bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility and safety of endobronchial ultrasound‐guided transbronchial needle aspiration and endoscopic ultrasound with an echobronchoscope‐guided fine needle aspiration in children with mediastinal pathology
Authors: Gulla Krishna Mohan , Gunathilaka Ganganath , Jat Kana Ram , Sankar Jhuma , Karan Madan , Lodha Rakesh , Kabra Sushil K 
Published: March 2019

AbstractBackgroundEndobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) and endoscopic ultrasound with an echobronchoscope‐guided fine needle aspiration (EUS‐B‐FNA) are useful modalities in the evaluation of mediastinal pathologies in adults. However, sparse data are available in children.ObjectiveTo describe the utility and safety of EBUS‐TBNA and EUS‐B‐FNA in children with mediastinal pathologies of unknown etiology.DesignChart review.SettingPediatric Chest and Tuberculosis Clinics, Department of Pediatrics, AIIMS, New Delhi from May 2015 to March 2018.PatientsChildren <18 years of age with mediastinal pathologies of undefined etiology.MethodsCase records of children who underwent EBUS‐TBNA and EUS‐B‐FNA were reviewed. Data on demographic profile, clinical features, laboratory investigations, the technique of EBUS‐TBNA/ EUS –B‐ FNA, complications, and findings were collected.ResultsThirty children (19 males) with mean (SD) age of 9.6 (±3.5) years underwent endobronchial procedures. Median (IQR) weight(kg) and height(cm) were 29 (19.5, 35) and 134 (125, 150) respectively. Tuberculosis was the most common preprocedure clinical diagnosis (73.3%), followed by lymphoma (13.3%). Presenting features were fever (80%), cough (53.3%), hepatomegaly (13%), peripheral lymphadenopathy (21.7%), and positive tuberculin skin test (63.3%). Approximately one fourth were on antitubercular therapy without definite evidence of TB. Conscious sedation was used for the procedures: midazolam and fentanyl (n = 22), propofol (n = 8). Transesophageal, transtracheal, and both routes were used in 20 (66.6%), 7 (23.3%), and 3 (10.1%), respectively. Lymph‐nodes were sampled in 24 children (subcarinal in 16, right paratracheal in 4 and both in 4). Mean (SD) size of lymph node (in cm) on EBUS was 1.93(±0.5) and median (IQR) number of FNAC needle passes per node were 2 (2, 4). The diagnosis was confirmed in 11 (36.6%, tuberculosis in 10 by GeneXpert/ MGIT/ cytopath and lymphoma in one) patients. Only 3.3% had a minor complication.ConclusionEBUS‐TBNA and EUS‐B‐FNA are helpful in children with undiagnosed mediastinal pathology with fair diagnostic yield and excellent patient safety profile.
Investigation Of Crystallisation Conditions to Produce CL‐20/HMX Cocrystal for Polymer‐bonded Explosives
Authors: Herrmannsdörfer Dirk , Gerber Peter , Heintz Thomas , Herrmann Michael J. , Klapötke Thomas M. 
Published: March 2019

AbstractSince its discovery in 2012, multiple techniques to generate the CL‐20/HMX cocrystal have been published. However, as yet no assessment or trial has been reported of crystallisation methods capable of producing the cocrystal in a size region and production scale suitable for its use in polymer bonded explosives (PBX). This paper provides insight into the selection of suitable crystallisation methods, solvent selection and process optimisation with a focus on the efficient production of high‐quality cocrystals for use in PBX. Through extensive solvent screening, acetonitrile was identified as the best solvent for solution‐based crystallisation, due to its capability to produce compact parallelepipedic crystals and its comparably wide cocrystal phase region. Crystallisation conducted at 60 °C was found to increase the conversion rate and the material efficiency compared to room temperature. By application of an advanced seeding procedure, high‐quality cocrystals in the size region of 180–250 μm were produced in laboratory‐scale antisolvent and cooling crystallisations. By pilot‐plant‐scale batch reaction cocrystallization, cocrystals with a volume‐weighted mean diameter of 33 μm were produced in quantities of 250 g per day.
Identification of a α‐helical molten globule intermediate and structural characterization of β‐cardiotoxin, an all β‐sheet protein isolated from the venom of Ophiophagus hannah (king cobra)
Authors: Roy Amrita , Qingxiang Sun , Alex Chapeaurouge , Rajagopalan Nandhakishore , Jobichen Chacko , Sivaraman J. , Kini R. Manjunatha 
Published: March 2019

Abstractβ‐Cardiotoxin is a novel member of the snake venom three‐finger toxin (3FTX) family. This is the first exogenous protein to antagonize β‐adrenergic receptors and thereby causing reduction in heart rates (bradycardia) when administered into animals, unlike the conventional cardiotoxins as reported earlier. 3FTXs are stable all β‐sheet peptides with 60–80 amino acid residues. Here, we describe the three‐dimensional crystal structure of β‐cardiotoxin together with the identification of a molten globule intermediate in the unfolding pathway of this protein. In spite of the overall structural similarity of this protein with conventional cardiotoxins, there are notable differences observed at the loop region and in the charge distribution on the surface, which are known to be critical for cytolytic activity of cardiotoxins. The molten globule intermediate state present in the thermal unfolding pathway of β‐cardiotoxin was however not observed during the chemical denaturation of the protein. Interestingly, circular dichroism (CD) and NMR studies revealed the presence of α‐helical secondary structure in the molten globule intermediate. These results point to substantial conformational plasticity of β‐cardiotoxin, which might aid the protein in responding to the sometimes conflicting demands of structure, stability, and function during its biological lifetime.
Sea cucumber extract TBL‐12 inhibits the proliferation, migration, and invasion of human prostate cancer cells through the p38 mitogen‐activated protein kinase and intrinsic caspase apoptosis pathway
Authors: Yuan Lei , Huang Xubin , Zhou Kai , Zhu Xun , Huang Bin , Qiu Shaopeng , Cao Kaiyuan , Xu Lin 
Published: March 2019

AbstractBackgroundSea cucumber is a kind of nutritious echinoderm that has multiple biological activities, including antioxidant, antibacterial, and antitumor activities. However, there is no extensive study on the antitumor effect of sea cucumber extract on prostate cancer (PCa). TBL‐12 is a new sea cucumber extract. In this study, we investigated the in vivo anti‐PCa effect of TBL‐12 and its in vitro effects on the proliferation, apoptosis, migration, and invasion of the human PCa cell lines LNCaP, 22RV1, PC‐3, and DU145, and evaluated its possible mechanisms.MethodsCell proliferation was analyzed by cell counting kit‐8 and colony formation assays. Scratch migration assay and transwell invasiveness assay were used to observe TBL‐12 effect on the migration and invasion of PCa cells. Matrix metalloproteinase 2 (MMP‐2) and MMP‐9 expression and enzymatic activity was determined by Western blot analysis, quantitative reverse‐transcription polymerase chain reaction, and gelatin zymography. Apoptosis level was detected by flow cytometry analysis. Western blot analysis was used to analyze p38 mitogen‐activated protein kinase (MAPK) and apoptosis pathways. Angiogenic array analysis was used to explore autocrine and paracrine growth factors in PCa cell lines. Xenograft tumor model was built to observe the in vivo anticancer effect.ResultsTBL‐12 could significantly inhibit tumor growth in xenograft PCa mice in vivo, and dramatically inhibit the proliferation, colony formation, migration, and invasiveness of PCa cells in vitro (P < 0.05 and
P < 0.001). The expression and enzyme activity of MMP‐2 and MMP‐9 were significantly suppressed by TBL‐12 (
P < 0.01), and decreased phosphorylation level of p38 in PCa cells was detected (
P < 0.001). Furthermore, TBL‐12 could reinforce the MMP‐2/MMP‐9 inhibitory effect of SB203580, a specific inhibitor of the p38 MAPK pathway (
P < 0.05). Besides, TBL‐12 could induce the apoptosis of PCa cells by activating caspase‐9, caspase‐7, and poly(ADP‐ribose) polymerase and suppressing survivin, and inhibit the secretion of angiogenin, angiopoietin‐2, and vascular endothelial growth factor in PCa cells.ConclusionsSea cucumber extract TBL‐12 could suppress the proliferation and metastasis of human PCa cells by inhibiting MMP‐2 and MMP‐9 via blocking the p38 MAPK pathway, inducing apoptosis through intrinsic caspase apoptosis pathway and inhibiting the secretion of angiogenic factors. Our findings may be of importance and significance for the research and clinical applications of sea cucumber extract in PCa treatment.
Genome‐wide identification and analysis of genes associated with RNA interference in Bemisia tabaci
Authors: Tian Lixia , Zeng Yang , Xie Wen , Wu Qingjun , Wang Shaoli , Zhou Xuguo , Zhang Youjun 
Published: March 2019

ABSTRACTBackgroundAs a method of RNA‐mediated gene silencing, RNA interference (RNAi) is a useful reverse genetic tool with which to study gene function, and holds great promise for pest management. Bemisia tabaci is a cosmopolitan pest that causes extensive damage to crops. The mechanism underlying RNAi efficiency in B. tabaci is not well known. We identified and analyzed candidate genes in the RNAi pathway to understand the RNAi mechanism and provide a basis for the application of RNAi in pest management.ResultsWe identified 33 genes putatively involved in the RNAi pathway from the B. tabaci Q genome. Phylogenetic and structural analyses confirmed the characteristics of these genes. Furthermore, quantitative real‐time reverse transcription polymerase chain reaction (qRT‐PCR) and transcriptomic analysis profiled gene expression patterns during different developmental stages. Gene expression levels estimated by qRT‐PCR and RNA‐seq analyses were significantly correlated. Moreover, gene functions were verified by RNAi. When accompanied by knockdown of AGO2, Dicer2 and Sid1, the efficiency of CYP6DB3 RNAi decreased correspondingly.ConclusionIn this study, we annotated and validated genes involved in B. tabaci RNAi. A better understanding of the building blocks of the RNAi process in B. tabaci facilitates integration of this novel biotechnology into the management of this emerging pest, either directly or indirectly. © 2019 Society of Chemical Industry
Spatial assessment of pesticide leaching risk to groundwater: sub‐national decision making and model output aggregation
Authors: Dowling Thomas PF , Beulke Sabine , Garratt James 
Published: March 2019

AbstractBACKGROUNDThis study compares standard regulatory methodology (fixed scenarios and models) to spatial modelling at a 1 km landscape resolution for the evaluation of predicted environmental concentrations of pesticides in groundwater. The use of spatial modelling in the decision‐making processes is discussed and three options for the sub‐national evaluation and restriction of substances based on spatial environmental fate modelling are examined. Wheat and sugar beet are tested with two modified FOCUS substances (A and D) in the PEARL and GeoPEARL models. The 80th percentile value in time and space, aggregated to three different sub‐national divisions of interest to a regulator, is used as a regulatory relevant output.RESULTSMeans and medians of predicted environmental concentrations at the national level are not useful summary statistics in the age of extensive and freely available geospatial data. A better statistic to use is the P80 (or other desired threshold/percentile combination) in time and space of predicted environmental concentration, combined with flexible and adaptable sub‐divisions of the country based on the desired protective target.CONCLUSIONTier 3b modelling is shown to provide an increase in localism and regulatory nuance over Tier 1 scenarios when combined with soil and aquifer type sub‐national units. © 2019 Society of Chemical Industry
Modelling the potential effects of climate factors on Dubas bug (Ommatissus lybicus) presence/absence and its infestation rate: A case study from Oman
Authors: Al Kindi Khalifa M , Kwan Paul , Andrew Nigel R , Welch Mitchell 
Published: March 2019

AbstractBACKGROUNDOmmatissus lybicus de Bergevin (Hemiptera: Tropiduchidae) (Dubas Bug, DB) is an insect pest attacking date palms. It occurs in Arab countries including Oman. In this paper, the logistic, ordinary least square, and geographical weighted regressions were applied to model the absence/presence and density of DB against climate factors. A method is proposed for modelling spatially correlated prorations annually over the study period, based on annual and seasonal outbreaks. The historical 2006–2015 climate data were obtained from weather stations located in nine governorates in northern Oman, while dataloggers collected the 2017 microclimate data in eight of these nine governorates.RESULTSLogistic regression model showed the percentages of correctly predicted values using a cut‐off point of 0.5 were 90%, 88% and 84%, indicating good classification accuracy. OLS and GWR models showed an overall trend of strong linear correlation between DB infestation levels and short‐ and long‐term climate factors. The three models suggested that precipitation, elevation, temperature, humidity, wind direction and wind speed are important in influencing the spatial distribution and the presence/absence of dense DB populations.CONCLUSIONThe results provide an improved understanding of climate factors that impact DB's spread and is considered useful for managing DB infestations in date palm plantations. © 2019 Society of Chemical Industry
Human Genomic Safe Harbors and the Suicide Gene-Based Safeguard System for iPSC-Based Cell Therapy
Authors: Kimura Yasuyoshi , Shofuda Tomoko , Higuchi Yuichiro , Nagamori Ippei , Oda Masaaki , Nakamori Masayuki , Onodera Masafumi , Kanematsu Daisuke , Yamamoto Atsuyo , Katsuma Asako , Suemizu Hiroshi , Nakano Toru , Kanemura Yonehiro , Mochizuki Hideki 
Published: March 2019

Abstract
The use of human induced pluripotent stem cells (hiPSCs) and recent advances in cell engineering have opened new prospects for cell-based therapy. However, there are concerns that must be addressed prior to their broad clinical applications and a major concern is tumorigenicity. Suicide gene approaches could eliminate wayward tumor-initiating cells even after cell transplantation, but their efficacy remains controversial. Another concern is the safety of genome editing. Our knowledge of human genomic safe harbors (GSHs) is still insufficient, making it difficult to predict the influence of gene integration on nearby genes. Here, we showed the topological architecture of human GSH candidates, AAVS1, CCR5, human ROSA26, and an extragenic GSH locus on chromosome 1 (Chr1-eGSH). Chr1-eGSH permitted robust transgene expression, but a 2 Mb-distant gene within the same topologically associated domain showed aberrant expression. Although knockin iPSCs carrying the suicide gene, herpes simplex virus thymidine kinase (HSV-TK), were sufficiently sensitive to ganciclovir in vitro, the resulting teratomas showed varying degrees of resistance to the drug in vivo. Our findings suggest that the Chr1-eGSH is not suitable for therapeutic gene integration and highlight that topological analysis could facilitate exploration of human GSHs for regenerative medicine applications. Our data indicate that the HSV-TK/ganciclovir suicide gene approach alone may be not an adequate safeguard against the risk of teratoma, and suggest that the combination of several distinct approaches could reduce the risks associated with cell therapy. Stem Cells Translational Medicine 2019;8:627&638
EP4 Antagonist-Elicited Extracellular Vesicles from Mesenchymal Stem Cells Rescue Cognition/Learning Deficiencies by Restoring Brain Cellular Functions
Authors: Chen Shih-Yin , Lin Meng-Chieh , Tsai Jia-Shiuan , He Pei-Lin , Luo Wen-Ting , Herschman Harvey , Li Hua-Jung 
Published: March 2019

Abstract
Adult brains have limited regenerative capacity. Consequently, both brain damage and neurodegenerative diseases often cause functional impairment for patients. Mesenchymal stem cells (MSCs), one type of adult stem cells, can be isolated from various adult tissues. MSCs have been used in clinical trials to treat human diseases and the therapeutic potentials of the MSC-derived secretome and extracellular vesicles (EVs) have been under investigation. We found that blocking the prostaglandin E2/prostaglandin E2 receptor 4 (PGE2/EP4) signaling pathway in MSCs with EP4 antagonists increased EV release and promoted the sorting of specific proteins, including anti-inflammatory cytokines and factors that modify astrocyte function, blood–brain barrier integrity, and microglial migration into the damaged hippocampus, into the EVs. Systemic administration of EP4 antagonist-elicited MSC EVs repaired deficiencies of cognition, learning and memory, inhibited reactive astrogliosis, attenuated extensive inflammation, reduced microglial infiltration into the damaged hippocampus, and increased blood–brain barrier integrity when administered to mice following hippocampal damage. Stem Cells Translational Medicine 2019
Randomised trials with provision for early stopping for benefit (or harm): The impact on the estimated treatment effect
Authors: Walter S.D. , Guyatt G.H. , Bassler D. , Briel M. , Ramsay T. , Han H.D. 
Published: March 2019

Stopping rules for clinical trials are primarily intended to control Type I error rates if interim analyses are planned, but less is known about the impact that potential stopping has on estimating treatment benefit. In this paper, we derive analytic expressions for (1) the over‐estimation of benefit in studies that stop early, (2) the under‐estimation of benefit in completed studies, and (3) the overall bias in studies with a stopping rule. We also examine the probability of stopping early and the situation in meta‐analyses.Numerical evaluations show that the greatest concern is with over‐estimation of benefit in stopped studies, especially if the probability of stopping early is small. The overall bias is usually less than 10% of the true benefit, and under‐estimation in completed studies is also typically small. The probability of stopping depends on the true treatment effect and sample size. The magnitude of these effects depends on the particular rule adopted, but we show that the maximum overall bias is the same for all stopping rules. We also show that an essentially unbiased meta‐analysis estimate of benefit can be recovered, even if some component studies have stopping rules. We illustrate these methods using data from three clinical trials.The results confirm our earlier empirical work on clinical trials. Investigators may consult our numerical results for guidance on potential mis‐estimation and bias in the treatment effect if a stopping rule is adopted. Particular concern is warranted in studies that actually stop early, where interim results may be quite misleading.
Renewable Biomass‐Derived Hierarchically Porous Carbonaceous Sponge (CS)/g‐C3N4Composites as Adsorption and Photocatalytic Materials
Authors: Tu Dan , Liao Huiwei , Deng Qiulin , Liu Xiang , Shang Ronggang , Zhang Xiaoyong 
Published: March 2019

AbstractIn this work, the preparation, characterization and removal capability of hierarchically porous carbonaceous sponges and their g‐C3N4/CS composites were described. Possessing a hierarchically porous structure and extremely large surface areas, g‐C3N4/CS composites are demonstrated to have advantages in adsorption and photocatalytic activities. The adsorption and photocatalytic activities of the as‐prepared catalysts were evaluated by the degradation of RhB, MO, and phenol. The best results showed that 97% decomposition of RhB was obtained by using g‐C3N4/CS‐60 composites within 20 min at 25 °C under visible light irradiation. Furthermore, the g‐C3N4/CS‐60 composites showed remarkable regeneration stability, which maintains high photocatalytic activity after the samples are saturated. Additionally, the degradation mechanisms of RhB and the photocatalytic mechanism are explained in this paper.
Fabrication of Large Area Crack‐Free 2D and 3D WO3 Inverse Opal Films by “Dynamic Hard Template Infiltration Strategy”
Authors: Li Hua , Li Shali , Robichaud Jacques , Su Bao‐Lian , Djaoued Yahia 
Published: March 2019

AbstractLarge‐area crack‐free 2D and 3D WO3 inverse opal (IO) films, using a wide range of sizes of sacrificial PS spheres as colloidal crystal template, were fabricated by “dynamic hard template infiltration strategy”. First a dynamic PS opal film was formed floating on the surface of water followed by infiltration of a preformed WO3 sol underneath the PS opal film. The resultant PS/WO3 opal composite film was then deposited on various types of substrates (rigid and flexible) and 2D WO3 IO films were obtained following the removal of the PS template by chemical method. Based on this strategy, multiple layer WO3 IOs were fabricated through a layer by layer route. The WO3 IO films deposited on indium tin oxide coated conductive (ITO) substrates were used as active electrode in the fabrication of electrochromic devices, demonstrating their advanced properties for electrochromic application.
Transesterification instead of N‐Alkylation: An Intriguing Reaction
Authors: Giannakopoulou Erofili , Pardali Vasiliki , Skrettas Ioannis , Zoidis Grigoris 
Published: March 2019

AbstractAn intriguing transesterification reaction is reported here for the first time. Different carbocyclic N‐1 alkoxycarbonyl methyl substituted hydantoins were treated with alkyl halides and sodium hydride as a base, in the presence of N,N‐dimethylformamide. Under these typical N‐alkylation reaction conditions, hydantoin alkyl acetates were also isolated, along with the expected N‐alkylated products. Additional experiments were also performed to investigate the role of N,N‐dimethylformamide in the transesterification reaction and a possible mechanism is also proposed.
Selective Inhibition of IRE1 Signalling mediated by MKC9989: New Insights from Molecular Docking and Molecular Dynamics Simulations
Authors: Carlesso Antonio , Eriksson Leif A. 
Published: March 2019

AbstractMKC9989 is an inhibitor of IRE1α endonuclease activity that binds selectively to Lysine907 through Schiff base formation. Consistent with the experimental scenario, using Molecular Docking and Molecular Dynamics (MD), we herein further validate MKC9989 selectivity towards two critical Lysines, Lys907 and Lys599, located in the RNase and kinase domain, respectively.