TY - JOUR A1 - Jozi Najafabadi, Azam A1 - Haberland, Christian A1 - Ryberg, Trond A1 - Verwater, Vincent F. A1 - Breton, Eline le A1 - Handy, Mark R. A1 - Weber, Michael T1 - 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 JF - Solid earth : SE ; an interaktive open access journal of the European Geosciences Union N2 - 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). Y1 - 2021 U6 - https://doi.org/10.5194/se-12-1087-2021 SN - 1869-9529 SN - 1869-9510 VL - 12 IS - 5 SP - 1087 EP - 1109 PB - Copernicus CY - Göttingen ER - TY - BOOK A1 - Schenck, Marcia C. T1 - Remembering African Labor Migration to the Second World BT - Socialist Mobilities between Angola, Mozambique, and East Germany. T3 - Palgrave Macmillan Transnational History Series N2 - 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. KW - Open access KW - Third World KW - Second World KW - East Germany KW - Angola KW - Mozambique KW - Socialism KW - Labor Migration Y1 - 2022 SN - 978-3-031-06775-4 SN - 978-3-031-06778-5 SN - 978-3-031-06776-1 U6 - https://doi.org/10.1007/978-3-031-06776-1 SN - 2634-6273 SN - 2634-6281 PB - Palgrave Macmillan CY - Cham ER - TY - GEN A1 - Hänel, Hilkje C. T1 - The intricacies of ideology and ignorance BT - a reply to Mason T2 - Social epistemology review & reply collective : SERRC Y1 - 2021 UR - https://wp.me/p1Bfg0-62M SN - 2471-9560 VL - 10 IS - 7 SP - 58 EP - 62 PB - Social epistemology review & reply collective CY - [Erscheinungsort nicht ermittelbar] ER - TY - JOUR A1 - Perottoni, Hélio D. A1 - Limberg, Guilherme A1 - Amarante, João A. S. A1 - Rossi, Silvia A1 - Queiroz, Anna B. A. A1 - Santucci, Rafael M. A1 - Pérez-Villegas, Angeles A1 - Chiappini, Cristina T1 - The unmixed debris of Gaia-Sausage/Enceladus in the form of a pair of halo stellar overdensities JF - Astrophysical journal letters N2 - 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. Y1 - 2022 U6 - https://doi.org/10.3847/2041-8213/ac88d6 SN - 2041-8213 VL - 936 IS - 1 PB - IOP Publishing CY - Bristol ER - TY - JOUR A1 - Klaus, Benita A1 - Müller, Patrick A1 - van Wickeren, Nora A1 - Dordevic, Milos A1 - Schmicker, Marlen A1 - Zdunczyk, Yael A1 - Brigadski, Tanja A1 - Lessmann, Volkmar A1 - Vielhaber, Stefan A1 - Schreiber, Stefanie A1 - Müller, Notger Germar T1 - Structural and functional brain alterations in patients with myasthenia gravis JF - Brain communications N2 - 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. KW - myasthenia gravis KW - neuroplasticity KW - VBM KW - neuropsychological testing KW - BDNF Y1 - 2022 U6 - https://doi.org/10.1093/braincomms/fcac018 SN - 2632-1297 VL - 4 IS - 1 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Menze, Inga A1 - Müller, Notger Germar A1 - Zähle, Tino A1 - Schmicker, Marlen T1 - Individual response to transcranial direct current stimulation as a function of working memory capacity and electrode montage JF - Frontiers in human neuroscience N2 - 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. KW - tDCS KW - electrode montage KW - individual differences KW - working memory KW - capacity KW - distractor inhibition KW - frontoparietal network Y1 - 2023 U6 - https://doi.org/10.3389/fnhum.2023.1134632 SN - 1662-5161 VL - 17 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Menze, Inga A1 - Müller, Patrick A1 - Müller, Notger Germar A1 - Schmicker, Marlen T1 - Age-related cognitive effects of the COVID-19 pandemic restrictions and associated mental health changes in Germans JF - Scientific reports N2 - 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. Y1 - 2022 U6 - https://doi.org/10.1038/s41598-022-11283-9 SN - 2045-2322 VL - 12 IS - 1 PB - Nature portfolio CY - Berlin ER - TY - JOUR A1 - Zielhofer, Christoph A1 - Schmidt, Johannes A1 - Reiche, Niklas A1 - Tautenhahn, Marie A1 - Ballasus, Helen A1 - Burkart, Michael A1 - Linstädter, Anja A1 - Dietze, Elisabeth A1 - Kaiser, Knut A1 - Mehler, Natascha T1 - The lower Havel River Region (Brandenburg, Germany) BT - a 230-Year-Long historical map record indicates a decrease in surface water areas and groundwater levels JF - Water N2 - 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. KW - long-term hydrological changes KW - historical maps KW - review of written KW - sources KW - preindustrial to industrial period KW - hydro-engineering history; KW - effects of global warming KW - drying trend KW - wetlands KW - drainage works to KW - create cropland KW - Lower Havel River Region KW - Brandenburg KW - Germany Y1 - 2022 U6 - https://doi.org/10.3390/w14030480 SN - 2073-4441 VL - 14 IS - 3 PB - MDPI CY - Basel ER - TY - JOUR A1 - Ring, Raphaela M. A1 - Eisenmann, Clemens A1 - Kandil, Farid A1 - Steckhan, Nico A1 - Demmrich, Sarah A1 - Klatte, Caroline A1 - Kessler, Christian S. A1 - Jeitler, Michael A1 - Boschmann, Michael A1 - Michalsen, Andreas A1 - Blakeslee, Sarah B. A1 - Stöckigt, Barbara A1 - Stritter, Wiebke A1 - Koppold-Liebscher, Daniela A. T1 - Mental and behavioural responses to Bahá’í fasting: Looking behind the scenes of a religiously motivated intermittent fast using a mixed methods approach JF - Nutrients N2 - 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. KW - intermittent food restriction KW - mindfulness KW - self-efficacy KW - well-being KW - mixed methods KW - health behaviour KW - coping ability KW - religiously motivated KW - dry fasting Y1 - 2022 U6 - https://doi.org/10.3390/nu14051038 SN - 2072-6643 VL - 14 IS - 5 PB - MDPI CY - Basel ER - TY - BOOK A1 - Meinel, Christoph A1 - Döllner, Jürgen Roland Friedrich A1 - Weske, Mathias A1 - Polze, Andreas A1 - Hirschfeld, Robert A1 - Naumann, Felix A1 - Giese, Holger A1 - Baudisch, Patrick A1 - Friedrich, Tobias A1 - Böttinger, Erwin A1 - Lippert, Christoph A1 - Dörr, Christian A1 - Lehmann, Anja A1 - Renard, Bernhard A1 - Rabl, Tilmann A1 - Uebernickel, Falk A1 - Arnrich, Bert A1 - Hölzle, Katharina T1 - Proceedings of the HPI Research School on Service-oriented Systems Engineering 2020 Fall Retreat N2 - 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. N2 - Der Entwurf und die Realisierung dienstbasierender Architekturen wirft eine Vielzahl von Forschungsfragestellungen aus den Gebieten der Softwaretechnik, der Systemmodellierung und -analyse, sowie der Adaptierbarkeit und Integration von Applikationen auf. Komponentenorientierung und WebServices sind zwei Ansätze für den effizienten Entwurf und die Realisierung komplexer Web-basierender Systeme. Sie ermöglichen die Reaktion auf wechselnde Anforderungen ebenso, wie die Integration großer komplexer Softwaresysteme. "Service-Oriented Systems Engineering" repräsentiert die Symbiose bewährter Praktiken aus den Gebieten der Objektorientierung, der Komponentenprogrammierung, des verteilten Rechnen sowie der Geschäftsprozesse und berücksichtigt auch die Integration von Geschäftsanliegen und Informationstechnologien. Die Klausurtagung des Forschungskollegs "Service-oriented Systems Engineering" findet einmal jährlich statt und bietet allen Kollegiaten die Möglichkeit den Stand ihrer aktuellen Forschung darzulegen. Bedingt durch die Querschnittstruktur des Kollegs deckt dieser Bericht ein weites Spektrum aktueller Forschungsthemen ab. Dazu zählen unter anderem 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; sowie Services Specification, Composition, and Enactment. T3 - Technische Berichte des Hasso-Plattner-Instituts für Digital Engineering an der Universität Potsdam - 138 KW - Hasso Plattner Institute KW - research school KW - Ph.D. retreat KW - service-oriented systems engineering KW - Hasso-Plattner-Institut KW - Forschungskolleg KW - Klausurtagung KW - Service-oriented Systems Engineering Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-504132 SN - 978-3-86956-513-2 SN - 1613-5652 SN - 2191-1665 IS - 138 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - De Freitas, Jessica K. A1 - Johnson, Kipp W. A1 - Golden, Eddye A1 - Nadkarni, Girish N. A1 - Dudley, Joel T. A1 - Böttinger, Erwin A1 - Glicksberg, Benjamin S. A1 - Miotto, Riccardo T1 - Phe2vec BT - Automated disease phenotyping based on unsupervised embeddings from electronic health records JF - Patterns N2 - 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. Y1 - 2021 U6 - https://doi.org/10.1016/j.patter.2021.100337 SN - 2666-3899 VL - 2 IS - 9 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Klippert, Monika A1 - Stolpmann, Robert A1 - Grum, Marcus A1 - Thim, Christof A1 - Gronau, Norbert A1 - Albers, Albert T1 - Knowledge transfer quality improvement BT - the quality enhancement of knowledge transfers in product engineering T2 - Procedia CIRP N2 - 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. KW - knowledge transfer KW - product generation engineering KW - improvement KW - quality KW - intervention Y1 - 2023 U6 - https://doi.org/10.1016/j.procir.2023.02.171 SN - 2212-8271 VL - 119 SP - 919 EP - 925 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Panzer, Marcel A1 - Gronau, Norbert T1 - Enhancing economic efficiency in modular production systems through deep reinforcement learning T2 - Procedia CIRP N2 - 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. KW - modular production KW - production control KW - multi-agent system KW - deep reinforcement learning KW - discrete event simulation Y1 - 2024 U6 - https://doi.org/10.1016/j.procir.2023.09.229 SN - 2212-8271 VL - 121 SP - 55 EP - 60 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Grdseloff, Nastasja A1 - Boulday, Gwenola A1 - Roedel, Claudia J. A1 - Otten, Cecile A1 - Vannier, Daphne Raphaelle A1 - Cardoso, Cecile A1 - Faurobert, Eva A1 - Dogra, Deepika A1 - Tournier-Lasserve, Elisabeth A1 - Abdelilah-Seyfried, Salim T1 - Impaired retinoic acid signaling in cerebral cavernous malformations JF - Scientific reports N2 - 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. KW - Developmental biology KW - Molecular medicine Y1 - 2023 U6 - https://doi.org/10.1038/s41598-023-31905-0 SN - 2045-2322 VL - 13 IS - 1 PB - Nature Portfolio CY - Berlin ER - TY - JOUR A1 - Lewkowicz, Daniel A1 - Wohlbrandt, Attila A1 - Böttinger, Erwin T1 - Economic impact of clinical decision support interventions based on electronic health records JF - BMC Health Services Research N2 - 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. KW - Economic evaluation KW - Electronic health record KW - Clinical decision support KW - Behavioral economics Y1 - 2020 U6 - https://doi.org/10.1186/s12913-020-05688-3 SN - 1472-6963 VL - 20 PB - BioMed Central CY - London ER - TY - JOUR A1 - Wachs, Sebastian A1 - Wettstein, Alexander A1 - Bilz, Ludwig A1 - Gamez-Guadix, Manuel T1 - Motivos del discurso de odio en la adolescencia y su relación con las normas sociales BT - Adolescents' motivations to perpetrate hate speech and links with social norms JF - Comunicar : revista científica de comunicación y educación N2 - 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. KW - Hate speech KW - cyberhate KW - motives KW - social norms KW - injunctive norms KW - peer KW - pressure Y1 - 2022 U6 - https://doi.org/10.3916/C71-2022-01 SN - 1134-3478 SN - 1988-3293 VL - 30 IS - 71 SP - 9 EP - 20 PB - Grupo Comunicar CY - Huelva ER - TY - JOUR A1 - Smith, Taylor A1 - Boers, Niklas T1 - Global vegetation resilience linked to water availability and variability JF - Nature Communications N2 - 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. Y1 - 2023 U6 - https://doi.org/10.1038/s41467-023-36207-7 SN - 2041-1723 VL - 14 IS - 1 PB - Springer Nature CY - London ER - TY - JOUR A1 - Falkenhagen, Undine A1 - Knöchel, Jane A1 - Kloft, Charlotte A1 - Huisinga, Wilhelm T1 - Deriving mechanism-based pharmacodynamic models by reducing quantitative systems pharmacology models BT - an application to warfarin JF - CPT: Pharmacometrics & Systems Pharmacology N2 - 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. Y1 - 2023 U6 - https://doi.org/10.1002/psp4.12903 SN - 2163-8306 VL - 12 IS - 4 SP - 432 EP - 443 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Moreno-Romero, Jordi A1 - Probst, Aline V. A1 - Trindade, Inês A1 - Kalyanikrishna, A1 - Engelhorn, Julia A1 - Farrona, Sara T1 - Looking At the Past and Heading to the Future BT - Meeting Summary of the 6th European Workshop on Plant Chromatin 2019 in Cologne, Germany JF - Frontiers in Plant Science N2 - 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. KW - EWPC2019 KW - chromatin KW - epigenetics KW - transcription KW - nucleus Y1 - 2020 U6 - https://doi.org/10.3389/fpls.2019.01795 SN - 1664-462X VL - 10 IS - 1795 SP - 1 EP - 12 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Dellepiane, Sergio A1 - Vaid, Akhil A1 - Jaladanki, Suraj K. A1 - Coca, Steven A1 - Fayad, Zahi A. A1 - Charney, Alexander W. A1 - Böttinger, Erwin A1 - He, John Cijiang A1 - Glicksberg, Benjamin S. A1 - Chan, Lili A1 - Nadkarni, Girish T1 - Acute kidney injury in patients hospitalized with COVID-19 in New York City BT - Temporal Trends From March 2020 to April 2021 JF - Kidney medicine Y1 - 2021 U6 - https://doi.org/10.1016/j.xkme.2021.06.008 SN - 2590-0595 VL - 3 IS - 5 SP - 877 EP - 879 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Datta, Suparno A1 - Sachs, Jan Philipp A1 - Freitas da Cruz, Harry A1 - Martensen, Tom A1 - Bode, Philipp A1 - Morassi Sasso, Ariane A1 - Glicksberg, Benjamin S. A1 - Böttinger, Erwin T1 - FIBER BT - enabling flexible retrieval of electronic health records data for clinical predictive modeling JF - JAMIA open N2 - 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. KW - databases KW - factual KW - electronic health records KW - information storage and KW - retrieval KW - workflow KW - software/instrumentation Y1 - 2021 U6 - https://doi.org/10.1093/jamiaopen/ooab048 SN - 2574-2531 VL - 4 IS - 3 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Cope, Justin L. A1 - Baukmann, Hannes A. A1 - Klinger, Jörn E. A1 - Ravarani, Charles N. J. A1 - Böttinger, Erwin A1 - Konigorski, Stefan A1 - Schmidt, Marco F. T1 - Interaction-based feature selection algorithm outperforms polygenic risk score in predicting Parkinson’s Disease status JF - Frontiers in genetics N2 - 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. KW - epistasis KW - machine learning KW - feature selection KW - parkinson's disease KW - PPMI (parkinson's progression markers initiative) Y1 - 2021 U6 - https://doi.org/10.3389/fgene.2021.744557 SN - 1664-8021 VL - 12 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Zenner, Alexander M. A1 - Böttinger, Erwin A1 - Konigorski, Stefan T1 - StudyMe BT - a new mobile app for user-centric N-of-1 trials JF - Trials N2 - 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. Y1 - 2022 U6 - https://doi.org/10.1186/s13063-022-06893-7 SN - 1745-6215 VL - 23 PB - BioMed Central CY - London ER - TY - JOUR A1 - Lewkowicz, Daniel A1 - Böttinger, Erwin A1 - Siegel, Martin T1 - Economic evaluation of digital therapeutic care apps for unsupervised treatment of low back pain BT - Monte Carlo Simulation JF - JMIR mhealth and uhealth N2 - 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. KW - cost-utility analysis KW - cost KW - probabilistic sensitivity analysis KW - Monte Carlo simulation KW - low back pain KW - pain KW - economic KW - cost-effectiveness KW - Markov model KW - digital therapy KW - digital health app KW - mHealth KW - mobile health KW - health app KW - mobile app KW - orthopedic KW - QUALY KW - DALY KW - quality-adjusted life years KW - disability-adjusted life years KW - time horizon KW - veteran KW - statistics Y1 - 2023 U6 - https://doi.org/10.2196/44585 SN - 2291-5222 VL - 11 PB - JMIR Publications CY - Toronto ER - TY - JOUR A1 - Konigorski, Stefan A1 - Wernicke, Sarah A1 - Slosarek, Tamara A1 - Zenner, Alexander M. A1 - Strelow, Nils A1 - Ruether, Darius F. A1 - Henschel, Florian A1 - Manaswini, Manisha A1 - Pottbäcker, Fabian A1 - Edelman, Jonathan A. A1 - Owoyele, Babajide A1 - Danieletto, Matteo A1 - Golden, Eddye A1 - Zweig, Micol A1 - Nadkarni, Girish N. A1 - Böttinger, Erwin T1 - StudyU: a platform for designing and conducting innovative digital N-of-1 trials JF - Journal of medical internet research N2 - 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. KW - digital interventions KW - N-of-1 trial KW - SCED KW - single-case experimental design KW - web application KW - mobile application KW - app KW - digital health Y1 - 2022 U6 - https://doi.org/10.2196/35884 SN - 1439-4456 SN - 1438-8871 VL - 24 IS - 7 PB - Healthcare World CY - Richmond, Va. ER - TY - JOUR A1 - Barbolini, Natasha A1 - Woutersen, Amber A1 - Dupont-Nivet, Guillaume A1 - Silvestro, Daniele A1 - Tardif-Becquet, Delphine A1 - Coster, Pauline M. C. A1 - Meijer, Niels A1 - Chang, Cun A1 - Zhang, Hou-Xi A1 - Licht, Alexis A1 - Rydin, Catarina A1 - Koutsodendris, Andreas A1 - Han, Fang A1 - Rohrmann, Alexander A1 - Liu, Xiang-Jun A1 - Zhang, Y. A1 - Donnadieu, Yannick A1 - Fluteau, Frederic A1 - Ladant, Jean-Baptiste A1 - Le Hir, Guillaume A1 - Hoorn, M. Carina T1 - Cenozoic evolution of the steppe-desert biome in Central Asia JF - Science Advances N2 - 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. Y1 - 2020 U6 - https://doi.org/10.1126/sciadv.abb8227 SN - 2375-2548 VL - 6 IS - 41 PB - American Association for the Advancement of Science CY - Washington ER - TY - JOUR A1 - Woutersen, Amber A1 - Jardine, Phillip E. A1 - Giovanni Bogota-Angel, Raul A1 - Zhang, Hong-Xiang A1 - Silvestro, Daniele A1 - Antonelli, Alexandre A1 - Gogna, Elena A1 - Erkens, Roy H. J. A1 - Gosling, William D. A1 - Dupont-Nivet, Guillaume A1 - Hoorn, Carina T1 - A novel approach to study the morphology and chemistry of pollen in a phylogenetic context, applied to the halophytic taxon Nitraria L.(Nitrariaceae) JF - PeerJ N2 - 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. KW - FTIR KW - LM KW - SEM KW - Paratethys KW - Tibet KW - Sporopollenin KW - Mediterranean KW - Steppe-desert KW - Australia KW - Palynology Y1 - 2018 U6 - https://doi.org/10.7717/peerj.5055 SN - 2167-8359 VL - 6 PB - PeerJ Inc. CY - London ER - TY - JOUR A1 - Vaid, Akhil A1 - Somani, Sulaiman A1 - Russak, Adam J. A1 - De Freitas, Jessica K. A1 - Chaudhry, Fayzan F. A1 - Paranjpe, Ishan A1 - Johnson, Kipp W. A1 - Lee, Samuel J. A1 - Miotto, Riccardo A1 - Richter, Felix A1 - Zhao, Shan A1 - Beckmann, Noam D. A1 - Naik, Nidhi A1 - Kia, Arash A1 - Timsina, Prem A1 - Lala, Anuradha A1 - Paranjpe, Manish A1 - Golden, Eddye A1 - Danieletto, Matteo A1 - Singh, Manbir A1 - Meyer, Dara A1 - O'Reilly, Paul F. A1 - Huckins, Laura A1 - Kovatch, Patricia A1 - Finkelstein, Joseph A1 - Freeman, Robert M. A1 - Argulian, Edgar A1 - Kasarskis, Andrew A1 - Percha, Bethany A1 - Aberg, Judith A. A1 - Bagiella, Emilia A1 - Horowitz, Carol R. A1 - Murphy, Barbara A1 - Nestler, Eric J. A1 - Schadt, Eric E. A1 - Cho, Judy H. A1 - Cordon-Cardo, Carlos A1 - Fuster, Valentin A1 - Charney, Dennis S. A1 - Reich, David L. A1 - Böttinger, Erwin A1 - Levin, Matthew A. A1 - Narula, Jagat A1 - Fayad, Zahi A. A1 - Just, Allan C. A1 - Charney, Alexander W. A1 - Nadkarni, Girish N. A1 - Glicksberg, Benjamin S. T1 - Machine learning to predict mortality and critical events in a cohort of patients with COVID-19 in New York City: model development and validation JF - Journal of medical internet research : international scientific journal for medical research, information and communication on the internet ; JMIR N2 - 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. KW - machine learning KW - COVID-19 KW - electronic health record KW - TRIPOD KW - clinical KW - informatics KW - prediction KW - mortality KW - EHR KW - cohort KW - hospital KW - performance Y1 - 2020 U6 - https://doi.org/10.2196/24018 SN - 1439-4456 SN - 1438-8871 VL - 22 IS - 11 PB - Healthcare World CY - Richmond, Va. ER - TY - JOUR A1 - Döll, Stefanie A1 - Djalali Farahani-Kofoet, Roxana A1 - Zrenner, Rita A1 - Henze, Andrea A1 - Witzel, Katja T1 - Tissue-specific signatures of metabolites and proteins in asparagus roots and exudates JF - Horticulture research N2 - 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. Y1 - 2021 U6 - https://doi.org/10.1038/s41438-021-00510-5 SN - 2052-7276 SN - 2662-6810 VL - 8 IS - 1 PB - Nanjing Agricultural Univ. CY - Nanjing ER - TY - CHAP A1 - Löw, Martina A1 - Sayman, Volkan A1 - Schwerer, Jona A1 - Wolf, Hannah ED - Löw, Martina ED - Sayman, Volkan ED - Schwerer, Jona ED - Wolf, Hannah T1 - Am Ende der Globalisierung BT - über die Refiguration von Räumen T2 - Am Ende der Globalisierung Y1 - 2021 SN - 978-3-8394-5402-2 SN - 978-3-8376-5402-8 U6 - https://doi.org/10.14361/9783839454022 SP - 9 EP - 22 PB - transcript CY - Bielefeld ER - TY - JOUR A1 - Kapidzic, Sanja A1 - Frey, Felix A1 - Neuberger, Christoph A1 - Stieglitz, Stefan A1 - Mirbabaie, Milad T1 - Crisis communication on Twitter BT - differences between user types in top tweets about the 2015 “refugee crisis” in Germany JF - International journal of communication N2 - The study explores differences between three user types in the top tweets about the 2015 “refugee crisis” in Germany and presents the results of a quantitative content analysis. All tweets with the keyword “Flüchtlinge” posted for a monthlong period following September 13, 2015, the day Germany decided to implement border controls, were collected (N = 763,752). The top 2,495 tweets according to number of retweets were selected for analysis. Differences between news media, public and private actor tweets in topics, tweet characteristics such as tone and opinion expression, links, and specific sentiments toward refugees were analyzed. We found strong differences between the tweets. Public actor tweets were the main source of positive sentiment toward refugees and the main information source on refugee support. News media tweets mostly reflected traditional journalistic norms of impartiality and objectivity, whereas private actor tweets were more diverse in sentiments toward refugees. KW - refugee crisis 2015 KW - Germany KW - social media KW - Twitter KW - user types Y1 - 2023 UR - https://ijoc.org/index.php/ijoc/article/view/18172/4022 SN - 1932-8036 VL - 17 SP - 735 EP - 754 PB - The Annenberg Center for Communication CY - Los Angeles, Calif. ER - TY - JOUR A1 - Toumoulin, Agathe A1 - Tardif-Becquet, Delphine A1 - Donnadieu, Yannick A1 - Licht, Alexis A1 - Ladant, Jean-Baptiste A1 - Kunzmann, Lutz A1 - Dupont-Nivet, Guillaume T1 - Evolution of continental temperature seasonality from the Eocene greenhouse to the Oligocene icehouse BT - a model-data comparison JF - Climate of the past : an interactive open access journal of the European Geosciences Union N2 - At the junction of greenhouse and icehouse climate states, the Eocene-Oligocene Transition (EOT) is a key moment in Cenozoic climate history. While it is associated with severe extinctions and biodiversity turnovers on land, the role of terrestrial climate evolution remains poorly resolved, especially the associated changes in seasonality. Some paleobotanical and geochemical continental records in parts of the Northern Hemisphere suggest the EOT is associated with a marked cooling in winter, leading to the development of more pronounced seasons (i.e., an increase in the mean annual range of temperature, MATR). However, the MATR increase has been barely studied by climate models and large uncertainties remain on its origin, geographical extent and impact. In order to better understand and describe temperature seasonality changes between the middle Eocene and the early Oligocene, we use the Earth system model IPSL-CM5A2 and a set of simulations reconstructing the EOT through three major climate forcings: pCO(2) decrease (1120, 840 and 560 ppm), the Antarctic ice-sheet (AIS) formation and the associated sea-level decrease. Our simulations suggest that pCO(2) lowering alone is not sufficient to explain the seasonality evolution described by the data through the EOT but rather that the combined effects of pCO(2) , AIS formation and increased continentality provide the best data-model agreement.pCO(2) decrease induces a zonal pattern with alternating increasing and decreasing seasonality bands particularly strong in the northern high latitudes (up to 8 degrees C MATR increase) due to sea-ice and surface albedo feedback. Conversely, the onset of the AIS is responsible for a more constant surface albedo yearly, which leads to a strong decrease in seasonality in the southern midlatitudes to high latitudes (> 40 degrees S). Finally, continental areas that emerged due to the sea-level lowering cause the largest increase in seasonality and explain most of the global heterogeneity in MATR changes (1MATR) patterns. The Delta MATR patterns we reconstruct are generally consistent with the variability of the EOT biotic crisis intensity across the Northern Hemisphere and provide insights on their underlying mechanisms. Y1 - 2022 U6 - https://doi.org/10.5194/cp-18-341-2022 SN - 1814-9324 SN - 1814-9332 VL - 18 IS - 2 SP - 341 EP - 362 PB - Copernicus CY - Göttingen ER - TY - JOUR A1 - Tardif-Becquet, Delphine A1 - Fluteau, Frédéric A1 - Donnadieu, Yannick A1 - Le Hir, Guillaume A1 - Ladant, Jean-Baptiste A1 - Sepulchre, Pierre A1 - Licht, Alexis A1 - Poblete, Fernando A1 - Dupont-Nivet, Guillaume T1 - The origin of Asian monsoons BT - a modelling perspective JF - Climate of the Past N2 - The Cenozoic inception and development of the Asian monsoons remain unclear and have generated much debate, as several hypotheses regarding circulation patterns at work in Asia during the Eocene have been proposed in the few last decades. These include (a) the existence of modern-like monsoons since the early Eocene; (b) that of a weak South Asian monsoon (SAM) and little to no East Asian monsoon (EAM); or (c) a prevalence of the Intertropical Convergence Zone (ITCZ) migrations, also referred to as Indonesian-Australian monsoon (I-AM). As SAM and EAM are supposed to have been triggered or enhanced primarily by Asian palaeogeographic changes, their possible inception in the very dynamic Eocene palaeogeographic context remains an open question, both in the modelling and field-based communities. We investigate here Eocene Asian climate conditions using the IPSL-CM5A2 (Sepulchre et al., 2019) earth system model and revised palaeogeographies. Our Eocene climate simulation yields atmospheric circulation patterns in Asia substantially different from modern conditions. A large high-pressure area is simulated over the Tethys ocean, which generates intense low tropospheric winds blowing southward along the western flank of the proto-Himalayan-Tibetan plateau (HTP) system. This low-level wind system blocks, to latitudes lower than 10 degrees N, the migration of humid and warm air masses coming from the Indian Ocean. This strongly contrasts with the modern SAM, during which equatorial air masses reach a latitude of 20-25 degrees N over India and southeastern China. Another specific feature of our Eocene simulation is the widespread subsidence taking place over northern India in the midtroposphere (around 5000 m), preventing deep convective updraught that would transport water vapour up to the condensation level. Both processes lead to the onset of a broad arid region located over northern India and over the HTP. More humid regions of high seasonality in precipitation encircle this arid area, due to the prevalence of the Intertropical Convergence Zone (ITCZ) migrations (or Indonesian-Australian monsoon, I-AM) rather than monsoons. Although the existence of this central arid region may partly result from the specifics of our simulation (model dependence and palaeogeographic uncertainties) and has yet to be confirmed by proxy records, most of the observational evidence for Eocene monsoons are located in the highly seasonal transition zone between the arid area and the more humid surroundings. We thus suggest that a zonal arid climate prevailed over Asia before the initiation of monsoons that most likely occurred following Eocene palaeogeographic changes. Our results also show that precipitation seasonality should be used with caution to infer the presence of a monsoonal circulation and that the collection of new data in this arid area is of paramount importance to allow the debate to move forward. KW - earth system model KW - early eocene KW - tibetan plateau KW - climate-change KW - oligocene climate KW - summer monsoon KW - global monsoon KW - ice sheet KW - part 1 KW - China Y1 - 2020 U6 - https://doi.org/10.5194/cp-16-847-2020 SN - 1814-9332 SN - 1814-9324 VL - 16 IS - 3 SP - 847 EP - 865 PB - Copernicus Publications CY - Göttingen ER - TY - JOUR A1 - König, Johanna A1 - Block, Andrea A1 - Becker, Mathias A1 - Fenske, Kristin A1 - Hertel, Johannes A1 - Van der Auwera, Sandra A1 - Zymara, Kathleen A1 - Voelzke, Henry A1 - Freyberger, Harald Jürgen A1 - Grabe, Hans Joergen T1 - Assessment of subjective emotional valence and long-lasting impact of life events BT - development and psychometrics of the Stralsund Life Event List (SEL) JF - BMC Psychiatry N2 - Background: Life events (LEs) are associated with future physical and mental health. They are crucial for understanding the pathways to mental disorders as well as the interactions with biological parameters. However, deeper insight is needed into the complex interplay between the type of LE, its subjective evaluation and accompanying factors such as social support. The "Stralsund Life Event List" (SEL) was developed to facilitate this research. Methods: The SEL is a standardized interview that assesses the time of occurrence and frequency of 81 LEs, their subjective emotional valence, the perceived social support during the LE experience and the impact of past LEs on present life. Data from 2265 subjects from the general population-based cohort study "Study of Health in Pomerania" (SHIP) were analysed. Based on the mean emotional valence ratings of the whole sample, LEs were categorized as "positive" or "negative". For verification, the SEL was related to lifetime major depressive disorder (MDD; Munich Composite International Diagnostic Interview), childhood trauma (Childhood Trauma Questionnaire), resilience (Resilience Scale) and subjective health (SF-12 Health Survey). Conclusions: The SEL is a valid instrument that enables the analysis of the number and frequency of LEs, their emotional valence, perceived social support and current impact on life on a global score and on an individual item level. Thus, we can recommend its use in research settings that require the assessment and analysis of the relationship between the occurrence and subjective evaluation of LEs as well as the complex balance between distressing and stabilizing life experiences. KW - Positive life events KW - Negative life events KW - General population KW - Emotional valence KW - Depressive disorder Y1 - 2018 U6 - https://doi.org/10.1186/s12888-018-1649-3 SN - 1471-244X VL - 18 PB - BioMed Central CY - London ER - TY - JOUR A1 - Herrmann, Matthias L. A1 - Boden, Cindy A1 - Maurer, Christoph A1 - Kentischer, Felix A1 - Mennig, Eva A1 - Wagner, Sören A1 - Conzelmann, Lars O. A1 - Förstner, Bernd R. A1 - Rapp, Michael A. A1 - von Arnim, Christine A. F. A1 - Denkinger, Michael A1 - Eschweiler, Gerhard W. A1 - Thomas, Christine T1 - Anticholinergic drug exposure increases the risk of delirium in older patients undergoing elective surgery JF - Frontiers in medicine N2 - IntroductionPostoperative delirium (POD) is a common and serious adverse event of surgery in older people. Because of its great impact on patients' safety and quality of life, identification of modifiable risk factors could be useful. Although preoperative medication intake is assumed to be an important modifiable risk factor, the impact of anticholinergic drugs on the occurrence of POD seems underestimated in elective surgery. The aim of this study was to investigate the association between preoperative anticholinergic burden and POD. We hypothesized that a high preoperative anticholinergic burden is an independent, potentially modifiable predisposing and precipitating factor of POD in older people. MethodsBetween November 2017 and April 2019, 1,470 patients of 70 years and older undergoing elective orthopedic, general, cardiac, or vascular surgery were recruited in the randomized, prospective, multicenter PAWEL trial. Anticholinergic burden of a sub-cohort of 899 patients, who did not receive a multimodal intervention for preventing POD, was assessed by two different tools at hospital admission: The established Anticholinergic Risk Scale (ARS) and the recently developed Anticholinergic Burden Score (ABS). POD was detected by confusion assessment method (CAM) and a validated post discharge medical record review. Logistic regression analyses were performed to evaluate the association between anticholinergic burden and POD. ResultsPOD was observed in 210 of 899 patients (23.4%). Both ARS and ABS were independently associated with POD. The association persisted after adjustment for relevant confounding factors such as age, sex, comorbidities, preoperative cognitive and physical status, number of prescribed drugs, surgery time, type of surgery and anesthesia, usage of heart-lung-machine, and treatment in intensive care unit. If a patient was taking one of the 56 drugs listed in the ABS, risk for POD was 2.7-fold higher (OR = 2.74, 95% CI = 1.55-4.94) and 1.5-fold higher per additional point on the ARS (OR = 1.54, 95% CI = 1.15-2.02). ConclusionPreoperative anticholinergic drug exposure measured by ARS or ABS was independently associated with POD in older patients undergoing elective surgery. Therefore, identification, discontinuation or substitution of anticholinergic medication prior to surgery may be a promising approach to reduce the risk of POD in older patients. KW - delirium KW - acute encephalopathy KW - surgery KW - anticholinergic KW - geriatric KW - postoperative Y1 - 2022 U6 - https://doi.org/10.3389/fmed.2022.871229 SN - 2296-858X VL - 9 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Jara-Muñoz, Julius A1 - Melnick, Daniel A1 - Li, Shaoyang A1 - Socquet, Anne A1 - Cortés-Aranda, Joaquín A1 - Brill, Dominik A1 - Strecker, Manfred R. T1 - The cryptic seismic potential of the Pichilemu blind fault in Chile revealed by off-fault geomorphology JF - Nature communications N2 - 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 similar to 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. Y1 - 2022 U6 - https://doi.org/10.1038/s41467-022-30754-1 SN - 2041-1723 VL - 13 IS - 1 PB - Nature Research CY - Berlin ER - TY - JOUR A1 - Haugk, Charlotte A1 - Jongejans, Loeka L. A1 - Mangelsdorf, Kai A1 - Fuchs, Matthias A1 - Ogneva, Olga A1 - Palmtag, Juri A1 - Mollenhauer, Gesine A1 - Mann, Paul J. A1 - Overduin, P. Paul A1 - Grosse, Guido A1 - Sanders, Tina A1 - Tuerena, Robyn E. A1 - Schirrmeister, Lutz A1 - Wetterich, Sebastian A1 - Kizyakov, Alexander A1 - Karger, Cornelia A1 - Strauss, Jens T1 - Organic matter characteristics of a rapidly eroding permafrost cliff in NE Siberia (Lena Delta, Laptev Sea region) JF - Biogeosciences N2 - Organic carbon (OC) stored in Arctic permafrost represents one of Earth's largest and most vulnerable terrestrial carbon pools. Amplified climate warming across the Arctic results in widespread permafrost thaw. Permafrost deposits exposed at river cliffs and coasts are particularly susceptible to thawing processes. Accelerating erosion of terrestrial permafrost along shorelines leads to increased transfer of organic matter (OM) to nearshore waters. However, the amount of terrestrial permafrost carbon and nitrogen as well as the OM quality in these deposits is still poorly quantified. We define the OM quality as the intrinsic potential for further transformation, decomposition and mineralisation. Here, we characterise the sources and the quality of OM supplied to the Lena River at a rapidly eroding permafrost river shoreline cliff in the eastern part of the delta (Sobo-Sise Island). Our multi-proxy approach captures bulk elemental, molecu- lar geochemical and carbon isotopic analyses of Late Pleistocene Yedoma permafrost and Holocene cover deposits, discontinuously spanning the last similar to 52 kyr. We showed that the ancient permafrost exposed in the Sobo-Sise cliff has a high organic carbon content (mean of about 5 wt %). The oldest sediments stem from Marine Isotope Stage (MIS) 3 interstadial deposits (dated to 52 to 28 cal ka BP) and are overlaid by last glacial MIS 2 (dated to 28 to 15 cal ka BP) and Holocene MIS 1 (dated to 7-0 cal ka BP) deposits. The relatively high average chain length (ACL) index of n-alkanes along the cliff profile indicates a predominant contribution of vascular plants to the OM composition. The elevated ratio of isoand anteiso-branched fatty acids (FAs) relative to mid- and long-chain (C >= 20) n-FAs in the interstadial MIS 3 and the interglacial MIS 1 deposits suggests stronger microbial activity and consequently higher input of bacterial biomass during these climatically warmer periods. The overall high carbon preference index (CPI) and higher plant fatty acid (HPFA) values as well as high C/N ratios point to a good quality of the preserved OM and thus to a high potential of the OM for decomposition upon thaw. A decrease in HPFA values downwards along the profile probably indicates stronger OM decomposition in the oldest (MIS 3) deposits of the cliff. The characterisation of OM from eroding permafrost leads to a better assessment of the greenhouse gas potential of the OC released into river and nearshore waters in the future. Y1 - 2022 U6 - https://doi.org/10.5194/bg-19-2079-2022 SN - 1726-4170 SN - 1726-4189 VL - 19 IS - 7 SP - 2079 EP - 2094 PB - Copernicus CY - Göttingen ER - TY - JOUR A1 - Voglimacci-Stephanopoli, Joëlle A1 - Wendleder, Anna A1 - Lantuit, Hugues A1 - Langlois, Alexandre A1 - Stettner, Samuel A1 - Schmitt, Andreas A1 - Dedieu, Jean-Pierre A1 - Roth, Achim A1 - Royer, Alain T1 - Potential of X-band polarimetric synthetic aperture radar co-polar phase difference for arctic snow depth estimation JF - Cryosphere N2 - Changes in snowpack associated with climatic warming has drastic impacts on surface energy balance in the cryosphere. Yet, traditional monitoring techniques, such as punctual measurements in the field, do not cover the full snowpack spatial and temporal variability, which hampers efforts to upscale measurements to the global scale. This variability is one of the primary constraints in model development. In terms of spatial resolution, active microwaves (synthetic aperture radar - SAR) can address the issue and outperform methods based on passive microwaves. Thus, high-spatial-resolution monitoring of snow depth (SD) would allow for better parameterization of local processes that drive the spatial variability of snow. The overall objective of this study is to evaluate the potential of the TerraSAR-X (TSX) SAR sensor and the wave co-polar phase difference (CPD) method for characterizing snow cover at high spatial resolution. Consequently, we first (1) investigate SD and depth hoar fraction (DHF) variability between different vegetation classes in the Ice Creek catchment (Qikiqtaruk/Herschel Island, Yukon, Canada) using in situ measurements collected over the course of a field campaign in 2019; (2) evaluate linkages between snow characteristics and CPD distribution over the 2019 dataset; and (3) determine CPD seasonality considering meteorological data over the 2015-2019 period. SD could be extracted using the CPD when certain conditions are met. A high incidence angle (>30 circle) with a high topographic wetness index (TWI) (>7.0) showed correlation between SD and CPD (R2 up to 0.72). Further, future work should address a threshold of sensitivity to TWI and incidence angle to map snow depth in such environments and assess the potential of using interpolation tools to fill in gaps in SD information on drier vegetation types. Y1 - 2022 U6 - https://doi.org/10.5194/tc-16-2163-2022 SN - 1994-0416 SN - 1994-0424 VL - 16 IS - 6 SP - 2163 EP - 2181 PB - Copernicus CY - Göttingen ER - TY - JOUR A1 - Zech, Philipp A1 - Schuch, Felipe A1 - Pérez Chaparro, Camilo Germán Alberto A1 - Kangas, Maria A1 - Rapp, Michael A. A1 - Heissel, Andreas T1 - Exercise, Comorbidities, and Health-Related Quality of Life in People Living with HIV BT - The HIBES Cohort Study JF - International Journal of Environmental Research and Public Health N2 - (1) Background: People with HIV (PWH) may perform more than one type of exercise cumulatively. The objective of this study is to investigate recreational exercise and its association with health-related quality of life (HRQOL) and comorbidities in relation to potential covariates. (2) Methods: The HIBES study (HIV-Begleiterkrankungen-Sport) is a cross-sectional study for people with HIV. The differences between non-exercisers versus exercisers (cumulated vs. single type of exercises) were investigated using regression models based on 454 participants. (3) Results: Exercisers showed a higher HRQOL score compared to non-exercisers (Wilcox r = 0.2 to 0.239). Psychological disorders were identified as the main covariate. Participants performing exercise cumulatively showed higher scores in duration, frequency, and intensity when compared to participants performing only one type of exercise. The mental health summary score was higher for the cumulated and single type of exercise if a psychological disorder existed. Duration and intensity were associated with an increase of HRQOL, whilst a stronger association between psychological disorders and exercise variables were evident. Exercise duration (minutes) showed a significant effect on QOL (standardized beta = 0.1) and for participants with psychological disorders (standardized beta = 0.3), respectively. (4) Conclusions: Psychological disorders and other covariates have a prominent effect on HRQOL and its association with exercise. For PWH with a psychological disorder, a stronger relationship between HRQOL with exercise duration and intensity emerged. However, differentiation of high-HRQOL individuals warrants further investigation by considering additional factors. KW - HIV KW - exercise intensity KW - quality of life KW - comorbidity Y1 - 2020 U6 - https://doi.org/10.3390/ijerph17145138 SN - 1660-4601 SN - 1661-7827 VL - 17 IS - 14 PB - MDPI AG CY - Basel ER - TY - JOUR A1 - Deeken, Friederike A1 - Reichert, Markus A1 - Zech, Hilmar A1 - Wenzel, Julia A1 - Wedemeyer, Friederike A1 - Aguilera, Alvaro A1 - Aslan, Acelya A1 - Bach, Patrick A1 - Bahr, Nadja Samia A1 - Ebrahimi, Claudia A1 - Fischbach, Pascale Christine A1 - Ganz, Marvin A1 - Garbusow, Maria A1 - Großkopf, Charlotte M. A1 - Heigert, Marie A1 - Hentschel, Angela A1 - Karl, Damian A1 - Pelz, Patricia A1 - Pinger, Mathieu A1 - Riemerschmid, Carlotta A1 - Rosenthal, Annika A1 - Steffen, Johannes A1 - Strehle, Jens A1 - Weiss,, Franziska A1 - Wieder, Gesine A1 - Wieland, Alfred A1 - Zaiser, Judith A1 - Zimmermann, Sina A1 - Walter, Henrik A1 - Lenz, Bernd A1 - Deserno, Lorenz A1 - Smolka, Michael N. A1 - Liu, Shuyan A1 - Ebner-Priemer, Ulrich Walter A1 - Heinz, Andreas A1 - Rapp, Michael A. T1 - Patterns of Alcohol Consumption Among Individuals With Alcohol Use Disorder During the COVID-19 Pandemic and Lockdowns in Germany JF - JAMA Network Open N2 - Importance Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence. Objective To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms. Design, Setting, and Participants This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021). Main Outcomes and Measures Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates. Results Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year’s Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = −5.45; 95% CI, −8.00 to −2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = −11.10; 95% CI, −13.63 to −8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = −6.14; 95% CI, −9.96 to −2.31; P = .002) and in participants with severe AUD (β = −6.26; 95% CI, −10.18 to −2.34; P = .002). Conclusions and Relevance This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals. Y1 - 2022 U6 - https://doi.org/10.1001/jamanetworkopen.2022.24641 SN - 2574-3805 VL - 5 SP - 1 EP - 11 PB - JAMA Network / American Medical Association CY - Chicago, Illinois, USA ET - 8 ER - TY - JOUR A1 - Brahms, Markus A1 - Heinzel, Stephan A1 - Rapp, Michael A. A1 - Mückstein, Marie A1 - Hortobágyi, Tibor A1 - Stelzel, Christine A1 - Granacher, Urs T1 - The acute effects of mental fatigue on balance performance in healthy young and older adults – A systematic review and meta-analysis JF - Acta Psychologica N2 - Cognitive resources contribute to balance control. There is evidence that mental fatigue reduces cognitive resources and impairs balance performance, particularly in older adults and when balance tasks are complex, for example when trying to walk or stand while concurrently performing a secondary cognitive task. We conducted a systematic literature search in PubMed (MEDLINE), Web of Science and Google Scholar to identify eligible studies and performed a random effects meta-analysis to quantify the effects of experimentally induced mental fatigue on balance performance in healthy adults. Subgroup analyses were computed for age (healthy young vs. healthy older adults) and balance task complexity (balance tasks with high complexity vs. balance tasks with low complexity) to examine the moderating effects of these factors on fatigue-mediated balance performance. We identified 7 eligible studies with 9 study groups and 206 participants. Analysis revealed that performing a prolonged cognitive task had a small but significant effect (SMDwm = −0.38) on subsequent balance performance in healthy young and older adults. However, age- and task-related differences in balance responses to fatigue could not be confirmed statistically. Overall, aggregation of the available literature indicates that mental fatigue generally reduces balance in healthy adults. However, interactions between cognitive resource reduction, aging and balance task complexity remain elusive. KW - Cognitive fatigue KW - Exertion KW - Tiredness KW - Postural control KW - Gait KW - Sway Y1 - 2022 U6 - https://doi.org/10.1016/j.actpsy.2022.103540 SN - 1873-6297 VL - 225 SP - 1 EP - 13 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Clausen, Sünje A1 - Brünker, Felix A1 - Stieglitz, Stefan T1 - Towards responsible augmentation BT - identifying characteristics of AI-based technology with ethical implications for knowledge workers T2 - ACIS 2023 proceedings N2 - Artificial intelligence (AI)-based technologies can increasingly perform knowledge work tasks, such as medical diagnosis. Thereby, it is expected that humans will not be replaced by AI but work closely with AI-based technology (“augmentation”). Augmentation has ethical implications for humans (e.g., impact on autonomy, opportunities to flourish through work), thus, developers and managers of AI-based technology have a responsibility to anticipate and mitigate risks to human workers. However, doing so can be difficult as AI encompasses a wide range of technologies, some of which enable fundamentally new forms of interaction. In this research-in-progress paper, we propose the development of a taxonomy to categorize unique characteristics of AI-based technology that influence the interaction and have ethical implications for human workers. The completed taxonomy will support researchers in forming cumulative knowledge on the ethical implications of augmentation and assist practitioners in the ethical design and management of AI-based technology in knowledge work. KW - artificial intelligence KW - augmentation KW - taxonomy KW - human-AI interaction KW - ethics Y1 - 2023 UR - https://aisel.aisnet.org/acis2023/123/ PB - Australasian Association for Information Systems CY - Wellington ER - TY - JOUR A1 - Agthe, Maria A1 - Kayser, Daniela Niesta A1 - Schwarz, Sascha A1 - Maner, Jon K. T1 - Antecedents of the red-romance effect BT - men's attractiveness and women's fertility JF - PLOS ONE / Public Library of Science N2 - The color red has been implicated in a variety of social processes, including those involving mating. While previous research suggests that women sometimes wear red strategically to increase their attractiveness, the replicability of this literature has been questioned. The current research is a reasonably powered conceptual replication designed to strengthen this literature by testing whether women are more inclined to display the color red 1) during fertile (as compared with less fertile) days of the menstrual cycle, and 2) when expecting to interact with an attractive man (as compared with a less attractive man and with a control condition). Analyses controlled for a number of theoretically relevant covariates (relationship status, age, the current weather). Only the latter hypothesis received mixed support (mainly among women on hormonal birth control), whereas results concerning the former hypothesis did not reach significance. Women (N = 281) displayed more red when expecting to interact with an attractive man; findings did not support the prediction that women would increase their display of red on fertile days of the cycle. Findings thus suggested only mixed replicability for the link between the color red and psychological processes involving romantic attraction. They also illustrate the importance of further investigating the boundary conditions of color effects on everyday social processes. Y1 - 2023 U6 - https://doi.org/10.1371/journal.pone.0284035 SN - 1932-6203 VL - 18 IS - 4 PB - PLOS CY - San Fransisco ER - TY - JOUR A1 - Schmicker, Marlen A1 - Frühling, Insa A1 - Menze, Inga A1 - Glanz, Wenzel A1 - Müller, Patrick A1 - Noesselt, Toemme A1 - Müller, Notger Germar T1 - The potential role of gustatory function as an early diagnostic marker for the risk of alzheimer's disease in subjective cognitive decline JF - Journal of Alzheimer's disease reports : JADR N2 - Background: Patients with subjective cognitive decline (SCD) report memory deterioration and are at an increased risk of converting to Alzheimer's disease (AD) although psychophysical testing does not reveal any cognitive deficit. Objective: Here, gustatory function is investigated as a potential predictor for an increased risk of progressive cognitive decline indicating higher AD risk in SCD. Methods: Measures of smell and taste perception as well as neuropsychological data were assessed in patients with subjective cognitive decline (SCD): Subgroups with an increased likelihood of the progression to preclinical AD (SCD+) and those with a lower likelihood (SCD-) were compared to healthy controls (HC), patients with mild cognitive impairment and AD patients. The Sniffin' Sticks test contained 12 items with different qualities and taste was measured with 32 taste stripes (sweet, salty, bitter, sour) of different concentration. Results: Only taste was able to distinguish between HC/SCD- and SCD+ patients. Conclusion: This study provides a first hint of taste as a more sensitive marker than smell for detecting preclinical AD in SCD. Longitudinal observation of cognition and pathology are necessary to further evaluate taste perception as a predictor of pathological objective decline in cognition. KW - Alzheimer's disease KW - dementia KW - diagnostic marker KW - early diagnosis KW - subjective cognitive decline KW - taste Y1 - 2023 U6 - https://doi.org/10.3233/ADR220092 SN - 2542-4823 VL - 7 IS - 1 SP - 249 EP - 262 PB - IOS Press CY - Clifton, VA ER - TY - JOUR A1 - Xiong, Yingquan A1 - Delic, Denis A1 - Zeng, Shufei A1 - Chen, Xin A1 - Chu, Chang A1 - Hasan, Ahmed A. A1 - Krämer, Bernhard K. A1 - Klein, Thomas A1 - Yin, Lianghong A1 - Hocher, Berthold T1 - Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy-effects of salt, ARB, DPP4 inhibitor and SGLT2 blocker JF - BMC nephrology N2 - Background Host factors such as angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine-subtype-2 (TMPRSS2) are important factors for SARS-CoV-2 infection. Clinical and pre-clinical studies demonstrated that RAAS-blocking agents can be safely used during a SARS-CoV-2 infection but it is unknown if DPP-4 inhibitors or SGLT2-blockers may promote COVID-19 by increasing the host viral entry enzymes ACE2 and TMPRSS2. Methods We investigated telmisartan, linagliptin and empagliflozin induced effects on renal and cardiac expression of ACE2, TMPRSS2 and key enzymes involved in RAAS (REN, AGTR2, AGT) under high-salt conditions in a non-diabetic experimental 5/6 nephrectomy (5/6 Nx) model. In the present study, the gene expression of Ace2, Tmprss2, Ren, Agtr2 and Agt was assessed with qRT-PCR and the protein expression of ACE2 and TMPRSS2 with immunohistochemistry in the following experimental groups: Sham + normal diet (ND) + placebo (PBO); 5/6Nx + ND + PBO; 5/6Nx + high salt-diet (HSD) + PBO; 5/6Nx + HSD + telmisartan; 5/6Nx + HSD + linagliptin; 5/6Nx + HSD + empagliflozin. Results In the kidney, the expression of Ace2 was not altered on mRNA level under disease and treatment conditions. The renal TMPRSS2 levels (mRNA and protein) were not affected, whereas the cardiac level was significantly increased in 5/6Nx rats. Intriguingly, the elevated TMPRSS2 protein expression in the heart was significantly normalized after treatment with telmisartan, linagliptin and empagliflozin. Conclusions Our study indicated that there is no upregulation regarding host factors potentially promoting SARS-CoV-2 virus entry into host cells when the SGLT2-blocker empagliflozin, telmisartan and the DPP4-inhibitor blocker linagliptin are used. The results obtained in a preclinical, experimental non-diabetic kidney failure model need confirmation in ongoing interventional clinical trials. KW - SARS CoV-2 host factors KW - 5/6 nephrectomy KW - High-salt diet KW - ARB KW - DPP4 inhibitor KW - SGLT2 blocker Y1 - 2022 U6 - https://doi.org/10.1186/s12882-022-02747-1 SN - 1471-2369 VL - 23 IS - 1 PB - Springer Nature CY - London ER - TY - JOUR A1 - Heistermann, Maik A1 - Francke, Till A1 - Scheiffele, Lena A1 - Petrova, Katya Dimitrova A1 - Budach, Christian A1 - Schrön, Martin A1 - Trost, Benjamin A1 - Rasche, Daniel A1 - Güntner, Andreas A1 - Doepper, Veronika A1 - Förster, Michael A1 - Köhli, Markus A1 - Angermann, Lisa A1 - Antonoglou, Nikolaos A1 - Zude, Manuela A1 - Oswald, Sascha T1 - Three years of soil moisture observations by a dense cosmic-ray neutron sensing cluster at an agricultural research site in north-east Germany JF - Earth system science data : ESSD N2 - Cosmic-ray neutron sensing (CRNS) allows for the estimation of root-zone soil water content (SWC) at the scale of several hectares. In this paper, we present the data recorded by a dense CRNS network operated from 2019 to 2022 at an agricultural research site in Marquardt, Germany - the first multi-year CRNS cluster. Consisting, at its core, of eight permanently installed CRNS sensors, the cluster was supplemented by a wealth of complementary measurements: data from seven additional temporary CRNS sensors, partly co-located with the permanent ones; 27 SWC profiles (mostly permanent); two groundwater observation wells; meteorological records; and Global Navigation Satellite System reflectometry (GNSS-R). Complementary to these continuous measurements, numerous campaign-based activities provided data by mobile CRNS roving, hyperspectral im-agery via UASs, intensive manual sampling of soil properties (SWC, bulk density, organic matter, texture, soil hydraulic properties), and observations of biomass and snow (cover, depth, and density). The unique temporal coverage of 3 years entails a broad spectrum of hydro-meteorological conditions, including exceptional drought periods and extreme rainfall but also episodes of snow coverage, as well as a dedicated irrigation experiment. Apart from serving to advance CRNS-related retrieval methods, this data set is expected to be useful for vari-ous disciplines, for example, soil and groundwater hydrology, agriculture, or remote sensing. Hence, we show exemplary features of the data set in order to highlight the potential for such subsequent studies. The data are available at doi.org/10.23728/b2share.551095325d74431881185fba1eb09c95 (Heistermann et al., 2022b). Y1 - 2023 U6 - https://doi.org/10.5194/essd-15-3243-2023 SN - 1866-3508 SN - 1866-3516 VL - 15 IS - 7 SP - 3243 EP - 3262 PB - Copernics Publications CY - Katlenburg-Lindau ER - TY - JOUR A1 - Shams, Boshra A1 - Wang, Ziqian A1 - Roine, Timo A1 - Aydogan, Dogu Baran A1 - Vajkoczy, Peter A1 - Lippert, Christoph A1 - Picht, Thomas A1 - Fekonja, Lucius Samo T1 - Machine learning-based prediction of motor status in glioma patients using diffusion MRI metrics along the corticospinal tract JF - Brain communications N2 - Shams et al. report that glioma patients' motor status is predicted accurately by diffusion MRI metrics along the corticospinal tract based on support vector machine method, reaching an overall accuracy of 77%. They show that these metrics are more effective than demographic and clinical variables. Along tract statistics enables white matter characterization using various diffusion MRI metrics. These diffusion models reveal detailed insights into white matter microstructural changes with development, pathology and function. Here, we aim at assessing the clinical utility of diffusion MRI metrics along the corticospinal tract, investigating whether motor glioma patients can be classified with respect to their motor status. We retrospectively included 116 brain tumour patients suffering from either left or right supratentorial, unilateral World Health Organization Grades II, III and IV gliomas with a mean age of 53.51 +/- 16.32 years. Around 37% of patients presented with preoperative motor function deficits according to the Medical Research Council scale. At group level comparison, the highest non-overlapping diffusion MRI differences were detected in the superior portion of the tracts' profiles. Fractional anisotropy and fibre density decrease, apparent diffusion coefficient axial diffusivity and radial diffusivity increase. To predict motor deficits, we developed a method based on a support vector machine using histogram-based features of diffusion MRI tract profiles (e.g. mean, standard deviation, kurtosis and skewness), following a recursive feature elimination method. Our model achieved high performance (74% sensitivity, 75% specificity, 74% overall accuracy and 77% area under the curve). We found that apparent diffusion coefficient, fractional anisotropy and radial diffusivity contributed more than other features to the model. Incorporating the patient demographics and clinical features such as age, tumour World Health Organization grade, tumour location, gender and resting motor threshold did not affect the model's performance, revealing that these features were not as effective as microstructural measures. These results shed light on the potential patterns of tumour-related microstructural white matter changes in the prediction of functional deficits. KW - machine learning KW - support vector machine KW - tractography KW - diffusion MRI; KW - corticospinal tract Y1 - 2022 U6 - https://doi.org/10.1093/braincomms/fcac141 SN - 2632-1297 VL - 4 IS - 3 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - de Carvalho Souza, Alyson Matheus A1 - Barrocas, Roberta A1 - Fischer, Martin H. A1 - Arnaud, Emanuel A1 - Moeller, Korbinian A1 - Rennó-Costa, César T1 - Combining virtual reality and tactile stimulation to investigate embodied finger-based numerical representations JF - Frontiers in psychology / Frontiers Research Foundation N2 - Finger-based representation of numbers is a high-level cognitive strategy to assist numerical and arithmetic processing in children and adults. It is unclear whether this paradigm builds on simple perceptual features or comprises several attributes through embodiment. Here we describe the development and initial testing of an experimental setup to study embodiment during a finger-based numerical task using Virtual Reality (VR) and a low-cost tactile stimulator that is easy to build. Using VR allows us to create new ways to study finger-based numerical representation using a virtual hand that can be manipulated in ways our hand cannot, such as decoupling tactile and visual stimuli. The goal is to present a new methodology that can allow researchers to study embodiment through this new approach, maybe shedding new light on the cognitive strategy behind the finger-based representation of numbers. In this case, a critical methodological requirement is delivering precisely targeted sensory stimuli to specific effectors while simultaneously recording their behavior and engaging the participant in a simulated experience. We tested the device's capability by stimulating users in different experimental configurations. Results indicate that our device delivers reliable tactile stimulation to all fingers of a participant's hand without losing motion tracking quality during an ongoing task. This is reflected by an accuracy of over 95% in participants detecting stimulation of a single finger or multiple fingers in sequential stimulation as indicated by experiments with sixteen participants. We discuss possible application scenarios, explain how to apply our methodology to study the embodiment of finger-based numerical representations and other high-level cognitive functions, and discuss potential further developments of the device based on the data obtained in our testing. KW - virtual reality KW - numerical cognition KW - finger counting KW - embodied cognition KW - cognitive science KW - virtual environment Y1 - 2023 U6 - https://doi.org/10.3389/fpsyg.2023.1119561 SN - 1664-1078 VL - 14 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Stübler, Sabine A1 - Kloft, Charlotte A1 - Huisinga, Wilhelm T1 - Cell-level systems biology model to study inflammatory bowel diseases and their treatment options JF - CPT: pharmacometrics & systems pharmacology N2 - To help understand the complex and therapeutically challenging inflammatory bowel diseases (IBDs), we developed a systems biology model of the intestinal immune system that is able to describe main aspects of IBD and different treatment modalities thereof. The model, including key cell types and processes of the mucosal immune response, compiles a large amount of isolated experimental findings from literature into a larger context and allows for simulations of different inflammation scenarios based on the underlying data and assumptions. In the context of a large and diverse virtual IBD population, we characterized the patients based on their phenotype (in contrast to healthy individuals, they developed persistent inflammation after a trigger event) rather than on a priori assumptions on parameter differences to a healthy individual. This allowed to reproduce the enormous diversity of predispositions known to lead to IBD. Analyzing different treatment effects, the model provides insight into characteristics of individual drug therapy. We illustrate for anti-TNF-alpha therapy, how the model can be used (i) to decide for alternative treatments with best prospects in the case of nonresponse, and (ii) to identify promising combination therapies with other available treatment options. Y1 - 2023 U6 - https://doi.org/10.1002/psp4.12932 SN - 2163-8306 VL - 12 IS - 5 SP - 690 EP - 705 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Kaya, Mustafa Yücel A1 - Dupont-Nivet, Guillaume A1 - Frieling, Joost A1 - Fioroni, Chiara A1 - Rohrmann, Alexander A1 - Altıner, Sevinç Özkan A1 - Vardar, Ezgi A1 - Tanyas, Hakan A1 - Mamtimin, Mehmut A1 - Zhaojie, Guo T1 - The Eurasian epicontinental sea was an important carbon sink during the Palaeocene-Eocene thermal maximum JF - Communications earth and environment N2 - The Palaeocene-Eocene Thermal Maximum (ca. 56 million years ago) offers a primary analogue for future global warming and carbon cycle recovery. Yet, where and how massive carbon emissions were mitigated during this climate warming event remains largely unknown. Here we show that organic carbon burial in the vast epicontinental seaways that extended over Eurasia provided a major carbon sink during the Palaeocene-Eocene Thermal Maximum. We coupled new and existing stratigraphic analyses to a detailed paleogeographic framework and using spatiotemporal interpolation calculated ca. 720–1300 Gt organic carbon excess burial, focused in the eastern parts of the Eurasian epicontinental seaways. A much larger amount (2160–3900 Gt C, and when accounting for the increase in inundated shelf area 7400–10300 Gt C) could have been sequestered in similar environments globally. With the disappearance of most epicontinental seas since the Oligocene-Miocene, an effective negative carbon cycle feedback also disappeared making the modern carbon cycle critically dependent on the slower silicate weathering feedback. Y1 - 2022 U6 - https://doi.org/10.1038/s43247-022-00451-4 SN - 2662-4435 VL - 3 IS - 1 PB - Springer Nature CY - London ER -