AIM To determine whether immunohistochemical B7-H3 expression is associated with magnetic resonance imaging (MRI)-derived tumour volume, peritumoral brain oedema volume, and oedema index in adult gliomas. METHODS This retrospective radiopathological correlation study included 99 consecutive patients with histopathologically confirmed intracranial gliomas surgically treated between 2013 and 2021. B7-H3 expression (clone RBT-B7H3, Bio SB, USA) was evaluated using staining intensity, percentage of positive tumour cells, and a composite immunoreactive score (IRS). Tumour volume (TV), peritumoral brain oedema volume (PTBE), and oedema index (EI) were calculated from orthogonal MRI measurements. Spearman correlation and crude and adjusted linear regression were used. Adjusted models included age, sex, tumour grade, and Ki-67. RESULTS Median TV was 29.31 cm3 (IQR 12.17-49.12), median PTBE was 84.51 cm3 (IQR 47.59-178.18), and median EI was 4.56 (IQR 3.83-5.00). B7-H3 IRS correlated strongly with TV (r = 0.921, p < 0.001) and PTBE (r = 0.920, p < 0.001), but not with EI (r = -0.105, p = 0.299). After adjustment, B7-H3 IRS remained associated with ln(TV) (beta = 0.228, 95% CI 0.190-0.265, p < 0.001) and ln(PTBE) (beta = 0.178, 95% CI 0.152-0.204, p < 0.001), but not with EI (beta = 0.001, 95% CI -0.083 to 0.084, p = 0.990). CONCLUSION B7-H3 expression is independently associated with MRI-derived tumour volume and peritumoral brain oedema volume in adult gliomas, but not with oedema index, supporting its relationship with absolute MRI-visible lesion burden.

AIM To evaluate the prognostic value of the CHA2DS2-VASc score in relation to major adverse cardiovascular events (MACE) and cardiovascular mortality in patients with non-ST elevation myocardial infarction (NSTEMI), and to assess its association with clinical and echocardiographic characteristics. METHODS This prospective, observational, cohort study included 311 NSTEMI patients admitted to the Internal Medicine Clinic at the University Clinical Centre Tuzla between January 2023 and April 2024. The patients were stratified into intermediate-risk (score < 4) and high-risk (score ≥ 4) groups based on the CHA2DS2-VASc score at admission. Demographic, clinical, and echocardiographic data were collected, including electrocardiography (ECG) and transthoracic echocardiography. All patients were followed for 3 months (90 days) to assess the occurrence of MACE and cardiovascular mortality. RESULTS The patients in the high-risk group were older and had significantly lower left ventricular ejection fractions and larger left atrial diameters compared with the intermediate-risk group. During the 3-month follow-up, MACE occurred in 11.9% of high-risk and 3.9% of intermediate-risk patients; cardiovascular mortality was observed exclusively in the high-risk group (2.5%). A higher CHA2DS2-VASc score was significantly associated with cardiovascular mortality (p = 0.003), but not with overall MACE (p = 0.393). Moderate predictive accuracy for mortality (AUC = 0.64) and shorter event-free survival in the high-risk group (log-rank p = 0.005) were observed. CONCLUSION The CHA2DS2-VASc score showed potential as a simple and accessible tool for early identification of NSTEMI patients at risk of cardiovascular death. Its significant association with mortality supports its role as a supplementary risk stratification tool, although these findings require validation in larger, multicentre studies.

AIM To investigate the relationship between coronary artery calcium (CAC) score and left ventricular global longitudinal strain (LV GLS) in patients with arterial hypertension who had a negative treadmill exercise stress test but mild to intermediate coronary stenosis on coronary computed tomography angiography (CCTA). METHODS A total of 53 hypertensive patients (mean age 54.8 ± 4.8 years; 50.9% male) with 30-50% coronary stenosis on CCTA were included. Patients with diabetes, malignancy, or established coronary/peripheral artery disease were excluded. CAC score, left ventricular ejection fraction (LVEF, Simpson's method), and LV GLS (speckle-tracking echocardiography) were measured. Groups were stratified by GLS (< 18.5% vs. ≥ 18.5%) and LVEF (< 60% vs. ≥ 60%), and CAC score differences were assessed using the Mann-Whitney U test. RESULTS The median CAC score was 27 (IQR 16-44.5), median LVEF 60% (IQR 58-63%), and mean GLS 19.37 ± 0.89%. No overall association was found between CAC score and LV function by LVEF or GLS. In patients with left anterior descending (LAD) stenosis (30-50%), reduced LV function was linked to significantly higher CAC score. Median CAC score was higher in patients with GLS ≤ 18.5% (157 vs. 44.5; p = 0.019) and LVEF <60% (157 vs. 44.5; p = 0.019). No significant associations were found in right coronary artery (RCA), circumflex artery (Cx), or three-vessel stenosis subgroups. CONCLUSION Higher CAC score in hypertensive patients with mild LAD stenosis and negative stress testing identify those at risk of subclinical LV dysfunction.

This text is a review of a book: Senadin Lavić, Semiotika Bosne: Etnofaulizam, nasilje i strah u krivotvorinama hegemonije, Unviersity of Sarajevo – Faculty of Political Sciences, Sarajevo, 2025.

This text is a report on the conference marking 35 years of the work of the European Commission for Democracy through Law (Venice Commission), held at Bocconi University in Milan on 15–16 May 2025.

AIM To determine the prevalence of irritable bowel syndrome (IBS)-related symptoms and associated factors among medical students in Bosnia and Herzegovina. METHODS This cross-sectional online survey included 176 medical students from the universities of Sarajevo and Zenica between November 2022 and December 2023. IBS-related symptoms were assessed using the Serbian-language Rome III questionnaire, and test anxiety using the Westside Test Anxiety Scale. Categorical variables were compared using Pearson's χ² test. RESULTS Eighty-four students (47.7%) met the symptom-based Rome III criteria. The IBS-related symptoms group included 75 females (89.3%) compared with 54 (58.7%) in the comparison group (p<0.001). Sweets consumption at least four times weekly was reported by 53 (63.1%) and 45 (48.9%) students, respectively (p = 0.021). Test-anxiety distributions differed between groups (p < 0.001); extremely high anxiety was reported by 12 (14.3%) students with IBS-related symptoms and one (1.1%) without symptoms. Other sociodemographic and lifestyle characteristics were not associated with IBS-related symptoms. CONCLUSION IBS-related symptoms were frequent in this medical-student sample and were associated with female sex, frequent sweets consumption, and test anxiety. The cross-sectional, self-reported design precludes causal interpretation and clinical confirmation of IBS.

AIM To determine if heat-not-burn (HNB) tobacco products are a safe alternative to cigarette smoking by inducing decreased decline of cardiorespiratory function. METHODS A clinical observational, cross-sectional study was conducted in the period between February and June 2025. It analysed and identified the effects of HNB tobacco products on cardiorespiratory symptoms in 60 adults below 55 years of age with confirmed arterial hypertension, 30 in the HNB users group (≥ 6 months of HNB use and no history of conventional cigarette use (CCU)), and 30 in the non-HNB user group (no history of HNB or CCU). RESULTS The gender distribution among the groups was similar. HNB tobacco product users reported significantly more respiratory (daily and nighttime shortness of breath, coughing) and cardiologic symptoms (choking, shortness of breath during physical activity). The following parameters were significantly reduced in the HNB tobacco product users: forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and forced expiratory flow at 75% (FEF75) (p = 0.01), SO2 (p < 0.001), pO2 (p = 0.001), HCO3- (p < 0.001), total cholesterol (p = 0.001), and basophils (p < 0.001), while the following parameters were significantly increased in the same group: right ventricular systolic pressure (RVSP) (p = 0.002), hsCRP (p < 0.001), monocytes (p < 0.001), eosinophils (p < 0.001), D-dimer (p < 0.001), and platelet count (p = 0.003). CONCLUSION HNB tobacco product use in adults with arterial hypertension was associated with worse cardiorespiratory symptoms, impaired pulmonary function, signs of early right ventricular dysfunction, and systemic inflammation.

AIM To evaluate and compare the effects of topically applied diclofenac, ketoprofen, and piroxicam on key inflammatory mediators, including interleukin-17 (IL-17), prostaglandin E2 (PGE2), and signal transducer and activator of transcription 3 (STAT3), in a rat model of collagen-induced arthritis (CIA). METHODS Thirty male Wistar rats were assigned to five groups: three experimental groups receiving topical diclofenac, ketoprofen, or piroxicam, respectively, a positive control group receiving a placebo patch, and a negative control group without collagen injection. CIA was induced using bovine type II collagen and incomplete Freund's adjuvant, with arthritis severity assessed through macroscopic scoring. NSAID patches were applied to the right hind paw for 6 hours daily over 5 days. Immunological parameters were quantified via enzyme-linked immunosorbent assay (ELISA). Statistical analysis included ANOVA, Kruskal-Wallis, and mixed-effects models to evaluate drug effects over time. RESULTS A significant difference was observed in tissue PGE₂ levels (F(4,25) = 4.235; p=0.009; η² = 0.404), with diclofenac showing significantly lower values compared to the negative control and ketoprofen groups, while no significant differences were found for IL-17 or STAT3. CONCLUSION Topical NSAIDs demonstrated selective anti-inflammatory effects, primarily through significant suppression of tissue PGE₂, confirming effective local COX pathway inhibition. The absence of significant changes in IL-17 and STAT3 suggests that short-term topical therapy mainly targets prostaglandin-mediated inflammation rather than upstream cytokine or transcriptional pathways involved in rheumatoid arthritis pathogenesis, warranting further investigation into their long-term therapeutic benefits.

The study aimed to assess the motivational level of female football players participating in the National Championship by determining the Global Motivational Force (GMF) based on intrinsic and extrinsic factors. Motivation, understood as the internal drive that provokes, supports, and directs human activity, represents a key determinant of sports performance and a significant performance generator. This study followed a quantitative, cross-sectional research design. A questionnaire containing 14 items related to intrinsic and extrinsic motivational factors, validated by previous studies, was administered to 152 female athletes competing in the 2024 Women’s National Championship. The data were analysed to quantify the overall motivational level and identify dominant motivational sources. Findings revealed that 73% of the participants rated intrinsic motivational factors as “very important,” emphasising passion for the sport, athletic aspirations, and self-sufficiency. Extrinsic factors, including material benefits and the coach’s leadership style, were considered highly important by 70% of the athletes. The Global Motivational Force (GMF) was calculated as 5.61, and the Global Motivational Instrumentality (GMI) as 5.32, indicating a high level of intrinsic motivation complemented by valuable external incentives. Intrinsic motivation plays a decisive role in female football players’ engagement and performance, while extrinsic motivators also significantly contribute to maintaining their commitment and success in competitive sports.

Aims: The aim of this study was to quantitatively evaluate and compare the antioxidant activity of ethanolic extracts of lemon and grapefruit peels, as well as their mixture, using the DPPH spectrophotometric method, and to assess their free-radical-scavenging activity at different concentrations. Study Design: A laboratory-based quantitative experimental study was designed to evaluate the antioxidant activity of the samples. Methodology: Ethanolic extracts of lemon peel (Citrus limon), grapefruit peel (Citrus paradisi), and their mixture were prepared. Antioxidant activity was determined using the DPPH (2,2-diphenyl-1-picrylhydrazyl) spectrophotometric method by measuring absorbance at 517 nm. Different extract concentrations (approximately 10–50 μL, according to the experimental design) were tested. The relationship between concentration and absorbance was analysed using linear regression. Results: All tested extracts exhibited concentration-dependent antioxidant activity. Lemon peel extract had the highest absorbance values (approximately 0.20 at 20 μL, 0.33 at 30 μL, and 0.53 at 50 μL), indicating the strongest antioxidant activity among the samples. Grapefruit extract had lower absorbance values (approximately 0.09 at 10 μL, 0.11 at 20 μL, and 0.24 at 50 μL), whereas the mixture exhibited intermediate values (approximately 0.11 at 10 μL, 0.19 at 30 µg/mL, and 0.26 at 40 μL). Strong linear correlations between concentration and absorbance were observed, with coefficients of determination (R²) of 0.9979 for lemon, 0.9852 for grapefruit, and 0.9804 for the mixture, confirming the reliability of the method. Conclusion: All tested extracts exhibited significant antioxidant activity, which increased with increasing concentration. Lemon peel extract showed the highest antioxidant activity, followed by the extract mixture, whereas grapefruit peel extract demonstrated the lowest activity. The results confirm the reliability of the DPPH method for assessing the antioxidant capacity of plant extracts and indicate the potential application of citrus peels as a natural source of antioxidants in the food, pharmaceutical, and cosmetic industries.

Neonatal screening using Dried Blood Spot (DBS) cards is an important and successful public health facility in Europe, enabling early detection of congenital disorders for early treatment and prevention of overt disease. Biobanks of stored DBS cards offer significant potential for biomedical research. Biobanking and secondary use of DBS cards also raise ethical and legal issues, particularly concerning the rights of parents and children. This study provides a comprehensive overview of legislation and legal practices governing DBS biobanking across 29 European countries, based on a survey conducted in collaboration with the International Society for Neonatal Screening. Findings reveal a highly heterogeneous landscape: 15 countries have national legislation, five have regional guidelines, and nine lack formal regulations. Only four countries require explicit parental consent for DBS storage, with considerable variation in approval processes for research use. A harmonization of practices, with the European General Data Protection Regulation (GDPR) as a basis for future regulation, supplemented by clearer guidance on ‘public interest’ and robust safeguards for individual rights may lead to more transparent and consistent governance, which is essential to balance scientific progress with the protection of parental and children’s rights in DBS-based research across Europe.

Abstract Androgen receptor splice variant 7 (AR-V7) is associated with resistance to androgen receptor-targeting therapies in prostate cancer, but its prevalence and clinical relevance in non-prostatic cancers remain incompletely characterized. A systematic review was conducted in accordance with PRISMA guidelines. Thirty-four studies, including 4855 clinical cases and 60 cell lines, were included. Overall, AR-V7 positivity was reported in 948/4855 clinical cases (19.5%); however, this represents a descriptive estimate across heterogeneous tumor types, study designs, and detection methods. Breast cancer accounted for 4057 of 4855 clinical cases (83.6%) and 815 of 948 AR-V7-positive cases (86.0%), with a within-cancer prevalence of 20.1%. However, after excluding the TCGA cohort in which AR-V7 was inferred through splice-junction analysis, the prevalence of AR-V7-positive breast cancer decreased to 9%. Higher tumor-specific proportions were observed in salivary duct carcinoma (55.2%), hepatocellular carcinoma (57.1%), and non-muscle-invasive bladder cancer (82.6%), but these estimates were based on smaller cohorts and should be interpreted cautiously. AR-V7 was present in several treatment-naive non-prostatic cancers, suggesting that it may represent a preexisting molecular feature in selected contexts. Current evidence suggests that AR-V7 warrants further investigation as a candidate biomarker. Standardized detection methods and prospective studies are needed before its clinical utility can be established.

BACKGROUND Luminal proteases have been implicated in epithelial barrier dysfunction and visceral hypersensitivity in irritable bowel syndrome (IBS), yet their impact on the enteric nervous system (ENS), the principal regulator of gastrointestinal function, remains unknown. OBJECTIVE To investigate whether faecal mediators differentially activate enteric neurons across IBS subtypes and whether proteolytic and proteomic profiles explain neuronal phenotypes. DESIGN The effects of faecal supernatants (FSN) from 21 IBS-D (diarrhoea-predominant), 9 IBS-C (constipation-predominant) and 18 healthy control (HC) patients recruited across centres in three countries on guinea pig distal colon submucous plexus neurons were assessed using a neuroimaging technique. Faecal proteolytic activities and proteomic profiles were analysed. RESULTS IBS-D and IBS-C supernatants evoked significantly stronger neuronal activation than HC, demonstrating that FSN directly modulate ENS. In IBS-D, but not IBS-C, effects were mediated by serine and cysteine proteases and PAR-1. Proteome analysis revealed a significant difference in 47 proteins between IBS-D and HC, including several immunoglobulin components, underlying the role of microinflammation in IBS-D. A combination of amylases, trypsin-2 and an immunoglobulin protein demonstrated high diagnostic performance to distinguish IBS-D from HC. CONCLUSION These findings uncover a previously unrecognised luminal-ENS axis in IBS and reveal fundamentally different pathological mechanisms between IBS-D and IBS-C. IBS-D is characterised by proteases and PAR-1-dependent neuronal activation and a distinct immune-enriched faecal proteome, whereas mediators in IBS-C act independently of these factors. These findings establish a functional link between faecal protease activity, ENS signalling and molecular biomarkers, highlighting new therapeutic and diagnostic avenues for subtype-specific management of IBS.

The Internet of Things (IoT)-enabled smart healthcare systems improve quality of life (QoL) but face more threats leading to an increase in abuse of the system. A key security technique is four-step threat modelling during system design, based on the four-layer IoT reference model. The objective of this article is to provide a review of studies published in the period 2014–2025 utilizing Google Scholar, IEEE Xplore and Web of Science. The search was conducted using the following keyword combinations: (threat modelling OR threat analysis) AND (Internet of Things) AND (smart healthcare). The review is based on 19 studies dealing with practical threat modelling or analysis of smart IoT healthcare systems. The reviewed studies reveal that threat modelling is rarely subjected to systematic validation, leaving it largely theoretical rather than practical. This recurring pattern highlights a methodological limitation that reduces the applicability and impact of current research. Moreover, they show that current research seldom addresses higher-level, context-rich layers where privacy, safety and QoL impacts are most significant. This consistent focus on lower layers suggests a systemic limitation, as threats propagate across multiple levels. Lack of automation, reliance on new technologies and no standardized methodology may explain why many studies fail to cover all security layers and threat modelling steps. To tackle IoT-enabled smart healthcare security issues, four solutions are proposed: (i) embedding thorough threat modelling into healthcare policies, (ii) performing comprehensive four-step threat modelling for IoT healthcare systems, (iii) developing a standardized approach and (iv) fostering automated, industry-specific threat modelling frameworks.

Colorectal cancer remains a leading cause of cancer-related mortality worldwide, with automated polyp classification from endoscopic images offering a promising avenue for improving early detection. Existing approaches rely on single convolutional neural network (CNN) backbones with manually designed classification heads, limiting both representational capacity and deployment flexibility. This paper presents a swarm intelligence-augmented multi-backbone deep learning framework for eight-class gastrointestinal lesion classification on the Kvasir benchmark. Four CNN backbones (ResNet50, DenseNet121, MobileNetV2, EfficientNetB3) are independently fine-tuned using a two-phase transfer learning protocol and their penultimate-layer features concatenated into a 5888-dimensional representation, reduced to 256 dimensions via PCA. Five swarm intelligence algorithms—Particle Swarm Optimization, Artificial Bee Colony, JADE, L-SHADE, and CMA-ES—are benchmarked on the classification head architecture search task; all independently converge to tanh activation, a consistent pattern across independently initialized algorithms that is suggestive of, though not conclusive evidence for, particular geometric properties of PCA-transformed deep feature spaces. The PSO-optimized single-layer head (284 units, tanh) outperforms a manually designed three-layer baseline by 0.75% while using 67% fewer parameters. SI-guided class weight optimization yields targeted F1 improvements on the two most clinically significant classes (polyps: +0.015, ulcerative-colitis: +0.013). The fixed-head classifier trained on fused four-backbone features achieves 91.08% accuracy on Kvasir v2 (multi-seed mean 91.47% ± 0.49 across nine converging seeds; one seed failed to converge and is disclosed rather than excluded), below end-to-end DenseNet121 (92.25%; Wilcoxon p = 0.31, not statistically significant), while enabling classifier updates in under 30 s; a three-backbone subset dropping the weakest backbone (EfficientNetB3) reaches 92.33%, exceeding the full four-backbone fusion. Cross-dataset evaluation on Kvasir v1-to-v2 confirms near-zero generalization gaps across dataset scales; a restricted two-class evaluation on HyperKvasir (the only two of eight classes with usable labeled data) reaches 96.28% accuracy, and dual Grad-CAM with SI minimal sufficient region analysis, validated quantitatively against Kvasir-SEG ground-truth masks, provides spatially grounded, clinically interpretable explanations.