TY - JOUR A1 - Belinsky, Martin G. A1 - Rink, Lori A1 - Cai, Kathy Q. A1 - Capuzzi, Stephen J. A1 - Hoang, Yen A1 - Chien, Jeremy A1 - Godwin, Andrew K. A1 - von Mehren, Margaret T1 - Somatic loss of function mutations in neurofibromin 1 and MYC associated factor X genes identified by exome-wide sequencing in a wild-type GIST case JF - BMC Cancer N2 - Approximately 10–15 % of gastrointestinal stromal tumors (GISTs) lack gain of function mutations in the KIT and platelet-derived growth factor receptor alpha (PDGFRA) genes. An alternate mechanism of oncogenesis through loss of function of the succinate-dehydrogenase (SDH) enzyme complex has been identified for a subset of these “wild type” GISTs. KW - gastrointestinal stromal tumor (GIST) KW - wild type KW - KIT KW - PDGFRA KW - succinate dehydrogenase (SDH) KW - NF1 KW - MAX Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-6292 SN - 1471-2407 VL - 15 IS - 887 ER - TY - JOUR A1 - Munchel, Sarah A1 - Hoang, Yen A1 - Yue, Zhao A1 - Cottrell, Joseph A1 - Klotzle, Brandy A1 - Godwin, Andrew K. A1 - Koestler, Devin A1 - Beyerlein, Peter A1 - Fan, Jian-Bing A1 - Bibikova, Marina A1 - Chien, Jeremy T1 - Targeted or whole genome sequencing of formalin fixed tissue samples: potential applications in cancer genomics JF - Oncotarget N2 - Current genomic studies are limited by the poor availability of fresh-frozen tissue samples. Although formalin-fixed diagnostic samples are in abundance, they are seldom used in current genomic studies because of the concern of formalin-fixation artifacts. Better characterization of these artifacts will allow the use of archived clinical specimens in translational and clinical research studies. To provide a systematic analysis of formalin-fixation artifacts on Illumina sequencing, we generated 26 DNA sequencing data sets from 13 pairs of matched formalin-fixed paraffin-embedded (FFPE) and fresh-frozen (FF) tissue samples. The results indicate high rate of concordant calls between matched FF/FFPE pairs at reference and variant positions in three commonly used sequencing approaches (whole genome, whole exome, and targeted exon sequencing). Global mismatch rates and C·G > T·A substitutions were comparable between matched FF/FFPE samples, and discordant rates were low (<0.26%) in all samples. Finally, low-pass whole genome sequencing produces similar pattern of copy number alterations between FF/FFPE pairs. The results from our studies suggest the potential use of diagnostic FFPE samples for cancer genomic studies to characterize and catalog variations in cancer genomes. KW - cancer genomics KW - FFPE DNA KW - whole exome sequencing KW - whole genome sequencing KW - copy number alteration Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-6307 SN - 1949-2553 VL - 6 IS - 28 SP - 25943 EP - 25961 ER - TY - JOUR A1 - Radivoievych, Aleksandar A1 - Kolp, Benjamin A1 - Grebinyk, Sergii A1 - Prylutska, Svitlana A1 - Ritter, Uwe A1 - Zolk, Oliver A1 - Glökler, Jörn A1 - Frohme, Marcus A1 - Grebinyk, Anna T1 - Silent Death by Sound: C60 Fullerene Sonodynamic Treatment of Cancer Cells JF - International Journal of Molecular Sciences N2 - The acoustic pressure waves of ultrasound (US) not only penetrate biological tissues deeper than light, but they also generate light emission, termed sonoluminescence. This promoted the idea of its use as an alternative energy source for photosensitizer excitation. Pristine C60 fullerene (C60), an excellent photosensitizer, was explored in the frame of cancer sonodynamic therapy (SDT). For that purpose, we analyzed C60 effects on human cervix carcinoma HeLa cells in combination with a low-intensity US treatment. The time-dependent accumulation of C60 in HeLa cells reached its maximum at 24 h (800 ± 66 ng/106 cells). Half of extranuclear C60 is localized within mitochondria. The efficiency of the C60 nanostructure’s sonoexcitation with 1 MHz US was tested with cell-based assays. A significant proapoptotic sonotoxic effect of C60 was found for HeLa cells. C60′s ability to induce apoptosis of carcinoma cells after sonoexcitation with US provides a promising novel approach for cancer treatment. KW - ultrasound KW - C60 fullerene KW - sonodynamic therapy KW - HeLa cells KW - apoptosis Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-16877 SN - 1422-0067 VL - 24 IS - 2 PB - MDPI ER - TY - JOUR A1 - Alekseeva, Victoriia A1 - Nechyporenko, Alina A1 - Frohme, Marcus A1 - Gargin, Vitaliy A1 - Meniailov, Ievgen A1 - Chumachenko, Dmytro T1 - Intelligent Decision Support System for Differential Diagnosis of Chronic Odontogenic Rhinosinusitis Based on U-Net Segmentation JF - Electronics N2 - The share of chronic odontogenic rhinosinusitis is 40% among all chronic rhinosinusitis. Using automated information systems for differential diagnosis will improve the efficiency of decision-making by doctors in diagnosing chronic odontogenic rhinosinusitis. Therefore, this study aimed to develop an intelligent decision support system for the differential diagnosis of chronic odontogenic rhinosinusitis based on computer vision methods. A dataset was collected and processed, including 162 MSCT images. A deep learning model for image segmentation was developed. A 23 convolutional layer U-Net network architecture has been used for the segmentation of multi-spiral computed tomography (MSCT) data with odontogenic maxillary sinusitis. The proposed model is implemented in such a way that each pair of repeated 3 × 3 convolutions layers is followed by an Exponential Linear Unit instead of a Rectified Linear Unit as an activation function. The model showed an accuracy of 90.09%. To develop a decision support system, an intelligent chatbot allows the user to conduct an automated patient survey and collect patient examination data from several doctors of various profiles. The intelligent information system proposed in this study made it possible to combine an image processing model with a patient interview and examination data, improving physician decision-making efficiency in the differential diagnosis of Chronic Odontogenic Rhinosinusitis. The proposed solution is the first comprehensive solution in this area. KW - CT data KW - deep learning KW - image segmentation KW - U-Net KW - decision support system KW - chronic odontogenic rhinosinusitis KW - machine learning KW - artificial intelligence Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-17088 SN - 2079-9292 VL - 12 IS - 5 PB - MDPI ER - TY - JOUR A1 - Radivoievych, Aleksandar A1 - Schnepel, Sophia A1 - Prylutska, Svitlana A1 - Ritter, Uwe A1 - Zolk, Oliver A1 - Frohme, Marcus A1 - Grebinyk, Anna T1 - From 2D to 3D In Vitro World: Sonodynamically-Induced Prooxidant Proapoptotic Effects of C60-Berberine Nanocomplex on Cancer Cells JF - Cancers N2 - Recently, sonodynamic therapy (SDT) has emerged as a promising non-invasive approach for treating cancer by activating sensitizers with ultrasound (US). In this context, we investigated C60 fullerene (C60) as a nanocarrier for the promising drug Berberine (Ber)—both potential aromatic sonosensitizers. The preferential mitochondrial accumulation of C60 and the proapoptotic effects of Ber also make the C60-Berberine nanocomplex (C60-Ber) a good candidate for direct induction of the intrinsic apoptotic cell death under US action. The in vitro research on C60-Ber can provide insights into novel, non-invasive cancer treatments. These findings lead to the development of targeted therapies with reduced side effects, inspire interdisciplinary collaboration, and open new avenues for drug delivery and cancer therapy research. KW - berberine KW - C60 fullerene KW - apoptosis KW - sonodynamic therapy KW - ultrasound Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19438 VL - 16 IS - 18 ER - TY - JOUR A1 - Nechyporenko, Alina A1 - Frohme, Marcus A1 - Strelchuk, Yaroslav A1 - Omelchenko, Vladyslav A1 - Gargin, Vitaliy A1 - Ishchenko, Liudmyla A1 - Alekseeva, Victoriia T1 - Galvanic Skin Response and Photoplethysmography for Stress Recognition Using Machine Learning and Wearable Sensors JF - Applied Sciences N2 - This study investigates stress recognition using galvanic skin response (GSR) and photoplethysmography (PPG) data and machine learning, with a new focus on air raid sirens as a stressor. It bridges laboratory and real-world conditions and highlights the reliability of wearable sensors in dynamic, high-stress environments such as war and conflict zones. The study involves 37 participants (20 men, 17 women), aged 20–30, who had not previously heard an air raid siren. A 70 dB “S-40 electric siren” (400–450 Hz) was delivered via headphones. The protocol included a 5 min resting period, followed by 3 min “no-stress” phase, followed by 3 min “stress” phase, and finally a 3 min recovery phase. GSR and PPG signals were recorded using Shimmer 3 GSR+ sensors on the fingers and earlobes. A single session was conducted to avoid sensitization. The workflow includes signal preprocessing to remove artifacts, feature extraction, feature selection, and application of different machine learning models to classify the “stress “and “no-stress” states. As a result, the best classification performance was shown by the k-Nearest Neighbors model, achieving 0.833 accuracy. This was achieved by using a particular combination of heart rate variability (HRV) and GSR features, which can be considered as new indicators of siren-induced stress. KW - galvanic skin response KW - machine learning KW - photoplethysmography KW - stress Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19803 VL - 14 IS - 24 PB - MDPI ER - TY - CHAP A1 - Nechyporenko, Alina A1 - Reshetnik, Viktor A1 - Frohme, Marcus A1 - Alekseeva, Victoriia A1 - Lupyr, Andrii A1 - Gargin, Vitaliy ED - Chumachenko, Dmytro ED - Golland, Polina ED - Yakovlev, Sergiy T1 - Evaluation of Bone Radiodensity in Smokers T2 - Proceedings of the 4th International Workshop of IT-professionals on Artificial Intelligence (ProfIT AI 2024) 2024, Cambridge, MA, USA, September 25-27, 2024 N2 - One of the most prevalent harmful habits that affect people daily is smoking. The aim of our study was to investigate changes in the bone density of the human paranasal sinuses under the influence of smoking using uncertainty calculation. Material and Methods. The study involved 150 male and female individuals aged 20-40 years, which helps to exclude other factors that could influence the reduction in bone radiodensity (e.g., menopause in women, age-related changes, etc.). The participants were divided into three groups based on the duration of their smoking habits. Results. Smoking has almost no effect on the maximum bone density. All groups show nearly identical values. In the first group, consisting of individuals who smoked for up to 5 years, the maximum density is 75.22 ± 37.61 Hu. In the second group, those who smoked for up to 10 years have a density of 84.22 ± 42.11 Hu, while in the third control group, the density is 74.29 ± 37.15 Hu. On the other hand, smoking has a greater impact on the minimum radiological bone density of the upper wall of the maxillary sinus. The lowest values are found in the group of individuals who smoked for 10 or more years, with a minimum density of 23.86 ± 11.93 Hu. For those who smoked for up to 5 years, the radiological bone density was 52.65 ± 26.32 Hu. In the control group, the density values were slightly higher than those of individuals who smoked for up to 5 years, with the highest values being 58.12 ± 29.06 Hu. Conclusion. The study investigated changes in the bone density of the human paranasal sinuses under the influence of smoking, utilizing uncertainty calculation. It was found that the most sensitive indicator to nicotine exposure is the minimum radiological density, which can significantly increase the risk of developing complications. Specifically, the lowest radiological density was observed in the group of individuals who smoked for 10 years or more, with a value of 23.86 ± 11.93 Hu. KW - bone radiodensity KW - computer tomography KW - paranasal sinus KW - uncertainty Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19616 UR - https://ceur-ws.org/Vol-3777/short8.pdf IS - 3777 SP - 238 EP - 244 ER - TY - CHAP A1 - Reshetnik, Viktor A1 - Muryzina, Irina A1 - Frohme, Marcus A1 - Alekseeva, Victoriia A1 - Dzyza, Alla A1 - Nechyporenko, Alina ED - Chumachenko, Dmytro ED - Golland, Polina ED - Yakovlev, Sergiy T1 - Uncertainty Estimation Method for Determining Bone Density in Patients with Infiltrating Intraductal Carcinoma Undergoing Anti-Cancer Therapy T2 - Proceedings of the 4th International Workshop of IT-professionals on Artificial Intelligence (ProfIT AI 2024) 2024, Cambridge, MA, USA, September 25-27, 2024 N2 - Identification of a bone density is crucial in all branches of medicine. Assessing bone density is a labor-intensive process. Bone density is quite unstable and depends on many factors, both physiological (aging, hormonal balance) and pathological (medication use, various underlying conditions). The aim of our study is to determine bone density in patients with malignant breast tumors undergoing anti-cancer therapy. Material and Methods. The study included 50 women aged 60-70 years who were diagnosed with infiltrating intraductal carcinoma. According to established protocols, MSCT is recommended for this category of women at intervals of once every six months. The first MSCT scan was performed immediately after the diagnosis was made, before the start of treatment, and the second scan was conducted six months later. Results. The maximum radiological density was 75.8954±37.9477 Hu in the group of women who had been receiving treatment for six months, compared to 93.9388±46.9694 Hu in the group of patients who did not take the drug. Meanwhile, the minimum density showed a slight increase from 29.7295±14.8647 Hu to 38.6919±19.3460 Hu, which can be attributed to the compensatory mechanisms of the body. Conclusions. In the course of this study, bone density in patients with infiltrating intraductal carcinoma undergoing anti-cancer therapy was determined using uncertainty estimation. It was found that after six months, the first to respond to changes in density was the maximum bone density. KW - infiltrarive intraductal adenocarcinoma KW - multislice computer tomography KW - radiological bone density Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19628 UR - https://ceur-ws.org/Vol-3777/short6.pdf IS - 3777 SP - 222 EP - 228 ER - TY - CHAP A1 - Rykova, Eugenia A1 - Walther, Mathias ED - of Hawai’i at Manoa, University T1 - AphaDIGITAL – Digital Speech Therapy Solution for Aphasia Patients with Automatic Feedback Provided by a Virtual Assistant T2 - Proceedings of the 57th Hawaii International Conference on System Sciences N2 - This paper introduces aphaDIGITAL – a mobile application for speech and language therapy (SLT) support of German-speaking people with aphasia. The app includes automatic speech recognition and text analysis components, which allows giving detailed feedback to the users on different types of errors. Furthermore, the exercises are accompanied by an avatar-based SLT assistant, which is created for this specific purpose. The user performs the exercises, individually configured for her by the SLT practitioner, on a mobile device. Data collection and processing are carried out on the server. KW - automatic speech recognition KW - digital health KW - embodied conversational agent KW - language technology KW - speech and language therapy Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19453 SN - 978-0-9981331-7-1 SP - 3385 EP - 3394 ER - TY - CHAP A1 - Strelchuk, Yaroslav A1 - Nechyporenko, Alina A1 - Frohme, Marcus A1 - Gargin, Vitaliy A1 - Lupyr, Andrii A1 - Alekseeva, Victoriia ED - Shakhovska, Nataliya ED - Jiao, Jianbo ED - Izonin, Ivan ED - Chretien, Stephane T1 - Detection of stress using photoplethysmography T2 - Proceedings of the 7th International Conference on Informatics & Data-Driven Medicine (IDDM 2024) N2 - Stress is an important factor affecting human health, and its timely detection can significantly improve quality of life. This study addresses the current issue of identifying stress states using photoplethysmography signals obtained from the wearable Shimmer 3 sensor. The purpose of the study was to establish an effective approach for stress detection, specifically through the analysis of heart rate variability changes during different states: rest and stress. A distinctive feature of the research is the use of the air raid siren sound as a stress factor. The research methodology includes the collection and analysis of biosignals, allowing for the assessment of cardiovascular system functioning under the impact of stress factors. The results of the study demonstrated significant differences in heart rhythm indicators depending on the person's state, highlighting the potential of these metrics as a tool for health monitoring and stress detection. The paper proposes a new approach to using photoplethysmography for assessing stress responses, which may contribute to the development of personalized stress management methods. KW - air raid signal KW - cardiovascular system health KW - early stress detection KW - health monitoring KW - heart rate variability KW - personalized stress management KW - photoplethysmography KW - stress KW - wearable sensors Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19896 UR - https://ceur-ws.org/Vol-3892/short3.pdf VL - 3892 SP - 196 EP - 202 PB - RWTH Aachen ER - TY - CHAP A1 - Nechyporenko, Alina A1 - Frohme, Marcus A1 - Omelchenko, Vladyslav A1 - Alekseeva, Victoriia A1 - Lupyr, Andrii A1 - Gargin, Vitaliy ED - Shakhovska, Nataliya ED - Kovác, Michal ED - Izonin, Ivan ED - Chrétien, Stéphane T1 - Identification of Personality Based on the Sphenoid Sinus Structure Using Machine Learning T2 - Proceedings of the 6th International Conference on Informatics & Data-Driven Medicine, Bratislava, Slovakia, November 17-19, 2023 N2 - The aim of our study is to develop a new, simple, and effective method for identification of personality based on the characteristics of the sphenoid sinus structure, using machine learning for subsequent implementation into routine medical practice in Ukraine. The study involved 200 multislice computed tomography (MSCT) scans of individuals of various genders and ages. During the study, we obtained results with an accuracy exceeding 70%. KW - identification of personality KW - multislice computed tomography KW - deep learning Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0074-3609-1 UR - https://ceur-ws.org/Vol-3609/short2.pdf VL - 3609 SP - 167 EP - 173 PB - CEUR-WS.org ER - TY - JOUR A1 - Rykova, Eugenia A1 - Walther, Mathias T1 - Evaluation of German Automatic Speech Recognition solutions in the context of speech and language therapy support of people with aphasia JF - Loquens N2 - Those who suffer from aphasia benefit from digital speech and language therapy solutions, and automatic speech recognition (ASR) has been already used for giving feedback on the correctness of the answers in naming exercises. AphaDIGITAL application is to provide German-speaking users with detailed feedback on phonemic/phonetic and semantic errors, based on automatic speech and language processing. For this purpose, open-source ASR solutions for German were evaluated on different corpora of atypical speech, including two small datasets with aphasic speech samples. Character error rate, the number of precisely recognized items and empty outputs served as evaluation metrics. The four selected models are generally robust to the deteriorated condition of speech and audio quality and consistently outperform commercial models in atypical speech recognition. Applying error acceptance threshold, additional use of phonemic error rate, and other valuable insights for ASR implementation in aphaDIGITAL are discussed. KW - Aphasia KW - automatic speech recognition KW - digital health KW - speech and language therapy Y1 - 2025 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-20615 VL - 12 PB - Centro de Ciencias Humanas y Sociales, Madrid ER - TY - GEN A1 - Fischer, Susanne T1 - Experimentelle Therapieentwicklung für die akute lymphatische Leukämie T2 - Wissenschaftliche Beiträge 2013 N2 - Bei Leukämie handelt es sich um eine Entartung von Vorläuferzellen der weißen Blutzellen (Leukozyten). Die hier betrachtete Form dieser Erkrankung ist die akute lymphatische Leukämie(ALL ), bei der vor allem Rückfallpatienten eine schlechte Diagnose haben. Demnach wird nach neuen Therapien gesucht, die neue Angriffspunkte für die Behandlung der ALL bieten. Die getestete Substanz 5-Azacytidin hat zwei therapeutische Wirkmechanismen. Zum einen das Hervorrufen des selbstinduzierte Zelltod (Apoptose) und zum anderen einen epigenetischen Effekt. Der epigenetische Effekt bewirkt eine Veränderung der Genregulation (Veränderung der Genaktivität) ohne die DNA - Sequenz zu beeinflussen. Dies kann mithilfe eines Screenings (Micoarraytechnologie) in behandelten und unbehandelten Proben verglichen werden. Da das Screening sehr global ist, erfolgt für eine Auswahl therapeutisch relevanter Gene eine Verifizierung mittels einer molekularbiologischen Methode (qRT -PCR ). Dabei wurden Gene mit erhöhter Aktivität bestätigt, MA EL; TM EM56; IL 1B; BCL 6; MS4A1 und FLT 3. Für jedes dieser Gene konnte ein positiver Nutzen für die Therapie einer ALL diskutiert werden. Für FLT 3 erfolgte sogar eine positive Kombination mit einer anderen therapeutischen Substanz. Der therapeutische Einsatz des 5-Azacytidins kann zukünftig eine wichtige Therapieoption für Patienten mit ALL darstellen. Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-3146 SN - 0949-8214 VL - 17 SP - 13 EP - 16 ER - TY - GEN A1 - Sinning, Denise A1 - Köhler, Kernt A1 - Litzke, Lutz-Ferdinand A1 - Schönian, Gabriele A1 - Frohme, Marcus A1 - Kuhls, Katrin T1 - Leishmania siamensis als Erreger von autochthoner kutaner Leishmaniose bei Pferden in Deutschland - eine neue Infektionskrankheit in Mitteleuropa? T2 - Wissenschaftliche Beiträge 2014 N2 - Aus mitteleuropäischer Sicht ist die durch Parasiten verursachte und von Sandmücken übertragene Leishmaniose eine in Ländern tropischer und subtropischer Regionen auftretende Infektionskrankheit. In zunehmendem Maße werden jedoch autochthone Fälle in Mitteleuropa, insbesondere in Süddeutschland, verzeichnet. Dies ist vermutlich auf die globale Erwärmung und die Ausdehnung des Verbreitungsgebietes der Sandmücken nach Norden zurückzuführen. Die vorliegende Arbeit befasst sich mit der Identifizierung und phylogenetischen Charakterisierung der Erreger dieser Fälle. Dazu wurden verschiedene Marker im Leishmaniengenom sequenziert und mit bekannten Arten verglichen. Die untersuchte DNA stammte von autochthonen kutanen Leishmaniosen bei Pferden und einem Rind, die in den letzten zehn Jahren in Deutschland und der Schweiz auftraten. Aufgrund identischer Sequenzen konnten die Parasiten als L. siamensis identifiziert bzw. verifiziert werden, eine erst im Jahr 2008 neu beschriebene Art, die in Thailand humane viszerale Leishmaniose verursacht. Die phylogenetischen Analysen zeigten die Ähnlichkeit von L. siamensis mit weiteren bisher nicht identifizierten Stämmen aus Martinique und Ghana, die kutane Leishmaniose bei Menschen verursachen. Um die Frage zu beantworten, ob sich die Leishmaniose zu einer in Mitteleuropa endemischen zoonotischen Krankheit entwickeln könnte, müssen weitere Studien über kompatible Vektoren, mögliche Reservoire und zur Virulenz durchgeführt werden. Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-3295 SN - 0949-8214 VL - 18 SP - 17 EP - 25 ER - TY - JOUR A1 - Böttcher, René A1 - Hoogland, A. Marije A1 - Dits, Natasja A1 - Verhoef, Esther A1 - Kweldam, Charlotte A1 - Waranecki, Piotr A1 - Bangma, Chris H. A1 - van Leenders, Geert J.L.H. A1 - Jenster, Guido T1 - Novel long non-coding RNAs are specific diagnostic and prognostic markers for prostate cancer JF - Oncotarget N2 - Current prostate cancer (PCa) biomarkers such as PSA are not optimal in distinguishing cancer from benign prostate diseases and predicting disease outcome. To discover additional biomarkers, we investigated PCa-specific expression of novel unannotated transcripts. Using the unique probe design of Affymetrix Human Exon Arrays, we identified 334 candidates (EPCATs), of which 15 were validated by RT-PCR. Combined into a diagnostic panel, 11 EPCATs classified 80% of PCa samples correctly, while maintaining 100% specificity. High specificity was confirmed by in situ hybridization for EPCAT4R966 and EPCAT2F176 (SChLAP1) on extensive tissue microarrays. Besides being diagnostic, EPCAT2F176 and EPCAT4R966 showed significant association with pT-stage and were present in PIN lesions. We also found EPCAT2F176 and EPCAT2R709 to be associated with development of metastases and PCa-related death, and EPCAT2F176 to be enriched in lymph node metastases. Functional significance of expression of 9 EPCATs was investigated by siRNA transfection, revealing that knockdown of 5 different EPCATs impaired growth of LNCaP and 22RV1 PCa cells. Only the minority of EPCATs appear to be controlled by androgen receptor or ERG. Although the underlying transcriptional regulation is not fully understood, the novel PCa-associated transcripts are new diagnostic and prognostic markers with functional relevance to prostate cancer growth. KW - long non-coding RNA KW - prostate cancer KW - in situ hybridization KW - exon array KW - biomarker Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-6329 SN - 1949-2553 VL - 6 IS - 6 SP - 4036 EP - 4050 ER - TY - JOUR A1 - Hoogland, A. Marije A1 - Böttcher, René A1 - Verhoef, Esther A1 - Jenster, Guido A1 - van Leenders, Geert J.L.H. T1 - Gene-expression analysis of gleason grade 3 tumor glands embedded in low- and high-risk prostate cancer JF - Oncotarget N2 - The Gleason score (GS) of prostate cancer on diagnostic biopsies is an important parameter for therapeutic decision-making. Biopsy GS under-estimates the actual GS at radical prostatectomy in a significant number of patients due to samplingartifact. The aim of this study was to identify markers that are differentially expressed in Gleason grade 3 (GG3) tumor glands embedded in GS 4 + 3 = 7 and GS 3 + 3 = 6 prostate cancer using laser capture microdissection and RNA sequencing. GG3 tumor glands embedded in nine GS 3 + 3 = 6 and nine GS 4 + 3 = 7 prostate cancers were isolated by laser capture microdissection of frozen radical prostatectomy specimens. After RNA amplification and RNA sequencing, differentially expressed genes in both GG3 components were identified by a 2log fold change > 1.0 and p-value < 0.05. We applied immunohistochemistry on a tissue micro-array representing 481 radical prostatectomy samples for further validation on protein level. A total of 501 genes were up-regulated and 421 down-regulated in GG3 glands embedded in GS 4 + 3 = 7 as compared to GS 3 + 3 = 6 prostate cancer. We selected HELLS, ZIC2 and ZIC5 genes for further validation. ZIC5 mRNA was up-regulated 17 fold (p = 8.4E–07), ZIC2 8 fold (p = 1.3E–05) and HELLS 2 fold (p = 0.006) in GG3 glands derived from GS 4 + 3 = 7. HELLS expression of ≥ 1% occurred in 10% GS < 7, 17% GS 7 and 43% GS >7 prostate cancer (p < 0.001). Using a cut-off of ≥ 1%, protein expression of ZIC5 was present in 28% GS < 7, 43% GS 7 and 57% GS > 7 cancer (p < 0.001). ZIC2 was neither associated with GS nor outcome in our validation set. HELLS was independently predictive for biochemical-recurrence after radical prostatectomy (HR 2.3; CI 1.5–3.6; p < 0.01). In conclusion, HELLS and ZIC5 might be promising candidate markers for selection of biopsy GS 6 prostate cancer being at risk for up-grading at prostatectomy. KW - prostate cancer KW - RNA sequencing KW - laser capture microdissection KW - immunohistochemistry Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-6573 SN - 1949-2553 VL - 7 IS - 25 SP - 37846 EP - 37856 ER - TY - GEN A1 - Tomaschewski, Georg A1 - Ebner, Lothar T1 - Extrakt aus roten Weintrauben - Gewinnung und Einsatz in „Functional Foods“ T2 - Wissenschaftliche Beiträge 2004 N2 - Um die ersten widersprüchlichen Studien über die Wirkung von Rotwein auf Herz-Kreislauf-Erkrankungen vergleichbar zu machen, hat in den 80er Jahren die Weltgesundheitsorganisation (WHO) in vielen Ländern der Erde ein wissenschaftliches Untersuchungsprogramm durchgeführt. Im MONICA-Projekt (World Health Organisation Multinational Monitoring of Trends and Determinants of Cardiovascular Disease) wurden die Ernährungsgewohnheiten und die HK-Mortalität (Herz-Kreislauf Mortalität) in verschiedenen Ländern der Welt verglichen. Die HK-Mortalität nimmt in Europa von Nord nach Süd ab. Als Maß für die Ernährungsgewohnheiten der Bevölkerung wurde der tägliche Verbrauch an Milchfett in Kalorien verglichen und der HK-Mortalität gegenübergestellt. Zu den Ergebnissen wurden von französischen Forschern differenzierte Aussagen getroffen. [1] Aus diesen epidemiologischen Untersuchungen ergibt sich, dass die Häufigkeit der Herz-Kreislauf-Erkrankungen in Europa und selbst innerhalb Frankreichs von Norden nach Süden abnimmt. Auf Grund des täglichen Verzehrs von Milchfett in Frankreich, vergleichbar mit dem in Deutschland, müssten die Franzosen auch die gleiche Häufigkeit an Herz-Kreislauf-Erkrankungen haben. Das ist aber nicht der Fall, die Sterblichkeitsrate ist in Deutschland etwa doppelt so hoch. Allgemein wird das Phänomen von Medizinern und Ernährungsphysiologen als „French Paradoxon“ bezeichnet. Der Nord-Süd-Abfall bei den Herz- Kreislauf-Erkrankungen wird auf den höheren Verzehr von Obst und Gemüse und auf den Genuss von Wein in den südlichen Ländern Europas zurückgeführt. Y1 - 2004 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-4069 SN - 0949-8214 VL - 9 SP - 74 EP - 81 ER - TY - JOUR A1 - Stumper, Nele A1 - Berger, Jörn A1 - Klotsche, Jens A1 - Gedat, Egbert A1 - Hoff, Paula A1 - Schmittat, Gabriela A1 - Burmester, Gerd-Rüdiger A1 - Krönke, Gerhard A1 - Backhaus, Marina A1 - Haugen, Ida Kristin A1 - Ohrndorf, Sarah T1 - To optimise the diagnostic process of rheumatic diseases affecting the hands using fluorescence optical imaging (FOI) JF - RMD Open N2 - Background Accurate and rapid diagnosis of rheumatic diseases is essential for further treatment decision. Different rheumatic diseases present characteristic patterns (image features) in fluorescence optical imaging (FOI). We developed an atlas of FOI image features and tested its ability to differentiate various rheumatic diseases. Methods FOI images from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), connective tissue diseases (CTD) and osteoarthritis (OA) were analysed by two readers blinded for diagnosis and calibrated against each other, using the prima vista mode (PVM) and an automated 5-phase model. Twenty-six different reoccurring typical signal enhancement patterns (features) indicating inflamed joints, nail or skin were defined and all FOI images were scored accordingly. The feature frequency in each patient cohort and phase (PVM, 5-phase) was counted. Contingency tables were created with categorical variable counts and diagnosis using common formulae. Findings Four hundred thirty-eight patients with RA (n=117), PsA (n=110), CTD (n=121) and OA (n=90) were included. Once the data had been categorised, a two-step diagnostic pathway was developed: in the first step, OA was best distinguished from the other diseases with high specificity by five patterns (specificity >0.9, diagnostic OR between 2.34 and 8.24). In a second step, the remaining autoimmune diseases were differentiated from each other by a certain number of features (five for RA, 12 for PsA and four for CTD). Interpretation This was the first study to show that feature analysis in FOI helps to differentiate typical rheumatic diseases from each other, potentially simplifying and speeding up the diagnostic process. Therefore, FOI could be considered an additional component of a wider range of imaging techniques used in rheumatology. Y1 - 2025 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-20698 VL - 11 IS - 3 PB - EULAR ER - TY - JOUR A1 - Gedat, Egbert A1 - Berger, Jörn A1 - Kiesel, Denise A1 - Failli, Vieri A1 - Briel, Andreas A1 - Welker, Pia T1 - Features Found in Indocyanine Green-Based Fluorescence Optical Imaging of Inflammatory Diseases of the Hands JF - Diagnostics N2 - Rheumatologists in Europe and the USA increasingly rely on fluorescence optical imaging (FOI, Xiralite) for the diagnosis of inflammatory diseases. Those include rheumatoid arthritis, psoriatic arthritis, and osteoarthritis, among others. Indocyanine green (ICG)-based FOI allows visualization of impaired microcirculation caused by inflammation in both hands in one examination. Thousands of patients are now documented and most literature focuses on inflammatory arthritides, which affect synovial joints and their related structures, making it a powerful tool in the diagnostic process of early undifferentiated arthritis and rheumatoid arthritis. However, it has become gradually clear that this technique has the potential to go even further than that. FOI allows visualization of other types of tissues. This means that FOI can also support the diagnostic process of vasculopathies, myositis, collagenoses, and other connective tissue diseases. This work summarizes the most prominent imaging features found in FOI examinations of inflammatory diseases, outlines the underlying anatomical structures, and introduces a nomenclature for the features and, thus, supports the idea that this tool is a useful part of the imaging repertoire in rheumatology clinical practice, particularly where other imaging methods are not easily available. KW - optical diagnosis imaging KW - fluorescence optical imaging KW - indocyanine green fluorescence KW - image feature KW - image analysis KW - rheumatoid disease Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-16359 SN - 2075-4418 VL - 12 IS - 8 PB - MDPI ER - TY - CHAP A1 - Rykova, Eugenia A1 - Walther, Mathias ED - Luz de Araujo, Pedro Henrique ED - Baumann, Andreas ED - Gromann, Dagmar ED - Krenn, Brigitte ED - Roth, Benjamin ED - Wiegand, Michael T1 - Linguistic and extralinguistic factors in automatic speech recognition of German atypical speech T2 - Proceedings of the 20th Conference on Natural Language Processing (KONVENS 2024) N2 - Automatic speech recognition (ASR) has been already used in speech and language therapy, including diagnostic tasks and practice exercises for people with aphasia (PWA). The lack of relevant data makes it difficult to evaluate the algorithms’ suitability for German-speaking PWA. For the current project, four open-source ASR models were selected based on their performance on other types of atypical speech, and the details of their evaluation are presented in this paper. The four selected models are generally robust to speakers’ gender and age. The one-word recognition yields better results for words of moderate length. Speech rate should be neither too slow nor too quick for lower error rates both in words and phrases, and the latter should be also of moderate length. Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19915 UR - https://aclanthology.org/2024.konvens-main.36/ SP - 358 EP - 367 PB - Association for Computational Linguistics CY - Wien ER - TY - JOUR A1 - Rothe, Felix A1 - Berger, Jörn A1 - Welker, Pia A1 - Fiebelkorn, Richard A1 - Kupper, Stefan A1 - Kiesel, Denise A1 - Gedat, Egbert A1 - Ohrndorf, Sarah T1 - Fluorescence optical imaging feature selection with machine learning for differential diagnosis of selected rheumatic diseases JF - Frontiers in Medicine N2 - Background and objective: Accurate and fast diagnosis of rheumatic diseases affecting the hands is essential for further treatment decisions. Fluorescence optical imaging (FOI) visualizes inflammation-induced impaired microcirculation by increasing signal intensity, resulting in different image features. This analysis aimed to find specific image features in FOI that might be important for accurately diagnosing different rheumatic diseases. Patients and methods: FOI images of the hands of patients with different types of rheumatic diseases, such as rheumatoid arthritis (RA), osteoarthritis (OA), and connective tissue diseases (CTD), were assessed in a reading of 20 different image features in three phases of the contrast agent dynamics, yielding 60 different features for each patient. The readings were analyzed for mutual differential diagnosis of the three diseases (One-vs-One) and each disease in all data (One-vs-Rest). In the first step, statistical tools and machine-learning-based methods were applied to reveal the importance rankings of the features, that is, to find features that contribute most to the model-based classification. In the second step machine learning with a stepwise increasing number of features was applied, sequentially adding at each step the most crucial remaining feature to extract a minimized subset that yields the highest diagnostic accuracy. Results: In total, n = 605 FOI of both hands were analyzed (n = 235 with RA, n = 229 with OA, and n = 141 with CTD). All classification problems showed maximum accuracy with a reduced set of image features. For RA-vs.-OA, five features were needed for high accuracy. For RA-vs.-CTD ten, OA-vs.-CTD sixteen, RA-vs.-Rest five, OA-vs.-Rest eleven, and CTD-vs-Rest fifteen, features were needed, respectively. For all problems, the final importance ranking of the features with respect to the contrast agent dynamics was determined. Conclusions: With the presented investigations, the set of features in FOI examinations relevant to the differential diagnosis of the selected rheumatic diseases could be remarkably reduced, providing helpful information for the physician. KW - rheumatoid arthritis KW - osteoarthritis KW - connective tissue disease KW - gradient boosting machine KW - forward selection algorithm Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-17922 SN - 2296-858X VL - 10 PB - Frontiers ER - TY - GEN A1 - Gossing, Wilhelm A1 - Radke, Lars A1 - Frohme, Marcus A1 - Biering, Henrik T1 - ECS-Komplex – ein neuer Biomarker bei Wachstumshormonstörungen? T2 - Wissenschaftliche Beiträge 2016 N2 - Störungen im Metabolismus des Wachstumshormons können sich als Wachstumshormonmangel oder -überschuss (Akromegalie) äußern. In beiden Fällen handelt es sich um seltene Krankheiten, die aufwendig behandelt werden müssen, da jeder Patient anders auf seine jeweilige Medikation anspricht. Zur Bestimmung des individuellen Ansprechverhaltens auf die medikamentöse Behandlung wird Insulin-like Growth Factor 1 verwendet, das jedoch als unzuverlässig für die Therapiekontrolle gilt. Um die Diagnostik und Therapie von Wachstumshormonstörungen zu verbessern, wurde in dieser Pilotstudie der Nutzen des neuen potenziellen Biomarkers Elongin B/C-Cullin5-Socs-box Komplex (ECS-Komplex) überprüft. Die fünf Proteine des Komplexes üben zusammen einen negativen Feedback-Mechanismus auf den Wachstumshormonrezeptor aus und regulieren ihn in Abhängigkeit vom Wachstumshormonspiegel im Blut. Für diese Pilotstudie wurden vier Patienten mit Wachstumshormondefizienz und 15 Patienten mit Akromegalie rekrutiert. Die Messung von Unterschieden in der Expression der Gene auf RNA-Ebene in Blutproben der Patienten erlaubt erste Aussagen über deren Eignung als therapeutische Marker für diese Krankheiten. N2 - Growth hormone (GH) dysfunctions can occur as a GH-deficiency (GHD) or an overproduction of GH, leading to acromegaly. Both are rare diseases, which have to be treated for many years before the correct individual dosage is found and a mitigation of symptoms can be achieved. Current medical therapy is determined by the levels of the insulin-like growth factor-1, which is considered to be an unreliable theranostic tool. In order to improve the diagnosis and therapy of patients with GH-dysfunctions, we investigated the benefits of the novel potential biomarker Elongin B/C-Cullin5-Socs-box complex (ECS-complex). Together, these proteins regulate the growth hormone receptor levels according to the blood GH concentration through a negative feedback loop. For this study, we were able to recruit four patients with a GHD and 15 patients with acromegaly. The detected differential expression of the ECS-complex in patients with growth hormone dysfunctions allows for first conclusions about the potential of those proteins as predictive biomarker molecules for individualized therapies. Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-5308 SN - 0949-8214 VL - 20 SP - 23 EP - 29 ER - TY - CHAP A1 - Meyer, Stephan ED - Opper, Janet ED - Rolfes, Vasilija ED - Roth, Phillip H. T1 - „Theorie“ und Praxis des Risikorechts T2 - Chancen und Risiken der Stammzellforschung N2 - Der Beitrag möchte Kernelemente der deutschen und europäischen Dogmatik zum Umgang des Rechts mit ungewissen Rechtsgutgefährdungen interdisziplinär zugänglich machen. Dieser „Theorie“ wird die rechtliche Praxis – in Gestalt von Rechtsetzung und Rechtsprechung – vorgehalten und werden dabei Abweichungen von den Rationalitätsanforderungen der dogmatischen Grundkonzeption identifiziert. Diese Abweichungen führen dazu, dass das Recht – in praktischer Hinsicht – berechtigte Erwartungen an die Intensität des Grundrechtsschutzes von Forschung, Entwicklung und Anwendung neuer Technologien nach einem erratischen Muster verfehlt. Deshalb wird anschließend überlegt, wie mit diesem Befund rechtspolitisch umzugehen ist. Der Umstand, dass es sich bei der Stammzellenforschung gerade um ein Gebiet der Medizin handelt, kann die Aufrechterhaltung einer innovationsfreundlichen politischen Haltung begünstigen. Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-17093 UR - https://elibrary.bwv-verlag.de/book/99.105025/9783830541530 SN - 978-3-8305-4153-0 SP - 279 EP - 292 PB - Berliner Wissenschafts-Verlag CY - Berlin ER - TY - THES A1 - Körner, Benjamin T1 - Human-Robot-Interaction - Evaluation, Konzeption und Umsetzung einer Anwendung für den NAO-Roboter der Firma Aldebaran Robotics zur Förderung autistischer Kinder N2 - Entwicklung einer prototypischen Anwendung für den NAO-Roboter der Firma Aldebaran Robotics, die therapeutisch unterstützend bei der Förderung der sozialen Interaktion mit autistischen Kindern eingesetzt werden kann. KW - NAO KW - Roboter KW - human-robot interaction KW - Autismus KW - socially assistive robotics Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-4423 ER - TY - GEN A1 - Bortz, Birgit A1 - Marczok, Stefanie A1 - Pospisil, Heike T1 - Genomweite Identifizierung von chromosomalen Bruchpunkten bei Tumoren unterschiedlicher Gewebe T2 - Wissenschaftliche Beiträge 2016 N2 - Aufgrund der jährlich ansteigenden Anzahl an Krebsneuerkrankungen und der tödlichen Verläufe von malignen Tumoren gewinnt die vollständige Aufklärung der Tumorgenese und -progression immer mehr an Bedeutung. Für diese können Untersuchungen zu Bruchpunkten, die eine Kopienzahlvariation (CNV) in Krebsgenomen bewirken, genutzt werden. Es wurde eine Pipeline entwickelt, die in der Lage ist, CNVs, Bruchpunktregionen (BPRs) und Gene genomweit mit Hilfe von SNP-Array-Daten zu detektieren. Dazu wurden 2.820 Tumorproben aus 8 Tumorentitäten untersucht und mit 432 Proben aus gesundem Gewebe verglichen. In den Tumorproben wurden vierfach mehr BPRs detektiert, wobei unter 5 % der Gene in den Normalproben betroffen sind. Wir identifizierten 31 hochspezifische BPRs. Die am häufigsten vorkommende Variation umschließt das Gen KIAA0513, welches in Verbindung mit der Apoptose steht. Anhand der hier entwickelten Pipeline können erste Einblicke in CNV- und Bruchpunkt-Muster in Tumorgenomen gewonnen werden, die zu einem verbesserten Verständnis der Tumorgenese und somit zu einer verbesserten Diagnostik und Therapie von Krebserkrankungen führen können. N2 - The number of new cancer cases and the deadly courses of malignant tumors are still rising. An entire clarification of tumorigenesis and progression is required for better diagnostics and therapies. Here, we present an analysis of genomic breakpoint patterns, which might cause copy number variations (CNVs) in cancer genomes. Thus, a pipeline was developed which uses SNP array data for the genome-wide detection of CNVs, breakpoint regions (BPRs) and genes. 2,820 tumor samples from eight tumor entities were analyzed and compared with 432 samples from healthy tissue. Four times more BPRs were detected in the tumor samples and only less than 5 % of the affected genes were found to be involved in healthy tissues. We identified 31 highly specific BPRs. The most commonly occurring variation found in our study encloses the KIAA0513 gene, which is associated with apoptosis. Based on these results, new insights in tumorigenesis are expected. Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-5286 SN - 0949-8214 VL - 20 SP - 7 EP - 14 ER - TY - JOUR A1 - Ummanni, Ramesh A1 - Mundt, Frederike A1 - Pospisil, Heike A1 - Venz, Simone A1 - Scharf, Christian A1 - Barett, Christine A1 - Fälth, Maria A1 - Köllermann, Jens A1 - Walther, Reinhard A1 - Schlomm, Thorsten A1 - Sauter, Guido A1 - Bokemeyer, Carsten A1 - Sültmann, Holger A1 - Schuppert, Andreas A1 - Brümmendorf, Tim H. A1 - Balabanov, Stefan T1 - Identification of Clinically Relevant Protein Targets in Prostate Cancer with 2D-DIGE Coupled Mass Spectrometry and Systems Biology Network Platform JF - PLoS ONE N2 - Prostate cancer (PCa) is the most common type of cancer found in men and among the leading causes of cancer death in the western world. In the present study, we compared the individual protein expression patterns from histologically characterized PCa and the surrounding benign tissue obtained by manual micro dissection using highly sensitive two-dimensional differential gel electrophoresis (2D-DIGE) coupled with mass spectrometry. Proteomic data revealed 118 protein spots to be differentially expressed in cancer (n = 24) compared to benign (n = 21) prostate tissue. These spots were analysed by MALDI-TOF-MS/MS and 79 different proteins were identified. Using principal component analysis we could clearly separate tumor and normal tissue and two distinct tumor groups based on the protein expression pattern. By using a systems biology approach, we could map many of these proteins both into major pathways involved in PCa progression as well as into a group of potential diagnostic and/or prognostic markers. Due to complexity of the highly interconnected shortest pathway network, the functional sub networks revealed some of the potential candidate biomarker proteins for further validation. By using a systems biology approach, our study revealed novel proteins and molecular networks with altered expression in PCa. Further functional validation of individual proteins is ongoing and might provide new insights in PCa progression potentially leading to the design of novel diagnostic and therapeutic strategies. Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-6432 SN - 1932-6203 VL - 6 IS - 2 ER - TY - JOUR A1 - Standfuß, Christoph A1 - Pospisil, Heike A1 - Klein, Andreas T1 - SNP microarray analyses reveal copy number alterations and progressive genome reorganization during tumor development in SVT/t driven mice breast cancer JF - BMC Cancer N2 - Tumor development is known to be a stepwise process involving dynamic changes that affect cellular integrity and cellular behavior. This complex interaction between genomic organization and gene, as well as protein expression is not yet fully understood. Tumor characterization by gene expression analyses is not sufficient, since expression levels are only available as a snapshot of the cell status. So far, research has mainly focused on gene expression profiling or alterations in oncogenes, even though DNA microarray platforms would allow for high-throughput analyses of copy number alterations (CNAs). KW - breast cancer KW - genome reorganization KW - copy number alteration KW - CNV KW - fragile site Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-6414 SN - 1471-2407 VL - 12 IS - 380 ER - TY - JOUR A1 - Hannemann, Juliane A1 - Meyer-Staeckling, Sönke A1 - Kemming, Dirk A1 - Alpers, Iris A1 - Joosse, Simon A. A1 - Pospisil, Heike A1 - Kurtz, Stefan A1 - Görndt, Jennifer A1 - Püschel, Klaus A1 - Riethdorf, Sabine A1 - Pantel, Klaus A1 - Brandt, Burkhard T1 - Quantitative High-Resolution Genomic Analysis of Single Cancer Cells JF - PLoS ONE N2 - During cancer progression, specific genomic aberrations arise that can determine the scope of the disease and can be used as predictive or prognostic markers. The detection of specific gene amplifications or deletions in single blood-borne or disseminated tumour cells that may give rise to the development of metastases is of great clinical interest but technically challenging. In this study, we present a method for quantitative high-resolution genomic analysis of single cells. Cells were isolated under permanent microscopic control followed by high-fidelity whole genome amplification and subsequent analyses by fine tiling array-CGH and qPCR. The assay was applied to single breast cancer cells to analyze the chromosomal region centred by the therapeutical relevant EGFR gene. This method allows precise quantitative analysis of copy number variations in single cell diagnostics. Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-6426 SN - 1932-6203 VL - 6 IS - 11 ER - TY - GEN A1 - Standfuß, Christoph A1 - Klein, Andreas A1 - Pospisil, Heike T1 - Einfluss von Kopienzahlvariationen auf die Tumorentwicklung T2 - Wissenschaftliche Beiträge 2013 N2 - Tumorentstehung ist ein Prozess, bei dem die Abläufe innerhalb der Zelle schrittweise verändert werden. Die vielfältigen Interaktionen bei der Tumorentstehung sind jedoch bislang nicht vollständig erforscht. Bisher wurden vorwiegend Genexpressionsanalysen genutzt, die jedoch nur eine Zeitaufnahme aller Genexpressionen innerhalb der Zelle darstellen und somit allein nicht ausreichend zur Charakterisierung eines Tumors. Wir haben mithilfe von Affymetrix Mouse Diversity Genotyping Microarrays Mausbrustdrüsengewebe entsprechend unserem Dreistufen-Mausmodell analysiert und die Kopienzahländerungen berechnet. Wir fanden eine zunehmende stufenweise Änderung von den transgenen zu den Tumorproben. Die Berechnung von chromosomalen Segmenten mit gleicher Kopienzahl zeigte deutliche Fragmentmuster. Unsere Analysen zeigen, dass die Tumorentstehung ein schrittweiser Prozess ist, der sowohl durch Amplifikationen als auch Deletionen chromosomaler Abschnitte definiert ist. Wir fanden charakteristisch konservierte Fragmentierungsmuster und individuelle Unterschiede welche zur Tumorgenese beitragen. Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-3435 SN - 0949-8214 VL - 17 SP - 27 EP - 30 ER - TY - JOUR A1 - Siptroth, Julienne A1 - Moskalenko, Olga A1 - Krumbiegel, Carsten A1 - Ackermann, Jörg A1 - Koch, Ina A1 - Pospisil, Heike T1 - Variation of butyrate production in the gut microbiome in type 2 diabetes patients JF - International Microbiology N2 - Background Diabetes mellitus type 2 is a common disease that poses a challenge to the healthcare system. The disease is very often diagnosed late. A better understanding of the relationship between the gut microbiome and type 2 diabetes can support early detection and form an approach for therapies. Microbiome analysis offers a potential opportunity to find markers for this disease. Next-generation sequencing methods can be used to identify the bacteria present in the stool sample and to generate a microbiome profile through an analysis pipeline. Statistical analysis, e.g., using Student’s t-test, allows the identification of significant differences. The investigations are not only focused on single bacteria, but on the determination of a comprehensive profile. Also, the consideration of the functional microbiome is included in the analyses. The dataset is not from a clinical survey, but very extensive. Results By examining 946 microbiome profiles of diabetes mellitus type 2 sufferers (272) and healthy control persons (674), a large number of significant genera (25) are revealed. It is possible to identify a large profile for type 2 diabetes disease. Furthermore, it is shown that the diversity of bacteria per taxonomic level in the group of persons with diabetes mellitus type 2 is significantly reduced compared to a healthy control group. In addition, six pathways are determined to be significant for type 2 diabetes describing the fermentation to butyrate. These parameters tend to have high potential for disease detection. Conclusions With this investigation of the gut microbiome of persons with diabetes type 2 disease, we present significant bacteria and pathways characteristic of this disease. KW - NGS KW - type 2 diabetes KW - gut KW - butyrate KW - statistical analysis Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-17802 VL - 26 SP - 601 EP - 610 PB - Springer Nature ER - TY - CHAP A1 - Welzel, Felix A1 - Hauschultz, Mike Thomas A1 - Friedo, Maria Helene A1 - Just, Verena A1 - Richetta, Maria A1 - Foitzik, Andreas T1 - Concept for a Portable Measuring Device for the Quantitative Detection of Legionella T2 - Open Conference Proceedings N2 - According to the drinking water regulation, drinking water systems must be tested for harmful contamination at specified intervals. To meet the legal requirements and save costs and time, a portable analysis method is to be developed. For this purpose, a concept study was conducted. It describes a portable measuring device for the quantitative detection of legionella using real-time PCR. The study includes the construction elements and conditions that are necessary for the collection, processing, and evaluation of the sample. It was found that commercially available PCR systems do not meet the size requirements and can only be represented by an in-house development. In addition, a microfluidic system must be developed that is designed for one-time use and low production cost. Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-17616 VL - 2 SP - 15 EP - 17 PB - TIB Open Publishing ER - TY - CHAP A1 - Strauch, Jessica A1 - Wellmann, Martin A1 - Friedo, Maria Helene A1 - Welzel, Felix A1 - Foitzik, Andreas T1 - Miniaturisierung einer Smartwatch für Hautfeuchtesensorik T1 - Miniaturisation of a smartwatch for skin moisture sensing T2 - Open Conference Proceedings N2 - Das Ziel des Projekts ist, den Zustand der Haut von Neurodermitis-Patienten bei verschiedenen Bedingungen und Belastungszuständen erfassen zu können. Dazu wurde ein Prototyp gefertigt, in den ein Mikrosensor zur Bestimmung der Umgebungsfeuchtigkeit, ein Controller mit Bluetooth zur Datenübertragung, sowie ein Lithium-Akku zur Energieversorgung verbaut wurden. N2 - The aim of the project is to be able to record the condition of the skin of neurodermatitis patients under different conditions and stress states. For this purpose, a prototype was manufactured in which a microsensor for determining the ambient humidity, a controller with Bluetooth for data transmission, and a lithium battery for power supply were integrated. Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-17653 VL - 2 SP - 193 EP - 195 PB - TIB Open Publishing ER -