TY  - JOUR
A1  - Gröbner, Susanne N.
A1  - Worst, Barbara C.
A1  - Weischenfeldt, Joachim
A1  - Buchhalter, Ivo
A1  - Kleinheinz, Kortine
A1  - Rudneva, Vasilisa A.
A1  - Johann, Pascal D.
A1  - Balasubramanian, Gnana Prakash
A1  - Segura-Wang, Maia
A1  - Brabetz, Sebastian
A1  - Bender, Sebastian
A1  - Hutter, Barbara
A1  - Sturm, Dominik
A1  - Pfaff, Elke
A1  - Hübschmann, Daniel
A1  - Zipprich, Gideon
A1  - Heinold, Michael
A1  - Eils, Jürgen
A1  - Lawerenz, Christian
A1  - Erkek, Serap
A1  - Lambo, Sander
A1  - Waszak, Sebastian
A1  - Blattmann, Claudia
A1  - Borkhardt, Arndt
A1  - Kuhlen, Michaela
A1  - Eggert, Angelika
A1  - Fulda, Simone
A1  - Gessler, Manfred
A1  - Wegert, Jenny
A1  - Kappler, Roland
A1  - Baumhoer, Daniel
A1  - Stefan, Burdach
A1  - Kirschner-Schwabe, Renate
A1  - Kontny, Udo
A1  - Kulozik, Andreas E.
A1  - Lohmann, Dietmar
A1  - Hettmer, Simone
A1  - Eckert, Cornelia
A1  - Bielack, Stefan
A1  - Nathrath, Michaela
A1  - Niemeyer, Charlotte
A1  - Richter, Günther H.
A1  - Schulte, Johannes
A1  - Siebert, Reiner
A1  - Westermann, Frank
A1  - Molenaar, Jan J.
A1  - Vassal, Gilles
A1  - Witt, Hendrik
A1  - Burkhardt, Birgit
A1  - Kratz, Christian P.
A1  - Witt, Olaf
A1  - van Tilburg, Cornelis M.
A1  - Kramm, Christof M.
A1  - Fleischhack, Gudrun
A1  - Dirksen, Uta
A1  - Rutkowski, Stefan
A1  - Frühwald, Michael
A1  - Hoff, Katja von
A1  - Wolf, Stephan
A1  - Klingebeil, Thomas
A1  - Koscielniak, Ewa
A1  - Landgraf, Pablo
A1  - Koster, Jan
A1  - Resnick, Adam C.
A1  - Zhang, Jinghui
A1  - Liu, Yanling
A1  - Zhou, Xin
A1  - Waanders, Angela J.
A1  - Zwijnenburg, Danny A.
A1  - Raman, Pichai
A1  - Brors, Benedikt
A1  - Weber, Ursula D.
A1  - Northcott, Paul A.
A1  - Pajtler, Kristian W.
A1  - Kool, Marcel
A1  - Piro, Rosario M.
A1  - Korbel, Jan O.
A1  - Schlesner, Matthias
A1  - Eils, Roland
A1  - Jones, David T. W.
A1  - Lichter, Peter
A1  - Chavez, Lukas
A1  - Zapatka, Marc
A1  - Pfister, Stefan M.
T1  - The landscape of genomic alterations across childhood cancers
JF  - Nature
N2  - Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7–8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.
KW  - cancer genomics
KW  - oncogenesis
KW  - paediatric cancer
KW  - predictive markers
KW  - translational research
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229579
VL  - 555
ER  - 
TY  - JOUR
A1  - Hebestreit, Helge
A1  - Zeidler, Cornelia
A1  - Schippers, Christopher
A1  - de Zwaan, Martina
A1  - Deckert, Jürgen
A1  - Heuschmann, Peter
A1  - Krauth, Christian
A1  - Bullinger, Monika
A1  - Berger, Alexandra
A1  - Berneburg, Mark
A1  - Brandstetter, Lilly
A1  - Deibele, Anna
A1  - Dieris-Hirche, Jan
A1  - Graessner, Holm
A1  - Gündel, Harald
A1  - Herpertz, Stephan
A1  - Heuft, Gereon
A1  - Lapstich, Anne-Marie
A1  - Lücke, Thomas
A1  - Maisch, Tim
A1  - Mundlos, Christine
A1  - Petermann-Meyer, Andrea
A1  - Müller, Susanne
A1  - Ott, Stephan
A1  - Pfister, Lisa
A1  - Quitmann, Julia
A1  - Romanos, Marcel
A1  - Rutsch, Frank
A1  - Schaubert, Kristina
A1  - Schubert, Katharina
A1  - Schulz, Jörg B.
A1  - Schweiger, Susann
A1  - Tüscher, Oliver
A1  - Ungethüm, Kathrin
A1  - Wagner, Thomas O. F.
A1  - Haas, Kirsten
T1  - Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study
JF  - Orphanet Journal of Rare Diseases
N2  - Background
In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process.
Study design
This multi-center, prospective controlled study has a two-phase cohort design.
Methods
Two cohorts of 682 patients each are sequentially recruited from 11 university-based German Centers for Rare Diseases (CRD): the standard care cohort (control, somatic expertise only) and the innovative care cohort (experimental, combined somatic and mental health expertise). Individuals aged 12 years and older presenting with symptoms and signs which are not explained by current diagnoses will be included. Data will be collected prior to the first visit to the CRD’s outpatient clinic (T0), at the first visit (T1) and 12 months thereafter (T2).
Outcomes
Primary outcome is the percentage of patients with one or more confirmed diagnoses covering the symptomatic spectrum presented. Sample size is calculated to detect a 10 percent increase from 30% in standard care to 40% in the innovative dual expert cohort. Secondary outcomes are (a) time to diagnosis/diagnoses explaining the symptomatology; (b) proportion of patients successfully referred from CRD to standard care; (c) costs of diagnosis including incremental cost effectiveness ratios; (d) predictive value of screening instruments administered at T0 to identify patients with mental disorders; (e) patients’ quality of life and evaluation of care; and f) physicians’ satisfaction with the innovative care approach.
Conclusions
This is the first multi-center study to investigate the effects of a mental health specialist working in tandem with a somatic expert physician in CRDs. If this innovative approach proves successful, it will be made available on a larger scale nationally and promoted internationally. In the best case, ZSE-DUO can significantly shorten the time to diagnosis for a suspected rare disease.
KW  - rare diseases
KW  - multi‑center cohort study
KW  - dual guidance
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300440
VL  - 17
IS  - 1
ER  - 
TY  - JOUR
A1  - Wienrich, Carolin
A1  - Carolus, Astrid
A1  - Markus, André
A1  - Augustin, Yannik
A1  - Pfister, Jan
A1  - Hotho, Andreas
T1  - Long-term effects of perceived friendship with intelligent voice assistants on usage behavior, user experience, and social perceptions
JF  - Computers
N2  - Social patterns and roles can develop when users talk to intelligent voice assistants (IVAs) daily. The current study investigates whether users assign different roles to devices and how this affects their usage behavior, user experience, and social perceptions. Since social roles take time to establish, we equipped 106 participants with Alexa or Google assistants and some smart home devices and observed their interactions for nine months. We analyzed diverse subjective (questionnaire) and objective data (interaction data). By combining social science and data science analyses, we identified two distinct clusters—users who assigned a friendship role to IVAs over time and users who did not. Interestingly, these clusters exhibited significant differences in their usage behavior, user experience, and social perceptions of the devices. For example, participants who assigned a role to IVAs attributed more friendship to them used them more frequently, reported more enjoyment during interactions, and perceived more empathy for IVAs. In addition, these users had distinct personal requirements, for example, they reported more loneliness. This study provides valuable insights into the role-specific effects and consequences of voice assistants. Recent developments in conversational language models such as ChatGPT suggest that the findings of this study could make an important contribution to the design of dialogic human–AI interactions.
KW  - intelligent voice assistant
KW  - smart speaker
KW  - social relationship
KW  - social role
KW  - long-term analysis
KW  - social interaction
KW  - human–computer interaction
KW  - anthropomorphism
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313552
SN  - 2073-431X
VL  - 12
IS  - 4
ER  - 
TY  - JOUR
A1  - Weigel, Tobias
A1  - Schmitz, Tobias
A1  - Pfister, Tobias
A1  - Gaetzner, Sabine
A1  - Jannasch, Maren
A1  - Al-Hijailan, Reem
A1  - Schürlein, Sebastian
A1  - Suliman, Salwa
A1  - Mustafa, Kamal
A1  - Hansmann, Jan
T1  - A three-dimensional hybrid pacemaker electrode seamlessly integrates into engineered, functional human cardiac tissue in vitro
JF  - Scientific Reports
N2  - Pacemaker systems are an essential tool for the treatment of cardiovascular diseases. However, the immune system’s natural response to a foreign body results in the encapsulation of a pacemaker electrode and an impaired energy efficiency by increasing the excitation threshold. The integration of the electrode into the tissue is affected by implant properties such as size, mechanical flexibility, shape, and dimensionality. Three-dimensional, tissue-like electrode scaffolds render an alternative to currently used planar metal electrodes. Based on a modified electrospinning process and a high temperature treatment, a conductive, porous fiber scaffold was fabricated. The electrical and immunological properties of this 3D electrode were compared to 2D TiN electrodes. An increased surface of the fiber electrode compared to the planar 2D electrode, showed an enhanced electrical performance. Moreover, the migration of cells into the 3D construct was observed and a lower inflammatory response was induced. After early and late in vivo host response evaluation subcutaneously, the 3D fiber scaffold showed no adverse foreign body response. By embedding the 3D fiber scaffold in human cardiomyocytes, a tissue-electrode hybrid was generated that facilitates a high regenerative capacity and a low risk of fibrosis. This hybrid was implanted onto a spontaneously beating, tissue-engineered human cardiac patch to investigate if a seamless electronic-tissue interface is generated. The fusion of this hybrid electrode with a cardiac patch resulted in a mechanical stable and electrical excitable unit. Thereby, the feasibility of a seamless tissue-electrode interface was proven.
KW  - biomedical materials
KW  - cardiac device therapy
KW  - hybrid pacemaker
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177368
VL  - 8
IS  - 14545
ER  -