المؤلفون: Julia Sauer, Jan Graßhoff, Niklas M. Carbon, Willi M. Koch, Steffen Weber-Carstens, Philipp Rostalski

المصدر: Annals of Intensive Care, Vol 14, Iss 1, Pp 1-14 (2024)

مصطلحات موضوعية: Mechanical ventilation, Patient–ventilator asynchrony, Automation, Surface electromyography, Esophageal pressure, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9

الوصف: Abstract Background Characterizing patient–ventilator interaction in critically ill patients is time-consuming and requires trained staff to evaluate the behavior of the ventilated patient. Methods In this study, we recorded surface electromyography ( $$\textrm{sEMG}$$ sEMG ) signals from the diaphragm and intercostal muscles and esophageal pressure ( $$P_{\textrm{es}}$$ P es ) in mechanically ventilated patients with ARDS. The sEMG recordings were preprocessed, and two different algorithms (triangle algorithm and adaptive thresholding algorithm) were used to automatically detect inspiratory patient effort. Based on the detected inspirations, major asynchronies (ineffective, auto-, and double triggers and double efforts), delayed and synchronous triggers were computationally classified. Reverse triggers were not considered in this study. Subsequently, asynchrony indices were calculated. For the validation of detected efforts, two experts manually annotated inspiratory patient activity in $$P_{\textrm{es}}$$ P es , blinded toward each other, the $$\textrm{sEMG}$$ sEMG signals, and the algorithmic results. We also classified patient–ventilator interaction and calculated asynchrony indices with manually detected inspirations in $$P_{\textrm{es}}$$ P es as a reference for automated asynchrony classification and asynchrony index calculation. Results Spontaneous breathing activity was recognized in 22 out of the 36 patients included in the study. Evaluation of the accuracy of the algorithms using 3057 inspiratory efforts in $$P_{\textrm{es}}$$ P es demonstrated reliable detection performance for both methods. Across all datasets, we found a high sensitivity (triangle algorithm/adaptive thresholding algorithm: 0.93/0.97) and a high positive predictive value (0.94/0.89) against expert annotations in $$P_{\textrm{es}}$$ P es . The average delay of automatically detected inspiratory onset to the $$P_{\textrm{es}}$$ P es reference was $$-$$ - 79 ms/29 ms for the two algorithms. Our findings also indicate that automatic asynchrony index prediction is reliable. For both algorithms, we found the same deviation of $$0.06\pm 0.13$$ 0.06 ± 0.13 to the $$P_{\textrm{es}}$$ P es -based reference. Conclusions Our study demonstrates the feasibility of automating the quantification of patient–ventilator asynchrony in critically ill patients using noninvasive sEMG. This may facilitate more frequent diagnosis of asynchrony and support improving patient–ventilator interaction.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2110-5820Test

الوصول الحر: https://doaj.org/article/2d7f22b652424178bb510591ea798207Test

المؤلفون: Julia Sauer, Agnes A. Steixner-Kumar, Svenja Gabler, Maciej Motyka, Jörg F. Rippmann, Stefan Brosa, Dennis Boettner, Tanja Schönberger, Charlotte Lempp, Vanessa Frodermann, Eric Simon, Oliver Krenkel, Ehsan Bahrami

المصدر: Frontiers in Immunology, Vol 15 (2024)

مصطلحات موضوعية: NASH - non-alcoholic steatohepatitis, inflammation, monocyte-derived macrophage (MDM), NK cells, liver fibrosis, Immunologic diseases. Allergy, RC581-607

الوصف: Chronic liver diseases, such as non-alcoholic steatohepatitis (NASH)-induced cirrhosis, are characterized by an increasing accumulation of stressed, damaged, or dying hepatocytes. Hepatocyte damage triggers the activation of resident immune cells, such as Kupffer cells (KC), as well as the recruitment of immune cells from the circulation toward areas of inflammation. After infiltration, monocytes differentiate into monocyte-derived macrophages (MoMF) which are functionally distinct from resident KC. We herein aim to compare the in vitro signatures of polarized macrophages and activated hepatic stellate cells (HSC) with ex vivo-derived disease signatures from human NASH. Furthermore, to shed more light on HSC activation and liver fibrosis progression, we investigate the effects of the secretome from primary human monocytes, macrophages, and NK cells on HSC activation. Interleukin (IL)-4 and IL-13 treatment induced transforming growth factor beta 1 (TGF-β1) secretion by macrophages. However, the supernatant transfer did not induce HSC activation. Interestingly, PMA-activated macrophages showed strong induction of the fibrosis response genes COL10A1 and CTGF, while the supernatant of IL-4/IL-13-treated monocytes induced the upregulation of COL3A1 in HSC. The supernatant of PMA-activated NK cells had the strongest effect on COL10A1 induction in HSC, while IL-15-stimulated NK cells reduced the expression of COL1A1 and CTGF. These data indicate that other factors, aside from the well-known cytokines and chemokines, might potentially be stronger contributors to the activation of HSCs and induction of a fibrotic response, indicating a more diverse and complex role of monocytes, macrophages, and NK cells in liver fibrosis progression.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2024.1232070/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/8f49c0488c064420b392c7d96dc7899eTest

المؤلفون: Sarah Bitzer, Mozhgan Dehghan Harati, Karim C. El Kasmi, Daniela Schloesser, Julia Sauer, Heiko Olbrich, Michael Schuler, Florian Gantner, Ralf Heilker

المصدر: SLAS Discovery, Vol 28, Iss 4, Pp 149-162 (2023)

مصطلحات موضوعية: hiPSC-derived macrophages, Upscaling, High-content-imaging, Miniaturization, Efferocytosis, Medicine (General), R5-920, Biotechnology, TP248.13-248.65

الوصف: Macrophages play a pivotal role in drug discovery due to their key regulatory functions in health and disease. Overcoming the limited availability and donor variability of human monocyte-derived macrophages (MDMs), human induced pluripotent stem cell (iPSC)-derived macrophages (IDMs) could provide a promising tool for both disease modeling and drug discovery. To access large numbers of model cells for medium- to high-throughput application purposes, an upscaled protocol was established for differentiation of iPSCs into progenitor cells and subsequent maturation into functional macrophages. These IDM cells resembled MDMs both with respect to surface marker expression and phago- as well as efferocytotic function. A statistically robust high-content-imaging assay was developed to quantify the efferocytosis rate of IDMs and MDMs allowing for measurements both in the 384- and 1536-well microplate format. Validating the applicability of the assay, inhibitors of spleen tyrosine kinase (Syk) were shown to modulate efferocytosis in IDMs and MDMs with comparable pharmacology. The miniaturized cellular assay with the upscaled provision of macrophages opens new routes to pharmaceutical drug discovery in the context of efferocytosis-modulating substances.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2472555223000308Test; https://doaj.org/toc/2472-5552Test

الوصول الحر: https://doaj.org/article/682b49992ecd4d21b4b00356826270d2Test

المؤلفون: Claudia Salm, Julia Sauer, Nadine Binder, Aline Pfefferle, Mario Sofroniou, Gloria Metzner, Erik Farin-Glattacker, Sebastian Voigt-Radloff, Andy Maun

المصدر: BMC Geriatrics, Vol 22, Iss 1, Pp 1-10 (2022)

مصطلحات موضوعية: inappropriate prescribing, potentially inappropriate medications, potential prescribing omissions, polypharmacy, multimorbidity, functional disability, Geriatrics, RC952-954.6

الوصف: Abstract Background Older patients at risk of functional decline are frequently affected by polypharmacy. This is associated with a further loss of independence. However, a relationship between functional disability and medications, such as ‘Potentially Inappropriate Medications’ (PIMs) and ‘Potential Prescribing Omissions’ (PPOs), as itemised for (de) prescribing in practice-orientated medication lists, has yet to be established. Methods As part of a randomised comparative effectiveness trial, LoChro, we conducted a cross-sectional analysis of the association between PIMs and PPOs measured using the ‘Screening Tool of Older Persons’ Prescription Criteria / Screening Tool To Alert to Right Treatment’ (STOPP/START) Version 2, with functional disability assessed using the ‘World Health Organization Disability Assessment Schedule 2.0’ (WHODAS). Individuals aged 65 and older at risk of loss of independence were recruited from the inpatient and outpatient departments of the local university hospital. Multiple linear regression analysis was used to model the potential prediction of functional disability using the numbers of PIMs and PPOs, adjusted for confounders including multimorbidity. Results Out of 461 patients, both the number of PIMs and the number of PPOs were significantly associated with an increase in WHODAS-score (Regression coefficients B 2.7 [95% confidence interval: 1.5-3.8] and 1.5 [95% confidence interval: 0.2-2.7], respectively). In WHODAS-score prediction modelling the contribution of the number of PIMs exceeded the one of multimorbidity (standardised coefficients beta: PIM 0.20; multimorbidity 0.13; PPO 0.10), whereas no significant association between the WHODAS-score and the number of medications was seen. 73.5 % (339) of the participants presented with at least one PIM, and 95.2% (439) with at least one PPO. The most common PIMs were proton pump inhibitors and analgesic medication, with frequent PPOs being pneumococcal and influenza vaccinations, as well as osteoporosis prophylaxis. Conclusions The results indicate a relationship between inappropriate prescribing, both PIMs and PPOs, and functional disability, in older patients at risk of further decline. Long-term analysis may help clarify whether these patients benefit from interventions to reduce PIMs and PPOs.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2318Test

الوصول الحر: https://doaj.org/article/ddd005af925c41ea973a61a4322f3768Test

المؤلفون: Eike Petersen, Julia Sauer, Jan GraBhoff, Philipp Rostalski

المصدر: IEEE Access, Vol 8, Pp 30905-30917 (2020)

مصطلحات موضوعية: Adaptive signal processing, biomedical signal processing, electrocardiography, electromyography, electrophysiology, empirical mode decomposition, Electrical engineering. Electronics. Nuclear engineering, TK1-9971

الوصف: Electromyographic (EMG) measurements of the respiratory muscles provide a convenient and noninvasive way to assess respiratory muscle function and detect patient activity during assisted mechanical ventilation. However, surface EMG measurements of the diaphragm and intercostal muscles are substantially contaminated by cardiac activity due to the vicinity of the cardiac muscles. Many algorithmic solutions to this problem have been proposed, yet a conclusive performance comparison of the most promising candidates currently is missing. The objective of this work is to provide a quantitative performance comparison of six previously proposed cardiac artifact removal algorithms operating on single-channel EMG measurements, and two newly proposed, improved versions of these algorithms. Algorithmic performance is evaluated quantitatively based on four different measures of separation success, using both synthetic validation signals and electromyographic measurements of the respiratory muscles in eight subjects. The compared algorithms are two versions of the empirical template subtraction algorithm, two model-based Bayesian filtering procedures, a wavelet denoising approach, an empirical mode decomposition (EMD) based approach, and classical high-pass filtering. Different algorithms perform well with respect to different performance measures. Template subtraction algorithms yield the best results if the characteristics of the raw signal are of interest, while filtering algorithms like simple high-pass filtering, wavelet denoising, and EMD-based denoising show superior performance for calculating a cleaned envelope signal. No algorithm completely removes the cardiac interference, but the characteristic errors introduced by the considered algorithms differ. Hence, the choice of the algorithm to use should be made depending on the target application. Finally, we also demonstrate that our empirical SNR measure, which can be calculated without knowledge of the true, undisturbed signals, correlates strongly with the exact reconstruction error. Thus, it represents a reliable indicator for algorithm performance on real measurement data.

وصف الملف: electronic resource

العلاقة: https://ieeexplore.ieee.org/document/8988257Test/; https://doaj.org/toc/2169-3536Test

الوصول الحر: https://doaj.org/article/c86c45d959894c58b381f7764baffa20Test

المؤلفون: Julia Sauer, Agnes A. Steixner-Kumar, Svenja Gabler, Maciej Motyka, Jörg F. Rippmann, Stefan Brosa, Dennis Boettner, Tanja Schönberger, Charlotte Lempp, Vanessa Frodermann, Eric Simon, Oliver Krenkel, Ehsan Bahrami

مصطلحات موضوعية: Immunology, Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies), Autoimmunity, Cellular Immunology, Humoural Immunology and Immunochemistry, Immunogenetics (incl. Genetic Immunology), Innate Immunity, Transplantation Immunology, Tumour Immunology, Immunology not elsewhere classified, Genetic Immunology, Animal Immunology, Veterinary Immunology, NASH - non-alcoholic steatohepatitis, inflammation, monocyte-derived macrophage (MDM), NK cells, liver fibrosis

الوصف: Chronic liver diseases, such as non-alcoholic steatohepatitis (NASH)-induced cirrhosis, are characterized by an increasing accumulation of stressed, damaged, or dying hepatocytes. Hepatocyte damage triggers the activation of resident immune cells, such as Kupffer cells (KC), as well as the recruitment of immune cells from the circulation toward areas of inflammation. After infiltration, monocytes differentiate into monocyte-derived macrophages (MoMF) which are functionally distinct from resident KC. We herein aim to compare the in vitro signatures of polarized macrophages and activated hepatic stellate cells (HSC) with ex vivo-derived disease signatures from human NASH. Furthermore, to shed more light on HSC activation and liver fibrosis progression, we investigate the effects of the secretome from primary human monocytes, macrophages, and NK cells on HSC activation. Interleukin (IL)-4 and IL-13 treatment induced transforming growth factor beta 1 (TGF-β1) secretion by macrophages. However, the supernatant transfer did not induce HSC activation. Interestingly, PMA-activated macrophages showed strong induction of the fibrosis response genes COL10A1 and CTGF, while the supernatant of IL-4/IL-13-treated monocytes induced the upregulation of COL3A1 in HSC. The supernatant of PMA-activated NK cells had the strongest effect on COL10A1 induction in HSC, while IL-15-stimulated NK cells reduced the expression of COL1A1 and CTGF. These data indicate that other factors, aside from the well-known cytokines and chemokines, might potentially be stronger contributors to the activation of HSCs and induction of a fibrotic response, indicating a more diverse and complex role of monocytes, macrophages, and NK cells in liver fibrosis progression.

العلاقة: https://figshare.com/articles/dataset/Table_1_Diverse_potential_of_secretome_from_natural_killer_cells_and_monocyte-derived_macrophages_in_activating_stellate_cells_xlsx/25530688Test

الإتاحة: https://doi.org/10.3389/fimmu.2024.1232070.s002Test
https://figshare.com/articles/dataset/Table_1_Diverse_potential_of_secretome_from_natural_killer_cells_and_monocyte-derived_macrophages_in_activating_stellate_cells_xlsx/25530688Test

المؤلفون: Daniela Schloesser, Laura Lindenthal, Julia Sauer, Kyoung-Jin Chung, Triantafyllos Chavakis, Eva Griesser, Praveen Baskaran, Ulrike Maier-Habelsberger, Katrin Fundel-Clemens, Ines Schlotthauer, Carolin Kirsten Watson, Lee Kim Swee, Frederik Igney, John Edward Park, Markus S. Huber-Lang, Matthew-James Thomas, Karim Christian El Kasmi, Peter J. Murray

المصدر: The Journal of cell biology. 222(2)

مصطلحات موضوعية: Mice, Macrophages, Animals, Humans, CD24 Antigen, CD47 Antigen, Apoptosis, Cell Biology, Senescence-Associated Secretory Phenotype, Aminoacyltransferases, Up-Regulation

الوصف: Progressive accrual of senescent cells in aging and chronic diseases is associated with detrimental effects in tissue homeostasis. We found that senescent fibroblasts and epithelia were not only refractory to macrophage-mediated engulfment and removal, but they also paralyzed the ability of macrophages to remove bystander apoptotic corpses. Senescent cell-mediated efferocytosis suppression (SCES) was independent of the senescence-associated secretory phenotype (SASP) but instead required direct contact between macrophages and senescent cells. SCES involved augmented senescent cell expression of CD47 coinciding with increased CD47-modifying enzymes QPCT/L. SCES was reversible by interfering with the SIRPα-CD47-SHP-1 axis or QPCT/L activity. While CD47 expression increased in human and mouse senescent cells in vitro and in vivo, another ITIM-containing protein, CD24, contributed to SCES specifically in human epithelial senescent cells where it compensated for genetic deficiency in CD47. Thus, CD47 and CD24 link the pathogenic effects of senescent cells to homeostatic macrophage functions, such as efferocytosis, which we hypothesize must occur efficiently to maintain tissue homeostasis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a0f12212643337fdd05e29ba8092f43Test
https://pubmed.ncbi.nlm.nih.gov/36459066Test

المؤلفون: Julia Sauer, Tanja Kautenburger, Jeannette Kiefer, Konrad Klaus Richter, Malle Soom, Stefan Wölfl

المساهمون: The Pennsylvania State University CiteSeerX Archives

المصدر: http://carcin.oxfordjournals.org/content/26/6/1064.full.pdfTest.

الوصف: Butyrate may enhance toxicological defence in primary, adenoma and tumor human colon cells by favourably modulating expression of glutathione S-transferases genes, an approach in nutrigenomics

وصف الملف: application/pdf

العلاقة: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.337.2345Test; http://carcin.oxfordjournals.org/content/26/6/1064.full.pdfTest

الإتاحة: http://carcin.oxfordjournals.org/content/26/6/1064.full.pdfTest

المؤلفون: Björn-Ole Stüben, Gabriel A. Plitzko, Julia Sauerbeck, Philipp Busch, Nathaniel Melling, Matthias Reeh, Jakob R. Izbicki, Thomas Rösch, Kai Bachmann, Michael Tachezy

المصدر: Scientific Reports, Vol 13, Iss 1, Pp 1-9 (2023)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract To determine whether a new surgical method using a flexible endoscope (FlexVATS) to perform sparing debridement and apply negative-pressure therapy without extensive decortication may be an alternative treatment option for empyema. Surgical treatment of pleural empyema is associated with considerable postoperative complications and mortality rates, and alternative treatment options are being explored to improve patient outcomes. This was a prospective case series. Seventeen consecutive patients treated with FlexVATS between February 2021 and August 2022 were included in the study. Only patients for whom FlexVATS was the first therapeutic intervention for pleural empyema were included. Treatment success, defined as infection resolution, was the primary endpoint of the study. The secondary endpoints were length of hospital stay, 90-day mortality, and empyema cavity volume reduction. Patients who had previously been treated for pleural empyema by either drainage or surgery were excluded. The trial was performed as a single-centre study at a tertiary medical centre in Germany. In total, 17 patients with pleural empyema were included in the study. The median (IQR) duration of vacuum treatment was 15 days (8–35 days). Twelve of the 17 (71%) patients were successfully treated, and a significant reduction in the empyema cavity volume was observed. 41% of the dressing changes were performed outside the operating room. Compared with a historic cohort of conventionally treated patients (decortication via VATS or thoracotomy), the 90-day mortality rates tended to be lower without reaching statistical significance. Three patients (18%) died in hospital during treatment. No negative pressure-therapy-related complications were observed. FlexVATS therapy is a promising alternative therapy for both healthy and debilitated patients with pleural empyema. Larger randomised trials are required to validate this treatment option.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/3952b185a26040fa90e7b54416bea1edTest

المؤلفون: Stephanie A. Tammen, Gregory G. Dolnikowski, Lynne M. Ausman, Zhenhua Liu, Julia Sauer, FRISO, Simonetta, Sang Woon Choi

المساهمون: Stephanie A., Tammen, Gregory G., Dolnikowski, Lynne M., Ausman, Zhenhua, Liu, Julia, Sauer, Friso, Simonetta, Sang Woon, Choi

مصطلحات موضوعية: epigenetic, DNA methylation, DNA hydroxymethylation, alcohol, liver, ageing, nutrition, gene-nutrient interactions

الوصف: BACKGROUND:Aging and chronic alcohol consumption are both modifiers of DNA methylation, but it is not yet known whether chronic alcohol consumption also alters DNA hydroxymethylation, a newly discovered epigenetic mark produced by oxidation of methylcytosine. Furthermore, it has not been tested whether aging and alcohol interact to modify this epigenetic phenomenon, thereby having an independent effect on gene expression.METHODS:Old (18 months) and young (4 months) male C57BL/6 mice were pair-fed either a Lieber-DeCarli liquid diet with alcohol (18% of energy) or an isocaloric Lieber-DeCarli control diet for 5 weeks. Global DNA hydroxymethylation and DNA methylation were analyzed from hepatic DNA using a new liquid chromatography-tandem mass spectrometry method. Hepatic mRNA expression of the Tet enzymes were measured via quantitative real-time polymerase chain reaction.RESULTS:In young mice, mild chronic alcohol exposure significantly reduced global DNA hydroxymethylation compared with control mice (0.22 ± 0.01 vs. 0.29 ± 0.06%, p = 0.004). Alcohol did not significantly alter hydroxymethylcytosine levels in old mice. Old mice fed the control diet showed decreased global DNA hydroxymethylation compared with young mice fed the control diet (0.24 ± 0.02 vs. 0.29 ± 0.06%, p = 0.04). This model suggests an interaction between aging and alcohol in determining DNA hydroxymethylation (pinteraction = 0.009). Expression of Tet2 and Tet3 was decreased in the old mice relative to the young (p < 0.005).CONCLUSIONS:The observation that alcohol alters DNA hydroxymethylation indicates a new epigenetic effect of alcohol. This is the first study demonstrating the interactive effects of chronic alcohol consumption and aging on DNA hydroxymethylation.

وصف الملف: STAMPA

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/25070523; info:eu-repo/semantics/altIdentifier/wos/WOS:000341181900006; volume:38; issue:8; firstpage:2178; lastpage:2185; numberofpages:8; journal:ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH; http://hdl.handle.net/11562/872603Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84906791160

الإتاحة: https://doi.org/10.1111/acer.12477Test
http://hdl.handle.net/11562/872603Test