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8 pages, 7899 KB  
Proceeding Paper
Spatially Resolved Monitoring of the Curing Degree in the Liquid Resin Infusion Process Using Near-Infrared Hyperspectral Imaging
by Xabier Zurutuza, Laura Arévalo, Janusz Poplawski, Cristian Builes, Mario Román, Tania Grandal, Arantzazu Núñez, Rubén Ruiz, Daniel Maestro-Watson and Luka Eciolaza
Eng. Proc. 2026, 133(1), 72; https://doi.org/10.3390/engproc2026133072 - 6 May 2026
Viewed by 285
Abstract
To ensure consistent quality in composite aerostructures, advanced non-invasive monitoring techniques are needed to detect global and local deviations during manufacturing. This study presents a real-time, spatially resolved method for monitoring the curing stage of Liquid Resin Infusion (LRI) using Near-Infrared Hyperspectral Imaging [...] Read more.
To ensure consistent quality in composite aerostructures, advanced non-invasive monitoring techniques are needed to detect global and local deviations during manufacturing. This study presents a real-time, spatially resolved method for monitoring the curing stage of Liquid Resin Infusion (LRI) using Near-Infrared Hyperspectral Imaging (NIR-HSI). Unlike traditional point-based tools such as disposable dielectric sensors, NIR-HSI enables full-field, non-contact assessment of the chemical evolution of the resin, providing valuable spatial information for detecting inhomogeneities caused by temperature gradients or uneven resin flow, factors known to affect the final mechanical properties of composites. Previous investigations demonstrated that hyperspectral data acquired during LRI correlate with the degree of cure estimated from a dielectric sensor. In the present study, we extend this analysis through a new experimental campaign designed to validate our earlier findings and strengthen the predictive model. To improve robustness and generalizability, the curing temperature, a key driver of cure kinetics, was systematically varied to introduce controlled changes in cure behavior. This increased variability enhances model reliability and supports more accurate prediction of curing progression under realistic manufacturing conditions. Full article
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23 pages, 1806 KB  
Article
Human-Centric Zero Trust Identity Architecture for the Fifth Industrial Revolution: A JEPA-Driven Approach to Adaptive Identity Governance
by Jovita T. Nsoh
Electronics 2026, 15(9), 1878; https://doi.org/10.3390/electronics15091878 - 29 Apr 2026
Viewed by 426
Abstract
The Fifth Industrial Revolution (Industry 5.0) foregrounds human–machine collaboration, sustainability, and resilience as organizing principles for next-generation cyber-physical systems. Yet the identity and access management (IAM) architectures inherited from Industry 4.0 remain perimeter-centric, policy-static, and blind to the behavioral dynamics of human–AI teaming. [...] Read more.
The Fifth Industrial Revolution (Industry 5.0) foregrounds human–machine collaboration, sustainability, and resilience as organizing principles for next-generation cyber-physical systems. Yet the identity and access management (IAM) architectures inherited from Industry 4.0 remain perimeter-centric, policy-static, and blind to the behavioral dynamics of human–AI teaming. This paper introduces the Human-Centric Zero Trust Identity Architecture (HC-ZTIA), a novel framework that repositions identity as the adaptive control plane for Industry 5.0 environments. HC-ZTIA integrates three mutually reinforcing innovations: (1) a Joint Embedding Predictive Architecture (JEPA)-driven Behavioral Identity Assurance Engine (BIAE) that learns abstract world models of operator and machine-agent behavior to perform continuous, context-aware identity verification without relying on raw biometric surveillance; (2) a Privacy-Preserving Adaptive Authorization Protocol (PP-AAP) employing zero-knowledge proofs and federated policy evaluation to enforce least-privilege access across human, non-human, and hybrid identity classes while satisfying data-minimization mandates; and (3) a Resilience-Oriented Trust Degradation Model (RO-TDM) that provides formally verified fail-safe identity governance under adversarial, degraded, or disconnected operating conditions characteristic of operational technology (OT) and critical infrastructure. The framework is grounded in the Agile-Infused Design Science Research Methodology (A-DSRM) and formally extends National Institute of Standards and Technology (NIST) SP 800-207 and the Cybersecurity and Infrastructure Security Agency (CISA) Zero Trust Maturity Model by addressing five identified gaps in human-centric identity governance. Simulation results, validated through Monte Carlo trials with 95% confidence intervals, provide preliminary evidence that HC-ZTIA reduces identity-related breach exposure by 73.2% (±4.1%) while maintaining sub-200 ms authorization latency under the simulated conditions, offering a principled bridge between Zero Trust rigor and Industry 5.0 human-centricity. Full article
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16 pages, 1036 KB  
Article
Clinical Predictors and Pathogen Resistance Dynamics in Hospitalized Patients with Urinary Tract Infections: A 2025 Institutional Study
by Ruxandra Laza, Ioana-Melinda Luput-Andrica, Adelina-Raluca Marinescu, Talida-Georgiana Cut, Alexandra Herlo, Andra-Elena Saizu, Andreea-Cristina Floruncut, Narcisa Nicolescu, Romanita Jumanca, Daniela-Ica Rosoha, Voichita Elena Lazureanu and Romosan Ana-Maria
Microorganisms 2026, 14(4), 916; https://doi.org/10.3390/microorganisms14040916 - 18 Apr 2026
Viewed by 434
Abstract
The escalating prevalence of antimicrobial resistance (AMR) in Gram-negative uropathogens represents a critical bottleneck in global clinical management. This study evaluated shifting resistance phenotypes and patient risk profiles to identify independent predictors of multidrug resistance (MDR). A comprehensive retrospective analysis was conducted on [...] Read more.
The escalating prevalence of antimicrobial resistance (AMR) in Gram-negative uropathogens represents a critical bottleneck in global clinical management. This study evaluated shifting resistance phenotypes and patient risk profiles to identify independent predictors of multidrug resistance (MDR). A comprehensive retrospective analysis was conducted on a cohort of 318 patients, utilizing statistical modeling to evaluate the impact of demographics, prolonged hospitalization, and comorbidities on MDR. Findings revealed a significant longitudinal exacerbation of resistance since 2012. A majority of Klebsiella pneumoniae strains and nearly all Myroides and Providencia species exhibited high-level resistance to cephalosporin/beta-lactamase inhibitor combinations. While high-dose piperacillin-tazobactam remains a therapeutic alternative, its utility is increasingly constrained by escalating Minimum Inhibitory Concentrations (MICs) for Klebsiella and Escherichia coli (E. coli). Statistical modeling identified advanced age as the primary independent driver, with MDR risk increasing linearly with every additional year of age. Furthermore, indwelling catheterization was strongly associated with resistant infections, while human immunodeficiency virus (HIV) status emerged as a significant cofactor in the selection of highly resistant strains. These findings underscore the need for a critical recalibration of therapeutic frameworks, prioritizing precision-guided stewardship. Pharmacodynamic optimization, through extended or continuous infusion regimens and individualized loading doses, is essential to mitigate the clinical burden of resistant pathogens within vulnerable geriatric cohorts. Full article
(This article belongs to the Special Issue Infectious Disease Surveillance in Romania: Third Edition)
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14 pages, 252 KB  
Article
Severe Reactions to Rituximab in Children: A Cohort Study of Rituximab-Induced Serum Sickness and Anaphylaxis
by Camille Feltesse, Jean-François Delisle, Roxane Labrosse, Colette Deslandres, Nadia Roumeliotis, Jean Jacques De Bruycker, Véronique Phan, Thomas Pincez and Yves Pastore
Children 2026, 13(4), 442; https://doi.org/10.3390/children13040442 - 24 Mar 2026
Viewed by 491
Abstract
Background/Objectives: Severe infusion-related reactions to rituximab are rare; we aim to extend our knowledge about them in children, focusing on rituximab-induced serum sickness (RISS) and anaphylaxis. Methods: We conducted a monocentric retrospective study on children and adolescents who received rituximab. Patients were defined [...] Read more.
Background/Objectives: Severe infusion-related reactions to rituximab are rare; we aim to extend our knowledge about them in children, focusing on rituximab-induced serum sickness (RISS) and anaphylaxis. Methods: We conducted a monocentric retrospective study on children and adolescents who received rituximab. Patients were defined as having RISS if they had fever and at least rash and/or arthralgia, 1 to 30 days following infusion, and without another diagnosis to explain symptoms. Anaphylaxis was defined according to the diagnostic criteria proposed by the World Allergy Organization. Results: 1534 rituximab infusions in 391 patients were analyzed. Seven patients developed RISS; all received rituximab for an autoimmune disease, including four for immune thrombocytopenia (ITP). Six patients had fever, rash, and arthralgia. C-reactive protein or sedimentation rate was increased in all patients, and complement was decreased in 83%. Evolution was favorable within a few days with corticosteroids and/or intravenous immunoglobulins. Rituximab was reinfused in one patient, which resulted in an immediate anaphylactoid reaction. Lower doses of rituximab were less likely to induce RISS. RISS was associated with a greater chance of achieving ITP remission. Seven patients developed anaphylaxis; five successfully received further infusions using desensitization protocols. Conclusions: RISS in children is a severe complication of rituximab infusion. Our study suggests that it may be more frequent in individuals treated for autoimmune conditions, especially ITP. The classical triad of fever, rash, and arthralgia appeared to be frequently present, and biological inflammation and/or low complement can further support the diagnosis. In contrast to anaphylaxis, where rituximab may be safely rechallenged upon desensitization protocol, treatment alternatives should be pursued in patients experiencing RISS, given the higher risk of severe RISS recurrence. Full article
(This article belongs to the Section Pediatric Allergy and Immunology)
13 pages, 1033 KB  
Article
Therapeutic Effects of Single and Combined Anti-Disseminated Intravascular Coagulation (DIC) Drugs in a Rat Venom-Induced Consumption Coagulopathy (VICC) Model Using Yamakagashi (Rhabdophis tigrinus) Venom
by Akihiko Yamamoto, Takashi Ito and Toru Hifumi
Toxins 2026, 18(3), 151; https://doi.org/10.3390/toxins18030151 - 23 Mar 2026
Viewed by 805
Abstract
Yamakagashi (Rhabdophis tigrinus) is a widely distributed snake species in Japan. Yamakagashi causes venom-induced consumption coagulopathy (VICC) when the amount of infused venom is high, and bites can be fatal if antivenom treatment is delayed. However, yamakagashi antivenom is an unapproved [...] Read more.
Yamakagashi (Rhabdophis tigrinus) is a widely distributed snake species in Japan. Yamakagashi causes venom-induced consumption coagulopathy (VICC) when the amount of infused venom is high, and bites can be fatal if antivenom treatment is delayed. However, yamakagashi antivenom is an unapproved treatment, and its storage capacity is limited, preventing its prompt administration. Therefore, we investigated the application of commercially available drugs, namely tranexamic acid and antithrombin III, in the treatment of VICC caused by yamakagashi venom in a rat model. Furthermore, we investigated the combination of each drug with recombinant thrombomodulin α. Administration of tranexamic acid or antithrombin III alone failed to extend rat survival or correct changes in blood coagulation markers, such as prothrombin time, fibrinogen concentrations, and D-dimer levels, in yamakagashi venom-treated rats. However, combined administration of recombinant thrombomodulin α and tranexamic acid extended rat survival and partially restored blood coagulation markers. Therefore, the combination of recombinant thrombomodulin α and tranexamic acid might represent a useful therapeutic regimen for yamakagashi venom exposure. Full article
(This article belongs to the Section Animal Venoms)
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21 pages, 1057 KB  
Article
Signaling Organizational Artificial Intelligence Adoption in Recruitment Materials: Role of Perceived Innovation Ability in Organizational Attractiveness
by Jialin Cheng and Shunhong Ji
Behav. Sci. 2026, 16(3), 455; https://doi.org/10.3390/bs16030455 - 19 Mar 2026
Viewed by 647
Abstract
Although previous studies have examined factors influencing organizational appeal, how AI-adoption signals influence prospective applicants remains unclear. Building on signaling theory, this study explores whether, when, and how organizations’ AI-adoption signals enhance their attractiveness to potential applicants. Two experiments were conducted to test [...] Read more.
Although previous studies have examined factors influencing organizational appeal, how AI-adoption signals influence prospective applicants remains unclear. Building on signaling theory, this study explores whether, when, and how organizations’ AI-adoption signals enhance their attractiveness to potential applicants. Two experiments were conducted to test the hypothesized model. Study 1 (N = 145) employed a scenario-based design to compare organizational attractiveness between AI-adoption signal and no-signal conditions, confirming that AI-adoption signals are significantly positively associated with organizational attractiveness. Study 2 (N = 240) recruited active job seekers and validated a moderated mediation model: perceived innovation ability mediates the positive association between AI-adoption signals and organizational attractiveness, especially among job seekers with high AI self-efficacy. By conceptualizing AI adoption as an organizational signal, this research extends signaling theory to the context of technology-infused recruitment and offers practical insights for designing more effective recruitment strategies in the digital era. Full article
(This article belongs to the Special Issue The Impact of Technology on Human Behavior)
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15 pages, 487 KB  
Review
Determinants of Efficacy and Optimization of Chimeric Antigen Receptor T-Cell Therapy for Treating Multiple Myeloma: Current Status and Future Perspectives
by Hiroshi Yasui, Noriko Doki, Wei Yan, Kohzoh Imai and Tadao Ishida
Cells 2026, 15(4), 380; https://doi.org/10.3390/cells15040380 - 23 Feb 2026
Viewed by 859
Abstract
Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of relapsed and refractory multiple myeloma (MM), with BCMA-directed products demonstrating unprecedented response rates in heavily pretreated patients. Despite these advances, variabilities in response durability, treatment-related toxicities, and the emergence of resistance underscore [...] Read more.
Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of relapsed and refractory multiple myeloma (MM), with BCMA-directed products demonstrating unprecedented response rates in heavily pretreated patients. Despite these advances, variabilities in response durability, treatment-related toxicities, and the emergence of resistance underscore the need for strategies that extend beyond CAR construct design alone. Accumulating evidence has indicated that the therapeutic outcomes of this approach are determined by a complex interplay between tumor burden, antigen dynamics, CAR T-cell functional fitness, and host immune context at the time of infusion. Effector-to-target balance and antigen load, in particular, have emerged as modifiable biological determinants of efficacy and safety, with pre-infusion disease control and response to bridging therapy exerting a profound influence on post-infusion CAR T-cell expansion, persistence, and clinical outcomes. Soluble BCMA (sBCMA) has also gained increasing attention as a practical biomarker that integrates tumor burden and antigen dynamics to facilitate the biologically informed optimization of treatment timing and patient selection. In addition to tumor- and antigen-related factors, the intrinsic properties of CAR T-cell products—including the spatial organization and clustering of CAR molecules on the T-cell surface—represent an additional layer of biological determinants that correlate with treatment responses. The quantitative functional assessment of CAR T-cell products may complement conventional clinical and tumor-based biomarkers and improve the prediction of therapeutic potency prior to infusion. This review summarizes recent advances in CAR T-cell therapy for treating MM, focusing on key mechanisms of resistance, the optimization of pre-infusion disease control, the integration of biological markers into clinical decision-making, and emerging combinations and sequential strategies. We also propose a design-oriented and patient-centered framework that integrates CAR engineering with disease biology and host immune factors to enhance the consistency, durability, and safety of CAR T-cell therapy. Such biologically guided optimization strategies will likely prove critical for fully realizing the transformative potential of CAR T-cell therapy across the evolving treatment continuum of MM. Full article
(This article belongs to the Section Cell and Gene Therapy)
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21 pages, 4347 KB  
Article
Microwave-Assisted Bio-Based Chemical Recycling of Fiber-Reinforced Composites from Construction and Demolition Waste
by Gonzalo Murillo-Ciordia and Cecilia Chaine
Polymers 2026, 18(3), 362; https://doi.org/10.3390/polym18030362 - 29 Jan 2026
Viewed by 900
Abstract
Fiber-reinforced polymer composites (FRPCs) are increasingly used in construction due to their high performance and low environmental footprint. However, their widespread adoption has raised concerns over end-of-life management, particularly under European regulations mandating high recycling rates for construction and demolition waste (CDW). This [...] Read more.
Fiber-reinforced polymer composites (FRPCs) are increasingly used in construction due to their high performance and low environmental footprint. However, their widespread adoption has raised concerns over end-of-life management, particularly under European regulations mandating high recycling rates for construction and demolition waste (CDW). This study evaluates different systems for the chemical recycling of FRPCs through microwave (MW)-assisted solvolysis using green solvents, including deep eutectic solvents (DESs) and biobased acetic acid. The process targets thermoset resin depolymerization while preserving fiber integrity, operating at reduced temperatures (≤230 °C) and lower energy demand than conventional techniques, such as pyrolysis. A systematic experimental design was applied to CDW-derived polyester composites and extended to industrial epoxy and vinyl ester composites. Among the tested solvents, glacial acetic acid + ZnCl2 (5 wt.%), achieved the highest degradation efficiency, exceeding 94% in small-scale trials and maintaining over 78% upon upscaling. Recovered fibers showed moderate property retention, with tensile strength and elongation losses of ~30% and ~45% for infusion-based epoxy composites, while those from pultrusion-based epoxy composites exhibited 16–19% and retained similar properties to the virgin material, respectively. The method facilitates fiber recovery with limited degradation and aligns with circular economy principles through solvent reuse and minimizing environmental impact. Full article
(This article belongs to the Special Issue Chemical Recycling of Polymers, 2nd Edition)
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20 pages, 832 KB  
Article
Effect of Wheat Gluten Films Infused with Mint and Clove Essential Oils on the Shelf Life of Fresh Minced Chicken
by Arsenios Anthomelides, Alexia Gkourogianni, Ioanna S. Kosma and Anastasia V. Badeka
Foods 2026, 15(2), 390; https://doi.org/10.3390/foods15020390 - 21 Jan 2026
Viewed by 656
Abstract
The need for active biodegradable packaging materials with the ability to improve the microbiological stability of highly perishable foods was investigated in the present study. Specifically, wheat gluten-based films infused with spearmint (Mentha spicata L.) and clove (Syzygium aromaticum L.) essential [...] Read more.
The need for active biodegradable packaging materials with the ability to improve the microbiological stability of highly perishable foods was investigated in the present study. Specifically, wheat gluten-based films infused with spearmint (Mentha spicata L.) and clove (Syzygium aromaticum L.) essential oils (EOs)were studied by linking the physicochemical and mechanical properties of the film to the microbiological quality and shelf-life behavior of minced chicken under aerobic refrigerated storage. The packaged samples tested were packaging without film (Control), a wheat gluten film (WGF), WGF with 2% spearmint EO (WGF + 2% SPR), and 2% clove EO (WGF + 2% CL) stored at 4 ± 1 °C for 8 days, under aerobic conditions. Shelf-life extension was evaluated based on established microbiological spoilage criteria, indicating delayed microbial growth in samples packaged with EO-enhanced films compared with the Control. Microbiological analyses (TVC, yeast, Pseudomonas spp., B. Thermosphacta, Enterobacteriaceae, LAB) showed that WGF + 2% CL delayed the time required to reach the spoilage threshold for TVC (7 log CFU/g) by 2 days compared with the Control, while WGF and WGF + 2% SPR extended shelf life by 1 day. Physicochemical properties (pH and objective color) also showed better pH stability and limited color changes in the packaged samples. Mechanical properties resulted in improved film antioxidant activity and flexibility and reduced tensile strength for the EO-enhanced films. Overall, WGFs enhanced with EOs seem to improve minced chicken meat quality during refrigerated storage through the combined effect of antimicrobial activity and modified film properties, highlighting their potential as active packaging materials under the specific conditions studied. Full article
(This article belongs to the Special Issue Sustainable Uses and Applications of By-Products of the Food Industry)
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16 pages, 3029 KB  
Article
Durable Anti-Icing Slippery Surface with Y-Shaped Composite Porous Structure Prepared by Two-Step Anodic Oxidation
by Chanxi Yan, Gaoping Liu, Qing Zhu, Yashi Zhou and Yuan Yuan
Coatings 2026, 16(1), 135; https://doi.org/10.3390/coatings16010135 - 20 Jan 2026
Viewed by 481
Abstract
Ice accumulation on power transmission lines poses serious threats to operational safety and can lead to substantial social and economic impacts. While various anti-icing coatings have been investigated, their performance is often limited by the effectiveness and durability of anti-icing. Slippery lubricant-infused porous [...] Read more.
Ice accumulation on power transmission lines poses serious threats to operational safety and can lead to substantial social and economic impacts. While various anti-icing coatings have been investigated, their performance is often limited by the effectiveness and durability of anti-icing. Slippery lubricant-infused porous surfaces (SLIPSs) have shown remarkable anti-icing properties and durability, aided by their lubricant-infused and self-healing capability. In this study, SLIPSs were successfully fabricated on aluminum substrates using a two-step anodization process. The effects of the anodizing parameter of the current density on pore diameter and depth at each stage were systematically investigated. Compared to untreated aluminum and superhydrophobic coatings (SHCs), SLIPSs presented good anti-icing properties. First, at −6 °C, droplets slid off the surface completely within 4340.5 ms without pinning, indicating sustained droplet-shedding capability. It also significantly delayed ice formation, extending the freezing time to 80 min—eight times longer than that of the untreated surface. Moreover, the SLIPSs also exhibited ultra-low ice adhesion, with an initial strength of only 6.93 kPa. Meanwhile, after 100 frosting–defrosting cycles, SLIPSs could still maintain low ice adhesion strength (<20 kPa). The prepared SLIPS with a Y-shaped pore structure demonstrates good potential for anti-icing. Full article
(This article belongs to the Special Issue Durability of Transmission Lines)
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19 pages, 6951 KB  
Article
Smart Packaging System with Betalains and Rosemary Essential Oil to Extend Food Shelf Life and Monitor Quality During Storage
by Noemi Takebayashi-Caballero, Carlos Regalado-González, Aldo Amaro Reyes, Silvia Lorena Amaya-Llano, José Ángel Granados-Arvizu, Genoveva Hernández Padrón, Víctor Castaño-Meneses and Monserrat Escamilla-García
Polysaccharides 2026, 7(1), 5; https://doi.org/10.3390/polysaccharides7010005 - 8 Jan 2026
Viewed by 1091
Abstract
Smart packaging is an alternative that may not only replace plastic containers, but also enable food quality monitoring. In this study, an innovative packaging system was developed using a starch-chitosan polymer matrix, infused with rosemary essential oil (REO) as an antimicrobial agent, and [...] Read more.
Smart packaging is an alternative that may not only replace plastic containers, but also enable food quality monitoring. In this study, an innovative packaging system was developed using a starch-chitosan polymer matrix, infused with rosemary essential oil (REO) as an antimicrobial agent, and betalain extract as a food quality indicator. Betalain extract, derived from beet waste, can change color with pH, making it a useful natural indicator for monitoring food freshness. This packaging system is beneficial for foods that produce metabolites related to degradation, which alter pH and allow for the visual detection of changes in product quality. The objective of this work was to develop a smart packaging system with betalains and rosemary essential oil (REO) to extend food shelf life and monitor quality during storage. REO demonstrated antimicrobial activity, but its effect did not differ significantly among the microorganisms tested. On the other hand, the betalain extract (35.75% BE v/v) completely inhibited the growth of Listeria innocua and Salmonella spp. at concentrations of 50% (v/v; 0.82 ± 0.04 mg betalain/g), showing its potential as an antimicrobial agent. The interactions between chitosan and betalains were primarily associated with electrostatic interactions between the positively charged amino groups of chitosan and the negatively charged carboxyl groups of betalains. In contrast to starch, these interactions could result from interactions between the C=O groups of betalain carboxyls and water, which, in turn, interact with the hydroxyl groups of starch through hydrogen bonding. Despite the results obtained in this study, certain limitations need to be addressed in future research, such as the variability in antimicrobial activity among different bacterial strains, which could reveal differences in the efficacy of betalains and essential oils against other pathogens. Full article
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17 pages, 2279 KB  
Article
Canagliflozin Promotes Structural and Functional Changes in Proximal Tubular Cell Mitochondria of Hypertensive–Diabetic Mice
by Mayra Trentin-Sonoda, Yan Burelle, Alex Gutsol, Robert L. Myette and Richard L. Hébert
Int. J. Mol. Sci. 2025, 26(24), 11988; https://doi.org/10.3390/ijms262411988 - 12 Dec 2025
Viewed by 726
Abstract
The kidneys have a high-energy demand, relying on great rates of mitochondrial oxidative phosphorylation. Excessive glucose in the tubules leads to defective fatty acid oxidation, playing a key role in tubular injury and diabetic kidney disease progression. Besides its glucose-lowering action, canagliflozin (CANA) [...] Read more.
The kidneys have a high-energy demand, relying on great rates of mitochondrial oxidative phosphorylation. Excessive glucose in the tubules leads to defective fatty acid oxidation, playing a key role in tubular injury and diabetic kidney disease progression. Besides its glucose-lowering action, canagliflozin (CANA) promotes kidney protective effects. We aimed to investigate whether the demonstrated kidney protective effects are extended to mitochondrial function and remodeling in proximal tubular cells from hypertensive–diabetic mice. Four weeks after streptozocin (STZ) induction of type 1 diabetes in genetic hypertensive (Lin) mice, they were fed either CANA-infused chow or a regular diet for 1 week. CANA treatment reverted the albuminuric state in LinSTZ mice. In PTECs from male mice, CANA promoted a complex mitochondrial network with less spherical and more branched organelles, with evidence of increased fusion. Those improvements reflected on the mitochondria bioenergetics, where CANA treatment induced an augmented baseline and maximum respiration rate, ATP production, and mitochondria membrane potential in PTECs, compared to LinSTZ. In females, CANA produced a milder response, increasing the mitochondrial network without affecting bioenergetics. In conclusion, in vivo CANA treatment positively affects proximal tubular cells’ mitochondria in male hypertensive–diabetic mice with a minor impact in females. The improvement in mitochondrial function and structure might be key to the kidney-protective effects of CANA. Full article
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17 pages, 2526 KB  
Article
Intravenous Lidocaine Modulates the Perioperative Hepatic Inflammatory Response: Implications for Personalized Medicine in Thoracic Surgery
by Ana Isabel Galve, Ignacio Garutti, Elena Vara, Guillermo González, Gabriel Cusati, Lisa Rancan, Luis Huerta, Javier Casanova and Carlos Simón
J. Pers. Med. 2025, 15(12), 620; https://doi.org/10.3390/jpm15120620 - 11 Dec 2025
Viewed by 647
Abstract
Purpose: Lung resection surgery (LRS) induces a strong local and systemic inflammatory response that may extend to peripheral organs, including the liver. This study aimed to evaluate the potential effect of intravenous lidocaine on hepatic inflammatory and apoptotic responses during lung resection [...] Read more.
Purpose: Lung resection surgery (LRS) induces a strong local and systemic inflammatory response that may extend to peripheral organs, including the liver. This study aimed to evaluate the potential effect of intravenous lidocaine on hepatic inflammatory and apoptotic responses during lung resection surgery with one-lung ventilation (OLV) in an experimental porcine model. Methods: Eighteen mini pigs were randomly assigned to three groups: lidocaine (LIDO), control (CON), and sham (SHAM). Animals underwent left caudal lobectomy. The LIDO group received a continuous intravenous infusion of lidocaine (1.5 mg/kg/h) during surgery. The CON group received the same volume of saline, and the SHAM group underwent thoracotomy without lobectomy or OLV. Different samples were collected at baseline, during surgery, and 24 h postoperatively to assess inflammatory cytokines and apoptosis-related proteins. Liver biopsy was taken 24 h after de surgery. Results: One-lung ventilation and lung resection surgery increased the expression of proinflammatory markers in the liver biopsy and enhanced apoptotic protein expression and iNOS production. Lidocaine administration attenuated these effects, showing lower levels of inflammatory mediators, a better balance between iNOS and eNOS, and reduced apoptotic activity compared with controls. Conclusions: Our findings suggest that intravenous lidocaine may serve as a personalized perioperative strategy to attenuate systemic inflammatory and apoptotic responses, contributing to improved hepatic protection during thoracic surgery. Full article
(This article belongs to the Special Issue New Insights into Personalized Medicine for Anesthesia and Pain)
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14 pages, 623 KB  
Article
Linezolid Serum Concentration Variability Among Critically Ill Patients Based on Renal Function and Continuous Renal Replacement Therapy Administration
by Stefano Agliardi, Beatrice Brunoni, Gianluca Gazzaniga, Leonardo Baggio, Riccardo Giossi, Greta Guarnieri, Stefania Paccagnini, Matteo Laratta, Thomas Langer, Sara Santambrogio, Gianpaola Monti, Romano Danesi, Francesco Scaglione, Arianna Pani and Roberto Fumagalli
Antibiotics 2025, 14(12), 1188; https://doi.org/10.3390/antibiotics14121188 - 21 Nov 2025
Cited by 1 | Viewed by 1199
Abstract
Background: Linezolid standard dosing is typically applied in ICU without adjustments, even in renal impairment. This study examines serum concentration variability by renal function or CRRT administration in patients receiving 1200 mg/day of linezolid. Methods: This retrospective, single-center, non-randomized observational study was conducted [...] Read more.
Background: Linezolid standard dosing is typically applied in ICU without adjustments, even in renal impairment. This study examines serum concentration variability by renal function or CRRT administration in patients receiving 1200 mg/day of linezolid. Methods: This retrospective, single-center, non-randomized observational study was conducted at Niguarda Hospital (Milan, Italy) on data from the two-year period 2023–2024. ICU patients receiving linezolid, with a renal function determination and trough TDM performed at steady-state were included and stratified by renal function or CRRT status. Results: 54 patients were included, with 18 (33%) undergoing CRRT (CVVH). CRRT patients presented higher median linezolid concentrations (4.6 mg/L) than non-CRRT patients (3.2 mg/L), and a lower risk of underdosing (17% vs. 39%). CRRT patients showed significantly lower concentrations (4.6 mg/L vs. 10 mg/L, p = 0.007) than non-CRRT patients with renal function ≤ 30 mL/min, with fewer out-of-range levels (39% vs. 91%, p = 0.008) and overdosing (22% vs. 73%, p = 0.018). A significant inverse correlation was found between renal function and linezolid levels (Spearman’s rho = −0.61, p < 0.001), with CRRT patients exhibiting concentrations comparable to those of individuals with moderately impaired renal function. Continuous infusion resulted in significantly higher median concentrations (7.2 mg/L) than extended infusion (2.7 mg/L), with an increased risk of overdosing (47% vs. 17%; p = 0.018). Conclusions: After standard-dosing administration, linezolid levels vary widely in critically ill patients. Renal function significantly affects pharmacokinetics: severe impairment increases overdose risk, while ARC may cause underdosing. Standard-dosing appears adequate in CRRT patients, with levels similar to moderate-impairment. Continuous infusion aids target attainment in normal or ARC patients but raises overdose risk in severe impairment. TDM-based personalized dosing seems crucial to optimize therapy and reduce toxicity or failure. Full article
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13 pages, 610 KB  
Article
High Rate of Cytokine Release Syndrome-Related Coagulopathy with Low Incidence of Bleeding and Thrombosis in Patients Treated with B-Cell Maturation Antigen (BCMA)-Targeted Chimeric Antigen Receptor T-Cells (CAR-T)
by Ariela Arad, Maya Katz, Eyal Lebel, Yosef Kalish, Miri Assayag, Batia Avni, Shlomo Elias, Sigal Grisariu, Ela Shai, Shlomit Kfir-Erenfeld, Nathalie Asherie, Moshe E. Gatt, Polina Stepensky and Eran Zimran
Cancers 2025, 17(21), 3551; https://doi.org/10.3390/cancers17213551 - 2 Nov 2025
Cited by 1 | Viewed by 1140
Abstract
Background: B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated substantial efficacy in relapsed and/or refractory multiple myeloma. While toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have been well characterized, the incidence [...] Read more.
Background: B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated substantial efficacy in relapsed and/or refractory multiple myeloma. While toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have been well characterized, the incidence and clinical consequences of the coagulopathy associated with CRS remain underexplored. Methods: We conducted a prospective analysis of 108 adult patients with multiple myeloma or light chain amyloidosis treated with the academic anti-BCMA CAR-T HBI0101 in a single-center trial (NCT04720313). Coagulopathy was evaluated via serial fibrinogen measurements, with hypofibrinogenemia defined as <200 mg/dL and severe coagulopathy as <100 mg/dL. Laboratory markers, tocilizumab and blood product use, and thrombotic and bleeding complications were recorded. Patients received a short (3-day) or extended course of enoxaparin thromboprophylaxis as well as fresh frozen plasma in cases of severe coagulopathy. Results: CRS grades 1–3 occurred in 100 patients (93%). Hypofibrinogenemia was observed in 79 patients (73%), including 20 (19%) with severe coagulopathy. Fibrinogen levels were significantly associated with CRS severity (p < 0.001), number of tocilizumab doses (p < 0.001), peak levels of the inflammation markers LDH (p = 0.001) and ferritin (p = 0.006), and neutropenia (p = 0.33). Five thrombotic events (4.6%) and three minor bleeding events (2.7%) occurred within 3 months post-CAR-T infusion and were not associated with degree of coagulopathy or CRS. No cases of major bleeding or fatal thrombosis occurred. Conclusions: CRS-related coagulopathy is common following BCMA-targeted CAR-T treatment and correlates closely with CRS severity. Despite the high rate of laboratory coagulopathy, thrombosis and bleeding events were infrequent, suggesting the benefit of the prophylactic strategies used. Full article
(This article belongs to the Special Issue CAR T-Cell Therapy and Multiple Myeloma)
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