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User-centered design approach to visualize PROMs for molecular tumor boards
No full textIntegrating Patient-Reported Outcome Measures (PROMs) into Molecular Tumor Boards (MTBs) remains challenging due to the complexity of data visualization and integration into clinical workflows. This work, as part of the German PM4Onco project, aims to identify visualization requirements for PROMs and develop a prototype for PROMs integration in cBioPortal, facilitating broader application within oncology care. We employed a qualitative research approach, including developing personas for MTB stakeholders, conducting a literature-based requirements analysis, organizing a co-design workshop to create low-fidelity prototypes, and evaluating the highest-rated prototype variant through an online survey distributed to MTB physicians across Germany. Seven specialist groups were identified, with key needs including intuitive visualization, clear axis labeling, and longitudinal symptom tracking. The resulting mid-fidelity mockup incorporated PROMs data within cBioPortal’s timeline view and a detailed PROMs tab, featuring trend indicators, line graphs, and customizable health displays. Usability evaluation by MTB members yielded a SUS score of 67, indicating an initial indicator of acceptable usability, with suggestions for improvements like threshold scores and deeper clinical data integration. While PROMs offer critical patient insights, they remain underused in MTBs. Our early-stage prototype demonstrates potential for addressing this gap, with future work focusing on implementation, broader testing, and international validation.Bundesministerium für Bildung und Forschunghttps://doi.org/10.13039/50110000234
Measuring Abdominal Skin‐Surface Distances Using Photos for Perforator Mapping Analysis—A Validation Study on 3D‐Printed DIEP‐Flap Models
No full textABSTRACT Background We present a novel method for accurately measuring skin‐surface distances using standard smartphone photos and Photoshop, validated on 3D‐printed DIEP‐flap models and on calibration grid‐patterns. Materials and Methods Distance measurements are acquired in Photoshop in a calibration plane between dots on a grid‐pattern as well as between perforators on photos of 3D‐printed models and compared against ground‐truth. Margins of errors are calculated from fitted linear models. Results Submillimeter accuracy can be achieved within errors of ±0.45 mm (80% probability) and ±0.8 mm (95% probability) for measuring distances on the dot‐grid. On the 3D‐printed DIEP‐models, distance measurements are accurate within ±1.75 mm (80% probability) and ±3.1 mm (95% probability). Conclusions We introduce a simple yet highly accurate technique to measure skin‐surface distances using normal photos. Depending on the scenario, submillimeter or conservatively very low millimetre errors can be achieved, sufficiently accurate for clinical use, whilst maintaining topographic relationships of the measurements.Bayrisches Forschungsinstitut für Digitale TransformationBayerisch‐Kalifornischen Hochschulzentrum 10.13039/50110001417
Spot Melting Strategy for Contour Melting in Electron Beam Powder Bed Fusion
No full textSpot melting is an emerging alternative to traditional line melting in electron beam powder bed fusion, dividing a layer into thousands of individual spots. This method allows for an almost infinite number of spot arrangements and spot melting sequences to tailor material and part properties. To enhance the productivity of spot melting, the number of spots can be reduced by increasing the beam diameter. However, this results in rough surfaces due to the staircase effect. The classical approach to counteract these effects is to melt a contour that surrounds the infill area. Creating effective contours is challenging because the melted area ought to cover the artifacts from the staircase effect and avoid porosity in the transition area between the infill and contour, all while minimizing additional energy and melt time. In this work, we propose an algorithm for generating a spot melting sequence for contour lines surrounding the infill area. Additionally, we compare three different approaches for combining the spot melting of infill and contour areas, each utilizing a combination of large infill spots and small contour spots. The quality of the contours is evaluated based on optical inspection as well as the porosity between infill and contour using electron optical images, balanced against the additional energy input. The most suitable approach is used to build a complex brake caliper.The authors gratefully acknowledge funding by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-Project ID 61375930-SFB 814-“Additive Manufacturing” TP T07.Deutsche Forschungsgemeinschaft (DFG, German Research Foundation
Effects of intrarenal afferent stimulation by bradykinin on renal sympathetic nerve activity: tonic inhibition contributing to renal function
No full textBradykinin (BK) may increase renal sodium excretion by decreasing tubular ENaC activity. Afferent renal nerve activity (ARNA) putatively controls renal sympathetic nerve activity (RSNA) involved in renal sodium handling. We recently found tonic sympatho-inhibition due to intrarenal ARNA stimulation by the TRPV1 agonist capsaicin (CAP). Since BK is known to augment TRPV1 effects, we hypothesized that intrarenally applied BK also tonically inhibits RSNA. Four groups of rats (n = 8; BK, CAP, HOE + BK, NaCl-control) were equipped with arterial and venous catheters for blood pressure (BP) and heart rate (HR) recordings and drug application; bipolar electrodes for RSNA and ARNA recordings, renal arterial catheter for intrarenal administration (IRA) of bradykinin (BK: 10−5 M, 20 µl and 10–4 M; 2.5, 5, 10 µl), capsaicin (CAP 3.3, 6.6, 10 and 33*10−7 M, 10 µl). The B2-receptor antagonist HOE-140 (10–4 M, 40 µl) was administered intravenously (IV) just before IRA BK (HOE + BK), finally the NK1-receptor blocker RP67580 (10−2 M, 15 µl; IV) was applied in all groups at the end of the experiment. IRA BK and CAP momentarily increased ARNA. IRA CAP, IRA BK, and IRA HOE + BK, decreased RSNA from 4.2 ± 0.8 to 1.3 ± 0.2 µV*sec (BK, P < 0.01), 3.6 ± 0.5 to 0.9 ± 0.2 µV*sec (CAP, P < 0.01) and 3.2 ± 0.3 to 0.8 ± 0.1 µV*sec (HOE-BK, P < 0.01). Suppressed RSNA (BK, CAP, HOE + BK) was unmasked by IV RP67580: 1.6 ± 0.5 to 8.6 ± 2.9 µV*sec (BK, P < 0.01); 1.0 ± 0.2 to 6.1 ± 1.5 µV*sec (CAP, P < 0.01); 0.8 ± 0.2 to 4.5 ± 0.8 µV*sec (HOE-BK, P < 0.05). IRA BK was associated with momentary increases of RSNA, abolished by HOE-140. Intrarenal stimulation of renal afferent nerves by BK induced tonic renal sympathodepression likely augmenting sodium and water excretion.Open Access funding enabled and organized by Projekt DEAL.Deutsche Forschungsgemeinschafthttps://doi.org/10.13039/501100001659Universitätsklinikum Erlangen (8546
Curvature-corrected retinal registration of diagnostic OCT with instrument-integrated OCT
No full textVitreoretinal surgery, requiring precise microscale tissue manipulation, is well-suited for robotic assistance. Image registration enhances surgeons’ visual perception by aligning high-resolution preoperative OCT images with the intraoperative environment, improving visibility of anatomical features not seen in microscope images. However, optical distortions from the cornea, lens, eye curvature, and scanning patterns challenge the use of diagnostic data in robotic navigation. This study introduces a novel technique for curvature-corrected retinal registration, integrating diagnostic OCT with instrument-integrated OCT. The pipeline comprises feature extraction, curvature correction, initial alignment, and fine registration. Experiments using an artificial model eye and ex vivo porcine eye validate the method. Curvature correction achieves accuracy comparable to existing methods, with deviations of 17 m for the model eye and 460 m for the porcine eye. Post-registration, the fiducial marker error reduces to 103 m for the model eye and 318 m for the porcine eye. Our method provides intraoperative diagnostic context, enabling reliable topological assistance in retinal robotic systems.Open Access funding enabled and organized by Projekt DEAL.Friedrich-Alexander-Universität Erlangen-Nürnberg (1041
Relative positions of half-sided modular inclusions
No full textLet K1⊂Hand K2⊂Hbe half-sided modular inclusions in a common standard subspace H . We prove that the inclusion K1⊂K2holds if and only if we have an inclusion of spectral subspaces of the generators of the positive one-parameter groups associated to the half-sided modular inclusions K1⊂Hand K2⊂H. From this we give a characterization of this situation in terms of (operator-valued) symmetric inner functions. We illustrate these characterizations with some examples of non-trivial phenomena occurring in this setting.Open Access funding enabled and organized by Projekt DEAL.Friedrich-Alexander-Universität Erlangen-Nürnberg (1041
CircRNAs: functions and emerging roles in cancer and immunotherapy
No full textBackground Circular RNAs (circRNAs) are emerging as promising tools in cancer and immunotherapy, with unique characteristics that offer potential therapeutic applications. Main body This review outlines the discovery, biogenesis, and mechanisms of circRNAs, emphasizing their roles in cancer and immune regulation. CircRNAs modulate immune responses by acting as miRNA sponges, binding RNA-binding proteins, or serving as translation templates. These interactions influence T cells, NK cells, macrophages, and immune checkpoints. The review also explores circRNAs’ roles in different cancers, focusing on target identification, immune effects, and mechanisms of action. Additionally, it examines circRNA-based therapies, including vaccines, CAR-T cell therapy, and database applications. Conclusion Despite their potential, technical hurdles must be overcome to advance circRNAs’ clinical use in cancer immunotherapy. Future research should focus on addressing these challenges to fully realize the therapeutic potential of circRNAs.Noncommunicable Chronic Diseases-National Science and Technology Major ProjectMinistry of Education in China Liberal arts and Social Sciences FoundationYouth Science and Technology Elite Talent Project of Guizhou Provincial Department of Educatio
Merkmale der trabekulären Textur und der paraspinalen Muskulatur zur Vorhersage der ersten Wirbelkörperfraktur: Eine QCT-Analyse aus der AGES-Kohorte
No full text1 Zusammenfassung
1.1 Hintergrund und Ziele
Osteoporose bedingte Wirbelkörperfrakturen sind häufig und begünstigen das Auftreten weiterer Wirbelkörperfrakturen (Ballane et al., 2017; Lorentzon et al., 2024). Sie sind mit erheblichen gesundheitlichen und sozioökonomischen Belastungen verbunden und gehen mit einer erhöhten Mortalität einher (Ballane et al., 2017). Angesichts der steigenden Belastung des Gesundheitssystems ist die Optimierung der Prädiktion osteoporotischer Wirbelkörperfrakturen sowie deren frühzeitige Diagnostik und Intervention von Bedeutung (Allam et al., 2023). Obwohl die Bestimmung der arealen Knochendichte (aBMD) mittels Dual-Röntgen-Absorptiometrie (DXA) sowie der volumetrischen Knochendichte (vBMD) durch Quantitative Computertomographie (QCT) als zuverlässige Prädiktoren für das Frakturrisiko von Wirbelkörpern gelten, besteht weiterhin ein erheblicher Forschungsbedarf zur Verbesserung der Frakturvorhersage (Engelke et al., 2015, 2008). Ziele dieser Studie mit dem Titel “Merkmale der trabekulären Textur und der paraspinalen Muskulatur zur Vorhersage der ersten Wirbelkörperfraktur: Eine QCT Analyse aus der AGES-Kohorte“ sind es zu untersuchen, ob die Vorhersage des Frakturrisikos über die herkömmliche BMD-Messung hinaus verbessert werden kann und ob zusätzliche, leicht messbare Parameter zur Frakturrisiko-Vorhersage identifiziert werden können, die mit hoher Präzision auf verschiedenen CT-Scannern anwendbar sind (Engelke et al., 2009). Mit Hilfe von Daten aus der Age, Gene/Environment Susceptibility Reykjavik (AGES-Reykjavik) Kohorte untersuchten wir, ob trabekuläre Textur- und paraspinale Muskelparameter die Vorhersage der ersten inzidenten Wirbelkörperfraktur verbessern.
1.2 Methoden
In dieser Studie wurden Computertomographie (CT) Scans der Lendenwirbel L1 und L2 aus einer Teilgruppe der AGES-Reykjavik-Studie analysiert, die mehr als 5.000 isländische Teilnehmer im Alter von etwa 67 bis 95 umfasst. Insgesamt wurden 843 Probanden analysiert, von denen 167 eine Wirbelkörperfraktur innerhalb von 5 Jahren erlitten haben. Die Kontrollgruppe bestand aus 676 frakturlosen Probanden der AGES-Kohorte. Die Bildanalyse der CT-Scans mittels QCT und dem Medical Imaging Analysis Framework für die Wirbelsäule (MIAF- Spine) umfasste die Messung der BMD, der Dicke der Kortikalis und von Parametern, die die trabekuläre Architektur und die autochthone Muskulatur charakterisieren. Fünfzig Variablen, darunter eine BMD, eine trabekuläre Textur und eine Muskeluntergruppe dienten als Prädiktoren und umfassten jeweils Alter, Body-Mass-Index (BMI) und die entsprechenden Parameter der QCT-Analyse. Die Anzahl der Variablen in jeder Untergruppe wurde durch schrittweise logistische Regression reduziert, um multivariable Frakturvorhersagemodelle zu erstellen. Die Modellgenauigkeit wurde mit Hilfe des Likelihood-Ratio-Tests (LRT) und der Fläche unter der Kurve (AUC) bewertet. Mit Hilfe der Bootstrap-Analysen wurde die Stabilität der Modelle überprüft.
1.3 Ergebnisse und Beobachtungen
Insgesamt wurden 826 CT-Scans (486 Frauen und 340 Männer) aus einer Teilgruppe von 843 Probanden analysiert. 96 Frauen und 78 Männer hatten bereits vorbestehende Wirbelkörperfrakturen und wurden aus der Analyse ausgeschlossen. Die Untersuchung fokussierte sich auf die Vorhersage des Risikos für die erste Wirbelkörperfraktur. Die Analyse zeigte, dass bei Frauen 17 der anfänglich 50 untersuchten Faktoren signifikant mit zukünftigen Frakturen assoziiert waren, bei Männern waren es 11. Knochen- und Texturmodelle sagten Frakturen bei Frauen (p<0,001) und Männern (p<0,01) signifikant besser voraus als die Kombination aus Alter und BMI. Das Muskelmodell verbesserte die Vorhersage nur bei Männern (p=0,03). Der LRT zeigte eine signifikante Verbesserung der Frakturvorhersage durch die Kombination von BMD mit Textur (Frauen und Männer, p<0,05), sowie mit Muskelmodellen (nur Männer, p=0,03). Allerdings stiegen die AUC-Werte dadurch nicht signifikant an (AUC Frauen: Alter & BMI: 0,57, BMD: 0,69, kombiniert: 0,69; AUC Männer: Alter & BMI: 0,63, BMD: 0,71, kombiniert: 0,73–0,77).
1.4 Schlussfolgerung und Diskussion
Unsere Studie zeigt, dass BMD weiterhin der wichtigste Prädiktor zur Vorhersage von Wirbelkörperfrakturen bleibt. Trabekuläre Textur- und Muskelparameter können die Vorhersage der ersten inzidenten Wirbelkörperfraktur gegenüber Alter und BMI verbessern. Gegenüber zur BMD war die Verbesserung der Vorhersage jedoch nur gering. Da keine Finite- Elemente- Analyse (FEA) durchgeführt wurde, bleibt offen, ob eine Festigkeitsbestimmung die Vorhersage weiter optimieren könnte. Künftige Studien sind erforderlich, um diese Erkenntnisse zu validieren und weiterzuentwickeln
Fortgeschrittene Synchronisationskonzepte für Multistatische, Phasenkohärente Lokalisierungsnetzwerke
No full textTime and frequency synchronization have been the focus of extensive research over the past several decades, particularly in the domains of wireless communication, distributed radar, and sensor networks. In these systems, precise coordination among spatially distributed nodes is essential for coherent signal processing, accurate data fusion, and reliable system performance. With the emergence of advanced technologies such as 5G/6G networks, cooperative sensing, integrated sensing and communication (ISAC), and distributed MIMO radar, the demands on synchronization have become increasingly stringent. These applications require tightly aligned transmissions and phase-coherent processing across multiple nodes to support high-resolution sensing, wide-area situational awareness, and efficient spectrum utilization.
In radar imaging systems -- especially those employing distributed or multistatic architectures -- synchronization plays a central role in determining system performance. Accurate time synchronization ensures consistent alignment of transmitted and received radar pulses, which is vital for maintaining range accuracy and preserving the temporal integrity of echoes. Frequency synchronization is equally critical, as it maintains phase coherence across channels, directly influencing Doppler estimation, interferometric processing, and the quality of synthetic aperture radar (SAR) imaging. Coherent fusion of signals from spatially separated nodes enables extended aperture synthesis, enhanced angular resolution, and robust target detection and tracking.
Furthermore, in joint communication and sensing (JCAS) systems -- key components of future 6G infrastructure -- tight synchronization between radar and communication elements is essential to enable concurrent data transmission and environmental sensing within shared spectral and hardware resources. Consequently, advanced synchronization strategies are not only fundamental to robust communication and precise localization, but also indispensable for enabling the next generation of radar imaging and ISAC capabilities in dynamic, multi-node environments.
Nevertheless, in response to the increasing synchronization requirements, recent research has increasingly focused on exploiting advanced techniques for the estimation and correction of time offset and frequency skew under real-world conditions.
This thesis presents advanced methods for time and frequency synchronization in multi-static phase-coherent localization networks, with a particular focus on radar systems mounted on autonomous aerial vehicles (AAVs). A novel real-time wireless synchronization scheme is developed and fully implemented on a high-end radio frequency system-on-chip field-programmable gate array (FPGA) platform. The proposed solution integrates a two-way synchronization protocol inspired by the precision time protocol (PTP), incorporating quadrature phase shift keying (QPSK) modulation, Reed–Solomon error correction, Costas loop-based carrier recovery, and Kalman filtering. High-precision timestamps are derived from disciplined digitally compensated temperature-controlled crystal oscillators (DCTCXOs) to ensure sub-nanosecond timing accuracy. Observed timestamps obtained through PTP exchange are iteratively refined using a recursive Kalman filter, which is particularly well suited to the dynamic and parallel processing capabilities of FPGA platforms. This enables effective compensation of clock offset and frequency skew, even under real-world channel conditions and over long distances between nodes. Owing to the deterministic processing time of the FPGA, the proposed synchronization system achieves exceptional precision, with clock offset deviations in the nanosecond range and clock rate deviations limited to only a few parts per billion. Experimental validation confirms the robustness and performance of the synchronization framework, making it highly suitable for distributed radar sensing and localization applications requiring coherent signal processing across spatially separated nodes
Characterization of Tumor and Immune Cells in Breast Cancer Organoids
No full textAbstract
Background and aims: Breast cancer (BC) is the most common malignancy among women, representing a significant global health concern. Metastasis is the leading cause of BC-related mortality, highlighting the need to identify metastasis-related markers to improve prognosis and refine therapeutic strategies.
The immune system, in particular T cells, plays a critical role in tumor surveillance and defense. This study aims to characterize tumor-immune interactions using a coculture model of patient-derived BC organoids and primary T cells, offering deeper insights into tumor immunogenicity.
Methods: Patient-derived BC organoids with a receptor-positive genetic background were established and characterized using flow cytometry, immunofluorescence (IF) - immunohistochemistry (IHC) and Hematoxylin and Eosin (HE) staining. Tumor cell markers, cell viability and cellular heterogeneity were assessed. The metastatic potential was evaluated by analyzing the expression of metastasis-related genes via quantitative polymerase chain reaction (qPCR) and by evaluating cancer stem cell markers using the Aldefluor assay.
To investigate tumor-immune interactions, T cells from healthy donors (HD) were isolated, characterized (CD3, CD4, CD8) and cocultured with BC organoids for 24 hours. The percentage of activation markers (CD69, CD137), human leukocyte antigen (HLA), Mucin 1 (Muc1) and programmed cell death protein 1 (PD1) was analyzed by flow cytometry. Interferon (IFN) γ levels in the coculture supernatant were quantified using enzyme-linked immunosorbent assay (ELISA) and T cell migration into BC organoids was assessed by IF staining.
Results: BC organoids exhibited distinct tumor marker expression and cellular heterogeneity. IF - IHC analysis revealed a similar distribution of Muc1 and CD44. Compared to the MCF7 cell line, BC organoids exhibited higher aldehyde dehydrogenase (ALDH) percentage, indicating the presence of a subpopulation of stem and progenitor cells. Additionally, the expression of metastasis-related genes was elevated in the BC organoids compared to the non-metastatic MCF7 cells, suggesting a higher metastatic potential.
Coculturing with T cells resulted in increased percentage of activation markers, enhanced IFNγ production in T cells and upregulation of HLA molecules in the organoids. Notably, IF analysis revealed T cell infiltration into the inner regions of BC organoids, leading to tumor cell lysis.
Discussion: BC organoids effectively recapitulate key characteristics of the original tumor, including metastatic potential, subtype, cellular heterogeneity and the tumor microenvironment (TME).
This study successfully established a patient-derived BC organoid - T cell coculture system, demonstrating that T cells infiltrate tumor organoids and become activated upon tumor contact. These findings underscore the potential of organoid-based models for studying tumor immunogenicity and advancing personalized therapeutic strategies