Highlights • MBM tumors show significant intertumor and intratumor heterogeneity in cellular composition, gene mutations, and pathway enrichment.• Therapy-treated tumors (P2, P4) exhibited immune activation, while untreated tumors (P1, P3) showed cold tumor signatures.• P1 and P4 tumors were enriched in CAFs, correlating with epithelial-mesenchymal transition and angiogenesis pathways.• Proteomic analysis revealed activation of oncogenic pathways like JAK-STAT, NF-κB, MAPK, and EMT, driving tumor progression.

This paper presents a method for extending decision-making policies in active perception tasks for multi-agent systems within partially observable environments. Multiple agents obtain their policies by training in an environment of a certain size. Those policies are then used in the environments larger in size, that are divided into sub-environments of size similar (or smaller) to one that the agents were trained in. Learned policies are adapted accordingly by proposed Action-Space Reduced Policy (ASRP). By leveraging Multi-Agent Reinforcement Learning (MARL) within a POMDP framework, agents can use their learned policies across environments of differing complexity without requiring retraining. The consensus mechanism allows agents to maintain a common belief state, supporting collaborative decision-making based on observations from all agents involved. Validation of the method is conducted on the scenario of multi-agent exploration missions, demonstrating the use of extended policies and enhanced perception accuracy. Simulation results indicate expected success rates and decision-making times, regardless of the environment’s dimensionality. Potential applications for scalable, multi-agent perception systems are discussed, along with directions for future research.

The development of technology has influenced agricultural production and the establishment of the Agriculture 4.0 system in practice. This research is focused on the selection of equipment and machinery suppliers for the needs of the MAMEX Company. When selecting suppliers, an approach based on the application of an intuitionistic fuzzy set for decision-making was used. This approach allows the uncertainty present in decision-making to be incorporated, considered, and, hopefully, reduced in order to make a final decision on which of the observed suppliers is the most suitable for this company. Ten criteria were used that enable the application of sustainability in the supply chain. Eight local suppliers of equipment and machinery were observed with these criteria. The results obtained by applying the SWARA (Step-wise Weight Assessment Ratio Analysis) method showed that the most important criterion for selecting suppliers is the reliability and quality of equipment and machinery, while the results of the CORASO (COmpromise Ranking from Alternative Solutions) method showed that the SUP2 supplier is the best choice for establishing partnership relations with the MAMEX company. This supplier should help the MAMEX company improve its business and achieve better results in the market. The contribution of this research is to improve the application of intuitionistic fuzzy sets in decision-making, and to emphasize the importance of equipment and machinery in agricultural production in the Agriculture 4.0 system.

Orthography and pronunciation in the French language are two categories in complete disparity. This discrepancy is reflected in the fact that when pronouncing French, far fewer phonemes are produced than are represented by graphemes in the written form. The goal of this paper is to present the concept of silent morphology, or inaudible morphemes in French, using examples of agreement in gender and number. For this study, we have built a written corpus of allophone French learners L2 called Didacquis, consisting of 30 written productions (narrative and argumentative texts on topics such as studies, travel, and friendships) by 12 learners at the post-initial (PI) stage based on grammatical profiles that show the developmental pathways of acquisition routes (Bartning & Schlyter, 2004). In this context allophone learners refers to people whose first language is not French. The results are interpreted through the Pienemann’s Processability Theory (1998). The conclusion is that understanding these letters in French is exclusively contextual due to the presence of silent morpheme endings and the phenomenon of homophony.

Microneedle arrays are a promising tool in the development of transdermal biosensing devices, and considerable research effort is being devoted to the development, microfabrication, optimization, and testing of different microneedle-based sensing platforms.[1] To date, microneedles have been fabricated from various materials in different shapes, sizes, and densities, with the aim of enhancing the performance of biosensors and developing user-friendly microneedle devices.[1] And we have demonstrated sensing of small molecules and macromolecules using both silicon and polymer based microneedle arrays [2-4]. However, one of the main challenges yet to be addressed is devices remaining fully functional and providing an accurate electrochemical response after skin insertion.[5] Such failure can mainly occur due to delamination or damage of the sensing layer during skin insertion. To address the above-mentioned challenges, we developed a microneedle array featuring recessed microcavities or 3D polymer lattices.[6-8] Those features are conductive microscale pockets located at the tip of the microneedles which can i) accommodate a biosensing layer and conduct electrochemical measurements, ii) protect the sensing layer from delamination during insertion and removal from the skin, and iii) position the sensing layer deep in the skin enabling proper access to the interstitial fluid. In our work, we illustrated that microcavities protect against delamination of the sensing layer during multiple skin applications, unlike microneedles without microcavities. The retained functionality of the sensing platform in glucose, urea and insulin sensing has been successfully demonstrated via ex vivo and in vivo tests. The aim of this work is to set the foundation for a new kind of microneedle design, involving the engineering of the microneedle surface to develop transdermal sensing devices suitable for practical application. This will not just help to advance transdermal sensing technology by overcoming challenges but also reduce the cost and duration of wearable sensor fabrication, and improve the reliability of microneedle-based diagnostics and health monitoring. References: [1] Nano Today 30 (2020) 100828. [2] Advanced Functional Materials 32 (2022) 200985. [3] Biosensors and Bioelectronics 222 (2023) 114955. [4] Biosensors & Bioelectronics, 192 (2021), 113496. [5] Nature Biomedical Engineering 5 (2021) 64-76. [6] ACS Materials Letters 5 (2023) 1851-1858 [7] ACS Sensors 9 (2024), 932–941. [8] Advanced Materials, 36 (2024), 2412999.

Inflammation, oxidative stress, and androgen activity are key features in benign prostate hyperplasia (BPH). Risks associated with the long-term use of 5α-reductase inhibitors have led to the search for alternative therapies, including food supplements. This study investigates the effectiveness of the combination of pollen extracts, namely Graminex®G96® (G) and Teupol 25P (T), towards oxidative stress and inflammation on human macrophages and benign prostate hyperplasia cells (BPH-1), both of which are LPS stimulated. The Nrf2-dependent antioxidant intracellular cascade as well as the NF-ĸB-driven inflammatory cascades were analyzed. The anti-proliferative effect of G and T, alone and in association, were evaluated on prostatic adenocarcinoma cells (PC-3) and BPH-1 cells. Finally, the inhibitory activity of GT on 5α-reductase was investigated in PC-3 cells by measuring epiandrosterone amounts, with the 5α-reductase inhibitor finasteride administered for comparison. All experiments were conducted in triplicate; data are presented as mean values ± standard deviations. Statistical analysis was performed using one-way analysis of variance. Our work demonstrates that GT promotes Nrf2-dependent antioxidant responses and counteracts the NF-ĸB-driven pathway in macrophages. GT is effective in counteracting the expression of pro-inflammatory cytokines and the generation of reactive oxygen species by promoting HO-1-dependent antioxidant responses in BPH-1 cells. GT reduces PC-3 and BPH-1 proliferation when associated with finasteride through a statistically significant inhibition of 5α-reductase activity. Data obtained in vitro and in silico demonstrate the potential efficacy of a multitargeted approach in the treatment of BPH.

There are differing results in recent literature concerning aneurysmal wall enhancement (AWE) after endovascular treatment (ET) of intracranial aneurysms (IAs). The aim of this retrospective study is to investigate if the presence of AWE of unruptured treated IAs via stent-assisted coiling (SAC) is associated with higher reperfusion rates. The clinical courses of 58 patients with IAs after ET via SAC were examined over the timespan of up to 5 years, assessing for AWE in T1 SPACE FS and T1 SE FS blood suppression sequences after contrast administration, events of reperfusion and need for retreatment. 58 patients were included (23 with AWE, 35 without). 18 of 23 patients (78.3%) with AWE showed reperfusion after treatment, compared to 15 of 35 patients (42.9%) without AWE. Reperfusion rates were significantly higher in patients with AWE, compared to those without AWE (p = 0.0139) also after propensity score matching (p = 0.0456). In patients with unruptured IAs treated exclusively with SAC, AWE on follow-up MRI was significantly associated with higher reperfusion rates. AWE may serve as an early imaging biomarker of post-treatment instability.

The analysis of carotid arteries, particularly plaques, in multi-sequence Magnetic Resonance Imaging (MRI) data is crucial for assessing the risk of atherosclerosis and ischemic stroke. In order to evaluate metrics and radiomic features, quantifying the state of atherosclerosis, accurate segmentation is important. However, the complex morphology of plaques and the scarcity of labeled data poses significant challenges. In this work, we address these problems and propose a semi-supervised deep learning-based approach designed to effectively integrate multi-sequence MRI data for the segmentation of carotid artery vessel wall and plaque. The proposed algorithm consists of two networks: a coarse localization model identifies the region of interest guided by some prior knowledge on the position and number of carotid arteries, followed by a fine segmentation model for precise delineation of vessel walls and plaques. To effectively integrate complementary information across different MRI sequences, we investigate different fusion strategies and introduce a multi-level multi-sequence version of U-Net architecture. To address the challenges of limited labeled data and the complexity of carotid artery MRI, we propose a semi-supervised approach that enforces consistency under various input transformations. Our approach is evaluated on 52 patients with arteriosclerosis, each with five MRI sequences. Comprehensive experiments demonstrate the effectiveness of our approach and emphasize the role of fusion point selection in U-Net-based architectures. To validate the accuracy of our results, we also include an expert-based assessment of model performance. Our findings highlight the potential of fusion strategies and semi-supervised learning for improving carotid artery segmentation in data-limited MRI applications.

Traumatic hip dislocations in children are rare injuries. They are mostly sustained after low-energy trauma in younger children, and after high-energy trauma in older children and adolescents. In 90 % of cases dislocation is posterior. Since this condition is an orthopedic emergency, it requires urgent reduction in order to avoid complications such as recurrent or habitual dislocation or avascular necrosis (AVN) of the femoral head. A 3-year old girl presented sustained posterior dislocation of the right hip after twisting injury. Clinically, the right leg was shortened, and in the position of adduction, with limited passive motion of the right hip joint. Plain pelvis X-ray revealed right hip joint dislocation. Emergency closed reduction was made after sedation by Allis maneuver, and one and a half hip spica cast was applied. After three weeks, the cast was removed and patients referred to physical therapy with allowed weight-bearing on the injured leg. At 8-month follow-up, clinical and radiographic findings were normal. Careful evaluation, complete history, thorough clinical exam and imaging are required in rare cases of pediatric traumatic hip joint dislocation, with prompt closed reduction, in order to achieve favorable clinical outcomes.

Virtual Reality (VR) is increasingly recognized as a transformative tool for soft skills training, offering immersive and interactive environments that enhance learning outcomes. The eXcape project leverages VR to develop realistic scenarios that can be designed to practice and learn critical soft skills, such as communication, teamwork, problem-solving, adaptability, and leadership. This paper presents a systematic approach to designing these scenarios ensuring effective skill acquisition and transferability. We discuss the methodology employed in scenario creation, key pedagogical considerations, and the challenges encountered in designing immersive training experiences.

The design process for motor yachts primarily relies on the experience of designers, who draw upon their knowledge gained from working on similar hull forms. However, when a new concept is to be developed, the experience garnered from standard platforms may not suffice for achieving a successful design within a short timeframe. Designing a motor yacht involves considering multiple aspects of ship hydrodynamics, including resistance, propulsion, seakeeping, and maneuverability. While these factors have been extensively discussed for different types of ships, a comprehensive joint investigation of hulls, such as those of motor yachts, is noticeably absent in the available literature. This paper aims to fill that gap by providing guidelines for the design of motor yachts with lengths ranging from 20 to 40 m. As part of a preliminary study, a series of 15 yacht hulls were developed, starting from a reference hull form. The resistance, seakeeping and maneuverability performance of these hulls were assessed under specified environmental conditions and speeds, following the ISO 22834:2022 guidelines for comfort assessment. The calculations produced response surfaces detailing the hydrodynamic properties for this series of yachts as functions of the main dimensions of the hulls. Ultimately, these responses assist in identifying optimal design solutions for the main dimensions of a new motor yacht within the 20 to 40 m length range.

Phytoremediation is a plant-driven process, widely regarded as a cost-effective and environmentally friendly in situ approach for remediating contaminated soil and water by taking up contaminants including potentially toxic elements (PTEs). In the last two decades, substantial research has focused on elucidating the mechanisms of phytoremediation and enhancing its efficiency, primarily through the identification of optimal plant species and the use of various amendments. Nevertheless, real-scale application of phytoremediation remains rare, and several critical questions need to be addressed, including selection of most effective species, improved effectiveness of phytoremediation process, and managing the safe utilisation of contaminated biomass. This review specifically focuses on phytoremediation of potentially toxic metals and metalloids in major metallophyte groups (wild herbaceous species, trees, and agricultural crops) recognizing the most efficient species for the anthropogenically influenced soils in Europe. It summarises the current state of knowledge regarding the use of respective plant species, highlighting the phytoremediation efficiency, critically examining existing and novel phytoremediation enhancement strategies and biomass utilisation pathways for each particular group. Future perspectives and research needed to refine the efficiency and economic viability of the phytoremediation process in Europe lay in better recognition of underlying physiological mechanism for metal stress tolerance, particularly among the most effective species and genera, application of synergistic enhancing techniques for delineated group of metallophytes and development of sustainable and cost-effective biomass utilisation routes.

With engineering plastics increasingly replacing traditional materials in various drive and control gear systems across numerous industrial sectors, material selection for any gearwheel critically impacts its mechanical and thermal properties. This paper investigates the engagement of steel and Polyvinylidene Fluoride (PVDF) gear pairs tested under several load conditions to determine polymer gears’ characteristic service life and failure modes. Furthermore, recognizing that the application of polymer gears is limited by insufficient data on their temperature-dependent mechanical properties, this study establishes a correlation between the tribological contact, meshing temperatures, and wear coefficients of PVDF gears. The results demonstrate that the flank surface wear of the PVDF gears is directly proportional to the temperature and load level of the tested gears. Several distinct load-induced failure modes have been detected and categorized into three groups: abrasive wear resulting from the hardness disparity between the engaging surfaces, thermal failure caused by heat accumulation at higher load levels, and tooth fracture occurring due to stiffness changes induced by the compromised tooth cross-section after numerous operating cycles at a specific wear rate.