bluuebunny/crossref_metadata_2025_split huggingface dataset:
A decision-support framework to optimize border control for global outbreak mitigation
Authors: Zlojutro Aleksa , Rey David , Gardner Lauren 
Published: February 2019

AbstractThe introduction and spread of emerging infectious diseases is increasing in both prevalence and scale. Whether naturally, accidentally or maliciously introduced, the substantial uncertainty surrounding the emergence of novel viruses, specifically where they may come from and how they will spread, demands robust and quantifiably validated outbreak control policies that can be implemented in real time. This work presents a novel mathematical modeling framework that integrates both outbreak dynamics and outbreak control into a decision support tool for mitigating infectious disease pandemics that spread through passenger air travel. An ensemble of border control strategies that exploit properties of the air traffic network structure and expected outbreak behavior are proposed. A stochastic metapopulation epidemic model is developed to evaluate and rank the control strategies based on their effectiveness in reducing the spread of outbreaks. Sensitivity analyses are conducted to illustrate the robustness of the proposed control strategies across a range of outbreak scenarios, and a case study is presented for the 2009 H1N1 influenza pandemic. This study highlights the importance of strategically allocating outbreak control resources, and the results can be used to identify the most robust border control policy that can be implemented in the early stages of an outbreak.
On-chip combined radiotherapy and chemotherapy testing on soft-tissue sarcoma spheroids to study cell death using flow cytometry and clonogenic assay
Authors: Patra Bishnubrata , Lafontaine Julie , Bavoux Maeva , Zerouali Karim , Glory Audrey , Ahanj Mohsen , Carrier Jean-François , Gervais Thomas , Wong Philip 
Published: February 2019

AbstractRadiotherapy (RT) and chemotherapy (CT) are the major therapeutics to treat cancer patients. Conventional in vitro 2D models are insufficient to study the combined effects of RT and CT towards optimized dose selection or drug screening. Soft-tissue sarcomas (STS) are rare cancers with profound social impacts as they affect patients of all ages. We developed a microfluidic device to form and culture STS spheroids to study the combined cytotoxicities of RT and CT. Uniformly-sized spheroids of two different cell lines, STS 93 and STS 117, were formed in the device. RT doses of 0.5 Gy, 2 Gy, and 8 Gy were used in combination with CT, doxorubicin at 2 µM and 20 µM. The spheroids culture chambers within the device were arranged in a 3 × 5 matrix form. The device was made “peelable”, which enabled us to collect spheroids from each treatment condition separately. Collected spheroids were dissociated into single cells and evaluated using flow cytometry and clonogenic assays. Through this workflow, we observed that STS 93 spheroids treated with doxorubicin die through apoptosis, whereas RT induced death through other pathways. Spheroids from the p53 mutant STS 117 cell line were more resistant to RT and doxorubicin. The developed device could be used for the discovery of new drugs and RT synergies.
Identification of FDA-approved drugs targeting the Farnesoid X Receptor
Authors: van de Wiel Sandra M. W. , Bijsmans Ingrid T. G. W. , van Mil Saskia W. C. , van de Graaf Stan F. J. 
Published: February 2019

AbstractThe farnesoid X receptor (FXR) belongs to the nuclear receptor family and is activated by bile acids. Multiple, chemically rather diverse, FXR agonists have been developed and several of these compounds are currently tested in clinical trials for NAFLD and cholestasis. Here, we investigated possible FXR-agonism or antagonism of existing FDA/EMA-approved drugs. By using our recently developed FRET-sensor, containing the ligand binding domain of FXR (FXR-LBD), 1280 FDA-approved drugs were screened for their ability to activate FXR in living cells using flow cytometry. Fifteen compounds induced the sensor for more than twenty percent above background. Real-time confocal microscopy confirmed that avermectin B1a, gliquidone, nicardipine, bepridil and triclosan activated the FRET sensor within two minutes. These compounds, including fluticasone, increased mRNA expression of FXR target genesOSTαandOSTβin Huh7 cells, and in most cases also ofMRP2,SHPandFGF19. Finally, avermectin B1a, gliquidone, nicardipine and bepridil significantly increased IBABP promoter activity in a luciferase reporter assay in a dose-dependent manner. In conclusion, six FDA/EMA-approved drugs currently used in the clinical practice exhibit moderate agonistic FXR activity. This may on the one hand explain (undesired) side-effects, but on the other hand may form an opportunity for polypharmacology.
Quantitative Analysis of CT Images in Patients with Pyrrolizidine Alkaloid-Induced Sinusoidal Obstruction Syndrome
Authors: Wang Chao , Wu Xingwang , Xie Wentao , Ren Xiaofei , Zhang Weiping , Xu Jianming 
Published: February 2019

AbstractThis study evaluated hepatic lesion volumes on contrast-enhanced computed tomography (CT) images in patients with pyrrolizidine alkaloid-induced sinusoidal obstruction syndrome (PA-SOS) and the association of lesion volume with the clinical severity and prognosis of the disease. Twenty-five patients with PA-SOS were included in this study, and all patients were subjected to a complete CT imaging series. The imaging results were quantitatively analyzed by a threshold-based region growing algorithm. The liver volumes and hepatic lesion volumes of the patients were estimated. Based on clinical presentations, PA-SOS was classified into three categories: mild, moderate and severe. The associations of hepatic lesion volumes with liver function test parameters and the clinical severity and prognosis of the disease were analyzed. Based on estimations using the threshold-based region growing algorithm, hepatic lesion volumes in patients with mild PA-SOS were significantly lower than those in patients with moderate and severe PA-SOS (P < 0.05). The ratio of hepatic lesion volume to liver volume (Ratio) varied based on alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum total bilirubine levels; clinical severity; and disease prognosis, and the differences were statistically significant (P < 0.05). In conclusion, the threshold-based region growing algorithm can be employed to quantitatively analyze enhanced CT images of PA-SOS patients. And the ratio of hepatic lesion volume to liver volume in patients with PA-SOS is associated with a more serious clinical course and a poorer outcome.
Prevalence and serological profile of anti-DFS70 positive subjects from a routine ANA cohort
Authors: Carbone Teresa , Pafundi Vito , Tramontano Giuseppina , Gilio Michele , Padula Maria Carmela , Padula Angela Anna , D’Angelo Salvatore 
Published: February 2019

AbstractAnti-Dense Fine Speckled 70 (DFS70) antibodies are a common finding in clinical laboratory referrals. High prevalence of DFS70 autoantibodies in healthy population and usual negative association with Antinuclear Antibody (ANA)-associated autoimmune rheumatic diseases (AARD) were reported. The aim of this study was to evaluate the prevalence of DFS70 autoantibodies and their association with other autoantibodies in the context of a routine ANA referral cohort. Consecutive sera submitted for ANA screening were analyzed for anti-DFS70 antibodies by indirect immunofluorescence (IIF) (n = 3175, 1030 men and 2145 women) then confirmed by immunoblotting. Anti-DFS70 positive samples were also assayed for a large spectrum of other circulating autoantibodies. The prevalence of anti-DFS70 antibodies was 1.7% in the whole population and 4.6% in the ANA-positive samples. Comparison between DFS70 IIF and immunoblotting showed an excellent correlation between the two methods. The prevalence of anti-DFS70 positive was significantly higher in females (2.1%, 45/2145) than in males (1.0%, 10/1030). Of note, no concomitant autoantibodies were found in the DFS70-positive male group compared with DFS70-positive females group that showed other serum autoantibodies in the 51% of cases. Anti-DFS70 reactivity in male population may represent an useful biomarker predicting the absence of other autoantibodies. On the contrary, the serological profile of DFS70-positive females required further investigations in order to define the presence of concomitant disease-marker autoantibodies.
Urinary proteome signature of Renal Cysts and Diabetes syndrome in children
Authors: Ricci Pierbruno , Magalhães Pedro , Krochmal Magdalena , Pejchinovski Martin , Daina Erica , Caruso Maria Rosa , Goea Laura , Belczacka Iwona , Remuzzi Giuseppe , Umbhauer Muriel , Drube Jens , Pape Lars , Mischak Harald , Decramer Stéphane , Schaefer Franz , Schanstra Joost P. , Cereghini Silvia , Zürbig Petra 
Published: February 2019

AbstractRenal Cysts and Diabetes Syndrome (RCAD) is an autosomal dominant disorder caused by mutations in the HNF1B gene encoding for the transcriptional factor hepatocyte nuclear factor-1B. RCAD is characterized as a multi-organ disease, with a broad spectrum of symptoms including kidney abnormalities (renal cysts, renal hypodysplasia, single kidney, horseshoe kidneys, hydronephrosis), early-onset diabetes mellitus, abnormal liver function, pancreatic hypoplasia and genital tract malformations. In the present study, using capillary electrophoresis coupled to mass spectrometry (CE-MS), we investigated the urinary proteome of a pediatric cohort of RCAD patients and different controls to identify peptide biomarkers and obtain further insights into the pathophysiology of this disorder. As a result, 146 peptides were found to be associated with RCAD in 22 pediatric patients when compared to 22 healthy age-matched controls. A classifier based on these peptides was generated and further tested on an independent cohort, clearly discriminating RCAD patients from different groups of controls. This study demonstrates that the urinary proteome of pediatric RCAD patients differs from autosomal dominant polycystic kidney disease (PKD1, PKD2), congenital nephrotic syndrome (NPHS1, NPHS2, NPHS4, NPHS9) as well as from chronic kidney disease conditions, suggesting differences between the pathophysiology behind these disorders.
Recombination analysis of Human mastadenovirus C whole genomes
Authors: Rivailler Pierre , Mao Naiying , Zhu Zhen , Xu Wenbo 
Published: February 2019

AbstractThis study aims at analyzing all publicly available HAdV-C whole genome sequences (WGSs) and describes the genetic relationships between these genomes as well as identifies potential hotspots for recombination throughout the viral genome. In addition to the 4 prototypical genomic sequences, this analysis identified 20 HAdV-C WGSs which should be relevant for future recombination analysis of HAdV-C. This report confirmed the recombinogenic property of HAdV-C genomes and identified two main regions for breakpoints, within the hexon gene and around the fiber genomic region. No obvious recombination was detected between HAdV-Cs and non-human mastadenoviruses or non-C HAdVs. Finally, it highlighted the need for a surveillance of HAdVs in order to detect novel recombinant types that might represent health risks and develop possible prevention measures. Genetic analyses of recombination between recently collected HAdV-Cs and the assessment of their potential virulence are necessary steps towards the establishment of a surveillance of HAdVs in the future.
Environmental Toxicant Induced Epigenetic Transgenerational Inheritance of Prostate Pathology and Stromal-Epithelial Cell Epigenome and Transcriptome Alterations: Ancestral Origins of Prostate Disease
Authors: Klukovich Rachel , Nilsson Eric , Sadler-Riggleman Ingrid , Beck Daniel , Xie Yeming , Yan Wei , Skinner Michael K. 
Published: February 2019

AbstractProstate diseases include prostate cancer, which is the second most common male neoplasia, and benign prostatic hyperplasia (BPH), which affects approximately 50% of men. The incidence of prostate disease is increasing, and some of this increase may be attributable to ancestral exposure to environmental toxicants and epigenetic transgenerational inheritance mechanisms. The goal of the current study was to determine the effects that exposure of gestating female rats to vinclozolin has on the epigenetic transgenerational inheritance of prostate disease, and to characterize by what molecular epigenetic mechanisms this has occurred. Gestating female rats (F0 generation) were exposed to vinclozolin during E8-E14 of gestation. F1 generation offspring were bred to produce the F2 generation, which were bred to produce the transgenerational F3 generation. The transgenerational F3 generation vinclozolin lineage males at 12 months of age had an increased incidence of prostate histopathology and abnormalities compared to the control lineage. Ventral prostate epithelial and stromal cells were isolated from F3 generation 20-day old rats, prior to the onset of pathology, and used to obtain DNA and RNA for analysis. Results indicate that there were transgenerational changes in gene expression, noncoding RNA expression, and DNA methylation in both cell types. Our results suggest that ancestral exposure to vinclozolin at a critical period of gestation induces the epigenetic transgenerational inheritance of prostate stromal and epithelial cell changes in both the epigenome and transcriptome that ultimately lead to prostate disease susceptibility and may serve as a source of the increased incidence of prostate pathology observed in recent years.
Printed Microwave Metamaterial-Antenna Circuitries on Nickel Oxide Polymerized Palm Fiber Substrates
Authors: Elwi Taha A. 
Published: February 2019

AbstractIn this paper, the novelty of exploring the applications of the Iraqi Palm Tree Remnants (IPTR) mixed with Nickel Oxide Nanoparticles (NONP) hosted in Polyethylene (PE), called INP substrates, is utilized by printing metamaterial (MTM) based high gain microwave antennas on them. The proposed INP substrates are mainly created from pressed flexible organic fibers to suite the ink jet printing technologies. The complex relative constitutive parameters are characterized in terms of permittivity (ε) and permeability (μ) within the frequency range from 2 GHz up to 6 GHz using an open end dielectric probe and a T-stub transmission line technique. To validate the feasibility of the INP substrates, a very fine antenna structure of based a miniaturized Hilbert MTM based dipoles is printed on. A material printer with Sliver Nanoparticles Conductive Ink (SNPCI) is used to print the antenna structure. Commercial software packages, CST Microwave Studio (MWS) and Ansys High Frequency Structure Simulator (HFSS), are used to simulate the proposed antenna based on the measured constitutive parameters. A negligible difference is found between the measured and simulated results. Finally, an attractive effect on the retrieved constitutive parameters of the proposed MTM is found due to the proposed INP substrate.
Comparative antitumor studies of organoruthenium complexes with 8-hydroxyquinolines on 2D and 3D cell models of bone, lung and breast cancer
Authors: Ruiz Maria C , Kljun Jakob , Turel Iztok , Di Virgilio Ana L , León Ignacio E 
Published: February 2019

Abstract
The purpose of this work was to screen the antitumor actions of two metal organoruthenium-8-hydroxyquinolinato (Ru-hq) complexes to find a potential novel agent for bone, lung and breast chemotherapies. We showed that ruthenium compounds (1 and 2) impaired the cell viability of human bone (MG-63), lung (A549) and breast (MCF7) cancer cells with greater selectivity and specificity than cisplatin. Besides, complexes 1 and 2 decreased proliferation, migration and invasion on cell monolayers at lower concentrations (2.5–10 μM). In addition, both compounds induced genotoxicity revealed by the micronucleus test, which led to G2/M cell cycle arrest and induced the tumor cells to undergo apoptosis. On the other hand, in multicellular 3D models (multicellular spheroids; MCS), 1 and 2 overcame CDDP presenting lower IC50 values only in MCS of lung origin. Moreover, 1 outperformed 2 in MCS of bone and breast origin. Finally, our findings revealed that both compounds inhibited the cell invasion of multicellular spheroids, showing that complex 1 exhibited the most important antimetastatic action. Taken together, these results indicate that compound 1 is an interesting candidate to be tested on in vivo models as a novel strategy for anticancer therapy.
Ancient and primordial collisional families as the main sources of X-type asteroids of the inner main belt
Authors: Delbo Marco , Avdellidou Chrysa , Morbidelli Alessandro 
Published: February 2019

Aims. The near-Earth asteroid population suggests the existence of an inner main belt source of asteroids that belongs to the spectroscopic X complex and has moderate albedos. The identification of such a source has been lacking so far. We argue that the most probable source is one or more collisional asteroid families that have escaped discovery up to now.
Methods. We apply a novel method to search for asteroid families in the inner main-belt population of asteroids belonging to the X complex with moderate albedo. Instead of searching for asteroid clusters in orbital element space, which could be severely dispersed when older than some billions of years, our method looks for correlations between the orbital semimajor axis and the inverse size of asteroids. This correlation is the signature of members of collisional families that have drifted from a common centre under the effect of the Yarkovsky thermal effect.
Results. We identify two previously unknown families in the inner main belt among the moderate-albedo X-complex asteroids. One of them, whose lowest numbered asteroid is (161) Athor, is ~3 Gyr old, whereas the second one, whose lowest numbered object is (689) Zita, could be as old as the solar system. Members of this latter family have orbital eccentricities and inclinations that spread them over the entire inner main belt, which is an indication that this family could be primordial, that is, it formed before the giant planet orbital instability.
Conclusions. The vast majority of moderate-albedo X-complex asteroids of the inner main belt are genetically related, as they can be included into a few asteroid families. Only nine X-complex asteroids with moderate albedo of the inner main belt cannot be included in asteroid families. We suggest that these bodies formed by direct accretion of the solids in the protoplanetary disc, and are thus surviving planetesimals.
VEGF-C et vaisseaux lymphatiques
Authors: Ndiaye Papa Diogop , Pagès Gilles 
Published: February 2019

Le système lymphatique est formé de vaisseaux qui drainent les liquides interstitiels dans tout l’organisme. La circulation de la lymphe dans les vaisseaux lymphatiques est unidirectionnelle : des tissus vers les ganglions lymphatiques puis les veines. Les ganglions sont des filtres mécaniques mais aussi des barrières immunitaires pouvant bloquer la progression de certains pathogènes et des cellules cancéreuses. Cependant, la plupart des études portant sur le système lymphatique et la cancérogenèse mettent en évidence le rôle de ce réseau dans la dissémination métastatique, les cellules tumorales l’empruntant afin d’atteindre d’autres organes. Des travaux récents décrivent pourtant un rôle bénéfique du système lymphatique et du VEGF-C (vascular endothelial growth factor C), l’un des principaux facteurs responsables du développement des vaisseaux lymphatiques dans les tumeurs. Dans cette revue, nous illustrerons ce rôle ambivalent et émergeant du VEGF-C et du système lymphatique dans l’agressivité des cancers.
Mechanisms of Metastasis and Cell Mobility – The Role of Metabolism
Authors: Gründker Carsten , Läsche Matthias , Hellinger Johanna , Emons Günter 
Published: February 2019

AbstractTumour metastasis is responsible for more than 90% of tumour-associated mortality. About one third of breast cancer patients in the early stage develop metastases. The transformation in tumour development referred to as the “metastatic cascade” or “metastatic cycle” is a complex and multi-stage event. While it is generally recognised that epithelial-mesenchymal transformation (EMT) plays a crucial role in cancer progression and metastasis, the metabolic events in this process have received little attention to date. We would therefore like to provide a brief overview here of the influence of the metabolism on the progression and metastasis of tumours.
The Prognostic Impact of Grading in FIGO IB and IIB Squamous Cell Cervical Carcinomas
Authors: Brambs Christine , Höhn Anne , Hentschel Bettina , Fischer Uta , Bilek Karl , Horn Lars-Christian 
Published: February 2019

Abstract
Background Tumor grade is one of the more controversial factors, and the data regarding its prognostic impact in squamous cell carcinoma (SCC) of the uterine cervix are controversial.
Methods The histological slides of 467 surgically treated FIGO stage IB1 to IIB cervical SCC were re-examined regarding the prognostic impact of the histological tumor grade based on the degree of keratinization (conventional tumor grade) according to the WHO recommendation on recurrence-free and overall survival as well as on the prediction of pelvic lymph node involvement.
Results 46.0% presented with well-differentiated tumors (G1, n = 215), 30.6% with moderate (G2, n = 143) and 23.3% with poor differentiation (G3, n = 109). The recurrence-free survival was significantly reduced in patients with poorly differentiated tumors (G1: 81.4%, G2: 70.6%, G3: 64.2%; p = 0.008). There was no impact on overall survival. Because of the lack of survival differences between G1- and G2-tumors, they were merged into low-grade tumors, and their prognostic outcome was compared to the high-grade group (G3-tumors). Based on this binary conventional grading system there was a significantly longer recurrence-free (low-grade: 77.1% vs. high-grade: 64.2%; p = 0.008) and overall survival (low-grade: 76.0% vs. high-grade: 65.1%; p = 0.031) in the low-grade group. However, both the conventional three-tiered and the binary grading systems (separating tumors into a low- and high-grade group) failed to predict pelvic lymph node involvement (p = 0.9 and 0.76, respectively).
Conclusion A binary grading model for the conventional tumor grade (based on the degree of keratinization) in SCC of the uterine cervix may be suitable for the prognostic survival evaluation but failed to predict pelvic lymph node involvement.