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.

<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>

<p><strong>Aim:</strong> 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. <strong>Methods:</strong> 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&reg; 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. <strong>Results:</strong> 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. <strong>Conclusion:</strong> 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.</p>

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.

Lava tubes, a common volcanic feature on terrestrial planets, offer critical insights into lava flow processes and may serve as future potential habitats for space crews and other facilities on the Moon and Mars. Seismic detection of these features is challenging as the irregular morphology and rough cave ceilings and walls generate complex seismic wavefields dominated by strong scattering and reverberation rather than pure reflections. Here we present observations of enhanced backscattering in seismic data collected above terrestrial lava tubes. We show that the spatial and frequency characteristics of wavefield intensity can be related to the dimensions of the lava tubes. Our findings suggest that, when geological indicators such as collapse pits are present, this method would enable mapping lava tubes on Earth and, by proxy, on the Moon and Mars, and that the approach is readily adaptable for future planetary exploration.

Introduction Reperfusion failure (RF) describes a condition in which patients suffering a large vessel occlusion (LVO) stroke present insufficient tissue reperfusion and recovery despite optimal mechanical thrombectomy (MT) results. Approximately 50% of patients suffering from LVO are affected. Our current understanding of the underlying pathomechanisms is limited and mostly based on rodent models. The goal of this study was to further characterize RF by applying advanced multimodal hemodynamic imaging in stroke patients. Methods Patients from the IMPreST study with LVO stroke and successful recanalization [corresponding to thrombolysis in cerebral ischemia grade (TICI) 2b-3] were included. Follow-ups with blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) and non-invasive optimal vessel analysis (NOVA) imaging were performed (<72 h, 7 days and 90 days). Demographic and clinical data (NIHSS and mRS) were collected. Results Of the 49 patients included in IMPreST, 18 patients met the inclusion criteria. Based on the perfusion weighted imaging (PWI) of the affected area compared to the contralateral side after MT, patients were stratified into three groups: hypoperfusion (n = 3), normalization (n = 8), and hyperperfusion (n = 7). The hyperperfusion group tended to show poorest clinical outcome (mRS 3 months: 2.5 [Q1–Q3 2.0–3.0] vs. normalization: 1 [Q1–Q3 0.75–3.0], p = 0.169) and had significantly lower BOLD-CVR values at visit one and two compared to hypoperfusion and normalization groups, indicating impaired cerebrovascular reactivity (visit1 hyperperfusion group −0.01 [Q1–Q3–0.02 – 0.07], normalization group 0.12 [0.09, 0.19], hypoperfusion group, 0.09 [0.09, 0.11] p = 0.049, visit2 hyperperfusion group 0.07 [Q1–Q3 0.03–0.10], normalization group 0.17 [0.16, 0.18], hypoperfusion group 0.10 [0.09, 0.11], p = 0.014). Discussion We found three patterns of reperfusion after successful MT of LVO stroke: normalization, hypo- and hyperperfusion of the ischemic area on days at < 72 h after stroke. There was substantial inhomogeneity in perfusion and clinical outcomes between the three groups. Next to poorest clinical outcome, the hyperperfusion-group showed poorest cerebrovascular reserve, reflecting findings of RF in rodent models. Thus, we suggest that RF includes both hypo- as well as hyperperfusion. Early detection using advanced imaging would allow a better identification of patients at risk for poor clinical outcome. Clinical trial registration http://clinicaltrials.gov, Identifier (NCT04035746).

Pseudomonas aeruginosa is an opportunistic pathogen that frequently causes infections in immunocompromised patients and is involved in outbreaks of hospital-acquired infections with a high mortality rate. Aminoglycosides are a large category of antibiotics that bind specifically to 16S rRNA in 30S ribosomal subunits and disturb protein translation. This antibiotic class plays a significant bactericidal role against a wide range of Gram-negative bacteria such as P. aeruginosa. Among different aminoglycoside resistance mechanisms, inactivation of drugs by plasmid-encoded aminoglycoside-modifying enzymes (AMEs) is a common determinant of aminoglycoside resistance in  P. aeruginosa. These plasmids are spread worldwide, and they are transferred to a wide range of different species. This study aims to detect resistance mechanisms and  identify the most prevalent aminoglycoside resistance genes in P. aeruginosa clinical isolates, collected from the University Clinical Centre Tuzla. This study included a total of 230 clinical P. aeruginosa isolates. Antimicrobial susceptibility tests were performed using the disk diffusion method and the Vitek2 system. Isolates displaying increased MIC values for aminoglycoside antibiotics were included in the multiplex PCR reaction, for the detection of aminoglycoside-modifying enzyme genes. The most prevalent genotype among isolates was aac (6')-I. All aac (6')-I genotyped isolates also displayed a high rate of resistance to other classes of antibiotics, and they were characterized as multidrug-resistant (MDR) or extensively drug-resistant (XDR). Results indicate that the aminoglycoside-resistance genes are highly prevalent and could easily spread among P. aeruginosa strains.