Search Results (7,042)

This study aimed to evaluate the penetration and bonding performance of three restorative materials—high-viscosity glass ionomer cement (Riva Self Cure HV), resin-modified glass ionomer cement (Riva Light Cure) and a bioactive resin (Activa BioActive Restorative™)—in the healthy and carious dentine of permanent molars. Forty extracted human molars with sound or decayed dentine were restored following standardised protocols and subsequently divided into slices. So, twenty-four samples were used for each group (sound and carious dentine) for interface analysis using confocal laser scanning microscopy, field emission scanning electron microscopy and energy dispersive X-ray spectroscopy, and another eight simples were used for each group (sound and carious dentine) for Vickers microhardness testing. Results showed that both glass ionomer cements achieved consistent chemical bonding in healthy dentine and demonstrated better interfacial adaptation compared to carious dentine, where partially demineralised areas showed weaker bonding. The bioactive resin exhibited good adhesion in sound dentine due to the adhesive system but showed poorer interaction in decayed dentine with signs of interfacial separation. Elemental analysis revealed similar compositions among materials, with no significant differences in material concentrations among the ionomers, while there were significant differences with the other materials. On the other hand, some variations were observed in the sulphur, fluoride and strontium content depending on dentine condition. Microhardness values were higher in healthy dentine than in carious dentine for all materials (p < 0.001), except the high-viscosity glass ionomer, which maintained stable hardness in both substrates (36.33 ± 6.23 VHN vs. 34.56 ± 4.31 VHN; p = 0.605). These findings highlight the relevance of material selection and dentine condition in minimally invasive restorative dentistry. Full article

Real-time coordination of heterogeneous multi-agent systems in dynamic and partially observable environments poses significant challenges. To address this, we propose a framework that integrates fuzzy inference systems with real-valued genetic algorithms to optimize decision-making under strict time constraints and sensory uncertainty. We evaluate the proposed method in the RoboCup Soccer Simulation 2D League, where 22 autonomous agents coordinate through a fuzzy-evaluated action sequence search. Spatial heuristics are encoded as fuzzy rules, and optimization based on genetic algorithms refines evaluation function parameters according to performance metrics such as number of shots, goal area entries, and scoring rates. The resulting control strategy remains interpretable; spatial heat maps reveal emergent behaviors such as coordinated positioning and ridgeline passing patterns near the penalty area. The experiments against established RoboCup teams, serving as benchmarks, demonstrate the competitive performance of our trained agents while enabling analyses of evolving decision structures and agent behaviors. Our method provides a transparent and adaptable framework for controlling heterogeneous agents in uncertain real-time environments, with broad applicability to robotics, autonomous systems, and distributed control systems. Full article

To explore effects of sleep restriction (SR) on next-morning cognitive recovery of young males under thermoneutral environments, three SR conditions, namely the mild (ending at 01:20), moderate (ending at 02:30) and severe sleep restriction (ending at 03:40), were carried out on participants in a thermoneutral environment. During experiments, the subjective sleepiness, perceived workload, and thermal sensation were surveyed. Electrocardiogram (ECG) data were recoded continuously to conduct the heart rate variability (HRV) analysis. In addition, the Deary–Liewald task (including the Simple Response Time task and the Choice Response Time task), Stroop task and Corsi Block task were completed. Results revealed significant increases in sleepiness and perceived workloads during SR. In addition, mean heart rate reduced significantly during moderate (ΔHR = −9.48, p < 0.05) and severe SRs (ΔHR = −9.69, p < 0.01), although it returned to the baseline level in the next morning. The root mean square of successive differences (RMSSD) was elevated during all SRs (Mild SR ΔRMSSD = 27.34, p < 0.05; Moderate SR ΔRMSSD = 33.06, p < 0.01; Severe SR ΔRMSSD = 24.61, p < 0.05) but reduced to baseline the next morning. Furthermore, the sustained attention (SRT) and selective attention performances (CRT) were impaired significantly under moderate (SRT ΔPI = −0.59, p < 0.05; CRT ΔPI = −0.24, p < 0.05) and severe SR (SRT ΔPI = −0.39, p < 0.05; CRT ΔPI = −0.42, p < 0.01). However, the sustained attention performance was restored the next morning even after severe SR, whereas the selective attention performance remained impaired (ΔPI = −0.36, p < 0.01). Significant reductions were observed in the Stroop task performance only after the severe SR (ΔPI = −0.17, p < 0.05), while short-term memory was slightly affected either during or after all SRs (p > 0.05). The overall cognitive performance reduced significantly after the moderate and severe SRs (Moderate SR ΔOPI = −0.30, p < 0.05; Severe SR ΔOPI = −0.40, p < 0.05), even in the next morning. Findings suggest that cognitive impairments caused by mild and moderate SRs could be partially recovered the next morning, while severe SR produced significant impairments in complex cognitive functions, potentially linked to parasympathetic dysregulation and failure of prefrontal compensatory mechanisms. Preliminary findings from this study offer initial implications for cognitive preservation strategies in office environments after night-time overwork. Full article

Objectives: Few studies have reported in vivo measurements of electron density (ED) and effective atomic number (Z_eff) in normal brain tissue. To address this gap, dual-energy computed tomography (DECT)-derived ED and Z_eff maps were used to characterize normal-appearing adult brain tissues, evaluate age-related changes, and investigate correlations with myelin partial volume (V_my) from synthetic magnetic resonance imaging (MRI). Materials and Methods: Thirty patients were retrospectively analyzed. The conventional computed tomography (CT) value (CT_conv), ED, Z_eff, and V_my were measured in the normal-appearing gray matter (GM) and white matter (WM) regions of interest. V_my and DECT-derived parameters were compared between WM and GM. Correlations between V_my and DECT parameters and between age and DECT parameters were analyzed. Results: V_my was significantly greater in WM than in GM, whereas CT_conv, ED, and Z_eff were significantly lower in WM than in GM (all p < 0.001). Z_eff exhibited a stronger negative correlation with V_my (ρ = −0.756) than CT_conv (ρ = −0.705) or ED (ρ = −0.491). ED exhibited weak to moderate negative correlations with age in nine of the 14 regions. In contrast, Z_eff exhibited weak to moderate positive correlations with age in nine of the 14 regions. CT_conv exhibited negligible to insignificant correlations with age: Conclusions: This study revealed distinct GM–WM differences in ED and Z_eff along with opposing age-related changes in these quantities. Therefore, myelin may have substantially contributed to the lower Z_eff observed in WM, which underlies the GM–WM contrast observed on non-contrast-enhanced CT. Full article

Objective: The aim of this study was to evaluate and compare the clinical behavior of indirect onlays/overlays made of lithium disilicate and composite resin and to investigate risk factors associated with restoration failures. Methods: 112 indirect partial coverage posterior restorations (onlays and overlays) placed in 51 adult patients between January 2014 and December 2020 were examined. The restorations were evaluated using selected FDI criteria (color match, surface gloss, anatomic form, fracture of restorative material, tooth cracks and fractures, marginal discoloration, marginal integrity and recurrence of initial pathology). The survival of the restorations was analyzed using Kaplan–Meier method. Risk factors (type of restoration, type of tooth, tooth vitality, smoking) were investigated using Cox regression analysis. Risk estimation was conducted for each evaluated criterion (p < 0.05). Results: For composite restorations, the estimated survival rate was 94.2% after 5 years, dropping to 74.3% in 7.9 years and continued falling to less than 60% after 8.2 years. On the contrary, for lithium disilicate restorations the estimated survival rate was 90.9% after 5 years, dropped to 85.2% after 5.5 years remaining stable thereafter. Lithium disilicate onlays demonstrated significantly better performance than lithium disilicate overlays. Cox regression analysis did not reveal any significant association between the survival of the indirect partial restorations and restoration material, tooth type, restoration type and history of endodontic treatment. However, smoking was found to be a statistically significant risk factor (p < 0.05). Conclusions: Lithium disilicate and composite indirect restorations exhibited comparable survival rates at the early observation period. However, lithium disilicate partial coverage restorations demonstrated more favorable clinical behavior compared to composite in the long term, with statistical significance observed in ceramic vs. composite onlays. Full article

Oak wood is a popular construction material in Europe. In the course of its service life, this wood is subject to structural changes resulting from the environmental conditions to which it is exposed, in addition to the effects of aging. Samples of naturally occurring historic European oak (Quercus robur L.) were obtained from foundation piles that were utilized to reinforce the riverbanks in Poland, the Vistula River basin, dating to the 2nd century, as well as from a 14th-century settlement on the river in Slupsk. Reference wood was also obtained from contemporary harvesting operations in the vicinity of Slupsk, Poland. The presence of structural changes resulting from partial wood degradation was confirmed through the utilization of FTIR spectroscopy analysis, SEM with BSD microscopy, and chromatic parameters. The differences in the color of historic and reference wood were significant (based on Kruskal–Wallis test = 46.38, where p < 0.001). The results of chemical analysis showed an increase in the proportion of lignin and a decrease in carbohydrate components for the old wood. A higher degree of change in lignin content was observed in historic wood (32–38%) compared to the fresh wood sample (25%). Our study showed that the collected data can be applied to the preparation database of heritage wood materials. Full article

Background/Objectives: The breast implant exchange/explantation rate has been increasing in recent years due to various types of long-term complications or adverse effects, such as implant migration, rippling, or capsular contracture. To reduce complications such as migration and/or implant–pocket mismatch, surgical meshes may provide implant support. Here, we present a case series about the use of a non-absorbable synthetic bra-shaped mesh in revision surgery of the breast, using implants that do not adhere to the surrounding tissues. Methods: In this retrospective case series, eight patients underwent breast revision surgery between 2021 and 2024 due to implant-related long-term complications following aesthetic surgery. Surgical revision included implant exchange, total or partial capsulectomy, creation of a pre-pectoral implant pocket for the new implant, and positioning of the non-absorbable synthetic mesh, acting as an internal support for the implants. BREAST-Qs were collected from all patients. Results: Of the eight patients included, the following symptoms were observed: symptomatic capsular contracture (n = 3), implant migration (n = 4), and breast animation deformity (n = 2). After revision surgery, during the follow-up period of 6–42 months, neither infection nor seroma occurred. No implant-related complications were registered. The BREAST-Q analysis revealed the highest patient satisfaction in the domain “satisfaction with the implants” (median score 87.5%). Conclusions: In revision surgery after breast augmentation, the synthetic, non-absorbable and titanized pocket-like mesh may provide implant support and avoid recurrence of complications related to implant position. However, due to the small and heterogeneous patient group, larger studies are needed to validate these preliminary findings. Full article

Background: Regional cerebral blood flow (rCBF) is a putative biomarker for neuropsychiatric disorders, including major depressive disorder (MDD). Methods: Here, we show that rCBF can be predicted from resting-state functional MRI (rsfMRI) at the voxel level while correcting for partial volume averaging (PVA) artifacts. Cortical patterns of MDD-related CBF differences decoded from rsfMRI using a PVA-corrected approach showed excellent agreement with CBF measured using single-photon emission computed tomography (SPECT) and arterial spin labeling (ASL). A support vector machine algorithm was trained to decode cortical voxel-wise CBF from temporal and power-spectral features of voxel-level rsfMRI time series while accounting for PVA. Three datasets, Amish Connectome Project (N = 300; 179 M/121 F, both rsfMRI and ASL data), UK Biobank (N = 8396; 3097 M/5319 F, rsfMRI data), and Amen Clinics Inc. datasets (N = 372: N = 183 M/189 F, SPECT data), were used. Results: PVA-corrected CBF values predicted from rsfMRI showed significant correlation with the whole-brain (r = 0.54, p = 2 × 10⁻⁵) and 31 out of 34 regional (r = 0.33 to 0.59, p < 1.1 × 10⁻³) rCBF measures from 3D ASL. PVA-corrected rCBF values showed significant regional deficits in the UKBB MDD group (Cohen’s d = −0.30 to −0.56, p < 10⁻²⁸), with the strongest effect sizes observed in the frontal and cingulate areas. The regional deficit pattern of MDD-related hypoperfusion showed excellent agreement with CBF deficits observed in the SPECT data (r = 0.74, p = 4.9 × 10⁻⁷). Consistent with previous findings, this new method suggests that perfusion signals can be predicted using voxel-wise rsfMRI signals. Conclusions: CBF values computed from widely available rsfMRI can be used to study the impact of neuropsychiatric disorders such as MDD on cerebral neurophysiology. Full article

Background/Objectives: Current bone-based landmark approaches have shown variable accuracy and poor reproducibility. We validated a two-point “tuberculum sellae–anterior clinoid process” (TS–ACP) line traced on routine 3D-computed tomography angiography (CTA) for predicting distal dural ring (DDR) position and quantified the interobserver agreement. Methods: We retrospectively reviewed data from 85 patients (87 aneurysms) who were treated via clipping between June 2012 and December 2024. Two blinded neurosurgeons classified each aneurysm as extradural, intradural, or straddling the TS–ACP line. The intraoperative DDR inspection served as the reference standard. Diagnostic accuracy, χ² statistics, and Cohen’s κ were calculated. Results: The TS–ACP line landmarks were identifiable in all cases. The TS–ACP line classification correlated strongly with operative findings (χ² = 138.3, p = 6.4 × 10⁻²⁹). The overall accuracy was 89.7% (78/87), and sensitivity and specificity for identifying intradural aneurysms were 94% and 82%, respectively. The interobserver agreement was substantial (κ = 0.78). Nine aneurysms were misclassified, including four cavernous-sinus lesions that partially crossed the DDR. Retrospective fusion using constructive interference in steady-state magnetic resonance imaging corrected these errors. Conclusions: The TS–ACP line represents a rapid, reproducible tool that reliably localizes the DDR on standard 3D-CTA, showing higher accuracy than previously reported single-landmark techniques. Its high accuracy and substantial inter-observer concordance support incorporation into routine preoperative assessments. Because the method depends on only two easily detectable bony points, it is well-suited for automated implementation, offering a practical pathway toward artificial intelligence-assisted stratification of paraclinoid aneurysms. Full article

Rheumatoid arthritis (RA) is an autoimmune disease affecting the synovium. Mitochondrial dysfunction is considered a critical factor in the pathogenesis of RA. The aim of the study was to determine the effect of methotrexate and tofacitinib on mitochondrial function and oxidative stress in an in vitro study on the model synovial cell line SW982. TNF-alpha-stimulated SW982 cells, as well as control untreated cells, were incubated with methotrexate and tofacitinib. A metabolic test was performed to assess mitochondrial function. The oxidative stress generated after the application of the therapeutics was determined by a chromatographic analysis. The results obtained showed an increase in ATP levels (p < 0.0001) and a decrease in proton leak (p < 0.0003) after treatment with tofacitinib. The opposite trend was observed—reduced ATP production (p < 0.0096) and increased levels of proton leak (p < 0.0001)—after treatment with methotrexate. A two-fold increase in 8-ISOPGF2A was measured in comparison to TNF-alpha-stimulated and untreated cells. The dynamics of mitochondrial activity and oxidative stress were monitored in a certified RA model cell line after the administration of two different therapeutics. Methotrexate was found to induce mitochondrial dysfunction and oxidative stress in vitro, while tofacitinib partially improved mitochondrial parameters. Full article

Triple-negative breast cancer (TNBC) urgently requires new therapeutic strategies due to the limited efficacy of conventional treatments. Recently, PANoptosis, an integrated form of apoptosis, necroptosis, and pyroptosis, has emerged as a promising target in cancer therapy, though effective agents remain scarce. Paclitaxel, a Taxus-derived natural product, is often combined with other drugs to enhance efficacy, yet optimal combinations are limited. This study investigates the synergistic antitumor effects of paclitaxel and cephalomannine in TNBC, focusing on oxygen-regulated cell death pathways. Network pharmacology and molecular docking revealed that the combination targets multiple cell death- and inflammation-related proteins, including BCL2L1, MAPK14, SYK, TNF, and ADAM17, suggesting multi-target synergy. In vitro, the combination significantly inhibited MDA-MB-231 cell viability, proliferation, and migration, while inducing apoptosis and necrosis. Mechanistically, co-treatment markedly increased intracellular ROS levels and γ-H2AX expression, indicating oxidative stress and DNA damage, both of which were reversible by ROS inhibition. Further analysis demonstrated that the treatment activated the p38 and p53 pathways, regulated the Bax/Bcl-2 ratio, and initiated mitochondrial apoptosis. It also promoted RIPK1/RIPK3/MLKL phosphorylation and MLKL membrane translocation, triggering necroptosis, as well as upregulated NLRP3, cleaved Caspase-1, and GSDMD, inducing pyroptosis. The use of specific inhibitors partially reversed these effects, confirming the involvement of ROS-mediated PANoptosis. Similar antitumor effects were also observed in BT-549 cells, indicating the broad applicability of this combination in TNBC. MCF-10A cells exhibited mild but acceptable cytotoxicity, reflecting manageable side effects typical of chemotherapeutic agents. In vivo experiments further validated the combination’s antitumor efficacy and safety. In summary, paclitaxel and cephalomannine synergistically induce PANoptosis in TNBC through oxygen-regulated cell death pathways, offering a novel therapeutic strategy based on oxidative stress modulation by natural compounds. Full article

The Internet of Things (IoT) has promoted emerging applications that require massive device collaboration, heavy computation, and stringent latency. Unmanned aerial vehicle (UAV)-assisted mobile edge computing (MEC) systems can provide flexible services for user devices (UDs) with wide coverage. The optimization of both latency and energy consumption remains a critical yet challenging task due to the inherent trade-off between them. Joint association, offloading, and computing resource allocation are essential to achieving satisfying system performance. However, these processes are difficult due to the highly dynamic environment and the exponentially increasing complexity of large-scale networks. To address these challenges, we introduce a carefully designed cost function to balance the latency and the energy consumption, formulate the joint problem into a partially observable Markov decision process, and propose two multi-agent deep-reinforcement-learning-based schemes to tackle the long-term problem. Specifically, the multi-agent proximal policy optimization (MAPPO)-based scheme uses centralized learning and decentralized execution, while the closed-form enhanced multi-armed bandit (CF-MAB)-based scheme decouples association from offloading and computing resource allocation. In both schemes, UDs act as independent agents that learn from environmental interactions and historic decisions, make decision to maximize its individual reward function, and achieve implicit collaboration through the reward mechanism. The numerical results validate the effectiveness and show the superiority of our proposed schemes. The MAPPO-based scheme enables collaborative agent decisions for high performance in complex dynamic environments, while the CF-MAB-based scheme supports independent rapid response decisions. Full article

Lactic acid bacteria (LAB) are a promising source of postbiotics with potential applications in the cosmetic industry; however, strains isolated from fermented vegetables are rarely studied. This study aimed to characterize the bioactivity of postbiotics produced by Lactiplantibacillus pentosus B1 isolated from fermented beetroot juice. An organic extract (ELCFS) and a lyophilizate (LLCFS) were prepared from cell free supernatant of B1 and assessed for antimicrobial activity (MIC, MBC), biofilm inhibition and eradication ability against Staphylococcus aureus, Escherichia coli, Streptococcus pyogenes and Cutibacterium acnes. Stability (temperature, time) and cytotoxicity were also examined. Metabolite composition was determined by GC-MS. MIC values were 10 g/L for ELCFS and 10–20 g/L for LLCFS. ELCFS completely inhibited biofilm formation at 10 g/L, and LLCFS at 25 g/L; partial inhibition was observed at lower concentrations (e.g., E. coli—32.99% at 1 g/L ELCFS; S. aureus and S. pyogenes—74.01% and 95.67%, respectively, at 5 g/L). Complete eradication of mature biofilm was obtained at 2.5 g/L (ELCFS) and 12.5 g/L (LLCFS), while a significant partial effect was observed from 0.04 g/L ELCFS for E. coli (29.3%) and 0.2 g/L LLCFS for S. pyogenes (23.2%). C. acnes showed the lowest sensitivity. A reduction in viability of eucaryotic cells was observed at ≥ 5 g/L ELCFS (90.32%) and 12.5—50 g/L LLCFS (55.87—89.20%). Importantly, concentrations causing partial inhibition and eradication of biofilm did not show cytotoxicity towards fibroblasts. The preparations were thermostable and retained activity over time; only incubation of ELCFS at elevated temperature significantly reduced its antimicrobial activity against the C. acnes strain. GC-MS analysis revealed five organic acids, with lactic acid dominating. The results confirm the potential of L. pentosus B1 as a source of stable, effective, and safe postbiotics for cosmetology applications. Full article

A total of 24 novel steroidal derivatives were synthesized, including 1,3,4-thia(selena)diazolines and structurally unique spirothiadiazolines, obtained through intramolecular cyclization under standard acetylation conditions. This strategy was further extended to the construction of a novel dimeric compound bearing a thiadiazoline linker. Seleno- and thiosemicarbazone precursors were derived from various functionalized steroidal monomers and dimers via straightforward synthetic protocols. Key intermediates included aldehyde 7 and ketones 16, 19, and 24. Rotameric equilibria were observed in certain thiosemicarbazones, attributed to partial double-bond character in the N–CS bond. Cyclization yielded heterocyclic systems as epimeric mixtures, and in some cases, inseparable mixtures of isomers were obtained due to low diastereoselectivity. Full structural elucidation of epimeric pairs was achieved using 2D NMR and IR spectroscopy, with compounds 2, 3, 5, 11, 17, 27, 28a, and 28b further confirmed by single-crystal X-ray diffraction. Preliminary antiproliferative assays against human cancer cell lines revealed GI₅₀ values below 10 µM for compounds 21, 22, and 27. Full article

We previously demonstrated that the activation of FGFR signaling in GIST may be a mechanism of GIST resistance to imatinib mesylate (IM). We show here that IM-resistant GIST cells lacking secondary KIT mutations overexpress claudin-1 on both transcriptional and translational levels. In contrast, a knockdown of CLDN1 or inhibition of its activity by PDS-0330 effectively restored GIST’s sensitivity to IM both in vitro and in vivo. This was evidenced by the increased expression of apoptotic markers (e.g., cleaved PARP and caspase-3) and the decreased proliferation rate of IM-resistant GIST T-1R cells treated with a combination of IM and PDS-0330 (or siRNA CLDN1). In concordance with these findings, a significant synergy was observed between IM and PDS-0330 in GIST T-1R cells. Importantly, decreased tumor size and weight were observed in IM-resistant GIST xenografts treated with a combination of IM and PDS-0330. Furthermore, the combined treatment of IM-resistant tumors induced an increase in intratumoral apoptosis and other changes, as defined by the histopathologic response rate. Based on the co-immunoprecipitation and immunofluorescence microscopy data, we also demonstrated the strong interaction pattern between CLDN1 and FGFR2. Of note, the inhibition or knockdown of CLDN1 effectively decreased the phosphorylation of FGFR2 and FRS-2, a well-known FGFR adaptor protein, thereby illustrating CLDN1’s ability to regulate FGFR-signaling and thereby promote FGFR-mediated survival in KIT-inhibited GIST. Consequently, CLDN1 inhibition in GIST effectively disrupted the FGFR-mediated pathway and re-sensitized tumor cells to IM. In concordance with these data, molecular profiling of CLDN1-inhibited GIST T-1R cells illustrated a significant decrease in the majority of FGFR transcripts, including FGFR2, 3, and 4. Additionally, several FGFR ligands (e.g., FGF14, -19, and -23) were also down-regulated in PDS-0330-treated GIST. Notably, exogenous FGF-2 increased CLDN1 expression in a time-dependent manner. In contrast, pan-FGFR inhibitors effectively reduced CLDN1 levels in IM-resistant GIST T-1R cells, thereby illustrating a cross-talk between CLDN1- and FGFR-mediated pathways in IM-resistant GIST. Based on subcellular fractionation and immunofluorescence microscopy data, we also observed partial relocalization of CLDN1 into the cytoplasm in IM-resistant GIST. Notably, PDS-0330 effectively abrogated this relocalization, suggesting that changes in CLDN1 subcellular distribution might also impact GIST resistance to IM. Lastly, based on our small cohort clinical study (n = 24), we observed the increased expression of CLDN1 in most “high-risk” primary GIST known to be associated with poor prognosis and aggressive behavior, thereby illustrating the prognostic value of increased CLDN1 expression in GIST and providing a further rationale to evaluate the effectiveness of CLDN1 inhibition for GIST therapy. Full article