680 results on '"Engeli, A."'
Search Results
2. Prednisolone Versus Colchicine for Acute Gout in Primary Care: statistical analysis plan for the pragmatic, multicenter, randomized, and double-blinded COPAGO non-inferiority trial
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Adrian Richter, Julia Truthmann, Eva Hummers, Julia Freyer Martins Pereira, Ildikó Gágyor, Franziska Schuster, Amelie Witte, Susanne Böhm, Alexandra Greser, Petra Kamin, Sylvia Stracke, Marcus Dörr, Robin Bülow, Stefan Engeli, Jean François Chenot, and Till Ittermann
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Medicine (General) ,R5-920 - Abstract
Abstract Background To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In addition, in previous trials of treating acute gout patients with concomitant comorbidities were often excluded due to contraindications to naproxen. Study design This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial compares prednisolone with colchicine in terms of non-inferiority in patients with acute gout. Patients presenting to their general practitioner with acute gout can be included if the gout attack has occurred within the last 2 days. A total of 60 practices in the vicinity of three university medical centers (Greifswald, Göttingen, and Würzburg) participate in the study. The intervention group receives 30 mg prednisolone for 5 days, while the group of standard care receives low-dose colchicine (day 1: 1.5 mg; days 2–5: 1 mg). The first dose of treatment is provided at day 0 when patients present to the general practitioner due to an acute gout attack. From day 0 to day 6, patients will be asked to complete a study diary on daily basis regarding pain quantification. For safety reasons, potential side effects and the course of systolic blood pressure are also assessed. Statistical analysis plan N = 314 patients have to be recruited to compensate for 10% of dropout and to allow for showing non-inferiority of prednisolone compared to colchicine with a power of 90%. We use permuted block randomization with block sizes of 2, 4, and 6 to avoid imbalanced treatment arms in this multi-center study; patients are randomized in a 1:1 ratio. The absolute level of pain on day 3 (in the last 24 h) is the primary outcome and measured on a numerical rating scale (NRS: 0–10). Using a multiple linear regression model adjusted for age, sex, and pain at baseline, prednisolone is considered non-inferior if the effect estimate including the confidence intervals is lower than a margin of 1 unit on the NRS. Average response to treatment, joint swelling and tenderness, physical function of the joint, and patients’ global assessment of treatment success are secondary outcomes. Discussion The trial will provide evidence from a direct comparison of colchicine and prednisolone regarding their efficacy of pain reduction in acute gout patients of primary care and to indicate possible safety signals. Trial registration ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered).
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- 2024
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3. Wave optics of the solar gravity lens
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Engeli, Sara and Saha, Prasenjit
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Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
It is well known that the solar gravitational field can be considered as a telescope with a prime focus at locations beyond 550 au. In this work we present a new derivation of the wave-optical properties of the system, by adapting the arrival-time formalism from gravitational lensing. At the diffraction limit the angular resolution is similar to that of a notional telescope with the diameter of the Sun, and the maximum light amplification is $8{\pi}4GM /(c^2{\lambda})$, enough to detect a 1 W laser on Proxima Centauri b pointed in the general direction of the Sun. Extended sources, however, would be blurred by the wings of the point spread function into the geometrical-optics regime of gravitational lensing. Broad-band sources would have to further contend with the solar corona. Imaging an exoplanet surface as advocated in the literature, without attempting to reach the diffraction limit, appears achievable. For diffraction-limited imaging (sub-km scales from 100 pc) nearby neutron stars appear to be most plausible targets.
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- 2022
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4. Prednisolone Versus Colchicine for Acute Gout in Primary Care (COPAGO): protocol for a two-arm multicentre, pragmatic, prospective, randomized, double-blind, controlled clinical trial of prednisolone and colchicine for non-inferiority with a parallel group design
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Julia Truthmann, Julia Freyer Martins Pereira, Adrian Richter, Franziska Schuster, Amelie Witte, Susanne Böhm, Alexandra Greser, Petra Kamin, Sylvia Stracke, Marcus Dörr, Robin Bülow, Stefan Engeli, Ildikó Gágyor, Eva Hummers, and Jean-François Chenot
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Primary care ,Acute gout ,Prednisolone ,Colchicine ,Pragmatic ,Randomized controlled trial ,Medicine (General) ,R5-920 - Abstract
Abstract Background Gout is the most common form of rheumatic disease in which monosodium urate crystals are deposited in the joints followed by acute inflammatory reactions. There are various approved drugs that can be prescribed for pain relief during an acute gout attack. However, to date, no direct comparison of efficacy of colchicine and prednisolone for the treatment of acute gout attacks has been investigated. Furthermore, the majority of previous research studies were not only conducted in tertiary centres but also excluded patients with common comorbidities due to contraindications to naproxen. Methods This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial investigates whether prednisolone (intervention) is non-inferior to treatment with colchicine (active control) in patients with acute gout. Adult patients presenting with acute gout to their general practitioners in 60 practices across 3 university sites (Greifswald, Göttingen, and Würzburg) are eligible to participate in the study. Participants in the intervention group receive 30 mg prednisolone for 5 days. Those in the control group receive low-dose colchicine (day 1: 1.5 mg; days 2–5: 1 mg). The primary outcome is the absolute level of the most severe pain on day 3 (in the last 24 h) measured with an 11-item numerical rating scale. Day 0 is the day patients take their study medication for the first time. They are then asked to fill out a study diary the same time each day for pain quantification. Pain scores are used for comparison between the two medications. Secondary outcomes are average response to treatment, swelling, tenderness and physical function of the joint, patients’ global assessment of treatment success, use of additional pain medication and non-pharmacological pain therapies. For safety reasons, potential side effects and course of systolic blood pressure are assessed. Discussion This trial will provide evidence on the effectiveness of pain reduction and side effects of colchicine and prednisolone in acute gout in primary care. Trial registration ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered). URL of trial registry record: https://clinicaltrials.gov/study/NCT05698680
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- 2023
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5. Impact of advanced age on the gastric emptying of water under fasted and fed state conditions
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Tzakri, Theodora, Senekowitsch, Stefan, Wildgrube, Toni, Sarwinska, Dorota, Krause, Julius, Schick, Philipp, Grimm, Michael, Engeli, Stefan, and Weitschies, Werner
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- 2024
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6. Prednisolone Versus Colchicine for Acute Gout in Primary Care (COPAGO): protocol for a two-arm multicentre, pragmatic, prospective, randomized, double-blind, controlled clinical trial of prednisolone and colchicine for non-inferiority with a parallel group design
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Truthmann, Julia, Freyer Martins Pereira, Julia, Richter, Adrian, Schuster, Franziska, Witte, Amelie, Böhm, Susanne, Greser, Alexandra, Kamin, Petra, Stracke, Sylvia, Dörr, Marcus, Bülow, Robin, Engeli, Stefan, Gágyor, Ildikó, Hummers, Eva, and Chenot, Jean-François
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- 2023
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7. Neurometabolic profile of the amygdala in smokers assessed with 1H-magnetic resonance spectroscopy
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Colette A Steinegger, Niklaus Zoelch, Andreas Hock, Anke Henning, Etna JE Engeli, Christopher R Pryce, Erich Seifritz, Marcus Herdener, and Lea M Hulka
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Amygdala ,Glutamate ,Glutamine ,Magnetic resonance spectroscopy ,Nicotine addiction ,Smoking ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Tobacco smoking is one of the main causes of premature death worldwide and quitting success remains low, highlighting the need to understand the neurobiological mechanisms underlying relapse. Preclinical models have shown that the amygdala and glutamate play an important role in nicotine addiction. The aims of this study were to compare glutamate and other metabolites in the amygdala between smokers and controls, and between different smoking states. Furthermore, associations between amygdalar metabolite levels and smoking characteristics were explored.A novel non-water-suppressed proton magnetic resonance spectroscopy protocol was applied to quantify neurometabolites in 28 male smokers (≥15 cigarettes/day) and 21 non-smoking controls, matched in age, education, verbal IQ, and weekly alcohol consumption. Controls were measured once (baseline) and smokers were measured in a baseline state (1–3 h abstinence), during withdrawal (24 h abstinence) and in a satiation state (directly after smoking). Baseline spectroscopy data were compared between groups by independent t-tests or Mann-Whitney-U tests. Smoking state differences were investigated by repeated-measures analyses of variance (ANOVAs). Associations between spectroscopy data and smoking characteristics were explored using Spearman correlations.Good spectral quality, high anatomical specificity (98% mean gray matter) and reliable quantification of most metabolites of interest were achieved in the amygdala. Metabolite levels did not differ between groups, but smokers showed significantly higher glutamine levels at baseline than satiation. Glx levels were negatively associated with pack-years and smoking duration.In summary, this study provides first insights into the neurometabolic profile of the amygdala in smokers with high anatomical specificity. By applying proton magnetic resonance spectroscopy, neurometabolites in smokers during different smoking states and non-smoking controls were quantified reliably. A significant shift in glutamine levels between smoking states was detected, with lower concentrations in satiation than baseline. The negative association between Glx levels and smoking quantity and duration may imply altered glutamate homeostasis with more severe nicotine addiction.
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- 2024
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8. Neurometabolic profile of the amygdala in smokers assessed with 1H-magnetic resonance spectroscopy
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Steinegger, Colette A, Zoelch, Niklaus, Hock, Andreas, Henning, Anke, Engeli, Etna JE, Pryce, Christopher R, Seifritz, Erich, Herdener, Marcus, and Hulka, Lea M
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- 2024
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9. Clinical-pharmacological drug information center of Hannover Medical School: experiences and analysis from a tertiary care university hospital
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Johannes Heck, Dirk O. Stichtenoth, Ruxandra Sabau, Christoph Schröder, Stefan Engeli, Thorben Pape, Nina O’Connell, Carsten Schumacher, Olaf Krause, and Felix Koop
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Medicine ,Science - Abstract
Abstract Drug information centers (DICs) are institutions dedicated to provide objective, independent, and up-to-date information on drugs and their rational use. To overcome the lack of recent DIC reports from central Europe, we analyzed all queries (n = 594) submitted to the DIC run by the Institute for Clinical Pharmacology of Hannover Medical School between October 2018 and April 2022. Approximately one in three queries (31.1%; 185/594) was submitted by internists. 82.8% (492/594) of the queries were patient-specific, while the remaining 17.2% (102/594) were general queries. Adverse drug reactions (ADRs), indications/contraindications, and pharmacodynamic interactions (PDIs) represented the three most frequently addressed query categories, being involved in 44.8% (266/594), 43.3% (257/594), and 34.3% (204/594) of all queries, respectively (assignment of more than one category per query was possible). As compared to general queries, patient-specific queries were statistically significantly more often related to ADRs, PDIs, and pharmacokinetic interactions (PKIs) (ADRs: 35.3% vs. 46.7%, P = 0.034; PDIs: 14.7% vs. 38.4%, P
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- 2022
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10. Cue-induced cocaine craving enhances psychosocial stress and vice versa in chronic cocaine users
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Ann-Kathrin Kexel, Bruno Kluwe-Schiavon, Markus R. Baumgartner, Etna J. E. Engeli, Monika Visentini, Clemens Kirschbaum, Erich Seifritz, Beate Ditzen, Leila M. Soravia, and Boris B. Quednow
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Abstract Stress and craving, it has been found, contribute to the development and maintenance of and relapse in cocaine use disorder. Chronic cocaine users (CU), previous research has shown, display altered physiological responses to psychosocial stress and increased vegetative responding to substance-related cues. However, how psychosocial stress and cue-induced craving interact in relation to the CU’s physiological responses remains largely unknown. We thus investigated the interaction between acute psychosocial stress and cocaine-cue-related reactivity in 47 CU and 38 controls. In a crossed and balanced design, the participants were randomly exposed to a video-based cocaine-cue paradigm and the Trier Social Stress Test (TSST) or vice versa to investigate possible mutually augmenting effects of both stressors on physiological stress responses. Over the course of the experimental procedure, plasma cortisol, ACTH, noradrenaline, subjective stress, and craving were assessed repeatedly. To estimate the responses during the cocaine-cue paradigm and TSST, growth models and discontinuous growth models were used. Overall, though both groups did not differ in their endocrinological responses to the TSST, CU displayed lower ACTH levels at baseline. The TSST did not elevate craving in CU, but when the cocaine-cue video was shown first, CU displayed an enhanced cortisol response to the subsequent TSST. In CU, cocaine-cues robustly evoked craving but no physiological stress response, while cue-induced craving was intensified after the TSST. Taken together, though CU did not show an altered acute stress response during the TSST, stress and craving together seemed to have mutually augmenting effects on their stress response.
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- 2022
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11. Evaluation of the genotoxic potential of acrylamide: Arguments for the derivation of a tolerable daily intake (TDI value)
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Guth, Sabine, Baum, Matthias, Cartus, Alexander T., Diel, Patrick, Engel, Karl-Heinz, Engeli, Barbara, Epe, Bernd, Grune, Tilman, Haller, Dirk, Heinz, Volker, Hellwig, Michael, Hengstler, Jan G., Henle, Thomas, Humpf, Hans-Ulrich, Jäger, Henry, Joost, Hans-Georg, Kulling, Sabine E., Lachenmeier, Dirk W., Lampen, Alfonso, Leist, Marcel, Mally, Angela, Marko, Doris, Nöthlings, Ute, Röhrdanz, Elke, Roth, Angelika, Spranger, Joachim, Stadler, Richard, Steinberg, Pablo, Vieths, Stefan, Wätjen, Wim, and Eisenbrand, Gerhard
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- 2023
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12. Accumbal-thalamic connectivity and associated glutamate alterations in human cocaine craving: A state-dependent rs-fMRI and 1H-MRS study
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Engeli, Etna J.E., Russo, Andrea G., Ponticorvo, Sara, Zoelch, Niklaus, Hock, Andreas, Hulka, Lea M., Kirschner, Matthias, Preller, Katrin H., Seifritz, Erich, Quednow, Boris B., Esposito, Fabrizio, and Herdener, Marcus
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- 2023
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13. An analysis of 45 large-scale wastewater sites in England to estimate SARS-CoV-2 community prevalence
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Mario Morvan, Anna Lo Jacomo, Celia Souque, Matthew J. Wade, Till Hoffmann, Koen Pouwels, Chris Lilley, Andrew C. Singer, Jonathan Porter, Nicholas P. Evens, David I. Walker, Joshua T. Bunce, Andrew Engeli, Jasmine Grimsley, Kathleen M. O’Reilly, and Leon Danon
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Science - Abstract
Wastewater surveillance could provide a means of monitoring SARS-CoV-2 prevalence that does not rely on testing individuals. Here, the authors report results from England’s national wastewater surveillance program, use it to estimate prevalence, and compare estimates with those from population-based prevalence surveys.
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- 2022
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14. Course of disease and risk factors for hospitalization in outpatients with a SARS-CoV-2 infection
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Eik Schäfer, Christian Scheer, Karen Saljé, Anja Fritz, Thomas Kohlmann, Nils-Olaf Hübner, Matthias Napp, Lizon Fiedler-Lacombe, Dana Stahl, Bernhard Rauch, Matthias Nauck, Uwe Völker, Stephan Felix, Guglielmo Lucchese, Agnes Flöel, Stefan Engeli, Wolfgang Hoffmann, Klaus Hahnenkamp, and Mladen V. Tzvetkov
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Medicine ,Science - Abstract
Abstract We analyzed symptoms and comorbidities as predictors of hospitalization in 710 outpatients in North-East Germany with PCR-confirmed SARS-CoV-2 infection. During the first 3 days of infection, commonly reported symptoms were fatigue (71.8%), arthralgia/myalgia (56.8%), headache (55.1%), and dry cough (51.8%). Loss of smell (anosmia), loss of taste (ageusia), dyspnea, and productive cough were reported with an onset of 4 days. Anosmia or ageusia were reported by only 18% of the participants at day one, but up to 49% between days 7 and 9. Not all participants who reported ageusia also reported anosmia. Individuals suffering from ageusia without anosmia were at highest risk of hospitalization (OR 6.8, 95% CI 2.5–18.1). They also experienced more commonly dyspnea and nausea (OR of 3.0, 2.9, respectively) suggesting pathophysiological connections between these symptoms. Other symptoms significantly associated with increased risk of hospitalization were dyspnea, vomiting, and fever. Among basic parameters and comorbidities, age > 60 years, COPD, prior stroke, diabetes, kidney and cardiac diseases were also associated with increased risk of hospitalization. In conclusion, due to the delayed onset, ageusia and anosmia may be of limited use in differential diagnosis of SARS-CoV-2. However, differentiation between ageusia and anosmia may be useful for evaluating risk for hospitalization.
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- 2022
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15. Accumbal-thalamic connectivity and associated glutamate alterations in human cocaine craving: A state-dependent rs-fMRI and 1H-MRS study
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Etna J.E. Engeli, Andrea G. Russo, Sara Ponticorvo, Niklaus Zoelch, Andreas Hock, Lea M. Hulka, Matthias Kirschner, Katrin H. Preller, Erich Seifritz, Boris B. Quednow, Fabrizio Esposito, and Marcus Herdener
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Cocaine craving ,Nucleus accumbens ,Prefrontal cortex ,Thalamus ,Functional connectivity ,Glutamate ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Craving is a core symptom of cocaine use disorder and a major factor for relapse risk. To date, there is no pharmacological therapy to treat this disease or at least to alleviate cocaine craving as a core symptom. In animal models, impaired prefrontal-striatal signalling leading to altered glutamate release in the nucleus accumbens appear to be the prerequisite for cocaine-seeking. Thus, those network and metabolic changes may constitute the underlying mechanisms for cocaine craving and provide a potential treatment target. In humans, there is recent evidence for corresponding glutamatergic alterations in the nucleus accumbens, however, the underlying network disturbances that lead to this glutamate imbalance remain unknown. In this state-dependent randomized, placebo-controlled, double-blinded, cross-over multimodal study, resting state functional magnetic resonance imaging in combination with small-voxel proton magnetic resonance spectroscopy (voxel size: 9.4 × 18.8 × 8.4 mm3) was applied to assess network-level and associated neurometabolic changes during a non-craving and a craving state, induced by a custom-made cocaine-cue film, in 18 individuals with cocaine use disorder and 23 healthy individuals. Additionally, we assessed the potential impact of a short-term challenge of N-acetylcysteine, known to normalize disturbed glutamate homeostasis and to thereby reduce cocaine-seeking in animal models of addiction, compared to a placebo. We found increased functional connectivity between the nucleus accumbens and the dorsolateral prefrontal cortex during the cue-induced craving state. However, those changes were not linked to alterations in accumbal glutamate levels. Whereas we additionally found increased functional connectivity between the nucleus accumbens and a midline part of the thalamus during the cue-induced craving state. Furthermore, obsessive thinking about cocaine and the actual intensity of cocaine use were predictive of cue-induced functional connectivity changes between the nucleus accumbens and the thalamus. Finally, the increase in accumbal-thalamic connectivity was also coupled with craving-related glutamate rise in the nucleus accumbens. Yet, N-acetylcysteine had no impact on craving-related changes in functional connectivity. Together, these results suggest that connectivity changes within the fronto-accumbal-thalamic loop, in conjunction with impaired glutamatergic transmission, underlie cocaine craving and related clinical symptoms, pinpointing the thalamus as a crucial hub for cocaine craving in humans.
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- 2023
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16. An analysis of 45 large-scale wastewater sites in England to estimate SARS-CoV-2 community prevalence
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Morvan, Mario, Jacomo, Anna Lo, Souque, Celia, Wade, Matthew J., Hoffmann, Till, Pouwels, Koen, Lilley, Chris, Singer, Andrew C., Porter, Jonathan, Evens, Nicholas P., Walker, David I., Bunce, Joshua T., Engeli, Andrew, Grimsley, Jasmine, O’Reilly, Kathleen M., and Danon, Leon
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- 2022
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17. Clinical-pharmacological drug information center of Hannover Medical School: experiences and analysis from a tertiary care university hospital
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Heck, Johannes, Stichtenoth, Dirk O., Sabau, Ruxandra, Schröder, Christoph, Engeli, Stefan, Pape, Thorben, O’Connell, Nina, Schumacher, Carsten, Krause, Olaf, and Koop, Felix
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- 2022
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18. Cue-induced cocaine craving enhances psychosocial stress and vice versa in chronic cocaine users
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Kexel, Ann-Kathrin, Kluwe-Schiavon, Bruno, Baumgartner, Markus R., Engeli, Etna J. E., Visentini, Monika, Kirschbaum, Clemens, Seifritz, Erich, Ditzen, Beate, Soravia, Leila M., and Quednow, Boris B.
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- 2022
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19. Course of disease and risk factors for hospitalization in outpatients with a SARS-CoV-2 infection
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Schäfer, Eik, Scheer, Christian, Saljé, Karen, Fritz, Anja, Kohlmann, Thomas, Hübner, Nils-Olaf, Napp, Matthias, Fiedler-Lacombe, Lizon, Stahl, Dana, Rauch, Bernhard, Nauck, Matthias, Völker, Uwe, Felix, Stephan, Lucchese, Guglielmo, Flöel, Agnes, Engeli, Stefan, Hoffmann, Wolfgang, Hahnenkamp, Klaus, and Tzvetkov, Mladen V.
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- 2022
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20. Prescriptions for potentially inappropriate medication (PIM)—prevalence and rank list of the most common active substances
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Wohlgemuth, Anne, primary, Michalowsky, Bernhard, additional, Hoffmann, Wolfgang, additional, Platen, Moritz, additional, Engeli, Stefan, additional, Wucherer, Diana, additional, and Ittermann, Till, additional
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- 2024
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21. Low‐fat hypocaloric diet reduces neprilysin in overweight and obese human subjects
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Christine Henke, Sven Haufe, Doreen Ziehl, Stefan R. Bornstein, Jeanette Schulz‐Menger, Martin Heni, Stefan Engeli, Jens Jordan, and Andreas L. Birkenfeld
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Neprilysin ,Hypocaloric low‐fat diet ,Natriuretic peptides ,Heart failure ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims Neprilysin (NEP), a zinc metallopeptidase, degrades a variety of bioactive peptides including natriuretic peptides terminating their biological action on arterial blood pressure and natriuresis. Pharmacological inhibition of NEP reduces mortality in patients with heart failure with reduced ejection fraction. Physiological interventions reducing NEP levels are unknown in humans. Because obesity leads to increased NEP levels and increases the risk for heart failure, we hypothesized that weight loss reduces NEP concentrations in plasma and tissue. Methods and results We randomized overweight to obese human subjects to a low‐fat or low‐carbohydrate hypocaloric 6 month weight loss intervention. Soluble NEP was determined in plasma, and NEP mRNA was analysed from subcutaneous adipose tissue before and after diet. Low‐fat diet‐induced weight loss reduced soluble NEP levels from 0.83 ± 0.18 to 0.72 ± 0.18 μg/L (P = 0.038), while subcutaneous adipose tissue NEP mRNA expression was reduced by both dietary interventions [21% (P = 0.0057) by low‐fat diet and 16% (P = 0.048) by low‐carbohydrate diet]. We also analysed the polymorphisms of the gene coding for NEP, rs9827586 and rs701109, known to be associated with plasma NEP levels. For both single‐nucleotide polymorphisms, minor allele carriers (A/A) had higher baseline plasma NEP levels (rs9827586: β = 0.53 ± 0.23, P
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- 2021
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22. Exploring the weight bias of professionals working in the field of obesity with a mobile IAT: a pilot study
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Tobias Jungnickel, Ute von Jan, Stefan Engeli, and Urs-Vito Albrecht
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Background: Obesity is common in many industrialized nations and often accompanied by related health issues. Furthermore, individuals living with overweight or obesity are often confronted with stigmatization in their daily lives. These problems may be aggravated if the objectivity of health care professionals is compromised due to (unconscious) prejudices. If pharmaceutical companies, regulatory agencies, and health insurers are also susceptible to these biases, decisions related to the development, approval, and reimbursement of obesity-related therapies may be negatively impacted. Materials and Methods: The ‘Implicit Association Test’ (IAT) is a psychometric test allowing to measure these attitudes and could therefore assist to reveal unconscious preferences. A self-developed mobile version, in the form of a ResearchKit-based IAT app was employed in the presented study. The objective was to determine (potential) weight bias and its characteristics for professionals attending a national obesity-related conference in Germany (G1), compared to a control group (without stated interest in the topic, G2) – both using the mobile app – and a historical control (G3) based on data provided by Project Implicit acquired by a web app. Results: Explicit evaluations of G1 were neutral at a higher percentage compared with G2 and G3, while implicit preference toward lean individuals did not differ significantly between G2 and G3, and G1. Conclusion: The greater discrepancy between the (more neutral) explicit attitude and the unconscious preference pointing in the anti-obesity direction could indicate an underestimated bias for the professional participants in G1. Implicit preference is often ingrained from childhood on, and difficult to overcome. Thus, even for professionals, it may unconsciously influence decisions made in the care they provide. Professionals in any given health care sector directed at obesity care should thus be made aware of this inconsistency to enable them to consciously counteract this potential effect.
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- 2022
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23. Intragastric Carbon Dioxide Release Prolongs the Gastric Residence Time of Postprandially Administered Caffeine
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Stefan Senekowitsch, Constantin Foja, Toni Wildgrube, Philipp Schick, Christoph Rosenbaum, Julius Krause, Friederike Brokmann, Marie-Luise Kromrey, Stefan Engeli, Werner Weitschies, and Michael Grimm
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salivary tracer technique ,caffeine ,effervescent granules ,in vivo study ,carbon dioxide ,sparkling water ,Pharmacy and materia medica ,RS1-441 - Abstract
Sparkling water is said to increase gastric motility by the release of carbon dioxide, thereby potentially affecting the pharmacokinetics of orally administered drugs. The hypothesis of the present work was that the induction of gastric motility by intragastric release of carbon dioxide from effervescent granules could promote the mixing of drugs into the chyme under postprandial conditions, resulting in a prolonged drug absorption. For this purpose, an effervescent and a non-effervescent granule formulation of caffeine as a marker for gastric emptying were developed. In a three-way crossover study with twelve healthy volunteers, the salivary caffeine pharmacokinetics, after administration of the effervescent granules with still water and the administration of the non-effervescent granules with still and sparkling water, were investigated after intake of a standard meal. While the administration of the effervescent granules with 240 mL of still water led to a significantly prolonged gastric residence of the substance compared to the administration of the non-effervescent granules with 240 mL still water, the application of the non-effervescent granules with 240 mL sparkling water did not prolong gastric residence via mixing into caloric chyme. Overall, the mixing of caffeine into the chyme following the administration of the effervescent granules did not seem to be a motility mediated process.
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- 2023
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24. Estimating SARS-CoV-2 prevalence from large-scale wastewater surveillance: insights from combined analysis of 44 sites in England
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M. Morvan, A. Lojacomo, C. Souque, M. Wade, T. Hoffmann, K. Pouwels, A. Singer, J. Bunce, A. Engeli, J. Grimsley, K. O'Reilly, and L. Danon
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Infectious and parasitic diseases ,RC109-216 - Abstract
Purpose: Accurate surveillance of the COVID-19 pandemic can be weakened by under-reporting of cases, particularly due to asymptomatic or pre-symptomatic infections, resulting in bias. Quantification of SARS-CoV-2 RNA in wastewater (WW) can be used to infer infection prevalence, but uncertainty in sensitivity and considerable variability has meant that accurate measurement remains elusive. Methods & Materials: Data from 44 sewage sites in England, covering 31% of the population, are used in this analysis where samples are available from July 2020 to present day. Samples include the raw SARS-CoV-2 gene copy number and associated meta-data. To establish the sensitivity and specificity of the WW data, we compare to population representative prevalence surveys available across England (the ONS Covid Infection Survey - CIS). The WW data were mapped to sub-regional data of the CIS and fitted using mathematical modelling. First, a phenomenological model was developed to model how infected individuals shed SARS-CoV-2 into WW and how the markers may degrade in time and compare this to the data. Second, we develop a model to estimate SARS-CoV-2 prevalence directly from WW data which is trained on the CIS data. Results: Data from 44 sewage sites in England, shows that SARS-CoV-2 prevalence is estimated to within 1.1% of estimates from representative prevalence surveys (with 95% confidence). Using machine learning and phenomenological models, differences between sampled sites, particularly the WW flow rate, influence prevalence estimation and require careful interpretation. SARS-CoV-2 signals in WW appear 4-5 days earlier in comparison to clinical testing data but are coincident with prevalence surveys suggesting that WW surveillance can be a leading indicator for asymptomatic viral infections. Conclusion: Wastewater-based epidemiology complements and strengthens traditional surveillance, with significant implications for public health. Using WW to quantify infection prevalence requires knowledge of additional meta-data and outbreak detection needs to account for unexplained aberrations in WW data to improve reliability
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- 2022
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25. Design Automation and Additive Manufacturing for Anatomically Diversified Medical Simulators
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Klahn, Christoph, Bührer, Kaspar, Engeli, Reto, and Meboldt, Mirko
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- 2020
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26. Self-regulation of the dopaminergic reward circuit in cocaine users with mental imagery and neurofeedbackResearch in Context
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Matthias Kirschner, Ronald Sladky, Amelie Haugg, Philipp Stämpfli, Elisabeth Jehli, Martina Hodel, Etna Engeli, Sarah Hösli, Markus R. Baumgartner, James Sulzer, Quentin J.M. Huys, Erich Seifritz, Boris B. Quednow, Frank Scharnowski, and Marcus Herdener
- Subjects
Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Enhanced drug-related reward sensitivity accompanied by impaired sensitivity to non-drug related rewards in the mesolimbic dopamine system are thought to underlie the broad motivational deficits and dysfunctional decision-making frequently observed in cocaine use disorder (CUD). Effective approaches to modify this imbalance and reinstate non-drug reward responsiveness are urgently needed. Here, we examined whether cocaine users (CU) can use mental imagery of non-drug rewards to self-regulate the ventral tegmental area and substantia nigra (VTA/SN). We expected that obsessive and compulsive thoughts about cocaine consumption would hamper the ability to self-regulate the VTA/SN activity and tested if real-time fMRI (rtfMRI) neurofeedback (NFB) can improve self-regulation of the VTA/SN. Methods: Twenty-two CU and 28 healthy controls (HC) were asked to voluntarily up-regulate VTA/SN activity with non-drug reward imagery alone, or combined with rtfMRI NFB. Results: On a group level, HC and CU were able to activate the dopaminergic midbrain and other reward regions with reward imagery. In CU, the individual ability to self-regulate the VTA/SN was reduced in those with more severe obsessive-compulsive drug use. NFB enhanced the effect of reward imagery but did not result in transfer effects at the end of the session. Conclusion: CU can voluntary activate their reward system with non-drug reward imagery and improve this ability with rtfMRI NFB. Combining mental imagery and rtFMRI NFB has great potential for modifying the maladapted reward sensitivity and reinstating non-drug reward responsiveness. This motivates further work to examine the use of rtfMRI NFB in the treatment of CUD. Keywords: Cocaine use disorder, Dopamine, Mental imagery, Neurofeedback, Real-time fMRI, Reward sensitivity, Treatment
- Published
- 2018
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27. A Riemann-Roch-Hirzebruch formula for traces of differential operators
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Engeli, Markus and Felder, Giovanni
- Subjects
Mathematics - Quantum Algebra ,Mathematics - Algebraic Geometry - Abstract
Let D be a holomorphic differential operator acting on sections of a holomorphic vector bundle on an n-dimensional compact complex manifold. We prove a formula, conjectured by Feigin and Shoikhet, for the Lefschetz number of D as the integral over the manifold of a differential form. The class of this differential form is obtained via formal differential geometry from the canonical generator of the Hochschild cohomology of the algebra of differential operators in a formal neighbourhood of a point. If D is the identity, the formula reduces to the Riemann--Roch--Hirzebruch formula., Comment: 31 pages, 1 figure. Misprints corrected and appendix with analytical details added in v3
- Published
- 2007
28. Neural mapping of anhedonia across psychiatric diagnoses: A transdiagnostic neuroimaging analysis
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Anna-Chiara Schaub, Matthias Kirschner, Nina Schweinfurth, Laura Mählmann, Cedric Kettelhack, Etna E. Engeli, Jessica P.K. Doll, Stefan Borgwardt, Undine E. Lang, Stefan Kaiser, Marc Walter, Marcus Herdener, Johannes Wrege, and André Schmidt
- Subjects
Anhedonia ,Transdiagnostic ,Neuroimaging ,Neural correlate ,Putamen ,Cerebellum ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Anhedonia has been associated with abnormal reward-related striatal dopamine functioning in patients with different psychiatric disorders. Here, we tested whether anhedonia expression mapped onto striatal volume across several psychiatric diagnoses.T1-weighted images from 313 participants including 89 healthy controls (HC), 22 patients with opioid use disorder (OUD), 50 patients with major depressive disorder (MDD), 45 patients with borderline personality disorder (BPD), 49 patients with first-episode psychosis (FEP), 43 patients with cocaine use disorder (CUD) and 15 patients with schizophrenia (SZ) were included. Anhedonia was assessed with subscores of the Beck Depression Inventory (BDI) and/or the Scale for the Assessment of Negative Symptoms (SANS). Voxel-based morphometry (VBM) was conducted for identifying dimensional symptom-structure associations using region of interest (ROI, dorsal and ventral striatum) and whole-brain analyses, as well as for group comparisons of striatal volume.ROI analyses revealed significant negative relationships between putamen volume and BDI and SANS anhedonia scores across OUD, MDD, BPD, CUD and SZ patients (n = 175) and MDD, FEP and SZ patients (n = 114), respectively. Whole-brain VBM analyses confirmed these associations and further showed negative relationships between anhedonia severity and volume of the bilateral cerebellum. There were group differences in right accumbens volume, which however were not related to anhedonia expression across the different diagnoses.Our findings indicate volumetric abnormalities in the putamen and cerebellum as a common neural substrate of anhedonia severity that cut across psychiatric entities.
- Published
- 2021
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29. Currently available murine Leydig cell lines can be applied to study early steps of steroidogenesis but not testosterone synthesis
- Author
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Engeli, Roger T., Fürstenberger, Cornelia, Kratschmar, Denise V., and Odermatt, Alex
- Published
- 2018
- Full Text
- View/download PDF
30. Trends in COVID-19 Vaccination Intent, Determinants and Reasons for Vaccine Hesitancy: Results from Repeated Cross-Sectional Surveys in the Adult General Population of Greece during November 2020–June 2021
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Vana Sypsa, Sotirios Roussos, Vasiliki Engeli, Dimitrios Paraskevis, Sotirios Tsiodras, and Angelos Hatzakis
- Subjects
COVID-19 ,vaccination intention ,vaccination hesitancy ,repeated cross-sectional surveys ,Medicine - Abstract
Vaccine hesitancy is a major barrier to achieving large-scale COVID-19 vaccination. We report trends in vaccination intention and associated determinants from surveys in the adult general population in Greece. Four cross-sectional phone surveys were conducted in November 2020 and February, April and May 2021 on nationally representative samples of adults in Greece. Multinomial logistic regression was used on the combined data of the surveys to evaluate independent predictors of vaccination unwillingness/uncertainty. Vaccination intention increased from 67.6% in November 2020 to 84.8% in May 2021. Individuals aged 65 years or older were more willing to be vaccinated (May 2021: 92.9% vs. 79.5% in 18–39 years, p < 0.001) but between age-groups differences decreased over time. Vaccination intention increased substantially in both men and women, though earlier among men, and was higher in individuals with prograduate education (May 2021: 91.3% vs. 84.0% up to junior high). From multivariable analysis, unwillingness and/or uncertainty to be vaccinated was associated with younger age, female gender (in particular in the April 2021 survey), lower educational level and living with a child ≤12 years old. Among those with vaccine hesitancy, concerns about vaccine effectiveness declined over time (21.6% in November 2020 vs. 9.6% in May 2021, p = 0.014) and were reported more often by men; safety concerns remained stable over time (66.3% in November 2020 vs. 62.1% in May 2021, p = 0.658) and were reported more often by women. In conclusion, vaccination intention increased substantially over time. Tailored communication is needed to address vaccine hesitancy and concerns regarding vaccine safety.
- Published
- 2022
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31. Quantization of SL(2,R)^* as Bialgebra
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Engeli, Markus R.
- Subjects
Mathematics - Quantum Algebra ,Mathematical Physics - Abstract
We quantize the Poisson-Lie group SL(2,R)^* as a bialgebra using the product of Kontsevich. The coproduct is a deformation of the coproduct that comes from the group structure. The resulting bialgebra structure is isomorphic to the quantum universal enveloping algebra U_hsl(2,R)., Comment: 11 pages, 2 figures, LaTeX2e
- Published
- 2002
32. Modern pharmacological treatment of obese patients
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Marcus May, Christoph Schindler, and Stefan Engeli
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
There are many angles to consider in drug treatment of obese patients. On the one hand, some specific weight loss drugs are available, on the other, several drugs are associated with unintentional weight changes. When treating an obese patient for any given disease, several physiological changes may influence the pharmacokinetic properties of the drugs required. Thus, increased body weight may influence the efficacy and safety of some drug treatments. Even more complicated is the situation after weight reduction surgery. Due to the various changes to the gastrointestinal tract induced by the different surgical techniques used, and the dynamic changes in body composition thereafter, drug dosing has to be constantly reconsidered. Whereas all of these issues are of clinical importance, none of them have been investigated in the necessary depth and broadness to ensure safe and efficacious drug treatment of the massively obese patient. Individual considerations have to be based on comorbidities, concomitant medication, and on specific drug properties, for example, lipophilicity, volume of distribution, and metabolism. In this article we summarize the data available on different aspects of drug treatment in the obese patient with the hope of improving patient care.
- Published
- 2020
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33. Disclosive Data: Who uses it, why, and what difference does it make?
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Andrew Engeli and Aidan Tolland
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Demography. Population. Vital events ,HB848-3697 - Abstract
The Secure Research Service of the Office for National Statistics provides secure access to sensitive detailed data that are not publicly available. It provides access for Approved Researchers working on defined and approved projects, which serve the public good, within the framework of the Digital Economy Act 2017. SRS data can’t be downloaded, but users can access the data at their desk if they are part of a government organisation (subject to connection criteria being met), or in an Office for National Statistics (ONS) approved Safe Setting if not. In this paper, we examine the 2,612 projects that have been run using disclosive data through our service since its inception in 2002, and we map out patterns of data usage. In particular, we are interested in understanding; • Who are the primary users of disclosive data for research (internal ONS, academics, OGD, charities, commercial users)? • What are the primary sectors of research interest for which disclosive data access is requested? (Business, labour market, education, trade, health, population, etc.)? • What are the predominant patterns of team working? (single researcher, multi-researchers)? • What are the methodologies used to analyse the data? • What statistical tools are being used in carrying our projects? • Where are the researchers conducting the analysis based (NUTS1,2,3 classification)? • What are the outputs and impacts of disclosive data research? The paper will conclude by proposing a classification of research projects based on a Hierarchical Cluster Analysis of the dataset collated for this presentation.
- Published
- 2019
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34. The networked researcher, the editorial manager, and the traveller: the profiles of international political scientists and the determinants of internationalisation
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Tronconi F., Engeli I., Tronconi F., and Engeli I.
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Europeanisation ,Political Science and International Relations ,Higher education ,Political science as a profession ,Globalisation - Abstract
The concept of internationalisation, when referring to the work of social scientists within academic institutions, takes on different meanings and involves different activities. This contribution aims to shed light on the international activities of political scientists across Europe and to investigate the various meanings and practices of internationalisation. The analysis relies on the PROSEPS survey, involving some 1,800 political scientists across 37 European countries. We identify three distinct profiles of international scholars: the networked researcher, the editorial manager, and the traveller. These profiles differ according to 1) the building of international research networks, 2) the involvement in the activities of the international publishing industry, 3) the research and teaching exchanges with foreign academic institutions. Determinants, such as gender, family status, career stage, availability of institutional and financial support, and geographical location, are considered as potential drivers or inhibitors of internationalisation. Our analysis shows that the internationalisation of academic practices follows contrasting paths according to the type of international profile.
- Published
- 2022
35. Adipokine concentrations in lipoaspirates may have a role in wound healing
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Christian Herold, Stefan Engeli, Bibiana Beckmann, Peter M. Vogt, and Hans-Oliver Rennekampff
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adipokines ,fat ,lipofilling ,Surgery ,RD1-811 - Abstract
Objectives: In addition to its use as a volume filler, fat grafting may have a potential role in wound healing based on the concentration of growth factors in the lipoaspirate. In this study, we compare the quantitative and qualitative concentration of the various growth factors and adipokines using the Shippert or the Coleman techniques to prepare the lipoaspirate. Methods: We measured leptin, adiponectin and the growth factors, i.e., acidic fibroblast growth factor (aFGF), basic FGF (bFGF), keratinocyte growth factor (KGF), bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) by ELISA in solid and liquid fractions obtained with both techniques in human fat obtained with Coleman technique and Shippert technique. Results: All of these peptides, except BMP-2, were detected in relevant quantities in the solid fraction. The Coleman but not the Shippert technique resulted in statistically higher adiponectin concentrations in the solid tissue fraction. The other four growth factors occurred in significantly higher concentrations in the solid fractions compared to the liquid fractions, independent of the processing technique. Conclusion: In summary, we demonstrated that KGF, aFGF, bFGF and VEGF, as well as leptin and adiponectin, are contained in fat suspensions obtained by liposuction and in the supernatant. Only the concentration of adiponectin was in the range reported to contribute to wound healing.
- Published
- 2017
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36. Salivary nitrate/nitrite and acetaldehyde in humans: potential combination effects in the upper gastrointestinal tract and possible consequences for the in vivo formation of N-nitroso compounds—a hypothesis
- Author
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Gerhard Eisenbrand, Matthias Baum, Alexander T. Cartus, Patrick Diel, Karl-Heinz Engel, Barbara Engeli, Bernd Epe, Tilman Grune, Sabine Guth, Dirk Haller, Volker Heinz, Michael Hellwig, Jan G. Hengstler, Thomas Henle, Hans-Ulrich Humpf, Henry Jäger, Hans-Georg Joost, Sabine Kulling, Dirk W. Lachenmeier, Alfonso Lampen, Marcel Leist, Angela Mally, Doris Marko, Ute Nöthlings, Elke Röhrdanz, Angelika Roth, Joachim Spranger, Richard Stadler, Stefan Vieths, Wim Wätjen, and Pablo Steinberg
- Subjects
Upper Gastrointestinal Tract ,Nitrates ,ddc:570 ,Health, Toxicology and Mutagenesis ,Humans ,Acetaldehyde ,General Medicine ,Saliva ,Toxicology ,Nitrites ,Nitrate, Nitrite, Acetaldehyde, N-nitroso compounds, Upper gastrointestinal tract, Combination effects ,Nitroso Compounds - Abstract
Subsequent to the dietary uptake of nitrate/nitrite in combination with acetaldehyde/ethanol, combination effects resulting from the sustained endogenous exposure to nitrite and acetaldehyde may be expected. This may imply locoregional effects in the upper gastrointestinal tract as well as systemic effects, such as a potential influence on endogenous formation of N-nitroso compounds (NOC). Salivary concentrations of the individual components nitrate and nitrite and acetaldehyde are known to rise after ingestion, absorption and systemic distribution, thereby reflecting their respective plasma kinetics and parallel secretion through the salivary glands as well as the microbial/enzymatic metabolism in the oral cavity. Salivary excretion may also occur with certain drug molecules and food constituents and their metabolites. Therefore, putative combination effects in the oral cavity and the upper digestive tract may occur, but this has remained largely unexplored up to now. In this Guest Editorial, published evidence on exposure levels and biokinetics of nitrate/nitrite/NOx, NOC and acetaldehyde in the organism is reviewed and knowledge gaps concerning combination effects are identified. Research is suggested to be initiated to study the related unresolved issues. published
- Published
- 2022
37. Intragastric Carbon Dioxide Release Prolongs the Gastric Residence Time of Postprandially Administered Caffeine
- Author
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Senekowitsch, Stefan, primary, Foja, Constantin, additional, Wildgrube, Toni, additional, Schick, Philipp, additional, Rosenbaum, Christoph, additional, Krause, Julius, additional, Brokmann, Friederike, additional, Kromrey, Marie-Luise, additional, Engeli, Stefan, additional, Weitschies, Werner, additional, and Grimm, Michael, additional
- Published
- 2023
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38. Does serotonin system stimulation increase pro-social behavior? A comparative pharmacological neuroscientific study in healthy humans
- Author
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Belinger, L., primary, Engeli, E.J.E., additional, Rieser, N.M., additional, Becciolini, L., additional, Herdener, M., additional, and Preller, K.H., additional
- Published
- 2023
- Full Text
- View/download PDF
39. Simplifying cannabis use disorder screening: exploring motives for cannabis use and demographic factors
- Author
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Heckel, N., primary, Nordt, C., additional, Engeli, E.J.E., additional, and Herdener, M., additional
- Published
- 2023
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40. Züri Can – a pilot project to foster low-risk cannabis use within the novel Swiss regulatory framework
- Author
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Nordt, C., primary, Engeli, E.J.E., additional, Heckel, N., additional, Buschner, M., additional, Duerler, P., additional, and Herdener, M., additional
- Published
- 2023
- Full Text
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41. N-acetylcysteine modulates prefrontal response to cocaine cues
- Author
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Engeli, E., primary, Preller, K.H., additional, Rieser, N.M., additional, Klar, J., additional, Zoelch, N., additional, Hock, A., additional, Staempfli, P., additional, Hulka, L.M., additional, Kirschner, M., additional, Seifritz, E., additional, Quednow, B.B., additional, and Herdener, M., additional
- Published
- 2023
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42. Tax harmonization in the European Union and the eurozone: a multilateral analysis of tax systems
- Author
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Sonja Engeli Pippin and Mehmet Serkan Tosun
- Subjects
tax harmonization ,tax burden ,European Union ,eurozone ,fiscal decentralization ,tax systems ,Finance ,HG1-9999 - Abstract
This exploratory study takes a new look at the tax systems of countries in the Organisation of Economic Co-operation and Development (OECD). We measure a country’s tax system using time-series cross-sectional data on tax collection variables as well as a cross-sectional metric assessing tax administration and enforcement. More specifically, we examine the countries’ (i) overall tax burden, (ii) income tax reliance, and (iii) fiscal decentralization as well as some “non-rate” variables related to tax administration and enforcement. The purpose is to compare European Union (EU) member states and those countries in the eurozone with other OECD countries and over time in order to test (1) whether EU member states and eurozone countries have tax systems that are more similar to each other than to other countries, and (2) whether some tax harmonization is taking place - within the EU (eurozone) and other countries. The descriptive analysis and graphical representation, as well as first empirical tests, show that the tax systems of EU member states and eurozone countries are significantly different from other countries’tax systems. Yet, we do not find much tax harmonization in the EU (eurozone) countries over time. Future research might delve more into the question what drives harmonization with the intention of eventually formulating policy strategies.
- Published
- 2016
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43. Longitudinal changes in cocaine intake and cognition are linked to cortical thickness adaptations in cocaine users
- Author
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Sarah Hirsiger, Jürgen Hänggi, Jürgen Germann, Matthias Vonmoos, Katrin H. Preller, Etna J.E. Engeli, Matthias Kirschner, Caroline Reinhard, Lea M. Hulka, Markus R. Baumgartner, Mallar M. Chakravarty, Erich Seifritz, Marcus Herdener, and Boris B. Quednow
- Subjects
Computer applications to medicine. Medical informatics ,R858-859.7 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: Cocaine use has been consistently associated with decreased gray matter volumes in the prefrontal cortex. However, it is unclear if such neuroanatomical abnormalities depict either pre-existing vulnerability markers or drug-induced consequences. Thus, this longitudinal MRI study investigated neuroplasticity and cognitive changes in relation to altered cocaine intake. Methods: Surface-based morphometry, cocaine hair concentration, and cognitive performance were measured in 29 cocaine users (CU) and 38 matched controls at baseline and follow-up. Based on changes in hair cocaine concentration, CU were classified either as Decreasers (n = 15) or Sustained Users (n = 14). Surface-based morphometry measures did not include regional tissue volumes. Results: At baseline, CU displayed reduced cortical thickness (CT) in lateral frontal regions, and smaller cortical surface area (CSA) in the anterior cingulate cortex, compared to controls. In Decreasers, CT of the lateral frontal cortex increased whereas CT within the same regions tended to further decrease in Sustained Users. In contrast, no changes were found for CSA and subcortical structures. Changes in CT were linked to cognitive performance changes and amount of cocaine consumed over the study period. Conclusions: These results suggest that frontal abnormalities in CU are partially drug-induced and can recover with decreased substance use. Moreover, recovery of frontal CT is accompanied by improved cognitive performance confirming that cognitive decline associated with cocaine use is potentially reversible. Keywords: Cognition, Endophenotype, Cocaine-related disorders, Prefrontal cortex
- Published
- 2019
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44. Processability of different IN738LC powder batches by selective laser melting
- Author
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Engeli, Roman, Etter, Thomas, Hövel, Simone, and Wegener, Konrad
- Published
- 2016
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45. Evaluation of the genotoxic potential of acrylamide : Arguments for the derivation of a tolerable daily intake (TDI value)
- Author
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Sabine Guth, Matthias Baum, Alexander T. Cartus, Patrick Diel, Karl-Heinz Engel, Barbara Engeli, Bernd Epe, Tilman Grune, Dirk Haller, Volker Heinz, Michael Hellwig, Jan G. Hengstler, Thomas Henle, Hans-Ulrich Humpf, Henry Jäger, Hans-Georg Joost, Sabine E. Kulling, Dirk W. Lachenmeier, Alfonso Lampen, Marcel Leist, Angela Mally, Doris Marko, Ute Nöthlings, Elke Röhrdanz, Angelika Roth, Joachim Spranger, Richard Stadler, Pablo Steinberg, Stefan Vieths, Wim Wätjen, and Gerhard Eisenbrand
- Subjects
Non-linear dose response ,Tolerable daily intake ,Genotoxic carcinogen ,Thresholded MoA ,Risk assessment ,Acrylamide ,ddc:570 ,Acrylamide, Non-linear dose response, Genotoxic carcinogen, Thresholded MoA, Risk assessment, Tolerable daily intake ,General Medicine ,Toxicology ,Food Science - Abstract
This opinion of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) presents arguments for an updated risk assessment of diet-related exposure to acrylamide (AA), based on a critical review of scientific evidence relevant to low dose exposure. The SKLM arrives at the conclusion that as long as an appropriate exposure limit for AA is not exceeded, genotoxic effects resulting in carcinogenicity are unlikely to occur. Based on the totality of the evidence, the SKLM considers it scientifically justified to derive a tolerable daily intake (TDI) as a health-based guidance value. published
- Published
- 2023
46. Ultrafine particles and ozone perturb norepinephrine clearance rather than centrally generated sympathetic activity in humans
- Author
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Heusser, Karsten, Tank, Jens, Holz, Olaf, May, Marcus, Brinkmann, Julia, Engeli, Stefan, Diedrich, André, Framke, Theodor, Koch, Armin, Großhennig, Anika, Jan Danser, A. H., Sweep, Fred C. G. J., Schindler, Christoph, Schwarz, Katharina, Krug, Norbert, Jordan, Jens, and Hohlfeld, Jens M.
- Published
- 2019
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47. High Intensity High Volume Interval Training Improves Endurance Performance and Induces a Nearly Complete Slow-to-Fast Fiber Transformation on the mRNA Level
- Author
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Julian Eigendorf, Marcus May, Jan Friedrich, Stefan Engeli, Norbert Maassen, Gerolf Gros, and Joachim D. Meissner
- Subjects
energy metabolism ,interval training ,myosin heavy chain ,performance parameter ,muscular aerobic capacity ,systemic aerobic capacity ,Physiology ,QP1-981 - Abstract
We present here a longitudinal study determining the effects of two 3 week-periods of high intensity high volume interval training (HIHVT) (90 intervals of 6 s cycling at 250% maximum power, Pmax/24 s) on a cycle ergometer. HIHVT was evaluated by comparing performance tests before and after the entire training (baseline, BSL, and endpoint, END) and between the two training sets (intermediate, INT). The mRNA expression levels of myosin heavy chain (MHC) isoforms and markers of energy metabolism were analyzed in M. vastus lateralis biopsies by quantitative real-time PCR. In incremental tests peak power (Ppeak) was increased, whereas V˙O2peak was unaltered. Prolonged time-to-exhaustion was found in endurance tests with 65 and 80% Pmax at INT and END. No changes in blood levels of lipid metabolites were detected. Training-induced decreases of hematocrit indicate hypervolemia. A shift from slow MHCI/β to fast MHCIIa mRNA expression occurred after the first and second training set. The mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), a master regulator of oxidative energy metabolism, decreased after the second training set. In agreement, a significant decrease was also found for citrate synthase mRNA after the second training set, indicating reduced oxidative capacity. However, mRNA expression levels of glycolytic marker enzyme glyceraldehyde-3-phosphate dehydrogenase did not change after the first and second training set. HIHVT induced a nearly complete slow-to-fast fiber type transformation on the mRNA level, which, however, cannot account for the improvements of performance parameters. The latter might be explained by the well-known effects of hypervolemia on exercise performance.
- Published
- 2018
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48. Modeling Chronic Toxicity: A Comparison of Experimental Variability With (Q)SAR/Read-Across Predictions
- Author
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Christoph Helma, David Vorgrimmler, Denis Gebele, Martin Gütlein, Barbara Engeli, Jürg Zarn, Benoit Schilter, and Elena Lo Piparo
- Subjects
(Q)SAR ,read-across ,LOAEL ,experimental variability ,lazar ,Therapeutics. Pharmacology ,RM1-950 - Abstract
This study compares the accuracy of (Q)SAR/read-across predictions with the experimental variability of chronic lowest-observed-adverse-effect levels (LOAELs) from in vivo experiments. We could demonstrate that predictions of the lazy structure-activity relationships (lazar) algorithm within the applicability domain of the training data have the same variability as the experimental training data. Predictions with a lower similarity threshold (i.e., a larger distance from the applicability domain) are also significantly better than random guessing, but the errors to be expected are higher and a manual inspection of prediction results is highly recommended.
- Published
- 2018
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49. Currently available murine Leydig cell lines can be applied to study early steps of steroidogenesis but not testosterone synthesis
- Author
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Roger T. Engeli, Cornelia Fürstenberger, Denise V. Kratschmar, and Alex Odermatt
- Subjects
Endocrinology ,Pharmaceutical science ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Androgen biosynthesis in males occurs to a large extent in testicular Leydig cells. This study focused on the evaluation of three murine Leydig cell lines as potential screening tool to test xenobiotics interfering with gonadal androgen synthesis. The final step of testosterone (T) production in Leydig cells is catalyzed by the enzyme 17β-hydroxysteroid dehydrogenase 3 (17β-hsd3). The endogenous 17β-hsd3 mRNA expression and Δ4-androstene-3,17-dione (AD) to T conversion were determined in the murine cell lines MA-10, BLTK1 and TM3. Additionally, effects of 8-Br-cAMP and forskolin stimulation on steroidogenesis and T production were analyzed. Steroids were quantified in supernatants of cells using liquid chromatography–tandem mass spectrometry. Unstimulated cells incubated with AD produced only very low T but substantial amounts of the inactive androsterone. Stimulated cells produced low amounts of T, moderate amounts of AD, but high amounts of progesterone. Gene expression analyses revealed barely detectable 17β-hsd3 levels, absence of 17β-hsd5 (Akr1c6), but substantial 17β-hsd1 expression in all three cell lines. Thus, MA-10, BLTK1 and TM3 cells are not suitable to study the expression and activity of the gonadal T synthesizing enzyme 17β-hsd3. The low T production reported in stimulated MA-10 cells are likely a result of the expression of 17β-hsd1. This study substantiates that the investigated Leydig cell lines MA-10, BLTK1, and TM3 are not suitable to study gonadal androgen biosynthesis due to altered steroidogenic pathways. Furthermore, this study emphasizes the necessity of mass spectrometry-based steroid quantification in experiments using steroidogenic cells such as Leydig cells.
- Published
- 2018
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50. Inhibition of Vascular c‐Jun N‐Terminal Kinase 2 Improves Obesity‐Induced Endothelial Dysfunction After Roux‐en‐Y Gastric Bypass
- Author
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Petia Doytcheva, Thomas Bächler, Erika Tarasco, Vincenzo Marzolla, Michael Engeli, Giovanni Pellegrini, Simona Stivala, Lucia Rohrer, Francesco Tona, Giovanni G. Camici, Paul M. Vanhoutte, Christian M. Matter, Thomas A. Lutz, Thomas F. Lüscher, and Elena Osto
- Subjects
bariatric surgery ,c‐Jun N‐terminal kinase ,endothelial function ,glucagon‐like peptide‐1 ,NO ,obesity ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundRoux‐en‐Y gastric bypass (RYGB) reduces obesity‐associated comorbidities and cardiovascular mortality. RYGB improves endothelial dysfunction, reducing c‐Jun N‐terminal kinase (JNK) vascular phosphorylation. JNK activation links obesity with insulin resistance and endothelial dysfunction. Herein, we examined whether JNK1 or JNK2 mediates obesity‐induced endothelial dysfunction and if pharmacological JNK inhibition can mimic RYGB vascular benefits. Methods and ResultsAfter 7 weeks of a high‐fat high‐cholesterol diet, obese rats underwent RYGB or sham surgery; sham–operated ad libitum–fed rats received, for 8 days, either the control peptide D‐TAT or the JNK peptide inhibitor D‐JNKi‐1 (20 mg/kg per day subcutaneous). JNK peptide inhibitor D‐JNKi‐1 treatment improved endothelial vasorelaxation in response to insulin and glucagon‐like peptide‐1, as observed after RYGB. Obesity increased aortic phosphorylation of JNK2, but not of JNK1. RYGB and JNK peptide inhibitor D‐JNKi‐1 treatment blunted aortic JNK2 phosphorylation via activation of glucagon‐like peptide‐1–mediated signaling. The inhibitory phosphorylation of insulin receptor substrate‐1 was reduced, whereas the protein kinase B/endothelial NO synthase pathway was increased and oxidative stress was decreased, resulting in improved vascular NO bioavailability. ConclusionsDecreased aortic JNK2 phosphorylation after RYGB rapidly improves obesity‐induced endothelial dysfunction. Pharmacological JNK inhibition mimics the endothelial protective effects of RYGB. These findings highlight the therapeutic potential of novel strategies targeting vascular JNK2 against the severe cardiovascular disease associated with obesity.
- Published
- 2017
- Full Text
- View/download PDF
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