The liver is a central metabolic organ that regulates numerous physiological processes, including glucose and lipid metabolism, detoxification, and the synthesis of essential proteins and bile. Bile acids (BAs), synthesized from cholesterol in hepatocytes, not only facilitate the emulsification and absorption of dietary fats but also act as potent signaling molecules through receptors such as the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease globally, closely linked with obesity, insulin resistance, and other components of metabolic syndrome. In MASLD, the metabolism of BAs is markedly disrupted, resulting in alterations in their synthesis, composition, and signaling activity. These changes contribute to hepatic steatosis, inflammation, and fibrosis, thereby exacerbating metabolic dysfunction and liver damage. The altered profiles and signaling activity of BAs in MASLD patients suggest that BAs act not only as biomarkers of disease severity, but also as active mediators of its pathogenesis. Modulators of BA signaling pathways, especially FXR agonists, are the focus of intense research for their potential to beneficially influence liver steatosis and inflammation in MASLD. Recent research has yielded promising results, indicating potential therapeutic application and the introduction of novel agents aimed at modulating BA homeostasis and function. This minireview outlines the physiological roles of BAs, seeks to advance the elucidation of the mechanisms by which their dysregulation contributes to MASLD progression, and highlights current and emerging therapeutic approaches. A deeper understanding of these complex interactions is essential for improving the diagnosis, prognosis and treatment of MASLD.

Wastewaters from the textile industry have a high content of organic matter, high coloration, various minerals and metals, and often toxic and carcinogenic substances. Azo dyes are the most common used dyes in the textile industry. Due to their complex structure, the removal of azo dyes from wastewater is challenging. In this study, electrooxidation and the electro-Fenton process, as one of the most effective Electrochemical Advanced Oxidation Processes (EAOPs) for the removal of organic pollutants in wastewater, were used for the treatment of synthetic wastewater containing “Bemacid Red” dye as a pollutant. Several process parameters affecting the efficiency of OH. formation and dye degradation were examined. Stainless steel (SS) was used as the cathode material, and the anodes used were mixed metal oxides (MMO) - Ru mixed oxide (titanium substrate coated with 6g Ru/m2) and Ru-Ir mixed oxide (titanium substrate coated with 6g Ru- Ir/m2). The results showed that the Ru:SS electrode pair is more efficient comapred to the Ru-Ir:SS pair, and that the electro-Fenton process is more efficient compared to electrooxidation.

We introduce TROOP, a tree-based Riccati optimistic online planner, that is designed to generate near-optimal control laws for discrete-time switched linear systems with switched quadratic costs. The key challenge that we address is balancing computational resources against control performance, which is important as constructing near-optimal inputs often requires substantial amount of computations. TROOP addresses this trade-off by adopting an online best-first search strategy inspired by A⋆, allowing for efficient estimates of the optimal value function. The control laws obtained guarantee both near-optimality and stability properties for the closed-loop system. These properties depend on the planning depth, which determines how far into the future the algorithm explores and is closely related to the amount of computations. TROOP thus strikes a balance between computational efficiency and control performance, which is illustrated by numerical simulations on an example.

Introduction Ibrutinib has made significant contributions to the treatment of chronic lymphocytic leukemia (CLL) with recognized cardiovascular toxicities in some patients. This study aimed to assess the incidence of cardiotoxicity in CLL patients treated with ibrutinib and identify associated risk factors. Methods This retrospective cohort study analyzed 79 CLL patients treated with ibrutinib at the University Clinical Center of Serbia. Patient characteristics, treatment outcomes, and cardiovascular events were analyzed to determine the incidence of cardiotoxicity and its potential predictors. Results The median age at diagnosis was 58 years, with 63.3% male patients. Pre-existing cardiovascular conditions were present in 55.7% of patients. Cardiotoxicity occurred in 29.1% of patients, with atrial fibrilation developing in 10.1% patients (37.5% grade 3), leading to therapy discontinuation in 62.5% of those affected. Also, we diagnosed hypertension in 15.2%, heart failure in 7.6%, and myocardial infarction in 2.5% of patients. Furthermore, one case (1.3%) of sudden cardiac death was recorded. The administration of ibrutinib was ceased in 9 patients due to cardiotoxic effects. Patients with prior cardiovascular disease had a threefold increased risk of developing cardiotoxicity (HR=2.850; p=0.031). A history of hypertension was significantly associated withthe worsening of hypertension during ibrutinib therapy (HR=7.935; p=0.009). No significant associations were found between cardiotoxicity and other factors such as age, sex, number of prior treatment lines, clinical stage, or cytogenetic abnormalities. Discussion This study underscores the importance of cardiovascular monitoring in CLL patients undergoing ibrutinib therapy, particularly those with pre-existing cardiovascular conditions. These findings highlight the need for individualized treatment planning and close follow-up to mitigate the risk of cardiotoxicity and optimize patient outcomes.

A caesarean section (CS) is an obstetric surgical intervention and mode of delivery which aims to finish the pregnancy surgically. CS are one of the most important surgical interventions in modern obstetrics and have lead to a significant reduction of fetal and maternal mortality. However, it is important to take into consideration that CS can have risks and lead to unwanted short-term and long-term consequences. One of the main questions of modern obstetric is the ideal CS rate, including ways to reduce an undesirably high CS rate. The ideal CS rate ranging between 10 to 20% according to various research, but some countries have reached rates exceeding 50%, while in other, less developed countries, the issue of accessibility for CS still exists and consequently leads to a high mortality rate. Significant inequality exists in CS accessibility between developed and less developed areas of countries, and countries themselves. In some cases it is even desirable to increase CS rates in order to reduce negative patient outcome.

<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>

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.

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.

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.

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.

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSION 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.

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.

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.