Search Results (59,247)

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical and chemotherapeutic approaches, the presence of metastatic or recurrent disease is still detrimental to the patient’s outcome. Major advances in understanding the molecular mechanisms of OS are needed to substantially improve outcomes for patients being treated for OS. This review integrates new data on the molecular biology, pathophysiology, and immune landscape of OS, as well as introducing salient areas of tumorigenesis underpinning these findings, such as chromothripsis; kataegis; cancer stem cell dynamics; and updated genetic, epigenetic, and glycosylation modifiers. In addition, we review promising biomarkers, diagnostic platforms, and treatments, including immunotherapy, targeted small molecule inhibitors, and nanomedicine. Using genomic techniques, we have defined OS for its significant genomic instability due to TP53 and RB1 mutations, chromosomal rearrangements, and aberrant glycosylation. The TME is also characterized as immunosuppressive and populated by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, ultimately inhibiting immune checkpoint inhibitors. Emerging fields such as glycomics and epigenetics, as well as stem cell biology, have defined promising biomarkers and targets. Preclinical studies have identified that glycan-directed CAR therapies could be possible, as well as metabolic inhibitors and 3D tumor models, which presented some preclinical success and could allow for tumoral specificity and enhanced efficacy. OS is a biologically and clinically complex disease; however, advances in exploring the molecular and immunologic landscape of OS present new opportunities in biomarkers and the development of new treatment options with adjunctive care. Successful treatments in the future will require personalized, multi-targeted approaches to account for tumor heterogeneity and immune evasion. This will help us turn the corner in providing improved outcomes for patients with this resilient malignancy. Full article

Tribological performance is critical for the longevity and efficiency of machined components in industries such as aerospace, automotive, and biomedical. This study investigates whether electrical discharge machining recast layers can serve as a cost-effective and time-efficient alternative to conventional tungsten inert gas cladding coatings for enhancing surface properties. The samples were prepared using electrical discharge machining and tungsten inert gas cladding. For electrical discharge machining, various combinations of electrical and non-electrical parameters were applied using Taguchi’s L18 orthogonal array. Similarly, tungsten inert gas cladding coatings were prepared using a suitable combination of current, voltage, powder size, and speed. The samples were characterized using, scanning electron microscopy, optical microscopy, microhardness testing, tribological testing, energy-dispersive X-ray spectroscopy, X-ray diffraction analysis and profilometry. The electrical discharge machining recast layers exhibited superior tribological performance compared to tungsten inert gas cladding coatings. This improvement is attributed to the formation of carbides, such as TiC and Ti₆C_3.75. The coefficient of friction and specific wear rate were reduced by 11.11% and 1.57%, respectively, while microhardness increased by 10.93%. Abrasive wear was identified as the predominant wear mechanism. This study systematically compares electrical discharge machining recast layers with tungsten inert gas cladding coatings. The findings suggest that optimized electrical discharge machining recast layers can serve as effective coatings, offering cost and time savings. Full article

Salinity is a major abiotic stress limiting black gram (Vigna mungo) productivity, particularly in arid and semi-arid regions. Saline soils negatively impact plant growth, nodulation, nitrogen fixation, and yield. This study evaluated the efficacy of co-inoculating salt-tolerant plant growth-promoting bacteria Paenibacillus sp. SPR11 and Bradyrhizobium yuanmingense PR3 on black gram performance under saline field conditions (EC: 8.87 dS m⁻¹; pH: 8.37) with low organic carbon (0.6%) and nutrient deficiencies. In vitro assays demonstrated the biocontrol potential of SPR11, inhibiting Fusarium oxysporum and Macrophomina phaseolina by 76% and 62%, respectively. Germination assays and net house experiments under 300 mM NaCl stress showed that co-inoculation significantly improved physiological traits, including germination rate, root length (61.39%), shoot biomass (59.95%), and nitrogen fixation (52.4%) in nitrogen-free media. Field trials further revealed enhanced stress tolerance markers: chlorophyll content increased by 54.74%, proline by 50.89%, and antioxidant enzyme activities (SOD, CAT, PAL) were significantly upregulated. Electrolyte leakage was reduced by 55.77%, indicating improved membrane stability. Agronomic performance also improved, with co-inoculated plants showing increased root length (7.19%), grain yield (15.55 q ha⁻¹; 77.04% over control), total biomass (26.73 q ha⁻¹; 57.06%), and straw yield (8.18 q ha⁻¹). Pod number, seed count, and seed weight were also enhanced. Nutrient analysis showed elevated uptake of nitrogen, phosphorus, potassium, and key micronutrients (Zn, Fe) in both grain and straw. To the best of our knowledge, this is the very first field-based report demonstrating the synergistic benefits of co-inoculating Paenibacillus sp. SPR11 and Bradyrhizobium yuanmingense PR3 in black gram under saline, nutrient-poor conditions without external nitrogen inputs. The results highlight a sustainable strategy to enhance legume productivity and resilience in salt-affected soils. Full article

Electrospun nanofibrous membranes have gained considerable attention in bone tissue engineering due to their ability to mimic the extracellular matrix and provide a suitable environment for cell attachment and proliferation. This study investigates the fabrication, characterization, and biocompatibility of poly(L-lactic acid) (PLA)-based membranes enhanced with periclase (MgO) and gold nanoparticles (AuNPs). The membranes were fabricated using an optimized electrospinning process and subsequently characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Fourier-transform infrared spectroscopy (FT-IR), and contact angle measurements. Additionally, in vitro biodegradation studies in simulated body fluid (SBF) and cytocompatibility tests with osteoblast-like cells were conducted. The results demonstrated that the incorporation of MgO and AuNPs significantly influenced the structural and chemical properties of the membranes, improving their wettability and bioactivity. SEM imaging confirmed uniform fiber morphology with well-distributed nanoparticles. FT-IR spectroscopy indicated successful integration of bioactive components into the PLA matrix. Cytocompatibility assays showed that modified membranes promoted higher osteoblast adhesion and proliferation compared to pristine PLA membranes. Furthermore, biodegradation studies revealed a controlled degradation rate suitable for guided bone regeneration applications. These findings suggest that electrospun PLA membranes enriched with MgO and AuNPs present a promising biomaterial for GBR applications, offering improved bioactivity, mechanical stability, and biocompatibility. Full article

Hodgkin’s Lymphoma (HL) affects approximately 8500 individuals annually in the United States. The 5-year relative survival rate has improved to 88.5%, driven by transformative advances in immunotherapy and precision oncology. The integration of Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) has redefined treatment paradigms. The phase III SWOG S1826 trial established nivolumab plus doxorubicin, vinblastine, and dacarbazine (N + AVD) as an emerging new standard for advanced-stage HL, achieving a 2-year progression-free survival (PFS) of 92% compared to 83% for BV plus AVD (HR 0.48, 95% CI: 0.33–0.70), with superior safety, particularly in patients over 60. In relapsed/refractory HL, pembrolizumab outperforms BV, with a median PFS of 13.2 versus 8.3 months (HR 0.65, 95% CI: 0.48–0.88), as demonstrated in the KEYNOTE-204 trial. Emerging strategies, including novel ICI combinations, minimal residual disease (MRD) monitoring via circulating tumor DNA (ctDNA), and artificial intelligence (AI)-driven diagnostics, promise to further personalize therapy. This review synthesizes HL’s epidemiology, pathogenesis, diagnostic innovations, and therapeutic advances, highlighting the role of precision medicine in addressing unmet needs and disparities in HL care. Full article

The blended system of solid waste micro-powders is of great significance for the efficient utilization of recycled micro-powder. In this study, a ternary blended cementitious system composed of fly ash, slag, and recycled micro-powder was constructed, and its effects on the workability, mechanical properties, shrinkage performance, and microstructure of recycled mortar were systematically investigated. The experimental results show that with the increasing dosage of slag and recycled micro-powder (partially replacing cement and fly ash), the standard consistency water demand of the cementitious system decreases and the setting time is prolonged. When the replacement levels of recycled micro-powder and slag are both 10%, the 3-day, 7-day, and 28-day mechanical strengths of the mortar specimens are comparable to those of the reference group, with an increased flexural-to-compressive strength ratio and improved brittleness. SEM and mercury intrusion porosimetry (MIP) analyses revealed that systems incorporating low addition levels of recycled micro powder and slag powder exhibit calcium silicate hydrate (C-S-H) gel, acicular ettringite crystals, and a denser pore structure. However, at higher dosages (>10%), the porosity increases significantly and the pore structure deteriorates, resulting in reduced shrinkage performance. Overall, when the replacement rate of cement–fly ash by recycled micro-powder and slag is 10%, the ternary blended system exhibits optimal macroscopic performance and microstructure, providing a scientific basis for the resource utilization of solid waste. Full article

Alagille syndrome (ALGS) is a multisystem disorder characterized by a paucity of intrahepatic bile ducts and cholestasis, often requiring liver transplantation before adulthood. Due to the lack of genotype–phenotype correlation, case series are essential to understand disease presentation and prognosis. Data on Mexican ALGS patients are limited. Therefore, we aimed to characterize a large series of Mexican patients by consolidating cases from major institutions and independent geneticists, with the goal of generating one of the most comprehensive cohorts in Latin America. We retrospectively analyzed clinical records of pediatric ALGS patients, focusing on demographics, clinical features, laboratory and imaging results, biopsy findings, and transplant status. Genetic testing was performed for all cases without prior molecular confirmation. We identified 52 ALGS cases over 13 years; 22 had available clinical records. Of these, only 6 had molecular confirmation at study onset, prompting genetic testing in the remaining 16. We identified six novel JAG1 variants and several previously unreported phenotypic features. A liver transplantation rate of 13% was observed in the cohort. This study represents the largest molecularly confirmed ALGS cohort in Mexico to date. Novel genetic and clinical findings expand the known spectrum of ALGS and emphasize the need for improved therapies, such as IBAT inhibitors, which may alleviate symptoms and reduce the need for transplantation. Full article

A novel efficient method to evaluate time-periodic flows is applied to turbomachinery configurations in this paper (PSpTM). The technique reduces the overall computational cost of unsteady CFD calculations relative to conventional implicit approaches. The method is based on a pseudo-spectral definition of the time derivative rearranged in a time-marching fashion. The key advantage of this novel formulation compared with classical harmonic methods is that it requires minor modifications in the CFD solver structure. The method was implemented into an existing unstructured edge-based, second-order, compressible RANS solver. To benchmark the method, a well-established implicit time scheme based on a second-order backward implicit approach (BDF2) is used. Sample unsteady turbomachinery configurations are used to determine the accuracy and efficiency of the method. The accuracy of the solution is highly linked to the number of harmonics prescribed for the solution. An adequate level of accuracy was obtained while retaining a reduced number of harmonics, with approximately twice the number of harmonics of the unsteady perturbation. Notable savings in computational cost were observed when the PSpTM method was used with speed-up factors of between 2 and 10 with respect to the BDF2, depending on the case. However, the PSpTM method exhibits a poor periodic convergence rate, leaving room for further improvements in efficiency. However, even in its current form and with the current understanding, the method has a remarkable performance. Full article

To address the central cracking problem in continuous casting slabs of 38CrMoAl steel, high-temperature tensile tests were performed using a Gleeble-3800 thermal simulator to characterize the hot ductility of the steel within the temperature range of 600–1200 °C. The phase transformation behavior was computationally analyzed via the Thermo-Calc software, while the microstructure, fracture morphology, and precipitate characteristics were systematically investigated using a metallographic microscope (MM), a field-emission scanning electron microscope (FE-SEM), and transmission electron microscopy (TEM). Additionally, the effects of different holding times and cooling rates on the microstructure and precipitates of 38CrMoAl steel were also studied. The results show that the third brittle temperature region of 38CrMoAl steel is 645–1009 °C, and the fracture mechanisms can be classified into three types: (I) in the α single-phase region, the thickness of intergranular proeutectoid ferrite increases with rising temperature, leading to reduced hot ductility; (II) in the γ single-phase region, the average size of precipitates increases while the number density decreases with increasing temperature, thereby improving hot ductility; and (III) in the α + γ two-phase region, the precipitation of proeutectoid ferrite promotes crack propagation and the dense distribution of precipitates at grain boundaries causes stress concentration, further deteriorating hot ductility. Heat treatment experiments indicate that the microstructures of the specimen transformed under water cooling, air cooling, and furnace cooling conditions as follows: martensite + proeutectoid ferrite → bainite + ferrite → ferrite. The average size of precipitates first decreased, then increased, and finally decreased again with increasing holding time, while the number density exhibited the opposite trend. Therefore, when the holding time was the same, reducing the cooling rate could increase the average size of the precipitates and decrease their number density, thereby improving the hot ductility of 38CrMoAl steel. Full article

Objective: The accurate visualization of root canal systems on periapical radiographs is critical for successful endodontic treatment. This study aimed to evaluate and compare the effectiveness of several image enhancement algorithms—including a novel Total Variation–Contrast-Limited Adaptive Histogram Equalization (TV-CLAHE) technique—in improving the detectability of root canal configurations in mandibular incisors, using cone-beam computed tomography (CBCT) as the gold standard. A null hypothesis was tested, assuming that enhancement methods would not significantly improve root canal detection compared to original radiographs. Method: A retrospective analysis was conducted on 60 periapical radiographs of mandibular incisors, resulting in 420 images after applying seven enhancement techniques: Histogram Equalization (HE), Contrast-Limited Adaptive Histogram Equalization (CLAHE), CLAHE optimized with Pelican Optimization Algorithm (CLAHE-POA), Global CLAHE (G-CLAHE), k-Caputo Fractional Differential Operator (KCFDO), and the proposed TV-CLAHE. Four experienced observers (two radiologists and two dentists) independently assessed root canal visibility. Subjective evaluation was performed using an own scale inspired by a 5-point Likert scale, and the detection accuracy was compared to the CBCT findings. Quantitative metrics including Peak Signal-to-Noise Ratio (PSNR), Signal-to-Noise Ratio (SNR), image entropy, and Structural Similarity Index Measure (SSIM) were calculated to objectively assess image quality. Results: Root canal detection accuracy improved across all enhancement methods, with the proposed TV-CLAHE algorithm achieving the highest performance (93–98% accuracy), closely approaching CBCT-level visualization. G-CLAHE also showed substantial improvement (up to 92%). Statistical analysis confirmed significant inter-method differences (p < 0.001). TV-CLAHE outperformed all other techniques in subjective quality ratings and yielded superior SNR and entropy values. Conclusions: Advanced image enhancement methods, particularly TV-CLAHE, significantly improve root canal visibility in 2D radiographs and offer a practical, low-cost alternative to CBCT in routine dental diagnostics. These findings support the integration of optimized contrast enhancement techniques into endodontic imaging workflows to reduce the risk of missed canals and improve treatment outcomes. Full article

This study was conducted to investigate the effects of puffed jujube powder (PJP) supplementation in the diet on the slaughter characteristics, growth performance, meat quality, and serum antioxidant capacity of Hainan Black (HB) goats. Twenty-four healthy male HB goats, three months old with an initial body weight of 15.12 ± 3.67 kg, were randomly divided into three groups: the 10% PJP group (basal diet plus 10% PJP); the 20% PJP group (basal diet plus 20% PJP); and the control group (basal diet only). After a 10-day adaptation period, a feeding trial was carried out for 90 days in an ad libitum diet environment. The results show that the final body weight of the 20% PJP group was markedly higher (p < 0.05) than that of the control group (22.58 ± 0.94 kg vs. 20.45 ± 1.01 kg). The average daily gain of the 20% PJP group was 83.44 ± 1.78 g/d, which was substantially greater (p < 0.05) than the 59.22 ± 2.13 g/d of the control group. The feed intake of the 20% PJP group was 713.10 ± 4.54 g/d, notably higher (p < 0.05) than the 498.20 ± 4.33 g/d of the control group. In terms of slaughter characteristics, the carcass weight of the 20% PJP group was 13.99 ± 1.22 kg, considerably heavier (p < 0.05) than the 11.79 ± 1.38 kg of the control group. The muscle weight of the 20% PJP group was 11.43 ± 1.42 kg, distinctly greater (p < 0.05) than the 9.59 ± 1.99 kg of the control group. The slaughter rate of the 20% PJP group was 42.41%, showing a notable increase (p < 0.05) compared with the 37.42% of the control group, and the net meat rate of the 20% PJP group was 34.65%, with a significant rise (p < 0.05) compared with the 30.43% of the control group. Regarding serum antioxidant capacity and meat quality, the activities of serum antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), were conspicuously increased (p < 0.05) in the 20% PJP group. The meat shear force of the 20% PJP group was decreased by 12.9%, and the cooking loss was improved by 8.9% in comparison with the control group. In conclusion, the supplementation of 20% PJP in the diet was demonstrated to enhance the growth performance, improve the meat quality, and boost the antioxidant status of HB goats, thus presenting a feasible strategy for optimizing tropical goat production systems. Full article

In this study, we sought to improve the productivity of Far Eastern catfish (Silurus asotus) and tropical eel (Anguilla bicolor), which are high-value fish species in the Republic of Korea, as well as that of associated crops by applying biofloc technology (BFT)-based aquaponics systems. The following three systems were used: the flow-through system (FTS), BFT, and BFT aquaponics system (BAPs). Caipira lettuce (Lactuca sativa) was utilized and hydroponics (HP) was implemented to compare crop productivity. After 42 days of treatment, the BAPs and BFT systems improved fish productivity, with weight gain rates of 134.47 ± 1.80% in BAPs-cat, 130.38 ± 0.95% in BFT, and 114.21 ± 6.62% in FTS for S. asotus, and 70.61 ± 3.26% in BAPs-eel, 62.37 ± 7.04% in BFT, and 47.83 ± 1.09% in FTS for A. bicolor. During the experiment, the total ammonia nitrogen and NO₂⁻-N concentrations were stable in all plots. In the case of NO₃⁻-N, BFT showed an increasing tendency while both BAPs showed a decrease compared with that of the BFT. BAPs-cat (total weight: 224.1 ± 6.37 g) and HP (220.3 ± 7.17 g) resulted in similar growth. However, in BAPs-eel was 187.7 ± 3.46 g due to root degradation. Water content analysis showed that BAPs-cat and BAPs-eel contained sufficient K, Ca, P, and S, which are important for crop growth. Overall, the effect of BAPs on fish growth was higher than that of FTS. This study reveals that integrating BFT with aquaponics improves productivity for high-value fish and associated crops while maintaining stable water quality. This method offers sustainable, efficient production, reduces environmental impact, and provides insights for future research in sustainable aquaculture practices. Full article

In the casting and rolling production process, surface longitudinal cracks are a typical casting defect. Tracing the causes of longitudinal cracks online and controlling the key parameters leading to their formation in a timely manner can enhance the stability of casting and rolling production. To this end, the influencing factors of longitudinal cracks were analyzed, a data integration storage platform was constructed, and a tracing model was established using empirical rule analysis, statistical analysis, and intelligent analysis methods. During the initial production phase of a casting machine, longitudinal cracks occurred frequently. The tracing results using the LightGBM-SHAP method showed that the relative influence of the narrow left wide inner heat flow ratio of the mold was significant, followed by the heat flow difference on the wide symmetrical face of the mold and the superheat of the molten steel, with weights of 0.135, 0.066, and 0.048, respectively. Based on the tracing results, we implemented online emergency measures. By controlling the cooling intensity of the mold, we effectively reduced the recurrence rate of longitudinal cracks. Root cause analysis revealed that the total hardness of the mold-cooling water exceeded the standard, reaching 24 mg/L, which caused scaling on the mold copper plates and uneven cooling, leading to the frequent occurrence of longitudinal cracks. After strictly controlling the water quality, the issue of longitudinal cracks was brought under control. The online application of the tracing method for the causes of longitudinal cracks has effectively improved efficiency in resolving longitudinal crack problems. Full article

Background: In high-risk and frail patients with multivessel coronary artery disease (MV CAD), guidelines indicated complete revascularization with or without the use of cardiopulmonary bypass (CPB) bears a high morbidity and mortality risk. In cases where catheter interventions were deemed unsuitable and conventional coronary artery bypass grafting (CABG) posed an unacceptable perioperative risk, patients were scheduled for minimally invasive direct coronary artery bypass (MIDCAB) grafting or minimally invasive multivessel coronary artery bypass grafting (MICS-CABG). We called this approach “palliative revascularization.” This study assesses the safety and impact of palliative revascularization on clinical outcomes and overall survival. Methods: A consecutive series of 57 patients undergoing MIDCAB or MICS-CABG as a palliative surgery between 2008 and 2018 was included. The decision for palliative surgery was met in heart team after carefully assessing each case. The patients underwent single or double-vessel revascularization using the left internal thoracic artery and rarely radial artery/saphenous vein segments, both endoscopically harvested. Inpatient data could be completed for all 57 patients. The mean follow-up interval was 4.2 ± 3.7 years, with a follow-up rate of 91.2%. Results: Mean patient age was 79.7 ± 7.4 years. Overall, 46 patients (80.7%) were male, 26 (45.6%) had a history of atrial fibrillation and 25 (43.9%) of chronic kidney disease. In total, 13 patients exhibited a moderate EuroSCORE II, while 27 were classified as high risk, with a EuroSCORE II exceeding 5%. Additionally, 40 patients (70.2%) presented with three-vessel disease, 17 (29.8%) suffered an acute myocardial infarction within three weeks prior to surgery and 50.9% presented an impaired ejection fraction. There were 48 MIDCAB and nine MICS CABG with no conversions either to sternotomy or to CPB. Eight cases were planned as hybrid procedures and only 15 patients (26.3%) were completely revascularized. During the first 30 days, four patients (7%) died. A myocardial infarction occurred in only one case, no patient necessitated immediate reoperation. The one-, three- and five-year survival rates were 83%, 67% and 61%, respectively. Conclusions: MIDCAB and MICS CABG can be successfully conducted as less invasive palliative surgery in high-risk multimorbid patients with MV CAD. The early and mid-term results were better than predicted. A higher rate of hybrid procedures could improve long-term outcome in selected cases. Full article

Background: Optimal timing for surgery following acute rotator cuff tears remains unclear. This study examines how the timing of arthroscopic rotator cuff repair (RCR) affects retear rates and functional outcomes. Methods: This PROSPERO-registered review (CRD42024528249) followed PRISMA guidelines and included randomized trials, and cohort, studies on adults with imaging-confirmed full-thickness rotator cuff tears. Studies lacking timing data or key outcomes were excluded. Risk of bias was assessed using ROBINS-I. Meta-analysis of retear rates was performed comparing surgical timing. Qualitative analysis was conducted classifying results as early-beneficial, delayed-detrimental, or neutral. Results: Our review included 13 studies and 871 patients with an average age of 57.9. Meta-analysis of eight studies comparing retear rates between early and delayed RCR demonstrated a significant benefit associated with early intervention risk ratio 0.60 (95% CI: 0.38–0.96). Functional outcomes also favored early intervention with four studies demonstrating significantly greater postoperative functional improvements in the early intervention group. Conclusions: Early arthroscopic RCR decreased the rate of retear and improved functional outcomes. No study found early intervention to be detrimental or delayed intervention to be superior. These findings support consideration of early repair when clinically appropriate. Future studies should determine more finite timing guidelines. Full article