Search Results (317)

2,5-bis(hydroxymethy)lfuran (BHMF), a renewable compound with extensive industrial applications, can be obtained by selective hydrogenation of the C=O group of 5-hydroxymethylfurfural (HMF), a platform molecule derived from lignocellulosic biomass. In this work, we perform kinetic modeling of the selective liquid-phase hydrogenation of HMF to BHMF over a Cu/SiO₂ catalyst prepared by precipitation–deposition (PD) at a constant pH. Physicochemical characterization, using different techniques, confirms that the Cu/SiO₂–PD catalyst is formed by copper metallic nanoparticles of 3–5 nm in size highly dispersed on the SiO₂ surface. Before the kinetic study, the Cu/SiO₂-PD catalyst was evaluated in three solvents: tetrahydrofuran (THF), 2-propanol (2-POH), and water. The pattern of catalytic activity and BHMF yield for the different solvents was THF > 2-POH > H₂O. In addition, selectivity to BHF was the highest in THF. Thus, THF was chosen for further kinetic study. Several experiments were carried out by varying the initial HMF concentration (C⁰_HMF) between 0.02 and 0.26 M and the hydrogen pressure (P_H2) between 200 and 1500 kPa. In all experiments, BHMF selectivity was 97–99%. By pseudo-homogeneous modeling, an apparent reaction order with respect to HFM close to 1 was estimated for a C⁰_HMF between 0.02 M and 0.065 M, while when higher than 0.065 M, the apparent reaction order changed to 0. The apparent reaction order with respect to H₂ was nearly 0 when C⁰_HMF = 0.13 M, while for C⁰_HMF = 0.04 M, it was close to 1. The reaction orders estimated suggest that HMF is strongly absorbed on the catalyst surface, and thus total active site coverage is reached when the C⁰_HMF is higher than 0.065 M. Several Langmuir–Hinshelwood–Hougen–Watson (LHHW) kinetic models were proposed, tested against experimental data, and statistically compared. The best fitting of the experimental data was obtained with an LHHW model that considered non-competitive H₂ and HMF chemisorption and strong chemisorption of reactant and product molecules on copper metallic active sites. This model predicts both the catalytic performance of Cu/SiO₂-PD and its deactivation during liquid-phase HMF hydrogenation. Full article

Improving the corrosion resistance of magnesium (Mg) alloys is a long-term challenge, especially when cost-effectiveness is taken into account. In this work, Mg-1Bi and Mg-1Sn extruded alloys are prepared, and the effects of cost-effective Bi and Sn on the corrosion behavior of Mg alloys are comparatively studied. The corrosion resistance of the Mg-1Sn alloy (P_H: 2.83 ± 0.19 mm y⁻¹) is better than that of the Mg-1Bi alloy (P_H: 13.75 ± 1.12 mm y⁻¹), being about five times greater. In addition to the relatively low dislocation density in Mg-1Sn alloy, the difference in corrosion resistance is mainly attributed to two aspects of influence brought about by the addition of Sn and Bi. The Mg₂Sn phase introduced by the addition of Sn has a potential difference (PD) of ~30 mV, which is significantly lower than that (~90 mV) of the Mg₃Bi₂ phase introduced by adding Bi, thereby weakening the micro-couple corrosion tendency of the Mg-1Sn alloy. The addition of Bi has little effect on the corrosion film, while the addition of Sn makes the corrosion film on the Mg-1Sn alloy contain SnO₂, improving the compactness of the corrosion film and thereby enhancing the corrosion protection effect. Full article

Background/Objectives: Anatomical and functional damage of the mitral valve (MV) apparatus in patients with dilated cardiomyopathy (DCM) is secondary to left ventricular (LV) injury, leading to functional mitral regurgitation (FMR). Real-time four-dimensional echocardiography (RT 4DE) is a useful imaging technique in different pathologies, including DCM. Left atrial (LA) strain, as measured by left atrium quantification software, is an accurate technique for evaluating increased filling pressure. The MV has a complex three-dimensional morphology and motion. Four-dimensional echocardiography (4DE) has revolutionized clinical imaging of the mitral valve apparatus. This study aims (1) to characterize the mitral annulus (MA) parameters in patients with DCM and advanced-stage heart failure (HF) according to etiology and (2) to find correlations between left atrial function and MA remodeling in this group of patients, using 4DE quantification software. Methods: A total of 82 patients with DCM and an LV ejection fraction ≤ 40% were recruited. Conventional 2DE and RT 4DE were conducted in DCM patients with a compensated phase of HF before discharge. The measured parameters were left atrial reservoir strain (LASr), annular area (AA), annular perimeter (AP), anteroposterior diameter (A-Pd), posteromedial to anterolateral diameter (PM-ALd), commissural distance (CD), interregional distance (ITD), annular height (AH), nonplanar angle (NPA), tenting height (TH), tenting area (TA), and tenting volume (TV). Results: Measured parameters revealed more advanced damage of LA and MA parameters in ischemic compared to nonischemic etiology. Univariate analysis identified AA, AP, A-Pd, PM-ALd, CD, ITD, TH, TA, and TV (p < 0.0001) as determinants of LASr. Including these parameters in a stepwise multivariate logistic regression, PM-ALd (p = 0.03), TH (p = 0.043), and TV (p = 0.0001) were the best predictors of LAsr in these patients. Conclusions: The results of this study revealed the correlation between LA function depression and MA remodeling in patients with DCM. Full article

Background/Objectives: Environmental factors, including the differences in genotype-based housing (GbH), can act as confounding variables in studies using transgenic mouse models, potentially influencing experimental outcomes and limiting their reproducibility and translational value. Despite the widespread use of transgenic models in preclinical studies, the extent to which housing conditions can affect the behavioral and molecular parameters of interest remains poorly understood. This study aims to investigate how different GbH conditions influence visuo-spatial memory and gene expression in the A53T mouse model (JAX006823) of Parkinson’s disease (PD) during the pre-motor phase. Methods: A53T+ transgenic male mice and their non-transgenic littermates (A53T−) were housed in either mixed-genotype (MGH) or single-genotype (SGH) environments from postnatal day (PND) 30, with C57BL/6J mice serving as the controls. A behavioral assessment using the Novel Object Recognition and Object Location Tests was conducted at PND 180, followed by a qPCR analysis of Iba1, Gfapα, Bdnf, Tnfα, Il-1β, and Il-6 expression in the medial prefrontal cortex and the hippocampus. Results: The variations in GbH influenced behavior and mRNA expression differently in the A53T+ and A53T− animals. Specifically, the A53T− mice in SGH environments displayed behavioral and molecular profiles similar to the C57BL/6J controls, while the same was not evident in the MGH environments. In the A53T+ mice, the mRNA expression of Iba1, Gfapα, Bdnf, and Tnfα was sensitive to variations in GbH, while memory impairment was not. Conclusions: This study highlights the importance of considering environmental factors in studies using transgenic animal models. The obtained data suggests that GbH can influence the parameters of interest in preclinical research, implicating the need for the optimization of future study designs. Full article

Background: The emergence of checkpoint inhibitors (CPIs) has significantly improved survival outcomes in later-stage melanoma. However, the efficacy of these treatments remains limited, with around 50% of later-stage melanoma patients experiencing recurrence. As variable response rates to CPIs persist, the development of cancer vaccines has emerged as a potential strategy to augment antitumor immune responses. Results: This review compares two promising personalized therapeutic cancer vaccine trials in advanced melanoma: Elios Therapeutics’ Tumor Lysate (TL) vaccine and Moderna’s mRNA-4157 vaccine. The TL vaccine, which utilizes yeast cell wall particles (YCWPs) loaded with autologous tumor lysate, and the mRNA-4157 vaccine, which encodes up to 34 patient-specific neoantigens, both aim to stimulate robust tumor-specific immune responses. Both trials were phase 2b randomized studies, with Elios Therapeutics’ trial employing a double-blind, placebo-controlled design, while Moderna’s was open-label. Both trials had roughly equivalent sample sizes (n = 187 and n = 157, respectively) with similar demographics and disease characteristics. The TL trial reported improvements in disease-free survival (DFS) with a hazard ratio (HR) of 0.52 (p < 0.01) over 36 months, whereas the mRNA-4157 trial demonstrated improvements in recurrence-free survival (RFS) with an HR of 0.56 (p = 0.053) over 18 months. The TL vaccine exhibited lower rates of related grade 3 adverse events (<1%) compared to the mRNA vaccine (12%). Key differences between the two trials include the use of CPIs, with 100% of patients in the mRNA trial receiving pembrolizumab versus 37% of the patients in the TL trial receiving either an anti-PD-1 or anti-CTLA-4. The production processes also varied significantly, with the mRNA vaccine requiring individualized sequencing and a 9-week production time, while the TL vaccine utilized tumor lysate with a 1–3-day production time. Conclusions: While both vaccines demonstrated promising efficacy, future phase 3 trials are needed to further evaluate their potential as adjuvant therapies for melanoma. This review highlights the comparative strengths and limitations of these vaccine platforms, providing insight into the evolving landscape of adjuvant cancer vaccines. Full article

Background: The influence of gait speed on lower-extremity coordination while walking in people with Parkinson’s disease (pwPD) is poorly understood. This study sought to investigate the relationship between gait speed and hip–knee coordination and coordination variability in older adults and pwPD. Methods: A total of 27 pwPD and 21 healthy older adults were recruited. Participants walked in a straight line at slow, preferred, and fast walking speeds. Gait data were collected using inertial measurement units, and the kinematics of the hip and knee were calculated. Coordination and coordination variability at the hip–knee joint pair were determined using continuous relative phase. A repeated measures two-way ANCOVA tested the impact of gait speed on coordination and coordination variability, while group differences were evaluated using statistical parametric mapping (SPM). Results: Neither the healthy older adults nor the pwPD adjusted their hip–knee coordination in response to changes in gait speed. pwPD also displayed a trend towards restricted hip and knee joint excursion compared to older adults, which may further limit their ability to adapt gait strategies. Conclusions: These findings suggest that interventions addressing both joint excursion and motor adaptability may be important for improving gait function in individuals with Parkinson’s disease. Real-world applicability can be found in the potential of wearable sensors to become a valuable tool in routine clinical practice for both diagnosis and ongoing management. Trial registration: The study is registered in the German Clinical Trials Register (DRKS00022998). Full article

Background: Hormonal fluctuations during the menstrual cycle (MC) influence pain perception, potentially affecting exercise performance and rehabilitation in women. This effect may be more pronounced in individuals with primary dysmenorrhea (PD), requiring tailored physiotherapeutic and exercise interventions. Objective: To analyze the influence of MC phases on sensory electrical threshold (SET) and pain electrical threshold (PET) in eumenorrheic women with and without PD, considering the potential implications for physical activity and rehabilitation. Methods: An observational longitudinal study was conducted with 34 physically active women, divided into a control group (CG) and a PD group. SET and PET were measured using transcutaneous electrical nerve stimulation (TENS) at the forearm (peripheral site) and lower abdomen (pain-referred site) across five MC phases. Pain intensity was assessed using a Visual Analog Scale (VAS). Results: SET and PET were significantly lower in the premenstrual phase (p < 0.001), suggesting increased pain sensitivity. VAS scores were higher in the PD group during all phases, except for the follicular phase (p < 0.033), with the highest pain levels recorded in the menstrual and premenstrual phases. While no significant differences in SET and PET were found between groups across most phases, the PD group exhibited a significantly higher SET in the forearm during the premenstrual phase (p = 0.005), potentially indicating altered central pain modulation. Conclusions: MC-related hormonal fluctuations affect pain sensitivity, particularly in women with PD. These findings underscore the need for phase-specific exercise adaptations and rehabilitation strategies to improve performance, pain management, and recovery in physically active women. Full article

Introduction: Prostate cancer has been generally resistant to immunotherapy approaches. Radiation can be immunostimulatory, but the extent to which standard prostate cancer treatments induce immune activation has not been well described. The bone-targeted radiopharmaceutical Radium223 (Ra223) has been proposed to enrich immune function, but clinical studies have not fully delineated whether this is true, or by what mechanisms. Enzalutamide has been shown to increase PD-L1 expression on dendritic cells, which could impact immune activation, though the extent to which this is associated with other evidence of immune activation remains uncertain, and combination strategies remain of interest. We performed a randomized phase II trial to evaluate whether Radium223 (Ra223) added to enzalutamide would induce greater immune activation and clinical responses compared to enzalutamide alone in men with metastatic castration-resistant prostate cancer (mCRPC). Methods: Eligible patients were randomized 2:1 to Arm A (enzalutamide 160 mg PO daily + Ra223 55 kBq/kg IV q4 weeks × 6 doses) or Arm B (enzalutamide 160 mg PO daily). Blood was collected at treatment start and during treatment to measure soluble immune checkpoint biomarkers (BTLA, TIM3, HVEM, GITR, LAG3, PD-1, CTLA-4, PD-L1, PD-L2, ICOS). Immunophenotyping by mass cytometry time of flight (CyTOF) was performed to measure peripheral blood mononuclear cell populations before and after treatment. CyTOF was used to determine changes in circulating immune cell population subsets before and after treatment. Biopsies were performed of an active bone metastatic lesion prior to study treatment and after at least 3 months. IHC was subsequently performed to examine changes in immune cell population subsets before and after treatment, and changes in pSTAT3 levels. Results: In total, 30 patients were enrolled, with median age 68. The median duration of follow up was 36 months. PSA responses, PFS, and OS were not significantly different between the two arms; however, the study was not powered for clinical endpoints. Peripheral blood and bone biopsy specimens were analyzed for immune correlatives. Soluble receptor concentrations showed significantly increased expression of PDL-2 in the combination arm, but this was not seen on CyTOF. Otherwise, there were no significant differences in markers of immune activation/exhaustion or immune cell population subsets in the combination arm and enzalutamide monotherapy arm. IHC also did not show a significant difference in immune cell population subsets in bone biopsy specimens before and after treatment in both arms. However, treatment with the combination arm did show significantly increased levels of pSTAT3 (p = 0.04), which was not seen in the enzalutamide monotherapy arm. Conclusions: Our study showed an overall lack of evidence for immune activation or cytokine induction with the combination, which does not make a strong case for combinatorial immunotherapy approaches. However, the combination did induce higher levels of pSTAT3, which has been implicated in radio-resistance. Therefore, the addition of a STAT3 inhibitor to the combination may be of interest to improve efficacy. Full article

The present study aims to investigate a Pd catalyst on a complex multi-oxide medium-entropy support interlayer La₂O₃-CeO₂-ZrO₂-Al₂O₃ and its possible use as catalysts for methane abatement applications. The low-temperature N₂-adsorption, XRD, TEM, XPS, TPD, and TPR techniques were used to characterize the catalyst. The palladium deposition on the supports leads to the formation of PdO. After the catalytic tests, the metal-Pd phase was observed. The complete oxidation of methane on Pd/La-Ce-Zr-Al catalyst takes place at temperatures above 250 °C, and in the presence of water vapor, the reaction temperature increases to about 70 °C. The careful choice of constituent oxides provides a balance between structural stability and flexibility. The alumina and lanthanum oxide ensure the high specific surface area, while the simultaneous presence of zirconia and ceria leads to the formation of a mixed-oxide phase able to interact with palladium ions by incorporating and de-incorporating them at different conditions. The mechanism of Mars–van Kerevelen was considered as the most probable for the reaction of complete methane oxidation. The possibility of the practical application of Pd-modified La-Ce-Zr-Al catalyst is evaluated. The use of a mix of multiple rare and abundant oxides makes the proposed catalyst a cost-effective alternative. Full article

The simulation of damage in composite materials is an important research area that impacts different engineering applications from aerospace structures to renewable energy systems. This review provides a comprehensive analysis of current damage modeling approaches, including intra-layer and inter-layer failures. Various numerical strategies, such as continuum damage mechanics (CDM), cohesive zone models (CZM), extended finite element methods (XFEM), phase-field models (PFM), and peridynamics (PD), are examined to assess their efficiency in predicting crack initiation, propagation, and interaction. Additionally, the role of data-assisted (driven) techniques, such as machine learning, in enhancing predictive capabilities is explored. This review highlights the strengths and limitations of each approach, underscoring the need for further advancements in computational efficiency, multiscale modeling, and integration with experimental data. The findings serve as a foundation for future research into optimizing damage prediction techniques to improve the reliability and durability of composite structures. Full article

Fault diagnosis based on the partial discharge (PD) recognition has been widely applied on a gas-insulated line breaker (GILB) and gas-insulated switchgear (GIS) as a reliable online condition monitoring method. This paper dealt with insulation defect diagnosis based on a Random Forest (RF) algorithm with an optimized feature selection method. Four different types of insulation defect models, such as the free-moving particle (FMP) defect, the protrusion-on-conductor (POC) defect, the protrusion-on-enclosure (POE) defect, and the delamination defect, were prepared to simulate representative PD single pulses and PRPD patterns generated from the GILB. The PD signals generated from defect models were detected using the PRPD sensor which can detect phase-synchronized PD signals with the applied high-voltage (HV) signals without the need for additional equipment. Various statistical PD features were extracted from PD single pulses and PRPD patterns according to four kinds of PD defect models, and optimized features were selected with respect to variance importance analysis. Two kinds of PD datasets were established using all statistical features and top-ranked features. From the experimental results, the RF algorithm achieved accuracy rates exceeding 92%, and the PD datasets using only half of the statistical PD features could reduce the computational times while maintaining the accuracy rates. Full article

Partial discharges (PDs) are one of the leading causes of catastrophic power transformer failures. To prevent such failures, online PD monitoring systems are increasingly being implemented. In this paper, to the best of the authors’ knowledge, a case study analysis of short-term PD monitoring is presented for the first time using a combination of acoustic emission and ultra-high-frequency methods. Studies have shown that this approach, supported by selected statistical methods for analyzing the convergence (such as the confusion matrix and agreement metrics) of acoustic and electromagnetic pulse detection, improves the reliability of PD detection. Furthermore, it was shown that short-term PD monitoring enables the identification of time windows during which discharges occur periodically and the determination of the transformer phase containing the PD source. This, in turn, facilitates the application of the time difference of arrival (TDoA) technique for the precise localization of transformer insulation defects. Full article

Near-Infrared Spectroscopy (NIRS) is a non-invasive technique that measures the oxygenation variations of brain tissue in response to different stimuli. It has many advantages such as being easy to use, portable, and non-invasive. Several studies over the years have demonstrated the usefulness of NIRS in neurological and neurodegenerative diseases. NIRS remains relatively underutilized in clinical practice. The aim of this brief review was to describe the use of NIRS in neurological and neurodegenerative diseases and how its use can modify clinical, therapeutic, and rehabilitative approaches. A total of 54 relevant articles were selected from the PUBMED research database related to the diagnostic and prognostic role of fNIRS in the main neurological and neurodegenerative diseases; significant outcomes have been reported in a descriptive form with careful considerations. In addition, we excluded studies using fNIRS in co-registration with other neurophysiological techniques. The use of NIRS should be applied even in the field of neurological and neurodegenerative diseases; in dementia, NIRS can aid in differential diagnosis and predict possible evolutions from Mild Cognitive Impairment (MCI) to Alzheimer’s Disease (AD) stage; in stroke, it plays an important role especially in the post-acute phase, giving information about the patient’s chances of recovery; in Parkinson’s Disease (PD), the results showed the important role of cognitive aspects; in epilepsy, NIRS can localize the epileptic focus or potentially predict seizure onset. Full article

Formic acid has recently been considered one of the most promising liquid organic hydrogen carriers (LOHCs). Its decomposition to obtain H₂ has been fruitfully investigated during recent years using catalysts of a very diverse nature. Most of these catalysts lack stability, so finding stable materials under reaction conditions is highly desirable but challenging. In the present study, catalysts based on Pd nanoparticles supported on C₃N₄-modified activated carbon derived from biomass residues were developed, characterized, and assessed in the decomposition of formic acid in the liquid phase. These catalysts were prepared using a straightforward method that allowed different nitrogen contents to be achieved in the support and avoided the ex situ reduction in the Pd precursor. The results of the catalytic tests indicated the positive role of incorporating C₃N₄, leading to catalysts that displayed much better performance than the C₃N₄-free counterpart. The incorporation of C₃N₄ resulted in catalysts with small and well-distributed Pd nanoparticles, leaching resistance and modified electronic properties of the Pd species. As a result, promising catalytic activity was observed in the developed materials. Pd/AC_C₃N₄(19) attained an initial TOF of 2893 h⁻¹, and it preserved most of its catalytic activity for at least six consecutive reaction cycles, which is a remarkable characteristic of the developed catalytic system. Full article

Background: Antimicrobial consumption (AMC) patterns, besides prescribing behaviors, reflect the changing epidemiology of infectious diseases. Routine surveillance data have been used to investigate the development of AMC from 2017 to 2023 and the impact of COVID-19 within the context of the framing time periods. Methods: Data from 112 hospitals, continuously participating from 2017 to 2023 in the national surveillance system of hospital antimicrobial consumption based at the Robert Koch Institute, were analyzed according to the WHO ATC (Anatomical Therapeutic Chemical)/DDD (Defined Daily Dose) method and categorized according to the WHO AWaRe-classification. AMC was quantified by consumption density (CD) expressed in DDD/100 patient days (PD) and DDD/100 admissions (AD). The time period was subdivided into three phases: pre-pandemic phase (2017–2019), main pandemic phase (2020–2021) and transition phase (2022–2023). Linear regression models have been used to determine the presence of an overall trend, the change in intra-phasic trends and phase-specific mean consumption levels over time. Results: From 2017 to 2023 total antibiotic consumption decreased by 7% from 57.1 to 52.9 DDD/100 PD. Four main kinetic patterns emerged across different antibiotic classes: Pattern 1 displays a decreasing pre-pandemic trend, which slowed down throughout the pandemic and transition phase and was exhibited by second-generation cephalosporins and fluoroquinolones. Pattern 2 reveals a rising pre-pandemic trend, which decelerated in the pandemic phase and accelerated again in the transition phase and was expressed by aminopenicillins/beta-lactamase inhibitors, beta-lactamase sensitive pencillins, azithromycin and first-generation cephalosporins. Pattern 3 shows elevated mean consumption levels in the pandemic phase exhibited by carbapenems, glycopeptides, linezolid and third-generation cephalosporins. Pattern 4 reveals a rising trend throughout the pre-pandemic and pandemic phase, which reversed in the transition phase without achieving pre-pandemic levels and was expressed by beta-lactamase resistant penicillins, daptomycin, fosfomycin (parenteral) and ceftazidime/avibactam. Conclusions: Kinetic consumption patterns across different antibiotic classes might reflect COVID-19-related effects and associated changes in the epidemiology of co-circulating pathogens and health care supply. Broad-spectrum antibiotics with persisting elevated consumption levels throughout the transition phase require special attention and focused antimicrobial stewardship activities. Full article