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CT Angiography-derived fractional flow reserve in the emergency department: Insights from a matched cohort analysis
No full textRole of light and heavy alkalis in Cu(In,Ga)Se 2 absorbers
No full textIn this work, we investigate the distribution of single- and co-doped alkali elements—sodium (Na), potassium (K), and rubidium (Rb)—within the bulk and grain boundaries (GBs) of Cu(In,Ga)Se₂ (CIGSe) thin-film solar cells, and examine their electronic impact on device efficiency. Atomically resolved analysis using atom probe tomography reveals pronounced compositional fluctuations of both matrix and dopant elements between GBs and the bulk. We propose mechanisms governing the copper and indium (In) distribution by classifying Na as a light alkali element, Rb as a heavy alkali, and K as an intermediate case. Notably, a correlation is observed between alkali concentration and In enrichment at the GBs, which is attributed to donor-like defect state formation. These variations effectively impact the local electronic structure, with Na and K segregation reducing the n-type character of GBs, while Rb accumulation enhances it. Our findings, supported by density functional theory calculations, provide fundamental insights into the role of alkali metal dopants in tuning GB characteristics, offering guidance for optimized alkali insertion in CIGSe solar cells
Prospective validation of the modified metastatic colorectal cancer score (mCCS) in >600 patients with RAS-wild-type metastatic colorectal cancer treated with first-line panitumumab plus FOLFIRI/FOLFOX: final results of the non-interventional study VALIDATE
No full textExisting prognostic scores for metastatic colorectal cancer (mCRC) are based on randomized clinical trial data and focus on parameters evaluated at the start of first-line (1L) treatment. Unlike these, the modified mCRC prognostic score (mCCS) was developed using real-world data from the German tumor registry colorectal cancer (TKK) and is based on pre-1L treatment information. It predicts overall survival (OS) for patients with RAS-wild-type (WT) mCRC using five tumor characteristics identified as independent negative prognostic factors. The mCCS aims to facilitate risk-based treatment approaches and optimize mCRC treatment. The VALIDATE study was a prospective, non-interventional study designed to validate the modified mCCS, recruiting patients with RAS-WT mCRC in Germany and Austria. A total of 646 patients from 113 study sites were enrolled in VALIDATE and received 1L therapy with panitumumab in combination with FOLFOX/FOLFIRI. Patients were categorized into risk groups according to the modified mCCS. The prognostic value of the modified mCCS was prospectively validated by demonstrating significantly longer median OS of patients in the low-risk group (29.1 months [25.9, 32.1]) compared to those in the high-risk group (20.1 months, [15.0, 23.9]). Rates of secondary resections of metastases were ≥ 23% for low and intermediate-risk patients, indicating a pivotal opportunity for improved prognosis. During panitumumab administration, patient-reported quality of life was preserved, and the tolerability profile was manageable with no new safety signals. The modified mCCS could serve as a practical tool for oncologists in routine clinical practice to aid in treatment decision-making and effectively communicating prognosis to patients
Pruritus in primary biliary cholangitis: insights from the German PBC registry across secondary and tertiary care
No full textIntroduction and ObjectivesPruritus is a frequent and burdensome symptom in patients with primary biliary cholangitis (PBC), significantly affecting quality of life. Despite its clinical relevance, data on the prevalence and management, particularly across different levels of healthcare, remain limited. We aimed to assess prevalence, severity, and treatment of pruritus in PBC patients across secondary and tertiary care.Patients and MethodsWithin the German PBC registry, the intensity and management of pruritus were assessed cross-sectionally by treating physicians using a standardized 4-point verbal rating scale (absent, mild, moderate, severe), as well as by analyzing prescribed antipruritic medications.ResultsPruritus was reported in 23 % (n = 120/515) of patients and classified as mild, moderate, or severe in 59 (49 %), 41 (34 %), and 20 (17 %) cases, respectively. The prevalence of pruritus was 27 % (n = 96/360) for tertiary versus 16 % (n = 24/155) for secondary care (p = 0.006). Moderate or severe pruritus was observed in 13.3 % (n = 48/360) of patients at tertiary centers compared to 8.4 % (n = 13/155) at secondary centers (p = 0.137). Antipruritic therapies were used in only 22.5 % (n = 27/120) patients with pruritus, with bezafibrate being the most frequently prescribed medication (63 %, n = 17/27). Patients with pruritus were more likely to receive antipruritic therapies in tertiary than secondary care: 26 % (n = 25/96) vs. 8 % (n = 2/24) (p = 0.098).ConclusionsPruritus in patients with PBC is common and under-treated in the real-world scenario. Assessment and management vary by healthcare level, highlighting the need for standardized care and greater awareness of treatment options across all settings
Longitudinal characterization of inflammatory plasma protein signatures in ECT response
No full textBackgroundElectroconvulsive therapy (ECT) is an effective treatment for psychiatric disorders, but its molecular mechanisms are not yet fully elucidated. This study aimed to investigate longitudinal dynamics of inflammatory proteins during ECT and their association with clinical outcomes.MethodsProtein expression was measured in 30 patients at multiple time points during the course of ECT using the Olink® inflammation panel. A longitudinal mixed-effects model was used to assess temporal changes in protein levels and their association with symptom severity. Patient-specific correlation analyses examined associations between individual symptom improvement trajectories and protein dynamics. Proteins associated with symptom improvement underwent pathway enrichment analysis to identify underlying signaling mechanisms. A linear model assessed associations between baseline protein expression and treatment response.ResultsCystatin D showed significant longitudinal changes during ECT but was not associated with clinical response. Correlation analyses identified 18 immune-related proteins significantly linked to symptom improvement, with 17 showing negative correlations. Notably, IL-4 and IL-20 consistently emerged in both the correlation analysis and linear model, indicating a possible association with ECT-related molecular mechanisms. Pathway enrichment analysis revealed significant involvement of the JAK-STAT signaling pathway, aligning with existing evidence implicating this pathway in the pathophysiology of mood disorders and synaptic plasticity.ConclusionSymptom improvement during ECT is associated with reductions in specific inflammatory and neuroimmune markers, suggesting a potential link to the therapeutic mechanisms. These findings provide preliminary indications of immune involvement in ECT and emphasize the need for larger cohorts to validate results and further investigate immunomodulatory targets in psychiatric treatment
Durability of hydrocarbon ionomer-based cathode catalyst layers for PEM fuel cells under voltage cycling
No full textHydrocarbon (HC)-based proton-exchange membrane fuel cells have gained attention as a more sustainable alternative to conventional systems utilizing perfluorosulfonic acid (PFSA). While current optimizations have revealed performance parity of sulfo-phenylated poly(phenylene) ionomers in cathode catalyst layers (CLs), the long-term durability of CLs employing such HC ionomers remains insufficiently characterized. By applying a voltage cycling accelerated stress test (AST), this study finds a higher cathode CL degradation compared to a PFSA-based reference in a twofold sense: First, the CL's protonic resistance increases during the AST, which is not observed in the PFSA case. Second, the catalyst roughness factor decreases faster due to an accelerated Pt nanoparticle growth. While this decay of electrochemically active surface area scales expectedly with ionic conductivity (i.e., with ionomer volume fraction and relative humidity) within the same ionomer class, it is surprisingly found that even at a lower absolute number of sulfonic acid groups and lower ionic conductivity, the HC-based CL undergoes faster Pt agglomeration than the PFSA counterpart. As a speculative explanation, first evidence of a higher affinity of the utilized HC ionomer towards Pt ions is revealed, which may lead to an increased Pt content within the ionomer and hence to an enhanced ionic Pt transport
On the complexities of testing for compliance with human oversight requirements in AI regulation
No full textHuman oversight requirements are a core component of the European AI Act and in AI governance. In this paper, we highlight key challenges in testing for compliance with these requirements. A central difficulty lies in balancing simple, but potentially ineffective checklist-based approaches with resource-intensive and context-sensitive empirical testing of the effectiveness of human oversight of AI. Questions regarding when to update compliance testing, the context-dependent nature of human oversight requirements, and difficult-to-operationalize standards further complicate compliance testing. We argue that these challenges illustrate broader challenges in the future of sociotechnical AI governance, i.e. a future that shifts from ensuring “good” technological products to “good” sociotechnical systems
Impact of retinal thickness fluctuations with ranibizumab versus aflibercept in neovascular age-related macular degeneration (SALT): 12-month results from a multicentre, randomised, phase IV trial
No full textBackground/aims To compare fluctuations of central subfield retinal thickness (CSRT) in patients with neovascular age-related macular degeneration undergoing ranibizumab pro re nata versus aflibercept bimonthly treatment in a prospective 12 month, phase IV, randomised, multicentre study.Methods Ranibizumab was administered according to best-corrected visual acuity (BCVA) and/or disease activity detected on spectral domain optical coherence tomography. Aflibercept was administered at three initial monthly visits followed by bimonthly treatment. CSRT stability was evaluated between months 3 and 6. CSRT stability was compared between groups and correlated with functional outcomes at month 12.Results Fluctuations of CSRT showed a least-squares (LS) mean (95% CI) difference of −4.12 (−10.22 to 1.98) µm between ranibizumab (25.16 (20.09 to 30.24) µm) and aflibercept groups (29.28 (24.14 to 34.43) µm) (p=0.1850). A predefined analysis of retinal stability, adjusted for baseline CSRT, showed a LS mean (95% CI) difference of −6.53 (−12.47 to −0.58 µm) in favour of ranibizumab (23.53 (18.58 to 28.49) µm) versus aflibercept (30.06 (25.04 to 35.07) µm) (p=0.0315). Pearson’s correlation coefficient demonstrated no correlation between the mean amplitude of CSRT fluctuation between months 3 and 6, and BCVA at month 12 (r = −0.0888). Adverse event rates were low.Conclusions Numerical differences in retinal thickness fluctuations between months 3 and 6 were detected between treatment regimens. While the presence of fluctuations has previously been shown to have a negative impact on functional outcomes, our data showed no correlation between the mean amplitude of fluctuations and functional outcomes at month 12
Flowering synchrony and cultivar compatibility as key factors for optimising sweet cherry pollination and production
No full textEffective pollination management is essential for optimised yields in animal-pollinated crops. Sweet cherry (Prunus avium) is a crop with 82% of its production associated with animal pollination. Therefore, factors impacting pollination play a key role in sweet cherry production. These factors are often accounted for in pollinator management and orchard design; however, flower phenology, cultivar compatibility, and their impacts on yield are poorly understood and often not considered. We investigated how flowering overlap among cultivars and cultivar inter- and self-compatibility impact sweet cherry cultivars' suitability as pollen donors and recipients in Beira Interior, a key production region in Portugal. For this, we performed floral biology experiments in the field and under controlled greenhouse conditions. We compared the pollination success of compatible cultivars sharing one S-allele or none. We also assessed pollinator dependence and pollen limitation levels of the studied cultivars, as well as natural pollen deposition and fruit set levels. We observed that, although often overlooked, flower phenology is very important for determining suitable cultivar pairings, and flowering overlaps differ greatly from the existing literature, likely reflecting regional responses. Controlled hand pollination experiments revealed that pollen tube growth, a more straightforward and feasible pollination metric than fruit set in a mass-flowering crop with naturally low fruit set, can be effectively used to assess compatibility levels. Crossings between cultivars without common S-alleles and between cultivars sharing one S-allele resulted in similar pollen tube numbers and fruit set levels, indicating that both pairing types are suitable. Additionally, we detected pollination deficits in the studied cultivars, likely resulting from inadequate pollination services or poor pollen donor availability in the orchard. Altogether, we estimated the cultivar suitability of 81 different pairs of sweet cherry for the Beira Interior region. Our study highlights the importance of considering plant-related factors, namely flower phenology and cultivar compatibility, to develop targeted and effective management guidelines for sweet cherry producers, emphasising the significant impact these factors can have on production and the necessity of including them in orchard management and design
Responsible and trusted AI: an interdisciplinary perspective (2025)
No full textAs Artificial Intelligence (AI) continues to shape individual lives, institutional processes, and societal structures, ensuring its responsible and trusted development has become a critical imperative. However, meeting this imperative is far from straightforward. AI systems frequently lack transparency and are embedded in environments where the distribution of responsibility and accountability is unclear, normative standards are disputed, and system behavior is unpredictable. The Responsible and Trusted AI track at AISoLA 2025 addresses these and similar challenges by fostering interdisciplinary collaboration across philosophy, law, psychology, economics, sociology, political science, and informatics. This introduction outlines the motivation for the track, emphasizing the sociotechnical embeddedness of AI and the need for approaches that go beyond technical performance to consider questions related to trust and responsibility. It highlights three core themes explored in this year’s contributions: democratic legitimation and normative alignment, legal compliance and human oversight, and runtime safety in high-risk contexts. Together, these contributions underscore the importance of interdisciplinary discussions to navigate normative ambiguity, regulatory uncertainty, and behavioral unpredictability in AI systems. The track aims to advance dialogue and collaboration that support the development and deployment of AI systems that are not only effective but are also designed and implemented responsibly and can be trusted