Celiac disease is a chronic disorder of the digestive system caused by the intake of gluten in genetically predisposed individuals. It is characterized by a high prevalence and often delayed diagnosis due to nonspecific symptoms, such as chronic diarrhea, vomiting, loss of appetite, fatigue, and anemia, which are frequently pushed aside, or misattributed to other conditions. The disease often occurs in association with other autoimmune diseases. Having in mind a complex administrative structure of Bosnia and Herzegovina, there are also significant differences in the healthcare system among cantons, which ultimately affects the position of patients, as well as the availability of adequate healthcare. The aim of this paper is to present celiac disease through the perspective of the condition itself, as well as the challenges and opportunities faced by patients in the Herzegovina-Neretva Canton. The paper contains a theoretical overview of the disease, an analysis of the availability of gluten-free products, the offer within the hospitality sector, patients' healthcare rights, and finally, a presentation of the experience of a person living with celiac disease. The right to gluten-free foods in Herzegovina-Neretva Canton is granted to patients suffering from celiac disease (K90.0 morbus coeliacus) in the amount of 200 BAM per month, if they belong to the pediatric age group, if they are unemployed, or retired. At the same time, patients suffering from celiac disease who are employed are not entitled to gluten-free foods at the expense of the Health Insurance Institute of Herzegovina-Neretva Canton (ZZO HNK).  In the city of Mostar, four contracted pharmacies participate in the distribution of glutenfree food supplies covered by the Health Insurance Fund of the Herzegovina-Neretva Canton, while in the other parts of the Herzegovina-Neretva Canton there are another five pharmacies which are involved in distribution (territories of Čapljina, Čitluk, Jablanica, Prozor, and Konjic). The analysis of the three retail chains with the largest number of stores demonstrated that these retailers provide a diverse range of gluten-free food products. Restaurants in Mostar do not offer a satisfactory selection on their menus, which undoubtedly makes the social life of individuals with celiac disease more difficult, especially younger, socially active individuals who travel and work. Even dishes labeled as gluten-free on their menus are recommended to be checked with staff before ordering if they are being prepared under controlled conditions, and whether there is a possibility of gluten contamination from the preparation of other meals. A significant contribution to improving the quality of life of people with celiac disease is provided by the Association of People with Celiac Disease “Gluten free” in the Herzegovina-Neretva Canton, through various activities and initiatives addressed to city authorities, which has resulted in noticeable improvements in the quality of life of people with celiac disease over the past two years since the association was founded. 

Hereditary angioedema is a rare but potentially life-threatening disorder in which outcomes depend not only on correct diagnosis and effective medicines, but also on how health systems organize referral, laboratory confirmation, emergency pathways, reimbursement, home treatment, and long-term follow-up. Selected health systems in the Balkan Peninsula area provide a particularly informative setting for health-system comparison because neighboring countries with active hereditary angioedema expertise differ substantially in rare-disease governance, registry maturity, diagnostic infrastructure, treatment coverage, and patient-organization capacity. This Policy and Practice Review synthesizes international guidance, published regional literature, comparative country information from the Balkan Experts in Angioedema: Consensus and Ongoing Navigation (BEACON) initiative, and advocacy-informed implementation insights to assess current care delivery in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Greece, Romania, Serbia, Slovenia, and Türkiye. Across the region, the most consistent problems are prolonged diagnostic delay, unequal access to complement and genetic testing, approved-but-not-reimbursed modern therapies, hospital-only access to rescue medication, uneven use of home treatment and self-administration, incomplete emergency preparedness, and variable registry and advocacy infrastructure. Countries with stronger alignment between policy frameworks, specialist centers, registries, reimbursement pathways, and patient organizations appear better positioned to deliver guideline-concordant care, whereas fragmentation at any point in the care pathway reduces the practical value of therapeutic advances. The review argues that the main barriers to equitable hereditary angioedema care across the included health systems are now predominantly regulatory, financing, organizational, and educational rather than scientific. We therefore propose actionable recommendations for ministries and payers, specialist centers and professional societies, emergency-care systems, registry stakeholders, and patient organizations, with the goal of converting regional heterogeneity into a structured quality-improvement agenda.

The aim of this study was to characterise mandibular shape variation and asymmetry patterns in three sheep breeds from two geographical regions: Pramenka from Bosnia and Herzegovina, and Akkaraman and Kangal Akkaraman from Türkiye. Thirty-four male mandibles (10 Pramenka, 12 Akkaraman, 12 Kangal Akkaraman) were analysed by landmark-based geometric morphometrics, with eleven homologous landmarks digitised on lateral photographs. Generalised Procrustes Analysis, Principal Component Analysis (PCA), Discriminant Function Analysis (DFA), allometric regression, and Procrustes ANOVA were performed in MorphoJ. The first three principal components explained 63.37% of total shape variation. In the PCA morphospace, Akkaraman and Kangal Akkaraman specimens overlapped almost completely, whereas Pramenka formed a clearly separated cluster. DFA confirmed significant shape differences in all pairwise comparisons, with cross-validated classification accuracy of 79.2% between the two Anatolian breeds and 100% for both Pramenka comparisons. Shape differences were most pronounced in the pars incisiva, pars molaris, corpus mandibulae, and ramus mandibulae. Centroid size explained only 2.51% of shape variation (P = 0.3467), indicating no significant allometric effect. Fluctuating asymmetry exceeded directional asymmetry for both size and shape; directional asymmetry in shape nevertheless remained statistically significant, consistent with a degree of masticatory laterality.Mandibular morphology therefore differs primarily between geographically distant breeds, while the two Anatolian breeds remain morphologically close, and the observed asymmetry patterns point to developmental instability as the principal source. These data provide morphometric reference values for future work on breed differentiation, functional adaptation, and zooarchaeological identification of ovine remains.

 Lactose is a carbohydrate only found in the milk of mammals and it is one of the most important components of milk. Upon consumption by humans, the enzyme ß- galactosidase (lactase) breaks down lactose into glucose and galactose with the help of water in the small intestine, but its activity decreases or disappears completely when growing up, and consumption of lactose in adulthood can cause indigestion. In this research, based on literature data, it is explained why certain group of people in the world can digest lactose regardless of age, and some others cannot. It is also explained which products can potentially replace milk and milk products. However, the primary goal of this paper is to show the prevalence of lactose intolerance among the population of Bosnia and Herzegovina, and which dairy products cause them the most problems. Most of the previously conducted research showed that the phenomenon of lactase persistence is genetically determined. It occurs in Europeans in whom the activity of ß- galactosidase is constantly maintained and the European population is able to digest large amounts of lactose regardless of age. On the basis of the conducted survey on the occurrence of milk lactose intolerance among different groups of people in Bosnia and Herzegovina, it can be concluded that the number of people who are lactose intolerant is significantly low. The results show that more than half, i.e. 58 out of 100 subjects tolerate lactose well, while only 20 respondents do not tolerate lactose. The latter answered that among milk and dairy products milk causes them the greatest digestive and other disturbances due to the highest lactose content, while dairy products, primarily fermented milks such as kefir, ayran and yogurt, cause significantly fewer problems. 

BACKGROUND Candida auris is a widely distributed yeast that is considered a dangerous pathogen, with reported mortality rates ranging from 30% to 60%. This yeast shows a high level of resistance to several antifungal agents commonly used to treat systemic infections. The pathogen persists on contaminated surfaces, tolerates hospital-grade disinfectants, survives desiccation and spreads easily through direct or indirect contact. It has been reported on all five continents and is increasingly prevalent in Europe. OBJECTIVE To determine the distribution and antifungal susceptibility/resistance of Candida auris isolates identified in Europe until January 2025. METHODS This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were conducted in EBSCOhost, MEDLINE/PubMed, Scopus and SciELO databases using the terms 'Candida auris' and 'Candidozyma auris', combined with the name of each European country. It was limited to English or Spanish articles published until 31 January 2025, excluding reviews, meta-analyses and book chapters. RESULTS Ninety-one articles reporting antifungal susceptibility were retrieved, covering 2191 clinical isolates of C. auris from 16 countries. Most isolates were from Spain (n = 886, 40.44%), Italy (n = 553, 25.24%), Greece (n = 214, 9.77%), the United Kingdom (n = 182, 8.31%) and Russia (n = 108, 4.93%), accounting for 88.68% of cases. The remaining 248 isolates (11.32%) were reported across 11 other countries. Fluconazole resistance was found in 90.51% (1555/1718), while resistance to amphotericin B and echinocandins was 13.17% (223/1693) and 4.57% (76/1693), respectively. CONCLUSIONS Candida auris has been predominantly detected in Southern Europe, where the majority of clinical isolates exhibit resistance to fluconazole. Consensus is essential for timely diagnosis, targeted treatment and infection control to prevent its spread. New therapeutic options must be explored to manage Candida auris.

Cd, Cr, and Pb concentrations were analysed in 18 bottled drinking water samples from the Bosnia and Herzegovina (B&H) market, classified as natural spring water or still natural mineral water. Metal concentrations were determined using atomic absorption spectrometry with electrothermal atomisation in a graphite furnace. Cr was quantified in two samples, Pb in four samples, while Cd concentrations were below the limit of detection in all samples. All concentrations were below national regulatory limits. Health risks associated with Cr and Pb exposure through bottled water consumption were assessed for adolescents, adults, and pregnant women by calculating the hazard quotient (HQ), hazard index (HI), carcinogenic risk (CR), and total carcinogenic risk (TCR). Some exposure scenarios exceeded HQ and HI thresholds, suggesting potential non-carcinogenic effects, primarily due to Pb exposure. CR and TCR values across all exposure scenarios were below established thresholds, indicating generally acceptable or negligible carcinogenic risk. Given the limited sample set, the data on Cd, Cr, and Pb content, along with the health risk assessment, should be regarded as preliminary, serving as a starting point to guide future research. Considering the health implications of heavy metal exposure, continuous water-quality monitoring and a more comprehensive health risk assessment, including additional heavy metals and a larger sample set, are essential, as regulatory compliance does not necessarily imply the absence of health risks.

Dementia is a progressive condition that impairs cognitive processes such as memory, decision making, and the ability to manage daily activities. Recent estimates suggest that more than half of all dementia cases could be preventable by addressing their risk factors, including disease comorbidities such as diabetes and vision loss. Yet, we lack a comprehensive molecular map of dementia comorbidities. In this work, we analyzed Austrian nationwide hospital claims data, comprising 13 million hospital stays from 2015 to 2019, to systematically assess dementia-related risk across disease comorbidity patterns, covering both their molecular relationships and their epidemiological overrepresentation. We identified disease trajectories occurring before and at the time of dementia diagnosis, revealing both sex-specific and shared comorbidity patterns. Overall, we identified 51 potential risk factors, with a prominent contribution from endocrine and metabolic disorders. While Parkinson's disease emerged as a strong molecularly related driver of dementia, we also identified emerging and previously under chracterized risk factors, including vitamin D deficiency. This integrative framework provides a comprehensive view of dementia associated disease networks and identifies novel, potentially modifiable risk factors. These results offer new opportunities for targeted prevention strategies and advance our understanding of the complex interplay between comorbidities and dementia development.

Tumor evolution is driven by various mutational processes, ranging from single-nucleotide variants (SNVs) to large structural variants (SVs) to dynamic shifts in DNA methylation. Current short-read sequencing methods struggle to accurately capture the full spectrum of these genomic and epigenomic alterations due to inherent technical limitations. To overcome that, here we introduce an approach to identify and analyze the genomic and epigenetic events in different stages of tumoral evolution from long-read sequencing of single-cell derived sublines. We then use it to profile 23 sublines of a mouse cutaneous melanoma cell line, characterized with distinct growth phenotypes and treatment responses. We develop a computational framework for harmonization and joint analysis of different variant types in the evolutionary context. Uniquely, our framework enables detection of recurrent amplifications of putative driver genes, generated by independent SVs across different lineages, suggesting parallel evolution. In addition, our approach revealed gradual and lineage-specific methylation changes associated with aggressive clonal phenotypes. We also show our set of phylogeny-constrained variant calls along with openly released sequencing data can be a valuable resource for the development and benchmarking of computational methods. Tumor evolution involves genetic and epigenetic changes that are difficult to resolve with standard sequencing approaches. Here, authors use long-read sequencing of single cell-derived melanoma sublines to map mutations, structural variants and DNA methylation, revealing parallel genomic changes and lineage-specific epigenetic trajectories linked to tumor behavior.

Background: Plavac mali is a well-known native Croatian cultivar used for the production of premium wines. One of the locations known for this variety is the island of Hvar, in the southern Dalmatia subregion. Grape quality is influenced by the canopy microclimate, and one of the main practices for manipulating the canopy is defoliation. Aim: The aim was to investigate the impact of defoliation treatments on grape composition in two vineyards with different microclimates. Materials and Methods: The study was carried out in 2020 at two sites on the island of Hvar: the Selca vineyard, situated inland, and Sveta Nedjelja, situated on the southern side of the island. The experiment was set up as a randomized block design with three replicates of 20 vines per treatment. The defoliation treatments were control (C), basal defoliation before véraison (T1), basal defoliation at véraison (T2), and apical defoliation above the fruiting zone at véraison (T3). Total soluble solids (TSS), titratable acidity, and pH were determined according to OIV (2019) methods, and organic acids (tartaric, malic, citric) by HPLC. Individual polyphenolic compounds were extracted from freeze-dried grape skins and quantified by HPLC with diode-array and fluorescence detection, with results expressed as mg/kg of skin dry weight. Data were analyzed by one-way ANOVA with Duncan's multiple range test (p < 0.05) in XLSTAT. Results and Discussion: At both sites, the defoliation treatments affected TSS and polyphenolic profiles, increasing TSS and reducing the content of polyphenols. Treatments at Sveta Nedjelja accumulated excessive TSS, reaching over 110 °Oe. The highest content of polyphenolic compounds was found in T2 at the Selca vineyard and in T1 at the Sveta Nedjelja vineyard. Conclusion: In the context of a warm Mediterranean climate, this viticultural practice and its performance should be reconsidered.

Introduction: This study evaluated the accuracy of various cone-beam computed tomography (CBCT) reconstruction modalities, specifically the HyperSight (HS) detector, in comparison to standard computed tomography (CT) simulation for potential use in online adaptive radiotherapy. The research focused on the Hounsfield Unit (HU) to relative electron density (RED) conversion and its subsequent impact on volumetric modulated arc therapy (VMAT) dose calculations. Methods: Two tissue-equivalent phantoms, the advanced electron density and the CIRS Thorax phantom, were utilized. Imaging was performed on a SOMATOM go.Open Pro CT simulator and a Varian TrueBeam medical linear accelerator using CBCT, HS-CBCT, HS-iterative CBCT (iCBCT) and HS-iCBCT metal artifact reduction protocols. Calibration curves (HU-RED) were generated for two regions: RED <1.2 and 1.2≤ RED <1.8. VMAT plans (6 MV) were created in the Eclipse 18.1 treatment planning system (TPS), using an anisotropic analytical algorithm (AAA) and Acuros XB algorithm. Absolute dose measurements were conducted using an SNC125c ionization chamber and compared with TPS-calculated doses. Results: In the soft-tissue region (RED <1.2), all imaging modalities showed an excellent linear correlation with CT (r > 0.998), with HU deviations within ± 30 HU. In the high-density region (1.2 ≤ RED < 1.8), HS-CBCT demonstrated superior stability with the lowest root mean square error, 62.88 HU. Dosimetric results showed that 96.7% of all measurement points met the ± 3–4% agreement criteria. For the AAA algorithm, HS-iCBCT exhibited the highest precision (standard deviation = 0.59) and the lowest mean absolute error. The Friedman test confirmed a statistically significant difference between modalities (p < 0.05), with HS-iCBCT showing the most consistent performance. Conclusion: Both HS-CBCT and HS-iCBCT provide highly accurate HU-RED conversions and reliable dosimetric results for RED < 1.8.

This paper studies learning-based model predictive control (MPC) for stabilizing unknown discrete-time linear systems with hard input constraints and additive unbounded sub-Gaussian disturbances. We adopt a certainty-equivalence (CE) design that combines a switching MPC control law with online regularized least-squares (RLS) parameter estimation. The resulting switching control law blends the MPC with a saturated deadbeat controller, ensuring global closed-loop stability. Building upon non-asymptotic error bound of least-squares, we derive non-asymptotic, high-probability stability bounds for the closed-loop system under the proposed switching controller. Numerical experiments illustrate and support the theoretical findings.

OBJECTIVE To assess whether transfer-learning models applied to panoramic radiographs (PANs) can classify individuals at the threshold of legal majority (≥18 years). MATERIALS AND METHODS Vision Transformer (ViT) and EfficientNetV2 models were trained on PANs from Bosnian and Lebanese individuals aged 14-24.99 years (n = 1764), considering pooled and sex-specific datasets with and without augmentation. Binary classification, multiclass classification, and regression models were trained and evaluated. Model performance on an internal test set derived from the same sample was summarized using accuracy, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (ROC AUC). For regression and multiclass models, legal majority classification was additionally assessed by thresholding predicted ages or age categories at 18 years. External validation employed an independent Brazilian dataset (n = 1579; 14-24.99 years). Formal statistical comparison between internal and external performance employed two-proportion z-tests for accuracy and DeLong's test for ROC AUC. RESULTS On the internal test set, the best-performing binary classification model, EfficientNetV2 with augmentation on the pooled dataset, achieved an accuracy of 0.90, sensitivity of 0.92, specificity of 0.86, F1 score of 0.91, and ROC AUC of 0.93. Using the same pooled, augmented configuration, thresholded regression predictions achieved accuracies of 0.85 for EfficientNetV2 and 0.83 for ViT, whereas thresholded multiclass predictions achieved accuracies of 0.84 and 0.73, respectively. Compared with direct binary classification, these thresholded outputs showed no clear advantage, and multiclass models generally showed higher specificity but lower sensitivity. This same pattern was retained when thresholded models were evaluated on the external validation set, with thresholded regression remaining comparatively stable and thresholded multiclass performance declining more markedly, especially for ViT. Visualization maps (gradient-weighted class activation mapping [Grad-CAM] and occlusion sensitivity) confirmed attention to relevant dental structures. On external validation, the same binary EfficientNetV2 configuration achieved an accuracy of 0.81, sensitivity of 0.90, specificity of 0.61, F1 score of 0.87, and ROC AUC of 0.85. Sex-specific models performed similarly, showing no clear advantage over pooled training. Statistical testing confirmed significant AUC degradation on external validation for both models (EfficientNetV2: p = 0.004; ViT: p < 0.001), while the accuracy drop was significant only for ViT (p = 0.035). CONCLUSIONS This study demonstrated that transfer learning with EfficientNetV2 and Vision Transformer can distinguish minors from adults using PANs with high internal performance and acceptable external generalization. Direct binary classification provided the most robust approach for legal age assessment in the present dataset. The findings support the forensic potential of these models, while also indicating the need for further work to improve robustness and real-world applicability.

BackgroundThe comet assay is a sensitive and widely used technique for assessing DNA damage at the single-cell level. Despite its advantages, traditional manual scoring methods remain time-consuming, subjective and limited in scalability, posing challenges for high-throughput and standardized analysis.ObjectiveThis study aims to develop and evaluate a deep learning-based system for automated comet assay image classification, addressing limitations of manual and semi-automated approaches while enhancing accuracy, reproducibility and processing efficiency.MethodA YOLOv5-based object detection model was trained on a dataset of 875 annotated comet assay images, curated through a three-step expert-reviewed process. Various hyperparameters and data augmentation techniques were optimized to improve performance. The dataset was split into training, validation and test sets, and model performance was evaluated using mAP, precision, recall and confusion matrix analysis.ResultsThe model achieved strong performance, with mAP@0.5 reaching 0.98 and recall exceeding 0.8. Detailed analyses revealed robust learning behavior and generalization capacity. Visual outputs, including precision-recall curves and class-wise confusion matrices, confirmed high classification accuracy, although overlapping comet structures and class imbalance posed challenges. The model demonstrated improved scalability and processing speed compared to traditional tools, supporting its integration into web-based applications.ConclusionThe proposed YOLOv5-based system offers a scalable and accurate solution for automating comet assay analysis. It significantly enhances throughput and reduces human error, supporting its application in genotoxicity testing, biomonitoring and molecular epidemiology. Future work will focus on handling overlapping structures, benchmarking against existing tools and optimizing deployment in real-world laboratory settings.

The calcium (Ca2+) sensor calmodulin (CaM) genes CALM1, CALM2, and CALM3 were recently included in the American College Medical Genetics and Genomics (ACMG) secondary findings (SF) list, given their significance in causing long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). These three genes share identical protein sequences, posing potential challenges in variant interpretation. Using paralogue annotation (PA) to classify pathogenic variants and variants of uncertain significance (VUS) across these three paralogue genes, we performed a systematic, semi-automated curation of the CALM1, CALM2, and CALM3 variants. The analysis identified 173 unique CALM variants from ClinVar and Mastermind databases (75 CALM1, 59 CALM2, and 39 CALM3 variants). After paralogue annotation, we identified 126 unique variants in each of the three genes—378 cDNA variants in total. Out of 126 unique variants for each CALM gene, 63 were VUS, 62 were likely pathogenic/pathogenic (LP/P), and one was conflicting (192 VUS, 186 P/LP, and 3 C in total). Twelve unique variants in the CALM1, CALM2, or CALM3 genes had conflicting classifications between VUS and LP/P calls, which were resolved as LP/P. The application of paralogue annotation and variant curation resulted in an increased number of likely pathogenic/pathogenic variants (111% increase). Additionally, our analysis confirms that the majority of known pathogenic variants are predominantly located within the C-lobe of the CaM protein. This study highlights the benefits of paralogue annotation for accurate variant interpretation in CALM1, CALM2, and CALM3 genes, suggesting that a reduction in missed diagnoses is associated with calmodulinopathies.