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Longitudinal Effects of Lipid-Lowering Treatment on High-Risk Plaque Features and Pericoronary Adipose Tissue Attenuation Using Serial Coronary Computed Tomography
No full textAim: To evaluate the impact of different lipid-lowering treatment intensities on high-risk plaque features and pericoronary adipose tissue (PCAT) attenuation in patients undergoing serial coronary computed tomography angiography (CCTA). Methods: Individuals with suspected or known coronary artery disease (CAD) from 11 imaging centers who underwent serial CCTA examinations were retrospectively analyzed. Plaque volumes and PCAT were quantified, and the presence of high-risk plaque features was semi-quantitatively assessed using the plaque feature score (PFS). Results: In total, 216 consecutive patients (mean age 63.1 ± 9.7 years, 26.4% female) were included. The mean observation and treatment timespan between the CCTA scans was 824.5 (interquartile range (IQR) = 463.0–1323.0) days (27.5 months). The regression of high-risk features was more common with high-intensity versus low or no lipid-lowering treatment (HR = 4.6, 95%CI = 1.8–12.0, p < 0.001) and was associated with the attenuated increase in non-calcified plaque volume (p < 0.001). PCATmean decreased with increasing intensity of lipid-lowering treatment (p = 0.01) but no associations were observed between the changes in PCAT and PFS or plaque volumes. Lipid-lowering drug intensity was predictive of PFS regression (p < 0.001), whereas baseline PCATRCA was predictive for PFS progression (p = 0.03), both independent of age, cardiovascular risk factors, and baseline plaque volumes. Conclusions: PCAT predicts the progression of high-risk coronary plaque features. High-intensity lipid-lowering drugs may cause the regression of high-risk plaque features through a plaque ‘delipidization’ process. Future trials are now warranted, studying if this process is potentially associated with improved clinical outcomes.GRN Hospital Weinheim (Grigorios Korosoglou) received an institutional research grant from Siemens Healthineers for this study. Andreas A. Giannopoulos is supported by research funds from the Promedica Stiftung and the Iten-Kohaut foundation in collaboration with USZ Foundation.Siemens HealthineersPromedica StiftungIten-Kohaut foundationUSZ Foundatio
Wachstum und Charakterisierung von vertikalen GaN-auf-Si(111) PN-Strukturen für Leistungsanwendungen
No full textVertical GaN-on-Si(111) power devices present numerous advantages over their lateral counterpart, including a higher threshold voltage, improved thermal management, increased current density, potential avalanche breakdown capability, and the ability to attain a higher voltage rating without expanding the device footprint. In high-power applications, the vertical design proves to be area-efficient, thereby reducing costs. Additionally, utilizing silicon as a substrate not only takes advantage of the low-cost large-diameter silicon wafers but also facilitates a CMOS-compatible process flow, further reducing costs. As a result, the combination of GaN’s wide bandgap properties with silicon substrates in a vertical architecture promises high performance at a competitive price, making the technology attractive for its industrialization.
In vertical devices, the lightly doped drift region serves as the primary voltageblocking layer, with the breakdown voltage scaling with its thickness. Despite significant progress in GaN-on-Si epitaxy over the past two decades, the growth of thick GaN layers remains a challenge due to substantial thermal and lattice mismatch inherent in the heteroepitaxial system. For GaN-based vertical devices, a drift layer thickness of at least 6 μm is required to ensure a breakdown voltage of 1200 V. Achieving such thicknesses demands sophisticated strain engineering to compensate for thermal mismatch, as inadequate strain control results in high wafer bow, epilayer cracking, slip lines in the Si substrate, and in extreme cases, even wafer breakage. Moreover, the significant lattice mismatch between GaN and Si results in a high density of threading dislocations, which compromises device performance by increasing off-state leakage current and, in turn, reduces the breakdown voltage. Hence, the development of a buffer concept tailored specifically for vertical GaN-on-Si structures is essential. Such a buffer structure must effectively accommodate thick continuous GaN layers by introducing the appropriate amount of compressive lattice-mismatch stress to counteract the thermal mismatch, while simultaneously reducing the threading dislocation density to minimize the off-state leakage current.
In this work, a novel buffer concept was developed by implementing island growth in an AlN/Al0.1Ga0.9N superlattice. It was observed that islands form on V-pits present in the AlN nucleation layer, and the geometry of the islands can be effectively controlled by adjusting the growth temperature. Increasing the growth temperature enhanced the coalescence height of the islands, resulting in more efficient bending and subsequent annihilation of threading dislocations. As a consequence of the reduced threading dislocation density, compressive stress relaxation during the GaN growth was alleviated. This allowed for sufficient compressive stress to be incorporated into the active GaN layers to compensate for the tensile stress generated during cooling. Using this buffer concept, crack-free GaN-based PN structures with a drift layer thickness of 7.4 μm (10 μm total thickness) on 6” Si(111) substrates were achieved, with an absolute wafer bow <50 μm and a low threading dislocation density of 3.6 x 108 ± 7.4 x 107 cm−2. By optimizing the growth condition of the drift layer, the carbon background could be suppressed to <1 x 1016 cm−3, allowing for controllable free electron densities down to 0.9 x 1016 cm−3 and facilitating high electron mobilities up to ∼760 cm2/Vs. Electrical characterization of quasi-vertical PN diodes on 6” Si(111) demonstrated a record-high breakdown voltage of 1210 V, with a low Ron of 0.4mΩcm2 for a 7.4 μm thick drift layer featuring a net-ionized donor concentration of 0.9 x 1016 cm−3. This resulted in a high Baliga’s figure of merit of ∼3.6 GW/cm2. Furthermore, the diodes exhibited a remarkably low off-state leakage current, accompanied by a high soft-breakdown (at 1 μA/mm2) of ∼700 V, surpassing previously reported soft-breakdown values for vertical GaN-on-Si PN diodes. PN diodes fabricated on structures featuring varying drift layer thicknesses and a net-ionized donor concentration of 0.9 x 1016 cm−3 demonstrated a high critical electric field of ∼2.3 MV/cm, reflecting the excellent material quality. Furthermore, this work presents the first demonstration of the avalanche breakdown signature on vertical GaN-on-Si structures, where an increase in the breakdown voltage with increasing temperature was observed for drift layer thicknesses of 3 μm and 4.5 μm. As a result, non-destructive breakdown voltages of 580 V and 830 V were achieved, respectively, highlighting the excellent material quality. Fully-vertical PN diodes capable of 1230V non-destructive breakdown were demonstrated with a 7.4 μm thick drift layer, exceeding the state-of-the-art by more than 500 V. Furthermore, the fully vertical PN diode exhibited a remarkably low soft-breakdown (at 1 μA/mm2) of∼ 650 V and showed signs of avalanche breakdown, as well as a high on-state current.
This work demonstrates the feasibility of fabricating sufficiently thick and high quality GaN drift layers on large-scale Si(111) substrates by suitable buffer optimization. This advancement enables the attainment of breakdown voltages in the kilovolt range, paving the way for high-performance GaN-on-Si vertical power devices
Sitagliptin as a therapeutic approach for social anxiety disorder: the role of DPP4 and NPY in modulating social fear and comorbid depressive-like behavior in mice
No full textWe have previously shown that neuropeptide Y (NPY) reduces social fear in an animal model that closely mimics the key behavioral symptoms of social anxiety disorder (SAD). Since NPY cannot yet be routinely administered to patients, we investigated the effects of sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor approved for the treatment of type 2 diabetes mellitus, on social fear and comorbid depression in mice. In addition to its well-known effects on glucose metabolism, sitagliptin also prevents the degradation of NPY, thereby increasing its concentration in the blood and the brain. We show that sitagliptin administration via drinking water (50 and 100 mg/kg/day, for 4 weeks) not only reduced social fear but also prevented the onset of comorbid depressive-like behavior in outbred CD1 mice. A similar phenotype was observed in homozygous DPP4-deficient mice, emphasizing the role of DPP4 in regulating these behaviors. However, in NPY-deficient mice, sitagliptin showed reduced efficacy, suggesting that NPY plays an important role in mediating the effects of sitagliptin on social fear and comorbid depression. These findings have important clinical implications, indicating that early intervention with sitagliptin could be an effective strategy for treating SAD, alleviating both core symptoms and reducing the risk of developing comorbid mood disorders that often complicate treatment outcomes
Virtual contrast-enhanced maximum intensity projections from high-b-value diffusion-weighted breast MRI: a feasibility study
No full textBackground Maximum intensity projections (MIPs) facilitate rapid lesion detection both for contrast-enhanced (CE) and diffusion-weighted imaging (DWI) breast magnetic resonance imaging (MRI). We evaluated the feasibility of AI-based virtual CE subtraction MIPs as a reading approach. Materials and methods This Institutional Review Board-approved retrospective study includes 540 multi-parametric breast MRI examinations (performed from 2017 to 2020), including multi- b -value DWI (50, 750, and 1,500 s/mm²). A 2D U-Net was trained using unenhanced (UnE) images as inputs to generate virtual abbreviated CE (VAbCE) subtractions. Two radiologists evaluated lesion suspicion, image quality, and artifacts for UnE, VACE, and abbreviated CE (AbCE) images. Lesion conspicuity was compared between VAbCE and AbCE MIPs. Results Cancer detection rates for UE, VAbCE, and AbCE MIPs were 90.0%, 91.4%, and 94.3%, respectively. Single-slice reading demonstrated sensitivities of 88.6% (UnE), 91.4% (VAbCE), and 94.3% (AbCE). Inter-rater agreement (Cohen κ) for lesion suspicion scores was higher for VAbCE (0.53) than UnE alone (0.39) and comparable to AbCE (0.58). No significant difference in mean lesion conspicuity was observed for VACE MIPs compared to ACE ( p ≥ 0.670). No significant difference could be observed for quality ( p ≥ 0.108), and reading time ( p = 1.000) between methods. Fewer visually significant artifacts could be observed in VAbCE than in AbCE MIPs ( p ≤ 0.001). Conclusion VAbCE breast MRI improved inter-rater agreement and allowed for slightly improved sensitivity compared to UnE images, while AbCE still provided the overall highest sensitivity. Further research is necessary to investigate the diagnostic potential of VAbCE breast MRI. Relevance statement VAbCE breast MRI generated by neural networks allowed the derivation of MIPs for rapid visual assessment, showing a way for screening applications. Key Points Virtual abbreviated contrast-enhanced (VAbCE) MIPs provided comparable sensitivity to MIPs of unenhanced high b -value DWI and were slightly lower than AbCE MIPs. Adding VAbCE to unenhanced high b -value DWI significantly improved interrater agreement for lesion suspicion scoring. Single-slice evaluation of VAbCE MIPs provided a sensitivity comparable to unenhanced high b -value DWI MIPs. Graphical AbstractBayerisches Staatsministerium für Bildung und Kultus, Wissenschaft und Kunsthttp://dx.doi.org/10.13039/50110000456
Das Nutzen von Symmetrien für Near-Term Quantencomputing
No full textOur works [1–7] focus on algorithm development for current and near-term quantum computing platforms. Symmetries, which are mathematically described by groups, divide the full space of possibilities, the Hilbert space, into smaller sectors. If a symmetry is conserved within an application, then one of these smaller symmetry sectors will be sufficient to model it. Therefore, our works incorporate symmetries like translational invariance [1, 2, 5, 7], time-periodicity [3, 4] or electron number conservation [6] to improve algorithms for relevant system classes compared to symmetry-unaware standard methods.
In the first direction, we utilise symmetries for Hamiltonian simulation, where one aims to approximate the time evolution of a reproduced quantum system of interest on a quantum computer and predict the time-dependent properties of the system, such as correlations. Concretely, we improve Hamiltonian simulation algorithms for time-periodic systems by taking advantage of high-frequency expansions in works [3, 4]. In Ref. [5], we reduce the approximation error of product formulas by classical variational optimisation, and translational symmetry to scale up the system size n.
The second direction is state preparation, where one targets the recreation of a quantum state, typically a ground state, and the prediction of its properties that are too difficult to compute classically. In Ref. [6], we take advantage of the electron number conservation of fermionic systems for a symmetry-aware circuit ansatz and self-consistent configuration recovery. Paired with warm-starting and classical subsystem diagonalisation, it allows us to estimate the Fe(III)-NTA ground state energy within chemical accuracy via samples obtained from an ion-trap quantum computer.
The third direction is to use symmetry for the reduction of statistical uncertainty of quantum estimators, which are computed from measured bitstring values at the end of a quantum computation. Concretely, in Refs. [1, 2], we improve the sampling complexity for energy estimation of quantum lattice systems, which can be mapped efficiently to current quantum hardware. Our approach leverages translational invariance to construct more sample-efficient estimators, where their minimal improvement compared to local Pauli bases is guaranteed by an analytical lower bound. Further in Refs. [3, 4], we take advantage of the translational invariance of both the quantum state and observable to boost the number of observed bitstring values per ion trap hardware sample by the number of qubits.
[1] T. Eckstein, R. Mansuroglu, S. Wolf, L. Nützel, S. Tasler, M. Kliesch, and M. J. Hartmann, in Quantum Computing Theory in Practice 2025 (Freie Universität Berlin, 2025).
[2] T. Eckstein, R. Mansuroglu, S. Wolf, L. Nützel, S. Tasler, M. Kliesch, and M. J. Hartmann, arXiv preprint arXiv:2410.21251 10.48550/arXiv.2410.21251 (2024).
[3] T. Eckstein, R. Mansuroglu, P. Czarnik, J.-X. Zhu, M. J. Hartmann, L. Cincio, A. T. Sornborger, and Z. Holmes, in Quantum Computing Theory in Practice 2024 (University of Edinburgh, 2024).
[4] T. Eckstein, R. Mansuroglu, P. Czarnik, J.-X. Zhu, M. J. Hartmann, L. Cincio, A. T. Sornborger, and Z. Holmes, npj Quantum Information 10, 84 (2024).
[5] R. Mansuroglu, T. Eckstein, L. N¨utzel, S. A. Wilkinson, and M. J. Hartmann, Quantum Science and Technology 8, 025006 (2023).
[6] L. Nützel, A. Gresch, L. Hehn, L. Marti, R. Freund, A. Steiner, C. D. Marciniak, T. Eckstein, N. Stockinger, S. Wolf, et al., Quantum Science and Technology 10, 015066 (2025).
[7] S. Tasler, J. Old, L. Heunisch, V. Feulner, T. Eckstein, M. Müller, and M. J. Hartmann, arXiv preprint arXiv:2506.09028 10.48550/arXiv.2506.09028 (2025)
Bettina Völter, Michael R. Müller, Lena Inowlocki (Hrsg.) (2024): Bild und Biographie
No full textOpen Access funding enabled and organized by Projekt DEAL.Friedrich-Alexander-Universität Erlangen-Nürnberg (1041
Long-term follow-up of scar quality and satisfaction after surgical closure of congenital abdominal wall defects: a single center perspective
No full textPurpose Postoperative scarring remains a major concern for patients and parents following repair of congenital abdominal wall defects. This study evaluated perceptions of postoperative scars in children after omphalocele or gastroschisis repair, comparing self-assessments with parental evaluations. We hypothesized that parents perceive scarring more negatively than their children. Methods A single-center study was conducted among patients treated for omphalocele or gastroschisis at the Department of Pediatric Surgery, University Hospital Erlangen (2001–2011). Between July 2022 and March 2023, patients and their parents completed the Patient and Observer Scar Assessment Scale ( POSAS ) 2.0, Patient Scar Assessment Questionnaire ( PSAQ ), and Short Form-36 ( SF-36 ). Exclusion criteria were death or psychomotor impairment precluding reliable self-assessment. Results Twenty-eight participants (61% gastroschisis, 39% omphalocele) were included. Parents rated scar appearance more negatively than their children ( POSAS overall impression p = 0.040; appearance p = 0.002 in omphalocele). PSAQ revealed discrepancies regarding scar-related symptoms ( p = 0.006) and satisfaction ( p = 0.009 total; p = 0.038 omphalocele). Parents tended to underestimate children’s physical complaints ( p = 0.099). No differences were found between defect types. SF-36 indicated high overall quality of life (mean 79.9 ± 13.3). Conclusion Significant parent–child differences exist in scar perception. Parents emphasize cosmetic concerns, whereas children report physical symptoms. Larger studies are warranted to guide tailored postoperative support.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546
The economic burden of lung cancer in low- and lower-middle-income countries: a systematic review
No full textBackground Lung Cancer is one of the four most frequent malignant neoplasms in the world, and first in mortality. In 2020, lung cancer resulted in roughly 1.8 million deaths globally. Lung cancer is a major public health problem in low and lower-middle income countries, where high rates of tobacco smoking, environmental pollution, and limited access to healthcare resources contribute to a significant burden of the disease. The objective of our review was to compare costs among available countries and identify major cost drivers. Methods A systematic database search was performed according to PRISMA guidelines on Web of Science, PubMed, Cochrane, EBSCO, ISPOR, and Google Scholar using a pre-defined search string. Studies were screened for eligibility and included if they provided information about the direct and indirect costs of lung cancer in low- and lower-middle-income countries. Search cut off was on August 4, 2025. The data from included studies were extracted, quantitatively synthesized, and compared. Results Of 2,383 articles, 15 met the inclusion criteria. All studies were conducted in low- and lower-middle-income countries, with a time frame ranging from 2003 to 2025. Most studies estimated costs based on prevalence. Most studies reported total healthcare costs as direct costs related to lung cancer; seven studies reported on indirect costs. Total average direct costs ranged from USD 2,540.66 per patient in Nepal to USD 10,179.98 per patient in the first year of treatment in Bolivia. Indirect costs varied from USD 140,995,744.13 in Bangladesh to USD 320,427,043.97 in Vietnam for their given respective sample sizes. Cost estimates varied substantially even for the same country depending on study’s analytical focus, timeframe, and other methodological considerations. Conclusion In conclusion, the costs of lung cancer are substantial and increase with disease progression, encompassing both direct and indirect components. High out-of-pocket expenditures further intensify the economic burden on patients and may lead to an underestimation of the true societal costs. The lack of standardized methodologies and robust data highlights the need for further research to guide effective policy and resource allocation in LMICs. Trial registration Registration: PROSPERO, ID CRD42020160370
Correction: Application of analytical ultracentrifugation in gravitational sweep mode coupled with turbidity detection for analyzing polydisperse emulsions of aged biodiesel and alkanes
No full textCorrection for “Application of analytical ultracentrifugation in gravitational sweep mode coupled with turbidity detection for analyzing polydisperse emulsions of aged biodiesel and alkanes” by Julian Türck et al. , RSC Adv. , 2025, 15 , 47840–47849, https://doi.org/10.1039/D5RA05601B
Glutaminolysis impairment and immunometabolic dysregulation in U937 cells: Key mechanisms in occupational and environmental skin exposure to UV and benzo[a]pyrene
No full textDermal exposure to polycyclic aromatic hydrocarbons (PAHs) and UV irradiation in occupational and environmental settings poses a health risk by inducing skin toxicity, including immunomodulatory effects. This study investigated the effects of benzo[a]pyrene (B[a]P), a well-characterized PAH, at three concentrations (0.04 nM, 4 nM, and 4 µM) and UV irradiation on human monocytic U937 cells, employing both single and combined exposure scenarios. An integrated metabolomics and toxicological approach was utilized to assess cellular responses, with a focus on understanding the immunometabolic effects of these exposures. Our findings revealed that only the highest B[a]P concentration in combination with UV irradiation resulted in significant metabolic dysregulation and impaired cellular function. Notably, we observed a pronounced downregulation of glutaminolysis, a critical metabolic pathway for cellular energy production and biosynthesis. This was evidenced by decreased levels of glutamate and key intermediates within the tricarboxylic acid cycle (e.g., succinate, fumarate, malate, and citrate), as well as reduced levels of glycine, a precursor for glutathione synthesis. In parallel, toxicological assays revealed increased levels of oxidative stress markers, lipid peroxidation, and enhanced DNA damage. Furthermore, the combined exposure led to alterations in tryptophan metabolism and dysregulation of lipid species, particularly sphingolipids and phosphatidylinositols. These findings lead us to propose the hypothesis that metabolic disruption, specifically the impairment of glutaminolysis, initiated a cascade of events, including increased oxidative stress, lipid peroxidation, and ultimately, ferroptosis in our study. Our results indicate that the combined exposure to UV irradiation and B[a]P can induce immunometabolic reprogramming and significantly contribute to the pathogenesis of inflammatory skin diseases.Open Access funding enabled and organized by Projekt DEAL.Deutsche Gesetzliche Unfallversicherunghttp://dx.doi.org/10.13039/501100003417Friedrich-Alexander-Universität Erlangen-Nürnberg (1041