Search Results (10,794)

The automatic classification of ISUP (International Society of Urological Pathology) grade groups in prostate histopathological images remains challenging due to the high similarity between adjacent classes, class imbalance, and label noise. In this work, we propose a deep learning pipeline based on EfficientNet convolutional neural networks combined with a hybrid loss function that integrates ordinal regression and Focal Loss to better capture the ordered nature of ISUP grades. A noise-filtering strategy based on the entropy of predictions from multiple EfficientNet models was first applied to identify and remove high-uncertainty samples from the training set. The problem was then reformulated as an ordinal regression task to explicitly model the hierarchical relationship among grades. Experiments conducted on the PANDA dataset demonstrate that removing noisy samples improved performance from $\kappa =0.826$ to $\kappa =0.833$. Incorporating ordinal loss further increased performance to $\kappa =0.851$. The best configuration, combining ordinal regression and Focal Loss, achieved $\kappa =0.857$ and an accuracy of $0.669$, while reducing severe misclassifications and concentrating errors among adjacent classes. These results indicate that explicitly modeling ordinal structure and mitigating label noise are effective strategies for improving prostate cancer grading systems. Full article

Celastrol (CSL), a natural triterpenoid extracted from Tripterygium wilfordii, demonstrates a wide range of biological activities. In this study, we explored whether CSL alleviates kidney damage in spontaneously hypertensive rats (SHRs) through the modulation of the Nrf2/Ho-1 pathway, a crucial target in renal injury models. A total of 40 male SHRs, aged 6–8 weeks, were randomly allocated to four groups: the control group (CON, serving as the healthy control), the spontaneously hypertensive rat group (SHR), the SHR group treated with low-dose CSL (L-CSL + SHR, 0.5 mg/kg/d), and the SHR group treated with high-dose CSL (H-CSL + SHR, 1 mg/kg/d). All drugs were formulated using physiological saline as the solvent and administered via intraperitoneal injection. The control group received an equivalent volume of physiological saline via intraperitoneal injection, and all groups underwent continuous daily administration for 6 weeks. The results indicated that, in comparison with the control group, the serum levels of angiotensin, angiotensin-converting enzyme, and aldosterone in the SHR group were relatively high, and CSL treatment further downregulated these indices. Simultaneously, CSL downregulated pro-inflammatory factors (tumor necrosis factor-α and interleukin-1β) and upregulated interleukin-6. Regarding renal function-related indicators, CSL reduced malondialdehyde levels and enhanced the activities of antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase, and catalase. Moreover, CSL inhibited the overexpression of Keap1. Significantly, the mRNA levels of Nrf2, Nqo1, and Ho-1 in the CSL-treated groups were notably higher than those in the SHR group. These findings suggest that CSL mitigates renal pathological damage in SHR by activating the Nrf2/Ho-1 pathway, offering a potential therapeutic approach for hypertension-induced renal injury. Full article

Background and Objectives: Age-related macular degeneration (AMD) is a multifactorial retinal disease in which inflammation and blood-retinal barrier dysfunction may contribute to disease pathogenesis. Claudin-5 is a key tight-junction protein involved in endothelial barrier integrity. Hemogram-derived indices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) reflect systemic inflammatory status. This study aimed to evaluate circulating claudin-5 levels and systemic inflammatory indices in patients with wet and dry AMD and to investigate their associations with visual function. Materials and Methods: This prospective case–control study included 90 participants: 30 patients with wet AMD, 30 patients with dry AMD, and 30 healthy controls. All participants underwent detailed ophthalmologic examination, including best-corrected visual acuity (BCVA) assessment and optical coherence tomography. Serum claudin-5 levels were analyzed by enzyme-linked immunosorbent assay, and NLR, PLR, MLR, and PIV were calculated from complete blood count parameters. Group comparisons, correlation analyses, and age-adjusted analyses were performed using appropriate statistical methods. Results: Age differed significantly among the groups (p = 0.032), with the highest median age in the dry AMD group. BCVA (logMAR) also differed significantly (p < 0.001), and both AMD groups had worse visual acuity than controls. Median serum claudin-5 levels were 2.42 in controls, 3.28 in the wet AMD group, and 3.10 in the dry AMD group, with no significant between-group difference (p = 0.280). NLR, MLR, and PIV were also comparable among the groups (p = 0.310, p = 0.410, and p = 0.752, respectively). PLR differed among the groups (p = 0.019), and post hoc analysis showed higher PLR values in the dry AMD group than in the wet AMD group (p = 0.013). However, this difference was no longer statistically significant after adjustment for age (adjusted p = 0.098). Serum claudin-5 was not significantly correlated with age, BCVA, NLR, PLR, MLR, or PIV. Conclusions: Circulating claudin-5 did not differ significantly across AMD phenotypes and was not associated with age, visual function, or systemic inflammatory indices. Although PLR differed between wet and dry AMD before adjustment for age, the overall findings suggest that single-point peripheral serum measurements of claudin-5 may have limited utility in reflecting local retinal barrier-related changes in AMD. Larger longitudinal studies are needed to clarify its potential biomarker role. Full article

Serine protease-like proteases (SBTs) constitute a distinct class of serine proteases exclusive to plants. Despite the recognized importance of SBTs in various plants, knowledge concerning the evolution and function of SBT genes in Brassica napus is limited. In this study, a total of 140, 63, and 71 SBT genes were identified in B. napus, B. oleracea, and B. rapa, respectively. Phylogenetic analysis classified these 330 identified SBTs into five subfamilies, and collinearity analyses further indicated that gene redundancy and gene loss were strongly associated with polyploidization in Brassicaceae plants. Additionally, analyses of gene structure and conserved motifs suggested that evolutionary changes in exon-intron structures may contribute to the differentiation of coding regions, expression patterns, and even functions within the BnSBT family. Analysis of promoter cis-regulatory elements revealed their predominant association with hormonal responses, abiotic stress, and processes related to plant growth and development. Furthermore, eight differentially expressed genes (DEGs) were identified through a comparative analysis of RNA-Seq data from high- and low-yielding cultivars. qRT-PCR verification also revealed that these eight DEGs (BnSBT1.4b, BnSBT1.4c, BnSBT1.4d, BnSBT1.5c, BnSBT1.6b, BnSBT1.8a, BnSBT3.14a, and BnSBT3.14b) were significantly differentially expressed in the pericarp and seeds. They could be categorized into two distinct groups: BnSBT1.4b, BnSBT1.4c, BnSBT1.4d, BnSBT1.5c, and BnSBT1.8a were highly expressed in high-SPSI material, whereas BnSBT1.6b, BnSBT3.14a, and BnSBT3.14b were highly expressed in low-SPSI material. These results suggest that BnSBTs have diverse potential functions in regulating yield traits in Brassica napus. These findings offer key insights into Brassicaceae SBT genes and highlight the importance of BnSBTs in achieving high yields in Brassica napus. Full article

Background/Objectives: Trapeziometacarpal osteoarthritis (TMC OA) is a common disabling condition. This study compared clinical and radiographic outcomes of trapeziectomy with suspension arthroplasty and dual mobility TMC joint replacement in a prospective comparative cohort study design. Methods: A prospective comparative study was conducted on 122 patients contributing 129 hands with Eaton–Littler stage II–III TMC osteoarthritis. Patients were treated with trapeziectomy with suspension arthroplasty (58 patients, 60 hands) or TMC joint replacement with a dual mobility prosthesis (64 patients, 69 hands), based on surgical indication and shared decision-making. Clinical and radiographic evaluations were performed up to 24 months postoperatively. Results: Both techniques significantly improved pain, function, range of motion, and strength (p < 0.05). Joint replacement provided faster pain relief and functional recovery, with superior strength at all follow-up points. At 12 months, pain and functional outcomes were comparable between groups. No implant loosening or failures were observed. Conclusions: Both surgical techniques are effective for TMC osteoarthritis. Dual mobility TMC joint replacement allows faster recovery and greater strength, while achieving comparable mid-term clinical outcomes to suspension arthroplasty. Full article

The complex ocean dynamics in the Northwest Pacific high-seas fishing grounds shape phytoplankton communities, which serve as the foundation for commercially pelagic species. This study investigates how mesoscale eddies modulate phytoplankton groups’ structures by analyzing the spatiotemporal evolution of eight phytoplankton functional types (PFTs) from 2014 to 2023. Utilizing high-resolution AI-driven model data (AIGD-PFT) and a normalized radial distance grid (0–2 R), we quantified PFTs concentrations within cyclonic (CE) and anticyclonic (AE) eddies, validated by Biogeochemical Argo (BGC-Argo) and in situ measurements. Results reveal that diatoms and dinoflagellates dominate the region, accounting for 88.7% of phytoplankton with distinct seasonal peaks in spring and autumn, respectively. CE significantly enhance diatom and dinoflagellate concentration, particularly within the 0.4 R–1.2 R dynamic ring, while AE favor the aggregation of picophytoplankton, such as Prochlorococcus, in mid-to-low latitudes. Correlation analysis indicates that diatom abundance is strongly linked to dissolved oxygen and negatively correlated with sea surface height. We conclude that mesoscale eddies drive the spatial remodeling of phytoplankton communities by altering local physical and nutrient conditions. These findings provide a critical ecological context for assessing the habitat distribution and sustainable management of North Pacific fisheries across different trophic levels. Full article

Peripheral nerve injuries involving critical-sized gaps remain a major clinical challenge. Although autologous nerve grafting is considered the gold standard for peripheral nerve repair, its clinical application is limited by the availability of donor nerve tissue and the risk of donor-site morbidity, including sensory deficits and functional impairment. Therefore, nerve guidance conduits (NGCs) have emerged as a promising alternative when combined with bioactive modulation strategies. In this study, we evaluated bisvinyl sulfonemethyl (BVSM)-crosslinked gelatin conduits integrated with electrical stimulation (ES) at different frequencies (0, 2, 20, and 200 Hz) in a rat sciatic nerve defect model over a 4-week recovery period (n = 10 per group). Structural regeneration was assessed by morphometric analysis, electrophysiology, macrophage infiltration, CGRP immunoreactivity, retrograde Fluorogold tracing, quantitative PCR of growth factors and inflammatory cytokines, and behavioral testing. Among all stimulation paradigms, low-frequency ES at 2 Hz produced the most pronounced regenerative effects. The 2 Hz group demonstrated significantly greater axon number, axonal density, and regenerated nerve area compared with control and high-frequency groups (p < 0.05). Electrophysiological assessments revealed improved nerve conduction velocity, higher MAP amplitudes, and shorter latencies. Enhanced macrophage recruitment and elevated CGRP expression were observed, suggesting coordinated neuroimmune and neurochemical activation. Gene expression analysis indicated upregulation of neurotrophic factors and balanced inflammatory cytokine responses under low-frequency stimulation. In contrast, high-frequency stimulation (200 Hz) failed to enhance overall regeneration and showed reduced axonal metrics, suggesting possible overstimulation-associated suppression. Collectively, these findings demonstrate that BVSM-crosslinked conduits provide a stable and biocompatible regenerative scaffold, and that appropriately tuned low-frequency electrical stimulation (2 Hz) optimally enhances structural, molecular, and functional recovery. The integration of material engineering with bioelectrical modulation represents a promising strategy for next-generation bioelectronic interfaces in peripheral nerve repair. Full article

Erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is widely used in cancer therapy; however, hepatotoxicity limits its clinical use. This study investigated the protective effects of Liv-52, a polyherbal hepatoprotective formulation, against erlotinib-induced hepatotoxicity in rats and compared its efficacy with melatonin. The animals (n = 24, Wistar albino rats) were randomly categorized into four groups: healthy (HG), erlotinib (ERG), Liv-52 + erlotinib (LEG), and melatonin + erlotinib (MEG). Liv-52 (50 mg/kg/day, orally) and melatonin (10 mg/kg/day, orally) were administered once daily for two weeks. Erlotinib (10 mg/kg, orally) was given every other day to ERG, LEG, and MEG groups for two weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were measured. Hepatic malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) levels were analyzed. Additionally, double immunofluorescence staining was performed to evaluate apoptotic (poly[ADP-ribose] polymerase-1 [PARP-1], apoptosis-inducing factor [AIF]), inflammatory (cyclooxygenase-2 [COX-2]), and anti-inflammatory (interleukin-10 [IL-10]) biomarkers in liver tissues. Histopathological examination was also conducted to assess structural alterations. Erlotinib significantly increased MDA, ALT, AST, and LDH while decreasing tGSH, SOD, and CAT (p < 0.001). Strong immunoreactivity for PARP-1, AIF, IL-10, and COX-2, as well as severe hydropic degeneration and necrosis, was observed in ERG (p < 0.05). Both Liv-52 and melatonin significantly ameliorated biochemical, histopathological, apoptotic, and inflammatory alterations (p < 0.05). Notably, Liv-52 demonstrated superior hepatoprotective efficacy compared to melatonin. These findings indicate that Liv-52 effectively attenuates erlotinib-induced hepatotoxicity by modulating oxidative stress, inflammatory responses, and apoptotic pathways, thereby preserving liver function and structural integrity. Full article

Corn processing waste represents an abundant, renewable, and low-cost lignocellulosic resource with considerable potential for environmental remediation applications. Large quantities of residues generated during corn processing, including cobs, husks, bran, and other by-products, are produced annually and can be utilized directly as native biomass or converted through thermochemical processes into hydrochars and biochars. This systematic review provides a comparative analysis of native corn processing biomass, hydrochars produced via hydrothermal carbonization, and biochars obtained through pyrolysis, with a focus on their potential as adsorbents for the removal of organic and inorganic pollutants from soil and water systems. Particular attention is given to the influence of thermochemical conversion processes on the physicochemical properties of the materials, including surface chemistry, porosity, functional groups, and structural characteristics, which govern adsorption mechanisms such as ion exchange, electrostatic interactions, surface complexation, hydrogen bonding, and π–π interactions. Furthermore, the advantages and limitations of each material type are discussed, together with key environmental and techno-economic considerations related to their production and practical application, including indicative production costs (USD per kg of adsorbent) and cost–performance relationships in terms of adsorption capacity. By linking biomass conversion processes, material properties, and adsorption performance, this review aims to provide a comprehensive overview of corn processing waste valorization and to support the development of sustainable adsorbent materials for soil and water remediation. A total of 36 studies were included in the qualitative synthesis following PRISMA guidelines. Full article

Background/Objectives: Ankle–foot orthoses (AFOs) are commonly used to improve gait in children with cerebral palsy (CP), but their effect on specific gait patterns is underreported. This study evaluates the utilization of the Gait Pattern Classification System for Children with Spastic CP (GaP-CP) to investigate the effects of ankle–foot orthoses on gait kinematics, spatio-temporal parameters and the energy cost of walking. Methods: In this retrospective study, 66 ambulatory children with spastic CP underwent 3D gait analysis with and without AFOs or functional electrical stimulation. Gait patterns were classified according to GaP-CP. AFOs were articulated, flexible, or rigid. Thirty-six children also performed a 5 min walk test with gas exchange measurements. Step length, walking speed, and the energy cost of walking were calculated. Gait kinematics were analyzed with statistical nonparametric mapping. Non-parametric statistics were used to investigate orthotic effects for the total group and for each gait pattern. Results: Ankle kinematics improved in swing phase and initial contact (10 degrees less plantarflexion, p < 0.05) for the total group, dropfoot and genu recurvatum. During the stance phase, reduced knee extension in genu recurvatum (by 3 degrees, p < 0.05) and increased knee extension in crouch (by 3 degrees, p < 0.05) were observed. Median changes in non-dimensional step length were clinically significant (>0.039, p ≤ 0.02, effect size ≥ 0.55) for the total group and the dropfoot, genu recurvatum, and crouch subgroups, while changes in most gait indices, walking speed and the energy cost of walking were not clinically significant. Conclusions: The combined use of GaP-CP and kinematic analysis provided new insights into the effects of ankle–foot orthoses on gait. Articulated and flexible orthoses may not have provided adequate support for genu recurvatum and crouch gait, showing a potential value in gait pattern specific orthotic design to optimize gait kinematics. Full article

Background/Objectives: Plant-derived phytochemicals are being increasingly explored for their ability to treat various illnesses, especially those affecting the vasculature. High mobility group box 1 (HMGB1) acts as a crucial mediator during the late phase of sepsis, promoting the secretion of pro-inflammatory cytokines and thereby fueling inflammation and systemic complications. Higher plasma HMGB1 levels not only hinder accurate diagnosis and prognosis but also worsen disease outcomes in inflammatory states. Picropodophyllotoxin (PPT), a key bioactive ingredient isolated from the root of Podophyllum hexandrum, has shown a range of beneficial effects, including anti-cancer and anti-proliferative actions, across several tumor types. Nevertheless, its possible involvement in HMGB1-driven severe vascular inflammation remains unexplored. The current work aimed to investigate whether PPT could influence lipopolysaccharide (LPS)-induced HMGB1 activity and its related inflammatory signaling in human umbilical vein endothelial cells (HUVECs). Methods: A combination of in vitro and in vivo approaches was used to assess the anti-inflammatory action of PPT. These included measurements of endothelial barrier function, cell survival, leukocyte attachment and migration, levels of cell adhesion molecules, and the release of pro-inflammatory factors. Both cultured human endothelial cells and mouse disease models were used to thoroughly evaluate how PPT affects HMGB1-triggered inflammatory reactions. Results: The findings showed that PPT markedly reduced HMGB1 movement from inside HUVECs to the outside, thereby limiting its release into the environment. Moreover, PPT effectively decreased neutrophil sticking and migration, lowered the appearance of HMGB1 receptors, and prevented the activation of nuclear factor-κB (NF-κB), a master switch in inflammatory signaling. At the same time, PPT treatment strongly lowered tumor necrosis factor-α (TNF-α) production, adding to its anti-inflammatory profile. Conclusions: Taken together, these results indicate that PPT potently inhibits HMGB1-driven inflammatory processes by acting at several levels of the inflammatory cascade, such as HMGB1 movement, receptor binding, NF-κB activation, and subsequent cytokine release. Therefore, PPT stands out as a hopeful therapeutic option for HMGB1-related inflammatory diseases and deserves further exploration in preclinical and clinical studies. Full article

Background: Ulcerative Colitis and Crohn’s Disease are the most common forms of inflammatory bowel disease (IBD), with increasing prevalence both globally and in Poland. Many aspects of how a patient’s everyday function and treatment remain underexplored. Methods: This study recruited adult patients with IBD hospitalized in the Department of Digestive Tract Diseases of the Medical University of Lodz, Poland. The data were collected between June and July 2025 using an author-developed questionnaire assessing patients’ opinions on therapy, their expectations, and overall life satisfaction. Results: A total of 87 patients with IBD were included in the analysis. Overall, 59 patients (67.82%) reported strong satisfaction with their current treatment, indicating a generally positive perception of disease management. Higher treatment satisfaction was associated with patients’ perception that their preferences were respected by the gastroenterologist. Further analysis revealed significant associations between different types of treatment, disease activity, and patient-reported outcomes. Those patients who were treated with biological agents more frequently reported complete satisfaction with the treatment (41/52 vs. 18/35; p = 0.014), low-to-moderate disease activity (42/52 vs. 19/35; p = 0.016), and fewer limitations in their social lives (16/52 vs. 20/35; p = 0.026) compared to the remaining group. Furthermore, the study demonstrated that those patients who reported remission were less likely to have their physical activity limited (27/55 vs. 27/32; p = 0.002). There were significantly more patients under 50 years of age than older patients getting biological therapy (48/74 vs. 4/13; p = 0.045). Additionally, women in the studied group had a higher rate of IBD-related surgical interventions compared to men (15/36 vs. 9/51; p = 0.026). Despite the high overall satisfaction with treatment and physician communication, 20 patients (22.99%) admitted to taking additional, non-prescribed medication or dietary supplements. Similarly, 21 (24.14%) patients modified treatment regimens by discontinuing the medication intake or changing the prescribed dose. Furthermore, 57 patients (65.52%) reported that they feared the possibility of surgical intervention. Nonetheless, the majority of patients who underwent surgical treatment (22/24; 91.67%) were satisfied with the results. Reported rates of undergoing regular colorectal cancer screening were also unsatisfactory—4/37 (10.81%) patients with disease duration >8 years, suggesting inadequate awareness. Conclusions: Biological treatment can positively impact multiple aspects of patients’ lives by lowering the disease’s activity. Gastroenterologists should spend more time discussing patients’ preferences and concerns, as well as explaining the colorectal cancer screening rules. Full article

This study investigates the internal structure and functional consistency of a brief scale designed to assess the social regulation of learning in collaborative higher education environments. Social regulation is essential to understanding how students coordinate cognitive and socio-emotional processes during group work, but brief and valid instruments remain limited. A total of 973 undergraduate students responded to seven items on a seven-point Likert scale. Exploratory and confirmatory factor analyses were performed to evaluate the dimensionality of the instrument. The results supported a two-factor structure comprising coordination regulation and collective engagement regulation. Standardized loadings ranged from 0.772 to 0.935 and the factors showed a high latent correlation (r = 0.792), indicating that they are distinct yet strongly interdependent. The model demonstrated excellent fit according to incremental indices (CFI = 0.992, TLI = 0.988) and acceptable residual fit (SRMR = 0.064). Although the RMSEA value exceeded conventional thresholds (RMSEA = 0.137, this result should be interpreted with caution due to the limited number of items and degrees of freedom, as documented in prior methodological research), these findings highlight how shared planning, monitoring, and socio-emotional alignment function as interconnected processes that support effective collaboration in academic teams. Overall, the study provides empirical evidence that a parsimonious two-dimensional model can capture key regulatory dynamics relevant to fostering sustainable collaborative practices in higher education. Future research should examine measurement invariance across contexts and explore associations with student performance, engagement, and well-being. Full article

Shellfish aquaculture can alter sediment conditions and affect benthic ecosystem functioning, so dredging is widely applied as a management strategy to mitigate sediment deterioration. However, its ecological effectiveness remains uncertain. This study evaluated ecological quality under the disturbance of dredging in shellfish farming areas of Gamak Bay, South Korea, using multiple macrobenthic indices. Macrobenthic samples and environmental data were collected before (May 2025) and after dredging (August 2025). Five macrobenthic indices, including the AZTI Marine Biotic Index (AMBI), BENTIX, Benthic Polychaete/Amphipod ratio (BPA), Benthic Pollution Index (BPI), and Multivariate AMBI (M-AMBI), along with a composite index, were used to assess ecological quality. Temporal changes within groups were tested using Wilcoxon signed-rank tests, and differences between dredged and control stations were examined using Mann–Whitney U tests. Multivariate analyses were used to explore environmental gradients and community responses. Results showed clear seasonal variation in environmental conditions and macrobenthic community structure. Most indices indicated a decline in ecological quality after dredging, with higher AMBI values and lower BENTIX, BPI, and M-AMBI values at dredged stations. However, these changes were not statistically significant (p > 0.05), suggesting limited short-term effects of dredging. The proportion of stations with acceptable ecological status decreased slightly from May to August. Seasonal factors, particularly temperature and salinity, played a dominant role in structuring benthic communities. Overall, the findings indicate that the short-term dredging effects were weaker than seasonal environmental variability. A multi-index approach is recommended for robust ecological assessment, and long-term monitoring is necessary to fully evaluate the effectiveness of dredging in shellfish aquaculture systems. Full article

Hail events commonly affect the Western part of Catalonia, producing damage mainly in the agricultural sector. Comparison of the weather radar data with hail pad registers at ground level allows for the diagnosis of hail severity. However, limitations using individual radar fields have led to the use of quantiles of the vertical profiles of reflectivity for a period between 12 min before and after a hailfall. These profiles combine all radar parameters, and are less sensitive to radar functioning anomalies and hailfall nature. The explored dataset was divided into severe and non-severe registers, with two subsets: one larger (90% of cases) for modeling and the second one for validating the results. Results indicate a better estimation of severe hail, but the number of false alarms with non-severe cases was still high. In consequence, future work should focus on minimizing false alarms using more restrictive profile groups. The purpose of the study is the application of a real-time tool for improving surveillance tasks which provides better discrimination between severe and non-severe hail occurrences. Full article