OPEN FAU Online-Publikationssystem der Friedrich-Alexander-Universität Erlangen-Nürnberg
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Supported Lipid Bilayers as Stochastic Conveyor Belt for Delivery to the Near Field of Nanoscopic Structures
Get PDFPlacement of nanoscopic entities in the optical near field of a structure such as a plasmonic nanoantenna or the aperture of a scanning near-field optical microscopy (SNOM) remains a nontrivial task, which often requires sophisticated nanofabrication techniques. Here, we show that the fluidity and diffusion of lipid molecules in bilayer geometries can be exploited for facile delivery of nano-objects such as organic dye molecules, semiconductor quantum dots, and gold nanoparticles to the near field of well-defined surface structures. We demonstrate this in three different scenarios with substantial plasmonic enhancement of fluorescence.Max-Planck-Gesellschaft 10.13039/50110000418
Contactless radar-based heart rate estimation in palliative care – a feasibility study and possible use in symptom management
Get PDFBackground Heart rate (HR) monitoring is a medical standard to provide information about a patient’s health status. In palliative care, relationship and social engagement are crucial therapeutic concepts. For fear of disrupting communication, social contact, and care, continuous HR monitoring is underutilised despite its potential to inform on symptom burden and therapeutic effects. This study investigates radar-based HR monitoring as an innovative and burden-free approach for palliative care patients, compares its accuracy with conventional ECG methods, and shows potential for therapeutic guidance. Methods A single-centre, comparative clinical trial was conducted with palliative care patients at the ward of the Department of Palliative Medicine of the University Hospital of Erlangen. The HR measurements obtained with radar were compared with Holter ECG (study arm I, overnight) and Task Force ® Monitor (TFM)-based ECG validation recordings (study arm II, one hour). In addition, long-term radar measurements without validation were analysed in comparison with clinical health records (study arm III). Results Both validation methods showed correlation by scatter plot, modified Bland-Altman plot, and equivalence testing. N = 34 patients participated in study arm I. HR of 4,079 five-minute intervals was analysed. Radar measurements and ECG showed high agreement: difference of HRs was within 5 bpm in 3780 of 4079 (92.67%) and within ±13.4 bpm ( 1.96 times the SD of the mean) in 3979 (97.55%) intervals, respectively. In study arm II, n = 19 patients participated. 57,048 heart beats were analysed. The HR difference was within 5 bpm for 53,583 out of 57,048 beats (93.93%) and within 8.2 bpm ( ± 1.96 times the SD of the mean) in 55,439 beats (97.25%), respectively. Arm III showed HR changes extracted from radar data in correlation with symptoms and treatment. Conclusion Radar-based HR monitoring shows a high agreement in comparison with ECG-based HR monitoring and thus offers an option for continuous and above all burden-free HR assessment, with the potential for use in symptom management in palliative care, among others. Further research and technological advancements are still necessary to fully realize this innovative approach in enhancing palliative care practices.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546
Interoperability Working Group: core dataset and information systems for data integration and data exchange in the Medical Informatics Initiative
No full textZusammenfassung Die Arbeitsgruppe Interoperabilität der Medizininformatik-Initiative (MII) ist die Plattform für die Abstimmung übergreifender Vorgehensweisen, Datenstrukturen und Schnittstellen zwischen den Datenintegrationszentren (DIZ) der Universitätskliniken und nationalen bzw. internationalen Interoperabilitätsgremien. Ziel ist die gemeinsame inhaltliche und technische Ausgestaltung einer über das Forschungsdatenportal für Gesundheit nutzbaren verteilten Infrastruktur zur Sekundärnutzung klinischer Versorgungsdaten. Wichtige Rahmenbedingungen sind dabei Datenschutz und IT-Sicherheit für die Nutzung von Gesundheitsdaten in der biomedizinischen Forschung. Hierfür werden in dezidierten Taskforces geeignete Methoden eingesetzt, um prozessuale, syntaktische und semantische Interoperabilität für Datennutzungsprojekte zu ermöglichen. So wurde der MII-Kerndatensatz, bestehend aus mehreren Modulen mit zugehörigen Informationsmodellen, entwickelt und mittels des Standards HL7® FHIR® implementiert, um fachliche und technische Vorgaben für die interoperable Datenbereitstellung von Versorgungsdaten durch die DIZ zu ermöglichen. Zur näheren Beschreibung dieser Datensätze dienen internationale Terminologien und konsentierte Metadaten. Die Gesamtarchitektur, einschließlich übergreifender Schnittstellen, setzt die methodischen und rechtlichen Anforderungen an eine verteilte Datennutzungsinfrastruktur z. B. durch Bereitstellung pseudonymisierter Daten oder föderierte Analysen um. Mit diesen Ergebnissen der Arbeitsgruppe Interoperabilität stellt die MII eine zukunftsweisende Lösung für den Austausch und die Nutzung von Routinedaten vor, deren Anwendbarkeit über den Zweck der Forschung hinausgeht und eine wesentliche Rolle in der digitalen Transformation des Gesundheitswesens spielen kann.The interoperability Working Group of the Medical Informatics Initiative (MII) is the platform for the coordination of overarching procedures, data structures, and interfaces between the data integration centers (DIC) of the university hospitals and national and international interoperability committees. The goal is the joint content-related and technical design of a distributed infrastructure for the secondary use of healthcare data that can be used via the Research Data Portal for Health. Important general conditions are data privacy and IT security for the use of health data in biomedical research. To this end, suitable methods are used in dedicated task forces to enable procedural, syntactic, and semantic interoperability for data use projects. The MII core dataset was developed as several modules with corresponding information models and implemented using the HL7® FHIR® standard to enable content-related and technical specifications for the interoperable provision of healthcare data through the DIC. International terminologies and consented metadata are used to describe these data in more detail. The overall architecture, including overarching interfaces, implements the methodological and legal requirements for a distributed data use infrastructure, for example, by providing pseudonymized data or by federated analyses. With these results of the Interoperability Working Group, the MII is presenting a future-oriented solution for the exchange and use of healthcare data, the applicability of which goes beyond the purpose of research and can play an essential role in the digital transformation of the healthcare system.Open Access funding enabled and organized by Projekt DEAL.Friedrich-Alexander-Universität Erlangen-Nürnberg (1041
Oral mucosa - an examination map for confocal laser endomicroscopy within the oral cavity: an experimental clinical study
Get PDFObjectives Confocal laser endomicroscopy (CLE) is an optical method that enables microscopic visualization of oral mucosa. Previous studies have shown that it is possible to differentiate between physiological and malignant oral mucosa. However, differences in mucosal architecture were not taken into account. The objective was to map the different oral mucosal morphologies and to establish a “CLE map” of physiological mucosa as baseline for further application of this powerful technology. Materials and methods The CLE database consisted of 27 patients. The following spots were examined: (1) upper lip (intraoral) (2) alveolar ridge (3) lateral tongue (4) floor of the mouth (5) hard palate (6) intercalary line. All sequences were examined by two CLE experts for morphological differences and video quality. Results Analysis revealed clear differences in image quality and possibility of depicting tissue morphologies between the various localizations of oral mucosa: imaging of the alveolar ridge and hard palate showed visually most discriminative tissue morphology. Labial mucosa was also visualized well using CLE. Here, typical morphological features such as uniform cells with regular intercellular gaps and vessels could be clearly depicted. Image generation and evaluation was particularly difficult in the area of the buccal mucosa, the lateral tongue and the floor of the mouth. Conclusion A physiological “CLE map” for the entire oral cavity could be created for the first time. Clinical relevance This will make it possible to take into account the existing physiological morphological features when differentiating between normal mucosa and oral squamous cell carcinoma in future work.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546
New Concepts for Hemithioindigo Photoswitches and Machines
No full textMolecular switches and machines have reached almost every field of application, from medicine to materials science. Heat, pH changes, and chemical inputs are often required for their operation. However, there are also examples that operate under light irradiation, so-called photoswitches. Light as an energy source is of great interest, as its properties can be easily controlled by external electronic devices. Furthermore, light allows a high degree of spatiotemporal control without the generation of waste products. As a consequence, the field of molecular photoswitches has been vastly developed, encompassing different molecular frameworks. Among these, hemithioindigos (HTIs) represent a promising class since they possess many beneficial properties such as addressability with visible light and high thermal stability. To improve the performance of HTI photoswitches, the threefold substituted HTIs were further developed into fourfold substituted diaryl-HTIs and new design principles for high performance photoswitches were established in a systematic study. A combination of strong electron donor groups within the molecular setup and cross-conjugation were employed for this purpose. In addition, a further design element in the form of a pyridine ring was introduced to achieve late-stage modifications and metal-ion binding, which was finally exploited via a specific acid/base response of diaryl-HTIs for the application in logic operations.
In a further study, HTI photoswitches were considered under the aspect of sustainable chemistry. Here, a new synthetic strategy based on dynamic covalent chemistry of amines with alkyl bromides was established to reversibly convert a symmetric, non photoswitchable precursor into a diaryl-HTI ammonium salt photoswitch. The resulting photoswitches showcase high performance and the symmetric precursor experienced a gain of function. Interestingly, the ammonium HTI species could be reverted back to the symmetric precursor in a dealkylation step and functionalization of the recycled precursor with another alkyl residue can be accomplished. Additionally, a new level of control was established to influence the recyclability in an on/off manner and to generate long-lived and thermally stable ammonium salts. This was achieved via a reversible exchange of the counterions. In summary, a new basis for the design of novel, recyclable photoswitches was developed, which holds great potential for future applications.
Finally, a novel approach to introduce directionality in HTI-based molecular motors was tackled. Conventionally, the directionality of HTI motor motion originates from the stereoinformation of the sulfoxide. Within this concept, the transfer of stereochemical information from a chiral ligand in a metal complex to the HTI architecture is envisioned. For this purpose, HTI ligands for the complexation of metal ions were designed. The coordinating nature of sulfur together with nitrogen containing heterocycles incorporated in the HTI core or in the periphery was used to construct bidentate ligands. This approach allows the design of new HTI motors with beneficial properties such as strongly red-shifted absorptions and accelerated rotational motions
Author Correction: Mobilise-D insights to estimate real-world walking speed in multiple conditions with a wearable device
Get PDFSERPINC1 c.1247dupC: a novel SERPINC1 gene mutation associated with familial thrombosis results in a secretion defect and quantitative antithrombin deficiency
Get PDFBackground Antithrombin (AT) is an important anticoagulant in hemostasis. We describe here the characterization of a novel AT mutation associated with clinically relevant thrombosis. A pair of sisters with confirmed type I AT protein deficiency was genetically analyzed on suspicion of an inherited SERPINC1 mutation. A frameshift mutation, c.1247dupC, was identified and the effect of this mutation was examined on the cellular and molecular level. Methods Plasmids for the expression of wild-type (WT) and mutated SERPINC1 coding sequence (CDS) fused to green fluorescent protein ( GFP ) or hemagglutinin ( HA ) tag were transfected into HEK293T cells. Subcellular localization and secretion of the respective fusion proteins were analyzed by confocal laser scanning microscopy and Western blot. Results The c.1247dupC mutation results in a frameshift in the CDS of the SERPINC1 gene and a subsequently altered amino acid sequence (p.Ser417LysfsTer48). This alteration affects the C-terminus of the AT antigen and results in impaired secretion as confirmed by GFP- and HA-tagged mutant AT analyzed in HEK293T cells. Conclusion The p.Ser417LysfsTer48 mutation leads to impaired secretion, thus resulting in a quantitative AT deficiency. This is in line with the type I AT deficiency observed in the patients.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546
Correction: Assessing real-world gait with digital technology? Validation, insights and recommendations from the Mobilise-D consortium
Get PDFCrosslinking degree variations enable programming and controlling soft fracture via sideways cracking
Get PDFLarge deformations of soft materials are customarily associated with strong constitutive and geometrical nonlinearities that originate new modes of fracture. Some isotropic materials can develop strong fracture anisotropy, which manifests as modifications of the crack path. Sideways cracking occurs when the crack deviates to propagate in the loading direction, rather than perpendicular to it. This fracture mode results from higher resistance to propagation perpendicular to the principal stretch direction. It has been argued that such fracture anisotropy is related to deformation-induced anisotropy resulting from the microstructural stretching of polymer chains and, in strain-crystallizing elastomers, strain-induced crystallization mechanisms. However, the precise variation of the fracture behavior with the degree of crosslinking remains to be understood. Leveraging experiments and computational simulations, here we show that the tendency of a crack to propagate sideways in the two component Elastosil P7670 increases with the degree of crosslinking. We explore the mixing ratio for the synthesis of the elastomer that establishes the transition from forward to sideways fracturing. To assist the investigations, we construct a novel phase-field model for fracture where the critical energy release rate is directly related to the crosslinking degree. Our results demonstrate that fracture anisotropy can be modulated during the synthesis of the polymer. Then, we propose a roadmap with composite soft structures with low and highly crosslinked phases that allow for control over fracture, arresting and/or directing the fracture. The smart combination of the phases enables soft structures with enhanced fracture tolerance and reduced stiffness. By extending our computational framework as a virtual testbed, we capture the fracture performance of the composite samples and enable predictions based on more intricate composite unit cells. Overall, our work offers promising avenues for enhancing the fracture toughness of soft polymers.EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)10001066
“sCT-Feasibility” - a feasibility study for deep learning-based MRI-only brain radiotherapy
Get PDFBackground Radiotherapy (RT) is an important treatment modality for patients with brain malignancies. Traditionally, computed tomography (CT) images are used for RT treatment planning whereas magnetic resonance imaging (MRI) images are used for tumor delineation. Therefore, MRI and CT need to be registered, which is an error prone process. The purpose of this clinical study is to investigate the clinical feasibility of a deep learning-based MRI-only workflow for brain radiotherapy, that eliminates the registration uncertainty through calculation of a synthetic CT (sCT) from MRI data. Methods A total of 54 patients with an indication for radiation treatment of the brain and stereotactic mask immobilization will be recruited. All study patients will receive standard therapy and imaging including both CT and MRI. All patients will receive dedicated RT-MRI scans in treatment position. An sCT will be reconstructed from an acquired MRI DIXON-sequence using a commercially available deep learning solution on which subsequent radiotherapy planning will be performed. Through multiple quality assurance (QA) measures and reviews during the course of the study, the feasibility of an MRI-only workflow and comparative parameters between sCT and standard CT workflow will be investigated holistically. These QA measures include feasibility and quality of image guidance (IGRT) at the linear accelerator using sCT derived digitally reconstructed radiographs in addition to potential dosimetric deviations between the CT and sCT plan. The aim of this clinical study is to establish a brain MRI-only workflow as well as to identify risks and QA mechanisms to ensure a safe integration of deep learning-based sCT into radiotherapy planning and delivery. Discussion Compared to CT, MRI offers a superior soft tissue contrast without additional radiation dose to the patients. However, up to now, even though the dosimetrical equivalence of CT and sCT has been shown in several retrospective studies, MRI-only workflows have still not been widely adopted. The present study aims to determine feasibility and safety of deep learning-based MRI-only radiotherapy in a holistic manner incorporating the whole radiotherapy workflow. Trial registration NCT06106997.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546