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Funded Projects in the Start-up Fund Medical Research

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Contacts

anschubfonds.medizin@uni-bielefeld.de

Dr. Rebecca Förster
Consultant for Research and Career Development
Phone: +49 521 106-67872

Bettina Janzen
Assistance Research and Career Development Unit
Phone.: +49 521 106-67896

The aim of the funded research projects is to prepare applications for third-party funding in thematic areas of the two research priorities "Brain - Impairment - Participation" and "Intelligent Systems - Assistance-Interprofessional Networking" as well as the two perspective fields "Microbial Diversity in the Human Habitat" and "Data Science for Medical Care".

Eight projects were selected for funding in the second round of calls for proposals from the Start-up Fund Medical Research; three projects in the call for early-career scientists.

Projects of the first funding line of the second call

Beteiligte:

  • PD Dr. rer. nat. Max Töpper (Protestant Hospital of the Bethel Foundation),
  • Univ.-Prof. Dr. med. Wolf-Rüdiger Schäbitz (Protestant Hospital of the Bethel Foundation),
  • Dr. med. Frédéric Zuhorn (Protestant Hospital of the Bethel Foundation),
  • Prof. Dr. phil. Gernot Horstmann (Faculty for Psychology and Sport Science, Bielefeld University),
  • Dr. rer. nat. Kim Austerschmidt (Faculty for Psychology and Sport Science, Bielefeld University),
  • Dr. med. Michael Klemm (Praxisgemeinschaft Wehler, Menzel, Klemm und Partner)

Abstract:
Neither in legal regulations nor in official guidelines for driving fitness, there are clear recommendations as to when driving is possible or permitted again after stroke. For that reason, we plan to examine practical driving skills of 20 stroke patients and 20 healthy drivers in a longitudinal on‐road study. Patients with stroke in the supply area of the arteria cerebri media are being examined twice, two months after the incident (after rehabilitation) and six months after the incident. For healthy control subjects, likewise two practical driving sessions are planned four months apart. Practical driving sessions are accompanied and evaluated by a driving instructor and an approved expert on fitness to drive. In addition, drivingrelevant cognitive, sensory, and motor variables are collected in both assessments. Twelve months after the second driving session, a telephone catamnesis is planned to collect data about accidents that may have occurred in the meantime. The study will help to investigate whether and to what extent driving skills are limited after stroke and may improve in the following four months. In addition, we examine whether and to what extent driving‐relevant cognitive, sensory, and motor predictors of practical driving behavior are associated with driving skills and the improvement of driving skills over time. Catamnesis data will provide information on the extent to which patients' accident frequency is increased in the 12 months following study participation and can be predicted by the combination of cognitive, sensory, and motor variables.

Beteiligte:

  • Dr. rer. nat. Julia Siemann (Protestant Hospital of the Bethel Foundation),
  • Prof. Dr. Johanna Kißler (Faculty for Psychology and Sport Science, Bielefeld University)

Abstract:
Dysfunctional emotion regulation is a transdiagnostic feature of mental disorders in children, adoles-cents and adults and is therefore of great interest in clinical research. Emotional reactivity as well as associated brain maturation processes reach their peak in adolescence. Dysfunctional emotion reg-ulation is an overarching part of various psychiatric syndromes across the lifespan, often associated with recurrent hospitalizations that are a strain on both the sufferer and the health care system. Such inpatient experiences are neither conducive for the everyday transfer of the measures developed there, nor do they lead to any relief on the part of the payers, treatment providers or patients. This research project aims to optimize these stressful factors by teaching patients (1) multimodal innovative treatment measures during their stay. These consist of (2) stimulation of the brain with a very weak electrical current (transcranial direct current stimulation = tDCS), during which the patients (3) undergo a neuropsychological training in emotion regulation. The focus is on emotional pro-cessing, emotion regulation and its brain-physiological correlates as well as symptom severity before versus after treatment (pre-post-treatment comparison), transfer effects of the improvements on eve-ryday life, and the acceptance of this innovative therapy method among patients, relatives and pro-fessionals. In addition, brain activity parameters (fMRI activation and connectivity thereof) will be collected, which will be used in a subsequent study to determine predictors (by means of classifica-tion) for the success of the treatment. This project aims at objectively assessing the treatment success by behavioral, neuropsychological as well as neuronal parameters in patients with neuropsychiatric impairments over the life span (in-cluding underage and adult patients). Thus, the present research project shall be a basis for future multicenter effectiveness studies (DFG project) in the field of emotion regulation in children, adoles-cents and adults. Finally, the research project seeks to initiate further collaborative projects that will develop innovative treatment approaches in the context of the patients' lifes in order to improve their participation.

Beteiligte:

  • Dr.-Ing. Anna-Lisa Vollmer (Medical School EWL, Bielefeld University),
  • Prof. Dr. med. Michael Siniatchkin (Protestant Hospital of the Bethel Foundation),
  • Prof. Dr. med. Winfried Barthlen (Protestant Hospital of the Bethel Foundation)

Abstract:
Physiotherapy is important in children after trauma or surgery in order to prevent pneumonia, cardiovascular impairment and/or constraint joints as well as in therapy of children with depressive disorder. However, experienced pediatric physiotherapists are scarce and expensive. In this study we want to deploy humanoid robots that adopt typical movements and motivation tasks to support physiotherapists in mobilizing children on the pediatric ward and in an ambulatory setting. Robots are especially suited for this task because children are generally positive about robots and their embodiment is beneficial for demonstrating movement exercises and for exerting influence on motivation and compliance. Their transfer, however, hinges on their integration into clinical and ambulatory everyday practice and routines, and their acceptance, the compliance, and the commitment of children, parents, and medical caregivers. In the mid‐term, we aim to evaluate their efficiency by validated instruments and scoring systems. The expected findings of the proposed project will provide a basis for further funding by national institutions to investigate the efficiency of robots in mobilization and rehabilitation of normal children as well as children with disabilities.

Beteiligte:

  • Univ.-Prof. Dr. med. Dr. rer. nat. Holger Sudhoff (Klinikum Bielefeld),
  • Dr. rer. nat. Felix Oppel (Klinikum Bielefeld),
  • Prof. Dr. med. Matthias Simon (Protestant Hospital of the Bethel Foundation)

Abstract:
Vestibular Schwannomas (VSs) and Meningiomas (MGs) are tumor diseases in the head and neck area, brain or spinal cord. They share a common subtype deficient for the tumor suppressor NF2 and have a similar pathogenesis. Despite their predominantly benign nature, they can severely damage the brain and structures in the head and neck area due to their location. This can compromise vital functions like food uptake, speech and hearing or lead to metal impairment. Surgical treatment of VSs can further cause paralysis of the facial nerve and hearing loss, whereas excision of MGs can result in brain or spinal cord damage causing neurological problems, seizures, and paralysis of the peripheral limbs. This way, VS and MG can strongly reduce life quality of affected patients and their participation in society. In our study we aim to test molecular‐targeted drugs that specifically inhibit cell signaling in primary VS and MG cells to create new treatment options. This should enable a reduction of tumor size before surgery in order to minimize damage from the tumor removal procedure. So far, no drug treatment options against VS and MG exist in clinics. In order to stand out from previous studies in this field, we will focus on finding synergistic drug combinations that can target VS and MG cells much more effectively than single drugs. Moreover, we will separately analyze cells from female and male patients to reveal sex‐specific differences in drug vulnerabilities. MGs are twice as common in females when compared to males. Altogether, we are confident that our alliance of the departments of otolaryngology and neurosurgery can find new drug targeting strategies against VS and MG to prepare subsequent clinical studies that should improve patients’ life quality and ability to participate in society.

Beteiligte:

  • Prof. Dr. Thomas Beblo (Protestant Hospital of the Bethel Foundation),
  • Dr. Benjamin Iffland (Faculty for Psychology and Sport Science, Bielefeld University),
  • Prof. Dr. med. Michael Siniatchkin (Protestant Hospital of the Bethel Foundation),
  • Dr. Hanna Kley (Faculty for Psychology and Sport Science, Bielefeld University)

Abstract
Depressive disorders are usually accompanied by cognitive impairments, such as attention problems. At the brain level, associated abnormalities in basic activity are evident. Since these impairments have negative effects on the treatment and the participation of the patients in occupational and social activities, there are some attempts to treat them with established neuropsychological therapy methods. Although mindfulness‐based practices are known to have a positive impact on cognitive functioning, in addition to positively affecting other depressive symptoms, mindfulness‐based practices have not yet been tested against established neuropsychological treatments in depressed patients. Given the broad effects of mindfulness‐based therapy, it would already be a success if the effects of this therapy were not inferior to an established neuropsychological training program. Therefore, with this pilot study, we address the question of whether mindfulness‐based training is at least not significantly inferior to an established training program. In order to exclude age‐correlated pathological brain processes, we focus on young patients between 16 and 21 years with a depressive episode. They will be randomized to two treatment arms: They will receive either "Rehacom®", a proven PC‐based cognitive training program, or a modified version of "Mindfulness‐Based Cognitive Therapy (MBCT)", a mindfulness‐based therapeutic procedure for depressive patients. In both cases, the patients are examined neurophysiologically (BRAIN), neuropsychologically and with regard to further depressive symptoms (IMPAIRMENT) and everyday functionality (PARTICIPATION) before randomization and after implementation of the four‐week intervention.

Projects of the second funding line ("Early-career Scientists") of the second call

Beteiligte:

  • Dr. med. Isabell Greeve (Protestant Hospital of the Bethel Foundation),
  • Dr. rer. nat. Julia Hofhuis (Medical School EWL, Bielefeld University),
  • Dr. rer. nat. Matthias Plessner (Medical School EWL, Bielefeld University)

Abstract
Aquaporin 4 (AQP4), a water‐selective membrane channel expressed mainly in astrocyte processes at the blood‐brain barrier, is the target structure for autoantibodies in neuromyelitis optica spectrum diseases (NMOSD). These autoantibodies cause inflammatory diseases of the central nervous system (CNS) and elicit a clinical picture that is difficult to distinguish from other chronic inflammatory CNS diseases, such as multiple sclerosis (MS). AQP4 is expressed in various isoforms, of which one is generated by Functional Translational Readthrough (FTR) – as codiscovered by the applicant. All isoforms are involved in the formation of clusters, which are prerequisites for functional water transport as well as autoantibody binding. In the proposed project, we will for the first time investigate the disease relevance of FTR, also with regard to sexspecific expression and pathogenicity, using the elongated AQP4 isoforms (AQP4x). We will analyze the function of AQP4x in aggregation of isoforms and binding of autoantibodies to provide the basis for more sensitive and targeted diagnostics and therapy.

Beteiligte:

  • Dr. rer. nat. Oliver Dräger (Medical School EWL, Bielefeld University)
  • Dr. rer. nat. Beatrice Windmöller (Medical School EWL, Bielefeld University)
  • PD Dr. med. Wilfried Witte (Protestant Hospital of the Bethel Foundation)

Abstract
Migraine is a common neurovascular disorder with complex molecular mechanisms and a variety of genetic backgrounds including a loss of function mutation in TWIK‐related spinal cord potassium channel (TRESK). While prevalences in childhood are similar in both sexes, migraine incidences increase in women with rising age affecting females three times more often than men. There is evidence that this disparity in men and women suffering from migraine may be mediated by sex hormones, which were shown to affect the excitability and sensitization of trigeminal nociceptors by modulating the transient receptor potential vanilloid 1 (TRPV1) receptor. This receptor was further shown to be influenced by the inhibition of TRESK, leading to the activation of TRPV1 and subsequent higher levels of calcitonin generelated peptide (CGRP), which is a central mediater of migraine pathophysiology. As animal models are ethically questionable and experimental results are not perfectly transferable to humans, induced pluripotent stem cells (iPSCs) derived from patients are state‐of‐the‐art technique for investigating pathophysiology of different diseases. In the proposed project we aim to establish a cohort of migraine patient‐derived iPSCs and matched controls in cooperation with Priv.‐Doz. Dr. Witte (Department of Anesthesiology, intensive care, emergency medicine, transfusion medicine and pain therapy, EvKB, Bielefeld, Germany). iPSCs will be used to generate patient‐specific nociceptive neurons that enable the analysis of sex‐specific differences in migraine pathology with focus on TRESK‐TRPV1 signaling.

Beteiligte:

  • Dr. rer. nat. Kathrin Hermenau (Protestant Hospital of the Bethel Foundation),
  • Dr.-Ing. Birte Richter (Medical School EWL, Bielefeld University)

Abstract
For adolescents as "digital natives," the smartphone represents an essential and important daily companion. However, this has barely been used in psychotherapy with adolescents so far, although digital programs could take over a bridging function between psychotherapeutic sessions and the adolescents' everyday life and thus improve the success of the therapy. To fill this gap, we developed the transdiagnostic therapy‐accompanying app RADIUS FLEX. After its implementation in inpatient psychotherapy, we would now like to further develop the program for use in the outpatient setting. Through intelligent analysis and feedback systems, therapists will be supported in assessing symptom progression and risks of suicidality. In a feasibility study, we plan to evaluate the use of the supporting digital program in outpatient psychotherapy with regard to use, acceptance, and satisfaction, and to investigate the perceived benefits with regard to patient‐therapist relationship, everyday functionality, self‐efficacy, and symptom reduction. In 40 therapies, therapists will use RADUIS FLEX in outpatient psychotherapy with adolescents after extensive training. Therapists and patients will be interviewed at the beginning of therapy, at the end, and 3 months later. This allows a participatory approach for possible further development of the app.

Six projects were selected for funding in the first round of calls for proposals from the Start-up Fund Medical Research.

Projects of the first call

Participants:

  • Prof. Dr. Christiane Fuchs (Fakultät für Wirtschaftswissenschaften, Universität Bielefeld),
  • Prof. Dr. Sebastian Rehberg (Evangelisches Klinikum Bethel),
  • Prof. Dr. Martin Rudwaleit (Klinikum Bielefeld),
  • PD Dr. med. Wilfried Witte (Evangelisches Klinikum Bethel)

 

Abstract:

Chronic musculoskeletal pain is a common reason for a medical consultation, for a sick leave certificate, medical assessments and early retirement. The causes are degenerative joint changes, inflammatory rheumatic diseases and chronic pain syndromes such as fibromyalgia. The distinction of these illnesses in the primary care can be difficult, and many patients are referred to rheumatology for further work-up. The large number of patients with chronic pain leads to long waiting periods until first presentation in the rheumatological setting. The proposed scientific project pursues the goal of an optimized referral strategy with an adequate preselection for urgent appointments in rheumatology, together with simultaneous detection of possible fibromyalgia syndrome already in primary care. It tests a new, simple referral path with standardized assessments in primary care, in specialized rheumatology and in specialized pain therapy and includes the analysis of context factors relevant for fibromyalgia. This simultaneous assessment of a potential inflammatory rheumatic disease and of a chronic pain condition in primary care is the first of its kind. The referral path can contribute to an early rheumatological presentation of patients with a higher probability of an inflammatory rheumatic disease and otherwise may help primary care physicians to reliably detect and treat fibromyalgia already in primary care. Furthermore, an analysis of contextual factors such as level of education, employment status, possible migration background, occurrence of depression and other psychological symptoms and the ability to resilience will improve the understanding of the development of fibromyalgia and identify possible therapeutic approaches. The project has the potential to enhance the management of care for patients with pain in Bielefeld and OWL by optimizing referral to rheumatology and to specialized pain therapy. In addition, a network structure of the institutions involved in this project will be established.

 

Participants:

  • Prof. Dr. Christoph Kayser (Fakultät für Biologie and CITEC, Universität Bielefeld),
  • Prof. Dr.-Ing. Franz Kummert (Technische Fakultät and CITEC, Universität Bielefeld),
  • Jun. Prof. Dr. Michael Römer (Fakultät für Wirtschaftswissenschaften, Universität Bielefeld),
  • PD Dr. med. habil. Ingo Todt (Klinikum Bielefeld)

Abstract:

Hearing problems represent one of the greatest medical challenges of our time (global burdens of disease). Not only older people are affected, but also many young patients worldwide. A crucial group of hearing losses can be treated with cochlear-implants (CI). However, the rehabilitative care of cochlear-implant patients is a challenge due to the increasing number of implants worldwide (approx. 15% annually), the lack of a follow-up infrastructure and the risk of infection. Autonomous AI-based systems are seen as a possibility to solve the challenges of comprehensive therapeutic and technical postoperative care efficiently, cost-effectively and also in rural or less developed regions. The goal of the measure planned here is the conception and implementation of an open AI-based application, which in a first step performs individualized hearing and speech therapy analysis and supports aftercare. In a later step, the system should pave the way to an autonomous AI-based adjustment of cochlear-implants. For this purpose, the first step will be the creation of an operation algorithm (ENT Clinic, Klinikum Mitte) and the creation of a battery of behavioral tests (University of Bielefeld, Cognitive Neuroscience). The latter will be adapted and optimized to the special requirements of a cochlear-implant patient (University of Bielefeld, Economics, Decision Analytics), and finally the implementation into an AI based software (University of Bielefeld, Research Institute for Cognition and Robotics). Subsequently, the functional evaluation of the software is performed on a group of patients to verify the technical functionality, the acceptance by users and the therapeutic benefit. On the basis of this application, the functionality of the app is to be extended and the direct incorporation into a cochlear-implant system is to be implemented in a publicly funded project with an existing industrial partner, in order to be able to use an autonomous system for individualized aftercare in the future. This system would set new standards in terms of quality, efficiency and participation in CI aftercare due to the integration of hearing and speech therapy, technical adaptation and its autonomous AI concept.

Participants:

  • Prof. Dr. med. Randolf Klingebiel (Evangelisches Klinikum Bethel),
  • Dr. rer. nat. Christian Poth (Fakultät für Psychologie und Sportwissenschaft and CITEC, Universität Bielefeld),
  • Prof. Dr. Helge Ritter (Technische Fakultät and CITEC, Universität Bielefeld),
  • Dr. med. Andreas Rogalewski (Evangelisches Klinikum Bethel),
  • Prof. Dr. med. Wolf-Rüdiger Schäbitz (Evangelisches Klinikum Bethel),
  • Prof. Dr. Werner Schneider (Fakultät für Psychologie und Sportwissenschaft and CITEC, Universität Bielefeld)

Abstract:

Strokes and Alzheimer's dementia are two of the most serious neurological diseases. Neurocognitive deficits (e.g. in perception) lead to a restriction of self-directed life. Despite the personal and social significance of these diseases, the diagnosis of associated cognitive deficits has been insufficient so far. However, targeted diagnostics is a premise for specific rehabilitative and possible medicinal therapy approaches. The overall goal of this research project is therefore to develop and evaluate a new diagnostic method for detecting cognitive deficits after strokes and in Alzheimer's disease. This method is based on temporally and spatially highly resolved measurement of eye movements in a series of simple tasks, such as eye movements away from appearing target stimuli, the so-called antisaccades. In contrast to current tests, this method captures profiles of basic neurocognitive processes such as attention and memory skills comprehensively, reliably and in a short testing time. This allows an analysis of neuro-cognitive profiles in comparison with healthy control persons of the same age, in order to enable a considerably more reliable and earlier detection of cognitive impairments. This could improve participation and maintenance of self-directed life by providing better starting points for therapy, rehabilitation and prophylactic measures.

Participants:

  • apl. Prof. Dr. Jörn Kalinowski (Fakultät für Biologie and CeBiTec, Universität Bielefeld),
  • apl. Prof. Dr. rer. nat. Alexander Sczyrba (Technische Fakultät and CeBiTec, Universität Bielefeld),
  • Prof. Dr. Dr. Holger Sudhoff (Klinikum Bielefeld)

Abstract:
Chronic rhinosinusitis (CRS) is marked by an inflamed mucosa of nasal and paranasal sinuses and accompanied by a significantly reduced quality of live. Since the prevalence of CRS in Europe is rather high (10%) (Hastan et al., 2011) and no guidelines for the treatment of CRS are available, long lasting clinical histories with healthcare costs adding up to several billion € annually are caused by CRS. The progression and particularly the exacerbation of CRS is most frequently induced by bacterial infections and/or a shift in the nasal microbiome. The exact microbiome alterations and their specific influences are still unknown. This study focuses on establishing a workflow to detect microbiome changes in CRS patients down to the species level by a fast 16S rDNA-based amplicon sequencing technique. For this purpose, we will characterize the microbiome from the nasal cavity of healthy persons and compare this with data derived from CRS patients. To further reduce the influence of the individual biological variance we additionally plan to characterize the microbiome of the same CRS patient before and after treatment of CRS. By bioinformatic analysis of the derived sequencing data we plan to unravel microbiome-shifts occurring during the healing of CRS. All the detected commensal bacterial species taking part on this shift are screened for species with existing culture protocols. Finally, these bacteria are cultured in the lab. The obtained data is condensed in a scientific publication e.g. with a methodical scope focusing on the derived protocols and/or a paper wrapping up the microbiome data obtained during this research endeavor. The expected novel findings will provide a basis for further funding by national funding organizations.

Participants:

  • Dr. med. Stefan Kreisel (Evangelisches Klinikum Bethel),
  • Prof. Dr. rer. nat. Angelika Schlarb (Fakultät für Psychologie und Sportwissenschaft, Universität Bielefeld)

Abstract:

The aging of society has an impact on the healthcare system. In order to meet the needs and requirements of elderly people, care needs to be adapted. On the one hand, there must be a stronger focus on the treatment of age-associated acute diseases. On the other hand, multimorbidity and the associated or resulting vulnerability of older people in the form of physical frailty and cognitive impairments are risks that must be taken into account throughout the entire care chain. It is mainly the correlation between acute disease and age-related vulnerability that determines the degree of impairment in the further course of the disease. One syndrome in which the detrimental consequences of this interaction are immediately apparent is delirium, which occurs on average in about 5% of hospital patients over the age of 65; in the post-operative setting, the incidence can reach values of up to 40%. The consequences are serious, since delirium is associated with increased morbidity, especially an increase in persistent cognitive deficits and institutionalization. It is only treatable to a limited extent, but is easily accessible for prevention. In addition to factors that can hardly be influenced, which are related to vulnerability, modifiable – and therefore preventable – risk factors, e.g. perioperative infections, sensory stress and the prescription of age-appropriate medication play an important role in the multifactorial genesis of the syndrome. The probability of postoperative delirium increased by up to a fourfold by chronic sleep disorders - although it remains unclear whether these are pathophysiologically causative or a proxy for other underlying risks. An interventional modification of this potential delirium risk, with the aim of improving the quality of sleep preoperatively in the sense of prehabilitation (and controlling age-appropriate, delirious sleep medication), could reduce the post-operative incidence of delirium given elective surgery and also contribute to elucidating the pathophysiology of the syndrome. The project will aim work to prepare a randomized clinical intervention study. For this purpose, Ia.) the state of research will be reviewed; Ib.) methods and techniques for sleep promotion will be adapted to the elderly and to the pre-hospital phase of planned elective surgery and Ic.) tested in a pilot study. In addition, II.) for the implementation of this pilot study, but also to establish a regional cross-sectoral research infrastructure,   primary care physicians and relevant departments of the Evangelisches Klinikum Bethel (EvKB) and the Klinikum Bielefeld will be integrated into a research network.

Participants:

  • Dr. med. Jens Conrad (Evangelisches Klinikum Bethel),
  • Jun. Prof. Dr. PH Christoph Dockweiler (Fakultät für Gesundheitswissenschaften, Universität Bielefeld),
  • Dr. med. Andreas Elsner (Orthopädische Gemeinschaftspraxis am Bültmannshof),
  • Prof. Dr. Thomas Schack (Fakultät für Psychologie und Sportwissenschaft and CITEC, Universität Bielefeld),
  • Prof. Dr. med. Thomas Vordemvenne (Evangelisches Klinikum Bethel)

 

Abstract

Virtual reality (VR) applications are a rapidly growing branch. Thus, these technologies are also increasingly used in the field of medicine. In combination with 3D motion analysis, these systems have great potential for musculoskeletal rehabilitation. This study investigates an innovative system for individualized, adaptive virtual rehabilitation of the upper extremity. In this pilot study 40 patients with injuries of the upper extremity are randomly assigned to either the "standard group" or "VR group". In the 4-week extended ambulant physiotherapy (EAP), surveys and examinations of the function of the upper extremity are conducted at the beginning and end of the 2nd and 4th week. In addition, a survey/interview on the acceptance of the system is conducted at the end of week 4. Acceptance is also surveyed among the participating users (therapists, doctors). With the results of this pilot study we plan a follow-up study with the aim to investigate the benefit of individualized, adaptive virtual rehabilitation of the upper extremity.


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