Introduction: Intracranial stenting during endovascular thrombectomy (EVT) is a common practice in the setting of failed reperfusion or severe stenosis. Immediate stent patency requires periprocedural antiplatelet therapy (APT). How APT intensity interacts with prior intravenous thrombolysis (IVT) to influence hemorrhagic risk remains uncertain. We aimed to assess whether the APT regimen modifies the association of IVT with early intracranial hemorrhage after intracranial stenting during EVT. Methods: This was a subanalysis of the RESISTANT registry, a multicenter, international, retrospective cohort (2016 to 2023) of adults with acute ischemic stroke who underwent intracranial stenting during EVT. APT regimens were categorized as conservative (intravenous or oral aspirin alone, or aspirin plus an oral P2Y12 inhibitor) and aggressive (any regimen including intravenous GPIIb/IIIa inhibitor or intravenous cangrelor). Four main groups were compared according to the APT regimen (conservative/aggressive) and the use of IVT (+/-). The primary outcome was a composite of sICH and parenchymal hematoma types 1 and 2 (sICH-PH2-PH1). Multivariable logistic regression models were used to evaluate the interaction between IVT and APT, adjusting for clinically relevant covariates. Results: Among the 823 included patients, 44 (5.3%) received conservative APT with IVT, 130 (15.8%) received conservative APT without IVT, 145 (17.6%) received aggressive APT with IVT, and 504 (61.2%) received aggressive APT without IVT. Among patients who received IVT, sICH-PH2-PH1 rates were 9.3% with conservative APT and 10.7% with aggressive APT; among those without IVT, rates were 3.2% and 9.9%, respectively. Administration of IVT (adjusted odds ratio [aOR] 5.84, 95%CI 1.07 to 43.92; p=0.05) and aggressive APT (aOR 4.81, 95% CI 1.41 to 30.22; p=0.03) were each associated with higher odds of hemorrhagic complications, with a significant IVT by APT interaction (P interaction =0.05; Figures 1 and 2 ). Within the aggressive APT plus IVT subgroup, sICH-PH2-PH1 occurred in 20% of patients treated with cangrelor and 6.1% treated with a glycoprotein IIb/IIIa inhibitor ( Figure 3 ). Conclusion: Among patients requiring intracranial stenting, aggressive periprocedural APT and prior IVT are each associated with higher hemorrhagic risk, with the combination showing the worst observed crude outcome. Prospective evaluation of protocolized APT pathways in the IVT setting is warranted.

In this study, a model was developed to calculate the power required for the circumferential cutting of solid wood in the longitudinal direction, considering the relevant technological parameters and mechanical properties of the wood. Based on measurements of different combinations and using the Response surface method (RSM) and Central composite design (CCD), a model was created that, in its derived version, considers the cutting width and depth, the diameter and speed of the tool, the number of cutting edges and sharpness of the cutting edge, the feed rate of the workpiece, and the density and moisture content of the wood. The model can be used to calculate the cutting power of various tree species with densities ranging from 400 to 700 kg/m3, moisture contents from 8 to 16%, and a wide range of cutting-edge sharpness, from a sharp cutting edge with a tip radius of 5 µm to a blunt cutting edge with a tip radius of 35 µm. The model is designed for a rake angle of 20°, the value most frequently used in practise. ANOVA analysis was used to determine the suitability of the model, which is highly significant with an R2 value of 0.93 and an average deviation of the calculated values from the measured values of 8.8%. The model is robust and therefore useful in the wood industry for predicting energy consumption in the processing of solid wood.

Pannexins are transmembrane glycoproteins that share structural and functional similarities with the gap junction proteins innexins and connexins. They play a critical role in paracrine and intracellular signalling, including purinergic signalling via the release of extracellular ATP. The role of pannexins in renal function and the pathophysiology of renal diseases is being intensely studied. However, there are no data on the subcellular localization of pannexin 1 expression in the rat kidney. We studied the distribution of pannexin 1 in the rat kidney, combining light microscopy with immunofluorescent immunohistochemistry and transmission electron microscopy with immunogold pannexin labelling. We found strong expression of pannexin in glomerular podocytes, proximal tubules and collecting ducts; moderate expression in the endothelium of glomerular and peritubular capillaries; thin descending and thick ascending limbs of the loop of Henle; and weaker pannexin 1 expression in the distal tubular epithelium. We described the detailed ultrastructural localization of pannexin 1 expression. This is the first study describing the ultrastructural distribution of pannexin 1 in the rat kidney, one of the most used preclinical models in renal physiology and pathology research. These results provide previously missing data on the precise distribution of pannexin 1 in the rat kidney, which is a prerequisite for a proper understanding of its role in renal physiology and pathophysiology.

Health literacy (HL) and physical literacy (PL) are hypothesized to be important determinants of physical activity (PA) in older individuals. The aim of the study was to evidence possible associations between PL, HL, and PA, evidencing structural comparison of exercising and nonexercising postmenopausal women. The sample included 62 females (+60 years of age) divided into exercising (E; n=37) and nonexercising groups (NE; n=25). Participants were tested on HL (via the European Health Literacy Survey Questionnaire), PL (via the Perceived Physical Literacy Questionnaire), and PA (via the Nordic Physical Activity Questionnaire – short) in controlled settings. Group-specific Pearson’s correlation matrices were calculated to examine associations among PL, HL, and PA. Between-group differences in correlations were tested using Fisher’s z-transformation with false discovery rate correction, and structural patterns were further explored using correlation network analysis. Fisher’s z tests identified significant between-group differences in selected associations, with E women showing a stronger bridging role of PL and weaker cognitive constraints on PA. Network analyses further demonstrated greater connectivity and cognitive dominance in NE women, whereas E women exhibited more differen- tiated and functionally organized relational structures. The results suggest that PA-related interventions targeting older women should move beyond information provision and explicitly promote PL development.

Objective: The objective of this study is to compare the analgesic effects of functional magnetic stimulation (FMS) and interferential current therapy (IFC) in patients with knee osteoarthritis (KOA) before and after treatment. Methods: This prospective pilot study included 30 patients with KOA, who were randomly assigned to two groups: FMS (n = 15) and IFC (n = 15). Both groups received 20 treatment sessions over four weeks. Pain intensity was assessed using the visual analog scale (VAS) pre- and post-treatment. Non-parametric statistical tests were applied due to the small sample size and non-normal distribution of the data. Results: In the FMS group, the median VAS score decreased significantly from pre-intervention (Me = 7.0; IQR, 5.0-7.0) to post-intervention (Me = 2.0; IQR, 1.0-2.0), with z = −3.43, p < 0.001. In the IFC group, there was also a significant decrease in the median VAS score from pre-intervention (Me = 7.0; IQR, 5.5-8.0) to post-intervention (Me = 5.0; IQR, 4.0-6.0), z = −3.47, p < 0.001. The Mann-Whitney U test demonstrated a statistically significant difference; the median ΔVAS was significantly higher in the FMS group (Me = 4; IQR, 3.5-6.0) than in the IFC group (Me = 2; IQR, 1.0-2.0) (U = 45, Z = −4.576, p < 0.001). Conclusion: FMS may be a more effective non-invasive treatment option for pain reduction in patients with KOA compared with IFC.

Introduction: Klotho acts as a coreceptor for the phosphaturic hormone fibroblast growth factor-23 (FGF-23) and exists in both a membrane-bound and a soluble form (sKlotho) found in blood and urine. Klotho protein is moderately expressed in kidney proximal tubule and more abundant in the distal convolution (DC), which includes the distal convoluted tubule (DCT) and connecting tubule (CNT). However, the function of Klotho in the DC, particularly its role in sKlotho release and regulation of mineral metabolism, remains unclear. Methods: scRNA-seq was performed on isolated mouse DC cells. Four novel gene-modified mouse models were generated with Klotho deleted in the entire DC, the late DCT/CNT, the DCT only, and pan-tubular. Results: Using scRNA-seq on isolated mouse DC tubules, we showed that Klotho is more abundant in the late-DCT/CNT than in the early DCT. The composite data from three DC specific Klotho knockout mice support DC to be the primary source of urinary sKlotho, with 80% coming from the late-DCT/CNT and only 20% from the DCT. Notably, mice lacking Klotho in the entire DC (Kl-KODC) maintained normal serum sKlotho, FGF-23, and phosphate homeostasis. Bulk RNA-seq of isolated fluorescent DC segments from Kl-KODC_Tomato mice revealed suppressed signaling by mitogen activated protein kinase and downregulation of several genes involved in kidney calcium ion handling (Trpv5, Vdr, Pth1r, Klk1). Consistently, the Kl-KODC mice exhibited profound hypercalciuria and reduced bone density. On the other hand, pan-tubular Klotho deficiency in mice led to severe phosphate imbalance and loss of both serum/urine sKlotho. Conclusions: DC-derived Klotho regulates urinary sKlotho levels and controls calcium ion reabsorption, while Klotho in proximal tubule maintains phosphate homeostasis and likely regulates circulating sKlotho levels.

Translocator protein (TSPO) regulates mitochondrial function, inflammation, and oxidative stress; however, its role in acute myocardial injury (MI) remains incompletely understood. While previous studies have examined TSPO ligands in cardiac injury, the interplay between TSPO modulation and nitric oxide (NO) signaling in AMI has not been systematically investigated. The aim of this study was to investigate the effects of TSPO modulation by PK11195, alone or in combination with nitric oxide synthase (NOS) inhibition by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME), on cardiometabolic, inflammatory, oxidative stress, and histopathological parameters in an experimental model of isoprenaline-induced MI in rats. Male Wistar albino rats were divided into four groups: control (C); isoprenaline + saline-treated (ISO); isoprenaline + PK11195-treated (IP); and isoprenaline + PK11195 + L-NAME-treated (IPLN) groups. Isoprenaline administration induced MI, evidenced by elevated cardiac biomarkers, electrocardiographic (ECG) alterations, and histopathological damage. PK11195 treatment significantly attenuated MI and reduced pro-inflammatory cytokine levels while increasing anti-inflammatory cytokine levels, indicating protective effects. Nevertheless, TSPO modulation was associated with adverse metabolic effects, notably elevated fibrinogen and plasma homocysteine levels. Co-administration of L-NAME mechanistically demonstrated that NO availability is essential for PK11195 cardioprotective effects, as NOS inhibition partially abolished cardioprotection and modified oxidative stress parameters. Overall, TSPO modulation exerts complex actions in acute MI through regulating mitochondrial function, inflammatory signaling, and NO pathways, suggesting that TSPO is a potential, multifaceted therapeutic target.

BACKGROUND Minimally invasive surgery is rapidly expanding globally, yet there is insufficient knowledge of how to scale this technology safely and equitably across diverse health systems. We aimed to identify health-system factors associated with safe implementation of minimally invasive surgery globally, using minimally invasive cholecystectomy as a tracer procedure. METHODS We conducted a multicentre, prospective cohort study of consecutive adults undergoing cholecystectomy between July 31 and Nov 19, 2023, in 1218 hospitals across 109 countries. Data were collected by more than 10 000 health-care workers using a core measurement set mapped to the WHO Health System Building Blocks and the Global Patient Safety Action Plan. The primary outcome was 30-day procedure-specific complications, with multilevel logistic regression used to examine associations between health-system features and patient outcomes. This study is registered on ClinicalTrials.gov (NCT06223061). FINDINGS Among 52 187 included patients, the adjusted procedure-specific complication rate varied 40-fold between hospitals, from 0·3% in the lowest risk quintile to 12·1% in the highest risk quintile. Despite large structural differences across income groups in access to minimally invasive surgery, diagnostics, and emergency services, country income level was not independently associated with complication rates (adjusted odds ratio [OR] 0·81 [95% CI 0·59-1·10] for upper-middle income vs high income and 0·99 [0·70-1·39] for lower-middle income or low income vs high income). Three modifiable hospital-level factors were strongly associated with safer outcomes: establishment of local simulation-based training facilities (adjusted OR 0·78 [0·71-0·86]; p<0·0001), adoption of intraoperative safety and communication strategies (0·87 [0·79-0·96]; p=0·0046), and on-site CT diagnostics (0·79 [0·65-0·97]; p=0·0220). Training facilities showed the greatest benefit in hospitals with limited infrastructure and an inexperienced workforce: the number needed to treat to prevent a procedure-specific complication was 21 (95% CI 14-35; p<0·0001). INTERPRETATION Safe implementation of minimally invasive surgery varies widely worldwide but is not defined by national income level; differences in outcomes reflect the ability of health systems to adopt and safely deploy new surgical techniques. We identified for the first time that the presence of local simulation-based training facilities is independently associated with improved patient outcomes. Simulation appears to be fundamental to the safe delivery of minimally invasive surgery, particularly in resource-constrained settings. Together with safety systems and diagnostic capacity, these findings offer actionable targets for health systems seeking to equitably scale up essential surgical technologies. FUNDING NIHR Global Health Research Unit and Wellcome Leap SAVE Programme.

Early identification of the risk of malignant transformation in oral potentially malignant disorders (OPMDs) is critical for improving outcomes in oral squamous cell carcinoma (OSCC). This comprehensive review examines immunological biomarkers obtained from minimally invasive oral cytobrush (OCB) specimens for the early detection of OSCC within a precision medicine framework. The objectives were to (1) identify and characterise key immunological biomarkers associated with early oral carcinogenesis; (2) evaluate the diagnostic utility of OCB sampling for detecting these biomarkers; and (3) explore the potential of OCB-based profiling to support personalised screening and patient management. The review highlights the potential advantages of OCB compared with conventional diagnostic methods, as reported in the literature, particularly its ability to capture early malignant changes through immunological analysis. Evidence is discussed for biomarker pathways related to cell-cycle and differentiation dysregulation (p53, Ki-67, CKs), inflammation-driven epithelial transformation (IL-1β, IL-6, IL-8, TNF-α), and immune suppression and checkpoint activation (PD-L1, B7-H6). OCB provides reliable and patient-friendly cyto-salivary samples that are suitable for immunological and molecular analyses. Aberrant biomarker expression detected in OCB specimens correlates with epithelial dysplasia and reflects early non-invasive neoplastic transformation, supporting the diagnostic value of integrated biomarker panels. Overall, OCB-based immunoanalysis represents a practical, non-invasive approach for the early detection of OSCC. Emerging technologies, including AI and multi-omics approaches, may further support the precision and predictive values of immunological analysis for OSCC. When combined with relevant biomarker pathways reflecting tumour biology and host immune responses, this strategy could offer a strong foundation for precision-medicine screening. It may also support personalised monitoring in patients with OPMDs.

This study aims to examine how the design of the work environment and its key dimensions—job design, employee involvement in goal setting and decision-making, as well as teamwork practices and open communication—affect productivity, organizational identification, and workforce stability in organizations in Bosnia and Herzegovina. Using a quantitative research approach and linear regression analysis on a sample of employees from the industrial sector, the results indicate that the work environment exerts a statistically significant and consistent effect on all observed outcomes. Among the analyzed components, employee involvement in decision-making proved to be the most significant factor, indicating that a sense of appreciation and the ability to influence one's own work have a strong effect on employees' motivation, loyalty, and willingness to stay in the organization. The results show that the impact of work environment design on employee performance is largely realized through strengthening employees’ connection to the organization. When the work environment is designed to ensure pleasant working conditions in which employees are actively involved in work processes, it becomes a powerful source of employee motivation and engagement. Therefore, a policy of adequately designing the work environment does not represent merely a short-term solution, but rather a realistic and sustainable approach to strengthening organizational stability and long-term success.

Modification of the contents of alloying elements with a narrower interval of Cr, Ni and Al can be obtained austenitic-martensitic steel 17-7PH which by, a subsequent heat treatment, can have values of mechanical and chemical properties required for components of automotive engine. Studies have confirmed that the rod dimensions 16mm made of steel 17-7PH with modified content of chromium, nickel and aluminum in combination with heat treatment solution annealing and precipitation hardening, gave values of mechanical properties, satisfying the requirements for steel with standard chemical composition.After aging was obtained martensitic austenitic microstru-cture, with a high percentage of martensite with a slight presence of delta ferrite.

This study explores first-year Electrical Engineering and Computer Science students’ use and perception of artificial intelligence (AI) tools in a programming course, and their preferences for future development. We conducted an anonymous exploratory survey, consisting of items with predefined response options and open-ended items. Responses to the former and open-ended items were analyzed using descriptive statistics and inductive thematic analysis, respectively. Additionally, we clustered students using the Affinity Propagation algorithm based on their expressed preferences for possible improvements of AI tools The findings show that AI tools are not universally effective, with seven student clusters identified based on differing needs and expectations. Students expressed a need for AI tools that offer more detailed error explanations and guidance rather than just delivering correct solutions. The most common concern among students is the provision of correct solutions without adequate explanations of the underlying mistakes, leading to a lack of deeper understanding This study takes an exploratory approach by examining students’ perceptions and preferences for the design and capabilities of AI tools in helping them learn programming. Clustering students by preferences reveals distinct approaches that may be needed for different groups of learners. Given the limited research on such desires or on applying clustering to them, our analysis offers valuable insights into distinct viewpoints that can guide the design of future personalized educational AI tools

Na temelju sačuvanih bilježaka Balda Bogišića i drugih dostupnih izvora rad analizira Bogišićevu ulogu u procesu pregovora o sadržaju bračnog ugovora između crnogorske princeze Jelene Petrović Njegoš i talijanskog prijestolonasljednika Viktora Emanuela III. Pregovori su održani u Rimu u listopadu 1896. godine, a rezultirali su potpisivanjem ugovora čije su odredbe uključivale niz pravnih, dinastičkih i međunarodnih pitanja. U radu se ukazuje na to kako je cijeli proces predstavljao diplomatsku misiju najviše razine u okviru koje su Bogišićev pravni autoritet i diplomatska vještina bili izrazito važni za zaštitu interesa Crne Gore.