bluuebunny/crossref_metadata_2025_split huggingface dataset:
USF1 defect drives p53 degradation duringHelicobacter pyloriinfection and accelerates gastric carcinogenesis
Authors: Costa Lionel , Corre Sébastien , Michel Valérie , Le Luel Krysten , Fernandes Julien , Ziveri Jason , Jouvion Gregory , Danckaert Anne , Mouchet Nicolas , Da Silva Barreira David , Torres Javier , Camorlinga Margarita , D'Elios Mario Milco , Fiette Laurence , De Reuse Hilde , Galibert Marie-Dominique , Touati Eliette 
Published: December 2019

ObjectiveHelicobacter pylori(Hp) is a major risk factor for gastric cancer (GC).Hppromotes DNA damage and proteasomal degradation of p53, the guardian of genome stability.Hpreduces the expression of the transcription factor USF1 shown to stabilise p53 in response to genotoxic stress. We investigated whetherHp-mediated USF1 deregulation impacts p53-response and consequently genetic instability. We also explored in vivo the role of USF1 in gastric carcinogenesis.DesignHuman gastric epithelial cell lines were infected withHp7.13, exposed or not to a DNA-damaging agent camptothecin (CPT), to mimic a genetic instability context. We quantified the expression ofUSF1,p53and their target genes, we determined their subcellular localisation by immunofluorescence and examined USF1/p53 interaction.Usf1-/-and INS-GAS mice were used to strengthen the findings in vivo and patient data examined for clinical relevance.ResultsIn vivo we revealed the dominant role of USF1 in protecting gastric cells againstHp-induced carcinogenesis and its impact on p53 levels. In vitro,Hpdelocalises USF1 into foci close to cell membranes.Hpprevents USF1/p53 nuclear built up and relocates these complexes in the cytoplasm, thereby impairing their transcriptional function.Hpalso inhibits CPT-induced USF1/p53 nuclear complexes, exacerbating CPT-dependent DNA damaging effects.ConclusionOur data reveal that the depletion of USF1 and its de-localisation in the vicinity of cell membranes are essential events associated to the genotoxic activity ofHpinfection, thus promoting gastric carcinogenesis. These findings are also of clinical relevance, supporting USF1 expression as a potential marker of GC susceptibility.
Long-term prognosis of ulcerative colitis and its temporal changes between 1986 and 2015 in a population-based cohort in the Songpa-Kangdong district of Seoul, Korea
Authors: Cha Jae Myung , Park Sang Hyoung , Rhee Kyoung Hoon , Hong Sung Noh , Kim Young-Ho , Seo Seung In , Kim Kyung Ho , Jeong Seung Kyu , Lee Ji Hyun , Park Sun Yong , Park Hyunju , Kim Joo Sung , Im Jong Pil , Yoon Hyuk , Kim Sung Hoon , Jang Jisun , Kim Jeong Hwan , Suh Seong O , Kim Young Kyun , Ye Byong Duk , Yang Suk-Kyun 
Published: December 2019

ObjectiveNo population-based study has evaluated the natural course of UC over three decades in non-Caucasians. We aimed to assess the long-term natural course of Korean patients with UC in a population-based cohort.DesignThis Korean population-based, Songpa-Kangdong IBD cohort included all patients (n=1013) newly diagnosed with UC during 1986–2015. Disease outcomes and their predictors were evaluated.ResultsDuring the median follow-up of 105 months, the overall use of systemic corticosteroids, thiopurines and antitumour necrosis factor (anti-TNF) agents was 40.8%, 13.9% and 6.5%, respectively. Over time, the cumulative risk of commencing corticosteroids decreased, whereas that of commencing thiopurines and anti-TNF agents increased. During follow-up, 28.7% of 778 patients with proctitis or left-sided colitis at diagnosis experienced proximal disease extension. A total of 28 patients (2.8%) underwent colectomy, demonstrating cumulative risks of colectomy at 1, 5, 10, 20 and 30 years after diagnosis of 1.0%, 1.9%, 2.2%, 5.1% and 6.4%, respectively. Multivariate Cox regression analysis revealed that extensive colitis at diagnosis (HR 8.249, 95% CI 2.394 to 28.430), ever use of corticosteroids (HR 6.437, 95% CI 1.440 to 28.773) and diagnosis in the anti-TNF era (HR 0.224, 95% CI 0.057 to 0.886) were independent predictors of colectomy. The standardised mortality ratio in patients with UC was 0.725 (95% CI 0.508 to 1.004).ConclusionKorean patients with UC may have a better clinical course than Western patients, as indicated by a lower colectomy rate. The overall colectomy rate has continued to decrease over the past three decades.
Valve regurgitation in patients surviving endocarditis and the subsequent risk of heart failure
Authors: Østergaard Lauge , Dahl Anders , Bruun Niels Eske , Oestergaard Louise Bruun , Lauridsen Trine Kiilerich , Torp-Pedersen Christian , Mortensen Rikke , Smerup Morten , Valeur Nana , Koeber Lars , Hassager Christian , Ihlemann Nikolaj , Fosbøl Emil Loldrup 
Published: December 2019

BackgroundSignificant valve regurgitation is common in patients surviving native valve infective endocarditis (IE), however the associated risk of heart failure (HF) subsequent to hospital discharge after IE is sparsely described.MethodsWe linked data from the East Danish Endocarditis Registry with administrative registries from 2002 to 2016 and included patients treated medically for IE who were discharged alive. Left-sided valve regurgitation was assessed by echocardiography at IE discharge and examined for longitudinal risk of HF. Multivariable adjusted Cox analysis was used to assess the associated risk of HF in patients with regurgitation (moderate or severe) compared with patients without regurgitation.ResultsWe included 192 patients, 87 patients with regurgitation at discharge (30 with aortic regurgitation and 57 with mitral regurgitation) and 105 patients without. The cumulative risk of HF at 5 years of follow-up was 28.7% in patients with regurgitation at IE discharge and 12.4% in patients without regurgitation; the corresponding multivariable adjusted HR was 3.53 (95% CI 1.72 to 7.25). We identified an increased associated risk of HF for patients with aortic regurgitation (HR=2.91, 95% CI 1.14 to 7.43) and mitral regurgitation (HR=3.95, 95% CI 1.80 to 8.67) compared with patients without regurgitation. During follow-up, 21.9% and 5.7% underwent left-sided valve surgery among patients with and without regurgitation.ConclusionIn patients surviving IE, treated medically, we observed that severe or moderate left-sided native valve regurgitation was associated with a significantly higher risk of HF compared with patients without regurgitation at IE discharge. Close monitoring of these patients is needed to initiate surgery timely.
Multicentre study on the consistency of PD-L1 immunohistochemistry as predictive test for immunotherapy in non-small cell lung cancer
Authors: Butter Rogier , 't Hart Nils A , Hooijer Gerrit K J , Monkhorst Kim , Speel Ernst-Jan , Theunissen Paul , Thunnissen Erik , Von der Thüsen Jan H , Timens Wim , van de Vijver Marc J 
Published: December 2019

AimsInvestigate the impact of interlaboratory- and interobserver variability of immunohistochemistry on the assessment of programmed death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC).MethodsTwo tissue microarrays (TMAs) were constructed from 50 (TMA-A) and 51 (TMA-B) resected NSCLC cases, and distributed among eight centres. Immunostaining for PD-L1 was performed using Agilent’s 22C3 pharmDx Assay (pharmDx) and/or a 22C3 laboratory developed test (LDT). The interlaboratory variability of staining- and interobserver variability of scoring for PD-L1 were assessed in selected critical samples (samples at the cut-off of positivity) and non-critical samples. Also, PD-L1 epitope deterioration in time in stored unstained slides was analysed. Krippendorff’s alpha values (0=maximal, 1=no variability) were calculated as measure for variability.ResultsFor interlaboratory variability of immunostaining, the percentage of PD-L1 positive cases among centres ranged 40%–51% (1% cut-off) and 23%–30% (50% cut-off). Alpha values at 1% cut-off were 0.88 (pharmDx) and 0.87 (LDT) and at 50% cut-off 0.82 (pharmDx) and 0.95 (LDT). Interobserver variability of scoring resulted in PD-L1 positive cases ranging 29%–55% (1% cut-off) and 14%–30% (50% cut-off) among pathologists. Alpha values were at 1% cut-off 0.83 (TMA-A) and 0.66 (TMA-B), and at 50% cut-off 0.77 (TMA-A) and 0.78 (TMA-B). Interlaboratory variability of staining was higher (p<0.001) in critical samples than in non-critical samples at 50% cut-off. Furthermore, PD-L1 epitope deterioration in unstained slides was observed after 12 weeks.ConclusionsThe results provide insight in factors contributing to variability of immunohistochemical assessment of PD-L1, and contribute to more reliable predictive testing for PD-L1.
GLUT1-dependent glycolysis regulates exacerbation of fibrosis via AIM2 inflammasome activation
Authors: Cho Soo Jung , Moon Jong-Seok , Nikahira Kiichi , Yun Ha Seon , Harris Rebecca , Hong Kyung Sook , Huang Huarong , Choi Augustine M K , Stout-Delgado Heather 
Published: December 2019

BackgroundIdiopathic pulmonary fibrosis (IPF) is a rapidly progressive, fatal lung disease that affects older adults. One of the detrimental natural histories of IPF is acute exacerbation of IPF (AE-IPF), of which bacterial infection is reported to play an important role. However, the mechanism by which bacterial infection modulates the fibrotic response remains unclear.ObjectivesAltered glucose metabolism has been implicated in the pathogenesis of fibrotic lung diseases. We have previously demonstrated that glucose transporter 1 (GLUT1)-dependent glycolysis regulates fibrogenesis in a murine fibrosis model. To expand on these findings, we hypothesised that GLUT1-dependent glycolysis regulates acute exacerbation of lung fibrogenesis during bacterial infection via AIM2 inflammasome activation.ResultsIn our current study, using a murine model ofStreptococcus pneumoniae(S. pneumoniae) infection, we investigated the potential role of GLUT1 on mediating fibrotic responses to an acute exacerbation during bleomycin-induced fibrosis. The results of our current study illustrate that GLUT1 deficiency amelioratesS. pneumoniae-mediated exacerbation of lung fibrosis (wild type (WT)/phosphate buffered saline (PBS), n=3; WT/S. pneumoniae, n=3; WT/Bleomycin, n=5 ; WT/Bleomycin+S. pneumoniae, n=7;LysM-Cre-Glut1fl/f/PBS, n=3;LysM-Cre-Glut1fl/fl/S. pneumoniae, n=3;LysM-Cre-Glut1fl/fl/Bleomycin, n=6;LysM-Cre-Glut1fl/fl/Bleomycin+S. pneumoniae, n=9, p=0.041). Further, the AIM2 inflammasome, a multiprotein complex essential for sensing cytosolic bacterial DNA as a danger signal, is an important regulator of this GLUT1-mediated fibrosis and genetic deficiency of AIM2 reduced bleomycin-induced fibrosis afterS. pneumoniaeinfection (WT/PBS, n=6; WT/Bleomycin+S. pneumoniae, n=15; Aim2−/−/PBS, n=6, Aim2−/−/Bleomycin+S. pneumoniae, n=11, p=0.034). GLUT1 deficiency reduced expression and function of the AIM2 inflammasome, and AIM2-deficient mice showed substantial reduction of lung fibrosis afterS. pneumoniaeinfection.ConclusionOur results demonstrate that GLUT1-dependent glycolysis promotes exacerbation of lung fibrogenesis duringS. pneumoniaeinfection via AIM2 inflammasome activation.
Modeling Uncertainty in the Wings Method Using Interval Arithmetic
Authors: Michnik Jerzy , Grabowski Artur 
Published: December 2019

This paper introduces a novel approach to support decision-making by combining the Weighted Influence Nonlinear Gauge System (WINGS) method with interval arithmetic. This approach allows to include uncertain judgments and/or different opinions in a decision process. Our research aims at increasing the ability of WINGS to model decisions in situations of uncertainty and at extending the reach of its practical applications. The new, relatively simple and transparent method can become a useful and practical tool for the decision makers. Mathematical correctness of the proposed methodology is proven. Based on the new method, a procedure for solving a complex decision problem is created. Its applicability is illustrated by two case studies. Choosing the best option for the organization’s competitive position in a health-care organization shows how the proposed method works with uncertain judgments. Its usefulness for group decision-making is illustrated by applying it to a decision concerning allocation of public funds for sport development in a small commune.
Random Graph Modeling
Authors: Drobyshevskiy Mikhail , Turdakov Denis 
Published: December 2019

Random graph (RG) models play a central role in complex networks analysis. They help us to understand, control, and predict phenomena occurring, for instance, in social networks, biological networks, the Internet, and so on.Despite a large number of RG models presented in the literature, there are few concepts underlying them. Instead of trying to classify a wide variety of very dispersed models, we capture and describe concepts they exploit considering preferential attachment, copying principle, hyperbolic geometry, recursively defined structure, edge switching, Monte Carlo sampling, and so on. We analyze RG models, extract their basic principles, and build a taxonomy of concepts they are based on. We also discuss how these concepts are combined in RG models and how they work in typical applications like benchmarks, null models, and data anonymization.
ARRB1-Promoted NOTCH1 Degradation Is Suppressed by OncomiR miR-223 in T-cell Acute Lymphoblastic Leukemia
Authors: Shu Yi , Wang Yi , Lv Wen-Qiong , Peng Dan-Yi , Li Juan , Zhang Hang , Jiang Guang-Jie , Yang Bi-Jie , Liu Shan , Zhang Jia , Chen Yan-Hua , Tang Shi , Wan Ke-Xing , Yuan Jun-Tao , Guo Wei , Fu Guo , Qi Xin-Kun , Liu Zhi-Dai , Liu Hai-Yan , Yang Chao , Zhang Ling-Huan , Liu Fang-Jie , Yu Jie , Zhang Peng-Hui , Qu Bin , Zhao Hui , He Tong-Chuan , Zou Lin 
Published: December 2019

Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is a type of aggressive leukemia with inferior prognosis. Although activating mutations of NOTCH1 are observed in most T-ALL cases, these mutations alone are not sufficient to drive the full development of T-ALL. β-Arrestins (ARRB) are versatile and multifunctional adapter proteins that regulate diverse cellular functions, including promoting the development of cancer. However, the role of ARRBs in T-ALL has largely remained elusive. In this study, we showed that ARRB1 is expressed at low levels in assayed T-ALL clinical samples and cell lines. Exogenous ARRB1 expression inhibited T-ALL proliferation and improved the survival of T-ALL xenograft animals. ARRB1 facilitated NOTCH1 ubiquitination and degradation through interactions with NOTCH1 and DTX1. Mechanistically, the oncogenic miRNA (oncomiR) miR-223 targets the 3′-UTR of ARRB1 (BUTR) and inhibits its expression in T-ALL. Furthermore, overexpression of the ARRB1-derived miR-223 sponge suppressed T-ALL cell proliferation and induced apoptosis. Collectively, these results demonstrate that ARRB1 acts as a tumor suppressor in T-ALL by promoting NOTCH1 degradation, which is inhibited by elevated miR-223, suggesting that ARRB1 may serve as a valid drug target in the development of novel T-ALL therapeutics.
Significance: These findings highlight a novel tumor suppressive function of the adaptor protein β-arrestin1 in T-ALL.
DC-HIL/Gpnmb Is a Negative Regulator of Tumor Response to Immune Checkpoint Inhibitors
Authors: Chung Jin-Sung , Ramani Vijay , Kobayashi Masato , Fattah Farjana , Popat Vinita , Zhang Song , Cruz Ponciano D. , Gerber David E. , Ariizumi Kiyoshi 
Published: December 2019

Abstract

Purpose:
Immune checkpoint inhibitors (ICI) benefit only a minority of treated patients with cancer. Identification of biomarkers distinguishing responders and nonresponders will improve management of patients with cancer. Because the DC-HIL checkpoint differs from the PD1 pathway in expression and inhibitory mechanisms, we examined whether DC-HIL expression regulates ICI responsiveness.

Experimental Design:
Plasma samples were collected from patients with advanced non–small cell lung carcinoma (NSCLC) (n = 76) at baseline and/or follow-up after ICI monotherapy. Blood-soluble DC-HIL (sDC-HIL) was determined and analyzed for correlation with the early tumor response. To study the mechanisms, we measured effect of anti-DC-HIL versus anti-PDL1 mAb on growth of mouse tumor cells in experimentally metastatic lung. Influence of DC-HIL to anti-PDL1 treatment was assessed by changes in tumor response after deletion of host-DC-HIL gene, injection of DC-HIL–expressing myeloid-derived suppressor cells (MDSC), or induction of sDC-HIL expression.

Results:
Nonresponders expressed significantly higher levels of baseline sDC-HIL levels than responders. Among patients (n = 28) for fluctuation with time, nonresponders (14/15 cases) showed increasing or persistently elevated levels. Responders (12/13) had decreasing or persistently low levels. Among various tumors, B16 melanoma exhibited resistance to anti-PDL1 but responded to anti-DC-HIL mAb. Using B16 melanoma and LL2 lung cancer, we showed that deletion of host-derived DC-HIL expression converted the resistant tumor to one responsive to anti-PDL1 mAb. The responsive state was reversed by infusion of DC-HIL+MDSC or induction of sDC-HIL expression.

Conclusions:
sDC-HIL in the blood and probably DC-HIL receptor expressed by MDSC play an important role in regulating response to ICI in advanced NSCLC.
Effect of Recanalization on Cerebral Edema in Ischemic Stroke Treated With Thrombolysis and/or Endovascular Therapy
Authors: Thorén Magnus , Dixit Anand , Escudero-Martínez Irene , Gdovinová Zuzana , Klecka Lukas , Rand Viiu-Marika , Toni Danilo , Vilionskis Aleksandras , Wahlgren Nils , Ahmed Niaz 
Published: December 2019

Background and Purpose—
A large infarct and expanding cerebral edema (CED) due to a middle cerebral artery occlusion confers a 70% mortality unless treated surgically. Reperfusion may cause blood-brain barrier disruption and a risk for cerebral edema and secondary parenchymal hemorrhage (PH). We aimed to investigate the effect of recanalization on development of early CED and PH after recanalization therapy.

Methods—
From the SITS-International Stroke Treatment Registry, we selected patients with signs of artery occlusion at baseline (either Hyperdense Artery Sign or computed tomography/magnetic resonance imaging angiographic occlusion). We defined recanalization as the disappearance of radiological signs of occlusion at 22 to 36 hours. Primary outcome was moderate to severe CED and secondary outcome was PH on 22- to 36-hour imaging scans. We used logistic regression with adjustment for baseline variables and PH.

Results—
Twenty two thousand one hundred eighty-four patients fulfilled the inclusion criteria (n=18 318 received intravenous thrombolysis, n=3071 received intravenous thrombolysis+thrombectomy, n=795 received thrombectomy). Recanalization occurred in 64.1%. Median age was 71 versus 71 years and National Institutes of Health Stroke Scale score 15 versus 16 in the recanalized versus nonrecanalized patients respectively. Recanalized patients had a lower risk for CED (13.0% versus 23.6%), adjusted odds ratio (aOR), 0.52 (95% CI, 0.46–0.59), and a higher risk for PH (8.9% versus 6.5%), adjusted odds ratio, 1.37 (95% CI, 1.22–1.55), than nonrecanalized patients.

Conclusions—
In patients with acute ischemic stroke, recanalization was associated with a lower risk for early CED even after adjustment for higher rate for PH in recanalized patients.
Genetic diversity and structure of Euphausia superba in the South Shetland Islands using the mitochondrial ND6 gene
Authors: Dong Yao , Qi Guangrui , Feng Chunlei , Wang Wei , Zhang Fengying , Zhao Ming , Wang Lumin , Ma Lingbo , Ma Chunyan 
Published: December 2019

Abstract
Euphausia superba is an abundant element in the marine plankton on the planet. Despite substantial research on this species, there is no comprehensive understanding of the population genetics of E. superba yet. In this study, the ND6 gene was used to assess the genetic variation in E. superba. In the South Shetland Islands, the population of E. superba shows abundant genetic variation, but we found a lack of genetic structure. An analysis of the demographic history suggested that a sudden expansion has been responsible for its high biomass. Our study could not only broaden our comprehension of E. superba, but also provide more scientific information on fisheries resources exploitation, biodiversity conservation and the maintenance of a proper ecological balance.
Transcriptomic analysis of genes involved in reproduction at different ages in Daphnia pulex (Branchiopoda, Cladocera)
Authors: Guo Chun-Yang , Cao Xiao , Lin Chong-Yuan , Liu Meng-Di , Xu Shan-Liang , Wang Dan-Li , Zhao Yun-Long 
Published: December 2019

Abstract
Daphnia pulex is a freshwater microcrustacean that is known for its cyclical parthenogenesis. In D. pulex, parthenogenetic reproduction switches to sexual reproduction when the living conditions worsen. However, this transformation also occurs over age under favourable living conditions. Thus, there might be a relationship between aging and reproductive conversion. We performed Illumina RNA sequencing, generating 51 712 680 and 59 854 588 raw reads from 1 day-old D. pulex and 25 day-old D. pulex, respectively. From these reads, 60 776 transcripts were assembled and 36 569 (60.15%) unigenes were annotated. A number of significantly differentially expressed genes associated with growth, aging, and reproduction were identified and Quantitative real-time PCR for six genes confirmed the transcriptome data. RNA interference (RNAi) of the caspase-3 gene (casp3) that is a key gene for growth, development, aging, and reproduction, was conducted, which achieved an 80% reduction in casp3 mRNA expression. Meanwhile, the mRNA expression of upstream genes jnk and akt, and sir2 (encoding a substrate of casp3) were also detected. The change of jnk mRNA expression before and after RNAi was not significant () and the mRNA levels of sir2 decreased, while akt increased after casp3 RNAi (). The results indicated the interrelationships of some genes in the senescence pathway and helped to identify the molecular mechanism of the aging progress in D. pulex. Overall, the difference in mRNA expression profile during aging of D. pulex forms a basis for further studies aimed at understanding the role of the transcriptional level in regulating aging and reproductive transformation.
The Monstrosity of God Made Flesh
Authors: Jobe Sarah C. 
Published: December 2019

Abstract
Three times over the course of thirty-eight years, Karl Barth images God as the monster Leviathan (once each in the Epistle to the Romans, Church Dogmatics II.1 and& IV.3.1). Barth’s imagination for God in monstrous form emerges from his interpretation of Romans 11:35, in which the apostle Paul quotes a line from Job 41:11, a poem about Leviathan, to describe the greatness of God. Using monster theory and a close reading of Barth, this article will discuss how God as Leviathan answers one of Barth’s primary questions—namely, how it is that Jesus saves human beings from their headlong rush into the abyss. Moving from Barth’s exegetical insights, through Barth’s soteriology, the article ends with the ethics of a God made monstrous flesh—an ethics that Barth explicitly links to the status of prisoners and all those depicted as monstrous and cast into the abyss.