Search Results (5,059)

Access to clean water remains a global challenge, particularly in areas where populations rely on surface water. These water sources must be treated. Coagulation with chemicals causes environmental problems and adverse effects on human health. Natural coagulants obtained from papaya (Carica papaya) waste are presented as an alternative that is safe for human health, non-polluting, and biodegradable. The effectiveness of these natural coagulants is compared to that of aluminum sulfate using jar tests and synthetic and natural surface water, with statistical tools to model treatment processes. All coagulants have competitive results, reaching turbidity remotion levels above 90%. However, in equivalent tested ranges, natural coagulants require lower dosages and perform better with high initial water turbidity due to their polymeric bridging mechanisms and adsorption processes through the action of their functional groups, as detected by FTIR analysis. Additional testing with contaminated water from the Valsequillo dam confirms the use of these coagulants to treat water, with papaya seed coagulant yielding the best results and requiring lower doses, making it a competitive alternative. It can be concluded that papaya-based coagulants obtained from waste can be used as an eco-friendly alternative to aluminum sulfate in physicochemical treatments to purify surface water for human consumption. Full article

Background/Objectives: Neuroblastoma (NB) is an aggressive pediatric malignancy that accounts for nearly 15% of all childhood cancer-related deaths, with high-risk cases showing a poor 20% prognosis and limited response to current therapies. Survivin, encoded by the BIRC5 gene, is an anti-apoptotic protein frequently overexpressed in NB and linked to treatment resistance and unfavorable clinical outcomes. Methods and Results: An analysis of 1235 NB patient datasets revealed a significant association between elevated BIRC5 expression and reduced overall and event-free survival, highlighting survivin as an important therapeutic target in NB. To explore this strategy, we evaluated the efficacy of YM-155, a small-molecule survivin inhibitor, across multiple NB cell lines. YM-155 displayed potent cytotoxic activity in six NB cell lines with IC₅₀ values ranging from 8 to 212 nM and significantly inhibited colony formation and 3D spheroid growth in a dose-dependent manner. Mechanistic analyses revealed that YM-155 downregulated survivin at both mRNA and protein levels, induced apoptosis by about 2–7-fold, and caused G0/G1 phase cell cycle arrest. Moreover, YM-155 treatment enhanced p53 expression, suggesting reactivation of tumor suppressor pathways. Notably, combining YM-155 and the chemotherapeutic agent etoposide resulted in synergistic inhibition of NB growth with ED75 values ranging from 0.17 to 1, compared to either agent alone. In the xenograft mouse model, YM-155 inhibited tumor burden in contrast to controls by about 3-fold, and without any notable toxic effects in vivo. Conclusion: Overall, our findings identify YM-155 as a promising therapeutic agent for high-risk NB by directly targeting survivin and enhancing chemosensitivity. These results support continued preclinical development of survivin inhibitors as part of rational combination strategies in pediatric cancer treatment. Full article

Background: The 4CMenB vaccine (Bexsero^®) contains surface proteins from Neisseria meningitidis serogroup B and is recommended from 2 months of age. The most frequently reported adverse events are fever, injection site pain, and fatigue. Thus, this study aimed to estimate the incidence of local and systemic adverse events associated with the administration of the 4CMenB (Bexsero^®) vaccine. Methods: A systematic review and meta-analysis of clinical trials published up to 28 February 2025 were conducted using PubMed, ScienceDirect, and Web of Science. Human studies available in English, Spanish, French, German, or Italian were exclusively included. Adverse events following the first dose of the vaccine were analyzed. Pooled proportions with 95% confidence intervals were calculated, and heterogeneity across studies was assessed using the I² statistics. Results: Ten clinical trials comprising 13,345 participants were included. The most common adverse event was local pain (occurring in up to 94% of cases), followed by induration, erythema, and edema, with frequencies ranging from 25% to 45%. The most frequently reported systemic events were irritability (up to 75%), fatigue (51–59%), fever (up to 60%), headache (42–49%), and persistent crying (50–65%). Most adverse events were mild and self-limiting. Conclusions: The 4CMenB (Bexsero) vaccine exhibits a favorable safety profile, characterized by a predominance of mild and transient local adverse events. Although several systemic events were reported, their overall frequency was generally low. These findings support the continued inclusion of Bexsero^® in routine childhood immunization programs. Full article

Experimental measurement of dose distributions is a pivotal step in the quality assurance of radiotherapy treatments, especially for those relying on high delivery accuracy such as hadron therapy. This study investigated the response of a polymer gel dosimeter to determine its suitability in performing geometric beam characterizations for hadron therapy under high-quenching conditions. Different extraction energies of proton and carbon ion beams were considered. Gel dose–response linearity and long-term stability were confirmed through optical measurements. Gel phantoms were irradiated with pencil beams and analyzed via magnetic resonance imaging. A multi-echo T₂-weighted sequence was used to reconstruct depth–dose profiles and transversal distributions acquired by the gels, which were benchmarked against reference data. As expected, a response-quenching effect in the Bragg peak region was noted. Nonetheless, the studied gel formulation proved reliable in acquiring the geometric characteristics of the beams, even without correcting for the quenching effect. Indeed, depth–dose distributions acquired by the gels showed an excellent agreement with measured particle range with respect to reference values, with mean discrepancies of 0.5 ± 0.2 mm. Single-spot transverse FWHM values at increasing depths also presented an average agreement within 1 mm with values determined with radiochromic films, thus supporting the excellent spatial resolving capabilities of the dosimetric gel. Full article

Purpose: This paper aims to calculate the gross tumor volume (GTV) receiving low radiation doses in patients submitted to “metabolism-guided” lattice radiation therapy and relative possible implications with clinical outcomes. Material and Methods: We reviewed plans for treating voluminous masses via “metabolism-guided” LATTICE-01 irradiation. The aim was to deliver high-dose radiation to spherical deposits (vertices) within a bulky tumor mass. These were placed at tumor areas with differing PET metabolism. We evaluated the relationships between GTV volumes and dose-volumetric histograms (mean, maximum, minimum, and % GTV received 0.5, 1, 2, 3 Gy). Results: Sixty-two plans of treatment met the inclusion criteria as established. The median GTV volume was 315.9 cc (range = 10.54–2605.9 cc). A median of two Vertices was allocated within the GTVs (range 1–9) and were planned to receive a dose of ≥10 Gy/1 fraction (median 12 Gy, range 10–15 Gy). Median V3Gy percentage was 51.58% (range 2–100%), median V2Gy percentage was 67.80% (range 1.60–100%), median V1Gy percentage was 83.70% (range 0.80–100%), and median V0.5Gy percentage was 88.49% (range 17.60–100%). Conclusions: In the present series, we performed a dosimetric evaluation of the GTV’s volume exposed to low doses during the metabolic guided lattice irradiation process. Combining high- and low-dose radiotherapy based on a spatially fractionated (LATTICE) approach could reactivate the immune system against cancer cells. These observations could be useful for planning prospective studies on immunotherapy combined with the lattice technique. Full article

The integration of nanoengineered materials into concrete systems has emerged as a promising strategy for enhancing structural performance and sustainability. This study presents a hybrid experimental-analytical investigation into the use of multilayer graphene as a smart admixture in high-performance concrete. The research combines mechanical testing, microstructural characterization, and a multi-objective optimization model to determine the optimal graphene dosage that maximizes strength gains while minimizing carbon emissions. Concrete specimens incorporating multilayer graphene (ranging from 0.01% to 0.10% by weight of cement) were tested over 7 to 90 days for compressive, tensile, and flexural strengths. Simultaneously, X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray analyses revealed crystallinity enhancement, pore densification, and favorable elemental redistribution due to graphene inclusion. A normalized composite objective function was formulated to balance three maximization targets—compressive, tensile, and flexural strength—and one minimization goal—carbon emission. The highest objective score (Z = 1.047) was achieved at 0.10% graphene dosage, indicating the optimal balance of strength performance and environmental efficiency. This dual-framework study not only confirms graphene’s reinforcing effects experimentally but also validates the 0.10% dosage through mathematical scoring. The outcomes position of multilayer graphene as a powerful additive for high-strength, low-carbon concrete, especially suited for infrastructure in hot and arid environments. The proposed optimization approach provides a scalable pathway for performance-based graphene dosing in future innovative concrete formulations. Full article

Marine actinomycetes constitute a vigorous source of bioactive compounds with potential anti-tumor activity. This study investigates the antitumor activity and classification of actinomycetes isolated from 32 marine soil samples collected across four seasons from Tyr City Beach, Lebanon. A total of 80 morphologically diverse isolates were recovered and characterized, with dominant genera including Streptomyces, Kocuria, and Micrococcus. Among these, three promising strains—Kocuria rosea, Micrococcus luteus, and Streptomyces longisporoflavus—were selected for further analysis. Crude extracts were tested against human colorectal adenocarcinoma (Caco-2) and human hepatocellular carcinoma (HepG-2) cancer cell lines using MTT and Western blot assays. At the highest concentration (8 µg/µL), the extracts reduced cell viability to 24–37% in Caco-2 and 12–25% in HepG-2. The IC₅₀ values ranged from 1.72 to 3.53 µg/µL, depending on the extract and cell line. Western blot analysis showed dose-dependent increases in the Bax/Bcl-2 ratio, with fold changes reaching 4.35 (Kocuria), 11.39 (Micrococcus), and 14.25 (Streptomyces) in HepG-2 cells. The p53 protein expression also increased significantly, with fold changes up to 7.79 in Caco-2 and 3.0 in HepG-2 cells. These results indicate that marine actinomycetes from the Lebanese coastline hold strong potential as a source of antitumor agents targeting apoptosis pathways. Full article

Background: Frailty is known to elevate the risk of all-cause mortality and shorten life expectancy. Although the effects of diet on health are well documented, the specific interaction between diet quality and frailty remains unexplored. This research aims to examine the combined effects of various diet quality scores and frailty on all-cause mortality and life expectancy among middle-aged and older adults. Methods: A total of 151,628 participants were sourced from the UK Biobank for analysis. Frailty phenotype (FP) and frailty index (FI), as two different approaches, were used to assess frailty status. Diet quality was evaluated through seven diet quality scores: the Alternate Healthy Eating Index (AHEI), Dietary Approaches to Stop Hypertension (DASH) score, Mediterranean diet (MED) score, Dietary Inflammatory Index (DII), and three plant-based diet indices (overall PDI, healthful PDI, and unhealthful PDI). Cox proportional hazards models were applied to calculate adjusted hazard ratios (HRs) for overall mortality and predict life expectancy differences. Results: Over a median follow-up period of 12.2 years, 8231 deaths were identified. After accounting for potential confounding factors, frail individuals in the unhealthier tertile of diet scores exhibited markedly elevated mortality risks, ranging from 1.99 to 2.07 based on the frailty index and 2.79 to 3.06 based on the frailty phenotype, compared to their robust counterparts in the healthier tertile. Regardless of frailty categories, a healthier diet was associated with longer life expectancy and with lower mortality risk in a dose–response relationship. Conclusions: The healthier tertile of diet scores was found to mitigate the detrimental effects of frailty, emphasizing diet quality as a modifiable factor in promoting healthier aging. Evidence suggests that it is never too late to adopt healthier dietary habits for significant health benefits. Full article

This study aimed to evaluate the potential benefits of co-digesting rapeseed oil cake, a by-product of biodiesel production, with microalgal biomass. Anaerobic fermentation was carried out under mesophilic conditions using various doses of press residue as a co-substrate. The results demonstrate that the addition of rapeseed oil cake enhances biogas production. The highest biogas yield was achieved during co-digestion with 1 g VS·L⁻¹ of microalgal biomass and 0.5 g VS·L⁻¹ of rapeseed oil cake. The average methane content in the biogas was 62.42%. The average hydrogen sulfide concentration ranged from 400 to 700 ppm. The maximum energy yield of 3.76 kWh·kg⁻¹ DM was obtained from co-digesting microalgal and rapeseed oil cake biomass in a 2:1 ratio. Full article

Honey is a valuable natural product prized for its nutritional and therapeutic properties, including antioxidant, antimicrobial, and anti-inflammatory effects. However, in addition to health-promoting compounds, honey may also contain plant-derived toxins, contaminants, and degradation products. Certain phytotoxins—such as pyrrolizidine alkaloids, grayanotoxins, triptolide, celastrol, gelsedine-type alkaloids, and tutin—can be transferred to honey from specific plant sources and pose health risks, particularly at high doses or with long-term exposure. Furthermore, compounds like 5-hydroxymethylfurfural, trace metals, pesticide residues, and Clostridium botulinum spores may present additional risks, especially to sensitive groups such as infants. Consumers often assume that natural products are inherently safe, which may lead to unintentional exposure to harmful substances. Adverse effects can range from chronic toxicity to, in extreme cases, death. Therefore, raising awareness among consumers and vendors is essential to reduce the intake of honey from unverified sources. Continuous monitoring of honey composition and further studies on the toxicodynamics of rare contaminants are crucial to ensuring safety while preserving the therapeutic benefits of this remarkable natural substance. Full article

Aphid control often relies on synthetic pesticides, but their overuse has raised concerns about resistance development and negative impact on wildlife and human health. Consequently, the search for new biopesticide agents has gained significant attention. Nemertide alpha-1, a peptide toxin from the marine nemertean worm Lineus longissimus (Gunnerus, 1770), is known for its pesticide activity but has less documented biological safety. This study investigates the aphid feeding deterrence and biological safety of the experimental biopesticide nemertide alpha-1. Nemertide alpha-1 demonstrated a clear dose-dependent repellent effect on the penetration behaviour of the green peach aphid (Myzus persicae, Sulzer). It also demonstrates bacteriostatic and bactericidal effects in an MIC (Minimum Inhibitory Concentration) assay, respectively, on E. coli (MIC: 112.5 µM) and S. aureus (MIC: 28.4 µM). In a bacterial liposome leakage assay, nemertide alpha-1 exhibits a less pronounced effect than the melittin control (20% maximum leakage at 100 µM), strengthening the hypothesis on the specificity of its neurotoxic mode of action. It is not toxic to mammalian cell U-937 GTB with only a slight decline in the percentage of survival at the highest concentration tested (80 µM). Finally, nemertide alpha-1 displays thermal stability over time for four weeks in three different conditions: cold (6 °C), room temperature (20–24 °C), and physiological temperature (37 °C). Nemertide alpha-1 deters green peach aphid feeding in the low micromolar range and exhibits low antimicrobial properties and very low toxicity to human cells. Its potential utility is further underscored by thermal stability over time. Full article

The aim of this study was to synthesize, characterize, and investigate the biomedical effects of nanoscale cerium phosphate obtained via different synthesis techniques, as well as to evaluate the influence of various CePO₄ concentrations on cells involved in skin structure regeneration (human mesenchymal stem cells, keratinocytes, and fibroblasts) and establish their antioxidant properties. Methods and Results: Cerium(III) orthophosphate was obtained by precipitation with ammonium dihydrogen phosphate from a nitrate solution. By changing the initial concentrations of the solutions and the drying and annealing temperatures, the best conditions for obtaining nanosized phosphate powders were established. The structure of rhabdophane was obtained by X-ray diffraction analysis, and the particle sizes were measured by transmission electron microscopy. The particle sizes ranged from 2 to 10 nm in the transverse direction and 20 to 50 nm in the longitudinal direction. Studies on cell lines have shown a high level of safety, as well as the regenerative potential of CePO₄ nanoparticles, which have a stimulating effect on the proliferation of MSCs at concentrations of 10⁻² to 10⁻³ M for 48 h after application and stimulate the metabolism of human keratinocytes and fibroblasts at a wide range of concentrations (10⁻³ to 10⁻⁵ M). A dose-dependent antioxidant effect of small CePO₄ nanoparticles at a concentration of 10⁻² to 10⁻⁵ has been established, which is stronger than ascorbic acid. Conclusions: A method for obtaining cerium phosphate nanoparticles with beneficial biomedical effects was developed. The non-cytotoxicity and regenerative potential of CePO₄ were established at a wide range of concentrations on different cell lines that are involved in the healing of skin wounds, as were their antioxidant properties. Full article

Background: We evaluated the long-term treatment outcomes of patients with clinically localized and locally advanced prostate cancer (PC) who underwent high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT). The primary objective was to identify the optimal timing for discontinuing prostate-specific antigen (PSA) monitoring after HDR-BT. Methods: This analysis included 338 patients with PC who received HDR-BT combined with EBRT between 2006 and 2022 and had a minimum follow-up of 5 years. The patients were stratified based on their PSA levels, and factors associated with recurrence were identified. Results: The median observation period was 8.9 years (range, 5.0–19.0 years). The 10-year recurrence-free survival rate was 92.0%, with 26 recurrences. PSA levels at 5 and 7 years were significantly correlated with oncological outcomes after HDR-BT. Multivariate analysis revealed that a PSA level of >0.2 ng/mL at 5 years was an independent poor prognostic factor for recurrence (hazard ratio, 117.57; 95% confidence interval, 6.22–2223.37; p = 0.001). No patient with a PSA level of ≤0.2 ng/mL at 7 years developed recurrences. Conclusions: Based on our long-term data, we propose that PSA monitoring may be safely discontinued in patients with a PSA level of ≤0.2 ng/mL 7 years after HDR-BT because the risk of recurrence beyond this point is exceedingly low. Full article

This study aimed to evaluate the scientific reliability of 3D-printed silicone boluses fabricated with patient-specific molds, focusing on fabrication-related uncertainties such as internal air bubbles, thickness variations, and density differences, thereby providing evidence for clinical quality assurance. Custom silicone boluses were fabricated using 3D-printed molds with varying vacuum degassing times (1, 5, and 10 min). Air bubble size and depth were quantified using scanner image analysis, while density and Hounsfield unit (HU) values were compared with a commercial bolus. Dosimetric evaluation was performed using a VitalBeam linear accelerator (6 MV photons, Varian Medical Systems, Palo Alto, CA, USA) and a MatriXX 2D detector (IBA Dosimetry, Schwarzenbruck, Germany), comparing treatment planning system (TPS) calculated doses with measured doses across a 3 × 3 grid. Surface dose distributions were further analyzed using EBT3 film. Results showed that bubble size increased with longer vacuum times, interpreted as coalescence due to limited degassing and silicone viscosity. The density of 3D boluses ranged from 0.980 to 1.104 g/cm³ (commercial: 0.988 g/cm³), with HU values of +240 to +250 (commercial: −110). In point-wise comparisons, mean dose differences were less than 1% for 1- and 5 min samples and approximately 1% for 10 min, with all conditions within |Δ| ≤ 3%. Film analysis confirmed equivalent surface dose distributions. These findings demonstrate, for the first time, that microscopic bubbles in 3D-printed silicone boluses have negligible clinical impact, supporting their safe adoption without requiring complex degassing procedures. Full article

Background/Objectives: While pentadecanoic acid (C15:0), present in whole dairy fat, has broad anticancer activities at high concentrations, the presence of C15:0 anticancer activities at naturally occurring circulating concentrations is less clear. Methods: Using an independent service to run the Eurofins OncoPanel^TM Cell Proliferation Assay, C15:0 was screened for dose-dependent antiproliferation activities against 94 human cancer cell lines at 10 concentrations ranging between 1.5 nM and 50 µM. Oncogenic alterations were compared between cell lines in which C15:0 did or did not have antiproliferation activities. Results: C15:0 had dose-dependent antiproliferation activities (EC50 ≤ 50 µM) among 13 (13.8%) cancer cell lines, most of which were non-Hodgkin B-cell lymphomas (n = 8, 61.5% of C15:0-responsive cell lines), but also included liver (n = 2, 15.4%), breast (n = 2, 15.4%), and lung (n = 1, 7.7%) cancers. C15:0 had robust antiproliferation activities (EC₅₀, IC₅₀ and GI₅₀ ≤ 50 µM) in four cell lines, all of which were non-Hodgkin B-cell lymphomas. When comparing oncogenic alterations among C15:0-responsive versus non-responsive cancer cell lines (n = 79 with available data on DepMap), 4 of 18 (22%) C15:0-responsive cell lines had a CCND3 mutation compared to 1 of 61 (1.6%) non-responsive cell lines (p = 0.007, OR = 17.1, 95% CI 1.8–165). Three of four (75%) of the most C15:0-responsive B-cell lymphomas had the CCND3 alteration (p = 0.0004, OR = 180, 95% CI 8.9–3632). Conclusions: C15:0 has selective dose-dependent anticancer activities at naturally occurring concentrations. The potential use of C15:0 against cancers with CCND3 genetic alterations warrants further exploration. Further, there is a need to better understand the potential role of nutritional C15:0 deficiencies and CCND3 alterations on the observed rise in certain types of cancers, especially among young adults. Full article