@article{HeisselSanchezPietreketal.2023, author = {Heissel, Andreas and Sanchez, Alba and Pietrek, Anou F. and Bergau, Theresa and Stielow, Christiane and Rapp, Michael A. and Van der Kaap-Deeder, Jolene}, title = {Validating the German Short Basic Psychological Need Satisfaction and Frustration Scale in Individuals with Depression}, series = {Healthcare}, volume = {11}, journal = {Healthcare}, number = {3}, publisher = {MDPI}, address = {Basel}, issn = {2227-9032}, doi = {10.3390/healthcare11030412}, pages = {18}, year = {2023}, abstract = {Satisfaction and frustration of the needs for autonomy, competence, and relatedness, as assessed with the 24-item Basic Psychological Need Satisfaction and Frustration Scale (BPNSFS), have been found to be crucial indicators of individuals' psychological health. To increase the usability of this scale within a clinical and health services research context, we aimed to validate a German short version (12 items) of this scale in individuals with depression including the examination of the relations from need frustration and need satisfaction to ill-being and quality of life (QOL). This cross-sectional study involved 344 adults diagnosed with depression (Mage (SD) = 47.5 years (11.1); 71.8\% females). Confirmatory factor analyses indicated that the short version of the BPNSFS was not only reliable, but also fitted a six-factor structure (i.e., satisfaction/frustration X type of need). Subsequent structural equation modeling showed that need frustration related positively to indicators of ill-being and negatively to QOL. Surprisingly, need satisfaction did not predict differences in ill-being or QOL. The short form of the BPNSFS represents a practical instrument to measure need satisfaction and frustration in people with depression. Further, the results support recent evidence on the importance of especially need frustration in the prediction of psychopathology.}, language = {en} } @article{WyckmansOttoSeboldetal.2019, author = {Wyckmans, Florent and Otto, A. Ross and Sebold, Miriam and Daw, Nathaniel and Bechara, Antoine and Saeremans, M{\´e}lanie and Kornreich, Charles and Chatard, Armand and Jaafari, Nemat and No{\"e}l, Xavier}, title = {Reduced model-based decision-making in gambling disorder}, series = {Scientific reports}, volume = {9}, journal = {Scientific reports}, publisher = {Nature Publ. Group}, address = {London}, issn = {2045-2322}, doi = {10.1038/s41598-019-56161-z}, pages = {10}, year = {2019}, abstract = {Compulsive behaviors (e.g., addiction) can be viewed as an aberrant decision process where inflexible reactions automatically evoked by stimuli (habit) take control over decision making to the detriment of a more flexible (goal-oriented) behavioral learning system. These behaviors are thought to arise from learning algorithms known as "model-based" and "model-free" reinforcement learning. Gambling disorder, a form of addiction without the confound of neurotoxic effects of drugs, showed impaired goal-directed control but the way in which problem gamblers (PG) orchestrate model-based and model-free strategies has not been evaluated. Forty-nine PG and 33 healthy participants (CP) completed a two-step sequential choice task for which model-based and model-free learning have distinct and identifiable trial-by-trial learning signatures. The influence of common psychopathological comorbidities on those two forms of learning were investigated. PG showed impaired model-based learning, particularly after unrewarded outcomes. In addition, PG exhibited faster reaction times than CP following unrewarded decisions. Troubled mood, higher impulsivity (i.e., positive and negative urgency) and current and chronic stress reported via questionnaires did not account for those results. These findings demonstrate specific reinforcement learning and decision-making deficits in behavioral addiction that advances our understanding and may be important dimensions for designing effective interventions.}, language = {en} } @article{KaminskiSchlagenhaufRappetal.2018, author = {Kaminski, Jakob A. and Schlagenhauf, Florian and Rapp, Michael A. and Awasthi, Swapnil and Ruggeri, Barbara and Deserno, Lorenz and Banaschewski, Tobias and Bokde, Arun L. W. and Bromberg, Uli and B{\"u}chel, Christian and Quinlan, Erin Burke and Desrivieres, Sylvane and Flor, Herta and Frouin, Vincent and Garavan, Hugh and Gowland, Penny and Ittermann, Bernd and Martinot, Jean-Luc and Martinot, Marie-Laure Paillere and Nees, Frauke and Orfanos, Dimitri Papadopoulos and Paus, Tomas and Poustka, Luise and Smolka, Michael N. and Fr{\"o}hner, Juliane H. and Walter, Henrik and Whelan, Robert and Ripke, Stephan and Schumann, Gunter and Heinz, Andreas}, title = {Epigenetic variance in dopamine D2 receptor}, series = {Translational Psychiatry}, volume = {8}, journal = {Translational Psychiatry}, publisher = {Nature Publ. Group}, address = {New York}, organization = {IMAGEN Consortium}, issn = {2158-3188}, doi = {10.1038/s41398-018-0222-7}, pages = {11}, year = {2018}, abstract = {Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure.}, language = {en} } @article{HeroldTheobaldGronwaldetal.2022, author = {Herold, Fabian and Theobald, Paula and Gronwald, Thomas and Rapp, Michael A. and M{\"u}ller, Notger Germar}, title = {Going digital - a commentary on the terminology used at the intersection of physical activity and digital health}, series = {European review of aging and physical activity}, volume = {19}, journal = {European review of aging and physical activity}, publisher = {Springer}, address = {Berlin ; Heidelberg}, issn = {1861-6909}, doi = {10.1186/s11556-022-00296-y}, pages = {7}, year = {2022}, abstract = {In recent years digital technologies have become a major means for providing health-related services and this trend was strongly reinforced by the current Coronavirus disease 2019 (COVID-19) pandemic. As it is well-known that regular physical activity has positive effects on individual physical and mental health and thus is an important prerequisite for healthy aging, digital technologies are also increasingly used to promote unstructured and structured forms of physical activity. However, in the course of this development, several terms (e.g., Digital Health, Electronic Health, Mobile Health, Telehealth, Telemedicine, and Telerehabilitation) have been introduced to refer to the application of digital technologies to provide health-related services such as physical interventions. Unfortunately, the above-mentioned terms are often used in several different ways, but also relatively interchangeably. Given that ambiguous terminology is a major source of difficulty in scientific communication which can impede the progress of theoretical and empirical research, this article aims to make the reader aware of the subtle differences between the relevant terms which are applied at the intersection of physical activity and Digital Health and to provide state-of-art definitions for them.}, language = {en} } @article{HeisselBollmannKangasetal.2021, author = {Heißel, Andreas and Bollmann, Julian and Kangas, Maria and Abdulla, K and Rapp, Michael A. and S{\´a}nchez Fern{\`a}ndez, Alba Cristina}, title = {Validation of the German version of the work and social adjustment scale in a sample of depressed patients}, series = {BMC health services research}, volume = {21}, journal = {BMC health services research}, publisher = {BioMed Central}, address = {London}, issn = {1472-6963}, doi = {10.1186/s12913-021-06622-x}, pages = {1 -- 11}, year = {2021}, abstract = {Background Depression is one of the key factors contributing to difficulties in one's ability to work, and serves as one of the major reasons why employees apply for psychotherapy and receive insurance subsidization of treatments. Hence, an increasing and growing number of studies rely on workability assessment scales as their primary outcome measure. The Work and Social Assessment Scale (WSAS) has been documented as one of the most psychometrically reliable and valid tools especially developed to assess workability and social functioning in patients with mental health problems. Yet, the application of the WSAS in Germany has been limited due to the paucity of a valid questionnaire in the German language. The objective of the present study was to translate the WSAS, as a brief and easy administrable tool into German and test its psychometric properties in a sample of adults with depression. Methods Two hundred seventy-seven patients (M = 48.3 years, SD = 11.1) with mild to moderately severe depression were recruited. A multistep translation from English into the German language was performed and the factorial validity, criterion validity, convergent validity, discriminant validity, internal consistency, and floor and ceiling effects were examined. Results The confirmatory factor analysis results confirmed the one-factor structure of the WSAS. Significant correlations with the WHODAS 2-0 questionnaire, a measure of functionality, demonstrated good convergent validity. Significant correlations with depression and quality of life demonstrated good criterion validity. The WSAS also demonstrated strong internal consistency (α = .89), and the absence of floor and ceiling effects indicated good sensitivity of the instrument. Conclusions The results of the present study demonstrated that the German version of the WSAS has good psychometric properties comparable to other international versions of this scale. The findings recommend a global assessment of psychosocial functioning with the sum score of the WSAS.}, language = {en} } @article{PerezChaparroSchuchZechetal.2021, author = {P{\´e}rez Chaparro, Camilo Germ{\´a}n Alberto and Schuch, Felipe Barreto and Zech, Philipp and Kangas, Maria and Rapp, Michael A. and Heißel, Andreas}, title = {Recreational exercising and self-reported cardiometabolic diseases in German people living with HIV}, series = {International journal of environmental research and public health : IJERPH / Molecular Diversity Preservation International}, volume = {18}, journal = {International journal of environmental research and public health : IJERPH / Molecular Diversity Preservation International}, number = {21}, publisher = {MDPI}, address = {Basel, Schweiz}, issn = {1660-4601}, doi = {10.3390/ijerph182111579}, pages = {1 -- 10}, year = {2021}, abstract = {Exercise is known for its beneficial effects on preventing cardiometabolic diseases (CMDs) in the general population. People living with the human immunodeficiency virus (PLWH) are prone to sedentarism, thus raising their already elevated risk of developing CMDs in comparison to individuals without HIV. The aim of this cross-sectional study was to determine if exercise is associated with reduced risk of self-reported CMDs in a German HIV-positive sample (n = 446). Participants completed a self-report survey to assess exercise levels, date of HIV diagnosis, CD4 cell count, antiretroviral therapy, and CMDs. Participants were classified into exercising or sedentary conditions. Generalized linear models with Poisson regression were conducted to assess the prevalence ratio (PR) of PLWH reporting a CMD. Exercising PLWH were less likely to report a heart arrhythmia for every increase in exercise duration (PR: 0.20: 95\% CI: 0.10-0.62, p < 0.01) and diabetes mellitus for every increase in exercise session per week (PR: 0.40: 95\% CI: 0.10-1, p < 0.01). Exercise frequency and duration are associated with a decreased risk of reporting arrhythmia and diabetes mellitus in PLWH. Further studies are needed to elucidate the mechanisms underlying exercise as a protective factor for CMDs in PLWH.}, language = {en} } @article{GellertHaeuslerSuhretal.2018, author = {Gellert, Paul and H{\"a}usler, Andreas and Suhr, Ralf and Gholami, Maryam and Rapp, Michael A. and Kuhlmey, Adelheid and Nordheim, Johanna}, title = {Testing the stress-buffering hypothesis of social support in couples coping with early-stage dementia}, series = {PLoS one}, volume = {13}, journal = {PLoS one}, number = {1}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0189849}, pages = {14}, year = {2018}, abstract = {Purpose: To test whether the negative relationship between perceived stress and quality of life (Hypothesis 1) can be buffered by perceived social support in patients with dementia as well as in caregivers individually (Hypothesis 2: actor effects) and across partners (Hypothesis 3: partner effects and actor-partner effects). Method: A total of 108 couples (N = 216 individuals) comprised of one individual with early-stage dementia and one caregiving partner were assessed at baseline and one month apart. Moderation effects were investigated by applying linear mixed models and actor-partner interdependence models. Results: Although the stress-quality of life association was more pronounced in caregivers (beta = -.63, p<.001) compared to patients (beta= -.31, p<.001), this association was equally moderated by social support in patients (beta = .14, p<.05) and in the caregivers (beta =.13, p<.05). From one partner to his or her counterpart, the partner buffering and actor-partner-buffering effect were not present. Conclusion: The stress-buffering effect has been replicated in individuals with dementia and caregivers but not across partners. Interventions to improve quality of life through perceived social support should not only focus on caregivers, but should incorporate both partners.}, language = {en} } @article{HeinzKieferSmolkaetal.2020, author = {Heinz, Andreas and Kiefer, Falk and Smolka, Michael N. and Endrass, Tanja and Beste, Christian and Beck, Anne and Liu, Shuyan and Genauck, Alexander and Romund, Lydia and Rapp, Michael A. and Tost, Heike and Spanagel, Rainer}, title = {Addiction research consortium: losing and regaining control over drug intake (ReCoDe) - from trajectories to mechanisms and interventions}, series = {Addiction Biology}, volume = {25}, journal = {Addiction Biology}, number = {2}, publisher = {John Wiley \& Sons, Inc.}, address = {New Jersey}, pages = {6}, year = {2020}, abstract = {One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake.}, language = {en} } @article{SchraplauBlockHaeusleretal.2021, author = {Schraplau, Anne and Block, Andrea and H{\"a}usler, Andreas and Wippert, Pia-Maria and Rapp, Michael A. and V{\"o}ller, Heinz and Bonaventura, Klaus and Mayer, Frank}, title = {Mobile diagnostics and consultation for the prevention of the metabolic syndrome and its secondary diseases in Brandenburg—study protocol of a regional prospective cohort study}, series = {Pilot and Feasibility Studies}, volume = {7}, journal = {Pilot and Feasibility Studies}, publisher = {BioMed Central (Springer Nature)}, address = {London}, issn = {2055-5784}, doi = {10.1186/s40814-021-00898-w}, pages = {1 -- 11}, year = {2021}, abstract = {Background The metabolic syndrome (MetS) is a risk cluster for a number of secondary diseases. The implementation of prevention programs requires early detection of individuals at risk. However, access to health care providers is limited in structurally weak regions. Brandenburg, a rural federal state in Germany, has an especially high MetS prevalence and disease burden. This study aims to validate and test the feasibility of a setup for mobile diagnostics of MetS and its secondary diseases, to evaluate the MetS prevalence and its association with moderating factors in Brandenburg and to identify new ways of early prevention, while establishing a "Mobile Brandenburg Cohort" to reveal new causes and risk factors for MetS. Methods In a pilot study, setups for mobile diagnostics of MetS and secondary diseases will be developed and validated. A van will be equipped as an examination room using point-of-care blood analyzers and by mobilizing standard methods. In study part A, these mobile diagnostic units will be placed at different locations in Brandenburg to locally recruit 5000 participants aged 40-70 years. They will be examined for MetS and advice on nutrition and physical activity will be provided. Questionnaires will be used to evaluate sociodemographics, stress perception, and physical activity. In study part B, participants with MetS, but without known secondary diseases, will receive a detailed mobile medical examination, including MetS diagnostics, medical history, clinical examinations, and instrumental diagnostics for internal, cardiovascular, musculoskeletal, and cognitive disorders. Participants will receive advice on nutrition and an exercise program will be demonstrated on site. People unable to participate in these mobile examinations will be interviewed by telephone. If necessary, participants will be referred to general practitioners for further diagnosis. Discussion The mobile diagnostics approach enables early detection of individuals at risk, and their targeted referral to local health care providers. Evaluation of the MetS prevalence, its relation to risk-increasing factors, and the "Mobile Brandenburg Cohort" create a unique database for further longitudinal studies on the implementation of home-based prevention programs to reduce mortality, especially in rural regions. Trial registration German Clinical Trials Register, DRKS00022764; registered 07 October 2020—retrospectively registered.}, language = {en} } @article{HeisselPietrekSchwefeletal.2020, author = {Heissel, Andreas and Pietrek, Anou F. and Schwefel, Melanie and Abula, Kahar and Wilbertz, Gregor and Heinzel, Stephan and Rapp, Michael A.}, title = {STEP.De study}, series = {BMJ open}, volume = {10}, journal = {BMJ open}, number = {4}, publisher = {BMJ Publishing Group}, address = {London}, issn = {2044-6055}, doi = {10.1136/bmjopen-2019-036287}, pages = {10}, year = {2020}, abstract = {Introduction Although exercise therapy has widely been shown to be an efficacious treatment modality for depression, evidence for its effectiveness and cost efficiency is lacking. The Sport/Exercise Therapy for Depression study is a multicentre cluster-randomised effectiveness trial that aims to compare the effectiveness and cost efficiency of exercise therapy and psychotherapy as antidepressant treatment.
Methods and analysis 480 patients (aged 18-65) with an International Classification of Diseases diagnosis associated with depressive symptoms are recruited. Up to 30 clusters (psychotherapists) are randomly assigned to allocate patients to either an exercise or a psychotherapy treatment as usual in a 2: 1 ratio. The primary outcome (depressive symptoms) and the secondary outcomes (work and social adjustment, quality of life) will be assessed at six measurement time points (t0: baseline, t1: 8 weeks after treatment initiation, t2: 16 weeks after treatment initiation, t3/ 4/5: 2, 6, 12 months after treatment). Linear regression analyses will be used for the primary endpoint data analysis. For the secondary endpoints, mixed linear and logistic regression models with fixed and random factors will be added. For the cost efficiency analysis, expenditures in the 12 months before and after the intervention and the outcome difference will be compared between groups in a multilevel model. Recruitment start date was 1 July 2018 and the planned recruitment end date is 31 December 2020.
Ethics and dissemination The study protocol was approved by the ethics committee of the University of Potsdam (No. 17/2018) and the Freie Universitat Berlin (No. 206/2018) and registered in the ISRCTN registry. Informed written consent will be obtained from all participants. The study will be reported in accordance with the Consolidated Standards of Reporting Trials and the Recommendations for Interventional Trials statements. The results will be published in peer-reviewed academic journals and disseminated to the public.}, language = {en} } @article{SchulzeMerzThieretal.2022, author = {Schulze, Susanne and Merz, Sibille and Thier, Anne and Tallarek, Marie and K{\"o}nig, Franziska and Uhlenbrock, Greta and N{\"u}bling, Matthias and Lincke, Hans-Joachim and Rapp, Michael A. and Spallek, Jacob and Holmberg, Christine}, title = {Psychosocial burden in nurses working in nursing homes during the Covid-19 pandemic}, series = {BMC health services research}, volume = {22}, journal = {BMC health services research}, number = {1}, publisher = {BMC}, address = {London}, issn = {1472-6963}, doi = {10.1186/s12913-022-08333-3}, pages = {13}, year = {2022}, abstract = {Background The Covid-19 pandemic led to increased work-related strain and psychosocial burden in nurses worldwide, resulting in high prevalences of mental health problems. Nurses in long-term care facilities seem to be especially affected by the pandemic. Nevertheless, there are few findings indicating possible positive changes for health care workers. Therefore, we investigated which psychosocial burdens and potential positive aspects nurses working in long-term care facilities experience during the Covid-19 pandemic. Methods We conducted a mixed-methods study among nurses and nursing assistants working in nursing homes in Germany. The survey contained the third German version of the Copenhagen Psychosocial Questionnaire (COPSOQ III). Using Welch's t-tests, we compared the COPSOQ results of our sample against a pre-pandemic reference group of geriatric nurses from Germany. Additionally, we conducted semi-structured interviews with geriatric nurses with a special focus on psychosocial stress, to reach a deeper understanding of their experiences on work-related changes and burdens during the pandemic. Data were analysed using thematic coding (Braun and Clarke). Results Our survey sample (n = 177) differed significantly from the pre-pandemic reference group in 14 out of 31 COPSOQ scales. Almost all of these differences indicated negative changes. Our sample scored significantly worse regarding the scales 'quantitative demands', 'hiding emotions', 'work-privacy conflicts', 'role conflicts', 'quality of leadership', 'support at work', 'recognition', 'physical demands', 'intention to leave profession', 'burnout', 'presenteeism' and 'inability to relax'. The interviews (n = 15) revealed six main themes related to nurses' psychosocial stress: 'overall working conditions', 'concern for residents', 'management of relatives', 'inability to provide terminal care', 'tensions between being infected and infecting others' and 'technicisation of care'. 'Enhanced community cohesion' (interviews), 'meaning of work' and 'quantity of social relations' (COPSOQ III) were identified as positive effects of the pandemic. Conclusions Results clearly illustrate an aggravation of geriatric nurses' situation and psychosocial burden and only few positive changes due to the Covid-19 pandemic. Pre-existing hardships seem to have further deteriorated and new stressors added to nurses' strain. The perceived erosion of care, due to an overemphasis of the technical in relation to the social and emotional dimensions of care, seems to be especially burdensome to geriatric nurses.}, language = {en} } @article{YeZhangWarbyetal.2022, author = {Ye, Fangyuan and Zhang, Shuo and Warby, Jonathan and Wu, Jiawei and Gutierrez-Partida, Emilio and Lang, Felix and Shah, Sahil and Saglamkaya, Elifnaz and Sun, Bowen and Zu, Fengshuo and Shoaee, Safa and Wang, Haifeng and Stiller, Burkhard and Neher, Dieter and Zhu, Wei-Hong and Stolterfoht, Martin and Wu, Yongzhen}, title = {Overcoming C-60-induced interfacial recombination in inverted perovskite solar cells by electron-transporting carborane}, series = {Nature Communications}, volume = {13}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, address = {London}, issn = {2041-1723}, doi = {10.1038/s41467-022-34203-x}, pages = {12}, year = {2022}, abstract = {Inverted perovskite solar cells still suffer from significant non-radiative recombination losses at the perovskite surface and across the perovskite/C-60 interface, limiting the future development of perovskite-based single- and multi-junction photovoltaics. Therefore, more effective inter- or transport layers are urgently required. To tackle these recombination losses, we introduce ortho-carborane as an interlayer material that has a spherical molecular structure and a three-dimensional aromaticity. Based on a variety of experimental techniques, we show that ortho-carborane decorated with phenylamino groups effectively passivates the perovskite surface and essentially eliminates the non-radiative recombination loss across the perovskite/C-60 interface with high thermal stability. We further demonstrate the potential of carborane as an electron transport material, facilitating electron extraction while blocking holes from the interface. The resulting inverted perovskite solar cells deliver a power conversion efficiency of over 23\% with a low non-radiative voltage loss of 110mV, and retain >97\% of the initial efficiency after 400h of maximum power point tracking. Overall, the designed carborane based interlayer simultaneously enables passivation, electron-transport and hole-blocking and paves the way toward more efficient and stable perovskite solar cells. Effective transport layers are essential to suppress non-radiative recombination losses. Here, the authors introduce phenylamino-functionalized ortho-carborane as an interfacial layer, and realise inverted perovskite solar cells with efficiency of over 23\% and operational stability of T97=400h.}, language = {en} } @article{FoerstnerBoettgerMoldavskietal.2023, author = {F{\"o}rstner, Bernd Rainer and B{\"o}ttger, Sarah Jane and Moldavski, Alexander and Bajbouj, Malek and Pfennig, Andrea and Manook, Andre and Ising, Marcus and Pittig, Andre and Heinig, Ingmar and Heinz, Andreas and Mathiak, Klaus and Schulze, Thomas G. and Schneider, Frank and Kamp-Becker, Inge and Meyer-Lindenberg, Andreas and Padberg, Frank and Banaschewski, Tobias and Bauer, Michael and Rupprecht, Rainer and Wittchen, Hans-Ulrich and Rapp, Michael A. and Tschorn, Mira}, title = {The associations of positive and negative valence systems, cognitive systems and social processes on disease severity in anxiety and depressive disorders}, series = {Frontiers in psychiatry}, volume = {14}, journal = {Frontiers in psychiatry}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-0640}, doi = {10.3389/fpsyt.2023.1161097}, pages = {10}, year = {2023}, abstract = {Background Anxiety and depressive disorders share common features of mood dysfunctions. This has stimulated interest in transdiagnostic dimensional research as proposed by the Research Domain Criteria (RDoC) approach by the National Institute of Mental Health (NIMH) aiming to improve the understanding of underlying disease mechanisms. The purpose of this study was to investigate the processing of RDoC domains in relation to disease severity in order to identify latent disorder-specific as well as transdiagnostic indicators of disease severity in patients with anxiety and depressive disorders. Methods Within the German research network for mental disorders, 895 participants (n = 476 female, n = 602 anxiety disorder, n = 257 depressive disorder) were recruited for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) and included in this cross-sectional study. We performed incremental regression models to investigate the association of four RDoC domains on disease severity in patients with affective disorders: Positive (PVS) and Negative Valance System (NVS), Cognitive Systems (CS) and Social Processes (SP). Results The results confirmed a transdiagnostic relationship for all four domains, as we found significant main effects on disease severity within domain-specific models (PVS: \& beta; = -0.35; NVS: \& beta; = 0.39; CS: \& beta; = -0.12; SP: \& beta; = -0.32). We also found three significant interaction effects with main diagnosis showing a disease-specific association. Limitations The cross-sectional study design prevents causal conclusions. Further limitations include possible outliers and heteroskedasticity in all regression models which we appropriately controlled for. Conclusion Our key results show that symptom burden in anxiety and depressive disorders is associated with latent RDoC indicators in transdiagnostic and disease-specific ways.}, language = {en} } @article{WuertzKozakRoszkowskiCambriaetal.2020, author = {Wuertz-Kozak, Karin and Roszkowski, Martin and Cambria, Elena and Block, Andrea and Kuhn, Gisela A. and Abele, Thea and Hitzl, Wolfgang and Drießlein, David and M{\"u}ller, Ralph and Rapp, Michael A. and Mansuy, Isabelle M. and Peters, Eva M. J. and Wippert, Pia-Maria}, title = {Effects of Early Life Stress on Bone Homeostasis in Mice and Humans}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {18}, publisher = {Molecular Diversity Preservation International}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms21186634}, pages = {24}, year = {2020}, abstract = {Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (μCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.}, language = {en} } @article{HeisselPietrekKangasetal.2023, author = {Heissel, Andreas and Pietrek, Anou F. and Kangas, Maria and Van der Kaap-Deeder, Jolene and Rapp, Michael A.}, title = {The Mediating Role of Rumination in the Relation between Basic Psychological Need Frustration and Depressive Symptoms}, series = {Journal of Clinical Medicine}, volume = {12}, journal = {Journal of Clinical Medicine}, edition = {2}, publisher = {MDPI}, address = {Basel, Schweiz}, issn = {2077-0383}, doi = {10.3390/jcm12020395}, pages = {1 -- 10}, year = {2023}, abstract = {Research within the framework of Basic Psychological Need Theory (BPNT) finds strong associations between basic need frustration and depressive symptoms. This study examined the role of rumination as an underlying mechanism in the association between basic psychological need frustration and depressive symptoms. A cross-sectional sample of N = 221 adults (55.2\% female, mean age = 27.95, range = 18-62, SD = 10.51) completed measures assessing their level of basic psychological need frustration, rumination, and depressive symptoms. Correlational analyses and multiple mediation models were conducted. Brooding partially mediated the relation between need frustration and depressive symptoms. BPNT and Response Styles Theory are compatible and can further advance knowledge about depression vulnerabilities.}, language = {en} } @article{PietrekKangasKliegletal.2022, author = {Pietrek, Anou F. and Kangas, Maria and Kliegl, Reinhold and Rapp, Michael A. and Heinzel, Stephan and Van der Kaap-Deeder, Jolene and Heissel, Andreas}, title = {Basic psychological need satisfaction and frustration in major depressive disorder}, series = {Frontiers in Psychiatry - Mood Disorders}, journal = {Frontiers in Psychiatry - Mood Disorders}, publisher = {Frontiers Media S.A.}, address = {Lausanne, Schweiz}, issn = {1664-0640}, doi = {10.3389/fpsyt.2022.962501}, pages = {1 -- 10}, year = {2022}, abstract = {Basic psychological needs theory postulates that a social environment that satisfies individuals' three basic psychological needs of autonomy, competence, and relatedness leads to optimal growth and well-being. On the other hand, the frustration of these needs is associated with ill-being and depressive symptoms foremost investigated in non-clinical samples; yet, there is a paucity of research on need frustration in clinical samples. Survey data were compared between adult individuals with major depressive disorder (MDD; n = 115; 48.69\% female; 38.46 years, SD = 10.46) with those of a non-depressed comparison sample (n = 201; 53.23\% female; 30.16 years, SD = 12.81). Need profiles were examined with a linear mixed model (LMM). Individuals with depression reported higher levels of frustration and lower levels of satisfaction in relation to the three basic psychological needs when compared to non-depressed adults. The difference between depressed and non-depressed groups was significantly larger for frustration than satisfaction regarding the needs for relatedness and competence. LMM correlation parameters confirmed the expected positive correlation between the three needs. This is the first study showing substantial differences in need-based experiences between depressed and non-depressed adults. The results confirm basic assumptions of the self-determination theory and have preliminary implications in tailoring therapy for depression.}, language = {en} } @article{GarbusowNebeSommeretal.2019, author = {Garbusow, Maria and Nebe, Stephan and Sommer, Christian and Kuitunen-Paul, S{\"o}ren and Sebold, Miriam and Schad, Daniel and Friedel, Eva and Veer, Ilya M. and Wittchen, Hans-Ulrich and Rapp, Michael A. and Ripke, Stephan and Walter, Henrik and Huys, Quentin J. M. and Schlagenhauf, Florian and Smolka, Michael N. and Heinz, Andreas}, title = {Pavlovian-To-Instrumental Transfer and Alcohol Consumption in Young Male Social Drinkers}, series = {Journal of Clinical Medicine}, volume = {8}, journal = {Journal of Clinical Medicine}, number = {8}, publisher = {MDPI}, address = {Basel}, issn = {2077-0383}, doi = {10.3390/jcm8081188}, pages = {14}, year = {2019}, abstract = {In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, p(SVC) = 0.04, x = 26, y = -6, z = -12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (r(s) = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies.}, language = {en} } @article{SeboldChenOenaletal.2022, author = {Sebold, Miriam and Chen, Hao and {\"O}nal, Aleyna and Kuitunen-Paul, S{\"o}ren and Mojtahedzadeh, Negin and Garbusow, Maria and Nebe, Stephan and Wittchen, Hans-Ulrich and Huys, Quentin J. M. and Schlagenhauf, Florian and Rapp, Michael A. and Smolka, Michael N. and Heinz, Andreas}, title = {Stronger prejudices are associated with decreased model-based control}, series = {Frontiers in psychology}, volume = {12}, journal = {Frontiers in psychology}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-1078}, doi = {10.3389/fpsyg.2021.767022}, pages = {10}, year = {2022}, abstract = {Background: Prejudices against minorities can be understood as habitually negative evaluations that are kept in spite of evidence to the contrary. Therefore, individuals with strong prejudices might be dominated by habitual or "automatic" reactions at the expense of more controlled reactions. Computational theories suggest individual differences in the balance between habitual/model-free and deliberative/model-based decision-making. Methods: 127 subjects performed the two Step task and completed the blatant and subtle prejudice scale. Results: By using analyses of choices and reaction times in combination with computational modeling, subjects with stronger blatant prejudices showed a shift away from model-based control. There was no association between these decision-making processes and subtle prejudices. Conclusion: These results support the idea that blatant prejudices toward minorities are related to a relative dominance of habitual decision-making. This finding has important implications for developing interventions that target to change prejudices across societies.}, language = {en} } @article{GorupecBrehmerTiberiusetal.2022, author = {Gorupec, Natalia and Brehmer, Nataliia and Tiberius, Victor and Kraus, Sascha}, title = {Tackling uncertain future scenarios with real options}, series = {The Irish journal of management}, volume = {41}, journal = {The Irish journal of management}, number = {1}, publisher = {Sciendo}, address = {Warsaw}, issn = {2451-2834}, doi = {10.2478/ijm-2022-0003}, pages = {69 -- 88}, year = {2022}, abstract = {Real options are widely applied in strategic and operational decision-making, allowing for managerial flexibility in uncertaincontexts. Increased scholarly interest has led to an extensive but fragmented research landscape. We aim to measure andsystematize the research field quantitatively. To achieve this goal, we conduct bibliometric performance analyses and bibliographiccoupling analyses with an in-depth content review. The results of the performance analyses show an increasing interest in realoptions since the beginning of the 2000s and identify the most influential journals and authors. The science mappings reveal sixand seven research clusters over the last two decades. Based on an in-depth analysis of their themes, we develop a researchframework comprising antecedents, application areas, internal and external contingencies, and uncertainty resolution throughreal option valuation or reasoning. We identify several gaps in that framework, which we propose to tackle in future research.}, language = {en} } @article{JaraMunozMelnickLietal.2022, author = {Jara Mu{\~n}oz, Julius and Melnick, Daniel and Li, Shaoyang and Socquet, Anne and Cort{\´e}s-Aranda, Joaqu{\´i}n and Brill, Dominik and Strecker, Manfred}, title = {The cryptic seismic potential of the Pichilemu blind fault in Chile revealed by off-fault geomorphology}, series = {Nature Communications}, volume = {13}, journal = {Nature Communications}, publisher = {Springer Nature}, address = {London}, issn = {2041-1723}, doi = {10.1038/s41467-022-30754-1}, pages = {13}, year = {2022}, abstract = {The first step towards assessing hazards in seismically active regions involves mapping capable faults and estimating their recurrence times. While the mapping of active faults is commonly based on distinct geologic and geomorphic features evident at the surface, mapping blind seismogenic faults is complicated by the absence of on-fault diagnostic features. Here we investigated the Pichilemu Fault in coastal Chile, unknown until it generated a Mw 7.0 earthquake in 2010. The lack of evident surface faulting suggests activity along a partly-hidden blind fault. We used off-fault deformed marine terraces to estimate a fault-slip rate of 0.52 ± 0.04 m/ka, which, when integrated with satellite geodesy suggests a 2.12 ± 0.2 ka recurrence time for Mw~7.0 normal-faulting earthquakes. We propose that extension in the Pichilemu region is associated with stress changes during megathrust earthquakes and accommodated by sporadic slip during upper-plate earthquakes, which has implications for assessing the seismic potential of cryptic faults along convergent margins and elsewhere.}, language = {en} } @book{KubanRottaNolteetal.2023, author = {Kuban, Robert and Rotta, Randolf and Nolte, J{\"o}rg and Chromik, Jonas and Beilharz, Jossekin Jakob and Pirl, Lukas and Friedrich, Tobias and Lenzner, Pascal and Weyand, Christopher and Juiz, Carlos and Bermejo, Belen and Sauer, Joao and Coelh, Leandro dos Santos and Najafi, Pejman and P{\"u}nter, Wenzel and Cheng, Feng and Meinel, Christoph and Sidorova, Julia and Lundberg, Lars and Vogel, Thomas and Tran, Chinh and Moser, Irene and Grunske, Lars and Elsaid, Mohamed Esameldin Mohamed and Abbas, Hazem M. and Rula, Anisa and Sejdiu, Gezim and Maurino, Andrea and Schmidt, Christopher and H{\"u}gle, Johannes and Uflacker, Matthias and Nozza, Debora and Messina, Enza and Hoorn, Andr{\´e} van and Frank, Markus and Schulz, Henning and Alhosseini Almodarresi Yasin, Seyed Ali and Nowicki, Marek and Muite, Benson K. and Boysan, Mehmet Can and Bianchi, Federico and Cremaschi, Marco and Moussa, Rim and Abdel-Karim, Benjamin M. and Pfeuffer, Nicolas and Hinz, Oliver and Plauth, Max and Polze, Andreas and Huo, Da and Melo, Gerard de and Mendes Soares, F{\´a}bio and Oliveira, Roberto C{\´e}lio Lim{\~a}o de and Benson, Lawrence and Paul, Fabian and Werling, Christian and Windheuser, Fabian and Stojanovic, Dragan and Djordjevic, Igor and Stojanovic, Natalija and Stojnev Ilic, Aleksandra and Weidmann, Vera and Lowitzki, Leon and Wagner, Markus and Ifa, Abdessatar Ben and Arlos, Patrik and Megia, Ana and Vendrell, Joan and Pfitzner, Bjarne and Redondo, Alberto and R{\´i}os Insua, David and Albert, Justin Amadeus and Zhou, Lin and Arnrich, Bert and Szab{\´o}, Ildik{\´o} and Fodor, Szabina and Ternai, Katalin and Bhowmik, Rajarshi and Campero Durand, Gabriel and Shevchenko, Pavlo and Malysheva, Milena and Prymak, Ivan and Saake, Gunter}, title = {HPI Future SOC Lab - Proceedings 2019}, number = {158}, editor = {Meinel, Christoph and Polze, Andreas and Beins, Karsten and Strotmann, Rolf and Seibold, Ulrich and R{\"o}dszus, Kurt and M{\"u}ller, J{\"u}rgen}, publisher = {Universit{\"a}tsverlag Potsdam}, address = {Potsdam}, isbn = {978-3-86956-564-4}, issn = {1613-5652}, doi = {10.25932/publishup-59791}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-597915}, publisher = {Universit{\"a}t Potsdam}, pages = {xi, 301}, year = {2023}, abstract = {The "HPI Future SOC Lab" is a cooperation of the Hasso Plattner Institute (HPI) and industry partners. Its mission is to enable and promote exchange and interaction between the research community and the industry partners. The HPI Future SOC Lab provides researchers with free of charge access to a complete infrastructure of state of the art hard and software. This infrastructure includes components, which might be too expensive for an ordinary research environment, such as servers with up to 64 cores and 2 TB main memory. The offerings address researchers particularly from but not limited to the areas of computer science and business information systems. Main areas of research include cloud computing, parallelization, and In-Memory technologies. This technical report presents results of research projects executed in 2019. Selected projects have presented their results on April 9th and November 12th 2019 at the Future SOC Lab Day events.}, language = {en} } @article{HongKimThornbergetal.2022, author = {Hong, Jun Sung and Kim, Dong Ha and Thornberg, Robert and Wachs, Sebastian and Wright, Michelle F.}, title = {Racial discrimination to bullying behavior among White and Black adolescents in the USA: from parents' perspectives}, series = {International journal of environmental research and public health}, volume = {19}, journal = {International journal of environmental research and public health}, number = {12}, publisher = {MDPI AG}, address = {Basel}, issn = {1660-4601}, doi = {10.3390/ijerph19127084}, pages = {11}, year = {2022}, abstract = {The present study proposes and tests pathways by which racial discrimination might be positively related to bullying victimization among Black and White adolescents. Data were derived from the 2016 National Survey of Children's Health, a national survey that provides data on children's physical and mental health and their families. Data were collected from households with one or more children between June 2016 to February 2017. A letter was sent to randomly selected households, who were invited to participate in the survey. The caregivers consisted of 66.9\% females and 33.1\% males for the White sample, whose mean age was 47.51 (SD = 7.26), and 76.8\% females and 23.2\% males for the Black sample, whose mean age was 47.61 (SD = 9.71). In terms of the adolescents, 49.0\% were females among the White sample, whose mean age was 14.73 (SD = 1.69). For Black adolescents, 47.9\% were females and the mean age was 14.67(SD = 1.66). Measures for the study included bullying perpetration, racial discrimination, academic disengagement, and socio-demographic variables of the parent and child. Analyses included descriptive statistics, bivariate correlations, and structural path analyses. For adolescents in both racial groups, racial discrimination appears to be positively associated with depression, which was positively associated with bullying perpetration. For White adolescents, racial discrimination was positively associated with academic disengagement, which was also positively associated with bullying perpetration. For Black adolescents, although racial discrimination was not significantly associated with academic disengagement, academic disengagement was positively associated with bullying perpetration.}, language = {en} } @article{JoziNajafabadiHaberlandRybergetal.2021, author = {Jozi Najafabadi, Azam and Haberland, Christian and Ryberg, Trond and Verwater, Vincent F. and Breton, Eline le and Handy, Mark R. and Weber, Michael}, title = {Relocation of earthquakes in the southern and eastern Alps (Austria, Italy) recorded by the dense, temporary SWATH-D network using a Markov chain Monte Carlo inversion}, series = {Solid earth : SE ; an interaktive open access journal of the European Geosciences Union}, volume = {12}, journal = {Solid earth : SE ; an interaktive open access journal of the European Geosciences Union}, number = {5}, publisher = {Copernicus}, address = {G{\"o}ttingen}, organization = {AlpArray Working Grp, AlpArray SWATH-D Working Grp}, issn = {1869-9529}, doi = {10.5194/se-12-1087-2021}, pages = {1087 -- 1109}, year = {2021}, abstract = {In this study, we analyzed a large seismological dataset from temporary and permanent networks in the southern and eastern Alps to establish high-precision hypocenters and 1-D V-P and V-P/V-S models. The waveform data of a subset of local earthquakes with magnitudes in the range of 1-4.2 M-L were recorded by the dense, temporary SWATH-D network and selected stations of the AlpArray network between September 2017 and the end of 2018. The first arrival times of P and S waves of earthquakes are determined by a semi-automatic procedure. We applied a Markov chain Monte Carlo inversion method to simultaneously calculate robust hypocenters, a 1-D velocity model, and station corrections without prior assumptions, such as initial velocity models or earthquake locations. A further advantage of this method is the derivation of the model parameter uncertainties and noise levels of the data. The precision estimates of the localization procedure is checked by inverting a synthetic travel time dataset from a complex 3-D velocity model and by using the real stations and earthquakes geometry. The location accuracy is further investigated by a quarry blast test. The average uncertainties of the locations of the earthquakes are below 500m in their epicenter and similar to 1.7 km in depth. The earthquake distribution reveals seismicity in the upper crust (0-20 km), which is characterized by pronounced clusters along the Alpine frontal thrust, e.g., the Friuli-Venetia (FV) region, the Giudicarie-Lessini (GL) and Schio-Vicenza domains, the Austroalpine nappes, and the Inntal area. Some seismicity also occurs along the Periadriatic Fault. The general pattern of seismicity reflects head-on convergence of the Adriatic indenter with the Alpine orogenic crust. The seismicity in the FV and GL regions is deeper than the modeled frontal thrusts, which we interpret as indication for southward propagation of the southern Alpine deformation front (blind thrusts).}, language = {en} } @book{Schenck2022, author = {Schenck, Marcia C.}, title = {Remembering African Labor Migration to the Second World}, series = {Palgrave Macmillan Transnational History Series}, journal = {Palgrave Macmillan Transnational History Series}, publisher = {Palgrave Macmillan}, address = {Cham}, isbn = {978-3-031-06775-4}, issn = {2634-6273}, doi = {10.1007/978-3-031-06776-1}, pages = {XXVII, 377}, year = {2022}, abstract = {This open access book is about Mozambicans and Angolans who migrated in state-sponsored schemes to East Germany in the late 1970s and throughout the 1980s. They went to work and to be trained as a vanguard labor force for the intended African industrial revolutions. While they were there, they contributed their labor power to the East German economy.  This book draws on more than 260 life history interviews and uncovers complex and contradictory experiences and transnational encounters. What emerges is a series of dualities that exist side by side in the memories of the former migrants: the state and the individual, work and consumption, integration and exclusion, loss and gain, and the past in the past and the past in the present and future. By uncovering these dualities, the book explores the lives of African migrants moving between the Third and Second worlds.  Devoted to the memories of worker-trainees, this transnational study comes at a time when historians are uncovering the many varied, complicated, and important connections within the global socialist world.}, language = {en} } @misc{Haenel2021, author = {H{\"a}nel, Hilkje C.}, title = {The intricacies of ideology and ignorance}, series = {Social epistemology review \& reply collective : SERRC}, volume = {10}, journal = {Social epistemology review \& reply collective : SERRC}, number = {7}, publisher = {Social epistemology review \& reply collective}, address = {[Erscheinungsort nicht ermittelbar]}, issn = {2471-9560}, pages = {58 -- 62}, year = {2021}, language = {en} } @article{PerottoniLimbergAmaranteetal.2022, author = {Perottoni, H{\´e}lio D. and Limberg, Guilherme and Amarante, Jo{\~a}o A. S. and Rossi, Silvia and Queiroz, Anna B. A. and Santucci, Rafael M. and P{\´e}rez-Villegas, Angeles and Chiappini, Cristina}, title = {The unmixed debris of Gaia-Sausage/Enceladus in the form of a pair of halo stellar overdensities}, series = {Astrophysical journal letters}, volume = {936}, journal = {Astrophysical journal letters}, number = {1}, publisher = {IOP Publishing}, address = {Bristol}, issn = {2041-8213}, doi = {10.3847/2041-8213/ac88d6}, pages = {7}, year = {2022}, abstract = {In the first billion years after its formation, the galaxy underwent several mergers with dwarf satellites of various masses. The debris of Gaia-Sausage/Enceladus (GSE), the galaxy responsible for the last significant merger of the Milky Way, dominates the inner halo and has been suggested to be the progenitor of both the Hercules-Aquila Cloud (HAC) and Virgo Overdensity (VOD). We combine SEGUE, APOGEE, Gaia, and StarHorse distances to characterize the chemodynamical properties and verify the link between HAC, VOD, and GSE. We find that the orbital eccentricity distributions of the stellar overdensities and GSE are comparable. We also find that they have similar, strongly peaked, metallicity distribution functions, reinforcing the hypothesis of common origin. Furthermore, we show that HAC and VOD are indistinguishable from the prototypical GSE population within all chemical-abundance spaces analyzed. All these evidences combined provide a clear demonstration that the GSE merger is the main progenitor of the stellar populations found within these halo overdensities.}, language = {en} } @article{KlausMuellervanWickerenetal.2022, author = {Klaus, Benita and M{\"u}ller, Patrick and van Wickeren, Nora and Dordevic, Milos and Schmicker, Marlen and Zdunczyk, Yael and Brigadski, Tanja and Lessmann, Volkmar and Vielhaber, Stefan and Schreiber, Stefanie and M{\"u}ller, Notger Germar}, title = {Structural and functional brain alterations in patients with myasthenia gravis}, series = {Brain communications}, volume = {4}, journal = {Brain communications}, number = {1}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {2632-1297}, doi = {10.1093/braincomms/fcac018}, pages = {12}, year = {2022}, abstract = {Myasthenia gravis is an autoimmune disease affecting neuromuscular transmission and causing skeletal muscle weakness. Additionally, systemic inflammation, cognitive deficits and autonomic dysfunction have been described. However, little is known about myasthenia gravis-related reorganization of the brain. In this study, we thus investigated the structural and functional brain changes in myasthenia gravis patients. Eleven myasthenia gravis patients (age: 70.64 +/- 9.27; 11 males) were compared to age-, sex- and education-matched healthy controls (age: 70.18 +/- 8.98; 11 males). Most of the patients (n = 10, 0.91\%) received cholinesterase inhibitors. Structural brain changes were determined by applying voxel-based morphometry using high-resolution T-1-weighted sequences. Functional brain changes were assessed with a neuropsychological test battery (including attention, memory and executive functions), a spatial orientation task and brain-derived neurotrophic factor blood levels. Myasthenia gravis patients showed significant grey matter volume reductions in the cingulate gyrus, in the inferior parietal lobe and in the fusiform gyrus. Furthermore, myasthenia gravis patients showed significantly lower performance in executive functions, working memory (Spatial Span, P = 0.034, d = 1.466), verbal episodic memory (P = 0.003, d = 1.468) and somatosensory-related spatial orientation (Triangle Completion Test, P = 0.003, d = 1.200). Additionally, serum brain-derived neurotrophic factor levels were significantly higher in myasthenia gravis patients (P = 0.001, d = 2.040). Our results indicate that myasthenia gravis is associated with structural and functional brain alterations. Especially the grey matter volume changes in the cingulate gyrus and the inferior parietal lobe could be associated with cognitive deficits in memory and executive functions. Furthermore, deficits in somatosensory-related spatial orientation could be associated with the lower volumes in the inferior parietal lobe. Future research is needed to replicate these findings independently in a larger sample and to investigate the underlying mechanisms in more detail. Klaus et al. compared myasthenia gravis patients to matched healthy control subjects and identified functional alterations in memory functions as well as structural alterations in the cingulate gyrus, in the inferior parietal lobe and in the fusiform gyrus.}, language = {en} } @article{MenzeMuellerZaehleetal.2023, author = {Menze, Inga and M{\"u}ller, Notger Germar and Z{\"a}hle, Tino and Schmicker, Marlen}, title = {Individual response to transcranial direct current stimulation as a function of working memory capacity and electrode montage}, series = {Frontiers in human neuroscience}, volume = {17}, journal = {Frontiers in human neuroscience}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1662-5161}, doi = {10.3389/fnhum.2023.1134632}, pages = {14}, year = {2023}, abstract = {Introduction Attempts to improve cognitive abilities via transcranial direct current stimulation (tDCS) have led to ambiguous results, likely due to the method's susceptibility to methodological and inter-individual factors. Conventional tDCS, i.e., using an active electrode over brain areas associated with the targeted cognitive function and a supposedly passive reference, neglects stimulation effects on entire neural networks. Methods We investigated the advantage of frontoparietal network stimulation (right prefrontal anode, left posterior parietal cathode) against conventional and sham tDCS in modulating working memory (WM) capacity dependent transfer effects of a single-session distractor inhibition (DIIN) training. Since previous results did not clarify whether electrode montage drives this individual transfer, we here compared conventional to frontoparietal and sham tDCS and reanalyzed data of 124 young, healthy participants in a more robust way using linear mixed effect modeling. Results The interaction of electrode montage and WM capacity resulted in systematic differences in transfer effects. While higher performance gains were observed with increasing WM capacity in the frontoparietal stimulation group, low WM capacity individuals benefited more in the sham condition. The conventional stimulation group showed subtle performance gains independent of WM capacity. Discussion Our results confirm our previous findings of WM capacity dependent transfer effects on WM by a single-session DIIN training combined with tDCS and additionally highlight the pivotal role of the specific electrode montage. WM capacity dependent differences in frontoparietal network recruitment, especially regarding the parietal involvement, are assumed to underlie this observation.}, language = {en} } @article{MenzeMuellerMuelleretal.2022, author = {Menze, Inga and M{\"u}ller, Patrick and M{\"u}ller, Notger Germar and Schmicker, Marlen}, title = {Age-related cognitive effects of the COVID-19 pandemic restrictions and associated mental health changes in Germans}, series = {Scientific reports}, volume = {12}, journal = {Scientific reports}, number = {1}, publisher = {Nature portfolio}, address = {Berlin}, issn = {2045-2322}, doi = {10.1038/s41598-022-11283-9}, pages = {16}, year = {2022}, abstract = {Restrictive means to reduce the spread of the COVID-19 pandemic have not only imposed broad challenges on mental health but might also affect cognitive health. Here we asked how restriction-related changes influence cognitive performance and how age, perceived loneliness, depressiveness and affectedness by restrictions contribute to these effects. 51 Germans completed three assessments of an online based study during the first lockdown in Germany (April 2020), a month later, and during the beginning of the second lockdown (November 2020). Participants completed nine online cognitive tasks of the MyBrainTraining and online questionnaires about their perceived strain and impact on lifestyle factors by the situation (affectedness), perceived loneliness, depressiveness as well as subjective cognitive performance. The results suggested a possible negative impact of depressiveness and affectedness on objective cognitive performance within the course of the lockdown. The younger the participants, the more pronounced these effects were. Loneliness and depressiveness moreover contributed to a worse evaluation of subjective cognition. In addition, especially younger individuals reported increased distress. As important educational and social input has partly been scarce during this pandemic and mental health problems have increased, future research should also assess cognitive long-term consequences.}, language = {en} } @article{ZielhoferSchmidtReicheetal.2022, author = {Zielhofer, Christoph and Schmidt, Johannes and Reiche, Niklas and Tautenhahn, Marie and Ballasus, Helen and Burkart, Michael and Linst{\"a}dter, Anja and Dietze, Elisabeth and Kaiser, Knut and Mehler, Natascha}, title = {The lower Havel River Region (Brandenburg, Germany)}, series = {Water}, volume = {14}, journal = {Water}, number = {3}, publisher = {MDPI}, address = {Basel}, issn = {2073-4441}, doi = {10.3390/w14030480}, pages = {23}, year = {2022}, abstract = {Instrumental data show that the groundwater and lake levels in Northeast Germany have decreased over the past decades, and this process has accelerated over the past few years. In addition to global warming, the direct influence of humans on the local water balance is suspected to be the cause. Since the instrumental data usually go back only a few decades, little is known about the multidecadal to centennial-scale trend, which also takes long-term climate variation and the long-term influence by humans on the water balance into account. This study aims to quantitatively reconstruct the surface water areas in the Lower Havel Inner Delta and of adjacent Lake Gulpe in Brandenburg. The analysis includes the calculation of surface water areas from historical and modern maps from 1797 to 2020. The major finding is that surface water areas have decreased by approximately 30\% since the pre-industrial period, with the decline being continuous. Our data show that the comprehensive measures in Lower Havel hydro-engineering correspond with groundwater lowering that started before recent global warming. Further, large-scale melioration measures with increasing water demands in the upstream wetlands beginning from the 1960s to the 1980s may have amplified the decline in downstream surface water areas.}, language = {en} } @article{RingEisenmannKandiletal.2022, author = {Ring, Raphaela M. and Eisenmann, Clemens and Kandil, Farid and Steckhan, Nico and Demmrich, Sarah and Klatte, Caroline and Kessler, Christian S. and Jeitler, Michael and Boschmann, Michael and Michalsen, Andreas and Blakeslee, Sarah B. and St{\"o}ckigt, Barbara and Stritter, Wiebke and Koppold-Liebscher, Daniela A.}, title = {Mental and behavioural responses to Bah{\´a}'{\´i} fasting: Looking behind the scenes of a religiously motivated intermittent fast using a mixed methods approach}, series = {Nutrients}, volume = {14}, journal = {Nutrients}, number = {5}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu14051038}, pages = {23}, year = {2022}, abstract = {Background/Objective: Historically, fasting has been practiced not only for medical but also for religious reasons. Baha'is follow an annual religious intermittent dry fast of 19 days. We inquired into motivation behind and subjective health impacts of Baha'i fasting. Methods: A convergent parallel mixed methods design was embedded in a clinical single arm observational study. Semi-structured individual interviews were conducted before (n = 7), during (n = 8), and after fasting (n = 8). Three months after the fasting period, two focus group interviews were conducted (n = 5/n = 3). A total of 146 Baha'i volunteers answered an online survey at five time points before, during, and after fasting. Results: Fasting was found to play a central role for the religiosity of interviewees, implying changes in daily structures, spending time alone, engaging in religious practices, and experiencing social belonging. Results show an increase in mindfulness and well-being, which were accompanied by behavioural changes and experiences of self-efficacy and inner freedom. Survey scores point to an increase in mindfulness and well-being during fasting, while stress, anxiety, and fatigue decreased. Mindfulness remained elevated even three months after the fast. Conclusion: Baha'i fasting seems to enhance participants' mindfulness and well-being, lowering stress levels and reducing fatigue. Some of these effects lasted more than three months after fasting.}, language = {en} } @book{MeinelDoellnerWeskeetal.2021, author = {Meinel, Christoph and D{\"o}llner, J{\"u}rgen Roland Friedrich and Weske, Mathias and Polze, Andreas and Hirschfeld, Robert and Naumann, Felix and Giese, Holger and Baudisch, Patrick and Friedrich, Tobias and B{\"o}ttinger, Erwin and Lippert, Christoph and D{\"o}rr, Christian and Lehmann, Anja and Renard, Bernhard and Rabl, Tilmann and Uebernickel, Falk and Arnrich, Bert and H{\"o}lzle, Katharina}, title = {Proceedings of the HPI Research School on Service-oriented Systems Engineering 2020 Fall Retreat}, number = {138}, publisher = {Universit{\"a}tsverlag Potsdam}, address = {Potsdam}, isbn = {978-3-86956-513-2}, issn = {1613-5652}, doi = {10.25932/publishup-50413}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-504132}, publisher = {Universit{\"a}t Potsdam}, pages = {vi, 144}, year = {2021}, abstract = {Design and Implementation of service-oriented architectures imposes a huge number of research questions from the fields of software engineering, system analysis and modeling, adaptability, and application integration. Component orientation and web services are two approaches for design and realization of complex web-based system. Both approaches allow for dynamic application adaptation as well as integration of enterprise application. Service-Oriented Systems Engineering represents a symbiosis of best practices in object-orientation, component-based development, distributed computing, and business process management. It provides integration of business and IT concerns. The annual Ph.D. Retreat of the Research School provides each member the opportunity to present his/her current state of their research and to give an outline of a prospective Ph.D. thesis. Due to the interdisciplinary structure of the research school, this technical report covers a wide range of topics. These include but are not limited to: Human Computer Interaction and Computer Vision as Service; Service-oriented Geovisualization Systems; Algorithm Engineering for Service-oriented Systems; Modeling and Verification of Self-adaptive Service-oriented Systems; Tools and Methods for Software Engineering in Service-oriented Systems; Security Engineering of Service-based IT Systems; Service-oriented Information Systems; Evolutionary Transition of Enterprise Applications to Service Orientation; Operating System Abstractions for Service-oriented Computing; and Services Specification, Composition, and Enactment.}, language = {en} } @article{DeFreitasJohnsonGoldenetal.2021, author = {De Freitas, Jessica K. and Johnson, Kipp W. and Golden, Eddye and Nadkarni, Girish N. and Dudley, Joel T. and B{\"o}ttinger, Erwin and Glicksberg, Benjamin S. and Miotto, Riccardo}, title = {Phe2vec}, series = {Patterns}, volume = {2}, journal = {Patterns}, number = {9}, publisher = {Elsevier}, address = {Amsterdam}, issn = {2666-3899}, doi = {10.1016/j.patter.2021.100337}, pages = {9}, year = {2021}, abstract = {Robust phenotyping of patients from electronic health records (EHRs) at scale is a challenge in clinical informatics. Here, we introduce Phe2vec, an automated framework for disease phenotyping from EHRs based on unsupervised learning and assess its effectiveness against standard rule-based algorithms from Phenotype KnowledgeBase (PheKB). Phe2vec is based on pre-computing embeddings of medical concepts and patients' clinical history. Disease phenotypes are then derived from a seed concept and its neighbors in the embedding space. Patients are linked to a disease if their embedded representation is close to the disease phenotype. Comparing Phe2vec and PheKB cohorts head-to-head using chart review, Phe2vec performed on par or better in nine out of ten diseases. Differently from other approaches, it can scale to any condition and was validated against widely adopted expert-based standards. Phe2vec aims to optimize clinical informatics research by augmenting current frameworks to characterize patients by condition and derive reliable disease cohorts.}, language = {en} } @inproceedings{KlippertStolpmannGrumetal.2023, author = {Klippert, Monika and Stolpmann, Robert and Grum, Marcus and Thim, Christof and Gronau, Norbert and Albers, Albert}, title = {Knowledge transfer quality improvement}, series = {Procedia CIRP}, volume = {119}, booktitle = {Procedia CIRP}, publisher = {Elsevier}, address = {Amsterdam}, issn = {2212-8271}, doi = {10.1016/j.procir.2023.02.171}, pages = {919 -- 925}, year = {2023}, abstract = {Developing a new product generation requires the transfer of knowledge among various knowledge carriers. Several factors influence knowledge transfer, e.g., the complexity of engineering tasks or the competence of employees, which can decrease the efficiency and effectiveness of knowledge transfers in product engineering. Hence, improving those knowledge transfers obtains great potential, especially against the backdrop of experienced employees leaving the company due to retirement, so far, research results show, that the knowledge transfer velocity can be raised by following the Knowledge Transfer Velocity Model and implementing so-called interventions in a product engineering context. In most cases, the implemented interventions have a positive effect on knowledge transfer speed improvement. In addition to that, initial theoretical findings describe factors influencing the quality of knowledge transfers and outline a setting to empirically investigate how the quality can be improved by introducing a general description of knowledge transfer reference situations and principles to measure the quality of knowledge artifacts. To assess the quality of knowledge transfers in a product engineering context, the Knowledge Transfer Quality Model (KTQM) is created, which serves as a basis to develop and implement quality-dependent interventions for different knowledge transfer situations. As a result, this paper introduces the specifications of eight situation-adequate interventions to improve the quality of knowledge transfers in product engineering following an intervention template. Those interventions are intended to be implemented in an industrial setting to measure the quality of knowledge transfers and validate their effect.}, language = {en} } @inproceedings{PanzerGronau2024, author = {Panzer, Marcel and Gronau, Norbert}, title = {Enhancing economic efficiency in modular production systems through deep reinforcement learning}, series = {Procedia CIRP}, volume = {121}, booktitle = {Procedia CIRP}, publisher = {Elsevier}, address = {Amsterdam}, issn = {2212-8271}, doi = {10.1016/j.procir.2023.09.229}, pages = {55 -- 60}, year = {2024}, abstract = {In times of increasingly complex production processes and volatile customer demands, the production adaptability is crucial for a company's profitability and competitiveness. The ability to cope with rapidly changing customer requirements and unexpected internal and external events guarantees robust and efficient production processes, requiring a dedicated control concept at the shop floor level. Yet in today's practice, conventional control approaches remain in use, which may not keep up with the dynamic behaviour due to their scenario-specific and rigid properties. To address this challenge, deep learning methods were increasingly deployed due to their optimization and scalability properties. However, these approaches were often tested in specific operational applications and focused on technical performance indicators such as order tardiness or total throughput. In this paper, we propose a deep reinforcement learning based production control to optimize combined techno-financial performance measures. Based on pre-defined manufacturing modules that are supplied and operated by multiple agents, positive effects were observed in terms of increased revenue and reduced penalties due to lower throughput times and fewer delayed products. The combined modular and multi-staged approach as well as the distributed decision-making further leverage scalability and transferability to other scenarios.}, language = {en} } @article{GrdseloffBouldayRoedeletal.2023, author = {Grdseloff, Nastasja and Boulday, Gwenola and Roedel, Claudia J. and Otten, Cecile and Vannier, Daphne Raphaelle and Cardoso, Cecile and Faurobert, Eva and Dogra, Deepika and Tournier-Lasserve, Elisabeth and Abdelilah-Seyfried, Salim}, title = {Impaired retinoic acid signaling in cerebral cavernous malformations}, series = {Scientific reports}, volume = {13}, journal = {Scientific reports}, number = {1}, publisher = {Nature Portfolio}, address = {Berlin}, issn = {2045-2322}, doi = {10.1038/s41598-023-31905-0}, pages = {11}, year = {2023}, abstract = {The capillary-venous pathology cerebral cavernous malformation (CCM) is caused by loss of CCM1/Krev interaction trapped protein 1 (KRIT1), CCM2/MGC4607, or CCM3/PDCD10 in some endothelial cells. Mutations of CCM genes within the brain vasculature can lead to recurrent cerebral hemorrhages. Pharmacological treatment options are urgently needed when lesions are located in deeply-seated and in-operable regions of the central nervous system. Previous pharmacological suppression screens in disease models of CCM led to the discovery that treatment with retinoic acid improved CCM phenotypes. This finding raised a need to investigate the involvement of retinoic acid in CCM and test whether it has a curative effect in preclinical mouse models. Here, we show that components of the retinoic acid synthesis and degradation pathway are transcriptionally misregulated across disease models of CCM. We complemented this analysis by pharmacologically modifying retinoic acid levels in zebrafish and human endothelial cell models of CCM, and in acute and chronic mouse models of CCM. Our pharmacological intervention studies in CCM2-depleted human umbilical vein endothelial cells (HUVECs) and krit1 mutant zebrafish showed positive effects when retinoic acid levels were increased. However, therapeutic approaches to prevent the development of vascular lesions in adult chronic murine models of CCM were drug regiment-sensitive, possibly due to adverse developmental effects of this hormone. A treatment with high doses of retinoic acid even worsened CCM lesions in an adult chronic murine model of CCM. This study provides evidence that retinoic acid signaling is impaired in the CCM pathophysiology and suggests that modification of retinoic acid levels can alleviate CCM phenotypes.}, language = {en} } @article{LewkowiczWohlbrandtBoettinger2020, author = {Lewkowicz, Daniel and Wohlbrandt, Attila and B{\"o}ttinger, Erwin}, title = {Economic impact of clinical decision support interventions based on electronic health records}, series = {BMC Health Services Research}, volume = {20}, journal = {BMC Health Services Research}, publisher = {BioMed Central}, address = {London}, issn = {1472-6963}, doi = {10.1186/s12913-020-05688-3}, pages = {12}, year = {2020}, abstract = {Background Unnecessary healthcare utilization, non-adherence to current clinical guidelines, or insufficient personalized care are perpetual challenges and remain potential major cost-drivers for healthcare systems around the world. Implementing decision support systems into clinical care is promised to improve quality of care and thereby yield substantial effects on reducing healthcare expenditure. In this article, we evaluate the economic impact of clinical decision support (CDS) interventions based on electronic health records (EHR). Methods We searched for studies published after 2014 using MEDLINE, CENTRAL, WEB OF SCIENCE, EBSCO, and TUFTS CEA registry databases that encompass an economic evaluation or consider cost outcome measures of EHR based CDS interventions. Thereupon, we identified best practice application areas and categorized the investigated interventions according to an existing taxonomy of front-end CDS tools. Results and discussion Twenty-seven studies are investigated in this review. Of those, twenty-two studies indicate a reduction of healthcare expenditure after implementing an EHR based CDS system, especially towards prevalent application areas, such as unnecessary laboratory testing, duplicate order entry, efficient transfusion practice, or reduction of antibiotic prescriptions. On the contrary, order facilitators and undiscovered malfunctions revealed to be threats and could lead to new cost drivers in healthcare. While high upfront and maintenance costs of CDS systems are a worldwide implementation barrier, most studies do not consider implementation cost. Finally, four included economic evaluation studies report mixed monetary outcome results and thus highlight the importance of further high-quality economic evaluations for these CDS systems. Conclusion Current research studies lack consideration of comparative cost-outcome metrics as well as detailed cost components in their analyses. Nonetheless, the positive economic impact of EHR based CDS interventions is highly promising, especially with regard to reducing waste in healthcare.}, language = {en} } @article{SmithBoers2023, author = {Smith, Taylor and Boers, Niklas}, title = {Global vegetation resilience linked to water availability and variability}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, address = {London}, issn = {2041-1723}, doi = {10.1038/s41467-023-36207-7}, pages = {11}, year = {2023}, abstract = {Quantifying the resilience of vegetated ecosystems is key to constraining both present-day and future global impacts of anthropogenic climate change. Here we apply both empirical and theoretical resilience metrics to remotely-sensed vegetation data in order to examine the role of water availability and variability in controlling vegetation resilience at the global scale. We find a concise global relationship where vegetation resilience is greater in regions with higher water availability. We also reveal that resilience is lower in regions with more pronounced inter-annual precipitation variability, but find less concise relationships between vegetation resilience and intra-annual precipitation variability. Our results thus imply that the resilience of vegetation responds differently to water deficits at varying time scales. In view of projected increases in precipitation variability, our findings highlight the risk of ecosystem degradation under ongoing climate change. Vegetation dynamics depend on both the amount of precipitation and its variability over time. Here, the authors show that vegetation resilience is greater where water availability is higher and where precipitation is more stable from year to year.}, language = {en} } @article{FalkenhagenKnoechelKloftetal.2023, author = {Falkenhagen, Undine and Kn{\"o}chel, Jane and Kloft, Charlotte and Huisinga, Wilhelm}, title = {Deriving mechanism-based pharmacodynamic models by reducing quantitative systems pharmacology models}, series = {CPT: Pharmacometrics \& Systems Pharmacology}, volume = {12}, journal = {CPT: Pharmacometrics \& Systems Pharmacology}, number = {4}, publisher = {Wiley}, address = {Hoboken}, issn = {2163-8306}, doi = {10.1002/psp4.12903}, pages = {432 -- 443}, year = {2023}, abstract = {Quantitative systems pharmacology (QSP) models integrate comprehensive qualitative and quantitative knowledge about pharmacologically relevant processes. We previously proposed a first approach to leverage the knowledge in QSP models to derive simpler, mechanism-based pharmacodynamic (PD) models. Their complexity, however, is typically still too large to be used in the population analysis of clinical data. Here, we extend the approach beyond state reduction to also include the simplification of reaction rates, elimination of reactions, and analytic solutions. We additionally ensure that the reduced model maintains a prespecified approximation quality not only for a reference individual but also for a diverse virtual population. We illustrate the extended approach for the warfarin effect on blood coagulation. Using the model-reduction approach, we derive a novel small-scale warfarin/international normalized ratio model and demonstrate its suitability for biomarker identification. Due to the systematic nature of the approach in comparison with empirical model building, the proposed model-reduction algorithm provides an improved rationale to build PD models also from QSP models in other applications.}, language = {en} } @article{MorenoRomeroProbstTrindadeetal.2020, author = {Moreno-Romero, Jordi and Probst, Aline V. and Trindade, In{\^e}s and Kalyanikrishna, and Engelhorn, Julia and Farrona, Sara}, title = {Looking At the Past and Heading to the Future}, series = {Frontiers in Plant Science}, volume = {10}, journal = {Frontiers in Plant Science}, number = {1795}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1664-462X}, doi = {10.3389/fpls.2019.01795}, pages = {1 -- 12}, year = {2020}, abstract = {In June 2019, more than a hundred plant researchers met in Cologne, Germany, for the 6th European Workshop on Plant Chromatin (EWPC). This conference brought together a highly dynamic community of researchers with the common aim to understand how chromatin organization controls gene expression, development, and plant responses to the environment. New evidence showing how epigenetic states are set, perpetuated, and inherited were presented, and novel data related to the three-dimensional organization of chromatin within the nucleus were discussed. At the level of the nucleosome, its composition by different histone variants and their specialized histone deposition complexes were addressed as well as the mechanisms involved in histone post-translational modifications and their role in gene expression. The keynote lecture on plant DNA methylation by Julie Law (SALK Institute) and the tribute session to Lars Hennig, honoring the memory of one of the founders of the EWPC who contributed to promote the plant chromatin and epigenetic field in Europe, added a very special note to this gathering. In this perspective article we summarize some of the most outstanding data and advances on plant chromatin research presented at this workshop.}, language = {en} } @article{DellepianeVaidJaladankietal.2021, author = {Dellepiane, Sergio and Vaid, Akhil and Jaladanki, Suraj K. and Coca, Steven and Fayad, Zahi A. and Charney, Alexander W. and B{\"o}ttinger, Erwin and He, John Cijiang and Glicksberg, Benjamin S. and Chan, Lili and Nadkarni, Girish}, title = {Acute kidney injury in patients hospitalized with COVID-19 in New York City}, series = {Kidney medicine}, volume = {3}, journal = {Kidney medicine}, number = {5}, publisher = {Elsevier}, address = {Amsterdam}, issn = {2590-0595}, doi = {10.1016/j.xkme.2021.06.008}, pages = {877 -- 879}, year = {2021}, language = {en} } @article{DattaSachsFreitasdaCruzetal.2021, author = {Datta, Suparno and Sachs, Jan Philipp and Freitas da Cruz, Harry and Martensen, Tom and Bode, Philipp and Morassi Sasso, Ariane and Glicksberg, Benjamin S. and B{\"o}ttinger, Erwin}, title = {FIBER}, series = {JAMIA open}, volume = {4}, journal = {JAMIA open}, number = {3}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {2574-2531}, doi = {10.1093/jamiaopen/ooab048}, pages = {10}, year = {2021}, abstract = {Objectives: The development of clinical predictive models hinges upon the availability of comprehensive clinical data. Tapping into such resources requires considerable effort from clinicians, data scientists, and engineers. Specifically, these efforts are focused on data extraction and preprocessing steps required prior to modeling, including complex database queries. A handful of software libraries exist that can reduce this complexity by building upon data standards. However, a gap remains concerning electronic health records (EHRs) stored in star schema clinical data warehouses, an approach often adopted in practice. In this article, we introduce the FlexIBle EHR Retrieval (FIBER) tool: a Python library built on top of a star schema (i2b2) clinical data warehouse that enables flexible generation of modeling-ready cohorts as data frames. Materials and Methods: FIBER was developed on top of a large-scale star schema EHR database which contains data from 8 million patients and over 120 million encounters. To illustrate FIBER's capabilities, we present its application by building a heart surgery patient cohort with subsequent prediction of acute kidney injury (AKI) with various machine learning models. Results: Using FIBER, we were able to build the heart surgery cohort (n = 12 061), identify the patients that developed AKI (n = 1005), and automatically extract relevant features (n = 774). Finally, we trained machine learning models that achieved area under the curve values of up to 0.77 for this exemplary use case. Conclusion: FIBER is an open-source Python library developed for extracting information from star schema clinical data warehouses and reduces time-to-modeling, helping to streamline the clinical modeling process.}, language = {en} } @article{CopeBaukmannKlingeretal.2021, author = {Cope, Justin L. and Baukmann, Hannes A. and Klinger, J{\"o}rn E. and Ravarani, Charles N. J. and B{\"o}ttinger, Erwin and Konigorski, Stefan and Schmidt, Marco F.}, title = {Interaction-based feature selection algorithm outperforms polygenic risk score in predicting Parkinson's Disease status}, series = {Frontiers in genetics}, volume = {12}, journal = {Frontiers in genetics}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1664-8021}, doi = {10.3389/fgene.2021.744557}, pages = {9}, year = {2021}, abstract = {Polygenic risk scores (PRS) aggregating results from genome-wide association studies are the state of the art in the prediction of susceptibility to complex traits or diseases, yet their predictive performance is limited for various reasons, not least of which is their failure to incorporate the effects of gene-gene interactions. Novel machine learning algorithms that use large amounts of data promise to find gene-gene interactions in order to build models with better predictive performance than PRS. Here, we present a data preprocessing step by using data-mining of contextual information to reduce the number of features, enabling machine learning algorithms to identify gene-gene interactions. We applied our approach to the Parkinson's Progression Markers Initiative (PPMI) dataset, an observational clinical study of 471 genotyped subjects (368 cases and 152 controls). With an AUC of 0.85 (95\% CI = [0.72; 0.96]), the interaction-based prediction model outperforms the PRS (AUC of 0.58 (95\% CI = [0.42; 0.81])). Furthermore, feature importance analysis of the model provided insights into the mechanism of Parkinson's disease. For instance, the model revealed an interaction of previously described drug target candidate genes TMEM175 and GAPDHP25. These results demonstrate that interaction-based machine learning models can improve genetic prediction models and might provide an answer to the missing heritability problem.}, language = {en} } @article{ZennerBoettingerKonigorski2022, author = {Zenner, Alexander M. and B{\"o}ttinger, Erwin and Konigorski, Stefan}, title = {StudyMe}, series = {Trials}, volume = {23}, journal = {Trials}, publisher = {BioMed Central}, address = {London}, issn = {1745-6215}, doi = {10.1186/s13063-022-06893-7}, pages = {15}, year = {2022}, abstract = {N-of-1 trials are multi-crossover self-experiments that allow individuals to systematically evaluate the effect of interventions on their personal health goals. Although several tools for N-of-1 trials exist, there is a gap in supporting non-experts in conducting their own user-centric trials. In this study, we present StudyMe, an open-source mobile application that is freely available from https://play.google.com/store/apps/details?id=health.studyu.me and offers users flexibility and guidance in configuring every component of their trials. We also present research that informed the development of StudyMe, focusing on trial creation. Through an initial survey with 272 participants, we learned that individuals are interested in a variety of personal health aspects and have unique ideas on how to improve them. In an iterative, user-centered development process with intermediate user tests, we developed StudyMe that features an educational part to communicate N-of-1 trial concepts. A final empirical evaluation of StudyMe showed that all participants were able to create their own trials successfully using StudyMe and the app achieved a very good usability rating. Our findings suggest that StudyMe provides a significant step towards enabling individuals to apply a systematic science-oriented approach to personalize health-related interventions and behavior modifications in their everyday lives.}, language = {en} } @article{LewkowiczBoettingerSiegel2023, author = {Lewkowicz, Daniel and B{\"o}ttinger, Erwin and Siegel, Martin}, title = {Economic evaluation of digital therapeutic care apps for unsupervised treatment of low back pain}, series = {JMIR mhealth and uhealth}, volume = {11}, journal = {JMIR mhealth and uhealth}, publisher = {JMIR Publications}, address = {Toronto}, issn = {2291-5222}, doi = {10.2196/44585}, pages = {14}, year = {2023}, abstract = {Background: Digital therapeutic care (DTC) programs are unsupervised app-based treatments that provide video exercises and educational material to patients with nonspecific low back pain during episodes of pain and functional disability. German statutory health insurance can reimburse DTC programs since 2019, but evidence on efficacy and reasonable pricing remains scarce. This paper presents a probabilistic sensitivity analysis (PSA) to evaluate the efficacy and cost-utility of a DTC app against treatment as usual (TAU) in Germany. Objective: The aim of this study was to perform a PSA in the form of a Monte Carlo simulation based on the deterministic base case analysis to account for model assumptions and parameter uncertainty. We also intend to explore to what extent the results in this probabilistic analysis differ from the results in the base case analysis and to what extent a shortage of outcome data concerning quality-of-life (QoL) metrics impacts the overall results. Methods: The PSA builds upon a state-transition Markov chain with a 4-week cycle length over a model time horizon of 3 years from a recently published deterministic cost-utility analysis. A Monte Carlo simulation with 10,000 iterations and a cohort size of 10,000 was employed to evaluate the cost-utility from a societal perspective. Quality-adjusted life years (QALYs) were derived from Veterans RAND 6-Dimension (VR-6D) and Short-Form 6-Dimension (SF-6D) single utility scores. Finally, we also simulated reducing the price for a 3-month app prescription to analyze at which price threshold DTC would result in being the dominant strategy over TAU in Germany. Results: The Monte Carlo simulation yielded on average a euro135.97 (a currency exchange rate of EUR euro1=US \$1.069 is applicable) incremental cost and 0.004 incremental QALYs per person and year for the unsupervised DTC app strategy compared to in-person physiotherapy in Germany. The corresponding incremental cost-utility ratio (ICUR) amounts to an additional euro34,315.19 per additional QALY. DTC yielded more QALYs in 54.96\% of the iterations. DTC dominates TAU in 24.04\% of the iterations for QALYs. Reducing the app price in the simulation from currently euro239.96 to euro164.61 for a 3-month prescription could yield a negative ICUR and thus make DTC the dominant strategy, even though the estimated probability of DTC being more effective than TAU is only 54.96\%. Conclusions: Decision-makers should be cautious when considering the reimbursement of DTC apps since no significant treatment effect was found, and the probability of cost-effectiveness remains below 60\% even for an infinite willingness-to-pay threshold. More app-based studies involving the utilization of QoL outcome parameters are urgently needed to account for the low and limited precision of the available QoL input parameters, which are crucial to making profound recommendations concerning the cost-utility of novel apps.}, language = {en} } @article{KonigorskiWernickeSlosareketal.2022, author = {Konigorski, Stefan and Wernicke, Sarah and Slosarek, Tamara and Zenner, Alexander M. and Strelow, Nils and Ruether, Darius F. and Henschel, Florian and Manaswini, Manisha and Pottb{\"a}cker, Fabian and Edelman, Jonathan A. and Owoyele, Babajide and Danieletto, Matteo and Golden, Eddye and Zweig, Micol and Nadkarni, Girish N. and B{\"o}ttinger, Erwin}, title = {StudyU: a platform for designing and conducting innovative digital N-of-1 trials}, series = {Journal of medical internet research}, volume = {24}, journal = {Journal of medical internet research}, number = {7}, publisher = {Healthcare World}, address = {Richmond, Va.}, issn = {1439-4456}, doi = {10.2196/35884}, pages = {12}, year = {2022}, abstract = {N-of-1 trials are the gold standard study design to evaluate individual treatment effects and derive personalized treatment strategies. Digital tools have the potential to initiate a new era of N-of-1 trials in terms of scale and scope, but fully functional platforms are not yet available. Here, we present the open source StudyU platform, which includes the StudyU Designer and StudyU app. With the StudyU Designer, scientists are given a collaborative web application to digitally specify, publish, and conduct N-of-1 trials. The StudyU app is a smartphone app with innovative user-centric elements for participants to partake in trials published through the StudyU Designer to assess the effects of different interventions on their health. Thereby, the StudyU platform allows clinicians and researchers worldwide to easily design and conduct digital N-of-1 trials in a safe manner. We envision that StudyU can change the landscape of personalized treatments both for patients and healthy individuals, democratize and personalize evidence generation for self-optimization and medicine, and can be integrated in clinical practice.}, language = {en} } @misc{BarboliniWoutersenDupontNivetetal.2020, author = {Barbolini, Natasha and Woutersen, Amber and Dupont-Nivet, Guillaume and Silvestro, Daniele and Tardif-Becquet, Delphine and Coster, Pauline M. C. and Meijer, Niels and Chang, Cun and Zhang, Hou-Xi and Licht, Alexis and Rydin, Catarina and Koutsodendris, Andreas and Han, Fang and Rohrmann, Alexander and Liu, Xiang-Jun and Zhang, Y. and Donnadieu, Yannick and Fluteau, Frederic and Ladant, Jean-Baptiste and Le Hir, Guillaume and Hoorn, M. Carina}, title = {Cenozoic evolution of the steppe-desert biome in Central Asia}, series = {Science Advances}, volume = {6}, journal = {Science Advances}, number = {41}, publisher = {American Association for the Advancement of Science}, address = {Washington}, issn = {2375-2548}, doi = {10.1126/sciadv.abb8227}, pages = {16}, year = {2020}, abstract = {The origins and development of the arid and highly seasonal steppe-desert biome in Central Asia, the largest of its kind in the world, remain largely unconstrained by existing records. It is unclear how Cenozoic climatic, geological, and biological forces, acting at diverse spatial and temporal scales, shaped Central Asian ecosystems through time. Our synthesis shows that the Central Asian steppe-desert has existed since at least Eocene times but experienced no less than two regime shifts, one at the Eocene-Oligocene Transition and one in the mid-Miocene. These shifts separated three successive "stable states," each characterized by unique floral and faunal structures. Past responses to disturbance in the Asian steppe-desert imply that modern ecosystems are unlikely to recover their present structures and diversity if forced into a new regime. This is of concern for Asian steppes today, which are being modified for human use and lost to desertification at unprecedented rates.}, language = {en} } @article{WoutersenJardineGiovanniBogotaAngeletal.2018, author = {Woutersen, Amber and Jardine, Phillip E. and Giovanni Bogota-Angel, Raul and Zhang, Hong-Xiang and Silvestro, Daniele and Antonelli, Alexandre and Gogna, Elena and Erkens, Roy H. J. and Gosling, William D. and Dupont-Nivet, Guillaume and Hoorn, Carina}, title = {A novel approach to study the morphology and chemistry of pollen in a phylogenetic context, applied to the halophytic taxon Nitraria L.(Nitrariaceae)}, series = {PeerJ}, volume = {6}, journal = {PeerJ}, publisher = {PeerJ Inc.}, address = {London}, issn = {2167-8359}, doi = {10.7717/peerj.5055}, pages = {31}, year = {2018}, abstract = {Nitraria is a halophytic taxon (i.e., adapted to saline environments) that belongs to the plant family Nitrariaceae and is distributed from the Mediterranean, across Asia into the south-eastern tip of Australia. This taxon is thought to have originated in Asia during the Paleogene (66-23 Ma), alongside the proto-Paratethys epicontinental sea. The evolutionary history of Nitraria might hold important clues on the links between climatic and biotic evolution but limited taxonomic documentation of this taxon has thus far hindered this line of research. Here we investigate if the pollen morphology and the chemical composition of the pollen wall are informative of the evolutionary history of Nitraria and could explain if origination along the proto-Paratethys and dispersal to the Tibetan Plateau was simultaneous or a secondary process. To answer these questions, we applied a novel approach consisting of a combination of Fourier Transform Infrared spectroscopy (FTIR), to determine the chemical composition of the pollen wall, and pollen morphological analyses using Light Microscopy (LM) and Scanning Electron Microscopy (SEM). We analysed our data using ordinations (principal components analysis and non-metric multidimensional scaling), and directly mapped it on the Nitrariaceae phylogeny to produce a phylomorphospace and a phylochemospace. Our LM, SEM and FTIR analyses show clear morphological and chemical differences between the sister groups Peganum and Nitraria. Differences in the morphological and chemical characteristics of highland species (Nitraria schoberi, N. sphaerocarpa, N. sibirica and N. tangutorum) and lowland species (Nitraria billardierei and N. retusa) are very subtle, with phylogenetic history appearing to be a more important control on Nitraria pollen than local environmental conditions. Our approach shows a compelling consistency between the chemical and morphological characteristics of the eight studied Nitrariaceae species, and these traits are in agreement with the phylogenetic tree. Taken together, this demonstrates how novel methods for studying fossil pollen can facilitate the evolutionary investigation of living and extinct taxa, and the environments they represent.}, language = {en} } @article{VaidSomaniRussaketal.2020, author = {Vaid, Akhil and Somani, Sulaiman and Russak, Adam J. and De Freitas, Jessica K. and Chaudhry, Fayzan F. and Paranjpe, Ishan and Johnson, Kipp W. and Lee, Samuel J. and Miotto, Riccardo and Richter, Felix and Zhao, Shan and Beckmann, Noam D. and Naik, Nidhi and Kia, Arash and Timsina, Prem and Lala, Anuradha and Paranjpe, Manish and Golden, Eddye and Danieletto, Matteo and Singh, Manbir and Meyer, Dara and O'Reilly, Paul F. and Huckins, Laura and Kovatch, Patricia and Finkelstein, Joseph and Freeman, Robert M. and Argulian, Edgar and Kasarskis, Andrew and Percha, Bethany and Aberg, Judith A. and Bagiella, Emilia and Horowitz, Carol R. and Murphy, Barbara and Nestler, Eric J. and Schadt, Eric E. and Cho, Judy H. and Cordon-Cardo, Carlos and Fuster, Valentin and Charney, Dennis S. and Reich, David L. and B{\"o}ttinger, Erwin and Levin, Matthew A. and Narula, Jagat and Fayad, Zahi A. and Just, Allan C. and Charney, Alexander W. and Nadkarni, Girish N. and Glicksberg, Benjamin S.}, title = {Machine learning to predict mortality and critical events in a cohort of patients with COVID-19 in New York City: model development and validation}, series = {Journal of medical internet research : international scientific journal for medical research, information and communication on the internet ; JMIR}, volume = {22}, journal = {Journal of medical internet research : international scientific journal for medical research, information and communication on the internet ; JMIR}, number = {11}, publisher = {Healthcare World}, address = {Richmond, Va.}, issn = {1439-4456}, doi = {10.2196/24018}, pages = {19}, year = {2020}, abstract = {Background: COVID-19 has infected millions of people worldwide and is responsible for several hundred thousand fatalities. The COVID-19 pandemic has necessitated thoughtful resource allocation and early identification of high-risk patients. However, effective methods to meet these needs are lacking. Objective: The aims of this study were to analyze the electronic health records (EHRs) of patients who tested positive for COVID-19 and were admitted to hospitals in the Mount Sinai Health System in New York City; to develop machine learning models for making predictions about the hospital course of the patients over clinically meaningful time horizons based on patient characteristics at admission; and to assess the performance of these models at multiple hospitals and time points. Methods: We used Extreme Gradient Boosting (XGBoost) and baseline comparator models to predict in-hospital mortality and critical events at time windows of 3, 5, 7, and 10 days from admission. Our study population included harmonized EHR data from five hospitals in New York City for 4098 COVID-19-positive patients admitted from March 15 to May 22, 2020. The models were first trained on patients from a single hospital (n=1514) before or on May 1, externally validated on patients from four other hospitals (n=2201) before or on May 1, and prospectively validated on all patients after May 1 (n=383). Finally, we established model interpretability to identify and rank variables that drive model predictions. Results: Upon cross-validation, the XGBoost classifier outperformed baseline models, with an area under the receiver operating characteristic curve (AUC-ROC) for mortality of 0.89 at 3 days, 0.85 at 5 and 7 days, and 0.84 at 10 days. XGBoost also performed well for critical event prediction, with an AUC-ROC of 0.80 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. In external validation, XGBoost achieved an AUC-ROC of 0.88 at 3 days, 0.86 at 5 days, 0.86 at 7 days, and 0.84 at 10 days for mortality prediction. Similarly, the unimputed XGBoost model achieved an AUC-ROC of 0.78 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. Trends in performance on prospective validation sets were similar. At 7 days, acute kidney injury on admission, elevated LDH, tachypnea, and hyperglycemia were the strongest drivers of critical event prediction, while higher age, anion gap, and C-reactive protein were the strongest drivers of mortality prediction. Conclusions: We externally and prospectively trained and validated machine learning models for mortality and critical events for patients with COVID-19 at different time horizons. These models identified at-risk patients and uncovered underlying relationships that predicted outcomes.}, language = {en} } @article{DoellDjalaliFarahaniKofoetZrenneretal.2021, author = {D{\"o}ll, Stefanie and Djalali Farahani-Kofoet, Roxana and Zrenner, Rita and Henze, Andrea and Witzel, Katja}, title = {Tissue-specific signatures of metabolites and proteins in asparagus roots and exudates}, series = {Horticulture research}, volume = {8}, journal = {Horticulture research}, number = {1}, publisher = {Nanjing Agricultural Univ.}, address = {Nanjing}, issn = {2052-7276}, doi = {10.1038/s41438-021-00510-5}, pages = {14}, year = {2021}, abstract = {Comprehensive untargeted and targeted analysis of root exudate composition has advanced our understanding of rhizosphere processes. However, little is known about exudate spatial distribution and regulation. We studied the specific metabolite signatures of asparagus root exudates, root outer (epidermis and exodermis), and root inner tissues (cortex and vasculature). The greatest differences were found between exudates and root tissues. In total, 263 non-redundant metabolites were identified as significantly differentially abundant between the three root fractions, with the majority being enriched in the root exudate and/or outer tissue and annotated as 'lipids and lipid-like molecules' or 'phenylpropanoids and polyketides'. Spatial distribution was verified for three selected compounds using MALDI-TOF mass spectrometry imaging. Tissue-specific proteome analysis related root tissue-specific metabolite distributions and rhizodeposition with underlying biosynthetic pathways and transport mechanisms. The proteomes of root outer and inner tissues were spatially very distinct, in agreement with the fundamental differences between their functions and structures. According to KEGG pathway analysis, the outer tissue proteome was characterized by a high abundance of proteins related to 'lipid metabolism', 'biosynthesis of other secondary metabolites' and 'transport and catabolism', reflecting its main functions of providing a hydrophobic barrier, secreting secondary metabolites, and mediating water and nutrient uptake. Proteins more abundant in the inner tissue related to 'transcription', 'translation' and 'folding, sorting and degradation', in accord with the high activity of cortical and vasculature cell layers in growth- and development-related processes. In summary, asparagus root fractions accumulate specific metabolites. This expands our knowledge of tissue-specific plant cell function.}, language = {en} }