Introduction Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer that accounts for approximately 15% of all lung cancers. Despite advancements in treatment, real-world clinical practice in developing countries often reveals less favorable outcomes than those observed in randomized clinical trials. Material and methods A retrospective analysis was conducted on all patients with extensive-stage SCLC (ES-SCLC) diagnosed or treated at a single center in Bosnia and Herzego-vina. Medical and electronic health records were reviewed to collect data on patients diagnosed with ES-SCLC between 2013 and 2023. The analysis included patient demographics, clinical characteristics, treatment outcomes, and adverse events. Results Ninety-four patients with ES-SCLC were included in the study. Of these, 89.4% were prescribed first-line treatment, and 63.8% received first- line chemotherapy based on cisplatin and etoposide. The median progression- free survival in patients treated with first-line ES-SCLC was five months, with a response rate of 57.5%. The median overall survival of patients treated with first-line chemotherapy in our study was seven months. The most common side effect was hematologic toxicity. Conclusions Our results showed that the outcomes of patients with ES-SCLC in real clinical practice are poor. Further studies of real-world treatment outcomes are essential to validate the findings from randomized controlled trials. Ongoing research is needed to explore strategies for improving outcomes and addressing the unmet needs of patients with ES-SCLC.

Background/Objectives: Children remain underserved in pharmaceutical development, with off-label prescribing still prevalent in part due to a lack of age-appropriate formulations. This study aimed to evaluate the national uptake of Pediatric Use Marketing Authorisation (PUMA)-labelled medicines in Croatia from 2017 to 2024. Methods: We conducted a retrospective, descriptive pharmacoepidemiological study using the IMS (Intercontinental Medical Statistics) and IQVIA (Information, Quintiles, VIA; formerly IMS Health and Quintiles) datasets to track utilization and the expenditure of all PUMA products. Utilization was assessed using defined daily doses per 1000 inhabitants per day (DDDs/1000/day) and annual product dispensation counts. Results: Over the study period, five PUMA medicines entered the Croatian market, with usage rising from 853 packages in 2018 to 9232 in 2024. The DDDs/1000/day increased 33.8-fold, while the expenditure escalated nearly 5.8-fold, from EUR 145,898 to EUR 844,145. Midazolam and melatonin were the most frequently prescribed, yet the overall utilization remained marginal relative to pediatric needs. Conclusions: In conclusion, while regulatory availability of PUMA products has improved, their clinical adoption in Croatia remains limited. Addressing economic, educational, and policy barriers is essential to close the gap between authorization and utilization.

Aim to investigate the prevalence of cervical cytology abnormalities over five years and to correlate it with patient’s age and presence/absence of HPV infection. Methods Pap findings of 614 women with documented cervical abnormalities and Pap findings of HPV-positive women (regardless of whether the Pap test showed an intraepithelial abnormality) were included in this study. Results The majority of women included in the study (36.5%) were aged 30-39 years. The most common abnormalities included atypical squamous cells-ASC (47.4%) and low-grade intraepithelial lesions (LSIL)-15.1%. Out of 614 women, 270 (43.9%) were positive for HPV. HR HPV positivity was found in 256 (41.7%). The proportion of HPV infection positivity decreases with age, especially in the two oldest age groups (women older than 60), p=0.03. The analysis showed a higher ratio of Pap smear abnormalities in groups of patients older than 40 years of age (p=0.02). The youngest age group (patients younger than 20 years of age) showed no other lesions than ASC, while women younger than 40 had no SCC on Pap smear. (p<0.01). Out of 256 HR HPV- positive women 42.2% (n=108) showed Pap abnormalities. HR HPV-positive women more commonly had HSIL lesions, but without statistical significance (p>0.05). Conclusion The results obtained contribute to the knowledge about HPV prevalence and the incidence of squamous cell abnormalities and confirm the necessity for further implementation of HPV vaccination and organized cervical cancer screening program on national level. Keywords: cervical dysplasia, Pap smear, screening.

<p style="font-size: 11pt; color: #000000; font-weight: 400;"><strong>Aim </strong>to investigate the prevalence of cervical cytology abnormalities over five years and to correlate it with patient&rsquo;s age and presence/absence of HPV infection.</p> <p style="font-size: 11pt; color: #000000; font-weight: 400;"><strong>Methods</strong> Pap findings of 614 women with documented cervical abnormalities and Pap findings of HPV-positive women (regardless of whether the Pap test showed an intraepithelial abnormality) were included in this study.</p> <p style="font-size: 11pt; color: #000000; font-weight: 400;"><strong>Results </strong>The majority of women included in the study (36.5%) were aged 30-39 years. The most common abnormalities included atypical squamous cells-ASC (47.4%) and low-grade intraepithelial lesions (LSIL)-15.1%. Out of 614 women, 270 (43.9%) were positive for HPV. HR HPV positivity was found in 256 (41.7%). The proportion of HPV infection positivity decreases with age, especially in the two oldest age groups (women older than 60), <em>p</em>=0.03. The analysis showed a higher ratio of Pap smear abnormalities in groups of patients older than 40 years of age (<em>p</em>=0.02). The youngest age group (patients younger than 20 years of age) showed no other lesions than ASC, while women younger than 40 had no SCC on Pap smear. (<em>p</em>&lt;0.01). Out of 256 HR HPV- positive women 42.2% (n=108) showed Pap abnormalities. HR HPV-positive women more commonly had HSIL lesions, but without statistical significance (<em>p</em>&gt;0.05).</p> <p style="font-size: 11pt; color: #000000; font-weight: 400;"><strong>Conclusion</strong> The results obtained contribute to the knowledge about HPV prevalence and the incidence of squamous cell abnormalities and confirm the necessity for further implementation of HPV vaccination and organized cervical cancer screening program on national level.</p> <p style="font-size: 11pt; color: #000000; font-weight: 400;"><strong>Keywords:</strong> cervical dysplasia, Pap smear, screening</p>

AimAcute respiratory infections caused by viral pathogens are the most common reason for hospitalization of children. Annually, 150 million infants worldwide are diagnosed with bronchiolitis, and 2-3% of them are hospitalized. This study aimed to compare bronchiolitis severity before and after the COVID-19 pandemic. MethodsThis retrospective study was conducted at the Department of Pulmonology, Paediatric Clinic, Clinical Centre University of Tuzla, covering the period from November 1st, 2018, to April th 30, 2019 (pre-COVID period) and November 1st, 2023, to April 30th, 2024 (post-COVID period). A total 129 children under the age of 2 years were involved. Results No significant differences in the age, body mass, comorbidities, duration of hospitalization, use of oxygen therapy, and mechanical ventilation was found. There was a significant reduction in antibiotic in the post-COVID group (p=0.0173), and a significant increase in the use of aminophylline and inhalation therapy drugs in the post-COVID group. There was a significantly higher number of isolated respiratory syncytial virus (RSV) cases in the post-COVID group, 32 (42.7%). prevalence of fully vaccinated children was significantly higher in the pre-COVID period compared to the post-COVID period,  34 (74.4%?) and  29 (45.3%), respectively. Conclusion This study reveals a significant increase in the severity of bronchiolitis and an increase in RSV cases after the COVID-19 pandemic. Keywords: anti-bacterial agents,coinfection, oxygen inhalation therapy,respiratory syncytial virus infections, vaccination.

AIM This study aimed to reveal the prevalence of the insulin resistance (IR) identified by triglyceride glucose index (TyG index) among students of University of Sarajevo. The impact of visceral fat level and waist to hip ratio measures on TyG value in students has been investigated. PATIENTS AND METHODS Study included 160 apparently healthy students, both genders, aged from 19-27 years. Two groups were formed: Group1, TyG <4,49 and Group 2, TyG³4,49. A short interview, questionnaire, anthropometric measures, visceral fat level (VFL), blood pressure and biochemical parameters were applied. The statistical level of significance was P<0,05. RESULTS Forty-five students (28, 1%) were insulin resistant. There was a significant difference in TyG value (P<0,001), [group 1- 4,19 (3,93-4,34 vs. group 2 - 4,59 (4,55-4,74)]. Fasting blood glucose (FBG) and lipid parameters-total cholesterol, triglycerides and very low-density lipoprotein cholesterol (TC, TG and VLDL-C) were significantly higher in group TyG ³4,49 compared to TyG <4,49 group, with exception of HDL-C of LDL-C (P>0.05). Stepwise linear regression analysis showed significant impact of waist to hip ratio on TyG value (P=0,001). CONCLUSION The prevalence of IR measured by TyG in university students was 28,1%. The impact of waist to hip ratio on value of TyG index points on possible application of both parameters in visceral obesity and insulin resistance assessment in apparently healthy individuals.

Aim To assess whether colorectal carcinoma (CRC) survivors 5 years post-fluoropyrimidine (5-fluorouracil and capecitabine) chemotherapy (ChemT) have increased presence of subclinical coronary artery disease (CAD), lower iron and altered blood cell composition. Methods This prospective, 2 year, single-center study used invasive coronary angiography to detect the presence of CAD among ChemT (N=45) and control group patients (age, gender-matched, cancer-naïve (N=45). Full blood count and iron levels were compared between two groups. Results Coronary angiography in 90 patients (mean age 65±7 years; 60% male) identified significantly higher presence of CAD in CRC ChemT patient group compared to control: 80% vs. 55 % (p=0.013). CRC ChemT patients had lower red blood cell count (4.45± 0.56 vs. 4.68± 0.50 x109/L; p=0.044), platelet count (214.18±50.99 vs. 251.00 ±156.40 x109/L; p=0.002) and white blood cell count (5.50 ±1.62 vs. 7.67±1.72 x109/L; p=0.000). Mean corpuscular hemoglobin concentration was higher in CRC ChemT patients (342.11 g/L ±15.74 vs. 336.42 g/L ±10.29: p=0.046), and iron deficiency was more prevalent (ChemT20.40 µmol/L ±3.891vs. control 23.37 µmol/L ±4.10: p=0.001). Conclusion Our study shows that among CRC survivors who underwent 5-FU and capecitabine therapy there is a significantly higher prevalence of CAD accompanied by long-term impairment in blood erythropoiesis. Keywords: coronary artery disease, coronary angiography, erythropoiesis.

AIM This study aims to identify independent risk factors associated with postoperative respiratory complications (PRC) in patients undergoing coronary artery bypass surgery (CABG). METHODS A retrospective cohort study was conducted on 98 patients (82 male, 16 female) who underwent CABG at the Cardiovascular Surgery Clinic, University Hospital Tuzla. The incidence of PRC and potential risk factors were analyzed. Univariate analysis was performed to assess associations, followed by multivariable logistic regression to adjust for confounding factors. Independent risk factors were identified, including diabetes mellitus, smoking, hypertension, gender, and preoperative oxygen saturation <94%. RESULTS PRC were observed in 48 patients (48.97%). Preoperative factors significantly associated with PRC included diabetes mellitus, smoking, hypertension, and low preoperative oxygen saturation. Intraoperative and postoperative factors, such as prolonged surgery duration (>180 min), mechanical ventilation >120 min, and blood transfusion exceeding 500 ml/24 h, were also identified as risk factors. Multivariable logistic regression confirmed that prolonged surgery duration, extended respiratory support, and transfusions >500 ml/24 h were independent predictors of PRC. CONCLUSION This study highlights the importance of perioperative risk stratification in preventing PRC. Reducing prolonged mechanical ventilation and minimizing unnecessary transfusions may improve postoperative outcomes. Further studies with larger cohorts are needed to refine risk prediction models and optimize perioperative management strategies.

Image‐based plant phenotyping has diverse applications, ranging from providing quantitative traits for genetic breeding to enhancing management practices for indoor and outdoor production systems. Misidentification of cell lines or ecotypes/varieties is a major problem across all biological research disciplines. With the 1000 Arabidopsis Genome Project facilitating the use of various ecotypes, it is crucial to verify the identity of ecotypes in discovery‐based genetic screens involving hundreds of ecotypes. To address this issue, an RGB image analysis pipeline was established for the accurate recognition of different Arabidopsis thaliana ecotypes. In the developed pipeline, the most crucial aspects for accurately capturing traits and training deep learning models were identified as follows: (i) assessment of data complexity using spatial‐temporal features of the RGB spectrum and data entropy, the latter defined as the variability within the dataset; (ii) data redefinition in instances of high data complexity; and (iii) data partitioning based on extracted morphological similarity among ecotype replicates. The pipeline includes several supervised deep learning models integrated into an auto‐optimization subsystem. Extensive hyperparameter tuning was performed to identify the best‐performing models for single‐image and image‐sequence ecotype classification. Two external datasets were evaluated to demonstrate the robustness of the pipeline, regardless of how they were collected. A graphical user interface is provided to prepare these images for input into the pipeline in cases of extreme variability. The pipeline can automatically verify ecotypes in large‐scale studies and extract traits for further analysis and correlation, as needed, using datasets from a variety of sources.

<p><strong>Background: </strong>Acquired demyelinating diseases (ADD) of central nervous system encompasses a wide spectrum of neurological symptoms depending on the location and the severity of demyelination. The aim of this study is to present the frequency and the clinical, immunological, and radiological characteristics of ADD in pediatric patients at the Pediatric Clinic, Clinical Center University of Sarajevo.</p> <p><strong>Methods:</strong> This is a retrospective observational study, conducted between 2017-2024, that included patients under 18 years with ADD. The diagnosis is established through clinical evaluation, characteristic MRI findings, immunological markers, and the exclusion of alternative conditions that mimic ADD, following the IPMSSG (International Pediatric Multiple Sclerosis Study Group ) 2010 criteria. We classified the patients into two groups based on the disease course: monophasic, multiphasic group which is further subdivided into multiple sclerosis (MS) and non-MS multiphasic group.</p> <p><strong>Results</strong>: Forty-one patients with ADD were included in the study. Seventeen patients (17/41, 41.46%) remained monophasic, whereas twenty-four patients (24/41, 58.54%) exhibited a multiphasic course. Within the multiphasic group 22/24 patients (91.67%) were diagnosed with multiple sclerosis (MS), and 2/24 (8.33%) had a non-MS multiphasic disease course.</p> <p><strong>Conclusion:</strong> In this study, we presented the frequency and the clinical, immunological, and radiological characteristics of acquired demyelinating diseases in pediatric patients. Recognizing these distinct clinical patterns is crucial for enhancing early diagnostic accuracy and optimizing management strategies in this patient population. Ultimately, our study supports the need for a prospective, multicentric investigation to further consolidate data and refine our understanding of ADD epidemiology in our region.</p>

AIM Due to increasing use of mitochondrial DNA (mtDNA) sequencing in both forensic practice and clinical disease research, this study explores the optimization of the next-generation sequencing (NGS) method for whole mitochondrial genome analysis on the Illumina MiSeq platform. METHODS Initial attempts using pre-made commercial primers were unsuccessful, leading to the design of novel custom-designed primers in our laboratory and optimization of sequencing chemistry and protocols. A comprehensive protocol was developed, involving long-range amplification, enzymatic fragmentation, and the use of IDT® for Illumina DNA/RNA UD Indexes and MiSeq Reagent Nano Kit v2 (300 cycles), whereby DNA extraction, quantification, and library preparation were all performed according to optimized protocols. RESULTS Successful amplification was confirmed using gel electrophoresis and Agilent Bioanalyzer, with optimized conditions yielding clear, specific amplicons 9.8 and 8.5 kb in length. Sequencing results demonstrated high-quality reads with an average coverage depth of 742x and a GC content of 43-45%. The study highlights the efficiency of custom primers and individual library normalization for reliable mtDNA sequencing. CONCLUSION These findings advance the application of NGS in forensic and clinical settings by enhancing the detection of rare mutations and mitochondrial heteroplasmy, paving the way for routine mtDNA analysis using NGS technology.

In this reflection, I share my journey from being a participant in the first Connect Symposium in 2017 to returning as a junior organizer and lecturer in 2025. What began as a formative experience during my undergraduate studies became a turning point in my academic path, guiding me through a PhD and deeper engagement with the European research landscape. The symposium offered far more than lectures — it introduced me to the importance of science communication, regional cooperation, and networking, all of which shaped my career. Eight years later, I return to Neum alongside a student colleague I met during that first Connect, now ready to pass on what we once received. As we focus this year on “Towards the EU Research Area,” I hope our stories and experiences will inspire a new generation to see science not just as a profession, but as a shared, cross-border endeavor.

Glioblastoma (GBM) remains a major clinical challenge due to limited therapeutic success despite standard treatments including surgery, radiotherapy, and temozolomide (TMZ). Recent evidence links hyperglycemia to cancer progression, and altered glucose metabolism has emerged as a key factor in GBM development. Metformin, an antidiabetic drug, has shown promise in improving survival in GBM patients, possibly due to its ability to cross the blood-brain barrier and target metabolic pathways involved in tumor growth. Preclinical studies suggest metformin may enhance TMZ efficacy by acting on glioma stem cells and overcoming resistance mechanisms. Its activation of AMPK and modulation of Wnt signaling further support its therapeutic potential. However, while early studies and clinical trials have explored metformin’s safety and efficacy, its direct impact on GBM survival remains unclear. Ongoing research aims to clarify its mechanisms and identify responsive patient subgroups. Novel strategies, including PPARγ agonists and nanoerythrosome-based drug delivery systems, are also under investigation to improve metformin’s therapeutic profile. Rigorous clinical trials and mechanistic studies are essential to determine the role of metformin as adjunct therapy in GBM treatment.

As the leading cause of global mortality, cardiovascular diseases demand improved and innovative strategies for early detection and risk assessment to enhance prevention and timely treatment. This comprehensive review examines the potential of combining high-sensitivity cardiac troponins (hs-cTns) and homocysteine (Hcy) as complementary biomarkers for enhanced cardiovascular risk prediction. hs-cTn assays have revolutionized cardiovascular diagnostics by enabling the detection of minimal myocardial injury, improving early diagnosis of acute coronary syndrome, and providing robust prognostic information in both symptomatic and asymptomatic populations. Hcy, while established as a marker of vascular dysfunction, presents an interpretative challenge due to multiple confounding factors and inconsistent therapeutic responses. Emerging evidence demonstrates significant correlations between elevated Hcy and troponins across various clinical conditions, suggesting that their combined assessment—reflecting both myocardial injury and vascular dysfunction—may improve cardiovascular risk stratification. While initial findings are promising, additional studies are required to validate the clinical value of the combined marker approach. Future development of personalized interpretation algorithms, and multi-marker panels incorporating these biomarkers, may significantly advance cardiovascular medicine and enable more effective population-specific risk management strategies.