bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methionine Commits Cells to Differentiate Into Plasmablasts Through Epigenetic Regulation of BTB and CNC Homolog 2 by the Methyltransferase EZH2
Authors: Zhang Mingzeng , Iwata Shigeru , Hajime Maiko , Ohkubo Naoaki , Todoroki Yasuyuki , Miyata Hiroko , Ueno Masanobu , Hao He , Zhang Tong , Fan Jie , Nakayamada Shingo , Yamagata Kaoru , Tanaka Yoshiya 
Published: January 2020

ObjectivePlasmablasts play important roles in autoimmune diseases, including systemic lupus erythematosus (SLE). Activation of mechanistic target of rapamycin complex 1 (mTORC1) is regulated by amino acid levels. In patients with SLE, mTORC1 is activated in B cells and modulates plasmablast differentiation. However, the detailed mechanisms of amino acid metabolism in plasmablast differentiation remain elusive. We undertook this study to evaluate the effects of methionine in human B cells.MethodsPurified CD19+ cells from healthy donors (n = 21) or patients with SLE (n = 35) were cultured with Toll‐like receptor 7/9 ligand, interferon‐α (IFNα), and B cell receptor crosslinking, and we determined the types of amino acids that were important for plasmablast differentiation and amino acid metabolism. We also identified the transcriptional regulatory mechanisms induced by amino acid metabolism, and we assessed B cell metabolism and its relevance to SLE.ResultsThe essential amino acid methionine strongly committed cells to plasmablast differentiation. In the presence of methionine, Syk and mTORC1 activation synergistically induced methyltransferase EZH2 expression. EZH2 induced H3K27me3 at BTB and CNC homolog 2 (Bach2) loci and suppressed Bach2 expression, leading to induction of B lymphocyte–induced maturation protein 1 and X‐box binding protein 1 expression and plasmablast differentiation. CD19+ cells from patients with SLE overexpressed EZH2, which was correlated with disease activity and autoantibody production.ConclusionOur findings show that methionine activated signaling by controlling immunologic metabolism in B cells and played an important role in the differentiation of B cells into plasmablasts through epigenome modification of Bach2 by the methyltransferase EZH2.
Versuchstechnische Untersuchungen zu Korrosionsschäden an Winkelstützmauern
Authors: Rebhan Matthias J. , Vorwagner Alois , Burtscher Stefan L. , Kwapisz Maciej , Marte Roman 
Published: January 2020

AbstractStützbauwerke unterliegen, wie andere Bauwerke auch, einer Alterung und Beeinflussung durch ihre Umwelt. Bei Bauwerken aus Stahlbeton resultiert dies oftmals in Betonabplatzungen, vermehrter Rissbildung oder der Korrosion von Bewehrungselementen. Winkelstützmauern werden zumeist in schlanker Bauweise und damit mit einem hohen Bewehrungsgrad hergestellt. Die Hauptbewehrung liegt dabei auf der erdberührten Rückseite und ist von außen nicht sichtbar. Bei der Untersuchung von Stützmauern wurden – besonders in der Arbeitsfuge von Fundament und aufgehender Mauer – vermehrt Korrosionserscheinungen gefunden. Diese beeinflussen die Tragfähigkeit und damit auch die Standsicherheit stark. Großflächigere Untersuchungen haben auch gezeigt, dass das Ausmaß der Korrosion entlang der Arbeitsfuge stark unterschiedlich sein kann. Es ist mit herkömmlichen Methoden schwierig bzw. zumeist nicht möglich, die Bereiche außerhalb der Untersuchungsstellen zu beurteilen. In diesem Beitrag erfolgt ein Überblick zu Schadensbildern, deren Ursachen sowie die Möglichkeiten von Bauwerksuntersuchungen. Darauf aufbauend wird ein Konzept zur messtechnischen Überwachung von Korrosionsschäden an der Hauptbewehrung vorgestellt. Abschließend werden Messergebnisse aus einer experimentellen Versuchsreihe den Ergebnissen einer numerischen Parameterstudie zur Bewehrungskorrosion gegenübergestellt.
Postoperative pressure injuries in adults having surgery under general anaesthesia: systematic review of perioperative risk factors
Authors: Haisley M , Sørensen J A , Sollie M 
Published: January 2020

Abstract

Background
Pressure injuries (PIs) after surgery affect thousands of people worldwide. Their management is expensive, a cost that can be reduced with proper preventive measures. Patients having surgery under general anaesthesia are at risk of developing PI, yet no specific tool has been developed to assess the risk in these patients. This review aimed to summarize the published data on perioperative risk factors associated with the development of PI in adults having surgery under general anaesthesia.

Methods
All studies reporting on risk factors associated with the development of PI were included. Data were extracted from all articles and meta-analysis was performed when three or more studies reported on a specific variable.

Results
The analysis identified five factors significantly associated with the development of PIs: cardiovascular disease, respiratory disease, diabetes mellitus, low haemoglobin level and longer duration of surgery. Factors not associated included serum albumin concentration, use of vasopressors during surgery, use of corticosteroids, sex and age.

Conclusion
Cardiovascular disease, respiratory disease, diabetes mellitus, anaemia and duration of surgery should be taken into consideration when trying to identify surgical patients at high risk of developing PIs. These factors could be used to predict PIs after surgery.
The novel GLP‐1/GIP analogue DA5‐CH reduces tau phosphorylation and normalizes theta rhythm in the icv. STZ rat model of AD
Authors: Li Cheng , Liu Weizhen , Li Xiaohui , Zhang Zijuan , Qi Huaxin , Liu Shijin , Yan Ningning , Xing Ying , Hölscher Christian , Wang Zhiju 
Published: January 2020

AbstractIntroductionAlzheimer's disease (AD) is the most common progressive neurodegenerative disease for which there is no cure. Recent studies have shown a close link between type 2 diabetes and AD, which suggested that drugs for type 2 diabetes may be effective for AD. GLP‐1 and GIP are incretin hormones that can ameliorate diabetes.MethodsIn the present study, we tested the novel dual GLP‐1/GIP receptor agonist DA5‐CH in the icv. streptozotocin (STZ)‐induced insulin desensitization model of AD in rats to explore the protective effects of DA5‐CH.ResultsThe results show that DA5‐CH could reverse the STZ‐induced working memory impairments in a Y‐maze tests, and spatial memory impairments in the water maze task, and decrease the levels of phosphorylated tauS396 protein in the hippocampus. In EEG recordings, STZ treatment diminished the power of the theta band frequency. DA5‐CH was able to increase the energy of theta band activity in the hippocampal CA1 region. The drug also increased the expression of synapse‐related proteins in the hippocampus. After DA5‐CH treatment, mitochondrial stress was alleviated as shown by the improved ratio of Bax/Bcl‐2 in the hippocampus. Growth factor signaling was also normalized as shown by the increased level of the transcription factor P‐CREBS133. In addition, we were able to show that DA5‐CH can cross the blood–brain barrier at an increased rate compared with other dual GLP‐1/GIP or single GLP‐1 receptor agonists.ConclusionTherefore, our results demonstrate that DA5‐CH has neuroprotective effects in the STZ‐induced animal model and that DA5‐CH has potential to treat neurodegenerative disorders such as AD.
Intranasal deferoxamine can improve memory in healthy C57 mice, suggesting a partially non‐disease‐specific pathway of functional neurologic improvement
Authors: Fine Jared M. , Kosyakovsky Jacob , Baillargeon Amanda M. , Tokarev Julian V. , Cooner Jacob M. , Svitak Aleta L. , Faltesek Katherine A. , Frey William H. , Hanson Leah R. 
Published: January 2020

AbstractIntroductionIntranasal deferoxamine (IN DFO) has been shown to decrease memory loss and have beneficial impacts across several models of neurologic disease and injury, including rodent models of Alzheimer's and Parkinson's disease.MethodsIn order to assess the mechanism of DFO, determine its ability to improve memory from baseline in the absence of a diseased state, and assess targeting ability of intranasal delivery, we treated healthy mice with IN DFO (2.4 mg) or intraperitoneal (IP) DFO and compared behavioral and biochemical changes with saline‐treated controls. Mice were treated 5 days/week for 4 weeks and subjected to behavioral tests 30 min after dosing.ResultsWe found that IN DFO, but not IP DFO, significantly enhanced working memory in the radial arm water maze, suggesting that IN administration is more efficacious as a targeted delivery route to the brain. Moreover, the ability of DFO to improve memory from baseline in healthy mice suggests a non‐disease‐specific mechanism of memory improvement. IN DFO treatment was accompanied by decreased GSK‐3β activity and increased HIF‐1α activity.ConclusionsThese pathways are suspected in DFO's ability to improve memory and perhaps represent a component of the common mechanism through which DFO enacts beneficial change in models of neurologic disease and injury.
Corporate governance beyond the shareholder–stakeholder dichotomy: Lessons from Japanese corporations' environmental performance
Authors: Endo Kazumi 
Published: January 2020

AbstractAlthough corporate environmental performance (CEP) is determined by corporate governance (CG) typified by board and ownership structures, in‐depth research on stakeholder‐oriented CG is sparse. This study seeks to fill this void and promote an alternative vision of good governance. Japanese corporations have often been criticized for their stakeholder‐oriented practices such as less independent boards and the dominance of stable domestic shareholders. However, these practices are not necessarily problematic if effective monitoring mechanisms are in place. Using a database of Japanese listed corporations over 2012–2015, this study shows that both board size and composition enhance CEP, confirming the advisory function of boards. Contrastingly, foreign blockholders, who are expected to play a monitoring role, significantly constrain CEP. Japanese corporations are evolving toward a hybrid CG that aims to narrow the shareholder–stakeholder divide, and the findings will offer useful lessons for the modification of shareholder‐oriented CG.
Police endorsement of color‐blind racial beliefs and propensity to interact with youth of color
Authors: April Keisha , Cole Lindsey M. , Goldstein Naomi E.S. 
Published: January 2020

AbstractThe beliefs of police, as the point of first contact with the justice system, may help to explain disproportionate minority contact between police and young people. Color‐blind racial beliefs, a form of implicit racism in which racial differences are denied, are more strongly endorsed by police than by laypeople. Using a 2 (youth race) × 3 (offense severity) experimental design, 339 officers participated in an online study examining the influence of youth race, offense severity, and officers' color‐blind racial beliefs on officers' reported likelihood of interacting with young people. Officers with lower levels of color‐blind beliefs reported they would be less likely to interact with Black youth. Additionally, attrition analyses indicated that officers assigned to the Black youth condition were more likely to drop out when asked to complete the measure of color‐blind beliefs. Policy and practice implications are discussed, with a focus on promoting greater discussion of color‐blind ideologies in multicultural trainings for police officers and increasing frank discussions about race and racial issues.
Patient‐reported symptom burden as a prognostic factor in treatment with first‐line cetuximab plus chemotherapy for unresectable metastatic colorectal cancer: Results of Phase II QUACK trial
Authors: Ooki Akira , Morita Satoshi , Iwamoto Shigeyoshi , Hara Hiroki , Tanioka Hiroaki , Satake Hironaga , Kataoka Masato , Kotaka Masahito , Kagawa Yoshinori , Nakamura Masato , Shingai Tatsushi , Ishikawa Masashi , Miyake Yasuhiro , Suto Takeshi , Hashiguchi Yojiro , Yabuno Taichi , Sakamoto Junichi , Tsuji Akihito , Ando Masahiko , Yamaguchi Kensei 
Published: January 2020

AbstractBackgroundIt remains unclear whether patients’ self‐perceptions of symptoms at baseline clinically impact the prognostic relevance, treatment efficacy, or toxicity profiles in metastatic colorectal cancer (mCRC) patients treated with the first‐line cetuximab and standard chemotherapy.MethodsThe data were collected from a prospective trial that assessed the relationships between quality of life (QOL), treatment efficacy, and adverse events (AEs).ResultsThe analysis of 137 mCRC patients revealed a significant association between the presence of baseline tumor‐related symptoms and a lower overall survival (OS) compared to the absence of symptoms (HR, 2.49; 95% CI, 1.37‐4.62; P = .003). The asymptomatic responders had favorable outcomes compared to the symptomatic nonresponders (2‐year OS rates: 83.6% and 35.9%, respectively), while the symptomatic responders had similar outcomes to the asymptomatic nonresponders. The median postprogression survival differed significantly: 10.2 months for the symptomatic patients and 15.9 months for the asymptomatic patients (HR, 2.29; 95% CI, 1.25‐4.29, P = .008). The objective response rates and patient toxicity profiles were similar irrespective of the severity of baseline symptoms.ConclusionBaseline symptoms were associated with worse OS but not with impaired treatment efficacy or more frequent AEs in mCRC patients treated with cetuximab in addition to chemotherapy.
Structural Investigation of Hybrid Peptide Foldamers Composed of α‐Dipeptide Equivalent β‐Oxy‐δ5‐amino Acids
Authors: Reja Rahi M. , Kumar Vivek , George Gijo , Patel Rajat , Puneeth Kumar DRGKoppalu R. , Raghothama Srinivasarao , Gopi Hosahudya N. 
Published: January 2020

AbstractDue to their equivalent lengths, δ‐amino acids can serve as surrogates of α‐dipeptides. However, δ‐amino acids with proteinogenic side chains have not been well studied because of synthetic difficulties and because of their insolubility in organic solvents. Recently we reported the spontaneous supramolecular gelation of δ‐peptides composed of β(O)‐δ5‐amino acids. Here, we report the incorporation of β(O)‐δ5‐amino acids as guests into the host α‐helix, α,γ‐hybrid peptide 12‐helix and their single‐crystal conformations. In addition, we studied the solution conformations of hybrid peptides composed of 1:1 alternating α and β(O)‐δ5‐amino acids. In contrast to the control α‐helix structures, the crystal structure of peptides with β(O)‐δ5‐amino acids exhibit α‐helical conformations consisting of both 13‐ and 10‐membered H‐bonds. The α,δ‐hybrid peptide adopted mixed 13/11‐helix conformation in solution with alternating H‐bond directionality. Crystal‐structure analysis revealed that the α,γ4‐hybrid peptide accommodated the guest β(O)‐δ5‐amino acid without significant deviation to the overall helix folding. The results reported here emphasize that β(O)‐δ5‐amino acids with proteinogenic side chains can be accommodated into regular α‐helix or 12‐helix as guests without much deviation of the overall helix folding of the peptides.
Increasing Complexity: A Practical Synthetic Approach to Three‐Dimensional, Cyclic Sulfoximines and First Insights into Their in Vitro Properties
Authors: Boulard Emilie , Zibulski Vivien , Oertel Luisa , Lienau Philip , Schäfer Martina , Ganzer Ursula , Lücking Ulrich 
Published: January 2020

AbstractA short synthetic approach with broad scope to access five‐ to seven‐membered cyclic sulfoximines in only two to three steps from readily available thiophenols is reported. Thus, simple building blocks were converted to complex molecular structures by a sequence of S‐alkylation and one‐pot sulfoximine formation, followed by intramolecular cyclization. Seventeen structurally diverse cyclic sulfoximines were prepared in high overall yields. In vitro evaluation of these underrepresented, three‐dimensional, cyclic sulfoximines with respect to properties relevant to medicinal chemistry did not reveal any intrinsic flaw for application in drug discovery.
Platelet Function: Meloxicam Intravenous in Whole Blood Samples From Healthy Volunteers
Authors: Jahr Jonathan S. , Searle Shawn , McCallum Stewart , Mack Randall , Minger Kim , Freyer Alex , Du Wei , Hobson Sue 
Published: January 2020

AbstractNonsteroidal anti‐inflammatory drugs (NSAIDs) are effective treatments for pain but may induce bleeding events due to platelet dysfunction associated with inhibition of cyclooxygenase (COX)‐1 impairing thromboxane production. An intravenous nanocrystal formulation of meloxicam, a COX‐2 preferential nonsteroidal anti‐inflammatory drug, is under development for the treatment of moderate to severe pain. This single‐center ex vivo study evaluated the effect of meloxicam intravenous and ketorolac on platelet function in whole blood samples from healthy volunteers. Each whole blood sample was aliquoted to allow analysis using a platelet function analyzer under negative control (untreated), positive control (2 therapeutic ketorolac concentrations), and meloxicam intravenous (1 therapeutic, 3 supratherapeutic concentrations) using both collagen with epinephrine and collagen with adenosine diphosphate reagent cartridges. The platelet function analyzer determines closure time by simulating platelet adhesion and aggregation following vascular injury. The final analysis set included data from 8 subjects. The collagen with adenosine diphosphate analysis (sensitive to thrombocytopathies) showed no significant differences in closure time for meloxicam‐ or ketorolac‐treated samples and untreated control. The collagen with epinephrine analysis (sensitive to aspirin‐induced platelet abnormalities) produced no significant difference in closure time between any meloxicam concentration and untreated control. Ketorolac was associated with significantly longer closure times vs untreated control at both the 2.5‐ and 5‐µg/mL concentrations (P = .003 and .0257, respectively) and vs meloxicam at several concentrations. Similar results were observed when all analyzed samples were included. Meloxicam intravenous had no significant effect on closure times at therapeutic or supratherapeutic concentrations in this ex vivo study.
A Phase 1, Randomized, Placebo‐Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Subcutaneous Tezepelumab in Healthy Japanese Men
Authors: Sakamoto Kei , Matsuki Shunji , Irie Shin , Uchida Naoki , Hayashi Nobuya , Horiuchi Masato , Ren Song 
Published: January 2020

AbstractTezepelumab, a human immunoglobulin G2 monoclonal antibody against thymic stromal lymphopoietin, is currently under clinical development for the treatment of severe, uncontrolled asthma. This phase 1, randomized, placebo‐controlled, single‐ascending‐dose study assessed the safety, tolerability, pharmacokinetics, and immunogenicity of subcutaneous tezepelumab in healthy Japanese men. Participants were assigned to 1 of 3 tezepelumab dose cohorts (35, 105, or 280 mg; n = 8 per cohort) and randomized (6:2) to receive a single subcutaneous dose of tezepelumab or placebo, with a follow‐up period of 84 to 112 days. The overall incidences and severities of treatment‐emergent adverse events were similar across tezepelumab doses and between the tezepelumab and placebo groups. Tezepelumab was absorbed slowly, reaching a maximum serum concentration (mean, 5.2‐39.7 µg/mL) after 7 to 10 days. Area under the concentration‐time curve (mean, 207.2‐1612.0 µg · day /mL) increased in an approximate dose‐proportional manner. Tezepelumab had a long terminal serum half‐life (mean, 23.9‐26.3 days) and a small apparent distribution volume, suggesting limited distribution into peripheral tissues. No participants developed anti‐tezepelumab antibodies. Single‐dose, subcutaneous administration of tezepelumab 35 to 280 mg resulted in an acceptable safety profile with linear pharmacokinetics in healthy Japanese men. No clear differences in tezepelumab safety and pharmacokinetics between Japanese and non‐Japanese populations were identified.
The relation between corporate social responsibility certification and financial performance: An empirical study in Spain
Authors: Brotons José M. , Sansalvador Manuel E. 
Published: January 2020

AbstractThe relation between corporate social responsibility (CSR) and financial performance (FP) has been widely dealt with in specialized literature. This study has two points of interest: first, we develop a new tool which financially quantifies the value contributed to companies that are committed to CSR; then, we make a practical application of this tool through an empirical study focused on Spanish companies. This study is especially innovative because of the fuzzy methodology used and the way it defines CSR through the IQNet SR10 certification of social responsibility systems. In addition, the measurement of CSR through IQNet SR10 certification is a completely new approach to the subject. An interesting conclusion can be drawn from the empirical study: IQNet SR10 CSR certification increases the value of businesses. However, neither size nor the economic sector they belong to influence this relationship significantly.
Vertebrate scavenger guild composition and utilization of carrion in an East Asian temperate forest
Authors: Inagaki Akino , Allen Maximilian L. , Maruyama Tetsuya , Yamazaki Koji , Tochigi Kahoko , Naganuma Tomoko , Koike Shinsuke 
Published: January 2020

AbstractScavenging is a common feeding behavior by many species that plays an important role in ecosystem stability and function while also providing ecosystem services. Despite its importance, facultative scavenging on large animal carcasses has generally been overlooked in Asian temperate forest ecosystems. The aim of this study was to determine the composition and feeding behavior of the facultative scavenger guild as it relates to sika deer (Cervus nippon) carcasses in Japanese forests. There are no obligate scavengers or large predators that kill adult ungulates, but humans fill the role of large predators by culling deer for population management. We documented nine vertebrate species scavenging on deer carcasses and found that mammals were more frequent scavengers than birds and also fed for longer durations. This result suggests that there is a facultative scavenger guild composed mainly of mammals in our forest ecosystem and that carcass utilization by birds was restricted to only forest species. Raccoon dogs (Nyctereutes procyonoides) and Asian black bears (Ursus thibetanus) were the most frequent scavenger species and also fed for longer durations than other scavengers. There were significant seasonal differences in scavenging by Asian black bear, Japanese marten (Martes melampus), and mountain hawk‐eagle (Nisaetus nipalensis), suggesting the availability of other food resources may alter facultative scavenging by each species. Our results support that scavenging is widespread in this system and likely has important functions including building links in the food web.