 48% of respondents. Additionally, specialized palliative care teams were available according to 66% of SUS respondents compared with 82% in the private system (p = 0.001). These findings underscore persistent disparities in mBC treatment, likely driven by limited governmental health investment. Full article
(This article belongs to the Section Breast Cancer)
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14 pages, 1132 KB  
Article
Dynamics of the Novel Cardiac Biomarkers sST2, H-FABP, GDF-15 and suPAR in HFrEF Patients Undergoing Heart Failure Therapy, a Pilot Study
by Bernhard Ohnewein, Zornitsa Shomanova, Peter Jirak, Vera Paar, Albert Topf, Lidia Pylypenko, Max Schäbinger, Fabian Volg, Uta C. Hoppe, Rudin Pistulli, Naufal Zagidullin, Michael Lichtenauer and Lukas J. Motloch
J. Clin. Med. 2025, 14(16), 5668; https://doi.org/10.3390/jcm14165668 - 11 Aug 2025
Cited by 1 | Viewed by 2997
Abstract
Background: Despite improvements in medical therapy, heart failure with reduced ejection fraction (HFrEF) is a major burden on the healthcare system and remains a leading cause of death with a 5-year mortality rate of more than 60%. Novel therapeutic agents such as angiotensin-receptor-neprilysin-inhibitors [...] Read more.
Background: Despite improvements in medical therapy, heart failure with reduced ejection fraction (HFrEF) is a major burden on the healthcare system and remains a leading cause of death with a 5-year mortality rate of more than 60%. Novel therapeutic agents such as angiotensin-receptor-neprilysin-inhibitors (ARNIs) lead to significant improvement in clinical outcomes. Optimal therapy monitoring under these novel drugs is crucial for improving the outcome. In this trial, the diagnostic potential of four novel cardiovascular biomarkers—GDF-15, sST2, H-FABP, and suPAR—was evaluated during follow-up in patients with HFrEF. Methods: In this prospective cohort pilot study, 70 patients with HFrEF with ischemic (n = 34) and non-ischemic (n = 36) origin were included. All included patients were on a stable treatment regimen and in a non-decompensated state. The clinical parameters NYHA class, LVEF, MPI/Tei index and ESC Score 2 and the laboratory parameters sST2 (remodeling, inflammation), GDF-15 (remodeling, inflammation), H-FABP (subclinical ischemia and ischemia), suPAR (remodeling, inflammation) and NT-proBNP were assessed before ARNI therapy initiation and at 3 to 6 months at follow-up. Before starting ARNI therapy with sacubitril/valsartan patients had stable and well-established heart failure therapy. Results: There was a sufficient response to therapy with significant improvement in ejection fraction from 29.9% to 38.5% (p < 0.001) and a significant decrease in NT-proBNP from 1402 pg/mL to 572.0 pg/mL (p = 0.003). Interestingly, along with that, a significant increase in sST2 levels from 9602 pg/mL to 12,001 pg/mL (p = 0.039) but no significant change in H-FABP (p = 0.397), GDF-15 (p = 0.382) or suPAR (p = 0.328) were observed. Furthermore, the baseline sST2 level correlated with the risk of cardiovascular events calculated with the ESC Score 2 and the GDF15 level at follow-up correlated with the right ventricular global function, assessed with the MPI/Tei index and this correlation persisted after correction for confounders (r = 0.323, p = 0.039; r = 0.504, p = 0.011). Conclusions: The novel biomarker sST2 but not H-FABP, GDF-15 and suPAR was significantly affected by medical therapy with ARNIs. Monitoring sST2 might offer new opportunities for therapy guidance and disease management. However, these results are hypothesis generating and should be interpreted with caution, given the pilot nature of this study. Full article
(This article belongs to the Special Issue Clinical Management of Patients with Heart Failure—2nd Edition)
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28 pages, 3228 KB  
Article
Examination of Eye-Tracking, Head-Gaze, and Controller-Based Ray-Casting in TMT-VR: Performance and Usability Across Adulthood
by Panagiotis Kourtesis, Evgenia Giatzoglou, Panagiotis Vorias, Katerina Alkisti Gounari, Eleni Orfanidou and Chrysanthi Nega
Multimodal Technol. Interact. 2025, 9(8), 76; https://doi.org/10.3390/mti9080076 - 25 Jul 2025
Viewed by 1078
Abstract
Virtual reality (VR) can enrich neuropsychological testing, yet the ergonomic trade-offs of its input modes remain under-examined. Seventy-seven healthy volunteers—young (19–29 y) and middle-aged (35–56 y)—completed a VR Trail Making Test with three pointing methods: eye-tracking, head-gaze, and a six-degree-of-freedom hand controller. Completion [...] Read more.
Virtual reality (VR) can enrich neuropsychological testing, yet the ergonomic trade-offs of its input modes remain under-examined. Seventy-seven healthy volunteers—young (19–29 y) and middle-aged (35–56 y)—completed a VR Trail Making Test with three pointing methods: eye-tracking, head-gaze, and a six-degree-of-freedom hand controller. Completion time, spatial accuracy, and error counts for the simple (Trail A) and alternating (Trail B) sequences were analysed in 3 × 2 × 2 mixed-model ANOVAs; post-trial scales captured usability (SUS), user experience (UEQ-S), and acceptability. Age dominated behaviour: younger adults were reliably faster, more precise, and less error-prone. Against this backdrop, input modality mattered. Eye-tracking yielded the best spatial accuracy and shortened Trail A time relative to manual control; head-gaze matched eye-tracking on Trail A speed and became the quickest, least error-prone option on Trail B. Controllers lagged on every metric. Subjective ratings were high across the board, with only a small usability dip in middle-aged low-gamers. Overall, gaze-based ray-casting clearly outperformed manual pointing, but optimal choice depended on task demands: eye-tracking maximised spatial precision, whereas head-gaze offered calibration-free enhanced speed and error-avoidance under heavier cognitive load. TMT-VR appears to be accurate, engaging, and ergonomically adaptable assessment, yet it requires age-specific–stratified norms. Full article
(This article belongs to the Special Issue 3D User Interfaces and Virtual Reality—2nd Edition)
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21 pages, 20797 KB  
Article
The Urate-Lowering Effects and Renal Protective Activity of Iridoid Glycosides from Paederia foetida in Rats with Hyperuricemia-Induced Kidney Injury: A Pharmacological and Molecular Docking Study
by Haifeng Zhou, Xinyi Yue, Longhai Shen, Lifeng Wu, Xiaobo Li and Tong Wu
Molecules 2025, 30(15), 3098; https://doi.org/10.3390/molecules30153098 - 24 Jul 2025
Viewed by 588
Abstract
(1) Background: The urate-lowering effects of three iridoid glycosides, which are paederosidic acid, paederosidic acid methyl ester, and paederoside, isolated from Paederia foetida and the protection they provide against hyperuricemia-induced kidney injury were investigated in a rat model. (2) Methods: A hyperuricemia (HUA) [...] Read more.
(1) Background: The urate-lowering effects of three iridoid glycosides, which are paederosidic acid, paederosidic acid methyl ester, and paederoside, isolated from Paederia foetida and the protection they provide against hyperuricemia-induced kidney injury were investigated in a rat model. (2) Methods: A hyperuricemia (HUA) rat model was established in Sprague-Dawley (SD) rats through intraperitoneal potassium oxonate (PO) and intragastrical adenine for 2 weeks. Subsequently, rats in the pharmaceutical intervention groups received corresponding drug treatments at a concentration of 40 mg/kg/day, maintained consistently for 7 days. (3) Results: The results showed that three compounds reduced serum urate (SU), creatinine (CRE), and blood urea nitrogen (BUN) levels and that the urinary excretion levels of uric acid, urine urea nitrogen, and creatinine increased. Furthermore, the administration of three iridoid glycosides enhanced renal filtration capacity, as demonstrated by the elevated 24 h creatinine clearance rate (CCR) and 24 h uric acid clearance rate (CUA); improved the fraction excretion of uric acid (FEUA); and attenuated renal damage. Finally, three iridoid glycosides promoted uric acid excretion in HUA rats by downregulating URAT1 and GLUT9 and upregulating ABCG2, OAT1, and OAT3. Moreover, the molecular docking results further corroborated the finding that the three compounds can bind to multiple sites of the uric acid transporter via hydrogen, P-π, and hydrophobic bonds. (4) Conclusions: The three iridoid glycosides were found to lower SU levels by increasing uric acid excretion. They are promising natural products for the prevention of HUA and HUA-induced kidney injury. Full article
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Article
Demographic and Clinical Profile of Patients with Osteogenesis Imperfecta Hospitalized Due to Coronavirus Disease (COVID)-19: A Case Series of 13 Patients from Brazil
by Luana Lury Morikawa, Luiz Felipe Azevedo Marques, Adriele Evelyn Ferreira Silva, Patrícia Teixeira Costa, Lucas Silva Mello, Andrea de Melo Alexandre Fraga and Fernando Augusto Lima Marson
Healthcare 2025, 13(15), 1779; https://doi.org/10.3390/healthcare13151779 - 23 Jul 2025
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Abstract
Background: Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder characterized by bone fragility, most often caused by pathogenic variants in type I collagen genes. In this context, we aimed to describe the clinical and epidemiological characteristics of patients with OI who [...] Read more.
Background: Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder characterized by bone fragility, most often caused by pathogenic variants in type I collagen genes. In this context, we aimed to describe the clinical and epidemiological characteristics of patients with OI who were hospitalized for coronavirus disease (COVID)-19 in Brazil between 2020 and 2024. Methods: We conducted a retrospective descriptive analysis using data from the Brazilian Unified Health System (SUS, which stands for the Portuguese Sistema Único de Saúde) through the Open-Data-SUS platform. Patients with a confirmed diagnosis of OI and hospitalization due to COVID-19 were included. Descriptive statistical analysis was performed to evaluate demographic, clinical, and outcome-related variables. We included all hospitalized COVID-19 cases with a confirmed diagnosis of OI between 2020 and 2024. Results: Thirteen hospitalized patients with OI and COVID-19 were identified. Most were adults (9; 69.2%), male (7; 53.8%), self-identified as White (9; 69.2%), and all were residents of urban areas (13; 100.0%). The most frequent symptoms were fever (10; 76.9%), cough (9; 69.2%), oxygen desaturation (9; 69.2%), dyspnea (8; 61.5%), and respiratory distress (7; 53.8%). Two patients had heart disease, one had chronic lung disease, and one was obese. As for vaccination status, five patients (38.5%) had been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Four patients (30.8%) required admission to an intensive care unit (ICU), and six (46.2%) required noninvasive ventilatory support. Among those admitted to the ICU, only two required invasive mechanical ventilation. The clinical outcome was death in two cases (15.4%). Both patients were male, White, and had not been vaccinated against SARS-CoV-2. One was 47 years old, was not admitted to the ICU, but required noninvasive ventilation. Despite the underlying condition most patients had favorable outcomes, consistent with an international report. Conclusions: This is the first report to describe the clinical and epidemiological profile of patients with OI hospitalized for COVID-19 in Brazil, providing initial insights into how a rare bone disorder intersects with an acute respiratory infection. The generally favorable outcomes observed—despite the underlying skeletal fragility—suggest that individuals with OI are not necessarily at disproportionate risk of severe COVID-19, particularly when appropriately monitored. The occurrence of deaths only among unvaccinated patients underscores the critical role of SARS-CoV-2 vaccination in this population. Although pharmacological treatment data were unavailable, the potential protective effects of bisphosphonates and vitamin D merit further exploration. These findings support the need for early preventive strategies, systematic vaccination efforts, and dedicated clinical protocols for rare disease populations during infectious disease outbreaks. Full article
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