BackgroundRecent research highlights the pivotal role of gut microbiota and bile acids as modulators of metabolic homeostasis in type 2 diabetes (T2D). The concomitant use of probiotics and ursodeoxycholic acid (UDCA) may potentiate glycemic and lipid control via complementary mechanisms.ObjectiveTo evaluate the metabolic effects of probiotic supplementation and its combination with UDCA in metformin-treated T2D patients.MethodsIn this monocentric, prospective, randomized, double-blind, controlled trial, 90 patients with T2D on metformin therapy were randomized into three groups: metformin-only (MG), metformin plus probiotic (MPG), and metformin plus probiotic plus UDCA (MPUG). The intervention lasted 4 weeks. Primary outcomes included changes in fasting glucose, postprandial glucose and HbA1c. Secondary outcomes included lipid profile, C-reactive protein (CRP), and fecal levels of probiotics and UDCA. Two visits were conducted during the study - at the beginning and at the end. Visits involved patient interviews, clinical data collection, anthropometric measurements, blood biochemical analyses, and stool sample analysis for the presence of probiotic culture and UDCA concentrations.ResultsAfter 4 weeks, the MPUG group showed a significant reduction in fasting glucose (-1.7 mmol/L; 95% CI: -2.2 to -1.2), postprandial glucose (-1.3 mmol/L; 95% CI: -1.8 to -0.7), and HbA1c (-0.49%; 95% CI: -0.66 to -0.31) compared to the MG group. Total cholesterol and LDL cholesterol were also significantly reduced, while HDL increased. The concentration of Lactobacillus rhamnosus GG was highest in the MPUG group. No serious adverse events were reported.ConclusionCo-administration of probiotics and UDCA for four weeks in metformin-treated T2D patients significantly improves short-term glycemic control and lipid profiles. These promising results warrant validation in larger, longer-term clinical trials.
Efficient and consistent string processing is critical in the exponentially growing genomic data era. Locally Consistent Parsing (LCP) addresses this need by partitioning an input genome string into short, exactly matching substrings (“cores”), ensuring consistency across partitions. Compared to the popular sketching techniques, LCP produces fewer cores, enabling a more compact representation and faster analyses. Here, we present the first iterative implementation of LCP with Lcptools and introduce LCPan, an efficient variation graph constructor, which we show generates variation graphs >12×\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\times$$\end{document} faster than vg, while using >13×\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\times$$\end{document} less memory.
Predicting three-dimensional thermal loads during tokamak disruptions is essential for ITER yet remains weakly developed. We present a physics-based workflow that couples MHD simulations of vertical displacement events with field line tracing on a realistic 3D first wall model and a transient wall thermal response. The approach is validated against JET discharges with beryllium main chamber armour, reproducing key global dynamics, non-axisymmetric current features, and the occurrence (or absence) of melting, thereby building confidence in the methodology. We then apply the same workflow to ITER-relevant conditions with tungsten (W) armour, consistent with the new 2024 ITER re-baseline, to assess disruption heat loads and their 3D localization. The resulting analysis demonstrates the resilience of the ITER W first wall against these events and provides predictions for the energy deposition and current flow profiles. Beyond these studies, the workflow enables scenario-by-scenario estimates of disruption-induced thermal loading, allowing to assess the disruption-budget consumption for these events in future devices.
Security Operations Centers (SOCs) are pivotal in modern enterprises. Tasked to monitor complex network environments constantly under attack, SOCs can be active 24/7 and can include hundreds of operators supported by state-of-the-art technologies. Abundant research has studied the internal processes of SOCs, highlighting their pros and cons, as well as the challenges faced by SOC analysts -- such as dealing with the overwhelming number of false alarms triggered by automated security mechanisms. In this context, we wonder: given that"someone"must triage the alarms, and that such triaging must be grounded on established knowledge or evidence-based reasoning, can SOC employees justify why a certain decision was taken while triaging alarms? Answering such a research question (RQ) can better guide future efforts. We hence tackle this RQs. First, via a systematic literature review across 257 research documents, we provide evidence that such RQ received limited attention so far. Then, we partner-up with a real-world SOC and carry out a field study (n=12) with SOC employees. We show them real alarms raised in their SOC, and inquire whether such alarms are indicative of true security problems or not. Then, we ask to explain their decision. We found that while most analysts were able to separate"true from false"alarms (the decision was correct in 83% of the cases), a correct justification was hardly provided (only 39% of the provided explanations reflected the actual root cause). Ultimately, our results highlight the need for decision-support systems that help SOC analysts not only make the right call -- but also understand and articulate why it is right.
This study assesses the impacts of climate change (CC) on maize production in Bosnia and Herzegovina, comparing ten maize-producing municipalities and using Gradiška as a case study. Agroclimatic indicators and ISAREG-based soil water balance simulations were used to evaluate regional suitability for future maize production. Projections indicate substantial increases in average temperatures of 2 to 6 Celsius by the end of the century, depending on the RCP scenario, together with important reductions in accumulated mean precipitation, particularly during summer. Rising temperatures accelerate maize phenology, shortening growth cycles and enabling double-cropping opportunities for short-season cycles. Medium-season cycles may become feasible in most regions, while long-season cycles remain constrained in high-altitude areas due to thermal requirements. Rainfed maize in Gradiška is expected to face increased relative evapotranspiration deficits under future ‘hot & dry’ conditions, with potential relative yield losses due to water deficit of up to 12%. Irrigated maize shows a variation in irrigation requirements from −26% to +8% relative to the baseline, which reflects the combined effect of a shortened crop growth cycle under higher temperatures and increased evapotranspiration demand under drier conditions. Regions with high soil water-holding capacity are the most resilient, while areas with shallow soils or Mediterranean climates are more vulnerable under future conditions. The findings underscore the need for agronomic adaptation measures to the projected CC impacts, including supplemental irrigation, drought-tolerant cultivars, and potential adjustment of sowing.
Background/Objectives: Clear cell renal cell carcinoma is the most common subtype of kidney cancer and exhibits marked biological heterogeneity, even among tumors of the same histological grade. Although tumor grade remains a key prognostic parameter, the molecular alterations associated with tumor differentiation are not fully understood. This study aimed to evaluate grade-dependent tissue-level expression patterns of proteins involved in cellular stress response, growth regulation, stemness, and apoptosis in clear cell renal cell carcinoma. Methods: Protein expression of heat shock protein 70, insulin-like growth factor 1, octamer-binding transcription factor 4, and apoptosis-inducing factor were analyzed in human clear cell renal cell carcinoma samples and normal renal cortex. Low-grade and high-grade tumors were compared using immunofluorescence staining combined with semi-quantitative and quantitative image analysis. The proportion of positive signals and the number of positive cells were assessed across tissue compartments. In addition, publicly available transcriptomic data from The Cancer Genome Atlas kidney renal clear cell carcinoma cohort were analyzed to explore associations between gene expression levels and overall survival. Results: Distinct grade-dependent expression patterns were observed for all investigated proteins. Heat shock protein 70, insulin-like growth factor 1, and octamer-binding transcription factor 4 showed a higher expression in normal renal tissue with a progressive reduction across tumor grades. In contrast, apoptosis-inducing factor exhibited increased expression in tumor tissue, particularly in low-grade tumors, with a relative decrease in high-grade carcinomas. Stromal compartments of tumor tissue showed minimal or no expression for most markers. Transcriptomic survival analysis did not reveal significant differences in overall survival between high- and low-expression groups for any of the investigated genes. Grade-stratified transcriptomic analysis of the TCGA KIRC cohort revealed consistent patterns for HSP70 family members and OCT4, with progressive grade-dependent mRNA reduction toward higher grades, while IGF1 showed an inverse mRNA trend and AIFM1 showed a uniform reduction across all tumor grades without a clear inter-grade pattern. Conclusions: The findings demonstrate that stress response, growth-related, stemness-associated, and apoptotic proteins display distinct grade-dependent tissue-level expression patterns in clear cell renal cell carcinoma, with the expression profiles of high-grade tumors being of particular translational interest given the aggressive clinical behavior and therapeutic resistance characteristic of this disease stage. These alterations appear to reflect tumor differentiation and biological behavior rather than independent prognostic value, highlighting the complexity of molecular regulation in renal tumorigenesis.
The neutrophil to lymphocyte ratio (NLR) serves as a marker of systemic inflammation and is an established prognostic factor in non-small cell lung cancer (NSCLC). However, its predictive value for treatment response, particularly when evaluated through three-dimensional CT volumetry, remains ambiguous. This study investigates whether pretreatment NLR and treatment-related changes in NLR correlate with volumetric tumor response to platinum-based neoadjuvant chemotherapy (NACT). Adult patients with histologically confirmed NSCLC who received platinum-based NACT and had evaluable pre- and posttreatment CT imaging were included in the analysis. Tumor response was defined as a ≥30% reduction using three-dimensional CT volumetry. We analyzed pretreatment NLR, posttreatment NLR, changes in NLR (ΔNLR), and the NLR ratio. To enhance statistical stability, additional analyses utilized log-transformed NLR values. Associations were examined through non-parametric tests, correlation analysis, and both univariable and multivariable logistic regression models adjusted for age, sex, histology, disease stage, performance status, and baseline tumor volume. A total of 70 patients were included, with 33 (47.1%) achieving a volumetric response. NLR decreased during treatment (median ΔNLR = -0.42), yet no significant differences were noted between responders and non-responders regarding pretreatment NLR (p = 0.773), posttreatment NLR (p = 0.920), ΔNLR (p = 0.514), or NLR ratio (p = 0.630). None of the NLR-derived parameters showed significant associations with treatment response in univariable or multivariable models, including those utilizing log-transformed variables. Furthermore, the NLR ratio exhibited substantial instability, reflected in wide confidence intervals. In conclusion, within this cohort, neither pretreatment nor dynamic NLR parameters were significantly associated with CT-based volumetric tumor response following platinum-based NACT.
Doping remains one of the most important problems in sports, but legal issues related to anti-doping are relatively understudied in this context. This study aimed to evaluate the reliability and validity of a newly designed questionnaire aimed at evaluating antidoping legal knowledge among sport officials.The participants included 211 sport officers (coaches, medical professionals, nutritionists; 41.7±7. years of age, 71 females) from Croatia and Bosnia and Herzegovina, who were tested on a newly designed questionnaire on knowledge of legal anti-doping regulations for sport officials (Q-LADR-O). Additionally, data on sociodemographic characteristics, sport-related factors, and doping-related factors were collected. In the first phase, a subsample of 56 participants was tested and retested on the Q-LADR-O in the time frame of 7--10 days to evaluate the reliability of the tool.Among the 20 original questionnaire items, 18 had appropriate test-retest reliability (Cohen’s kappa > 0.61, absolute agreement > 80%). Factor analysis identified two distinct latent structures reflecting (i) rights and obligation under the anti-doping code and (ii) anti-doping testing and legislation. The validity of the Q-LADR-O was confirmed by significant differences between medical staff and coaches/nutritionists (6.71 ±1.79 and 4.21 ± 1.2 for medical staff and coaches/nutritionists, respectively, t test = 8.71, p < 0.01) and a significant correlation between the Q-LADR-O and sport-officiating level (Spearman’s R = 0.21, p < 0.05) and between the Q-LADR-O and the number of doping tests of athletes officiated (Spearman’s R = 0.55, p < 0.05).Considering its proper reliability and validity, Q-LADR-O can contribute to more effective anti-doping education, primarily by reducing unintentional rule violations. Further intervention studies are warranted.
Cascade reservoirs on the Drina River (Bosnia and Herzegovina) are heavily modified water bodies that require reliable biological tools for assessing trophic status and ecological potential. Under the Water Framework Directive (WFD), assessments of surface water ecological status and potential rely on biological quality elements, since aquatic communities integrate and respond to prevailing environmental conditions and thus serve as reliable indicators of water quality. This study aims to (i) describe phytoplankton diversity, biomass, and functional-group composition along the Drina reservoir cascade, (ii) examine monthly changes across the studied reservoirs, (iii) determine trophic status and ecological potential, and (iv) provide a preliminary estimate of total phosphorus thresholds that may support future setting of ecological potential boundaries. Phytoplankton composition and functional groups were analysed in three longitudinally connected reservoirs of the Drina River during four monthly surveys in 2024. A total of 80 phytoplankton taxa were recorded, with diatoms dominating most of the study period. The highest biomasses were recorded for Fragilaria crotonensis, Dinobryon divergens, Acanthoceras zachariasii and Sphaerocystis sp., while the dominant functional groups were P, E, A, and F. Phytoplankton assemblage structure showed moderate spatial differentiation among the reservoirs. Mean chlorophyll a and Carlson’s Trophic State Index indicated eutrophic conditions in the Višegrad Reservoir and mesotrophic conditions in the Perućac and Zvornik reservoirs, while biomass showed a pronounced summer maximum, particularly in Perućac. Ecological potential was generally classified as good or better, except for a moderate classification in the Zvornik Reservoir in late summer. The good/moderate TP boundary was estimated at 39 µg L−1, linking EQR-based ecological assessment with the onset of eutrophic conditions. Overall, this study represents the first application of the phytoplankton functional group approach in cascade reservoirs in Bosnia and Herzegovina and may provide a valuable basis for the development of a phytoplankton-based monitoring framework in lakes and reservoirs, which is currently lacking.
This article is about the Bosnian animated series Bruca Braca Bruda Brada which deals with contemporary social issues in Bosnia and Herzegovina, focusing on Švrakino selo, a predominantly working-class neighbourhood on the outskirts of Sarajevo. The series’ creators are Helem Nejse, a Sarajevo-based hip-hop band. The humour stands out because of the linguistic subtlety through which contemporary society is portrayed, focusing especially on the Sarajevo area. Stylistically, the slang, the wordplay, the counter-images of real-life politicians, criminals and events are all part of a layered storyline, painting an image of a society trapped for over three decades in the limbo of expectations of a better life. The analytical framework consists of the following units, superficially functioning as general knowledge scripts: names, nationalism, (local) patriotism, know-it-all and corruption. However, these scripts, in the context of the analysed material, become restricted, making the humorous interpretation challenging not only to an international audience, but also to native speakers in some instances. Stylistic traits of the selected material are observed, together with additional linguistic devices that enhance humour. Culture-specific expressions and other important contextual segments are also explained where necessary.
Stress echocardiography (SE) has evolved beyond its traditional role of detecting coronary artery disease (CAD) through a single marker-regional wall motion abnormality (RWMA). This conventional approach, while guideline-embedded, faces a declining positivity rate and reduced prognostic power in today's diverse patient population. In response, SE has undergone a conceptual transformation into a multi-marker, comprehensive functional assessment of patient vulnerability. The modern multi-marker protocol, known as the ABCDE-SE, integrates five steps during a single stress test: Step A assesses RWMA for ischemia; Step B quantifies pulmonary congestion via B-lines and E/e'; Step C evaluates left ventricular volume response; Step D measures coronary flow velocity reserve for microvascular function; and Step E determines heart rate reserve for autonomic function. Each step identifies distinct pathophysiological mechanisms and actionable therapeutic targets, significantly refining risk stratification.Developed and validated over the past decade with the SE 2030 study (2016-2030), the flagship project of SIECVI, Italian Society of Echocardiography and Cardiovascular Imaging, and adopted by 50 laboratories from 20 countries, the ABCDE protocol represents a universal and widely accessible platform, applicable to all patients with suspected cardiac disease. It paves the way for personalized medicine by enabling tailored therapies targeted to the specific vulnerabilities.
Simple Summary Feline patients may frequently develop anemia in association with a variety of underlying concurrent conditions, primarily as a direct consequence of metabolic disorders or infectious agents such as hemoplasmas. Additionally, anemia may arise as a part of a primary myeloproliferative disease, particularly associated with retroviral infections. Recent data from owners and veterinarians indicate that feline hemoplasmosis, despite its worldwide occurrence, is not routinely considered as the differential diagnosis for anemia in cats of Bosnia and Herzegovina. The infection is often underdiagnosed and overlooked, primarily due to the absence of reliable rapid testing methods and lack of hemoplasmosis PCR testing availability in Bosnia and Herzegovina, prior to this study. This is the first reported case of PCR-confirmed hemoplasmosis in Bosnia and Herzegovina. It further provides detailed information on patients’ signalment, clinical and molecular diagnostic approaches, treatment, and long-term follow-up. Despite being immunocompromised due to feline immunodeficiency virus infection, no recurrence of hemoplasmosis or retroviral reactivation was observed over an almost five-year period. This case also emphasizes the importance of considering hemoplasmosis in anemic cats, particularly those that do not respond to the treatment, and demonstrates the value of molecular methods in establishing definitive diagnosis.
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