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10 pages, 687 KB  
Review
Testicular Torsion in Inguinal Cryptorchidism: Report on Two Patients and Literature Review
by Fabio Baldanza, Francesco Grasso, Maria Sergio, Maria Patti, Valentina Maggiore, Gregorio Serra, Mario Giuffré, Giovanni Corsello, Maria Rita Di Pace and Marco Pensabene
Children 2025, 12(11), 1531; https://doi.org/10.3390/children12111531 (registering DOI) - 13 Nov 2025
Abstract
Background/Objectives: Undescended testis (UT) is a common congenital urological condition in boys, with an incidence of 2–8%. Orchiopexy is the recommended surgical treatment for UT, ideally performed before 12 months of age, with a latest window of 18 months. Testicular torsion (TT) is [...] Read more.
Background/Objectives: Undescended testis (UT) is a common congenital urological condition in boys, with an incidence of 2–8%. Orchiopexy is the recommended surgical treatment for UT, ideally performed before 12 months of age, with a latest window of 18 months. Testicular torsion (TT) is a pediatric urological emergency, occurring in 3.8 per 100,000 boys. While both UT and TT are common conditions individually, their co-occurrence in children under 18 months is rare and represents a challenging clinical scenario, especially when diagnosis and treatment are delayed, increasing the risk of testicular necrosis. Methods: This report describes two cases of testicular torsion in undescended testes in infants under 1 year of age. Both patients were presented to the hospital more than 24 h after symptom onset. Such delay led to the possibility of testicular salvage being lost due to necrosis. The first case involved a 10-month-old infant with bilateral undescended testis, who underwent orchiectomy after 36 h of torsion. The second case involved a 7-month-old baby, where a delayed diagnosis led to orchiectomy following 36 h of torsion. Both children were previously on the waiting list for orchiopexy, and in both cases contralateral orchiopexy was performed. A review of the literature on PubMed using the key-words “cryptorchid”, “undescended testis”, and “testicular torsion” revealed 36 cases of UT complicated by TT in children under 18 months, showing a high incidence of orchiectomies due to delayed diagnosis. Conclusions: Testicular torsion in undescended testis in children under 18 months is rare but associated with a high risk of gonadal necrosis. The key to improving testicular salvage rates is timely diagnosis and intervention, ideally within 6 h of symptom onset. Delayed presentation due to atypical clinical signs, such as inguinal swelling or nonspecific symptoms, complicates early detection and thus testicular salvage. Therefore, it is crucial for both parents and pediatricians to recognize the potential for torsion in cryptorchidic patients, emphasizing the importance of early surgical intervention, including orchiopexy, to prevent torsion and its associated complications. Full article
(This article belongs to the Section Pediatric Surgery)
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11 pages, 267 KB  
Article
Functional Effects of Single-Stage vs. Multi-Stage Incubation Systems and Parental Flock Age on Embryonic Development, Oxidative Stress, and Performance of Male Broiler Chickens
by Geise Linzmeier, Fernando de C. Tavernari, Aline Zampar, João V. Strapazzon, Paulo V. Oliveira, Roger Wagner, Aleksandro S. da Silva and Marcel M. Boiago
Poultry 2025, 4(4), 55; https://doi.org/10.3390/poultry4040055 (registering DOI) - 13 Nov 2025
Abstract
It is well established that both the age of the breeder hen and the type of incubator can influence the efficiency of the hatching process. However, there is a lack of information in the literature regarding the interaction between these two factors. This [...] Read more.
It is well established that both the age of the breeder hen and the type of incubator can influence the efficiency of the hatching process. However, there is a lack of information in the literature regarding the interaction between these two factors. This study evaluated the effects of incubator type (multi-stage vs. single-stage) and breeder hen age (35 and 61 weeks) on the hatching parameters, embryonic oxidative stress, performance, carcass yield, and meat quality of male broiler chickens. The embryo livers from the multi-stage incubator presented significantly higher NADP oxidase (NOX) values (p = 0.022), indicating elevated oxidative stress. A significant interaction between breeder age and incubator type was observed for the thiol concentrations, with embryos from older hens incubated in the multi-stage system showing higher thiol levels compared to those from the single-stage system. Birds from these older breeders demonstrated increased breast yield, feed intake, and weight gain, without significant changes in feed conversion ratio. Additionally, the single-stage incubator was associated with reduced embryonic oxidative stress, lower egg weight loss during incubation, and improved early performance of chicks during the first week post-hatch. In conclusion, beyond the previously recognized benefits of single-stage incubation systems, our findings highlight their potential to mitigate oxidative stress in embryos, thereby enhancing early chick development. Full article
10 pages, 1509 KB  
Article
Survey of the Trunk Wood Mycobiome of an Ancient Tilia × europaea L.
by Ales Eichmeier, Milan Spetik, Lucie Frejlichova, Jakub Pecenka, Jana Cechova, Lukas Stefl and Pavel Simek
Appl. Microbiol. 2025, 5(4), 131; https://doi.org/10.3390/applmicrobiol5040131 (registering DOI) - 13 Nov 2025
Abstract
The genus Tilia (Malvaceae) comprises long-lived broadleaf trees of considerable ecological, cultural, and historical importance in temperate Europe and Asia. Among these, Tilia × europaea L. (common European linden) is a key native species in Central and Northern Europe, with individuals documented to [...] Read more.
The genus Tilia (Malvaceae) comprises long-lived broadleaf trees of considerable ecological, cultural, and historical importance in temperate Europe and Asia. Among these, Tilia × europaea L. (common European linden) is a key native species in Central and Northern Europe, with individuals documented to live for several centuries. While the phyllosphere and soil-associated microbiomes of linden have been studied, the internal fungal communities inhabiting ancient trees remain poorly understood. In this study, the complete mycobiome of linden tree wood was analyzed. Wood-inhabiting fungi (the wood mycobiome) include endophytes, saprotrophs, and potential pathogens that can strongly influence host vitality and ecosystem processes. Advances in high-throughput amplicon sequencing (HTAS) now provide unprecedented opportunities to characterize these hidden communities. In this study, we investigated the trunk wood mycobiome of an ancient T. × europaea L. individual using a culture-independent HTAS approach. The results reveal a diverse fungal assemblage, including taxa like Arthinium or Phialemonium not previously reported from living linden wood, and highlight potential implications for tree health and longevity. This work provides a first baseline characterization of the internal mycobiome of the ancient Tilia tree and contributes to broader efforts to conserve its biological and cultural value. Full article
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40 pages, 8701 KB  
Review
Overview of Isolation Enhancement Techniques in MIMO Antenna Systems
by Paola Gómez-Ramírez, José Alfredo Tirado-Méndez and Erik Fritz-Andrade
Electronics 2025, 14(22), 4412; https://doi.org/10.3390/electronics14224412 (registering DOI) - 12 Nov 2025
Abstract
Multiple-Input Multiple-Output (MIMO) antenna systems are key to improving wireless channel capacity and reliability. Yet, their inherent need for compact configurations introduces a significant challenge: electromagnetic coupling between closely placed radiating elements. This undesirable phenomenon diminishes efficiency, increases signal correlation, and compromises electromagnetic [...] Read more.
Multiple-Input Multiple-Output (MIMO) antenna systems are key to improving wireless channel capacity and reliability. Yet, their inherent need for compact configurations introduces a significant challenge: electromagnetic coupling between closely placed radiating elements. This undesirable phenomenon diminishes efficiency, increases signal correlation, and compromises electromagnetic isolation. To mitigate these issues, researchers have proposed diverse isolation techniques, such as Defected Ground Structures (DGS), metamaterials, fractal geometries, and neutralization lines. These techniques are crucial for boosting isolation and facilitating antenna miniaturization without compromising overall electromagnetic performance, making them indispensable for modern compact communication systems. This article provides a comprehensive review of these techniques, dissecting their fundamental operating principles and analyzing the electromagnetic isolation results previously documented in the literature. Furthermore, experimental findings derived from the fabrication and characterization of prototypes, aiming to confirm the practical efficacy of these isolation methods, are presented. Full article
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24 pages, 248126 KB  
Article
Image Matching for UAV Geolocation: Classical and Deep Learning Approaches
by Fatih Baykal, Mehmet İrfan Gedik, Constantino Carlos Reyes-Aldasoro and Cefa Karabağ
J. Imaging 2025, 11(11), 409; https://doi.org/10.3390/jimaging11110409 (registering DOI) - 12 Nov 2025
Abstract
Today, unmanned aerial vehicles (UAVs) are heavily dependent on Global Navigation Satellite Systems (GNSSs) for positioning and navigation. However, GNSS signals are vulnerable to jamming and spoofing attacks. This poses serious security risks, especially for military operations and critical civilian missions. In order [...] Read more.
Today, unmanned aerial vehicles (UAVs) are heavily dependent on Global Navigation Satellite Systems (GNSSs) for positioning and navigation. However, GNSS signals are vulnerable to jamming and spoofing attacks. This poses serious security risks, especially for military operations and critical civilian missions. In order to solve this problem, an image-based geolocation system has been developed that eliminates GNSS dependency. The proposed system estimates the geographical location of the UAV by matching the aerial images taken by the UAV with previously georeferenced high-resolution satellite images. For this purpose, common visual features were determined between satellite and UAV images and matching operations were carried out using methods based on the homography matrix. Thanks to image processing, a significant relationship has been established between the area where the UAV is located and the geographical coordinates, and reliable positioning is ensured even in cases where GNSS signals cannot be used. Within the scope of the study, traditional methods such as SIFT, AKAZE, and Multiple Template Matching were compared with learning-based methods including SuperPoint, SuperGlue, and LoFTR. The results showed that deep learning-based approaches can make successful matches, especially at high altitudes. Full article
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14 pages, 347 KB  
Article
Dark Matter and Static, Spherically-Symmetric Solutions of the Extended Einstein Equations
by Chris Vuille and Andrei Ludu
Mod. Math. Phys. 2025, 1(3), 9; https://doi.org/10.3390/mmphys1030009 (registering DOI) - 12 Nov 2025
Abstract
In this paper we present a brief review of extended general relativity in four dimensions and solve versions of the extended equations for the case of static spherical symmetry in various contexts, for a previously studied Lagrangian. The exterior vacuum yields a Schwarzschild [...] Read more.
In this paper we present a brief review of extended general relativity in four dimensions and solve versions of the extended equations for the case of static spherical symmetry in various contexts, for a previously studied Lagrangian. The exterior vacuum yields a Schwarzschild solution with an additional scalar field potential that falls off logarithmically, the latter essentially an inverse square force. That is probably not adequate as a dark matter force, but might contribute. When a constant density field of ions holds sway in the exterior, a solution identical to the cosmological constant extension of Schwarzschild occurs, together with a scalar field potential declining as r3/2, however it is not asymptotically flat. An inverse square declining distribution of ionic material, according to perturbation theory, results in an additional linear gravity potential that would provide further attraction in the gravity term. A limited exact solution in the same case yields a cubic equation with a Schwarzschild solution, corresponding to A=0, and two MOND-like possible potentials, one vanishing at infinity, but a better solution must be found. The approximate solution is complex (one of many) and the system requires further study. Ionic matter is ubiquitous in the universe and provides a source for the scalar field, which suggests that the extended Einstein equations could be of utility in the dark matter problem, provided such an electromagnetic scalar force could be found and differentiated from the usual, far stronger electromagnetic forces. Further, it’s possible that the strong photon flux outside stars might have an influence, and is under current investigation. These calculations show that extending the concept of curvature and working in four dimensions with larger operators may bring new tools to the study of physics and unified field theories. Full article
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26 pages, 4654 KB  
Article
Small Molecule Compounds Inhibit Varicella-Zoster Virus Replication by Targeting the Portal Protein–Capsid Interface
by Julius Svensmark, Emily Polk, Ellyn Kornfeind, Whitney Lane, Melissa A. Visalli and Robert J. Visalli
Viruses 2025, 17(11), 1496; https://doi.org/10.3390/v17111496 (registering DOI) - 12 Nov 2025
Abstract
The Varicella-zoster virus (VZV) open reading frame 54 (ORF54) gene encodes an 87 kDa monomer that oligomerizes to form the pORF54 portal dodecamer. Located at a single viral capsid vertex, the portal facilitates the translocation of the newly synthesized viral genome into the [...] Read more.
The Varicella-zoster virus (VZV) open reading frame 54 (ORF54) gene encodes an 87 kDa monomer that oligomerizes to form the pORF54 portal dodecamer. Located at a single viral capsid vertex, the portal facilitates the translocation of the newly synthesized viral genome into the preformed empty capsid. Previously described α-methylbenzyl thiourea compounds were shown to inhibit VZV DNA encapsidation, likely by targeting pORF54. In this study, drug resistant isolates were obtained via passage of VZV in increasing concentrations of one analog, Compound I (Comp I). Mutations identified in four compound resistant isolates (amino acids 48, 304, 324 and 407) all localized to a region of the portal that was predicted to interface with capsid proteins. The portal is known to undergo significant conformational changes at the portal–capsid interface during DNA encapsidation. A set of recombinant viruses was designed to reveal the chemical and physical importance of each of the resistance mutations at the portal–capsid Full article
(This article belongs to the Special Issue Advances in Small-Molecule Viral Inhibitors)
17 pages, 353 KB  
Article
Spanglish in the US, Belize and Gibraltar: On the Importance of Comparative Research
by Osmer Balam
Languages 2025, 10(11), 283; https://doi.org/10.3390/languages10110283 (registering DOI) - 12 Nov 2025
Abstract
Even though it has been previously suggested that Spanglish is not exclusive to the US, research on this sociolinguistic phenomenon has focused on the US Hispanophone context, thus providing a limited understanding of how the US compares to Belize and Gibraltar, two language [...] Read more.
Even though it has been previously suggested that Spanglish is not exclusive to the US, research on this sociolinguistic phenomenon has focused on the US Hispanophone context, thus providing a limited understanding of how the US compares to Belize and Gibraltar, two language contact situations where Spanglish is also attested. This paper fills this gap by bringing together insights from scholarship on these three contexts where Spanish has been in prolonged contact with English. To this end, this article highlights some of the key debates and discussions regarding Spanglish. It also introduces the reader to some similarities between the US, Belize and Gibraltar and posits that there are Spanglish phenomena, which necessarily entail the reevaluation of the role that structural hybridity plays in Spanglish. Lastly, through an overview of comparative analyses that have been conducted more recently, we illustrate the importance of this work in elucidating our knowledge of the remarkable patterns of uniformity and variability that characterize the dynamic nature of Spanglish varieties in different parts of the world today. Full article
21 pages, 2392 KB  
Article
Synergistic Inhibition of Triple-Negative Breast Cancer by Acetylsalicylic Acid and Recombinant Human APE1/Ref-1 in a Mouse Xenograft Model
by Hao Jin, Yu Ran Lee, Sungmin Kim, Eunju Choi, Ka-Young Lee, Hee Kyoung Joo, Eun-Ok Lee, Cuk-Seong Kim, Je Ryong Kim, Sang Hun Lee and Byeong Hwa Jeon
Biomedicines 2025, 13(11), 2767; https://doi.org/10.3390/biomedicines13112767 (registering DOI) - 12 Nov 2025
Abstract
Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited therapeutic options due to the lack of estrogen, progesterone, and HER2 receptors. This study investigated the synergistic anticancer effects of recombinant human apurinic/apyrimidinic endonuclease 1/redox factor-1 (rhAPE1/Ref-1) and acetylsalicylic acid (ASA), [...] Read more.
Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited therapeutic options due to the lack of estrogen, progesterone, and HER2 receptors. This study investigated the synergistic anticancer effects of recombinant human apurinic/apyrimidinic endonuclease 1/redox factor-1 (rhAPE1/Ref-1) and acetylsalicylic acid (ASA), a combination that has not been previously tested in vivo. Methods: We treated MDA-MB-231 TNBC cells with rhAPE1/Ref-1, ASA, or their combination to assess cell viability and apoptosis in vitro. In vivo, a murine xenograft model was established to evaluate the efficacy of the combination treatment on tumor growth, tumor-specific biomarkers, and key apoptotic proteins. The safety profile of the combination therapy was also assessed by monitoring hematological parameters. Results: While monotherapy with either rhAPE1/Ref-1 or ASA had minimal effects, their combination significantly reduced cell viability and enhanced apoptosis in vitro by increasing DNA fragmentation. These synergistic cytotoxic effects were significantly inhibited by the receptor for advanced glycation end-products (RAGE) siRNA, suggesting that RAGE acts as an important mediator. In the xenograft model, the combination treatment suppressed tumor growth by approximately 70%, an effect comparable to paclitaxel (PTX). This was confirmed by a significant reduction in the plasma levels of TNBC biomarkers (CEA, CA27-29, and CA15-3) and increased tumor apoptosis via the upregulation of p53 and Bax and downregulation of Bcl-2. Notably, ASA, alone or combined with rhAPE1/Ref-1, induced the expression of RAGE in MDA-MB-231 tumors. In contrast to PTX, the combination of rhAPE1/Ref-1 and ASA did not cause hematological toxicity, such as anemia or thrombocytopenia. Conclusions: The combination of rhAPE1/Ref-1 and ASA represents a promising new therapeutic strategy for TNBC by enhancing apoptosis and significantly inhibiting tumor progression in a mouse xenograft model. Full article
(This article belongs to the Special Issue Molecular Research in Breast Cancer)
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18 pages, 294 KB  
Article
Development of the Procedural Waste Index (PWI): A Framework for Quantifying Waste in Manufacturing Standard Operating Procedures
by Jomana A. Bashatah
Systems 2025, 13(11), 1015; https://doi.org/10.3390/systems13111015 (registering DOI) - 12 Nov 2025
Abstract
Standard operating procedures (SOPs) serve as critical control mechanisms in manufacturing systems, yet systematic approaches for quantifying procedural inefficiencies remain theoretically underdeveloped. Unlike traditional qualitative SOP analysis methods that rely on expert intuition and subjective assessment, current procedural optimization approaches lack the systematic [...] Read more.
Standard operating procedures (SOPs) serve as critical control mechanisms in manufacturing systems, yet systematic approaches for quantifying procedural inefficiencies remain theoretically underdeveloped. Unlike traditional qualitative SOP analysis methods that rely on expert intuition and subjective assessment, current procedural optimization approaches lack the systematic rigor applied to physical process improvement. While lean manufacturing principles have demonstrated effectiveness in physical process optimization, their systematic application to procedural analysis represents an unexplored theoretical domain with significant potential for manufacturing systems improvement. This research addresses this gap by developing the Procedural Waste Index (PWI) framework, which establishes the first systematic theoretical integration of lean waste identification principles with procedural analysis. The framework extends the seven wastes of lean manufacturing to procedural analysis through systematic mapping to procedural elements identified via the extended Procedure Representation Language (e-PRL), creating a quantitative approach that enables the objective measurement of procedural efficiency where only subjective assessment methods previously existed. The PWI framework provides the following three key advantages over existing approaches: (1) systematic waste identification using proven lean principles rather than ad hoc improvement methods, (2) quantitative measurement capability enabling objective assessment and statistical process control, and (3) multi-perspective analytical framework through three complementary calculation methodologies (weighted aggregation, maximum constraint identification, and root mean square analysis) providing comprehensive analytical perspectives on procedural waste across discrete manufacturing contexts. The theoretical framework demonstrates practical applicability through a systematic analysis of a respirator fit testing procedure, revealing inventory waste as the primary inefficiency (70.0% waste score). This represents the first quantitative procedural waste assessment in the manufacturing literature, contributing to the foundational theory for systematic procedural optimization while establishing a methodology for future empirical validation studies. Full article
18 pages, 6430 KB  
Article
Evaluation of Biocontrol Efficacy of Bacillus velezensis HAB-2 Combined with Pseudomonas hunanensis and Enterobacter soli Against Cowpea Fusarium Wilt
by Wei Wei, Tianlong Qi, Jinpeng Lu, Xi Wei, Peilin Wu, Justice Norvienyeku, Weiguo Miao and Wenbo Liu
Microorganisms 2025, 13(11), 2578; https://doi.org/10.3390/microorganisms13112578 (registering DOI) - 12 Nov 2025
Abstract
Cowpea Fusarium wilt (CFW) is a soilborne fungal disease caused by Fusarium oxysporum f. sp. tracheiphilum (Fot), leading to substantial yield losses globally. This study evaluates the biocontrol potential of Bacillus velezensis HAB-2 and develops a microbial combination for effective disease management. B. [...] Read more.
Cowpea Fusarium wilt (CFW) is a soilborne fungal disease caused by Fusarium oxysporum f. sp. tracheiphilum (Fot), leading to substantial yield losses globally. This study evaluates the biocontrol potential of Bacillus velezensis HAB-2 and develops a microbial combination for effective disease management. B. velezensis HAB-2 suppressed F. oxysporum f. sp. tracheiphilum AIQBFO93 growth by 69.8% in vitro and exhibited multiple plant growth-promoting traits. Pot experiments demonstrated that HAB-2 alone achieved a 47.62% control rate against CFW. Furthermore, two compatible plant growth-promoting rhizobacteria (PGPR), Pseudomonas hunanensis HD33 and Enterobacter soli HD42, were isolated from the rhizosphere soil of cowpea previously treated with HAB-2. These two strains were combined with HAB-2 at different concentrations in 15 microbial combinations. The combined application of the three strains provided more consistent disease control, with the optimal combination demonstrating a 15.15% higher control rate than HAB-2 alone. Compared to the untreated control, this combination significantly increased cowpea fresh weight, leaf area, and plant height by 10.60%, 8.04%, and 7.81%, respectively, and upregulated the expression of defense-related genes, indicating enhanced resistance. These results confirm that B. velezensis HAB-2 is an effective biocontrol agent against wilt disease, and its synergistic application with functionally complementary PGPR strains provides a viable strategy for sustainable crop disease management. Full article
(This article belongs to the Section Plant Microbe Interactions)
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23 pages, 11803 KB  
Article
Rearward Seating Orientation Decreases Trust and Increases Motion Sickness in Autonomous Vehicles
by Leonhard Rottmann, Alina Waldmann, Aniella Johannsen and Mark Vollrath
Appl. Sci. 2025, 15(22), 12027; https://doi.org/10.3390/app152212027 (registering DOI) - 12 Nov 2025
Abstract
As the development of autonomous vehicles (AVs) progresses, new seating arrangements are emerging. Face-to-face seating is common in SAE L4 AV concepts and is intended to facilitate social interaction during autonomous driving, enabling previously unfeasible non-driving related tasks (NDRTs). However, this is countered [...] Read more.
As the development of autonomous vehicles (AVs) progresses, new seating arrangements are emerging. Face-to-face seating is common in SAE L4 AV concepts and is intended to facilitate social interaction during autonomous driving, enabling previously unfeasible non-driving related tasks (NDRTs). However, this is countered by the unpopularity of rearward seating orientations, which is particularly pronounced in cars. In order to develop countermeasures to address this unpopularity, a deeper understanding of the underlying mechanisms is required. This study validates a model that predicts the acceptance of AVs and takes seating orientation into account. To this end, a study with N = 46 participants was conducted to investigate the influence of seating orientation on AV acceptance and related factors such as transparency, trust, and motion sickness. Additionally, internal human–machine interfaces (iHMIs) were evaluated in regard to their ability to compensate for the disadvantages of a rearward seating orientation. To achieve a realistic implementation of a fully functional SAE L4 AV, an experimental vehicle was equipped with a steering and pedal robot, performing self-driven journeys on a test track. The iHMIs provided information about upcoming maneuvers and detected road users. While engaged in a social NDRT, participants experienced a total of six journeys. Seating orientation and iHMI visualization were manipulated between journeys. Rearward-facing passengers showed lower levels of trust and higher levels of motion sickness than forward-facing passengers. However, the iHMIs had no effect on acceptance or related factors. Based on these findings, an updated version of the model is proposed, showing that rearward-facing passengers in autonomous vehicles pose a particular challenge for trust calibration and motion sickness mitigation. During NDRTs, iHMIs which depend on the attention of AV occupants for information transfer appear to be ineffective. Implications for future research and design of iHMIs to address this challenge are discussed. Full article
(This article belongs to the Special Issue Autonomous Vehicles: Advances and Prospects)
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16 pages, 354 KB  
Article
A Biased Random-Key Genetic Algorithm for Maximum Flow with Minimum Labels
by Donatella Granata and Andrea Raiconi
Mathematics 2025, 13(22), 3621; https://doi.org/10.3390/math13223621 (registering DOI) - 12 Nov 2025
Abstract
In this work, we propose a novel Biased Random-Key Genetic Algorithm (BRKGA) to solve the Maximum Flow with Minimum Number of Labels (MF-ML) problem, a challenging NP-Complete variant of the classical Maximum Flow problem defined on graphs in which arcs have both capacities [...] Read more.
In this work, we propose a novel Biased Random-Key Genetic Algorithm (BRKGA) to solve the Maximum Flow with Minimum Number of Labels (MF-ML) problem, a challenging NP-Complete variant of the classical Maximum Flow problem defined on graphs in which arcs have both capacities and labels assigned. Labels give a qualitative characterization of each connection, in contexts where a solution that is as homogeneous as possible is sought. The MF-ML problem aims to maximize the flow from a source to a sink on a capacitated network while minimizing the number of distinct arc labels used, a modeling framework with applications such as water purification in distribution systems. Our proposed algorithm encodes solutions as random-key vectors, which are decoded into feasible solutions. The BRKGA demonstrates superior performance when compared to a Skewed Variable Neighborhood Search (VNS) approach previously proposed to solve MF-ML. In particular, on the largest considered graphs, BRKGA-MFML outperformed VNS in 55 out of 81 scenarios, with an average improvement per scenario that reaches 7.18%. Full article
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24 pages, 1863 KB  
Article
Divergent Avian Influenza H10 Viruses from Sympatric Waterbird Species in Italy: Zoonotic Potential Assessment by Molecular Markers
by Marzia Facchini, Maria Alessandra De Marco, Sara Piacentini, Angela Di Martino, Cesare Ernesto Maria Gruber, Claudia Cotti, Giuseppina Di Mario, Laura Calzoletti, Concetta Fabiani, Mauro Delogu, Anna Teresa Palamara, Paola Stefanelli and Simona Puzelli
Microorganisms 2025, 13(11), 2575; https://doi.org/10.3390/microorganisms13112575 (registering DOI) - 12 Nov 2025
Abstract
Avian influenza viruses (AIVs) of H10 subtype are able to circulate in domestic and wild bird populations but can also spill over and adapt to mammals, posing a continuous risk to biodiversity conservation, veterinary health, and public health. In the present study, we [...] Read more.
Avian influenza viruses (AIVs) of H10 subtype are able to circulate in domestic and wild bird populations but can also spill over and adapt to mammals, posing a continuous risk to biodiversity conservation, veterinary health, and public health. In the present study, we assessed the zoonotic potential of nine H10 AIVs isolated from waterbirds during surveillance and research studies carried out in Italy between 1994 and 2007. Overall, six H10NX strains from wild mallards (n. 1 H10N2, n. 5 H10N7), one H10N7 strain from domestic mallards, and two H10N8 strains from Eurasian coots were sequenced by next-generation sequencing (NGS). HA phylogenetic analysis indicated a marked divergence between viruses from these two sympatric waterbird species and showed a close relationship between three H10N7 strains from wild mallard and one H10N7 isolate of domestic origin. Sequence analysis revealed the presence of several molecular markers, associated with increased zoonotic potential, including the PB2-A588V mutation found in the Eurasian coot H10N8 viruses and previously linked to mammalian adaptation in H10 strains. Molecular analysis also showed that all H10 viruses were susceptible to the major approved classes of influenza antivirals (inhibitors of neuraminidase, matrix-2, and polymerase acid protein). Moreover, phenotypic assay confirmed their susceptibility to oseltamivir and zanamivir drugs. From an ecological perspective, we found that different H10 gene pools seem to be harboured in different waterbird species sharing the same environment; additionally, a bidirectional transmission of H10 mallard isolates occurred between natural and anthropic ecosystems. Overall, our findings account for the need of continuous monitoring of AIVs belonging to the H10 subtype. Full article
(This article belongs to the Section Virology)
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51 pages, 7121 KB  
Case Report
Total Reversal of ALS Confirmed by EMG Normalization, Structural Reconstitution, and Neuromuscular–Molecular Restoration Achieved Through Computerized Brain-Guided Reengineering of the 1927 Nobel Prize Fever Therapy: A Case Report
by M. Marc Abreu, Mohammad Hosseine-Farid and David G. Silverman
Diseases 2025, 13(11), 371; https://doi.org/10.3390/diseases13110371 (registering DOI) - 12 Nov 2025
Abstract
Background: Neurological disorders are the leading cause of disability, affecting over three billion people worldwide. Amyotrophic lateral sclerosis (ALS) is among the most feared and uniformly fatal neurodegenerative diseases, with no therapy capable of restoring lost function. Methods: We report the first application [...] Read more.
Background: Neurological disorders are the leading cause of disability, affecting over three billion people worldwide. Amyotrophic lateral sclerosis (ALS) is among the most feared and uniformly fatal neurodegenerative diseases, with no therapy capable of restoring lost function. Methods: We report the first application of therapeutic fever to ALS using Computerized Brain-Guided Intelligent Thermofebrile Therapy (CBIT2). This fully noninvasive treatment, delivered through an FDA-approved computerized platform, digitally reengineers the 1927 Nobel Prize-recognized malarial fever therapy into a modern treatment guided by the Brain–Eyelid Thermoregulatory Tunnel. CBIT2 induces therapeutic fever through synchronized hypothalamic feedback, activating heat shock proteins, which are known to restore proteostasis and neuronal function. Case presentation: A 56-year-old woman was diagnosed with progressive ALS at the Mayo Clinic, with electromyography (EMG) demonstrating fibrillation and fasciculation indicative of denervation corroborated by neurological and MRI findings; the patient was informed that she had an expected survival of three to five years. A neurologist from Northwestern University confirmed the diagnosis and thus maintained the patient on FDA-approved ALS drugs (riluzole and edaravone). Her condition rapidly worsened despite pharmacological treatment, and she underwent CBIT2, resulting in (i) electrophysiological reversal with complete disappearance of denervation; (ii) biomarker correction, including reductions in neurofilament and homocysteine, IL-10 normalization (previously linked to mortality), and robust HSP70 induction; (iii) restoration of gait, swallowing, respiration, speech, and cognition; (iv) reconstitution of tongue structure; and (v) return to complex motor tasks, including golf, pickleball, and swimming. Discussion: This case provides the first documented evidence that ALS can be reversed through digitally reengineered fever therapy aligned with thermoregulation, which induces heat shock response and upregulates heat shock proteins, resulting in the patient no longer meeting diagnostic criteria for ALS and discontinuation of ALS-specific medications. Beyond ALS, shared protein-misfolding pathology suggests that CBIT2 may extend to Alzheimer’s, Parkinson’s, and related disorders. By modernizing this Nobel Prize-recognized therapeutic principle with computerized precision, CBIT2 establishes a framework for large-scale clinical trials. A century after fever therapy restored lost brain function and so decisively reversed dementia paralytica such that it earned the 1927 Nobel Prize in Medicine, CBIT2 now safely harnesses the therapeutic power of fever through noninvasive, intelligent, brain-guided thermal modulation. Amid a global brain health crisis, fever-based therapies may offer a path to preserve thought, memory, movement, and independence for the more than one-third of humanity currently affected by neurological disorders. Full article
(This article belongs to the Special Issue Research Progress in Neurodegenerative Diseases)
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