Molecular chaperones are central regulators of the proteostasis network, ensuring proteome integrity through protein folding, the prevention of aggregation, and targeted degradation. These mechanisms are essential for limiting proteotoxic stress and preventing the accumulation of pathogenic proteins. Consequently, chaperone dysfunction is linked to various diseases including genetic chaperonopathies caused by pathogenic mutations. The most commonly affected chaperones include small heat shock proteins (sHSPs; HSPB1, HSPB3, HSPB5, HSPB8), Hsp60 (HSPD1), Hsp70 (HSPA9/mortalin), and the CCT/TRiC complex. sHSPs are ATP-independent chaperones critical under stress conditions and are characterized by intrinsically disordered regions (IDRs), particularly in flexible terminal regions. Although structurally important, IDRs are frequently targets of disease-associated mutations. In this study, intrinsic disorder in chaperones linked to genetic chaperonopathies was analyzed using bioinformatics tools, followed by a focused evaluation of highly disordered proteins and their disease associations. The results highlight intrinsic disorder as a conserved and functionally essential feature. HSPB1 and HSPB8 show high disorder levels, consistent with roles in neural proteostasis and neuropathies. HSPB3 and HSPB5 exhibit moderate disorder but harbor mutations linked to muscle and cardiac diseases. In contrast, HSPB6 dysfunction is mainly driven by post-translational modifications, rather than mutations. Overall, genetic chaperonopathies can be viewed as intrinsic-disorder-related diseases.

After encountering allogeneic nonself, monocytes differentiate to DCs, which in turn activate the adaptive immune system that drives transplant rejection. The downstream mechanisms of allorecognition are largely unknown. We analyzed scRNA-seq data sets to identify transcriptional changes in monocytes occurring after allostimulation. Hspa1a, which encodes HSP70, was upregulated in monocytes after allostimulation in contrast to syngeneic controls in mice lacking T, B, and NK cells. Similar findings were seen in scRNA-seq data derived from kidney biopsies of rejecting transplant patients. To validate the role of HSP70 in innate allorecognition and transplantation, we performed allogeneic bone marrow plug and kidney transplantation into WT, Hspa1a/Hspa1b–/–, and DSG-treated (HSP70 inhibitor) B6 mice and examined the graft immune infiltrate. Histology, T cell infiltration, and survival were assessed in kidney transplanted mice. In both models, DSG-treated or HSP70-KO recipients displayed significantly reduced infiltration by monocyte-derived DCs (mo-DC). Chronic rejection of Balb/c kidney grafts in WT B6 recipients was attenuated in DSG-treated and HSP70-KO recipients as indicated by a reduction in Banff score. Further experiments demonstrated that in vitro allostimulated immature HSP70-KO BMDC showed less maturation compared with WT BMDC. Targeting HSP70 in innate immune cells offers a novel approach to reduce chronic kidney graft rejection.

Purpose To compare federated learning (FL) and centralized learning (CL) performance for brain tumor classification and segmentation and examine whether specific configurations confer measurable performance advantages. Materials and Methods In this systematic review and meta-analysis, Medline, EMBASE, PubMed, Web of Science, and Scopus were searched from inception to March 4, 2026. Classification accuracy was pooled using random-effects meta-analysis, with heterogeneity quantified using I2; other metrics were summarized descriptively. Paired differences in classification accuracy and Dice similarity coefficient (DSC) were assessed using the Wilcoxon signed-rank test. Mixed-effects meta-regression and subgroup analyses evaluated whether specific configurations were associated with performance differences. Results Of 3,880 records identified, 50 studies were included (26 classification/detection, 26 segmentation; 2 in both). Within-study differences between FL and CL performance were -0.87 percentage points (pp) for classification accuracy (95% CI [-3.32, +1.44]; P = .41, k = 13) and -1.29 pp for segmentation DSC (95% CI [-4.23, +0.81]; Holm-corrected P = .50, k = 11). In unmatched single-arm analyses, pooled classification accuracy was 96.77% for FL (k = 18) versus 96.86% for CL (k = 9); the pooled DSC for segmentation was 84.95% (k = 24) versus 84.61% (k = 11). Heterogeneity was high (I2=93.3-96.5%); the 95% prediction interval for FL accuracy was 86.72-100%. Aggregation strategy, training sample size, task category, and independent and identically distributed (IID) versus non-IID partitioning were not associated with performance differences (all P ≥ .38). Conclusion There was no evidence of paired differences between FL and CL in brain tumor classification accuracy or segmentation DSC, and no specific configuration conferred a measurable performance advantage. © RSNA, 2026.

Marketing of foods high in fat, sugar and salt shapes the food preferences and intake of children and adolescents. The primary aim of this study was to culturally adapt and validate the Scale of Effects of Social Media on Eating Behavior (SESMEB) for assessing the influence of social media on the eating habits of adolescents in the Republic of Srpska, Bosnia and Herzegovina, and to examine whether this influence differs by sex, place of residence, nutritional status and school attended. A cross-sectional study was conducted in six secondary schools in the city of Doboj in May 2023 and included 362 adolescents attending the third and fourth grades. The SESMEB scale was cross-culturally adapted into Serbian through forward and back-translation, expert panel review and pre-testing. Internal consistency was assessed by Cronbach’s alpha and corrected item-total correlations, the factor structure by exploratory factor analysis, and test–retest reproducibility in a subsample of 14 respondents by the intraclass correlation coefficient (ICC). Group differences were tested by t -test and ANOVA. The adapted scale showed good internal consistency (Cronbach’s alpha = 0.865), with corrected item-total correlations from 0.346 to 0.638; the data were suitable for factor analysis (KMO = 0.857; Bartlett’s test χ 2 (153) = 2312.380; p  < 0.001). Exploratory factor analysis identified three subscales accounting for 51.5% of the variance, which could not be clearly separated. Test–retest analysis showed no significant difference between administrations ( t  = 0.552; p  = 0.591; ICC > 0.7). Mean scores for all 18 items denoted no perceived influence, with 55.0–76.8% of respondents reporting no effect on their food-related attitudes and practices. Girls scored higher than boys for following nutrition-related content ( p  < 0.05) and for the increase in the desire to eat ( p  = 0.048); differences also emerged by place of residence ( p  = 0.041) and school attended ( p  = 0.008; p  = 0.004). Adopted version of the SESMEB scale is a reliable instrument for assessing the perceived effects of social media on adolescent eating behavior. Most respondents reported no such influence, even though this population is intensively exposed to digital marketing of energy-dense products, suggesting that self-report may underestimate the actual effect of that exposure.

Background/Objectives: Diabetic cardiomyopathy (DCM) is a major cardiovascular complication of diabetes mellitus characterized by progressive myocardial remodeling driven by oxidative stress, inflammation, and fibrosis. The interleukin-33 (IL-33)/soluble suppression of tumorigenicity 2 (sST2) signaling axis has recently emerged as an important regulator of cardiac remodeling and a potential therapeutic target in DCM. N-acetylcysteine (NAC) and glycine exhibit complementary antioxidant and anti-inflammatory properties; however, their combined effects on circulating IL-33 and sST2 levels and myocardial structural remodeling in experimental diabetes remain insufficiently investigated. This study evaluated the effects of NAC and glycine, administered alone or in combination, on oxidative stress, inflammatory biomarkers, cardiac morphology, and serum sST2 levels in streptozotocin-induced diabetic rats. Methods: Thirty-four adult Wistar rats were randomly assigned to five groups: healthy controls, untreated diabetic animals, diabetic animals treated with NAC (100 mg/kg/day), glycine (250 mg/kg/day), or combined NAC and glycine for 12 weeks. Diabetes was induced by a single intraperitoneal injection of streptozotocin (55 mg/kg). Serum concentrations of sST2, IL-33, malondialdehyde (MDA), and superoxide dismutase (SOD) activity were determined. Cardiac remodeling was evaluated by stereological and histopathological analyses. Results: Experimental diabetes significantly increased serum sST2, IL-33, and MDA concentrations and induced marked myocardial remodeling characterized by expansion of the interstitial and perivascular compartments, increased connective tissue deposition, and reduced cardiomyocyte volume density. Both NAC and glycine significantly attenuated these biochemical and structural abnormalities compared with untreated diabetic animals. Treatment effects varied across outcomes. The combined NAC and glycine regimen was associated with particularly pronounced reductions in sST2 and IL-33 and with preservation of myocardial architecture, whereas the magnitude of improvement in oxidative stress markers differed between treatment groups. Conclusions: NAC and glycine, administered either alone or in combination, attenuated several biochemical and structural alterations associated with streptozotocin-induced diabetes. The magnitude of these effects varied across the assessed outcomes, with the combined regimen showing particularly favorable effects on circulating sST2 and IL-33 levels and myocardial structural remodeling, while some oxidative stress parameters showed greater improvement with NAC monotherapy. These outcome-dependent effects highlight the potential complementary actions of NAC and glycine without implying uniform superiority of the combined regimen. Overall, these findings provide an experimental basis for further investigation of NAC- and glycine-based therapeutic approaches for diabetes-associated myocardial remodeling.

MicroRNAs (miRNAs) are key post-transcriptional regulators implicated in neuroinflammatory and neurodegenerative processes underlying multiple sclerosis (MS). This study aimed to identify candidate miRNAs associated with MS and investigate their involvement in disease-related molecular pathways. An integrated in silico workflow was used to identify MS-associated genes, predict regulatory miRNAs, and characterize enriched pathways. Candidate miRNAs were validated in serum EV-enriched fractions from treated and untreated MS patients and healthy controls using quantitative polymerase chain reaction (qPCR). In silico analysis prioritized four miRNAs (miR-204-5p, miR-17-5p, miR-21-5p, and miR-106a-5p) for validation. Their predicted target genes were enriched in pathways related to immune regulation and central nervous system function, including Th17 cell differentiation, MAPK signaling, cytokine signaling, and axon guidance. qPCR revealed significant differences in miR-21-5p and miR-106a-5p expression between MS patients and healthy controls, while miR-204-5p differed between untreated MS patients and healthy controls. Among the four miRNAs evaluated, miR-21-5p was significantly associated with MS status and showed moderate discrimination between MS patients and healthy controls (AUC = 0.7204). These findings identify serum EV-enriched miRNAs as candidate biomarkers of MS, although validation in larger and longitudinal cohorts is required.

BACKGROUND Irritable Bowel Syndrome (IBS) is heterogenous disorder of gut-brain interaction, with a key role for the dysregulated host-gut microbiota interplay. IBS subtyping is based only on symptoms of bowel habits, reflecting limited insight into underlying biological mechanisms. Aims: This study aimed to define microbiota-based IBS phenotypes and to compare these to traditional stool-based subtyping. Methods: The study utilised data from the Maastricht IBS cohort. Gut microbiota composition was analysed using shotgun metagenomic sequencing. Faecal volatile organic compounds (VOCs) were measured by gas chromatography mass spectrometry. Dietary intake and gastrointestinal and mental health symptoms were assessed using a food frequency questionnaire, the Dutch Healthy Diet-15 index, the Gastrointestinal Symptom Rating Scale, and Hospital Anxiety and Depression scores, respectively. Machine-learning approaches were applied to identify microbiota-based phenotypical clusters, which were compared with established Rome III subtypes, and associated with faecal VOCs, gastrointestinal symptom severity, diet and mental health. Results: 178 IBS patients and 134 healthy controls were included. Gut microbiota composition distinguished IBS patients from healthy controls with an AUCROC 0·8. This discriminatory profile was not associated with Rome III subtypes, while statistically significant associations were found with faecal VOCs profiles (i.e. R=0·67, p=4·46e-4) and symptom severity scores of abdominal pain (p=0·05), reflux (p=0·03), and diarrhoea (p=0·01) and depression (p<0·001). Dietary associations varied across clusters. Conclusion: These results suggest that gut microbiota profiling might provide a basis to define relevant IBS endotypes. Further exploration and validation efforts into this direction are needed using longitudinal studies to refine IBS patient stratification ultimately. .

The production of plum spirits is deeply rooted in the traditions of the Balkan countries, where it ranks among the most popular types of spirit. Various plum varieties are employed to achieve the most aromatic spirit possible. This study investigated the distribution of major and minor volatile compounds in plum distillates produced by blending two plum varieties, Stanley and Požegača. Two blending approaches were evaluated: (i) blending during fermentation and (ii) maceration of fresh Požegača fruit in raw Stanley distillate followed by redistillation. The varieties were combined in three ratios, 90:10, 70:30, and 50:50, with the aim of enhancing the plum aroma of the resulting spirits. Major volatile compounds were analysed by GC-FID, while minor volatile compounds were characterised using GC × GC-MS. All distillates exhibited typical profiles of major volatile compounds. Blending plum varieties proved to be an effective strategy for improving the flavour profile of plum spirits. The relative abundance of minor volatile compounds varied mainly according to plum variety and its proportion in the blend. Fermentation blending resulted in higher relative abundances of α-terpineol, heptanal, benzaldehyde, and γ-dodecalactone, whereas maceration increased the relative abundance of benzyl alcohol, 2-phenylethanol, octanoic acid, and (E)-β-damascenone. Even though maceration blending yielded elevated relative abundances of minor volatile compounds, it did not enhance the sensory qualities of the resulting spirits. Samples containing a higher proportion of Požegača were perceived as having greater aromatic and odour intensity than those containing Stanley. In contrast, the inclusion of Stanley resulted in a more favourable mouthfeel.

ABSTRACT This paper presents the seismic assessment of a 23-story reinforced concrete residential building in Sarajevo, constructed in 1969. The structural system consists of relatively thin walls and slabs, adapted to implement tunnel formwork technology. The walls were designed and detailed with relatively limited reinforcement, so they do not meet the requirements of contemporary seismic codes. Nonlinear dynamic analyses were performed in SAP2000 and DIANA FEA software packages using earthquake acceleration records. The building exhibits satisfactory global response under moderate shaking but develops nonlinear behavior, reinforcement yielding, and cracking in the lower wall zones during stronger events, confirming its seismic vulnerability.

Contemporary urban development is characterized by increasing population mobility, rising motorization, and the negative impacts of transport on quality of life and the environment. In response to these challenges, the concept of sustainable urban mobility has been developed, integrating transport and spatial planning, environmental protection, and socio-economic development. The aim of this paper is to analyze contemporary transport planning concepts in the context of sustainable urban mobility, present European experiences, and assess the possibilities for their implementation in Bosnia and Herzegovina. The research applies methods of scientific literature review, analysis of the European Union's strategic documents, and a comparative analysis of best practice examples. Particular attention is devoted to Sustainable Urban Mobility Plans (SUMPs), including an analysis of the experiences of Vienna, Copenhagen, Ljubljana, and Barcelona. The results indicate that successful sustainable mobility requires integrated planning, institutional coordination, the development of alternative transport modes, and continuous monitoring of outcomes. In Bosnia and Herzegovina, the greatest potential lies in improving public transport, promoting active mobility, implementing intelligent transport systems, and strengthening institutional capacities.

AttractAdria is a Horizon Europe initiative that strengthens research and innovation ecosystems in the Adriatic region by improving research careers and capacity in personalised preventive healthcare. Its ecosystem-based approach combines institutional reform, research-support hubs, mentorship, training, mobility and academia-industry collaboration. Transferable skills are developed alongside competencies in biomarkers, genomics, glycomics, digital health, artificial intelligence, and clinical and translational research. By linking widening-region institutions with international partners, healthcare providers, industry, policymakers and funders, the project aims to improve career development, talent circulation and the region's ability to translate multidisciplinary research into responsible preventive-health innovation.

BACKGROUND Intratumoral bacteria are increasingly recognized as active contributors to neutrophil-driven inflammation and disease progression in solid tumors. Yet, in clear cell renal cell carcinoma (ccRCC), where myeloid inflammation is a key feature of aggressive disease, live bacterial presence, their intratumoral distribution, and interaction with the tumor microenvironment remain unexplored. METHODS We genetically characterized the microbiome of primary ccRCC tumors across two independent cohorts (TRACERx: 616 samples, 143 patients; The Cancer Genome Atlas [TCGA]: 511 samples and patients), confirming live bacterial presence through culture. Multi-regional sampling enabled within-tumor analysis of bacterial distribution. Associations with the tumor microenvironment were explored at scale using bulk RNA sequencing (RNA-seq) across both cohorts and corroborated in depth through spatial transcriptomics and in vitro infection assays. FINDINGS Across both cohorts, the commensal Cutibacterium emerged as the dominant genus, accumulating in discrete niches enriched toward the tumor center and associating with more advanced (TRACERx p = 0.024; TCGA p = 0.0011) tumors and shorter progression-free survival (TRACERx p = 0.0022; TCGA p = 4.4 × 10-4). Both across and within tumors, Cutibacterium accumulation associated with neutrophil recruitment and myeloid inflammation. In vitro, Cutibacterium induced sustained expression of neutrophil-attracting chemokines in macrophages, recapitulating patient tumor findings. CONCLUSIONS These findings establish intratumoral bacteria as novel prognostic components of the ccRCC tumor microenvironment and suggest an active role in shaping local myeloid inflammation, laying the groundwork for investigating their potential as therapeutic targets. FUNDING This work was supported by the Francis Crick Institute (Cancer Research UK, MRC, Wellcome Trust). TRACERx Renal is funded by Cancer Research UK (C50947/A18176).

BACKGROUND Unintentional poisoning is a preventable cause of injury-related morbidity and mortality, yet global patterns, trends, and inequalities remain incompletely characterised. Within the Global Burden of Disease (GBD) framework, unintentional poisoning includes poisoning by carbon monoxide and poisoning by other means, a category largely informed by pesticide poisoning codes plus some indirect capture of other poisoning as part of the GBD re-distribution process. Poisonings by pharmaceuticals and illicit substances are not captured in the GBD definition of poisoning. We aimed to quantify this GBD-defined burden and assess regional variation, sociodemographic gradients, and case fatality between 1990 and 2023. METHODS We analysed GBD 2023 estimates for 204 countries and territories, modelling deaths, incidence, and disability-adjusted life-years (DALYs) using standard GBD cause-of-death and non-fatal estimation methods with 95% uncertainty intervals. We stratified results by age, sex, region, and Socio-demographic Index (SDI), and derived case fatality from modelled deaths and incidence. FINDINGS In 2023, unintentional poisoning from carbon monoxide and other means caused 2·54 million incident poisonings, 69 805 deaths, and 3·68 million DALYs globally, with age-standardised DALY rates declining by 47·5% since 1990. Carbon monoxide accounted for 641 932 poisonings, 30 890 deaths and 1·34 million DALYs, with the highest burdens in central and eastern Europe and central Asia. Most regions showed substantial long-term declines, and the global age-standardised DALY rate for carbon monoxide poisoning declined by 58·2% since 1990. Poisoning by other means caused 1·90 million incident cases, 38 914 deaths, and 2·34 million DALYs, with the greatest burden in sub-Saharan Africa. Most regions showed declining age-standardised DALY rates for poisoning by other means; however, there was no clear change (with the 95% uncertainty interval including zero) in the global estimate, driven by wide uncertainty intervals in several regions (including sub-Saharan Africa). Mortality and DALYs were inversely associated with SDI, and derived case fatality was highest in low-SDI regions. INTERPRETATION Global reductions in GBD-defined unintentional poisoning by carbon monoxide and other means are consistent with decades of regulatory and environmental interventions. These include bans of highly toxic pesticides, improved heating and ventilation systems, emissions controls, and adoption of carbon monoxide alarms. Stark inequalities persist in some regions and in low-SDI settings. Compared with previous GBD publications, this study provides a detailed global assessment of unintentional poisoning by carbon monoxide and other means up to 2023, integrating incidence, DALYs, and comparative case fatality across regions. FUNDING Gates Foundation and the Australian National Health and Medical Research Council.

Intracranial aneurysm rupture is associated with substantial morbidity and mortality, yet aneurysm detection remains challenging, particularly for small lesions and on routine non-angiographic imaging examinations. To support the development and evaluation of artificial intelligence (AI) algorithms for intracranial aneurysm detection and localization, the Radiological Society of North America (RSNA), in collaboration with the American Society of Neuroradiology (ASNR), the Society of Neurointerventional Surgery (SNIS), and the European Society of Neuroradiology (ESNR), curated the RSNA Intracranial Aneurysm (RSNA-ICA) Dataset. Developed for the 2025 RSNA Intracranial Aneurysm Detection Challenge, RSNA-ICA is a large, publicly available, expert-annotated dataset comprising 7202 CTA, MRA, and MRI series from 4278 adult patients collected across 21 institutions in 12 countries spanning five continents. The dataset includes 2566 CTA, 2166 MRA, and 2470 MRI series from patients with and without intracranial saccular aneurysms, providing substantial geographic and imaging diversity. Expert annotations indicate both aneurysm presence and location, and 178 series additionally include three-dimensional segmentations of challenge-defined vascular locations. RSNA-ICA was used to develop and evaluate algorithms in the 2025 RSNA Intracranial Aneurysm Detection Challenge. Of the 7202 image series, 5041 are publicly available through MIRA, while the remainder were used for challenge public and private test sets. The dataset is freely available to the research community for noncommercial use and provides a comprehensive resource for advancing AI-based aneurysm detection across both angiographic and routine neuroimaging examinations.