Search Results (1,638)

As a crucial strategy for mitigating climate change and achieving electricity independence, renewable energy sources (RESs) are gaining widespread importance. This study explores achieving electricity autonomy for Nisyros Island, Greece, through RESs. Four scenarios are evaluated, including standalone wind and photovoltaic systems, alongside hybrid options combining both. Each scenario is designed to meet the island’s electricity demands while considering economic feasibility and minimal environmental impact. The research findings are that wind-based scenarios offer the most cost-effective solutions, with a three wind turbine setup emerging as the most economical option for full coverage of electricity demands. Hybrid approaches, particularly those incorporating more wind turbines, are also financially viable. Real-world consumption data are integrated into the analysis, providing valuable insights for Nisyros’ energy future. Overall, the study demonstrates Nisyros’ potential to achieve electricity independence through RESs, with wind resource assessments suggesting that the island could become autonomous. This approach would promote environmental sustainability by reducing the given dependence on fossil fuels. Additionally, it would bring economic benefits for the island’s residents in the renewable energy sector. Furthermore, this work allows for the island to achieve electricity independence through renewable energy in alignment with the EU’s climate goals. Full article

Musculoskeletal ultrasound (US) imaging faces challenges such as operator experience, limited spatial flexibility, and high personnel costs. This study introduces an Automated Robotic Ultrasound Scanning (ARUS) system that integrates key technological advancements to automate the ultrasound scanning procedure with the robot, including anatomical target localization, automatic trajectory generation, deep-learning-based segmentation, and 3D reconstruction of musculoskeletal structures. The ARUS system consists of a robotic arm, ultrasound imaging, and stereo vision for precise anatomical area detection. A Graphical User Interface (GUI) facilitates a flexible selection of scanning trajectories, improving user interaction and enabling customized US scans. To handle complex and dynamic curvatures on the skin, together with anatomical area detection, the system employs a hybrid position–force control strategy based on the generated trajectory, ensuring stability and accuracy. Additionally, the utilized RA-UNet model offers multi-label segmentation on the bone and muscle tissues simultaneously, which incorporates residual blocks and attention mechanisms to enhance segmentation accuracy and robustness. A custom musculoskeletal phantom was used for validation. Compared to the reference 3D reconstruction result derived from the MRI scan, ARUS achieved a 3D reconstruction root mean square error (RMSE) of 1.22 mm, with a mean error of 0.94 mm and a standard deviation of 0.77 mm. The ARUS system extends 3D musculoskeletal imaging capacity by enabling both bones and muscles to be segmented and reconstructed into 3D shapes in real time and simultaneously. These features suggest significant potential as a cost-effective and reliable option for musculoskeletal examination and diagnosis in real-time applications. Full article

Background: Ipilimumab and nivolumab (ipi/nivo) improved overall survival (OS) compared to sunitinib in the pivotal Checkmate 214 trial of metastatic renal cell carcinoma (mRCC) with International Metastatic RCC Database Consortium (IMDC) intermediate/poor risk disease. We evaluated the efficacy and toxicity of ipi/nivo in older and frailer populations in a real-world mRCC cohort. Methods: Analysis was conducted on a real-world cohort with mRCC (N = 551) treated with first-line ipi/nivo from the Canadian Kidney Cancer information system (CKCis) database from January 2014 to December 2021. A comparison was made between outcomes and toxicity in patients 1. <70 versus (vs.) ≥70 yo, 2. <75 vs. ≥75 yo, and 3. KPS ≥70 vs. <70 yo. OS, progression-free survival (PFS), and time to treatment failure (TTF) were calculated by Kaplan–Meier analysis. Log-rank tests were used for comparison between groups. Results: Ipi/nivo treatment had no impact on survival outcomes or toxicity for patients >70 yo and >75 yo when controlled for IMDC. However, when comparing patients with KPS > 70 vs. KPS < 70, patients with a poor performance status had decreased median OS at 54.5 m vs. 10.8 m (p-value < 0.0001) and PFS at 11.6 vs. 3.1 m (p-value < 0.0001). Conclusions: The use of ipi/nivo in mRCC demonstrated similar survival outcomes and toxicity in an older patient population. In patients with a poor performance status, it was associated with inferior OS and PFS. We believe that ipi/nivo is a reasonable treatment option for these patient populations, particularly in older patients. Full article

We show that the discrete real option game model proposed in the recent literature can be extended to the case of imperfect information. As a result, the model can cover a wider range of applications. However, we also observe that the effectiveness of implementing the subsidy is affected by the imperfect informational structure. Full article

Parasitic gastrointestinal worms (i.e., helminths) remain a significant global health and economic burden. The increasing inefficacy of current anthelmintic drugs against parasitic diseases necessitates the discovery of novel therapeutic options. This study investigated the anthelmintic properties and therapeutic potential of stonefish ichthyocrinotoxins (i.e., secreted skin toxins). xWORM (xCELLigence Worm Real-Time Motility Assay) was used to evaluate the anthelmintic activity of ichthyocrinotoxins from two stonefish species, Synanceia horrida (Estuarine Stonefish) and Synanceia verrucosa (Reef Stonefish), against the infective third-stage larvae of Nippostrongylus brasiliensis (Rodent Hookworm). Both toxins demonstrated potent anthelmintic effects, with S. horrida ichthyocrinotoxin exhibiting greater potency (IC₅₀ = 196.0 µg/mL) compared to ichthyocrinotoxin from S. verrucosa (IC₅₀ = 329.7 µg/mL). Fractionation revealed that the anthelmintic activity of S. verrucosa is likely driven by synergistic interactions between the large (>3 kDa) and small (<3 kDa) components. In contrast, the small components isolated from S. horrida ichthyocrinotoxin were responsible for the majority of the observed activity, making them a more attractive therapeutic candidate. Furthermore, despite the cytotoxicity of crude S. horrida ichthyocrinotoxin against human skin and bile duct cell lines, the isolated small components exhibited potent anthelmintic effects (IC₅₀ = 70.5 µg/mL) with negligible cytotoxicity (<10% decrease in survival at 100 µg/mL). While further research is necessary to fully characterise these compounds and assess their clinical suitability, this study highlights the potential of stonefish ichthyocrinotoxins as a novel source of anthelmintic therapeutics. Full article

The problem of early crack formation caused by temperature stresses in hardening concrete is very relevant for massive monolithic reinforced concrete structures. The aim of the work is to develop a method for thermal cracking risk prediction during the construction of massive monolithic reinforced concrete structures. The innovation of the research consists in taking into account the dependence of the concrete elastic modulus and strength on the time and temperature of hardening. The significance of the study lies in analysis of methods for reducing the risk of early cracking using the example of a real structure. The object of the study is a fragment of a massive monolithic dock wall. The analysis is performed by the finite element method using a program developed by the authors in the MATLAB environment. Verification of the developed software was performed by comparison with the solution in ANSYS using a linear elastic model without time dependence of the elastic modulus. Next, various options were used to set the dependence of the mechanical characteristics of concrete on the time and temperature of hardening. An analysis was conducted of the possibility of reducing the risk of early cracking by reducing the length of the concrete block, correcting the heat exchange conditions of the surfaces, and reducing the heat generation of concrete. Full article

While neuromodulation devices for managing neurological conditions have significantly advanced, there remains a substantial gap in FDA-approved devices specifically designed for pediatric patients. Devices like deep brain stimulators (DBS), vagus nerve stimulators (VNS), and spinal cord stimulators (SCS) are primarily approved for adults, with few options for children. To meet pediatric needs, off-label use is common; however, unique challenges to pediatric device development—such as ethical concerns, small trial populations, and financial disincentives due to the limited market size—continue to hinder progress. This review examines these barriers to pediatric neuromodulation device development and FDA (Food and Drug Administration) approval, as well as the current efforts, such as FDA initiatives and consortia support, that address regulatory and financial challenges. Furthermore, we discuss pathways like the Humanitarian Device Exemptions and Real-World Evidence programs that aim to streamline the approval process and address unmet clinical needs in pediatric care. Addressing these barriers could expand access to effective neuromodulation treatments and improve patient care. Full article

Belzutifan is a new HIF-α inhibitor mainly used in two different indications: von Hippel–Lindau syndrome-associated renal cell carcinoma, haemangioblastomas and pancreatic neuroendocrine tumours, as well as sporadic advanced pre-treated renal cell carcinoma. Although efficacy has been demonstrated in phase II and III studies, belzutifan is still not approved in many countries. In addition, von Hippel–Lindau syndrome is a rare disease. Therefore, there is virtually no real-world experience data of belzutifan efficacy available. We aim to determine the real-world efficacy and tolerability of belzutifan in patients with von Hippel–Lindau syndrome-associated tumours and in patients with sporadic advanced tyrosine kinase- and immune checkpoint inhibitors pre-treated for renal cell carcinoma. A retrospective analysis of five patients treated with belzutifan between 2023 and 2024 at a Swiss cancer centre was conducted. In this case series, all patients consistently benefitted from belzutifan with response to treatment. This case series provides real-world evidence that belzutifan is an effective and well-tolerated treatment option for patients with von Hippel–Lindau syndrome-associated renal cell carcinoma, haemangioblastomas and sporadic advanced pre-treated renal cell carcinoma. Full article

The prolonged use of X-rays has led to an increased exposure of medical personnel to radiation, resulting in a more than 40% higher incidence of cancer compared to patients and other groups. Therefore, this article presents an alternative for protecting medical personnel, which involves designing and constructing an articulated robotic arm for minimally invasive stereotactic localization in operating rooms. The project’s main objective is for the robotic arm to assist doctors in minimally invasive procedures, including needle insertion into the patient. The methodology was developed in four stages: the first stage involved direct kinematic analysis, where the Denavit–Hartenberg parameters and robot motion equations were determined; the second stage involved the design and modeling of the robot’s links and joints; the third stage involved obtaining the robot’s dynamics using Jacobian matrices with inertial properties extracted from the elements; and the fourth stage involved the implementation of the robot using structural components (actual measurements), axes, transmissions, motors, 3D printing of the design, and an embedded system for control. The results show that the prototype can accurately assist doctors in minimally invasive procedures. Additionally, the robot provides a versatile solution for medical robotics with compact devices that can be adapted to various environments and are easy to operate. Furthermore, the prototype’s performance in real scenarios promises to enhance healthcare professionals’ capabilities and reduce radiation exposure risks. In conclusion, the prototype proves to be a viable option for protecting medical personnel exposed to radiation. Moreover, as a first version, several aspects for improvement were identified, including strengthening communications, improving the appearance, simplifying control, and optimizing needle actions for confined spaces. Full article

Background: Endovascular treatment of venous disease is introducing new therapeutic options in neuroradiology. These procedures are technically challenging and require extensive physician training. Currently, training is mainly conducted on animal models, which presents drawbacks such as ethical concerns and anatomical differences from human vascular architecture. There is no training model that simulates treating intracranial venous disease using original instruments in a real angiography suite. Methods: This work presents the development of a venous system model for endovascular training simulations for integration into the existing Hamburg ANatomical NEurointerventional Simulator (HANNES) for arterial interventions. Results: The manufacturing process established at HANNES and the material used for the arterial vascular models were successfully transferred to the larger 3D-printed vein models. The application test was conducted in a real angiography suite with original instruments by an experienced neurointerventional physician to evaluate the system in terms of geometric mapping, flow, haptics and probing. Conclusion: This newly developed model provides a first approach to simulate an endovascular intervention in the venous system within the HANNES environment. Future expansions might include specific treatment simulations for conditions such as arteriovenous malformations, dural arteriovenous fistulas, sinus vein thrombosis and hydrocephalus. Full article

This study proposes a method for selecting suitable edge hardware and Artificial Intelligence (AI) models to be deployed on these edge devices. Edge AI, which enables devices at the network periphery to perform intelligent tasks locally, is rapidly expanding across various domains. However, selecting appropriate edge hardware and AI models is a multi-faceted challenge due to the wide range of available options, diverse application requirements, and the unique constraints of edge environments, such as limited computational power, strict energy constraints, and the need for real-time processing. Ad hoc approaches often lead to non-optimal solutions and inefficiency problems. Considering these issues, we propose a method based on the ISO/IEC 25010:2011 quality standard, integrating Multi-Criteria Decision Analysis (MCDA) techniques to assess both the hardware and software aspects of Edge AI applications systematically. For the proposed method, we conducted an experiment consisting of two stages: In the first stage of the experiment, to show the applicability of the method across different use cases, we tested the method with four scenarios on UAVs, each presenting distinct edge requirements. In the second stage of the experiment, guided by the method’s recommendations for Scenario I, where the STM32H7 series microcontrollers were identified as the suitable hardware and the object detection model with Single Shot Multi-Box Detector (SSD) architecture and MobileNet backbone as the suitable AI model, we developed a TensorFlow Lite model from scratch to enhance the efficiency and versatility of the model for object detection tasks across various categories. This additional TensorFlow Lite model is aimed to show how the proposed method can guide the further development of optimized AI models tailored to the constraints and requirements of specific edge hardware. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important common comorbidity in subjects with type 2 diabetes, and liver fibrosis is a factor directly related to its prognosis. Glucagon-like peptide-1 receptor agonists are useful treatment options for MASLD; however, the efficacy of oral semaglutide in treating liver steatosis/fibrosis has not been fully elucidated. Methods: A secondary analysis of a multicenter, retrospective, observational study investigating the efficacy and safety of oral semaglutide in Japanese subjects with type 2 diabetes in a real-world clinical setting (the Sapporo-Oral SEMA study) was conducted. Subjects in the original cohort were divided into groups as follows: subjects with suspected MASLD (alanine aminotransferase > 30 U/L) were placed in an overall group; a subpopulation from an overall group at high risk for hepatic fibrosis (fibrosis-4 (FIB-4) index ≥ 1.3 or platelet count < 200,000/µL) was placed in a high-risk group; and the remaining subjects were placed in a low-risk group. Changes in the hepatic steatosis index and FIB-4 index after oral semaglutide induction were explored using a paired t-test or the Wilcoxon signed-rank test. Results: Overall, 169 subjects (including 131 that switched from other medications) were analyzed, and 67 and 102 subjects were selected for the high-risk and low-risk groups, respectively. Oral semaglutide significantly improved the hepatic steatosis index (from 46.1 to 44.6, p < 0.001) and FIB-4 index (from 1.04 to 0.96, p < 0.001) as well as several metabolic parameters in all cohorts. The efficacy of semaglutide in treating liver fibrosis was confirmed by the addition of, and switching from, existing agent groups. Furthermore, improvement in the FIB-4 index was significantly negatively correlated with the baseline FIB-4 index. Conclusions: The induction of oral semaglutide might be a useful treatment option for subjects with type 2 diabetes at high risk for liver fibrosis, even when switching from conventional medications for diabetes. Full article

Although pancreatic cancer presents with one of the most unfavorable prognoses, its treatment options are very limited. Mitochondria-targeting moieties, considered a new and prominent treatment modality, are expected to demonstrate synergistic anticancer effects due to their distinct mechanism compared to conventional chemotherapeutic approaches. This study evaluated the therapeutic potential of mitochondria-accumulating self-assembly peptides, referred to as Mito-FFs, utilizing both in vitro and in vivo pancreatic cancer models. Cellular viability assays revealed a concentration-dependent decrease in the survival of MIA-PACA2 pancreatic cancer cells upon exposure to Mito-FF treatment (p < 0.05). Subsequent in vitro Mito-FF treatments prompted the use of several molecular analyses, including Real-time PCR, Western blot analysis, and MitoSOX staining, which collectively indicated an upsurge in apoptosis, a concurrent reduction in the antioxidant enzyme expression, and an elevation in mitochondrial ROS levels (p < 0.05). In a murine xenograft model of pancreatic cancer, the intravenous administration of Mito-FF yielded a notable reduction in the tumor volume. Moreover, it upregulated the expression of pro-apoptotic markers, such as cleaved PARP and c-caspase 3, while concurrently downregulating the expression of an anti-apoptotic marker, MCL-1, as evidenced by both Western blot analysis and immunohistochemical staining (p < 0.05). It also resulted in the reduced expression of antioxidant enzymes like HO-1, catalase, and SOD2 within excised tumor tissues, as confirmed using Western blot analysis (p < 0.05). Cumulatively, the findings underscore the significant anticancer efficacy of Mito-FF against pancreatic cancer cells, predominantly mediated through the induction of apoptosis, suppression of antioxidant enzyme expression, and enhancement of mitochondrial ROS levels within the tumor microenvironment. Full article

Objective: The objective of this study was to evaluate the efficacy of a very-low-absorbable geraniol formulation, administered as a food supplement, in patients with irritable bowel syndrome (IBS) in a real-world setting in Italy. Methods: This open-label study was conducted in Italy on patients diagnosed with IBS and treated for 4 weeks with 240 mg/day of Palmarosa essential oil, absorbed on 960 mg of ginger root powder to obtain a very-low-absorbable geraniol formulation. Baseline characteristics, including demographic and symptoms were recorded using the IBS Severity Scoring System (IBS-SSS). After 28 ± 7 days, the patients were asked to complete the IBS-SSS questionnaire again. The primary objective was to confirm the effects of a very-low-absorbable geraniol formulation on self-reported symptoms of IBS and the quality of life of affected individuals. The secondary objective was to confirm the effect of the treatment on the different IBS subtypes. Results: A total of 1585 patients were included in the study, with a mean age of 44.8 years and 56.4% women. Following the 4-week supplementation period, significant decreases were observed in the patients’ IBS-SSS (−67.9%) and all the primary IBS symptoms, such as abdominal distention (−82.3%), unsatisfaction with bowel habits (−46.2%), and interference with quality of life (QoL) (−64.9%) (all p < 0.01). The patients’ stool type improved significantly. Treatment was effective in all IBS subtypes. Conclusions: Treatment with very-low-adsorbable geraniol food supplement was associated with improvements in symptoms and bowel habits in all IBS subtypes in a real-world setting in Italy. These findings support the use of geraniol as an effective option for patients with IBS regardless of the disease subtype. Full article

Unmanned aerial vehicles (UAVs) are highly versatile and cost-effective, making them an attractive option for various applications. In UAV networks, it is essential to implement a digital signature scheme to ensure the integrity and authentication of commands sent to UAVs. Moreover, this digital signature scheme not only maintains the real-time performance of UAVs while executing commands but also protects the identity privacy of the signer. To meet these needs, we propose an efficient threshold attribute-based proxy signature (t-ABPS) scheme that integrates a threshold predicate specifically designed for UAV networks. The formal security proof for the t-ABPS scheme demonstrates its existential unforgeability under selective-attribute and chosen-message attacks (EUF-sA-CMA) in the random oracle model. This scheme also ensures the identity privacy of the signer. Furthermore, we evaluate the computational costs and communication costs associated with the proposed scheme. Our analysis indicates that the t-ABPS scheme is more computationally efficient than other existing attribute-based proxy signature schemes, but it has higher communication costs. Full article