@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. <br /> 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. <br /> 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}
}
@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}
}
@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{WachsWettsteinBilzetal.2022,
  author    = {Wachs, Sebastian and Wettstein, Alexander and Bilz, Ludwig and Gamez-Guadix, Manuel},
  title     = {Motivos del discurso de odio en la adolescencia y su relaci{\´o}n con las normas sociales},
  series = {Comunicar : revista cient{\´i}fica de comunicaci{\´o}n y educaci{\´o}n},
  volume    = {30},
  journal   = {Comunicar : revista cient{\´i}fica de comunicaci{\´o}n y educaci{\´o}n},
  number    = {71},
  publisher = {Grupo Comunicar},
  address   = {Huelva},
  issn      = {1134-3478},
  doi       = {10.3916/C71-2022-01},
  pages     = {9 -- 20},
  year      = {2022},
  abstract  = {Hate speech has become a widespread phenomenon, however, it remains largely unclear why adolescents engage in it and which factors are associated with their motivations for perpetrating hate speech. To this end, we developed the multidimensional "Motivations for Hate Speech Perpetration Scale" (MHATE) and evaluated the psychometric properties. We also explored the associations between social norms and adolescents' motivations for hate speech perpetration. The sample consisted of 346 adolescents from Switzerland (54.6\% boys; Mage=14; SD=0.96) who reported engagement in hate speech as perpetrators. The analyses revealed good psychometric properties for the MHATE, including good internal consistency. The most frequently endorsed subscale was revenge, followed by ideology, group conformity, status enhancement, exhilaration, and power. The results also showed that descriptive norms and peer pressure were related to a wide range of different motivations for perpetrating hate speech. Injunctive norms, however, were only associated with power. In conclusion, findings indicate that hate speech fulfills various functions. We argue that knowing the specific motivations that underlie hate speech could help us derive individually tailored prevention strategies (e.g., anger management, promoting an inclusive classroom climate). Furthermore, we suggest that practitioners working in the field of hate speech prevention give special attention to social norms surrounding adolescents.},
  language  = {es}
}
@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{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}
}