bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD44 standard isoform is involved in maintenance of cancer stem cells of a hepatocellular carcinoma cell line
Authors: Asai Ryoma , Tsuchiya Hiroyuki , Amisaki Masataka , Makimoto Kazuki , Takenaga Ai , Sakabe Tomohiko , Hoi Shotaro , Koyama Shigemi , Shiota Goshi 
Published: January 2019

AbstractHepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Cancer stem cells (CSCs) have attracted attention as a novel therapeutic target for cancer because they play important roles in the development and aggravation of cancer. CD44 is expressed as a standard isoform (CD44s) and several variant isoforms. CD44v is a major isoform expressed on CSCs of a variety of tumors and has been extensively studied. However, HCC tissues dominantly express CD44s, whose function in CSCs remains unclear. In the present study, we investigated the roles of CD44s in CSCs of HCC. Knock‐out of the CD44 gene in HuH7 HCC cells on which only CD44s is expressed resulted in decreased spheroid formation and increased drug sensitivity. The expression of CSC marker genes, including CD133 and EpCAM, was significantly downregulated in the spheroids of CD44‐deficient cells compared with those in the spheroids of HuH7 cells. In addition, CD44 deficiency impaired antioxidant capacity, concomitant with downregulation of glutathione peroxidase 1 (GPX1) and thioredoxin. Because GPX1 uses the reduced form of glutathione (GSH) to regenerate oxidized cellular components, GSH levels were significantly increased in the CD44‐deficient cells. We also found that NOTCH3 and its target genes were downregulated in the spheroids of CD44‐deficient cells. NOTCH3 expression in HCC tissues was significantly increased compared with that in adjacent nontumor liver tissues and was correlated with CD44 expression. These results suggest that CD44s is involved in maintenance of CSCs in a HCC cell line, possibly through the NOTCH3 signaling pathway.
BRCA1 affects the resistance and stemness of SKOV3‐derived ovarian cancer stem cells by regulating autophagy
Authors: You Yue , Bi Fang‐Fang , Jiang Ying , Xu Ye‐Tao , An Yuan‐Yuan , Li Da , Yang Qing 
Published: January 2019

AbstractBreast cancer 1 (BRCA1) and autophagy both play a significant role in drug resistance. However, little is known about the dynamic cross talk between BRCA1 and autophagy in the regulation of drug sensitivity. Here, we investigated the drug resistance‐associated regulation of BRCA1 in epithelial ovarian cancer stem cells (EOCSCs). The results indicated that BRCA1 could regulate drug resistance in EOCSCs. Autophagy played a significant role in the stemness maintenance and was a key mechanism underlying the survival against chemotherapy in EOCSCs. Further investigation found that BRCA1 could regulate drug resistance of EOCSCs through autophagy. Meanwhile, changes in the level of autophagy provided feedback regarding the expression of BRCA1. Inhibition of autophagy activity could effectively reduce the resistance of EOCSCs caused by BRCA1. In addition, BRCA1 was able to regulate cellular apoptosis and cell cycle progression under the action of cisplatin through autophagy, indirectly affecting the drug sensitivity of EOCSCs. The present results highlight a novel relationship between BRCA1 and autophagy, which may provide insight into the etiology of BRCA1‐associated ovarian cancer, and improve our understanding of resistance mechanisms in ovarian cancer.
Identification and Quantification of (t)RNA Modifications in Pseudomonas aeruginosa by Liquid Chromatography–Tandem Mass Spectrometry
Authors: Grobe Svenja , Doberenz Sebastian , Ferreira Kevin , Krueger Jonas , Brönstrup Mark , Kaever Volkhard , Häussler Susanne 
Published: January 2019

AbstractTransfer RNA (tRNA) modifications impact the structure and function of tRNAs, thus affecting the efficiency and fidelity of translation. In the opportunistic pathogen Pseudomonas aeruginosa translational regulation plays an important but less defined role in adaptation to changing environments. In this study, we have explored tRNA modifications in P. aeruginosa through LC‐MS/MS approaches. Neutral loss scanning (NLS) demonstrated the potential to identify previously unknown modifications, whereas multiple reaction monitoring (MRM) was able to detect modifications with high specificity and sensitivity. In this study, the MRM‐based external calibration method allowed for quantification of the four canonical and 32 modified ribonucleosides, out of which 21 tRNA modifications were quantified in the total tRNA pool of P. aeruginosa PA14. We also purified the single tRNA isoacceptors tRNA‐ArgUCU, tRNA‐LeuCAA, and tRNA‐TrpCCA and determined their specific modification patterns, both qualitatively and quantitatively. Deeper insights into the nature and dynamics of tRNA modifications in P. aeruginosa should pave the way for further studies on post‐transcriptional gene regulation as a relatively unexplored molecular mechanism of controlling bacterial pathogenicity and mode of growth.
3‐Hydroxyisobutyryl‐CoA hydrolase deficiency in an Iranian child with novel HIBCH compound heterozygous mutations
Authors: Karimzadeh Parvaneh , Saberi Mohammad , Sheidaee Kobra , Nourbakhsh Mitra , Keramatipour Mohammad 
Published: January 2019

Key Clinical MessageWe report a patient presenting with developmental delay, Leigh‐like abnormalities on MRI and elevated 3‐hydroxyisovaleric acid levels. Upon whole‐exome sequencing, he was diagnosed with 3‐hydroxyisobutyryl‐CoA hydrolase (HIBCH) deficiency, and hence subjected to specific dietary treatment. HIBCH deficiency should be considered in the differential diagnosis of Leigh‐like disease and/or organic aciduria.
Transient Dipnictyl Analogues of Acrylamides, R−E=E′−CONR2, and a Related Diphosphadigalletane from Na[OCP] and (R2N)2ECl (E, E′=P, As, Ga)
Authors: Borger Jaap E. , Le Corre Grégoire , Mei Yanbo , Suter Riccardo , Schrader Erik , Grützmacher Hansjörg 
Published: January 2019

AbstractThe reaction of Na[OCP] with (R2N)2ECl (E=P or As; R=alkyl) granted direct access to transient amine‐substituted diphospha‐ and arsaphospha‐acrylamide analogues, (R2N)E=P(CONR2)1. Their facile formation allowed for a comprehensive reactivity study. Dimerization yielded the four‐membered rings (R2N)2E2P2(CONR2)2, whereas in the presence of excess Na[OCP], a stepwise [2+2] cycloaddition occured, leading to the sodium salts of carboxotripnictides [(R2N)EP2CO(CONR2)]−. These salts served as a reservoir of1, either by extrusion of Na[OCP] or by reaction with the appropriate (R2N)2ECl, giving the [4+2]‐cycloaddition products (R2N)EP(C6H10)(CONR2) in the presence of 2,3‐dimethylbutadiene. The formal conjugate addition product K[(tBuO)(R2N)PP(CONR2)] was obtained by reaction of Na[(R2N)PP2CO(CONR2)] withtBuOK. In addition, a rare diphosphadigalletane with a ladder‐type (R2N)2Ga2P2(CONR2)2core was isolated from the reaction of Na[OCP] with (R2N)2GaCl (R=alkyl). The unprecedented pnictogenyl carboxamide compounds were thoroughly characterized, including single‐crystal X‐ray structure determinations, and mechanisms for their formation were investigated by DFT calculations.
A Self‐Assembled ATP Probe for Melanoma Cell Imaging
Authors: Cheng Hong‐Bo , Sun ZhengWang , Kwon Nahyun , Wang Rui , Cui Yixin , Park Chang Ook , Yoon Juyoung 
Published: January 2019

AbstractIn this investigation, a new terpyridine metal complex was developed as a probe for selective detection of ATP and imaging of melanoma cells. The probe takes advantage of the ability of the metal complex to be transformed to its imaging competent turn‐on state through assembly with ATP.
Merging Visible‐Light Catalysis for the Direct Late‐Stage Group‐16–Trifluoromethyl Bond Formation
Authors: Ghiazza Clément , Billard Thierry , Tlili Anis 
Published: January 2019

AbstractThe use of visible light activation/photoredox chemistry for the generation of radical‐centered chalcogen–CF3 has gained widespread interest in the last past three years. Its subsequent reactivity for the synthesis of new chalcogen–CF3‐containing building blocks gained much attention. To date several methodologies have been developed addressing several challenges in modern organofluorine chemistry and enabled substantial progress in substrates scope and reaction conditions. This review describes these advancements with a particular focus on the reaction mechanisms.
Experimental study of hydrodynamics and bubble size distribution of an external loop airlift reactor
Authors: Lu Xia , Ding Yigang , Yu Jiuyang , Long Bingwen , Zheng Xiaotao 
Published: January 2019

AbstractThe most important factors influencing the performance of an external loop airlift reactor (ELALR) are local hydrodynamics and bubble size distribution (BSD). In this work, we studied the hydrodynamic characters and BSD in a laboratory scale ELALR. The velocity field of the riser was captured using the particle image velocimetry (PIV) technique and the bubble size distribution (BSD) was determined by digital image analysis (DIA). The results of the PIV measurement show that the flow has an unsteady structure, and the wake oscillation phenomena of the bubble and the vortex shedding are periodically asymmetrical. The gas holdup calculated by DIA correlates with the experimental data when the superficial gas velocity is < 0.02 m · s−1. With an increase in the superficial gas velocity, the probability density function (PDF) curve becomes flatter, changing from the unimodal to the bimodal. For the bimodal PDF curve, the peak of the small bubble is ∼1.5 mm, while the peak of lager bubble shifts from 4.5 to 5.5 mm with the increase in the superficial gas velocity. This work helps to provide insight into the mixing performance of the ELALR.
2,4‐Disubstituted 5‐Nitroimidazoles Potent against Clostridium difficile
Authors: Spitz Cédric , Mathias Fanny , Péchiné Séverine , Doan Tri Hanh Dung , Innocent Jean , Pellissier Sylvain , Di Giorgio Carole , Crozet Maxime D. , Janoir Claire , Vanelle Patrice 
Published: January 2019

AbstractMetronidazole is one of the first‐line treatments for non‐severe Clostridium difficile infections (CDI). However, resistance limits its use in cases of severe and complicated CDI. Structure–activity relationships previously described for the 5‐nitroimidazole series have shown that functionalization at the 2‐ and 4‐positions can impart better activity against parasites and anaerobic bacteria than metronidazole. Herein we report the synthesis of new 2,4‐disubstituted 5‐nitroimidazole compounds that show potent antibacterial activity against C. difficile. We used a vicarious nucleophilic substitution of hydrogen (VNS) reaction to introduce a phenylmethylsulfone at the 4‐position and a unimolecular radical nucleophilic substitution (SRN1) reaction to introduce an ethylenic function at the 2‐position of the 5‐nitroimidazole scaffold.
The role of dose escalation and proton therapy in perioperative or definitive treatment of chondrosarcoma and chordoma: An analysis of the National Cancer Data Base
Authors: Palm Russell F. , Oliver Daniel E. , Yang George Q. , Abuodeh Yazan , Naghavi Arash O. , Johnstone Peter A. S. 
Published: January 2019

BackgroundChordomas and chondrosarcomas are a rare but challenging subset of tumors to treat; however, previous studies have shown benefits from proton therapy, which are thought to be primarily driven by prescription conformality permitting homogeneous tumor dosing and the allowance of higher doses. No retrospective studies to date have directly compared the outcomes of conventional and particle therapy or examined the role of high doses (specifically ≥70 Gy) in definitive radiotherapy (DRT) or perioperative radiotherapy (PRT) for both types of malignancies.MethodsA total of 863 patients with chondrosarcoma and 715 patients with chordoma treated with nonpalliative proton or conventional radiation therapy with a dose range of 20 to 80 Gy and at least 15 months of follow‐up were identified from the National Cancer Data Base for the years 2003‐2014. The primary endpoint of overall survival (OS) was evaluated, and clinical features, including age, sex, grade, clinical stage, and Charlson‐Deyo comorbidity index, were compared.ResultsPatients receiving DRT were older and had more advanced disease. In DRT for chondrosarcoma, a high dose (40.6% vs 16.9%; P = .006) and proton therapy (75.0% vs 19.1%; P = .046) were associated with improved OS at 5 years in a multivariate analysis. In DRT for chordoma, proton therapy was associated with improved OS at 5 years in a multivariate analysis (100% vs 34.1%; P = .031), and a high dose for chordoma was significant for improved OS in a univariate analysis with both DRT (79.0% vs 54.1%; P = .027) and PRT (83.3% vs 77.4%; P = .007).ConclusionsIn the largest retrospective series to date, dose escalation and proton radiotherapy were associated with improved OS in patients with chondrosarcoma and chordoma despite limited follow‐up and access to particle therapy.
Synthesis and Characterization of Oxazaborinin Phosphonate for Blue OLED Emitter Applications
Authors: Köhling Jonas , Kozel Volodymyr , Jovanov Vladislav , Pajkert Romana , Tverdomed Sergey N. , Gridenco Oleg , Fugel Malte , Grabowsky Simon , Röschenthaler Gerd‐Volker , Wagner Veit 
Published: January 2019

AbstractA blue‐light emitting material based on a boron complex containing heteroaromatic phosphonate ligand is synthesized and characterized. The Phospho‐Fries rearrangement is used in the synthesis route of the ligand as a convenient method of introducing phosphonate groups into phenols. Structural, thermal and photophysical properties of the resulting oxazaborinin phosphonate compound have been characterized. DFT geometry optimizations were studied as well as the spatial position and symmetry of the HOMO and LUMO. Good thermal stability up to 250 °C enables vacuum deposition methods next to solution processing. Combining the work function with the optical band gap from UV‐Vis measurements shows that band alignment is possible with standard contact materials. Photoluminescence reveals an emission peak at 428 nm, which is suitable for a blue light‐emitter.
Organotypic Culture of Bone‐Like Structures Using Composite Ceramic‐Fibrin Scaffolds
Authors: Iordachescu Alexandra , Williams Richard L. , Hulley Philippa A. , Grover Liam M. 
Published: January 2019

AbstractWe have developed an organotypic culture system that allows the production of bone tissue features on a centimeter scale. A composite, calcium phosphate–strained fibrin gel system is able to organize itself in the presence of osteoblastic cells, creating basic hierarchical units as seen in vivo, and can be modified to produce a range of other tissues that require such directional structuring. Constructs evolve over time into multi‐compositional structures containing a high mineral content and terminally differentiated, osteocyte‐like cells. These tissues can be cultured over extended durations (exceeding 1 year) and are responsive to a variety of chemical and biological agents. The platform can reduce the number of animals used in experimentation by acting as an intermediate stage in which more personalized research conditions can be generated. We provide a thorough description of the protocol used to successfully culture and modify this system, as well as guidance on compositional characterization. © 2019 by John Wiley & Sons, Inc.
Switchability of Gabapentin Formulations: A Randomized Trial to Assess Bioequivalence Between Neurontin and Gabasandoz on the Individual Subject Level
Authors: Van Lancker Griet , Van Bortel Luc , Delafontaine Brant , Boussery Koen , Swart Eleonora , Chahbouni Abdel , Van Bocxlaer Jan , Colin Pieter 
Published: January 2019

Generic substitution of antiepileptic drugs is generally not advised by neurologists. The present study investigated the switchability of gabapentin 800 mg tablets (Neurontin and Gabasandoz) using an individual bioequivalence (IBE) study design with two batches of each product and assessed whether between‐batch and between‐formulation variability in exposure play a significant role in the within‐subject variability. The trial was analyzed according to the US Food and Drug Administration (FDA) framework to establish IBE. The IBE was shown between both products with the 95% upper confidence bound of the IBE criterion being −2.01 and −2.31 for area under the concentration‐time curve from zero to infinity (AUC0–inf) and peak plasma concentration (Cmax), respectively. Subject‐by‐formulation variability (1.35%) was negligible compared with the within‐subject variability of AUC0–inf with Neurontin (19.0%) and Gabasandoz (23.6%). Inclusion of an additional batch did not significantly change this within‐subject variability (20.2% and 23.6%, respectively). This study shows that substitution of gabapentin 800 mg tablets of Neurontin and Gabasandoz should be possible without affecting clinical outcomes.
Reef‐to‐ridge ecological perspectives of high‐energy storm events in northeast Australia
Authors: Turton Stephen M. 
Published: January 2019

AbstractTropical cyclones (TCs) are the dominant high‐energy storm (HES) events affecting marine, coastal, and terrestrial ecosystems in northeast Australia. My study provides the first synthetic analysis of ecological effects of TCs on key ecosystems along a reef‐to‐ridge gradient in the region. This gradient includes outer and mid‐shelf, and nearshore coral reefs, seagrass communities, mangrove forests, and lowland, and upland rain forests. Firstly, I synthesize published research on ecological effects of HES events on natural ecosystems along the reef‐to‐ridge gradient, with a particular focus on evaluating their ecological resistance and resilience to HES events. Secondly, utilizing two case studies, I compare and contrast the large‐scale wind energy effects of two severe tropical cyclones (TC Larry and TC Yasi) on natural ecosystems along their respective reef‐to‐ridge gradients, with a focus on damage patterns and early stages of recovery for key ecosystems. Finally, I consider the likely effects of climate change on future HES events, and how these may affect the resistance and resilience of ecosystems along the reef‐to‐ridge gradient. Damage patterns for ecosystems along the reef‐to‐ridge gradient for both TCs were largely determined by distance from the TC track, side of track, shelf position in the case of reefs, topography in the case of forests, forest type, and forest integrity (contiguous vs. fragmented). Major structural damage to coral reefs and contiguous rain forests after both TCs was patchy, suggesting some degree of larger‐scale resistance of these ecosystems to HES events. In the case of littoral forests, small forest remnants, regrowth forests, and riparian forests much lower levels of resistance to high‐energy winds were observed, due to patch size and edge effects. Apart from mangroves, most intact ecosystems along the reef‐to‐ridge gradient have shown early stages of recovery. However, small forests remnants and riparian forests in the agricultural matrix had lower levels of recovery compared with areas of contiguous forest. Anthropogenic climate change may reduce the resistance and resilience of ecosystems along the reef‐to‐ridge gradient to cope with future HES events, due to increased wind and wave energy, higher storm surges, higher intensity rainfall, and larger river plume events.
Variable color patterns influence continental range size and species–area relationships on islands
Authors: Franzén Markus , Forsman Anders , Betzholtz Per‐Eric 
Published: January 2019

AbstractIt has been hypothesized that species with more variable color patterns should have higher establishment success and be less sensitive to environmental changes and local extinction compared with species that do not vary in color. This difference in colonization/extinction balance should manifest as larger continental range distributions and modulate the species–area relationship on true islands. We evaluated these predictions using data for 1216 species of butterflies and moths that differed with regard to inter‐individual variation in color pattern. We show that species with more variable color patterns have larger continental range sizes in Europe compared with non‐variable species. We also provide rare evidence that the slope of the species–area relationship on islands is steeper for species having non‐variable color patterns, suggesting that to preserve 60% of non‐variable species would require an area twice as large compared to what would be needed to preserve 60% of variable species. Our findings suggest that combining information on ecological characteristics with presence/absence data from small and medium sized islands can help identify traits that drive species range patterns at the continental scale, and that individual variation in color pattern can be used as a proxy for ecological generalization and the ability to cope with environmental change.
Individual and temporal variation in pathogen load predicts long‐term impacts of an emerging infectious disease
Authors: Wells Konstans , Hamede Rodrigo K. , Jones Menna E. , Hohenlohe Paul A. , Storfer Andrew , McCallum Hamish I. 
Published: January 2019

AbstractEmerging infectious diseases increasingly threaten wildlife populations. Most studies focus on managing short‐term epidemic properties, such as controlling early outbreaks. Predicting long‐term endemic characteristics with limited retrospective data is more challenging. We used individual‐based modeling informed by individual variation in pathogen load and transmissibility to predict long‐term impacts of a lethal, transmissible cancer on Tasmanian devil (Sarcophilus harrisii) populations. For this, we employed approximate Bayesian computation to identify model scenarios that best matched known epidemiological and demographic system properties derived from 10 yr of data after disease emergence, enabling us to forecast future system dynamics. We show that the dramatic devil population declines observed thus far are likely attributable to transient dynamics (initial dynamics after disease emergence). Only 21% of matching scenarios led to devil extinction within 100 yr following devil facial tumor disease (DFTD) introduction, whereasDFTDfaded out in 57% of simulations. In the remaining 22% of simulations, disease and host coexisted for at least 100 yr, usually with long‐period oscillations. Our findings show that pathogen extirpation or host–pathogen coexistence are much more likely than theDFTD‐induced devil extinction, with crucial management ramifications. Accounting for individual‐level disease progression and the long‐term outcome of devil–DFTDinteractions at the population‐level, our findings suggest that immediate management interventions are unlikely to be necessary to ensure the persistence of Tasmanian devil populations. This is because strong population declines of devils after disease emergence do not necessarily translate into long‐term population declines at equilibria. Our modeling approach is widely applicable to other host–pathogen systems to predict disease impact beyond transient dynamics.