Polyploid giant cancer cells (PGCCs) are characterized by enlarged nuclei, association with tumors, and resistance to treatment, contributing significantly to cellular heterogeneity. These cells arise from endoreplication and cell fusion, often triggered by stressors such as radiation and chemotherapy. PGCCs exhibit chromosomal instability and aneuploidy, leading to poor prognosis in various cancers. Key features include the ability to produce progeny cells via amitotic division and the expression of cancer stem cell markers. PGCC formation and function involve signaling pathways like cell fusion (GCM1/syncytin-1), cell cycle control, stress response, and EMT. Understanding these pathways is crucial for identifying therapeutic targets. Current therapeutic strategies targeting PGCCs involve drugs like azacitidine, decitabine, and zoledronic acid, as well as DNMT inhibitors in combination therapies. These approaches aim to reverse drug resistance and enhance antitumor efficacy. Furthermore, microRNAs (miRNAs) are pivotal in regulating gene expression and influencing the cell cycle, proliferation, and apoptosis. Cataloging miRNAs and understanding their function is critical for developing potential cancer treatments. Researchers are exploring miRNA-based modulation of signaling pathways to block tumor growth. This review highlights the complex biology of PGCCs and emphasizes the need for targeted therapies to improve cancer treatment outcomes.

Background/Objectives: Ivy leaf extract has been shown to alleviate bronchial infection symptoms through various mechanisms, including anti-inflammatory effects. However, its impact on adaptive immunity, particularly dendritic cell (DC)/T-cell interactions, remains unexplored. This study investigated the immunomodulatory potential of ivy leaf extract (EA 575®) using human monocyte-derived DCs (MoDCs). Methods: Immature MoDCs (imMoDCs) were differentiated with IL-4/GM-CSF and matured with LPS/IFN-γ (mMoDCs). MoDCs, treated with EA 575® during differentiation, were co-cultured with purified T cells. Results: EA 575® (non-cytotoxic up to 100 µg/mL) inhibited MoDC differentiation and maturation by reducing the expression of CD1a, CD83, CD40, CD86, HLA-DR, Dectin-1, CD206, CD209, HIF-1α, and proinflammatory cytokines (IL-12, IL-23, IL-27, IL-1β, IL-6, TNF-α). EA 575®-treated mMoDCs suppressed allogeneic T-cell proliferation and reduced Th1 (IFN-γ), Th17 (IL-17A, IL-22), Th9 (IL-9), Th21 (IL-21), TNF-α, and IL-6 responses. Effects were dose-dependent, with higher concentrations (100 µg/mL) showing stronger inhibition. At lower concentrations (20 µg/mL), EA 575® increased Th2 (IL-4, IL-5) and IL-10 responses, and the frequencies of CD4+ T cells with Treg properties, such as CD25hiFoxp3+, Tr1 (IL-10+Foxp3−), and IL-35+ Foxp3+ cells. Immunoregulatory mechanisms mediated by EA 575®-treated mMoDCs correlated with the upregulation of tolerogenic markers (PD-L1, ILT3, ILT4, IDO1) on mMoDCs and the increased frequency of exhausted CD4+ T cells (PD-1+CD69+) and cytotoxic T cells (Granzyme B+PD-1+). Conclusions: EA 575® induces tolerogenic DCs with significant anti-inflammatory and immunoregulatory properties, a previously undescribed phenomenon. Lower concentrations primarily enhance immunoregulatory responses, while higher concentrations exert more pronounced anti-inflammatory effects.

Abstract The present study explores linkages between the relational driver (brand involvement) and relationship outcomes (affective brand commitment and brand community identification) of consumer brand engagement among luxury and neo-luxury brands. The sample consisted of 616 consumers, compromising 311 owners of the Hugo Boss brand and 305 owners of the Massimo Dutti brand. Structural equation modelling (SEM) and multi-group analysis were used to test the proposed hypotheses. Findings suggest that brand involvement positively influences the three facets of consumer brand engagement - cognitive, affective, and behavioural, in the context of luxury and neo-luxury consumption. Moreover, the affective component of consumer brand engagement strongly predicts affective brand commitment for luxury and neo-luxury brands. Our findings indicate that the brand community identification with luxury and neo-luxury brands is only driven by affective consumer engagement.

Extreme weather events, which are becoming more frequent due to climate change, result in intensified nutrient losses and may override effects of agricultural mitigation measures. Using a landscape connectivity approach, we study the potential of water flow attenuation in upstream forest areas to prevent or mitigate waterlogging and flooding of downstream arable land, thereby contributing to reduced phosphorus (P) losses. We use soil distribution maps, high-resolution elevation data, land use maps and distributed modelling to quantify water storage potential and possible P reductions. In three out of four study catchments (119-915 km2), calculated storage potential of detention basins located in upstream wetland and forest areas was sufficient to retain water volumes (0.7-3.6 million m3) corresponding to discharge volumes produced during an episode with a 50 -year return period. Furthermore, it was estimated that 9-57 % of targeted annual P load reductions from arable land could be reached if stored water volumes bypass arable land without causing waterlogging/flooding leading to P mobilization and transport. As water storage potential is site-specific, prioritization and selection criteria need to be developed in collaboration with relevant stakeholders to achieve cost-efficient implementation of these measures. The methodology and results of this study have significant potential for application in landscapes with a mixture of forests and arable agriculture to aid land owners and managers to secure food production and improve water quality.

Abstract In the modern business environment, big data analytics and data mining techniques are increasingly recognized as tools for improving fiscal discipline and more efficient management of public revenues. This paper explores the possibility of applying the knowledge discovery process from databases to detect patterns of financial behavior that may indicate tax non-compliance. A quantitative approach based on the analysis of secondary data from ten joint-stock companies from the Federation of Bosnia and Herzegovina, for which financial statements and tax debt data are available, was used. The relationship between key financial indicators (EPS, financial stability ratio, total asset turnover ratio and debt ratio) and the amount of tax debt was examined using descriptive statistics and regression analysis. The results show that lower profitability and poorer financial stability significantly correlate with higher tax debt, while high operational efficiency and debt have a more complex and statistically marginal impact. The findings confirm the possibility of using publicly available financial data for early identification of risky taxpayers, which opens up space for further development of predictive models in the domain of tax analytics.

Objectives To examine the association between cigarette price increase and youth smoking initiation in Bosnia and Herzegovina (B&H), and to assess additional factors—including parental smoking, peer influence, pocket money, anti-tobacco media exposure and smoking in school environments—that potentially affect smoking initiation among adolescents. Design A pseudopanel study using WHO Global Youth Tobacco Survey (GYTS) data from two compatible surveys conducted in 2018 (Republic of Srpska) and 2019 (Federation of B&H). A split-population duration model was employed to estimate the hazard of youth smoking initiation. Setting Primary and secondary schools across two entities in B&H, covering both urban and rural areas. Participants A total of 9702 students aged 13–15 years completed the surveys. Inclusion criteria involved being enrolled in grades 7–9 of primary school or the first year of secondary school. No additional exclusion criteria were applied beyond incomplete or invalid survey responses. Interventions None. Primary outcome measure Self-reported smoking initiation, defined as having tried or experimented with cigarette smoking, even one or two puffs. Results A 10% increase in cigarette prices was associated with a 4.9% reduction in the probability of youth smoking initiation (price elasticity of −0.491, p<0.001). Exposure to antitobacco media messages was linked to a lower likelihood of smoking initiation. Conversely, parental smoking, peer influence, observing smoking within school premises and having greater disposable pocket money all showed significant positive associations with youth smoking initiation. Conclusions Raising cigarette prices constitutes an effective measure to discourage smoking initiation among youth in B&H, operating both directly and indirectly through reductions in parental and peer smoking. Nonetheless, non-price factors play a substantial role, highlighting the complexity of adolescent smoking behaviour and the necessity for a comprehensive, multifaceted tobacco control strategy. Trial registration Not applicable (observational study).

Abstract Green innovations are applied in various industries to promote corporate sustainability by adopting sustainable development practices. However, very little is known about how the knowledge management process influences corporate green innovation. To contribute to the development of this issue, this study explores the relationships between knowledge management, corporate sustainable development and green innovation. Data was collected from 210 respondents from private companies in a developing country context and analyzed using the structural equation modeling technique. The findings provide several conclusions. First, the components of knowledge management (application, acquisition and sharing of knowledge) significantly improve the dimensions of corporate sustainable development (environmental, economic and social dimensions). Second, sustainable environmental practices have no effect on the adoption and application of green innovations by companies, however, sustainable social practices have a positive effect on green innovations. The results of this research also show that investing in knowledge management is of great importance for achieving sustainable development, as well as investing in the application of sustainable social practices.

Abstract Although a significant number of studies analyzing the impact of transformational leadership on job performance has been recognized, there is a lack of research considering this construct in the context of managerial performance, and along with interpersonal characteristics. To fill this gap, this paper has been built on Mintzberg’s (1973) premise according to which interpersonal skills play an important role in achieving not only managerial performance but also their leadership styles. In other words, it has been argued that transformational leadership behaves as a mediator in the relationship between social skills and managerial performance. Given the main findings, the paper contributes to practical thinking by indicating the importance of including social skills training focused on building social flexibility and presentation skills, so that managers could have a greater positive impact on managerial performance. As a consequence, it is well known that their better performance increases overall organizational success, which is a valuable lesson for a developing country setting in which this research has been conducted. Contributions to theory and practice are offered after which direction for further research follows.

Neuroinvasive arboviruses such as tick-borne encephalitis virus (TBEV), West Nile virus (WNV), Usutu virus (USUV), and Toscana virus (TOSV) have (re-)emerged with increasing incidence and geographic range. We analyzed the epidemiology of arboviral infections in Croatia during the 2024 transmission season. A total of 154 patients with neuroinvasive diseases (NID), 1596 horses, 69 dead birds, and 7726 mosquitoes were tested. Viral RNA was detected using RT-qPCR. IgM/IgG-specific antibodies were detected using commercial ELISA or IFA, with confirmation of cross-reactive samples by virus neutralization test. RT-qPCR-positive samples were Sanger sequenced. Arboviral etiology was confirmed in 33/21.42% of patients with NID. WNV was most frequently detected (17/11.03%), followed by TBEV (10/6.49%), USUV (5/3.24%), and TOSV (1/0.64%). WNV infections were reported in regions previously known as endemic, while in one continental county, WNV was recorded for the first time. USUV infections re-emerged after a six-year absence. In addition to human cases, acute WNV infections were recorded in 11/395 (2.78%) of horses and two dead crows. WNV IgG seropositivity was detected in 276/1168 (23.63%) and TBEV IgG seropositivity in 68/428 (15.88%) horses. None of the tested mosquito pools were positive for WNV and USUV RNA. Phylogenetic analysis showed the circulation of WNV lineage 2 and Usutu Europe 2 lineage. Climate conditions in 2024 in Croatia were classified as extremely warm, which could, at least in part, impact the quite intense arboviral season. The spreading of flaviviruses in Croatia highlights the need for continuous surveillance in humans, animals, and vectors (“One Health”).

Beetroot (Beta vulgaris L.) is a plant grown for its roots, which are used to obtain sugar, feed animals, and for human use. Beetroot skin, a by-product of food processing, is a significant source of bioactive compounds, including dietary fiber and antioxidants. The primary objective of this work was to utilize beetroot skin powder to produce value-added nougat. Analytical methods, like antioxidant activity tests, proximate analysis, and sensory assessments, are used to determine the impact of beetroot skin powder on the final product. The beetroot skin powder extract had a remarkable content of phytochemicals and antioxidant activity. The inhibitory effect of the extract was tested on enzymes linked to metabolic syndrome, oxidative stress, and inflammation. The beetroot skin powder extract inhibited α-glucosidase, α-amylase, lipase, and lipoxygenase enzymes. The characterization of value-added nougat illustrates the multifunctionality of beetroot peel powder within its composition, serving as a significant source of natural compounds with antioxidant, coloring, and flavoring properties. This enhances sensory attributes, including color, aroma, and texture, augmenting product diversity and consumer appeal. This is evidenced by the increase in the total content of betalains (3.77 ± 0.09 mg/g DW.) and polyphenols (69.48 ± 2.88 mg GAE/100 g DW.), which lead to high antioxidant activity (73.89 ± 3.65 mM Trolox/100 g DW.) for the nougat sample with 6% added beetroot powder. Thus, beetroot skin powder replaced chemically synthesized additives with antioxidants and natural pigments, improving life quality and implicitly capitalizing on beetroot processing by-products, supporting circular economy principles at the global level.

Objectives: To assess amide proton transfer weighted (APTw) MR imaging capabilities in differentiating high-grade glial tumors across alpha-thalassemia/mental retardation X-linked (ATRX) expression, tumor-suppressor protein p53 expression (p53), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation, isocitrate dehydrogenase (IDH) status, and proliferation marker Ki-67 (Ki-67 index) as a preoperative diagnostic aid. Material & Methods: A total of 42 high-grade glioma WHO grade 4 (HGG) patients were evaluated prospectively (30 males and 12 females). All patients were examined using conventional MRI, including the following: T1w-MPRAGE pre- and post-contrast administration, conventional T2w and 3D FLAIR, and APTw imaging with a 3T MR scanner. Receiver operating characteristic (ROC) curves were calculated for the APTw% mean, median, and max signal for the different molecular biomarkers. A logistic regression model was constructed for combined mean and median APTw% signals for p53 expression. Results: The whole-tumor max APTw% signal could significantly differentiate MGMTp from non-MGMTp HGG, p = 0.035. A cutoff of 4.28% max APTw% signal yielded AUC (area under the curve) = 0.702, with 70.6% sensitivity and 66.7% specificity. The mean/median APTw% signals differed significantly in p53 normal versus p53-overexpressed HGG s: 1.81%/1.83% vs. 1.15%/1.18%, p = 0.002/0.006, respectively. Cutoffs of 1.25%/1.33% for the mean/median APTw% signals yielded AUCs of 0.786/0.757, sensitivities of 76.9%/76.9%, and specificities of 50%/66.2%, p = 0.002/0.006, respectively. A logistic regression model with a combined mean and median APTw% signal for p53 status yielded an AUC = 0.788 and 76.9% sensitivity and 66.2% specificity. ATRX-, IDH- wild type (wt) vs. mutation (mut), and the level of Ki-67 did not differ significantly, but trends were found: IDH-wt and low Ki-67 showed higher mean/median/max APTw% signals vs. IDH-mut and high Ki-67, respectively. ATRX-wt vs. mutation showed higher mean and median APTw% signals but lower max APTw% signal. Conclusions: APTw imaging can potentially be a useful marker for the stratification of p53 expression and MGMT status in high-grade glioma in the preoperative setting and potentially aid surgical decision-making.