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Ana Paparella Karaman, Tomislav Ivanović, Krešimir Mustapić, Katarina Vukojević, Lukáš Minař́ık, Merica Glavina Durdov, Petar Đolonga

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.

I. Letica, P. Todorović, Patricija Bajt, Nikola Pavlović, Nela Kelam, M. Raguž, I. Mikulić, Ludvig Letica et al.

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.

Nela Kelam, P. Todorović, Patricija Bajt, Nikola Pavlović, Tomislav Rakić, Katarina Vukojević, Anita Racetin

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.

Demir Bedak, R. Sejdinović, B. Prnjavorac, Halida Hakic-Beslagic, Ajdin Ibrahimović, A. Mahmutovic, Omer Bedak

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.

Emir Trnačević, Alma Trnacevic, Mejrema Mahmutovic, Humera Porobic Jahic, Amela Bećirović, Jasmina Selimović

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.

Eric Lim, Shireesha Potla, Jaya A R Dantas, Takeshi Hamamura, Sender Dovchin, Stephanie Dryden, A. Tankosić

Background: Australia’s increasingly multicultural landscape has seen a rise in culturally and linguistically diverse populations, many of whom face subtle and systemic forms of discrimination known as “new racism”. Objective: Underpinned by a person-centred and holistic framework, which recognises individuals as experts in their own lived experiences and emphasises strength-based, culturally situated understandings of well-being, this paper reports on a study that explores how culturally and racially marginalised diverse people in Australia cope with the mental health impacts of new racism. Design: A qualitative descriptive approach was employed in this study. Participants: Thirty participants from ten culturally and linguistically diverse communities participated in eight focus groups, providing rich insights into their lived experiences. Methods: Data were collected through semi-structured focus-group interviews conducted between March and June 2025. Data were analysed using Braun and Clarke’ method of thematic analysis. Results: Thematic analysis revealed four key coping strategies: (1) acceptance of immutable identity traits to foster resilience, (2) emotional ventilation within culturally safe spaces, (3) self-growth and empowerment through reflection and adaptive practices, and (4) assertive responses to racism when necessary. While some participants reported psychological distress, many demonstrated resilience and resourcefulness, challenging deficit-based assumptions often found in the existing literature. Findings underscore the importance of culturally responsive mental healthcare, including peer support, emotional safe spaces, and strength-based interventions. Conclusions: This study offers a holistic understanding of how culturally and racially marginalised people cope with new racism and its mental health impacts. The findings highlight the critical need for person-centred, culturally responsive, and equity-focused mental health support, providing actionable guidance for nursing practice and policy development.

G. Scarlata, Andrej Belančić, Davor Štimac, Almir Fajkić, T. Meštrović, Ludocico Abenavoli

Shigellosis remains a significant global cause of infectious colitis, increasingly complicated by multidrug-resistant strains and the microbiota-disrupting effects of broad-spectrum antibiotics. Although conventional antimicrobial therapy can reduce symptom duration and bacterial shedding, it also contributes to gut dysbiosis, loss of colonization resistance, and further selection for antimicrobial resistance. These challenges have renewed interest in precision antimicrobial strategies, particularly bacteriophage therapy, which provides strain-level specificity and preserves the gut microbiota. This narrative review evaluates the biological rationale, preclinical and early clinical evidence, safety considerations, and translational challenges associated with bacteriophage therapy targeting Shigella spp. The historical development and mechanistic basis of phage therapy are summarized, with emphasis on the advantages of obligately lytic phages, receptor-specific targeting, self-amplification at infection sites, and activity against both planktonic and biofilm-associated bacteria. Recent microbiota research indicates that shigellosis is closely associated with early and persistent disruption of gut ecology, including depletion of short-chain fatty acids-producing taxa and reduced microbial resilience. Phage-based approaches may reduce pathogen burden while preserving beneficial microbial communities. Evidence from in vitro systems, animal models, human intestinal organoids, and a Phase 1 clinical trial demonstrates targeted efficacy and favorable safety profiles for Shigella-specific phages and phage cocktails. Major barriers to clinical adoption include immune interactions, phage resistance dynamics, genomic safety screening, regulatory classification, and the need for standardized susceptibility testing. Future directions emphasize the development of personalized phage therapy platforms that integrate rapid diagnostics, phage libraries, metagenomics, and artificial intelligence-assisted matching to enable scalable, precision treatment.

Viviana Cadena, A. Khan, Miralem Mehic, Jesus Lopez, Saeefa Rubaiyet Nowmi, Samee U. Khan, Mohammad Saidur Rahman

Entanglement-based quantum key distribution (QKD) offers robust key distribution through intrinsically correlated measurements, ensuring that any eavesdropping attempt introduces detectable disturbances. Although practical implementations are primarily limited to fixed fiber networks, extending QKD to mobile platforms like drones or small satellites introduces challenges in optical alignment, weight, and power consumption. This work outlines the core components and architecture for implementing BBM92-based QKD in mobile settings. A compact polarization Sagnac interferometer that utilizes a periodically poled potassium titanyl phosphate crystal provides a stable and efficient method for generating entangled photon pairs. The supporting subsystems include a polarization compensation system, detector module, and an acquisition, pointing, and tracking (APT) system. To assess performance under realistic conditions, we simulate photon loss, detector efficiency, and quantum bit error rates (QBERs) using the Simulator for Quantum Networks and Channels framework. The results show an average key generation rate of 5.43 bits/s, a final secure key length of 45.27 bits per block, and a QBER of 4.5%.

Mirza Pašić, Giulia Tagliazucchi, Mugdim Pašić, Bernardo Balboni

This study explores the entrepreneurial intentions of university students from different educational, economic, and social backgrounds by comparing four European Union (EU) countries (Italy, Austria, Sweden, Greece) to an EU-candidate country (Bosnia and Herzegovina). Data were collected through surveys on a convenience sample of 301 students. The hierarchical regression and formal statistical hypothesis testing assess and compare the role of individual factors and contextual activating factors. In doing so, the paper adopts and adapts the EPIC tool, making it suitable for cross-country comparison. The results indicate a lack of significance of the risk-taking dimension, and a striking similarity in the influence of resources as a contextual activating factor, despite the differences of the investigated countries. In addition, the results indicate the individual mindset dimensions that significantly contribute to the entrepreneurial intentions of EU students (innovation-oriented, persistence, and peculiarity), and the different predictors for students from Bosnia and Herzegovina (innovation-oriented and action-oriented). The paper contributes to the stream of research on entrepreneurial intentions in higher education by assessing the individual and contextual factors within a fine-grained cross-cultural comparison. Insights for institutions and policymakers to enhance support and resources for aspiring entrepreneurs can ultimately be derived.

OBJECTIVES The objective of the present study was to explore whether gender differences exist in waist-to-height ratio (WtHR) values and to assess the correlation between WtHR and other obesity indicators after categorising older adults of Bosnian descent based on the presence or absence of abdominal obesity. METHODS The study included 151 inhabitants of the Geriatric Centre in Sarajevo, Bosnia and Herzegovina, aged 65 years and older (66 males and 85 females). Anthropometric indices and blood pressure values were measured by standard methods. WtHR was calculated using the following formula: waist circumference (WC) (cm)/height (cm). Differences between compared groups were analysed using the Student's t-test, Mann-Whitney U test or chi-square test. Correlations were assessed by Spearman's or Pearson's test. RESULTS Females had significantly higher WtHR values compared to males. Significant positive correlation was determined between WtHR and body mass index (BMI), WC, hip circumference (HC), neck circumference (NC), mid-upper arm circumference (MUAC), calf circumference (CC), and the weight-adjusted waist index (WWI) in both male and female elderly individuals. In elderly participants with abdominal obesity, there was a statistically significant positive correlation between WtHR and all of the tested anthropometric indices. Amongst elderly participants without abdominal obesity, a statistically significant positive correlation was observed between WtHR and BMI, WC, MUAC, and the WWI. However, no statistically significant correlations were observed between WtHR and HC, NC or CC in elderly participants without abdominal obesity. CONCLUSIONS The results of this study imply that WtHR is a valid parameter for assessing abdominal obesity in elderly individuals. The observed WtHR values indicate that women are at greater health risk than men. Given the high prevalence of sarcopenic obesity in older adults and the demonstrated limitations of BMI, we propose that WtHR should be incorporated into routine clinical practice for obesity assessment in this age group.

Jasna Salkić, Nina Čamdžić, E. Hodžić, Elnur Smajić

Abstract Objective: To investigate the clinical and pathological features of a rare benign primary cardiac tumour. Methods: A retrospective analysis was conducted on 13 patients diagnosed with cardiac myxoma (CM) over a six-year period. Patient data including demographics, clinical presentation, imaging, laboratory, echocardiographic, histopathological characteristics, surgical intervention details, and postoperative outcomes were reviewed. Results: The mean age of patients included in the study was 57,69±13,47 (range 29 to 80 years), with a female predominance. The most common location of the tumour was left atrium (69.2%), followed by the right atrium (23.1%) and the left ventricle (7.7%). The most common clinical presentation included a combination of dyspnea, angina, fatigue and palpitations (76.9%). Followed by a syncope (15.4%), while one patient was asymptomatic. There was significant association with left ventricular location of CM and the presence of arrhythmia (p=0.004). Besides usually observed histological findings, glandular structures with mucin forming glands were present in 30.8% of cases and calcifications in 15.4%. All patients underwent surgical resection with favorable short-term outcomes. Conclusion: Cardiac myxoma is a rare but clinically significant neoplasm requiring prompt diagnosis and surgical management. Echocardiography remains essential for detection, and histopathology reveals a spectrum of features. Despite the study’s small sample size, findings highlight the importance of early recognition and support the need for larger multicentric studies to better define its prevalence and behavior.

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