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Publikacije (45418)

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Fatima Efendic, Andreas Hermann, M. Frech

Fatty-acid-hydroxylase-associated neurodegeneration (FAHN) is a rare neurodegenerative disorder caused by loss-of-function mutations in the FA2H gene, leading to impaired enzymatic activity and resulting in myelin sheath instability, demyelination, and axonal degeneration. In this study, we established a human in vitro model using neurons and oligodendrocytes derived from induced pluripotent stem cells (hiPSCs) of a FAHN patient. This coculture system enabled the investigation of myelination processes and myelin integrity in a disease-relevant context. Analyses using immunofluorescence and Western blot revealed impaired expression and localisation of key myelin proteins in oligodendrocytes and cocultures. FA2H-deficient cells showed reduced myelination, shortened internodes, and disrupted formation of the nodes of Ranvier. Additionally, we identified autophagy defects—a hallmark of many neurodegenerative diseases—including reduced p62 expression, elevated LC3B levels, and impaired fusion of autophagosomes with lysosomes. This study presents a robust hiPSC-based model to study FAHN, offering new insights into the molecular pathology of the disease. Our findings suggest that FA2H mutations compromise both the structural integrity of myelin and the efficiency of the autophagic machinery, highlighting potential targets for future therapeutic interventions.

Introduction: Non-ST elevation myocardial infarction (NSTEMI) carries a substantial risk of early major adverse cardiovascular events (MACE) despite advances in therapy. Easily obtainable biochemical and echocardiographic markers may improve early risk stratification, particularly in patients managed without revascularization. This prospective study assessed the prognostic significance of inferior vena cava (IVC) diameter, serum uric acid, homocysteine, and selected hematological indices in predicting 90-day MACE in NSTEMI patients treated with conservative medical therapy. Unlike prior studies that examined these biomarkers individually, our study integrates biochemical (uric acid, homocysteine), echocardiographic (IVC diameter), and hemogram-derived indices into a combined model for early risk stratification in conservatively treated NSTEMI patients. Methods: A total of 170 consecutive NSTEMI patients admitted to the University Clinical Center Tuzla between February 2022 and January 2023 were included. All patients received guideline-directed medical therapy. Clinical, echocardiographic, and laboratory data were obtained within 24 hours of admission. The primary endpoint was MACE (cardiac death, reinfarction, or urgent coronary revascularization) within 90 days. Logistic regression identified independent predictors; discriminatory ability was assessed using receiver operating characteristic (ROC) analysis, and Kaplan-Meier curves evaluated event-free survival. Results: MACE occurred in 87 patients (51.2%). Compared to event-free patients, those with MACE had larger IVC diameters (20.25 ± 2.52 mm vs. 18.36 ± 2.16 mm; p < 0.001), higher uric acid (432.8 ± 47.3 μmol/L vs. 358.9 ± 44.6 μmol/L; p < 0.001), and elevated homocysteine levels (18.42 ± 4.13 μmol/L vs. 13.39 ± 2.88 μmol/L; p < 0.001). In multivariate analysis, uric acid (OR per 10 μmol/L = 1.32; 95% CI: 1.05-1.65; p = 0.015) and homocysteine (OR per 1 μmol/L = 1.23; 95% CI: 1.06-1.42; p = 0.005) remained independent predictors. ROC analysis showed excellent discrimination for homocysteine (AUC: 0.844) and uric acid (AUC: 0.830). IVC diameter was associated with lower MACE-free survival (log-rank p = 0.036) but lost significance after adjustment. Conclusion: Elevated homocysteine and uric acid independently predicted 90-day MACE in NSTEMI patients managed without revascularization. While IVC diameter was not independently predictive, its combination with biochemical markers may enhance risk stratification and guide early post-discharge management. These findings warrant validation in larger multicenter studies.

Fatima Juković-Bihorac, S. Đuričić, Emir Begagić, Hakija Bečulić, A. Efendic, S. Vranić, Mirza Pojskić

Background/Objectives: This study aimed to evaluate the diagnostic and prognostic utility of B7-H3 expression in differentiating low-grade gliomas (LGGs) from high-grade gliomas (HGGs) and to examine its association with clinical outcomes. Methods: This retrospective study included 99 patients with histopathologically confirmed gliomas (42 LGGs and 57 HGGs). B7-H3 expression was assessed using immunohistochemistry and scored by immunoreactive score (IRS). Results: B7-H3 expression was significantly higher in HGG compared to LGG (p < 0.001). The total IRS (B7-H3 A × B) demonstrated strong discriminative power (AUC = 0.816). High B7-H3 expression independently predicted disease progression (OR = 4.9, 95% CI: 2.4–10.1; p < 0.001) and was associated with IDH wild-type status and elevated Ki-67 index. Patients with high B7-H3 had significantly shorter overall survival (median 6 months vs. 42 months) and progression-free survival (median 3 months vs. 25 months) (both p < 0.001). Cox regression confirmed high B7-H3 as an independent predictor of mortality (HR = 2.9, 95% CI: 1.7–4.7; p < 0.001) and progression (HR = 2.6, 95% CI: 1.6–4.2; p < 0.001). Conclusions: B7-H3 expression is a reliable biomarker for distinguishing HGG from LGG and is independently associated with worse survival outcomes. Its assessment may aid in glioma classification and prognostication.

Lukas Lenhart, M. Gander, R. Steiger, Agnieszka Dąbkowska-Mika, Malik Galijašević, S. Mangesius, M. Fuchs, Kathrin Sevecke et al.

Background: Comorbid personality disorders (PDs) in patients with anorexia nervosa (AN) are associated with increased psychopathology, higher suicide risk, and poorer treatment response and outcomes. This study aimed to examine associations between gray matter (GM) volume and PDs in female adolescents with AN before and after short-term psychotherapeutic and nutritional therapy. Methods: Eighteen female adolescents with acute AN, mean age 15.9 years, underwent 3T magnetic resonance imaging before and after weight restoration. The average interval between scans was 2.6 months. Structural brain changes were analyzed using voxel-based morphometry. PDs were assessed using the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID II) and the Assessment of Identity Development Questionnaire. Results: SCID-II total scores showed significant positive associations with GM volume in the mid-cingulate cortex at both time points and in the left superior parietal–occipital lobule at baseline. The histrionic subscale correlated with GM volume in the thalamus bilaterally and the left superior parietal–occipital lobule in both assessments, as well as with the mid-cingulate cortex at follow-up. Borderline and antisocial subscales were associated with GM volume in the thalamus bilaterally at baseline and in the right mid-cingulate cortex at follow-up. Conclusions: PDs in female adolescent patients with AN may be specifically related to GM alterations in the thalamus, cingulate, and parieto-occipital regions, which are present during acute illness and persist after weight restoration therapy.

Amel Krkalić, Admir Keserovic, Harun Selimović, Harun Mandra, A. Jogunčić, Ragib Pugonja

Aim To assess Qualitiy of life (QoL) in adults by comparing two groups, the one with diagnosed hearing loss (HL) and the other without hearing complaints. Methods This cross-sectional study included 110 consecutive voluntary adult  patients divided in two groups: patients with hearing loss and control group. All participants , after examination , answered to a questionnaires on sociodemographic, clinical data and the World health Organization Quality of Life- Short version (WHOQOL-BREF). Results: Among 110 adults  participants, 59  were with hearing loss (hearing loss group – HLG) and 19  in hearing loss  with hearing aid group (HLHAG) and 51 in control group.  Consistently  higher score  in the domains of physical health (p=0.036) and psychological health (p=0.024) in control group was found; other domains did not reach statistical significance Significant differences between the HLHAG and control group in physical health (mean difference = -11.3; p=0.036) and psychological health (mean difference = -11.3; p=0.029) was confirmed. Conculsion Hearing loss could decrease QoL. Therefore, it is very important to recognize hearing impairment in a timely manner and to take a serious approach to treatment.

Mohammed Benjelloun, N. El Messaoudi, Y. Miyah, J. Georgin, Dison S. P. Franco, Elma Šehović, Y. Dehmani, Salah Knani

Arta Dodaj, Kristina Sesar, Monika Bošnjak, Nino Silic, Marija Marušić, Andrea Leko, Petra Topić, Antonio Vukoja et al.

There is little research on sexting in the LGBTQ+ population, especially among LGBTQ+ adolescents and emerging adults who face particular challenges such as body image concerns. The aim of this study was therefore to investigate the role of body image factors (body surveillance, body shame, control beliefs) in predicting sexting motivations and behavior in LGBTQ+ youth, adolescents and emerging adults. A total of 847 LGBTQ+ individuals (366 adolescents and 481 emerging adults) from Bosnia and Herzegovina and Croatia participated in the online study. The results suggest that, on average, LGBTQ+ adolescents are more motivated to sext than LGBTQ+ emerging adults, but do not differ in the frequency of sexting behavior. The body shame was significantly positively correlated with sexting motivation, while other body-related variables were not correlated with sexting (motivation and behavior). Additionally, among adolescents, control beliefs were negatively correlated with sexting motivation. The strength of these correlations differs between adolescents and emerging adults and is stronger in adolescents. The results of this study provide novel evidence of the complex interplay between body image and sexting motivation and behavior in adolescents and emerging adults, highlighting that body variables are generally more important for adolescents than for emerging LBTQ+.

Emina Dervišević, Nina Čamdžić, Edina Lazović, A. Salihbegović, F. Sessa, Hajrudin Spahović, Stefano D'Errico

Hypothermia-related deaths present significant diagnostic challenges due to non-specific and often inconsistent autopsy findings. This study investigated the histological and immunohistochemical alterations associated with primary and secondary hypothermia in an experimental Rattus norvegicus model, focusing on the effects of benzodiazepine and alcohol ingestion. Twenty-one male rats were divided into three groups: control (K), benzodiazepine-treated (B), and alcohol-treated (A). After two weeks of substance administration, hypothermia was induced and multiple organ samples were analyzed. Histologically, renal tissue showed hydropic and vacuolar degeneration, congestion, and acute tubular injury across all groups, with no significant differences in E-cadherin expression. Lung samples revealed congestion, emphysema, and hemorrhage, with more pronounced vascular congestion in the alcohol and benzodiazepine groups. Cardiac tissue exhibited vacuolar degeneration and protein denaturation, particularly in substance-exposed animals. The spleen showed preserved architecture but increased erythrocyte infiltration and significantly elevated myeloperoxidase (MPO)-positive granulocytes in the intoxicated groups. Liver samples demonstrated congestion, focal necrosis, and subcapsular hemorrhage, especially in the alcohol group. Immunohistochemical analysis revealed statistically significant differences in MPO expression in both lung and spleen tissues, with the highest levels observed in the benzodiazepine group. Similarly, CK7 and CK20 expression in the gastroesophageal junction was significantly elevated in both alcohol- and benzodiazepine-treated animals compared to the controls. In contrast, E-cadherin expression in the kidney did not differ significantly among the groups. These findings suggest that specific histological and immunohistochemical patterns, particularly involving pulmonary, cardiac, hepatic, and splenic tissues, may help differentiate primary hypothermia from substance-related secondary hypothermia. The study underscores the value of integrating toxicological, histological, and molecular analyses to enhance the forensic assessment of hypothermia-related fatalities. Future research should aim to validate these markers in human autopsy series and explore additional molecular indicators to refine diagnostic accuracy in forensic pathology.

Bryony Goulding Mew, Darije Custovic, E. Soreq, R. Lorenz, Inês Violante, Stefano Sandrone, Adam Hampshire

Industry 4.0 marks a new phase of industrial transformation, driven by the integration of advanced technologies such as industrial robotics, the Internet of Things (IoT), artificial intelligence (AI), cloud computing, and cyber‑physical systems (CPS). The Republic of Korea and Singapore are global frontrunners in this domain, ranking first and second worldwide in robot density per 10,000 manufacturing workers. This paper explores how the strategic integration of robotics with key Industry 4.0 technologies contributes to smart manufacturing and enhanced industrial performance. Using a comparative case study approach, the research analyzes national policies, investments in R&D and education, 5G infrastructure, and support for innovation ecosystems that have enabled these countries to develop flexible, automated, and intelligent production systems. Findings indicate that both Korea and Singapore have successfully combined robotics with IoT, big data analytics, and cloud platforms to create efficient and adaptive manufacturing environments. The study emphasizes that robotization alone is not sufficient; its effectiveness depends on alignment with broader digital transformation strategies. Based on longitudinal data from 2013 to 2023, sourced from the International Federation of Robotics (IFR), the OECD, and national innovation agencies, the research highlights how coordinated implementation of Industry 4.0 technologies fosters sustainable and globally competitive manufacturing.

Maria C. Tavares, Maria F. R. Almeida, José Vale, Amra Kapo

The historical evolution of auditing reflects an increasing complexity in organizational demands, culminating in the emergence of Audit 5.0—an approach that integrates emerging technologies with professional judgment. This study aims to analyze how technological adoption influences risk assessment and materiality determination in financial auditing within a practical, real-world context. The research, qualitative in nature, combines narrative and thematic analysis of the literature, ethnography in a professional setting, and task analysis, developed over four years of experience in a firm of Chartered Accountants. The findings reveal that although digital tools enhance efficiency and accuracy, professional judgment remains essential to ensure the ethics, reliability, and contextualization of audited information. This study contributes to the advancement of understanding regarding the complementarity between technology and the human factor, proposing paths toward more robust and digitally adapted auditing practices.

Sara Deumić, Ahmed El Sayed, Mahmoud Hsino, Andrzej Kulesa, Neira Crnčević, Naida Vladavić, Aja Borić, M. Avdić

Water supply and sewage drainage pipes have a critical role to play in the provision of clean water and sanitation, and pipe material selection influences infrastructure life, water quality, and microbial communities. Zinc-containing compounds are highly valued due to their mechanical properties, anticorrosion behavior, and antimicrobial properties. However, the effect of zinc salts, such as zinc sulfate heptahydrate and zinc chloride, on biofilm-forming bacteria, including Escherichia coli and Enterococcus faecalis, is not well established. This study investigates the antibacterial properties of these zinc salts under simulated pipeline conditions using minimum inhibitory concentration assays, biofilm production assays, and antibiotic sensitivity tests. Findings indicate that zinc chloride is more antimicrobial due to its higher solubility and bioavailability of Zn2+ ions. At higher concentrations, zinc salts inhibit the development of a biofilm, whereas sub-inhibitory concentrations enhance the growth of biofilm, suggesting a stress response in bacteria. zinc chloride also enhances antibiotic efficacy against E. coli but induces resistance in E. faecalis. These findings highlight the dual role of zinc salts in preventing biofilm formation and modulating antimicrobial resistance, necessitating further research to optimize material selection for water distribution networks and mitigate biofilm-associated risks in pipeline systems.

Gender diversity and the inclusion of women in leadership roles are increasingly recognized as critical drivers of organizational equity and sustainability, particularly through their influence on workforce diversity, employee development, and fair compensation practices. While these effects are well-documented in developed economies, evidence from transitional contexts remains limited. This study explores the impact of female leadership on the social dimension of Environmental, Social, and Governance (ESG) performance in private sector companies in Bosnia and Herzegovina. Focusing on three key outcome areas—inclusive hiring, investment in employee training, and average employee compensation—it examines whether a higher share of women in decision-making positions correlates with stronger ESG-related practices. Using original data from 131 firms that applied for the 2024 United Nations Development Programme’s SDG Business Pioneers Award, the analysis reveals a positive association between female leadership and all three outcome variables. These findings suggest that gender-inclusive leadership contributes meaningfully to socially responsible business practices, even in transitional economies. By providing empirical insights from Bosnia and Herzegovina, this study adds to the growing body of research on gender and sustainability. It highlights the potential of female leadership as a lever for advancing ESG goals and offers practical implications for policymakers and corporate actors aiming to align business strategy with inclusive and sustainable development.

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