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Publikation Adaptive immune receptor repertoire (AIRR) community guide to TR and IG gene annotation(Springer, 28.05.2022) Babrak, Lmar; Marquez, Susanna; Busse, Christian; Lees, William; Miho, Enkelejda; Ohlin, Mats; Rosenfeld, Aaron; Stervbo, Ulrik; Watson, Corey; Schramm, Chaim; Langerak, Anton W.High-throughput sequencing of adaptive immune receptor repertoires (AIRR, i.e., IG and TR) has revolutionized the ability to carry out large-scale experiments to study the adaptive immune response. Since the method was first introduced in 2009, AIRR sequencing (AIRR-Seq) has been applied to survey the immune state of individuals, identify antigen-specific or immune-state-associated signatures of immune responses, study the development of the antibody immune response, and guide the development of vaccines and antibody therapies. Recent advancements in the technology include sequencing at the single-cell level and in parallel with gene expression, which allows the introduction of multi-omics approaches to understand in detail the adaptive immune response. Analyzing AIRR-seq data can prove challenging even with high-quality sequencing, in part due to the many steps involved and the need to parameterize each step. In this chapter, we outline key factors to consider when preprocessing raw AIRR-Seq data and annotating the genetic origins of the rearranged receptors. We also highlight a number of common difficulties with common AIRR-seq data processing and provide strategies to address them.04A - Beitrag SammelbandPublikation Probabilistic maps for deep brain stimulation – Impact of methodological differences(Elsevier, 2022) Nordin, Teresa; Vogel, Dorian; Osterlund, Erik; Johansson, Johannes; Fytagoridis, Anders; Blomstedt, Patric; Hemm-Ode, Simone; Wardell, KarinBackground Group analysis of patients with deep brain stimulation (DBS) has the potential to help understand and optimize the treatment of patients with movement disorders. Probabilistic stimulation maps (PSM) are commonly used to analyze the correlation between tissue stimulation and symptomatic effect but are applied with different methodological variations. Objective To compute a group-specific MRI template and PSMs for investigating the impact of PSM model parameters. Methods Improvement and occurrence of dizziness in 68 essential tremor patients implanted in caudal zona incerta were analyzed. The input data includes the best parameters for each electrode contact (screening), and the clinically used settings. Patient-specific electric field simulations (n = 488) were computed for all DBS settings. The electric fields were transformed to a group-specific MRI template for analysis and visualization. The different comparisons were based on PSMs representing occurrence (N-map), mean improvement (M-map), weighted mean improvement (wM-map), and voxel-wise t-statistics (p-map). These maps were used to investigate the impact from input data (clinical/screening settings), clustering methods, sampling resolution, and weighting function. Results Screening or clinical settings showed the largest impacts on the PSMs. The average differences of wM-maps were 12.4 and 18.2% points for the left and right sides respectively. Extracting clusters based on wM-map or p-map showed notable variation in volumes, while positioning was similar. The impact on the PSMs was small from weighting functions, except for a clear shift in the positioning of the wM-map clusters. Conclusion The distribution of the input data and the clustering method are most important to consider when creating PSMs for studying the relationship between anatomy and DBS outcome.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Comparison of plasma ionization- and secondary electrospray ionization- high-resolution mass spectrometry for real-time breath analysis(Schweizerische Chemische Gesellschaft, 23.02.2022) Zeng, Jiafa; Christen, Alexandra; Dev Singh, Kapil; Frey, Urs; Sinues, PabloReal-time breath analysis by high-resolution mass spectrometry (HRMS) is a promising method to noninvasively retrieve relevant biochemical information. In this work, we conducted a head-to-head comparison of two ionization techniques: Secondary electrospray ionization (SESI) and plasma ionization (PI), for the analysis of exhaled breath. Two commercially available SESI and PI sources were coupled to the same HRMS device to analyze breath of two healthy individuals in a longitudinal study. We analyzed 58 breath specimens in both platforms, leading to 2,209 and 2,296 features detected by SESI-HRMS and by PI-HRMS, respectively. 60% of all the mass spectral features were detected in both platforms. However, remarkable differences were noted in terms of the signal-to-noise ratio (S/N), whereby the median (interquartile range, IQR) S/N ratio for SESI-HRMS was 115 (IQR = 408), whereas for PI-HRMS it was 5 (IQR = 5). Differences in the mass spectral profiles for the same samples make the inter-comparability of both techniques problematic. Overall, we conclude that both techniques are excellent for real-time breath analysis because of the very rich mass spectral fingerprints. However, further work is needed to fully understand the exact metabolic insights one can gather using each of these platforms.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Deep brain stimulation: emerging tools for simulation, data analysis, and visualization(Frontiers, 11.04.2022) Wårdell, Karin; Nordin, Teresa; Zsigmond, Peter; Westin, Carl-Fredrik; Hariz, Marwan; Vogel, Dorian; Hemm-Ode, SimoneDeep brain stimulation (DBS) is a well-established neurosurgical procedure for movement disorders that is also being explored for treatment-resistant psychiatric conditions. This review highlights important consideration for DBS simulation and data analysis. The literature on DBS has expanded considerably in recent years, and this article aims to identify important trends in the field. During DBS planning, surgery, and follow up sessions, several large data sets are created for each patient, and it becomes clear that any group analysis of such data is a big data analysis problem and has to be handled with care. The aim of this review is to provide an update and overview from a neuroengineering perspective of the current DBS techniques, technical aids, and emerging tools with the focus on patient-specific electric field (EF) simulations, group analysis, and visualization in the DBS domain. Examples are given from the state-of-the-art literature including our own research. This work reviews different analysis methods for EF simulations, tractography, deep brain anatomical templates, and group analysis. Our analysis highlights that group analysis in DBS is a complex multi-level problem and selected parameters will highly influence the result. DBS analysis can only provide clinically relevant information if the EF simulations, tractography results, and derived brain atlases are based on as much patient-specific data as possible. A trend in DBS research is creation of more advanced and intuitive visualization of the complex analysis results suitable for the clinical environment.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Heading direction is significantly biased by preceding whole-body roll-orientation while lying(Frontiers, 18.04.2022) Tarnutzer, Alexander Andrea; Duarte da Costa, Vasco; Baumann, Denise; Hemm-Ode, SimoneBackground: After a prolonged static whole-body roll-tilt, a significant bias of the internal estimates of the direction of gravity has been observed when assessing the subjective visual vertical. Objective: We hypothesized that this post-tilt bias represents a more general phenomenon, broadly affecting spatial orientation and navigation. Specifically, we predicted that after the prolonged roll-tilt to either side perceived straight-ahead would also be biased. Methods: Twenty-five healthy participants were asked to rest in three different lying positions (supine, right-ear-down, and left-ear-down) for 5 min (“adaptation period”) prior to walking straight-ahead blindfolded for 2 min. Walking was recorded with the inertial measurement unit sensors attached to different body locations and with sensor shoe insoles. The raw data was segmented with a gait–event detection method. The Heading direction was determined and linear mixed-effects models were used for statistical analyses. Results: A significant bias in heading into the direction of the previous roll-tilt position was observed in the post-adaptation trials. This bias was identified in both measurement systems and decreased again over the 2-min walking period. Conclusions: The bias observed further confirms the influence of prior knowledge on spatial orientation and navigation. Specifically, it underlines the broad impact of a shifting internal estimate of direction of gravity over a range of distinct paradigms, illustrating similar decay time constants. In the broader context, the observed bias in perceived straight-ahead emphasizes that getting up in the morning after a good night's sleep is a vulnerable period, with an increased risk of falls and fall-related injuries due to non-availability of optimally tuned internal estimates of the direction of gravity and the direction of straight-ahead.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation ICU Cockpit: a platform for collecting multimodal waveform data, AI-based computational disease modeling and real-time decision support in the intensive care unit(Oxford University Press, 13.05.2022) Boss, Jens Michael; Narula, Gagan; Straessle, Christian; Willms, Jan; Suter, Susanne; Buehler, Christof; Muroi, Carl; Mack, David Jule; Seric, Marko; Baumann, Daniel; Keller, Emanuela; Azzati, Jan; Brodbeck, Dominique; Lüthy, RahelICU Cockpit: a secure, fast, and scalable platform for collecting multimodal waveform data, online and historical data visualization, and online validation of algorithms in the intensive care unit. We present a network of software services that continuously stream waveforms from ICU beds to databases and a web-based user interface. Machine learning algorithms process the data streams and send outputs to the user interface. The architecture and capabilities of the platform are described. Since 2016, the platform has processed over 89 billion data points (N = 979 patients) from 200 signals (0.5–500 Hz) and laboratory analyses (once a day). We present an infrastructure-based framework for deploying and validating algorithms for critical care. The ICU Cockpit is a Big Data platform for critical care medicine, especially for multimodal waveform data. Uniquely, it allows algorithms to seamlessly integrate into the live data stream to produce clinical decision support and predictions in clinical practice.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Automatic landmark identification for surgical 3d-navigation – A proposed method for marker-free dental surgical navigation systems(De Gruyter, 04.07.2022) Bischofberger, Micha; Schkommodau, Erik; Böhringer, StephanThis paper proposes a conceptual method to calculate the pose of a stereo-vision camera relative to an artificial mandible without additional markers. The general method for marker-free navigation has four steps: 1) parallel image acquisition by a stereo-vision camera, 2) automatic identification of 2d point pairs (landmark pairs) in a left and a right image, 3) calculation of related 3d points in the joint camera coordinate system and 4) matching of 3d points generated to a preoperative 3d model (i.e., CT data based). To identify and compare landmarks in the acquired stereo images, well-known algorithms for landmark detection, description and matching were compared within the developed approach. Finally, the BRISK algorithm (Leutenegger S, Chli M, Siegwart RY. BRISK: Binary Robust invariant scalable keypoints. Proceedings of the IEEE International Conference on Computer Vision; 2011: 2548–2555) was used. The proposed method was implemented in MATLAB and validated with one artificial mandible. The accuracy evaluation of the camera positions calculated resulted in an average deviation error of 1.45 mm ± 0.76 mm to the real camera displacement. This value was calculated using only stereo images with over 100 reconstructed landmark pairs each. This provides the basis for marker-free navigation.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Characterization of a cotton-wool like composite bone graft material(Springer, 18.07.2022) Rohr, Nadja; Brunner, Claudia; Bellon, Benjamin; Fischer, Jens; de Wild, MichaelBone graft materials are applied in patients to augment bone defects and enable the insertion of an implant in its ideal position. However, the currently available augmentation materials do not meet the requirements of being completely resorbed and replaced by new bone within 3 to 6 months. A novel electrospun cotton-wool like material (Bonewool, Zurich Biomaterials LLC, Zurich, Switzerland) consisting of biodegradable poly(lactic-co-glycolic) acid (PLGA) fibers with incorporated amorphous ß-tricalcium phosphate (ß-TCP) nanoparticles has been compared to a frequently used bovine derived hydroxyapatite (Bio-Oss, Geistlich Pharma, Wolhusen, Switzerland) in vitro. The material composition was determined and the degradation behavior (calcium release and pH in different solutions) as well as bioactivity has been measured. Degradation behavior of PLGA/ß-TCP was generally more progressive than for Bio-Oss, indicating that this material is potentially completely resorbable.01A - Beitrag in wissenschaftlicher Zeitschrift