@article{MoratinThoeleLangetal.2023, author = {Moratin, Helena and Th{\"o}le, Anna and Lang, Josephine and Ehret Kasemo, Totta and St{\"o}th, Manuel and Hagen, Rudolf and Scherzad, Agmal and Hackenberg, Stephan}, title = {Ag- but not ZnO-nanoparticles disturb the airway epithelial barrier at subtoxic concentrations}, series = {Pharmaceutics}, volume = {15}, journal = {Pharmaceutics}, number = {10}, issn = {1999-4923}, doi = {10.3390/pharmaceutics15102506}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357403}, year = {2023}, abstract = {Inhalation is considered to be the most relevant source of human exposure to nanoparticles (NPs); however, only a few investigations have addressed the influence of exposing the respiratory mucosal barrier to subcytotoxic doses. In the nasal respiratory epithelium, cells of the mucosa represent one of the first contact points of the human organism with airborne NPs. Disruption of the epithelial barrier by harmful materials can lead to inflammation in addition to potential intrinsic toxicity of the particles. The aim of this study was to investigate whether subtoxic concentrations of zinc oxide (ZnO)- and silver (Ag)-NPs have an influence on upper airway barrier integrity. Nasal epithelial cells from 17 donors were cultured at the air-liquid interface and exposed to ZnO- and Ag-NPs. Barrier function, quantified by transepithelial electrical resistance (TEER), decreased after treatment with 10 µg/mL Ag-NPs, but FITC-dextran permeability remained stable and no change in mRNA levels of tight junction proteins and E-cadherin was detected by real-time quantitative PCR (RT-qPCR). The results indicate that subtoxic concentrations of Ag-NPs may already induce damage of the upper airway epithelial barrier in vitro. The lack of similar disruption by ZnO-NPs of similar size suggests a specific effect by Ag-NPs.}, language = {en} } @article{EngertDollVonaetal.2023, author = {Engert, Jonas and Doll, Julia and Vona, Barbara and Ehret Kasemo, Totta and Spahn, Bjoern and Hagen, Rudolf and Rak, Kristen and Voelker, Johannes}, title = {mRNA abundance of neurogenic factors correlates with hearing capacity in auditory brainstem nuclei of the rat}, series = {Life}, volume = {13}, journal = {Life}, number = {9}, issn = {2075-1729}, doi = {10.3390/life13091858}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357392}, year = {2023}, abstract = {Neural stem cells (NSCs) have previously been described up to the adult stage in the rat cochlear nucleus (CN). A decreasing neurogenic potential was observed with critical changes around hearing onset. A better understanding of molecular factors affecting NSCs and neurogenesis is of interest as they represent potential targets to treat the cause of neurologically based hearing disorders. The role of genes affecting NSC development and neurogenesis in CN over time on hearing capacity has remained unclear. This study investigated the mRNA abundance of genes influencing NSCs and neurogenesis in rats' CN over time. The CN of rats on postnatal days 6, 12, and 24 were examined. Real-time quantitative polymerase chain reaction arrays were used to compare mRNA levels of 84 genes relevant to NSCs and neurogenesis. Age- and hearing-specific patterns of changes in mRNA abundance of neurogenically relevant genes were detected in the rat CN. Additionally, crucial neurogenic factors with significant and relevant influence on neurogenesis were identified. The results of this work should contribute to a better understanding of the molecular mechanisms underlying the neurogenesis of the auditory pathway.}, language = {en} } @article{BasslerKnoblichGerhardHartmannetal.2023, author = {Bassler, Miriam C. and Knoblich, Mona and Gerhard-Hartmann, Elena and Mukherjee, Ashutosh and Youssef, Almoatazbellah and Hagen, Rudolf and Haug, Lukas and Goncalves, Miguel and Scherzad, Agmal and St{\"o}th, Manuel and Ostertag, Edwin and Steinke, Maria and Brecht, Marc and Hackenberg, Stephan and Meyer, Till Jasper}, title = {Differentiation of salivary gland and salivary gland tumor tissue via Raman imaging combined with multivariate data analysis}, series = {Diagnostics}, volume = {14}, journal = {Diagnostics}, number = {1}, issn = {2075-4418}, doi = {10.3390/diagnostics14010092}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355558}, year = {2023}, abstract = {Salivary gland tumors (SGTs) are a relevant, highly diverse subgroup of head and neck tumors whose entity determination can be difficult. Confocal Raman imaging in combination with multivariate data analysis may possibly support their correct classification. For the analysis of the translational potential of Raman imaging in SGT determination, a multi-stage evaluation process is necessary. By measuring a sample set of Warthin tumor, pleomorphic adenoma and non-tumor salivary gland tissue, Raman data were obtained and a thorough Raman band analysis was performed. This evaluation revealed highly overlapping Raman patterns with only minor spectral differences. Consequently, a principal component analysis (PCA) was calculated and further combined with a discriminant analysis (DA) to enable the best possible distinction. The PCA-DA model was characterized by accuracy, sensitivity, selectivity and precision values above 90\% and validated by predicting model-unknown Raman spectra, of which 93\% were classified correctly. Thus, we state our PCA-DA to be suitable for parotid tumor and non-salivary salivary gland tissue discrimination and prediction. For evaluation of the translational potential, further validation steps are necessary.}, language = {en} } @article{StebaniBlaimerZableretal.2023, author = {Stebani, Jannik and Blaimer, Martin and Zabler, Simon and Neun, Tilmann and Pelt, Dani{\"e}l M. and Rak, Kristen}, title = {Towards fully automated inner ear analysis with deep-learning-based joint segmentation and landmark detection framework}, series = {Scientific Reports}, volume = {13}, journal = {Scientific Reports}, doi = {10.1038/s41598-023-45466-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357411}, year = {2023}, abstract = {Automated analysis of the inner ear anatomy in radiological data instead of time-consuming manual assessment is a worthwhile goal that could facilitate preoperative planning and clinical research. We propose a framework encompassing joint semantic segmentation of the inner ear and anatomical landmark detection of helicotrema, oval and round window. A fully automated pipeline with a single, dual-headed volumetric 3D U-Net was implemented, trained and evaluated using manually labeled in-house datasets from cadaveric specimen (N = 43) and clinical practice (N = 9). The model robustness was further evaluated on three independent open-source datasets (N = 23 + 7 + 17 scans) consisting of cadaveric specimen scans. For the in-house datasets, Dice scores of 0.97 and 0.94, intersection-over-union scores of 0.94 and 0.89 and average Hausdorf distances of 0.065 and 0.14 voxel units were achieved. The landmark localization task was performed automatically with an average localization error of 3.3 and 5.2 voxel units. A robust, albeit reduced performance could be attained for the catalogue of three open-source datasets. Results of the ablation studies with 43 mono-parametric variations of the basal architecture and training protocol provided task-optimal parameters for both categories. Ablation studies against single-task variants of the basal architecture showed a clear performance beneft of coupling landmark localization with segmentation and a dataset-dependent performance impact on segmentation ability.}, language = {en} } @article{KuzkinaRoessleSegeretal.2023, author = {Kuzkina, A. and R{\"o}ßle, J. and Seger, A. and Panzer, C. and Kohl, A. and Maltese, V. and Musacchio, T. and Blaschke, S. J. and Tamg{\"u}ney, G. and Kaulitz, S. and Rak, K. and Scherzad, A. and Zimmermann, P. H. and Klussmann, J. P. and Hackenberg, S. and Volkmann, J. and Sommer, C. and Sommerauer, M. and Doppler, K.}, title = {Combining skin and olfactory α-synuclein seed amplification assays (SAA)—towards biomarker-driven phenotyping in synucleinopathies}, series = {npj Parkinson's Disease}, volume = {9}, journal = {npj Parkinson's Disease}, issn = {2373-8057}, doi = {10.1038/s41531-023-00519-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357687}, year = {2023}, abstract = {Seed amplification assays (SAA) are becoming commonly used in synucleinopathies to detect α-synuclein aggregates. Studies in Parkinson's disease (PD) and isolated REM-sleep behavior disorder (iRBD) have shown a considerably lower sensitivity in the olfactory epithelium than in CSF or skin. To get an insight into α-synuclein (α-syn) distribution within the nervous system and reasons for low sensitivity, we compared SAA assessment of nasal brushings and skin biopsies in PD (n = 27) and iRBD patients (n = 18) and unaffected controls (n = 30). α-syn misfolding was overall found less commonly in the olfactory epithelium than in the skin, which could be partially explained by the nasal brushing matrix exerting an inhibitory effect on aggregation. Importantly, the α-syn distribution was not uniform: there was a higher deposition of misfolded α-syn across all sampled tissues in the iRBD cohort compared to PD (supporting the notion of RBD as a marker of a more malignant subtype of synucleinopathy) and in a subgroup of PD patients, misfolded α-syn was detectable only in the olfactory epithelium, suggestive of the recently proposed brain-first PD subtype. Assaying α-syn of diverse origins, such as olfactory (part of the central nervous system) and skin (peripheral nervous system), could increase diagnostic accuracy and allow better stratification of patients.}, language = {en} } @article{LinzBrandsKertelsetal.2021, author = {Linz, Christian and Brands, Roman C. and Kertels, Olivia and Dierks, Alexander and Brumberg, Joachim and Gerhard-Hartmann, Elena and Hartmann, Stefan and Schirbel, Andreas and Serfling, Sebastian and Zhi, Yingjun and Buck, Andreas K. and K{\"u}bler, Alexander and Hohm, Julian and Lapa, Constantin and Kircher, Malte}, title = {Targeting fibroblast activation protein in newly diagnosed squamous cell carcinoma of the oral cavity - initial experience and comparison to [\(^{18}\)F]FDG PET/CT and MRI}, series = {European Journal of Nuclear Medicine and Molecular Imaging}, volume = {48}, journal = {European Journal of Nuclear Medicine and Molecular Imaging}, number = {12}, issn = {1619-7070}, doi = {10.1007/s00259-021-05422-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307246}, pages = {3951-3960}, year = {2021}, abstract = {Purpose While [\(^{18}\)F]-fluorodeoxyglucose ([\(^{18}\)F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT. Methods Ten consecutive, treatment-na{\"i}ve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [\(^{18}\)F]FDG and [\(^{68}\)Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection. Detection of the primary tumor, as well as the presence and number of lymph node and distant metastases was analysed. Intensity of tracer accumulation was assessed by means of maximum (SUV\(_{max}\)) and peak (SUV\(_{peak}\) standardized uptake values. Histological work-up including immunohistochemical staining for FAP served as standard of reference. Results [\(^{18}\)F]FDG and FAP-directed PET/CT detected all primary tumors with a SUVmax of 25.5 ± 13.2 (FDG) and 20.5 ± 6.4 (FAP-directed) and a SUVpeak of 16.1 ± 10.3 ([\(^{18}\)F]FDG) and 13.8 ± 3.9 (FAP-directed), respectively. Regarding cervical lymph node metastases, FAP-directed PET/CT demonstrated comparable sensitivity (81.3\% vs. 87.5\%; P = 0.32) and specificity (93.3\% vs. 81.3\%; P = 0.16) to [\(^{18}\)F]FDG PET/CT. FAP expression on the cell surface of cancer-associated fibroblasts in both primary lesions as well as lymph nodes metastases was confirmed in all samples. Conclusion FAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.}, language = {en} } @article{SprinzlMageleSchoergetal.2023, author = {Sprinzl, Georg Mathias and Magele, Astrid and Schoerg, Philipp and Hagen, Rudolf and Rak, Kristen and Kurz, Anja and Van de Heyning, Paul and Calvino, Miryam and Lassaletta, Luis and Gavil{\´a}n, Javier}, title = {A novel representation of audiological and subjective findings for acoustical, bone conduction and direct drive hearing solutions}, series = {Journal of Personalized Medicine}, volume = {13}, journal = {Journal of Personalized Medicine}, number = {3}, issn = {2075-4426}, doi = {10.3390/jpm13030462}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311210}, year = {2023}, abstract = {Background: The benefit of hearing rehabilitation is often measured using audiological tests or subjective questionnaires/interviews. It is important to consider both aspects in order to evaluate the overall benefits. Currently, there is no standardized method for reporting combined audiological and patient reported subjective outcome measures in clinical practice. Therefore, this study focuses on showing the patient's audiological, as well as subjective outcomes in one graph using data from an existing study. Method: The present paper illustrated a graph presenting data on four quadrants with audiological and subjective findings. These quadrants represented speech comprehension in quiet (unaided vs. aided) as WRS\% at 65 dB SPL, speech recognition in noise (unaided vs. aided) as SRT dB SNR, sound field threshold (unaided vs. aided) as PTA\(_4\) in dB HL, wearing time and patient satisfaction questionnaire results. Results: As an example, the HEARRING graph in this paper represented audiological and subjective datasets on a single patient level or a cohort of patients for an active bone conduction hearing implant solution. The graph offered the option to follow the user's performance in time. Conclusion: The HEARRING graph allowed representation of a combination of audiological measures with patient reported outcomes in one single graph, indicating the overall benefit of the intervention. In addition, the correlation and consistency between some results (e.g., aided threshold and aided WRS) can be better visualized. Those users who lacked performance benefits on one or more parameters and called for further insight could be visually identified.}, language = {en} } @article{FriedrichSchneiderBuerkleinetal.2023, author = {Friedrich, Maximilian U. and Schneider, Erich and Buerklein, Miriam and Taeger, Johannes and Hartig, Johannes and Volkmann, Jens and Peach, Robert and Zeller, Daniel}, title = {Smartphone video nystagmography using convolutional neural networks: ConVNG}, series = {Journal of Neurology}, volume = {270}, journal = {Journal of Neurology}, number = {5}, doi = {10.1007/s00415-022-11493-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324526}, pages = {2518-2530}, year = {2023}, abstract = {Background Eye movement abnormalities are commonplace in neurological disorders. However, unaided eye movement assessments lack granularity. Although videooculography (VOG) improves diagnostic accuracy, resource intensiveness precludes its broad use. To bridge this care gap, we here validate a framework for smartphone video-based nystagmography capitalizing on recent computer vision advances. Methods A convolutional neural network was fine-tuned for pupil tracking using > 550 annotated frames: ConVNG. In a cross-sectional approach, slow-phase velocity of optokinetic nystagmus was calculated in 10 subjects using ConVNG and VOG. Equivalence of accuracy and precision was assessed using the "two one-sample t-test" (TOST) and Bayesian interval-null approaches. ConVNG was systematically compared to OpenFace and MediaPipe as computer vision (CV) benchmarks for gaze estimation. Results ConVNG tracking accuracy reached 9-15\% of an average pupil diameter. In a fully independent clinical video dataset, ConVNG robustly detected pupil keypoints (median prediction confidence 0.85). SPV measurement accuracy was equivalent to VOG (TOST p < 0.017; Bayes factors (BF) > 24). ConVNG, but not MediaPipe, achieved equivalence to VOG in all SPV calculations. Median precision was 0.30°/s for ConVNG, 0.7°/s for MediaPipe and 0.12°/s for VOG. ConVNG precision was significantly higher than MediaPipe in vertical planes, but both algorithms' precision was inferior to VOG. Conclusions ConVNG enables offline smartphone video nystagmography with an accuracy comparable to VOG and significantly higher precision than MediaPipe, a benchmark computer vision application for gaze estimation. This serves as a blueprint for highly accessible tools with potential to accelerate progress toward precise and personalized Medicine.}, language = {en} } @article{EngertSpahnBieniussaetal.2023, author = {Engert, Jonas and Spahn, Bjoern and Bieniussa, Linda and Hagen, Rudolf and Rak, Kristen and Voelker, Johannes}, title = {Neurogenic stem cell niche in the auditory Thalamus: in vitro evidence of neural stem cells in the rat medial geniculate body}, series = {Life}, volume = {13}, journal = {Life}, number = {5}, issn = {2075-1729}, doi = {10.3390/life13051188}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319387}, year = {2023}, abstract = {The medial geniculate body (MGB) is a nucleus of the diencephalon representing a relevant segment of the auditory pathway and is part of the metathalamus. It receives afferent information via the inferior brachium of the inferior colliculus and transmits efferent fibers via acoustic radiations to the auditory cortex. Neural stem cells (NSCs) have been detected in certain areas along the auditory pathway. They are of great importance as the induction of an adult stem cell niche might open a regenerative approach to a causal treatment of hearing disorders. Up to now, the existence of NSCs in the MGB has not been determined. Therefore, this study investigated whether the MGB has a neural stem cell potential. For this purpose, cells were extracted from the MGB of PND 8 Sprague-Dawley rats and cultured in a free-floating cell culture assay, which showed mitotic activity and positive staining for stem cell and progenitor markers. In differentiation assays, the markers β-III-tubulin, GFAP, and MBP demonstrated the capacity of single cells to differentiate into neuronal and glial cells. In conclusion, cells from the MGB exhibited the cardinal features of NSCs: self-renewal, the formation of progenitor cells, and differentiation into all neuronal lineage cells. These findings may contribute to a better understanding of the development of the auditory pathway.}, language = {en} } @article{StefanakisBasslerWalczuchetal.2023, author = {Stefanakis, Mona and Bassler, Miriam C. and Walczuch, Tobias R. and Gerhard-Hartmann, Elena and Youssef, Almoatazbellah and Scherzad, Agmal and St{\"o}th, Manuel Bernd and Ostertag, Edwin and Hagen, Rudolf and Steinke, Maria R. and Hackenberg, Stephan and Brecht, Marc and Meyer, Till Jasper}, title = {The impact of tissue preparation on salivary gland tumors investigated by Fourier-transform infrared microspectroscopy}, series = {Journal of Clinical Medicine}, volume = {12}, journal = {Journal of Clinical Medicine}, number = {2}, issn = {2077-0383}, doi = {10.3390/jcm12020569}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304887}, year = {2023}, abstract = {Due to the wide variety of benign and malignant salivary gland tumors, classification and malignant behavior determination based on histomorphological criteria can be difficult and sometimes impossible. Spectroscopical procedures can acquire molecular biological information without destroying the tissue within the measurement processes. Since several tissue preparation procedures exist, our study investigated the impact of these preparations on the chemical composition of healthy and tumorous salivary gland tissue by Fourier-transform infrared (FTIR) microspectroscopy. Sequential tissue cross-sections were prepared from native, formalin-fixed and formalin-fixed paraffin-embedded (FFPE) tissue and analyzed. The FFPE cross-sections were dewaxed and remeasured. By using principal component analysis (PCA) combined with a discriminant analysis (DA), robust models for the distinction of sample preparations were built individually for each parotid tissue type. As a result, the PCA-DA model evaluation showed a high similarity between native and formalin-fixed tissues based on their chemical composition. Thus, formalin-fixed tissues are highly representative of the native samples and facilitate a transfer from scientific laboratory analysis into the clinical routine due to their robust nature. Furthermore, the dewaxing of the cross-sections entails the loss of molecular information. Our study successfully demonstrated how FTIR microspectroscopy can be used as a powerful tool within existing clinical workflows.}, language = {en} } @article{HackenbergMeyerHaefneretal.2022, author = {Hackenberg, Stephan and Meyer, Till Jasper and H{\"a}fner, Johannes and Scheich, Matthias and St{\"o}th, Manuel and Al-Tinawi, Fadi and Neun, Tilmann and Mlynski, Robert and Hagen, Rudolf and Scherzad, Agmal}, title = {Surgical management of tympanojugular paragangliomas using the flexible CO\(_2\) laser}, series = {European Archives of Oto-Rhino-Laryngology}, volume = {279}, journal = {European Archives of Oto-Rhino-Laryngology}, number = {12}, doi = {10.1007/s00405-022-07416-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324164}, pages = {5623-5630}, year = {2022}, abstract = {Purpose Surgery is a standard therapy for tympanojugular paragangliomas (TJP). Maintaining the quality of life (QoL) requires functional preservation. The flexible CO\(_2\) laser allows contact-free tumor removal. This retrospective study compares the postoperative functional outcomes of TJP surgery with and without the flexible CO\(_2\) laser. Methods Between 2005 and 2019, 51 patients with TJP were surgically treated at a tertiary hospital. Until 2012, 17 patients received conventional surgery. Thereafter, the flexible laser was used in 34 patients. Tumor extend, pre- and postoperative cranial nerve function, and complications were compared between the groups. Results The cohort consisted of 33 class A and B tumors and 18 class C and D tumors. Preoperative embolization was performed in 17 cases. Class C/D TJP were usually removed via an infratemporal fossa type A approach. Gross total tumor removal was achieved in 14/18 class C/D tumors. 3/51 patients suffered from long-term partial or complete facial palsy. No differences in post-therapeutic cranial nerve function or complications were noted between the conventional and laser group. One recurrence was observed after complete tumor resection. Conclusion The flexible CO\(_2\) laser was shown to be a safe and effective alternative to conventional bipolar cauterization, which is appreciated by the surgeon in these highly vascularized tumors. Both techniques allowed a high tumor control rate and good long-term results also from a functional point of view.}, language = {en} } @article{TecleHackenbergScheichetal.2023, author = {Tecle, Nyat-Eyob and Hackenberg, Stephan and Scheich, Matthias and Scherzad, Agmal and Hagen, Rudolf and Gehrke, Thomas}, title = {Surgical management of lateral neck abscesses in children: a retrospective analysis of 100 cases}, series = {European Journal of Pediatrics}, volume = {182}, journal = {European Journal of Pediatrics}, number = {1}, doi = {10.1007/s00431-022-04676-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324179}, pages = {431-438}, year = {2023}, abstract = {Cervical abscesses are relatively common infections in pediatric patients. There is an ongoing debate about the necessity and time point of surgical drainage. The identification of a focus of infection might play an important role in facilitating a therapeutic decision. In a retrospective study, 100 pediatric patients aged 1-18 years who underwent incision and drainage of a lateral cervical abscess at our institution were analyzed. Patients were divided into two groups based on whether a focus of infection could be identified or not. Data collection included patient characteristics, microbiological results, antibiotic regimen, and clinical course. A focus of infection was found in 29\% (29/100) of the patients, most frequently in the tonsils. A causative microorganism was found in 75\% (75/100) of all patients, with Staphylococcus aureus and Streptococcus pyogenes being the most common pathogens. All patients received an empiric antibiotic therapy in addition to surgery. Antibiotic medication was changed in 31\% in both groups (9/29 with a focus of infection and 22/71 without a focus of infection) during therapy. Children without an identified focus of infection generally were younger and had more comorbidities reducing immune response while also showing differences in the pathogens involved. There were no complications associated to surgery or antibiotic therapy in any of the patients involved. Conclusion: Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding the microorganisms involved. But the focus of infection seems not to have an impact on patient's outcome. What is Known: • Neck abscesses are a relatively common disease in the pediatric population and may cause serious complications. • Therapy in general consists of intravenous antibiotics with or without surgery. What is New: • The focus identification has no impact on patient's outcome. • Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding their medical history, age, and the microorganisms involved.}, language = {en} } @article{MertensAndriesKurzetal.2022, author = {Mertens, Griet and Andries, Ellen and Kurz, Anja and Tȧvora-Vieira, Dayse and Calvino, Miryam and Amann, Edda and Anderson, Ilona and Lorens, Artur}, title = {Towards a consensus on an ICF-based classification system for horizontal sound-source localization}, series = {Journal of Personalized Medicine}, volume = {12}, journal = {Journal of Personalized Medicine}, number = {12}, issn = {2075-4426}, doi = {10.3390/jpm12121971}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297319}, year = {2022}, abstract = {The study aimed to develop a consensus classification system for the reporting of sound localization testing results, especially in the field of cochlear implantation. Against the background of an overview of the wide variations present in localization testing procedures and reporting metrics, a novel classification system was proposed to report localization errors according to the widely accepted International Classification of Functioning, Disability and Health (ICF) framework. The obtained HEARRING_LOC_ICF scale includes the ICF graded scale: 0 (no impairment), 1 (mild impairment), 2 (moderate impairment), 3 (severe impairment), and 4 (complete impairment). Improvement of comparability of localization results across institutes, localization testing setups, and listeners was demonstrated by applying the classification system retrospectively to data obtained from cohorts of normal-hearing and cochlear implant listeners at our institutes. The application of our classification system will help to facilitate multi-center studies, as well as allowing better meta-analyses of data, resulting in improved evidence-based practice in the field.}, language = {en} } @article{TopsakalAgrawalAtlasetal.2022, author = {Topsakal, Vedat and Agrawal, Sumit and Atlas, Marcus and Baumgartner, Wolf-Dieter and Brown, Kevin and Bruce, Iain A. and Dazert, Stefan and Hagen, Rudolf and Lassaletta, Luis and Mlynski, Robert and Raine, Christopher H. and Rajan, Gunesh P. and Schmutzhard, Joachim and Sprinzl, Georg Mathias and Staecker, Hinrich and Usami, Shin-ichi and Van Rompaey, Vincent and Zernotti, Mario and Heyning, Paul van de}, title = {Minimally traumatic cochlear implant surgery: expert opinion in 2010 and 2020}, series = {Journal of Personalized Medicine}, volume = {12}, journal = {Journal of Personalized Medicine}, number = {10}, issn = {2075-4426}, doi = {10.3390/jpm12101551}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288196}, year = {2022}, abstract = {This study aimed to discover expert opinion on the surgical techniques and materials most likely to achieve maximum postoperative residual hearing preservation in cochlear implant (CI) surgery and to determine how these opinions have changed since 2010. A previously published questionnaire used in a study published in 2010 was adapted and expanded. The questionnaire was distributed to an international group of experienced CI surgeons. Present results were compared, via descriptive statistics, to those from the 2010 survey. Eighteen surgeons completed the questionnaire. Respondents clearly favored the following: round window insertion, slow array insertion, and the peri- and postoperative use of systematic antibiotics. Insertion depth was regarded as important, and electrode arrays less likely to induce trauma were preferred. The usefulness of dedicated soft-surgery training was also recognized. A lack of agreement was found on whether the middle ear cavity should be flushed with a non-aminoglycoside antibiotic solution or whether a sheath or insertion tube should be used to avoid contaminating the array with blood or bone dust. In conclusion, this paper demonstrates how beliefs about CI soft surgery have changed since 2010 and shows areas of current consensus and disagreement.}, language = {en} } @article{KoepingShehataDielerSchneideretal.2018, author = {K{\"o}ping, Maria and Shehata-Dieler, Wafaa and Schneider, Dieter and Cebulla, Mario and Oder, Daniel and M{\"u}ntze, Jonas and Nordbeck, Peter and Wanner, Christoph and Hagen, Rudolf and Schraven, Sebastian P.}, title = {Characterization of vertigo and hearing loss in patients with Fabry disease}, series = {Orphanet Journal of Rare Diseases}, volume = {13}, journal = {Orphanet Journal of Rare Diseases}, doi = {10.1186/s13023-018-0882-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222818}, year = {2018}, abstract = {Background Fabry Disease (FD) is an X-linked hereditary lysosomal storage disorder which leads to a multisystemic intralysosomal accumulation of globotriaosylceramid (Gb3). Besides prominent renal and cardiac organ involvement, patients commonly complain about vestibulocochlear symptoms like high-frequency hearing loss, tinnitus and vertigo. However, comprehensive data especially on vertigo remain scarce. The aim of this study was to examine the prevalence and characteristics of vertigo and hearing loss in patients with FD, depending on renal and cardiac parameters and get hints about the site and the pattern of the lesions. Methods Single-center study with 57 FD patients. Every patient underwent an oto-rhino-laryngological examination as well as videonystagmography and vestibular evoked myogenic potentials (VEMPs) and audiological measurements using pure tone audiometry and auditory brainstem response audiometry (ABR). Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class. Results More than one out of three patients (35.1\%) complained about hearing loss, 54.4\% about vertigo and 28.1\% about both symptom. In 74\% a sensorineural hearing loss of at least 25 dB was found, ABR could exclude any retrocochlear lesion. Caloric testing showed abnormal values in 71.9\%, VEMPs were pathological in 68\%. A correlation between the side or the shape of hearing loss and pathological vestibular testing could not be revealed. Conclusions Hearing loss and vertigo show a high prevalence in FD. While hearing loss seems due to a cochlear lesion, peripheral vestibular as well as central nervous pathologies cause vertigo. Thus, both the site of lesion and the pathophysiological patterns seem to differ.}, language = {en} } @article{NoyaletIlgenBuerkleinetal.2022, author = {Noyalet, Laurent and Ilgen, Lukas and B{\"u}rklein, Miriam and Shehata-Dieler, Wafaa and Taeger, Johannes and Hagen, Rudolf and Neun, Tilmann and Zabler, Simon and Althoff, Daniel and Rak, Kristen}, title = {Vestibular aqueduct morphology and Meniere's disease - development of the vestibular aqueduct score by 3D analysis}, series = {Frontiers in Surgery}, volume = {9}, journal = {Frontiers in Surgery}, issn = {2296-875X}, doi = {10.3389/fsurg.2022.747517}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312893}, year = {2022}, abstract = {Improved radiological examinations with newly developed 3D models may increase understanding of Meniere's disease (MD). The morphology and course of the vestibular aqueduct (VA) in the temporal bone might be related to the severity of MD. The presented study explored, if the VA of MD and non-MD patients can be grouped relative to its angle to the semicircular canals (SCC) and length using a 3D model. Scans of temporal bone specimens (TBS) were performed using micro-CT and micro flat panel volume computed tomography (mfpVCT). Furthermore, scans were carried out in patients and TBS by computed tomography (CT). The angle between the VA and the three SCC, as well as the length of the VA were measured. From these data, a 3D model was constructed to develop the vestibular aqueduct score (VAS). Using different imaging modalities it was demonstrated that angle measurements of the VA are reliable and can be effectively used for detailed diagnostic investigation. To test the clinical relevance, the VAS was applied on MD and on non-MD patients. Length and angle values from MD patients differed from non-MD patients. In MD patients, significantly higher numbers of VAs could be assigned to a distinct group of the VAS. In addition, it was tested, whether the outcome of a treatment option for MD can be correlated to the VAS.}, language = {en} } @article{BieniussaKahramanSkornickaetal.2022, author = {Bieniussa, Linda and Kahraman, Baran and Skornicka, Johannes and Schulte, Annemarie and Voelker, Johannes and Jablonka, Sibylle and Hagen, Rudolf and Rak, Kristen}, title = {Pegylated insulin-like growth factor 1 attenuates hair cell loss and promotes presynaptic maintenance of medial olivocochlear cholinergic fibers in the cochlea of the progressive motor neuropathy mouse}, series = {Frontiers in Neurology}, volume = {13}, journal = {Frontiers in Neurology}, issn = {1664-2295}, doi = {10.3389/fneur.2022.885026}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276669}, year = {2022}, abstract = {The progressive motor neuropathy (PMN) mouse is a model of an inherited motor neuropathy disease with progressive neurodegeneration. Axon degeneration associates with homozygous mutations of the TBCE gene encoding the tubulin chaperone E protein. TBCE is responsible for the correct dimerization of alpha and beta-tubulin. Strikingly, the PMN mouse also develops a progressive hearing loss after normal hearing onset, characterized by degeneration of the auditory nerve and outer hair cell (OHC) loss. However, the development of this neuronal and cochlear pathology is not fully understood yet. Previous studies with pegylated insulin-like growth factor 1 (peg-IGF-1) treatment in this mouse model have been shown to expand lifespan, weight, muscle strength, and motor coordination. Accordingly, peg-IGF-1 was evaluated for an otoprotective effect. We investigated the effect of peg-IGF-1 on the auditory system by treatment starting at postnatal day 15 (p15). Histological analysis revealed positive effects on OHC synapses of medial olivocochlear (MOC) neuronal fibers and a short-term attenuation of OHC loss. Peg-IGF-1 was able to conditionally restore the disorganization of OHC synapses and maintain the provision of cholinergic acetyltransferase in presynapses. To assess auditory function, frequency-specific auditory brainstem responses and distortion product otoacoustic emissions were recorded in animals on p21 and p28. However, despite the positive effect on MOC fibers and OHC, no restoration of hearing could be achieved. The present work demonstrates that the synaptic pathology of efferent MOC fibers in PMN mice represents a particular form of "efferent auditory neuropathy." Peg-IGF-1 showed an otoprotective effect by preventing the degeneration of OHCs and efferent synapses. However, enhanced efforts are needed to optimize the treatment to obtain detectable improvements in hearing performances.}, language = {en} } @article{HerrmannMuellerGraffKaulitzetal.2022, author = {Herrmann, David P. and M{\"u}ller-Graff, Franz-Tassilo and Kaulitz, Stefan and Cebulla, Mario and Kurz, Anja and Hagen, Rudolf and Neun, Tilmann and Rak, Kristen}, title = {Application of intentional facial nerve stimulation during cochlear implantation as an electrophysiological tool to estimate the intracochlear electrode position}, series = {Scientific Reports}, volume = {12}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-022-17732-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300197}, year = {2022}, abstract = {This proof of concept describes the use of evoked electromyographic (EMG) activation of the facial nerve for intraoperative monitoring of the electrode insertion during cochlear implantation (CI). Intraoperative EMG measurements from the facial nerve were conducted in nine patients undergoing CI implantation. Electric current pulses were emitted from contacts on the CI array during and immediately after electrode insertion. For control, the results of EMG measurements were compared to postoperative flat panel volume computed tomography scans with secondary reconstruction (fpVCT\(_{SECO}\)). During insertion, the EMG response evoked by the electrical stimulation from the CI was growing with the stimulating contact approaching the facial nerve and declined with increasing distance. After full insertion, contacts on the apical half of the CI array stimulated higher EMG responses compared with those on the basal half. Comparison with postoperative imaging demonstrated that electrode contacts stimulating high EMG responses had the shortest distances to the facial nerve. It could be demonstrated that electrically evoked EMG activation of the facial nerve can be used to monitor the progress during CI electrode insertion and to control the intracochlear electrode position after full insertion.}, language = {en} } @article{RadeloffWeissHagenetal.2021, author = {Radeloff, Katrin and Weiss, Dorothee and Hagen, Rudolf and Kleinsasser, Norbert and Radeloff, Andreas}, title = {Differentiation behaviour of adipose-derived stromal cells (ASCs) seeded on polyurethane-fibrin scaffolds in vitro and in vivo}, series = {Biomedicines}, volume = {9}, journal = {Biomedicines}, number = {8}, issn = {2227-9059}, doi = {10.3390/biomedicines9080982}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245030}, year = {2021}, abstract = {Adipose-derived stromal cells (ASCs) are a promising cell source for tissue engineering and regenerative medicine approaches for cartilage replacement. For chondrogenic differentiation, human (h)ASCs were seeded on three-dimensional polyurethane (PU) fibrin composites and induced with a chondrogenic differentiation medium containing TGF-ß3, BMP-6, and IGF-1 in various combinations. In addition, in vitro predifferentiated cell-seeded constructs were implanted into auricular cartilage defects of New Zealand White Rabbits for 4 and 12 weeks. Histological, immunohistochemical, and RT-PCR analyses were performed on the constructs maintained in vitro to determine extracellular matrix (ECM) deposition and expression of specific cartilage markers. Chondrogenic differentiated constructs showed a uniform distribution of cells and ECM proteins. RT-PCR showed increased gene expression of collagen II, collagen X, and aggrecan and nearly stable expression of SOX-9 and collagen I. Rabbit (r)ASC-seeded PU-fibrin composites implanted in ear cartilage defects of New Zealand White Rabbits showed deposition of ECM with structures resembling cartilage lacunae by Alcian blue staining. However, extracellular calcium deposition became detectable over the course of 12 weeks. RT-PCR showed evidence of endochondral ossification during the time course with the expression of specific marker genes (collagen X and RUNX-2). In conclusion, hASCs show chondrogenic differentiation capacity in vitro with the expression of specific marker genes and deposition of cartilage-specific ECM proteins. After implantation of predifferentiated rASC-seeded PU-fibrin scaffolds into a cartilage defect, the constructs undergo the route of endochondral ossification.}, language = {en} } @article{MoratinIckrathScherzadetal.2021, author = {Moratin, Helena and Ickrath, Pascal and Scherzad, Agmal and Meyer, Till Jasper and Naczenski, Sebastian and Hagen, Rudolf and Hackenberg, Stephan}, title = {Investigation of the immune modulatory potential of zinc oxide nanoparticles in human lymphocytes}, series = {Nanomaterials}, volume = {11}, journal = {Nanomaterials}, number = {3}, issn = {2079-4991}, doi = {10.3390/nano11030629}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234016}, year = {2021}, abstract = {Zinc oxide nanoparticles (ZnO-NP) are commonly used for a variety of applications in everyday life. In addition, due to its versatility, nanotechnology supports promising approaches in the medical sector. NP can act as drug-carriers in the context of targeted chemo- or immunotherapy, and might also exhibit autonomous immune-modulatory characteristics. Knowledge of potential immunosuppressive or stimulating effects of NP is indispensable for the safety of consumers as well as patients. In this study, primary human peripheral blood lymphocytes of 9 donors were treated with different sub-cytotoxic concentrations of ZnO-NP for the duration of 1, 2, or 3 days. Flow cytometry was performed to investigate changes in the activation profile and the proportion of T cell subpopulations. ZnO-NP applied in this study did not induce any significant alterations in the examined markers, indicating their lack of impairment in terms of immune modulation. However, physicochemical characteristics exert a major influence on NP-associated bioactivity. To allow a precise simulation of the complex molecular processes of immune modulation, a physiological model including the different components of an immune response is needed.}, language = {en} }