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Effect of dynamic light at the coronary care unit on the length of hospital stay and development of delirium： a retrospective cohort study

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Journal of Geriatric Cardiology 2018年第9期15卷 567-573页

作者： tobias Pustjens Antonius MC Schoutens Loes Janssen Wilfred F Heesen Department of Cardiology Division of Cardiology Viecuri Medical Centre Venlo the Netherlands Flux Plus Tilburg the Netherlands Department of Clinical Epidemiology Viecuri Medical Centre Venlo the Netherlands

Background Disturbed circadian rhythm is a potential cause of delirium and is linked to disorganisation of the circadian rhythmicity. Dynamic light （DL） could reset the circadian rhythm by activation of the suprachiasmatic nucleus to prevent delirium. Evidence regarding the effects of light therapy is predominantly focused on psychiatric disorders and circadian rhythm sleep disorders. In this study, we investi- gated the effect of DL on the total hospital length of stay （LOS） and occurrence of delirium in patients admitted to the Coronary Care Unit （CCU）. Methods This was a retrospective cohort study. Patients older than 18 years, who were hospitalized longer than 12 h at the CCU and had a total hospital LOS for at least 24 h, were included. Patients were assigned to a room with DL （n = 369） or regular lighting condi- tions （n = 379）. DL was administered at the CCU by two ceiling-mounted light panels delivering light with a colour temperature between 2700 and 6500 degrees Kelvin. Reported outcome data were： total hospital LOS, delirium incidence, consultation of a geriatrician and the amount of prescripted antipsychotics. Results Between May 2015 and May 2016, data from 748 patients were collected. Baseline charac- teristics, including risk factors provoking delirium, were equal in both groups. Median total hospital LOS in the DL group was 100.5 （70.8-186.0） and 101.0 （73.0-176.4） h in the control group （P = 0.935）. The incidence of delirium in the DL and control group was 5.4% （20/369） and 5.0% （19/379）, respectively （P = 0.802）. No significant differences between the DL and control group were observed in secon- dary endpoints. Subgroup analysis based on age and CCU LOS also showed no differences. Conclusion Our study suggests exposure to DL as an early single approach does not result in a reduction of total hospital LOS or reduced incidence of delirium. When delirium was diagnosed, it was associated with poor hospital outcome.

关键词： Delirium Dynamic light application Length of hospital stay

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Short sequence motif dynamics in the SARS-CoV-2 genome suggest a role for cytosine deamination in CpG reduction

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Journal of Molecular Cell Biology 2021年第3期13卷 225-227页

作者： Mukhtar Sadykov tobias Mourier Qingtian Guan Arnab Pain King Abdullah University of Science and Technology(KAUST) Pathogen Genomics LaboratoryBiological and Environmental Science and Engineering(BESE)Thuwal-Jeddah 23955-6900Saudi Arabia Research Center for Zoonosis Control Global Institution for Collaborative Research and Education(GI-CoRE)Hokkaido UniversityN20 W10 Kita-KuSapporo 001-0020Japan

Dear Editor,The apolipoprotein B editing complex(APOBEC)protein family members are host antiviral enzymes known for catalyzing cytosine to uracil(C>U)deamination in foreign single-stranded DNA(ssDNA)and RNA(ssRNA)(Blanc and Davidson,2010;Salter and Smith,2018).Enzymatic target motifs for most of the APOBEC enzymes have been experimentally identified,among which the most common ones are 5′-[T/U]C-3′and 5′-CC-3′for DNA/RNA substrates(Salter and Smith,2018;McDaniel et al.,2020).It was recently suggested that SARS-CoV-2 undergoes genome editing by host-dependent RNA-editing proteins such as APOBEC(Di Giorgio et al.,2020;Rice et al.,2020;Simmonds,2020;Schmidt et al.,2021).

关键词： al. APOB editing

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Identification of seed protein and oil related QTL in 944 RILs from a diallel of early-maturing European soybean

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The Crop Journal 2021年第1期9卷 238-247页

作者： Xintian Zhu Willmar L.Leiser Volker Hahn tobias Würschum State Plant Breeding Institute University of Hohenheim70593 StuttgartGermany

Soybean[Glycine max(L.)Merr.]is a global protein source and is currently expanding in Central and Northern *** and oil content are two important quality traits that have been studied in different germplasm,however,their genetic architecture in earlymaturing European soybean has not been investigated *** this study,we therefore performed QTL mapping for both traits using 944 recombinant inbred lines derived from eight families from a half-diallel crossing *** identified five QTL for each trait,with the QTL on chromosomes 8,15,and 20 being identified for both protein content and oil *** known major QTL on chromosome 20 was detected in four families whereas the other QTL were only found in single *** analyses revealed the QTL to have pleiotropic but inverse effects on both *** effect of the major QTL was comparable between families,illustrating that it is largely independent from the genetic ***,our results illustrate the quantitative nature of protein and oil content in early European ***-assisted selection for the QTL is possible,but the inverse effect on protein and oil content should be kept in mind.

关键词： QTL mapping Soybean Protein content Oil content

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Effect of paracellular permeation enhancers on intestinal permeability of two peptide drugs,enalaprilat and hexarelin, in rats

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Acta Pharmaceutica Sinica B 2021年第6期11卷 1667-1675页

作者： David Dahlgren tobias Olander Markus Sjoblom Mikael Hedeland Hans Lennernas Department of Pharmaceutical Biosciences Translational Drug Discovery and DevelopmentUppsala UniversityUppsala 75236Sweden Department of Neuroscience Division of PhysiologyUppsala UniversityUppsala 75236Sweden Department of Medicinal Chemistry Analytical Pharmaceutical ChemistryUppsala UniversityUppsala 75236Sweden Department of Chemistry Environment and Feed HygieneNational Veterinary Institute(SVA)Uppsala 75189Sweden

Transcellular permeation enhancers are known to increase the intestinal permeability of enalaprilat,a 349 Da peptide,but not hexarelin(887 Da).The primary aim of this paper was to investigate if paracellular permeability enhancers affected the intestinal permeation of the two *** was investigated using the rat single-pass intestinal perfusion model with concomitant blood *** luminal compositions included two paracellular permeation enhancers,chitosan(5 mg/mL) and ethylenediaminetetraacetate(EDTA,1 and 5 mg/mL),as well as low luminal tonicity(100 mOsm) with or without *** were evaluated by the change in lumen-to-blood permeability of hexarelin and enalaprilat,and the blood-to-lumen clearance of ^(51)chromium-labeled EDTA(CL_(Cr-EDTA)),a clinical marker for mucosal barrier *** two paracellular permeation enhancers increased the mucosal permeability of both peptide drugs to a similar *** data in this study suggests that the potential for paracellular permeability enhancers to increase intestinal absorption of hydrophilic peptides with low molecular mass is greater than for those with transcellular ***,the mucosal blood-to-lumen flux of ^(51)Cr-EDTA was increased by the two paracellular permeation enhancers and by luminal *** contrast,luminal hypotonicity did not affect the lumen-to-blood transport of enalaprilat and *** suggests that hypotonicity affects paracellular solute transport primarily in the mucosal crypt region,as this area is protected from luminal contents by a constant water flow from the crypts.

关键词： Permeation enhancers Absorption-modifying excipients Oral peptide delivery Intestinal permeability Intestinal perfusion Pharmaceutical development

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The Promotion of Building Culture in Rural Germany

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Built Heritage 2019年第2期3卷 37-49页

作者： Xiaoping Xie tobias Krüger Leibniz Institute of Ecological Urban and Regional Development(IOER) DresdenGermany

Over the past two decades,building culture has increasingly caught the attention of the architectural and planning *** building culture is to be understood in the broadest sense as the sum of all cultural,economic,technological,social and ecological factors influencing the quality and process of planning and construc*** the revitalisation and promotion of building culture is central to discussions on urban areas,these are generally ignored in regard to rural *** article aims to provide an overview of how building culture has been promoted in Germany’s rural areas,thereby contributing to international research on this *** paper adopts a general descriptive approach in examining the promotion of building culture in rural *** provides background knowledge on institutional promotion and demonstrates the diverse approaches implemented in representative villages as best practices *** German experience confirms that the promotion of building culture is a meaningful and effective measure to help revitalise rural ***,the three selected rural municipalities show how stakeholders from civil society are increasingly involved in measures to implement and promote building culture in the local context.

关键词： building culture Baukultur rural Germany institutional promotion rural revitalisation civil society initiative

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Treatment plan improvement by multidisciplinary case conferences for patients with colorectal cancer and synchronous liver metastases

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Hepatobiliary Surgery and Nutrition 2018年第2期7卷 147-148页

作者： Markus Rentsch tobias S.Schiergens Department of General VisceralVascularand Transplant SurgeryMedical Center of the University of MunichMunichGermany

Aggressive treatments of metastasized colorectal cancer have been shown to be promising strategies,offering survival probabilities between 40%and 50%in selected patients(1,2).These achievements,however,were only possible on the basis of improvements in surgical techniques and the introduction of potent chemotherapeutic and biological drugs,combined in meticulously defined regimens(2).Naturally,this requires multidisciplinary teamwork and individually tailored therapeutic *** factors influence this individualized decision process,such as the quality and interpretation of imaging,the availability of a portfolio of systemic and locally ablative treatment options besides surgery,the availability of innovative treatment options within clinical studies,and last but not least,the experience of all health care professionals involved in the various treatment steps,in particular the surgeons(2,3).Several surgical concepts have been proposed in the past to address metastatic disease at two sites in patients with synchronously metastasized colorectal cancer,such as the liver-first approach,simultaneous resection of the primary and synchronous liver metastases,two-step liver resection,or the conventional colon/rectum-first and liver-second approach—with or without systemic chemotherapy.

关键词： patients colorectal metastases

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Epigenetics and pancreatic cancer:Pathophysiology and novel treatment aspects

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World Journal of Gastroenterology 2014年第24期20卷 7830-7848页

作者： Daniel Neureiter Tarkan Jger Matthias Ocker tobias Kiesslich Institute of Pathology Paracelsus Medical University/Salzburger Landeskliniken (SALK)5020 SalzburgAustria Department of Surgery Paracelsus Medical University/Salzburger Landeskliniken (SALK)5020 SalzburgAustria Experimental Medicine Oncology Bayer Pharma AG13342 BerlinGermany Department of Internal Medicine I Paracelsus Medical University/Salzburger Landeskliniken (SALK)5020 SalzburgAustria Institute of Physiology and Pathophysiology Paracelsus Medical University5020 SalzburgAustria

An improvement in pancreatic cancer treatment represents an urgent medical goal. Late diagnosis and high intrinsic resistance to conventional chemotherapy has led to a dismal overall prognosis that has remained unchanged during the past decades. Increasing knowledge about the molecular pathogenesis of the disease has shown that genetic alterations, such as mutations of K-ras, and especially epigenetic dysregulation of tumor-associated genes, such as silencing of the tumor suppressor p16ink4a, are hallmarks of pancreatic cancer. Here, we describe genes that are commonly affected by epigenetic dysregulation in pancreatic cancer via DNA methylation, histone acetylation or miRNA (microRNA) expression, and review the implications on pancreatic cancer biology such as epithelial-mesenchymal transition, morphological pattern formation, or cancer stem cell regulation during carcinogenesis from PanIN (pancreatic intraepithelial lesions) to invasive cancer and resistance development. Epigenetic drugs, such as DNA methyltransferases or histone deactylase inhibitors, have shown promising preclinical results in pancreatic cancer and are currently in early phases of clinical development. Combinations of epigenetic drugs with established cytotoxic drugs or targeted therapies are promising approaches to improve the poor response and survival rate of pancreatic cancer patients.

关键词： Pancreatic cancer Epigenetics DNA methylation Histone modification microRNA Targeted therapy Epithelial-mesenchymal transition

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Making Data and Workflows Findable for Machines

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Data Intelligence 2020年第1期2卷 40-46,303页

作者： tobias Weigel Ulrich Schwardmann Jens Klump Sofiane Bendoukha Robert Quick Deutsches Klimarechenzentrum Bundesstrasse 45aHamburg 20146Germany Gesellschaft für wissenschaftliche Datenverarbeitung Gottingen Am Faßberg 1137077 GottingenGermany CSIRO KensingtonWA 6151CanberraAustralia Indiana University Bloomington BloomingtonIN 47405USA

Research data currently face a huge increase of data objects with an increasing variety of types(data types,formats)and variety of workflows by which objects need to be managed across their lifecycle by data *** desire to shorten the workflows from data generation to analysis and publication,and the full workflow needs to become transparent to multiple stakeholders,including research administrators and *** poses challenges for research infrastructures and user-oriented data services in terms of not only making data and workflows findable,accessible,interoperable and reusable,but also doing so in a way that leverages machine support for better *** primary need to be addressed is that of findability,and achieving better findability has benefits for other aspects of data and workflow *** this article,we describe how machine capabilities can be extended to make workflows more findable,in particular by leveraging the Digital Object Architecture,common object operations and machine learning techniques.

关键词： Findability Workflows Automation FAIR data Data infrastructures Data services

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Involvement of CYP347W1 in neurotoxin 3-nitropropionic acid-based chemical defense in mustard leaf beetle Phaedon cochleariae

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Insect Science 2022年第2期29卷 453-466页

作者： Nanxia Fu tobias Becker Wolfgang Brandt Maritta Kunert Antje Burse Wilhelm Boland Department of Bioorganic Chemistry Max Planck Institute for Chemical EcologyJenaGermany Key Laboratory of Tea Biology and Resource Utilization Tea Research InstituteChinese Academy of Agricultural SciencesHangzhouChina Department of Bioorganic Chemistry Leibniz Institute of Plant BiochemistryHalle(Saale)Germany Department of Natural Product Biosynthesis Max Planck Institute for Chemical EcologyJenaGermany Department of Medical Technology and Biotechnology Ernst Abbe Hochschule JenaJenaGermany

Chrysomelina beetlesstore 3-nitropropionic acid in form of a pretoxin,isoxazolin-5-one glucoside-conjugated ester,to protect themselves against *** we identified a cytochrome P450 monooxygenase,CYP347W1,to be involved in the production of the 3-nitropropionic acid moiety of the isoxazolin-5-one glucoside *** down CYP347W1 led to a significant depletion in the concentration of the isoxazolin-5-one glucoside ester and an increase in the concentration of the isoxazolin-5-one glucoside in the larval *** assays with the heterologously expressed CYP347W1 showed freeβ-alanine was not the direct *** modeling indicated thatβ-alanine-CoA ester can fit into CYP347W1’s active ***,we proved that Phaedon cochleariae eggs are not able to de novo synthesize 3-NPA,although both isoxazolin-5-one glucoside and its 3-NPA-conjugated ester are present in the *** results provide direct evidence for the involvement of CYP347W1 in the biosynthesis of a *** chemical defense compound.

关键词： chemical defense isoxazolin-5-one glucoside isoxazolin-5-one glucoside ester leaf beetles P450 3-nitropropionic acid(3-NPA)

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Modeling uncertainties of reservoir flushing simulations

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International Journal of Sediment Research 2023年第5期38卷 698-710页

作者： Camila Bergmann Goulart tobias Bleninger Hugo de Oliveira Fagundes Fernando Mainardi Fan Department of Environmental Engineering Federal University of Parana Institute of Hydraulic Research Federal University of Rio Grande do Sul

Every dam or barrage construction affects the watercourse and the retention of sediment that previously was carried by the river, which can lead to siltation of the reservoir and obstruction of water intakes over time, reducing their capacities. However, the information available regarding the effect of sediment and drawdown parameters, sediment management at reservoirs, as well as different equational approaches,is scarce. The current research aims to evaluate the effect of parameters associated with numerical modeling of sediment management in reservoirs considering scenarios with different drawdowns,transport equations, sediment size distributions, and thickness of the initial sediment layer. The case study of the Aimore s Hydropower Plant(HPP) is used, applying the Delft3D-FLOW model for twodimensional modeling. All parameters influenced the volume of mobilized sediment, among which the initial layer thickness was the parameter that resulted in the greatest changes in simulated results. In general, the results show that the uncertainties in the input parameters outweigh the uncertainties between the techniques, which found large variations in results when evaluating the use of different transport equations. These results indicate the importance of proper estimation of model parameters for predicting effects with accuracy and the need for such studies before planning and management operations are evaluated to avoid environmental harm and energy waste.

关键词： Reservoir sedimentation Sediment transport modeling Flushing Sediment management

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