Search Results (5,647)

Background: Simultaneous pancreas–kidney transplantation (SPK) is the standard treatment for selected patients with type 1 diabetes mellitus and end-stage renal disease. Textbook Outcome (TO), a composite of perioperative and long-term quality indicators, provides a benchmark for optimal results. This study analyzed factors associated with failure to achieve TO after SPK. Methods: We retrospectively analyzed 119 SPK recipients (1980–2022). TO was defined according to IQTIG criteria: (i) patient survival ≥ 3 years, (ii) insulin independence at discharge, (iii) kidney function at discharge (GFR ≥ 20 mL/min), (iv) insulin-free survival ≥ 3 years, and (v) sustained kidney function ≥ 3 years. Predictors of TO failure were identified by logistic regression. Long-term survival was assessed by Kaplan–Meier analysis. Results: Ninety-two patients were eligible for TO assessment; 52% achieved TO. Compared with TO patients, non-TO patients had older donors (median 30 vs. 25.5 years, p = 0.017), older recipients (44 vs. 39 years, p = 0.012), longer kidney cold ischemia time (CIT; 13.0 vs. 9.7 h, p = 0.005), and more pancreatic complications (p = 0.009). In multivariate analysis, donor age (OR 1.050, p = 0.030) and kidney CIT (OR 1.180, p = 0.029) independently predicted TO failure. Cut-offs were donor age ≤ 37 years and kidney CIT ≤ 11.5 h. Patients achieving TO had significantly better long-term survival (15 years, p = 0.0077). Conclusions: Younger donor age and shorter kidney CIT independently predict TO achievement, which is associated with superior long-term survival. Optimized donor selection and perioperative management may improve SPK outcomes. Full article

Background: Tumor spread through air spaces (STAS) has been proposed as a histopathological marker of aggressive tumor biology in adenocarcinoma of the lung (ADCL). Its independent prognostic significance and clinical implications regarding surgical strategy remain controversial. This study evaluated clinicopathological correlates and the prognostic impact of STAS in a homogeneous cohort of resected ADCL. Methods: We retrospectively analyzed 100 patients with primary ADCL resected between 2009 and 2018. STAS was classified as absent, low (1–4 clusters), or high (≥5) by an experienced pathologist. Associations between STAS and clinical, surgical, and pathological variables were tested with univariate analyses and multivariable logistic regression. Overall survival (OS) was evaluated using Kaplan–Meier and Cox regression. Results: STAS was present in 46% of tumors and was significantly associated with a higher pathological N category (pN0-pN3; p = 0.005), more advanced UICC stage (p = 0.049), lymphovascular invasion (LVI; p = 0.008), and perineural invasion (PnI; p = 0.012). In univariate survival analysis, patients with STAS had shorter OS than patients without STAS (p = 0.047). After limited resection, OS did not differ (p = 0.864), whereas after radical anatomical resection, patients with STAS showed reduced OS (p = 0.034). In multivariable Cox regression analysis, STAS did not retain independent prognostic significance. Conclusions: STAS is frequent in resected ADCL and correlates with adverse pathological features and reduced OS in univariate models. In multivariate analysis, STAS did not emerge as an independent prognostic factor. These findings support the interpretation of STAS as a marker of aggressive tumor biology rather than an independent determinant of prognosis or surgical decision-making. Full article

Consumer exposure to chemicals in the EU is currently assessed separately for different products without aggregating exposure from different sources. A more integrated ap proach represents a promising opportunity to improve comprehensive risk evaluation and transparency across the value chain. This study develops aggregate consumer expo sure and risk assessment methods that involve calculation of exposure and risk for each pathway using the risk characterization ratio (RCR) as a uniform risk metric. Aggregate risk is obtained by adding up pathway-specific RCRs. The developed methodology re presents a new approach by evaluating exposure of seven population groups via all path ways and by using key input values normalized to body weight to reflect population-specific differences. The study demonstrates the practical applicability of the methodol o gy by assessing consumer exposure to the antioxidant ethylene bis[3,3-bis(3-tert-butyl-4-hydroxyphenyl)butyrate] (Hostanox^® O 3), resulting from its use in food and drinking water contact materials, textiles and sealants. This case study demonstrates aggregate RCRs well below one for all groups. The highest aggregate RCRs are found for infants and toddlers, reflecting their proportionally higher food consumption and skin surface area. The methodology is transparent and can easily be applied to other substances, e.g., by industry stakeholders and authorities, if the substance concentration in products can be established. This study may inform further development of aggregate exposure and risk methods in EU regulatory frameworks. Full article

Coari Lake is a critical area in the Amazon due to the oil exploration that began in the 1980s. The present study evaluates the impact on Coari Lake and the Solimões River in order to identify the origin of the sedimentary organic matter. This research is of great importance as it constitutes a crucial follow-up assessment, conducted 13 years after the initial survey by the same research group. Aliphatic hydrocarbons found in the new collected samples ranged from n-C14 to n-C34, with Cmax at C29–C31 and CPI values between 2.5 and 5.1, suggesting predominantly terrestrial biogenic inputs. Although the total n-alkane concentrations increased from 2012 to 2025, values remained within natural background ranges and as well as those ones associated with contaminated sediments. Aromatic hydrocarbons were strongly dominated by perylene, further supporting a biogenic origin. Monoaromatic and polyaromatic triterpenoids derived from α-amyrin, β-amyrin and lupeol were consistently detected, reflecting contributions from higher-plant material. No petrogenic indicators such as hopanes, steranes or unresolved complex mixtures were identified in any sample. Principal Component Analysis confirmed a temporal increase in hydrocarbon abundance while maintaining stable source signatures. Overall, the results demonstrate that Coari Lake sediments are still dominated by natural organic matter. Full article

Introduction: The global disease burden of aortic valve disease is already substantial and is projected to rise significantly in the coming decades. Aortic valve replacement (AVR) with a biological prosthesis has become highly popular and commonly used. This study aims to assess long-term outcomes after biological AVR with regard to structural and non-structural deterioration. Methods: In this single-centre retrospective study, 918 patients undergoing surgical AVR with a biological prosthesis at the University Hospital Frankfurt from January 2006 to July 2009 were included. The primary endpoints were freedom from reoperation and from structural and non-structural deterioration, and the secondary was long-term survival. Follow-up was completed in 95.6% with a median of 7.6 years, accounting 6610 patient-years. The mean age was 74.9 years and a median EuroSCORE II (range) was 3.34 (0.77–62.4). Twenty-two percent of surgeries were either emergent or urgent. Many patients had concomitant surgery, while coronary artery bypass grafting in 45.3% of patients was the most common. Three prosthetic valve models were used in our patient population: Carpentier Edwards Perimount (CEP) Model 2900, Model 3000 and Medtronic Mosaic (MM). Results: Reoperation occurred in 36 patients (3.9%) due to endocarditis (2.0%), aortic root aneurysm (0.1%), isolated or combined aortic stenosis or aortic regurgitation (1.9%). Freedom from reoperation at 5, 10 and 15 years was 97 ± 0.6%, 95.6 ± 0.8% and 90.3 ± 2.3%, respectively. Freedom from major stroke at 5, 10 and 15 years was 97.9 ± 0.0%, 96.4 ± 0.8%, and 96.1 ± 0.08%, and freedom from major bleeding event at 5, 10 and 15 years was 98.5 ± 0.4%, 95.7 ± 0.9% and 92.7 ± 2.2%, respectively. A subgroup analysis of the Carpentier Edwards (CEP) valves and the Medtronic Mosaic (MM) valves showed no significant differences regarding the primary endpoints. The overall survival at 5, 10 and 15 years was 67 ± 1.7%, 39.8 ± 1.8%, and 15.1 ± 2.2% respectively. The Kaplan–Meier survival estimator was 96 ± 2.2 months. Conclusion: This study showed a good long-term survival of surgical AVR with biological prostheses in relatively high-risk and elderly patient population. All biological prosthetic valves showed good long-term durability with low levels of complications and reoperations. The different models did not show any significant differences. Surgical AVR remains a valuable therapeutic option even though transcatheter aortic valve implantation has been greatly expanded since its introduction. Full article

This paper presents a modular evaluation questionnaire designed to assess Knowledge and Technology Transfer (KT) events in Higher Education Institutions (HEIs). KT is central to the HEI’s third mission, contributing to societal and economic progress. This mandate is critically highlighted by the need to disseminate digitalization competencies in rapidly evolving fields, notably immersive technologies—including Virtual Reality (VR), Augmented Reality (AR), and Mixed Reality (MR)—which are foundational for virtual worlds. Traditionally, transfer success relies on overall outcome indicators (patents, collaborations), which fail to capture the immediate impact of individual transfer events. Our questionnaire addresses this gap by evaluating event-level success and its alignment with the target groups: companies, citizens, and students. Developed via expert workshops in the context of virtual worlds, the tool’s modular design supports flexible adaptation and broad applicability across different event types. It captures participant reactions, knowledge acquisition, and behavioral intentions, along with process items. This provides immediate, actionable insights into event success, enabling HEIs to optimize resource allocation and make informed adjustments tailored to audience needs. Future studies should validate the questionnaire’s psychometric properties and assess long-term effects. Ultimately, this tool strengthens the capacity of HEIs to optimize transfer activities and cultivate stronger partnerships. Full article

Due to the increasing antibiotic resistance of microorganisms, chronic diseases, and cancer, new-generation drugs such as imidazole derivatives are being sought. Recent advances in nanotechnology enable the potential use of nanomaterials, especially nanoparticles, as drug carriers for such compounds, but also systems capable of crossing biological barriers. This study aimed to perform a preliminary toxicological assessment of nanoparticles containing BzIm-DEA ((Z)-5-benzylidene-3-[2-(diethylamino)ethyl]-2-phenyl-3,5-dihydro-4H-imidazol-4-one) embedded in chitosan films, using chicken chorioallantoic membrane (CAM) as an alternative in vivo test. Fertilized chicken eggs were treated with this therapeutic agent at various concentrations of BzIm-DEA and incubated until the 11th day of embryogenesis. No morphological abnormalities, angiogenesis-related disorders, or increased mortality were observed in any of the experimental groups. A significant increase in Apaf-1 mRNA expression was detected in CAM tissue at a dose of D3 BzIm-DEA, while no significant changes were observed for caspase-3 and catalase compared to the control group. Moreover, no changes in gene expression were observed in the liver. Immunohistochemical localization and analysis of PCNA and b-catenin expression in chicken embryonic liver did not reveal any dose-dependent changes. Within the scope of this preliminary assessment, chitosan nanoparticles loaded with BzIm-DEA did not produce gross acute embryotoxicity or major disruptions to angiogenic development under the tested conditions, providing preliminary evidence of biocompatibility as a nanoparticle carrier system. Full article

The territory of the Republic of Armenia (RA) lies within the central Arabia–Eurasia collision zone and is characterized by rugged mountain landscapes, complex geology, active faulting, and seismicity. Armenia is highly vulnerable to seismic and landslide hazards, with more than 2504 active landslides mapped in the country. A significant landslide in the Tumanyan Community, Lori Marz, was activated in January 2018 and threatened critical infrastructure, including the railway linking Armenia to Georgia and the M6 interstate highway. The landslide’s activation was driven by groundwater, a nearby water reservoir leak, and adjacent infrastructure. Preliminary hazard analysis revealed that further movement of the landslide could dam the Debed River, leading to potentially catastrophic downstream impacts. In response, the Minister of Emergency Situations of RA requested urgent studies by the Institute of Geological Sciences of NAS RA. Surveys began on 22 January 2018, involving an interdisciplinary approach including geotechnical study, UAV-based digital mapping, and application of geophysical methods, such as MASW, microtremor recordings, GPR, and VES. The combination of these methods provided reliable information on the landslide’s geotechnical structure, identified the sliding plane, and allowed for numerical slope stability modeling, which confirmed the landslide’s unstable condition and susceptibility to reactivation from earthquakes or elevated groundwater. Based on this complex research, protective measures were developed and applied, including, in particular, horizontal drilling to dewater the sliding plane. These emergency measures stabilized the landslide, mitigating immediate threats to infrastructure and ensuring relative safety. Full article

This paper evaluates a data-driven classification approach of operational wind turbine blades based on consecutive tower-radar measurements that are each compressed in a two-dimensional slow-time to range representation (radargram). Like many real-world machine learning systems, installed tower-radar systems face some key challenges: (i) transferability to new operational contexts, (ii) impediments due to evolving environmental and operational conditions (EOCs), and (iii) limited explainability of their deep neural decisions. These challenges are addressed here with a set of structured machine learning studies. The unique field data comes from a sensor box equipped with a frequency-modulated continuous wave (FMCW) radar (33.4–36 GHz frequency range). Relevant parts of the radargram that contribute to a decision of the used convolutional neural networks were identified by a class-sensitive visualization technique named GuidedGradCAM (Guided Gradient-weighted Class Activation Mapping). The following main contributions are provided to the field of tower-radar monitoring (TRM) in the context of wind energy applications: (i) every individual rotor blade holds a number of characteristic structural features revealed by the radar sensor, which can be used to discriminate rotor blades from the same turbine via neural networks; (ii) those unique features are not agnostic to changing EOCs; and (iii) pixel-level distortions reveal the necessity of low-level information for a precise rotor blade classification. Full article

Liquid biopsy (LB) offers a minimally invasive approach to characterizing and monitoring glioblastoma (GB), a tumor marked by extensive heterogeneity, limited surgical accessibility and rapid molecular evolution. By analyzing circulating tumor-derived components such as circulating tumor DNA (ctDNA), extracellular vesicles (EVs), circulating RNA species and circulating tumor cells (CTC), LB provides dynamic molecular information that cannot be captured by neuroimaging or single-site tissue sampling. Cerebrospinal fluid (CSF) currently yields the highest sensitivity for detecting tumor-specific alterations, while plasma enables repeat monitoring despite lower biomarker abundance. EVs have gained particular prominence due to their ability to preserve DNA, RNA, and protein cargo that reflects key genomic changes, treatment resistance mechanisms, and immune evasion. Although advances are substantial, clinical implementation remains constrained by low analyte concentrations, methodological variability, limited standardization and the high cost of testing, which is rarely reimbursed by insurers. This review summarizes current evidence on circulating biomarkers in GB and highlights research priorities essential for integrating LB into future diagnostic and therapeutic workflows. Full article

Background/Objectives: Progress in diagnostic and therapeutic strategies has resulted in an increasing prevalence of adults with congenital heart disease (ACHD), including those involving genetically determined syndromes. This study aimed to characterize prevalence, congenital phenotypes, heart failure (HF) stages, comorbidity burden, and current medical management of ACHD and concomitant genetically determined syndromes enrolled in a prospective HF-focused registry. Methods: The PATHFINDER-CHD Registry is a German-based (est. 2022) multicenter observational registry. This web-based platform consecutively tracks ACHD patients across the heart failure spectrum, including those with current or prior HF, as well as those at high structural or functional risk. HF stage was classified using a modified ACC/AHA scheme adapted for CHD; functional capacity was graded according to the Perloff classification. Baseline demographics, CHD anatomy, prior surgical/interventional treatment, cardiac and extracardiac comorbidities, and medication were collected from medical records. Results: Among 1987 enrolled ACHD, 107 (5.4%) had a genetic syndrome (n = 65, 60.7% women; mean age 33.5 ± 9.4 years; range 18–68). Most common syndromes were trisomy 21 (n = 49; 45.8%) and 22q11.2 deletion (n = 27; 25.2%); 31 patients (30.0) had rarer syndromes. Predominant CHD diagnoses were atrioventricular septal defect (n = 42, 39.3%), tetralogy of Fallot (n = 19, 17.8%), and pulmonary atresia with ventricular septal defect (n = 7, 6.5%). A systemic left ventricle was present in 102 (95.3%); 40 (37.4%) had primarily cyanotic CHD, and 7 (6.5%) an Eisenmenger physiology. Most patients (n = 71; 66.4%) had undergone definite surgical repair; 25 patients (23.3%) had at least one catheter intervention, including transcatheter valve implantation in 17 cases (15.9%). HF stage was mainly B (n = 30, 28.0%) or C (n = 75, 70.1%). Perloff functional class I/II was present in 97 (90.7%). Leading cardiac comorbidities included intrinsic aortopathy (n = 49, 45.8%), pulmonary arterial hypertension (n = 12, 11.2%), and arrhythmias (n = 10, 9.3%). Frequent extracardiac comorbidities were thyroid dysfunction (n = 34, 31.8%), kidney disease (n = 16, 15.0%), hyperuricemia (n = 13, 12.1%), and depression (n = 15, 14.0%). Pharmacotherapy was used in 66 patients (61.7%). Beta-blockers (n = 25, 23.4%) were common, while ACEi/ARB (n = 9, 8.4%), diuretics (n = 10, 9.3%), MRAs (n = 8, 7.5%), and SGLT2 inhibitors (n = 3; 2.8%) were infrequently prescribed; no patient received ARNI or digitalis. For targeted treatment of pulmonary arterial hypertension, phosphodiesterase-5 inhibitors (n = 7, 6.5%), endothelin receptor antagonists (n = 6, 5.6%), or prostacyclin analogues (n = 1, 0.9%) were used. As oral anticoagulants, vitamin K antagonists or direct oral anticoagulants (DOACs) were prescribed in 17 cases (15.9%). Forty-one patients (38.3%) received thyroid hormone replacement. Conclusions: Syndromic ACHD constitute a small but clinically high-risk subgroup within an HF-oriented registry, marked by complex CHD, substantial cardio–extracardiac multimorbidity (notably aortopathy, PAH, thyroid disease, renal dysfunction, depression), and low utilization of contemporary HF therapies. These data support specialized, interdisciplinary, longitudinal care pathways and prospective studies addressing outcomes and evidence-based HF management in syndromic ACHD. Full article

Endophytic fungi are a viable option for obtaining metabolites identical or analogous to those produced by the host plant. However, research on the ability of these microorganisms to biosynthesize these metabolites is still scarce, although important to enable their use for this purpose, contributing to the preservation of the host plant. The metabolomic study of fungal (Penicillium sumatraense, Penicillium miczynskii, Penicillium osmophilum, and Penicillium chermesinum) and plant extracts was carried out using UHPLC/ESI-MS/MS analyses combined with exploratory analysis by Molecular Networking (MN). Antioxidant activity by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical method was performed on fungal and plant extracts. The exploratory analysis by MN showed 75 MS features that were detected in the fungi and the host plant; of these, four compounds were putatively identified. The analysis showed 539 MS features with structural similarity to both biological matrices. Fungal extracts showed more promising antioxidant activities when compared to the plant extract. UHPLC combined with Molecular Networking proved to be a powerful strategy to guide the identification of microorganisms capable of biosynthesizing metabolites produced by the host plant. The strategy allowed for an early and efficient evaluation of crude extracts and provided unprecedented information regarding the chemical profile of A. jahnii and its endophytic fungi. Full article

Bovines are suitable hosts and can be affected by fly infestations. Flies pose a significant threat to cattle livestock in Latin America (LA), causing substantial economic repercussions to animal production (reduced productivity, veterinary expenses, and decreased animal welfare) and damage to human health. The most important flies affecting cattle in Argentina, Brazil, Colombia, Mexico, and Uruguay are Haematobia irritans, Dermatobia hominis, and Cochliomyia hominivorax. Due to production losses and the consequent economic costs associated with these flies, control measures must be implemented, primarily relying on insecticidal products. However, decision-making for preventing and treating animals with insecticides varies due to differences in environmental conditions across countries and regions, production systems, animal populations, infestation levels, animal welfare, and the prevalence of myiasis, among other factors. Although insecticides remain the most effective option for fly control in cattle, resistant populations have developed, rendering them less effective. To overcome fly resistance to insecticides, non-chemical (mechanical, environmental, biological, and genetic) methods are being integrated into alternative control and eradication strategies. The use of integrated livestock fly control contributes to safeguarding animal, public, and environmental health. This review is designed to support individuals and institutions, both civil and governmental, addressing the ongoing challenge posed by flies affecting livestock. Full article

Endothelial integrity is essential for cardiovascular health, and circulating endothelial progenitor cells, particularly endothelial colony-forming cells (ECFCs), are key contributors to vascular repair and maintenance. Long non-coding RNAs (lncRNAs) have emerged as novel epigenetic regulators of endothelial physiology and pathology. Building on our previous work identifying the lncRNA KLRK1-AS1 as a positive modulator of ECFC wound healing, we aimed to elucidate its role in endothelial biology. Cord blood-derived ECFCs were subjected to siRNA-mediated silencing of KLRK1-AS1, followed by blinded evaluations of monolayer morphology, barrier stability using ECIS impedance measurements, assessments of proliferation, and spheroid-based angiogenic activity. SiRNA-mediated silencing of KLRK1-AS1 induced detectable alterations in ECFC monolayer morphology (p = 0.047), while proliferation remained unaffected. Notably, KLRK1-AS1 knockdown significantly compromised endothelial barrier integrity, resulting in a 44% reduction in impedance after 48 h (p < 0.001), suggesting weakened intercellular contacts. In contrast, loss of KLRK1-AS1 enhanced angiogenic behaviour, demonstrated by an increased number of sprouts (+62%, p = 0.031). Together, these findings indicate that KLRK1-AS1 supports a quiescent, stable endothelial phenotype, with intact barrier function, while its depletion shifts ECFCs toward a more angiogenic, activated state. Our results identify KLRK1-AS1 as a previously unrecognised regulator of endothelial function. Full article

Aggressive metastatic progression often develops in bladder cancer patients with acquired cisplatin or gemcitabine resistance. The potential of the natural isothiocyanates allyl-isothiocyanate (AITC), butyl-isothiocyanate (BITC), and phenylethyl-isothiocyanate (PEITC) to inhibit adhesion and migration of cisplatin- or gemcitabine-resistant and sensitive RT112, T24, and TCCSUP bladder cancer cell lines was investigated. Parameters determined were: cell interaction with collagen or fibronectin, chemotaxis, and membrane receptors involved in adhesion (total and activated integrins β1, β4, β5, CD44s, and CD44v3-v7). CD44s’ location and adhesion- and migration-related signaling proteins were determined. AITC blocked adhesion of almost all sensitive and resistant cancer cells. PEITC and BITC suppressed fibronectin interaction of sensitive and resistant RT112. All three isothiocyanates diminished chemotaxis in all cell lines. Integrin expression was differentially altered but CD44s and CD44v were not altered. BITC and PEITC translocated CD44s from the cell membrane to cytoplasm. The tumor suppressor E-cadherin increased, whereas focal adhesion kinase (FAK), linked to integrin signaling, was deactivated after isothiocyanate treatment. Blocking FAK, β1, β4, or β5 was associated with reduced chemotaxis. Thus, AITC, BITC, and PEITC blocked adhesion and migration in cisplatin- and gemcitabine-resistant bladder cancer cells. This was associated with altered integrin expression and signaling, CD44s translocation, and enhanced E-cadherin. Full article