Search Results (979)

Before the American Heart Association introduced the cardiovascular–kidney–metabolic (CKM) syndrome concept in 2023, clinical care was largely organ-specific. This retrospective study analyzed diagnostic patterns and gaps in 406 patients with hypertension referred to and evaluated at the University Hospital Basel Hypertension Centre in 2017, 2019, or 2022 to identify blind spots in the assessment of cardio–kidney–liver–metabolic health. Electronic health records were used to assess CKM-relevant diagnostics, including lipid profiles, N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography, kidney function (estimated glomerular filtration rate: eGFR, urinary albumin-to-creatinine ratio: uACR), and hepatic assessment (Fib-4 score, abdominal ultrasound). Previously undetected conditions were identified according to contemporary criteria for dyslipidemia, chronic kidney disease (CKD), suspected heart failure (HF), diabetes, and suspected metabolic dysfunction-associated steatotic liver disease (MASLD). Although 94% of participants had laboratory data, key CKM parameters were inconsistently assessed. Of the participants, 39% had neither NT-proBNP measurement nor echocardiography, and 27% lacked hepatic ultrasound or sufficient data for Fib-4 calculation. Previously unrecognized comorbidities were common (suspected HF 21%, CKD 6%, suspected MASLD 3%). Lipoprotein(a) testing increased from 0% in 2017 to 23.7% in 2022, indicating growing awareness. Despite specialized care, diagnostic fragmentation persisted, underlining the need for systematic, interdisciplinary screening and informing the design of prospective registries such as the Swiss CKLM Registry to integrate patient-centered cardio–kidney–liver–metabolic care. Full article

The synergy between additively manufactured (AM) polymers and functional PVD coatings is crucial for advanced applications, yet the reliability of these hybrid systems is dictated by the residual stresses induced during deposition. This work presents the first in-depth, nanoscale profiling of residual stresses in Ti6Al4V and SS316 coatings on 3D-printed Acrylonitrile Styrene Acrylate (ASA) and Silicon (Si) substrates. A cutting-edge methodology combining Focused Ion Beam (FIB) milling with Digital Image Correlation (DIC), rigorously interpreted through the non-integral eigenstrain theory, is employed. Our findings reveal a consistent pattern of compressive stresses near the coating surface but expose a significant tensile stress peak at the coating-substrate interface, a feature not observed on reference silicon substrates. High-resolution electron microscopy and elemental analysis suggest that this stress concentration is associated with the presence of a thin, brittle oxide interlayer formed on the substrate surface. Furthermore, this study quantifies the dominant effect of the low-stiffness polymer substrate, which leads to a strain relief magnitude an order of magnitude higher than in rigid substrates. This work provides critical quantitative data on the failure-driving mechanisms in these emerging material systems and establishes a robust, optimized metrological protocol for their characterization. Full article

Background: Patients with metabolic syndrome represent a particularly vulnerable population for alcohol-related liver disease progression. However, real-world longitudinal data evaluating the impact of alcohol abstinence on liver fibrosis dynamics in this group remain limited. Methods: We conducted a prospective observational study including hospitalized adults with metabolic syndrome and chronic alcohol consumption. Clinical, laboratory, and non-invasive fibrosis markers—fibrosis-4 index (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), and transient elastography—were assessed at baseline and after 6 and 12 months of individual follow-up. Patients were classified according to alcohol consumption status during follow-up. Longitudinal and comparative analyses were performed. Results: At baseline, patients were classified as having alcoholic steatosis (56.3%), alcoholic steatohepatitis (25.0%), or alcoholic cirrhosis (18.7%). During follow-up, 72.9% of patients achieved sustained alcohol abstinence. Abstinent patients demonstrated significant improvements in liver stiffness, FIB-4, and APRI scores at 12 months (all p < 0.001), while non-abstinent patients showed progressive worsening of fibrosis markers. Gamma-glutamyl transferase levels were independently associated with fibrosis severity at baseline. Conclusions: This prospective real-world study suggests that alcohol abstinence is associated with favorable longitudinal changes in non-invasive liver fibrosis markers in patients with metabolic syndrome. Given the non-invasive nature of the diagnostic approach and the relatively small sample size, these findings should be considered hypothesis-generating. Further studies with larger cohorts are warranted to better elucidate the interaction between metabolic risk factors, alcohol consumption, and liver disease progression. Full article

Primary biliary cholangitis (PBC) is an autoimmune-mediated disease characterized by chronic, non-suppurative, small-duct lymphocytic cholangitis. The prognosis largely depends on early disease recognition and treatment. Suboptimal response to first-line therapy (ursodeoxycholic acid) is associated with risk for disease progression. Reliable biomarkers are also required to enhance risk stratification. The traditional gold standard for assessing fibrosis is liver biopsy, but it is invasive and unsuitable for serial evaluations. Hence, trends are towards non-invasive surrogate biomarkers (blood-based and imaging biomarkers respectively) which have a much better safety profile. Blood-based biomarkers include: (i) Fibrosis-4 [Fib-4], (ii) Aspartate Aminotransferase to Platelet Ratio Index [APRI], (iii) Enhanced Liver Fibrosis score [ELF], and (iv) total bile acid to platelet ratio [TPR]. They show much potential but are not particularly sensitive tests. Ultrasound-based imaging biomarkers are increasingly being utilized for liver stiffness measurement (LSM), with vibration-controlled transient elastography (VCTE) emerging as the preferred technique. However, despite its growing popularity, VCTE is limited by technical issues. Hence, currently, none of the non-invasive tests fulfill the prerequisites to be the new gold standard as defined by the FDA. Nonetheless, there may be value to combining LSM with various serum biomarkers such as Fib-4, APRI, as aforementioned. The hope is to create nomograms for predicting liver-related events and decision tree algorithms. Newer studies are investigating microbiota in the gut-liver axis, biomolecules such as nanovesicles/nanofibers, and metabolic reprogramming as it pertains to e.g., proteomics and lipidomics. These approaches hold much promise, and if validated, could significantly change the management of PBC. Full article

Silicon carbide (SiC) is the leading wide bandgap semiconductor for high-power and high-temperature electronics, but the high defect density still limits device performance. This study investigates how inclusions, Basal Plane Dislocations (BPDs), and Threading Screw Dislocations (TSDs) in 4H-SiC substrates affect epitaxial defect formation. Twenty 200 mm SiC wafers were analyzed after epitaxial growth in two industrial Chemical Vapor Deposition (CVD) reactors, one using Trichlorosilane/Ethylene (Reactor A) and the other Silane/Propane (Reactor B). Defects were characterized using Candela (KLA), Altair (KLA), XRTmicron LAB (Rigaku), SICA (Lasertec), and Crossbeam (ZEISS) dual-beam SEM system. Statistical correlation showed that the conversion rate of embedded particles decreases with particle depth and increases with particle size. Reactor A exhibited lower propagation rates, indicating better suppression of substrate-related defects. SEM/FIB-EDX analyses suggested that carbon inclusions generate pits while metallic inclusions induce triangular defects. Dislocation analysis confirmed a strong correlation between TSDs and BPDs with carrots and triangular defects. BPD conversion rates were estimated at about 98.3% (Reactor A) and 99.8% (Reactor B). These results emphasize the importance of substrate quality and buffer layer optimization to minimize defect propagation. Full article

Stormwater runoff represents a significant vector for the transport of organic pollutants and pathogens into aquatic ecosystems, posing serious environmental and public health risks. Although extensively employed for bank stabilization, traditional gabion structures demonstrate constrained efficacy in pollutant removal. In this study, an enhanced ecological gabion (EG) system was developed by integrating a stratified configuration of functional fillers (ceramsite, maifanite, and biochar) with vegetation (Iris germanica). This design leverages synergistic effects to enhance the concurrent removal of dissolved organic matter (DOM), particulate organic matter (POM), and fecal indicator bacteria (FIB) from simulated stormwater. The system was evaluated in continuous flow experiments through comparison with a traditional gravel gabion (TG). Results showed that, compared with the TG, the EG exhibited markedly enhanced removal performance, with chemical oxygen demand (COD), NH₄⁺–N, and TN removal efficiencies being approximately 2.48, 3.68, and 3.56 times those of the TG, respectively. In addition, the EG exhibited significantly higher removal efficiencies for both particulate organic carbon (POC) and dissolved organic carbon (DOC) than the TG, with increases of 329% and 137%, respectively. Fluorescence spectroscopy and particle size distribution analyses revealed that the EG effectively transformed and removed diverse DOM components and fine particulates. The stratified filler media synergistically enhanced pollutant retention, with biochar serving as the primary agent for nutrient and pathogen adsorption. These findings demonstrate the viability of the EG as an integrated, eco-friendly solution for enhanced stormwater purification in riparian zones, providing a compact and multifunctional alternative to conventional end-of-pipe systems. Full article

Lacustrine shales are key targets for shale oil exploration, yet the quantitative characterization of their complex and heterogeneous pore systems remains a significant challenge, constraining effective reservoir evaluation and development. This study investigates lacustrine shales from the Second Member of the Kongdian Formation by integrating N₂ adsorption, mercury intrusion porosimetry, and focused ion beam scanning electron microscopy with fractal analysis. A Mamba-based deep learning model was applied to improve two-dimensional (2D) pore segmentation, and three-dimensional (3D) pore surface point clouds were reconstructed for 3D surface fractal characterization to reduce artifacts associated with conventional 3D reconstruction. The results indicate that the pore system is dominated by inorganic pores, mainly irregular interparticle pores and dissolution pores, while organic pores are scarce. Pore sizes are predominantly concentrated in the range of 5 to 200 nm. Adsorption-derived fractal dimensions exhibit systematic lithofacies differences, with D₁ and D₂ averaging around 2.47 and 2.56, respectively. These trends are consistent with the 3D pore surface fractal dimension derived from pore surface point clouds (mean 2.48), which supplements the bulk statistical results with direct geometric quantification of surface roughness. The heterogeneity of the pore system is influenced by the coupled effects of mineral composition, organic matter content, and diagenesis. Specifically, the enrichment of clay minerals and dolomite increases the irregularity of pore morphology and results in higher fractal dimensions. In contrast, samples enriched in feldspars and calcite are supported by a rigid granular framework that corresponds to lower 3D surface complexity. Ultimately, these fractal dimensions effectively quantify pore network complexity and reservoir heterogeneity in the Kong 2 shales, offering quantitative support for reservoir characterization and lacustrine shale oil exploration. Full article

ZnMgAl layered double hydroxides (LDHs) were synthesised via coprecipitation, and oleic acid and stearic acid were grafted onto their surfaces via dehydration condensation to obtain two nano-lubricant additives, OA-ZnMgAl LDH and SA-ZnMgAl LDH. These surface modifications significantly improved the dispersion stability of ZnMgAl LDH in lubricating oil. Tribological tests showed that, at their respective optimal concentrations for friction reduction or wear resistance, ZnMgAl LDH, OA-ZnMgAl LDH, and SA-ZnMgAl LDH reduced the coefficient of friction by 3%, 20%, and 16%, and decreased the wear scar diameter by 7%, 9%, and 14%, respectively, compared with the base oil (XMP-Mobil 320). To clarify the lubrication mechanism, the wear morphology and chemical composition were analysed using 3D optical profilometry, X-ray photoelectron spectroscopy, scanning electron microscopy, and FIB-SEM. The results indicate that LDHs react with the steel surface under load and shear to form a multilayer protective film consisting of an inner oxide layer and an outer graphite layer, preventing direct contact between friction pairs. In addition, the rolling and filling effects of partially unreacted LDHs further reduce friction and wear. Full article

Background & Aims: The accurate, noninvasive assessment of hepatic steatosis is essential in living liver donor evaluation, where disease prevalence is low, and donor safety is paramount. This study evaluated commonly used noninvasive diagnostic tools for detecting hepatic steatosis in a real-world donor screening setting. Methods: We analyzed 108 living liver donor candidates (18–53 years) with complete MRI, CT, transient elastography (FibroScan^®), and biochemical data obtained during routine donor evaluation. Hepatic steatosis was defined as an MRI-proton density fat fraction (PDFF) ≥5%, which served as the noninvasive reference standard. Diagnostic performance metrics, receiver operating characteristic (ROC) analyses, and correlations with serum fibrosis indices (FIB-4 and APRI) were assessed. Results: MRI-PDFF identified hepatic steatosis in 21 donors (19.4%). Controlled attenuation parameter (CAP), measured by transient elastography, demonstrated high sensitivity (90.5%) and negative predictive value (97.1%), supporting its role as a rule-out screening tool. CT showed excellent specificity (97.7%) but lower sensitivity (61.9%), consistent with a confirmatory role when MRI is unavailable. Serum fibrosis indices were generally low and did not correlate strongly with imaging-based steatosis. Conclusions: In the low-prevalence setting of living liver donor evaluation, CAP-based transient elastography provides effective noninvasive screening for hepatic steatosis, while MRI-PDFF serves as a confirmatory reference when indicated. These findings support a stepwise, clinically practical diagnostic approach that prioritizes donor safety and workflow efficiency. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) commonly arises from chronic liver diseases that show progressing fibrosis and cirrhosis. The molecular mechanisms driving the transition from advanced fibrosis to overt malignancy remain poorly defined, representing a key knowledge gap in current hepatology research. This review delineates shared pathways like TGFβ/SMAD, WNT/β-catenin, Hedgehog, NOTCH, Hippo/YAP-TAZ and MAPK, linking fibrosis to HCC and opening avenues for dual antifibrotic/antitumor therapies. Results and Conclusions: So far, validated biomarker tools for fibrosis, like FIB-4, Enhanced Liver Fibrosis (ELF) and combined direct/indirect markers of liver damage and tissue remodeling, are used for fibrosis staging, while HCC detection leverages serum parameters like α-fetoprotein (AFP) or, more recently, multi-omics approaches (miRNA, cfDNA, metabolomics). Understanding the interconnection of these pathways can lead to novel targeted therapies (e.g., TGFβ inhibitors) that may show dual antifibrotic and antitumor activity in future studies. Full article

Knowledge about the potential roles of pets as reservoirs for plasmid-mediated quinolone resistance is still limited in Türkiye. Thus, in our study, the presence of plasmid-mediated quinolone genes (qnrA, qnrB and qnrS) was examined by multiplex Polymerase Chain Reaction (PCR) in 101 fecal Escherichia coli (Escherichia coli) strains isolated from healthy dogs. Moreover, the relationship between the presence of qnr genes and prevalence of quinolone resistance, extended spectrum beta-lactamase (ESBL) and plasmid replicon types, mostly detected among fecal E. coli isolates (F, K, FIB, N, FIA, FIC, and Y) were investigated. A total of 41 strains (40.6%) carried at least one qnr gene. Qnr genes were found in 38.8% of quinolone-resistant and 40.9% of quinolone-susceptible strains. ESBL production was detected in 27 strains, 10 of which also harbored a qnr gene. Among qnr-positive strains, 19 (46.3%) carried both IncK and IncF plasmids (p < 0.001). IncF plasmids were significantly more prevalent in quinolone-resistant strains than in susceptible ones (p < 0.001), suggesting a potential link between qnr carriage, quinolone resistance, and IncF plasmids. To our knowledge, this is the first study investigating the relationship between qnr genes and specific plasmid replicon types in E. coli from healthy dogs in Türkiye. Our findings suggest that domestic animals may serve as reservoirs for antibiotic-resistant E. coli, underscoring the importance of a One Health approach. Full article

The high reactivity of lanthanide metals poses a challenge to the electrochemical anodizing of surfaces for nanostructured coatings. This paper presents the first systematic experimental investigation of anodic oxidation of lanthanide gadolinium in aqueous solutions of citric, boric, oxalic, and tartaric acids. The voltage-current-time responses of anodizing of gadolinium, Al/Gd and Al/Nb/Gd systems were investigated. Anodic thin films were characterized using modern analysis techniques: SEM, FIB, and EDX. Morphology and voltage-current-time response analysis of anodized Al/Nb/Gd systems made it possible to establish the niobia cork-like effect and to develop a growth model. Full article

Background: Plasma fibrinogen (FIB) levels exhibit a significant elevation during the acute phase of ischemic stroke (IS), and their dynamic fluctuations serve as important biomarkers for stroke onset, disease progression, and long-term prognosis. Tong-Qiao-Huo-Xue Decoction (TQHXD) is highly effective in treating blood stasis syndromes affecting the head and face. Nevertheless, the association between TQHXD and FIB in the underlying mechanism of treating IS warrants further investigation. Methods: Proteomics analysis predicted the potential therapeutic targets of TQHXD for IS. An in vivo model of middle cerebral artery occlusion followed by reperfusion (MCAO/R) was created in mice. To explore the interaction between FIB and NLRP3, as well as to verify the particular healing outcomes of TQHXD. Results: An increased blood–brain barrier (BBB) permeability was observed after MCAO/R, accompanied by substantial accumulation of FIB in the brain. In vivo experiments demonstrated that FIB triggered the activation of the NLRP3 inflammasome in microglia. Proteomic analysis revealed a significant increase in FIB levels following model induction, which were markedly reduced after treatment with TQHXD; KEGG pathway enrichment analysis indicated that these changes were primarily associated with the NOD-like receptor signaling pathway. Laser speckle contrast imaging showed that TQHXD treatment significantly improved cerebral blood flow and attenuated brain injury in mice. Fluorescence imaging, ELISA, and Western blotting results collectively demonstrated that TQHXD effectively reduced FIB accumulation and suppressed NLRP3 inflammasome activation. MD and pull-down experiments further demonstrated a strong interaction strength between FIB and NLRP3. Conclusions: FIB accumulates in the ischemic penumbra following CIRI, while TQHXD can effectively down-regulate FIB expression and inhibit NLRP3 inflammasome activation to mitigate CIRI. These findings provide a novel theoretical foundation and treatment direction for stroke management in clinical settings. Full article

Background/Objectives: Non-invasive fibrosis scores are widely used for risk stratification in metabolic dysfunction-associated steatotic liver disease (MASLD); however, their performance in obese individuals remains controversial. The Fibrosis-4 (FIB-4) index is commonly recommended as a first-line tool, yet it may underestimate fibrosis risk in severe obesity. The BAST score, which incorporates metabolic and anthropometric parameters, has been proposed as an alternative. This study aimed to characterize both the degree and direction of discordance between FIB-4 and BAST in obese patients with MASLD. Methods: This predefined secondary analysis included 2950 adults with obesity (BMI ≥ 30 kg/m²) and MASLD from the multicenter OBREDI-TR cohort. Fibrosis risk categories were assigned using standard cut-offs for FIB-4 and BAST, and agreement was assessed using weighted Cohen’s kappa. Associations among discordance patterns, obesity class, and the visceral adiposity index (VAI) were evaluated using chi-square tests and general linear models. Results: Overall agreement between FIB-4 and BAST was very poor (κ = 0.041, p < 0.001). Discordance was observed in 22.3% of patients and increased markedly with obesity severity. In class III obesity, discordance was predominantly driven by low-risk classification according to FIB-4 despite high-risk classification according to BAST. Patients with this discordant pattern exhibited significantly higher VAI values than concordant cases (p < 0.001), independently of the study center. Conclusions: In obese patients with MASLD, particularly those with morbid obesity, FIB-4 frequently classifies patients as low risk, while BAST identifies elevated fibrosis risk. This systematic discordance suggests that FIB-4 may underestimate fibrosis burden in the context of severe obesity and visceral adiposity, supporting the need for a phenotype-oriented, multimodal approach to fibrosis risk assessment. Full article

This study addresses a long-term failure to achieve the good ecological status for fish fauna required by the European Water Framework Directive (WFD) in the salmonid–rhithral zone in Bavaria, Germany. To identify the causes, we compared extensive fish population data from the Eger River with data from its twin river, the Röslau. The proportion of autochthonous cold, oligo-stenothermic fish species is significantly lower in the Eger (4.97% vs. 37.31%). In addition, continuous water temperature measurements were taken at five locations from spring to early autumn in 2023. The Eger showed significantly higher water temperatures throughout the measurement period. In midsummer, differences in daily maximum temperatures exceeded 10 °C at the same altitude. The proportion of cold-water fish in the population appeared to be negatively related to the mean of summer water temperature peaks (MWTP) (R = 0.95, p < 0.01). Accordingly, restoration measures in the Eger would need to reduce the MWTP from the current 19.1–20.5 °C to at least 16–16.5 °C, which requires more detailed data on the thermal footprint of individual hydraulic structures. The anthropogenic thermal impact on the Eger was overlooked as the root cause of the problem for many years, which largely explains the ineffectiveness of previous restoration measures. At least within the salmonid–rhithral zone, we consider the ability of the standardized fish-based assessment tool (fiBS) to detect thermal deterioration to be sufficient, provided it is applied with due care. Full article