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.

Antimicrobial resistance (AMR) in poultry-associated Escherichia coli (E. coli) is a persistent One Health concern, particularly when ESBL/pAmpC determinants co-occur with resistance to multiple antimicrobial classes. Between March and October 2024, we investigated commensal E. coli from three interconnected compartments of the poultry production chain in Bosnia and Herzegovina (parent-breeder flocks, commercial broiler farms, hatchery-associated material). A total of 333 samples were examined, and 99 E. coli isolates were recovered (29.7%). Phenotypic characterization included ESBL confirmation, disk diffusion susceptibility testing, and EUVSEC broth microdilution. Targeted real-time PCR assays were used to screen key ESBL/pAmpC-associated genes and selected carbapenemase and plasmid-mediated colistin resistance targets within the targeted panel. ESBL phenotypes were detected in 52/99 isolates (52.5%), and multidrug resistance was highly prevalent across compartments (93/99; 93.9%). ESBL/pAmpC-associated genes were detected in 91/99 isolates (91.9%), with blaTEM predominating. Gene pattern analysis indicated that blaTEM occurred most frequently as a single determinant and as part of the predominant multi-gene combinations, most notably blaTEM + blaCMY and blaTEM + blaCTX-M, while blaSHV was sporadic. Carbapenemase genes (blaKPC, blaNDM, blaGES, blaOXA-48) and mcr-1 to mcr-9 were not detected. Overall, our findings indicate a substantial ESBL/MDR burden throughout the poultry production chain, supporting the need for strengthening antimicrobial stewardship and biosecurity measures across both farms and hatcheries.

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.

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.

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.

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 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.

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.

OBJECTIVES Aortic stenosis (AS) is the most common valvular heart disease, with transcatheter aortic valve implantation (TAVI) now preferred for select severe cases. This study evaluated the early safety and performance of the new Myval Octacor Transcatheter Heart Valve (THV) (Meril Life Sciences), for which limited clinical data exist. METHODS The authors retrospectively analyzed 43 consecutive patients with severe AS who underwent TAVI using the Myval Octacor THV at a tertiary cardiac center. Primary outcomes included all-cause mortality, stroke, major vascular complications, conduction abnormalities, new pacemaker implantation, paravalvular leak, and valve failure at 30 days follow-up. RESULTS The median age was 81 years (IQR: 7), and 22 patients (51.2%) were female. Coronary artery disease was present in 24 (55.8%). Technical success rate was 100%. Mean pressure gradient decreased significantly post-procedure (55 mm Hg [IQR: 24] vs 5 mm Hg [IQR: 2]; P ≤ .001). No in-hospital deaths occurred. Two patients (4.7%) received permanent pacemakers during hospitalization, and 3 (7.0%) required pacemakers within a week because of conduction issues. Two patients (4.7%) experienced Bleeding Academic Research Consortium Type 3a bleeding. At 30 days, 42 patients remained in follow-up (98%), with 55% improved to New York Heart Association Class I. No vascular complications, stroke, acute kidney injury, valve thrombosis, or endocarditis occurred. One patient had valve failure from a significant paravalvular leak and 1 noncardiac death occurred 2 weeks post-discharge. CONCLUSIONS Early outcomes suggest that the Myval Octacor THV is a safe and effective option for TAVI in severe AS; however, larger studies with longer follow-up are required.