Research

Nano-Physiomanalysis for workload control

Improving workload control for patients and athletes is the long-term goal of our scientific work (see Funding A-C). As the first research group worldwide, we have described both a workload-dependent release of cell-free DNA circulating in the blood (cfDNA) and a release of extracellular vesicles (EVs) during a classical cardiopulmonary exercise test (see Literature 1-4).

EVs and cfDNA are macromolecular, heterogeneous molecular complexes, which are insufficiently detected by classical molecular OMICs methods - such as genomics, proteomics, metabolomics. Both nano-complexes allow inferences about their cellular (see Lit. 4, 5; Funding A), or their endogenous (see InteIlectual Property I.) or exogenous (see IP II.-III.) origin. For this nano-molecular, organotropic, quantitative analysis, we are developing new, highly sensitive measurement methods (see Lit. 5; IP I.-III.).

We combine this nano-analytics with the classical monitoring of the functional behavior of the physical condition - the physiome. The progressing digitalization enables us to collect and process increasingly large data volumes in real time and to use them for the decentralized training control of patients telemedically in the internet-based sports support (see Lit. 6, Fund. C).

A new field of performance diagnostics, Exercise Radiomics, is the first area in which we use deep-learning algorithms to analyze skin surface temperature patterns in motion (see Lit. 7; Fund. D). In the future, the development of improved AI algorithms will depend very significantly on data quality. A long-standing research focus of the department is dark-field research on socially sensitive items, such as substance abuse and doping (see Lit. 8).


  1. Beiter T, Fragasso A, Hudemann J, Nieß AM, Simon, P. (2011). Short-term treadmill running as a model for studying cell-free DNA kinetics in vivo. Clinical Chemistry, 57(4), 633-636.
  2. Breitbach S, Tug S, Simon P (2012). Circulating cell-free DNA: an up-coming molecular marker in exercise physiology. Sports Med 42(7):565-586.
  3. Frühbeis C, Helmig S, Tug S, Simon P*, Krämer-Albers EM. (2015). Physical exercise induces rapid release of small extracellular vesicles into the circulation. J Extracell Vesicles 4:28239. (*equal contribution)
  4. Brahmer A, Neuberger E, Esch-Heisser L, Haller N, Jorgensen MM, Baek R, Möbius W, Simon P*, Krämer-Albers EM* (2019). Platelets, endothelial cells and leukocytes contribute to the exercise-triggered release of extracellular vesicles into the circulation. J Extracell Vesicles 8(1):1615820. (*equal contribution)
  5. Ehlert T, Tug S, Brahmer A, Neef V, Heid F, Werner C, ... ,Simon, P. (2017). Establishing PNB-qPCR for quantifying minimal ctDNA concentrations during tumour resection. Scientific reports, 7(1), 1-8.
  6. Pfirrmann D, Huber Y, Schattenberg JM, Simon P. (2019). Web-based exercise as an effective complementary treatment for patients with nonalcoholic fatty liver disease: intervention study. Journal of medical Internet research, 21(1), e11250.
  7. Hillen B, Pfirrmann D, Nägele M, Simon P (2020). Infrared thermography in exercise physiology: The dawning of exercise radiomics. Sports Med 50(2):263-282.
  8. Ulrich R, Pope HG Jr, Cléret L, Petróczi A, Nepusz T, Schaffer J, Kanayama G, Comstock RD, Simon P (2018). Doping in two elite athletics competitions assessed by randomized-response surveys. Sports Med 48(1):211-219.

I. Simon P, Himmelreich R (2018): “Cell free DNA amplification” (F58373 DE) 102018222357.2

II. Simon P (2007): “Detection of transgenic DNA (tDNA)“, PCT/EP2007/003385 (5402P366)

III. Simon P (2006): „Nachweis von transgener DNA (tDNA)“, Schutzrecht DE 10 2006 021 257.6 (5402P366)


A) “Healthy Campus Mainz” Bahrmer GEK (2018-2023) Cooperative Grant: 1.518 Mio. €

B) “Blood-derived mediators of exercise induced innate and acquired stress resilience” Boehringer Ingelheim Foundation (2018-2020) Cooperative Grant: 525.100 €

C) “Decide“ Decentralized digital Environment for Consultation, data Integration, Decision making and patient Empowerment; BMBF (2021-2025) Cooperative Grant: 5.47 Mio. €

D) “INNOSPOMED - Innovative sports medical performance diagnostics, based on a novel evaluation of thermographic camera data by means of neural networks and the analytical comparison to classical parameters of sports medical performance diagnostics”, Central innovation program for SMEs (ZIM) (2020-2022) 480.000 €

In the following, we present current research areas and projects of the Department of Sports Medicine.

Molecular exercise physiology is concerned with the changes that physical exercise causes at the level of proteins, RNA and ultimately also at the level of human genetic material - DNA. In particular, the question is addressed as to which mechanisms a training stimulus sets in motion in order to cause desirable effects in our body in the ideal case or undesirable effects in the case of overtraining, for example. Conversely, molecular exercise physiology poses the question of which molecular or genetic prerequisites make a certain performance possible in the first place.

A.1
Liquid Biopsy – Improving cfDNA Quantification
A.2
Exercise as a model to study cell-free DNA in relation to inflammatory processes in health and disease
A.3
Exercise induced cell communication through extracellular vesicles
A.4
Doping in sports and doping detectability

Publications::

  • Brahmer A, Krämer-Albers E. M. (2020). “Brainstorming”: Extracellular Vesicles in Physical Activity and Neuronal Health. Trillium Extracellular Vesicles 2020
  • Brahmer A, Neuberger E, Esch-Heisser L, Haller N, Jorgensen MM, Simon P, Krämer-Albers, EM. (2019). Platelets, endothelial cells and leukocytes contribute to the exercise-triggered release of extracellular vesicles into the circulation. Journal of extracellular vesicles, 8(1), 1615820.
  • Frühbeis C, Helmig S, Tug S, Simon P, Krämer-Albers EM. (2015). Physical exercise induces rapid release of small extracellular vesicles into the circulation. Journal of extracellular vesicles, 4(1), 28239.
  • Helmig S, Frühbeis C, Krämer-Albers, EM, Simon P, Tug S. (2015). Release of bulk cell free DNA during physical exercise occurs independent of extracellular vesicles. European journal of applied physiology, 115(11), 2271-2280.

 

 

 

 

 

 

Contact person: Univ.-Prof. Dr. Dr. Perikles Simon

Circulating cell-free DNA (cfDNA) is an important, commonly studied marker to assess the inflammatory state in patients with sepsis, liver disease, and autoimmune diseases such as systemic lupus erythematosus (SLE). Physical exercise causes acute physiological changes that result in the induction of inflammatory signaling processes, immune cell shifts, cytokine release, and increases in cfDNA (Breitbach et al. 2012 PMID: 22694348). We have established a reliable and cost-effective qPCR assay for the detection of cfDNA in plasma (Breitbach et al. 2014 PMID: 24595313). Exercise leads in healthy athletes to an acute increase in cfDNA concentration by 5-fold during cycling exercise or 15-fold during running exercise (Tug et al. 2016 PMID: 27617485, Brahmer et al. 2019 PMID: 31191831, Breitbach et al. 2014 PMID: 24876361). Here, cfDNA is predominantly derived from cells of the hematopoietic lineage (Tug et al. 2015 PMID: 25826002). In ongoing experiments, we are investigating cell type-specific DNA methylation profiles to further sub-characterize the proportional assignment of cell types. Currently, the release mechanisms as well as relevant key factors that cause the exercise-induced increases in cfDNA in response to physical exertion and its involvement in inflammatory signaling processes are unknown. To identify relevant factors influencing cfDNA release and its clinical relevance, we are investigating cfDNA and inflammatory cytokines in patients with LUPUS, non-alcoholic fatty liver disease (NAFLD), and healthy untrained subjects, respectively, after 8 -12 weeks of exercise intervention.

Contact person: Dr. Elmo Neuberger

Extracellular vesicles (EVs) are membrane-enclosed units with sizes in the nanometer range that are able to transport a wide range of bioactive components (proteins, lipids, metabolites, nucleic acids) in a protected manner. Diverse acute and chronic sports interventions trigger the release of EVs into the bloodstream, and these are likely to be involved in the health-promoting physiological adaptation processes induced by regular exercise. In collaboration with the Institute of Developmental Biology and Neurobiology, Extracellular Vesicles Research Group (University of Mainz), we are investigating the release kinetics, cellular origin, cargo and functions of EVs released into the bloodstream in response to physical exercise - ExerVs.

Contact person: Dr. Alexandra Brahmer

Doping in sport is widespread. An anonymous questionnaire survey shows that between 43.6% and 70.1% of participants in the World Athletics Championships and the Pan-Arab Games, respectively, have violated doping guidelines at least once in a year (Ulrich et al., 2018. PMID: 28849386). In addition to conventional doping, so-called gene doping has come into focus, which is an abusive use of gene therapy for the purpose of performance enhancement. History shows that biotechnological progress is typically misused for doping purposes. Gene transfer using viral vectors is one conceivable scenario, although research in this area remains highly experimental (Neuberger et al., 2012 PMID: 22508654 / Neuberger & Simon 2017 PMID: 28578328). To facilitate the detectability of gene doping, we have established several PCR methods that can detect gene doping with the highest sensitivity and specificity (Beiter et al. 2008 PMID: 19203085, Beiter et al., 2011 PMID: 20811468, Moser et al. 2012 PMID: 22539489, Moser et al. 2014 PMID: 25375130). The reproducibility of EPO gene doping detection was validated in a multi-laboratory study in non-human primates (Neuberger et al. 2016 PMID: 26752352). In addition to direct detection of doping agents, indirect detection methods such as the transcriptional approach are also being pursued (Neuberger et al. 2011 PMID: 22031504, Neuberger & Simon 2014 DOI: 10.5960/dzsm.2014.140). No clinical test has 100% sensitivity and 100% specificity, and both values are dependent on prevalence. This has important implications for antidoping laboratories that could improve the validity of their tests (Simon et al. 2018 PMID: 30300193).

Contact person: Dr. Elmo Neuberger

 

Another research focus of the Department of Sports Medicine is web-based physical activity management for patients with various underlying diseases. Regular physical activity is recommended by medical societies for prevention and therapy (secondary and tertiary prevention) of many diseases. Guided exercise programs are an effective means of support. However, promising therapeutic exercise care, especially taking into account individual exercise recommendations, is difficult to implement in the context of classroom sessions, even with considerable effort on the part of the therapeutic staff. Individual needs, inadequate infrastructure and time commitments (e.g. shift work) represent major hurdles in permanent presence care. Due to further developments in network quality and improved infrastructure for data traffic, the Internet is becoming a natural addition to the service spectrum of care. Thus, a web-based assistance system can be a useful addition that contributes to health promotion in a sustainable way. To date, interventions have been successfully implemented with untrained healthy individuals as well as patients suffering from non-alcoholic fatty liver, depression, cancer, cystic fibrosis or systemic lupus erythematosus.

  • HELP: Hepatic inflammation and physical performance in patients with non-alcoholic steatohepatitis
  • iPEP: Internet-based perioperative exercise program for patients with barrett’s carcinoma scheduled for esophagectomy
  • ExDEP: Exercise for depression
  • COMMED: Cystic fibrosis online mentoring program - microbiome, exercise & diet
  • SLEEP: Systemic lupus erythematosus exercise program
  • SPEER: Sports effects on emotion regulation and stress resilience

Contact person: Dr. Alexandra Brahmer, Dr. Nils Haller, Keito Philippi, Barlo Hillen

Publications:

  • Boedecker SC, Philippi K, Neuberger E, Schmidt S, Pfirrmann D, Haller N, Schwarting A, Simon P, Weinmann-Menke J. The effect of 12-week internet-based individualized exercise program in adults with systemic lupus erythematosus: A randomized controlled trial. JMIR Research Protocols 2020. https://doi.org/10.2196/preprints.18291
  • Haller N, Lorenz S, Pfirrmann D, Koch C, Lieb K, Dettweiler U, Simon P, Jung P. Individualized Web-Based Exercise for the Treatment of Depression: Randomized Controlled Trial. JMIR Ment Health 2018;5(4):e10698.
  • Hillen B, Simon P, Grimminger P.P, Gockel I, Pfirrmann D. Use of a Perioperative Web-Based Exercise Program for a Patient with Barrett’s Carcinoma Scheduled for Esophagectomy. Case Rep Oncol 2019;12:755–764.
  • Pfirrmann D, Huber Y, Schattenberg JM, Simon P.  Web-Based Exercise as an Effective Complementary Treatment for Patients With Nonalcoholic Fatty Liver Disease: Intervention Study. J Med Internet Res 2019;21(1):e11250.
  • Pfirrmann D, Haller N, Huber Y, Jung P, Lieb K, Gockel I, Poplawska K, Schattenberg JM, Simon P. Applicability of a Web-Based, Individualized Exercise Intervention in Patients With Liver Disease, Cystic Fibrosis, Esophageal Cancer, and Psychiatric Disorders: Process Evaluation of 4 Ongoing Clinical Trials. JMIR Res Protoc 2018;7(5):e106.
  • Pfirrmann D, Tug S, Brosteanu O, Mehdorn M, Busse M, Grimminger PP, et al. Internet-based perioperative exercise program in patients with Barrett's carcinoma scheduled for esophagectomy [iPEP - study] a prospective randomized-controlled trial. BMC Cancer 2017 Jun 14;17(1):413.

 

"Load Management" describes the planning, monitoring and adaptation of a training load. The cooperation project is a scientific collaboration to work on various sports science issues with a focus on the further development of load management for athletes. The cooperation partner is the University of Salzburg and Prof. Dr. Thomas Stöggl.

Contact person: Dr. Nils Haller

Publications:

  • Haller N, Tug S, Breitbach S, Jörgensen A, Simon P.  Increases in circulating cell-free DNA during aerobic running depend on intensity and duration. International journal of sports physiology and performance 2017; 12(4), 455-462.
  • Haller N, Helmig S, Taenny P, Petry J, Schmidt S, Simon P.  Circulating cell-free DNA as a marker for exercise load in intermittent sports. PloS one 2018; 13(1).
  • Haller N, Ehlert T, Schmidt S, Ochmann D, Sterzing B, Grus F, Simon P. Circulating cell-free DNA for Monitoring Player Load in Professional Football. International Journal of Sports Physiology and Performance 2019; 14(6), 718-726.
  • Haller N, Ehlert T, Schmidt S, Simon P. Circulating DNA as a Monitoring Tool in Professional Soccer. ACSM Orlando 2019.

 

The Johannes Gutenberg University Mainz (JGU) will establish a holistic student health management (SGM). The model project "Healthy Studying in Mainz" is a cooperation project between the JGU University Medical Center, JGU and BARMER. It is funding the model project with around 1.5 million euros as part of the law to strengthen health promotion and prevention (§ 20g SGB V). The aim of the "Healthy Studying in Mainz" model project is to gather scientific findings on prevention and health promotion among students in order to use them to create evidence-based measures to maintain and promote health for the approximately 32,000 students in Mainz. The model project "Healthy Studying in Mainz" focuses on five key topics that are of enormous relevance for the health of students and are considered and worked on in the project from an interdisciplinary perspective: "Exercise," "Nutrition," "Communication and Media Use," "Medical Prevention," and "Mental Health." The Department of Sports Medicine is particularly concerned with questions relating to physical activity behavior in a health context. The focus here is on the survey of fitness and physical activity with its consequences for the musculoskeletal system and its influence on the internal organs. Based on these findings, programs are developed to promote an active lifestyle and, if necessary, provide support for everyday integration. (https://gesund.uni-mainz.de).

Contact person: Dennis Edelmann, Kristin Kalo

Publications:

  • Dietz P, Reichel JL, Edelmann D, Werner AM, Tibubos AN, Schäfer M, Simon P, Letzel S, Pfirrmann D.  A Systematic Umbrella Review on the Epidemiology of Modifiable Health Influencing Factors and on Health Promoting Interventions Among University Students. Front. Public Health 2020; 8:137.
  • Edelmann D, Dietz P, Reichel J, Werner A, Schäfer M, Tibubos AN, Deci N, Letzel S, Simon P, Pfirrmann D.  Physische Aktivität und Sitzverhalten von Studierenden an der Johannes Gutenberg-Universität. Vortrag im Rahmen der 60. Jahrestagung der Deutschen Gesellschaft für Arbeitsmedizin und Umweltmedizin vom 2.-9. September 2020 in München.

On the occasion of the Corona Pandemic, a science-based sustainable exercise offer is to be created for the citizens of Mainz. Our goal is to support citizens, regardless of age, gender, and current ability, to engage in regular, at best lifelong, physical activity and thus contribute to a healthy lifestyle. Regular exercise contributes not only to physical health but also to mental and psychological health. The social aspect of sports plays a decisive role here. Doing something together for your own health, going outside, doing sports together and respecting the rules of fair play creates solidarity. "Mainz läuft" aims to create a new sense of community in this sense. This includes the conception and creation of training and exercise areas in Mainz. Sports students from JGU accompany and support the groups as running coaches and mentors. As part of the project, there is the opportunity to write a bachelor's or master's thesis or to get involved in the form of an internship.

On the occasion of the corona pandemic, a science-based sustainable exercise offer is to be created for the people of Mainz. Our goal is to support interested groups of people, regardless of age, gender and current ability, to engage in regular, at best lifelong, physical activity and thus contribute to a healthy lifestyle.

Regular exercise contributes not only to physical health but also to mental and psychological health. The social aspect of sports plays a decisive role here. Doing something together for your own health, going outside, doing sports together and respecting the rules of fair play creates solidarity. "Mainz läuft" is intended to create a new sense of community in this sense.

As part of a university teaching project, various charitable activities are planned on an ongoing basis for specific target groups such as children, young people and families in Mainz. JGU sports students accompany and support the groups as running coaches and mentors.

Contact person: Dr. Anne Huber

 

A comprehensive, national cooperation project funded by the Federal Ministry for Economic Affairs and Energy (BMWi) as part of the "Central Innovation Programme for SMEs (ZIM)" programme. Innovative sports medicine performance diagnostics based on a novel evaluation of thermographic camera data using neural networks and the analytical comparison to classic parameters of sports medicine performance diagnostics. The cooperation partners are OptoPrecision GmbH and the Institute for Computer Science at the Johannes Gutenberg University Mainz.

Infrared thermography (IRT) is a non-invasive measurement tool for collecting the radiant temperature of the body surface (Tsr). IRT is an emerging technology resulting from recent advances in camera lenses, detector technology, and advancing data processing capabilities. We are investigating the applicability of IRT in the context of dynamic measurements in exercise physiology and are observing specific changes in Tsr for different types of exercise (Abb.6&7). At the end of exercise tests or during prolonged physical exercise, IRT showed a surface radiation pattern (Psr). In addition, we are investigating how influencing factors, such as skin blood flow, or environmental factors can be resolved by innovative technological approaches. or a more refined analysis, it will be necessary to develop and implement a standardized and accurate pattern recognition technology. We call this approach "Exercise Radiomics".

Contact person: Barlo Hillen

Publications:

  • Hillen B, Pfirrmann D, Nägele M. et al. Infrared Thermography in Exercise Physiology: The Dawning of Exercise Radiomics. Sports Med  2020; 50, 263–282.
  • Hillen B, Simon P. The Temperature Surface Radiation Pattern - A non-invasive Insight into Skin Blood Flow Response to Exercise. MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, Volume: 51 Issue: 6 Pages: 491-492, JUN 2019.