bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transplacental delivery of genome editing components causes mutations in embryonic cardiomyocytes of mid‐gestational murine fetuses
Authors: Nakamura Shingo , Ishihara Masayuki , Ando Naoko , Watanabe Satoshi , Sakurai Takayuki , Sato Masahiro 
Published: January 2019

AbstractGenome editing, as exemplified by CRISPR/Cas9, is now recognized as a powerful tool for the engineering of endogenous target genes. It employs only two components, namely, Cas9 in the form of DNA, mRNA, or protein; and guide RNA (gRNA), which is specific to a target gene. When these components are transferred to cells, they create insertion/deletion mutations (indels) within a target gene. Therefore, when fetuses within the uteri of pregnant murine females are exposed to these reagents, fetal cells incorporating them should show mutations in the target gene. To examine a possible genome editing of fetal cells in vivo, we intravenously administered a solution containing plasmid DNA–FuGENE complex to pregnant wild‐type female mice [which had been successfully mated with enhanced green fluorescent protein (EGFP)‐expressing male transgenic mice] on day 12.5 of gestation. The plasmid DNA induces the expression of gRNA, which was targeted at the EGFP cDNA, and that of the Cas9 gene. All fetuses in the pregnant females should express EGFP systemically, since they are heterozygous (Tg/+) for the transgene. Thus, the delivery of CRISPR system targeted at EGFP in the fetuses will cause a reduced expression of EGFP as a result of the genome editing of EGFP genomic sequence. Of the 24 fetuses isolated from three pregnant females 2 days after gene delivery, 3 were found to have reduced fluorescence in their hearts. Genotyping of the dissected hearts revealed the presence of the transgene construct (Cas9 gene) in all the samples. Furthermore, all the three samples exhibited mutations at the target loci, although normal cells were also present. Thus, transplacental delivery of gene editing components may be a useful tool for developing animal models with heart disorder for heart‐related disease research, and gene therapy in congenital heart defects such as hypertrophic cardiomyopathy (HCM). © 2019 IUBMB Life, 9999(9999):1–10, 2019
Poly (3‐hydroxybutyrate‐co‐3‐hydroxyvalerate)/fibrinogen/bredigite nanofibrous membranes and their integration with osteoblasts for guided bone regeneration
Authors: Kouhi Monireh , Jayarama Reddy Venugopal , Fathi Mohammadhossein , Shamanian Morteza , Valipouri Afsaneh , Ramakrishna Seeram 
Published: January 2019

AbstractGuided bone regeneration (GBR) has been established to be an effective method for the repair of defective tissues, which is based on isolating bone defects with a barrier membrane for faster tissue reconstruction. The aim of the present study is to develop poly (hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV)/fibrinogen (FG)/bredigite (BR) membranes with applicability in GBR. BR nanoparticles were synthesized through a sol–gel method and characterized using transmission electron microscopy and X‐ray diffractometer. PHBV, PHBV/FG, and PHBV/FG/BR membranes were fabricated using electrospinning and characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, contact angle, pore size, thermogravimetric analysis and tensile strength. The electrospun PHBV, PHBV/FG, and PHBV/FG/BR nanofibers were successfully obtained with the mean diameter ranging 240–410 nm. The results showed that Young's modulus and ultimate strength of the PHBV membrane reduced upon blending with FG and increased by further incorporation of BR nanoparticles, Moreover hydrophilicity of the PHBV membrane improved on addition of FG and BR. The in vitro degradation assay demonstrated that incorporation of FG and BR into PHBV matrix increased its hydrolytic degradation. Cell‐membrane interactions were studied by culturing human fetal osteoblast cells on the fabricated membrane. According to the obtained results, osteoblasts seeded on PHBV/FG/BR displayed higher cell adhesion and proliferation compared to PHBV and PHBV/FG membrane. Furthermore, alkaline phosphatase activity and alizarin red‐s staining indicated enhanced osteogenic differentiation and mineralization of cells on PHBV/FG/BR membranes. The results demonstrated that developed electrospun PHBV/FG/BR nanofibrous mats have desired potential as a barrier membrane for guided bone tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1154–1165, 2019.
HOX transcript antisense RNA is elevated in gastric carcinogenesis and regulated by the NF‐κB pathway
Authors: Zhang Zhun , Fan Bingbing , Liu Fengyan , Song Ning , Peng Yanping , Ma Wenzheng , Ma Rongtao , Dong Tianyi , Liu Shili 
Published: January 2019

AbstractThe expression pattern of HOX transcript antisense RNA (HOTAIR) in the progression of gastric cancer and the regulation of its expression are still unclear. In the current study, HOTAIR expressions in gastric tissues collected from patients with superficial gastritis, atrophic gastritis, atypical hyperplasia, and gastric cancer as well as normal controls was quantitatively examined. The results showed that the expression of HOTAIR was higher in gastric cancer than in normal tissues, but reached the highest level in atrophic gastritis, suggesting that HOTAIR may be involved in the molecular process of nonresolving inflammation. Then tumor necrosis factor‐α‐induced protein‐8 like‐2 (TIPE2), a known gene associated with nonresolving inflammation, was overexpressed and the results showed that the promotion in TIPE2 expression triggered HOTAIR reduction, this result was further verified by microarray analysis and TIPE2 knockout mice. Subsequently, the data obtained from HOTAIR knockdown experiment showed that it significantly enhanced colony forming capability and inhibited p27 expression in AGS cells. Furthermore, deletion constructs and luciferase‐based activity assays indicated that the −475 to −443bp region of HOTAIR promoter contained a crucial regulatory element. Transcription factor prediction with software TRANSFAC revealed that nuclear factor‐κB signaling protein p65 had a binding site in this region and might have roles in HOTAIR expression. The binding of phosphor‐p65 to HOTAIR promoter was verified by chromatin immunoprecipitation, and succeeding experiment results demonstrated that p65 reduction by p65 small interfering RNA and TIPE2 overexpression also decreased HOTAIR expression. Conclusively, our results suggest that HOTAIR was associated with nonresolving inflammation, and its expression is regulated by p65.
Effectiveness of different irrigation systems in the presence of intracanal‐separated file
Authors: Seven Naimenur , Cora Sabri 
Published: January 2019

AbstractThe aim of this study was to evaluate conventional syringe irrigation and three different irrigant activation techniques' effectiveness for smear layer removal in the absence and presence of intracanal‐separated file (SF) fragment. Mandibular anterior teeth (160 total) with single canal were used and each root canal preparation was finished with the ProTaper Universal F1. The samples were randomly divided into eight equal groups with n = 20 in each group. The Protaper Universal F3 file was used to simulate intracanal file separation in four groups. To remove the smear layer, final irrigation for each group was performed with conventional syringe irrigation (CSI), EndoActivator, Vibringe, and passive ultrasonic irrigation (PUI). The roots were divided into two longitudinal parts and evaluated with scanning electron microscopy, and two observers scored smear layers at 1, 2, and 3 mm away from the minor foramen. The data were analyzed using the Kruskal–Wallis and Mann–Whitney U tests (p < .05). PUI significantly removed the smear layer better at all levels than other nonseparated file groups (p < .05). In the presence of intracanal SF, PUI had the most efficiency loss. Sonic techniques and CSI revealed statistically better smear layer removal efficiency than PUI at 3 mm level in the presence of SF (p < .05). The intragroup score analysis at all levels revealed that there were less smear layers at 3 mm than at 1 mm in all SF groups (p < .001). As a conclusion, sonic/ultrasonic methods did not yield better irrigant by‐passing than CSI in the presence of intracanal SF.
Differentiation between glioblastoma, brain metastasis and subtypes using radiomics analysis
Authors: Artzi Moran , Bressler Idan , Ben Bashat Dafna 
Published: January 2019

BackgroundDifferentiation between glioblastoma and brain metastasis is highly important due to differing medical treatment strategies. While MRI is the modality of choice for the assessment of patients with brain tumors, differentiation between glioblastoma and solitary brain metastasis may be challenging due to their similar appearance on MRI.PurposeTo differentiate between glioblastoma and brain metastasis subtypes using radiomics analysis based on conventional post‐contrast T1‐weighted (T1W) MRI.Study TypeRetrospective.SubjectsData were acquired from 439 patients: 212 patients with glioblastoma and 227 patients with brain metastasis (breast, lung, and others).Field Strength/SequencePost‐contrast 3D T1W gradient echo images, acquired with 1.5 and 3.0 T MR systems.AssessmentAnalysis included image preprocessing, segmentation of tumor area, and features extraction including: patients' clinical information, tumor location, first‐ and second‐order statistical, morphological, wavelet features, and bag‐of‐features. Following dimension reduction, classification was performed using various machine‐learning algorithms including support‐vector machine (SVM), k‐nearest neighbor, decision trees, and ensemble classifiers.Statistical TestsFor classification, the data were divided into training (80%) and testing datasets (20%). Following optimization of the classifiers, mean sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) were calculated.ResultsFor the testing dataset, the best results for differentiation of glioblastoma from brain metastasis were obtained using the SVM classifier with mean accuracy = 0.85, sensitivity = 0.86, specificity = 0.85, and AUC = 0.96. The best classification results between glioblastoma and brain metastasis subtypes were obtained using SVM classifier with mean accuracy = 0.85, 0.89, 0.75, 0.90; sensitivity = 1.00, 0.60, 0.57, 0.11; specificity = 0.76, 0.92, 0.87, 0.99; and AUC = 0.98, 0.81, 0.83, 0.57 for the glioblastoma, breast, lung, and other brain metastases, respectively.Data ConclusionDifferentiation between glioblastoma and brain metastasis showed a high success rate based on postcontrast T1W MRI. Classification between glioblastoma and brain metastasis subtypes may require additional MR sequences with other tissue contrasts.Level of Evidence: 1Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019;50:519–528.
Are BRCA1 and BRCA2 gene mutation patients underscreened for pancreatic adenocarcinoma?
Authors: Roch Alexandra M. , Schneider Justine , Carr Rosalie A. , Lancaster William P. , House Michael G. , Zyromski Nicholas J. , Nakeeb Attila , Schmidt C. Max , Ceppa Eugene P. 
Published: January 2019

BackgroundBreast cancer (BRCA) mutations account for the highest proportion of hereditary causes of pancreatic ductal adenocarcinoma (PDAC). Screening is currently recommended only for patients with one first‐degree relative or two family members with PDAC. We hypothesized that screening all BRCA1/2 patients would identify a higher rate of pancreatic abnormalities.MethodsAll BRCA1/2 patients at a single academic center were retrospectively reviewed (2005‐2015). Pancreatic abnormalities were defined on cross‐sectional imaging as pancreatic neoplasm (cystic/solid) or main‐duct dilation.ResultsTwo hundred and four patients were identified with BRCA mutations. Forty‐seven (40%) had abdominal imaging (20 computerized tomography and 27 magnetic resonance imaging). Twenty‐one percent had pancreatic abnormalities (PDAC [n = 2] and intraductal papillary mucinous neoplasm [IPMN; n = 8]). The prevalence of pancreatic abnormalities and IPMN was higher in BRCA2 patients than in the general population (21% vs 8% and 17% vs 1%; P = 0.0007 and P < 0.0001, respectively), with no influence of family history. Similarly, BRCA1 patients had an increased prevalence of IPMN (8.3% vs 1%; P < 0.0001).ConclusionsIn this series, 4% and 17% of BRCA2 patients developed PDAC and IPMN, respectively. Eight percent of BRCA1 patients developed IPMN. Under current recommended screening, 60% of BRCA1/2 patients had incompletely pancreatic assessment. With no influence of family history, this study suggests all BRCA1/2 patients should undergo a high‐risk screening protocol that will identify a higher rate of precancerous pancreatic neoplasms amenable to curative resection.
Kinetics of Ag300 nanoclusters formation: The catalytically effective nucleus via a steady‐state approach
Authors: Kytsya Andriy , Bazylyak Liliya , Simon Paul , Zelenina Iryna , Antonyshyn Iryna 
Published: January 2019

AbstractThe kinetics of formation of silver nanoparticles consisting of nearly 300 metal atoms is investigated, which were prepared by reduction of silver nitrate with hydrazine in ethylene glycol at 25°C without any stabilizer other than the glycol solvent. The resulting sigmoidal kinetic curves are analyzed by using the 1997 Finke–Watzky two‐step mechanism of slow continuous nucleation with subsequent fast autocatalytic surface growth. The kinetics of homogeneous nucleation of metal nanoparticles was analyzed using the assumption about the stepwise adjunction of precursor and the quasi steady‐state approximation. The equations were proposed to calculate the concentration of the formed metal nanoparticles and their mean size from the experimentally determined values of the Finke–Watzky rate constants. It is shown that a stepwise nucleation process can be described in the terms of the catalytically effective nucleus concept and that the number of atoms in the catalytically effective nucleus can be estimated.
Enhancing soil physical quality and cotton yields through diversification of agricultural practices in central Brazil
Authors: Anghinoni Guilherme , Tormena Cássio Antonio , Lal Rattan , Zancanaro Leandro , Kappes Claudinei 
Published: January 2019

AbstractBrazil plays an important role in the global agricultural production, making Brazilian productive land use and management a critical issue. This study tested the hypothesis that soil physical quality (SPQ) of the Cerrado biome in central Brazil depends on appropriate crop rotation and tillage practices in cotton (Gossypium hyrsutum [L.])‐based cropping systems and is critical to achieve optimal cotton yields (COT). SPQ of an Oxisol was accessed for layers of 0.0–0.1, 0.1–0.2, and 0.2–0.4 m under conventional tillage (CT) and no‐tillage (NT) systems, in different farming systems, such as cotton monoculture, crop succession, and crop rotation in central Brazil. Variables studied were soil bulk density, total porosity, air permeability, pore continuity index, water content at field capacity, relative saturation at field capacity, the least limiting water range (LLWR), and COT. Soil sampling was performed in 2014, and COT was obtained in the 2013 and 2014 cropping seasons. Conservationist practices, such as crop diversity and absence of soil tillage, improved water availability, enlarged the LLWR, and indicated that brachiaria cultivation positively influences the SPQ, whereas continuous soil tillage and less crop diversity adversely affected SPQ. COT was positively influenced by SPQ aspects regarding the increased water access in the 0.2–0.4 m layer of NT and in the 0.0–0.1 m of CT management. Differences in SPQ, as indicated by the LLWR, were reflected in differences in COT, as well as in soil air permeability in the CT treatments for the 2014 cropping season. Other SPQ variables had no relation to COT.
Quantitative analysis of phenolic metabolites in Copaifera langsdorffii leaves from plants of different geographic origins cultivated under the same environmental conditions
Authors: Motta Erick V.S. , Sampaio Bruno L. , Costa Juliana C. , Teixeira Simone P. , Bastos Jairo K. 
Published: January 2019

AbstractIntroductionGalloylquinic acid derivatives and flavonoids are the main phenolic metabolites found in Copaifera langsdorffii leaves (Leguminosae, Detarioideae), a medicinal plant with potential therapeutic application in the treatment of kidney stones. The factors that affect metabolite production in this plant species are not well understood but may include environmental and genetic factors.ObjectiveTo quantify the variation in metabolite production over a 12‐month period for 10 groups of C. langsdorffii cultivated under the same environmental conditions.MethodsCopaifera langsdorffii seeds were collected from 10 different regions in southeast, Brazil and grown in the same field. HPLC‐UV was used to quantify nine galloylquinic acid derivatives and two flavonoids in leaf samples from mature trees. Climate data for humidity, radiation, precipitation and temperature were provided by the National Institute of Meteorology, Brazil. Multivariate analyses were performed to correlate chemical and environmental variables.ResultsThe overall effect of environmental factors on the production of phenolic metabolites was uniform among C. langsdorffii groups. Chemical variation between groups was present, but small, and probably due to differences in their genetics and physiology. Seasonal changes influenced the production of the major phenolic metabolites, with increases in temperature and radiation levels favouring metabolite production.ConclusionWhen C. langsdorffii trees are cultivated in the same environment, the production of the major secondary metabolites found in their leaves is very similar quantitatively, varying based on geographic location of original population and seasonal changes. This favours the standardisation of plant raw material for the production of a phytomedicine.
Synthesis and biological activity of analogs of the antifungal antibiotic UK‐2A. II. Impact of modifications to the macrocycle benzyl position
Authors: Owen W John , Meyer Kevin G , Meyer Stacy T , Li Fangzheng , Slanec Thomas J , Wang Nick X , Yao Chenglin 
Published: January 2019

ABSTRACTBACKGROUNDUK‐2A is an antifungal antibiotic produced by Streptomyces sp. 517‐02. Derivatization of its picolinamide OH to form the isobutyryl acetal led to the discovery of fenpicoxamid (InatreqTM active), which is currently under development as a fungicide by Dow AgroSciences LLC. This paper documents efforts to achieve additional efficacy enhancements through semi‐synthetic modification of the benzyl substituent of the UK‐2A macrocycle.RESULTSOf 34 analogs prepared, the most active had mitochondrial electron transport IC50 values 1.5‐ to 3.7‐fold higher than UK‐2A (IC50 0.86 nM). The cyclohexyl analog (38, IC50 1.23 nM) was the most intrinsically active derivative, and inhibited in vitro growth of Zymoseptoria tritici (EC50 2.8 ppb) and Leptosphaeria nodorum (EC50 6.2 ppb) more strongly than UK‐2A (EC50 5.3 and 11.3 ppb for Z. tritici and L. nodorum, respectively). Heterocyclic ring systems and polar linker functionalities resulted in substantial activity loss. Several analogs (20, 22, 23, 24, 36 and 38) translated Z. tritici in vitro growth inhibition activity to in planta disease control more effectively than did UK‐2A, with log D being a key factor in this regard.CONCLUSIONSUK‐2A is amenable to further modification at the benzyl position on the macrocycle, which provides opportunities for manipulation of physical properties while retaining strong intrinsic and antifungal activity. © 2019 Society of Chemical Industry
The Methodological Approach of the Long-Term Study
Authors: Paus-Hasebrink Ingrid , Kulterer Jasmin , Sinner Philip 
Published: January 2019

AbstractThis chapter outlines our study’s specific methodological approach as derived from its theoretical foundation. We deal with the questions of collecting, processing and analysing data from a qualitative longitudinal study over 12 years from 2005 to 2017 but also with questions of recruitment and panel maintenance, as well as ethical issues. This chapter, therefore, focuses on the ways in which the methodological design was revised and judiciously complemented, in order to grasp the complexity of the topic. Following the logic of triangulation, we developed and implemented a rich design, where all the components draw on, complement, and monitor each other in the processes of data collection and analysis. This means that we have to discuss the importance of transparency and comprehensibility in terms of intersubjectivity, paying special attention to the qualitative and longitudinal character of the study.
Topological strings, strips and quivers
Authors: Panfil Miłosz , Sułkowski Piotr 
Published: January 2019

AbstractWe find a direct relation between quiver representation theory and open topological string theory on a class of toric Calabi-Yau manifolds without compact four-cycles, also referred to as strip geometries. We show that various quantities that characterize open topological string theory on these manifolds, such as partition functions, Gromov-Witten invariants, or open BPS invariants, can be expressed in terms of characteristics of the moduli space of representations of the corresponding quiver. This has various deep consequences; in particular, expressing open BPS invariants in terms of motivic Donaldson-Thomas invariants, immediately proves integrality of the former ones. Taking advantage of the relation to quivers we also derive explicit expressions for classical open BPS invariants for an arbitrary strip geometry, which lead to a large set of number theoretic integrality statements. Furthermore, for a specific framing, open topological string partition functions for strip geometries take form of generalizedq-hypergeometric functions, which leads to a novel representation of these functions in terms of quantum dilogarithms and integral invariants. We also study quantum curves and A-polynomials associated to quivers, various limits thereof, and their specializations relevant for strip geometries. The relation between toric manifolds and quivers can be regarded as a generalization of the knots-quivers correspondence to more general Calabi-Yau geometries.
Comprehensive Application of Graphene: Emphasis on Biomedical Concerns
Authors: Syama S. , Mohanan P. V. 
Published: January 2019

Abstract
Graphene, sp2 hybridized carbon framework of one atom thickness, is reputed as the strongest material to date. It has marked its impact in manifold applications including electronics, sensors, composites, and catalysis. Current state-of-the-art graphene research revolves around its biomedical applications. The two-dimensional (2D) planar structure of graphene provides a large surface area for loading drugs/biomolecules and the possibility of conjugating fluorescent dyes for bioimaging. The high near-infrared absorbance makes graphene ideal for photothermal therapy. Henceforth, graphene turns out to be a reliable multifunctional material for use in diagnosis and treatment. It exhibits antibacterial property by directly interacting with the cell membrane. Potential application of graphene as a scaffold for the attachment and proliferation of stem cells and neuronal cells is captivating in a tissue regeneration scenario. Fabrication of 2D graphene into a 3D structure is made possible with the help of 3D printing, a revolutionary technology having promising applications in tissue and organ engineering. However, apart from its advantageous application scope, use of graphene raises toxicity concerns. Several reports have confirmed the potential toxicity of graphene and its derivatives, and the inconsistency may be due to the lack of standardized consensus protocols. The present review focuses on the hidden facts of graphene and its biomedical application, with special emphasis on drug delivery, biosensing, bioimaging, antibacterial, tissue engineering, and 3D printing applications.