754 results on '"Kieser, A."'
Search Results
2. Utility-based optimization of Fujikawa's basket trial design -- Pre-specified protocol of a comparison study
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Sauer, Lukas D, Ritz, Alexander, and Kieser, Meinhard
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Statistics - Methodology ,Statistics - Applications - Abstract
Basket trial designs are a type of master protocol in which the same therapy is tested in several strata of the patient cohort. Many basket trial designs implement borrowing mechanisms. These allow sharing information between similar strata with the goal of increasing power in responsive strata while at the same time constraining type-I error inflation to a bearable threshold. These borrowing mechanisms can be tuned using numerical tuning parameters. The optimal choice of these tuning parameters is subject to research. In a comparison study using simulations and numerical calculations, we are planning to investigate the use of utility functions for quantifying the compromise between power and type-I error inflation and the use of numerical optimization algorithms for optimizing these functions. The present document is the protocol of this comparison study, defining each step of the study in accordance with the ADEMP scheme for pre-specification of simulation studies., Comment: 26 pages, 1 figure; updated content in reaction to anonymous review: new section "Methodology of utility functions in basket trial designs", discussion of literature and four new scenario sets in section "Outcome scenarios", two new algorithms and detailed explanation in section "Optimization algorithms", new section "Discussion", further minor changes
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- 2024
3. Deep mouse brain two-photon near-infrared fluorescence imaging using a superconducting nanowire single-photon detector array
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Tamimi, Amr, Caldarola, Martin, Hambura, Sebastian, Boffi, Juan C., Noordzij, Niels, Los, Johannes W. N., Guardiani, Antonio, Kooiman, Hugo, Wang, Ling, Kieser, Christian, Braun, Florian, Fognini, Andreas, and Prevedel, Robert
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Physics - Optics ,Physics - Instrumentation and Detectors - Abstract
Two-photon microscopy (2PM) has become an important tool in biology to study the structure and function of intact tissues in-vivo. However, adult mammalian tissues such as the mouse brain are highly scattering, thereby putting fundamental limits on the achievable imaging depth, which typically resides around 600-800um. In principle, shifting both the excitation as well as (fluorescence) emission light to the shortwave near-infrared (SWIR, 1000-1700 nm) region promises substantially deeper imaging in 2PM, yet has proven challenging in the past due to the limited availability of detectors and probes in this wavelength region. To overcome these limitations and fully capitalize on the SWIR region, in this work we introduce a novel array of superconducting nanowire single-photon detectors (SNSPDs) and associated custom detection electronics for the use in near-infrared 2PM. The SNSPD array exhibits high efficiency and dynamic range, as well as low dark-count rates over a wide wavelength range. Additionally, the electronics and software permit seamless integration into typical 2PM systems. Together with a fluorescent dye emitting at 1105 nm, we report imaging depth of > 1.1mm in the in-vivo mouse brain, limited only by available labeling density and laser power. Our work further establishes SWIR 2PM approaches and SNSPDs as promising technologies for deep tissue biological imaging., Comment: 17 pages, 5+1 figures
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- 2023
4. Use of class IC antiarrhythmic drugs in patients with structural heart disease and implantable cardioverter defibrillator
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Zylla, Maura M., Wolfes, Julian, Schleberger, Ruben, Lawin, Dennis, Kieser, Meinhard, Reinke, Florian, Eckardt, Lars, Rillig, Andreas, Stellbrink, Christoph, Thomas, Dierk, Frey, Norbert, and Lugenbiel, Patrick
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- 2024
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5. A basket trial design based on power priors
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Baumann, Lukas, Sauer, Lukas, and Kieser, Meinhard
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Statistics - Methodology - Abstract
In basket trials a treatment is investigated in several subgroups. They are primarily used in oncology in early clinical phases as single-arm trials with a binary endpoint. For their analysis primarily Bayesian methods have been suggested, as they allow partial sharing of information based on the observed similarity between subgroups. Fujikawa et al. (2020) suggested an approach using empirical Bayes methods that allows flexible sharing based on easily interpretable weights derived from the Jensen-Shannon divergence between the subgroup-wise posterior distributions. We show that this design is closely related to the method of power priors and investigate several modifications of Fujikawa's design using methods from the power prior literature. While in Fujikawa's design, the amount of information that is shared between two baskets is only determined by their pairwise similarity, we also discuss extensions where the outcomes of all baskets are considered in the computation of the sharing weights. The results of our comparison study show that the power prior design has comparable performance to fully Bayesian designs in a range of different scenarios. At the same time, the power prior design is computationally cheap and even allows analytical computation of operating characteristics in some settings.
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- 2023
6. Sample size recalculation in three-stage clinical trials and its evaluation
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Björn Bokelmann, Geraldine Rauch, Jan Meis, Meinhard Kieser, and Carolin Herrmann
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Clinical trials ,Adaptive trial design ,Sample size adaptation ,Performance evaluation ,Medicine (General) ,R5-920 - Abstract
Abstract Background In clinical trials, the determination of an adequate sample size is a challenging task, mainly due to the uncertainty about the value of the effect size and nuisance parameters. One method to deal with this uncertainty is a sample size recalculation. Thereby, an interim analysis is performed based on which the sample size for the remaining trial is adapted. With few exceptions, previous literature has only examined the potential of recalculation in two-stage trials. Methods In our research, we address sample size recalculation in three-stage trials, i.e. trials with two pre-planned interim analyses. We show how recalculation rules from two-stage trials can be modified to be applicable to three-stage trials. We also illustrate how a performance measure, recently suggested for two-stage trial recalculation (the conditional performance score) can be applied to evaluate recalculation rules in three-stage trials, and we describe performance evaluation in those trials from the global point of view. To assess the potential of recalculation in three-stage trials, we compare, in a simulation study, two-stage group sequential designs with three-stage group sequential designs as well as multiple three-stage designs with recalculation. Results While we observe a notable favorable effect in terms of power and expected sample size by using three-stage designs compared to two-stage designs, the benefits of recalculation rules appear less clear and are dependent on the performance measures applied. Conclusions Sample size recalculation is also applicable in three-stage designs. However, the extent to which recalculation brings benefits depends on which trial characteristics are most important to the applicants.
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- 2024
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7. Transgenerational transmission of psychopathology: when are adaptive emotion regulation strategies protective in children?
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Arleta A. Luczejko, Naomi Leona Werkmann, K. Hagelweide, R. Stark, S. Weigelt, H. Christiansen, M. Kieser, K. Otto, C. Reck, R. Steinmayr, L. Wirthwein, A.-L. Zietlow, C. Schwenck, and the COMPARE-family research group
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Transgenerational transmission of mental disorders ,Emotion regulation ,Adaptive emotion regulation strategies ,Maladaptive emotion regulation strategies ,Psychopathology ,Parental mental illness ,Pediatrics ,RJ1-570 ,Psychiatry ,RC435-571 - Abstract
Abstract Background Children of parents with a mental illness (COPMI) have multiple psychological and developmental risks, including an increased lifetime risk of developing a mental illness themselves. Emotion regulation (ER) has been identified as a potential underlying mechanism of the transgenerational transmission of mental disorders. This study compares ER strategies in parents with and without a mental illness and their children. Further, it aims to examine the relationship between parents and children’s psychopathology with a focus on the role of parental and child ER. Methods Participants were 96 COPMI (77% female) and 99 children of parents without mental illness (COPWMI, 83% female) aged 4–16 years and their parents. Psychopathology and ER strategies of parents and children were assessed with a series of questionnaires. Results Both COPMI and their parents showed significantly more psychopathology and more maladaptive and adaptive ER strategies in comparison with COPWMI and their parents. Parent and child adaptive ER strategies mediated the relationship between the psychopathology of parents and children only when child maladaptive ER strategies were low. Conclusions The findings further our understanding of the processes by which parental psychopathology affects child outcomes. Our findings highlight the importance of implementing preventive programs that specifically target the reduction of maladaptive ER in children to interrupt the transgenerational transmission of psychopathological symptoms.
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- 2024
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8. Educational data augmentation in physics education research using ChatGPT
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Kieser, Fabian, Wulff, Peter, Kuhn, Jochen, and Küchemann, Stefan
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Physics - Physics Education - Abstract
Generative AI technologies such as large language models show novel potentials to enhance educational research. For example, generative large language models were shown to be capable to solve quantitative reasoning tasks in physics and concept tests such as the Force Concept Inventory. Given the importance of such concept inventories for physics education research, and the challenges in developing them such as field testing with representative populations, this study seeks to examine to what extent a generative large language model could be utilized to generate a synthetic data set for the FCI that exhibits content-related variability in responses. We use the recently introduced ChatGPT based on the GPT 4 generative large language model and investigate to what extent ChatGPT could solve the FCI accurately (RQ1) and could be prompted to solve the FCI as-if it were a student belonging to a different cohort (RQ2). Furthermore, we study, to what extent ChatGPT could be prompted to solve the FCI as-if it were a student having a different force- and mechanics-related misconception (RQ3). In alignment with other research, we found the ChatGPT could accurately solve the FCI. We furthermore found that prompting ChatGPT to respond to the inventory as-if it belonged to a different cohort yielded no variance in responses, however, responding as-if it had a certain misconception introduced much variance in responses that approximate real human responses on the FCI in some regards., Comment: 13 pages, 3 figures, 2 tables
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- 2023
9. Bright light therapy versus physical exercise to prevent co-occurring depression in adolescents and young adults with attention-deficit/hyperactivity disorder: a multicentre, three-arm, randomised controlled, pilot phase-IIa trial
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Mayer, Jutta S., Kohlhas, Laura, Stermann, Jacek, Medda, Juliane, Brandt, Geva A., Grimm, Oliver, Pawley, Adam D., Asherson, Philip, Sanchez, Judit Palacio, Richarte, Vanesa, Bergsma, Douwe, Koch, Elena D., Muntaner-Mas, Adrià, Ebner-Priemer, Ulrich W., Kieser, Meinhard, Retz, Wolfgang, Ortega, Francisco B., Colla, Michael, Buitelaar, Jan K., Kuntsi, Jonna, Ramos-Quiroga, Josep A., Reif, Andreas, and Freitag, Christine M.
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- 2024
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10. David vs. Goliath: comparing conventional machine learning and a large language model for assessing students' concept use in a physics problem
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Fabian Kieser, Paul Tschisgale, Sophia Rauh, Xiaoyu Bai, Holger Maus, Stefan Petersen, Manfred Stede, Knut Neumann, and Peter Wulff
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large language models ,machine learning ,natural language processing ,problem solving ,explainable AI ,Electronic computers. Computer science ,QA75.5-76.95 - Abstract
Large language models have been shown to excel in many different tasks across disciplines and research sites. They provide novel opportunities to enhance educational research and instruction in different ways such as assessment. However, these methods have also been shown to have fundamental limitations. These relate, among others, to hallucinating knowledge, explainability of model decisions, and resource expenditure. As such, more conventional machine learning algorithms might be more convenient for specific research problems because they allow researchers more control over their research. Yet, the circumstances in which either conventional machine learning or large language models are preferable choices are not well understood. This study seeks to answer the question to what extent either conventional machine learning algorithms or a recently advanced large language model performs better in assessing students' concept use in a physics problem-solving task. We found that conventional machine learning algorithms in combination outperformed the large language model. Model decisions were then analyzed via closer examination of the models' classifications. We conclude that in specific contexts, conventional machine learning can supplement large language models, especially when labeled data is available.
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- 2024
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11. Using Large Language Models to Probe Cognitive Constructs, Augment Data, and Design Instructional Materials
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Kieser, Fabian, Wulff, Peter, and Khine, Myint Swe, editor
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- 2024
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12. Refocusing on—Crimes Against—Humanity
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Kieser, Hans-Lukas, Kühne, Thomas, Series Editor, Mayersen, Deborah, Series Editor, Lawson, Tom, Series Editor, Rein, Mary Jane, editor, and Mamigonian, Marc A., editor
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- 2024
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13. Analysis and sample size calculation within the responder stratified exponential survival model
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Kilian, Samuel, Krisam, Johannes, and Kieser, Meinhard
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Statistics - Methodology - Abstract
The primary endpoint in oncology is usually overall survival, where differences between therapies may only be observable after many years. To avoid withholding of a promising therapy, preliminary approval based on a surrogate endpoint is possible. The approval can be confirmed later by assessing overall survival within the same study. In these trials, the correlation between surrogate endpoint and overall survival has to be taken into account for sample size calculation and analysis. For a binary surrogate endpoint, this relation can be modeled by means of the responder stratified exponential survival (RSES) model proposed by Xia, Cui, and Yang (2014). We derive properties of the model and confidence intervals based on Maximum Likelihood estimators. Furthermore, we present an approximate and an exact test for survival difference. Type I error rate, power, and required sample size for both newly developed tests are determined exactly. These characteristics are compared to those of the logrank test. We show that the exact test performs best. The power of the logrank test is considerably lower in some situations. We conclude that the logrank test should not be used within the RSES model. The proposed method for sample size calculation works well. The interpretability of our proposed methods is discussed., Comment: 16 pages, 7 figures
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- 2022
14. Theandric and Triune: John Owen and Christological Agency
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Kieser, Ty, primary
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- 2024
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15. 'When one has no REAL illness'—analysis of the knowledge component of mental health literacy in children and adolescents of parents with a mental illness
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Lina Kinzenbach, Katharina Praum, Markus Stracke, Christina Schwenck, Meinhard Kieser, Kathleen Otto, Corinna Reck, Ricarda Steinmayr, Linda Wirthwein, Anna-Lena Zietlow, Hanna Christiansen, and the COMPARE-family Research Group
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mental health literacy ,children of parents with a mental illness ,general knowledge about mental disorders ,specific disorder knowledge ,deductive qualitative approach ,Psychiatry ,RC435-571 - Abstract
Introduction and objectiveMental Health Literacy (MHL) is important in promoting youth mental health. One key aspect of MHL is knowledge about mental disorders, which is particularly relevant for populations at risk for developing mental disorders, such as children of parents with a mental illness (COPMI), representing a mechanism within the transgenerational transmission. Currently, COPMI’s level of disorder knowledge in general, and about the specific parental disorder has not been comprehensively researched. We, therefore, aimed to assess COPMI’s disorder knowledge and clarify its association with COPMI’s age and sex exploratively. To assess both general and disorder-specific knowledge, we took a novel approach that makes disorder knowledge comparable across samples and over time.MethodsA mixed method analysis of N = 181 semi-structured MHL interviews with COPMI (aged 5 to 17 years) was carried out in the COMPARE—family study in Germany. We conducted a DSM-oriented deductive qualitative content analysis to assess COPMI’s general and specific disorder knowledge. Chi-square tests served to identify age and sex differences.ResultsChildren revealed limited knowledge of mental disorders in general, whereas adolescents displayed more knowledge that was also partly consistent with descriptions of classification systems like the DSM-5. The level of specific knowledge about the parent’s disorder depended on the disorder group. More children displayed adequate knowledge of somatic and anxiety disorders compared to trauma and depressive disorders, and more adolescents displayed adequate knowledge of depressive and anxiety disorders. COPMI’s age and sex were found to be significantly associated with disorder knowledge: adolescents exhibited higher levels of adequate general and specific disorder knowledge, and males exhibited higher levels of adequate general disorder knowledge.ConclusionAssessing COPMI’s disorder knowledge and identifying associated age and sex differences yield valuable insights into the knowledge component of the MHL theory. Our findings can help to improve psychoeducational interventions for COPMI by orienting them to their prevailing levels of disorder knowledge. We recommend employing and extending the DSM-oriented deductive approach to assess knowledge within MHL. Analyses involving additional assessments within the COMPARE—family study are in preparation to identify potential knowledge gains over time, and associations to COPMI’s own well-being and mental health symptoms.
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- 2024
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16. Facial emotion recognition in children of parents with a mental illness
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Naomi Leona Werkmann, Arleta Angelika Luczejko, Klara Hagelweide, Rudolf Stark, Sarah Weigelt, Hanna Christiansen, Meinhard Kieser, Kathleen Otto, Corinna Reck, Ricarda Steinmayr, Linda Wirthwein, Anna-Lena Zietlow, Christina Schwenck, and the COMPARE-family research group
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transgenerational transmission of mental disorders ,facial emotion recognition ,parents with mental illness ,children of parents with mental illness (COPMI) ,multimodal assessment ,Psychiatry ,RC435-571 - Abstract
ObjectiveFacial emotion recognition (FER) is a fundamental social skill essential for adaptive social behaviors, emotional development, and overall well-being. FER impairments have been linked to various mental disorders, making it a critical transdiagnostic mechanism influencing the development and trajectory of mental disorders. FER has also been found to play a role in the transgenerational transmission of mental disorders, with the majority of research suggesting FER impairments in children of parents with a mental illness (COPMI). Previous research primarily concentrated on COPMI of parents with internalizing disorders, which does not cover the full spectrum of outpatient mental health service populations. Furthermore, research focuses on varying components of FER by using different assessment paradigms, making it challenging to compare study results. To address these gaps, we comprehensively investigated FER abilities in COPMI using multiple tasks varying in task characteristics.MethodsWe included 189 children, 77 COPMI and 112 children of parents without a diagnosed mental illness (COPWMI), aged 6 to 16 years. We assessed FER using three tasks with varying task demands: an emotional Go/NoGo task, a morphing task, and a task presenting short video sequences depicting different emotions. We fitted separate two-level hierarchical Bayesian models (to account for sibling pairs in our sample) for reaction times and accuracy rates for each task. Good model fit was assured by comparing models using varying priors.ResultsContrary to our expectations, our results revealed no general FER deficit in COPMI compared to COPWMI. The Bayesian models fitted for accuracy in the morphing task and Go/NoGo task yielded small yet significant effects. However, Bayes factors fitted for the models suggested that these effects could be due to random variations or noise in the data.ConclusionsOur study does not support FER impairments as a general feature of COPMI. Instead, individual factors, such as the type of parental disorder and the timing of its onset, may play a crucial role in influencing FER development. Future research should consider these factors, taking into account the diverse landscape of parental mental disorders.
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- 2024
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17. An orally active carbon monoxide-releasing molecule enhances beneficial gut microbial species to combat obesity in mice
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Djamal Eddine Benrahla, Shruti Mohan, Matija Trickovic, Florence Anne Castelli, Ghida Alloul, Arielle Sobngwi, Rosa Abdiche, Silas Kieser, Vanessa Demontant, Elisabeth Trawinski, Céline Chollet, Christophe Rodriguez, Hiroaki Kitagishi, François Fenaille, Mirko Trajkovski, Roberto Motterlini, and Roberta Foresti
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Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Carbon monoxide (CO), a gaseous signaling molecule, has shown promise in preventing body weight gain and metabolic dysfunction induced by high fat diet (HFD), but the mechanisms underlying these effects are largely unknown. An essential component in response to HFD is the gut microbiome, which is significantly altered during obesity and represents a target for developing new therapeutic interventions to fight metabolic diseases. Here, we show that CO delivered to the gut by oral administration with a CO-releasing molecule (CORM-401) accumulates in faeces and enriches a variety of microbial species that were perturbed by a HFD regimen. Notably, Akkermansia muciniphila, which exerts salutary metabolic effects in mice and humans, was strongly depleted by HFD but was the most abundant gut species detected after CORM-401 treatment. Analysis of bacterial transcripts revealed a restoration of microbial functional activity, with partial or full recovery of the Krebs cycle, β-oxidation, respiratory chain and glycolysis. Mice treated with CORM-401 exhibited normalization of several plasma and fecal metabolites that were disrupted by HFD and are dependent on Akkermansia muciniphila's metabolic activity, including indoles and tryptophan derivatives. Finally, CORM-401 treatment led to an improvement in gut morphology as well as reduction of inflammatory markers in colon and cecum and restoration of metabolic profiles in these tissues. Our findings provide therapeutic insights on the efficacy of CO as a potential prebiotic to combat obesity, identifying the gut microbiota as a crucial target for CO-mediated pharmacological activities against metabolic disorders.
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- 2024
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18. Assessment of Patient Care Activities and Readiness for Advanced Pharmacy Practice Experiences in Revised Third-Year Introductory Pharmacy Practice Experiences
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Maes, Marina L., Wen, Meng-Jung, Barnett, Susanne G., Porter, Andrea L., Walbrandt Pigarelli, Denise L., and Kieser, Mara A.
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- 2024
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19. Extension of a conditional performance score for sample size recalculation rules to the setting of binary endpoints
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Björn Bokelmann, Geraldine Rauch, Jan Meis, Meinhard Kieser, and Carolin Herrmann
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Adaptive designs ,Sample size recalculation ,Performance score ,Binary endpoint ,Medicine (General) ,R5-920 - Abstract
Abstract Background Sample size calculation is a central aspect in planning of clinical trials. The sample size is calculated based on parameter assumptions, like the treatment effect and the endpoint’s variance. A fundamental problem of this approach is that the true distribution parameters are not known before the trial. Hence, sample size calculation always contains a certain degree of uncertainty, leading to the risk of underpowering or oversizing a trial. One way to cope with this uncertainty are adaptive designs. Adaptive designs allow to adjust the sample size during an interim analysis. There is a large number of such recalculation rules to choose from. To guide the choice of a suitable adaptive design with sample size recalculation, previous literature suggests a conditional performance score for studies with a normally distributed endpoint. However, binary endpoints are also frequently applied in clinical trials and the application of the conditional performance score to binary endpoints is not yet investigated. Methods We extend the theory of the conditional performance score to binary endpoints by suggesting a related one-dimensional score parametrization. We moreover perform a simulation study to evaluate the operational characteristics and to illustrate application. Results We find that the score definition can be extended without modification to the case of binary endpoints. We represent the score results by a single distribution parameter, and therefore derive a single effect measure, which contains the difference in proportions $$p_{I}-p_{C}$$ p I - p C between the intervention and the control group, as well as the endpoint proportion $$p_{C}$$ p C in the control group. Conclusions This research extends the theory of the conditional performance score to binary endpoints and demonstrates its application in practice.
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- 2024
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20. Epstein-Barr virus-driven B cell lymphoma mediated by a direct LMP1-TRAF6 complex
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Fabian Giehler, Michael S. Ostertag, Thomas Sommermann, Daniel Weidl, Kai R. Sterz, Helmut Kutz, Andreas Moosmann, Stephan M. Feller, Arie Geerlof, Brigitte Biesinger, Grzegorz M. Popowicz, Johannes Kirchmair, and Arnd Kieser
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Science - Abstract
Abstract Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) drives viral B cell transformation and oncogenesis. LMP1’s transforming activity depends on its C-terminal activation region 2 (CTAR2), which induces NF-κB and JNK by engaging TNF receptor-associated factor 6 (TRAF6). The mechanism of TRAF6 recruitment to LMP1 and its role in LMP1 signalling remains elusive. Here we demonstrate that TRAF6 interacts directly with a viral TRAF6 binding motif within CTAR2. Functional and NMR studies supported by molecular modeling provide insight into the architecture of the LMP1-TRAF6 complex, which differs from that of CD40-TRAF6. The direct recruitment of TRAF6 to LMP1 is essential for NF-κB activation by CTAR2 and the survival of LMP1-driven lymphoma. Disruption of the LMP1-TRAF6 complex by inhibitory peptides interferes with the survival of EBV-transformed B cells. In this work, we identify LMP1-TRAF6 as a critical virus-host interface and validate this interaction as a potential therapeutic target in EBV-associated cancer.
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- 2024
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21. Adherence to the Obeid coronal malalignment classification and a residual malalignment below 20 mm can improve surgical outcomes in adult spine deformity surgery
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Baroncini, Alice, Frechon, Paul, Bourghli, Anouar, Smith, Justin S., Larrieu, Daniel, Pellisé, Ferran, Pizones, Javier, Kleinstueck, Frank, Alanay, Ahmet, Kieser, David, Cawley, Derek T., Boissiere, Louis, and Obeid, Ibrahim
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- 2023
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22. Cardiac surgery elicits pericardial inflammatory responses that are distinct compared with postcardiopulmonary bypass systemic inflammationCentral MessagePerspective
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Ali Fatehi Hassanabad, MD, MSc, Friederike I. Schoettler, MD, William D.T. Kent, MD, MSc, Corey A. Adams, MD, MSc, Daniel D. Holloway, MD, MSc, Imtiaz S. Ali, MD, Richard J. Novick, MD, MSc, Muhammad R. Ahsan, MBBS, Robert Scott McClure, MD, MSc, Ganesh Shanmugam, MD, William T. Kidd, MD, Teresa M. Kieser, MD, PhD, Paul W.M. Fedak, MD, PhD, and Justin F. Deniset, PhD
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cardiac surgery ,inflammation ,cardiopulmonary bypass ,pericardial space ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 ,Surgery ,RD1-811 - Abstract
Objectives: Cardiac surgery using cardiopulmonary bypass contributes to a robust systemic inflammatory process. Local intrapericardial postsurgical inflammation is believed to trigger important clinical implications, such as postoperative atrial fibrillation and postsurgical intrathoracic adhesions. Immune mediators in the pericardial space may underlie such complications. Methods: In this prospective pilot clinical study, 12 patients undergoing isolated coronary artery bypass graft surgery were enrolled. Native pericardial fluid and venous blood samples (baseline) were collected immediately after pericardiotomy. Postoperative pericardial fluid and venous blood samples were collected 48-hours after cardiopulmonary bypass and compared with baseline. Flow cytometry determined proportions of specific immune cells, whereas multiplex analysis probed for inflammatory mediators. Results: Neutrophils are the predominant cells in both the pericardial space and peripheral blood postoperatively. There are significantly more CD163lo macrophages in blood compared with pericardial effluent after surgery. Although there are significantly more CD163hi macrophages in native pericardial fluid compared with baseline blood, after surgery there are significantly fewer of these cells present in the pericardial space compared with blood. Postoperatively, concentration of interleukin receptor antagonist 6, and interleukin 8 were significantly higher in the pericardial space compared with blood. After surgery, compared with blood, the pericardial space has a significantly higher concentration of matrix metalloproteinase 3, matrix metalloproteinase 8, and matrix metalloproteinase 9. The same trend was observed with transformational growth factor β. Conclusions: Cardiac surgery elicits an inflammatory response in the pericardial space, which differs from systemic inflammatory responses. Future work should determine whether or not this distinct local inflammatory response contributes to postsurgical complications and could be modified to influence clinical outcomes.
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- 2023
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23. Outcome analysis for patients with subarachnoid hemorrhage and vasospasm including endovascular treatment
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Sina Burth, Jan Meis, Dorothea Kronsteiner, Helena Heckhausen, Klaus Zweckberger, Meinhard Kieser, Wolfgang Wick, Christian Ulfert, Markus Möhlenbruch, Peter Ringleb, and Silvia Schönenberger
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Subarachnoid hemorrhage ,Vasospasm ,Delayed cerebral ischemia ,Outcome ,Endovascular treatment ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract As a complication of subarachnoid hemorrhage (SAH), vasospasm substantially contributes to its morbidity and mortality. We aimed at analyzing predictors of outcome for these patients including the role of endovascular treatment (ET). Our database was screened for patients with SAH treated in our Neuro-ICU from 2009 to 2019. Clinical parameters including functional outcome (modified Rankin Scale, mRS of 0–2 or 3–6 at discharge and after a median follow-up of 18 months) and details about ET were gathered on 465 patients, 241 (52%) of whom experienced vasospasm. Descriptive analyses were performed to identify explanatory variables for the dichotomized mRS score. A logistic regression model was fitted on 241 patients with vasospasm including age, Hunt and Hess Score, extraventricular drainage (EVD), forced hypertension, ET and delayed cerebral ischemia (DCI). The model found a Hunt and Hess Score of 5 (OR = 0.043, p = 0.008), requirement of EVD (OR = 0.161, p
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- 2023
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24. Educational Data Augmentation in Physics Education Research Using ChatGPT
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Fabian Kieser, Peter Wulff, Jochen Kuhn, and Stefan Küchemann
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Generative AI technologies such as large language models show novel potential to enhance educational research. For example, generative large language models were shown to be capable of solving quantitative reasoning tasks in physics and concept tests such as the Force Concept Inventory (FCI). Given the importance of such concept inventories for physics education research, and the challenges in developing them such as field testing with representative populations, this study seeks to examine to what extent a generative large language model could be utilized to generate a synthetic dataset for the FCI that exhibits content-related variability in responses. We use the recently introduced ChatGPT based on the GPT 4 generative large language model and investigate to what extent ChatGPT could solve the FCI accurately (RQ1) and could be prompted to solve the FCI as if it were a student belonging to a different cohort (RQ2). Furthermore, we study, to what extent ChatGPT could be prompted to solve the FCI as if it were a student having a different force- and mechanics-related preconception (RQ3). In alignment with other research, we found that ChatGPT could accurately solve the FCI. We furthermore found that prompting ChatGPT to respond to the inventory as if it belonged to a different cohort yielded no variance in responses, however, responding as if it had a certain preconception introduced much variance in responses that approximate real human responses on the FCI in some regards.
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- 2023
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25. Turkey’s Violent Formation: New Social Contracts at the End of the Ottoman Empire
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Hans-Lukas Kieser and Hans-Lukas Kieser
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- 2024
26. Theandric and Triune: John Owen and Christological Agency
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Ty Kieser and Ty Kieser
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- 2024
27. Die sieben wichtigsten Tipps für die Gestaltung einer variablen Vertriebsvergütung
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Kieser, Heinz-Peter and Kieser, Heinz-Peter
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- 2023
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28. Aktuelle Entwicklungen der Vertriebsvergütung
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Kieser, Heinz-Peter and Kieser, Heinz-Peter
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- 2023
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29. Vorgehensweise bei der Einführung eines neuen Vergütungssystems
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Kieser, Heinz-Peter and Kieser, Heinz-Peter
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- 2023
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30. Motivatoren für Verkäufer
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Kieser, Heinz-Peter and Kieser, Heinz-Peter
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- 2023
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31. Fallbeispiele
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Kieser, Heinz-Peter and Kieser, Heinz-Peter
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- 2023
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32. Zehn Bausteine für eine motivierende variable Vergütung im Vertrieb
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Kieser, Heinz-Peter and Kieser, Heinz-Peter
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- 2023
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33. A Comparison of Methods for Enriching Network Meta-Analyses in the Absence of Individual Patient Data
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Proctor, Tanja, Zimmermann, Samuel, Seide, Svenja, and Kieser, Meinhard
- Abstract
During drug development, a biomarker is sometimes identified as separating a patient population into those with more and those with less benefit from evaluated treatments. Consequently, later studies might be targeted, while earlier ones are performed in mixed patient populations. This poses a challenge in evidence synthesis, especially if only aggregated data are available. Starting from this scenario, we investigate three commonly used network meta-analytic estimation methods, the naive estimation approach, the stand-alone analysis, and the network meta-regression. Additionally, we adapt and modify two methods, which are used in evidence synthesis to combine randomized controlled trials with observational studies, the enrichment-through-weighting approach, and the informative prior estimation. We evaluate all five methods in a simulation study with 32 scenarios using bias, root-mean-squared-error, coverage, precision, and power. Additionally, we revisit a clinical data set to exemplify and discuss the application. In the simulation study, none of the methods was observed to be clearly favorable over all investigated scenarios. However, the stand-alone analysis and the naive estimation performed comparably or worse than the other methods in all evaluated performance measures and simulation scenarios and are therefore not recommended. While substantial between-trial heterogeneity is challenging for all estimation approaches, the performance of the network meta-regression, the enriching-through weighting approach and the informative prior approach was dependent on the simulation scenario and the performance measure of interest. Furthermore, as these estimation methods are drawing slightly different assumptions, some of which require the presence of additional information for estimation, we recommend sensitivity-analyses wherever possible.
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- 2022
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34. An orally active carbon monoxide-releasing molecule enhances beneficial gut microbial species to combat obesity in mice
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Benrahla, Djamal Eddine, Mohan, Shruti, Trickovic, Matija, Castelli, Florence Anne, Alloul, Ghida, Sobngwi, Arielle, Abdiche, Rosa, Kieser, Silas, Demontant, Vanessa, Trawinski, Elisabeth, Chollet, Céline, Rodriguez, Christophe, Kitagishi, Hiroaki, Fenaille, François, Trajkovski, Mirko, Motterlini, Roberto, and Foresti, Roberta
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- 2024
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35. Outcome analysis for patients with subarachnoid hemorrhage and vasospasm including endovascular treatment
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Burth, Sina, Meis, Jan, Kronsteiner, Dorothea, Heckhausen, Helena, Zweckberger, Klaus, Kieser, Meinhard, Wick, Wolfgang, Ulfert, Christian, Möhlenbruch, Markus, Ringleb, Peter, and Schönenberger, Silvia
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- 2023
- Full Text
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36. Q-HAM: a multicenter upfront randomized phase II trial of quizartinib and high-dose Ara-C plus mitoxantrone in relapsed/refractory AML with FLT3-ITD
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Jaramillo, Sonia, Le Cornet, Lucian, Kratzmann, Markus, Krisam, Johannes, Görner, Martin, Hänel, Mathias, Röllig, Christoph, Wass, Maxi, Scholl, Sebastian, Ringhoffer, Mark, Reichart, Alexander, Steffen, Björn, Kayser, Sabine, Mikesch, Jan-Henrik, Schaefer-Eckart, Kerstin, Schubert, Jörg, Geer, Thomas, Martin, Sonja, Kieser, Meinhard, Sauer, Tim, Kriegsmann, Katharina, Hundemer, Michael, Serve, Hubert, Bornhäuser, Martin, Müller-Tidow, Carsten, and Schlenk, Richard F.
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- 2023
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37. High throughput single cell long-read sequencing analyses of same-cell genotypes and phenotypes in human tumors
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Shiau, Cheng-Kai, Lu, Lina, Kieser, Rachel, Fukumura, Kazutaka, Pan, Timothy, Lin, Hsiao-Yun, Yang, Jie, Tong, Eric L., Lee, GaHyun, Yan, Yuanqing, Huse, Jason T., and Gao, Ruli
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- 2023
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38. Accelerator mass spectrometry: an analytical tool with applications for a sustainable society
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Kieser, William E.
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- 2023
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39. Empathy and psychopathology in children and adolescents: the role of parental mental illness and emotion regulation
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Arleta A. Luczejko, Klara Hagelweide, Rudolf Stark, Sarah Weigelt, Hanna Christiansen, Meinhard Kieser, Kathleen Otto, Corinna Reck, Ricarda Steinmayr, Linda Wirthwein, Anna-Lena Zietlow, Christina Schwenck, the COMPARE-family research group, Stracke, Gilbert, Eitenmüller, Awounvo, Kirchner, Klose, Buntrock, Ebert, Schlarb, Margraf, Schneider, Friedrich, Teismann, Stark, Metzger, Brakemeier, Wardenga, Hauck, Glombiewski, Schröder, Heider, Jungmann, Witthöft, and Rief
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transgenerational transmission of mental disorders ,parents with mental illness ,children of parents with mental illness ,empathy ,emotion regulation ,Psychiatry ,RC435-571 - Abstract
ObjectiveAlthough empathy is known to be a strength, recent studies suggest that empathy can be a risk factor for psychopathology under certain conditions in children. This study examines parental mental illness as such a condition. Further, it aims to investigate whether maladaptive emotion regulation (ER) mediates the relationship between empathy and psychopathological symptoms of children.MethodsParticipants were 100 children of parents with a mental illness (55% female) and 87 children of parents without a mental illness (50% female) aged 6 - 16 years and their parents.ResultsGreater cognitive empathy was related to more psychopathological symptoms in COPMI, but not in COPWMI. In addition, in COPMI maladaptive ER mediated this relationship. In contrast, greater affective empathy was associated with more psychopathological symptoms regardless of whether parents had a mental illness.ConclusionOur findings highlight the importance of implementing preventive programs for COPMI that specifically target the reduction of maladaptive ER.
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- 2024
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40. Randomized phase III GnG study on two schedules of gemtuzumab ozogamicin as adjunct to intensive induction therapy and double-blinded intensive postremission therapy with or without glasdegib in patients with newly diagnosed acute myeloid leukemia
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Sonia Jaramillo, Johannes Krisam, Lucian Le Cornet, Markus Kratzmann, Lukas Baumann, Olga Eissymont, Martina Crysandt, Martin Görner, Sabine Kayser, Stefan Krause, Christoph Schliemann, Tobias Gaska, Martin Kaufmann, Jens Chemnitz, Markus Schaich, Alexander Hoellein, Uwe Platzbecker, Meinhard Kieser, Carsten Müller-Tidow, and Richard F. Schlenk
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2024
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41. Consensus statement—graft treatment in cardiovascular bypass graft surgery
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Maximilian Y. Emmert, Johannes Bonatti, Etem Caliskan, Mario Gaudino, Martin Grabenwöger, Martin T. Grapow, Paul Phillip Heinisch, Teresa Kieser-Prieur, Ki-Bong Kim, Attila Kiss, Fatima Mouriquhe, Markus Mach, Adrianna Margariti, John Pepper, Louis P. Perrault, Bruno K. Podesser, John Puskas, David P. Taggart, Om P. Yadava, and Bernhard Winkler
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CABG ,endothelium ,heart ,radial artery ,VEST ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Coronary artery bypass grafting (CABG) is and continues to be the preferred revascularization strategy in patients with multivessel disease. Graft selection has been shown to influence the outcomes following CABG. During the last almost 60 years saphenous vein grafts (SVG) together with the internal mammary artery have become the standard of care for patients undergoing CABG surgery. While there is little doubt about the benefits, the patency rates are constantly under debate. Despite its acknowledged limitations in terms of long-term patency due to intimal hyperplasia, the saphenous vein is still the most often used graft. Although reendothelialization occurs early postoperatively, the process of intimal hyperplasia remains irreversible. This is due in part to the persistence of high shear forces, the chronic localized inflammatory response, and the partial dysfunctionality of the regenerated endothelium. “No-Touch” harvesting techniques, specific storage solutions, pressure controlled graft flushing and external stenting are important and established methods aiming to overcome the process of intimal hyperplasia at different time levels. Still despite the known evidence these methods are not standard everywhere. The use of arterial grafts is another strategy to address the inferior SVG patency rates and to perform CABG with total arterial revascularization. Composite grafting, pharmacological agents as well as latest minimal invasive techniques aim in the same direction. To give guide and set standards all graft related topics for CABG are presented in this expert opinion document on graft treatment.
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- 2024
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42. Parenting stress in parents with and without a mental illness and its relationship to psychopathology in children: a multimodal examination
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Vanessa Seipp, Klara Hagelweide, Rudolf Stark, Sarah Weigelt, Hanna Christiansen, Meinhard Kieser, Kathleen Otto, Corinna Reck, Ricarda Steinmayr, Linda Wirthwein, Anna–Lena Zietlow, Christina Schwenck, the COMPARE-Family Research Group, Stracke, Gilbert, Eitenmüller, Awounvo, Kirchner, Klose, Buntrock, Ebert, Schlarb, Margraf, Schneider, Friedrich, Teismann, Stark, Metzger, Brakemeier, Wardenga, Hauck, Glombiewski, Schröder, Heider, Jungmann, Witthöft, and Rief
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parents with a mental illness ,parenting stress ,multimodal ,relational schema ,psychopathology of children ,psychophysiological arousal ,Psychiatry ,RC435-571 - Abstract
ObjectiveChildren of parents with a mental illness are at heightened risk to develop a mental illness themselves due to genetics and environmental factors. Although parenting stress (PS) is known to be associated with increased psychopathology in parents and children, there is no study investigating PS multimodally in a sample of parents with a mental illness. This study aims to compare PS of parents with and without a mental illness and further to examine the relationship between PS and psychopathology of children.MethodsParticipants were parents with a mental illness and parents without a mental illness and their children aged four to sixteen years. We assessed PS multimodally using a questionnaire, parents’ evaluation of children’s behavior (relational schemas) and psychophysiological arousal of parents during free speech task.ResultsSelf-reported PS was increased, and evaluation of children’s behavior was more negative and less positive in parents with a mental illness compared to parents without a mental illness. Children’s psychopathology was associated with self-reported PS and relational schemas of parents. Regarding psychophysiological arousal, parents with a mental illness showed reduced reactivity in heart rate from baseline to free speech task in comparison to parents without a mental illness.ConclusionsOur findings highlight the importance of implementing intervention programs to reduce PS for parents and children. In particular, parents with a mental illness might benefit from specific intervention programs in order to interrupt the transgenerational transmission of mental disorders.
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- 2024
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43. Critical Assessment of Metagenome Interpretation: the second round of challenges
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Meyer, Fernando, Fritz, Adrian, Deng, Zhi-Luo, Koslicki, David, Lesker, Till Robin, Gurevich, Alexey, Robertson, Gary, Alser, Mohammed, Antipov, Dmitry, Beghini, Francesco, Bertrand, Denis, Brito, Jaqueline J, Brown, C Titus, Buchmann, Jan, Buluç, Aydin, Chen, Bo, Chikhi, Rayan, Clausen, Philip TLC, Cristian, Alexandru, Dabrowski, Piotr Wojciech, Darling, Aaron E, Egan, Rob, Eskin, Eleazar, Georganas, Evangelos, Goltsman, Eugene, Gray, Melissa A, Hansen, Lars Hestbjerg, Hofmeyr, Steven, Huang, Pingqin, Irber, Luiz, Jia, Huijue, Jørgensen, Tue Sparholt, Kieser, Silas D, Klemetsen, Terje, Kola, Axel, Kolmogorov, Mikhail, Korobeynikov, Anton, Kwan, Jason, LaPierre, Nathan, Lemaitre, Claire, Li, Chenhao, Limasset, Antoine, Malcher-Miranda, Fabio, Mangul, Serghei, Marcelino, Vanessa R, Marchet, Camille, Marijon, Pierre, Meleshko, Dmitry, Mende, Daniel R, Milanese, Alessio, Nagarajan, Niranjan, Nissen, Jakob, Nurk, Sergey, Oliker, Leonid, Paoli, Lucas, Peterlongo, Pierre, Piro, Vitor C, Porter, Jacob S, Rasmussen, Simon, Rees, Evan R, Reinert, Knut, Renard, Bernhard, Robertsen, Espen Mikal, Rosen, Gail L, Ruscheweyh, Hans-Joachim, Sarwal, Varuni, Segata, Nicola, Seiler, Enrico, Shi, Lizhen, Sun, Fengzhu, Sunagawa, Shinichi, Sørensen, Søren Johannes, Thomas, Ashleigh, Tong, Chengxuan, Trajkovski, Mirko, Tremblay, Julien, Uritskiy, Gherman, Vicedomini, Riccardo, Wang, Zhengyang, Wang, Ziye, Wang, Zhong, Warren, Andrew, Willassen, Nils Peder, Yelick, Katherine, You, Ronghui, Zeller, Georg, Zhao, Zhengqiao, Zhu, Shanfeng, Zhu, Jie, Garrido-Oter, Ruben, Gastmeier, Petra, Hacquard, Stephane, Häußler, Susanne, Khaledi, Ariane, Maechler, Friederike, Mesny, Fantin, Radutoiu, Simona, Schulze-Lefert, Paul, Smit, Nathiana, and Strowig, Till
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Biological Sciences ,Bioinformatics and Computational Biology ,Networking and Information Technology R&D (NITRD) ,Archaea ,Metagenome ,Metagenomics ,Reproducibility of Results ,Sequence Analysis ,DNA ,Software ,Technology ,Medical and Health Sciences ,Developmental Biology ,Biological sciences - Abstract
Evaluating metagenomic software is key for optimizing metagenome interpretation and focus of the Initiative for the Critical Assessment of Metagenome Interpretation (CAMI). The CAMI II challenge engaged the community to assess methods on realistic and complex datasets with long- and short-read sequences, created computationally from around 1,700 new and known genomes, as well as 600 new plasmids and viruses. Here we analyze 5,002 results by 76 program versions. Substantial improvements were seen in assembly, some due to long-read data. Related strains still were challenging for assembly and genome recovery through binning, as was assembly quality for the latter. Profilers markedly matured, with taxon profilers and binners excelling at higher bacterial ranks, but underperforming for viruses and Archaea. Clinical pathogen detection results revealed a need to improve reproducibility. Runtime and memory usage analyses identified efficient programs, including top performers with other metrics. The results identify challenges and guide researchers in selecting methods for analyses.
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- 2022
44. Q-HAM: a multicenter upfront randomized phase II trial of quizartinib and high-dose Ara-C plus mitoxantrone in relapsed/refractory AML with FLT3-ITD
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Sonia Jaramillo, Lucian Le Cornet, Markus Kratzmann, Johannes Krisam, Martin Görner, Mathias Hänel, Christoph Röllig, Maxi Wass, Sebastian Scholl, Mark Ringhoffer, Alexander Reichart, Björn Steffen, Sabine Kayser, Jan-Henrik Mikesch, Kerstin Schaefer-Eckart, Jörg Schubert, Thomas Geer, Sonja Martin, Meinhard Kieser, Tim Sauer, Katharina Kriegsmann, Michael Hundemer, Hubert Serve, Martin Bornhäuser, Carsten Müller-Tidow, and Richard F. Schlenk
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Quizartinib ,Relapse ,Refractory ,Acute myeloid leukemia ,Measurable residual disease ,Matched threshold crossing approach ,Medicine (General) ,R5-920 - Abstract
Abstract Background About 50% of older patients with acute myeloid leukemia (AML) fail to attain complete remission (CR) following cytarabine plus anthracycline-based induction therapy. Salvage chemotherapy regimens are based on high-dose cytarabine (HiDAC), which is frequently combined with mitoxantrone (HAM regimen). However, CR rates remain low, with less than one-third of the patients achieving a CR. FLT3-ITD has consistently been identified as an unfavorable molecular marker in both relapsed and refractory (r/r)-AML. One-quarter of patients who received midostaurin are refractory to induction therapy and relapse rate at 2 years exceeds 40%. The oral second-generation bis-aryl urea tyrosine kinase inhibitor quizartinib is a very selective FLT3 inhibitor, has a high capacity for sustained FLT3 inhibition, and has an acceptable toxicity profile. Methods In this multicenter, upfront randomized phase II trial, all patients receive quizartinib combined with HAM (cytarabine 3g/m2 bidaily day one to day three, mitoxantrone 10mg/m2 days two and three) during salvage therapy. Efficacy is assessed by comparison to historical controls based on the matched threshold crossing approach with achievement of CR, complete remission with incomplete hematologic recovery (CRi), or complete remission with partial recovery of peripheral blood counts (CRh) as primary endpoint. During consolidation therapy (chemotherapy and allogeneic hematopoietic cell transplantation), patients receive either prophylactic quizartinib therapy or measurable residual disease (MRD)-triggered preemptive continuation therapy with quizartinib according to up-front randomization. The matched threshold crossing approach is a novel study-design to enhance the classic single-arm trial design by including matched historical controls from previous clinical studies. It overcomes common disadvantages of single-armed and small randomized studies, since the expected outcome of the observed study population can be adjusted based on the matched controls with a comparable distribution of known prognostic and predictive factors. Furthermore, balanced treatment groups lead to stable statistical models. However, one of the limitations of our study is the inability to adjust for unobserved or unknown confounders. Addressing the primary endpoint, CR/CRi/CRh after salvage therapy, the maximal sample size of 80 patients is assessed generating a desirable power of the used adaptive design, assuming a logistic regression is performed at a one-sided significance level α=0.05, the aspired power is 0.8, and the number of matching partners per intervention patient is at least 1. After enrolling 20 patients, the trial sample size will be recalculated in an interim analysis based on a conditional power argument. Conclusion Currently, there is no commonly accepted standard for salvage chemotherapy treatment. The objective of the salvage therapy is to reduce leukemic burden, achieve the best possible remission, and perform a hemopoietic stem-cell transplantation. Thus, in patients with FLT3-ITD mutation, the comparison of quizartinib with intensive salvage therapy versus chemotherapy alone appears as a logical consequence in terms of efficacy and safety. Ethics and dissemination Ethical approval and approvals from the local and federal competent authorities were granted. Trial results will be reported via peer-reviewed journals and presented at conferences and scientific meetings. Trial registration ClinicalTrials.gov NCT03989713; EudraCT Number: 2018-002675-17.
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- 2023
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45. Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II
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Oonk, Maaike HM, Slomovitz, Brian, Baldwin, Peter JW, van Doorn, Helena C, van der Velden, Jacobus, de Hullu, Joanne A, Gaarenstroom, Katja N, Slangen, Brigitte FM, Vergote, Ignace, Brännström, Mats, van Dorst, Eleonora BL, van Driel, Willemien J, Hermans, Ralph H, Nunns, David, Widschwendter, Martin, Nugent, David, Holland, Cathrine M, Sharma, Aarti, DiSilvestro, Paul A, Mannel, Robert, Boll, Dorry, Cibula, David, Covens, Al, Provencher, Diane, Runnebaum, Ingo B, Luesley, David, Ellis, Patricia, Duncan, Timothy J, Tjiong, Ming Y, Cruickshank, Derek J, Kjølhede, Preben, Levenback, Charles F, Bouda, Jiri, Kieser, Katharina E, Palle, Connie, Spirtos, Nicola M, O'Malley, David M, Leitao, Mario M, Geller, Melissa A, Dhar, Kalyan, Asher, Viren, Tamussino, Karl, Tobias, Daniel H, Borgfeldt, Christer, Lea, Jayanthi S, Bailey, Jo, Lood, Margareta, Eyjolfsdottir, Brynhildur, Attard-Montalto, Stephen, Tewari, Krishnansu S, Manchanda, Ranjit, Jensen, Pernille T, Persson, Par, Van Le, Linda, Putter, Hein, de Bock, Geertruida H, Monk, Bradley J, Creutzberg, Carien L, and van der Zee, Ate GJ
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Trials and Supportive Activities ,Clinical Research ,Cancer ,Evaluation of treatments and therapeutic interventions ,6.5 Radiotherapy and other non-invasive therapies ,Aged ,Female ,Humans ,Lymph Node Excision ,Lymphatic Metastasis ,Middle Aged ,Neoplasm Micrometastasis ,Neoplasm Staging ,Prospective Studies ,Radiation Dosage ,Sentinel Lymph Node ,Time Factors ,Treatment Outcome ,Vulvar Neoplasms ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
PurposeThe Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN).MethodsGROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences.ResultsFrom December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL.ConclusionInguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.
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- 2021
46. Emapalumab therapy for hemophagocytic lymphohistiocytosis before reduced-intensity transplantation improves chimerism
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Verkamp, Bethany, Jodele, Sonata, Sabulski, Anthony, Marsh, Rebecca, Kieser, Pearce, and Jordan, Michael B.
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- 2024
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47. Complications, Visual Acuity, and Refractive Error 3 Years after Secondary Intraocular Lens Implantation for Pediatric Aphakia
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Freedman, Sharon F., Wallace, David K., Enyedi, Laura B., Prakalapakorn, Sasapin, Jones, Sarah K., Hug, Denise, Stahl, Erin D., Dent, Rebecca J., Kong, Lingkun, Wang, Serena, Gallerson, Bryan K., Hutchinson, Amy K., Lenhart, Phoebe, Brower, Judy, Morrison, David G., Ruark, Scott T., Mets-Halgrimson, Rebecca, Yoon, Hawke, Ralay-Ranaivo, Hantamalala, Hamidullah, Aaliyah, Areaux, Raymond, Anderson, Jill S., Holleschau, Ann M., Superstein, Rosanne, Belanger, Caroline, Fallaha, Nicole, Hamel, Patrick, Thibeault, Maryse, Tamkins, Susanna M., Chang, Ta, Park, Hee-Jung S., Trumler, Anya A., Liu, Xiaonong, Astle, William F., Sanders, Emi N., Traboulsi, Elias, Ghasia, Fatema, McOwen, Diana C., Gray, Michael E., Yang, Michael B., Bowman, Corey S., Galvin, Jennifer, Therriault, Margaret, Smith, Heather, Whitaker, Michele E., Orge, Faruk, Grigorian, Adriana P., Baird, Alicia M., Strominger, Mitchell B., Chen, Vicki, Klein, Shelley, Kemmer, Jacquelyn D., Neiman, Alexandra E., Mendoza, Myra N., Frohwein, Jill J., Bremer, Don, Cassady, Cybil, Golden, Richard, Jordan, Catherine, Rogers, David, Oravec, Sara A., Yanovitch, Tammy L., Lunsford, Keven, Nye, Christina, Shea, Caroline, Stillman, SueAnn M., LaRoche, G. Robert, Van Iderstine, Stephen C., Robertson, Elisa, Cruz, Oscar A., Ghadban, Rafif, Govreau, Dawn, Larson, Scott A., Longmuir, Susannah, Shan, Xiaoyan, Clarke, Michael P., Taylor, Kate, Powell, Christine, Hammond, Benjamin P., Gearinger, Matthew D., Czubinski, Andrea, Hendricks, Dorothy H., Jin, Jing, Salvin, Jonathan H., Fisher, Alicia, Lee, Katherine A., Brooks, Daniel, Schweinler, Bonita R., Sala, Nicholas A., Sala, Allyson M., Summers, Allison I., Karr, Daniel J., Wilson, Lorri B., Rauch, Paula K., O'Hara, Mary, Gandhi, Nandini, Hashmi, Tania, Colburn, Jeffrey, Dittman, Eileen, Whitfill, Charles R., Wheeler, Amy M., McCourt, Emily A., Singh, Jasleen, Welnick, Nanastasia, Azar, Nathalie F., Baker, Joseph, Droste, Patrick J., Peters, Robert J., Hilbrands, Jan, Pineles, Stacy L., Bernardo, Marianne J., Peterson, Edward, Peterson, Charla H., Kumar, Kartik, Melese, Ephrem, Lingua, Robert, Grijalva, Jeff, Crouch, Earl R., jr., Crouch, Earl R., III, Ventura, Gaylord, Anninger, William, Benson, Shawn L., Karp, Karen A., Smith, Jordana M., Brickman-Kelleher, Jill, Ticho, Benjamin H., Khammar, Alexander J., Clausius, Deborah A., Guo, Suquin, Suh, Donny, Chamberlain, Carolyn, Schloff, Susan, Madigan, William P., Burkman, Donna, Christiansen, Stephen P., Ramsey, Jean E., McConnell, Kate H., Friedman, Ilana, Rosado, Jose, Sauberan, Donald P., Hemberger, Jody C., Davis, Patricia L., Rudaitis, Indre, Lowery, Robert S., Cupit, Shawn, Bothun, Erick D., Mohney, Brian G., Wernimont, Suzanne M., Neilsen, Rebecca A., Herlihy, Erin P., Baran, Francine, Gladstone, Amy, Smith, Justin, Mellott, Mei, Kieser, Troy, Erzurum, S. Ayse, Colon, Beth, Shah, Birva, Quebbemann, Micaela, Beck, Roy W., Austin, Darrell S., Boyle, Nicole M., Conner, Courtney L., Chandler, Danielle L., Donahue, Quayleen, Fimbel, Brooke P., Robinson, Julianne L., Hercinovic, Amra, Hoepner, James E., Kaplon, Joseph D., Henderson, Robert J., Melia, B. Michele, Ortiz, Gillaine, Woodard, Victoria C., Stutz, Kathleen M., Sutherland, Desirae R., Wu, Rui, Everett, Donald F., Diener-West, Marie, Baker, John D., Davis, Barry, Phelps, Dale L., Poff, Stephen W., Saunders, Richard A., Tychsen, Lawrence, Bradfield, Yasmin S., Foster, Nicole C., Plager, David A., Salchow, Daniel J., Birch, Eileen E., Manny, Ruth E., Silver, Jayne L., Weise, Katherine K., Verderber, Lisa C., Repka, Michael X., Dean, Trevano W., Kraker, Raymond T., Li, Zhuokai, Yen, Kimberly G., de Alba Campomanes, Alejandra G., Young, Marielle P., Rahmani, Bahram, Haider, Kathryn M., Whitehead, George F., Lambert, Scott R., Kurup, Sudhi P., Kraus, Courtney L., Cotter, Susan A., Holmes, Jonathan M., Hatt, Sarah R., and Traboulsi, Elias I.
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- 2024
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48. Minimally-invasive lag screw fixation technique for posterior malleolus fractures: A cadaveric study
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Fullarton, M., Vidakovic, H., Kieser, D.C., Hammer, N., and Wyatt, M.C.
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- 2024
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49. Statistical shape modelling of the thoracic spine for the development of pedicle screw insertion guides
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Wai, Gordon, Rusli, Wan, Ghouse, Shaaz, Kieser, David C., Kedgley, Angela, and Newell, Nicolas
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- 2023
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50. High throughput single cell long-read sequencing analyses of same-cell genotypes and phenotypes in human tumors
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Cheng-Kai Shiau, Lina Lu, Rachel Kieser, Kazutaka Fukumura, Timothy Pan, Hsiao-Yun Lin, Jie Yang, Eric L. Tong, GaHyun Lee, Yuanqing Yan, Jason T. Huse, and Ruli Gao
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Science - Abstract
Abstract Single-cell nanopore sequencing of full-length mRNAs transforms single-cell multi-omics studies. However, challenges include high sequencing errors and dependence on short-reads and/or barcode whitelists. To address these, we develop scNanoGPS to calculate same-cell genotypes (mutations) and phenotypes (gene/isoform expressions) without short-read nor whitelist guidance. We apply scNanoGPS onto 23,587 long-read transcriptomes from 4 tumors and 2 cell-lines. Standalone, scNanoGPS deconvolutes error-prone long-reads into single-cells and single-molecules, and simultaneously accesses both phenotypes and genotypes of individual cells. Our analyses reveal that tumor and stroma/immune cells express distinct combination of isoforms (DCIs). In a kidney tumor, we identify 924 DCI genes involved in cell-type-specific functions such as PDE10A in tumor cells and CCL3 in lymphocytes. Transcriptome-wide mutation analyses identify many cell-type-specific mutations including VEGFA mutations in tumor cells and HLA-A mutations in immune cells, highlighting the critical roles of different mutant populations in tumors. Together, scNanoGPS facilitates applications of single-cell long-read sequencing technologies.
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- 2023
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