TY - JOUR A1 - Weich, Alexander A1 - Higuchi, Takahiro A1 - Bundschuh, Ralph A. A1 - Lapa, Constantin A1 - Serfling, Sebastian E. A1 - Rowe, Steven P. A1 - Pomper, Martin G. A1 - Herrmann, Ken A1 - Buck, Andreas K. A1 - Derlin, Thorsten A1 - Werner, Rudolf A. T1 - Training on reporting and data system (RADS) for somatostatin-receptor targeted molecular imaging can reduce the test anxiety of inexperienced readers JF - Molecular Imaging and Biology N2 - Purpose For somatostatin receptor (SSTR)-positron emission tomography/computed tomography (PET/CT), a standardized framework termed SSTR-reporting and data system (RADS) has been proposed. We aimed to elucidate the impact of a RADS-focused training on reader’s anxiety to report on SSTR-PET/CT, the motivational beliefs in learning such a system, whether it increases reader’s confidence, and its implementation in clinical routine. Procedures A 3-day training course focusing on SSTR-RADS was conducted. Self-report questionnaires were handed out prior to the course (Pre) and thereafter (Post). The impact of the training on the following categories was evaluated: (1) test anxiety to report on SSTR-PET/CT, (2) motivational beliefs, (3) increase in reader’s confidence, and (4) clinical implementation. To assess the effect size of the course, Cohen’s d was calculated (small, d = 0.20; large effect, d = 0.80). Results Of 22 participants, Pre and Post were returned by 21/22 (95.5%). In total, 14/21 (66.7%) were considered inexperienced (IR, < 1 year experience in reading SSTR-PET/CTs) and 7/21 (33.3%) as experienced readers (ER, > 1 year). Applying SSTR-RADS, a large decrease in anxiety to report on SSTR-PET/CT was noted for IR (d =  − 0.74, P = 0.02), but not for ER (d = 0.11, P = 0.78). For the other three categories motivational beliefs, reader’s confidence, and clinical implementation, agreement rates were already high prior to the training and persisted throughout the course (P ≥ 0.21). Conclusions A framework-focused reader training can reduce anxiety to report on SSTR-PET/CTs, in particular for inexperienced readers. This may allow for a more widespread adoption of this system, e.g., in multicenter trials for better intra- and interindividual comparison of scan results. KW - PET/CT KW - neuroendocrine tumor KW - PRRT KW - peptide receptor radionuclide therapy KW - reporting and data system KW - SSTR-RADS KW - RADS Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324645 VL - 24 IS - 4 ER - TY - JOUR A1 - Li, Donghai A1 - Shan, Hangyong A1 - Rupprecht, Christoph A1 - Knopf, Heiko A1 - Watanabe, Kenji A1 - Taniguchi, Takashi A1 - Qin, Ying A1 - Tongay, Sefaattin A1 - Nuß, Matthias A1 - Schröder, Sven A1 - Eilenberger, Falk A1 - Höfling, Sven A1 - Schneider, Christian A1 - Brixner, Tobias T1 - Hybridized exciton-photon-phonon states in a transition-metal-dichalcogenide van-der-Waals heterostructure microcavity JF - Physical Review Letters N2 - Excitons in atomically thin transition-metal dichalcogenides (TMDs) have been established as an attractive platform to explore polaritonic physics, owing to their enormous binding energies and giant oscillator strength. Basic spectral features of exciton polaritons in TMD microcavities, thus far, were conventionally explained via two-coupled-oscillator models. This ignores, however, the impact of phonons on the polariton energy structure. Here we establish and quantify the threefold coupling between excitons, cavity photons, and phonons. For this purpose, we employ energy-momentum-resolved photoluminescence and spatially resolved coherent two-dimensional spectroscopy to investigate the spectral properties of a high-quality-factor microcavity with an embedded WSe\(_2\) van-der-Waals heterostructure at room temperature. Our approach reveals a rich multi-branch structure which thus far has not been captured in previous experiments. Simulation of the data reveals hybridized exciton-photon-phonon states, providing new physical insight into the exciton polariton system based on layered TMDs. KW - strong coupling KW - laser spectroscopy KW - transition metal dichalcogenide KW - coherent multidimensional spectroscopy KW - exciton Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-351303 UR - https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.128.087401 SN - 1079-7114 ET - accepted version ER - TY - JOUR A1 - Römer, Daniela A1 - Aguilar, Gonzalo Pacheco A1 - Meyer, Annika A1 - Roces, Flavio T1 - Symbiont demand guides resource supply: leaf-cutting ants preferentially deliver their harvested fragments to undernourished fungus gardens JF - The Science of Nature N2 - Leaf-cutting ants are highly successful herbivores in the Neotropics. They forage large amounts of fresh plant material to nourish a symbiotic fungus that sustains the colony. It is unknown how workers organize the intra-nest distribution of resources, and whether they respond to increasing demands in some fungus gardens by adjusting the amount of delivered resources accordingly. In laboratory experiments, we analyzed the spatial distribution of collected leaf fragments among nest chambers in Acromyrmex ambiguus leaf-cutting ants, and how it changed when one of the fungus gardens experienced undernourishment. Plant fragments were evenly distributed among nest chambers when the fungal symbiont was well nourished. That pattern changed when one of the fungus gardens was undernourished and had a higher leaf demand, resulting in more leaf discs delivered to the undernourished fungus garden over at least 2 days after deprivation. Some ants bypassed nourished gardens to directly deliver their resource to the chamber with higher nutritional demand. We hypothesize that cues arising from that chamber might be used for orientation and/or that informed individuals, presumably stemming from the undernourished chamber, may preferentially orient to them. KW - insect-fungus symbiosis KW - nutrition KW - pheromone trail KW - local cues KW - decision-making KW - decentralized control Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325080 VL - 109 IS - 3 ER - TY - JOUR A1 - Tamihardja, Jörg A1 - Lawrenz, Ingulf A1 - Lutyj, Paul A1 - Weick, Stefan A1 - Guckenberger, Matthias A1 - Polat, Bülent A1 - Flentje, Michael T1 - Propensity score-matched analysis comparing dose-escalated intensity-modulated radiation therapy versus external beam radiation therapy plus high-dose-rate brachytherapy for localized prostate cancer JF - Strahlentherapie und Onkologie N2 - Purpose Dose-escalated external beam radiation therapy (EBRT) and EBRT + high-dose-rate brachytherapy (HDR-BT) boost are guideline-recommended treatment options for localized prostate cancer. The purpose of this study was to compare long-term outcome and toxicity of dose-escalated EBRT versus EBRT + HDR-BT boost. Methods From 2002 to 2019, 744 consecutive patients received either EBRT or EBRT + HDR-BT boost, of whom 516 patients were propensity score matched. Median follow-up was 95.3 months. Cone beam CT image-guided EBRT consisted of 33 fractions of intensity-modulated radiation therapy with simultaneous integrated boost up to 76.23 Gy (D\(_{Mean}\)). Combined treatment was delivered as 46 Gy (D\(_{Mean}\)) EBRT, followed by two fractions HDR-BT boost with 9 Gy (D\(_{90\%}\)). Propensity score matching was applied before analysis of the primary endpoint, estimated 10-year biochemical relapse-free survival (bRFS), and the secondary endpoints metastasis-free survival (MFS) and overall survival (OS). Prognostic parameters were analyzed by Cox proportional hazard modelling. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation used the Common Toxicity Criteria for Adverse Events (v5.0). Results The estimated 10-year bRFS was 82.0% vs. 76.4% (p = 0.075) for EBRT alone versus combined treatment, respectively. The estimated 10-year MFS was 82.9% vs. 87.0% (p = 0.195) and the 10-year OS was 65.7% vs. 68.9% (p = 0.303), respectively. Cumulative 5‑year late GU ≥ grade 2 toxicities were seen in 23.6% vs. 19.2% (p = 0.086) and 5‑year late GI ≥ grade 2 toxicities in 11.1% vs. 5.0% of the patients (p = 0.002); cumulative 5‑year late grade 3 GU toxicity occurred in 4.2% vs. 3.6% (p = 0.401) and GI toxicity in 1.0% vs. 0.3% (p = 0.249), respectively. Conclusion Both treatment groups showed excellent long-term outcomes with low rates of severe toxicity. KW - long-term outcome KW - dose escalation KW - high-dose-rate brachytherapy boost KW - propensity score matching KW - toxicity Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325055 VL - 198 IS - 8 ER - TY - JOUR A1 - Bohnert, Simone A1 - Trella, Stefanie A1 - Preiß, Ulrich A1 - Heinsen, Helmut A1 - Bohnert, Michael A1 - Zwirner, Johann A1 - Tremblay, Marie-Ève A1 - Monoranu, Camelia-Maria A1 - Ondruschka, Benjamin T1 - Density of TMEM119-positive microglial cells in postmortem cerebrospinal fluid as a surrogate marker for assessing complex neuropathological processes in the CNS JF - International Journal of Legal Medicine N2 - Routine coronal paraffin-sections through the dorsal frontal and parieto-occipital cortex of a total of sixty cases with divergent causes of death were immunohistochemically (IHC) stained with an antibody against TMEM119. Samples of cerebrospinal fluid (CSF) of the same cases were collected by suboccipital needle-puncture, subjected to centrifugation and processed as cytospin preparations stained with TMEM119. Both, cytospin preparations and sections were subjected to computer-assisted density measurements. The density of microglial TMEM119-positive cortical profiles correlated with that of cytospin results and with the density of TMEM119-positive microglial profiles in the medullary layer. There was no statistically significant correlation between the density of medullary TMEM119-positive profiles and the cytospin data. Cortical microglial cells were primarily encountered in supragranular layers I, II, and IIIa and in infragranular layers V and VI, the region of U-fibers and in circumscribed foci or spread in a diffuse manner and high density over the white matter. We have evidence that cortical microglia directly migrate into CSF without using the glympathic pathway. Microglia in the medullary layer shows a strong affinity to the adventitia of deep vessels in the myelin layer. Selected rapidly fatal cases including myocardial infarcts and drowning let us conclude that microglia in cortex and myelin layer can react rapidly and its reaction and migration is subject to pre-existing external and internal factors. Cytospin preparations proved to be a simple tool to analyze and assess complex changes in the CNS after rapid fatal damage. There is no statistically significant correlation between cytospin and postmortem interval. Therefore, the quantitative analyses of postmortem cytospins obviously reflect the neuropathology of the complete central nervous system. Cytospins provide forensic pathologists a rather simple and easy to perform method for the global assessment of CNS affliction. KW - cerebrospinal fluid KW - forensic neuropathology KW - forensic neurotraumatology KW - immunohistochemistry KW - immunocytochemistry KW - biomarker Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325009 VL - 136 IS - 6 ER - TY - JOUR A1 - Serfling, Sebastian E. A1 - Lapa, Constantin A1 - Dreher, Niklas A1 - Hartrampf, Philipp E. A1 - Rowe, Steven P. A1 - Higuchi, Takahiro A1 - Schirbel, Andreas A1 - Weich, Alexander A1 - Hahner, Stefanie A1 - Fassnacht, Martin A1 - Buck, Andreas K. A1 - Werner, Rudolf A. T1 - Impact of tumor burden on normal organ distribution in patients imaged with CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT JF - Molecular Imaging and Biology N2 - Background CXCR4-directed positron emission tomography/computed tomography (PET/CT) has been used as a diagnostic tool in patients with solid tumors. We aimed to determine a potential correlation between tumor burden and radiotracer accumulation in normal organs. Methods Ninety patients with histologically proven solid cancers underwent CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT. Volumes of interest (VOIs) were placed in normal organs (heart, liver, spleen, bone marrow, and kidneys) and tumor lesions. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were determined. For CXCR4-positive tumor burden, maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA, defined as SUV\(_{mean}\) x TV), were calculated. We used a Spearman's rank correlation coefficient (ρ) to derive correlative indices between normal organ uptake and tumor burden. Results Median SUV\(_{mean}\) in unaffected organs was 5.2 for the spleen (range, 2.44 – 10.55), 3.27 for the kidneys (range, 1.52 – 17.4), followed by bone marrow (1.76, range, 0.84 – 3.98), heart (1.66, range, 0.88 – 2.89), and liver (1.28, range, 0.73 – 2.45). No significant correlation between SUV\(_{max}\) in tumor lesions (ρ ≤ 0.189, P ≥ 0.07), TV (ρ ≥ -0.204, P ≥ 0.06) or FTA (ρ ≥ -0.142, P ≥ 0.18) with the investigated organs was found. Conclusions In patients with solid tumors imaged with [\(^{68}\)Ga]Ga-PentixaFor PET/CT, no relevant tumor sink effect was noted. This observation may be of relevance for therapies with radioactive and non-radioactive CXCR4-directed drugs, as with increasing tumor burden, the dose to normal organs may remain unchanged. KW - CXCR4 KW - C-X-C motif chemokine receptor 4 KW - PET KW - [68Ga]PentixaFor KW - [177Lu]/[90Y]PentixaTher KW - theranostics KW - endoradiotherapy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324622 VL - 24 IS - 4 ER - TY - JOUR A1 - Straub, Anton A1 - Vollmer, Andreas A1 - Lâm, Thiên-Trí A1 - Brands, Roman C. A1 - Stapf, Maximilian A1 - Scherf-Clavel, Oliver A1 - Bittrich, Max A1 - Fuchs, Andreas A1 - Kübler, Alexander C. A1 - Hartmann, Stefan T1 - Evaluation of advanced platelet-rich fibrin (PRF) as a bio-carrier for ampicillin/sulbactam JF - Clinical Oral Investigations N2 - Objectives Mechanisms of wound healing are often impaired in patients with osteonecrosis of the jaw (ONJ). According to the guidelines for the treatment of this disease, early surgical intervention is indicated. However, surgery often faces complications such as wound healing disorders. The application of platelet-rich fibrin (PRF) after necrosectomy between bone and mucosa may constitute a promising approach to improve surgical results. An aspect that was not investigated until now is that PRF acts as a “bio-carrier” for antibiotics previously applied intravenously. Materials and methods We investigated the antimicrobial properties of PRF in 24 patients presenting ONJ undergoing systemic antibiosis with ampicillin/sulbactam. We measured the concentration of ampicillin/sulbactam in plasma and PRF and performed agar diffusion tests. Ampicillin/sulbactam was applied intravenously to the patient 10 minutes for blood sampling for PRF. No further incorporation of patients’ blood or PRF product with antibiotic drugs was obtained. Four healthy patients served as controls. Results Our results revealed that PRF is highly enriched with ampicillin/sulbactam that is released to the environment. The antibiotic concentration in PRF was comparable to the plasma concentration of ampicillin/sulbactam. The inhibition zone (IZ) of PRF was comparable to the standard ampicillin/sulbactam discs used in sensitivity testing. Conclusions The results of our study demonstrated that PRF is a reliable bio-carrier for systemic applied antibiotics and exhibits a large antimicrobial effect. Clinical relevance We describe a clinically useful feature of PRF as a bio-carrier for antibiotics. Especially when applied to poorly perfused tissues and bone such as in ONJ, the local release of antibiotics can reduce wound healing disorders like infections. KW - osteonecrosis of the jaw KW - osteoradionecrosis KW - antiresorptive drug-related osteonecrosis of the jaw KW - ARONJ KW - oral microbiome KW - agar diffusion test Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324515 VL - 26 IS - 12 ER - TY - JOUR A1 - Stein, Jan-Philipp A1 - Cimander, Paula A1 - Appel, Markus T1 - Power-posing robots: the influence of a humanoid robot’s posture and size on its perceived dominance, competence, eeriness, and threat JF - International Journal of Social Robotics N2 - When interacting with sophisticated digital technologies, people often fall back on the same interaction scripts they apply to the communication with other humans—especially if the technology in question provides strong anthropomorphic cues (e.g., a human-like embodiment). Accordingly, research indicates that observers tend to interpret the body language of social robots in the same way as they would with another human being. Backed by initial evidence, we assumed that a humanoid robot will be considered as more dominant and competent, but also as more eerie and threatening once it strikes a so-called power pose. Moreover, we pursued the research question whether these effects might be accentuated by the robot’s body size. To this end, the current study presented 204 participants with pictures of the robot NAO in different poses (expansive vs. constrictive), while also manipulating its height (child-sized vs. adult-sized). Our results show that NAO’s posture indeed exerted strong effects on perceptions of dominance and competence. Conversely, participants’ threat and eeriness ratings remained statistically independent of the robot’s depicted body language. Further, we found that the machine’s size did not affect any of the measured interpersonal perceptions in a notable way. The study findings are discussed considering limitations and future research directions. KW - robot KW - humanoid KW - embodiment KW - body language KW - posture KW - nonverbal communication Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324502 SN - 1875-4791 VL - 14 IS - 6 ER - TY - JOUR A1 - Hohm, Anna A1 - Happel, Oliver A1 - Hurtienne, Jörn A1 - Grundgeiger, Tobias T1 - User experience in safety–critical domains: a survey on motivational orientations and psychological need satisfaction in acute care JF - Cognition, Technology & Work N2 - The relevance of user experience in safety–critical domains has been questioned and lacks empirical investigation. Based on previous studies examining user experience in consumer technology, we conducted an online survey on positive experiences with interactive technology in acute care. The participants of the study consisted of anaesthesiologists, nurses, and paramedics (N = 55) from three German cities. We report qualitative and quantitative data examining (1) the relevance and notion of user experience, (2) motivational orientations and psychological need satisfaction, and (3) potential correlates of hedonic, eudaimonic, and extrinsic motivations such as affect or meaning. Our findings reveal that eudaimonia was the most salient aspect in these experiences and that the relevance of psychological needs is differently ranked than in experiences with interactive consumer technology. We conclude that user experience should be considered in safety–critical domains, but research needs to develop further tools and methods to address the domain-specific requirements. KW - user experience KW - healthcare KW - eudaimonia KW - hedonia KW - need satisfaction KW - meaning Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324486 SN - 1435-5558 VL - 24 IS - 2 ER - TY - JOUR A1 - Lux, Thomas J. A1 - Banck, Michael A1 - Saßmannshausen, Zita A1 - Troya, Joel A1 - Krenzer, Adrian A1 - Fitting, Daniel A1 - Sudarevic, Boban A1 - Zoller, Wolfram G. A1 - Puppe, Frank A1 - Meining, Alexander A1 - Hann, Alexander T1 - Pilot study of a new freely available computer-aided polyp detection system in clinical practice JF - International Journal of Colorectal Disease N2 - Purpose Computer-aided polyp detection (CADe) systems for colonoscopy are already presented to increase adenoma detection rate (ADR) in randomized clinical trials. Those commercially available closed systems often do not allow for data collection and algorithm optimization, for example regarding the usage of different endoscopy processors. Here, we present the first clinical experiences of a, for research purposes publicly available, CADe system. Methods We developed an end-to-end data acquisition and polyp detection system named EndoMind. Examiners of four centers utilizing four different endoscopy processors used EndoMind during their clinical routine. Detected polyps, ADR, time to first detection of a polyp (TFD), and system usability were evaluated (NCT05006092). Results During 41 colonoscopies, EndoMind detected 29 of 29 adenomas in 66 of 66 polyps resulting in an ADR of 41.5%. Median TFD was 130 ms (95%-CI, 80–200 ms) while maintaining a median false positive rate of 2.2% (95%-CI, 1.7–2.8%). The four participating centers rated the system using the System Usability Scale with a median of 96.3 (95%-CI, 70–100). Conclusion EndoMind’s ability to acquire data, detect polyps in real-time, and high usability score indicate substantial practical value for research and clinical practice. Still, clinical benefit, measured by ADR, has to be determined in a prospective randomized controlled trial. KW - colonoscopy KW - polyp KW - artificial intelligence KW - deep learning KW - CADe Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324459 VL - 37 IS - 6 ER - TY - JOUR A1 - Kanzow, Christian T1 - Y. Cui, J.-S. Pang: “Modern Nonconvex Nondifferentiable Optimization” JF - Jahresbericht der Deutschen Mathematiker-Vereinigung N2 - No abstract available. KW - Kanzow, C. Y. Cui, J.-S. Pang: “Modern Nonconvex Nondifferentiable Optimization” KW - Rezension Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324346 SN - 0012-0456 VL - 124 IS - 2 ER - TY - JOUR A1 - Appell, Jürgen A1 - Brito, Belén López A1 - Reinwand, Simon T1 - Counterexamples on compositions JF - Mathematische Semesterberichte N2 - We give a collection of 16 examples which show that compositions \(g\) \(\circ\) \(f\) of well-behaved functions \(f\) and \(g\) can be badly behaved. Remarkably, in 10 of the 16 examples it suffices to take as outer function \(g\) simply a power-type or characteristic function. Such a collection of examples may serve as a source of exercises for a calculus course. KW - composition of functions KW - examples and counterexamples Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324306 SN - 0720-728X VL - 70 IS - 1 ER - TY - JOUR A1 - Martin, Tamara A1 - Rommel, Kathrin A1 - Thomas, Carina A1 - Eymann, Jutta A1 - Kretschmer, Tanita A1 - Berner, Reinhard A1 - Lee-Kirsch, Min Ae A1 - Hebestreit, Helge T1 - Seltene Erkrankungen in den Daten sichtbar machen – Kodierung JF - Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz N2 - Seltene Erkrankungen (SE) werden durch die im deutschen Gesundheitssystem verwendete Diagnosenklassifikation ICD-10-GM (International Statistical Classification of Diseases and Related Health problems, 10th Revision, German Modification) nur zu einem kleinen Teil eindeutig erfasst. Daher sind Aussagen zur Häufigkeit von SE sowie zum speziellen Versorgungs- und Finanzierungsbedarf nicht möglich, was zu einer lückenhaften Datenlage als Entscheidungsgrundlage für Krankenkassen, Leistungserbringer und Gesundheitspolitik führt. Das Fehlen exakter Informationen behindert auch die wissenschaftliche Arbeit. Daher wird deutschlandweit ab 2023 die Verwendung der Alpha-ID-SE-Datei und der ORPHAcodes für die spezifische Erfassung von SE bei stationären Fällen verpflichtend. Die Alpha-ID-SE-Datei verknüpft die ICD-10-GM-Kodes mit den international anerkannten ORPHAcodes für die Diagnose von SE. Kommerzielle Anbieter stellen zunehmend die benötigten IT-Tools zur Kodierung von SE zur Verfügung. An mehreren Universitätskliniken mit Zentren für SE wurden Lösungen etabliert, die eine vollständige Kodierung gewährleisten sollen. Hierzu gehören finanzielle Anreize für die kodierenden Bereiche, konkrete Nachfragen nach dem Vorliegen einer SE beim Kodiervorgang und eine semiautomatische Kodierung bei Patient*innen, die schon einmal mit einer SE an der Einrichtung betreut worden waren. Eine Kombination der verschiedenen Ansätze verspricht die höchste Wahrscheinlichkeit einer vollständigen Kodierung. Für ein umfängliches Bild der SE im Gesundheitssystem und um dem speziellen Versorgungs- und Finanzierungsbedarf besser Rechnung tragen zu können, wäre auch im ambulanten Bereich eine möglichst spezifische und eindeutige Kodierung wünschenswert. Für komplexe SE und bisher undiagnostizierte Patient*innen wird zusätzlich eine strukturierte Erfassung des Phänotyps benötigt. N2 - The ICD-10-GM coding system used in the German healthcare system only captures a minority of rare disease diagnoses. Therefore, information on the incidence and prevalence of rare diseases as well as necessary (financial) resources for the expert care required for evidence-based decisions by health insurers, care providers, and politicians are lacking. Furthermore, the missing information complicates and sometimes even precludes the generation of scientific knowledge on rare diseases. Therefore, starting in 2023, all in-patient cases in Germany with a rare disease diagnosis must be coded by an ORPHAcode using the Alpha-ID-SE file. The file Alpha-ID-SE links the ICD-10-GM codes to the internationally established ORPHAcodes for rare diseases. Commercially available software tools progressively support the coding of rare diseases. In several centers for rare diseases linked to university hospitals, IT tools and procedures were established to realize a complete coding of rare diseases. These include financial incentives for the institutions providing rare disease codes, systematic queries asking for rare disease codes during the coding process, and a semi-automated coding process for all patients with a rare disease previously seen at the institution. A combination of the different approaches probably results in the most complete coding. To get the complete picture of rare disease epidemiology and care requirements, a specific and unique coding of out-patient cases is also desirable. Furthermore, a structured reporting of phenotype is required, especially for complex rare diseases and for yet undiagnosed cases. KW - Seltene Erkrankung KW - ORPHAcode KW - Alpha-ID-SE KW - Human Phenotype Ontology KW - Diagnose KW - rare diseases KW - ORPHAcode KW - Alpha-ID-SE KW - human phenotype ontology KW - diagnosis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324275 VL - 65 IS - 11 ER - TY - JOUR A1 - Dirks, Johannes A1 - Haase, Gabriele A1 - Cantaert, Tineke A1 - Frey, Lea A1 - Klaas, Moritz A1 - Rickert, Christian H. A1 - Girschick, Hermann A1 - Meffre, Eric A1 - Morbach, Henner T1 - A novel AICDA splice-site mutation in two siblings with HIGM2 permits somatic hypermutation but abrogates mutational targeting JF - Journal of Clinical Immunology N2 - Hyper-IgM syndrome type 2 (HIGM2) is a B cell intrinsic primary immunodeficiency caused by mutations in AICDA encoding activation-induced cytidine deaminase (AID) which impair immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM). Whereas autosomal-recessive AID-deficiency (AR-AID) affects both CSR and SHM, the autosomal-dominant form (AD-AID) due to C-terminal heterozygous variants completely abolishes CSR but only partially affects SHM. AR-AID patients display enhanced germinal center (GC) reactions and autoimmune manifestations, which are not present in AD-AID, suggesting that SHM but not CSR regulates GC reactions and peripheral B cell tolerance. Herein, we describe two siblings with HIGM2 due to a novel homozygous AICDA mutation (c.428-1G > T) which disrupts the splice acceptor site of exon 4 and results in the sole expression of a truncated AID variant that lacks 10 highly conserved amino acids encoded by exon 4 (AID-ΔE4a). AID-ΔE4a patients suffered from defective CSR and enhanced GC reactions and were therefore indistinguishable from other AR-AID patients. However, the AID-ΔE4a variant only partially affected SHM as observed in AD-AID patients. In addition, AID-ΔE4a but not AD-AID patients revealed impaired targeting of mutational hotspot motives and distorted mutational patterns. Hence, qualitative defects in AID function and altered SHM rather than global decreased SHM activity may account for the disease phenotype in these patients. KW - hyper-IgM syndrome type 2 (HIGM2) KW - AICDA KW - AID-ΔE4a KW - AD-AID KW - mutational targeting KW - somatic hypermutation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324253 VL - 42 IS - 4 ER - TY - JOUR A1 - Korte, Arthur T1 - Der Zusammenhang zwischen Genom und Phänotyp JF - BIOspektrum N2 - Understanding the causal relationship between genotype and phenotype is a major objective in biology. Genome-wide association studies (GWAS) correlate genetic polymorphisms with trait variation and have already identified causative variants for various traits in many different organisms, from humans to plants. Importantly, many adaptive traits, like the regulation of flowering time in plants, are not regulated by distinct genetic effects, but by more sophisticated gene regulatory networks. KW - Genom KW - Phänotyp KW - Genomweite Assoziationstudie (GWAS) Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324231 SN - 0947-0867 VL - 28 IS - 3 ER - TY - JOUR A1 - Tamburello, Mariangela A1 - Altieri, Barbara A1 - Sbiera, Iuliu A1 - Sigala, Sandra A1 - Berruti, Alfredo A1 - Fassnacht, Martin A1 - Sbiera, Silviu T1 - FGF/FGFR signaling in adrenocortical development and tumorigenesis: novel potential therapeutic targets in adrenocortical carcinoma JF - Endocrine N2 - FGF/FGFR signaling regulates embryogenesis, angiogenesis, tissue homeostasis and wound repair by modulating proliferation, differentiation, survival, migration and metabolism of target cells. Understandably, compelling evidence for deregulated FGF signaling in the development and progression of different types of tumors continue to emerge and FGFR inhibitors arise as potential targeted therapeutic agents, particularly in tumors harboring aberrant FGFR signaling. There is first evidence of a dual role of the FGF/FGFR system in both organogenesis and tumorigenesis, of which this review aims to provide an overview. FGF-1 and FGF-2 are expressed in the adrenal cortex and are the most powerful mitogens for adrenocortical cells. Physiologically, they are involved in development and maintenance of the adrenal gland and bind to a family of four tyrosine kinase receptors, among which FGFR1 and FGFR4 are the most strongly expressed in the adrenal cortex. The repeatedly proven overexpression of these two FGFRs also in adrenocortical cancer is thus likely a sign of their participation in proliferation and vascularization, though the exact downstream mechanisms are not yet elucidated. Thus, FGFRs potentially offer novel therapeutic targets also for adrenocortical carcinoma, a type of cancer resistant to conventional antimitotic agents. KW - FGF-pathway KW - FGFR KW - FGFR-inhibitors KW - adrenocortical development KW - adrenocortical tumors Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324420 VL - 77 IS - 3 ER - TY - JOUR A1 - Kanzow, Christian A1 - Mehlitz, Patrick T1 - Convergence properties of monotone and nonmonotone proximal gradient methods revisited JF - Journal of Optimization Theory and Applications N2 - Composite optimization problems, where the sum of a smooth and a merely lower semicontinuous function has to be minimized, are often tackled numerically by means of proximal gradient methods as soon as the lower semicontinuous part of the objective function is of simple enough structure. The available convergence theory associated with these methods (mostly) requires the derivative of the smooth part of the objective function to be (globally) Lipschitz continuous, and this might be a restrictive assumption in some practically relevant scenarios. In this paper, we readdress this classical topic and provide convergence results for the classical (monotone) proximal gradient method and one of its nonmonotone extensions which are applicable in the absence of (strong) Lipschitz assumptions. This is possible since, for the price of forgoing convergence rates, we omit the use of descent-type lemmas in our analysis. KW - non-Lipschitz optimization KW - nonsmooth optimization KW - proximal gradient method Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324351 SN - 0022-3239 VL - 195 IS - 2 ER - TY - JOUR A1 - Fortmann, Mats Ingmar A1 - Dirks, Johannes A1 - Goedicke-Fritz, Sybelle A1 - Liese, Johannes A1 - Zemlin, Michael A1 - Morbach, Henner A1 - Härtel, Christoph T1 - Immunization of preterm infants: current evidence and future strategies to individualized approaches JF - Seminars in Immunopathology N2 - Preterm infants are at particularly high risk for infectious diseases. As this vulnerability extends beyond the neonatal period into childhood and adolescence, preterm infants benefit greatly from infection-preventive measures such as immunizations. However, there is an ongoing discussion about vaccine safety and efficacy due to preterm infants’ distinct immunological features. A significant proportion of infants remains un- or under-immunized when discharged from primary hospital stay. Educating health care professionals and parents, promoting maternal immunization and evaluating the potential of new vaccination tools are important means to reduce the overall burden from infectious diseases in preterm infants. In this narrative review, we summarize the current knowledge about vaccinations in premature infants. We discuss the specificities of early life immunity and memory function, including the role of polyreactive B cells, restricted B cell receptor diversity and heterologous immunity mediated by a cross-reactive T cell repertoire. Recently, mechanistic studies indicated that tissue-resident memory (Trm) cell populations including T cells, B cells and macrophages are already established in the fetus. Their role in human early life immunity, however, is not yet understood. Tissue-resident memory T cells, for example, are diminished in airway tissues in neonates as compared to older children or adults. Hence, the ability to make specific recall responses after secondary infectious stimulus is hampered, a phenomenon that is transcriptionally regulated by enhanced expression of T-bet. Furthermore, the microbiome establishment is a dominant factor to shape resident immunity at mucosal surfaces, but it is often disturbed in the context of preterm birth. The proposed function of Trm T cells to remember benign interactions with the microbiome might therefore be reduced which would contribute to an increased risk for sustained inflammation. An improved understanding of Trm interactions may determine novel targets of vaccination, e.g., modulation of T-bet responses and facilitate more individualized approaches to protect preterm babies in the future. KW - preterm infants KW - immunization KW - vaccination KW - safety KW - mechanisms KW - resident memory T cells Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324261 VL - 44 IS - 6 ER - TY - JOUR A1 - Waltmann, Maria A1 - Schlagenhauf, Florian A1 - Deserno, Lorenz T1 - Sufficient reliability of the behavioral and computational readouts of a probabilistic reversal learning task JF - Behavior Research Methods N2 - Task-based measures that capture neurocognitive processes can help bridge the gap between brain and behavior. To transfer tasks to clinical application, reliability is a crucial benchmark because it imposes an upper bound to potential correlations with other variables (e.g., symptom or brain data). However, the reliability of many task readouts is low. In this study, we scrutinized the retest reliability of a probabilistic reversal learning task (PRLT) that is frequently used to characterize cognitive flexibility in psychiatric populations. We analyzed data from N = 40 healthy subjects, who completed the PRLT twice. We focused on how individual metrics are derived, i.e., whether data were partially pooled across participants and whether priors were used to inform estimates. We compared the reliability of the resulting indices across sessions, as well as the internal consistency of a selection of indices. We found good to excellent reliability for behavioral indices as derived from mixed-effects models that included data from both sessions. The internal consistency was good to excellent. For indices derived from computational modeling, we found excellent reliability when using hierarchical estimation with empirical priors and including data from both sessions. Our results indicate that the PRLT is well equipped to measure individual differences in cognitive flexibility in reinforcement learning. However, this depends heavily on hierarchical modeling of the longitudinal data (whether sessions are modeled separately or jointly), on estimation methods, and on the combination of parameters included in computational models. We discuss implications for the applicability of PRLT indices in psychiatric research and as diagnostic tools. KW - probabilistic reversal learning KW - reliability KW - reinforcement learning KW - computational modeling KW - hierarchical modeling Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324246 SN - 1554-3528 VL - 54 IS - 6 ER - TY - JOUR A1 - Herm, Lukas-Valentin A1 - Steinbach, Theresa A1 - Wanner, Jonas A1 - Janiesch, Christian T1 - A nascent design theory for explainable intelligent systems JF - Electronic Markets N2 - Due to computational advances in the past decades, so-called intelligent systems can learn from increasingly complex data, analyze situations, and support users in their decision-making to address them. However, in practice, the complexity of these intelligent systems renders the user hardly able to comprehend the inherent decision logic of the underlying machine learning model. As a result, the adoption of this technology, especially for high-stake scenarios, is hampered. In this context, explainable artificial intelligence offers numerous starting points for making the inherent logic explainable to people. While research manifests the necessity for incorporating explainable artificial intelligence into intelligent systems, there is still a lack of knowledge about how to socio-technically design these systems to address acceptance barriers among different user groups. In response, we have derived and evaluated a nascent design theory for explainable intelligent systems based on a structured literature review, two qualitative expert studies, a real-world use case application, and quantitative research. Our design theory includes design requirements, design principles, and design features covering the topics of global explainability, local explainability, personalized interface design, as well as psychological/emotional factors. KW - artificial intelligence KW - explainable artificial intelligence KW - XAI KW - design science research KW - design theory KW - intelligent systems Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-323809 SN - 1019-6781 VL - 32 IS - 4 ER -