bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?—A multicenter EBMT-PDWP study
Authors: Willasch Andre Manfred , Peters Christina , Sedláček Petr , Dalle Jean-Hugues , Kitra-Roussou Vassiliki , Yesilipek Akif , Wachowiak Jacek , Lankester Arjan , Prete Arcangelo , Hamidieh Amir Ali , Ifversen Marianne , Buechner Jochen , Kriván Gergely , Hamladji Rose-Marie , Diaz-de-Heredia Cristina , Skorobogatova Elena , Michel Gérard , Locatelli Franco , Bertaina Alice , Veys Paul , Dupont Sophie , Or Reuven , Güngör Tayfun , Aleinikova Olga , Sufliarska Sabina , Sundin Mikael , Rascon Jelena , Kaare Ain , Nemet Damir , Fagioli Franca , Klingebiel Thomas Erich , Styczynski Jan , Bierings Marc , Nagy Kálmán , Abecasis Manuel , Afanasyev Boris , Ansari Marc , Vettenranta Kim , Alseraihy Amal , Chybicka Alicja , Robinson Stephen , Bertrand Yves , Kupesiz Alphan , Ghavamzadeh Ardeshir , Campos Antonio , Pichler Herbert , Dalissier Arnaud , Labopin Myriam , Corbacioglu Selim , Balduzzi Adriana , Galimard Jacques-Emmanuel , Bader Peter ,   on behalf of the EBMT Paediatric Diseases Working Party
Published: March 2020

AbstractAlthough most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2–18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective “real-world-practice” study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.
A novel model of liver cancer stem cells developed from induced pluripotent stem cells
Authors: Afify Said M. , Sanchez Calle Anna , Hassan Ghmkin , Kumon Kazuki , Nawara Hend M. , Zahra Maram H. , Mansour Hager M. , Khayrani Apriliana Cahya , Alam Md Jahangir , Du Juan , Seno Akimasa , Iwasaki Yoshiaki , Seno Masaharu 
Published: March 2020

Abstract
Background
Liver cancer is the second most common cause of cancer-related death. Every type of tumours including liver cancer contains cancer stem cells (CSCs). To date, the molecular mechanism regulating the development of liver CSCs remains unknown.

Methods
In this study, we tried to generate a new model of liver CSCs by converting mouse induced pluripotent stem cells (miPSCs) with hepatocellular carcinoma (HCC) cell line Huh7 cells conditioned medium (CM). miPSCs treated with CM were injected into the liver of BALB/c nude mice. The developed tumours were then excised and analysed.

Results
The primary cultured cells from the malignant tumour possessed self-renewal capacity, differentiation potential and tumorigenicity in vivo, which were found rich in liver cancer-associated markers as well as CSC markers.

Conclusions
We established a model of liver CSCs converting from miPS and showed different stages of stemness during conversion process. Our CSC model will be important to assess the molecular mechanisms necessary to develop liver CSCs and could help in defeating liver cancer.
Serine-dependent redox homeostasis regulates glioblastoma cell survival
Authors: Engel Anna L. , Lorenz Nadja I. , Klann Kevin , Münch Christian , Depner Cornelia , Steinbach Joachim P. , Ronellenfitsch Michael W. , Luger Anna-Luisa 
Published: March 2020

AbstractBackgroundThe amino acid serine is an important substrate for biosynthesis and redox homeostasis. We investigated whether glioblastoma (GBM) cells are dependent on serine for survival under conditions of the tumour microenvironment.MethodsSerine availability in GBM cells was modulated pharmacologically, genetically and by adjusting serine and glycine concentrations in the culture medium. Cells were investigated for regulation of serine metabolism, proliferation, sensitivity to hypoxia-induced cell death and redox homeostasis.ResultsHypoxia-induced expression ofphosphoglycerate dehydrogenase (PHGDH)and the mitochondrialserine hydroxymethyltransferase (SHMT2)was observed in three of five tested glioma cell lines. Nuclear factor erythroid 2-related factor (Nrf) 2 activation also inducedPHGDHandSHMT2expression in GBM cells. Low levels of endogenous PHGDH as well asPHGDHgene suppression resulted in serine dependency for cell growth. Pharmacological inhibition of PHGDH with CBR-5884 reduced proliferation and sensitised cells profoundly to hypoxia-induced cell death. This effect was accompanied by an increase in reactive oxygen species and a decrease in the NADPH/NADP+ratio. Similarly, hypoxia-induced cell death was enhanced byPHGDHgene suppression and reduced byPHGDHoverexpression.ConclusionsSerine facilitates adaptation of GBM cells to conditions of the tumour microenvironment and its metabolism could be a plausible therapeutic target.
Active steroid hormone synthesis renders adrenocortical cells highly susceptible to type II ferroptosis induction
Authors: Weigand Isabel , Schreiner Jochen , Röhrig Florian , Sun Na , Landwehr Laura-Sophie , Urlaub Hanna , Kendl Sabine , Kiseljak-Vassiliades Katja , Wierman Margaret E. , Angeli José Pedro Friedmann , Walch Axel , Sbiera Silviu , Fassnacht Martin , Kroiss Matthias 
Published: March 2020

AbstractConditions of impaired adrenal function and tissue destruction, such as in Addison’s disease, and treatment resistance of adrenocortical carcinoma (ACC) necessitate improved understanding of the pathophysiology of adrenal cell death. Due to relevant oxidative processes in the adrenal cortex, our study investigated the role of ferroptosis, an iron-dependent cell death mechanism and found high adrenocortical expression of glutathione peroxidase 4 (GPX4) and long-chain-fatty-acid CoA ligase 4 (ACSL4) genes, key factors in the initiation of ferroptosis. By applying MALDI mass spectrometry imaging to normal and neoplastic adrenocortical tissue, we detected high abundance of arachidonic and adrenic acid, two long chain polyunsaturated fatty acids which undergo peroxidation during ferroptosis. In three available adrenal cortex cell models (H295R, CU-ACC1 and CU-ACC-2) a high susceptibility to GPX4 inhibition with RSL3 was documented with EC50 values of 5.7 × 10−8, 8.1 × 10−7 and 2.1 × 10−8 M, respectively, while all non-steroidogenic cells were significantly less sensitive. Complete block of GPX4 activity by RSL3 led to ferroptosis which was completely reversed in adrenal cortex cells by inhibition of steroidogenesis with ketoconazole but not by blocking the final step of cortisol synthesis with metyrapone. Mitotane, the only approved drug for ACC did not induce ferroptosis, despite strong induction of lipid peroxidation in ACC cells. Together, this report is the first to demonstrate extraordinary sensitivity of adrenal cortex cells to ferroptosis dependent on their active steroid synthetic pathways. Mitotane does not induce this form of cell death in ACC cells.
Helicobacter pylori-induced adrenomedullin modulates IFN-γ-producing T-cell responses and contributes to gastritis
Authors: Kong Hui , You Nan , Chen Han , Teng Yong-sheng , Liu Yu-gang , Lv Yi-pin , Mao Fang-yuan , Cheng Ping , Chen Weisan , Zhao Zhuo , Zou Quan-ming , Guo Gang , Zhang Jin-yu , Zhuang Yuan 
Published: March 2020

AbstractAdrenomedullin (ADM) is a multifunctional peptide that is expressed by many surface epithelial cells, but its relevance to Helicobacter pylori (H. pylori)-induced gastritis is unknown. Here, we found that gastric ADM expression was elevated in gastric mucosa of H. pylori-infected patients and mice. In H. pylori-infected human gastric mucosa, ADM expression was positively correlated with the degree of gastritis; accordingly, blockade of ADM resulted in decreased inflammation within the gastric mucosa of H. pylori-infected mice. During H. pylori infection, ADM production was promoted via PI3K–AKT signaling pathway activation by gastric epithelial cells in a cagA-dependent manner, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterized by the increased IFN-γ-producing T cells, whose differentiation was induced via the phosphorylation of AKT and STAT3 by ADM derived from gastric epithelial cells. ADM also induced macrophages to produce IL-12, which promoted the IFN-γ-producing T-cell responses, thereby contributing to the development of H. pylori-associated gastritis. Accordingly, blockade of IFN-γ or knockout of IFN-γ decreased inflammation within the gastric mucosa of H. pylori-infected mice. This study identifies a novel regulatory network involving H. pylori, gastric epithelial cells, ADM, macrophages, T cells, and IFN-γ, which collectively exert a pro-inflammatory effect within the gastric microenvironment.
Single-photon quantum regime of artificial radiation pressure on a surface acoustic wave resonator
Authors: Noguchi Atsushi , Yamazaki Rekishu , Tabuchi Yutaka , Nakamura Yasunobu 
Published: March 2020

AbstractElectromagnetic fields carry momentum, which upon reflection on matter gives rise to the radiation pressure of photons. The radiation pressure has recently been utilized in cavity optomechanics for controlling mechanical motions of macroscopic objects at the quantum limit. However, because of the weakness of the interaction, attempts so far had to use a strong coherent drive to reach the quantum limit. Therefore, the single-photon quantum regime, where even the presence of a totally off-resonant single photon alters the quantum state of the mechanical mode significantly, is one of the next milestones in cavity optomechanics. Here we demonstrate an artificial realization of the radiation pressure of microwave photons acting on phonons in a surface acoustic wave resonator. The order-of-magnitude enhancement of the interaction strength originates in the well-tailored, strong, second-order nonlinearity of a superconducting Josephson junction circuit. The synthetic radiation pressure interaction adds a key element to the quantum optomechanical toolbox and can be applied to quantum information interfaces between electromagnetic and mechanical degrees of freedom.
Rap1-GTPases control mTORC1 activity by coordinating lysosome organization with amino acid availability
Authors: Mutvei Anders P. , Nagiec Michal J. , Hamann Jens C. , Kim Sang Gyun , Vincent C. Theresa , Blenis John 
Published: March 2020

AbstractThe kinase mTOR complex 1 (mTORC1) promotes cellular growth and is frequently dysregulated in cancers. In response to nutrients, mTORC1 is activated on lysosomes by Rag and Rheb guanosine triphosphatases (GTPases) and drives biosynthetic processes. How limitations in nutrients suppress mTORC1 activity remains poorly understood. We find that when amino acids are limited, the Rap1-GTPases confine lysosomes to the perinuclear region and reduce lysosome abundance, which suppresses mTORC1 signaling. Rap1 activation, which is independent of known amino acid signaling factors, limits the lysosomal surface available for mTORC1 activation. Conversely, Rap1 depletion expands the lysosome population, which markedly increases association between mTORC1 and its lysosome-borne activators, leading to mTORC1 hyperactivity. Taken together, we establish Rap1 as a critical coordinator of the lysosomal system, and propose that aberrant changes in lysosomal surface availability can impact mTORC1 signaling output.
Polar coupling enabled nonlinear optical filtering at MoS2/ferroelectric heterointerfaces
Authors: Li Dawei , Huang Xi , Xiao Zhiyong , Chen Hanying , Zhang Le , Hao Yifei , Song Jingfeng , Shao Ding-Fu , Tsymbal Evgeny Y. , Lu Yongfeng , Hong Xia 
Published: March 2020

AbstractComplex oxide heterointerfaces and van der Waals heterostructures present two versatile but intrinsically different platforms for exploring emergent quantum phenomena and designing new functionalities. The rich opportunity offered by the synergy between these two classes of materials, however, is yet to be charted. Here, we report an unconventional nonlinear optical filtering effect resulting from the interfacial polar alignment between monolayer MoS2 and a neighboring ferroelectric oxide thin film. The second harmonic generation response at the heterointerface is either substantially enhanced or almost entirely quenched by an underlying ferroelectric domain wall depending on its chirality, and can be further tailored by the polar domains. Unlike the extensively studied coupling mechanisms driven by charge, spin, and lattice, the interfacial tailoring effect is solely mediated by the polar symmetry, as well explained via our density functional theory calculations, pointing to a new material strategy for the functional design of nanoscale reconfigurable optical applications.
Exploiting the role of nanoparticle shape in enhancing hydrogel adhesive and mechanical properties
Authors: Arno Maria C. , Inam Maria , Weems Andrew C. , Li Zehua , Binch Abbie L. A. , Platt Christopher I. , Richardson Stephen M. , Hoyland Judith A. , Dove Andrew P. , O’Reilly Rachel K. 
Published: March 2020

AbstractThe ability to control nanostructure shape and dimensions presents opportunities to design materials in which their macroscopic properties are dependent upon the nature of the nanoparticle. Although particle morphology has been recognized as a crucial parameter, the exploitation of the potential shape-dependent properties has, to date, been limited. Herein, we demonstrate that nanoparticle shape is a critical consideration in the determination of nanocomposite hydrogel properties. Using translationally relevant calcium-alginate hydrogels, we show that the use of poly(L-lactide)-based nanoparticles with platelet morphology as an adhesive results in a significant enhancement of adhesion over nanoparticle glues comprised of spherical or cylindrical micelles. Furthermore, gel nanocomposites containing platelets showed an enhanced resistance to breaking under strain compared to their spherical and cylindrical counterparts. This study opens the doors to a change in direction in the field of gel nanocomposites, where nanoparticle shape plays an important role in tuning mechanical properties.
First transcriptome of the Neotropical pest Euschistus heros (Hemiptera: Pentatomidae) with dissection of its siRNA machinery
Authors: Cagliari Deise , Dias Naymã Pinto , dos Santos Ericmar Ávila , Rickes Leticia Neutzling , Kremer Frederico Schmitt , Farias Juliano Ricardo , Lenz Giuvan , Galdeano Diogo Manzano , Garcia Flávio Roberto Mello , Smagghe Guy , Zotti Moisés João 
Published: March 2020

AbstractOver the past few years, the use of RNA interference (RNAi) for insect pest management has attracted considerable interest in academia and industry as a pest-specific and environment-friendly strategy for pest control. For the success of this technique, the presence of core RNAi genes and a functional silencing machinery is essential. Therefore, the aim of this study was to test whether the Neotropical brown stinkbugEuschistus heroshas the main RNAi core genes and whether the supply of dsRNA could generate an efficient gene silencing response. To do this, total mRNA of all developmental stages was sequenced on an Illumina platform, followed by ade novoassembly, gene annotation and RNAi-related gene identification. Once RNAi-related genes were identified, nuclease activities in hemolymph were investigated through anex vivoassay. To test the functionality of the siRNA machinery,E. herosadults were microinjected with ~28 ng per mg of insect of a dsRNA targeting theV-ATPase-Agene. Mortality, relative transcript levels ofV-ATPase-A, and the expression of the genes involved in the siRNA machinery,Dicer-2(DCR-2) andArgonaute 2(AGO-2), were analyzed. Transcriptome sequencing generated more than 126 million sequenced reads, and these were annotated in approximately 80,000 contigs. The search of RNAi-related genes resulted in 47 genes involved in the three major RNAi pathways, with the absence ofsid-likehomologous. Althoughex vivoincubation of dsRNA inE. heroshemolymph showed rapid degradation, there was 35% mortality at 4 days after treatment and a significant reduction inV-ATPase-Agene expression. These results indicated that although sid-likegenes are lacking, the dsRNA uptake mechanism was very efficient. Also, 2-fold and 4-fold overexpression ofDCR-2andAGO-2, respectively, after dsRNA supply indicated the activation of the siRNA machinery. Consequently,E. heroshas proven to be sensitive to RNAi upon injection of dsRNA into its hemocoel. We believe that this finding together with a publically available transcriptome and the validation of a responsive RNAi machinery provide a starting point for future field applications against one of the most important soybean pests in South America.
Size of portally deprived liver lobe after portal vein ligation and additional partial hepatectomy: Result of balancing proliferation and apoptosis
Authors: Wei Weiwei , Hua Chuanfeng , Zhang Tianjiao , Dirsch Olaf , Gremse Felix , Homeyer André , Settmacher Utz , Dahmen Uta 
Published: March 2020

AbstractThe liver has the ability to maintain its total size by adjusting the size of the individual liver lobes differently in response to regeneration- and atrophy-stimuli. Portal vein ligation (PVL) drives the ligated lobe to undergo atrophy whereas partial hepatectomy (PHx) drives the total remnant liver to regenerate. We hypothesize that the size of the PVL-lobe is dependent on the balance between the extent of PVL and the extent of PHx inducing a complex interplay between hepatocyte proliferation, apoptosis and autophagy. Lewis-rats were subjected to either 20%PVL + 70%PHx or 70%PVL + 20%PHx. Control groups consisted of 20%PVL and 70%PVL. Liver lobe weight, BrdU-proliferation-index, proliferating-cell-nuclear-antigen-mRNA-expression level, apoptotic density and autophagy-related-proteins were investigated. The PVL-liver lobe adjusted its weight differently, increasing by 40% after 20%PVL + 70%PHx, but decreasing by 25% after 70%PVL + 20%PHx. Additional resection induced a low, but substantial size-dependent hepatocyte proliferation rate (maximal 6.3% and 3.6% vs. 0.3% and significantly suppressed apoptotic density in the deportalized-liver-lobe (3 and 14 cells/mm2 comparing with above 26 cells/mm2, p < 0.01). Autophagy was more activated in PVL-liver lobe after simultaneous PHx than after PVL only. In summary, atrophy of the PVL-liver lobe after simultaneous PHx was counteracted by promoting hepatocyte proliferation, inducing autophagy and suppressing apoptosis in a PHx-extent-dependent manner.
Effects of stacking periodicity on the electronic and optical properties of GaAs/AlAs superlattice: a first-principles study
Authors: Jiang M. , Xiao H. Y. , Peng S. M. , Qiao L. , Yang G. X. , Liu Z. J. , Zu X. T. 
Published: March 2020

AbstractThe effects of stacking periodicity on the electronic and optical properties of GaAs/AlAs superlattice have been explored by density functional theory calculations. Among the (GaAs)m/(AlAs)m, (GaAs)1/(AlAs)m and (GaAs)m/(AlAs)1 (m = 1 to 5) superlattices, the band gaps of (GaAs)m/(AlAs)1 superlattices decrease significantly as the layer of GaAs increases, and the cut-off wavelengths are found to locate in the near infrared region. For (GaAs)m/(AlAs)1 SLs, the conduction bands shift toward Fermi level, resulting in the smaller band gap, while conduction bands of (GaAs)1/(AlAs)n SLs slightly shift to higher energy, which lead to comparable band gaps. The layer number of GaAs shows negligible effects on the reflectivity spectra of superlattice structures, while the absorption coefficient shows a red-shift with the increasing layer of GaAs, which is beneficial for the application of GaAs/AlAs superlattice in the field of near infrared detector. These results demonstrate that controlling the number of GaAs layers is a good method to engineer the optoelectronic properties of GaAs/AlAs superlattice.
A new clinical-genomic model to predict 10-year recurrence risk in primary operable breast cancer patients
Authors: Huang Tzu-Ting , Lei Lei , Chen Ching-Hsuan Andre , Lu Tzu-Pin , Jen Chung-Wen , Cheng Skye Hung-Chun 
Published: March 2020

AbstractThis study aimed to validate the long-term prognostic value of a new clinical-genomic model, Distant Genetic Model-Clinical Variable Model 6 (DGM-CM6), developed in Asia as a prognostic panel for all subtypes of breast cancer. We included 752 operable stage I–III breast cancer patients representing all subtypes treated from 2005 to 2014 as the validation cohort. The median follow-up was 95.8 months. The low- and high-risk patients classified by DGM-CM6 (RI-DR) had significant differences in 10-year distant recurrence-free interval (DRFI) (94.1% vs. 85.0%, P < 0.0001) and relapse-free survival (RFS) (90.0% vs. 80.5%, P = 0.0003). External validation using EMTAB-365 dataset showed similar observation (P < 0.0001). DGM-CM6 was an independent prognostic factor by multivariate analysis with hazard ratios of 3.1 (1.6–6.0) for RFS (P = 0.0009) and 3.8 (1.6–9.0) for DRFI (P = 0.0028). Comparing the C-index of DGM-CM6 and PAM50-ROR scores, the former performed better than the latter in predicting long-term DRFI and RFS, especially in N0, ER/PR-positive, and HER2-negative patients.
Straightforward synthesis of Sulfur/N,S-codoped carbon cathodes for Lithium-Sulfur batteries
Authors: Sevilla Marta , Carro-Rodríguez Jorge , Díez Noel , Fuertes Antonio B. 
Published: March 2020

AbstractAn upgrade of the scalable fabrication of high-performance sulfur-carbon cathodes is essential for the widespread commercialization of this technology. Herein we present a simple, cost-effective and scalable approach for the fabrication of cathodes comprising sulfur and high-surface area, N,S-codoped carbons. The method involves the use of a sulfur salt, i.e. sodium thiosulfate, as activating agent, sulfur precursor and S-dopant, and polypyrrole as carbon precursor and N-dopant. In this way, the production of the porous host and the incorporation of sulfur are combined in the same procedure. The porous hosts thus produced have BET surface areas in excess of 2000 m2 g−1, a micro-mesoporous structure, as well as sulfur and nitrogen contents of 5–6 wt% and ~2 wt%, respectively. The elemental sulfur content in the composites can be precisely modulated in the range of 24 to ca. 90 wt% by controlling the amount of sodium thiosulfate used. Remarkably, these porous carbons are able to accommodate up to 80 wt% sulfur exclusively within their porosity. When analyzed in lithium-sulfur batteries, these sulfur-carbon composites show high specific capacities of 1100 mAh g−1 at a low C-rate of 0.1 C and above 500 mAh g−1 at a high rate of 2 C for sulfur contents in the range of 50–80 wt%. Remarkably, the composites with 51–65 wt% S can still provide above 400 mAh g−1 at an ultra-fast rate of 4 C (where a charge and discharge cycle takes only ten minutes). The good rate capability and sulfur utilization was additionally assessed for cathodes with a high sulfur content (65–74%) and a high sulfur loading (>5 mg cm−2). In addition, cathodes of 4 mg cm−2 successfully cycled for 260 cycles at 0.2 C showed only a low loss of 0.12%/cycle.