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Lukas Lenhart, M. Gander, R. Steiger, Agnieszka Dąbkowska-Mika, Malik Galijašević, S. Mangesius, M. Fuchs, Kathrin Sevecke et al.

Background: Comorbid personality disorders (PDs) in patients with anorexia nervosa (AN) are associated with increased psychopathology, higher suicide risk, and poorer treatment response and outcomes. This study aimed to examine associations between gray matter (GM) volume and PDs in female adolescents with AN before and after short-term psychotherapeutic and nutritional therapy. Methods: Eighteen female adolescents with acute AN, mean age 15.9 years, underwent 3T magnetic resonance imaging before and after weight restoration. The average interval between scans was 2.6 months. Structural brain changes were analyzed using voxel-based morphometry. PDs were assessed using the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID II) and the Assessment of Identity Development Questionnaire. Results: SCID-II total scores showed significant positive associations with GM volume in the mid-cingulate cortex at both time points and in the left superior parietal–occipital lobule at baseline. The histrionic subscale correlated with GM volume in the thalamus bilaterally and the left superior parietal–occipital lobule in both assessments, as well as with the mid-cingulate cortex at follow-up. Borderline and antisocial subscales were associated with GM volume in the thalamus bilaterally at baseline and in the right mid-cingulate cortex at follow-up. Conclusions: PDs in female adolescent patients with AN may be specifically related to GM alterations in the thalamus, cingulate, and parieto-occipital regions, which are present during acute illness and persist after weight restoration therapy.

T.J. Carter, Jack Broadfoot, Sarah E. Coupland, B. Damato, Helen Evans, S. Fenwick, Leila Khoja, Tracey Krausa et al.

UK Guidelines for the management of uveal melanoma (UM) were first published in 2015 using an evidence-based systematic approach. The primary aim of this guideline was to optimise patient care by providing recommendations based on the best available scientific evidence. The resulting guideline reflected the strengths and weaknesses of the available evidence, made recommendations that were clinically impactful around prognostication, surveillance, and treatment for patients with primary lesions and metastatic disease. The guideline development process and content met the standards required by NICE and were ultimately NICE accredited. Here, we present an update to these guidelines, highlighting where practice or treatment has changed to such an extent that the original recommendations are now out of date. Presented here are updated guidelines on molecular and genetic testing, management of metastatic disease and clinical surveillance.

Maja Milošević Marković, B. Anicic, M. Lazarević, Milica Jakšić Karišik, Dijana D Mitić, B. Milovanović, Stefan Ivanović, I. Pećinar et al.

This study investigated the potential of Thymus serpyllum L. and Mentha × piperita L. essential oils (EOs), known for their bioactive properties, as adjunctive treatments targeting Basal cell carcinoma cancer stem cells (BCC CSCs). Primary cultures were established from ten BCC tumor samples and their distant resection margins as controls. The chemical composition of the EOs was analyzed by gas chromatography–mass spectroscopy (GC-MS) and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The biological effects were evaluated via colony and spheroid formation, scratch assays, MTT and neutral red cytotoxicity assays, and qRT-PCR for Hh (SHH, PTCH1, SMO, and GLI1) and Notch (Notch1 and JAG1) gene expression. GC analysis identified thymol, p-cymene, and linalool as the main components of the EO of T. serpyllum L., and menthone and menthol in the EO of M. × piperita L. IC50 values were 262 µg/mL for T. serpyllum L. and 556 µg/mL for M. × piperita L. and were applied in all experiments. Both EOs significantly reduced CSC clonogenicity and migration (p < 0.05). The EO of T. serpyllum L. downregulated SMO and GLI1, while the EO of M. × piperita L. upregulated PTCH1, Notch1, and JAG1 (p < 0.05). These findings suggest that both EOs exhibit anticancer effects in BCC CSCs by modulating key oncogenic pathways, supporting their potential in BCC therapy.

Vedad Herenda, Selma Jusufović, Adnan Mušanović

Aim To systematically review the efficacy and safety of fixed-dose combination (FDC) antihypertensive agents in chronic kidney disease (CKD). Methods This systematic review included studies from January 2014 to December 2023 that evaluated FDC antihypertensives in CKD. We searched The PubMed, Embase, and the Cochrane Library databases were searched. Inclusion criteria encompassed studies written in English and published in peer-reviewed journals. Exclusion criterias among others were review articles, editorials, letters, and conference abstracts. Results Six studies met inclusion criteria from 1156 identified publications. Analyzed studies were  included randomized trials (4), cohort studies (1), and retrospective analyses (1). FDCs improved medication adherence, blood pressure control, and renal outcomes. Significant blood pressure  puni naziv skraćenice (BP) reductions were noted with FDCs compared with free combinations. FDCs of renin-angiotensin system inhibitors and thiazide diuretics showed improved adherence, reduced major adverse cardiovascular events, and better renal function preservation. Some combinations losartan hidrochlortiazid demonstrated a more significant reduction of proteinuria and urinary protein-to-creatinine ratio (UPCR), indicating potential renoprotective effects. Conclusion While using FDC antihypertensives has shown promising results in improving patient outcomes in CKD, further large-scale, long-term randomized trials are urgently needed to confirm these findings and optimize treatment strategies. Keywords:  cardiovascular diseases, hypertension management, medication adherence, proteinuria, renoprotection  .

Objectives: This study aimed to analyze the clinical presentation, diagnostic process, therapeutic approaches, pathological features, and treatment outcomes of children diagnosed with Wilms tumor (WT) and evaluate the time intervals from symptom onset to seeking medical attention and subsequent diagnosis. Patients and methods: This retrospective study reviewed the records of 18 children (11 males, 7 females; median age: 3.72 years; range, 0.13 to 8.33 years) diagnosed with WT who underwent surgery between January 1, 2010, and December 31, 2023. Data on demographics, clinical presentation, treatment, and outcomes were collected and analyzed. All patients underwent radical nephrectomy and received preoperative and postoperative chemotherapy as per the UMBRELLA protocol of the International Society of Pediatric Oncology Renal Tumor Study Group. Results: The median age at diagnosis was 37 months. The most common presenting sign was a palpable abdominal mass (100%), followed by abdominal swelling (61%) and distension (67%). The mixed histopathological type was most prevalent (50%). The median time from symptom onset to seeking medical attention was 13.9 days, and the median from initial medical consultation to diagnosis was 9.9 days. Complications occurred in three (17%) patients, and one (6%) patient experienced relapse. The survival rate was 94%. Conclusion: This study's survival and relapse rates are comparable to global data, reflecting advances in the diagnosis and management of WT at our institution. However, further research is needed to address the study’s limitations and enhance outcomes, particularly in resource-limited settings.

V. Petrovic, M. Račić, Biljana Lakić

Abstract Objective. This study aimed to explore the influence of sociodemographic characteristics and lifestyle on the occurrence of anxiety and depression, and the interrelationship between metabolic syndrome (MS) and anxiety and depression. Methods. A total of 685 adults were divided into two groups (with and without MS) using the International Diabetes Federation’s definition of MS. In both groups, we used the Beck Inventory for Anxiety and Depression. The influence of sociodemographic and other characteristics on the occurrence of MS, anxiety, and depression was observed. The multivariate logistic regression model was appropriate for determining which variables (especially anxiety and depression) affected the presence of MS in the participants. Results. MS was observed in 37.5% of participants. Women with mild and severe anxiety were statistically significantly more represented in the group with MS than in the group without MS (26.2% : 12.0%, P=0.001; 16.7% : 4.8%, P=<0.001), as well as women with severe depression (6.3% : 1.9%, P=0.038), while there was no significant difference in men. Sociodemographic characteristics such as female gender, older age, employment status (retirees and homemakers), lower level of education, marital status (divorced and widowed), and more children affected the occurrence of anxiety and depression in participants. Physical inactivity during leisure time, high-risk drinking, and a higher level of cardiovascular risk showed significant influence on the presence of anxiety and depression, while smoking was inversely associated with the presence of depression but not with anxiety. Conclusion. The association between MS and anxiety and depression was confirmed. Women with MS were at a higher risk of anxiety and depression symptoms, whereas this was not confirmed in men.

Melanoma is a malignant tumor derived from melanocytes, predominantly located in the skin and mucosal surfaces. Although this cancer can spread to multiple organs, isolated metastasis to the spleen is exceptionally uncommon. When splenic involvement does occur, it typically forms part of widespread systemic dissemination, rather than appearing as a solitary lesion. This report discusses a 62-year-old male who underwent elective splenectomy following the discovery of a suspicious splenic mass. Three years earlier, he underwent excision of a pigmented nodular lesion in the right pectoral region. Histopathology revealed superficial spreading melanoma, Clark III, Breslow II, with 0.8 mm margins and no lymphovascular invasion, microsatellitosis, or mitoses. Re-excision and right axillary dissection confirmed metastatic melanoma in one of eight lymph nodes. Examination of the resection margins of the re-excised specimen showed no evidence of increased melanocytic activity. A follow-up abdominal CT identified a 7 mm, well-circumscribed, hypodense lesion in the inferior pole of the spleen, which lacked contrast enhancement. Due to inconclusive findings on both CT and ultrasound, surgical removal of the spleen was performed. Subsequent histological and immunohistochemical evaluation confirmed the lesion to be metastatic amelanotic melanoma (ICD-O code M8770/6). Solitary metastasis to the spleen from melanoma remains a clinical rarity and often manifests several years after the initial diagnosis. In such cases, surgical excision is considered the preferred treatment, offering potential for extended survival in the absence of additional metastatic disease.

Haris Smajlović, David Froelicher, Ariya Shajii, Bonnie Berger, Hyunghoon Cho, Ibrahim Numanagić

We present Shechi, an easy-to-use programming framework for secure high-performance computing on distributed datasets. Shechi automatically converts Pythonic code into a secure distributed equivalent using multiparty homomorphic encryption (MHE), combining homomorphic encryption (HE) and secure multiparty computation (SMC) techniques to enable efficient distributed computation. Shechi abstracts away considerations about the private and distributed aspects of the input data from end users through a familiar Pythonic syntax. Our framework introduces new data types for the efficient handling of distributed data as well as systematic compiler optimizations for cryptographic and distributed computations. We evaluate Shechi on a wide range of applications, including principal component analysis and complex genomic analysis tasks. Our results demonstrate Shechi’s ability to uncover optimizations missed even by expert developers, achieving up to 15× runtime improvements over the prior state-of-the-art solutions and a 40-fold improvement in code expressiveness compared to code manually optimized by experts. Shechi represents the first MHE compiler, extending secure computation frameworks to the analysis of sensitive distributed datasets.

Bryony Goulding Mew, Darije Custovic, E. Soreq, R. Lorenz, Inês Violante, Stefano Sandrone, Adam Hampshire

Bryony Goulding Mew, Darije Custovic, Eyal Soreq, R. Lorenz, Inês R. Violante, Stefano Sandrone, Adam Hampshire

Flexible behaviour requires cognitive-control mechanisms to efficiently mediate conflict between competing information and alternative actions. Whether a global neural resource mediates all forms of conflict or this is achieved within domain-specific systems remains unclear. We use a novel fMRI paradigm to orthogonally manipulate rule, response and stimulus-based conflict within a full-factorial design. Whole-brain voxelwise analyses show that activation patterns associated with these conflict types are distinct, but they partially overlap within the Multiple Demand Cortex (MDC) regions that are most commonly active during cognitive tasks. Region of interest analysis shows that most MDC sub-regions are activated for all conflict types, but to significantly varying levels. We propose that conflict resolution is an emergent property of distributed brain networks, the functional-anatomical components of which place on a continuous, not categorical, scale from domain-specialised to domain general. MDC brain regions place towards one end of that scale but still exhibit significant functional heterogeneity.

Jessica Rahman, Alana Delaforce, Danakai Bradford, Jane Li, Farah Magrabi, David Cook, A. Brankovic

Abstract Background Artificial intelligence (AI)–driven clinical decision support (CDS) tools offer promising solutions for health care delivery by optimizing resource allocation, detecting deterioration, and enabling early interventions. However, adoption remains limited due to insufficient validation and a lack of transparency and trust. Explainable AI (XAI) seeks to improve user understanding of AI outputs; however, how clinicians interpret and integrate these explanations into their decision-making remains underexplored. Furthermore, discrepancies in explanations, known as the “disagreement problem,” can undermine trust and, at worst, lead to poor clinical decisions. Objective This study examines clinicians’ perspectives on the role and value of explainability in AI-driven CDS tools within Australian critical care settings and the impact of discrepancies in AI-generated explanations on clinical decision-making. Methods Qualitative data were collected using semistructured interviews with 14 clinical experts, incorporating scenario-based exercises, and were analyzed using inductive thematic analysis. Results Clinicians valued explainability, particularly in complex or unfamiliar situations, when explanations were clear, plausible, and actionable. Trust and perceived usefulness extended beyond explanation quality, encompassing factors such as system accuracy, alignment with clinicians’ reasoning, workflow integration, and perceived reliability. Discrepancies in explanations generated by different XAI methods were not a major concern, provided that the AI-generated predictive alerts were accurate. Conclusions This study provides design recommendations for developing trustworthy, user-centric CDS tools that incorporate XAI. Findings highlight that explainability is critical for establishing initial trust in AI-driven tools by supporting perceived usefulness, but its importance diminishes over time and with user expertise and familiarity, as learned usefulness takes precedence. Recommendations highlight the importance of aligning the design and implementation of AI tools with clinicians’ needs to enhance trust, mitigate risks, and promote successful adoption for improved patient outcomes.

Industry 4.0 marks a new phase of industrial transformation, driven by the integration of advanced technologies such as industrial robotics, the Internet of Things (IoT), artificial intelligence (AI), cloud computing, and cyber‑physical systems (CPS). The Republic of Korea and Singapore are global frontrunners in this domain, ranking first and second worldwide in robot density per 10,000 manufacturing workers. This paper explores how the strategic integration of robotics with key Industry 4.0 technologies contributes to smart manufacturing and enhanced industrial performance. Using a comparative case study approach, the research analyzes national policies, investments in R&D and education, 5G infrastructure, and support for innovation ecosystems that have enabled these countries to develop flexible, automated, and intelligent production systems. Findings indicate that both Korea and Singapore have successfully combined robotics with IoT, big data analytics, and cloud platforms to create efficient and adaptive manufacturing environments. The study emphasizes that robotization alone is not sufficient; its effectiveness depends on alignment with broader digital transformation strategies. Based on longitudinal data from 2013 to 2023, sourced from the International Federation of Robotics (IFR), the OECD, and national innovation agencies, the research highlights how coordinated implementation of Industry 4.0 technologies fosters sustainable and globally competitive manufacturing.

Maria C. Tavares, M. Almeida, José Vale, Amra Kapo

The historical evolution of auditing reflects an increasing complexity in organizational demands, culminating in the emergence of Audit 5.0—an approach that integrates emerging technologies with professional judgment. This study aims to analyze how technological adoption influences risk assessment and materiality determination in financial auditing within a practical, real-world context. The research, qualitative in nature, combines narrative and thematic analysis of the literature, ethnography in a professional setting, and task analysis, developed over four years of experience in a firm of Chartered Accountants. The findings reveal that although digital tools enhance efficiency and accuracy, professional judgment remains essential to ensure the ethics, reliability, and contextualization of audited information. This study contributes to the advancement of understanding regarding the complementarity between technology and the human factor, proposing paths toward more robust and digitally adapted auditing practices.

Sara Deumić, Ahmed El Sayed, Mahmoud Hsino, Andrzej Kulesa, Neira Crnčević, Naida Vladavić, Aja Borić, M. Avdić

Water supply and sewage drainage pipes have a critical role to play in the provision of clean water and sanitation, and pipe material selection influences infrastructure life, water quality, and microbial communities. Zinc-containing compounds are highly valued due to their mechanical properties, anticorrosion behavior, and antimicrobial properties. However, the effect of zinc salts, such as zinc sulfate heptahydrate and zinc chloride, on biofilm-forming bacteria, including Escherichia coli and Enterococcus faecalis, is not well established. This study investigates the antibacterial properties of these zinc salts under simulated pipeline conditions using minimum inhibitory concentration assays, biofilm production assays, and antibiotic sensitivity tests. Findings indicate that zinc chloride is more antimicrobial due to its higher solubility and bioavailability of Zn2+ ions. At higher concentrations, zinc salts inhibit the development of a biofilm, whereas sub-inhibitory concentrations enhance the growth of biofilm, suggesting a stress response in bacteria. zinc chloride also enhances antibiotic efficacy against E. coli but induces resistance in E. faecalis. These findings highlight the dual role of zinc salts in preventing biofilm formation and modulating antimicrobial resistance, necessitating further research to optimize material selection for water distribution networks and mitigate biofilm-associated risks in pipeline systems.

Gender diversity and the inclusion of women in leadership roles are increasingly recognized as critical drivers of organizational equity and sustainability, particularly through their influence on workforce diversity, employee development, and fair compensation practices. While these effects are well-documented in developed economies, evidence from transitional contexts remains limited. This study explores the impact of female leadership on the social dimension of Environmental, Social, and Governance (ESG) performance in private sector companies in Bosnia and Herzegovina. Focusing on three key outcome areas—inclusive hiring, investment in employee training, and average employee compensation—it examines whether a higher share of women in decision-making positions correlates with stronger ESG-related practices. Using original data from 131 firms that applied for the 2024 United Nations Development Programme’s SDG Business Pioneers Award, the analysis reveals a positive association between female leadership and all three outcome variables. These findings suggest that gender-inclusive leadership contributes meaningfully to socially responsible business practices, even in transitional economies. By providing empirical insights from Bosnia and Herzegovina, this study adds to the growing body of research on gender and sustainability. It highlights the potential of female leadership as a lever for advancing ESG goals and offers practical implications for policymakers and corporate actors aiming to align business strategy with inclusive and sustainable development.

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