Rheumatoid arthritis (RA) is an autoimmune systemic disease in which pain remains a major and often refractory symptom even after clinical remission of the disease. Although historically attributed to joint inflammation, recent evidence reveals a multifactorial pathogenesis of RA pain, involving peripheral sensitization, central sensitization, and neuroimmune crosstalk. In these mechanisms, interleukin‐6 (IL‐6) plays a central role not only as one of the inflammatory mediators but also as a classic and trans‐signaling modulator for pain. This review synthesizes current mechanistic and clinical evidence on IL‐6 inhibitors, particularly sarilumab and tocilizumab, concerning their effect on pain in RA. Preclinical studies have already demonstrated that IL‐6 enhances the excitability of nociceptors through the upregulation of ion channels in dorsal root ganglia; it also promotes glial activation within the spinal cord; however, chronic pain sustains these processes. Blockade of IL‐6 receptor reverses these changes and alleviates mechanical hyperalgesia as well as allodynia in different models of diseases. Clinical trials of IL‐6 inhibitors have shown that these compounds provide major pain relief, sometimes better than tumor necrosis factor (TNF) inhibitors, most explicitly for patients with elevated baseline C‐reactive protein (CRP) or who do not respond to TNF inhibitors. Differences in their pharmacokinetics, receptor binding, and suppression of CRP may translate into differences in their analgesic profiles. However, it is analyzed that a subset of patients with persistently painful rheumatoid arthritis despite IL‐6 inhibition demonstrates the existence of non‐inflammatory drivers like nociplastic pain and the inadequacy of conventional indices of disease activity to capture the burden of pain.

BACKGROUND Hyponatremia is a common postoperative electrolyte disturbance in neurosurgical patients and may present with nonspecific neurocognitive symptoms that overlap with intracranial complications. Carbamazepine (CBZ), frequently used for seizure prophylaxis and pain syndromes, is a recognized cause of drug-induced hyponatremia with a syndrome of inappropriate antidiuretic hormone secretion (SIADH)-like profile. CASE SUMMARY A 62-year-old woman underwent elective left supraorbital craniotomy and microsurgical resection of a left anterior skull-base meningioma. Postoperatively, CBZ 400 mg was initiated twice daily for antiseizure prophylaxis. On postoperative day (POD) 2, she developed somnolence and cognitive slowing with serum sodium 131 mmol/L, which progressed to 123 mmol/L (POD 3) and 119 mmol/L (POD 7) despite isotonic saline and increased dietary sodium. Hypertonic saline (3% NaCl) was introduced with partial correction. Evaluation confirmed hypotonic hyponatremia (serum osmolality 254 mOsm/kg) with inappropriately concentrated urine (urine osmolality 560 mOsm/kg) and elevated urine sodium (68 mmol/L) in a clinically euvolemic patient; thyroid and adrenal functions were normal. Given the temporal association and SIADH-like pathophysiology, CBZ-induced hyponatremia was considered the most likely etiology. CBZ was discontinued and replaced with levetiracetam (titrated to 500 mg twice daily), followed by clinical improvement and steady sodium normalization (132 mmol/L at discharge; 136 mmol/L by POD 19), remaining normal at three-month follow-up. We searched PubMed and Google Scholar to for relevant literature review. CONCLUSION This case highlights CBZ as a potentially reversible cause of significant postoperative hyponatremia after meningioma surgery. Early sodium monitoring after CBZ initiation and prompt substitution with alternative antiseizure therapy should be considered when euvolemic hypotonic hyponatremia develops in the postoperative period.

Background Genomic research on rare diseases requires large-scale data sharing to identify pathogenic variants. Traditionally, this is achieved through centralized databases that require the physical transfer of genomic data to third-party servers. However, this approach presents significant challenges under data protection frameworks like the General Data Protection Regulation (GDPR), which considers genomic data inherently identifiable and imposes strict limitations on data sharing. Results To address these limitations, WiNGS-API introduces a federated, automated, and privacy-compliant platform that enables variant-level data sharing across institutions without requiring centralized data transfer. WiNGS-API has been deployed in seven centers, managing over 6,400 samples with single-nucleotide variants (SNV) calls, 1,500 with copy number variants (CNVs), and 500 with structural variants (SVs) from long-read sequencing. The system supports sample-based analysis for variant interpretation and automated trio-based filtering, which reduces candidate de novo variants for clinical review. Federated querying, enables the identification of additional carriers and false positives, as well as improved understanding of variants of unknown significance—outcomes not readily achievable with data from a single institution. Conclusions WiNGS-API bridges the gap between data privacy regulations and genomic collaboration, offering automated variant filtering, annotation, and genotype–phenotype correlation. It provides a scalable solution for multi-center genomic research. WiNGS represents a significant step toward secure, large-scale genomic data sharing, advancing the study of rare diseases while maintaining compliance with ethical and legal standards. WiNGS-API is publicly accessible at https://wings.esat.kuleuven.be/rest-api/api-docs/. Supplementary Information The online version contains supplementary material available at 10.1186/s13073-026-01627-9.

Future wireless communication systems will integrate both sub-6 GHz and millimeter wave (mmWave) frequency bands within multi-antenna architectures to meet the increasing demand for high data rates. In such multi-band systems, reliable information obtained from the sub-6 GHz band can be exploited to support communication at mmWave frequencies. To ensure that both systems experience similar multi-path propagation effects, the sub-6 GHz and mmWave antenna arrays have to be colocated and precisely aligned. However, such a configuration may adversely alter the radiation characteristics of the arrays, potentially degrading their performance. In this paper, we investigate the impact of positioning a mmWave antenna structure in front of a sub-6 GHz antenna structure. Through both simulations and measurements, we evaluate how the presence of the mmWave structure affects the radiation pattern of the csub-6 GHz one. The results demonstrate that the influence of the mmWave structure on the sub-6 GHz performance is minor, indicating that co-located configurations are feasible with negligible degradation.

Summary: Background: Supervised Exercise Therapy (SET) improves walking performance in patients with peripheral arterial disease (PAD) and intermittent claudication, yet implementation and adherence remain inconsistent. This study evaluated functional outcomes, ankle–brachial index (ABI), quality of life (QoL), and adherence to SET in a real-world clinical setting. Materials and methods: This monocentric retrospective cohort study included 190 patients with PAD Fontaine stage II treated at a university vascular outpatient clinic between 01.01.2018 and 31.12.2022. Exposure was participation in SET compared with standard care without SET. Claudication onset distance (COD), peak walking distance (PWD), and ABI were assessed at baseline and after 3, 6, 12, and 24 months. Health-related QoL was evaluated using the SF-36 questionnaire. Adherence and reasons for dropout or non-participation were extracted from medical records. Results: Of the 190 patients (mean age 71.4 years; 60.5% male), 32 (16.8%) completed 12 months of SET, while 158 (83.2%) served as the comparison group. SET participants were older and predominantly male. COD and PWD improved significantly after 6 months (p = .0001 and p = .041) and continued to rise through 24 months, whereas ABI showed no significant changes. Adherence to SET was low. Dropout was mainly related to clinical deterioration, comorbidities, or hospitalisation, with additional sociodemographic and motivational barriers contributing to non-participation. SF-36 scores did not differ significantly, although trends toward reduced pain and improved physical functioning were observed. Conclusions: In this single-centre cohort, SET was associated with improved walking performance but low adherence and no significant changes in ABI or overall QoL.

Background/Objectives: Cardiorenal syndrome type 2 (CRS-2) is characterized by progressive renal dysfunction caused by chronic heart failure (HF) and is associated with increased morbidity and mortality. However, the prognostic value of renal biomarkers in patients with CRS-2 hospitalized for decompensated HF remains unclear. Methods: This prospective observational cohort study included 200 consecutive patients hospitalized for decompensated HF in the Intensive Care Unit of the Clinic for Internal Medicine at the University Clinical Centre Tuzla between April and October 2025. CRS-2 was defined as chronic HF with chronic kidney disease persisting for ≥3 months before admission according to KDIGO criteria. Patients were followed for three months. The primary composite outcome was all-cause mortality or initiation of renal replacement therapy. Results: CRS-2 was identified in 130 patients (65.0%) and was associated with higher in-hospital mortality (32.3% vs. 11.4%, p = 0.002) and three-month mortality (44.6% vs. 21.4%, p = 0.002). Within the CRS-2 subgroup, patients who experienced the primary composite outcome had higher admission levels of cystatin C and urinary albumin-to-creatinine ratio (UACR) and lower estimated glomerular filtration rate (eGFR). ROC analysis demonstrated moderate discriminative ability of cystatin C (AUC 0.739) and UACR (AUC 0.733). In Cox regression analysis, cystatin C (HR 1.534, 95% CI 1.263–1.863, p < 0.001) and UACR (HR 1.003, 95% CI 1.001–1.006, p = 0.001) were significantly associated with the primary composite outcome. Conclusions: Renal dysfunction markers, particularly cystatin C and albuminuria, are associated with early adverse outcomes in CRS-2 patients hospitalized for decompensated HF. Routine assessment of these biomarkers may provide additional prognostic information and support risk assessment in this high-risk population.

Global development in recent decades has beencharacterized by increased resource consumption andgrowing environmental pressures, highlighting the need forsustainable economic and social progress. Tourism, despiteits significant contribution to economic growth, often putspressure on natural resources and ecosystems, underscoringthe need for sustainable development in territories withsubstantial rural characteristics, such as islands. Thispaper examines the role of green transformation as adriver of economic resilience and sustainable developmentof Croatian island economies. Research was conductedamong stakeholders in island destinations who are involvedin tourism planning, development and management, usinga structured questionnaire survey. The results from PartialLeast Squares Structural Equation Modeling (PLS-SEM)show that green transformation of tourism positivelyinfluences all four sustainability dimensions of destinationdevelopment, with the strongest effect on environmentalsustainability. These findings support decision-makers inshaping development strategies for island destinations.

Financial institutions face increasing cyber risk while operating under strict regulatory oversight. To manage this risk, they rely heavily on Cyber Threat Intelligence (CTI) to inform detection, response, and strategic security decisions. Artificial intelligence (AI) is widely suggested as a means to strengthen CTI. However, evidence of trustworthy production use in finance remains limited. Adoption depends not only on predictive performance, but also on governance, integration into security workflows and analyst trust. Thus, we examine how AI is used for CTI in practice within financial institutions and what barriers prevent trustworthy deployment. We report a mixed-methods, user-centric study combining a CTI-finance-focused systematic literature review, semi-structured interviews, and an exploratory survey. Our review screened 330 publications (2019--2025) and retained 12 finance-relevant studies for analysis; we further conducted six interviews and collected 14 survey responses from banks and consultancies. Across research and practice, we identify four recurrent socio-technical failure modes that hinder trustworthy AI-driven CTI: (i) shadow use of public AI tools outside institutional controls, (ii) license-first enablement without operational integration, (iii) attacker-perception gaps that limit adversarial threat modeling, and (iv) missing security for the AI models themselves, including limited monitoring, robustness evaluation and audit-ready evidence. Survey results provide additional insights: 71.4% of respondents expect AI to become central within five years, 57.1% report infrequent current use due to interpretability and assurance concerns and 28.6% report direct encounters with adversarial risks. Based on these findings, we derive three security-oriented operational safeguards for AI-enabled CTI deployments and release supporting materials (search strings, coded evidence matrix, and interview and survey instruments) to improve transparency and facilitate replication and adaptation in similar organizational settings.

Highlights What are the main findings? Visual mental imagery engages ventral and dorsal stream systems in a content- and stage-dependent manner, with evidence for stream interaction that varies across paradigms and populations. Structural and clinico-radiological evidence is broadly consistent with disconnection frameworks, suggesting that disruption of long-range pathways (e.g., inferior longitudinal fasciculus (ILF)/inferior fronto-occipital fasciculus (IFOF)/ superior longitudinal fasciculus (SLF)) may contribute to imagery deficits beyond focal cortical damage. What are the implications of the main findings? Stream-sensitive phenotyping (object vs. spatial imagery) and stage-aware paradigms are essential to develop interpretable neuroradiological biomarkers. Multimodal protocols combining structural MRI, diffusion imaging/tractography, functional connectivity, and lesion mapping can improve clinical interpretation of imagery complaints. Abstract Visual mental imagery, the ability to generate and manipulate internal visual experiences without direct sensory input, links perception with memory, planning, and higher cognition. In this targeted narrative review, we synthesize neuroimaging and lesion evidence on the brain basis of visual imagery, with a focus on neuroradiological correlates of the ventral and dorsal visual pathways. Unlike prior cognitive neuroscience reviews that primarily emphasize functional mechanisms, this review is neuroradiology-oriented and integrates lesion patterns and white-matter disconnection to support clinico-radiological interpretation of imagery complaints. Using a dual-stream framework, we contrast ventral occipito-temporal systems that preferentially support object imagery (appearance-based features such as form, faces/objects, and color, with texture remaining under-studied) with dorsal occipito-parietal systems that preferentially support spatial imagery (relations, transformations, and navigation). Across studies, imagery recruitment is strongly task- and stage-dependent: ventral regions are most often engaged during object-focused imagery, whereas parietal regions are prominent during spatial transformation tasks, with evidence for interaction between pathways when demands require both content and spatial operations. Structural and clinico-radiological findings indicate that imagery impairment can arise from focal posterior lesions and posterior neurodegenerative syndromes but also from network disruption affecting long-range connections that support top-down access to posterior representations. Finally, emerging work on aphantasia and hyperphantasia supports a network-level view in which imagery vividness relates to how effectively higher-order systems engage visual representations. We conclude that standardized, stream-sensitive tasks and multimodal approaches combining functional and structural imaging with lesion-based evidence are key to discovering clinically actionable biomarkers of imagery dysfunction.

Background/Objectives: Hidradenitis suppurativa (HS) is a chronic, immune-mediated inflammatory skin disease characterized by painful nodules, abscesses, sinus tracts, and progressive fibrosis. Vascular activation is becoming increasingly acknowledged as an important factor in HS pathogenesis; however, the effects of tumor necrosis factor alpha (TNF-α) blockade on vascular remodeling in HS remain poorly characterized. This study investigated the impact of TNF-α inhibition by adalimumab (ADA) on endothelial and fibroblast-associated markers in HS lesions. Methods: Formalin-fixed paraffin-embedded skin samples from 71 HS patients were analyzed, including treatment-naive (n = 38) and adalimumab-treated (n = 33) cases. Histopathology and immunofluorescence were performed using antibodies against CD31, von Willebrand factor (vWF), α-smooth muscle actin (αSMA), vimentin, Ki-67 (proliferation), and cleaved Caspase-3 (apoptosis). ImageJ software was used to determine the immunoexpression of selected markers and vascular density. Vascular density, assessed as vessel count per mm2, was designated as the primary endpoint. Sex-related differences were analyzed as exploratory endpoints. Results: Adalimumab-treated tissue exhibited significantly reduced vascular density (p < 0.01) compared to the treatment-naive group. Conversely, vimentin immunoexpression was significantly higher (p < 0.01) in the adalimumab-treated group. No significant differences were found in endothelial Ki-67 or cleaved Caspase-3 expression between treatment groups, indicating that the observed reduction in vascular density is not associated with direct effects on endothelial cell proliferation or apoptosis, but rather may occur indirectly through attenuation of the pro-angiogenic inflammatory milieu. Exploratory sex-stratified analysis revealed that treatment-naive males had significantly higher endothelial proliferation (Ki-67; p = 0.031) and vimentin expression (p = 0.017) compared to treatment-naive females. In the ADA-treated group, males exhibited significantly lower vascular density (p = 0.036) and higher endothelial apoptosis (p = 0.039) compared to females, whereas females showed a significant increase in vimentin expression following treatment (p = 0.008), suggesting possible sex-dependent differences in vascular remodeling. Conclusions: TNF-α blockade is associated with reduced vascular density, consistent with indirect anti-angiogenic effects, suggesting that adalimumab exerts disease-modifying effects on the microenvironment beyond inflammatory cytokine suppression. Sex-dependent differences in vascular regression underscore the importance of considering sex as a biological variable in HS pathogenesis and treatment response. These results highlight the significance of vascular interactions in HS and support adalimumab as a disease-modifying treatment. These exploratory findings require confirmation in longitudinal studies with paired biopsies.

This paper aims to investigate the impact of water use efficiency on income inequality in European countries, exploring how financial development moderates this relationship and controlling for economic, institutional and infrastructural control variables. This study uses Method of Moments Quantile Regression on a panel data set including 32 European countries from 2000 to 2021. The analysis uses the GINI coefficient as a measure of income inequality and assesses its relationship with water use efficiency, financial development and control variables. Water use efficiency has a statistically significant negative impact on income inequality across all quantiles, suggesting that more efficient water use contributes to reducing income disparities. This effect is stronger in countries with already lower levels of inequality. Financial development unexpectedly shows a positive relationship with income inequality, potentially indicating a misallocation of financial resources across income level categories. Government efficiency and inland waterways infrastructure have inequality-reducing effects, while the rule of law augments income inequality in the European Union. This study is limited by the lack of comparable research to benchmark findings against and by potential country-specific institutional, cultural and political factors not fully captured in the model. Future research could explore the role of water efficiency technologies, the impact of climate change on water accessibility and sustainable manufacturing practices in relation to income inequality. This research addresses a significant gap in the literature by examining the impact of water use efficiency on income inequality, presenting novel insights into how water resource management affects socioeconomic disparities in European countries.

Objectives. Our objective was to study the ecological relationship of many risk factors and personal characteristics with mean age at death (AD) after a 50-year follow-up of nearly extinct cohorts. Material and Methods. There were 16 cohorts totaling 12,763 middle-aged men enrolled in the Seven Countries Study (SCS), and 58 variables were measured, including traditional risk factors, dietary nutrition and anthropometric variables. A follow-up of 50 years allowed the use of AD as the end-point. Analysis included simple linear regression correlation and multivariate modelling using Principal Component Analysis and regression and Ridge regression. Results. Out of 58 variables, only 11 (10 nutrition-dietary items plus age) showed a significant linear correlation coefficient (R) ≥ 0.50 and a p value ≤ 0.05. Linear regression was computed by using as a predictor the dietary factor score derived from a Principal Component Analysis of the 11 significant variables, which were used as independent variables, whose coefficients were significantly related with AD, and the final R2 was 0.52. The Principal Component regression and Ridge regression documented the direct relationship of food groups of vegetable origin (including olive oil) with the AD and the inverse relationship for food groups of animal origin. Conclusions. A few variables, all related to diet and nutrition, were able to statistically explain about 50% of the different AD in 16 cohorts of men followed up with nearly until death. Other variables, including traditional cardiovascular disease risk factors, did not contribute in a significant way for this purpose.

Recognizing the problems and shortcomings of the intersection “Vraca”, as well as its importance in the economic, social and economic sense, it was undertaken a detailed operational and planning analysis in order to determine the need for capacity expansion and the selection of the most favorable solution for reconstruction, which would ensure the normal and safe traffic flow with a satisfactory level of service. The analysis was performed on the basis of data recorded in the field, traffic counting, measurement, visual inspection, as well as on the geodetic base data. In order to perform an operational intersection analysis, an analysis of its existing design and technical elements was performed in order to define the road conditions that are important for the capacity analysis. Intersection traffic conditions analysis was also carried out in terms of traffic control elements and traffic flows determined by traffic counting, as well as an analysis of intersection traffic safety. Guided by the principles of functionality, permeability, rational use of space and safety, the conceptual solution of the future intersection was proposed along with the pavement structure dimensioning and the proposal for intersection traffic management.