Markus Löffler

About Markus Löffler:

Prof. Dr. Markus Löffler Universität Leipzig Institut für Medizinische Informatik, Statistik und Epidemiologie Härtelstraße 16-18 04107 Leipzig

LHA ID: 7W2GKE4JDQ-2

Location:  Germany

ORCID: Not specified

Expertise: Not specified

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Project positions

Genetical Statistics and Systems Biology (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; MMML Demonstrators - Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; LIFE HNC - Head and Neck Cancer Group (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; MMML-MYC-SYS (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; LIFE Adult (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; GLA - German Lymphoma Alliance (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; MMML - Molecular mechanisms in malignant lymphoma (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; SepNet - German Competence Network Sepsis (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; HaematoSys - Systems biology of haematopoiesis and haematopoietic neoplasia (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; SMITH - Smart Medical Information Technology for Healthcare (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; LHA - Leipzig Health Atlas (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; POLAR - Polypharmacy, Drug Interactions, Risks (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; SMITH - Smart Medical Information Technology for Healthcare (University of Leipzig) ; Task Force COVID-19 Leipzig (Institute for Medical Informatics, Statistics and Epidemiology (IMISE))

Related items

LIFE HNC - Head and Neck Cancer Group

The aim of the Head and Neck Group within the Leipzig Research Center for Civilization Diseases (LIFE) is to facilitate improvements in the treatment and care of head and neck cancer patients through insights from molecular studies.

The Head and Neck Group within the Leipzig Research Center for Civilization Diseases (LIFE) investigates the molecular mechanisms and the diagnostic and prognostic factors of head and neck cancer. For this purpose, we collected phenotypic information from about 300 ...

Programme: LIFE Management Cluster

Public web page: http://life.uni-leipzig.de/

Start date: 1st Jan 2012

End date: 31st Dec 2012

LHA - Leipzig Health Atlas

The Leipzig Health Atlas (LHA) is an alliance of medical ontologists, medical systems biologists and clinical trials groups to design and implement a multi-functional and quality-assured atlas. It provides models, data and metadata on specific use cases from medical research fields in which our team has scientific and clinical expertise.

Programme: i:DSem - Integrative Datensemantik in der Systemmedizin

Public web page: https://www.health-atlas.de

Start date: 1st Apr 2016

End date: 28th Feb 2021

SMITH - Smart Medical Information Technology for Healthcare

Medical data routinely generated in everyday clinical practice is processed and made available to medical research in a standardized form. Patients benefit from reliable research results, more precise diagnoses and better treatments. In order to link data from care and research, the participating university hospitals in Aachen, Bonn, Essen, Halle, Hamburg, Jena and Leipzig have established sustainable Data Integration Centers. The network partners Ruhr University Bochum, the Düsseldorf University ...

Programme: MII - Medical Informatics Initiative

Public web page: https://www.smith.care/

Start date: 1st Jan 2018

Task Force COVID-19 Leipzig

This project serves as a container for all COVID-19 related assets, developed at the University of Leipzig and its partners.

Programme: NFDI - German National Research Data Infrastructure

Public web page: https://www.nfdi4health.de/task-force-covid-19

Start date: 20th May 2020

NFDI4Health: inactive since

NFDI4Health - the National Research Data Infrastructure for Personal Health Data - deals with data generated in clinical trials, epidemiological and public health studies. The collection and analysis of these data on health and disease status and important factors influencing it are an essential component for the development of new therapies, comprehensive care approaches and preventive measures in a modern health care system. Although these data already meet high content quality standards, they ...

Programme: NFDI - German National Research Data Infrastructure

Public web page: https://www.nfdi4health.de/en

POLAR - Polypharmacy, Drug Interactions, Risks

The aim of the project is to use methods and processes of the Medical Informatics Initiative (MII) to contribute to the detection of health risks in patients with polypharmacy. Polypharmacy occurs especially in elderly patients with multimorbidity. Polypharmacy associated with an increased risk for medication errors and drug-drug or drug-disease interactions, which either reduce or intensify the desired effect of individual active substances or lead to undesired adverse drug effects (ADE). In the ...

Programme: MII - Medical Informatics Initiative

Public web page: https://www.medizininformatik-initiative.de/en/POLAR

LIFE - Leipzig Research Center for Civilization Diseases: inactive since

Goal of the Leipzig Research Center for Civilization Diseases (LIFE) is the investigation of civilization diseases like depression, diabetes, allergies or cardiovascular diseases. For this purpose we collect as much data as possible regarding health and living conditions of the population in Leipzig and provide these data for scientists of the University of Leipzig and other research institutions.

Programme: LIFE Management Cluster

Public web page: http://life.uni-leipzig.de/

Start date: 1st Jan 2009

LIFE Adult

This population-based study examined 10,000 participants randomly selected from the Leipzig population (2011 to 2014). A follow-up is to be carried out from 2017 - 2020. The study mainly included people aged between 40 and 79. All participants underwent a 6-hour study program and people over 60 years of age were invited two more times to in-depth study of cognition and depression and the brain (MRI, EEG). Extensive measurements of genome, metabolome and transcriptome are available. The LIFE-ADULT ...

Programme: LIFE Management Cluster

Public web page: http://life.uni-leipzig.de/en/adults/life_adult.html

Start date: 1st Jan 2009

MMML - Molecular mechanisms in malignant lymphoma

During 2003 and 2011 the german cancer aid funded the molecular mechanisms in malignant lymphomas (MMML) project. It is based on strongly interacting networks of reference pathologists, lymphoma scientists, bioinformaticians and clinical trial groups. Within the project about 1000 lymphoma samples and controls were characterized by gene expression and copy number arrays. The datasets were supplemented by extensive histopathological and clinical descriptions of the lymphoma cases. The aim of the ...

Programme: This Project is not associated with a Programme

Public web page: Not specified

MMML-MYC-SYS

MMML-MYC-SYS is a interdisciplinary consortium where partners from clinical haemaoncological study groups, pathologists, geneticicts, cell biologists as well as mathematicians, statisticians and bioinformaticists have allied. The goal is to investigate the process of development of B-cell lymphoma under special consideration of mutation of MYC. MYC is known to support the development and growth of tumors. This consortium collected and evaluated comprehensive molecular-genetic data for this purpose. ...

Programme: This Project is not associated with a Programme

Public web page: http://www.mmmlmycsys.de/

Start date: 1st Jan 2013

Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP Trial)
SepNet - German Competence Network Sepsis

Severe sepsis and septic shock have a high mortality. Research has concentrated on adjunctive sepsis therapies; the role of supportive measures is comparatively unclear. In Europe the use of colloids is widespread, but there is no evidence on the role of either crystalloid or colloid volume therapy in sepsis. Recently, a higher incidence of kidney failure in sepsis was reported after administration of colloids.

Submitter: Christoph Beger

Studies: VISEP

Resources: VISEP metadata, VISEP trial data

IMISE Covid-19 Bulletins (in German)
Task Force COVID-19 Leipzig

A collection of Bulletins of the Institute for Medical Informatics, Statistics and Epidemiology (IMISE) about the COVID-19 pandemic in Leipzig and Saxony. This work was funded in the framework of the project SaxoCOV (Saxonian COVID-19 Research Consortium, SaxoCOV was financed by the Free State of Saxony).”

Submitter: René Hänsel

Investigation: Covid-19

Resources: Entwicklung der COVID-19 Epidemie in Sachsen und Deutschland

Study type: Not specified

VISEP
SepNet - German Competence Network Sepsis

Baseline Data and Endpoints for VISEP

Submitter: René Hänsel

Investigation: Efficacy of Volume Substitution and Insulin The...

Resources: VISEP metadata, VISEP trial data

Study type: Not specified

Entwicklung der COVID-19 Epidemie in Sachsen und Deutschland
Task Force COVID-19 Leipzig

A collection of Bulletins of the Institute for Medical Informatics, Statistics and Epidemiology (IMISE) about the COVID-19 pandemic in Leipzig and Saxony. This work was funded in the framework of the project SaxoCOV (Saxonian COVID-19 Research Consortium, SaxoCOV was financed by the Free State of Saxony).”

Submitter: René Hänsel

Biological problem addressed: Model Analysis Type

Investigation: Covid-19

Study: IMISE Covid-19 Bulletins (in German)

VISEP trial data
SepNet - German Competence Network Sepsis

The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids. We compared intensive insulin therapy with conventional insulin therapy and HES with Ringer’s lactate.

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: Efficacy of Volume Substitution and Insulin The...

Study: VISEP

VISEP metadata
SepNet - German Competence Network Sepsis

The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids. We compared intensive insulin therapy with conventional insulin therapy and HES with Ringer’s lactate.

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: Efficacy of Volume Substitution and Insulin The...

Study: VISEP

Transcriptional states of CAR-T infusion relate to neurotoxicity - lessons from high-resolution single-cell SOM expression portraying.
imSAVAR - Immune safety avatar: nonclinical mimicking of the immune system effects of immunomodulatory therapies

Abstract (Expand)

Anti-CD19 CAR-T cell immunotherapy is a hopeful treatment option for patients with B cell lymphomas, however it copes with partly severe adverse effects like neurotoxicity. Single-cell resolved molecular … data sets in combination with clinical parametrization allow for comprehensive characterization of cellular subpopulations, their transcriptomic states, and their relation to the adverse effects. We here present a re-analysis of single-cell RNA sequencing data of 24 patients comprising more than 130,000 cells with focus on cellular states and their association to immune cell related neurotoxicity. For this, we developed a single-cell data portraying workflow to disentangle the transcriptional state space with single-cell resolution and its analysis in terms of modularly-composed cellular programs. We demonstrated capabilities of single-cell data portraying to disentangle transcriptional states using intuitive visualization, functional mining, molecular cell stratification, and variability analyses. Our analysis revealed that the T cell composition of the patient's infusion product as well as the spectrum of their transcriptional states of cells derived from patients with low ICANS grade do not markedly differ from those of cells from high ICANS patients, while the relative abundancies, particularly that of cycling cells, of LAG3-mediated exhaustion and of CAR positive cells, vary. Our study provides molecular details of the transcriptomic landscape with possible impact to overcome neurotoxicity.

Authors: H. Loeffler-Wirth, M. Rade, A. Arakelyan, M. Kreuz, M. Loeffler, U. Koehl, K. Reiche, H. Binder

Date Published: 17th Oct 2022

Publication Type: Journal article

POLAR – „POLypharmazie, Arzneimittelwechselwirkungen und Risiken“ – wie können Daten aus der stationären Krankenversorgung zur Beurteilung beitragen?
SMITH - Smart Medical Information Technology for Healthcare

Abstract (Expand)

Zusammenfassung Hintergrund Mit der zunehmenden Anzahl eingenommener Arzneimittel steigt die Prävalenz von Medikationsrisiken. Hierzu zählen beispielsweise Arzneimittelwechselwirkungen, welche erwünschte … und unerwünschte Wirkungen einzelner Arzneistoffe reduzieren aber auch verstärken können. Fragestellung Das Verbundvorhaben POLAR (POLypharmazie, Arzneimittelwechselwirkungen und Risiken) hat das Ziel, mit Methoden und Prozessen der Medizininformatikinitiative (MII) auf Basis von „Real World Data“ (stationärer Behandlungsdaten von Universitätskliniken) einen Beitrag zur Detektion von Medikationsrisiken bei Patient:innen mit Polymedikation zu leisten. Im Artikel werden die konkreten klinischen Probleme dargestellt und am konkreten Auswertebeispiel illustriert. Material und Methoden Konkrete pharmakologische Fragestellungen werden algorithmisch abgebildet und an 13 Datenintegrationszentren in verteilten Analysen ausgewertet. Eine wesentliche Voraussetzung für die Anwendung dieser Algorithmen ist die Kerndatensatzstruktur der MII, die auf internationale IT-, Interoperabilitäts- und Terminologiestandards setzt. Ergebnisse In POLAR konnte erstmals gezeigt werden, dass stationäre Behandlungsdaten standortübergreifend auf der Basis abgestimmter, interoperabler Datenaustauschformate datenschutzkonform für Forschungsfragen zu arzneimittelbezogenen Problemen nutzbar gemacht werden können. Schlussfolgerungen Als Zwischenstand in POLAR wird ein erstes vorläufiges Ergebnis einer Analyse gezeigt. Darüber hinaus werden allgemeinere technische, rechtliche, kommunikative Chancen und Herausforderungen dargestellt, wobei der Fokus auf dem Fall der Verwendung stationärer Behandlungsdaten als „Real World Data“ für die Forschung liegt.

Authors: André Scherag, Wahram Andrikyan, Tobias Dreischulte, Pauline Dürr, Martin F Fromm, Jan Gewehr, Ulrich Jaehde, Miriam Kesselmeier, Renke Maas, Petra A Thürmann, Frank Meineke, Daniel Neumann, Julia Palm, Thomas Peschel, Editha Räuscher, Susann Schulze, Torsten Thalheim, Thomas Wendt, Markus Loeffler, D Ammon, W Andrikyan, U Bartz, B Bergh, T Bertsche, O Beyan, S Biergans, H Binder, M Boeker, H Bogatsch, R Böhm, A Böhmer, J Brandes, C Bulin, D Caliskan, I Cascorbi, M Coenen, F Dietz, F Dörje, T Dreischulte, J Drepper, P Dürr, A Dürschmid, F Eckelt, R Eils, A Eisert, C Engel, F Erdfelder, K Farker, M Federbusch, S Franke, N Freier, T Frese, M Fromm, K Fünfgeld, T Ganslandt, J Gewehr, D Grigutsch, W Haefeli, U Hahn, A Härdtlein, R Harnisch, S Härterich, M Hartmann, R Häuslschmid, C Haverkamp, O Heinze, P Horki, M Hug, T Iskra, U Jaehde, S Jäger, P Jürs, C Jüttner, J Kaftan, T Kaiser, K Karsten Dafonte, M Kesselmeier, S Kiefer, S Klasing, O Kohlbacher, D Kraska, S Krause, S Kreutzke, R Krock, K Kuhn, S Lederer, M Lehne, M Löbe, M Loeffler, C Lohr, V Lowitsch, N Lüneburg, M Lüönd, I Lutz, R Maas, U Mansmann, K Marquardt, A Medek, F Meineke, A Merzweiler, A Michel-Backofen, Y Mou, B Mussawy, D Neumann, J Neumann, C Niklas, M Nüchter, K Oswald, J Palm, T Peschel, H Prokosch, J Przybilla, E Räuscher, L Redeker, Y Remane, A Riedel, M Rottenkolber, F Rottmann, F Salman, J Schepers, A Scherag, F Schmidt, S Schmiedl, K Schmitz, G Schneider, A Scholtz, S Schorn, B Schreiweis, S Schulze, A K Schuster, M Schwab, H Seidling, S Semler, K Senft, M Slupina, R Speer, S Stäubert, D Steinbach, C Stelzer, H Stenzhorn, M Strobel, T Thalheim, M Then, P Thürmann, D Tiller, P Tippmann, Y Ucer, S Unger, J Vogel, J Wagner, J Wehrle, D Weichart, L Weisbach, S Welten, T Wendt, R Wettstein, I Wittenberg, R Woltersdorf, M Yahiaoui-Doktor, S Zabka, S Zenker, S Zeynalova, L Zimmermann, D Zöller, für das POLAR-Projekt

Date Published: 1st Sep 2022

Publication Type: Journal article

The Leipzig Health Atlas-An Open Platform to Present, Archive, and Share Biomedical Data, Analyses, and Models Online.
LHA - Leipzig Health Atlas

Abstract (Expand)

BACKGROUND: Clinical trials, epidemiological studies, clinical registries, and other prospective research projects, together with patient care services, are main sources of data in the medical research … domain. They serve often as a basis for secondary research in evidence-based medicine, prediction models for disease, and its progression. This data are often neither sufficiently described nor accessible. Related models are often not accessible as a functional program tool for interested users from the health care and biomedical domains. OBJECTIVE: The interdisciplinary project Leipzig Health Atlas (LHA) was developed to close this gap. LHA is an online platform that serves as a sustainable archive providing medical data, metadata, models, and novel phenotypes from clinical trials, epidemiological studies, and other medical research projects. METHODS: Data, models, and phenotypes are described by semantically rich metadata. The platform prefers to share data and models presented in original publications but is also open for nonpublished data. LHA provides and associates unique permanent identifiers for each dataset and model. Hence, the platform can be used to share prepared, quality-assured datasets and models while they are referenced in publications. All managed data, models, and phenotypes in LHA follow the FAIR principles, with public availability or restricted access for specific user groups. RESULTS: The LHA platform is in productive mode (https://www.health-atlas.de/). It is already used by a variety of clinical trial and research groups and is becoming increasingly popular also in the biomedical community. LHA is an integral part of the forthcoming initiative building a national research data infrastructure for health in Germany.

Authors: T. Kirsten, F. A. Meineke, H. Loeffler-Wirth, C. Beger, A. Uciteli, S. Staubert, M. Lobe, R. Hansel, F. G. Rauscher, J. Schuster, T. Peschel, H. Herre, J. Wagner, S. Zachariae, C. Engel, M. Scholz, E. Rahm, H. Binder, M. Loeffler

Date Published: 3rd Aug 2022

Publication Type: Journal article

Algorithmic surveillance of ICU patients with acute respiratory distress syndrome (ASIC): protocol for a multicentre stepped-wedge cluster randomised quality improvement strategy
SMITH - Smart Medical Information Technology for Healthcare

Abstract (Expand)

INTRODUCTION: The acute respiratory distress syndrome (ARDS) is a highly relevant entity in critical care with mortality rates of 40%. Despite extensive scientific efforts, outcome-relevant therapeutic … measures are still insufficiently practised at the bedside. Thus, there is a clear need to adhere to early diagnosis and sufficient therapy in ARDS, assuring lower mortality and multiple organ failure. METHODS AND ANALYSIS: In this quality improvement strategy (QIS), a decision support system as a mobile application (ASIC app), which uses available clinical real-time data, is implemented to support physicians in timely diagnosis and improvement of adherence to established guidelines in the treatment of ARDS. ASIC is conducted on 31 intensive care units (ICUs) at 8 German university hospitals. It is designed as a multicentre stepped-wedge cluster randomised QIS. ICUs are combined into 12 clusters which are randomised in 12 steps. After preparation (18 months) and a control phase of 8 months for all clusters, the first cluster enters a roll-in phase (3 months) that is followed by the actual QIS phase. The remaining clusters follow in month wise steps. The coprimary key performance indicators (KPIs) consist of the ARDS diagnostic rate and guideline adherence regarding lung-protective ventilation. Secondary KPIs include the prevalence of organ dysfunction within 28 days after diagnosis or ICU discharge, the treatment duration on ICU and the hospital mortality. Furthermore, the user acceptance and usability of new technologies in medicine are examined. To show improvements in healthcare of patients with ARDS, differences in primary and secondary KPIs between control phase and QIS will be tested. ETHICS AND DISSEMINATION: Ethical approval was obtained from the independent Ethics Committee (EC) at the RWTH Aachen Faculty of Medicine (local EC reference number: EK 102/19) and the respective data protection officer in March 2019. The results of the ASIC QIS will be presented at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: DRKS00014330.

Authors: Gernot Marx, Johannes Bickenbach, Sebastian Johannes Fritsch, Julian Benedict Kunze, Oliver Maassen, Saskia Deffge, Jennifer Kistermann, Silke Haferkamp, Irina Lutz, Nora Kristiana Voellm, Volker Lowitsch, Richard Polzin, Konstantin Sharafutdinov, Hannah Mayer, Lars Kuepfer, Rolf Burghaus, Walter Schmitt, Joerg Lippert, Morris Riedel, Chadi Barakat, André Stollenwerk, Simon Fonck, Christian Putensen, Sven Zenker, Felix Erdfelder, Daniel Grigutsch, Rainer Kram, Susanne Beyer, Knut Kampe, Jan Erik Gewehr, Friederike Salman, Patrick Juers, Stefan Kluge, Daniel Tiller, Emilia Wisotzki, Sebastian Gross, Lorenz Homeister, Frank Bloos, André Scherag, Danny Ammon, Susanne Mueller, Julia Palm, Philipp Simon, Nora Jahn, Markus Loeffler, Thomas Wendt, Tobias Schuerholz, Petra Groeber, Andreas Schuppert

Date Published: 1st Apr 2021

Publication Type: Journal article

The Human Blood Transcriptome in a Large Population Cohort and Its Relation to Aging and Health.
LIFE Adult, oBIG - omics Bioinformatics for Health

Abstract (Expand)

Background: The blood transcriptome is expected to provide a detailed picture of an organism's physiological state with potential outcomes for applications in medical diagnostics and molecular and … epidemiological research. We here present the analysis of blood specimens of 3,388 adult individuals, together with phenotype characteristics such as disease history, medication status, lifestyle factors, and body mass index (BMI). The size and heterogeneity of this data challenges analytics in terms of dimension reduction, knowledge mining, feature extraction, and data integration. Methods: Self-organizing maps (SOM)-machine learning was applied to study transcriptional states on a population-wide scale. This method permits a detailed description and visualization of the molecular heterogeneity of transcriptomes and of their association with different phenotypic features. Results: The diversity of transcriptomes is described by personalized SOM-portraits, which specify the samples in terms of modules of co-expressed genes of different functional context. We identified two major blood transcriptome types where type 1 was found more in men, the elderly, and overweight people and it upregulated genes associated with inflammation and increased heme metabolism, while type 2 was predominantly found in women, younger, and normal weight participants and it was associated with activated immune responses, transcriptional, ribosomal, mitochondrial, and telomere-maintenance cell-functions. We find a striking overlap of signatures shared by multiple diseases, aging, and obesity driven by an underlying common pattern, which was associated with the immune response and the increase of inflammatory processes. Conclusions: Machine learning applications for large and heterogeneous omics data provide a holistic view on the diversity of the human blood transcriptome. It provides a tool for comparative analyses of transcriptional signatures and of associated phenotypes in population studies and medical applications.

Authors: M. Schmidt, L. Hopp, A. Arakelyan, H. Kirsten, C. Engel, K. Wirkner, K. Krohn, R. Burkhardt, J. Thiery, M. Loeffler, H. Loeffler-Wirth, H. Binder

Date Published: 11th Mar 2021

Publication Type: Journal article

Dynamics of cytokines, immune cell counts and disease severity in patients with community-acquired pneumonia - Unravelling potential causal relationships
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Community acquired pneumonia (CAP) is a severe and often rapidly deteriorating disease. To better understand its dynamics and potential causal relationships, we analyzed time series data of …f cytokines, blood and clinical parameters in hospitalized CAP patients. METHODS Time series data of 10 circulating cytokines, blood counts and clinical parameters were related to baseline characteristics of 403 CAP patients using univariate mixed models. Bivariate mixed models were applied to analyze correlations between the time series. To identify potential causal relationships, we inferred cross-lagged relationships between pairs of parameters using latent curve models with structured residuals. RESULTS IL-6 levels decreased faster over time in younger patients (Padj = 0.06). IL-8, VCAM-1, and IL-6 correlated strongly with disease severity as assessed by the sequential organ failure assessment (SOFA) score (r = 0.49, 0.48, 0.46, respectively; all Padj \textless 0.001). IL-6 and bilirubin correlated with respect to their mean levels and slopes over time (r = 0.36 and r = 0.46, respectively; Padj \textless 0.001). A number of potential causal relationships were identified, e.g., a negative effect of ICAM-1 on MCP-1, or a positive effect of the level of creatinine on the subsequent VCAM-1 concentration (P \textless 0.001). CONCLUSIONS These results suggest that IL-6 trajectories of CAP patients are associated with age and run parallel to bilirubin levels. The time series analysis also unraveled directed, potentially causal relationships between cytokines, blood parameters and clinical outcomes. This will facilitate the development of mechanistic models of CAP, and with it, improvements in treatment or surveillance strategies for this disease. TRIAL REGISTRATION clinicaltrials.gov NCT02782013, May 25, 2016, retrospectively registered.

Authors: Maciej Rosolowski, Volker Oberle, Peter Ahnert, Petra Creutz, Martin Witzenrath, Michael Kiehntopf, Markus Loeffler, Norbert Suttorp, Markus Scholz

Date Published: 1st Dec 2020

Publication Type: Journal article

Integration of mathematical model predictions into routine workflows to support clinical decision making in haematology
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Individualization and patient-specific optimization of treatment is a major goal of modern health care. One way to achieve this goal is the application of high-resolution diagnostics together …r with the application of targeted therapies. However, the rising number of different treatment modalities also induces new challenges: Whereas randomized clinical trials focus on proving average treatment effects in specific groups of patients, direct conclusions at the individual patient level are problematic. Thus, the identification of the best patient-specific treatment options remains an open question. Systems medicine, specifically mechanistic mathematical models, can substantially support individual treatment optimization. In addition to providing a better general understanding of disease mechanisms and treatment effects, these models allow for an identification of patient-specific parameterizations and, therefore, provide individualized predictions for the effect of different treatment modalities. RESULTS In the following we describe a software framework that facilitates the integration of mathematical models and computer simulations into routine clinical processes to support decision-making. This is achieved by combining standard data management and data exploration tools, with the generation and visualization of mathematical model predictions for treatment options at an individual patient level. CONCLUSIONS By integrating model results in an audit trail compatible manner into established clinical workflows, our framework has the potential to foster the use of systems-medical approaches in clinical practice. We illustrate the framework application by two use cases from the field of haematological oncology.

Authors: Katja Hoffmann, Katja Cazemier, Christoph Baldow, Silvio Schuster, Yuri Kheifetz, Sibylle Schirm, Matthias Horn, Thomas Ernst, Constanze Volgmann, Christian Thiede, Andreas Hochhaus, Martin Bornhäuser, Meinolf Suttorp, Markus Scholz, Ingmar Glauche, Markus Loeffler, Ingo Roeder

Date Published: 1st Dec 2020

Publication Type: Journal article

Higher BMI, but not obesity-related genetic polymorphisms, correlates with lower structural connectivity of the reward network in a population-based study.
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND: Obesity is of complex origin, involving genetic and neurobehavioral factors. Genetic polymorphisms may increase the risk for developing obesity by modulating dopamine-dependent behaviors, … such as reward processing. Yet, few studies have investigated the association of obesity, related genetic variants, and structural connectivity of the dopaminergic reward network. METHODS: We analyzed 347 participants (age range: 20-59 years, BMI range: 17-38 kg/m(2)) of the LIFE-Adult Study. Genotyping for the single nucleotid polymorphisms rs1558902 (FTO) and rs1800497 (near dopamine D2 receptor) was performed on a microarray. Structural connectivity of the reward network was derived from diffusion-weighted magnetic resonance imaging at 3 T using deterministic tractography of Freesurfer-derived regions of interest. Using graph metrics, we extracted summary measures of clustering coefficient and connectivity strength between frontal and striatal brain regions. We used linear models to test the association of BMI, risk alleles of both variants, and reward network connectivity. RESULTS: Higher BMI was significantly associated with lower connectivity strength for number of streamlines (beta = -0.0025, 95%-C.I.: [-0.004, -0.0008], p = 0.0042), and, to lesser degree, fractional anisotropy (beta = -0.0009, 95%-C.I. [-0.0016, -0.00008], p = 0.031), but not clustering coefficient. Strongest associations were found for left putamen, right accumbens, and right lateral orbitofrontal cortex. As expected, the polymorphism rs1558902 in FTO was associated with higher BMI (F = 6.9, p < 0.001). None of the genetic variants was associated with reward network structural connectivity. CONCLUSIONS: Here, we provide evidence that higher BMI correlates with lower reward network structural connectivity. This result is in line with previous findings of obesity-related decline in white matter microstructure. We did not observe an association of variants in FTO or near DRD2 receptor with reward network structural connectivity in this population-based cohort with a wide range of BMI and age. Future research should further investigate the link between genetics, obesity and fronto-striatal structural connectivity.

Authors: F. Beyer, R. Zhang, M. Scholz, K. Wirkner, M. Loeffler, M. Stumvoll, A. Villringer, A. V. Witte

Date Published: 25th Oct 2020

Publication Type: Journal article

Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults.
Genetical Statistics and Systems Biology

Abstract (Expand)

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide … associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/beta-catenin, TGF-beta and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

Authors: E. Hofer, G. V. Roshchupkin, H. H. H. Adams, M. J. Knol, H. Lin, S. Li, H. Zare, S. Ahmad, N. J. Armstrong, C. L. Satizabal, M. Bernard, J. C. Bis, N. A. Gillespie, M. Luciano, A. Mishra, M. Scholz, A. Teumer, R. Xia, X. Jian, T. H. Mosley, Y. Saba, L. Pirpamer, S. Seiler, J. T. Becker, O. Carmichael, J. I. Rotter, B. M. Psaty, O. L. Lopez, N. Amin, S. J. van der Lee, Q. Yang, J. J. Himali, P. Maillard, A. S. Beiser, C. DeCarli, S. Karama, L. Lewis, M. Harris, M. E. Bastin, I. J. Deary, A. Veronica Witte, F. Beyer, M. Loeffler, K. A. Mather, P. R. Schofield, A. Thalamuthu, J. B. Kwok, M. J. Wright, D. Ames, J. Trollor, J. Jiang, H. Brodaty, W. Wen, M. W. Vernooij, A. Hofman, A. G. Uitterlinden, W. J. Niessen, K. Wittfeld, R. Bulow, U. Volker, Z. Pausova, G. Bruce Pike, S. Maingault, F. Crivello, C. Tzourio, P. Amouyel, B. Mazoyer, M. C. Neale, C. E. Franz, M. J. Lyons, M. S. Panizzon, O. A. Andreassen, A. M. Dale, M. Logue, K. L. Grasby, N. Jahanshad, J. N. Painter, L. Colodro-Conde, J. Bralten, D. P. Hibar, P. A. Lind, F. Pizzagalli, J. L. Stein, P. M. Thompson, S. E. Medland, P. S. Sachdev, W. S. Kremen, J. M. Wardlaw, A. Villringer, C. M. van Duijn, H. J. Grabe, W. T. Jr Longstreth, M. Fornage, T. Paus, S. Debette, M. Arfan Ikram, H. Schmidt, R. Schmidt, S. Seshadri

Date Published: 22nd Sep 2020

Publication Type: Journal article

Pro-Neurotensin depends on renal function and is related to all-cause mortality in chronic kidney disease
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Patients with chronic kidney disease (CKD) have a high risk of premature cardiovascular diseases (CVD) and show increased mortality. Pro-Neurotensin (NT) was associated with metabolic diseases …s and predicted incident CVD and mortality. However, Pro-NT regulation in CKD and its potential role linking CKD and mortality have not been investigated, so far. METHODS In a central lab, circulating Pro-NT was quantified in three independent cohorts comprising 4,715 participants (cohort 1: patients with CKD; cohort 2: general population study; cohort 3: non-diabetic population study). Urinary Pro-NT was assessed in part of the patients from cohort 1. Serum Pro-NT was further related to mortality in patients with advanced CKD. Tissue-specific Nts expression was investigated in two mouse models of diabetic CKD and compared to non-diabetic control mice. RESULTS Pro-NT significantly increased with deteriorating renal function (p\textless0.001). In meta-analysis of cohorts 1-3, Pro-NT was significantly and independently associated with estimated glomerular filtration rate (p\leq0.002). Patients in the middle/high Pro-NT tertiles at baseline had a higher all-cause mortality compared to the low Pro-NT tertile (Hazard ratio: 2.11, p=0.046). Mice with severe diabetic CKD did not show increased Nts mRNA expression in different tissues compared to control animals. CONCLUSIONS Circulating Pro-NT is associated with impaired renal function in independent cohorts comprising 4,715 subjects and is related to all-cause mortality in patients with end-stage kidney disease. Our human and rodent data are in accordance with the hypotheses that Pro-NT is eliminated by the kidneys and could potentially contribute to increased mortality observed in patients with CKD.

Authors: Anke Toenjes, Annett Hoffmann, Susan Kralisch, Abdul Rashid Qureshi, Nora Klöting, Markus Scholz, Dorit Schleinitz, Anette Bachmann, Juergen Kratzsch, Marcin Nowicki, Sabine Paeschke, Kerstin Wirkner, Cornelia Enzenbach, Ronny Baber, Joachim Beige, Matthias Anders, Ingolf Bast, Matthias Blüher, Peter Kovacs, Markus Löffler, Ming-Zhi Zhang, Raymond C. Harris, Peter Stenvinkel, Michael Stumvoll, Mathias Fasshauer, Thomas Ebert

Date Published: 1st Sep 2020

Publication Type: Journal article

VISEP V-VERL-join
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: Clinical Data

VISEP V-PAT-ODM
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: ODM Data

VISEP V-PAT-SPSS
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: Clinical Data

VISEP V-VERL-join-SPSS
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: Clinical Data

VISEP haemo_join-SPSS
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: Clinical Data

VISEP haemo_join-ODM
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: ODM Data

VISEP haemo_join
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: Clinical Data

VISEP Endpoint-ODM
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: ODM Data

VISEP Endpoint
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: Clinical Data

VISEP Endpoint-SPSS
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: Clinical Data

2 hidden items
Bulletin COVID-19 Leipzig 2022-03-22
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Torsten Thalheim, Markus Scholz, Markus Löffler

Submitter: René Hänsel

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Bulletin COVID-19 Leipzig 2022-11-28
Task Force COVID-19 Leipzig

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Löffler, Markus Scholz, Torsten Thalheim, Radosław dzikowski, Yuri Kheifetz, Tyll Krüger, Tomasz Ożański, Marcin Bodych, Maciej Filiński

Submitter: René Hänsel

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Bulletin COVID-19 Leipzig 2021-03-18
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Scholz, Markus Löffler, Peter Ahnert, Anne Dietrich, Dirk Hasenclever, Matthias Horn, Yuri Kheifetz, Tyll Krüger, Sibylle Schirm

Submitter: Christoph Beger

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Bulletin COVID-19 Leipzig 2020-10-16
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Löffler, Markus Scholz, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Kolja Nenoff, Sibylle Schirm

Submitter: Christoph Beger

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Bulletin COVID-19 Leipzig 2020-06-30
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Löffler, Markus Scholz, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Kolja Nenoff, Sibylle Schirm

Submitter: Christoph Beger

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Bulletin COVID-19 Leipzig 2020-05-28
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Scholz, Markus Löffler, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Kolja Nenoff, Sibylle Schirm

Submitter: Christoph Beger

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Bulletin COVID-19 Leipzig 2020-05-04
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Scholz, Markus Löffler, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Sibylle Schirm

Submitter: Christoph Beger

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Bulletin COVID-19 Leipzig 2020-04-26
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Scholz, Markus Löffler, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Sibylle Schirm

Submitter: Christoph Beger

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Bulletin COVID-19 Leipzig 2020-04-13
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Scholz, Markus Löffler, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Sibylle Schirm

Submitter: Christoph Beger

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Bulletin COVID-19 Leipzig 2020-04-19
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Scholz, Markus Löffler, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Sibylle Schirm

Submitter: Christoph Beger

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NHL
No description specified

Projects: HaematoSys - Systems biology of haematopoiesis and haematopoietic neoplasia, GLA - German Lymphoma Alliance

Web page: Not specified

LIFE Management Cluster
No description specified

Projects: LIFE Heart, LIFE - Leipzig Research Center for Civilization Diseases, LIFE HNC - Head and Neck Cancer Group, SepNet - German Competence Network Sepsis, GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer, LIFE Child, GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer, LIFE Adult

Web page: https://www.uniklinikum-leipzig.de/einrichtungen/life

i:DSem - Integrative Datensemantik in der Systemmedizin

Within the framework of the funding measure "i:DSem - Integrative Data Semantics in Systems Medicine", the Federal Ministry of Education and Research supports research projects that take up this approach. Interdisciplinary research projects are to create the basis so that in the future, for example, the attending physician will have application-oriented computer programmes at his or her disposal that will enable him or her to access all clinically relevant data. This should significantly support ...

Projects: LHA - Leipzig Health Atlas

Web page: https://www.gesundheitsforschung-bmbf.de/de/i-dsem-integrative-datensemantik-in-der-systemmedizin-3367.php

NFDI - German National Research Data Infrastructure

In the German National Research Data Infrastructure (NFDI), valuable data from science and research are systematically accessed, networked and made usable in a sustainable and qualitative manner for the entire German science system. Up to now, they have mostly been available on a decentralised, project-related or temporary basis. The NFDI aims to create a permanent digital repository of knowledge as an indispensable prerequisite for new research questions, findings and innovations. Relevant data ...

Projects: NFDI4Health, Task Force COVID-19 Leipzig, NFDI4Health - TA3 Services, Clinical Trials Leipzig

Web page: https://www.nfdi.de/?lang=en

MII - Medical Informatics Initiative

The medical informatics initiative was created to close the gap between research and healthcare. All of Germany’s university hospitals have joined forces with research institutions, businesses, health insurers, and patient advocacy groups to create a framework that harnesses research findings to the direct benefit of patients. The German Federal Ministry of Education and Research (BMBF) is investing around 160 million euros in the programme through 2021. The digitisation of medicine is creating ...

Projects: Methodical Use Case PheP, SMITH - Smart Medical Information Technology for Healthcare, POLAR - Polypharmacy, Drug Interactions, Risks

Web page: https://www.medizininformatik-initiative.de/en

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Health Atlas - Local Data Hub/Leipzig

The Health Atlas - Local Data Hub/Leipzig is an alliance of medical ontologists, medical systems biologists and clinical trials groups to design and implement a multi-functional and quality-assured atlas. It provides models, data and metadata on specific use cases from medical research fields.

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