Search Results (5,663)

Background: Endothelial cells (EC), crucial components of the vascular system, are adaptable cells that maintain homeostasis and respond to pathological events through structural and functional plasticity. Hepatocyte growth factor (HGF) is a multifunctional cytokine that has been demonstrated to have protective and disruptive influence on the blood barrier function. In endothelial biology, its role is also poorly characterized. The present study explores the impact of supraphysiological concentrations of HGF on mouse brain endothelial cells (MBECs), scrutinizing how it alters their integrity and morphology. Methods: Two groups of MBECs—control (CTR) and experimental (EXP)—were analyzed at two time points: early passage (p5) and late passage (p41). The EXP-groups (p5 and p41) were treated with HGF at a concentration of 4 µL/mL. Cellular morphology was assessed with brightfield microscopy; protein expression and localization of the tight junction marker (ZO-1) and the endothelial marker (Factor VII related antigen/von Willebrand factor, vWf) were analyzed using Western blotting, immunocytochemistry, and confocal microscopy. Intercellular barrier function was estimated via Transendothelial Electric Resistance (TEER) and Transendothelial Dextran Permeability (TEDP) assays. Results: Microscopical analysis demonstrated a change in the morphology of the MBECs from a longitudinal, spindle-like shape to a rounded, more spheroid, cobblestone-like morphology under high-dose HGF treatment. Western blotting revealed a progressive decrease of ZO-1 expression in the EXP-groups. The expression of vWf did not show significant differences. Qualitative immunocytochemical staining: vWf showed consistent expression across all groups. ZO-1 displayed a punctate, well-defined membrane and cytoplasmic localization pattern in the CTR-groups at p5 and p41. In contrast, the p5 EXP-group demonstrated a shift to a more diffuse cytoplasmic pattern. At p41, the EXP-group displayed a markedly reduced ZO-1 signal with no clear-cut membrane localization. Confocal analysis: ZO-1: punctate membrane-associated localization in CTR-groups at p5 and 41. The EXP-groups at p5 and p41 confirmed the diffuse cytoplasmic ZO-1 distribution. Phalloidin: well-organized actin cytoskeleton in CTR-groups, but rearrangement and stress fiber disorganization in the EXP-groups, especially at p41. The merged images confirmed reduced co-localization of ZO-1 with actin structures. Barrier function: TEER values dropped significantly in HGF-treated cells. TEDP to small and medium molecular weight dextran increased markedly under HGF treatment. Conclusions: Our data demonstrate that supraphysiological doses of HGF in an in vitro MBEC-barrier-like model disrupt TJ organization, leading to morphological changes and functional weakening of the MBEC-barrier-like structure, as shown by uncoupling between ZO-1/F-actin cytoskeleton, reduced TEER, and increased size-selective paracellular permeability (TEDP). Full article

Background: Uniportal video-thoracoscopic lobectomy has improved postoperative outcomes in lung cancer patients. Thus, thoracic surgeons are increasingly required to learn this new approach. Methods: We evaluate the path of a single surgeon switching from triportal video-thoracoscopic lobectomy to the uniportal, using the cumulative sum (CUSUM) analysis, in a single center to assess the learning curve, enrolling 107 uniportal video-thoracoscopic lobectomies consecutively performed. CUSUM analysis detected how many uniportal video-thoracoscopies occur to obtain changes in mean operation time, among all procedures consecutively performed. CUSUM analysis identified the cut-off at the 67th procedure; this value was used to divide all patients into two groups: group A (first 67 patients, early phase) and group B (40 patients, experienced phase). Then, we analyze the perioperative outcomes between the two groups. Results: Gender characteristics of the two groups were statistically similar. Median operative time decreased significantly after the early phase [188 min (IQR: 151–236) vs. 170.5 (IQR: 134–202) (p-value = 0.02)], respectively. Similarly, during the second phase, the conversions rate decreased: [10 (15%) (group A) vs. 1 (2%) (group B) (p-value = 0.04)], as did the postoperative complications [28 cases (42%) vs. 9 cases (22%) (p-value = 0.04)] and the length of stay [6 days (IQR 5–9.5) vs. 5 days (IQR 4–8) (p-value = 0.04)], giving evidence of skills acquired in the second phase. Conclusions: CUSUM analysis identified 67 uniportal lobectomies, after which operative time, conversion rate, and perioperative complications significantly decreased; the moving average analysis further supports a progressive reduction in operative time. Despite prior multiportal video-thoracoscopic experience, switching to uniportal video-thoracoscopy requires a distinct learning process. Full article

Background: Antinuclear antibodies (ANAs) play a crucial role in diagnosing systemic autoimmune rheumatic diseases, particularly systemic lupus erythematosus. The recommended standard for ANA detection is indirect immunofluorescence testing (IIFT) using human epithelial (HEp-2) cells. Since visual interpretation (VI) of IIFT images is time-consuming and labor-intensive, research is focusing on automated interpretation systems that use artificial intelligence (AI). Methods: Consecutive serum samples (number of sera = 143) from routine clinical care were collected from patients visiting our tertiary rheumatology center. ANA were detected by IIFT with visual interpretation and compared with IIFT using the AI-based interpretation system akiron^® NEO (Medipan, 15827 Blankenfelde-Mahlow, Germany). ANA titer levels and patterns were analyzed according to the Competent Level of the International Consensus on ANA Pattern classification. Results: Agreement of positive/negative ANA discrimination between AI-aided and VI-IIFT at the recommended cut-off of 80 was good (Cohen’s kappa [κ] 0.69) but significantly different (McNemar test, p < 0.0001). At a cut-off of ≥1/80, the agreement was improved (κ 0.76) and the difference between both methods was non-significant (p = 1.0000). The ANA pattern recognition agreement between both approaches was moderate (κ = 0.54). The direct comparison using only the akiron^® NEO HEp-2 cell ANA assay revealed a good agreement (0.67), which improved to very good (κ = 0.80) when differences between ANA patterns anti-cell (AC)4/5 and AC2 were neglected. Notably, titer levels in the automated evaluations were frequently assessed at higher values than in the gold standard interpretation. Conclusions: Our study demonstrates a good agreement for positive/negative ANA discrimination. ANA pattern recognition by AI-aided interpretation showed moderate to very good agreement with VI. Further research and algorithm refinement (e.g., improved pattern recognition and titer calibration) are necessary to support its future implementation as a reliable screening method. Full article

Fibroblast growth factor 21 (FGF21), a pleiotropic hormone, is a significant modulator of energy homeostasis. We evaluated serum FGF21 levels in patients with a deficiency of mitochondrial aminoacyl-tRNA synthetase (mt-aARSs). Six patients with mitochondrial aminoacyl tRNA synthetase deficiency and twelve healthy volunteers were included in this study. Whole-exome sequencing was used for molecular diagnosis. Serum FGF21 levels in the case group and healthy volunteers were analyzed using the enzyme-linked immunosorbent assay. Exome sequencing test revealed nine different pathogenic variants in the AARS2, EARS2, DARS2, SARS2, and WARS2 genes. A statistically significant difference was found between the serum FGF21 levels of the case and control groups: case group (n = 6), 882.49 ± 923.60 pg/mL; control group (n = 12), 20.89 ± 2.63 pg/mL (p < 0.001). The area under the ROC curve for FGF21 in the differential diagnosis of mitochondrial aminoacyl-tRNA synthetase deficiency was 1.000 (0.813–1.000). Sensitivity and specificity were 100%, and positive and negative predictive values were also 100% for an FGF21 cut-off value > 27.4 pg/mL. Assessment of FGF 21 levels as an indicator of mitochondrial damage in mt-aARSs deficiency may provide insight into the level of damage. Investigation of the biochemical mechanisms underlying the different levels of damage caused by different aminoacyl tRNA synthetases will be important in terms of elucidating clinical heterogeneity. Full article

Early diagnosis by newborn screening (NBS) has contributed to improved outcomes in children with cystic fibrosis (CwCF). Georgia’s two-tiered algorithm consists of a fixed immunoreactive trypsinogen (IRT) cut-off followed by a 39-variant CFTR genetic panel. We conducted a retrospective review of CwCF born in Georgia from 2007 to 2022 to evaluate false negative NBS frequency. We characterized CwCF whose diagnosis was delayed beyond 28 days of age despite positive NBS. Six cases were detailed demonstrating the impact of missed and delayed diagnoses. We examined IRT trends from 2018 to 2022 and cut-off approaches. Missed case detection by expanded CFTR variant assays was assessed. Of 390 CwCF born in Georgia, 18 (4.6%) had false negative NBS—6 due to lack of CFTR variant detection and 12 due to low IRT values. Thirty children had delayed diagnosis, with the majority related to sweat testing. Minoritized children made up 19% of the population but 43% of missed and 44% of delayed diagnoses. Black and Hispanic infants had higher odds of missed or delayed diagnosis compared to non-Hispanic White infants (OR = 2.7, p = 0.027 and OR = 6.1, p < 0.001, respectively). Average IRT values varied across kits and were lower in warmer seasons. Expanded CFTR assays would reduce missed cases. Our results informed recommendations for improvement at multiple steps in the NBS process. Full article

Kapton-H type is an optical plastic with a UV-Vis-NIR spectrum characterized by abrupt absorbance change at a wavelength of ca. 550 nm. Such sharp optical discontinuity, known as the fundamental absorption edge, has been investigated using the Tauc plot method, and a band gap energy (E_g) of (2.22 ± 0.05) eV for an indirect allowed electron transition model has been found. The Cody plot has also been applied, and a slightly lower band gap energy value (i.e., E_g = 2.33 ± 0.05 eV) has been found. The Urbach rule applied to the spectrum tail has provided an Urbach energy value (E_U) of ca. (185 ± 2) meV, which is quite a high value that is fully compatible with the highly disordered structure of this sterically rigid semi-crystalline polymer. The cut-on wavelength (550 nm), visible transparency (T% of ca. 80), and other relevant optical characteristics of the Kapton-H type have been also evaluated and compared with corresponding values of polyetherimide. Full article

Background: Mitral annular plane systolic excursion (MAPSE) is a simple and widely used M-mode echocardiographic marker of left-ventricular longitudinal function that correlates well with left ventricular ejection fraction (LVEF). Conventional chronic right ventricle (RV) pacing is associated with left ventricle (LV) dysfunction, inducing heart failure (HF) and leading to the development of pacing-induced cardiomyopathy (PiCM). The aim of this study is to ascertain the clinical usefulness of MAPSE in the assessment of LV function in patients with permanent RV pacing. Methods: We performed a cross-sectional association analysis, enrolling consecutive patients with pacemakers and chronic RV pacing burdens over 20% (Vp > 20%) from 2021 to 2024. All patients were assessed by standard transthoracic echocardiography (TTE) with LVEF and MAPSE among other parameters being assessed. We performed a correlation test using linear regression and plotted an ROC curve. Results: 409 patients (mean age = 68.7 year) were included, 225 men (55%) and 245 (59.9%) with dual-chamber pacemakers. The mean follow-up period was 18 ± 2 months, with HF incidence in the study group being 23.2%. The results showed that average, septal, and lateral MAPSE all correlate well with LVEF, but septal values seemed to provide the strongest correlation (r = 0.90, p < 0.001), and that a septal MAPSE cut off value of <10 mm (sensitivity 99.4, specificity 42.1, AUC = 0.89) was associated with impaired LVEF (<50%). Conclusions: MAPSE seems to corelate well with LVEF across the spectrum of HF in pts with chronic RV conventional pacing. Septal MAPSE shows the strongest correlation with LVEF, and a value of <10 mm is a cut-off for altered LVEF, making it a potentially useful marker of cardiac function in these pts. Full article

Background/Objective: Malnutrition and sarcopenia are common complications after ischemic stroke and have a negative impact on prognosis. The C-reactive protein/albumin ratio (CAR) reflects both inflammation and nutritional status, but its predictive role in this setting has not been widely studied. This study aimed to investigate the predictive value of CAR (C-reactive protein/albumin ratio) for malnutrition risk and probable sarcopenia in patients with ischemic stroke. Methods: In this prospective observational study, 197 patients with acute ischemic stroke were evaluated. Patients with chronic renal or hepatic failure, malignancy, active infection, and hand disability preventing grip strength measurement were excluded. Demographic data (age, sex), vascular risk factors, the NIHSS score, and laboratory parameters were recorded. The nutritional status of patients was assessed using the Nutritional Risk Screening-2002 (NRS-2002), and sarcopenia risk was evaluated with the SARC-F questionnaire. Handgrip strength was measured in patients with high SARC-F scores to define probable sarcopenia. CAR was calculated from serum CRP and albumin levels. Logistic regression was applied to identify independent predictors, and receiver operating characteristic (ROC) analyses were performed to determine the discriminatory ability and cut-off values of CAR. The nutritional status of patients admitted to the neurology clinic with acute ischemic stroke was assessed using the Nutritional Risk Screening-2002 (NRS-2002), and sarcopenia risk was evaluated with the SARC-F questionnaire. Handgrip strength was measured in patients with high SARC-F scores to define probable sarcopenia. CAR was calculated from serum CRP and albumin levels. Logistic regression and receiver operating characteristic (ROC) analyses were performed. Results: Malnutrition risk was identified in 32.5% of patients, and probable sarcopenia was identified in 19.3% of patients. ROC analysis showed that CAR had acceptable discriminatory power for both conditions. In multivariate analysis, CAR was consistently identified as an independent predictor of malnutrition risk and possible sarcopenia. ROC analysis for malnutrition risk showed an AUC of 0.750 (cut-off: 0.306; sensitivity 68.8%; specificity 75.2%). In regression analysis, CAR (OR = 2.13; 95% CI: 1.39–3.26; p < 0.001), age (OR = 1.05; 95% CI: 1.02–1.09; p = 0.003), and NIHSS (OR = 1.11; 95% CI: 1.01–1.23; p = 0.026) were independent predictors. For probable sarcopenia, ROC analysis revealed an AUC of 0.814 (cut-off: 0.320; sensitivity 81.6%; specificity 71.7%). Multivariate analysis identified CAR (OR = 1.73; 95% CI: 1.19–2.52; p = 0.004), age (OR = 1.11; 95% CI: 1.05–1.18; p < 0.001), and NIHSS (OR = 1.19; 95% CI: 1.05–1.35; p = 0.007) as independent predictors. Conclusions: CAR was identified as an independent predictor of both malnutrition risk and probable sarcopenia in ischemic stroke patients. CAR may serve as a reliable biomarker for early nutritional and functional risk stratification in clinical practice. Full article

Pain assessment in cats is challenging, especially for non-veterinarians. Most validated acute pain scales are designed for clinical use, limiting their applicability for pet owners. This study developed a feline acute pain assessment scale for owners and evaluated its criterion validity, internal consistency reliability, and agreement with three veterinary scales: Glasgow Composite Measure Pain Scale-Feline (CMPS-Feline), Feline Grimace Scale (FGS), and Colorado State University Feline Acute Pain Scale (CSU-FPS). Of 146 enrolled cats, 130 were analyzed after exclusions. The owner-assessed scale showed strong correlation with CMPS-Feline (rho = 0.66) and moderate correlations with FGS (rho = 0.53) and CSU-FPS (rho = 0.57) (all p < 0.001). Agreement was substantial with CMPS-Feline (kappa = 0.74), moderate with FGS (kappa = 0.44), and fair with CSU-FPS (kappa = 0.28) (all p < 0.001). Internal consistency was acceptable (Cronbach’s alpha = 0.76). Receiver operating characteristic analysis demonstrated good discriminatory ability for identifying cats requiring analgesia, with area under the curve values of 0.87 (CMPS-Feline), 0.79 (FGS), and 0.75 (CSU-FPS). A cut-off score of 9 achieved 96% sensitivity and 78% specificity relative to CMPS-Feline. These results support the scale’s potential as a valid tool for pain detection by cat owners in non-clinical settings. Full article

Background: Recent hypotheses suggest that mutations associated with alpha1 antitrypsin (AAT) deficiency (AATD) may influence the clinical presentation and progression of cystic fibrosis (CF). This study employs a longitudinal design to determine the prevalence of AATD mutations and assess their impact on CF. Methods: The study Finding AAT Deficiency in Obstructive Lung Diseases: Cystic Fibrosis (FADO-CF) is a retrospective cohort study evaluating people with CF from November 2020 to February 2024. On the date of inclusion, serum levels of AAT were measured and a genotyping of 14 mutations associated with AATD was performed. Historical information, including data on exacerbations, microbiological sputum isolations, and lung function, was obtained from the medical records, aiming at a temporal lag of 10 years. Results: The sample consisted of 369 people with CF (40.9% pediatrics). Of these, 58 (15.7%) cases presented at least one AATD mutation. The AATD allelic combinations identified were PI*MS in 47 (12.7%) cases, PI*MZ in 5 (1.4%) cases, PI*SS in 3 (0.8%) cases, PI*SZ in 2 (0.5%) cases, and PI*M/P_lowell in 1 (0.3%) case. The optimal cutoff value for AAT levels to detect AATD-associated mutation carriers was 129 mg/dL in the overall cohort (sensitivity of 73.0%; specificity 69.2%) and 99.5 mg/dL when excluding PI*MS cases (sensitivity 98.0%; specificity 90.9%), highlighting the need for lower thresholds in clinically severe genotypes to improve case detection. The number of mild exacerbations during the follow-up appeared to be associated with AATD mutations. Conclusions: AATD mutations are prevalent in CF and may impact certain clinical outcomes. If systematic screening was to be planned, we recommend considering the proposed cut-off points to select the population for genetic studies. Full article

Background: Childhood obesity remains a significant public health challenge globally. Croatia ranks among the leading European countries in terms of childhood overweight and obesity prevalence. Methods: The present cross-sectional study analysed overweight and obesity prevalence trends from 2003 to 2022 on a nationally representative sample containing data from five studies, two independent studies and three WHO COSI rounds. Data from a total of 11,817 children aged 7.00–8.99 were analysed. Weight categories were defined using the IOTF and WHO cut-offs. Overweight and obesity prevalence rates and trends overall and by sex and region were calculated, and binary regression models applied to investigate the relationship between the risk of overweight and several variables. p-value < 0.05 was used to define statistical significance. Results: Temporal trends and associations were investigated using the IOTF reference values. The prevalence of overweight (including obesity) had increased steadily from 2003 to 2015, thereafter continuing to increase at a slower rate, whereas the prevalence of severe obesity reduced over time. Even though boys had slightly higher prevalence rates of overweight, the growth in overweight prevalence in girls over time was significant. At the regional level, the lowest prevalence rates were detected in the capital (City of Zagreb region). The risk of overweight was at least 50% higher in all the other regions in Croatia, and a rising trend in overweight risk with time was particularly high among children in the Adriatic and Northern regions. Conclusions: Despite a deceleration in the rate of increase in overweight (including obesity) prevalence, Croatia is yet to reach a plateau observed in some other European countries. Unearthed regional differences warrant further investigation. Full article

Background: Interleukin-6 (IL-6) is used as a marker for infection and inflammation. After liver surgery, IL-6 is also crucial for hepatic regeneration. The value of IL-6 serum-levels to differentiate infection from imminent post-hepatectomy liver failure (PHLF) remains unclear. This review focuses on IL-6 and complications after liver resections, specifically PHLF and infections. Methods: A systematic review was performed in the PubMed, Embase, and Cochrane libraries from January 2000 to June 2025 according to PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). All English language human data publications were assessed. Results: Overall, 12 studies (n = 589 patients) evaluating perioperative serum IL-6 levels were included. Six publications reported PHLF rates, and two specifically addressed IL-6, PHLF, and infection. Several patient and surgical parameters influence IL-6 dynamics. Despite five randomized trials being published, the overall study quality was low, with a high risk of bias. In particular, IL-6 on the first postoperative day was associated with PHLF and infections, but multivariable analyses of confounding factors are lacking. A meta-analysis of studies with a specific cut-off calculation was precluded by heterogeneous cohorts and endpoints. Conclusions: IL-6 levels may have early diagnostic value regarding imminent infectious complications or PHLF early after liver resection, but the evidence is exploratory and limited by methodological weaknesses. At present, IL-6 as a single marker does not seem to show sufficient clinical discriminatory potential to differentiate between infection and impaired hepatic regeneration. Future studies should address confounding factors, ideal timepoints of assessment, different methods of serum IL-6 assays, specific cut-offs, and multi-marker combinations. Full article

Coriander is a significant crop, playing an essential role in daily life for various purposes, including flavouring curries and medicinal uses, among others. Despite its importance, coriander is still harvested manually. To address this, developed a self-propelled battery-operated coriander harvester, designed with ergonomics, environmental sustainability and affordability for small and marginal farmers in mind. The harvester is equipped with a main frame, a lead-acid battery, a BLDC motor, a reciprocating cutter bar, a PU conveyor belt, a collection bag, a handle, and transport wheels. The harvester was tested on the coriander crop, and the results were analyzed using Design Expert software to optimize various operational parameters. The harvester’s performance was evaluated at three forward speeds: 1.5 km/h, 2 km/h, and 2.5 km/h, resulting in covered areas of 0.114 ha, 0.164 ha, and 0.22 ha, with field efficiency values of 76%, 82%, and 88%, respectively. Optimal harvesting conditions were identified by design expert software at a forward speed of 1.64 km/h, with a conveyor driving pulley at level 3 (50.8 mm) and a cutting height at level 2 (75 mm). Under these conditions, the harvester achieved a harvesting efficiency of 97.24% and a cutting efficiency of 98.2%, with minimal conveying loss of 0.96%. The theoretical field capacity was 0.16 ha/h, the actual field capacity was 0.131 ha/h, and the overall field efficiency was 81.8%. Full article

Ensiling high-moisture alfalfa with peanut vine not only avoids alfalfa nutrient loss during the wilting stage but also maximizes the use of agricultural waste peanut vine. The appropriate mixed ratio of high-moisture alfalfa and peanut vine has been studied in our previous study. However, the effect of additives on improving the nutrition and fermentation quality of the mixed silage of alfalfa and peanut vine has not been investigated. This study aimed to assess the adaptation and association of Lactiplantibacillus plantarum, cellulase and tannin in the mixed silage of alfalfa and peanut vine alone or in combination on fermentation quality, chemical composition, and microbial communities. The harvested fresh alfalfa and dry peanut vine were cut into 2 cm lengths by a crop chopper and they were thoroughly mixed at a ratio of 7:3. The mixtures were treated with no addition (CK), L. plantarum (Lp, 1 × 10⁶ CFU/g fresh weight), cellulase (Ce, 5 g/kg fresh weight), tannin (Ta, 40 g/kg dry matter), and their combinations (LpCe, LpTa, CeTa, LpCeTa). After 45 days of fermentation, silage treated with Lp, Ce, and Ta had lower pH and ammonia-N (NH₃-N) content and higher concentrations of lactic acid compared with the CK group. LpCeTa-treated silage inhibited protein degradation by reducing pH value and ammonia-N concentrations during ensiling processes. The LpCeTa group increased (p < 0.05) water-soluble carbohydrate (WSC) content and reduced (p < 0.05) acid detergent fiber and neutral detergent fiber contents in mixed silage. Furthermore, the LpCeTa group increased the relative abundance of Lactobacillus and decreased the relative abundance of Enterococcus and Weissella as compared with the CK group. Results of the current study indicated that the combined use of L. plantarum, cellulase, and tannin could serve as a promising strategy for the preservation of ensiling fresh alfalfa mixed with peanut vine and provide a reference for the re-utilization of by-product. Full article

The high hardness and toughness of AISI 4130 alloy present significant challenges during machining, including excessive cutting forces, rapid tool wear, and poor surface finish control. To address these issues, this study combines numerical simulation with turning experiments to systematically investigate the effects of tool geometry and cutting parameters on cutting force, temperature, and surface roughness. Through Deform-3D finite element modeling, one-factor, and orthogonal simulation tests, it was found that the optimal tool geometric combination (λs = 2°, κ_r = 99°, γ₀ = 5°) reduces the cutting forces by 21.86% as compared to the baseline parameters. Experimental validation showed that the agreement between simulated and measured cutting forces was 86.73%–87.8%, with simulated values being 10%–13.27% higher due to idealized boundary conditions. Surface morphological analysis by Bruker Contour Elite K shows that the surface roughness of the workpiece decreases with an increasing cutting speed and increases with an increasing feed rate and depth of cut. The above studies provide a certain research basis for optimizing the tool angle and improving the cutting efficiency. Full article