Ždralovac peatland in the karst field Livanjsko polje in southwestern Bosnia and Herzegovina with an area of about 3.500 ha has always been drained and used for the regional people. But drainage, agriculture and climate change cause the peat drying in the summer and create the conditions for frequent fires and serious changes of peat properties. Since 1.000 ha of peatland was used for agriculture (abandoned areas for 25 years that are being cultivated again today), and the extracted peat is used as a raw material for the plant growing substrate. The presence of certain pollutants is a good indicator of the suitability of peat for the plant production. In this paper, the state of peat related to contamination with heavy metals, polycyclic aromatic hydrocarbons - PAHs and pesticide residues was investigated in undrained peat areas, reclamation areas and peat burning sites. The presence of heavy metals in concentrations higher than permitted was not recorded. The presence of combustion products PAHs was recorded on all surfaces, but only naphthalene exceeds the permitted concentrations of organic pollutants. Only pesticide residue of dichlorodiphenyltrichloroethane (DDT) was recorded in abandoned meliorated areas used in agriculture, and the concentration exceeded the level of uncontaminated land.

Egyptian blue (EB) was a prized, intense blue pigment in antiquity, its color commonly associated with wealth, status, and divinity. While frequently used in small quantities for decorative enhancements, Pompeii’s newly excavated “Blue Room”, a shrine in Regio IX Insula 10, is remarkable in that the entire room is covered with this historically famous pigment. Using a combination of visible (white light)-induced luminescence, SEM-EDS, and Raman spectroscopy, we were able to spatially map the large-scale distribution of EB in situ, identify the method of application, and calculate the total quantity of EB used. We estimate that between 2.7 and 4.9 kg of EB was applied in the fresco technique, corresponding to a total cost of between 93 and 168 denarii. These findings demonstrate how modern multi-scale characterization tools can be employed to provide valuable insights into material investment, artistic practice, and social status in an ancient Roman domestic context.

Abstract Introduction Relationship between changes in cardiac function, functional capacity, and patient-reported health status in heart failure (HF) remains incompletely defined, which may help inform endpoint selection and clarify how distinct clinical domains reflect treatment response. Methods This post hoc analysis of the randomized cardiac microcurrent (C-MIC) II trial, which evaluated the efficacy and safety of C-MIC therapy in patients with chronic HF with reduced ejection fraction on optimal guideline-directed medical therapy, included 65 ambulatory patients with non-ischaemic dilated cardiomyopathy, New York Heart Association (NYHA) Class III-IV symptoms, and baseline left ventricular ejection fraction (LVEF) 25–35%. Correlations between changes in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), 6-minute walk distance (6MWD), core lab-assessed LVEF (primary measure) and site-assessed LVEF, and peak oxygen uptake (peak VO2) were evaluated at 4 weeks, 2 months, 3 months, 4 months, and 6 months using Pearson coefficients with 95% confidence intervals (CI). Results The mean age was 60.0 ± 9.7 years and baseline LVEF was 29.8 ± 3.3%. Baseline 6MWD was 291.4 ± 61.6 m and KCCQ-OSS was 42.6 ± 22.7. From baseline to 6 months, changes in KCCQ-OSS (n = 63) and 6MWD (n = 61) showed modest correlations with core lab-assessed LVEF (r = 0.39; 95% CI: 0.16–0.58; P = .0015 and r = 0.39; 95% CI: 0.15–0.58; P = .0022, respectively). Changes in KCCQ-OSS and 6MWD correlated strongly (n = 62; r = 0.63; 95% CI: 0.46–0.76; P < .0001). Changes in KCCQ-OSS and 6MWD did not correlate significantly with changes in peak VO2 (P = .06 and P = .30, respectively). Changes in LVEF and peak VO2 (n = 55) demonstrated modest correlation (r = 0.41; 95% CI: 0.16–0.61; P = .002). Baseline correlations with peak VO2 were weak to modest but increased at 6 months for LVEF (n = 59; r = 0.56; 95% CI: 0.35–0.71; P < .0001). Conclusion In advanced HF, improvements in health status and submaximal functional capacity associate modestly with LVEF, while LVEF correlates more closely with peak VO2. Cardiac function, functional capacity, and health status represent related but distinct domains, supporting multidimensional assessment in HF trials.

Digital twins (DTs) are increasingly used to monitor and secure Industrial Control Systems (ICS), yet detecting stealthy False Data Injection Attacks (FDIAs) that manipulate system states within normal physical bounds remains challenging. Deep learning anomaly detectors often over-generalize such subtle manipulations, while classical fault detection methods do not scale well in highly correlated multivariate systems. We propose a closed-loop Information-Theoretic Digital Twin (IT-DT) framework for real-time anomaly detection. N4SID identification is combined with steady-state Kalman filtering to quantify residual distribution shifts via closed-form KL divergence, capturing both mean deviations and malicious cross-covariance shifts. Evaluations on the SWaT and WADI datasets show that IT-DT achieves F1-scores of 0.832 and 0.615, respectively, with better precision than deep learning baselines such as TranAD. Computational profiling indicates that the analytical approach requires minimal memory and provides approximately a 600x inference speedup over transformer-based methods on CPU hardware. This makes the framework suitable for resource-constrained industrial edge controllers without GPU acceleration.

Abstract Objective. This study aimed to investigate which of the two vitamin K antagonists, warfarin or acenocoumarol, provides more stable anticoagulation control in patients with mechanical heart valves and atrial fibrillation. Patients and Methods. This was a prospective, one-year clinical cohort study. In total, 73 outpatients with mechanical heart valves and atrial fibrillation who were already treated with warfarin or acenocoumarol were recruited from the Blood Transfusion Institute of the Federation of Bosnia and Herzegovina. The prothrombin time target values, expressed as the international normalized ratio (INR), were 2.0–3.0/4.0. Numerical data between the treatment groups were summarized descriptively. Results. Patients in the warfarin (N=35) and acenocoumarol (N=38) treatment groups were similar in terms of sex, age, body mass index, body surface area, and number of concomitant drugs known to interact with vitamin K antagonists. The number of INR measurements per patient, number of INR measurements within the therapeutic range per patient, mean time interval between successive INR measurements, and mean INR values across consecutive measurements were similar in both groups. However, compared to acenocoumarol, warfarin treatment seemed to be associated with more stable anticoagulation, i.e., with a higher mean time in the therapeutic range (TTR) (76.1±24.2 vs. 69.1±21.5%) and a smaller proportion of patients below all predefined TTR thresholds (<60%, <65%, and <70%). Conclusion. Our unadjusted descriptive results suggested that warfarin, compared to acenocoumarol, may provide more stable and therefore safer anticoagulation control in patients with mechanical heart valves and atrial fibrillation. To confirm this, larger prospective clinical studies are needed in patients with mechanical heart valves with or without atrial fibrillation.

Diabetes mellitus is a growing global health challenge, and digital health technologies offer new opportunities to support self-management. Mobile applications can benefit both patients and healthcare professionals; however, awareness and integration of these tools into community pharmacy practice remain limited. As accessible frontline providers, pharmacists are well positioned to promote digital health, yet their readiness and engagement require further investigation. A cross-sectional survey was conducted among community pharmacists in Serbia using a structured questionnaire. Developed through a consensus-based process, the instrument assessed pharmacists’ awareness, attitudes, and experiences with digital health technologies, focusing on mobile applications for diabetes self-management. Only 15.8% of pharmacists were aware of such applications, and 2.4% reported receiving relevant training. Higher digital health technology literacy was associated with greater awareness, confidence, and preference for digital learning. Most participants supported expanding pharmacists’ roles in advising patients on digital tools and expressed interest in structured education and official guidance. These findings indicate limited awareness and training in mobile health applications among community pharmacists. Enhancing digital competencies through targeted education and structured guidance may facilitate greater integration of digital tools into routine pharmacy practice and strengthen pharmacists’ roles in chronic disease management.

Background/Objectives: Patients with local/locally advanced gastric cancer (GC) undergo gastrectomy/lymphadenectomy, but recurrences are common and the disease usually progresses to death. Tertiary lymphoid structures (TLS) of varying maturity can be observed in the immune microenvironment of the primary tumor. The aim of the study was to analyze the association of TLSs and their immune cellular composition with clinicopathological variables and overall survival (OS). Methods: In a cohort of 92 GC patients who underwent gastrectomy, the characteristics of tumor core TLSs were assessed and the density of cytotoxic CD8+ T cells and regulatory FOXP3+ T cells was analyzed. Results: Patients with TLS had a better OS than patients without TLS, 19.4 months vs. 9.2 months (p = 0.001). Immature TLSs were more frequently associated with lymphovascular invasion and regional lymph node metastasis (p = 0.014 and p = 0.034). Mature TLSs had a higher FOXP3+ T lymphocyte density and lower CD8+/FOXP3+ ratio than immature TLSs (p = 0.029 and p = 0.013), and patients had a longer OS than patients with immature TLSs, 34.55 months vs. 15.2 months (p = 0.033). In patients with TLS-positive GC, cases with FOXP3+ T cells had a shorter OS, 12.7 months vs. 47.5 months (p < 0.001). Conclusions: The presence of FOXP3+ cells in TLS is associated with significantly shorter OS of patients with local/locally advanced GC.

Background and Objectives: Mitogen-activated protein kinases (p38, JNK, ERK1/2) regulate key cellular processes essential for kidney development. Disruptions in these signaling pathways can lead to congenital anomalies of the kidney and urinary tract (CAKUT), a major cause of pediatric kidney disease. This study investigates and compares the expression of these molecules in normal fetal kidneys and CAKUT-affected tissues. Materials and Methods: Forty-three human fetal kidney samples, including controls and specimens with horseshoe, hypoplastic, and dysplastic kidneys, were analyzed across developmental phases 2–4 using immunofluorescence. Quantitative image analysis and statistical comparisons were performed between developmental stages and phenotypes. Results: ERK1/2 expression increased during late development in control kidneys but was significantly reduced in hypoplastic kidneys. p38 showed phase-dependent alterations, with early upregulation in dysplastic kidneys and late elevation in horseshoe kidneys. JNK exhibited significant phase-dependent upregulation in horseshoe kidneys. P38 displayed dynamic expression associated with nephron maturation. Conclusions: MAPK pathways show distinct developmental and phenotype-specific expression patterns in human fetal kidneys. These differences reflect divergent pathogenic mechanisms in CAKUT and may support improved molecular characterization of congenital renal anomalies.

Background/Objectives: Congenital anomalies of the kidney and urinary tract (CAKUTs) represent the leading cause of pediatric chronic kidney disease, yet the molecular mechanisms underlying these malformations remain incompletely understood. While genetic studies have identified numerous CAKUT-associated genes, conventional knockout approaches often result in embryonic lethality or fail to reveal tissue-specific gene functions. This review aims to synthesize findings from conditional knockout mouse studies that have elucidated the spatiotemporal requirements of key signaling pathways during kidney development. Methods: We conducted a narrative synthesis of studies employing Cre-loxP conditional gene targeting in mouse models, identified through systematic searches of PubMed and cross-referencing of key primary research. Studies were selected based on their use of lineage-specific Cre drivers (Six2-Cre, Hoxb7-Cre, Foxd1-Cre) to investigate nephron progenitor maintenance, ureteric bud branching morphogenesis, and stromal–epithelial interactions. Results: Conditional knockout studies have redefined CAKUT pathogenesis as a disorder of dose-dependent signaling, temporal regulation, and inter-compartmental communication. WNT/β-catenin signaling operates in a biphasic, dose-dependent manner in nephron progenitors, with Six2-Cre-mediated β-catenin deletion causing premature progenitor depletion. BMP and FGF pathways demonstrate dose-dependent and context-specific functions in progenitor maintenance, while GDNF/RET signaling is essential for ureteric bud outgrowth and branching. Importantly, stromal-specific deletions have uncovered non-cell-autonomous mechanisms regulating nephron formation. Haploinsufficiency studies demonstrate that partial pathway disruption can reduce nephron endowment without overt CAKUT, predisposing to adult-onset hypertension and chronic kidney disease. Conclusions: Conditional gene targeting has mechanistically redefined CAKUT from a collection of structural malformations to a spectrum of disorders arising from quantitative perturbations in lineage-specific signaling networks. These findings establish that phenotypic severity is determined by the degree of pathway disruption, the developmental timing of insult, and the compartment affected, providing a framework for interpreting oligogenic interactions and variable penetrance in human CAKUTs.

Rheumatoid arthritis (RA) may present with extra-articular pulmonary manifestations, including rheumatoid lung nodules. Leflunomide is an effective disease-modifying antirheumatic drug, but increasing case reports suggest an association with accelerated pulmonary nodulosis. We describe a 61-year-old woman with long-standing seropositive RA who developed left-sided lower chest pain, generalized weakness, fatigue, and loss of appetite after switching from methotrexate to leflunomide 20 mg/day. CT imaging demonstrated multiple bilateral cavitary nodules predominantly in the lower lobes. Extensive evaluation (bronchoscopy with microbiology, QuantiFERON-TB Gold, and malignancy assessment) was negative, and video-assisted thoracoscopic surgery lung biopsy showed necrotizing granulomatous inflammation consistent with rheumatoid nodules. The leflunomide dose was initially reduced and then discontinued, and methotrexate was reintroduced; at the four-month follow-up, the patient was clinically well without synovitis, and a CT eight months later showed near-complete regression of prior nodules, with residual left basal fibrotic changes containing calcifications and a remaining non-cavitary right lower-lobe nodule. Clinicians should consider leflunomide-associated pulmonary nodulosis in RA patients with new cavitary nodules after excluding infectious and malignant etiologies, and discontinuation of the drug may lead to radiologic improvement.

Introduction: Traditional diagnostics rely on microscopy, dipstick tests, and the gold‑standard urine culture, which is reliable but time‑consuming. Flow cytometry for urinary analysis offers a fast, objective, and highly automated approach that can improve the selection of samples for culture and accelerate clinical decision‑making. Flow cytometry uses fluorescent and scatter detection to quantify cells, bacteria, and other particles in urine, processing thousands of events per sample and generating parameters that correlate with the presence of infection. Methods: This retrospective study included 200 hospitalized adult patients (>18 years) admitted to the Clinic for Infectious Diseases, University Clinical Center Tuzla in Tuzla, Bosnia and Herzegovina. A urinary tract infection (UTI) was diagnosed based on standardized clinical and laboratory criteria. Urine samples were analyzed using the Sysmex UF‑4000 flow cytometer, and diagnostic thresholds for leukocyte and bacterial counts were determined by receiver operating characteristic (ROC) analysis and Youden’s Index. Results: Among 200 hospitalized patients, females predominated (124 vs. 76). Optimal cut-offs were ≥120/µL for leukocytes (area under the curve (AUC) 0.88, sensitivity 91.2%, specificity 75.3%) and ≥1367/µL for bacteria (AUC 0.95, sensitivity 90.3%, specificity 90.7%). Sex-specific analyses showed higher accuracy in males, with cut-offs of ≥1012/µL for bacteria (AUC 0.97) and ≥122/µL for leukocytes (AUC 0.94), while in females, the best thresholds were ≥1797/µL for bacteria (AUC 0.94) and ≥113/µL for leukocytes (AUC 0.84). The empirically developed UTI risk score (0-2) further improved stratification: Score 0 strongly predicted negative cultures (NPV >97%), while Score 2 was highly associated with positive cultures (PPV >94%). Conclusions: Automated urine flow cytometry offers a fast and accurate screening tool for UTIs, with bacterial counts outperforming leukocytes in diagnostic reliability. Sex-specific cut-offs and the UTI risk score enhance clinical applicability by improving stratification and reducing unnecessary cultures. While findings support integration of flow cytometry into routine practice, the single-center design, hospitalized cohort, and exclusion of pregnant women and children limit broader generalization, warranting validation in larger, multicenter studies.