Search Results (331)

This study aimed to assess the use of selected raw materials, such as whole-grain oat flakes, pumpkin seeds, sunflower seeds, and flaxseeds, to obtain bars using baking and drying methods. Modifying the bars’ composition involved selecting the fibre preparation, replacing water with NFC juice, and using fresh apple juice and apple pomace. The Psyllium fibre preparation, also in the form of a mixture with apple fibre, was the most useful in dough cohesion and the quality of the bars. Baked bars were characterised by higher sensory quality than those obtained by drying. Microwave–convection drying was a good alternative to baking, primarily due to the lower temperature resulting in a lower acrylamide content and comparable product quality. The basic grain ingredients and fibre preparations mainly shaped the nutritional and energy value and the sensory and microbiological quality. Modifying the recipe using NFC or fresh juice and apple pomace allowed the bars to develop new properties and quality characteristics. The use of NFC juices resulted in a reduction in the pH of the bars, which is associated with a higher microbiological quality of the bars. All bars had low acrylamide content, significantly lower than the permissible level. Using fresh pomace or fibre preparations made from by-products is a possibility to increase the fibre content in the bars and a method of managing by-products. Full article

Various SARS-CoV-2 remdesivir resistance-associated substitutions (RAS) have been reported, but a comprehensive comparison of their resistance levels is lacking. We identified novel RAS and performed head-to-head comparisons with known RAS in Vero E6 cells. A remdesivir escape polyclonal virus exhibited a 3.6-fold increase in remdesivir EC₅₀ and mutations throughout the genome, including substitutions in nsp12 (E796D) and nsp14 (A255S). However, in reverse-genetics infectious assays, viruses harboring both these substitutions exhibited only a slight decrease in remdesivir susceptibility (1.3-fold increase in EC₅₀). The nsp12-E796D substitution did not impair viral fitness (Vero E6 cells or Syrian hamsters) and was reported in a remdesivir-treated COVID-19 patient. In replication assays, a subgenomic replicon containing nsp12-E796D+nsp14-A255S led to a 16.1-fold increase in replication under remdesivir treatment. A comparison with known RAS showed that S759A, located in the active site of nsp12, conferred the highest remdesivir resistance (106.1-fold increase in replication). Nsp12-RAS V166A/L, V792I, E796D or C799F, all adjacent to the active site, caused intermediate resistance (2.0- to 11.5-fold), whereas N198S, D484Y, or E802D, located farther from the active site, showed no resistance (≤2.0-fold). In conclusion, our classification system, correlating replication under remdesivir treatment with RAS location in nsp12, shows that most nsp12-RAS cause moderate resistance. Full article

Background/Objectives: Left/right discrimination (LRD) training is increasingly being used in the treatment of chronic low back pain (CLBP). However, it is unclear whether trunk LRD-performance is impaired in CLBP patients and whether clinical parameters are related to LRD-performance. Therefore, this cross-sectional study aimed to examine (1) whether LRD-performance differs between CLBP patients and pain-free individuals; (2) whether these differences depend on the low back pain (LBP) history in pain-free individuals; (3) if clinical factors are related to LRD-performance; (4) whether LRD-task difficulty influences these results. Methods: Participants included 150 pain-free persons (107 with no LBP-history; 43 with past LBP) and 150 patients with CLBP. All participants performed the LRD-task in a simple and complex condition. Outcomes were reaction time and accuracy. Results: CLBP patients were significantly slower (Cohen’s d = 0.47 to 0.50, p < 0.001) and less accurate (Cohen’s d = 0.30 to 0.55, p < 0.001) than pain-free individuals without LBP-history, but not compared to those with past LBP (Cohen’s d reaction time = 0.07 to 0.15, p = 0.55; Cohen’s d accuracy = 0.03 to 0.28, p-value = 0.28). All participant groups were slower and less accurate in the complex condition, but between-groups differences were independent of task difficulty. Linear mixed models showed that older age and lower education were independently associated with less accuracy. When controlling for demographics, pain intensity, disability, fear of movement, pain-related worry and pain duration were not related to LRD-performance in patients with CLBP. Conclusions: Patients with CLBP showed impaired trunk LRD-performance compared to pain-free persons without LBP history, but not compared to those with past LBP. When controlling for demographics, clinical parameters were not related to LRD-performance in patients with CLBP. Our findings indicate that LRD-performance may remain impaired after recovering from LBP. Full article

Background: There are only a few available options for early rehabilitation of severely impaired individuals who must remain bedbound, as most exercise paradigms focus on out-of-bed exercises. To enable these individuals to exercise, we developed a novel hybrid rehabilitation system combining a brain–computer interface (BCI), functional electrical stimulation (FES), and a robotic device. Methods: The BCI assessed the presence of a movement-related cortical potential (MRCP) and triggered the administration of FES to produce movement of the lower limb. The exercise trajectory was supported by the robotic device. To demonstrate the system, an experiment was conducted in an out-of-lab setting by ten able-bodied participants. During exercise, the performance of the BCI was assessed, and the participants evaluated the system using the NASA Task Load Index, Intrinsic Motivation Inventory, and by answering a few subjective questions. Results: The BCI reached a true positive rate of 62.6 ± 9.2% and, on average, predicted the movement initiation 595 ± 129 ms prior to the MRCP peak negativity. All questionnaires showed favorable outcomes for the use of the system. Conclusions: The developed system was usable by all participants, but its clinical feasibility is uncertain due to the total time required for setting up the system. Full article

Fever is a frequent complication in children receiving chemotherapy, primarily caused by bloodstream infections and non-infectious inflammation. Yet, the pathophysiological mechanisms remain unclear, and diagnostics are insufficient, which often results in continued antibiotic treatment despite negative blood cultures. In a nationwide study, we collected whole blood in PAXgene tubes from 168 febrile episodes in children with hematological malignancies, including 37 episodes with bacteremia, and performed single-cell RNA sequencing. We compared transcriptomic profiles between febrile children with and without bacteremia. In children with bacteremia, differentially expressed genes were related to immunoregulation and cardiac and vascular function. Children without bacteremia had distinct gene expression patterns, suggesting a viral or other inflammatory cause of fever. Several differentially expressed genes overlapped with previously published transcriptomics-based diagnostic signatures developed in immunocompetent children. In conclusion, blood transcriptomics provided novel insights into the pathophysiological mechanisms of febrile children with hematological malignancies. We found differentially expressed genes suggesting viral infections or non-bacterial inflammation as causes of fever in children with negative blood cultures, supporting early antibiotic discontinuation in children with cancer. Full article

Background/Objective: Sensory integration (SI) involves the central processing of visual, vestibular, and somatosensory inputs. It plays a key role in regulating movements such as gait. However, aging may impair these systems and SI, altering the gait. Therefore, this systematic review and meta-analysis aim to examine the relationship between gait parameters and SI during standing in healthy older adults. Methods: A systematic literature search was conducted in the Web of Science, PubMed, MEDLINE, and PEDro databases. Correlation coefficients between gait speed, sway (area and/or velocity) while standing under different SI conditions, and quotients were extracted. The Romberg Quotient (RQ) and Proprioception Quotient (PQ) were used to assess reliance on visual and somatosensory systems, respectively. The studies were grouped by condition, quotient, and outcome measures for the meta-analysis. Results: Thirteen studies (n = 719, mean age 72.5 years) were included. There were significant associations between gait speed and sway area during standing with eyes open on a stable surface (r: −0.235, p < 0.001), eyes closed on a stable surface (ECS) (r: −0.201, p < 0.001), eyes open on a compliant surface (r: −0.198, p < 0.001), and eyes closed on a compliant surface (r: −0.186, p < 0.004). No associations were found between gait speed and sway velocity in each condition, RQ, and PQ (p > 0.486 for all), except for the ECS (r: −0.149, p: 0.01). Conclusions: This study indicated a partial link between gait speed and SI in older adults. Future research should focus on dynamic SI evaluation to better understand this association. Full article

Recent diagnostic advances reveal that lymphatic disease in Noonan syndrome (NS) and other NS-like RASopathies often stems from central conducting lymphatic anomalies (CCLAs). The RAS/MAPK-ERK pathway plays a central role in lymphangiogenesis. Targeting this pathway with MEK-inhibitor trametinib has emerged as a promising therapeutic strategy for managing CCLAs in patients with NS-like RASopathies. This case series assessed the clinical outcomes of trametinib therapy in eight patients with NS-like RASopathies and CCLA, each offering unique insights into the therapeutic efficacy of MEK inhibition. In infants, a lower dose of 0.01 mg/kg/day and earlier discontinuation of trametinib therapy effectively alleviated the symptoms of congenital chylothorax and rescued the lymphatic phenotype, compared to similar published cases. Moreover, four patients aged >11 y showed a slower response and did not achieve complete symptomatic recovery. In conclusion, it is advised to consider trametinib therapy for patients with severe, therapy-refractory CCLA in patients with NS-like RASopathies. However, individual responses to trametinib therapy may vary, with some patients demonstrating more favorable outcomes than others. Further investigation into potential enhancers and suppressors of the lymphatic phenotype is necessary for more accurate treatment predictions. While these factors are likely genetic, we cannot rule out other intrinsic or physiological factors. Full article

Benign prostatic hyperplasia (BPH) is a common condition in intact male dogs, often progressing from subclinical to symptomatic stages with increasing clinical and structural impact. This study evaluated canine prostate-specific esterase (CPSE) as a biomarker for BPH progression, focusing on clinical severity, complexity, and ultrasonographic features. Seventy-one dogs were included: subclinical-BPH (n = 14), clinical-BPH (n = 26), BPH-prostatitis (n = 9), and controls (n = 22). CPSE levels, measured using a canine-specific enzyme-linked immunosorbent assay, were significantly correlated with clinical severity (ρ = 0.800, p ≤ 0.001) and complexity (ρ = 0.818, p ≤ 0.001). CPSE predicted mild (OR = 1.260, B = 0.231, p ≤ 0.001) and moderate severity (OR = 1.300, B = 0.262, p ≤ 0.001), as well as low (OR = 1.225, B = 0.203, p ≤ 0.05), moderate (OR = 1.235, B = 0.211, p ≤ 0.01), and high (OR = 1.346, B = 0.297, p ≤ 0.001) clinical complexity. CPSE showed a trend toward predicting structural alterations (OR = 1.227, B = 0.204, p = 0.069) and was associated with larger stippled areas, increased prostatic volume, and larger cysts/abscesses (all p ≤ 0.001). CPSE appears to be a promising marker for BPH progression. Full article

Fermentation is widely recognized for enhancing the sensory attributes and nutritional value in foods, with recent research focusing on non-alcoholic and root-based functional beverages. In this study, the genomic and fermentation characteristics of Kluyveromyces marxianus LRCC8279 (KM8279) and Saccharomyces cerevisiae LRCC8293 (SC8293) were analyzed, specifically for their application in root extract-based low-alcohol fermentations. Whole-genome sequencing revealed that both strains harbored key genes involved in glucose, fructose, and sucrose metabolism and genes implicated in ethanol production. Although SC8293 harbored maltose-metabolizing genes, including MAL13 and MAL31, these genes were absent in KM8279. This genetic difference was evident in the fermentation performance, manifesting as distinct variations in alcohol production depending on the carbohydrate source. A further investigation of fermentation conditions demonstrated that both strains maintained low alcohol levels and exhibited a consistent growth at 15–20 °C within 72 h. Fermentation using extracts from Pueraria lobata, Arctium lappa (AL), Zingiber officinale (ZO), and Platycodon grandifloras revealed that KM8279 markedly increased the production of volatile compounds, contributing to floral and fruity sensory attributes in ZO and AL, whereas SC8293 contributed to a more complex flavor profile in AL. Notably, KM8279-ZO and KM8279-AL fermentations maintained alcohol contents below 1%, indicating their potential application in non-alcoholic beverages. Future studies are needed to investigate the relationship between the key volatile compound production and associated genetic characteristics, along with sensory evaluations, to develop optimized flavor modulation strategies. Full article

Background/Objectives: The aim of this systematic review and meta-analysis was to investigate the effect of dietary supplements on male infertility. Methods: PubMed, Embase, and CENTRAL were searched from inception to May 2024. Randomized controlled trials with treatment durations of ≥12 weeks investigating the effect of dietary supplements on male infertility compared to placebo were included. Primary outcomes were pregnancy and live birth, while secondary outcomes were sperm concentration, sperm count, total motility, progressive motility, normal morphology, and DNA Fragmentation Index. Risk of bias was assessed using the revised Cochrane risk of bias (RoB2) tool. Data were meta-analyzed using random effects-restricted maximum likelihood models. Certainty of evidence was evaluated using the grading of recommendations, assessment, development and evaluation (GRADE) approach. Results: Of the 3137 articles identified, 50 were included. No effect on pregnancy and live birth was found. Different supplements improved single sperm parameters: Zinc and folic acid and ≥3 substance dietary supplements improved sperm concentration, selenium, carnitine, and coenzyme Q10 improved motility and alpha-lipoic acid improved normal morphology. Vitamin D, vitamin E, and omega-3 fatty acids showed no improvement in sperm parameters. The majority of studies had some concerns or high risk of bias, and certainty of evidence was generally low or very low. Conclusions: This study found no convincing evidence of an effect of any dietary supplements on male infertility. Larger and more well-conducted randomized controlled trials focusing on specific supplements and considering pregnancy outcomes are needed. Full article

Sadi Carnot’s seminal work laid the foundation for exploring the effects of thermodynamics across diverse domains of physics, stretching from quantum to cosmological scales. Here, we build on the principles of the original Carnot heat engine, and apply it in the context of a particular toy model black brane. This theoretical construct of an effectively two-dimensional, stable, and stationary gravitational object in four-dimensional spacetime derives from a hypothetical flat planet collapsed under the influence of gravity. By constructing a thermodynamic cycle involving three such black branes, we explore the possibility of energy extraction or mining, driven by the temperature gradients and gravitational potential differences characteristic of curved spacetime. Analytic solutions obtainable within this toy model illuminate key aspects of black hole thermodynamics in general, particularly for spacetimes that are not asymptotically flat. Central to these findings is the relation between gravitationally induced temperature ratios and entropy changes, which collectively offer a novel perspective on obtainable energy transfer processes around gravitational structures. This analysis highlights potential implications for understanding energy dynamics in gravitational systems in general, including for black hole evaporation and experimentally implemented black hole analogues. The presented findings not only emphasise the universality of the thermodynamic principles first uncovered by Carnot, but also suggest future research directions in gravitational thermodynamics. Full article

This retrospective, single-center study investigates the association between PET parameters and pathological response or disease recurrence in patients with soft tissue sarcoma (STS) treated with neoadjuvant chemotherapy (NACT). The maximum standardized uptake value (SUVmax_BL), metabolic tumor volume (MTV_BL), and total lesion glycolysis (TLG_BL) were measured at baseline [¹⁸F]FDG PET/CT and the change in percentage (ΔSUVmax, ΔMTV, ΔTLG) from baseline to early evaluation [¹⁸F]FDG PET/CT was calculated. The optimal cutoff values of the different PET parameters for pathological response, defined as <10% residual viable tumor (RVT) or >15% fibrosis/hyalinization, and recurrence-free survival were obtained for analysis. Forty-two patients who underwent baseline [¹⁸F]FDG PET/CT and NACT followed by surgery were included between January 2015 and January 2023. The primary diagnoses were angiosarcoma (n = 15), leiomyosarcoma (n = 15), sarcoma not otherwise specified (n = 9) and synovial sarcoma (n = 3). Twenty-eight (66.6%) patients underwent an early evaluation PET/CT. MTV_BL, TLG_BL, and ΔSUVmax (p = 0.024; p = 0.042, p = 0.009, respectively) values above the cutoff were associated with a pathological response based on RVT. ΔSUVmax, ΔMTV, and ΔTLG (p = 0.002; p = 0.019; p = 0.039, respectively) values above the cutoff were positively related to >15% fibrosis/hyalinization. MTV_BL, TLG_BL, and ΔMTV (p = 0.014; p = 0.022; p = 0.034, respectively) values above the cutoff were prognostic for the recurrence of disease. [¹⁸F]FDG PET/CT has a promising role in STS patients treated with NACT. Full article

Persistent high-risk Human Papillomavirus infection is the primary factor in cervical carcinogenesis. However, other host-related features are believed to play a role as well. Recent research suggests that the vaginal microbiome and the immune microenvironment play a significant role in the acquisition and persistence of Human Papillomavirus infection, as well as in the regression or progression of cervical intraepithelial lesions. Studies in this emerging field describe factors associated with this interaction, though the precise nature remains incompletely understood. In this narrative review, we aim to summarize the current literature on the topic and propose hypotheses and recommendations for future research and treatment strategies. Full article

This study investigates the size effect on the Seebeck coefficient (SC) in cement composites incorporating silicon carbide (SiC). Two specimen shapes, cubic (50 × 50 × 50 mm³) and beam (40 × 40 × 160 mm³), were analyzed with varying SiC substitution ratios (0%, 50%, and 100%) for fine aggregates. Thermal and electrical conductivities were measured to assess their influence on the SC. The results showed that a higher SiC content increased porosity, which reduced mechanical strength but significantly improved thermal and electrical conductivities. Thermal conductivity increased from 1.88 W/mK (0% substitution) to 11.89 W/mK (100% substitution), while electrical conductivity showed an improvement from 0.0056 S/m to 0.065 S/m. Cubic specimens exhibited higher SC values compared to beam specimens, with a maximum SC of 1374 μV/K at 100% SiC substitution, attributed to shorter thermal diffusion distances. The findings suggest that optimizing member size and SiC content can significantly improve the thermoelectric performance of cement composites, potentially enhancing energy efficiency in construction applications. Full article

Background/Objectives: Visceral adipose tissue (VAT) may play a direct role in the development of metabolic dysfunction-associated steatotic liver disease (MASLD) and its progression to metabolic dysfunction-associated steatohepatitis (MASH). In this study, we employed untargeted proteomics analyses on paired biopsies from VAT and liver tissues of patients with obesity, MASLD, and MASH. Our objective was to investigate tissue-specific protein expression patterns in search of a potential proteomic signature associated with MASH in both VAT and liver tissue. Methods: VAT and liver tissue were collected from 70 subjects with severe obesity (SWOs) and nine control study subjects without obesity (CON). SWOs were stratified on the basis of liver histology into LS− (no liver steatosis), LS+ (liver steatosis), and MASH. Peptides were extracted from frozen tissue and were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Raw files were analyzed with Spectronaut, proteins were searched against the human FASTA Uniprot database, and the significantly expressed proteins in the two tissues were analyzed. The p-values were false discovery rate (FDR) corrected. Results: A total of 59 VAT and 42 liver proteins were significantly differentially expressed between the four groups: LS−, LS+, MASH, and CON. The majority were upregulated, and many were related to lipid metabolism. In VAT, only one protein, the mitochondrial sulfide:quinone oxidoreductase (SQOR), was significantly downregulated in the MASH group only. In liver tissue from patients with MASH, six proteins were significantly altered compared with the three other groups. Correlation analyses between the top 10 positive VAT and liver proteins were dominated by inflammatory and detoxification proteins. Conclusions: The presence of MASH was not reflected in the VAT proteome, and both the VAT and the liver proteome were generally affected more by the presence of obesity than by MASLD severity. Several immunomodulating proteins correlated significantly between VAT and liver tissue and could reflect common pathophysiological characteristics. Full article