Search Results (13,594)

Cushing’s syndrome is one of the most common endocrine disorders in dogs and is typically managed with long-term medical treatment. Several pharmacological agents are available: trilostane, mitotane, ketoconazole, cabergoline, selegiline, and aminoglutethimide, but their comparative effects on survival remain unclear. This systematic review and meta-analysis compared the impact of these agents on survival outcomes in dogs with naturally occurring diseases. A comprehensive search of MEDLINE, Embase, Web of Science, Academic Search Complete, and the Cochrane Library was conducted between 1 September 2024 to 3 January 2025. Eligible studies included dogs diagnosed with Cushing’s syndrome that reported survival outcomes for at least one of the specified treatments. Five studies (n = 295 dogs) met the inclusion criteria, with trilostane and mitotane providing sufficient data for meta-analysis. Pooled mean difference in survival time across four studies was 85.1 days (95% CI: −255.9 to 85.7, p = 0.21) with substantial heterogeneity (I² = 89%), indicating no statistically significant difference between the drugs. In contrast, pooled survival rates at fixed intervals favored trilostane, with an 11% higher survival at 36 months (p = 0.005) and no heterogeneity observed (I² = 0%). These findings suggest trilostane may offer long-term survival benefits over mitotane. Full article

Background: Cardiovascular diseases (CVDs) remain the primary cause of global mortality, with arterial hypertension, ischemic heart disease (IHD), and cerebrovascular accident (CVA) forming a progressive continuum from early risk factors to severe outcomes. While numerous studies focus on isolated biomarkers, few integrate multidimensional visualization with artificial intelligence to reveal hidden, clinically relevant patterns. Methods: We conducted a comprehensive analysis of 106 patients using an integrated framework that combined clinical, biochemical, and lifestyle data. Parameters included renal function (glomerular filtration rate, cystatin C), inflammatory markers, lipid profile, enzymatic activity, and behavioral factors. After normalization and imputation, we applied correlation analysis, parallel coordinates visualization, t-distributed stochastic neighbor embedding (t-SNE) with k-means clustering, principal component analysis (PCA), and Random Forest modeling with SHAP (SHapley Additive exPlanations) interpretation. Bootstrap resampling was used to estimate 95% confidence intervals for mean absolute SHAP values, assessing feature stability. Results: Consistent patterns across outcomes revealed impaired renal function, reduced physical activity, and high hypertension prevalence in IHD and CVA. t-SNE clustering achieved complete separation of a high-risk group (100% CVD-positive) from a predominantly low-risk group (7.8% CVD rate), demonstrating unsupervised validation of biomarker discriminative power. PCA confirmed multidimensional structure, while Random Forest identified renal function, hypertension status, and physical activity as dominant predictors, achieving robust performance (Accuracy 0.818; AUC-ROC 0.854). SHAP analysis identified arterial hypertension, BMI, and physical inactivity as dominant predictors, complemented by renal biomarkers (GFR, cystatin) and NT-proBNP. Conclusions: This study pioneers the integration of multidimensional visualization and AI-driven analysis for CVD risk profiling, enabling interpretable, data-driven identification of high- and low-risk clusters. Despite the limited single-center cohort (n = 106) and cross-sectional design, the findings highlight the potential of interpretable models for precision prevention and transparent decision support in cardiovascular aging research. Full article

Lymphocyte-activation gene 3 (LAG3) is an immune checkpoint receptor and inhibitory regulator of T-cells. Here, we analyzed the prevalence of LAG3 rs870849 in B-cell lymphoma patients and the treatment outcomes according to the LAG3 genetic background and discovered that LAG3 germline variants may affect the risk of developing lymphoma and also affect the treatment outcome of DLBCL patients in the current CD19 CAR-T cell therapies. The LAG3 rs870849 was prevalent at high frequency in DLBCL patients. Significant differences in treatment outcomes to CAR-T cell therapy emerged in LAG3 I455hom versus I455Thet and T455hom carriers. The overall and complete response rates to CAR-T cell therapy were lower in the I455hom genetic subgroup with median PFS in the I455hom of 2 versus 20 months in the T455hom and I455Thet subgroups (p = 0.025). Median OS was 6 months in the LAG3 I455hom versus 41 months in the T455hom and I455Thet subgroups (p = 0.007). LAG3 rs870849 may affect treatment outcome in CAR-T cell therapy, with favorable outcomes in T455 carriers. Specific combinations of CTLA4 and LAG3 germline variants may cooperate to affect the response to CAR-T cell therapy. Full article

Electric arc furnace (EAF) waste, a mixture of dust and slag, was investigated as a potential secondary source of zinc. The waste primarily consisted of zinc and iron oxides, with the presence of refractory zinc ferrite, which hinders the complete recovery of zinc. This is the first study that examined the effect of mechanical treatment through high-energy planetary ball milling on the phase transformation, metal speciation, and leachability of the EAF waste. The raw material was characterized by particle size distribution, morphology, phase composition, and sequential extraction, and then subjected to milling at different rotation rates (100–400 rpm). The resulting powders were analyzed using XRD, SEM–EDS, and sequential leaching, and tested for acid (H₂SO₄) and alkaline (NaOH) leachability. Milling progressively reduced particle size, increased surface roughness, and induced structural changes, including the mechanical activation effect at low milling rates (100 rpm) and the synthesis of secondary franklinite at higher milling energies (200 rpm and 400 rpm). Sequential extraction revealed changes in zinc and iron speciation from acid-soluble to residual fractions for increased milling intensities. Leaching experiments showed rapid zinc dissolution in both acidic and alkaline solutions, while iron dissolved only in acid. The highest zinc extractions (67% in H₂SO₄, 55% in NaOH) were obtained from mechanically activated material at 100 rpm, while zinc leachability decreased for higher milling rates due to the induced mechanical synthesis of refractory phase. The kinetic model of leaching of the main components of the EAF was also established. Full article

Background: Remote ischemic conditioning (RIC) has shown promise as a neuroprotective strategy, but its application in children with cerebral palsy (CP) remains unexplored. We conducted a randomized controlled trial to evaluate the feasibility, safety, and tolerability of repeated, 6–7 sessions of RIC in children with unilateral CP. Methods: Fifty-one children aged 6–16 years with unilateral CP were randomized (1:1) to receive RIC or sham conditioning on the more affected arm. Primary feasibility outcomes included recruitment metrics, intervention adherence, retention, and protocol fidelity. Safety endpoints included continuous monitoring of oxygen saturation, blood pressure, heart rate, and adverse event incidence. Tolerability was assessed via child-reported pain ratings, conditioning pressure tolerance, skin integrity evaluations, and session adherence. Results: Of 148 children screened, 51 were randomized to RIC (n = 25), sham (n = 26) groups; 48 (94.1%) completed the intervention as allocated. Recruitment yielded 2.04 participants/month. Intervention adherence was 100% in both groups. RIC was well tolerated, with mean pain scores 2.8 ± 3.1 during inflation in RIC and 0.3 ± 0.8 in Sham group. No serious adverse events occurred. Physiological parameters remained stable across 314 conditioning sessions; no clinically significant hypoxemia, blood pressure derangements, or arrhythmias were detected. Minor adverse events (transient erythema, mild discomfort) were rare (2.22%) and self-limiting. Skin integrity was preserved, and no participants required session termination. Conclusions: Repeated RIC is feasible, safe, and tolerable in children with unilateral CP. These findings support the design of future trials using RIC as a priming agent to enhance pediatric neurorehabilitation outcomes. Full article

The design and production of goods have been completely transformed by additive manufacturing (AM), which makes it possible to create components with intricate and complex geometries that were previously impossible or impractical to produce. However, current technologies continue to produce coarse-surfaced metal components that typically exhibit fatigue properties, resulting in component failure and unfavorable friction coefficients on the printed part. Therefore, to improve the surface quality of the fabricated parts, post-processing of AM-created components is required. With emphasis on electroless nickel plating, ChemPolishing (CP), and ElectroPolishing (EP), this study investigates post-processing methods for stainless steel that is additively manufactured (AM). The rough surfaces created by additive manufacturing (AM) restrict direct use. While ElectroPolishing (EP) achieves high material removal rates but may not be consistent, ChemPolishing (CP) offers uniform smoothening. Nickel plating enhances additive manufacturing (AM) products’ resistance to wear and scratches and corrosion protection. To optimize nickel deposition, medium (6%–9%) and high (10%–13%) phosphorus nickel was tested using the L9 Taguchi design of experiments (DOE). Mechanical properties, including scratch resistance and adhesion, were evaluated using the TABER 5900 reciprocating (Taber Industries, North Tonawanda, NY, USA) abraser apparatus, a 5 N scratch test, and ASTM B-733 thermal shock method. Surface analysis was performed with the KEYENCE VHX-7000 microscope (Keyence Corporation, Itasca, IL, USA), and chemical composition before and after nickel deposition was assessed via the ThermoFisher Phenom XL scanning electron microscope (SEM, Thermo Fisher Scientific, Waltham, MA, USA) Optimal processing conditions, determined using Qualitek-4 software, Version 20.1.0 revealed improvements in both surface finish and mechanical robustness. This comprehensive analysis underscores the potential of nickel-coated additive manufacturing (AM) parts for enhanced performance, offering a pathway to more durable and efficient additive manufacturing (AM) applications. Full article

The linear construction model is characterized by resource-intensive processes that generate significant waste, whereas adopting circular economy principles facilitates sustainable, adaptable, and recyclable building practices to mitigate waste and conserve resources. The primary objective of this study is to empirically analyze the impact of barriers and drivers on sustainable construction practices and to evaluate the role of organizational culture in moderating this relationship. This study, grounded in Circular Economy theory, distributed 210 questionnaires using simple random sampling to large contractors (501–3000 employees) in Saudi Arabia’s Eastern Region, yielding 154 acceptable responses and a 73% completion rate. Data analysis was conducted using SmartPLS software, revealing that barriers, drivers and organizational culture positively impact sustainable construction practices, with organizational culture also positively moderating the connection among drivers and sustainable construction practices. However, organizational culture was not observed to substantially influence the connection between barriers and sustainable practices. The results highlight the main contribution of organizational culture in supporting sustainable development, offering significant theoretical contributions and practical implications for industry leaders and policymakers to develop regulatory framework and implement strategies that support sustainability. Full article

A novel inclusion complex of a fluorinated pyrazolopiperidine derivative (5-benzyl-7-(2-fluorobenzylidene)-2,3-bis(2-fluorophenyl)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo [4,3-c]pyridine hydrochloride, PP·HCl) with β-cyclodextrin (PPβCD) was designed, synthesized, and characterized as a potential therapeutic agent for chemotherapy-induced myelosuppression and lymphopenia. Encapsulation of PP within β-cyclodextrin increased aqueous solubility by approximately 3.4-fold and improved dissolution rate by 2.8-fold compared with the free compound. Structural analysis using IR, ^1H/^13C NMR, and TLC confirmed the formation of a stable 1:1 host–guest complex, and the disappearance of free PP signals further supported complete encapsulation. In vivo evaluation in a cyclophosphamide-induced myelosuppression model demonstrated that PPβCD accelerated hematopoietic recovery, restoring leukocyte and erythrocyte counts 35–40% faster than methyluracil, without any signs of systemic toxicity. These findings indicate that β-cyclodextrin complexation significantly enhances solubility, dissolution, and biological efficacy of the pyrazolopiperidine scaffold, supporting further preclinical development of PPβCD as a supportive therapy for chemotherapy-related hematological complications. Full article

Immunotherapy and RAF-targeted therapy have become standard treatments for melanoma, significantly improving outcomes compared to earlier therapies. When resistance to initial treatment develops, the older chemotherapy drug Dacarbazine is used. However, resistance to both therapies has emerged, promoting ongoing research to further enhance survival rates. Among various theories, autophagy is believed to play a critical role in acquired drug resistance, as increased autophagy has been observed in resistance to multiple anticancer agents. In this study, Dabrafenib was administered to melanoma cells with an RAF mutation, while Dacarbazine was given to cells with an Raf wild type. Both cell lines showed increased autophagy and FAO following treatment with the anticancer drugs. When FAO was blocked during drug treatment, melanoma cells became more susceptible to cell death. In xenograft models, B16F10 melanoma (Raf wild type) demonstrated regrowth due to acquired resistance after two weeks of Dacarbazine treatment. Conversely, a combination of Dacarbazine and the FAO inhibitors KN510 and KN713 (a combination of KN510 and KN713:KN510713) caused near-complete remission without regrowth. A375 melanoma (BRAF^V600E) developed resistance after four weeks of Dabrafenib treatment, yet the combination of Dabrafenib and KN510713 resulted in near-complete remission with no signs of regrowth. Based on these findings, combining FAO inhibitors with first-line therapies may be a promising approach for managing melanoma, regardless of RAF mutation status. Full article

Objective: This article evaluates the reconstructive potential and functional outcomes, as well as the risks and potential perioperative complications of using free flaps in patients with advanced-stage malignant laryngeal neoplasms who require salvage surgery and reconstruction. Additionally, it assesses the effectiveness of various flap harvesting and in-setting techniques, including the performance of microvascular anastomoses. Materials and Methods: This retrospective study included 13 male patients (age range 47–76 years) diagnosed with laryngeal neoplasms, who were referred to the Department of Otolaryngology at the University of Verona between 2017 and 2022. All patients underwent salvage total laryngectomy followed by concurrent reconstructive surgery utilizing microvascular flaps. Recovery of function (phonation) and incidence of complications were evaluated in a follow-up of at least three years. Results: Only one patient experienced necrotic failure of the microvascular free flap, probably due to post-op complications. The patient required revision on the 10th day after surgery and was reconstructed using a pedicled pectoralis major muscle flap. Two patients developed a pharyngocutaneous fistula. Other three patients had pharyngoesophageal stenosis, two experienced recurrence, and one patient passed away due to septic shock. All patients achieved satisfactory functional outcomes regarding vocalization, while complete oral intake was restored in eight patients. Conclusions: Considering the limited sample size, the findings suggest that microvascular flaps represent a feasible option for reconstructing advanced laryngeal tumors, though complication rate may still be considerable. Tailoring reconstructive approaches to individual patients may enhance surgical outcomes. Full article

High-quality playing surfaces enhance player experience and safety while serving as an appealing setting for spectators. Natural turfgrass provides optimal conditions at the beginning of the playing season but faces challenges under increasing field usage. Turfgrasses with high wear tolerance and quick recovery capacity are crucial for maintaining surface quality under intensive wear. Bermudagrass is the most used species in warm climates but needs winter overseeding in the transition zone. In Mediterranean climates, tall fescue (Schedonorus arundinaceus (Schreb.) Dumort, formerly Festuca arundinacea) has emerged as a promising species due to its tolerance to heat, drought, and salinity, alongside traits like deep rooting, shade adaptation, and wear resistance. The trial was conducted at the CeRTES experimental station in Rottaia, Pisa, Italy. Twenty-seven tall fescue cultivars and three cultivars of perennial ryegrass (Lolium perenne L.) were hand-seeded on 3 November 2022, at a rate of 43 g m⁻². The experimental design consisted of plots measuring 4.5 m² arranged in a randomized complete block design with three replications. The objective of the study is to evaluate the performance of twenty-seven cultivars of tall fescue with the aim of using the species in soccer fields with a permanent stand approach, with no need to manage spring and fall transitions. The field study encompasses determinations referring to the establishment stage, the maintenance at low cutting height stage (20 mm) and the subsequent stage of soccer use under different seasonal conditions (autumn, winter, and spring). Results showed that certain fescue cultivars, notably ‘Essential’, ‘Eyecandy’, and ‘FAG3/19-20208B’, exhibited quick establishment and adaptation to low cutting height (20 mm), and performed similarly to the reference ryegrasses ‘Gianna’ and ‘Mercitwo’ in terms of wear tolerance and recovery capacity across the three seasons. Moreover, most of the tested tall fescue cultivars performed well at a 20 mm mowing height, maintaining satisfactory quality and density. Among these, ‘Eyecandy’ and ‘Foxhound’ displayed finer leaf textures, comparable to those of the reference ryegrass. Full article

It is difficult to collect fine graphite particles because of the large size and small specific area of traditional flotation bubbles. The contrast experiment between nanobubble flotation and traditional flotation of micro-fine flake graphite in the Hegang area of Heilongjiang Province was carried out in this paper. Under the conditions of feed fineness 78% (−74 μm), pH 10.5, sodium hexametaphosphate 800 g/t, No. 2 oil 350 g/t, pulp concentration 10%, diesel 400 g/t, and pulp cycle time 3 min, the enhanced behavior of nanobubbles on micro-flake graphite flotation was discussed by studying the differences in the flotation rate, selectivity, pulp size, and concentrate size between traditional flotation and nanobubble flotation. The results showed that the nanobubble flotation completed the flotation 20 s earlier than the traditional flotation, and the final concentrate recovery of nanobubble flotation was 1.5 percentage points higher than the traditional flotation. In addition, the average particle size of the slurry from nanobubble flotation is 13 μm larger than that from traditional flotation. In addition, the minimum size of nanobubble flotation is only 2 μm, 11 μm smaller than the minimum size of traditional flotation. Nanobubbles effectively reduce the electrostatic repulsion between fine particles and enhance the hydrophobic attraction, making the hydrophobic aggregates of fine particle graphite more stable. At the same time, the presence of nanobubbles makes the surface hydrophobicity of graphite stronger, effectively promoting the recovery of fine particle graphite. Full article

Background/Objectives: Although neoadjuvant chemotherapy (NAC) is not universally recommended for resectable pancreatic ductal adenocarcinoma (PDAC), NAC with gemcitabine plus S-1 (NAC-GS) has become a commonly used regimen for resectable PDAC in Japan. Furthermore, the impact of achieving textbook outcomes (TO) in patients receiving NAC-GS remains unclear. Methods: This retrospective study included 265 patients who were diagnosed with resectable PDAC at our institution between January 2009 and December 2023. Patients were categorized into two groups: the NAC-GS group (n = 81; 2019–2023) and the upfront surgery (UFS) group (n = 164; 2009–2018). After comparing the clinical outcomes between groups, multivariate analyses for survival were performed. Additionally, outcomes stratified by the achievement of the modified TO were analyzed in the NAC-GS group. Results: The completion rate of NAC-GS was 90.1%. Patients in the NAC-GS group exhibited significantly longer survival than those in the UFS group (2-year recurrence-free survival: 61.4% vs. 37.9%, p < 0.01; 2-year overall survival: 83.2% vs. 61.2%, p < 0.01). Multivariate analyses identified lymph node metastasis, NAC-GS induction, and completion of adjuvant chemotherapy as factors significantly associated with improved survival. Moreover, among patients who received NAC-GS, those who achieved modified TO demonstrated significantly longer survival than those who did not. Conclusions: This study demonstrated the clinical efficacy of NAC-GS in patients with resectable PDAC. Induction of NAC-GS was significantly associated with improved long-term outcomes. In multidisciplinary treatment strategies for PDAC, achieving a modified TO may lead to improved survival of patients undergoing NAC-GS. Full article

Background: The impact of surgical resection on the survival and functional outcomes of patients with multiple brain metastases remains a critical question in neuro-oncology. Methods: This retrospective study involved 160 patients who underwent surgical resection of brain metastases from 2017 to 2020. Patients were classified by the number of metastases—single, oligometastatic, or multiple—and whether complete removal of the main symptomatic lesion was achieved. Outcomes such as survival rates, complications, and functional status were assessed. Results: Among the patients, 48.1% had a single metastasis, 21.9% were oligometastatic, and 30% had multiple metastases. Survival did not differ by number of metastases when the main lesion was completely resected and remaining lesions were radiated (p = 0.6172). Complete resection increased mean survival to 15.74 months compared with 4.5 months without it. Additionally, patients who underwent complete resection experienced fewer seizures (16.2% vs. 32.6%, p = 0.019), implying a lower seizure risk. Functional independence was maintained post-surgery. Conclusions: While multiple brain metastases are generally associated with poor outcomes, a trend toward longer survival was observed after complete resection of the index metastasis, though this was not statistically significant. Radiation of residual lesions remains important to support prognosis. Reducing the tumor volume is key to lowering seizure risk. This study supports the role of aggressive surgical interventions, paired with radiation, to potentially enhance outcomes in patients with multiple brain metastases. Full article

Background and Objectives: To evaluate the prognostic value of the Clinical–Pathologic Stage–Estrogen receptor status and Grade (CPS+EG) staging system, which combines clinical staging, pathological staging, oestrogen receptor (ER) status, and tumour grade in predicting survival outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant therapy (NACT). Materials and Methods: A retrospective review was performed on 245 female breast cancer patients who received anti-HER2 therapy alongside NACT at the Medical Oncology Department of Kartal Dr Lütfi Kırdar City Hospital, University of Health Sciences, from April 2012 to June 2024. The CPS+EG score was calculated using the MD Anderson Cancer Centre neoadjuvant treatment response calculator. Patients were categorised into two groups based on their CPS+EG score < 3 and ≥3. The primary outcomes assessed were disease-free survival (DFS) and overall survival (OS). Kaplan–Meier and log-rank tests were utilised for time-to-event analysis; Cox regression was used for multivariate analysis. A significance level of ≤0.05 was considered. Results: The median age of the patient cohort was 51 years (range: 27–82 years). Among these patients, 183 (74.6%) had a CPS+EG score less than 3, while 62 (25.3%) exhibited a score of 3 or higher. The median follow-up duration was 37.6 months. The pathological complete response (pCR) rate across the entire cohort was 51.8%. Specifically, the pCR rate was 56.3% in the group with CPS+EG scores below 3, and 38.7% in those with scores of 3 or higher (p = 0.017). Patients with CPS+EG scores less than 3 demonstrated superior overall survival (OS), which reached statistical significance in univariate analysis. Multivariate analysis identified the CPS+EG score as an independent prognostic factor for both overall survival and disease-free survival (DFS), with hazard ratios of 0.048 (95% CI: 0.004–0.577, p = 0.017) and 0.35 (95% CI: 0.14–0.86, p = 0.023), respectively. Conclusions: The CPS+EG score is an independent and practical prognostic marker, particularly for overall survival, in patients with HER2-positive breast cancer who have received neoadjuvant therapy. Patients with a CPS+EG score < 3 have higher pCR rates and survival rates. When used in conjunction with pCR, it can improve risk categorisation and contribute to the individualisation of adjuvant strategies in the post-neoadjuvant period. Due to its ease of calculation and lack of additional costs, this score can be instrumental in clinical practice for identifying high-risk patients. Our findings support the integration of the CPS+EG score into routine clinical decision-making processes, although prospective validation studies are necessary. Full article