BACKGROUND Inflammation-driven mechanisms play a central role in adverse outcomes after non-ST-elevation myocardial infarction (NSTEMI), yet simple, widely available biomarkers for early risk stratification remain insufficiently defined. Hemogram-derived indices and iron-related inflammatory markers may provide complementary prognostic information. OBJECTIVE To evaluate the prognostic significance of the mean platelet volume-to-monocyte ratio (MMR) and serum ferritin in predicting major adverse cardiovascular events (MACE) in patients with NSTEMI, and to assess the association of angiotensin-converting enzyme (ACE) inhibitor therapy with clinical outcomes. METHODS This prospective cohort study included 170 consecutive NSTEMI patients admitted to the University Clinical Center Tuzla between February 2022 and January 2023. All patients received dual antiplatelet therapy and high-intensity statins. The baseline evaluation included a complete blood count, serum ferritin, and C-reactive protein. MMR was calculated as the ratio of mean platelet volume to absolute monocyte count. Patients were followed for 12 months for the occurrence of MACE, defined as cardiovascular death, non-fatal myocardial infarction, urgent revascularization, stroke, or hospitalization for heart failure. RESULTS During follow-up, 103 patients (60.6%) experienced MACE. Admission MMR (18.1 ± 11.7 vs 13.2 ± 5.5; P = 0.003) and ferritin levels (284 ± 396 vs 152 ± 109 µg/L; P = 0.001) were significantly higher in patients with events. In multivariable analysis, both MMR (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02-1.11; P = 0.008) and ferritin (OR 1.28 per 100 µg/L, 95% CI 1.10-1.55; P = 0.003) independently predicted MACE, while ACE inhibitor therapy was associated with a lower risk (OR 0.24, 95% CI 0.08-0.70; P = 0.01). The combined model demonstrated good discriminative performance (AUC 0.72; 95% CI 0.64-0.80). CONCLUSION AND RELEVANCE Elevated admission MMR and ferritin were independently associated with a higher 1-year risk of MACE in patients with NSTEMI. ACE inhibitor therapy was associated with improved outcomes, although causality cannot be inferred. These findings suggest that readily available inflammatory biomarkers may complement established clinical parameters for early risk stratification and support continued guideline-directed pharmacotherapy in NSTEMI.

Chimeric Antigen Receptors (CAR) T-cell therapy is a ground-breaking discovery in immunotherapy, mainly known for its exceptional results in treating haematological malignancies. The latest research has revealed that the potential of CAR T-cell therapy extends far beyond its current capabilities and could represent a novel therapeutic approach for treating various cancers. This review aims to summarize the latest innovations in CAR T-cell therapy applied in cancer treatment, including multiple myeloma, osteosarcoma, glioblastoma, melanoma and various childhood malignancies. However, several challenges limit success of CAR T-cell therapy, including the antigen escape phenomenon, 'on-target off-tumour' toxicity, penetration into solid tumour tissue, alongside the cost-effectiveness concerns. The improvement of cancer immunotherapies currently available requires an increase in the effectiveness of CAR T-cells in managing refractory and solid cancers. This could be achieved by using CAR T-cells to target various antigens, enhancing their local delivery and tumour infiltration capabilities and utilizing CAR T-cells in combination with checkpoint blockade and immunotherapy, such as PD-1 blockade and CD19 CAR T-cell combined therapy. Although CAR T-cell treatment offers a lot of promise, its cost needs to be taken into account, especially in healthcare systems with limited funding. More importantly, frameworks for Health Technology Assessment (HTA) must adapt to incorporate ethical, sociological and psychological aspects. Reducing CAR T-cell toxicity is also essential, as it remains among biggest obstacles to their widespread application in clinical practice. Future research should therefore focus on enhancing our understanding of CAR T-cell therapy and expanding the application of immunotherapy in treatment.

This article examines the use of collaborative online international learning to support educator and educational leadership preparation. As part of a university partnership, the authors piloted virtual exchanges in 2021 and 2022 between university students in the United States (U.S.) and Bosnia and Herzegovina (B.H.). The pilot included 18 U.S. doctoral leadership students and 22 B.H. bachelor's, master's and doctoral students in religious pedagogy and theology. Qualitative case study methods were used to examine two COILs. The authors analyzed curricular and instructional materials, student reflections, faculty notes and correspondence and publicly available B.H. media accounts. Reported learning emphasized reflection focused on cultural attitudes, knowledge and skills; intercultural and interlinguistic awareness; intercultural team functioning and educational leadership, system and policy comparisons. Supports for and challenges to reported learning were structural, curricular and instructional in nature. Little research exists on the use of virtual exchange for educational leadership preparation. This study offers early lessons for using virtual technologies to incorporate an international and intercultural dimension into educational leadership preparation.

Introduction Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) are increasingly used biomarkers in the evaluation of mild traumatic brain injury (mTBI), primarily to reduce the frequent overuse of head computed tomography (head CT). However, their specificity may be compromised by orthopedic trauma, which commonly accompanies mTBI. The aim of this study was to assess whether orthopedic trauma is associated with higher serum concentrations of GFAP and UCH-L1 in CT-negative mTBI patients, thereby potentially reducing their specificity for detecting CT-positive mTBI. Materials and methods This prospective observational study included 67 CT-negative mTBI patients, of whom 29 (0.43) had orthopedic trauma and 38 (0.57) had none. Blood samples were obtained within 12 hours of injury and serum concentrations of GFAP and UCH-L1 were measured using a chemiluminescent microparticle immunoassay (CMIA) on the Alinity analyzer, following the manufacturer's instructions. Statistical analysis included Mann-Whitney U test, chi-square test, Kruskal-Wallis test, post-hoc Dunn's test and logistic regression analysis with P < 0.05 considered significant. Results Serum GFAP concentrations were significantly higher in patients with orthopedic injuries (median (IQR): 70.0 (30.8 to 226.5) pg/mL) than in those without (24.95 (5.52 to 49.15) pg/mL; P < 0.001). Similarly, UCH-L1 concentrations were higher in the orthopedic injury group (median (IQR): 2494.3 (670.1 to 5708.1) pg/mL) compared with those without trauma (262.8 (153.8-595.3) pg/mL; P < 0.001). Conclusions Orthopedic trauma is associated with higher serum concentrations of GFAP and UCH-L1 in CT-negative mTBI patients, which may reduce the specificity of these biomarkers for ruling out intracranial injury.

Background Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related disorders, but inappropriate or prolonged use carries potential health risks. Physicians, due to their access to medication and clinical knowledge, may be prone to self-medicating with PPIs without appropriate oversight. Objective To assess the prevalence and patterns of personal PPI use and self-medication among practicing physicians in Bosnia and Herzegovina, and to identify demographic and professional predictors of such behavior. Methods A cross-sectional, questionnaire-based survey was conducted among 448 physicians who responded to the study invitation, out of approximately 600 invited, from various healthcare levels in Bosnia and Herzegovina between January and May 2025. The survey collected data on PPI use history, consultation behavior, awareness of adverse effects, and adherence to treatment guidelines. Multivariable logistic regression was used to identify independent predictors of self-medication. Results A total of 65.4% of respondents reported past PPI use, during their medical practice, and 31.7% were current users. Over half (52.2%) admitted using PPIs without consulting another physician, and only 17.4% referred to clinical guidelines prior to use. Occasional use was the most common pattern (59.0%), while adverse effects were rarely reported (1.8%). No demographic or professional variable was significantly associated with self-medication with PPIs (defined as PPI use without consulting another physician) in the multivariable analysis. Conclusion Self-medication with PPIs is highly prevalent among physicians and frequently occurs without clinical consultation or adherence to guidelines. This behavior appears to be widespread across age groups, sexes, and care levels, highlighting the need for institutional interventions that promote rational prescribing and raise awareness about responsible self-care within the medical profession.

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.

Severe hypoglycemia increases the risk of cardiovascular disease (CVD) in people with diabetes. Large cohort studies and scientific statements show that severe hypoglycemia is linked to higher rates of coronary heart disease, cardiovascular events, and mortality in both type 1 and type 2 diabetes. This risk is especially high in individuals with significant vascular risk, such as older adults and those with multiple cardiovascular risk factors. Hypoglycemia triggers several pathophysiological changes that increase cardiovascular risk. These include activation of the sympathoadrenal system, promotion of proinflammatory and prothrombotic states, arrhythmogenic changes, and increased hemodynamic stress. Experimental evidence shows that recurrent hypoglycemia worsens microvascular dysfunction and promotes adverse cardiac remodeling, especially in people with diabetes. While the link between hypoglycemia and cardiovascular events is well established, the causality remains debated. Hypoglycemia may directly contribute to cardiovascular disease or indicate underlying vulnerability, especially in patients with advanced disease or comorbidities. Minimizing hypoglycemic episodes is recommended for all patients with diabetes, particularly those with established cardiovascular disease, due to the clear association with adverse outcomes.

The automotive industry is undergoing a significant transformation towards electric vehicles (EVs) with the main goal of reducing greenhouse gas emissions and for a sustainable and green environment. Different types of EVs are introduced every day in the market where selecting an optimal vehicle for purchase constitutes a complex decision-making. Therefore, the purpose of this research was to evaluate EVs in Albania using multi-criteria decision-making methods (MCDM). A total of 12 vehicles were analyzed based on 4 main criteria and 12 sub-criteria. The fuzzy Logarithm Methodology of Additive Weights (LMAW) method was applied to find the weights of the main criteria while the fuzzy Logarithmic Percentage Change-driven Objective Weighting (LOPCOW) method was applied to find the weights of the sub-criteria. For the EV ranking, the fuzzy Ranking of Alternatives with Weights of Criterion (RAWEC) method was applied. The findings showed that the most important criteria are the technical criteria and the Auto 11 vehicle showed the best results. The combination of Fuzzy LMAW-Fuzzy LOPCOW-Fuzzy RAWEC methods also constitutes the novelty of this research, which has not been applied before in this field. The contribution of this research consists in providing a comprehensive set of selection criteria to choose the best alternative of the EV fleet in Albania. Furthermore, the contribution of this research was the application of a hybrid methodology in the evaluation and selection of an electric vehicle as an ongoing choice faced by vehicle buyers.

This is a study of some key properties of sustainable materials based on natural by-products (straw or hemp shives) and binders with zero CO2 emissions (natural clay or CO2-activated binders based on by-products), which can be used in the interiors of building structures in the form tiles and suspended ceilings to stabilize their thermal and moisture properties and to adjust the acoustic properties. It is specifically a study of the acoustic properties of these natural based ecological composites and a study of their reaction to fire. These properties are key, together with hygroaccumulation properties, for the use of these materials in the field of building structures. The aim of the work was to determine the dependence of the type and dosage of the binder on the resulting behavior of the composites from the point of view of fire, and then further reactions of the action of fire on organic particles during short-term exposure to a small flame. Furthermore, it is about the results of the study of acoustic properties, from the point of view of sound absorption, as well as on the adjustment/stabilization of the relative humidity or fluctuations in the production of water vapor in the room (e.g., different short-term occupancy of the spaces by people). The results of this study provide important insights for optimizing the use of ecological composites in construction applications.

In this paper, we investigate an open-access fishery model which is used to examine the dynamics of the resource and industry and to explain the current economic status of the anchovy fishery. We consider the local character of the interior and boundary equilibrium points. Also, we show that the considered system of difference equations exhibits Neimark-Sacker bifurcation under certain conditions. The existence of the repelling curve and invariant curve is demonstrated. We show that in a certain parameter region the corresponding map of the considered system is an area-preserving map, so the positive equilibrium point in that case is stable. Also, we produce numerical simulations to support our findings.

In this paper, we study the dynamics and bifurcation of a two-dimensional discrete-time predator-prey model. The existence and local stability of the equilibrium points of the model are analyzed algebraically. It is shown that the model can undergo a transcritical bifurcation at equilibrium point on the $x$-axis and a Neimark-Sacker bifurcation in a small neighborhood of the unique positive equilibrium point. Some numerical simulations are presented to illustrate our theoretical results.  

Steatosis extends beyond the liver to the pancreas, heart, and skeletal muscle, yet prevailing definitions remain narrowly organ-focused. This narrative review introduces the Metabolic Steatotic Axis (MSA) as a framework that captures the dynamic, bidirectional interactions among these organs, driving systemic metabolic dysfunction. We synthesize evidence linking lipotoxicity, inflammatory signaling, and endocrine cross-talk into a self-amplifying network accelerating insulin resistance, β-cell failure, and cardiometabolic risk. The MSA concept provides a rationale for axis-based staging systems and composite biomarker panels to quantify cumulative disease burden better and refine risk stratification. We highlight phenotypic heterogeneity within MSA stages, the possible hierarchy of organ vulnerability, and the implications for prognosis and therapy. Viewing pharmacological and lifestyle interventions through the MSA lens reframes them as systemic modulators rather than organ-specific treatments, underscoring the need for multi-organ endpoints in clinical trials. Finally, we outline priorities for longitudinal imaging, multi-omics integration, and global harmonization to translate the MSA from a conceptual construct to a clinically actionable paradigm. By unifying fragmented observations into a systemic model, the MSA has the potential to reshape disease classification, therapeutic strategies, and precision medicine in metabolic disorders.