TY - JOUR A1 - Arboleda-Zapata, Mauricio A1 - Angelopoulos, Michael A1 - Overduin, Pier Paul A1 - Grosse, Guido A1 - Jones, Benjamin M. A1 - Tronicke, Jens T1 - Exploring the capabilities of electrical resistivity tomography to study subsea permafrost JF - The Cryosphere N2 - Sea level rise and coastal erosion have inundated large areas of Arctic permafrost. Submergence by warm and saline waters increases the rate of inundated permafrost thaw compared to sub-aerial thawing on land. Studying the contact between the unfrozen and frozen sediments below the seabed, also known as the ice-bearing permafrost table (IBPT), provides valuable information to understand the evolution of sub-aquatic permafrost, which is key to improving and understanding coastal erosion prediction models and potential greenhouse gas emissions. In this study, we use data from 2D electrical resistivity tomography (ERT) collected in the nearshore coastal zone of two Arctic regions that differ in their environmental conditions (e.g., seawater depth and resistivity) to image and study the subsea permafrost. The inversion of 2D ERT data sets is commonly performed using deterministic approaches that favor smoothed solutions, which are typically interpreted using a user-specified resistivity threshold to identify the IBPT position. In contrast, to target the IBPT position directly during inversion, we use a layer-based model parameterization and a global optimization approach to invert our ERT data. This approach results in ensembles of layered 2D model solutions, which we use to identify the IBPT and estimate the resistivity of the unfrozen and frozen sediments, including estimates of uncertainties. Additionally, we globally invert 1D synthetic resistivity data and perform sensitivity analyses to study, in a simpler way, the correlations and influences of our model parameters. The set of methods provided in this study may help to further exploit ERT data collected in such permafrost environments as well as for the design of future field experiments. Y1 - 2022 U6 - https://doi.org/10.5194/tc-16-4423-2022 SN - 1994-0424 VL - 16 SP - 4423 EP - 4445 PB - Copernicus CY - Katlenburg-Lindau ER - TY - JOUR A1 - Weber, Stephanie A1 - Puta, Christian A1 - Lesinski, Melanie A1 - Gabriel, Brunhild A1 - Steidten, Thomas A1 - Bär, Karl-Jürgen A1 - Herbsleb, Marco A1 - Granacher, Urs A1 - Gabriel, Holger H. W. T1 - Symptoms of anxiety and depression in young athletes using the hospital anxiety and depression scale JF - Frontiers in physiology N2 - Elite young athletes have to cope with multiple psychological demands such as training volume, mental and physical fatigue, spatial separation of family and friends or time management problems may lead to reduced mental and physical recovery. While normative data regarding symptoms of anxiety and depression for the general population is available (Hinz and Brahler, 2011), hardly any information exists for adolescents in general and young athletes in particular. Therefore, the aim of this study was to assess overall symptoms of anxiety and depression in young athletes as well as possible sex differences. The survey was carried out within the scope of the study "Resistance Training in Young Athletes" (KINGS-Study). Between August 2015 and September 2016, 326 young athletes aged (mean +/- SD) 14.3 +/- 1.6 years completed the Hospital Anxiety and Depression Scale (HAD Scale). Regarding the analysis of age on the anxiety and depression subscales, age groups were classified as follows: late childhood (12-14 years) and late adolescence (15-18 years). The participating young athletes were recruited from Olympic weight lifting, handball, judo, track and field athletics, boxing, soccer, gymnastics, ice speed skating, volleyball, and rowing. Anxiety and depression scores were (mean +/- SD) 4.3 +/- 3.0 and 2.8 +/- 2.9, respectively. In the subscale anxiety, 22 cases (6.7%) showed subclinical scores and 11 cases (3.4%) showed clinical relevant score values. When analyzing the depression subscale, 31 cases (9.5%) showed subclinical score values and 12 cases (3.7%) showed clinically important values. No significant differences were found between male and female athletes (p >= 0.05). No statistically significant differences in the HADS scores were found between male athletes of late childhood and late adolescents (p >= 0.05). To the best of our knowledge, this is the first report describing questionnaire based indicators of symptoms of anxiety and depression in young athletes. Our data implies the need for sports medical as well as sports psychiatric support for young athletes. In addition, our results demonstrated that the chronological classification concerning age did not influence HAD Scale outcomes. Future research should focus on sports medical and sports psychiatric interventional approaches with the goal to prevent anxiety and depression as well as teaching coping strategies to young athletes. KW - youth athletes KW - anxiety KW - depression KW - gender differences KW - late childhood KW - adolescents Y1 - 2018 U6 - https://doi.org/10.3389/fphys.2018.00182 SN - 1664-042X VL - 9 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Warschburger, Petra A1 - Kamrath, Clemens A1 - Lanzinger, Stefanie A1 - Sengler, Claudia A1 - Wiegand, Susanna A1 - Göldel, Julia Marlen A1 - Weihrauch-Blüher, Susann A1 - Holl, Reinhard A1 - Minden, Kirsten T1 - A prospective analysis of the long-term impact of the COVID-19 pandemic on well-being and health care among children with a chronic condition and their families BT - a study protocol of the KICK-COVID study JF - BMC pediatrics N2 - Background There is consistent evidence that the COVID-19 pandemic is associated with an increased psychosocial burden on children and adolescents and their parents. Relatively little is known about its particular impact on high-risk groups with chronic physical health conditions (CCs). Therefore, the primary aim of the study is to analyze the multiple impacts on health care and psychosocial well-being on these children and adolescents and their parents. Methods We will implement a two-stage approach. In the first step, parents and their underage children from three German patient registries for diabetes, obesity, and rheumatic diseases, are invited to fill out short questionnaires including questions about corona-specific stressors, the health care situation, and psychosocial well-being. In the next step, a more comprehensive, in-depth online survey is carried out in a smaller subsample. Discussion The study will provide insights into the multiple longer-term stressors during the COVID-19 pandemic in families with a child with a CC. The simultaneous consideration of medical and psycho-social endpoints will help to gain a deeper understanding of the complex interactions affecting family functioning, psychological well-being, and health care delivery. KW - Chronic conditions KW - COVID-19 KW - Children and adolescents KW - Parents KW - Risk perception KW - Psychosocial strain KW - Diabetes KW - Rheumatic diseases KW - Obesity Y1 - 2023 U6 - https://doi.org/10.1186/s12887-023-03912-7 SN - 1471-2431 VL - 23 IS - 1 PB - BioMed Central CY - London ER - TY - JOUR A1 - Cheng, Feng A1 - Dennis, Alice B. A1 - Osuoha, Josephine Ijeoma A1 - Canitz, Julia A1 - Kirschbaum, Frank A1 - Tiedemann, Ralph T1 - A new genome assembly of an African weakly electric fish (Campylomormyrus compressirostris, Mormyridae) indicates rapid gene family evolution in Osteoglossomorpha JF - BMC genomics N2 - Background Teleost fishes comprise more than half of the vertebrate species. Within teleosts, most phylogenies consider the split between Osteoglossomorpha and Euteleosteomorpha/Otomorpha as basal, preceded only by the derivation of the most primitive group of teleosts, the Elopomorpha. While Osteoglossomorpha are generally species poor, the taxon contains the African weakly electric fish (Mormyroidei), which have radiated into numerous species. Within the mormyrids, the genus Campylomormyrus is mostly endemic to the Congo Basin. Campylomormyrus serves as a model to understand mechanisms of adaptive radiation and ecological speciation, especially with regard to its highly diverse species-specific electric organ discharges (EOD). Currently, there are few well-annotated genomes available for electric fish in general and mormyrids in particular. Our study aims at producing a high-quality genome assembly and to use this to examine genome evolution in relation to other teleosts. This will facilitate further understanding of the evolution of the osteoglossomorpha fish in general and of electric fish in particular. Results A high-quality weakly electric fish (C. compressirostris) genome was produced from a single individual with a genome size of 862 Mb, consisting of 1,497 contigs with an N50 of 1,399 kb and a GC-content of 43.69%. Gene predictions identified 34,492 protein-coding genes, which is a higher number than in the two other available Osteoglossomorpha genomes of Paramormyrops kingsleyae and Scleropages formosus. A Computational Analysis of gene Family Evolution (CAFE5) comparing 33 teleost fish genomes suggests an overall faster gene family turnover rate in Osteoglossomorpha than in Otomorpha and Euteleosteomorpha. Moreover, the ratios of expanded/contracted gene family numbers in Osteoglossomorpha are significantly higher than in the other two taxa, except for species that had undergone an additional genome duplication (Cyprinus carpio and Oncorhynchus mykiss). As potassium channel proteins are hypothesized to play a key role in EOD diversity among species, we put a special focus on them, and manually curated 16 Kv1 genes. We identified a tandem duplication in the KCNA7a gene in the genome of C. compressirostris. Conclusions We present the fourth genome of an electric fish and the third well-annotated genome for Osteoglossomorpha, enabling us to compare gene family evolution among major teleost lineages. Osteoglossomorpha appear to exhibit rapid gene family evolution, with more gene family expansions than contractions. The curated Kv1 gene family showed seven gene clusters, which is more than in other analyzed fish genomes outside Osteoglossomorpha. The KCNA7a, encoding for a potassium channel central for EOD production and modulation, is tandemly duplicated which may related to the diverse EOD observed among Campylomormyrus species. KW - Campylomormyrus KW - Pacbio sequencing KW - Gene family KW - Osteoglossomorpha KW - Kv1 Y1 - 2023 U6 - https://doi.org/10.1186/s12864-023-09196-6 SN - 1471-2164 VL - 24 IS - 1 PB - BMC CY - London ER - TY - JOUR A1 - Cesca, Simone A1 - Sugan, Monica A1 - Rudzinski, Lukasz A1 - Vajedian, Sanaz A1 - Niemz, Peter A1 - Plank, Simon A1 - Petersen, Gesa A1 - Deng, Zhiguo A1 - Rivalta, Eleonora A1 - Vuan, Alessandro A1 - Linares, Milton Percy Plasencia A1 - Heimann, Sebastian A1 - Dahm, Torsten T1 - Massive earthquake swarm driven by magmatic intrusion at the Bransfield Strait, Antarctica JF - Communications earth and environment N2 - An earthquake swarm affected the Bransfield Strait, Antarctica, a unique rift basin in transition from intra-arc rifting to ocean spreading. The swarm, counting similar to 85,000 volcano-tectonic earthquakes since August 2020, is located close to the Orca submarine volcano, previously considered inactive. Simultaneously, geodetic data reported up to similar to 11 cm north-westward displacement over King George Island. We use a broad variety of geophysical data and methods to reveal the complex migration of seismicity, accompanying the intrusion of 0.26-0.56 km(3) of magma. Strike-slip earthquakes mark the intrusion at depth, while shallower normal faulting the similar to 20 km long lateral growth of a dike. Seismicity abruptly decreased after a Mw 6.0 earthquake, suggesting the magmatic dike lost pressure with the slipping of a large fault. A seafloor eruption is likely, but not confirmed by sea surface temperature anomalies. The unrest documents episodic magmatic intrusion in the Bransfield Strait, providing unique insights into active continental rifting. Y1 - 2022 U6 - https://doi.org/10.1038/s43247-022-00418-5 SN - 2662-4435 VL - 3 IS - 1 PB - Springer Nature CY - London ER - TY - JOUR A1 - Fehr, Jana A1 - Piccininni, Marco A1 - Kurth, Tobias A1 - Konigorski, Stefan T1 - Assessing the transportability of clinical prediction models for cognitive impairment using causal models JF - BMC medical research methodology N2 - Background Machine learning models promise to support diagnostic predictions, but may not perform well in new settings. Selecting the best model for a new setting without available data is challenging. We aimed to investigate the transportability by calibration and discrimination of prediction models for cognitive impairment in simulated external settings with different distributions of demographic and clinical characteristics. Methods We mapped and quantified relationships between variables associated with cognitive impairment using causal graphs, structural equation models, and data from the ADNI study. These estimates were then used to generate datasets and evaluate prediction models with different sets of predictors. We measured transportability to external settings under guided interventions on age, APOE & epsilon;4, and tau-protein, using performance differences between internal and external settings measured by calibration metrics and area under the receiver operating curve (AUC). Results Calibration differences indicated that models predicting with causes of the outcome were more transportable than those predicting with consequences. AUC differences indicated inconsistent trends of transportability between the different external settings. Models predicting with consequences tended to show higher AUC in the external settings compared to internal settings, while models predicting with parents or all variables showed similar AUC. Conclusions We demonstrated with a practical prediction task example that predicting with causes of the outcome results in better transportability compared to anti-causal predictions when considering calibration differences. We conclude that calibration performance is crucial when assessing model transportability to external settings. KW - Alzheimer's Disease KW - Clinical risk prediction KW - DAG KW - Causality; KW - Transportability Y1 - 2023 U6 - https://doi.org/10.1186/s12874-023-02003-6 SN - 1471-2288 VL - 23 IS - 1 PB - BMC CY - London ER - TY - JOUR A1 - Lupien, Rachel L. A1 - Russell, James M. A1 - Pearson, Emma J. A1 - Castaneda, Isla S. A1 - Asrat, Asfawossen A1 - Förster, Verena A1 - Lamb, Henry F. A1 - Roberts, Helen M. A1 - Schäbitz, Frank A1 - Trauth, Martin H. A1 - Beck, Catherine C. A1 - Feibel, Craig S. A1 - Cohen, Andrew S. T1 - Orbital controls on eastern African hydroclimate in the Pleistocene JF - Scientific reports N2 - Understanding eastern African paleoclimate is critical for contextualizing early human evolution, adaptation, and dispersal, yet Pleistocene climate of this region and its governing mechanisms remain poorly understood due to the lack of long, orbitally-resolved, terrestrial paleoclimate records. Here we present leaf wax hydrogen isotope records of rainfall from paleolake sediment cores from key time windows that resolve long-term trends, variations, and high-latitude effects on tropical African precipitation. Eastern African rainfall was dominantly controlled by variations in low-latitude summer insolation during most of the early and middle Pleistocene, with little evidence that glacial-interglacial cycles impacted rainfall until the late Pleistocene. We observe the influence of high-latitude-driven climate processes emerging from the last interglacial (Marine Isotope Stage 5) to the present, an interval when glacial-interglacial cycles were strong and insolation forcing was weak. Our results demonstrate a variable response of eastern African rainfall to low-latitude insolation forcing and high-latitude-driven climate change, likely related to the relative strengths of these forcings through time and a threshold in monsoon sensitivity. We observe little difference in mean rainfall between the early, middle, and late Pleistocene, which suggests that orbitally-driven climate variations likely played a more significant role than gradual change in the relationship between early humans and their environment. Y1 - 2022 U6 - https://doi.org/10.1038/s41598-022-06826-z SN - 2045-2322 VL - 12 IS - 1 PB - Macmillan Publishers Limited CY - London ER - TY - JOUR A1 - Essen, Anna A1 - Stern, Ariel Dora A1 - Haase, Christoffer Bjerre A1 - Car, Josip A1 - Greaves, Felix A1 - Paparova, Dragana A1 - Vandeput, Steven A1 - Wehrens, Rik A1 - Bates, David W. T1 - Health app policy BT - international comparison of nine countries' approaches JF - npj digital medicine N2 - An abundant and growing supply of digital health applications (apps) exists in the commercial tech-sector, which can be bewildering for clinicians, patients, and payers. A growing challenge for the health care system is therefore to facilitate the identification of safe and effective apps for health care practitioners and patients to generate the most health benefit as well as guide payer coverage decisions. Nearly all developed countries are attempting to define policy frameworks to improve decision-making, patient care, and health outcomes in this context. This study compares the national policy approaches currently in development/use for health apps in nine countries. We used secondary data, combined with a detailed review of policy and regulatory documents, and interviews with key individuals and experts in the field of digital health policy to collect data about implemented and planned policies and initiatives. We found that most approaches aim for centralized pipelines for health app approvals, although some countries are adding decentralized elements. While the countries studied are taking diverse paths, there is nevertheless broad, international convergence in terms of requirements in the areas of transparency, health content, interoperability, and privacy and security. The sheer number of apps on the market in most countries represents a challenge for clinicians and patients. Our analyses of the relevant policies identified challenges in areas such as reimbursement, safety, and privacy and suggest that more regulatory work is needed in the areas of operationalization, implementation and international transferability of approvals. Cross-national efforts are needed around regulation and for countries to realize the benefits of these technologies. Y1 - 2022 U6 - https://doi.org/10.1038/s41746-022-00573-1 SN - 2398-6352 VL - 5 IS - 1 PB - Macmillan Publishers Limited CY - Basingstoke ER - TY - JOUR A1 - Esmaeilishirazifard, Elham A1 - Usher, Louise A1 - Trim, Carol A1 - Denise, Hubert A1 - Sangal, Vartul A1 - Tyson, Gregory H. A1 - Barlow, Axel A1 - Redway, Keith F. A1 - Taylor, John D. A1 - Kremyda-Vlachou, Myrto A1 - Davies, Sam A1 - Loftus, Teresa D. A1 - Lock, Mikaella M. G. A1 - Wright, Kstir A1 - Dalby, Andrew A1 - Snyder, Lori A. S. A1 - Wuster, Wolfgang A1 - Trim, Steve A1 - Moschos, Sterghios A. T1 - Bacterial adaptation to venom in snakes and arachnida JF - Microbiology spectrum N2 - Notwithstanding their 3 to 5% mortality, the 2.7 million envenomation-related injuries occurring annually-predominantly across Africa, Asia, and Latin America-are also major causes of morbidity. Venom toxin-damaged tissue will develop infections in some 75% of envenomation victims, with E. faecalis being a common culprit of disease; however, such infections are generally considered to be independent of envenomation. Animal venoms are considered sterile sources of antimicrobial compounds with strong membrane-disrupting activity against multidrug-resistant bacteria. However, venomous bite wound infections are common in developing nations. Investigating the envenomation organ and venom microbiota of five snake and two spider species, we observed venom community structures that depend on the host venomous animal species and evidenced recovery of viable microorganisms from black-necked spitting cobra (Naja nigricollis) and Indian ornamental tarantula (Poecilotheria regalis) venoms. Among the bacterial isolates recovered from N. nigricollis, we identified two venom-resistant, novel sequence types of Enterococcus faecalis whose genomes feature 16 virulence genes, indicating infectious potential, and 45 additional genes, nearly half of which improve bacterial membrane integrity. Our findings challenge the dogma of venom sterility and indicate an increased primary infection risk in the clinical management of venomous animal bite wounds. IMPORTANCE Notwithstanding their 3 to 5% mortality, the 2.7 million envenomation-related injuries occurring annually-predominantly across Africa, Asia, and Latin America-are also major causes of morbidity. Venom toxin-damaged tissue will develop infections in some 75% of envenomation victims, with E. faecalis being a common culprit of disease; however, such infections are generally considered to be independent of envenomation. Here, we provide evidence on venom microbiota across snakes and arachnida and report on the convergent evolution mechanisms that can facilitate adaptation to black-necked cobra venom in two independent E. faecalis strains, easily misidentified by biochemical diagnostics. Therefore, since inoculation with viable and virulence gene-harboring bacteria can occur during envenomation, acute infection risk management following envenomation is warranted, particularly for immunocompromised and malnourished victims in resource-limited settings. These results shed light on how bacteria evolve for survival in one of the most extreme environments on Earth and how venomous bites must be also treated for infections. KW - drug resistance evolution KW - extremophiles KW - genome analysis KW - microbiome KW - multidrug resistance KW - venom Y1 - 2022 U6 - https://doi.org/10.1128/spectrum.02408-21 SN - 2165-0497 VL - 10 IS - 3 PB - American Society for Microbiology CY - Birmingham, Ala. ER - TY - JOUR A1 - Kelley, Kristin A1 - Hipp, Lena A1 - Protsch, Paula T1 - Organizational commitments to equality change how people view women’s and men’s professional success JF - Scientific reports N2 - To address women’s underrepresentation in high-status positions, many organizations have committed to gender equality. But is women’s professional success viewed less positively when organizations commit to women’s advancement? Do equality commitments have positive effects on evaluations of successful men? We fielded a survey experiment with a national probability sample in Germany (N = 3229) that varied employees’ gender and their organization’s commitment to equality. Respondents read about a recently promoted employee and rated how decisive of a role they thought intelligence and effort played in getting the employee promoted from 1 “Not at all decisive” to 7 “Very decisive” and the fairness of the promotion from 1 “Very unfair” to 7 “Very fair.” When organizations committed to women’s advancement rather than uniform performance standards, people believed intelligence and effort were less decisive in women’s promotions, but that intelligence was more decisive in men’s promotions. People viewed women’s promotions as least fair and men’s as most fair in organizations committed to women’s advancement. However, women’s promotions were still viewed more positively than men’s in all conditions and on all outcomes, suggesting people believed that organizations had double standards for success that required women to be smarter and work harder to be promoted, especially in organizations that did not make equality commitments. KW - human behaviour KW - psychology Y1 - 2024 U6 - https://doi.org/10.1038/s41598-024-56829-1 SN - 2045-2322 VL - 14 IS - 1 PB - Macmillan Publishers Limited, part of Springer Nature CY - London ER - TY - JOUR A1 - Verch, Ronald A1 - Stoll, Josefine A1 - Hadzic, Miralem A1 - Quarmby, Andrew James A1 - Völler, Heinz T1 - Whole-Body EMS Superimposed Walking and Nordic Walking on a Treadmill—Determination of Exercise Intensity to Conventional Exercise JF - Frontiers in physiology / Frontiers Research Foundation N2 - Electrical muscle stimulation (EMS) is an increasingly popular training method and has become the focus of research in recent years. New EMS devices offer a wide range of mobile applications for whole-body EMS (WB-EMS) training, e.g., the intensification of dynamic low-intensity endurance exercises through WB-EMS. The present study aimed to determine the differences in exercise intensity between WB-EMS-superimposed and conventional walking (EMS-CW), and CON and WB-EMS-superimposed Nordic walking (WB-EMS-NW) during a treadmill test. Eleven participants (52.0 ± years; 85.9 ± 7.4 kg, 182 ± 6 cm, BMI 25.9 ± 2.2 kg/m2) performed a 10 min treadmill test at a given velocity (6.5 km/h) in four different test situations, walking (W) and Nordic walking (NW) in both conventional and WB-EMS superimposed. Oxygen uptake in absolute (VO2) and relative to body weight (rel. VO2), lactate, and the rate of perceived exertion (RPE) were measured before and after the test. WB-EMS intensity was adjusted individually according to the feedback of the participant. The descriptive statistics were given in mean ± SD. For the statistical analyses, one-factorial ANOVA for repeated measures and two-factorial ANOVA [factors include EMS, W/NW, and factor combination (EMS*W/NW)] were performed (α = 0.05). Significant effects were found for EMS and W/NW factors for the outcome variables VO2 (EMS: p = 0.006, r = 0.736; W/NW: p < 0.001, r = 0.870), relative VO2 (EMS: p < 0.001, r = 0.850; W/NW: p < 0.001, r = 0.937), and lactate (EMS: p = 0.003, r = 0.771; w/NW: p = 0.003, r = 0.764) and both the factors produced higher results. However, the difference in VO2 and relative VO2 is within the range of biological variability of ± 12%. The factor combination EMS*W/NW is statistically non-significant for all three variables. WB-EMS resulted in the higher RPE values (p = 0.035, r = 0.613), RPE differences for W/NW and EMS*W/NW were not significant. The current study results indicate that WB-EMS influences the parameters of exercise intensity. The impact on exercise intensity and the clinical relevance of WB-EMS-superimposed walking (WB-EMS-W) exercise is questionable because of the marginal differences in the outcome variables. KW - electrical muscle stimulation KW - walking KW - Nordic walking KW - treadmill KW - exercise intensity Y1 - 2021 U6 - https://doi.org/10.3389/fphys.2021.715417 SN - 1664-042X VL - 12 SP - 1 EP - 9 PB - Frontiers Research Foundation CY - Lausanne, Schweiz ER - TY - JOUR A1 - Wachs, Sebastian A1 - Machimbarrena, Juan Manuel A1 - Wright, Michelle F. A1 - Gámez-Guadix, Manuel A1 - Yang, Soeun A1 - Sittichai, Ruthaychonnee A1 - Singh, Ritu A1 - Biswal, Ramakrishna A1 - Flora, Katerina A1 - Daskalou, Vassiliki A1 - Maziridou, Evdoxia A1 - Sung Hong, Jun A1 - Krause, Norman T1 - Associations between coping strategies and cyberhate involvement BT - evidence from adolescents across three world regions JF - International journal of environmental research and public health N2 - Cyberhate represents a risk to adolescents’ development and peaceful coexistence in democratic societies. Yet, not much is known about the relationship between adolescents’ ability to cope with cyberhate and their cyberhate involvement. To fill current gaps in the literature and inform the development of media education programs, the present study investigated various coping strategies in a hypothetical cyberhate scenario as correlates for being cyberhate victims, perpetrators, and both victim–perpetrators. The sample consisted of 6829 adolescents aged 12–18 years old (Mage = 14.93, SD = 1.64; girls: 50.4%, boys: 48.9%, and 0.7% did not indicate their gender) from Asia, Europe, and North America. Results showed that adolescents who endorsed distal advice or endorsed technical coping showed a lower likelihood to be victims, perpetrators, or victim–perpetrators. In contrast, if adolescents felt helpless or endorsed retaliation to cope with cyberhate, they showed higher odds of being involved in cyberhate as victims, perpetrators, or victim–perpetrators. Finally, adolescents who endorsed close support as a coping strategy showed a lower likelihood to be victim–perpetrators, and adolescents who endorsed assertive coping showed higher odds of being victims. In conclusion, the results confirm the importance of addressing adolescents’ ability to deal with cyberhate to develop more tailored prevention approaches. More specifically, such initiatives should focus on adolescents who feel helpless or feel inclined to retaliate. In addition, adolescents should be educated to practice distal advice and technical coping when experiencing cyberhate. Implications for the design and instruction of evidence-based cyberhate prevention (e.g., online educational games, virtual learning environments) will be discussed. KW - cyberhate KW - hate speech KW - coping strategies KW - cross-national KW - counter-speech Y1 - 2022 U6 - https://doi.org/10.3390/ijerph19116749 SN - 1660-4601 VL - 19 SP - 1 EP - 14 PB - MDPI CY - Basel, Schweiz ET - 11 ER - TY - BOOK ED - Kazepov, Yuri ED - Verwiebe, Roland T1 - Vienna BT - Still a just city? T3 - Built environment city studies N2 - This book explores and debates the urban transformations that have taken place in Vienna over the past 30 years and their consequences in policy fields such as labour and housing, political and social participation and the environment. Historically, European cities have been characterised by a strong association between social cohesion, quality of life, economic ambition and a robust State. Vienna is an excellent example for that. In more recent years, however, cities were pressured to change policy principles and mechanisms in the context of demographic shifts, post-industrial transformations and welfare recalibration which have led to worsened social conditions in many cities. Each chapter in this volume discusses Vienna's responses to these pressures in key policy arenas, looking at outcomes from the context-specific local arrangements. Against a theoretical framework debating the European city as a model of inclusion and social justice, authors explore the local capacity to innovate urban policies and to address new social risks, while paying attention to potential trade-offs. The book questions and assesses the city's resilience using time series and an institutional analysis of four key dimensions that characterise the European city model within the context of post-industrial transition: redistribution, recognition, representation and sustainability. It offers a multiscalar perspective of urban governance through labour, housing, participatory and environmental policies, bringing together different levels and public policy types. KW - Built Environment KW - Environment and Sustainability KW - Geography KW - Social Sciences KW - Urban Studies Y1 - 2021 SN - 978-0-367-68011-4 SN - 978-1-003133-82-7 SN - 978-0-367-68013-8 U6 - https://doi.org/10.4324/9781003133827 PB - Routledge CY - London ER - TY - GEN A1 - Caesar, Levke A1 - Rahmstorf, Stefan A1 - Feulner, Georg T1 - Reply to comment on 'On the relationship between Atlantic meridional overturning circulation slowdown and global surface warming' T2 - Environmental research letters N2 - In their comment on our paper (Caesar et al 2020 Environ. Res. Lett. 15 024003), Chen and Tung (hereafter C&T) argue that our analysis, showing that over the last decades Atlantic meridional overturning circulation (AMOC) strength and global mean surface temperature (GMST) were positively correlated, is incorrect. Their claim is mainly based on two arguments, neither of which is justified: first, C&T claim that our analysis is based on 'established evidence' that was only true for preindustrial conditions-this is not the case. Using data from the modern period (1947-2012), we show that the established understanding (i.e. deep-water formation in the North Atlantic cools the deep ocean and warms the surface) is correct, but our analysis is not based on this fact. Secondly, C&T claim that our results are based on a statistical analysis of only one cycle of data which was furthermore incorrectly detrended. This, too, is not true. Our conclusion that a weaker AMOC delays the current surface warming rather than enhances it, is based on several independent lines of evidence. The data we show to support this covers more than one cycle and the detrending (which was performed to avoid spurious correlations due to a common trend) does not affect our conclusion: the correlation between AMOC strength and GMST is positive. We do not claim that this is strong evidence that the two time series are in phase, but rather that this means that the two time series are not anti-correlated. KW - Atlantic meridional overturning circulation KW - global surface warming KW - ocean heat uptake Y1 - 2021 U6 - https://doi.org/10.1088/1748-9326/abc776 SN - 1748-9326 VL - 16 IS - 3 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Kupfer, Thomas A1 - Bauer, Evan B. A1 - van Roestel, Jan A1 - Bellm, Eric C. A1 - Bildsten, Lars A1 - Fuller, Jim A1 - Prince, Thomas A. A1 - Heber, Ulrich A1 - Geier, Stephan A1 - Green, Matthew J. A1 - Kulkarni, Shrinivas R. A1 - Bloemen, Steven A1 - Laher, Russ R. A1 - Rusholme, Ben A1 - Schneider, David T1 - Discovery of a Double-detonation Thermonuclear Supernova Progenitor JF - The astrophysical journal : an international review of spectroscopy and astronomical physics ; Part 2, Letters N2 - We present the discovery of a new double-detonation progenitor system consisting of a hot subdwarf B (sdB) binary with a white dwarf companion with a P (orb) = 76.34179(2) minutes orbital period. Spectroscopic observations are consistent with an sdB star during helium core burning residing on the extreme horizontal branch. Chimera light curves are dominated by ellipsoidal deformation of the sdB star and a weak eclipse of the companion white dwarf. Combining spectroscopic and light curve fits, we find a low-mass sdB star, M (sdB) = 0.383 +/- 0.028 M (circle dot) with a massive white dwarf companion, M (WD) = 0.725 +/- 0.026 M (circle dot). From the eclipses we find a blackbody temperature for the white dwarf of 26,800 K resulting in a cooling age of approximate to 25 Myr whereas our MESA model predicts an sdB age of approximate to 170 Myr. We conclude that the sdB formed first through stable mass transfer followed by a common envelope which led to the formation of the white dwarf companion approximate to 25 Myr ago. Using the MESA stellar evolutionary code we find that the sdB star will start mass transfer in approximate to 6 Myr and in approximate to 60 Myr the white dwarf will reach a total mass of 0.92 M (circle dot) with a thick helium layer of 0.17 M (circle dot). This will lead to a detonation that will likely destroy the white dwarf in a peculiar thermonuclear supernova. PTF1 J2238+7430 is only the second confirmed candidate for a double-detonation thermonuclear supernova. Using both systems we estimate that at least approximate to 1% of white dwarf thermonuclear supernovae originate from sdB+WD binaries with thick helium layers, consistent with the small number of observed peculiar thermonuclear explosions. Y1 - 2022 U6 - https://doi.org/10.3847/2041-8213/ac48f1 SN - 2041-8205 SN - 2041-8213 VL - 925 IS - 2 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Palmer, Matthew D. A1 - Gregory, Jonathan A1 - Bagge, Meike A1 - Calvert, Daley A1 - Hagedoorn, Jan Marius A1 - Howard, Tom A1 - Klemann, Volker A1 - Lowe, Jason A. A1 - Roberts, Chris A1 - Slangen, Aimee B. A. A1 - Spada, Giorgio T1 - Exploring the drivers of global and local sea‐level change over the 21st century and beyond JF - Earth's future N2 - We present a new set of global and local sea‐level projections at example tide gauge locations under the RCP2.6, RCP4.5, and RCP8.5 emissions scenarios. Compared to the CMIP5‐based sea‐level projections presented in IPCC AR5, we introduce a number of methodological innovations, including (i) more comprehensive treatment of uncertainties, (ii) direct traceability between global and local projections, and (iii) exploratory extended projections to 2300 based on emulation of individual CMIP5 models. Combining the projections with observed tide gauge records, we explore the contribution to total variance that arises from sea‐level variability, different emissions scenarios, and model uncertainty. For the period out to 2300 we further breakdown the model uncertainty by sea‐level component and consider the dependence on geographic location, time horizon, and emissions scenario. Our analysis highlights the importance of local variability for sea‐level change in the coming decades and the potential value of annual‐to‐decadal predictions of local sea‐level change. Projections to 2300 show a substantial degree of committed sea‐level rise under all emissions scenarios considered and highlight the reduced future risk associated with RCP2.6 and RCP4.5 compared to RCP8.5. Tide gauge locations can show large ( > 50%) departures from the global average, in some cases even reversing the sign of the change. While uncertainty in projections of the future Antarctic ice dynamic response tends to dominate post‐2100, we see substantial differences in the breakdown of model variance as a function of location, time scale, and emissions scenario. KW - climate change KW - CMIP5 models KW - RCP scenarios KW - sea-level projections KW - tide gauge observations Y1 - 2020 U6 - https://doi.org/10.1029/2019EF001413 SN - 2328-4277 VL - 8 IS - 9 SP - 1 EP - 25 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Garbulowski, Mateusz A1 - Smolinska, Karolina A1 - Çabuk, Uğur A1 - Yones, Sara A. A1 - Celli, Ludovica A1 - Yaz, Esma Nur A1 - Barrenas, Fredrik A1 - Diamanti, Klev A1 - Wadelius, Claes A1 - Komorowski, Jan T1 - Machine learning-based analysis of glioma grades reveals co-enrichment JF - Cancers N2 - Simple Summary Gliomas are heterogenous types of cancer, therefore the therapy should be personalized and targeted toward specific pathways. We developed a methodology that corrected strong batch effects from The Cancer Genome Atlas datasets and estimated glioma grade-specific co-enrichment mechanisms using machine learning. Our findings created hypotheses for annotations, e.g., pathways, that should be considered as therapeutic targets. Gliomas develop and grow in the brain and central nervous system. Examining glioma grading processes is valuable for improving therapeutic challenges. One of the most extensive repositories storing transcriptomics data for gliomas is The Cancer Genome Atlas (TCGA). However, such big cohorts should be processed with caution and evaluated thoroughly as they can contain batch and other effects. Furthermore, biological mechanisms of cancer contain interactions among biomarkers. Thus, we applied an interpretable machine learning approach to discover such relationships. This type of transparent learning provides not only good predictability, but also reveals co-predictive mechanisms among features. In this study, we corrected the strong and confounded batch effect in the TCGA glioma data. We further used the corrected datasets to perform comprehensive machine learning analysis applied on single-sample gene set enrichment scores using collections from the Molecular Signature Database. Furthermore, using rule-based classifiers, we displayed networks of co-enrichment related to glioma grades. Moreover, we validated our results using the external glioma cohorts. We believe that utilizing corrected glioma cohorts from TCGA may improve the application and validation of any future studies. Finally, the co-enrichment and survival analysis provided detailed explanations for glioma progression and consequently, it should support the targeted treatment. KW - glioma KW - machine learning KW - batch effect KW - TCGA KW - co-enrichment KW - rough sets Y1 - 2022 U6 - https://doi.org/10.3390/cancers14041014 SN - 2072-6694 VL - 14 IS - 4 PB - MDPI CY - Basel ER - TY - JOUR A1 - Nwosu, Ebuka Canisius A1 - Roeser, Patricia Angelika A1 - Yang, Sizhong A1 - Ganzert, Lars A1 - Dellwig, Olaf A1 - Pinkerneil, Sylvia A1 - Brauer, Achim A1 - Dittmann, Elke A1 - Wagner, Dirk A1 - Liebner, Susanne T1 - From water into sediment-tracing freshwater cyanobacteria via DNA analyses JF - Microorganisms : open access journal N2 - Sedimentary ancient DNA-based studies have been used to probe centuries of climate and environmental changes and how they affected cyanobacterial assemblages in temperate lakes. Due to cyanobacteria containing potential bloom-forming and toxin-producing taxa, their approximate reconstruction from sediments is crucial, especially in lakes lacking long-term monitoring data. To extend the resolution of sediment record interpretation, we used high-throughput sequencing, amplicon sequence variant (ASV) analysis, and quantitative PCR to compare pelagic cyanobacterial composition to that in sediment traps (collected monthly) and surface sediments in Lake Tiefer See. Cyanobacterial composition, species richness, and evenness was not significantly different among the pelagic depths, sediment traps and surface sediments (p > 0.05), indicating that the cyanobacteria in the sediments reflected the cyanobacterial assemblage in the water column. However, total cyanobacterial abundances (qPCR) decreased from the metalimnion down the water column. The aggregate-forming (Aphanizomenon) and colony-forming taxa (Snowella) showed pronounced sedimentation. In contrast, Planktothrix was only very poorly represented in sediment traps (meta- and hypolimnion) and surface sediments, despite its highest relative abundance at the thermocline (10 m water depth) during periods of lake stratification (May-October). We conclude that this skewed representation in taxonomic abundances reflects taphonomic processes, which should be considered in future DNA-based paleolimnological investigations. KW - Aphanizomenon KW - Planktothrix KW - Snowella KW - cyanobacteria sedimentation KW - lake monitoring KW - sedimentary ancient DNA KW - sediment traps KW - environmental reconstruction Y1 - 2021 U6 - https://doi.org/10.3390/microorganisms9081778 SN - 2076-2607 VL - 9 IS - 8 PB - MDPI CY - Basel ER - TY - JOUR A1 - Nwosu, Ebuka Canisius A1 - Roeser, Patricia Angelika A1 - Yang, Sizhong A1 - Pinkerneil, Sylvia A1 - Ganzert, Lars A1 - Dittmann, Elke A1 - Brauer, Achim A1 - Wagner, Dirk A1 - Liebner, Susanne T1 - Species-level spatio-temporal dynamics of cyanobacteria in a hard-water temperate lake in the Southern Baltics JF - Frontiers in microbiology N2 - Cyanobacteria are important primary producers in temperate freshwater ecosystems. However, studies on the seasonal and spatial distribution of cyanobacteria in deep lakes based on high-throughput DNA sequencing are still rare. In this study, we combined monthly water sampling and monitoring in 2019, amplicon sequence variants analysis (ASVs; a proxy for different species) and quantitative PCR targeting overall cyanobacteria abundance to describe the seasonal and spatial dynamics of cyanobacteria in the deep hard-water oligo-mesotrophic Lake Tiefer See, NE Germany. We observed significant seasonal variation in the cyanobacterial community composition (p < 0.05) in the epi- and metalimnion layers, but not in the hypolimnion. In winter-when the water column is mixed-picocyanobacteria (Synechococcus and Cyanobium) were dominant. With the onset of stratification in late spring, we observed potential niche specialization and coexistence among the cyanobacteria taxa driven mainly by light and nutrient dynamics. Specifically, ASVs assigned to picocyanobacteria and the genus Planktothrix were the main contributors to the formation of deep chlorophyll maxima along a light gradient. While Synechococcus and different Cyanobium ASVs were abundant in the epilimnion up to the base of the euphotic zone from spring to fall, Planktothrix mainly occurred in the metalimnetic layer below the euphotic zone where also overall cyanobacteria abundance was highest in summer. Our data revealed two potentially psychrotolerant (cold-adapted) Cyanobium species that appear to cope well under conditions of lower hypolimnetic water temperature and light as well as increasing sediment-released phosphate in the deeper waters in summer. The potential cold-adapted Cyanobium species were also dominant throughout the water column in fall and winter. Furthermore, Snowella and Microcystis-related ASVs were abundant in the water column during the onset of fall turnover. Altogether, these findings suggest previously unascertained and considerable spatiotemporal changes in the community of cyanobacteria on the species level especially within the genus Cyanobium in deep hard-water temperate lakes. KW - Cyanobium KW - picocyanobacteria diversity KW - amplicon sequencing KW - lake monitoring KW - ecological succession KW - lake stratification KW - psychrotolerant Y1 - 2021 U6 - https://doi.org/10.3389/fmicb.2021.761259 SN - 1664-302X VL - 12 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Köhler, Raphael H. A1 - Handorf, Dörthe A1 - Jaiser, Ralf A1 - Dethloff, Klaus A1 - Zängl, Günther A1 - Majewski, Detlev A1 - Rex, Markus T1 - Improved circulation in the Northern hemisphere by adjusting gravity wave drag parameterizations in seasonal experiments with ICON-NWP JF - Earth and Space Science : ESS N2 - The stratosphere is one of the main potential sources for subseasonal to seasonal predictability in midlatitudes in winter. The ability of an atmospheric model to realistically simulate the stratospheric dynamics is essential in order to move forward in the field of seasonal predictions in midlatitudes. Earlier studies with the ICOsahedral Nonhydrostatic atmospheric model (ICON) point out that stratospheric westerlies in ICON are underestimated. This is the first extensive study on the evaluation of Northern Hemisphere stratospheric winter circulation with ICON in numerical weather prediction (NWP) mode. Seasonal experiments with the default setup are able to reproduce the basic climatology of the stratospheric polar vortex. However, westerlies are too weak and major stratospheric warmings too frequent in ICON. Both a reduction of the nonorographic, and a reduction of the orographic gravity wave and wake drag lead to a strengthening of the stratospheric vortex and a bias reduction, in particular in January. However, the effect of the nonorographic gravity wave drag scheme on the stratosphere is stronger. Stratosphere-troposphere coupling is intensified and more realistic due to a reduced gravity wave drag. Furthermore, an adjustment of the subgrid-scale orographic drag parameterization leads to a significant error reduction in the mean sea level pressure. As a result of these findings, we present our current suggested improved setup for seasonal experiments with ICON-NWP.
Plain Language Summary Although seasonal forecasts for midlatitudes have the potential to be highly beneficial to the public sector, they are still characterized by a large amount of uncertainty. Exact simulations of the circulation in the stratosphere can help to improve tropospheric predictability on seasonal time scales. For this reason, we investigate how well the new German atmospheric model is able to simulate the stratospheric circulation. The model reproduces the basic behavior of the Northern Hemisphere stratospheric polar vortex, but the westerly circulation in winter is underestimated. The stratospheric circulation is influenced by gravity waves that exert drag on the flow. These processes are only partly physically represented in the model, but are very important and are hence parameterized. By adjusting the parameterizations for the gravity wave drag, the stratospheric polar vortex is strengthened, thereby yielding a more realistic stratospheric circulation. In addition, the altered parameterizations improve the simulated surface pressure pattern. Based upon this, we present our current suggested improved model setup for seasonal experiments. Y1 - 2021 U6 - https://doi.org/10.1029/2021EA001676 SN - 2333-5084 VL - 8 IS - 3 PB - American Geophysical Union CY - Malden, Mass. ER - TY - JOUR A1 - Hartmann, Stefanie A1 - Hasenkamp, Natascha A1 - Mayer, Jens A1 - Michaux, Johan A1 - Morand, Serge A1 - Mazzoni, Camila J. A1 - Roca, Alfred L. A1 - Greenwood, Alex D. T1 - Endogenous murine leukemia retroviral variation across wild European and inbred strains of house mouse JF - BMC genomics N2 - Background: Endogenous murine leukemia retroviruses (MLVs) are high copy number proviral elements difficult to comprehensively characterize using standard low throughput sequencing approaches. However, high throughput approaches generate data that is challenging to process, interpret and present. Results: Next generation sequencing (NGS) data was generated for MLVs from two wild caught Mus musculus domesticus (from mainland France and Corsica) and for inbred laboratory mouse strains C3H, LP/J and SJL. Sequence reads were grouped using a novel sequence clustering approach as applied to retroviral sequences. A Markov cluster algorithm was employed, and the sequence reads were queried for matches to specific xenotropic (Xmv), polytropic (Pmv) and modified polytropic (Mpmv) viral reference sequences. Conclusions: Various MLV subtypes were more widespread than expected among the mice, which may be due to the higher coverage of NGS, or to the presence of similar sequence across many different proviral loci. The results did not correlate with variation in the major MLV receptor Xpr1, which can restrict exogenous MLVs, suggesting that endogenous MLV distribution may reflect gene flow more than past resistance to infection. KW - Murine leukemia virus KW - Endogenous retrovirus KW - Xpr1 KW - XMRV KW - Genomic evolution KW - Markov cluster algorithm Y1 - 2015 U6 - https://doi.org/10.1186/s12864-015-1766-z SN - 1471-2164 VL - 16 PB - BioMed Central CY - London ER - TY - JOUR A1 - Romanowsky, Erik A1 - Handorf, Dörthe A1 - Jaiser, Ralf A1 - Wohltmann, Ingo A1 - Dorn, Wolfgang A1 - Ukita, Jinro A1 - Cohen, Judah A1 - Dethloff, Klaus A1 - Rex, Markus T1 - The role of stratospheric ozone for Arctic-midlatitude linkages JF - Scientific reports N2 - Arctic warming was more pronounced than warming in midlatitudes in the last decades making this region a hotspot of climate change. Associated with this, a rapid decline of sea-ice extent and a decrease of its thickness has been observed. Sea-ice retreat allows for an increased transport of heat and momentum from the ocean up to the tropo- and stratosphere by enhanced upward propagation of planetary-scale atmospheric waves. In the upper atmosphere, these waves deposit the momentum transported, disturbing the stratospheric polar vortex, which can lead to a breakdown of this circulation with the potential to also significantly impact the troposphere in mid- to late-winter and early spring. Therefore, an accurate representation of stratospheric processes in climate models is necessary to improve the understanding of the impact of retreating sea ice on the atmospheric circulation. By modeling the atmospheric response to a prescribed decline in Arctic sea ice, we show that including interactive stratospheric ozone chemistry in atmospheric model calculations leads to an improvement in tropo-stratospheric interactions compared to simulations without interactive chemistry. This suggests that stratospheric ozone chemistry is important for the understanding of sea ice related impacts on atmospheric dynamics. Y1 - 2019 U6 - https://doi.org/10.1038/s41598-019-43823-1 SN - 2045-2322 VL - 9 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Kahl, Sandra A1 - Kappel, Christian A1 - Joshi, Jasmin Radha A1 - Lenhard, Michael T1 - Phylogeography of a widely distributed plant species reveals cryptic genetic lineages with parallel phenotypic responses to warming and drought conditions JF - Ecology and Evolution N2 - To predict how widely distributed species will perform under future climate change, it is crucial to understand and reveal their underlying phylogenetics. However, detailed information about plant adaptation and its genetic basis and history remains scarce and especially widely distributed species receive little attention despite their putatively high adaptability. To examine the adaptation potential of a widely distributed species, we sampled the model plant Silene vulgaris across Europe. In a greenhouse experiment, we exposed the offspring of these populations to a climate change scenario for central Europe and revealed the population structure through whole-genome sequencing. Plants were grown under two temperatures (18°C and 21°C) and three precipitation regimes (65, 75, and 90 mm) to measure their response in biomass and fecundity-related traits. To reveal the population genetic structure, ddRAD sequencing was employed for a whole-genome approach. We found three major genetic clusters in S. vulgaris from Europe: one cluster comprising Southern European populations, one cluster of Western European populations, and another cluster containing central European populations. Population genetic diversity decreased with increasing latitude, and a Mantel test revealed significant correlations between FST and geographic distances as well as between genetic and environmental distances. Our trait analysis showed that the genetic clusters significantly differed in biomass-related traits and in the days to flowering. However, half of the traits showed parallel response patterns to the experimental climate change scenario. Due to the differentiated but parallel response patterns, we assume that phenotypic plasticity plays an important role for the adaptation of the widely distributed species S. vulgaris and its intraspecific genetic lineages. KW - climate adaptation KW - ddRAD KW - Silene vulgaris Y1 - 2021 U6 - https://doi.org/10.1002/ece3.8103 SN - 2045-7758 VL - 11 IS - 20 SP - 13986 EP - 14002 PB - John Wiley & Sons, Inc. CY - Hoboken ER - TY - JOUR A1 - Crawford, Tim A1 - Karamat, Fazeelat A1 - Lehotai, Nóra A1 - Rentoft, Matilda A1 - Blomberg, Jeanette A1 - Strand, Åsa A1 - Björklund, Stefan T1 - Specific functions for mediator complex subunits from different modules in the transcriptional response of arabidopsis thaliana to abiotic stress JF - Scientific reports N2 - Adverse environmental conditions are detrimental to plant growth and development. Acclimation to abiotic stress conditions involves activation of signaling pathways which often results in changes in gene expression via networks of transcription factors (TFs). Mediator is a highly conserved co-regulator complex and an essential component of the transcriptional machinery in eukaryotes. Some Mediator subunits have been implicated in stress-responsive signaling pathways; however, much remains unknown regarding the role of plant Mediator in abiotic stress responses. Here, we use RNA-seq to analyze the transcriptional response of Arabidopsis thaliana to heat, cold and salt stress conditions. We identify a set of common abiotic stress regulons and describe the sequential and combinatorial nature of TFs involved in their transcriptional regulation. Furthermore, we identify stress-specific roles for the Mediator subunits MED9, MED16, MED18 and CDK8, and putative TFs connecting them to different stress signaling pathways. Our data also indicate different modes of action for subunits or modules of Mediator at the same gene loci, including a co-repressor function for MED16 prior to stress. These results illuminate a poorly understood but important player in the transcriptional response of plants to abiotic stress and identify target genes and mechanisms as a prelude to further biochemical characterization. KW - regulate gene expression KW - signal transduction KW - circadian clock KW - plant Mediator KW - salicylic-acid KW - activation KW - jasmonate KW - network KW - defense KW - MED16 Y1 - 2020 U6 - https://doi.org/10.1038/s41598-020-61758-w SN - 2045-2322 VL - 10 IS - 1 SP - 1 EP - 18 PB - Macmillan Publishers Limited, part of Springer Nature CY - London ER - TY - JOUR A1 - Potente, Giacomo A1 - Léveillé-Bourret, Étienne A1 - Yousefi, Narjes A1 - Choudhury, Rimjhim Roy A1 - Keller, Barbara A1 - Diop, Seydina Issa A1 - Duijsings, Daniël A1 - Pirovano, Walter A1 - Lenhard, Michael A1 - Szövényi, Péter A1 - Conti, Elena T1 - Comparative genomics elucidates the origin of a supergene controlling floral heteromorphism JF - Molecular biology and evolution : MBE N2 - Supergenes are nonrecombining genomic regions ensuring the coinheritance of multiple, coadapted genes. Despite the importance of supergenes in adaptation, little is known on how they originate. A classic example of supergene is the S locus controlling heterostyly, a floral heteromorphism occurring in 28 angiosperm families. In Primula, heterostyly is characterized by the cooccurrence of two complementary, self-incompatible floral morphs and is controlled by five genes clustered in the hemizygous, ca. 300-kb S locus. Here, we present the first chromosome-scale genome assembly of any heterostylous species, that of Primula veris (cowslip). By leveraging the high contiguity of the P. veris assembly and comparative genomic analyses, we demonstrated that the S-locus evolved via multiple, asynchronous gene duplications and independent gene translocations. Furthermore, we discovered a new whole-genome duplication in Ericales that is specific to the Primula lineage. We also propose a mechanism for the origin of S-locus hemizygosity via nonhomologous recombination involving the newly discovered two pairs of CFB genes flanking the S locus. Finally, we detected only weak signatures of degeneration in the S locus, as predicted for hemizygous supergenes. The present study provides a useful resource for future research addressing key questions on the evolution of supergenes in general and the S locus in particular: How do supergenes arise? What is the role of genome architecture in the evolution of complex adaptations? Is the molecular architecture of heterostyly supergenes across angiosperms similar to that of Primula? KW - genome architecture KW - supergene KW - heterostyly KW - evolutionary genomics KW - chromosome-scale genome assembly KW - primula Y1 - 2022 U6 - https://doi.org/10.1093/molbev/msac035 SN - 0737-4038 SN - 1537-1719 VL - 39 IS - 2 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Tran, Quan Hong A1 - Bui, Ngoc Hong A1 - Kappel, Christian A1 - Dau, Nga Thi Ngoc A1 - Nguyen, Loan Thi A1 - Tran, Thuy Thi A1 - Khanh, Tran Dang A1 - Trung, Khuat Huu A1 - Lenhard, Michael A1 - Vi, Son Lang T1 - Mapping-by-sequencing via MutMap identifies a mutation in ZmCLE7 underlying fasciation in a newly developed EMS mutant population in an elite tropical maize inbred JF - Genes N2 - Induced point mutations are important genetic resources for their ability to create hypo- and hypermorphic alleles that are useful for understanding gene functions and breeding. However, such mutant populations have only been developed for a few temperate maize varieties, mainly B73 and W22, yet no tropical maize inbred lines have been mutagenized and made available to the public to date. We developed a novel Ethyl Methanesulfonate (EMS) induced mutation resource in maize comprising 2050 independent M2 mutant families in the elite tropical maize inbred ML10. By phenotypic screening, we showed that this population is of comparable quality with other mutagenized populations in maize. To illustrate the usefulness of this population for gene discovery, we performed rapid mapping-by-sequencing to clone a fasciated-ear mutant and identify a causal promoter deletion in ZmCLE7 (CLE7). Our mapping procedure does not require crossing to an unrelated parent, thus is suitable for mapping subtle traits and ones affected by heterosis. This first EMS population in tropical maize is expected to be very useful for the maize research community. Also, the EMS mutagenesis and rapid mapping-by-sequencing pipeline described here illustrate the power of performing forward genetics in diverse maize germplasms of choice, which can lead to novel gene discovery due to divergent genetic backgrounds. KW - EMS KW - MutMap KW - mutagenesis KW - CLE7 KW - tropical maize KW - fasciation KW - mapping Y1 - 2020 U6 - https://doi.org/10.3390/genes11030281 SN - 2073-4425 VL - 11 IS - 3 SP - 1 EP - 14 PB - MDPI CY - Basel ER - TY - JOUR A1 - Kappel, Christian A1 - Illing, Nicola A1 - Huu, Cuong Nguyen A1 - Barger, Nichole N. A1 - Cramer, Michael D. A1 - Lenhard, Michael A1 - Midgley, Jeremy J. T1 - Fairy circles in Namibia are assembled from genetically distinct grasses JF - Communications biology N2 - Fairy circles are striking regularly sized and spaced, bare circles surrounded by Stipagrostis grasses that occur over thousands of square kilometres in Namibia. The mechanisms explaining their origin, shape, persistence and regularity remain controversial. One hypothesis for the formation of vegetation rings is based on the centrifugal expansion of a single individual grass plant, via clonal growth and die-back in the centre. Clonality could explain FC origin, shape and long-term persistence as well as their regularity, if one clone competes with adjacent clones. Here, we show that for virtually all tested fairy circles the periphery is not exclusively made up of genetically identical grasses, but these peripheral grasses belong to more than one unrelated genet. These results do not support a clonal explanation for fairy circles. Lack of clonality implies that a biological reason for their origin, shape and regularity must emerge from competition between near neighbor individuals within each fairy circle. Such lack of clonality also suggests a mismatch between longevity of fairy circles versus their constituent plants. Furthermore, our findings of lack of clonality have implications for some models of spatial patterning of fairy circles that are based on self-organization. Christian Kappel et al. examine the genetic composition of fairy circles, regular circular patterns of grasses in the Namib Desert, using ddRAD-seq. They find that these grasses are made up of multiple unrelated genets rather than genetically identical grasses, suggesting non-clonality. Y1 - 2020 U6 - https://doi.org/10.1038/s42003-020-01431-0 SN - 2399-3642 VL - 3 IS - 1 PB - Springer Nature CY - London ER - TY - JOUR A1 - Albert, Justin Amadeus A1 - Owolabi, Victor A1 - Gebel, Arnd A1 - Brahms, Clemens Markus A1 - Granacher, Urs A1 - Arnrich, Bert T1 - Evaluation of the Pose Tracking Performance of the Azure Kinect and Kinect v2 for Gait Analysis in Comparison with a Gold Standard BT - A Pilot Study JF - Sensors N2 - Gait analysis is an important tool for the early detection of neurological diseases and for the assessment of risk of falling in elderly people. The availability of low-cost camera hardware on the market today and recent advances in Machine Learning enable a wide range of clinical and health-related applications, such as patient monitoring or exercise recognition at home. In this study, we evaluated the motion tracking performance of the latest generation of the Microsoft Kinect camera, Azure Kinect, compared to its predecessor Kinect v2 in terms of treadmill walking using a gold standard Vicon multi-camera motion capturing system and the 39 marker Plug-in Gait model. Five young and healthy subjects walked on a treadmill at three different velocities while data were recorded simultaneously with all three camera systems. An easy-to-administer camera calibration method developed here was used to spatially align the 3D skeleton data from both Kinect cameras and the Vicon system. With this calibration, the spatial agreement of joint positions between the two Kinect cameras and the reference system was evaluated. In addition, we compared the accuracy of certain spatio-temporal gait parameters, i.e., step length, step time, step width, and stride time calculated from the Kinect data, with the gold standard system. Our results showed that the improved hardware and the motion tracking algorithm of the Azure Kinect camera led to a significantly higher accuracy of the spatial gait parameters than the predecessor Kinect v2, while no significant differences were found between the temporal parameters. Furthermore, we explain in detail how this experimental setup could be used to continuously monitor the progress during gait rehabilitation in older people. KW - motion capture KW - evaluation KW - human motion KW - RGB-D cameras KW - digital health Y1 - 2020 U6 - https://doi.org/10.3390/s20185104 SN - 1424-8220 VL - 20 IS - 18 PB - MDPI CY - Basel ER - TY - JOUR A1 - Konak, Orhan A1 - Wegner, Pit A1 - Arnrich, Bert T1 - IMU-Based Movement Trajectory Heatmaps for Human Activity Recognition JF - Sensors N2 - Recent trends in ubiquitous computing have led to a proliferation of studies that focus on human activity recognition (HAR) utilizing inertial sensor data that consist of acceleration, orientation and angular velocity. However, the performances of such approaches are limited by the amount of annotated training data, especially in fields where annotating data is highly time-consuming and requires specialized professionals, such as in healthcare. In image classification, this limitation has been mitigated by powerful oversampling techniques such as data augmentation. Using this technique, this work evaluates to what extent transforming inertial sensor data into movement trajectories and into 2D heatmap images can be advantageous for HAR when data are scarce. A convolutional long short-term memory (ConvLSTM) network that incorporates spatiotemporal correlations was used to classify the heatmap images. Evaluation was carried out on Deep Inertial Poser (DIP), a known dataset composed of inertial sensor data. The results obtained suggest that for datasets with large numbers of subjects, using state-of-the-art methods remains the best alternative. However, a performance advantage was achieved for small datasets, which is usually the case in healthcare. Moreover, movement trajectories provide a visual representation of human activities, which can help researchers to better interpret and analyze motion patterns. KW - human activity recognition KW - image processing KW - machine learning KW - sensor data Y1 - 2020 U6 - https://doi.org/10.3390/s20247179 SN - 1424-8220 VL - 20 IS - 24 PB - MDPI CY - Basel ER - TY - JOUR A1 - Zhou, Lin A1 - Fischer, Eric A1 - Tunca, Can A1 - Brahms, Clemens Markus A1 - Ersoy, Cem A1 - Granacher, Urs A1 - Arnrich, Bert T1 - How We Found Our IMU BT - Guidelines to IMU Selection and a Comparison of Seven IMUs for Pervasive Healthcare Applications JF - Sensors N2 - Inertial measurement units (IMUs) are commonly used for localization or movement tracking in pervasive healthcare-related studies, and gait analysis is one of the most often studied topics using IMUs. The increasing variety of commercially available IMU devices offers convenience by combining the sensor modalities and simplifies the data collection procedures. However, selecting the most suitable IMU device for a certain use case is increasingly challenging. In this study, guidelines for IMU selection are proposed. In particular, seven IMUs were compared in terms of their specifications, data collection procedures, and raw data quality. Data collected from the IMUs were then analyzed by a gait analysis algorithm. The difference in accuracy of the calculated gait parameters between the IMUs could be used to retrace the issues in raw data, such as acceleration range or sensor calibration. Based on our algorithm, we were able to identify the best-suited IMUs for our needs. This study provides an overview of how to select the IMUs based on the area of study with concrete examples, and gives insights into the features of seven commercial IMUs using real data. KW - inertial measurement unit KW - pervasive healthcare KW - gait analysis KW - comparison of devices Y1 - 2020 U6 - https://doi.org/10.3390/s20154090 SN - 1424-8220 VL - 20 IS - 15 PB - MDPI CY - Basel ER - TY - JOUR A1 - Trautmann, Justin A1 - Zhou, Lin A1 - Brahms, Clemens Markus A1 - Tunca, Can A1 - Ersoy, Cem A1 - Granacher, Urs A1 - Arnrich, Bert T1 - TRIPOD BT - A treadmill walking dataset with IMU, pressure-distribution and photoelectric data for gait analysis JF - Data : open access ʻData in scienceʼ journal N2 - Inertial measurement units (IMUs) enable easy to operate and low-cost data recording for gait analysis. When combined with treadmill walking, a large number of steps can be collected in a controlled environment without the need of a dedicated gait analysis laboratory. In order to evaluate existing and novel IMU-based gait analysis algorithms for treadmill walking, a reference dataset that includes IMU data as well as reliable ground truth measurements for multiple participants and walking speeds is needed. This article provides a reference dataset consisting of 15 healthy young adults who walked on a treadmill at three different speeds. Data were acquired using seven IMUs placed on the lower body, two different reference systems (Zebris FDMT-HQ and OptoGait), and two RGB cameras. Additionally, in order to validate an existing IMU-based gait analysis algorithm using the dataset, an adaptable modular data analysis pipeline was built. Our results show agreement between the pressure-sensitive Zebris and the photoelectric OptoGait system (r = 0.99), demonstrating the quality of our reference data. As a use case, the performance of an algorithm originally designed for overground walking was tested on treadmill data using the data pipeline. The accuracy of stride length and stride time estimations was comparable to that reported in other studies with overground data, indicating that the algorithm is equally applicable to treadmill data. The Python source code of the data pipeline is publicly available, and the dataset will be provided by the authors upon request, enabling future evaluations of IMU gait analysis algorithms without the need of recording new data. KW - inertial measurement unit KW - gait analysis algorithm KW - OptoGait KW - Zebris KW - data pipeline KW - public dataset Y1 - 2021 U6 - https://doi.org/10.3390/data6090095 SN - 2306-5729 VL - 6 IS - 9 PB - MDPI CY - Basel ER - TY - JOUR A1 - Chromik, Jonas A1 - Kirsten, Kristina A1 - Herdick, Arne A1 - Kappattanavar, Arpita Mallikarjuna A1 - Arnrich, Bert T1 - SensorHub BT - Multimodal sensing in real-life enables home-based studies JF - Sensors N2 - Observational studies are an important tool for determining whether the findings from controlled experiments can be transferred into scenarios that are closer to subjects' real-life circumstances. A rigorous approach to observational studies involves collecting data from different sensors to comprehensively capture the situation of the subject. However, this leads to technical difficulties especially if the sensors are from different manufacturers, as multiple data collection tools have to run simultaneously. We present SensorHub, a system that can collect data from various wearable devices from different manufacturers, such as inertial measurement units, portable electrocardiographs, portable electroencephalographs, portable photoplethysmographs, and sensors for electrodermal activity. Additionally, our tool offers the possibility to include ecological momentary assessments (EMAs) in studies. Hence, SensorHub enables multimodal sensor data collection under real-world conditions and allows direct user feedback to be collected through questionnaires, enabling studies at home. In a first study with 11 participants, we successfully used SensorHub to record multiple signals with different devices and collected additional information with the help of EMAs. In addition, we evaluated SensorHub's technical capabilities in several trials with up to 21 participants recording simultaneously using multiple sensors with sampling frequencies as high as 1000 Hz. We could show that although there is a theoretical limitation to the transmissible data rate, in practice this limitation is not an issue and data loss is rare. We conclude that with modern communication protocols and with the increasingly powerful smartphones and wearables, a system like our SensorHub establishes an interoperability framework to adequately combine consumer-grade sensing hardware which enables observational studies in real life. KW - multimodal sensing KW - home-based studies KW - activity recognition KW - sensor KW - systems KW - ecological momentary assessment KW - digital health Y1 - 2022 U6 - https://doi.org/10.3390/s22010408 SN - 1424-8220 VL - 22 IS - 1 PB - MDPI CY - Basel ER - TY - JOUR A1 - Gmeiner, Michaela Silvia A1 - Warschburger, Petra T1 - Intrapersonal predictors of weight bias internalization among elementary school children BT - a prospective analysis JF - BMC Pediatrics N2 - Background Weight-related stigmatization is a widespread problem. Particularly the internalization of weight-related stereotypes and prejudices (weight bias internalization, WBI) is related to mental and physical health impairments. To date, little is known about the risk factors of WBI. Previous studies are mainly cross-sectional and based on adult samples. As childhood is a sensitive period for the development of a healthy self-concept, we examined predictors of WBI in children. Methods The final sample included 1,463 schoolchildren (6–11 years, 51.7% female) who took part in a prospective study consisting of three measurement waves. The first two waves delivered data on objective weight status and self-reported weight-related teasing, body dissatisfaction, relevance of one’s own figure, self-esteem and depressive symptoms; WBI was measured during the third wave. To examine predictors of WBI, we ran hierarchical regression analyses and exploratory mediation analyses. Results Lower parental education level, higher child weight status, female gender, experience of teasing, higher body dissatisfaction, higher figure-relevance, and higher depression scores were found to be predictive for higher WBI scores. Body dissatisfaction (only for girls) and the relevance of one’s own figure (both genders) mediated the association between self-esteem and WBI; no weight-related differences were observed. Conclusions Our study offers longitudinal evidence for variables that enable the identification of children who are at risk for WBI. Thus, the findings deliver starting points for interventions aimed at the prevention of adverse health developments that come along with WBI. KW - Weight bias internalization KW - Self-stigmatization KW - Weight KW - Children KW - Predictors Y1 - 2020 U6 - https://doi.org/10.1186/s12887-020-02264-w SN - 1471-2431 VL - 20 PB - BioMed Central CY - London 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 - 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 - 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 -