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.

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.

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.

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.

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.

The integration of quantum key distribution (QKD) into data centers represents a promising advance in secure communications. As cyber threats evolve and the volume of sensitive information grows, strengthening intra-data center security has become a strategic necessity for ensuring confidentiality and operational resilience. This paper explores the application of an entanglement-based QKD method for securing intra-connectivity within data centers, focusing on deploying the BBM92 protocol in a controlled environment. We detail the system architecture, technical requirements, and operational considerations, and we report simulation results from a 100-block BBM92 run: an average sifted key of 1224 bits per block, with 25% used for QBER estimation, reconciliation disclosures of 352 bits, and privacy amplification removing an additional 13 bits, yielding a final secure key of 554 bits per block at an average rate of 52 bps. Across the run, 86 keys were delivered to applications, enabling 43 IKEv2/IPsec sessions, with an initial ramp-up before reaching steady, near-linear key service. These findings indicate that entanglement-based QKD can provide robust, quantum-safe key distribution for data center environments while highlighting practical integration challenges and performance trade-offs.

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.

Abstract Fibroblast growth factor receptor 2 (FGFR2) alterations have emerged as an important targetable oncogenic driver in a biologically distinct subset of biliary tract cancers (BTCs), particularly intrahepatic cholangiocarcinoma (iCCA), alongside other actionable genomic events such as IDH1 mutations, BRAF V600E, HER2 amplification and MSI-H. FGFR2 fusions and mutations define a distinct molecular subgroup whose prevalence varies across geographic regions and etiologic backgrounds such as liver fluke–associated disease. Clinical studies of both reversible and irreversible FGFR inhibitors have demonstrated meaningful activity in FGFR2-rearranged iCCA, while also highlighting a characteristic toxicity profile dominated by on-target hyperphosphataemia. Parallel translational work using cfDNA-based liquid biopsy has mapped a spectrum of secondary kinase-domain mutations that underlie acquired resistance, informing the development of next-generation FGFR2-selective inhibitors (eg, lirafugratinib) and combination strategies with EGFR/ERBB blockade. Collectively, these data underscore the need for comprehensive molecular profiling and innovative umbrella trial designs to optimise targeted therapy in this rare, biologically heterogeneous malignancy.

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 Out-of-hospital cardiac arrest (OHCA) is a major public health challenge, with survival to hospital discharge rarely exceeding 10%. This study evaluated the association of dispatcher-assisted CPR (DA-CPR), advanced life support (ALS) training, and physician experience with OHCA outcomes in Mostar, Bosnia and Herzegovina, a resource-limited emergency medical service (EMS) system. Methods We conducted a retrospective cohort study encompassing all OHCA cases recorded in the Mostar region between 2013 and 2022. Dispatcher-assisted CPR was formally implemented in early 2018. Accordingly, patients were stratified into two groups: the pre-implementation period (2013–2017) and the post-implementation period (2018–2022). The primary outcome was return of spontaneous circulation (ROSC) and the secondary outcome was survival to hospital discharge. Results A total of 308 OHCA cases were included. ROSC was achieved in 88 patients (28.6%), and 14 patients (4.5%) survived to hospital discharge. Following DA-CPR implementation, ROSC increased from 22.7% to 33.5%. In adjusted logistic regression DA-CPR (OR = 1.857, 95% CI 1.075–3.208) and ALS-trained physician involvement (OR = 1.802, 95% CI 1.045–3.105) were independently associated with ROSC. Physician experience was not associated with ROSC or survival to hospital discharge, and no examined exposures were associated with survival to hospital discharge. Conclusions Dispatcher-assisted CPR and ALS-trained physician involvement were associated with higher odds of ROSC, while none of the examined variables showed an association with survival to hospital discharge. Early resuscitation gains did not translate into final outcomes in this resource-limited EMS system. Improving survival will require coordinated system strengthening, particularly public-access defibrillation and standardized post-resuscitation care.