Semmelweis University

To assess the diagnostic accuracy of ultrahigh-resolution (UHR) photon-counting detector (PCD)-CT for detecting obstructive and non-obstructive coronary in-stent restenosis (ISR), using invasive coronary angiography (ICA) as the reference. Consecutive patients with coronary stents who underwent clinically indicated coronary CT angiography (CCTA) on a dual-source PCD-CT were retrospectively identified from two academic centers. All UHR scans were reconstructed at 0.2mm and 0.4mm slice thickness, the latter served as an energy-integrating detector CT-like proxy. Series were assessed for the presence of non-obstructive (<50%) and obstructive (≥50%) ISR, with diagnostic accuracy validated against ICA in the overall cohort and in a sub-analysis of stents<3 mm in diameter. Fifty patients (16.0% women; 70.9±10.8years) with 106 coronary stents were included. ICA identified 17 non-obstructive and 27 obstructive ISR. Non-obstructive ISR was detected in 10 stents on 0.2mm UHR and 14 on 0.4mm EID-like standard-resolution reconstructions.Obstructive ISR was described in 26 (0.2mm) vs. 32 (0.4mm) stents, respectively. The proportion of evaluable stents increased from 91.5% based on 0.4mm to 99.1% with 0.2mm UHR. Compared with standard-resolution images, 0.2-mm UHR improved non-obstructive ISR sensitivity (90.5%vs82.9%), specificity (100.0%vs78.5%), and accuracy (96.2%vs80.2%); and in obstructive ISR, specificity (98.7%vs82.3%), positive predictive value (96.3%vs64.1%), and accuracy (98.1%vs84.9%). Thin-slice UHR achieved higher accuracy in small-caliber stents (<3mm), for both non-obstructive (94.1vs73.5%) and obstructive ISR (94.1%vs79.4%). UHR PCD-CT demonstrated excellent diagnostic accuracy and significant improvements in ISR detection compared to the quasi-standard reconstructions, including non-obstructive and small-caliber stent ISR.

Minimal residual disease (MRD) is a central biomarker in multiple myeloma (MM), offering unprecedented sensitivity for evaluating treatment efficacy and serving as a potential surrogate endpoint. We conducted a comprehensive analysis of clinical trials registered on ClinicalTrials.gov between 2014 and 2025. Interventional trials or observational studies investigating therapeutic interventions were included. Data on therapy response, MRD outcomes, measurement, and their role as primary, secondary, or adaptive endpoints were extracted. A total of 1336 studies met inclusion criteria. Among interventional trials, 86.4% included therapy response and 30.9% MRD as an outcome. Trials assessing MRD increased steadily from 6.7% in 2014 to 56.8% in 2025. Almost 50% of trials with recruiting (46.0%) or not yet recruiting (46.8%) status had an MRD outcome. MRD served as a primary outcome in 28.4% of trials with MRD assessment and guided therapeutic decisions in 7.5%. Most studies used next-generation flow or sequencing at a 10-5 threshold, though reporting heterogeneity persisted. MRD integration in trials has expanded substantially, reflecting its clinical and regulatory importance. Still, there is a need for coordinated evidence generation, standardization, and alignment with evolving EMA and HTA requirements. Future research should integrate patient experience data and emerging non-invasive MRD technologies to enhance clinical relevance and policy acceptance.

The treat-to-target (T2T) strategy, which involves predefined therapy objectives and a focused monitoring system, has substantially improved the management of rheumatoid arthritis (RA). These benefits probably result from a reduction in undertreatment, prevention of overtreatment and thus an improvement in long-term outcomes for both articular manifestations and comorbidities. However, T2T has also revealed a subgroup of patients who, despite following guideline-based treatment, do not reach the predefined outcomes. This finding has led to the emerging concept of 'difficult-to-treat' (D2T) RA. D2T-RA might reflect true pharmacological refractoriness, but D2T-RA is also increasingly recognized as having broader underlying causes, including psychosocial distress, comorbidities, chronic pain syndromes and patient or system-related barriers. If these underlying factors remain unidentified, unnecessary treatment escalation can occur, which could worsen long-term outcomes. Although T2T focuses on predefined targets and regular monitoring, which works well for the majority of patients, the structured multidomain approach characteristic of the D2T framework might provide a guide for managing patients who do not reach these targets despite guideline-based care. For this population, the D2T approach could offer better stratification and serve as a practical, precision-medicine-oriented extension of T2T by providing a more mechanism-informed, personalized management strategy. Integrating this D2T perspective into T2T practices keeps the strengths of T2T while also offering individualized care for patients with more complex disease trajectories, representing an unmet need.

The aim of this paper is to review the phenomenon of bistability, a basic working mode of NREM sleep. The perpetual oscillations between two opposite states in sleep slow waves, K-complexes as well as in the Cyclic Alternating Pattern (CAP) on a different time scale; appear spontaneously and can also be elicited by sensory stimulation, representing a response of the sleeping brain. Although there is extensive literature on bistability, its significance remains obscure. In this paper, spontaneous and elicited bistable patterns are reviewed and the global presence of bistable oscillations in NREM sleep is highlighted. We discuss the relationship of bistability with sleep homeostasis and the overlap with the CAP, with emphasis on A1 phase. We collect data along the hypothesis that bistability would provide a perpetual and flexible interface between the sleeping brain and the environment across the night, protecting the continuity of sleep and, in parallel, preserving the brain's adaptive connection with the environment.

Existing studies on the economic impact of schizophrenia are fragmented and vary in methodology, hindering an ample understanding of the total economic burden. To quantify the global economic burden of schizophrenia by synthesizing findings from systematic reviews and meta-analyses, and to assess variations by cost category, world region and income level. We conducted a protocol-driven umbrella review registered on PROSPERO (CRD42024504092). A systematic search of MEDLINE, EMBASE, Cochrane Library, and APA PsycINFO identified reviews reporting annual per-patient monetary cost estimates for schizophrenia. Monetary values were adjusted for inflation and converted to 2024 US dollars. Twenty-six systematic reviews involving 152 primary studies were included. The median annual per-patient total cost of schizophrenia across included primary studies was $33,236 (mean $47,872), with direct costs accounting for $23,126 (medical: $19,543; ancillary: $1,152) and indirect costs for $21,333. Costs were varied by income level: in high-income countries, the median total cost was $34,175, compared to $3,345 in upper-middle-income and $3,452 in lower-middle-income countries. Regional disparities were substantial, with Europe & Central Asia reporting the highest median costs among high-income settings. Data from low- and middle-income regions were limited or absent. Methodological heterogeneity, lack of standardization in cost reporting, and underrepresentation of low-resource settings limit generalizability. The included cost-of-illness estimates indicate that schizophrenia is associated with substantial annual per-patient costs, with hospitalization, long-term care, and productivity losses frequently among the largest reported components. However, the evidence base is heavily weighted toward high-income countries, and limited data from lower-resource settings constrain cross-country comparability. Future research should adopt standardized costing frameworks and expand data collection in underrepresented regions to improve the consistency, transparency, and geographic coverage of economic burden estimates.

Abstract Researchers’ performance is often evaluated quantitatively through metrics like the number of scientific papers, the number of citations these received, and the H-index, perpetuating the “Publish or Perish” culture. Yet such metrics have inherent biases favoring older, established researchers and fail to account for disciplinary differences or temporal relevance of contributions. To address this inequity, we aimed to create a global, age- and field-adjusted reference for evaluating scientific productivity. We developed a comprehensive worldwide reference database of researchers using publication and citation data from Scopus. The reference dataset includes 507,233 researchers from across the globe and facilitates the calculation of expected values for H-index, annual citations, and recent publications (within the past 5 years) for each percentile in every discipline. To account for disciplinary differences, we incorporated diverse publication types into the analysis tailored to each domain. The benchmarks utilized were stratified by career stage, assessed at each year after a researcher’s first publication. A composite score was developed to rank publication performance into deciles (D1–D10), where D1 represents the highest level of achievement. Importantly, only data from researchers within the same career stage and same scientific domain are used for comparison, ensuring fair and context-sensitive evaluations. To enhance accessibility, we established a web portal ( www.scientometrics.org/scopus ) to facilitate researcher benchmarking. This age- and discipline-normalized international database promotes the application of responsible metrics, offering a robust framework for global scientometric rankings. By providing an online analysis platform, we enable researchers, institutions, and policymakers to determine expected levels of scholarly output at the individual level while fostering fairness and equity in academic evaluation.