bluuebunny/crossref_metadata_2025_split huggingface dataset:
When economics, strategy, and racial ideology meet: inter-Axis connections in the wartime Indian Ocean
Authors: Kowner Rotem 
Published: June 2017

AbstractJapan’s relations with Germany and Italy during the Second World War were rather limited. Nevertheless, there were some regional nuances and growing cooperation as the war drew to its close. In the Indian Ocean, at least, and especially in the area around the Straits of Malacca and the Java Sea, the Japanese and German empires, and to a lesser extent the Italian empire too, did develop a rather intensive cooperation during the final two years of the war (1943–45). This cooperation encompassed several domains, such as the exchange of vital raw materials and military technology, coordinated naval activity, and even an ideological affinity that materialized in pressures to implement harsher racial policies towards Jewish communities in the region. This article examines the scope of this unique inter-Axis collaboration, the specific reasons for why which came into being in this region in particular, and the lessons we may draw from it.
Five Marks of Mission: History, Theology, Critique
Authors: Zink Jesse 
Published: June 2017

AbstractIn recent years the Five Marks of Mission have become the latest in a long series of mission ‘slogans’ in the Anglican Communion, but little attention has been paid to their origin or theological presuppositions. This paper traces the development of an Anglican definition of mission from the 1984 meeting of the Anglican Consultative Council, at which a four-fold definition was first put forth, to the present use of the Five Marks of Mission across many parts of the Communion. The strong influence of evangelical mission thinking on this definition is demonstrated, as is the contributions from African Anglican bishops. Anglican mission thinking has shifted from emphasizing pragmatism and coordination to providing a vision for the Communion to live into. Mission thinking has been a site of genuine cross-cultural interchange among Anglicans from diverse backgrounds.
Precision medicine for hepatocelluar carcinoma using molecular pattern diagnostics: results from a preclinical pilot study
Authors: Agarwal Rahul , Cao Yuan , Hoffmeier Klaus , Krezdorn Nicolas , Jost Lukas , Meisel Alejandro Rodriguez , Jüngling Ruth , Dituri Francesco , Mancarella Serena , Rotter Björn , Winter Peter , Giannelli Gianluigi 
Published: June 2017

AbstractThe aim of this study was to design a road map for personalizing cancer therapy in hepatocellular carcinoma (HCC) by using molecular pattern diagnostics. As an exploratory study, we investigated molecular patterns of tissues of two tumors from individual HCC patients, which in previous experiments had shown contrasting reactions to the phase 2 transforming growth factor beta receptor 1 inhibitor galunisertib. Cancer-driving molecular patterns encompass – inter alias – altered transcription profiles and somatic mutations in coding regions differentiating tumors from their respective peritumoral tissues and from each other. Massive analysis of cDNA ends and all-exome sequencing demonstrate a highly divergent transcriptional and mutational landscape, respectively, for the two tumors, that offers potential explanations for the tumors contrasting responses to galunisertib. Molecular pattern diagnostics (MPDs) suggest alternative, individual-tumor-specific therapies, which in both cases deviate from the standard sorafenib treatment and from each other. Suggested personalized therapies use kinase inhibitors and immune-focused drugs as well as low-toxicity natural compounds identified using an advanced bioinformatics routine included in the MPD protocol. The MPD pipeline we describe here for the prediction of suitable drugs for treatment of two contrasting HCCs may serve as a blueprint for the design of therapies for various types of cancer.
Circulation of HAdV-41 with diverse genome types and recombination in acute gastroenteritis among children in Shanghai
Authors: Li Peng , Yang Lang , Guo Jiayin , Zou Wenwei , Xu Xuebin , Yang Xiaoxia , Du Xinying , Qiu Shaofu , Song Hongbin 
Published: June 2017

AbstractHuman adenovirus F (HAdV-F) is one of the major causative species detected in acute gastroenteritis in children worldwide. HAdV-F is composed of serotypes 40 and 41. Most studies have reported the prevalence of HAdV-41 and focused on its epidemiologic characteristics. In this study, seventeen samples were identified as HAdV-41 out of 273 fecal specimens from children with acute diarrhea in Shanghai. Five isolates were isolated and subjected to whole genome sequencing and analysis to characterize the genetic variation and evolution. Full genome analysis revealed low genetic variation (99.07–99.92% identity) among the isolates, and InDels are observed in the E2A gene and the hexon gene compared to the reference strain NIVD103. Phylogenetic analysis showed that all isolates mainly formed two genome-type clusters but with incongruence in the trees of whole genomes and individual genes. The recombination breakpoints of the five isolates were inferred by the Recombination Detection Program (RDP) and varied in the number and location of the recombination events, indicating different evolution origins. Overall, our study highlights the genetic diversity of HAdV-41 isolates circulating in Shanghai, which may have evolved from inter-strain recombination.
Effect Of Microgravity On Aromatase Expression In Sertoli Cells
Authors: Cirelli Elisa , De Domenico Emanuela , Botti Flavia , Massoud Renato , Geremia Raffaele , Grimaldi Paola 
Published: June 2017

AbstractCytochrome P450-aromatase catalyzes estrogen biosynthesis from C19 steroids. In the testis, Sertoli cells express P450-aromatase and represent the primary source of estrogen during prepuberal age. This study focused on the effect of simulated microgravity (SM) on aromatase expression in primary mouse Sertoli cells. When cultured in Rotary Cell Culture System (RCCS), Sertoli cells, formed multicellular three dimensional spheroids (3D). Biological properties were first analyzed in terms of viability, cell cycle, expression of cytoskeletal components and growth factors in comparison to Sertoli cells cultured in spheroids at unit gravity (G). SM did not affect cell viability and proliferation, nor expression of the main cytoskeleton proteins and of growth factors like Kit Ligand (KL) and glial derived neurotrophic factor (GDNF). On the other hand, SM caused a strong increase in P450 aromatase mRNA and protein expression. Interestingly, P450-aromatase was no more inducible by 8-Br-cAMP. The presence of a functional aromatase was confirmed by enrichment of 17β-estradiol released in the medium by androgen precursors. We concluded that SM causes a significant upregulation of aromatase gene expression in Sertoli cells, leading to a consequent increase in 17β-estradiol secretion. High level of 17β-estradiol in the testis could have potentially adverse effects on male fertility and testicular cancer.
Glucocorticoids ameliorate TGF-β1-mediated epithelial-to-mesenchymal transition of airway epithelium through MAPK and Snail/Slug signaling pathways
Authors: Yang Hyun-Woo , Lee Seoung-Ae , Shin Jae-Min , Park Il-Ho , Lee Heung-Man 
Published: June 2017

AbstractChronic rhinosinusitis with nasal polyps (CRSwNP) is closely associated with tissue remodeling. Epithelial-to-mesenchymal transition (EMT), a process of tissue remodeling, can be a therapeutic target of CRSwNP. Glucocorticoids are a type of steroid hormone that is used primarily in medical therapy for patients with CRSwNP; however, their effects on EMT in the airway epithelium remain unknown. To investigate the effects of dexamethasone and fluticasone propionate, a class of glucocorticoids, on transforming growth factor-β1 (TGF-β1) -induced EMT, we used A549 cells, human primary nasal epithelial cells (hPNECs) and ex vivo organ culture of the inferior turbinate. TGF-β1 induced changes in cell morphology, suppressed the expression of E-cadherin and enhanced the expression of a-smooth muscle actin, vimentin and fibronectin in A549 cells. However, glucocorticoids inhibited EMT, migration and invasion enhancement by TGF-β1. We found that the induction of phosphorylated ERK, p38 and the activity of Snail and Slug transcription factors by TGF-β1 were suppressed by glucocorticoids. Glucocorticoids also had a similar effect in hPNECs and ex vivo organ cultures of the inferior turbinate. These findings suggest that glucocorticoids might be a useful therapy for preventing tissue remodeling by blocking the EMT initiated by TGF-β1-induced MAPK and Snail/Slug signaling pathways in CRSwNP.
Associations between radiologist-defined semantic and automatically computed radiomic features in non-small cell lung cancer
Authors: Yip Stephen S. F. , Liu Ying , Parmar Chintan , Li Qian , Liu Shichang , Qu Fangyuan , Ye Zhaoxiang , Gillies Robert J. , Aerts Hugo J. W. L. 
Published: June 2017

AbstractTumor phenotypes captured in computed tomography (CT) images can be described qualitatively and quantitatively using radiologist-defined “semantic” and computer-derived “radiomic” features, respectively. While both types of features have shown to be promising predictors of prognosis, the association between these groups of features remains unclear. We investigated the associations between semantic and radiomic features in CT images of 258 non-small cell lung adenocarcinomas. The tumor imaging phenotypes were described using 9 qualitative semantic features that were scored by radiologists, and 57 quantitative radiomic features that were automatically calculated using mathematical algorithms. Of the 9 semantic features, 3 were rated on a binary scale (cavitation, air bronchogram, and calcification) and 6 were rated on a categorical scale (texture, border definition, contour, lobulation, spiculation, and concavity). 32–41 radiomic features were associated with the binary semantic features (AUC = 0.56–0.76). The relationship between all radiomic features and the categorical semantic features ranged from weak to moderate (|Spearmen’s correlation| = 0.002–0.65). There are associations between semantic and radiomic features, however the associations were not strong despite being significant. Our results indicate that radiomic features may capture distinct tumor phenotypes that fail to be perceived by naked eye that semantic features do not describe and vice versa.
Defects in autophagosome-lysosome fusion underlie Vici syndrome, a neurodevelopmental disorder with multisystem involvement
Authors: Hori Ikumi , Otomo Takanobu , Nakashima Mitsuko , Miya Fuyuki , Negishi Yutaka , Shiraishi Hideaki , Nonoda Yutaka , Magara Shinichi , Tohyama Jun , Okamoto Nobuhiko , Kumagai Takeshi , Shimoda Konomi , Yukitake Yoshiya , Kajikawa Daigo , Morio Tomohiro , Hattori Ayako , Nakagawa Motoo , Ando Naoki , Nishino Ichizo , Kato Mitsuhiro , Tsunoda Tatsuhiko , Saitsu Hirotomo , Kanemura Yonehiro , Yamasaki Mami , Kosaki Kenjiro , Matsumoto Naomichi , Yoshimori Tamotsu , Saitoh Shinji 
Published: June 2017

AbstractVici syndrome (VICIS) is a rare, autosomal recessive neurodevelopmental disorder with multisystem involvement characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency, developmental delay, and hypopigmentation. Mutations in EPG5, a gene that encodes a key autophagy regulator, have been shown to cause VICIS, however, the precise pathomechanism underlying VICIS is yet to be clarified. Here, we describe detailed clinical (including brain MRI and muscle biopsy) and genetic features of nine Japanese patients with VICIS. Genetic dissection of these nine patients from seven families identified 14 causative mutations in EPG5. These included five nonsense, two frameshift, three splicing, one missense, and one multi-exon deletion mutations, and two initiation codon variants. Furthermore, cultured skin fibroblasts (SFs) from two affected patients demonstrated partial autophagic dysfunction. To investigate the function of EPG5, siRNA based EPG5 knock-down, and CRISPR/Cas9 mediated EPG5 knock-out HeLa cells were generated. EPG5-depleted cells exhibited a complete block of autophagic flux caused by defective autophagosome-lysosome fusion. Unexpectedly, endocytic degradation was normal in both VICIS SFs and EPG5 depleted cells, suggesting that EPG5 function is limited to the regulation of autophagosome-lysosome fusion.
Population-based study of effectiveness of neoadjuvant radiotherapy on survival in US rectal cancer patients according to age
Authors: Wu Leilei , Pang Shichao , Yao Qianlan , Jian Chen , Lin Ping , Feng Fangyoumin , Li Hong , Li Yixue 
Published: June 2017

AbstractRecent cancer researches pay more attention to younger patients due to the variable treatment response among different age groups. Here we investigated the effectiveness of neoadjuvant radiation on the survival of younger and older patients in stage II/III rectal cancer. Data was obtained from Surveillance, Epidemiology, and End Results (SEER) database (n = 12801). Propensity score matching was used to balance baseline covariates according to the status of neoadjuvant radiation. Our results showed that neoadjuvant radiation had better survival benefit (Log-rank P = 3.25e-06) and improved cancer-specific 3-year (87.6%; 95% CI: 86.4–88.7% vs. 84.1%; 95% CI: 82.8–85.3%) and 5-year survival rates (78.1%; 95% CI: 76.2–80.1% vs. 77%; 95% CI: 75.3–78.8%). In older groups (>50), neoadjuvant radiation was associated with survival benefits in stage II (HR: 0.741; 95% CI: 0.599–0.916; P = 5.80e-3) and stage III (HR: 0.656; 95% CI 0.564–0.764; P = 5.26e-08). Interestingly, neoadjuvant radiation did not increase survival rate in younger patients (< = 50) both in stage II (HR: 2.014; 95% CI: 0.9032–4.490; P = 0.087) and stage III (HR: 1.168; 95% CI: 0.829–1.646; P = 0.372). Additionally, neoadjuvant radiation significantly decreased the cancer-specific mortality in older patients, but increased mortality in younger patients. Our results provided new insights on the neoadjuvant radiation in rectal cancer, especially for the younger patients.
Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain
Authors: Vandersarren Lana , Bosteels Cedric , Vanheerswynghels Manon , Moon James J. , Easton Andrew J. , Van Isterdael Gert , Janssens Sophie , Lambrecht Bart N. , van Helden Mary J. 
Published: June 2017

AbstractPneumonia virus of mice (PVM) infection has been widely used as a rodent model to study the closely related human respiratory syncytial virus (hRSV). While T cells are indispensable for viral clearance, they also contribute to immunopathology. To gain more insight into mechanistic details, novel tools are needed that allow to study virus-specific T cells in C57BL/6 mice as the majority of transgenic mice are only available on this background. While PVM-specific CD8 T cell epitopes were recently described, so far no PVM-specific CD4 T cell epitopes have been identified within the C57BL/6 strain. Therefore, we set out to map H2-IAb-restricted epitopes along the PVM proteome. By means of in silico prediction and subsequent functional validation, we were able to identify a MHCII-restricted CD4 T cell epitope, corresponding to amino acids 37–47 in the PVM matrix protein (M37–47). Using this newly identified MHCII-restricted M37–47 epitope and a previously described MHCI-restricted N339–347 epitope, we generated peptide-loaded MHCII and MHCI tetramers and characterized the dynamics of virus-specific CD4 and CD8 T cell responses in vivo. The findings of this study can provide a basis for detailed investigation of T cell-mediated immune responses to PVM in a variety of genetically modified C57BL/6 mice.
Cell-specific expression of aquaporin-5 (Aqp5) in alveolar epithelium is directed by GATA6/Sp1 via histone acetylation
Authors: Flodby Per , Li Changgong , Liu Yixin , Wang Hongjun , Rieger Megan E. , Minoo Parviz , Crandall Edward D. , Ann David K. , Borok Zea , Zhou Beiyun 
Published: June 2017

AbstractEpigenetic regulation of differentiation-related genes is poorly understood. We previously reported that transcription factors GATA6 and Sp1 interact with and activate the rat proximal 358-bp promoter/enhancer (p358P/E) of lung alveolar epithelial type I (AT1) cell-specific gene aquaporin-5 (Aqp5). In this study, we found that histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) increased AQP5 expression and Sp1-mediated transcription of p358P/E. HDAC3 overexpression inhibited Sp1-mediated Aqp5 activation, while HDAC3 knockdown augmented AQP5 protein expression. Knockdown of GATA6 or transcriptional co-activator/histone acetyltransferase p300 decreased AQP5 expression, while p300 overexpression enhanced p358P/E activation by GATA6 and Sp1. GATA6 overexpression, SAHA treatment or HDAC3 knockdown increased histone H3 (H3) but not histone H4 (H4) acetylation within the homologous p358P/E region of mouse Aqp5. HDAC3 binds to Sp1 and HDAC3 knockdown increased interaction of GATA6/Sp1, GATA6/p300 and Sp1/p300. These results indicate that GATA6 and HDAC3 control Aqp5 transcription via modulation of H3 acetylation/deacetylation, respectively, through competition for binding to Sp1, and suggest that p300 modulates acetylation and/or interacts with GATA6/Sp1 to regulate Aqp5 transcription. Cooperative interactions among transcription factors and histone modifications regulate Aqp5 expression during alveolar epithelial cell transdifferentiation, suggesting that HDAC inhibitors may enhance repair by promoting acquisition of AT1 cell phenotype.
Differential depression of neuronal network activity by midazolam and its main metabolite 1-hydroxymidazolam in cultured neocortical slices
Authors: Balk Monika , Hentschke Harald , Rudolph Uwe , Antkowiak Bernd , Drexler Berthold 
Published: June 2017

AbstractThe benzodiazepine midazolam is widely used in critical care medicine. Midazolam has a clinically active metabolite, 1-hydroxymidazolam. The contribution of 1-hydroxymidazolam to the effects of midazolam is controversial. The aim of the current study was to compare the actions of midazolam and 1-hydroxymidazolam on network activity of cortical neurons. Midazolam depressed neuronal activity at a low concentration of 5 nM. When midazolam concentration was increased, it depressed neuronal discharge rates in a biphasic manner. In comparison, 1-hydroxymidazolam did not depress the cortical network activity at low nanomolar concentrations. Higher concentrations of 1-hydroxymidazolam consistently inhibited neuronal activity. Moreover, midazolam shortened cortical up states at low, but not at high concentrations, while the opposite effect was observed with 1-hydroxymidazolam. The network depressant action of midazolam at low concentrations was absent in slices from GABAAreceptor α1(H101R)mutant mice. The α1(H101R)mutation renders α1-subunit containing GABAAreceptors insensitive towards benzodiazepines. This GABAAreceptor subtype is thought to mediate sedation. As midazolam is more potent than its metabolite 1-hydroxymidazolam, the major clinical effects are thus likely caused by midazolam itself. However, 1-hydroxymidazolam could add to the effects of midazolam, especially after the application of high doses of midazolam, and in case of impaired drug metabolism.
Inverse problem for multi-body interaction of nonlinear waves
Authors: Marruzzo Alessia , Tyagi Payal , Antenucci Fabrizio , Pagnani Andrea , Leuzzi Luca 
Published: June 2017

AbstractThe inverse problem is studied in multi-body systems with nonlinear dynamics representing, e.g., phase-locked wave systems, standard multimode and random lasers. Using a general model for four-body interacting complex-valued variables we test two methods based on pseudolikelihood, respectively with regularization and with decimation, to determine the coupling constants from sets of measured configurations. We test statistical inference predictions for increasing number of sampled configurations and for an externally tunable temperature-like parameter mimicing real data noise and helping minimization procedures. Analyzed models with phasors and rotors are generalizations of problems of real-valued spherical problems (e.g., density fluctuations), discrete spins (Ising and vectorial Potts) or finite number of states (standard Potts): inference methods presented here can, then, be straightforward applied to a large class of inverse problems. The high versatility of the exposed techniques also concerns the number of expected interactions: results are presented for different graph topologies, ranging from sparse to dense graphs.
Transcriptome analysis reveals similarities between human blood CD3− CD56bright cells and mouse CD127+ innate lymphoid cells
Authors: Allan David S. J. , Cerdeira Ana Sofia , Ranjan Anuisa , Kirkham Christina L. , Aguilar Oscar A. , Tanaka Miho , Childs Richard W. , Dunbar Cynthia E. , Strominger Jack L. , Kopcow Hernan D. , Carlyle James R. 
Published: June 2017

AbstractFor many years, human peripheral blood natural killer (NK) cells have been divided into functionally distinct CD3−CD56brightCD16−and CD3−CD56dimCD16+subsets. Recently, several groups of innate lymphoid cells (ILC), distinct from NK cells in development and function, have been defined in mouse. A signature of genes present in mouse ILC except NK cells, defined by Immunological Genome Project studies, is significantly over-represented in human CD56brightcells, by gene set enrichment analysis. Conversely, the signature genes of mouse NK cells are enriched in human CD56dimcells. Correlations are based upon large differences in expression of a few key genes. CD56brightcells show preferential expression of ILC-associatedIL7R(CD127),TNFSF10(TRAIL),KIT(CD117),IL2RA(CD25), CD27,CXCR3, DPP4(CD26),GPR183, and MHC class II transcripts and proteins. This could indicate an ontological relationship between human CD56brightcells and mouse CD127+ILC, or conserved networks of transcriptional regulation. In line with the latter hypothesis, among transcription factors known to impact ILC or NK cell development,GATA3,TCF7(TCF-1),AHR,SOX4, RUNX2, andZEB1transcript levels are higher in CD56brightcells, whileIKZF3(AIOLOS),TBX21(T-bet),NFIL3(E4BP4),ZEB2,PRDM1(BLIMP1), andRORAmRNA levels are higher in CD56dimcells.
99mTc-labeled bevacizumab for detecting atherosclerotic plaque linked to plaque neovascularization and monitoring antiangiogenic effects of atorvastatin treatment in ApoE−/− mice
Authors: Tan Hui , Zhou Jun , Yang Xiangdong , Abudupataer Mieradilijiang , Li Xiao , Hu Yan , Xiao Jie , Shi Hongcheng , Cheng Dengfeng 
Published: June 2017

AbstractAtherosclerotic neovascularization plays a significant role in plaque instability as it provides additional lipids and inflammatory mediators to lesions, and resulting in intraplaque hemorrhage. Vascular endothelial growth factor-A (VEGF-A) is considered the predominant proangiogenic factor in angiogenesis. Bevacizumab, a humanized monoclonal antibody, specifically binds to all VEGF-A isoforms with high affinity. Therefore, in this study, we designed 99mTc-MAG3-bevacizumab as a probe, and then investigated its usefulness as a new imaging agent for the detection of plaque neovessels, while also assessing the therapeutic effect of atorvastatin treatment. The ApoE−/− mice treated with atorvastatin were used as the treatment group, and C57BL/6 J mice were selected as the control group. 99mTc-MAG3-bevacizumab uptake was visualized on atherosclerotic lesions by non-invasive in-vivo micro-SPECT/CT and ex-vivo BSGI planar imaging. The value of P/B in each part of the aorta of ApoE−/− mice was higher than in the treatment group and the C57BL/6 J mice, which was confirmed by Oil Red O staining, CD31 staining and VEGF immunohistochemistry staining. 99mTc-MAG3-bevacizumab imaging allowed for the non-invasive diagnosis and assessment of plaque neovascularization. Furthermore, this probe may be used as a new molecular imaging agent to assess the antiangiogenic effect of atorvastatin.