Institut für Medizintechnik und Medizininformatik
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Publikation Microstructures, phase and mechanical characterisation of Al2O3-ZrO2-TiO2 coating produced by atmospheric plasma spraying(Elsevier, 20.12.2024) Chang, Cynthia Sin Ting; Wyss, Marcus; Andrzejewski, Michal; Darut, Geoffrey; Graf, Lukas; Novak, Vladimir; Olbinado, Margie; Erpel, Susanne; Vogel, Alexander; Bode, Simon; de Wild, Michael; Salito, ArmandoThe microstructure, crystallographic phases, and mechanical properties of a newly developed Al2O3 – TiO2 – ZrO2 ternary ceramic coating were characterized. The coatings were produced by atmospheric plasma spraying as a preblended powder on Ti-6Al-4 V substrates using the new generation of the Debye-Larmor cascaded plasma torch. The 400 μm thick as-sprayed ternary ceramic coating is compact and neither delamination nor inter-/trans-granular cracks were found. The coating consists of single phase α-Al2O3, monoclinic m-ZrO2, and a nanocrystalline dual phase structure of α-Al2O3 and m-ZrO2. Ti is either present as ZrTiO4 or as solute in the dual phase. Cracking from the tip of the indent is rare and delamination was not observed after the progressive scratch test. The coating has potential in high wear applications for example in medical devices.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Machine learning for precision diagnostics of autoimmunity(Nature, 13.11.2024) Kruta, Jan; Carapito, Raphael; Trendelenburg, Marten; Martin, Thierry; Rizzi, Marta; Voll, Reinhard E.; Cavalli, Andrea; Natali, Eriberto; Meier, Patrick; Stawiski, Marc; Mosbacher, Johannes; Mollet, Annette; Santoro, Aurelia; Capri, Miriam; Giampieri, Enrico; Schkommodau, Erik; Miho, EnkelejdaEarly and accurate diagnosis is crucial to prevent disease development and define therapeutic strategies. Due to predominantly unspecific symptoms, diagnosis of autoimmune diseases (AID) is notoriously challenging. Clinical decision support systems (CDSS) are a promising method with the potential to enhance and expedite precise diagnostics by physicians. However, due to the difficulties of integrating and encoding multi-omics data with clinical values, as well as a lack of standardization, such systems are often limited to certain data types. Accordingly, even sophisticated data models fall short when making accurate disease diagnoses and presenting data analyses in a user-friendly form. Therefore, the integration of various data types is not only an opportunity but also a competitive advantage for research and industry. We have developed an integration pipeline to enable the use of machine learning for patient classification based on multi-omics data in combination with clinical values and laboratory results. The application of our framework resulted in up to 96% prediction accuracy of autoimmune diseases with machine learning models. Our results deliver insights into autoimmune disease research and have the potential to be adapted for applications across disease conditions.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Intracoronary ECG ST-segment shift remission time during reactive myocardial hyperemia. A new method to assess hemodynamic coronary stenosis severity(American Physiological Society, 01.10.2024) Bigler, Marius Reto; Kieninger-Gräfitsch, Andrea; Rohla, Miklos; Corpateaux, Noé; Waldmann, Frédéric; Wildhaber, Reto; Häner, Jonas; Seiler, ChristianFractional flow reserve (FFR) measurements are recommended for assessing hemodynamic coronary stenosis severity. Intracoronary ECG (icECG) is easily obtainable and highly sensitive in detecting myocardial ischemia due to its close vicinity to the myocardium. We hypothesized that the remission time of myocardial ischemia on icECG after a controlled coronary occlusion accurately detects hemodynamically relevant coronary stenosis. This retrospective, observational study included patients with chronic coronary syndrome undergoing hemodynamic coronary stenosis assessment immediately following a strictly 1-min proximal coronary artery balloon occlusion with simultaneous icECG recording. icECG was used for a beat-to-beat analysis of the ST-segment shift during reactive hyperemia immediately following balloon deflation. The time from coronary balloon deflation until the ST-segment shift reached 37% of its maximum level, i.e., icECG ST-segment shift remission time (τ-icECG in seconds), was obtained by an automatic algorithm. τ-icECG was tested against the simultaneously obtained reactive hyperemia FFR at a threshold of 0.80 as a reference parameter. From 120 patients, 139 icECGs (age, 68 ± 10 yr old) were analyzed. Receiver operating characteristic (ROC) analysis of τ-icECG for the detection of hemodynamically relevant coronary stenosis at an FFR of ≤0.80 was performed. The area under the ROC curve was equal to 0.621 (P = 0.0363) at an optimal τ-icECG threshold of 8 s (sensitivity, 61%; specificity, 67%). τ-icECG correlated inversely and linearly with FFR (P = 0.0327). This first proof-of-concept study demonstrates that τ-icECG, a measure of icECG ST segment-shift remission after a 1-min coronary artery balloon occlusion accurately detects hemodynamically relevant coronary artery stenosis according to FFR at a threshold of ≥8 s.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation In situ minimally invasive 3D printing for bone and cartilage regeneration - a scoping review(De Gruyter, 14.09.2024) Maintz, Michaela; Tomooka, Yukiko; Eugster, Manuela; Gerig, Nicolas; Sharma, Neha; Thieringer, Florian M.; Rauter, GeorgAdvancements in personalized medicine, three-dimensional (3D) printing, miniaturization, and robot-assistedsurgery are driving innovation in tissue engineering. A novelapproach, known asin situprinting, focuses on the direct depo-sition of materials at the surgical site. Using thein situprintingapproach, bone and/or cartilage defects can be addressed withhigh precision. Furthermore, highly customized 3D printed tis-sue constructs or implants can be deposited directly insidethe body. Currently, most applications ofin situprinting arelimited to areas near the skin or open surgeries. Even thougha minimally invasive approach would bring clinical benefits,only a few research groups have focused on this field. In thisscoping review, we provide an overview of the current stateofin situminimally invasive 3D printing technology for boneand cartilage regeneration and discuss its advantages and cur-rent challenges.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Optimizing neuroscience data management by combining REDCap, BIDS and SQLite. A case study in Deep Brain Stimulation(Frontiers Research Foundation, 05.09.2024) Stawiski, Marc; Bucciarelli, Vittoria; Vogel, Dorian; Hemm-Ode, SimoneNeuroscience studies entail the generation of massive collections of heterogeneous data (e.g. demographics, clinical records, medical images). Integration and analysis of such data in research centers is pivotal for elucidating disease mechanisms and improving clinical outcomes. However, data collection in clinics often relies on non-standardized methods, such as paper-based documentation. Moreover, diverse data types are collected in different departments hindering efficient data organization, secure sharing and compliance to the FAIR (Findable, Accessible, Interoperable, Reusable) principles. Henceforth, in this manuscript we present a specialized data management system designed to enhance research workflows in Deep Brain Stimulation (DBS), a state-of-the-art neurosurgical procedure employed to treat symptoms of movement and psychiatric disorders. The system leverages REDCap to promote accurate data capture in hospital settings and secure sharing with research institutes, Brain Imaging Data Structure (BIDS) as image storing standard and a DBS-specific SQLite database as comprehensive data store and unified interface to all data types. A self-developed Python tool automates the data flow between these three components, ensuring their full interoperability. The proposed framework has already been successfully employed for capturing and analyzing data of 107 patients from 2 medical institutions. It effectively addresses the challenges of managing, sharing and retrieving diverse data types, fostering advancements in data quality, organization, analysis, and collaboration among medical and research institutions.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Case report. One-stage craniectomy and cranioplasty digital workflow for three-dimensional printed polyetheretherketone implant for an extensive skull multilobular osteochondosarcoma in a dog(Frontiers Research Foundation, 29.08.2024) Hobert, Marc; Sharma, Neha; Benzimra, Caroline; Hinden, Sandro; Oevermann, Anna; Maintz, Michaela; Beyer, Michel; Thieringer, Florian; Guevar, JulienObjective: To report a digital workflow for use and long-term outcome of cranioplasty with a 3D-printed patient-specific Polyetheretherketone (PEEK) implant in a 12-y-old German Shepherd dog after surgical removal of an extensive occipital bone multilobular osteochondrosarcoma (MLO). Study design: Retrospective case report. Animal: A 12-year-old neutered female German Shepherd dog was presented with facial deformity, blindness, tetraparesis, and ataxia. Magnetic resonance imaging (MRI) and computed tomography (CT) identified a large skull-based mass extending extra-and intracranially with severe compression of the cerebellum and occipital lobes of the cerebrum. Methods: One-stage decompressive craniectomy using virtual surgical planned 3D-printed craniotomy cutting guides and the Misonix BoneScalpel® and reconstruction with a patient-specific 3D-printed PEEK cranial implant. Results: 3D-printed craniectomy cutting guides allowed an adequate fit of the cranial implant to the original skull. Misonix BoneScalpel® allowed performing a safe and extensive craniectomy. Postoperative CT (8 weeks after surgery) confirmed the PEEK cranial implant to be in place and without implant rejection. Clinically, the neurological examination identified only a right-hind limb delay in proprioception 8 weeks postoperatively, which remained unchanged at 18 months after surgery. Adjunctive treatment included metronomic chemotherapy. Eighteen months after surgery the dog passed away for reasons unrelated to the MLO, no implant-related complications were reported. Conclusion: 3D-printed craniectomy cutting guides, patient-specific PEEK cranial implant, and metronomic chemotherapy can lead to a successful long-term outcome in dogs with extensive skull MLO. Clinical significance: PEEK is an alternative biomaterial that can be used successfully for skull reconstruction.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Evaluation of the dimensional accuracy of robot-guided laser osteotomy in reconstruction with patient-specific implants. An accuracy study of digital high-tech procedures(MDPI, 19.06.2024) Msallem, Bilal; Veronesi, Lara; Beyer, Michel; Halbeisen, Florian S.; Maintz, Michaela; Franke, Adrian; Korn, Paula; Dragu, Adrian; Thieringer, Florian M.Background/Objective: With the rapid advancement in surgical technologies, new workflows for mandibular reconstruction are constantly being evaluated. Cutting guides are extensively employed for defining osteotomy planes but are prone to errors during fabrication and positioning. A virtually defined osteotomy plane and drilling holes in robotic surgery minimize potential sources of error and yield highly accurate outcomes. Methods: Ten mandibular replicas were evaluated after cutting-guided saw osteotomy and robot-guided laser osteotomy following reconstruction with patient-specific implants. The descriptive data analysis summarizes the mean, standard deviation (SD), median, minimum, maximum, and root mean square (RMS) values of the surface comparison for 3D printed models regarding trueness and precision. Results: The saw group had a median trueness RMS value of 2.0 mm (SD ± 1.7) and a precision of 1.6 mm (SD ± 1.4). The laser group had a median trueness RMS value of 1.2 mm (SD ± 1.1) and an equal precision of 1.6 mm (SD ± 1.4). These results indicate that robot-guided laser osteotomies have a comparable accuracy to cutting-guided saw osteotomies, even though there was a lack of statistical significance. Conclusions: Despite the limited sample size, this digital high-tech procedure has been shown to be potentially equivalent to the conventional osteotomy method. Robotic surgery and laser osteotomy offers enormous advantages, as they enable the seamless integration of precise virtual preoperative planning and exact execution in the human body, eliminating the need for surgical guides in the future.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Possible association of dose rate and the development of late visual toxicity for patients with intracranial tumours treated with pencil beam scanned proton therapy(BioMed Central, 17.06.2024) Meijers, Arturs; Daartz, Juliane; Knopf, Antje; Van Heerden, Michelle; Bizzocchi, Nicola; Vazquez, Miriam Varela; Bachtiary, Barbara; Pica, Alessia; Shih, Helen A.; Weber, Damien CharlesBackground and purpose Rare but severe toxicities of the optic apparatus have been observed after treatment of intracranial tumours with proton therapy. Some adverse events have occurred at unusually low dose levels and are thus difficult to understand considering dose metrics only. When transitioning from double scattering to pencil beam scanning, little consideration was given to increased dose rates observed with the latter delivery paradigm. We explored if dose rate related metrics could provide additional predicting factors for the development of late visual toxicities. Materials and methods Radiation-induced intracranial visual pathway lesions were delineated on MRI for all index cases. Voxel-wise maximum dose rate (MDR) was calculated for 2 patients with observed optic nerve toxicities (CTCAE grade 3 and 4), and 6 similar control cases. Additionally, linear energy transfer (LET) related dose enhancing metrics were investigated. Results For the index cases, which developed toxicities at low dose levels (mean, 50 GyRBE), some dose was delivered at higher instantaneous dose rates. While optic structures of non-toxicity cases were exposed to dose rates of up to 1 to 3.2 GyRBE/s, the pre-chiasmatic optic nerves of the 2 toxicity cases were exposed to dose rates above 3.7 GyRBE/s. LET-related metrics were not substantially different between the index and non-toxicity cases. Conclusions Our observations reveal large variations in instantaneous dose rates experienced by different volumes within our patient cohort, even when considering the same indications and beam arrangement. High dose rate regions are spatially overlapping with the radiation induced toxicity areas in the follow up images. At this point, it is not feasible to establish causality between exposure to high dose rates and the development of late optic apparatus toxicities due to the low incidence of injury.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Treatment verification in particle therapy(IOP Publishing, 01.06.2024) Gianoli, Chiara; De Simoni, M.; Knopf, Antje; Paganelli, Chiara; Gianoli, Chiara; Knopf, AntjeTo make the most of the physical and biological potentials of Particle Therapy (PT), it would be extremely desirable to verify dose deposition in vivo. In this chapter, we describe and compare in vivo range verification methods currently being proposed, developed or clinically implemented, including PET and prompt gamma imaging. The potential of other emerging techniques for indirect treatment verification will be also cited.04A - Beitrag SammelbandPublikation Organ motion in particle therapy and the role of imaging(IOP Publishing, 06/2024) Paganelli, Chiara; Molinelli, Silvia; Knopf, Antje; Paganelli, Chiara; Gianoli, Chiara; Knopf, AntjeOrgan motion is one of the main challenges to account for in particle therapy to plan and deliver an accurate treatment. In this chapter, we will explain the concept of organ motion in terms of inter- and intra-fraction variations. The current inter- and intra-fraction motion compensation techniques demanding for imaging will be also reported.04A - Beitrag SammelbandPublikation Conclusions and future perspectives of imaging in particle therapy(IOP Publishing, 06/2024) Paganelli, Chiara; Gianoli, Chiara; Knopf, Antje; Paganelli, Chiara; Gianoli, Chiara; Knopf, AntjeIn this chapter, we will consolidate the concluding remarks presented throughout the preceding chapters, with a specific emphasis on the technical and methodological advancements in image-guided particle therapy, as well as elucidating the future trajectory of this field.04A - Beitrag SammelbandPublikation Integration of imaging in clinical protocols of particle therapy(IOP Publishing, 06/2024) Trnkova, P.; Bolsi, Alessandra; Knopf, Antje; Hoffmann, A.; Paganelli, Chiara; Gianoli, Chiara; Knopf, Antje04A - Beitrag SammelbandPublikation Imaging in article therapy. Current practice and future trends(IOP Publishing, 06/2024) Paganelli, Chiara; Gianoli, Chiara; Knopf, Antje; Paganelli, Chiara; Gianoli, Chiara; Knopf, AntjeThe benefits of particle therapy (PT), stemming from its physical and radiobiological advantages, necessitate the use of dedicated imaging technologies and approaches to ensure precise treatment planning and delivery. This book endeavors to establish a fundamental understanding of imaging within the context of PT, alongside exploring current research and clinical perspectives on its role. The focus is directed towards examining near-room, in-room, and in-beam technologies, both those already in clinical use and those in the developmental stage, which play pivotal roles in treatment planning, delivery, and verification processes, enabling adjustments either offline or online. Concurrently, the text addresses methodological solutions derived from these imaging modalities to effectively address challenges such as range uncertainties, anatomical variations, and biological properties, thereby enhancing the accuracy of treatment modeling and adaptation.03 - SammelbandPublikation Differences in autophagy marker levels at birth in preterm vs. term infants(Nature, 29.05.2024) Künstle, Noëmi; Gorlanova, Olga; Marten, Andrea; Müller, Loretta; Sharma, Pawan; Röösli, Martin; Sinues, Pablo; Schär, Primo; Schürmann, David; Rüttimann, Céline; Da Silva Sena, Carla Rebeca; Nahum, Uri; Usemann, Jakob; Steinberg, Ruth; Yammine, Sophie; Schulzke, Sven; Latzin, Philipp; Frey, Urs; Beck, Fiona; Bovermann, Xenia; Casaulta, Carmen; Curdy, Marion; Da Silva Sena, Carla Rebeca; de Hoogh, Kees; Frauchiger, Bettina; Ho Dac, Léa Kim-Mi; Kieninger, Elisabeth; Korten, Insa; Oestreich, Marc-Alexander; Stöcklin, Benjamin; Streibel, Carmen; Wyler, FlorianBackground Preterm infants are susceptible to oxidative stress and prone to respiratory diseases. Autophagy is an important defense mechanism against oxidative-stress-induced cell damage and involved in lung development and respiratory morbidity. We hypothesized that autophagy marker levels differ between preterm and term infants. Methods In the prospective Basel-Bern Infant Lung Development (BILD) birth cohort we compared cord blood levels of macroautophagy (Beclin-1, LC3B), selective autophagy (p62) and regulation of autophagy (SIRT1) in 64 preterm and 453 term infants. Results Beclin-1 and LC3B did not differ between preterm and term infants. However, p62 was higher (0.37, 95% confidence interval (CI) 0.05;0.69 in log2-transformed level, p = 0.025, padj = 0.050) and SIRT1 lower in preterm infants (−0.55, 95% CI −0.78;−0.31 in log2-transformed level, padj < 0.001). Furthermore, p62 decreased (padj-value for smoothing function was 0.018) and SIRT1 increased (0.10, 95% CI 0.07;0.13 in log2-transformed level, padj < 0.001) with increasing gestational age. Conclusion Our findings suggest differential levels of key autophagy markers between preterm and term infants. This adds to the knowledge of the sparsely studied field of autophagy mechanisms in preterm infants and might be linked to impaired oxidative stress response, preterm birth, impaired lung development and higher susceptibility to respiratory morbidity in preterm infants. Impact To the best of our knowledge, this is the first study to investigate autophagy marker levels between human preterm and term infants in a large population-based sample in cord blood plasma. This study demonstrates differential levels of key autophagy markers in preterm compared to term infants and an association with gestational age. This may be linked to impaired oxidative stress response or developmental aspects and provide bases for future studies investigating the association with respiratory morbidity01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Tracking of a magnetically navigated millirobot with a magnetic-field camera(IEEE, 10.04.2024) Vergne, Céline; Pinto Inácio, José Miguel; Quirin, Thomas; Sargent, David; Madec, Morgan; Pascal, JorisA significant progress has been made in the development of magnetic micromanipulation for minimally invasive surgery. The development of systems to localize millimeter-sized robots during magnetic manipulation without line-of-sight detection remains, however, a challenging task. In this study, we focused on the development of a tracking system aiming to fill this gap. A robot, which consists of a cylindrical magnet of 1-mm diameter, is localized using a 2-D array of 3-D magnetoresistive sensors. The system, also called magnetic-field camera (MFC), provides tracking of the robot with a refresh rate of 2 Hz. The developed tracking algorithm reaches a mean absolute error (MAE) for the position and the orientation of, respectively, 0.56 mm and 5.13° in 2-D. This system can be added to the existing magnetic manipulation systems (MMSs) allowing closed-loop control of the navigation. The performances of the MFC are not affected by an exposure to strong magnetic fields. Exposures up to 3 T have been validated. Increasing the integrability of the MFC into MMSs. The presented tracking system makes it possible to target applications, such as minimally invasive eye surgery or drug delivery. The high spatial and magnetic resolutions allow the tracking of magnetic particles, down to 200- μm diameter, when placed close to the surface. The system could also be suitable for the localization of small objects for 2-D biomanipulation.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Technical note: development of a simulation framework, enabling the investigation of locally tuned single energy proton radiography(IOP Publishing, 07.02.2024) Lundberg, Måns; Meijers, Arturs; Souris, Kevin; Deffet, Sylvain; Weber, Damien C; Lomax, Antony; Knopf, AntjeRange uncertainties remain a limitation for the confined dose distribution that proton therapy can offer. The uncertainty stems from the ambiguity when translating CT Hounsfield Units (HU) into proton stopping powers. Proton Radiography (PR) can be used to verify the proton range. Specifically, PR can be used as a quality-control tool for CBCT-based synthetic CTs. An essential part of the work illustrating the potential of PR has been conducted using multi-layer ionization chamber (MLIC) detectors and mono-energetic PR. Due to the dimensions of commercially available MLICs, clinical adoption is cumbersome. Here, we present a simulation framework exploring locally-tuned single energy (LTSE) proton radiography and corresponding potential compact PR detector designs. Based on a planning CT data set, the presented framework models the water equivalent thickness. Subsequently, it analyses the proton energies required to pass through the geometry within a defined ROI. In the final step, an LTSE PR is simulated using the MCsquare Monte Carlo code. In an anatomical head phantom, we illustrate that LTSE PR allows for a significantly shorter longitudinal dimension of MLICs. We compared PR simulations for two exemplary 30 × 30 mm2proton fields passing the phantom at a 90° angle at an anterior and a posterior location in an iso-centric setup. The longitudinal distance over which all spots per field range out is significantly reduced for LTSE PR compared to mono-energetic PR. In addition, we illustrate the difference in shape of integral depth dose (IDD) when using constrained PR energies. Finally, we demonstrate the accordance of simulated and experimentally acquired IDDs for an LTSE PR acquisition. As the next steps, the framework will be used to investigate the sensitivity of LTSE PR to various sources of errors. Furthermore, we will use the framework to systematically explore the dimensions of an optimized MLIC design for daily clinical use.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Kidins220 regulates the development of B cells bearing the λ light chain(eLife Sciences Publications, 25.01.2024) Schaffer, Anna-Maria; Fiala, Gina Jasmin; Hils, Miriam; Natali, Eriberto; Babrak, Lmar; Herr, Laurenz Alexander; Romero-Mulero, Mari Carmen; Cabezas-Wallscheid, Nina; Rizzi, Marta; Miho, Enkelejda; Schamel, Wolfgang W.A.; Minguet, SusanaThe ratio between κ and λ light chain (LC)-expressing B cells varies considerably between species. We recently identified Kinase D-interacting substrate of 220 kDa (Kidins220) as an interaction partner of the BCR. In vivo ablation of Kidins220 in B cells resulted in a marked reduction of λLC-expressing B cells. Kidins220 knockout B cells fail to open and recombine the genes of the Igl locus, even in genetic scenarios where the Igk genes cannot be rearranged or where the κLC confers autoreactivity. Igk gene recombination and expression in Kidins220-deficient B cells is normal. Kidins220 regulates the development of λLC B cells by enhancing the survival of developing B cells and thereby extending the time-window in which the Igl locus opens and the genes are rearranged and transcribed. Further, our data suggest that Kidins220 guarantees optimal pre-BCR and BCR signaling to induce Igl locus opening and gene recombination during B cell development and receptor editing.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation The dengue-specific immune response and antibody identification with machine learning(Nature, 20.01.2024) Natali, Eriberto Noel; Horst, Alexander; Meier, Patrick; Greiff, Victor; Nuvolone, Mario; Babrak, Lmar Marie; Fink, Katja; Miho, EnkelejdaDengue virus poses a serious threat to global health and there is no specific therapeutic for it. Broadly neutralizing antibodies recognizing all serotypes may be an effective treatment. High-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) and bioinformatic analysis enable in-depth understanding of the B-cell immune response. Here, we investigate the dengue antibody response with these technologies and apply machine learning to identify rare and underrepresented broadly neutralizing antibody sequences. Dengue immunization elicited the following signatures on the antibody repertoire: (i) an increase of CDR3 and germline gene diversity; (ii) a change in the antibody repertoire architecture by eliciting power-law network distributions and CDR3 enrichment in polar amino acids; (iii) an increase in the expression of JNK/Fos transcription factors and ribosomal proteins. Furthermore, we demonstrate the applicability of computational methods and machine learning to AIRR-seq datasets for neutralizing antibody candidate sequence identification. Antibody expression and functional assays have validated the obtained results.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Author Correction. The dengue-specific immune response and antibody identification with machine learning(Nature, 20.01.2024) Natali, Eriberto Noel; Horst, Alexander; Meier, Patrick; Greiff, Victor; Nuvolone, Mario; Babrak, Lmar Marie; Fink, Katja; Miho, EnkelejdaDengue virus poses a serious threat to global health and there is no specific therapeutic for it. Broadly neutralizing antibodies recognizing all serotypes may be an effective treatment. High-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) and bioinformatic analysis enable in-depth understanding of the B-cell immune response. Here, we investigate the dengue antibody response with these technologies and apply machine learning to identify rare and underrepresented broadly neutralizing antibody sequences. Dengue immunization elicited the following signatures on the antibody repertoire: (i) an increase of CDR3 and germline gene diversity; (ii) a change in the antibody repertoire architecture by eliciting power-law network distributions and CDR3 enrichment in polar amino acids; (iii) an increase in the expression of JNK/Fos transcription factors and ribosomal proteins. Furthermore, we demonstrate the applicability of computational methods and machine learning to AIRR-seq datasets for neutralizing antibody candidate sequence identification. Antibody expression and functional assays have validated the obtained results.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation A review of the clinical introduction of 4D particle therapy research concepts(Elsevier, 01/2024) Knäusl, Barbara; Belotti, Gabriele; Bertholet, Jenny; Daartz, Juliane; Flampouri, Stella; Hoogeman, Mischa; Knopf, Antje; Lin, Haibo; Moerman, Astrid; Paganelli, Chiara; Rucinski, Antoni; Schulte, Reinhard; Shimizu, Shing; Stützer, Kristin; Zhang, Xiaodong; Zhang, Ye; Czerska, KatarzynaBackground and purpose: Many 4D particle therapy research concepts have been recently translated into clinics, however, remaining substantial differences depend on the indication and institute-related aspects. This work aims to summarise current state-of-the-art 4D particle therapy technology and outline a roadmap for future research and developments. Material and methods: This review focused on the clinical implementation of 4D approaches for imaging, treatment planning, delivery and evaluation based on the 2021 and 2022 4D Treatment Workshops for Particle Therapy as well as a review of the most recent surveys, guidelines and scientific papers dedicated to this topic. Results: Available technological capabilities for motion surveillance and compensation determined the course of each 4D particle treatment. 4D motion management, delivery techniques and strategies including imaging were diverse and depended on many factors. These included aspects of motion amplitude, tumour location, as well as accelerator technology driving the necessity of centre-specific dosimetric validation. Novel methodologies for X-ray based image processing and MRI for real-time tumour tracking and motion management were shown to have a large potential for online and offline adaptation schemes compensating for potential anatomical changes over the treatment course. The latest research developments were dominated by particle imaging, artificial intelligence methods and FLASH adding another level of complexity but also opportunities in the context of 4D treatments. Conclusion: This review showed that the rapid technological advances in radiation oncology together with the available intrafractional motion management and adaptive strategies paved the way towards clinical implementation.01A - Beitrag in wissenschaftlicher Zeitschrift