bluuebunny/crossref_metadata_2025 huggingface dataset:
β‐Glucuronidase‐ and OATP2B1‐mediated drug interaction of scutellarin in Dengzhan Xixin Injection: A formulation aspect
Authors: Shi Jinxin , Sun Chengpeng , Huang Huilian , Lin Wenhui , Gao Jian , Lin Yanhe , Zhang Zhanjun , Huo Xiaokui , Tian Xiangge , Yu Zhenlong , Zhang Baojing , Ma Xiaochi
Published: March 2020

Scutellarin is the major and active constituent of Dengzhan Xixin Injection (DZXX), a traditional Chinese medicine prepared from the aqueous extract of Erigeron breviscapus and widely used for the treatment of various cerebrovascular diseases in clinic. In present study, the possible pharmacokinetic differences of scutellarin after intravenous administration of scutellarin alone or DZXX were explored. Additional, the potential roles of β‐glucuronidase (GLU) and OATP2B1 in drug–drug interaction (DDI) between scutellarin and constituents of DZXX were further evaluated in vitro. The plasma concentration, urinary and biliary excretion of scutellarin in rats after administration of DZXX, were significantly higher than those received scutellarin, while pharmacokinetic profile of Apigenin 7‐O‐glucuronide (AG) in rats was similar no matter AG or DZXX group. Furthermore, higher concentration in brain and plasma, however, lower level of scutellarin in intestine were observed after intravenous administration of DZXX. Finally, AG and caffeoylquinic acid esters were found to significantly inhibit GLU and OATP2B1 in vitro, which might explain, at least in part, the pharmacokinetic DDI between scutellarin and other chemical constituents in DZXX. The findings provided deep insight into the prescription‐formulating principle in DZXX for treating the cerebrovascular diseases.
Covid‐19 and diabetes mellitus: unveiling the interaction of two pandemics
Authors: Maddaloni Ernesto , Buzzetti Raffaella
Published: March 2020

A novel RNA betacoronavirus causing coronavirus disease 2019 (Covid‐19) has now been declared pandemic disease by WHO. Guo et al published the first report of biochemical features in patients with diabetes and the further risk that this disease can determine to the progression of Covid‐19. Among different cytokines found significantly higher in patients with diabetes compared to those without, Interleukin‐6 (IL‐6), which is already increased in conditions of chronic inflammation, may play a more deleterious role in Covid‐19 infection. Targeting the overexpression of Il‐6 effects with a monoclonal antibody against IL‐6 receptor or using Janus Kinase inhibitors may be particularly helpful for treatment of Covid‐19 pneumonia in diabetes.
Hydrogen Sulfide Alleviates Liver Injury Through the S‐Sulfhydrated‐Kelch‐Like ECH‐Associated Protein 1/Nuclear Erythroid 2–Related Factor 2/Low‐Density Lipoprotein Receptor–Related Protein 1 Pathway
Authors: Zhao Shuang , Song Tianyu , Gu Yue , Zhang Yihua , Cao Siyi , Miao Qing , Zhang Xiyue , Chen Hongshan , Gao Yuanqing , Zhang Lei , Han Yi , Wang Hong , Pu Jun , Xie Liping , Ji Yong
Published: March 2020

Background and Aims

Protein S‐sulfhydration mediated by H2S has been shown to play important roles in several diseases. However, its precise role in liver disease and the related mechanism remain unclear.

Approach and Results

We showed that in streptozotocin (STZ)–treated and high‐fat diet (HFD)–treated low‐density lipoprotein receptor–negative (LDLr−/−) mice, the H2S donor GYY4137 ameliorated liver injury, decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, mitigated lipid deposition, and reduced hepatocyte death. Strikingly, S‐sulfhydration of Kelch‐like ECH‐associated protein 1 (Keap1) was decreased in the livers of patients with fatty liver under diabetic conditions. In STZ+HFD‐treated LDLr−/− mice and in high glucose–treated and oxidized low‐density lipoprotein (ox‐LDL)–treated primary mouse hepatocytes, the GYY4137‐mediated increase in Keap1 S‐sulfhydration induced nuclear erythroid 2‐related factor 2 (Nrf2) dissociation from Keap1, which enhanced the nuclear translocation of Nrf2 itself and the consequent expression of antioxidant proteins. Keap1 Cys151 mutation significantly reduced Keap1 S‐sulfhydration and abolished the hepatoprotective effects of H2S both in vivo and in vitro. Nrf2 deficiency inhibited the H2S‐induced beneficial impacts in Nrf2−/− mice. Similarly, in CCl4‐stimulated mice, GYY4137 increased Keap1 S‐sulfhydration, improved liver function, alleviated liver fibrosis, decreased hepatic oxidative stress, and activated the Nrf2 signaling pathway; and these effects were abrogated after Keap1 Cys151 mutation. Moreover, H2S increased the binding of Nrf2 to the promoter region of LDLr‐related protein 1 (Lrp1) and consequently up‐regulated LRP1 expression, but these effects were disrupted by Keap1 Cys151 mutation.

Conclusions

H2S‐mediated Keap1 S‐sulfhydration alleviates liver damage through activation of Nrf2. Hence, administration of exogenous H2S in the form of the H2S donor GYY4137 may be of therapeutic benefit in the context of concurrent hyperlipidemia and hyperglycemia–induced or CCl4‐stimulated liver dysfunction.
How does ayahuasca work from a psychiatric perspective? Pros and cons of the entheogenic therapy
Authors: Orsolini Laura , Chiappini Stefania , Papanti Duccio , Latini Roberto , Volpe Umberto , Fornaro Michele , Tomasetti Carmine , Vellante Federica , De Berardis Domenico
Published: March 2020

Objective

Ayahuasca is a hallucinogenic plant preparation, traditionally consumed in sacred ceremonies by indigenous North‐Westerner Amazonian countries like Colombia, Peru, Brazil, and Ecuador. It is fundamental to carefully balance benefits/risks related to the ayahuasca intake, both during ceremonies and experimental settings. The aim is at evaluating and comparing the potential therapeutic benefits versus health risks related to ayahuasca intake (both acutely and chronically), focusing on its application in psychedelic psychiatry.

Design

A comprehensive mini overview focusing on psychiatric outcomes following ayahuasca intake both in healthy volunteers and in clinical samples.

Results

Preclinical, observational, and experimental studies in healthy volunteers as well as in clinical samples suggest that ayahuasca may be beneficial as an antidepressant, emotional regulator, anxiolytic, and antiaddictive drug, by exerting fast‐acting and enduring clinical effects. Ayahuasca appears to be safe and well tolerated, nausea and emesis being the most reported and transient side effects. Some findings suggest not to use ayahuasca in bipolar or psychotic patients because of an increased risk of manic switch and/or psychotic onset.

Conclusions

Further research should be carried out in randomized, double‐blind, placebo‐controlled trials, by implementing neuroimaging studies, in order to better evaluate therapeutic potential of ayahuasca in mental disorders.
Successful use of nonantigen‐specific immunoadsorption with antihuman Ig‐columns in kidney graft antibody‐mediated rejection
Authors: Montagud‐Marrahi Enrique , Revuelta Ignacio , Cucchiari David , Piñeiro Gaston J. , Ventura‐Aguiar Pedro , Lozano Miquel , Cid Joan , Martorell Jaume , Solé Manel , Quintana Luis F. , Oppenheimer Federico , Diekmann Fritz , Poch Esteban , Campistol Josep M. , Blasco Miquel
Published: March 2020

Introduction

Nonantigen‐specific immunoadsorption (IA) has proven to be effective in acute antibody‐mediated rejection (aAMR). However, there is a lack of solid studies evaluating the safety and efficacy of IA with antihuman Ig‐columns in aAMR. For chronic‐active AMR (cAMR), no studies have evaluated the efficacy of nonantingen‐specific IA with antihuman Ig‐columns. The purpose of this study was to evaluate the role of nonantigen‐specific IA with antihuman Ig‐columns in the treatment of both aAMR and cAMR in kidney transplantation.

Material and Methods

In retrospective and observational study, kidney graft and recipient survival rates were assessed after treatment of aAMR and cAMR with nonantigen‐specific IA with Ig‐Flex columns (Therasorb) between January 2012 and May 2018. Protocols included nonantigen‐specific IA, rituximab, intravenous immunoglobulin, and rescue plasma exchange, if necessary.

Results

The study included 14 patients with AMR (acute in 9, chronic active in 5). For aAMR, mean follow‐up was 13 ± 6 months, and patient and graft survival were, respectively, of 100% and 83%, with a mean increase in estimated glomerular filtration rate (eGFR) of 7.98 ± 12.96, 10.18 ± 16.71, and 11.43 ± 13.85 mL/min/1.72 m2 (P > .05) at 3, 12 months after treatment, and at the end of follow‐up, respectively. For cAMR, mean follow‐up was 14 ± 8 months, and patient and graft survival were, respectively, of 100% and 60%, with an average increase in eGFR of 4.30 ± 7.86, 5.64 ± 10.47, and 14.5 ± 7.86 mL/min/m2 (P > .05) at 3, 12 months after IA treatment, and at the end of the follow‐up, respectively, although 40% did not respond and required chronic hemodialysis.

Conclusion

Nonantigen‐specific IA with Ig‐Flex columns was safe and effective for aAMR treatment in kidney transplantation. In cAMR, IA with Ig‐Flex columns was associated with a satisfactory kidney graft survival, suggesting that IA could potentially offer some benefits supporting its indication in cAMR.
Master's and doctoral engineering students' interest in industry, academia, and government careers
Authors: Choe Nathan H. , Borrego Maura
Published: March 2020

Background

Graduate education literature tends to focus on faculty careers with little attention to industry careers. However, more than one‐third of U.S. engineering doctorates enter industry.

Purpose

Our purpose is to understand engineering graduate students' interest in industry, academia, and government careers as it relates to their graduate engineering identities.

Design/Method

A total of 249 engineering thesis master's and doctoral students completed a survey about their graduate engineering identities and career preferences. We created regression models to predict students' likelihood of pursuing careers in industry, academia, and government. Then, we used cluster analysis to understand the extent to which students are considering multiple options and used chi‐squared and ANOVA tests to compare the clusters.

Results

In the regression model predicting an academic career, research recognition and research performance/competence were positive predictors and engineering performance/competence was a negative predictor. Regression models of industry and government described less than 10% of the variance. Four clusters emerged, which collectively demonstrate that engineering graduate students are considering careers in multiple sectors. Students with internships during graduate study were more likely to pursue industry careers. Master's students were underrepresented in the cluster with highest likelihood of an academic career. International students were keeping more options open than some domestic students. There were also differences by engineering discipline.

Conclusions

Engineering graduate students are considering multiple career sectors. Advisors and education researchers should focus not only on academic career preparation but also on industry and government career preparation, particularly on preparing for multiple options simultaneously.
Treatment of infantile neuroaxonal dystrophy with RT001: A di‐deuterated ethyl ester of linoleic acid: Report of two cases
Authors: Adams Darius , Midei Mark , Dastgir Jahannaz , Flora Christina , Molinari Robert J , Heerinckx Frederic , Endemann Sarah , Atwal Paldeep , Milner Peter , Shchepinov Mikhail S.
Published: March 2020

Background

Infantile neuroaxonal dystrophy (INAD) is a rare, autosomal recessive disease due to defects inPLA2G6and is associated with lipid peroxidation. RT001 is a di‐deuterated form of linoleic acid that protects lipids from oxidative damage.

Methods

We evaluated the pharmacokinetics (PK), safety, and effectiveness of RT001 in two subjects with INAD (subject 1: 34 months; subject 2: 10 months). After screening and baseline evaluations, subjects received 1.8 g of RT001 BD. PK analysis and clinical evaluations were made periodically.

Main findings

Plasma levels of deuterated linoleic acid (D2‐LA), deuterated arachidonic acid (D2‐AA), D2‐LA to total LA, and D2‐AA to total AA ratios were measured. The targeted plasma D2‐LA ratio (>20%) was achieved by month 1 and maintained throughout the study. RBC AA‐ratios were 0.11 and 0.18 at 6 months for subjects 1 and 2; respectively. No treatment‐related adverse events occurred. Limited slowing of disease progression and some return of lost developmental milestones were seen.

Conclusions

Oral RT001 was administered safely in two subjects with INAD. Early findings suggest that the compound was well tolerated, metabolized and incorporated in the RBC membrane. A clinical trial is underway to assess efficacy.
Iodinated contrast media and their effect on thyroid function – Routines and practices among diagnostic imaging departments in Norway
Authors: Rusandu Albertina , Sjøvold Bjørnar Heggdal , Hofstad Edvin , Reidunsdatter Randi Johansen
Published: March 2020

Introduction

In order to minimise adverse effects or patient injuries related to the effect of iodinated contrast media (ICM) on the thyroid, international guidelines and research recommend developing routines for identification and management of patients at risk of developing a thyroid dysfunction. This study aimed to investigate thyroid‐related ICM administration practices among diagnostic imaging departments in Norway.

Methods

The cross‐sectional survey included 24 hospitals and 75 respondents with a 69% response rate. The survey covered practices for assessment and management of at‐risk patients and the participants’ perceived rationale for the routines.

Results

The use of written checklists as recommended by international guidelines was quite modest (15%) and the respondents preferred various methods to identify risk and contraindications. Only 20% reported checking for any scheduled thyroid‐scintigraphy and/or radioactive‐iodine therapy. 42% indicated that they did not have thyroid‐related ICM routines, and the main perceived reason was lack of knowledge on the topic. Radiographers and radiologists expressed uncertainty about each other’s roles and routines.

Conclusion

This study revealed the need of optimisation of routines regarding ICM administration to patients at risk for thyroid dysfunction.
Flaming as part of aseptic technique increases CO2 (g) and decreases pH in freshwater culture media
Authors: Zepernick Brittany N. , Krausfeldt Lauren E. , Wilhelm Steven W.
Published: March 2020

Aseptic technique has historically served as a fundamental practice in microbiology, helping to maintain culture purity and integrity. This technique has been widely encouraged and employed for use with cultures of heterotrophic bacteria as well as freshwater and marine algae. Yet, recent observations have suggested that these approaches may bring their own influences. We observed variations in growth among replicate experimental cyanobacterial cultures upon flaming of the culture tube opening during sample transfer and collection. Investigation revealed the pH of culture media had decreased from the initial pH established during media preparation. Flaming of sterile culture media alone confirmed a significant decrease, by as much as 1.7 pH units, and correlated with increased flaming events over time. We hypothesized that the causative factor was the introduction of carbon dioxide (CO2) into the media. To test this hypothesis, qualitative and quantitative analyses were used to determine the primary driver of pH decline. We further assessed the direct effects of flaming and subsequent pH changes on Microcystis aeruginosa cultures, showing flame‐driven pH changes and/or the introduction of CO2 influenced experimental results. Our observations provide a cautionary tale of how classic and well‐accepted approaches may have unintended consequences, suggesting new approaches may be necessary in research areas assessing pH or carbon‐related effects on microbial communities.
HIGH RESOLUTION MASS SPECTROMETRY IN LIPIDOMICS
Authors: Züllig Thomas , Köfeler Harald C.
Published: March 2020

The boost of research output in lipidomics during the last decade is tightly linked to improved instrumentation in mass spectrometry. Associated with this trend is the shift from low resolution—toward high‐resolution lipidomics platforms. This review article summarizes the state of the art in the lipidomics field with a particular focus on the merits of high mass resolution. Following some theoretical considerations on the benefits of high mass resolution in lipidomics, it starts with a historical perspective on lipid analysis by sector instruments and moves further to today's instrumental approaches, including shotgun lipidomics, liquid chromatography–mass spectrometry, matrix‐assisted laser desorption ionization‐time‐of‐flight, and imaging lipidomics. Subsequently, several data processing and data analysis software packages are critically evaluated with all their pros and cons. Finally, this article emphasizes the importance and necessity of quality standards as the field evolves from its pioneering phase into a mature and robust omics technology and lists various initiatives for improving the applicability of lipidomics. © 2020 The Authors. Mass Spectrometry Reviews published by John Wiley & Sons Ltd. Mass Spec Rev
CCD urges government support to treat disability population
Authors: Canady Valerie A.
Published: March 2020

The largest coalition of national organizations working together to advocate for federal public policy on behalf of children and adults with disabilities is asking the U.S. Department of Health and Human Services (HHS) to prevent discriminatory rationing of coronavirus treatment.
High‐throughput screening of argan oil composition and authenticity using benchtop 1H NMR
Authors: Gunning Yvonne , Jackson Alex J. , Colmer Joshua , Taous Fouad , Philo Mark , Brignall Rachel M. , El Ghali Tibari , Defernez Marianne , Kemsley E. Kate
Published: March 2020

We use 60‐MHz benchtop nuclear magnetic resonance (NMR) to acquire 1H spectra from argan oils of assured origin. We show that the low‐field NMR spectrum of neat oil contains sufficient information to make estimates of compositional parameters and to inform on the presence of minor compounds. A screening method for quality and authenticity is presented based on nearest‐neighbour outlier detection. A variety of oil types are used to challenge the method. In a survey of retail‐purchased oils, several instances of fraud were found.
A phase‐field model for brittle fracture of anisotropic materials
Authors: Gmati Hela , Mareau Charles , Ammar Amine , El Arem Saber
Published: March 2020

In the present work, a phase field damage model is developed to address the numerical simulation of brittle fracture. This model successfully captures some important aspects of crack propagation, including crack branching and bifurcation. In addition, the proposed phase field model has been developed in the general framework of anisotropic elasticity. It can thus be used for the simulation of brittle fracture in polycrystalline materials, for which crack propagation is impacted by crystallographic orientation because of the anisotropic character of stiffness properties.
Solving fractional optimal control problems by new Bernoulli wavelets operational matrices
Authors: Barikbin Zahra , Keshavarz Elham
Published: March 2020

In this article, a new numerical method based on Bernoulli wavelet basis has been applied to give the approximate solution of the fractional optimal control problems. The new operational matrices of multiplication and fractional integration are constructed. The proposed method is applied to reduce the problem to the solution of a system of algebraic equations. The fractional derivative is considered in the Caputo sense. Convergence of the algorithm is proved and some results concerning the error analysis are obtained. Approximate solutions are given and in the cases when we have an exact solution, a comparison with the exact solution is presented to demonstrate the validity and applicability of the proposed method. In addition, we compare the obtained results with the results of other methods. Comparison shows the more accuracy of presented technique in comparison to other published methods.
User preferences and strategic interactions in platform ecosystems
Authors: Panico Claudio , Cennamo Carmelo
Published: March 2020

Research summary

User demand affects the emergence and growth of platform ecosystems through indirect network effects. But how do these effects play out in the strategies of platform providers and complementors as the ecosystem evolves? We study how user preferences for ecosystem innovativeness (complement novelty and quality) and ecosystem size (number of complementors/complements), and demand‐based economies of scale, shape the strategic interactions between the platform provider and the complementors in the ecosystem. Using an analytical model, we identify the conditions that give rise to a trade‐off between ecosystem innovativeness and size; when (and why) this trade‐off generates a tension between value co‐creation and appropriation among ecosystem participants; and the strategic implications for ecosystem competitiveness and for the different stages of the ecosystem's evolution.

Managerial summary

Managing complementors’ incentives is critical for the success of a platform ecosystem. Such incentives may be offered not only for joining the platform, but also for contributing high‐quality, innovative complements throughout the ecosystem's evolution. In this article, we show that demand‐side economies of scale are the driving force of complementors’ incentives, and hence the key success factor for platform strategies. The strength of user preferences ultimately determines whether a larger ecosystem can also be more innovative, in which case all ecosystem participants can gain; or if instead there is a trade‐off between size and innovativeness, which could also lead to a tension between value co‐creation and appropriation among the platform provider and its complementors. The different stages of the evolution of a platform ecosystem call for different strategies that adapt to the evolution of user preferences.
Carbon emission analyses of concretes made with recycled materials considering CO2 uptake through carbonation absorption
Authors: Xiao Jianzhuang , Xiao Yu , Liu Yun , Ding Tao
Published: March 2020

The effect of incorporation of recycled powder and CO2 absorption of concrete was not considered in the previous life cycle assessment studies. This study evaluated the carbon emission of recycled concrete with different replacement rate of recycled powder and recycled coarse aggregate, taking the carbon absorption in storage and service phase into consideration. The carbon absorption model of recycled concrete with recycled powder was optimized and validated by rapid carbonization tests. It is found that concrete with recycled powder has favorable carbon absorption capacity and can greatly reduce carbon emission. The carbon emission of recycled concrete with recycled powder decreased 12.4–52.2% when compared to normal concrete, and with the increase in the replacement of recycled materials, this advantage becomes more obvious. The evaluation results show that the raw material production and transportation phase are the two main contributors to the carbon emission of recycled concrete, accounting for 67.03–85.81% and 4.01–15.27%, respectively. The evaluation results also show the compensation benefits in storage and service phase from carbon absorption account for 1.58–26.93%. Meanwhile, the long‐distance delivery of natural coarse aggregates makes it possible for recycled concrete to be widely applied.
Detection of high‐impedance fault in distribution network based on time–frequency entropy of wavelet transform
Authors: Zhang Shu , Xiao Xianyong , He Zhengyou
Published: March 2020

Due to the characteristics of small, nonlinear, random, and unstable current, the high impedance faults (HIF) are not always effectively cleared by conventional over current relays. A new simple and effective algorithm of HIF detection in distribution network based on the wavelet time–frequency entropy is presented in this article. On the basis of analysis, the time–frequency distribution characteristics in the concerned frequency band of HIFs by wavelet transform. The feature sequence developed by the wavelet time–frequency entropy at the time sequence is employed to detect HIF at substation. This criterion is calculated from the sum of wavelet time–frequency entropy at the time sequence every half cycle. If the value of the criterion is more than the threshold during four cycles, the HIF event can be identified. The developed detection method has been tested with real‐world recorded signals from different HIF medium and PSCAD/EMTDC‐generated signals. The result shows that the proposed method is robust to transients generated during normal events such as capacitor bank switching, load switching, and harmonic load. It has good performance for antinoise ability by noise reduction coefficient improved appropriately. And the proposed method has better reliability than the traditional third‐harmonic‐based method. © 2020 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Teaching Introductory Economics to Promote Sustainability
Authors: Venkatesan Madhavi
Published: March 2020

This chapter addresses how sustainability can be incorporated within the Principles of Microeconomics and Principles of Macroeconomics curriculum. Examples of assignments along with case study assessments of the impact of the assignments as they relate to understanding and fostering sustainability in the student are provided.
Sustainability Education as a Pathway to Minority Participation in STEM
Authors: Xu Cassie , Smerdon Jason E. , DeFries Ruth , Unwin‐Kuruneri Natalie
Published: March 2020

Sustainability education offers higher education institutions opportunities to broaden the participation of groups traditionally underrepresented in the Science, Technology, Engineering, and Mathematics (STEM) fields. This chapter focuses on an exploratory case study that looks at how sustainability education can be used as a tool to increase student engagement and participation in STEM at the undergraduate level and why it should be considered as an important tool for addressing diversity challenges.
Colorectal cancer cell lines show striking diversity of their O-glycome reflecting the cellular differentiation phenotype
Authors: Madunić Katarina , Zhang Tao , Mayboroda Oleg A. , Holst Stephanie , Stavenhagen Kathrin , Jin Chunsheng , Karlsson Niclas G. , Lageveen-Kammeijer Guinevere S. M. , Wuhrer Manfred
Published: March 2020

Alterations in protein glycosylation in colorectal cancer (CRC) have been extensively studied using cell lines as models. However, little is known about theirO-glycome and the differences in glycan biosynthesis in different cell types. To provide a better understanding of the variation inO-glycosylation phenotypes and their association with other molecular features, an in-depthO-glycosylation analysis of 26 different CRC cell lines was performed. The releasedO-glycans were analysed on porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC–ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization. Associations between the observed glycan phenotypes with previously reported cell line transcriptome signatures were examined by canonical correlation analysis. Striking differences are observed between theO-glycomes of 26 CRC cell lines. Unsupervized principal component analysis reveals a separation between well-differentiated colon-like and undifferentiated cell lines. Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans. Moreover, the expression of glycan signatures associates with the expression of glycosyltransferases that are involved in their biosynthesis, providing a deeper insight into the regulation of glycan biosynthesis in different cell types. This untargeted in-depth screening of cell lineO-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
Verbesserte Patientensicherheit durch „clinical decision support systems“ in der Labormedizin
Authors: Eckelt F. , Remmler J. , Kister T. , Wernsdorfer M. , Richter H. , Federbusch M. , Adler M. , Kehrer A. , Voigt M. , Cundius C. , Telle J. , Thiery J. , Kaiser T.
Published: March 2020

Hintergrund

Labormedizinische Diagnostik ist für die Diagnosestellung, Therapieeinleitung und Überwachung von Patienten unverzichtbar. Unberücksichtigte oder fehlerhaft interpretierte Laborergebnisse haben unerwünschte Auswirkungen und gefährden die Patientensicherheit. „Clinical decision support systems“ (CDSS) könnten helfen, eine angemessene Interpretation und medizinische Reaktion zu unterstützen.

Ziel der Arbeit

Das Forschungsprojekt zur digitalen Labormedizin (Analyse- und Meldesystem zur Verbesserung der Patientensicherheit durch Echtzeitintegration von Laborbefunden [AMPEL]) hat zum Ziel, auf Basis der Diagnostik am Institut für Laboratoriumsmedizin der Universitätsmedizin Leipzig ein CDSS zu entwickeln, das die Behandler dabei unterstützt, notwendige medizinische Maßnahmen sicherzustellen.

Material und Methoden

In einer Literaturrecherche zu CDSS wird der aktuelle Stand der Technik beschrieben. Hierauf aufbauend wird das AMPEL-Projekt mit seinen Zielen, Herausforderungen und ersten Ergebnissen vorgestellt. Die Entwicklung der Regel- und Meldesysteme wird am klinischen Beispiel der schweren Hypokaliämie erläutert.

Ergebnisse und Diskussion

Durch die interdisziplinäre Entwicklung von Regel- und Meldesystemen auf Basis von klinischen Daten wurden spezifische, fachgebietsübergreifende CDSS erstellt, die auf hohe Akzeptanz stoßen. Erste Ergebnisse zur schweren Hypokaliämie belegen einen positiven Effekt auf die Patientenbehandlung. Bei der Entwicklung komplexerer Regelwerke, etwa zur Sepsisdiagnostik oder dem akuten Koronarsyndrom, stellt die begrenzte Verfügbarkeit standardisierter und digital verfügbarer klinischer Daten eine Herausforderung dar. Neben klassischen Entscheidungsbäumen in CDSS bieten Methoden des maschinellen Lernens eine vielversprechende Perspektive für zukünftige Entwicklungen.
Umgang mit psychischer Belastung bei Gesundheitsfachkräften im Rahmen der Covid-19-Pandemie
Authors: Petzold Moritz Bruno , Plag Jens , Ströhle Andreas
Published: March 2020

Hintergrund

Im Rahmen der aktuellen Covid-19-Pandemie stehen Gesundheitsfachkräfte aller Berufsgruppen vor großen Herausforderungen in der Bewältigung der Krise. Dabei treten zahlreiche außergewöhnliche Stressoren und Risiken nicht nur für die körperliche, sondern auch die psychische Gesundheit der Gesundheitsfachkräfte auf.

Ziel der Arbeit

Der Artikel fasst erste Empfehlungen zur Reduktion von Stress und psychischer Belastung bei Gesundheitsfachkräften im Rahmen der aktuellen Covid-19-Pandemie zusammen.

Methode

Dargestellt werden Empfehlungen zur Reduktion von Stress und psychischen Belastungen bei Gesundheitsfachkräften und wichtige Aspekte, die Führungskräfte zur Reduktion von Stress und psychischer Belastung bei ihren Mitarbeiter*innen beachten sollten. Insbesondere werden die Empfehlungen der Weltgesundheitsorganisation, des Internationalen Roten Kreuzes und der Vereinten Nationen berücksichtigt.

Ergebnisse

Eine Normalisierung psychischer Belastungen, eine ausreichende Befriedigung der Grundbedürfnisse, soziale Unterstützung, eine klare Kommunikation und Aufgabenverteilung und flexible Möglichkeiten zur Arbeitsgestaltung und Inanspruchnahme von Hilfsangeboten ohne Stigmatisierung scheinen besonders wichtige Maßnahmen zu sein.

Diskussion

Der Artikel verschafft Gesundheitsfachkräften und ihren Führungskräften einen ersten Überblick über wichtige Faktoren zum Erhalt der psychischen Gesundheit während der Covid-19-Pandemie.
Evaluation of the content and bioaccessibility of selected metals from barley grass
Authors: Parzych Sylwia , Kwiatkowski Piotr , Asztemborska Monika , Ruzik Lena
Published: March 2020

The evaluation of the content of zinc and copper in plant tissues of barley grass growing on enriched in zinc/copper solutions (sulphate, glycine complex, rutin complex) were studied by inductively coupled plasma mass spectrometry. The highest concentrations of Zn were found in the roots and leaves, growing on solutions enriched in the rutin-zinc(II) and sulphate solutions. The highest concentrations of Cu were found in the leaves, growing on solutions enriched in the glycine-copper(II) complex solutions. The research showed that the barley accumulates the zinc/copper from the nutrient solution, therefore, in the next step of the investigation the evaluation of bioaccessibility was carried out. The bioaccessibility of copper and zinc were evaluated from the various enriched cultivation solutions by the inductively coupled mass spectrometry coupled with size exclusion chromatography. Plants growing on solutions enriched in the zinc/copper complexes with amino acids (glycine) and flavonoids (rutin) accumulated excessive amounts of these elements in tissues. Additionally, the bioaccessibility is significantly higher than from the plant’s tissues growing on zinc/copper salts solutions.
Injuries of the isolated larynx-hyoid complex in post-mortem computed tomography (PMCT) and post-mortem fine preparation (PMFP) - a comparison of 54 forensic cases
Authors: Treitl Karla Maria , Aigner Laura Isabel , Gazov Evgenij , Fischer Florian , Schinner Regina , Schmid-Tannwald Christine , Kirchhoff Sonja , Scherr Michael Karl
Published: March 2020

Objectives

To assess the diagnostic accuracy (ACC) of post-mortem computed tomography (PMCT) for fractures of the isolated larynx-hyoid complex (LHC) in comparison to post-mortem fine preparation (PMFP).

Methods

This monocentric prospective study enclosed 54 LHCs that were extracted during autopsy, fixed in formalin, and underwent a PMCT scan (64-row multidetector CT, helical pitch). Two radiologists independently analyzed the LHC scans for image quality (IQ) and fractures (4-point Likert scales). A specialized forensic preparator dissected the specimens under the stereomicroscope. The PMFP results were standardized documented, and used as the standard of reference for the comparison to PMCT.

Results

The PMCT-IQ of 95% of the LHC images was rated as good or excellent. IQ was decreased by decay, incisions during autopsy, and separation of the hyoid from the cartilaginous components in 7, 3, and 12 specimens, respectively. PMFP detected 119 fractures in 34 LHCs (63.0%). PMCT identified 91 fractures in 32 specimens (59.3%). PMFP and PMCT significantly agreed concerning the location (Cohen’sκ = 0.762;p < 0.001) and the degree of dislocation (κ = 0.689;p < 0.001) of the fractures. Comparing PMCT to PMFP resulted in a sensitivity of 88.2%, a specificity of 90.0%, and an ACC of 88.9% for the LHC. The ACCs for the hyoid, thyroid, and cricoid were 94.4%, 87.0%, and 81.5%, respectively. PMCT procedure was significantly faster than PMFP (28.9 ± 4.1 min vs. 208.2 ± 32.5 min;p < 0,001).

Conclusions

PMCT can detect distinct injuries of the isolated LHC and may promptly confirm violence against the neck as cause of death. PMFP outmatches PMCT in the detection of decent injuries like tears of the cricoid cartilage.

Key Points

• Post-mortem computed tomography is able to assess fractures of the larynx-hyoid complex.

• Prospective monocentric in vitro study showed that post-mortem computed tomography of the larynx-hyoid complex is faster than post-mortem fine preparation.

• Post-mortem computed tomography can confirm violence against the neck as cause of death.
Therapeutic approaches in heart failure with preserved ejection fraction: past, present, and future
Authors: Wintrich Jan , Kindermann Ingrid , Ukena Christian , Selejan Simina , Werner Christian , Maack Christoph , Laufs Ulrich , Tschöpe Carsten , Anker Stefan D. , Lam Carolyn S. P. , Voors Adriaan A. , Böhm Michael
Published: March 2020

In contrast to the wealth of proven therapies for heart failure with reduced ejection fraction (HFrEF), therapeutic efforts in the past have failed to improve outcomes in heart failure with preserved ejection fraction (HFpEF). Moreover, to this day, diagnosis of HFpEF remains controversial. However, there is growing appreciation that HFpEF represents a heterogeneous syndrome with various phenotypes and comorbidities which are hardly to differentiate solely by LVEF and might benefit from individually tailored approaches. These hypotheses are supported by the recently presented PARAGON-HF trial. Although treatment with LCZ696 did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among HFpEF patients, subanalyses suggest beneficial effects in female patients and those with an LVEF between 45 and 57%. In the future, prospective randomized trials should focus on dedicated, well-defined subgroups based on various information such as clinical characteristics, biomarker levels, and imaging modalities. These could clarify the role of LCZ696 in selected individuals. Furthermore, sodium-glucose cotransporter-2 inhibitors have just proven efficient in HFrEF patients and are currently also studied in large prospective clinical trials enrolling HFpEF patients. In addition, several novel disease-modifying drugs that pursue different strategies such as targeting cardiac inflammation and fibrosis have delivered preliminary optimistic results and are subject of further research. Moreover, innovative device therapies may enhance management of HFpEF, but need prospective adequately powered clinical trials to confirm safety and efficacy regarding clinical outcomes. This review highlights the past, present, and future therapeutic approaches in HFpEF.
PTEN activation contributes to neuronal and synaptic engulfment by microglia in tauopathy
Authors: Benetatos Joseph , Bennett Rachel E. , Evans Harrison T. , Ellis Sevannah A. , Hyman Bradley T. , Bodea Liviu-Gabriel , Götz Jürgen
Published: March 2020

Phosphatase and tensin homolog (PTEN) regulates synaptic density in development; however, whether PTEN also regulates synapse loss in a neurodegenerative disorder such as frontotemporal lobar degeneration with Tau deposition (FTLD-Tau) has not been explored. Here, we found that pathological Tau promotes early activation of PTEN, which precedes apoptotic caspase-3 cleavage in the rTg4510 mouse model of FTLD-Tau. We further demonstrate increased synaptic and neuronal exposure of the apoptotic signal phosphatidylserine that tags neuronal structures for microglial uptake, thereby linking PTEN activation to synaptic and neuronal structure elimination. By applying pharmacological inhibition of PTEN's protein phosphatase activity, we observed that microglial uptake can be decreased in Tau transgenic mice. Finally, we reveal a dichotomous relationship between PTEN activation and age in FTLD-Tau patients and healthy controls. Together, our findings suggest that in tauopathy, PTEN has a role in the synaptotoxicity of pathological Tau and promotes microglial removal of affected neuronal structures.
Functional dissection of the DORNRÖSCHEN-LIKE enhancer 2 during embryonic and phyllotactic patterning
Authors: Comelli Petra , Glowa Dorothea , Frerichs Anneke , Engelhorn Julia , Chandler John W. , Werr Wolfgang
Published: March 2020

Main conclusion

The Arabidopsis DORNRÖSCHEN-LIKE enhancer 2 comprises a high-occupancy target region in the IM periphery that integrates signals for the spiral phyllotactic pattern and cruciferous arrangement of sepals.

Transcription of the DORNRÖSCHEN-LIKE (DRNL) gene marks lateral organ founder cells (LOFCs) in the peripheral zone of the inflorescence meristem (IM) and enhancer 2 (En2) in the DRNL promoter upstream region essentially contributes to this phyllotactic transcription pattern. Further analysis focused on the phylogenetically highly conserved 100-bp En2core element, which was sufficient to promote the phyllotactic pattern, but was recalcitrant to further shortening. Here, we show that En2core functions independent of orientation and create a series of mutations to study consequences on the transcription pattern. Their analysis shows that, first, in addition to in the inflorescence apex, En2core acts in the embryo; second, cis-regulatory target sequences are distributed throughout the 100-bp element, although substantial differences exist in their function between embryo and IM. Third, putative core auxin response elements (AuxREs) spatially activate or restrict DRNL expression, and fourth, according to chromatin configuration data, En2core enhancer activity in LOFCs correlates with an open chromatin structure at the DRNL transcription start. In combination, mutational and chromatin analyses imply that En2core comprises a high-occupancy target (HOT) region for transcription factors, which implements phyllotactic information for the spiral LOFC pattern in the IM periphery and coordinates the cruciferous array of floral sepals. Our data disfavor a contribution of activating auxin response factors (ARFs) but do not exclude auxin as a morphogenetic signal.
A practical guide to acute pain management in children
Authors: Gai Nan , Naser Basem , Hanley Jacqueline , Peliowski Arie , Hayes Jason , Aoyama Kazuyoshi
Published: March 2020

In the pediatric population, pain is frequently under-recognized and inadequately treated. Improved education and training of health care providers can positively impact the management of pain in children. The purpose of this review is to provide a practical clinical approach to the management of acute pain in the pediatric inpatient population. This will include an overview of commonly used pain management modalities and their potential pitfalls. For institutions that have a pediatric acute pain service or are considering initiating one, it is our hope to provide a useful tool to aid clinicians in the safe and effective treatment of pain in children.
Bioactive compounds and antioxidant activities of Quercus salicina Blume extract
Authors: Aung Thinzar , Bibat Marie Anna Dominique , Zhao Chang-Cheng , Eun Jong-Bang
Published: March 2020

Quercus salicina Blume (QS) is an oak species that is indigenous to Japan and Korea. Historically, extracts of leaves, stems, barks and buds from the QS tree had been extensively utilized as herbal medicines. As rich sources of natural antioxidants, QS extracts could prevent oxidative stress and the occurrence of related neurodegenerative diseases. In pharmaceutical applications, decoction or infusion of comminuted QS powder is prepared as an herbal tea for oral use. Various extraction methods and extracting mediums showed the potential antioxidant activities of QS extracts, as well as the different types and levels of bioactive compounds found in them. Due to their functional properties and possibly low-level of cytotoxicity, the potential application of QS extracts as a novel food ingredient could be considered. In this review paper, a brief overview about QS extracts and their bioactive components, antioxidant activities, toxicity and technological applications is described based on previous works.
Population dynamics and regulation of the Middle Spotted Woodpecker in strictly protected and managed forests in Western Poland
Authors: Kosiński Ziemowit , Walczak Łukasz
Published: March 2020

Analysis of ecological time series allows to assess the relative contribution of density-dependent and density-independent factors influencing the regulation of the population of a species. In this study, we investigated whether the annual fluctuation in the population of Middle Spotted WoodpeckersDendrocoptes mediuscan be attributed to the direct or delayed density-dependent regulation or to the density-independent factors such as weather conditions during the preceding winter and previous breeding season and/or disturbance in the habitat associated with sanitary felling and salvage logging of trees. This study was conducted in the Czeszewo Forest Reserve, which protects the remnants of semi-natural flood-plain forest, and in the Łówkowiec Forest, which is a managed oak-dominated stand, during 19 seasons (2001–2019). Time series diagnostic revealed that the growth rate of population of Middle Spotted Woodpecker in protected semi-natural riverine forest and in managed oak forest was determined by first-order negative feedback, suggesting an important role of direct density-dependent mortality in the regulation of an equilibrium in population size. The effect of density-dependent process varied between study sites, being lower in riverine forest, where population size has increased distinctly in recent years. In both study areas, we detected strong positive effects of wind chill temperature during the preceding winter on population growth rates. We did not find evidence for the assumption that the increase in population growth rate is affected by weather conditions in the previous breeding season and by the disturbance in the habitat associated with sanitary felling and salvage logging of trees. Our results suggest that Middle Spotted Woodpeckers can benefit from global climate warming by an enhanced rate of winter survival or an increase in the accessibility of food, e.g., insects and other arthropods. The lack of time-lag significant correlations between population fluctuations suggests local habitat conditions, e.g., forest management, can modify inter-annual variability in time series of the Middle Spotted Woodpecker.
Normative disagreement: a functional account for inferentialists
Authors: Köhler Sebastian
Published: March 2020

There was a time when meta-ethical expressivism seemed to be the only game in town for meta-ethical non-representationalists. In recent years, though, meta-ethical inferentialism has emerged as a promising non-representationalist alternative. So far, however, inferentialists lack something that would really allow them to draw level with expressivists. This is an explanation for the distinctive difference between normative and descriptive vocabulary when it comes to disagreement—something expressivists can explain in terms of the difference between representational and desire-like states and which constitutes one of the primary motivations for expressivism. This paper develops a novel and distinctive account for this difference on behalf of inferentialists, based on the differentfunctionsof these two vocabularies. Not only does this account help inferentialists, it also shows how non-representionalist accounts can capture the relevant disagreement phenomenawithoutappealing to the sorts of desire-like states expressivists tend to appeal to.