Abstract Introduction Endovascular therapy (EVT) has become an increasingly important part of acute stroke management. However, the lack of trained neurointerventionalists represents a key barrier in expanding availability of EVT in Europe. This project aimed to investigate the association between the number of neurointerventionalists and overall EVT rates. Patients and methods A cross-sectional analysis was conducted using publicly available data from the Global Burden of Disease Report 2021 and the Stroke Action Plan for Europe (Stroke Service Tracker). Data on the number of neurointerventionalists across 35 European countries were surveyed through a structured survey distributed via the Resident and Research Fellow Section (RRFS) of the European Academy of Neurology (EAN). Correlation analyses were performed to estimate the association between neurointerventionalist density per served population, EVT rates and stroke-related mortality and morbidity. Results Survey response rate was 71% (25/35 countries). The proportion of acute ischaemic stroke patients treated with EVT ranged from 0.05% to 14.96% of people with ischaemic stroke, and the number of neurointerventionalists ranged from 9 to 137 per country and from 0.3 to 7.5 per million inhabitants. There was a positive correlation between the number of neurointerventionalists per population served and EVT rates (Spearman coefficient ρ = 0.507; 95% CI, 0.209–0.719). Greater availability of trained neurointerventionalists was moderately associated with lower national ischaemic-stroke mortality (ρ = −0.473; 95% CI, −0.746 to −0.065) and lower overall disability-adjusted life years (ρ = −0.444; 95% CI, −0.729 to −0.027). Discussion and conclusion The number of neurointerventionalists correlates positively with the annual volume of EVT across European countries; higher EVT rates were also associated with lower stroke-related mortality and disability; however, these associations are unadjusted for other important confounders and causality cannot be inferred. These data suggest an urgent need to increase neurointerventional capacity in Europe, for example, by expanding dedicated national training programmes and enhancing support from national and international professional societies.

This study examines the key competencies required of teachers in contemporary education and their role in preparing future generations. These competencies are widely recognized as foundational to societal development across multiple domains. In this context, the 4Cs model in initial teacher education was developed to establish conceptual and pedagogical preconditions for integrating critical thinking, creativity, collaboration, and communication competencies into teacher education programs. The study investigated the perceptions of students enrolled in teacher education programs at the University of Sarajevo regarding instructional activities through which university teachers foster and develop 4Cs competencies in higher education teaching. The findings indicate that, from the students’ perspective, instructional activities most strongly support the development of communication competency, followed by critical thinking and collaboration, whereas creativity is the least consistently fostered. This finding suggests that the integration of 4Cs competencies in higher education remains predominantly declarative rather than transformative, revealing a gap between curricular expectations and pedagogical practice. Furthermore, the results indicate a highly significant correlation between instructional activities fostering critical thinking and creativity. Significant correlations were also observed among the other competency scales, indicating that these competencies are interrelated and mutually reinforcing rather than developed in isolation. These findings highlight practical implications for teacher education programs.

Background: Osteoarthritis (OA) is a heterogeneous joint disorder traditionally considered mechanically driven; however, evidence indicates that inflammatory mechanisms contribute to symptom expression. Exploratory analyses of peripheral biomarkers may provide insights into systemic inflammation in symptomatic knee OA, but formal phenotypic validation requires dedicated clustering or longitudinal studies. Objective: To examine associations between clinical pain, functional impairment, and circulating inflammatory biomarkers in patients with knee OA compared with healthy controls. Methods: In this prospective, single-center study, patients aged 40–80 years with radiographically confirmed knee OA and chronic knee pain were compared with age- and sex-matched healthy controls. Pain intensity and functional status were assessed using the Visual Analogue Scale (VAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Circulating inflammatory biomarkers, including cytokines and matrix metalloproteinases, were quantified using multiplex immunoassays. Statistical analyses included adjusted linear regression models, with age and BMI as covariates, and multiple testing correction using the Benjamini–Hochberg procedure (FDR alpha error 5%). Results: OA patients exhibited higher circulating levels of TNF-α, IL-6, IL-8, MMP-1, MMP-3, TNFSF13, TNFSF13B, and pentraxin-3 compared with controls (p < 0.01). No significant sex differences were observed. KOOSs correlated with IL-6 and IL-10 levels, suggesting an association between systemic inflammatory activity and functional limitation. All findings are presented as exploratory and associative. Conclusions: Patients with knee OA display systemic inflammatory biomarker differences associated with pain and functional impairment. These results support the role of inflammation in OA symptoms within an exploratory framework. Larger, longitudinal studies are warranted to validate these observations.

Everyday communication is dynamic and multisensory, often involving shifting attention, overlapping speech, and visual cues. Yet, most neural attention tracking studies are still limited to highly controlled lab settings, using clean, often audio‐only stimuli and requiring sustained attention to a single talker. This work addresses that gap by introducing a novel dataset from 24 normal‐hearing participants. We used a wearable electroencephalography (EEG) system (44 scalp electrodes and 20 cEEGrid electrodes) in an audiovisual (AV) paradigm with three conditions: sustained attention to a single talker in a two‐talker environment, attention switching between two talkers, and unscripted two‐talker conversations with a competing single talker. Analysis included temporal response functions (TRFs) modeling, optimal lag analysis, selective attention classification with decision windows ranging from 1.1 to 35 s, and comparisons of TRFs for attention to AV conversations versus side audio‐only talkers. Key findings show significant differences in the attention‐related P2 peak between attended and ignored speech across conditions for scalp EEG. Interestingly, our results revealed strong cross‐condition generalization, with models trained in one condition maintaining good performance when evaluated on the other two. No significant change in performance between switching and sustained attention suggests robustness for attention switches. Optimal lag analysis revealed a narrower peak for conversation compared to single‐talker AV stimuli, reflecting the additional complexity of multi‐talker processing. Classification of selective attention was consistently above chance (55%–70% accuracy) for scalp EEG, whereas cEEGrid data yielded lower correlations, highlighting the need for further methodological improvements. These results demonstrate that wearable EEG can reliably track selective attention in dynamic, multisensory listening scenarios and provide guidance for designing future AV paradigms and real‐world attention tracking applications.

Spinal muscular atrophy (SMA) therapies that restore SMN expression improve survival and motor function but often fail to fully stabilize distal motor units or sustain endurance. We propose a hypothesis-driven adjunctive approach, intended to complement SMN-restoring therapies, in which localized nanotube-enabled interfaces acting at or near the distal motor unit and neuromuscular junction enhance neuromuscular transmission reliability in surviving, remodeled motor units. The model predicts a temporal cascade: improved junctional reliability and reduced activity-dependent failure, followed by consistent motor unit output across repeated activation, and ultimately, enhanced endurance and functional reserve. Phenotype-specific responsiveness identifies patients most likely to benefit, specifically those with preserved-but-limited residual motor unit substrate accompanied by measurable neuromuscular junction instability. Drawing on shared mechanisms from ALS, spinal cord injury, and other neuromuscular disorders, we discuss mechanistic, translational, safety, regulatory, and ethical considerations. This framework links objective physiological constructs to functional outcomes, offering a mechanistically grounded path for adjunctive therapy development in SMA and related conditions.

This translational synthesis highlights the potential role of obesity-induced low-grade chronic inflammation in modulating clinical outcomes among patients with spondyloarthritis (SpA). Obesity transforms adipose tissue into a pro-inflammatory endocrine organ, where hypertrophic adipocytes release adipokines such as leptin alongside cytokines including TNF-α and IL-6, potentially contributing to macrophage polarization toward an M1 phenotype and activating NF-κB signaling pathways. This systemic immunometabolic priming may lower activation thresholds at the enthesis—the primary pathological site in SpA—potentially amplifying IL-23/IL-17 axis activity via Th17 bias, innate-like lymphocyte responses, and stromal–immune crosstalk under mechanical stress. Clinically, patients with SpA and obesity have been reported to demonstrate heightened disease activity (BASDAI, ASDAS), impaired function (BASFI), accelerated radiographic progression (syndesmophytes, enthesophytes), and diminished biologic response rates, potentially attributable to pharmacokinetic alterations (e.g., subtherapeutic TNF inhibitor levels) and pharmacodynamic resistance. Multisystem comorbidities, including non-alcoholic fatty liver disease, cardiovascular events, metabolic syndrome, sleep disturbances, and depression, further exacerbate morbidity and diminish quality of life. Therapeutic implications emphasize obesity as a modifiable disease modifier. Weight loss interventions, including hypocaloric diets, anti-inflammatory regimens (e.g., Mediterranean diet), multicomponent exercise, GLP-1 receptor agonists, and bariatric surgery, have been associated with reductions in inflammatory biomarkers, improved remission rates (MDA, DAPSA), and prolonged drug survival by restoring adipokine balance and disrupting mechano-inflammatory loops. Future randomized controlled trials should prioritize long-term evaluations of integrated multidisciplinary strategies that combine metabolic optimization with immunomodulatory therapies, addressing adherence challenges through psychological support and patient-tailored protocols, while elucidating dose–response relationships for GLP-1RAs and exercise in diverse SpA subtypes to establish precision management paradigms that mitigate cardiometabolic burden and improve holistic outcomes.

Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor that typically arises centrally in individuals with a significant smoking history. It is characterized by rapid progression and early metastatic spread, most commonly to the mediastinal lymph nodes, liver, bones, adrenal glands, and brain.1 SCLC is also known to be associated with several paraneoplastic syndromes, including Cushing’s syndrome, Lambert-Eaton myasthenic syndrome, and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Metastasis to the breast from SCLC is exceedingly rare, especially as an isolated site of metastases. Only sporadic cases have been reported in the literature, particularly as an isolated site of spread2. A 45-year-old female with a 30-pack-year smoking history presented with dyspnea. CT chest showed a right lower lobe mass measuring 5.7 cm and an adjacent right hilar component measuring 4.8 x 4.2 x 5.6 cm, with extensive hilar lymphadenopathy and bronchovascular encasement, concerning for malignancy. Bronchoscopy with endobronchial ultrasound-guided biopsy and partial debulking of the right main bronchus mass confirmed SCLC. Staging imaging revealed a suspicious mass in the left breast. Ultrasound of the left breast showed an irregular, hypoechoic, solid lesion with lobulated margins measuring 2.5 x 2.4 cm, without associated axillary lymph node involvement. MRI of the brain showed no additional sites of metastases, indicating the breast as an isolated extrathoracic site of disease. Core needle biopsy of the breast lesion confirmed metastatic small cell carcinoma, with immunohistochemical staining positive for TTF-1, synaptophysin, and chromogranin, supporting lung origin. The patient was subsequently started on systemic chemotherapy. This case highlights a rare instance of isolated breast metastasis from SCLC. Given the unusual site, new breast lesions in patients with lung cancer should raise the suspicion for metastases, even in the absence of widespread disease. Early biopsy is essential to delineate a (second) synchronous primary vs unusual site of metastases to help guide therapy, preventing misdiagnosis as a primary breast malignancy. This abstract is funded by: None

OBJECTIVES Transsphenoidal surgery for the resection of pituitary neoplasms has evolved over the years. The current study sought to summarize visual outcomes following transsphenoidal surgery for sellar and parasellar lesions and evaluate how these outcomes are reported across the literature. METHODS A systematic review was conducted in accordance with PRISMA guidelines. PubMed, EMBASE, Scopus and Cochrane Library database were searched from inception through October 2023. Studies were included if they reported pre- and post-operative visual outcomes for patients undergoing transsphenoidal resection of sellar or parasellar lesions. Reviews, abstracts, and non-English studies were excluded. Rates of pre- and postoperative visual loss, visual field defects, and visual acuity impairment were collected. Postoperative outcomes were categorized as improved, normalized, unchanged, or worsened. RESULTS Of 3828 studies identified, 236 met inclusion criteria and were included in the analysis. Pituitary adenomas accounted for 80% of cases, followed by craniopharyngiomas (14%) and meningiomas (4%). Preoperative visual loss, visual field defects, and visual acuity impairment were present in 55%, 51%, and 37% of patients, respectively. Postoperative improvement occurred in 76% of patients with visual loss, 73% with visual field defects, and 64% with visual acuity impairment, while 2%-11% experienced worsening of symptoms. Reporting completeness varied across studies, with fewer than half of studies reporting both pre- and post-operative outcomes. CONCLUSIONS Across all studies, approximately 76% of patients with preoperative visual impairment experienced postoperative improvement following transsphenoidal surgery. Reporting of visual outcomes remains highly variable, underscoring the need or standardized definitions and outcome measures in future research.

BACKGROUND Obstructive hydrocephalus caused by a membranous or synechial occlusion at the level of the superior medullary velum (SMV) is likely under-recognized and may be mislabeled as aqueductal stenosis. We aimed to describe the anatomical pattern of these "velar obstructions" and discuss their surgical targeting implications. METHODS We retrospectively rereviewed 94 patients previously classified as primary aqueductal stenosis (1995-2015) and identified 5 cases (5%) with an obstruction caudal to the aqueductal tectum, at the SMV. A targeted literature search retrieved 18 additional reports with midline sagittal magnetic resonance imaging compatible with a velar-level occlusion. In the primary series, morphometrics were obtained from calibrated imaging. Literature cases were used for qualitative/topographic assessment. The SMV was segmented into A (externally free) and B (covered by the lingula), and the occlusion site was classified as A, AB junction, or B. RESULTS In the combined cohort (n = 23), the AB junction was the most frequent site (12/23). In the primary series (n = 5; mean age: 34 years; range: 14-47), the sagittal depth of the dilated cavity averaged 24 mm (range: 17-33) and consistently exceeded the length of the aqueductal tectum. Morphometric patterns were heterogeneous. Across cases with reported treatment (20/23), endoscopic third ventriculostomy was the most common strategy, alone or combined with transaqueductal fenestration. CONCLUSIONS Velar occlusion is a distinct imaging-anatomical pattern that may influence endoscopic planning. Any endoscopic fenestration at the SMV level ("velarplasty") should be framed as investigational and must explicitly account for the nearby trochlear nerve decussation and vermian/lingular relationships.

OBJECTIVES Community-acquired bloodstream infections (CA-BSIs) are a major cause of mortality in older adults, yet prospective international data are limited. This study evaluated clinical features, microbiology, and mortality predictors in older patients with CA-BSI. METHODS This prospective, observational study was conducted in 72 referral centers across 16 countries between June 1 and September 1, 2024. Patients aged ≥65 years with confirmed CA-BSI were included. Demographic, clinical, laboratory, and treatment data were collected. The primary outcome was 30-day all-cause mortality. Univariate and multivariate logistic regression was used to identify predictors. RESULTS 574 patients were enrolled (median age 74 years; 48.1% female), and 30-day mortality was 26.3%. Urinary tract infection was the most common source (33.7%), and 30.5% had no identifiable origin. Gram-negative organisms predominated (58.6%). Independent mortality predictors included SOFA score ≥5, thrombocytopenia (<50,000/µL), Staphylococcus aureus bacteremia, pneumonia, bacteremia of unknown origin, and higher Charlson Comorbidity Index. Higher Katz Activities of Daily Living scores were protective. CONCLUSION CA-BSI in older adults is associated with high mortality. Outcomes are driven by comorbidity burden, functional status, infection severity, and causative pathogen, highlighting the need for early risk stratification and tailored management.

The Sarajevo ion accelerator (SARAI) benefits from the successful transfer of the CERN’s 750 MHz radiofrequency quadrupole (RFQ) technology, adapted for societal and medical applications. SARAI incorporates an industrial electron cyclotron resonance supernanogan ion source operating at 14.5 GHz, designed to generate alpha particles and ions that can be used for ion beam analysis and experimental and applied physics research. The system is equipped with a 4-electrode extraction subsystem capable of extracting and focusing multiple ion species at voltages up to 30 kV. The source is being optimized at CERN for injection into a 750 MHz RFQ, initially with protons, followed by helium and carbon ions. This paper reports on the progress of a novel idea of integrating a supernanogan ECR ion source with the RFQ to get higher currents than currently achievable in the emerging domain of compact linacs for societal applications. The project is in its infancy, so this paper focuses on the source commissioning preparation, reports on the initial high voltage holding tests on the source extraction system in vacuum, and discusses further plans and applications.

Global reporting of obesity is commonly based on comparisons over multiple decades1 and lacks a granular and systematic analysis of its dynamics. We used 4,050 population-based studies with measured height and weight data on 232 million participants to assess the worldwide dynamics of obesity from 1980 to 2024. The rise in obesity decelerated in school-aged children and adolescents throughout the 1990s in many high-income countries, and subsequently plateaued in most at age-standardized prevalences spanning 20 percentage points, from 3–4% for girls in Japan, Denmark and France to 23% for boys in the USA. There were indications of a small decline in obesity in children and adolescents in some high-income western countries (for example, Italy, Portugal and France) since the 2000s. Similar trends were seen in some countries in Central and Eastern Europe. In adults, the rise in obesity slowed down in high-income western countries about a decade after children, followed by a plateau or possibly a small reversal of the rise in some countries (for example, Spain). In most low-income and middle-income countries, the annual absolute change in prevalence has remained stable or increased over time, even though prevalence has surpassed that of high-income countries. These highly varied dynamics suggest that the social, economic and technological trends that influence the availability, affordability and use of different foods may have helped control the rise in obesity in high-income countries, but require policy interventions in low-income and middle-income countries. Global analysis of obesity trends from 1980 to 2024 in 200 countries and territories using data from 4,050 population-based studies reveals that framing obesity as a single global epidemic masks the highly varied dynamics across countries and age groups.

Background Despite its viral etiology and immunogenic features, cervical cancer shows limited and often short-lived benefit from programmed cell death protein 1 blockade, currently the only approved immunotherapy for this disease. This limitation highlights the need for a deeper understanding of its immune microenvironment to uncover alternative or complementary immunotherapeutic targets that may improve outcomes. Methods We integrated spatial proteomic and bulk transcriptomic profiling of the cervical cancer immune landscape. Immune subset markers (CD8, CD4, CD68, FoxP3, NKp46) and clinically actionable immune checkpoint molecules (HLA-E, CD47, CD73, CD276, CD155, Gal-9, PD-L1, CD70, LAG-3) were assessed by immunohistochemistry in 65 resected tumors, spatially resolved across tumor stroma and tumor epithelium niches. Expression patterns and correlations with clinicopathological variables, immunotypes, and survival were systematically analyzed. Key findings were cross-validated in The Cancer Genome Atlas cohort, and tumor-killing assays were conducted to evaluate the therapeutic potential of identified checkpoint axes. Results Immune infiltration was predominantly localized to the tumor stroma, with CD8+ and CD4+ T cells as dominant subsets. Within the tumor epithelium, CD8+ T cells and CD68+ macrophages were most abundant. Among checkpoints, HLA-E and CD47 showed the highest and most widespread expression, whereas CD276 and CD155 were enriched in the tumor epithelium, and CD73 and CD70 in the tumor stroma. Squamous cell carcinoma showed a stronger immunologic profile than adenocarcinoma. Immunotype stratification revealed distinct expression profiles and prognostic patterns. Elevated niche-defined expression of CD8, CD4, CD4-FoxP3, and NKp46 associated with improved survival. CD155 emerged as the only checkpoint consistently linked with poor survival across niches and cohorts, and associated with chemotherapy resistance. Notably, CD155 was the most promising functional target and was highly and selectively enriched in the tumor epithelium across all immunotypes, including immune-desert tumors where other immune markers were scarce. Conclusion This study reveals a complex, niche-specific and immunotype-specific immunoregulatory architecture in cervical cancer that extends well beyond programmed death-ligand 1. CD155 stands out as a compelling and underused therapeutic target, supporting a paradigm shift in targeting the T cell immunoreceptor with Ig and ITIM domains (TIGIT) axis. Its functional impact and selective enrichment in the tumor epithelium positions CD155 as a promising therapeutic target for both checkpoint inhibition and epithelial-directed approaches in cervical cancer.

Background/Objectives: Accurate post-mortem interval (PMI) estimation becomes increasingly difficult when bodies decompose under extreme heat. Hyperthermal Mediterranean environments accelerate soft-tissue degradation, induce early mummification, and distort classical thanatological indicators, often resulting in substantial PMI overestimation. This study analyzes three forensic cases affected by climate-driven decomposition anomalies and presents a climate-adaptive, AI-assisted diagnostic framework applied uniformly across all cases to improve PMI interpretation. Methods: A retrospective case series analysis was conducted on three individuals recovered during summer heatwaves. Crime scene investigation, post-mortem computed tomography (PMCT), autopsy, and genetic identification were integrated with 5–15-year meteorological datasets. Classical PMI estimations were compared with circumstantial data. A multimodal AI model, incorporating environmental features, decomposition morphology, and microenvironmental modifiers, was operationalized for each case using a hybrid Random Forest–LSTM architecture. Engineered indices included Accumulated Degree Days (ADD), a Decomposition Index, and climate-stress metrics (Thermal Load Index, Desiccation Pressure Factor, Microenvironmental Distortion Coefficient). Quantile regression provided calibrated prediction intervals. Results: Morphological assessments overestimated PMI in every case, suggesting intervals of 1–6 months despite true PMIs of approximately 20 days (Cases 1–2) or 36–48 h (Case 3). The AI model yielded conceptual outputs more consistent with verified PMIs, ~21 days (Case 1), ~23 days (Case 2), and ~42 h (Case 3), each accompanied by 50% and 90% prediction intervals. Explainability analyses identified thermal load, desiccation pressure, and microenvironmental distortion, particularly insulation in Case 3, as dominant drivers. Conclusions: Extreme heat fundamentally alters decomposition trajectories, rendering classical PMI methods unreliable. Applying a climate-aware, AI-assisted diagnostic framework across all three cases improved interpretability, providing uncertainty-aware estimates aligned with true PMIs. The AI framework is presented as a conceptual, non-trained, proof-of-concept system, and reported outputs represent operational demonstrations rather than validated predictions, offering a promising foundation for next-generation PMI diagnostics in hyperthermal forensic settings.