bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined CCNE1 high‐level amplification and overexpression is associated with unfavourable outcome in tubo‐ovarian high‐grade serous carcinoma
Authors: Chan Angela MY , Enwere Emeka , McIntyre John B , Wilson Holly , Nwaroh Chidera , Wiebe Nicholas , Ou Young , Liu Shuhong , Wiedemeyer Katharina , Rambau Peter F , Grevers Xin , Morris Donald G , Neri Paola , Gilks C Blake , Visser Frank , Le Nhu , Luo Li , Cook Linda S , Köbel Martin 
Published: May 2020

AbstractCCNE1 amplification is a recurrent alteration associated with unfavourable outcome in tubo‐ovarian high‐grade serous carcinoma (HGSC). We aimed to investigate whether immunohistochemistry (IHC) can be used to identify CCNE1 amplification status and to validate whether CCNE1 high‐level amplification and overexpression are prognostic in HGSC. A testing set of 528 HGSC samples stained with two optimised IHC assays (clones EP126 and HE12) was subjected to digital image analysis and visual scoring. DNA and RNA chromogenic in situ hybridisation for CCNE1 were performed. IHC cut‐off was determined by receiver operating characteristics (ROC). Survival analyses (endpoint ovarian cancer specific survival) were performed and validated in an independent validation set of 764 HGSC. Finally, combined amplification/expression status was evaluated in cases with complete data (n = 1114). CCNE1 high‐level amplification was present in 11.2% of patients in the testing set and 10.2% in the combined cohort. The optimal cut‐off for IHC to predict CCNE1 high‐level amplification was 60% positive tumour cells with at least 5% strong staining cells (sensitivity 81.6%, specificity 77.4%). CCNE1 high‐level amplification and overexpression were associated with survival in the testing and validation set. Combined CCNE1 high‐level amplification and overexpression was present in 8.3% of patients, mutually exclusive to germline BRCA1/2 mutation and significantly associated with a higher risk of death in multivariate analysis adjusted for age, stage and cohort (hazard ratio = 1.78, 95 CI% 1.38–2.26, p < 0.0001). CCNE1 high‐level amplification combined with overexpression identifies patients with a sufficiently poor prognosis that treatment alternatives are urgently needed. Given that this combination is mutually exclusive to BRCA1/2 germline mutations, a predictive marker for PARP inhibition, CCNE1 high‐level amplification combined with overexpression may serve as a negative predictive test for sensitivity to PARP inhibitors.
Design, Synthesis, Structure‐Activity Relationship and Docking Studies of Novel Functionalized Arylvinyl‐1,2,4‐Trioxanes as Potent Antiplasmodial as well as Anticancer Agents
Authors: Tiwari Mohit K. , Coghi Paolo , Agrawal Prakhar , Shyamlal Bharti Rajesh K. , Jun Yang Li , Yadav Lalit , Peng Yuzhong , Sharma Richa , Yadav Dharmendra K. , Sahal Dinkar , Kam Wai Wong Vincent , Chaudhary Sandeep 
Published: May 2020

AbstractA novel series of synthetic functionalized arylvinyl‐1,2,4‐trioxanes (8 a–p) has been prepared and assessed for their in vitro antiplasmodial activity against the chloroquine‐resistant Pf INDO strain of Plasmodium falciparum by using a SYBR green‐I fluorescence assay. Compounds 8 g (IC50=0.051 μM; SI=589.41) and 8 m (IC50=0.059 μM; SI=55.93) showed 11‐fold and >9‐fold more potent antiplasmodial activity, respectively, as compared to chloroquine (IC50=0.546 μM; SI=36.63). Different in silico docking studies performed on many target proteins revealed that the most active arylvinyl‐1,2,4‐trioxanes (8 g and 8 m) showed dihydrofolate reductase (DHFR) binding affinities on a par with those of chloroquine and artesunate. The in vitro cytotoxic potentials of 8 a–p were also evaluated against human lung (A549) and liver (HepG2) cancer cell lines along with immortalized normal lung (BEAS‐2B) and liver (LO2) cell lines. Following screening, five derivatives viz. 8 a, 8 h, 8 l, 8 m and 8 o (IC50=1.65–31.7 μM; SI=1.08–10.96) were found to show potent cytotoxic activity against (A549) lung cancer cell lines, with selectivity superior to that of the reference compounds artemisinin (IC50=100 μM), chloroquine (IC50=100 μM) and artesunic acid (IC50=9.85 μM; SI=0.76). In fact, the most active 4‐naphthyl‐substituted analogue 8 l (IC50=1.65 μM; SI >10) exhibited >60 times more cytotoxicity than the standard reference, artemisinin, against A549 lung cancer cell lines. In silico docking studies of the most active anticancer compounds, 8 l and 8 m, against EGFR were found to validate the wet lab results. In summary, a new series of functionalized aryl‐vinyl‐1,2,4‐trioxanes (8 a–p) has been shown to display dual potency as promising antiplasmodial and anticancer agents.
A Library of Thiazolidin‐4‐one Derivatives as Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitors: An Attempt To Discover Novel Antidiabetic Agents
Authors: Patel Ashish D. , Pasha Thopallada Y. , Lunagariya Paras , Shah Umang , Bhambharoliya Tushar , Tripathi Rati K. P. 
Published: May 2020

AbstractProtein tyrosine phosphatase 1B (PTP1B) is an important target for the treatment of diabetes. A series of thiazolidin‐4‐one derivatives 8–22 was designed, synthesized and investigated as PTP1B inhibitors. The new molecules inhibited PTP1B with IC50 values in the micromolar range. 5‐(Furan‐2‐ylmethylene)‐2‐(4‐nitrophenylimino)thiazolidin‐4‐one (17) exhibited potency with a competitive type of enzyme inhibition. structure–activity relationship studies revealed various structural facets important for the potency of these analogues. The findings revealed a requirement for a nitro group‐including hydrophobic heteroaryl ring for PTP1B inhibition. Molecular docking studies afforded good correlation with experimental results. H‐bonding and π–π interactions were responsible for optimal binding and effective stabilization of virtual protein‐ligand complexes. Furthermore, in‐silico pharmacokinetic properties of test compounds predicted their drug‐like characteristics for potential oral use as antidiabetic agents.Additionally, a binding site model demonstrating crucial pharmacophoric characteristics influencing potency and binding affinity of inhibitors has been proposed, which can be employed in the design of future potential PTP1B inhibitors.
Pharmacokinetic Parameters of HIV‐1 Protease Inhibitors
Authors: Nascimento André L. C. S. , Fernandes Richard P. , Quijia Christian , Araujo Victor H. S. , Pereira Juliana , Garcia Jerusa S. , Trevisan Marcello G. , Chorilli Marlus 
Published: May 2020

AbstractSince the beginning of the HIV epidemic, research has been carried out to control the virus. Understanding the mechanisms of replication has given access to the various classes of drugs that over time have transformed AIDS into a manageable chronic disease. The class of protease inhibitors (PIs) gained notice in anti‐retroviral therapy, once it was found that peptidomimetic molecules act by blocking the active catalytic center of the aspartic protease, which is directly related to HIV maturation. However, mutations in enzymatic internal residues are the biggest issue for these drugs, because a small change in biochemical interaction can generate resistance. Low plasma concentrations of PIs favor viral natural selection; high concentrations can inhibit even partially resistant enzymes. Food‐drug/drug‐drug interactions can decrease the bioavailability of PIs and are related to many side effects. Therefore, this review summarizes the pharmacokinetic properties of current PIs, the changes when pharmacological boosters are used and also lists the major mutations to help understanding of how long the continuous treatment can ensure a low viral load in patients.
Design, Synthesis, and Characterization of Novel CXCR4 Antagonists Featuring Cyclic Amines
Authors: Lin Yu , Li Zhanhui , Ma Haikuo , Wang Yujie , Wang Xu , Song Shiwei , Zhao Li , Wu Shuwei , Tian Sheng , Fu Chunyan , Luo Lusong , Zhu Fang , He Sudan , Zheng Jiyue , Zhang Xiaohu 
Published: May 2020

AbstractChemokine receptor CXCR4 and its natural ligand CXCL12 (also known as stromal cell‐derived factor‐1, or SDF‐1) regulate a broad range of physiological functions. Dysregulation of the CXCL12/CXCR4 axis is involved in numerous pathological conditions such as HIV infection, inflammation and cancer. Herein, we report the design, synthesis, and characterization of novel CXCR4 antagonists based on cyclic amine scaffolds. Compound 24 was identified as a potent CXCR4 receptor antagonist (competitive inhibition of 12G5 binding, IC50=24 nM; functional inhibition of CXCL12‐induced cytosolic calcium increase, IC50=0.1 nM). In addition, compound 24 potently inhibited cell migration in CXCR4/CXCL12‐mediated chemotaxis in a matrigel invasion assay. The absolute configuration of compound 24 was elucidated by X‐ray crystallography.
Manipulating the strength of organism–environment feedback increases nonlinearity and apparent hysteresis of ecosystem response to environmental change
Authors: Garnier Aurélie , Hulot Florence D. , Petchey Owen L. 
Published: May 2020

AbstractTheory predicts that organism–environment feedbacks play a central role in how ecological communities respond to environmental change. Strong feedback causes greater nonlinearity between environmental change and ecosystem state, increases the likelihood of hysteresis in response to environmental change, and augments the possibility of alternative stable regimes. To illustrate these predictions and their dependence on a temporal scale, we simulated a minimal ecosystem model. To test the predictions, we manipulated the feedback strength between the metabolism and the dissolved oxygen concentration in an aquatic heterotrophic tri‐trophic community in microecosystems. The manipulation consisted of five levels, ranging from low to high feedback strength by altering the oxygen diffusivity: free gas exchange between the microcosm atmosphere and the external air (metabolism not strongly affecting environmental oxygen), with the regular addition of 200, 100, or 50 ml of air and no gas exchange. To test for nonlinearity and hysteresis in response to environmental change, all microecosystems experienced a gradual temperature increase from 15 to 25°C and then back to 15°C. We regularly measured the dissolved oxygen concentration, total biomass, and species abundance. Nonlinearity and hysteresis were higher in treatments with stronger organism–environment feedbacks. There was no evidence that stronger feedback increased the number of observed ecosystem states. These empirical results are in broad agreement with the theory that stronger feedback increases nonlinearity and hysteresis. They therefore represent one of the first direct empirical tests of the importance of feedback strength. However, we discuss several limitations of the study, which weaken confidence in this interpretation. Research demonstrating the causal effects of feedback strength on ecosystem responses to environmental change should be placed at the core of efforts to plan for sustainable ecosystems.
Enzootic maintenance of sylvatic plague in Canada's threatened black‐tailed prairie dog ecosystem
Authors: Liccioli Stefano , Stephens Tara , Wilson Sian C. , McPherson Jana M. , Keating Laura M. , Antonation Kym S. , Bollinger Trent K. , Corbett Cindi R. , Gummer David L. , Lindsay L. Robbin , Galloway Terry D. , Shury Todd K. , Moehrenschlager Axel 
Published: May 2020

AbstractData paucity can seem to hinder science‐based approaches to the conservation of imperiled species. Yet, even individually limited datasets can improve understanding and management of complex ecological systems when carefully integrated. We demonstrate this approach to gain first insights on the transmission ecology of Yersinia pestis in Grasslands National Park (GNP), Canada, where both the bacterium and its rodent host, the nationally threatened black‐tailed prairie dog (BTPD, Cynomys ludovicianus), reach the northern limit of their distribution in North America. Primarily flea‐borne, Y. pestis causes sylvatic plague, a disease of exceptional relevance to both human health and wildlife conservation. We integrated data collected independently by multiple organizations in 2010–2017 across 17 BTPD colonies, where the species co‐occur with Richardson's ground squirrels (RGS, Urocitellus richardsonii). Available data included estimates of BTPD density and occupancy from visual counts and colony mapping; information on flea distribution, abundance, and prevalence of infection with Y. pestis from burrow swabbing, animal combing, and PCR assays; and the response of these variables to deltamethrin application on BTPD colony sections. Our analyses suggest that sylvatic plague in GNP is maintained at an enzootic level (i.e., chronic presence affecting a low proportion of individuals) with no evidence of widespread mortality, at least partially due to reduced flea activity after spring (percentage of prevalence in burrows: April–May = 11.69–33.89%; June–September: 1.75–3.19%), low prevalence of Y. pestis in flea samples (95% CI = 0.42–2.27%), and relatively low BTPD densities. Nonetheless, reducing flea prevalence through insecticide application had a positive effect on BTPD abundance, suggesting that enzootic plague is causing chronic mortality. Because flea prevalence on hosts was higher following drier years and higher on RGS than on BTPD (26.69% vs. 3.27%), insecticide application may be particularly important during dry periods and may need to take RGS and their movements into consideration. Differences between flea communities sampled by burrow swabbing and host combing suggest that plague surveillance should integrate both methods. Effects of projected climate change on vector life cycles, flea community composition, and host–parasite interactions warrant continued monitoring and an adaptive approach to species recovery actions and plague mitigation measures.
Genetic instability assessed by telomere length and micronucleus in physicians exposed to anesthetics
Authors: Braz Mariana G. , Silva Mariane A. P. , Figueiredo Drielle B. S. , Aun Aline G. , Marques Lais S. K. , Lara Juliana R. , Braz Leandro G. 
Published: May 2020

AbstractThis study evaluated both telomere length (TL) and micronucleus (MN) as indicators of genome instability in 40 anesthesiologists occupationally exposed to anesthetics and in 40 physicians without occupational exposure to anesthetics who were matched by age, sex, and lifestyle. Blood and buccal samples were collected from both groups at the same period. Anesthetic exposure assessment was performed. The studied groups were assessed regarding relative TL by quantitative polymerase chain reaction and MN by buccal MN assay. Mean trace concentrations of anesthetics were below two parts per million. No significant differences between groups were found for both biomarkers. However, MN frequency was slightly increased (1.9‐fold; p = .094) in the exposed group compared to the control group and in the exposed males (2.4‐fold; p = .090) compared to unexposed males. TL and age showed a significant negative correlation. Anesthetic occupational exposure below recommended levels is not associated with changes in TL and MN in anesthesiologists.
Are farmers using cropping system intensification technologies experiencing poverty reduction in the Great Lakes Region of Africa?
Authors: Dontsop Nguezet Paul Martin , Ainembabazi John Herbert , Alene Arega , Abdulaye Tahirou , Feleke Shiferaw , Nziguheba Generose , Khonje Makaiko , Mignouna Djana , Okafor Christopher , Njukwe Emmanuel , Van Asten Piet , Mapatano Sylvain , Vanlauwe Bernard , Manyong Victor 
Published: May 2020

AbstractThis study evaluated the poverty reduction impact of the adoption of cropping system intensification (CSI) technologies using the endogenous switching regression (ESR) model in the Great Lakes region of Africa that comprises Burundi, eastern DR Congo, and Rwanda. The study data came from a household survey of 1,495 sample households interviewed between October and December 2014. Results indicated that the adoption of the CSI technologies had increased crop yield, crop income, and per capita consumption expenditure in the region, resulting in poverty reduction. Among the three countries, eastern DR Congo witnessed the highest poverty reduction (13% points) followed by Rwanda (6% points) and Burundi (2% points). Considering the adoption rate and size of the target population in each country at baseline, an estimated 180 thousand poor individuals had escaped poverty due to the adoption of the CSI technologies. This presents important evidence in favor of promoting CSI technologies as part of poverty reduction strategy. Given the large population size that remains poor even after adoption, we suggest that research‐based poverty reduction strategies such as the CSI technologies should be complemented with development interventions.
Trader networks and options risk management
Authors: Boyd Naomi , Locke Peter , Sun Li 
Published: May 2020

AbstractWe examine the effect of trading partner concentration and a matrix of variables which dictate the relative importance of a trader to the network on a set of large member proprietary traders’ risk. An increased closeness centrality and concentration of trading among network partners are found to reduce price, volatility and rebalancing risk. We further explore the nature of trading concentration established through traders’ recurring trading relationships to find that trading with an established and small network has a positive, yet costly, effect on inventory management. Relationships among market makers are important to managing their portfolio of risk.
Colon cancer detection by using Poincaré sphere and 2D polarimetric mapping of ex vivo colon samples
Authors: Ivanov Deyan , Dremin Viktor , Bykov Alexander , Borisova Ekaterina , Genova Tsanislava , Popov Alexey , Ossikovski Razvigor , Novikova Tatiana , Meglinski Igor 
Published: May 2020

AbstractThis work is dedicated to the diagnosis and grading of colon cancer by a combined use of Poincaré sphere and 2D Stokes vector polarimetry mapping approaches. The major challenge consists in exploring the applicability of polarized light for noninvasive screening of the histological abnormalities within the samples of biological tissues. Experimental studies were conducted in ex vivo colon sample, excised after surgical procedure for colon tumor removal of G2‐adenocarcinoma lesion. Polarimetric measurements in linear and circular regime were carried via personally developed polarimetric, optical set‐up, using supercontinuous fiber laser with irradiation fixed at 635 nm. We apply the Poincaré sphere and two‐dimensional Stokes vector scanning approach for screening the corresponding tissue samples. A comparison between linear and circular polarization states is made both for quantitative and qualitative evaluations. It is shown that circular polarization has better diagnostic capabilities than linear polarization, with higher dynamic ranges of the polarimetric parameters and better values of the diagnostic quantities. In addition to the standard polarimetry parameters, utilized as essential diagnostic markers, we apply statistical analysis to obtain more detailed information in frame of the applied diagnostic approach.
Overexpression of Foxc1 regenerates crushed rat facial nerves by promoting Schwann cells migration via the Wnt/β‐catenin signaling pathway
Authors: Xia Wenzheng , Zhu Jin , Wang Xueyi , Tang Yinda , Zhou Ping , Wei Xiangyu , Chang Bowen , Zheng Xuan , Zhu Wanchun , Hou Meng , Li Shiting 
Published: May 2020

AbstractFacial paralysis can result in severe implications for patients. A good prognosis depends on the degree of nerve regeneration. Schwann cells (SCs) play an important role in facial nerve development and regeneration through migration. Forkhead box C1 (Foxc1), a member of the forkhead transcription factor family, is implicated in cell migration. However, the role of Foxc1 in the progression after facial nerve crush remains unknown. Our aim was to evaluate the effect of Foxc1 overexpression on SC migration and recovery of facial nerves after crush injury. The rat facial nerve crush injury model was established through the use of unilateral surgery. The results showed that the expression of Foxc1 was increased in the surgery group compared to that of the control group. SCs were isolated from the sciatic nerves and cultured. Foxc1, delivered by an adeno‐associated virus in vivo, or adenovirus in vitro, both induced overexpression of Foxc1, and increased the expression of CXCL12 and β‐catenin. After the transfection of Foxc1, the migration of SC was increased both in vitro and in vivo, was reduced by the inhibition of CXCL12 or β‐catenin. The facial nerve function and the nerve axon remyelination of the rats transfected with Foxc1 were significantly improved after nerve crush injury. Overall, the results demonstrated that overexpression of Foxc1 promoted SC migration by regulating CXCL12 via the Wnt/β‐catenin pathway, thus contributing to improved facial nerve function after crush injury.
Bank Accounts for All: How Do State Policies Matter?
Authors: Girard Tyler 
Published: May 2020

AbstractThis paper examines the relationship between state policies and bank account ownership in developing countries. While existing literatures broadly support a ‘market‐enabling’ approach, consisting of limited direct state intervention and proportionate regulation, statistical analyses frequently rely on problematic measurement techniques. This study adopts a novel and more comprehensive approach by using a modified index constructed from expert evaluations. Using ordinary least squares regression, the analysis suggests a positive relationship between a market‐enabling state policy framework and increased bank account ownership among the total population, but the relationship diminishes among key subpopulations: adult women, rural adults and the poorest 40 per cent of adults. © 2020 John Wiley & Sons, Ltd.