Search Results (131)

Background/Objectives: The clinical application of CAD/CAM restorative materials continues to evolve due to increasing demand for aesthetic, durable, and minimally invasive indirect restorations. Hybrid nanoceramics, such as Grandio disc (VOCO GmbH, Cuxhaven, Germany), are increasingly used in indirect restorative dentistry due to their favourable combination of mechanical strength, polishability, wear resistance, and bonding potential. One challenge associated with adhesive protocols for CAD/CAM materials lies in achieving durable bonds with resin cements. Extensive post-polymerization during fabrication reduces the number of unreacted monomers available for chemical interaction, thereby limiting the effectiveness of traditional adhesive strategies and necessitating specific surface conditioning approaches. This study aimed to evaluate, in a preliminary, non-inferential manner, the influence of several combined conditioning protocols on surface micromorphology, elemental composition, and descriptive SBS trends of a CAD/CAM hybrid nanoceramic. This work was designed as a preliminary pilot feasibility study. Due to the limited number of specimens (two discs per protocol, each providing two independent enamel bonding measurements), all bond strength outcomes were interpreted descriptively, without inferential statistical testing. This in vitro study investigated the effects of various surface conditioning protocols on the adhesive performance of CAD/CAM hybrid nanoceramics (Grandio disc, VOCO GmbH, Cuxhaven, Germany) to dental enamel. Hydrofluoric acid (HF) etching was performed to improve adhesion to indirect resin-based materials using two commercially available gels: 9.5% Porcelain Etchant (Bisco, Inc., Schaumburg, IL, USA) and 4.5% IPS Ceramic Etching Gel (Ivoclar Vivadent, Schaan, Liechtenstein), in combination with airborne-particle abrasion (APA), silanization, and universal adhesive application. HF may selectively dissolve the inorganic phase, while APA increases surface texture and micromechanical retention. However, existing literature reports inconsistent results regarding the optimal conditioning method for hybrid composites and nanoceramics, and the relationship between micromorphology, elemental surface changes, and adhesion remains insufficiently clarified. Methods: A total of ten composite specimens were subjected to five conditioning protocols combining airborne-particle abrasion with varying hydrofluoric acid (HF) concentrations and etching times. Bonding was performed using a dual-cure resin cement (BiFix QM) and evaluated by shear bond strength (SBS) testing. Surface morphology was examined through environmental scanning electron microscopy (ESEM), and elemental composition was analyzed via energy-dispersive X-ray spectroscopy (EDS). Results: indicated that dual treatment with HF and sandblasting showed descriptively higher SBS, with values ranging from 5.01 to 6.14 MPa, compared to 1.85 MPa in the sandblasting-only group. ESEM revealed that higher HF concentrations (10%) created more porous and irregular surfaces, while EDS indicated an increased fluorine presence trend and silicon reduction, indicating deeper chemical activation. However, extending HF exposure beyond 20 s did not further improve bonding, suggesting the importance of protocol optimization. Conclusions: The preliminary observations suggest a synergistic effect of mechanical and chemical conditioning on hybrid ceramic adhesion, but values should be interpreted qualitatively due to the pilot nature of the study. Manufacturer-recommended air abrasion alone may provide limited adhesion under high-stress conditions, although this requires confirmation in studies with larger sample sizes and ageing simulations. Future studies should address long-term durability and extend the comparison to other hybrid CAD/CAM materials and to other etching protocols. Full article

Background: This study examined the interplay between sociocultural internalization, perfectionism, and eating disorder (ED) symptoms. We pursued two complementary aims: (1) to identify latent profiles of women based on adaptive/maladaptive perfectionism and sociocultural internalization, and (2) to test perfectionism as a mediator between sociocultural internalization and ED symptoms. Methods: Participants comprised 203 Polish women aged 18–35 years (M = 25.1, SD = 3.5). Measures included the Eating Attitudes Test-26 (EAT-26), the Polish Adaptive and Maladaptive Perfectionism Questionnaire (KPAD), and the Sociocultural Attitudes Towards Appearance Questionnaire-3 (SATAQ-3). Latent profile analysis (LPA) was used to identify subgroups, followed by Kruskal–Wallis tests for between-profile comparisons. Mediation models were tested using the PROCESS macro (Model 4). Results: A three-profile solution provided the best fit (Entropy = 0.94). Profile 3 (high internalization and both perfectionism types; n = 58) reported the highest ED severity (EAT-26 total: M = 25.6, SD = 7.4), particularly in Dieting and Bulimia subscales. Profile 1 (low internalization, low maladaptive perfectionism; n = 64) showed the lowest scores (M = 12.3, SD = 5.2). No significant differences were found for the Oral Control subscale (H(2) = 2.53, p = 0.283). Mediation analyses indicated that maladaptive perfectionism significantly mediated associations between sociocultural internalization and ED symptoms (indirect effects b = 0.13–0.32, 95% CI excluding zero). Adaptive perfectionism was not a significant mediator. Conclusions: Results underscore maladaptive perfectionism as a key mechanism through which sociocultural pressures contribute to eating pathology. Implications include targeting internalization and perfectionistic concerns in prevention and treatment. Full article

Background: Filgotinib is an emerging Janus kinase 1 (JAK1) inhibitor being investigated for inflammatory bowel disease. This systematic review and network meta-analysis (NMA) evaluated the efficacy and safety of filgotinib in adult patients with moderate-to-severe crohn’s disease. Methods: We systematically searched PubMed, EMBASE, and Scopus through April 2025. Randomized controlled trials evaluating filgotinib versus placebo in adults with moderate-to-severe Crohn’s disease were included. Primary outcomes were clinical remission and endoscopic response. Study quality was assessed using the Cochrane Risk of Bias 2.0 tool. A network meta-analysis was performed to integrate direct and indirect evidence, reporting risk ratios (RRs) with 95% confidence intervals (CIs). Results: Five randomized controlled trials (from 4 publications) met the inclusion criteria. Filgotinib 200 mg significantly improved clinical remission compared with placebo (RR: 1.75 [1.40–2.19]) and 100 mg (RR: 1.38 [1.11–1.71]), while 100 mg showed no significant difference versus placebo (RR: 1.27 [0.99–1.63]). For endoscopic response, both 200 mg (RR: 1.72 [1.09–2.69]) and 100 mg (RR: 1.65 [1.02–2.69]) demonstrated significant benefit over placebo, though no difference was observed between active doses (RR: 1.04 [0.64–1.68]; I² = 57%). In the two-item patient-reported outcome, 200 mg showed significant improvement versus placebo (RR: 1.47 [1.20–1.80]) and 100 mg (RR: 1.26 [1.02–1.55]), while 100 mg remained insignificant versus placebo (RR: 1.17 [0.93–1.46]). Neither dose increased the risk of treatment-emergent adverse events, serious adverse events, or infections compared with placebo, with consistent homogeneity across analyses. Conclusions: Filgotinib 200 mg demonstrated superior efficacy across clinical, endoscopic, and patient-reported outcomes compared with 100 mg and placebo, with a favorable safety profile. The 100 mg dose showed limited efficacy and no advantage over placebo. Filgotinib represents a promising oral therapeutic option, particularly for biologic-naïve patients and in maintenance therapy, while also showing potential benefit in perianal fistulising crohn’s disease. Future trials should explore long-term safety and head-to-head comparisons with established biologics. Full article

Dietary supplements often promote their antioxidant content as an indicator of quality on the packaging. This study evaluated the redox potential and total antioxidant capacity of various dietary supplements, using different analytical methods to obtain the complexity of antioxidant measurements. A green approach for detecting total antioxidant capacity in dietary products utilized modern electrochemical techniques, including differential pulse voltammetry (DPV) and cyclic voltammetry (CV). These rapid “green” methods measure the redox potential of samples, providing information about the electron-donating ability of antioxidants without the use of harmful chemicals or sample treatments, with minimal environmental impact. ABTS and FRAP measurements were expressed as vitamin C equivalents to allow comparison with CV measurements and actual vitamin C content. This approach enabled indirect comparison of activities obtained using different standard substances through conversion to standard equivalents. The results revealed that the claims made on product labels and packaging often overestimated the antioxidant content and did not match the measured total antioxidant capacities obtained in the current study. Measured vitamin C levels in 10 samples fell within the declared ranges (0–950 mg), but six products contained 4.85% to 49.18% less, and two had significantly higher levels (4.20% and 32.22%) than their declared (p < 0.05). Total antioxidant capacity varied from the labeled values. Similar trends were observed across methods, except for DPPH. FRAP values were correlated with ABTS and CV (r = 0.797 and r = 0.757, respectively). The DPV method provided a more detailed assessment of the redox activity of selected products based on distinct oxidation peaks. The study highlights the importance of mandatory testing and quantification of antioxidants, as well as the need for regulation of antioxidant properties through normative standards. Full article

Background: Colorectal cancer is the third most common malignant cancer, and according to the predictions, the estimated number of new cases will grow in coming years. Therefore, an increase in the costs of the disease will increase as well. Therefore, there is a need for continuous research on the costs and the economic burden of colorectal cancer and for reviewing the research results systematically. The current paper presents a literature review regarding the state of knowledge about the costs of treatment and the economic burden of colorectal cancer. Methods: A total of 20 papers from MEDLINE database were included in the final analysis. The review is focused on the estimates of direct costs, i.e., treatment of colorectal cancer, screening after treatment, and indirect costs. Results: the vast majority of studies were focused on direct costs only, which clearly shows the literature gap. Metastatic colorectal cancer was the most frequent category for various treatment cost evaluation. The costs associated with the use of bevacizumab in various combinations were calculated most frequently. Conclusions: Further summarizing review and developing a methodology for standardized comparisons is necessary, specifically addressing indirect costs. Full article

Background: Prostate cancer is the second most common malignant cancer among men, and according to the predictions, the estimated number of new cases will substantially grow in the coming years. Therefore, the costs of the disease will increase as well. Methods: We conducted a literature review of the state of knowledge about the costs of treatment and the economic burden of prostate cancer. The vast majority of studies were focused on direct costs only, which clearly shows the literature gap. Results: We focused on the estimates of direct costs, i.e., treatment of prostate cancer, adjuvant and neoadjuvant treatment, and supportive and palliative care, and indirect costs. Cost-effectiveness analyses indicated that docetaxel combined with androgen deprivation therapy (ADT) was the most cost-effective strategy for metastatic hormone-sensitive prostate cancer (incremental cost-effectiveness ratio (ICER): USD 13,647). In contrast, novel therapies such as PARP inhibitors and whole-genome-sequencing-guided treatments were not cost-effective unless drug prices were reduced by 47–70%. In the United States, 5-year cumulative treatment costs ranged from USD 48,000 for conservative management to over USD 91,000 for radiotherapy, while out-of-pocket expenses averaged AUD 1172 in Australia. Indirect costs were also considerable, with Slovakia reporting an increase in sick leave costs from EUR 1.2 million in 2014 to EUR 2.1 million in 2022. Conclusions: Metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer were the most frequent categories for various treatment cost evaluations. A few specific combinations of drugs were cost-effective only under the condition of dropping the unit prices of a medication. Further summarizing, reviewing, and developing a methodology for standardized comparisons are needed. Full article

This study compiled a dataset of published works relating to fatigue testing in asphalt mixes, covering 2020–2025. The dataset was subjected to bibliometric and textual analyses, including a systematic review, to explore emerging trends and patterns in experimental protocols. Bibliometrix, VOSviewer, and IRaMuTeQ were employed to map the scientific landscape of 368 articles. Following PRISMA guidelines, the 100 most-cited articles were reviewed to identify prevailing test setups and parameters. The results showed a growing scientific production (9.1% per year), concentrated in a few high-impact journals and dominated by China, with emphasis on sustainability. A comparison between scientific output and a road quality index revealed a disconnect between academic research and field implementation. Five thematic clusters emerged: sustainable pavement management, mechanical characterization, binder modification, performance modeling, and evaluation of innovative materials. Indirect tensile and four-point bending tests were the most common loading modes. Considerable variability in protocols, frequent omissions of methodological details, and limited statistical treatment were also observed. The study highlighted the importance of standardized reporting and robust analysis, offering a reproducible framework to understand fatigue behavior and support future research. Full article

Gene therapies that induce the body to produce therapeutic anti-vascular endothelial growth factor (anti-VEGF) proteins are an emerging topic related to neovascular age-related macular degeneration (nAMD). Continuous delivery of anti-VEGF protein directly to the target tissue offers the possibility of lifelong efficacy without the need for repeated and frequent eye injections. This novel approach could revolutionize patient management through optimizing clinical outcomes while simplifying service delivery. However, such gene therapies are anticipated to face unique challenges related to patients’ access and health technology assessment (HTA), and their integration into real-world eyecare practices. This article presents key elements raised at the European Access Academy (EAA) Fall convention (held in Rome in October 2024) regarding anticipated HTA challenges for gene therapies in nAMD. The important role of HTA and policymakers in ensuring that emerging gene therapies are accessible to all eligible patients is also highlighted. This article mainly focuses on the need for a fit-for-purpose EU HTA framework to address the widely varying utilization of standard of care in nAMD clinical practice, and to incorporate considerations about the long-term durability of gene therapies in nAMD. The importance of integrating real-world evidence (RWE) into the EU HTA framework is also discussed. Full article

With increasing wastewater treatment demands and decarbonization goals, synergistic reduction in pollutants and green house gas (GHG) emissions is crucial. High process emissions like N₂O pose significant challenges, yet optimized carbon reduction strategies for conventional plants are lacking. This study developed three mathematical models to quantify the impact of dissolved oxygen (DO), influent salinity, and C/N ratio on direct emissions (CH₄, N₂O) and indirect emissions. Response Surface Methodology (RSM) optimized these factors to minimize GHG emissions under three accounting scenarios: (1) plants with CH₄ reuse systems: salinity = 0.5 g L⁻¹, DO = 3.67 mg L⁻¹, C/N = 12.75; (2) plants focusing solely on direct emissions: salinity = 0.5 g L⁻¹, DO = 3.35 mg L⁻¹, C/N = 3; and (3) plants assessing total emissions: salinity = 0.5 g L⁻¹, DO = 2.5 mg L⁻¹, C/N = 7.18. Key findings indicated that increasing salinity exacerbated greenhouse gas emissions. Elevated DO levels in the aerobic stage reduced N₂O emissions but increased indirect emissions in the A²/O process. Higher C/N ratios promoted anaerobic CH₄ production, but sufficient carbon reduced N₂O by enabling complete heterotrophic denitrification. A 60−day continuous GHG emissions monitoring campaign was conducted at a WWTP to validate the actual emission reductions achievable under the identified optimal control conditions. An analysis and comparison of operational and economic costs were also performed. The findings provide practical insights into sustainable GHG emission management and offer potential solutions to advance the synergistic reduction in GHG emissions and pollutants. Full article

Objective: Dinutuximab beta (DB) and naxitamab (NAXI) with GM-CSF are used for maintenance treatment of relapsed/refractory neuroblastoma. The objective of this study was to systematically assess comparative efficacy of the two therapies within their designated indications in accordance with established clinical guidelines. Methods: Relevant evidence was identified in systematic literature review. Individual patient data (IPD) from prospective clinical trials of DB were assessed and data on patients with disease in bone or bone marrow, as assessed in MRI, CT, mIBG or biopsy, with incomplete response to previous therapy were included. Patients with complete response, progressive disease and/or soft tissue disease were excluded. DB population was adjusted for sex, MYCN amplification, disease type (relapsed, refractory), and disease site (bone marrow and/or bone) to balance aggregated characteristics of NAXI population. More characteristics were included in sensitivity analyses, including DB treatment without interleukin-2, as currently recommended. Overall response rate (ORR) was assessed as best response. Results: Aggregated data for NAXI from Study 201 (n = 52) and Study 230 (n = 38) and IPD from DB studies (APN311-202, APN311-304, c = 77) met the inclusion criteria. Compared to NAXI, DB significantly extended progression-free survival (PFS): hazard ratio, DB vs. NAXI of 0.47 (95% CI: 0.26 to 0.87, p = 0.015). ORR was 60.1% (95% CI: 48.5% to 71.6%) for DB vs. 43.3% (33.1% to 53.6%) for NAXI (ORR odds ratio, DB vs. NAXI was 1.97, 95% CI: 1.02 to 3.80, p = 0.044). Sensitivity analyses and unadjusted comparisons supported the results. Conclusion: In the indirect comparison, dinutuximab beta significantly extended PFS and increased ORR compared to naxitamab. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that significantly affects patients’ quality of life. Dupilumab, a monoclonal antibody targeting interleukin (IL)-4 receptor alpha (IL-4Rα), has been the standard biologic therapy for moderate-to-severe AD. This review compares dupilumab with tralokinumab—a promising alternative that selectively neutralizes IL-13—by examining their distinct mechanisms, clinical efficacy, safety profiles, and practical considerations. While both biologics are highly effective, pivotal monotherapy trials indicate numerically higher efficacy rates for dupilumab. Regarding safety, while long-term data show comparable rates of serious adverse events, dupilumab is associated with a higher incidence of both conjunctivitis and injection-site reactions. Key practical differences include dupilumab’s broader indications and approval for infants (≥6 months), versus tralokinumab’s flexible maintenance dosing and notable efficacy in head and neck AD. By highlighting these key distinctions, this review aims to support personalized treatment selection in AD. However, no direct head-to-head clinical trials have yet compared dupilumab and tralokinumab, and the available evidence is based on indirect comparisons from separate pivotal studies. Full article

Background: Nutraceuticals have emerged as promising alternatives to conventional pharmacological treatments for managing joint pain and low-grade inflammation in physically active individuals. However, few clinical studies have evaluated the combined metabolic, inflammatory, and neuroendocrine effects of multi-ingredient supplements. This study aimed to evaluate the effects of Flector Softgel FS Integratore, a multi-component food supplement, on joint pain, inflammatory markers, metabolic health, and orexin-A levels in physically active adults. Methods: In this randomized, controlled, low-intervention study, 25 adult participants (aged 30–60 years and amateur athletes engaging in at least 3 sessions/week of moderate physical activity) were assigned to either a treatment group (n = 15 received Flector Softgel FS for 14 days) or a placebo group (n = 10). The supplement contained 500 mg of Cannabis sativa seed oil (THC-free), 250 mg of Boswellia serrata extract, 250 mg of fish oil, 160 mg of omega-3 fatty acids, and 0.6 mg of undenatured type II collagen (UC-II). Pain was assessed using the Visual Analog Scale (VAS). Metabolic parameters, inflammatory cytokines (IL-6, IL-8, TNF-α, IFN-γ, and IL-10), and serum orexin-A levels were measured before and after the intervention. Results: Compared with the placebo, the treatment group showed a significant reduction in VAS scores (p < 0.001), as well as improvements in BMI, insulin, and lipid profiles, and a decrease in pro-inflammatory cytokines (IL-6, IL-8, TNF-α, and IFN-γ). A reduction in orexin-A levels was also observed in the treatment group (p < 0.001), with a positive correlation between orexin-A and perceived pain. No adverse effects were reported. Conclusions: Flector Softgel FS Integratore may be effective in reducing joint pain and systemic inflammation while supporting metabolic health in active adults. These effects may involve indirect modulation of orexin-A, though the exact mechanisms remain to be clarified. Despite the promising results, conclusions regarding efficacy in comparison with NSAIDs should be approached with caution in the absence of a pharmacological control group. Further studies with larger samples and a longer duration are needed. Full article

Background/Objectives: Direct comparative data for infliximab and vedolizumab are limited due to lack of head-to-head trials. This systematic review and meta-analysis compared the efficacy and safety of infliximab and vedolizumab as intravenous or subcutaneous maintenance treatments for adults with moderately to severely active Crohn’s disease or ulcerative colitis. Methods: Medical databases, PubMed, Embase, and the Cochrane Library were systematically searched from January 2010 to May 2024 to identify Phase 1 to 3 randomized controlled trials. The primary and co-primary outcomes were the proportions of patients achieving clinical remission and clinical response at one year, respectively. Safety was also analyzed (PROSPERO CRD42023483599). Data for each outcome were pooled using a two-sided random-effects model in separate analyses for Crohn’s disease and ulcerative colitis. Results: Seven eligible Crohn’s disease trials and eight eligible ulcerative colitis trials contributed data for 1910 and 2372 patients, respectively. For Crohn’s disease, higher proportions of infliximab-treated patients achieved clinical remission (0.64 [95% confidence interval: 0.60–0.68]) and/or clinical response (0.71 [0.67–0.75]) at one year compared with vedolizumab-treated patients (0.40 [0.35–0.46] and 0.47 [0.43–0.51], respectively). For ulcerative colitis, similar proportions of infliximab- and vedolizumab-treated patients achieved clinical remission (0.54 [0.38–0.71] vs. 0.40 [0.35–0.44]) and/or clinical response (0.52 [0.45–0.58] vs. 0.58 [0.51–0.65]) at one year. Safety results showed no significant differences. Conclusions: An indirect comparison of maintenance treatment with infliximab and vedolizumab demonstrated that infliximab yields significantly better efficacy than vedolizumab in Crohn’s disease, whereas both agents yielded similar efficacy in ulcerative colitis. Full article

Background and Objectives: The aim of this study was to evaluate how the indirect pulp capping treatment approaches and material choices used by dentists actively practicing in Turkey vary according to demographic data. Materials and Methods: Dentists practicing in Turkey were included in this study. A 13-question survey was used and distributed to the participants via social media. The statistical analysis of the data obtained from this study was performed using IBM SPSS v23. The chi-square test was used to compare categorical variables between groups, and multiple comparisons of the proportions were analyzed using the Bonferroni correction. The results of the analysis are presented as frequencies (percentages) for categorical data. The significance level was set at p < 0.05. Results: A total of 402 dentists from across Turkey participated in this study. A total of 331 participants (82.3%) reported that they performed indirect pulp capping treatment. The most commonly used materials for indirect pulp capping were Ca(OH)₂;-containing liners (73.4%) and glass ionomer cement (58.3%). The use of amalgam and cotton roll isolation was more common among dentists working in the public sector, whereas rubber dam isolation and the use of contemporary materials such as MTA and Biodentine were more frequently observed among dentists working in the private sector. Conclusions: Significant differences were found in the dentists’ indirect pulp capping approaches and the materials they used based on their specialty, years of experience, and workplace setting. These findings suggest that dentists’ knowledge and experience regarding indirect pulp capping should be enhanced during their education and post-graduation training. Full article

The dynamic nature of infectious diseases introduces inherent challenges to the design of vaccine clinical trials, which consequently makes vaccine indirect treatment comparisons (ITCs) and meta-analyses (MAs) more challenging compared with regular pharmaceuticals. However, comparisons of efficacy and safety between vaccines are being frequently required in vaccine decision making due to a low number of head-to-head clinical trials in the vaccine landscape. The introduction of the European Union Health Technology Assessment (HTA) Regulation (EU HTAR) aims to harmonize HTA efforts across Europe. However, the EU HTAR could also escalate existing challenges for conducting vaccine MAs and ITCs. Such challenges include generating efficacy evidence in time for Joint Clinical Assessment (JCA), incorporating high levels of heterogeneity due to infectious disease-specific characteristics, and tackling a high number of PICOs per submission—likely driven by heterogeneity in the available data and differences in national vaccine calendars. Opportunities to tackle these challenges include introducing a stepwise approach to vaccine assessment in JCA, best-practice recommendations for conducting/interpreting vaccine MAs and ITCs, and condensing the number of PICOs to create larger ‘catch-all’ ITC networks. This perspective article explores these challenges and opportunities further. Full article