bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bringing Philosophy to Bear on Moral Injury and Posttraumatic Stress Disorder Construct Validation: Commentary on Farnsworth (2019)
Authors: Frankfurt Sheila B. , Coady Alanna 
Published: August 2019

AbstractFarnsworth (2019) proposed that posttraumatic stress disorder (PTSD) and moral injury (MI) can be differentiated using DSM‐5 PTSD's Criteria D. It was suggested that PTSD cognitions are descriptions about what the world is like whose accuracy can be targeted by cognitive therapies, whereas MI cognitions are prescriptions about what the world should be like, which cannot be assessed for truth or falsehood and so are unsuitable for cognitive therapies. We believe that this appeal to the is/ought distinction distorts the therapeutic challenge, and misconceptualizes moral thinking as manifested only in thin terms such as “ought/should.” In practical usage, it is unlikely that when people express cognitions they are only describing the world and not evaluating it as well. In this commentary, we will critique the prescriptivist view of trauma, suggest the importance of “thick terms,” and reconsider the purported differences between MI and PTSD. MI might be meaningfully different from PTSD, but it is premature to differentiate these constructs based on DSM‐5's Criteria D. A trauma theory that accounts for the interwoven descriptive and evaluative, cognitive as well as affective, elements of traumatic experiences will clarify both the PTSD diagnosis and MI model and improve treatment development and clinical care.
Advancement in the Biomedical Applications of the (Nano)gel Structures Based on Particular Polysaccharides
Authors: Chiriac Aurica P. , Ghilan Alina , Neamtu Iordana , Nita Loredana E. , Rusu Alina G. , Chiriac Vlad Mihai 
Published: August 2019

Abstract(Nano)gels from macromolecular compounds—natural, synthetic, or a combination thereof, suitable crosslinkers—and conferred characteristics—such as degradability, size, charge, amphiphilicity, responsiveness, and softness—are capable of responding to the challenges imposed by bioengineering applications. Polysaccharide‐based gels have received particular attention in this field. This review addresses recent advancement in the use of (nano)gel structures prepared only from compounds based on gellan gum, heparin, chondroitin sulfate, carrageenan, guar gum, galactose, or agarose, which represent an important part of the special class of natural polymers, the polysaccharides. Also, future trends are taken into discussion regarding the (nano)gels' use in biomedical applications such as biomimetics, biosensors, artificial muscles, and chemical separations in relation with their ability to be used as a vehicle for various biomolecules due to their physicochemical properties, biocompatibility, and biodegradability.
Gemcitabine‐induced epithelial‐mesenchymal transition‐like changes sustain chemoresistance of pancreatic cancer cells of mesenchymal‐like phenotype
Authors: El Amrani Mehdi , Corfiotti François , Corvaisier Matthieu , Vasseur Romain , Fulbert Maxence , Skrzypczyk Cécile , Deshorgues Anne‐Claire , Gnemmi Viviane , Tulasne David , Lahdaoui Fatima , Vincent Audrey , Pruvot François‐René , Van Seuningen Isabelle , Huet Guillemette , Truant Stéphanie 
Published: August 2019

AbstractGrowing body of evidence suggests that epithelial‐mesenchymal transition (EMT) is a critical process in tumor progression and chemoresistance in pancreatic cancer (PC). The aim of this study was to analyze the role of EMT‐like changes in acquisition of resistance to gemcitabine in pancreatic cells of the mesenchymal or epithelial phenotype. Therefore, chemoresistant BxPC‐3, Capan‐2, Panc‐1, and MiaPaca‐2 cells were selected by chronic exposure to increasing concentrations of gemcitabine. We show that gemcitabine‐resistant Panc‐1 and MiaPaca‐2 cells of mesenchymal‐like phenotype undergo further EMT‐like molecular changes mediated by ERK‐ZEB‐1 pathway, and that inhibition of ERK1/2 phosphorylation or ZEB‐1 expression resulted in a decrease in chemoresistance. Conversely, gemcitabine‐resistant BxPC‐3 and Capan‐2 cells of epithelial‐like phenotype did not show such typical EMT‐like molecular changes although the expression of the tight junction marker occludin could be found decreased. In pancreatic cancer patients, high ZEB‐1 expression was associated with tumor invasion and tumor budding. In addition, tumor budding was essentially observed in patients treated with neoadjuvant chemotherapy. These findings support the notion that gemcitabine treatment induces EMT‐like changes that sustain invasion and chemoresistance in PC cells.
Serum miR‐182 is a predictive biomarker for dichotomization of risk of hepatocellular carcinoma in rats
Authors: Livingstone Merricka C. , Johnson Natalie M. , Roebuck Bill D. , Kensler Thomas W. , Groopman John D. 
Published: August 2019

AbstractExploration of animal models leads to discoveries that can reveal candidate biomarkers for translation to human populations. Herein, a model of hepatocarcinogenesis and protection was used in which rats treated with aflatoxin (AFB1) daily for 28 days (200 µg/kg BW) developed tumors compared with rats completely protected from tumors by concurrent administration of the chemoprotective agent, 1‐[2‐cyano‐3‐,12‐dioxooleana‐1,9(11)‐dien‐28‐oyl]imidazole (CDDO‐Im). Differential expression of miRNAs in tumors (AFB1) and nontumor (AFB1 + CDDO‐Im) bearing livers and their levels in sera over the life‐course of the animals was determined. miRNA transcriptome analysis identified 17 miRNAs significantly upregulated at greater than five‐fold in the tumors. The ten most dysregulated miRNAs judged by fold‐change and biological significance were selected for further study, including liver‐specific miR‐122‐5p. Validation of sequencing results by real‐time PCR confirmed the upregulation of the majority of these miRNAs in tumors, including miR‐182, as well as miR‐224‐5p as the most dysregulated of these miRNAs (over 400‐fold). The longitudinal analysis of levels of miR‐182 in sera demonstrated significant and persistent increases (5.13‐fold; 95% CI: 4.59‐5.70). The increase in miR‐182 was detected months before any clinical symptoms were present in the animals. By the terminal time point of the study, in addition to elevated levels of serum miR‐182, serum miR‐122‐5p was also found to be increased (>1.5‐fold) in animals that developed hepatocarcinomas. Thus, using the data from an unbiased discovery approach of the tissue findings, serum miR‐182 was found to track across the complex, multistage process of hepatocarcinogenesis opening an opportunity for translation to human populations.
Identification of key candidate targets and pathways for the targeted treatment of leukemia stem cells of chronic myelogenous leukemia using bioinformatics analysis
Authors: Li Huayao , Liu Lijuan , Zhuang Jing , Liu Cun , Zhou Chao , Yang Jing , Gao Chundi , Liu Gongxi , Sun Changgang 
Published: August 2019

AbstractBackgroundChronic myelogenous leukemia (CML) is a myeloproliferative neoplasm that arises from the acquisition of constitutively active BCR‐ABL tyrosine kinase in hematopoietic stem cells. The persistence of bone marrow leukemia stem cells (LSCs) is the main cause of TKI resistance and CML relapse. Therefore, finding a key target or pathway to selectively target LSCs is of great significance for the thorough treatment of CML.MethodsIn this study, we aimed to identify key microRNAs, microRNA targets and pathways for the treatment of CML LSCs by integrating analyses of three microarray data profiles. We identified 51 differentially expressed microRNAs through integrated analysis of GSE90773 and performed functional gene predictions for microRNAs. Then, GSE11889 and GSE11675 were integrated to obtain differentially expressed genes (DEGs), and the overlapping DEGs were used as models to identify predictive functional genes. Finally, we identified 116 predictive functional genes. Clustering and significant enrichment analysis of 116 genes was based on function and signaling pathways. Subsequently, a protein interaction network was constructed, and module analysis and topology analysis were performed on the network.ResultsA total of 11 key candidate targets and 33 corresponding microRNAs were identified. The key pathways were mainly concentrated on the PI3K/AKT, Ras, JAK/STAT, FoxO and Notch signaling pathways. We also found that LSCs negatively regulated endogenous and exogenous apoptotic pathways to escape from apoptosis.ConclusionWe identified key candidate targets and pathways for CML LSCs through bioinformatics methods, which improves our understanding of the molecular mechanisms of CML LSCs. These candidate genes and pathways may be therapeutic targets for CML LSCs.
Investigation of Factors Affecting the Performance of in silico Volume Distribution QSAR Models for Human, Rat, Mouse, Dog & Monkey
Authors: Simeon Saw , Montanari Dino , Gleeson Matthew Paul 
Published: August 2019

AbstractVolume of distribution (Vdss) is a measure of how effectively a drug molecule is distributed throughout the body. Along with the clearance, it determines the half‐life and therefore the drug dosing interval. A number of different pre‐clinical approaches are available to predict the Vdss in human including quantitative structure activity relationship (QSAR) models. Vdss QSAR models have been reported for human and rat, but not important pre‐clinical species including dog, mouse and monkey. In this study, we have generated Vdss QSAR model on the human and commonly used pre‐clinical species, each of which differs in terms of size, chemical diversity and data quality. We discuss the model performance by species, assess the effect the domain of applicability and the relative merits of building chemical series‐specific models. In addition, we compare the intrinsic variability of the experimental logVdss data (∼1.2 fold error) to in‐vivo interspecies differences (∼2 fold error) and in silico based models (∼3 fold error). This prompted us to explore whether one species could be used to predict another, particularly where little data for that species is available. i. e. does the expansion in domain of applicability prove beneficial over and above any deterioration due to the use of response values from an alternative species.
Epigallocatechin‐3‐Gallate Attenuates Microglial Inflammation and Neurotoxicity by Suppressing the Activation of Canonical and Noncanonical Inflammasome via TLR4/NF‐κB Pathway
Authors: Zhong Xin , Liu Mingyan , Yao Weifan , Du Ke , He Miao , Jin Xin , Jiao Linchi , Ma Guowei , Wei Binbin , Wei Minjie 
Published: August 2019

ScopeIn this study, it has been investigated whether the neuroprotective efficacy of epigallocatechin‐3‐gallate (EGCG) is mediated by inhibition of canonical and noncanonical inflammasome activation via toll‐like receptor 4 (TLR4)/NF‐κB pathway both in LPS+Aβ‐induced microglia in vitro and in APP/PS1 mice in vivo.Methods and resultsIn BV2 cells, EGCG inhibits the expressions of Iba‐1, cleaved IL‐1β, and cleaved IL‐18 induced by LPS+Aβ. Then, the supernatants are used to treat SH‐SY5Y cells, and EGCG treatment significantly recovers the neurotoxicity from LPS+Aβ‐induced microglial conditioned media. Subsequently, it has been found that EGCG reduces the microglial expressions of caspase‐1 p20, NLRP3, and caspase‐11 p26. Furthermore, the expression levels of Toll‐like receptor 4 (TLR4), p‐IKK/IKK, and p‐NF‐κB/NF‐κB were decreased after EGCG treatment. As expected, when a caspase‐1 specific inhibitor Z‐YVAD‐FMK, and an IKK and caspase‐11 inhibitor wedelolactone are used for blocking, Z‐YVAD‐FMK and wedelolactone exacerbate the inhibitory efficacy than using EGCG alone. Finally, consistent with the results obtained in BV2 cells, EGCG treatment reduces microglial inflammation and neurotoxicity by suppressing the activation of canonical NLRP3 and noncanonical caspase‐11‐dependent inflammasome via TLR4/NF‐κB pathway in LPS+Aβ‐induced rat primary microglia and hippocampus of APP/PS1 mice.ConclusionEGCG attenuates microglial inflammation and neurotoxicity by inhibition of canonical NLRP3 and noncanonical caspase‐11‐dependent inflammasome activation via TLR4/NF‐κB pathway.
The Cxadr–Adam10 complex plays pivotal roles in tight junction integrity and early trophoblast development in mice
Authors: Jeong Yelin , Ock Sun‐A , Yoo Jae Gyu , Yu Dae‐Yeul , Choi Inchul 
Published: August 2019

AbstractUnderstanding preimplantation embryo development has important implications for assisted reproductive technologies (ARTs) after the introduction of in vitro fertilisation and embryo transfer because most embryonic losses occur during pre/peri‐implantation. Recent studies have shown that tight junctions (TJs) are important components for embryos to develop to the blastocyst stage. However, their biological function after cavitation has not been extensively studied. We examined TJ assembly focusing on coxsackievirus and adenovirus receptor (Cxadr) and A disintegrin and metalloproteinase 10 (Adam10) using siRNA and/or an Adam10‐specific inhibitor (GI254023X). TJ‐associated genes, including occludin and tight junction protein 1 (Tjp1), were downregulated in the Cxadr knockdown (KD) embryos but were unaltered in Adam10 KD embryos. However, Adam10 KD or chemical inhibition affected subcellular localisation of Adam10, Cxadr, and Tjp1, leading to disrupted TJ assembly. Furthermore, Cxadr KD or GI254023X‐treated blastocysts showed a relatively smaller outgrowth area and aberrant expression of transcription factor AP‐2γ, a trophoblast‐specific marker in the in vitro embryo outgrowth assay. In summary, we demonstrated that the Cxadr–Adam10 complex might moderate TJ integrity/stability and play pivotal roles during early embryonic development. Collectively, understanding the establishment of the TJ complex and its integrity will provide insight into translational research for predicting and selecting developmental competency for ART.
MRI Gibbs‐ringing artifact reduction by means of machine learning using convolutional neural networks
Authors: Zhang Qianqian , Ruan Guohui , Yang Wei , Liu Yilong , Zhao Kaixuan , Feng Qianjin , Chen Wufan , Wu Ed X. , Feng Yanqiu 
Published: August 2019

PurposeTo develop a machine learning approach using convolutional neural network for reducing MRI Gibbs‐ringing artifact.Theory and MethodsGibbs‐ringing artifact in MR images is caused by insufficient sampling of the high frequency data. Existing methods exploit smooth constraints to reduce intensity oscillations near sharp edges at the cost of blurring details. In this work, we developed a machine learning approach for removing the Gibbs‐ringing artifact from MR images. The ringing artifact was extracted from the original image using a deep convolutional neural network and then subtracted from the original image to obtain the artifact‐free image. Finally, its low‐frequency k‐space data were replaced with measured counterparts to enforce data fidelity further. We trained the convolutional neural network using 17,532 T2‐weighted (T2W) normal brain images and evaluated its performance on T2W images of normal and tumor brains, diffusion‐weighted brain images, and T2W knee images.ResultsThe proposed method effectively removed the ringing artifact without noticeable smoothing in T2W and diffusion‐weighted images. Quantitatively, images produced by the proposed method were closer to the fully‐sampled reference images in terms of the root‐mean‐square error, peak signal‐to‐noise ratio, and structural similarity index, compared with current state‐of‐the‐art methods.ConclusionThe proposed method presents a novel and effective approach for Gibbs‐ringing reduction in MRI. The convolutional neural network‐based approach is simple, computationally efficient, and highly applicable in routine clinical MRI.
High‐fidelity, high‐isotropic‐resolution diffusion imaging through gSlider acquisition with and T1 corrections and integrated ΔB0/Rx shim array
Authors: Liao Congyu , Stockmann Jason , Tian Qiyuan , Bilgic Berkin , Arango Nicolas S. , Manhard Mary Kate , Huang Susie Y. , Grissom William A. , Wald Lawrence L. , Setsompop Kawin 
Published: August 2019

Purpose and T1 corrections and dynamic multicoil shimming approaches were proposed to improve the fidelity of high‐isotropic‐resolution generalized slice‐dithered enhanced resolution (gSlider) diffusion imaging.MethodsAn extended reconstruction incorporating inhomogeneity and T1 recovery information was developed to mitigate slab‐boundary artifacts in short‐repetition time (TR) gSlider acquisitions. Slab‐by‐slab dynamic B0 shimming using a multicoil integrated ΔB0/Rx shim array and high in‐plane acceleration (Rinplane = 4) achieved with virtual‐coil GRAPPA were also incorporated into a 1‐mm isotropic resolution gSlider acquisition/reconstruction framework to achieve a significant reduction in geometric distortion compared to single‐shot echo planar imaging (EPI).ResultsThe slab‐boundary artifacts were alleviated by the proposed and T1 corrections compared to the standard gSlider reconstruction pipeline for short‐TR acquisitions. Dynamic shimming provided >50% reduction in geometric distortion compared to conventional global second‐order shimming. One‐millimeter isotropic resolution diffusion data show that the typically problematic temporal and frontal lobes of the brain can be imaged with high geometric fidelity using dynamic shimming.ConclusionsThe proposed and T1 corrections and local‐field control substantially improved the fidelity of high‐isotropic‐resolution diffusion imaging, with reduced slab‐boundary artifacts and geometric distortion compared to conventional gSlider acquisition and reconstruction. This enabled high‐fidelity whole‐brain 1‐mm isotropic diffusion imaging with 64 diffusion directions in 20 min using a 3T clinical scanner.
Effects of Local Coating on Strengthening and Crack Suppression of Notched PBX Beams
Authors: Wang Shengnan , Lan Lingang , Liu Yangyang , Tang Mingfeng , Wen Maoping 
Published: August 2019

AbstractNotched polymer‐bonded explosive (PBX) structure is a mechanically weak link of a weapon system. In addition to the inherent brittleness and low strength of the PBX material, local stress concentration induced by a notch also threats the structural and functional integrity of a weapon system. In this study, a convenient strengthening method of local coating is newly adopted to the notched region of PBX beams. In virtue of a three‐point bending test and digital image correlation measurement, the effects of local coating on strengthening and crack suppression of the beams are explored. Results demonstrate that, while relieving the stress concentration and improving the load‐carrying capability of the notched beams, the locally applied polymer coating can restrain the crack propagation in the PBX matrix, thus preventing the brittle fracture of the integral structure effectively. These explorations may provide significant inspiration for the potential application of local coating, and at the same time, lay foundation to the performance optimisation of energetic materials.
Solid+Solid=Liquid: An ON‐Switch for Sensitivity in Deep Eutectic Solvents?
Authors: Ahmed Yonis , Quintana Ashlee , Warmoth Gregory , Deplazes Stephan , Brand Adam , Mills Jeffrey , Schneider Stefan 
Published: August 2019

AbstractDeep Eutectic Solvents show the low volatility/toxicity of “classical” Ionic Liquids. The formation of a Deep Eutectic Solvent from two solids is the result of intermolecular bonds being weakened or broken and rearranged in completely new networks. The effect of these new bonding arrangements on physical properties like melting point, thermal stability, density, viscosity, and impact sensitivity of some binary mixtures of energetic nitrate salt and nitrogen containing ligands was investigated. With some exceptions the liquids showed increased sensitivity compared to their solid ingredients, which suggest that this might provide an ON‐switch for sensitivity. Furthermore, applying the Deep Eutectic Solvent concept to propellant and explosive development may allow incorporation of established energetic solids into liquid applications.
Degradation studies of dimethachlor in soils and water by UHPLC‐HRMS: putative elucidation of unknown metabolites
Authors: López‐Ruiz Rosalía , Romero‐González Roberto , Ortega‐Carrasco Elisabeth , Martínez Vidal José L , Garrido Frenich Antonia 
Published: August 2019

AbstractBACKGROUNDThe analytical control of the presence of dimethachlor and its metabolites in environmental samples, such as water and soils, is a main concern. Degradation of this pesticide has been evaluated in two types of soils and two different water conditions at two concentration levels. For that purpose, a new liquid chromatography‐mass spectrometry method has been developed and putative identification of new metabolites has been performed.RESULTSAn analytical method based on ultra‐high‐performance liquid chromatography coupled to Orbitrap mass spectrometry (UHPLC‐Orbitrap‐MS) was developed to monitor the degradation of dimethachlor in environmental samples (water and soils). The degradation of dimethachlor in soils and groundwater samples has been monitored from 1 to 110 days after application of a plant protection product at two doses. Concentration of the parent compound slowly decreased in both matrices. DT50 values ranged from 40 to 70 days. Some metabolites were detected in the commercial product and in the samples one day after the application of the plant protection product. In addition, three new metabolites were putatively identified during dimethachlor degradation by untargeted analysis.CONCLUSIONIn this study, the degradation of dimethachlor into its metabolites has been studied in soils and water, using a UHPLC‐Orbitrap‐MS validated method. A putative elucidation of new metabolites of dimethachlor has been carried out applying HRMS and software tools. Degradation results allowed for understanding the behavior of dimethachlor in soils and water, and provided information regarding the possible risk of this pesticide and its metabolites to the ecosystem. © 2019 Society of Chemical Industry
Efficacy of topical Citrullus colocynthis (bitter apple) extract oil in chemotherapy‐induced peripheral neuropathy: A pilot double‐blind randomized placebo‐controlled clinical trial
Authors: Rostami Nematollah , Mosavat Seyed Hamdollah , Heydarirad Ghazaleh , Arbab Tafti Roya , Heydari Mojtaba 
Published: August 2019

Chemotherapy‐induced peripheral neuropathy (CIPN) is one of the most common complications in patients with cancer. Citrullus colocynthis (bitter apple) has been used in traditional Persian medicine as an effective pain relief, especially for neuralgia. We designed a pilot clinical trial to evaluate the safety and efficacy of topical C. colocynthis oil in management of CIPN in breast cancer patients. Thirty‐four cancer patients with CIPN were randomly enrolled in two arms of a randomized, double‐blind, placebo‐controlled clinical trial. The patients were treated by topical C. colocynthis oil or placebo, two times per day for 2 months. Functional Assessment of Cancer Therapy/Gynecologic Oncology Group (FACT/GOG)‐Neurotoxicity (Ntx) score was set as the primary outcome measure. No significant improvement was observed in the total score of FACT/GOG‐Ntx scale (2.40 ± 1.90 vs. 1.05 ± 1.36, p = .879) in drug and placebo groups, respectively. There was also no significant improvement in the mean scores of FACT/GOG‐Ntx in the sensory, motor, hearing, and functional domains in the two study groups. According to the results of this preliminary study, topical C. colocynthis oil failed to improve the symptoms of CIPN compared with placebo.