bluuebunny/crossref_metadata_2025_split huggingface dataset:
One‐pot, fast cyclopropanation reaction of indandione with various aldehydes in the presence of cyanogen bromide and trimethylamine
Authors: Aalinejad Michael , Noroozi Pesyan Nader 
Published: May 2019

AbstractA new, fast, and easy one‐pot cyclopropanation reaction of aromatic and aliphatic aldehydes with 1H‐indene‐1,3(2H)‐dione and cyanogen bromide (BrCN) was developed for synthesizing 3′‐(aryl[alkyl])‐dispiro[indan‐2,1′‐cyclopropane‐2′,2′′‐indan]‐1,1′′,3,3′′‐tetrone in excellent yields in a short time (about 15 s) under basic media. All structures were characterized using IR, 1H NMR, and 13C NMR spectroscopy techniques.
An illustration of collaborative care with a focus on the role of fathers in Maudsley Anorexia Nervosa Treatment for Adults (MANTRA)
Authors: Treasure Janet , Schmidt Ulrike , Kan Carol 
Published: May 2019

AbstractThe aim of this case study is to illustrate the importance of collaborative care as part of Maudsley Anorexia Nervosa Treatment for Adults (MANTRA). Mothers are often at the foreground of providing support within the family. However, fathers have the potential to play a profound role. In this paper, we describe a patient with anorexia nervosa treated with the MANTRA. The formulation of this case included autistic spectrum traits in both the father and daughter leading to social isolation. We describe how the family members were engaged into treatment and how paternal support was used to promote social connection and an improved quality of life in the daughter. Some details of the case have been altered to maintain confidentiality.
Th17 immune response to adipose tissue‐derived mesenchymal stromal cells
Authors: Najar Mehdi , Lombard Catherine A. , Fayyad‐Kazan Hussein , Faour Wissam H. , Merimi Makram , Sokal Etienne M. , Lagneaux Laurence , Fahmi Hassan 
Published: May 2019

AbstractAdipose tissue‐derived mesenchymal stromal cells (ASCs) hold the promise of achieving successful immunotherapeutic results due to their ability to regulate different T‐cell fate. ASCs also show significant adaptability to environmental stresses by modulating their immunologic profile. Cell‐based therapy for inflammatory diseases requires a detailed understanding of the molecular relation between ASCs and Th17 lymphocytes taking into account the influence of inflammation and cell ratio on such interaction. Accordingly, a dose‐dependent increase in Th17 generation was only observed in high MSC:T‐cell ratio with no significant impact of inflammatory priming. IL‐23 receptor (IL‐23R) expression by T cells was not modulated by ASCs when compared to levels in activated T cells, while ROR‐γt expression was significantly increased reaching a maximum in high (1:5) unprimed ASC:T‐cell ratio. Finally, multiplex immunoassay showed substantial changes in the secretory profile of 15 cytokines involved in the Th17 immune response (IL‐1β, IL‐4, IL‐6, IL‐10, IL‐17A, IL‐17F, IL‐22, IL‐21, IL‐23, IL‐25, IL‐31, IL‐33, IFN‐γ, sCD40, and TNF‐α), which was modulated by both cell ratio and inflammatory priming. These findings suggest that Th17 lymphocyte pathway is significantly modulated by ASCs that may lead to immunological changes. Therefore, future ASC‐based immunotherapy should take into account the complex and detailed molecular interactions that depend on several factors including inflammatory priming and cell ratio.
Identification of EPHX2 and RMI2 as two novel key genes in cervical squamous cell carcinoma by an integrated bioinformatic analysis
Authors: Liu Jinhui , Nie Sipei , Gao Mei , Jiang Yi , Wan Yicong , Ma Xiaoling , Zhou Shulin , Cheng Wenjun 
Published: May 2019

AbstractCervical cancer is the fourth most common malignancy in women worldwide and cervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer. The dysregulation of genes plays a significant role in cancer. In the present study, we screened out differentially expressed genes (DEGs) of CESC in the GSE63514 data set from the Gene Expression Omnibus database. An integrated bioinformatics analysis was used to select hub genes, as well as to investigate their related prognostic signature, functional annotation, methylation mechanism, and candidate molecular drugs. As a result, a total of 1907 DEGs were identified (944 were upregulated and 963 were downregulated). In the protein–protein interaction network, three hub modules and 30 hub genes were identified. And two hub modules and 116 hub genes were screened out from four CESC‐related modules by the weighted gene coexpression network analysis. The gene ontology term enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed to better understand functions and pathways. Genes with a significant prognostic value were found by prognostic signature analysis. And there were five genes (EPHX2, CHAF1B, KIAA1524, CDC45, and RMI2) identified as significant CESC‐associated genes after expression validation and survival analysis. Among them, EPHX2 and RMI2 were noted as two novel key genes for the CESC‐associated methylation and expression. In addition, four candidate small molecule drugs for CESC (camptothecin, resveratrol, vorinostat, and trichostatin A) were defined. Further studies are required to explore these significant CESC‐associated genes for their potentiality in diagnosis, prognosis, and targeted therapy.
Anti‐inflammatory roles of microRNA 21 in lipopolysaccharide‐stimulated human dental pulp cells
Authors: Nara Keisuke , Kawashima Nobuyuki , Noda Sonoko , Fujii Mayuko , Hashimoto Kentaro , Tazawa Kento , Okiji Takashi 
Published: May 2019

AbstractmicroRNAs are small noncoding RNA molecules that regulate RNA silencing and posttranscriptional gene expression, and many microRNAs are involved in inflammatory processes. In particular, microRNA 21 (miR‐21) is upregulated in inflammatory environment and reported to induce anti‐inflammatory responses. However, the involvement of miR‐21 in pulpal inflammation and the precise mechanisms of anti‐inflammatory reactions induced by miR‐21 remain unclear. We hypothesized that miR‐21‐5p expression is induced in lipopolysaccharide (LPS)‐stimulated human dental pulp cells (hDPCs) and that miR‐21‐5p downregulates the proinflammatory cytokine expression in LPS‐stimulated hDPCs. We found that miR‐21‐5p was upregulated in LPS‐stimulated hDPCs concomitant with elevated proinflammatory cytokine expression and nuclear factor‐kappa B (NF‐κB) phosphorylation. miR‐21‐5p and cytokine expression were downregulated by BAY11‐7085 and caffeic acid phenylethyl ester (CAPE), specific and potent NF‐κB inhibitors. Enforced expression of miR‐21‐5p downregulated the Toll‐like receptor (TLR)/NF‐κB signaling via reducing the expression of TNF receptor‐associated factor 6 (TRAF6) and programmed cell death 4 (PDCD4), which further induced the decrease of proinflammatory cytokine expression. hDPCs forcibly overexpressing miR‐21‐5p downregulated the LPS‐induced expression of TNF receptor‐associated factor 6 (TRAF6; a component of the Toll‐like receptor [TLR]/NF‐κB signaling pathway), programmed cell death 4 (PDCD4, a positive regulator of the TLR/NF‐κB signaling pathway), and proinflammatory cytokines. In contrast, miR‐21‐5p inhibitor‐transfected hDPCs upregulated the expression of TRAF6, PDCD4, and inflammatory cytokines following LPS stimulation. These findings suggest that miR‐21‐5p expression was induced by the NF‐κB signaling pathway, which was in turn negatively regulated by miR‐21‐5p via downregulation of TRAF6 and PDCD4 expression in LPS‐stimulated hDPCs.
MiR‐455‐5p ameliorates HG‐induced apoptosis, oxidative stress and inflammatory via targeting SOCS3 in retinal pigment epithelial cells
Authors: Chen Pan , Miao Ying , Yan PuJun , Wang Xiao Jie , Jiang ChunXia , Lei Yi 
Published: May 2019

AbstractDiabetic retinopathy (DR) remains the leading cause of blindness in adults with diabetes mellitus. Numerous microRNAs (miRNAs) have been identified to modulate the pathogenesis of DR. The main purpose of this study was to evaluate the potential roles of miR‐455‐5p in high glucose (HG)‐treated retinal pigment epithelial (RPE) cells and underlying mechanisms. Our present investigation discovered that the expression of miR‐455‐5p was apparently downregulated in ARPE‐19 cells stimulated with HG. In addition, forced expression of miR‐455‐5p markedly enhanced cell viability and restrained HG‐induced apoptosis accompanied by decreased BCL2‐associated X protein (Bax)/B‐cell leukemia/lymphoma 2 (Bcl‐2) ratio and expression of apoptotic marker cleaved caspase‐3 during HG challenged. Subsequently, augmentation of miR‐455‐5p remarkably alleviated HG‐triggered oxidative stress injury as reflected by decreased the production of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) content as well as NADPH oxidase 4 expression, concomitant with enhanced the activities of superoxide dismutase, catalase, and GPX stimulated with HG. Furthermore, enforced expression of miR‐455‐5p effectively ameliorated HG‐stimulated inflammatory response as exemplified by repressing the secretion of inflammatory cytokines interleukin 1β (IL‐1β), IL‐6, and tumour necrosis factor‐α in ARPE‐19 cells challenged by HG. Most importantly, we successfully identified suppressor of cytokine signaling 3 (SOCS3) as a direct target gene of miR‐455‐5p, and miR‐455‐5p negatively regulated the expression of SOCS3. Mechanistically, restoration of SOCS3 abrogated the beneficial effects of miR‐455‐5p on apoptosis, accumulation of ROS, and inflammatory factors production in response to HG. Taken together, these findings demonstrated that miR‐455‐5p relieved HG‐induced damage through repressing apoptosis, oxidant stress, and inflammatory response by targeting SOCS3. The study gives evidence that miR‐455‐5p may serve as a new potential therapeutic agent for DR treatment.
The Misshapen subfamily of Ste20 kinases regulate proliferation in the aging mammalian intestinal epithelium
Authors: Li Qi , Nirala Niraj K. , Chen Hsi‐Ju , Nie Yingchao , Wang Wei , Zhang Biliang , Czech Michael P. , Wang Qi , Xu Lan , Mao Junhao , Ip Y. Tony 
Published: May 2019

AbstractThe intestinal epithelium has a high rate of cell turn over and is an excellent system to study stem cell‐mediated tissue homeostasis. The Misshapen subfamily of the Ste20 kinases in mammals consists of misshapen like kinase 1 (MINK1), mitogen‐activated protein kinase kinase kinase kinase 4 (MAP4K4), and TRAF2 and NCK interacting kinase (TNIK). Recent reports suggest that this subfamily has a novel function equal to the Hippo/MST subfamily as upstream kinases for Warts/Large tumor suppressor kinase (LATS) to suppress tissue growth. To study the in vivo functions of Mink1, Map4k4, and Tnik, we generated a compound knockout of these three genes in the mouse intestinal epithelium. The intestinal epithelia of the mutant animals were phenotypically normal up to approximately 12 months. The older animals then exhibited mildly increased proliferation throughout the lower GI tract. We also observed that the normally spatially organized Paneth cells in the crypt base became dispersed. The expression of one of the YAP pathway target genes Sox9 was increased while other target genes including CTGF did not show a significant change. Therefore, the Misshapen and Hippo subfamilies may have highly redundant functions to regulate growth in the intestinal epithelium, as illustrated in recent tissue culture models.
Retracted: Visible‐light‐driven mitigation of antibiotic oxytetracycline and disinfection of Escherichia coli using magnetic recyclable Ag‐modified zinc ferrite/diatomite ternary hybrid material
Authors: Wu Qiong , Zhang Zhaohong 
Published: May 2019

AbstractBACKGROUNDThe pharmaceutical residues in water are considered globally to be typical hazardous pollutants. Many technologies have been reported to eliminate these residues, such as photocatalysis, which has usually been applied in a suspension system with powdery photocatalyst. The disadvantage of this system, hindering its practical application, is its low recyclability. Ferrite‐based photocatalysts have been synthesized to resolve this problem. In this work, silver (Ag)‐modified zinc ferrite (ZnFe2O4) nanoparticles were immobilized onto porous mineral diatomite. The physicochemical properties of this composite were studied systematically, and its photocatalytic efficiency was investigated via the degradation of antibiotic oxytetracycline (OTC) and disinfection of bacteria Escherichia coli under visible light.RESULTSThe degradation rate increased after the catalyst was immobilized onto diatomite, due to the adsorption and degradation synergistic effect. The Ag cluster improved the visible‐light‐driven photoactivity of ZnFe2O4, and its optimal percentage was determined. The best catalyst dosage during the degradation process also was obtained. The optimal catalyst exhibited its removal rate of OTC (10 mg L−1 aqueous solution) as 90.5% in 2.5 h, and disinfection rate of E. coli as 87.2% in 2 h, under visible light irradiation. Moreover, the photocatalysis mechanism was illustrated.CONCLUSIONThis composite could be recovered simply from the water body via an external magnet, and indicated no obvious decrease of photoactivity after being recycled five times for photodegradation or photodisinfection tests. This nanocomposite showed good potential for application in wastewater remediation process, thanks to its high photocatalytic efficiency under visible light, as well as its good reusability and stability. © 2019 Society of Chemical Industry
Statistical optimization and kinetic analysis of the extraction of phenolic compounds from olive leaves
Authors: Lamprou George K , Vlysidis Anestis , Tzathas Konstantinos , Vlyssides Apostolos G 
Published: May 2019

AbstractBackgroundOlive leaves are considered to be one of the most abundant agricultural waste source rich in phenolic compounds. A new method for extracting the phenolic compounds contained in olive leaves was developed in this study. The method was based on the addition of sulfuric acid (H2SO4), hydrolyzing the olive leaves and producing extracts rich in phenolic compounds. Experimental runs were carried out according to a central composite design (CCD) comprising the most important factors that affect the extraction process.ResultsThe factors examined were extraction temperature, the addition of H2SO4 and the dilution of olive leaves with water. Maximum total phenolic content (TPC) was 86.4 mg GAE g–1 dry weight basis (db) at 31.9 °C, 6.4% H2SO4 (v/w) and 25.2 L : S (v/w). Validation runs on the optimum were very close to model predictions for TPC. Optimum oleuropein was 43.1 mg g−1 db at 40 °C, 2.0% H2SO4 (v/w) and 30 liquid : solid (v/w). Finally, the kinetics of TPC and oleuropein were studied at the optimum conditions designated by the CCD.ConclusionIn this study, a new cost‐effective extraction process of phenolic compounds from olive leaves was examined as the developed process employs low‐value chemicals (i.e. H2SO4) in small amounts offering through its simplicity the right conditions to scale this process up in industrial applications integrated within olive mill facilities. © 2019 Society of Chemical Industry
In vitro biosynthesis of optically pure d‐(−)‐acetoin from meso‐2,3‐butanediol using 2,3‐butanediol dehydrogenase and NADH oxidase
Authors: Cui Zhenzhen , Zhao Yujiao , Mao Yufeng , Shi Ting , Lu Lingxue , Ma Hongwu , Wang Zhiwen , Chen Tao 
Published: May 2019

AbstractBACKGROUNDAcetoin, especially the chiral l‐(+)‐ or d‐(−)‐enantiomer, is a high‐value industrial product that can be used as a pharmaceutical intermediate. However, the production of optically pure acetoin via conventional chemical synthesis is expensive. Classical microbial fermentations satisfy the criteria of green chemistry, but have numerous disadvantages, such as complicated process engineering, unsatisfactory titers or productivities, and difficult product separation due to the inevitable generation of by‐products and overly complex media. By contrast, enzymatic biocatalysis in cell‐free biosystems has numerous advantages in production of chemicals with high purity, whereas efficient enzymatic methods for the production of optically pure acetoin have rarely been reported.RESULTSAn efficient coupled two‐enzyme system composed of 2,3‐butanediol dehydrogenase and H2O‐forming NADH oxidase was constructed to produce optically pure acetoin without introducing any substrate or by‐product. A 2,3‐butanediol dehydrogenase and three NADH oxidases were purified, characterized and assembled into different two‐enzyme systems. The best system, composed of LL‐NOX and CG‐BDH, was then selected according to the acetoin titer. After optimization of the reaction conditions, 94.0% of meso‐2,3‐butanediol was converted to d‐(−)‐acetoin. Finally, 399.7 mmol L−1 d‐(−)‐acetoin with an enantiomeric excess of 91.2% was produced in 6 h without any detected by‐products.CONCLUSIONSTo our best knowledge, this is the first report on the production of optically pure d‐(−)‐acetoin from meso‐2,3‐butanediol in vitro using NADH oxidase to regenerate NAD+, as well as the best substrate conversion and acetoin titer among enzymatic biosynthesis. This work therefore provides an economical and green alternative for the in vitro production of d‐(−)‐acetoin. © 2019 Society of Chemical Industry
Evaluation of an automated process for disclosure of negative noninvasive prenatal test results
Authors: Kalejta Cassidi D. , Higgins Sonja , Kershberg Hilary , Greenberg Jeff , Alvarado Monica , Cooke Kerry , Bhatt Sucheta , Bulpitt Denise , Armour Jamie , Bejjani Bassem , Ryan Shawnia , Elms Amanda 
Published: May 2019

AbstractWe designed and implemented a novel automated negative non‐invasive prenatal test (NIPT) result disclosure process using a proprietary, HIPAA‐compliant web‐based portal. High‐risk pregnant patients who opted for NIPT from 04/2017 to 12/2018 were given the option to receive their negative result through the automated process. Patients were required to watch a brief educational video and answer evaluative questions before downloading their result. After completing the process, patients completed a survey regarding their opinion of the efficiency and convenience of the process and their satisfaction. A total of 10,170 women registered online during the study period, and 8,965 completed the automated process (88%). Out of 8,965 women, 2,121 women responded to the survey (24%). Most (2,030 of 2,101) strongly agreed/agreed that they could easily navigate the patient portal (97%); 1,852 of 1,966 strongly agreed/agreed that disclosure was efficient and convenient (94%); 1,852 of 1,960 strongly agreed/agreed that they felt informed after watching a short educational video (94%); and 1,903 of 1,967 strongly agreed/agreed that they preferred downloading results rather than waiting for their next doctor's appointment (97%). This study demonstrates high patient satisfaction with this automated and scalable solution in a high‐volume health system. As the utilization of genetic testing increases, we predict greater need for innovative healthcare delivery models.
Evaluation of life cycle defective adenovirus mutants for production of adeno‐associated virus vectors
Authors: Krüger‐Haag Alexandra , Lehmann Caroline , Schmidt Erika , Sonntag Florian , Hörer Markus , Kochanek Stefan 
Published: May 2019

AbstractBackgroundAdeno‐associated virus‐based vectors are efficient and safe drug candidates for different in vivo gene therapy applications. With increasing numbers of clinical studies based on AAV2 vectors that include not only rare, but also common diseases as a therapeutic target, there is an increased demand for the development of improved production technologies.MethodsIn the present study, we compared two life cycle defective adenovirus mutants as helper viruses for AAV2 vector production. They had deletions either in the gene coding for the preterminal protein (pTP) that is expressed early in the viral life cycle and is essential for genome replication or in the gene coding for the 100K protein, a protein with many functions, one of which is involved in virus assembly. AAV2 vector production efficiencies were evaluated by analyzing genome‐containing particles using a real‐time polymerase chain reaction and functional units were investigated by transduction assays.ResultsSomewhat contrary to our expectations, the ∆100K mutant virus showed only a moderate efficiency as a helper virus for AAV2 vector production, whereas the replication‐deficient ∆pTP mutant supported AAV2 production almost as efficiently as adenovirus wild‐type. We also showed that a temperature shift to 32°C together with extended incubation times improved AAV2 vector productivity.ConclusionsThe present study indicates the advantages of using a ∆pTP mutant adenovirus rather than adenovirus wild‐type as a helper virus for AAV2 production and also indicates that temperature shifts to lower temperatures may improve AAV2 vector production rates.
The shift in tuberculosis timing among people living with HIV in the course of antiretroviral therapy scale‐up in Malawi
Authors: Tweya Hannock , Feldacker Caryl , Mpunga James , Kanyerere Henry , Heller Tom , Ganesh Prakash , Nkosi Dave , Kalulu Mike , Sinkala George , Satumba Thomas , Phiri Sam 
Published: May 2019

AbstractIntroductionAlthough the use of antiretroviral therapy (ART) reduces HIV‐associated tuberculosis (TB), patients living with HIV receiving ART remain at a higher risk of developing TB compared to those without HIV. We investigated the incidence of TB and the proportion of HIV‐associated TB cases among patients living with HIV who are receiving ART.MethodsThe study used TB registration and ART programme data collected between 2008 and 2017 from an integrated, public clinic in urban Lilongwe, Malawi. ART initiation was based on either WHO clinical staging or CD4 cell count. The CD4 thresholds for ART initiation eligibility was initially 250 cells/μL then changed to 350 cells/μL in 2011, 500 cells/μL in 2014 and to universal treatment upon diagnosis from 2016. Using TB registration data, we calculated the proportion of TB/HIV patients who were already on ART when they registered for TB treatment by year of TB registration. ART registration data were used to examine TB incidence by calendar year of ART follow‐up and by time on ART.ResultsThe overall proportion of TB/patients living with HIV who started TB treatment while on ART increased from 21% in 2008 to 81% in 2017 but numbers remained relatively constant at 500 TB cases annually. The overall incidence rate of TB among patients on ART was 1.35/100 person‐years (95% CI 1.28 to 1.42). The incidence of TB by time on ART decreased from 6.4/100 person‐years in the first three months of ART to 0.4/100 person‐years after eight years on ART. TB incidence was highest in the first month on ART. The annual rate of TB among patients on ART rapidly decreased each calendar year and stabilized at 1% after 2013. Although the risk of developing TB decreased with year of ART initiation in univariable analysis, there was no significant association after adjusting for sex, age and reason for ART eligibility.ConclusionsThe decline in TB incidence over calendar years suggests protective effects of early ART initiation. The high TB incidence within the first month of ART highlights the need for more sensitive tools such as X‐ray and GeneXpert to identify patients living with HIV who have clinical and subclinical TB disease at ART initiation.