bluuebunny/crossref_metadata_2025 huggingface dataset:
Socially responsible human resource practices to improve the employability of people with disabilities
Authors: Kwan Chi Kin
Published: May 2019

Although the employment of people with disabilities (PWDs) has been recognized as an important human right, it is seldom emphasized in current corporate social responsibility (CSR) practice. Based on experiences with a job training program in hospitality for people with intellectual disabilities or Down syndrome offered by a hotel in Hong Kong, this paper explores how socially responsible human resource (HR) practices can support the employment of PWDs. An A‐B‐C‐D framework is proposed by the author to explore what business enterprises can contribute through HR strategy. Based on the results of interviews conducted with the hotel staff and social workers involved in the program, this study suggests that socially responsible HR practices can play an important role in improving the employability of PWDs by providing workplace accommodations, business‐oriented settings, a caring attitude, and job demands, showing how CSR and PWD employment are intertwined.
Across scales, pronghorn select sagebrush, avoid fences, and show negative responses to anthropogenic features in winter
Authors: Reinking Adele K. , Smith Kurt T. , Mong Tony W. , Read Mary J. , Beck Jeffrey L.
Published: May 2019

Pronghorn (Antilocapra americana) are endemic to western North America where they occupy expanses of grassland and sagebrush (Artemisia spp.) habitats. The Red Desert region in south‐central Wyoming, USA, has historically served as a stronghold for pronghorn populations, but many herds there have experienced declining population trends over the last two decades, concurrent with oil and natural gas development. These demographic changes and the potential for such energy development, its associated infrastructure, and other anthropogenic features including roads and fences to influence pronghorn habitat selection were the impetuses for our study. We sought to evaluate the potential effect of human‐induced disturbance on multi‐scale seasonal resource selection of 142 adult female pronghorn from 2013 to 2016 using 442 unique animal‐season‐year datasets. We utilized a traditional resource selection function to evaluate seasonal home‐range selection and a step‐selection function to assess fine‐scale, patch‐level seasonal selection. We also compared resource selection during daytime and nighttime hours with step‐selection analyses. At the seasonal home‐range scale, pronghorn selected for areas with more sagebrush during both seasons and areas farther from fences during summer. This trend was also apparent at the patch‐scale level, where pronghorn selected sagebrush‐dominant habitats and avoided crossing fences in all seasons during both day and night. Additionally at this scale, pronghorn selected areas farther from fences during daytime in summer. At the broader, home‐range scale, pronghorn selected areas with greater road density during summer, but with lower road densities and farther from wells during winter. Avoidance of anthropogenic features during winter was also observed at the finer, patch‐scale, with pronghorn selecting for increased density of roads and oil and natural gas wells during daytime in summer, but selecting areas farther from these features during daytime in winter. We recommend minimizing fencing and other forms of anthropogenic disturbance in high‐quality seasonal pronghorn habitats with high proportions of sagebrush, particularly during winter when risk‐avoidance responses may be amplified.
Developing an expert elicited simulation model to evaluate invasive species and fire management alternatives
Authors: Jarnevich Catherine S. , Cullinane Thomas Catherine , Young Nicholas E. , Backer Dana , Cline Sarah , Frid Leonardo , Grissom Perry
Published: May 2019

Invasive species can alter ecosystem properties and cause state shifts in landscapes. Resource managers charged with maintaining landscapes require tools to understand implications of alternative actions (or inactions) on landscape structure and function. Simulation models can serve as a virtual laboratory to explore these alternatives and their potential impacts on a landscape. To be useful, however, managers need to participate in model development to ensure that model structure can evaluate the response of key resources to plausible actions. Here, we detail development of a state‐and‐transition simulation model (STSM) to evaluate buffelgrass (Cenchrus ciliarisL. synPennisetum ciliare(L.) Link) in Saguaro National Park (SNP), Arizona,USA, through collaboration between managers and researchers. We integrate expert knowledge and research to create and parameterize a stochastic, spatially explicitSTSMto evaluate specific management objectives. We also develop a dynamic link between theSTSMand a fire behavior model to allow exploration of potential novel processes introduced to the ecosystem by buffelgrass invasion. Our projections show that buffelgrass can be expected to increase on the landscape and that the integration of fire into the model accelerates the projected rate of invasion and increases degradation of resources of management concern. We highlight the benefit of engaging end users in the modeling process so that the model is targeted to evaluate management objectives, in this case retention of saguaro cacti (Carnegiea gigantea(Engelm.) Britton & Rose) on the landscape. Being able to integrate an external model that can help address the unique characteristics of a problem such as the introduction of fire into the SNP desert ecosystem increases the ability of simulations to address complex ecological and management questions.
Gold(I) Complexes in Ionic Liquids: An Efficient Catalytic System for the C‐H Functionalization of Arenes and Heteroarenes under Mild Conditions
Authors: Baron Marco , Biffis Andrea
Published: May 2019

Use of ionic liquids bearing the proper counteranion as reaction solvents allows to boost the reactivity of gold(I) complexes as catalysts in the hydroarylation of alkynes with arenes and heteroarenes. Several commercial complexes of general structure LAuX have been tested as catalysts, with L=1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene standing out as the one delivering the best performance. Beside high activity, enabling the use of <1 mol‐% catalyst under mild conditions (low temperature, no need for an acid cocatalyst), gold‐based catalytic systems in ionic liquids also exhibit tunable chemo‐ and regioselectivity in these reactions and turn out to be recyclable, which renders them quite attractive for synthetic applications.
Practical Synthesis of β‐Ketothioesters by Acid‐Catalyzed Hydrolysis of Ketene N,S‐Acetals with Amino as the Leaving Group
Authors: Xu Qi , Zheng Baihui , Pan Ling , Liu Qun , Li Yifei
Published: May 2019

A Novel, general, and highly efficient methodology for the synthesis of β‐ketothioesters from ketene N,S‐acetals has been developed. In this acid‐catalyzed reaction, the amino group, including both alkylamino and arylamino groups, of α‐oxo ketene N,S‐acetals can be easily displaced in the presence of H2O as nucleophile (hydrolysis) instead of the alkylthiol group reported. This new method is simple and practical. A series of β‐ketothioesters were prepared in high yields with broad tolerance of substrates under mild reaction conditions.
Recent advances in nanomaterial‐based capillary electrophoresis
Authors: Kitte Shimeles Addisu , Fereja Tadesse Haile , Halawa Mohamed Ibrahim , Lou Baohua , Li Haijuan , Xu Guobao
Published: May 2019

This review gives a summary of applications of different nanomateials, such as gold nanoparticles (AuNPs), carbon‐based nanoparticles, magnetic nanoparticles (MNPs), and nano‐sized metal organic frameworks (MOFs), in electrophoretic separations. This review also emphasizes the recent works in which nanoparticles (NPs) are used as pseudostationary phase (PSP) or immobilized on the capillary surface for enhancement of separation in CE, CEC, and microchips electrophoresis.
Response of arid northeast Mexico to global climate changes during the late Pleistocene to the middle Holocene
Authors: Roy Priyadarsi D. , Vera‐Vera Guillermo , Curtis Jason H. , Sánchez‐Zavala José L. , Quiroz‐Jiménez Jesús David , Muthu Sankar Gowrappan
Published: May 2019

Anthropogenic global warming might cause expansion of the drylands and trigger socio‐economic challenges in the water‐deficit subtropical regions. Changes in hydroclimate during the intervals of variable global temperature over the recent geological past, however, could provide useful information about the possible responses of these arid ecosystems to the near future warmer conditions. We evaluated hydroclimates of two different parts of subtropical North America by generating new records of surface processes and regional vegetation from drought‐prone northeast Mexico and subsequently compared them with the paleoclimate of the central‐southern United States. Our study suggests that congruent changes occurred in both parts during ~13.5–9.5 cal ka BP, an interval with no warm pool in the northern Gulf of Mexico. The precipitation and erosion responded to temperature‐modulated variations in positions of the Inter‐Tropical Convergence Zone (ITCZ). Conditions were wetter than today in the subsequent warmer interval (~9.5–8.2 cal ka BP) with generally stable ITCZ and the highest summer insolation. Hydroclimate changes of both parts lacked congruency during ~8.2–6.8 cal ka BP as the northern Gulf of Mexico began hosting a warm pool. Similar to the modern conditions, this warm pool might have modified trajectories of the tropical storms. Erosion and abundance of C3 plants decreased in northeast Mexico. Higher wetness in the Mississippi River Basin and the southern Great Plains during this interval suggested that the storms made landfall more frequently in the central‐southern United States. © 2019 John Wiley & Sons, Ltd.
The impact of the US stock market opening on price discovery of government bond futures
Authors: Indriawan Ivan , Jiao Feng , Tse Yiuman
Published: May 2019

We examine price discovery in sequential markets for the 10‐year US Treasury note, German bund, and UK gilt futures over the period 2010–2017. We find that price discovery increases after the opening of the US stock market. Order flows in the bond futures markets are more informative for permanent price changes in the 30‐min period after the US stock market opens. A placebo test using US statutory holidays confirms our findings. A cross‐market analysis suggests that the increased price discovery in the bond futures is related to returns and net order flows of the US stock market.
A neural signature of metabolic syndrome
Authors: Kotkowski Eithan , Price Larry R. , Franklin Crystal , Salazar Maximino , Woolsey Mary , DeFronzo Ralph A. , Blangero John , Glahn David C. , Fox Peter T.
Published: May 2019

That metabolic syndrome (MetS) is associated with age‐related cognitive decline is well established. The neurobiological changes underlying these cognitive deficits, however, are not well understood. The goal of this study was to determine whether MetS is associated with regional differences in gray‐matter volume (GMV) using a cross‐sectional, between‐group contrast design in a large, ethnically homogenous sample. T1‐weighted MRIs were sampled from the genetics of brain structure (GOBS) data archive for 208 Mexican‐American participants: 104 participants met or exceeded standard criteria for MetS and 104 participants were age‐ and sex‐matched metabolically healthy controls. Participants ranged in age from 18 to 74 years (37.3 ± 13.2 years, 56.7% female). Images were analyzed in a whole‐brain, voxel‐wise manner using voxel‐based morphometry (VBM). Three contrast analyses were performed, a whole sample analysis of all 208 participants, and two post hoc half‐sample analyses split by age along the median (35.5 years). Significant associations between MetS and decreased GMV were observed in multiple, spatially discrete brain regions including the posterior cerebellum, brainstem, orbitofrontal cortex, bilateral caudate nuclei, right parahippocampus, right amygdala, right insula, lingual gyrus, and right superior temporal gyrus. Age, as shown in the post hoc analyses, was demonstrated to be a significant covariate. A further functional interpretation of the structures exhibiting lower GMV in MetS reflected a significant involvement in reward perception, emotional valence, and reasoning. Additional studies are needed to characterize the influence of MetS's individual clinical components on brain structure and to explore the bidirectional association between GMV and MetS.
Anticipatory alpha oscillation predicts attentional selection and hemodynamic response
Authors: Zhao Chenguang , Guo Jialiang , Li Dongwei , Tao Ye , Ding Yulong , Liu Hanli , Song Yan
Published: May 2019

In covert visual attention, one fundamental question is how advance knowledge facilitates subsequent neural processing and behavioral performance. In this study, with a rapid event‐related simultaneous electroencephalography (EEG) and functional near infrared spectroscopy recording in humans, we explored the potential contribution of anticipatory electrophysiological activation and hemodynamic activation by examining how anticipatory low‐frequency oscillations and changes in oxygenated hemoglobin (HbO) concentration influence the subsequent event‐related potential (ERP) marker of attentional selection. We found that expecting a target led to both a posterior lateralization of alpha‐band (8–12 Hz) oscillation power and a lateralization of HbO response over the visual cortex. Importantly, the magnitude of cue‐induced alpha lateralization was positively correlated with the nearby HbO lateralization in the visual cortex, and such a cue‐induced alpha lateralization predicted the subsequent target‐evoked N2pc amplitudes assumed to reflect attentional selection. Our results suggest that each individual's attentional selection biomarker as reflected by N2pc is predictable in advance via the anticipation‐induced alpha lateralization, and such cue‐induced alpha lateralization seems to play an important role in the functional coupling effects between the low‐frequency EEG and the nearby hemodynamic activation.
The Quality and Outcomes of Care Provided to Patients with Cirrhosis by Advanced Practice Providers
Authors: Tapper Elliot B. , Hao Shengchen , Lin Menghan , Mafi John N. , McCurdy Heather , Parikh Neehar D. , Lok Anna S.
Published: May 2019

Cirrhosis is morbid and increasingly prevalent, yet the U.S. health care system lacks enough physicians and specialists to adequately manage patients with cirrhosis. Although advanced practice providers (APPs) can expand access to cirrhosis‐related care, their impact on the quality of care remains unknown. We sought to determine the effect on care quality and outcomes for patients managed by APPs using a retrospective analysis of a nationally representative American commercial claims database (Optum), which included 389,257 unique adults with cirrhosis. We evaluated a complication of process measures (i.e., rates of hepatocellular carcinoma [HCC] screening, endoscopic varices screening, and use of rifaximin after hospitalization for hepatic encephalopathy) and outcomes (30‐day readmissions and survival). Compared with patients without APP care, patients with APP care had higher rates of HCC screening (adjusted odds ratio [OR] 1.23, 95% confidence interval 1.19, 1.27), varices screening (OR 1.20 [1.13, 1.27]), use of rifaximin after a discharge for hepatic encephalopathy (OR 2.09 [1.80, 2.43]), and reduced risk of 30‐day readmission (OR 0.68 [0.66, 0.70]). Gastroenterology/hepatology consultation was also associated with improved quality metric performance compared with primary care; however, shared visits between gastroenterologists/hepatologists and APPs were associated with the best performance and lower 30‐day readmissions compared with subspecialty consultation without an APP (OR 0.91 [0.87, 0.95]. Multivariate analysis adjusting for comorbidities, liver disease severity, and other factors including gastroenterology/hepatology consultation showed that patients seen by APPs were more likely to receive consistent HCC and varices screening over time, less likely to experience 30‐day readmissions, and had lower mortality (adjusted hazard ratio 0.57, 95% confidence interval 0.55, 0.60). Conclusion: APPs, particularly when working with gastroenterologists/hepatologists, are associated with improved quality of care and outcomes for patients with cirrhosis.
The mTORC2‐Akt1 Cascade Is Crucial for c‐Myc to Promote Hepatocarcinogenesis in Mice and Humans
Authors: Xu Zhong , Xu Meng , Liu Pin , Zhang Shu , Shang Runze , Qiao Yu , Che Li , Ribback Silvia , Cigliano Antonio , Evert Katja , Pascale Rosa M. , Dombrowski Frank , Evert Matthias , Chen Xi , Calvisi Diego F. , Chen Xin
Published: May 2019

Hepatocellular carcinoma (HCC) is a deadly form of liver cancer with limited treatment options. The c‐Myc transcription factor is a pivotal player in hepatocarcinogenesis, but the mechanisms underlying c‐Myc oncogenic activity in the liver remain poorly delineated. Mammalian target of rapamycin complex 2 (mTORC2) has been implicated in cancer by regulating multiple AGC kinases, especially AKT proteins. In the liver, AKT1 and AKT2 are widely expressed. While AKT2 is the major isoform downstream of activated phosphoinositide 3‐kinase and loss of phosphatase and tensin homolog–induced HCC, the precise function of AKT1 in hepatocarcinogenesis is largely unknown. In the present study, we demonstrate that mTORC2 is activated in c‐Myc‐driven mouse HCC, leading to phosphorylation/activation of Akt1 but not Akt2. Ablation of Rictor inhibited c‐Myc‐induced HCC formation in vivo. Mechanistically, we discovered that loss of Akt1, but not Akt2, completely prevented c‐Myc HCC formation in mice. Silencing of Rictor or Akt1 in c‐Myc HCC cell lines inhibited phosphorylated forkhead box o1 expression and strongly suppressed cell growth in vitro. In human HCC samples, c‐MYC activation is strongly correlated with phosphorylated AKT1 expression. Higher expression of RICTOR and AKT1, but not AKT2, is associated with poor survival of patients with HCC. In c‐Myc mice, while rapamycin, an mTORC1 inhibitor, had limited efficacy at preventing c‐Myc‐driven HCC progression, the dual mTORC1 and mTORC2 inhibitor MLN0128 effectively promoted tumor regression by inducing apoptosis and necrosis. Conclusion: Our study indicates the functional contribution of mTORC2/Akt1 along c‐Myc‐induced hepatocarcinogenesis, with AKT1 and AKT2 having distinct roles in HCC development and progression; targeting both mTORC1 and mTORC2 may be required for effective treatment of human HCC displaying c‐Myc amplification or overexpression.
Long Noncoding RNA H19 Contributes to Cholangiocyte Proliferation and Cholestatic Liver Fibrosis in Biliary Atresia
Authors: Xiao Yongtao , Liu Runping , Li Xiaojiaoyang , Gurley Emily C. , Hylemon Phillip B. , Lu Ying , Zhou Huiping , Cai Wei
Published: May 2019

Biliary atresia (BA) is a neonatal liver disease featuring cholestasis and severe liver fibrosis (LF). Despite advances in the development of surgical treatment, lacking an early diagnostic marker and intervention of LF invariably leads to death from end‐stage liver disease in the early years of life. We previously reported that knockout of sphingosine 1‐phosphate receptor 2 (S1PR2) protected mice from bile duct ligation (BDL)‐induced cholangiocyte proliferation and LF. Our recent studies further showed that both hepatic and serum exosomal long noncoding RNA H19 (lncRNAH19) levels are correlated with cholestatic injury in multidrug resistance 2 knockout (Mdr2–/–
) mice. However, the role of lncRNAH19 in BA progression remains unclear. Here, we show that both hepatic and serum exosomal H19 levels are positively correlated with severity of fibrotic liver injuries in BA patients. H19 deficiency protects mice from BDL‐induced cholangiocyte proliferation and LF by inhibiting bile‐acid–induced expression and activation of S1PR2 and sphingosine kinase 2 (SphK2). Furthermore, H19 acts as a molecular sponge for members of the microRNA let‐7 family, which results in up‐regulation of high‐mobility group AT‐hook 2 (HMGA2), a known target of let‐7 and enhancement of biliary proliferation. Conclusion: These results indicate that H19 plays a critical role in cholangiocyte proliferation and cholestatic liver injury in BA by regulating the S1PR2/SphK2 and let‐7/HMGA2 axis. Serum exosomal H19 may represent a noninvasive diagnostic biomarker and potential therapeutic target for BA.
Assessing mobile phone use by pregnant women in Nigeria: A capability perspective
Authors: Dasuki Salihu Ibrahim , Zamani Efpraxia D.
Published: May 2019

This paper explores the use of mobile phones to access maternal health care in sub‐Saharan Africa and whether it enhances capability and human development. Analysing focus groups and interviews on mobile phone uses by pregnant women in Nigeria based on the Technology Augmented Capability Approach, we show that the mobile phone as a technical object facilitates three broad capabilities for pregnant women, namely, (a) enhances their voice and choice to push for health care quality, (b) enhances their access to emergency services while maintaining entrepreneurial activities, and (c) enhances their health literacy and social connectedness. However, personal, social, and environmental factors influence the conversion of the use of the mobile phone into capabilities by the pregnant women.
Treatment of Autosomal Dominant Hypocalcemia Type 1 With the Calcilytic NPSP795 (SHP635)
Authors: Roberts Mary Scott , Gafni Rachel I , Brillante Beth , Guthrie Lori C , Streit Jamie , Gash David , Gelb Jeff , Krusinska Eva , Brennan Sarah C , Schepelmann Martin , Riccardi Daniela , Bin Khayat Mohd Ezuan , Ward Donald T , Nemeth Edward F , Rosskamp Ralf , Collins Michael T
Published: May 2019

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism caused by heterozygous, gain-of-function mutations of the calcium-sensing receptor gene (CAR). Individuals are hypocalcemic with inappropriately low parathyroid hormone (PTH) secretion and relative hypercalciuria. Calcilytics are negative allosteric modulators of the extracellular calcium receptor (CaR) and therefore may have therapeutic benefits in ADH1. Five adults with ADH1 due to four distinct CAR mutations received escalating doses of the calcilytic compound NPSP795 (SHP635) on 3 consecutive days. Pharmacokinetics, pharmacodynamics, efficacy, and safety were assessed. Parallel in vitro testing with subject CaR mutations assessed the effects of NPSP795 on cytoplasmic calcium concentrations (Ca2+i), and ERK and p38MAPK phosphorylation. These effects were correlated with clinical responses to administration of NPSP795. NPSP795 increased plasma PTH levels in a concentration-dependent manner up to 129% above baseline (p = 0.013) at the highest exposure levels. Fractional excretion of calcium (FECa) trended down but not significantly so. Blood ionized calcium levels remained stable during NPSP795 infusion despite fasting, no calcitriol supplementation, and little calcium supplementation. NPSP795 was generally safe and well-tolerated. There was significant variability in response clinically across genotypes. In vitro, all mutant CaRs were half-maximally activated (EC50) at lower concentrations of extracellular calcium (Ca2+o) compared to wild-type (WT) CaR; NPSP795 exposure increased the EC50 for all CaR activity readouts. However, the in vitro responses to NPSP795 did not correlate with any clinical parameters. NPSP795 increased plasma PTH levels in subjects with ADH1 in a dose-dependent manner, and thus, serves as proof-of-concept that calcilytics could be an effective treatment for ADH1. Albeit all mutations appear to be activating at the CaR, in vitro observations were not predictive of the in vivo phenotype or the response to calcilytics, suggesting that other parameters impact the response to the drug. © 2019 American Society for Bone and Mineral Research.
miR‐202‐5p protects rat against myocardial ischemia reperfusion injury by downregulating the expression of Trpv2 to attenuate the Ca2+ overload in cardiomyocytes
Authors: Li Yanbing , Li Qiang , Zhang Ou , Guan Xiaonan , Xue Yajun , Li Siyuan , Zhuang Xianjing , Zhou Boda , Miao Guobin
Published: May 2019

Background

This study was aimed to unveil micro RNA (miRNA) expression profiles in myocardial ischemia‐reperfusion (MI/R) rats and explore whether and how dysregulated miRNAs were involved in the initiation and progression of MI/R in a calcium‐dependent manner.

Method and Results

Rat model of MI/R was established and cardiomyocytes isolated from neonatal rats cardiomyocytes were induced. Both miRNA and messenger RNA expression profiles were analyzed by Microarray. Quantitative reverse‐transcription polymerase chain reaction, immunoblotting, bioinformatics analysis, dual‐luciferase reporter gene assay, hematoxylin and eosin, Evans blue, and triphenyl tetrazolium chloride were also used in this study. Serum concentrations of myocardial enzymes (phosphocreatine kinase [CK], creatine kinase [CK‐MB], lactate dehydrogenase [LDH]), cardiomyocytes loadage of Ca2+, as well as the expression level of inositol 1,4,5‐trisphosphate receptors (IP3R) and sarcoplasmic reticulum Ca2+‐ATPase 2a (SERCA2a) were measured, respectively. Effects of upregulation or downregulation of miR‐202‐5p or Trpv2 on these indicators were investigated in vivo and in vitro. In MI/R rats and hypoxia/reoxygenation‐induced NCMs, miR‐202‐5p was downregulated, while Trpv2 was upregulated. Trpv2 was a promising target of miR‐202‐5p and negatively regulated by miR‐202‐5p. Upregulation of miR‐202‐5p or downregulation of Trpv2 significantly reduced the serum concentration of myocardial enzymes, as well as cardiomyocyte‐produced reactive oxygen species, but inhibition of miR‐202‐5p or overexpression of Trpv2 brought the worsening situation for these indicators. Besides, upregulation of miR‐202‐5p upregulation or downregulation of Trpv2 also inhibited Ca2+ overload in cardiomyocytes, accompanied with the increase of SERCA2a and suppression of IP3R. The reduced damage degree and infarct size in myocardial tissue were contrarily worsened by miR‐202‐5p inhibitor.

Conclusion

Overexpression of miR‐202‐5p or downregulation of its downstream Trpv2 presented the cardioprotective effects to MI/R rats.
HOXB13 promotes proliferation, migration, and invasion of glioblastoma through transcriptional upregulation of lncRNA HOXC‐AS3
Authors: Wang Xi , Sun Yi , Xu Tuoye , Qian Kai , Huang Baosheng , Zhang Kaixin , Song Zewu , Qian Tengda , Shi Jing , Li Lixin
Published: May 2019

HOXB13 exerts a close relation in several human cancers. This study explored the role of HOXB13 in glioblastoma (GBM), a brain tissue with the highest aggressive rate and mortality in adults. Through microarray and immunohistochemistry analyses, HOXB13 was highly expressed in GBM tissues. Furthermore, we showed that high‐level expression of HOXB13 in GBM was associated with worse survival, suggesting that HOXB13 could be a prognostic marker for patients with GBM. GBM cells U87 and U251 overexpressing HOXB13 showed enhanced proliferation, migration, and invasion relative to the control cells, while knockdown of HOXB13 led to decreased cell proliferation, migration, and invasion abilities. In addition, dual‐luciferase report assay, chromatin immunoprecipitation assay, and quantitative real‐time polymerase chain reaction data showed that HOXB13 directly bound to HOXC‐AS3 promoter. HOXC‐AS3 was involved in HOXB13‐induced proliferation, migration, and invasion of GBM cells. In summary, this study revealed the prognostic potential of HOXB13 in GBM. We believed that HOXB13/HOXC‐AS3 signaling axis can be served as therapeutic targets for this highly aggressive cancer.
Molecular dynamics simulation study on the inhibitory effects of choline‐O‐sulfate on hIAPP protofibrilation
Authors: Paul Srijita , Paul Sandip
Published: May 2019

Type 2 diabetes mellitus (T2Dm) is a neurodegenerative disease, which occurs due to the self‐association of human islet amyloid polypeptide (hIAPP), also known as human amylin. It was reported experimentally that choline‐O‐sulfate (COS), a small organic molecule having a tertiary amino group and sulfate group, can prevent the aggregation of human amylin without providing the mechanism of the action of COS in the inhibition process. In this work, we investigate the influence of COS on the full‐length hIAPP peptide by performing 500 ns classical molecular dynamics simulations. From pure water simulation (without COS), we have identified the residues 11–20 and 23–36 that mainly participate in the fibril formation, but in the presence of 1.07 M COS these residues become totally free of β‐sheet conformation. Our results also show that the sulfate oxygen of COS directly interacts with the peptide backbone, which leads to the local disruption of peptide–peptide interaction. Moreover, the presence of favorable peptide‐COS vdW interaction energy and high coordination number of COS molecules in the first solvation shell of the peptide indicates the hydrophobic solvation of the peptide residues by COS molecules, which also play a crucial role in the prevention of β‐sheet formation. Finally, from the potential of mean force (PMFs) calculations, we observe that the free energy between two peptides is more negative in the absence of COS and with increasing concentration of COS, it becomes unfavorable significantly indicating that the peptide dimer formation is most stable in pure water, which becomes less favorable in the presence of COS. © 2019 Wiley Periodicals, Inc.
Functional suppression of Epiregulin impairs angiogenesis and aggravates left ventricular remodeling by disrupting the extracellular‐signal‐regulated kinase1/2 signaling pathway in rats after acute myocardial infarction
Authors: Cai Ying , Xie Kang‐Ling , Wu Huan‐Lin , Wu Kai
Published: May 2019

Acute myocardial infarction (AMI), a severe consequence of coronary atherosclerotic heart disease, is often associated with high mortality and morbidity. Emerging evidence have shown that the inhibition of the extracellular‐signal‐regulated kinase (ERK) signaling pathway appears to protect against AMI. Epiregulin (EREG) is an autocrine growth factor that is believed to activate the MEK/ERK signaling pathway. Therefore, the aim of the present study was to determine the expression patterns of EREG in AMI and to further study its effects on AMI induced experimentally in rats focusing on angiogenesis and left ventricular remodeling. Microarray‐based gene expression profiling of AMI was used to identify differentially expressed genes. To understand the biological significance of EREG and whether it is involved in AMI disease through the ERK1/2 signaling pathway, rats after AMI were treated with small interfering RNA (siRNA) against EREG, an ERK1/2 pathway inhibitor, PD98059, or both of them. The microarray data sets GSE66360 and GSE46395 showed that EREG was robustly induced in AMI. Both siRNA‐mediated depletion of EREG and PD98059 treatment were shown to significantly increase infarct size and left ventricular cardiomyocyte loss and enhance left ventricular remodeling. In addition, we also found that the ERK1/2 signaling pathway was inhibited following siRNA‐mediated EREG inhibition and PD98059 could enhance the effects of EREG inhibition on AMI. In conclusion, these findings highlight that the silencing of EREG inhibits angiogenesis and promotes left ventricular remodeling by disrupting the ERK1/2 signaling pathway, providing a novel therapeutic target for limiting AMI.
Chronic myeloid leukemia‐derived exosomes attenuate adipogenesis of adipose derived mesenchymal stem cells via transporting miR‐92a‐3p
Authors: Wan Zhuo , Chen Xutao , Gao Xiaotong , Dong Yan , Zhao Yingxin , Wei Mengying , Fan Wen , Yang Guodong , Liu Li
Published: May 2019

Cancer‐associated cachexia (CAC) has tremendous effects on the patient's tolerance to chemotherapy and the quality of life, especially in the advanced stages, such as the acute and terminal stages of chronic myeloid leukemia (CML). However, the underlying mechanisms and mediators remain unclear. Here, we showed that mice injected with CML‐derived exosomes had significant weight loss and great drop of body fat rate. In the meanwhile, we found that CML‐derived exosomes could be taken up by adipose tissue, and, in turn, suppressed the adipogenic ability of adipose‐derived mesenchymal stem cells (ADSCs). By RNA sequencing, miR‐92a‐3p was found highly expressed in both CML cells and the derivative exosomes. Mechanistically, miR‐92a‐3p inhibited adipogenesis of ADSCs via posttranscriptionally decreasing C/EBPα expression when transferred into the ADSCs with the exosomes, and encapsulating miR‐92a‐3p inhibitor into CML exosomes blocked the antiadipogenic effects of CML exosomes. In addition, we also found that miR‐92a‐3p was highly expressed in exosomes from some other types of cancers that cause cachexia. These results demonstrate that adipogenesis inhibition by tumor‐derived exosomes, mainly exosomal microRNAs like miR‐92a‐3p, are the main mediators for CAC.
Assessment of the expression pattern of mTOR‐associated lncRNAs and their genomic variants in the patients with breast cancer
Authors: Taherian‐Esfahani Zahra , Taheri Mohammad , Dashti Sepideh , Kholghi‐Oskooei Vahid , Geranpayeh Lobat , Ghafouri‐Fard Soudeh
Published: May 2019

The mechanistic target of rapamycin (mTOR) is a fundamental component of a signaling pathway that is involved in the pathogenesis of breast cancer via different mechanisms. This pathway is functionally linked with a number of small nucleolar RNA host genes (SNHGs). In the present project, we have searched for the expression quantitative trait loci (eQTLs) within SNHGs that are possibly involved in the pathogenesis of breast cancer. Following this in silico step, we have assessed expression levels of mTOR and four SNHGs in malignant and nonmalignant samples obtained from 80 patients with breast cancer. We also genotyped rs4615861 of SNHG3 and rs3087978 of SNHG5 in the peripheral blood of patients. SNHG12 expression was not detected in any of the assessed malignant or nonmalignant tissues. So this gene was excluded from further steps. Expression of mTOR and other three long noncoding RNAs (lncRNAs) were significantly increased in the malignant tissues compared with the nonmalignant tissues. When classifying patients into down‐/upregulation categorized based on the transcript levels of each gene in malignant tissue versus nonmalignant tissues, we noticed associations between expression of SNHG1 and stage (p = 0.03), expression of SNHG5 and grade (p = 0.05), as well as between expression of SNHG3 and history of oral contraceptive use (p = 0.04). We also detected higher levels of SNHG3 expression in estrogen receptor/progesterone receptor (ER/PR) negative tumors compared with the ER/PR positive tumors (p  = 0.003 and p = 0.01, respectively). Moreover, there was a trend toward higher expression of this lncRNA in HER2‐positive tumors compared with the HER2‐negative ones (p = 0.07). Combination of transcript levels of all genes could differentiate malignant tissues from nonmalignant tissues with the diagnostic power of 69% (p = 0.0001). The rs3087978 was associated with the expression of mTOR in malignant tissues in a way that TT and TG genotypes were associated with the higher and lower levels of expressions, respectively (p = 0.01). The current study underscores the significance of SNHGs in the pathogenesis of breast cancer.
Influence of Calcineurin Inhibitor and Sex on Mycophenolic Acid Pharmacokinetics and Adverse Effects Post–Renal Transplant
Authors: Meaney Calvin J. , Sudchada Patcharaporn , Consiglio Joseph D. , Wilding Gregory E. , Cooper Louise M. , Venuto Rocco C. , Tornatore Kathleen M.
Published: May 2019

Tacrolimus or cyclosporine is prescribed with mycophenolic acid posttransplant and contributes to interpatient variability in mycophenolic acid pharmacokinetics and response. Cyclosporine inhibits enterohepatic circulation of the metabolite mycophenolic acid glucuronide, which is not described with tacrolimus. This study investigated mycophenolic acid pharmacokinetics and adverse effects in stable renal transplant recipients and the association with calcineurin inhibitors, sex, and race. Mycophenolic acid and mycophenolic acid glucuronide area under the concentration‐time curve from 0 to 12 hours (AUC0‐12h) and apparent clearance were determined at steady state in 80 patients receiving cyclosporine with mycophenolate mofetil and 67 patients receiving tacrolimus with mycophenolate sodium. Gastrointestinal adverse effects and hematologic parameters were evaluated. Statistical models evaluated mycophenolic acid pharmacokinetics and adverse effects. Mycophenolic acid AUC0‐12h was 1.70‐fold greater with tacrolimus (68.9 ± 30.9 mg·h/L) relative to cyclosporine (40.8 ± 17.6 mg·h/L); P < .001. Target mycophenolic acid AUC0‐12h of 30–60 mg·h/L was achieved in 56.3% on cyclosporine compared with 34.3% receiving tacrolimus (P < .001). Mycophenolic acid clearance was 48% slower with tacrolimus (10.6 ± 4.7 L/h) relative to cyclosporine (20.5 ± 10.0 L/h); P < .001. Enterohepatic circulation occurred less frequently with cyclosporine (45%) compared with tacrolimus (78%); P < 0.001; with a 2.9‐fold greater mycophenolic acid glucuronide AUC0‐12h to mycophenolic acid AUC0‐12h ratio (P < .001). Race did not affect mycophenolic acid pharmacokinetics. Gastrointestinal adverse effect scores were 2.2‐fold higher with tacrolimus (P < .001) and more prominent in women (P = .017). Lymphopenia was more prevalent with tacrolimus (52.2%) than cyclosporine (22.5%); P < 0.001. Calcineurin inhibitors and sex contributed to interpatient variability in mycophenolic acid pharmacokinetics and adverse effects post–renal transplant, which could be attributed to differences in enterohepatic circulation.
3‐Color bipartite Ramsey number of cycles and paths
Authors: Bucić Matija , Letzter Shoham , Sudakov Benny
Published: May 2019

The ‐color bipartite Ramsey number of a bipartite graph is the least integer for which every ‐edge‐colored complete bipartite graph contains a monochromatic copy of . The study of bipartite Ramsey numbers was initiated, over 40 years ago, by Faudree and Schelp and, independently, by Gyárfás and Lehel, who determined the 2‐color Ramsey number of paths. In this paper we determine asymptotically the 3‐color bipartite Ramsey number of paths and (even) cycles.
The role of type 2 innate lymphoid cells in eosinophilic asthma
Authors: Salter Brittany M , Aw Michael , Sehmi Roma
Published: May 2019

Eosinophilic asthma has conventionally been proposed to be a T helper 2 driven disease but emerging evidence supports a central role of type 2 innate lymphoid cells (ILC2s). These are non-T, non-B cells that lack antigen specificity and produce more IL-5 and IL-13 than CD4+ T lymphocytes, on a cell per cell basis, in vitro. Although it is clear that ILC2s and CD4+ T cells work in concert with each other to drive type 2 immune responses, kinetic studies in allergic asthma suggest that ILC2s may act locally within the airways to “initiate” eosinophilic responses, whereas CD4+ T cells act locally and systemically to “perpetuate” eosinophilic inflammatory responses. Importantly, ILC2s are increased within the airways of severe asthmatics, with the greatest number of IL-5+IL-13+ILC2s being detected in sputum from severe asthmatics with uncontrolled eosinophilia despite high-dose steroid therapy. Although the precise relationship between ILC2s and steroid sensitivity in asthma remains unclear, controlling the activation of ILC2s within the airways may provide an effective therapeutic target for eosinophilic inflammation in airways diseases.
NLRP3 sets the table for a parasitic meal
Authors: Kumar Sushanth , Lukens John R
Published: May 2019

Discussion on new data suggesting that NLRP3-mediated activation of autophagic flux centrally contributes to the clearance of T. cruzi from macrophages.
MRI‐Based Radiomics Signature for the Preoperative Prediction of Extracapsular Extension of Prostate Cancer
Authors: Ma Shuai , Xie Huihui , Wang Huihui , Han Chao , Yang Jiejin , Lin Zhiyong , Li Yifan , He Qun , Wang Rui , Cui Yingpu , Zhang Xiaodong , Wang Xiaoying
Published: May 2019

Background

Radiomics approaches based on multiparametric MRI (mp‐MRI) have shown high accuracy in prostate cancer (PCa) management. However, there is a need to apply radiomics to the preoperative prediction of extracapsular extension (ECE).

Purpose

To develop and validate a radiomics signature to preoperatively predict the probability of ECE for patients with PCa, compared with the radiologists' interpretations.

Study Type

Retrospective.

Population

In total, 210 patients with pathology‐confirmed ECE status (101 positive, 109 negative) were enrolled.

Field Strength/Sequence

T2‐weighted imaging (T2WI), diffusion‐weighted imaging, and dynamic contrast‐enhanced imaging were performed on two 3.0T MR scanners.

Assessment

A radiomics signature was constructed to predict the probability of ECE prior to radical prostatectomy (RP). In all, 17 stable radiomics features of 1619 extracted features based on T2WI were selected. The same images were also evaluated by three radiologists. The predictive performance of the radiomics signature was validated and compared with radiologists' interpretations.

Statistical Tests

A radiomics signature was developed by a least absolute shrinkage and selection operator (LASSO) regression algorithm. Samples enrolled were randomly divided into two groups (143 for training and 67 for validation). Discrimination, calibration, and clinical usefulness were validated by analysis of the receiver operating characteristic (ROC) curve, calibration curve, and the decision curve, respectively. The predictive performance was then compared with visual assessments of three radiologists.

Results

The radiomics signature yielded an AUC of 0.902 and 0.883 in the training and validation cohort, respectively, and outperformed the visual assessment (AUC: 0.600–0.697) in the validation cohort. Pairwise comparisons demonstrated that the radiomics signature was more sensitive than the radiologists (75.00% vs. 46.88%–50.00%, all P < 0.05), but obtained comparable specificities (91.43% vs. (88.57%–94.29%); P ranged from 0.64–1.00).

Data Conclusion

A radiomics signature was developed and validated that outperformed the radiologists' visual assessments in predicting ECE status.

Level of Evidence: 4

Technical Efficacy Stage: 2

J. Magn. Reson. Imaging 2019;50:1914–1925.
Bi‐Cruciate Retaining Total Knee Arthroplasty Does Not Restore Native Tibiofemoral Articular Contact Kinematics During Gait
Authors: Tsai Tsung‐Yuan , Liow Ming Han Lincoln , Li Guoan , Arauz Paul , Peng Yun , Klemt Christian , Kwon Young‐Min
Published: May 2019

Bi‐cruciate retaining (BCR) total knee arthroplasty (TKA) design preserves both anterior and posterior cruciate ligaments with the potential to restore normal posterior femoral rollback and joint kinematics. Abnormal knee kinematics and “paradoxical” anterior femoral translation in conventional TKA designs have been suggested as potential causes of patient dissatisfaction. However, there is a paucity of data on the in vivo kinematics and articular contact behavior of BCR‐TKA. This study aimed to investigate in vivo kinematics, articular contact position, and pivot point location of the BCR‐TKA during gait. In vivo kinematics of 30 patients with unilateral BCR‐TKA during treadmill walking was determined using validated dual fluoroscopic imaging tracking technique. The BCR‐TKA exhibited less extension than the normal healthy knee between heel strike and 48% of gait cycle. Although the average external rotation trend observed for BCR TKA was similar to the normal healthy knee, the range of motion was not fully comparable. The lowest point of the medial condyle showed longer anteroposterior translation excursion than the lateral condyle, leading to a lateral‐pivoting pattern in 60% of BCR TKA patients during stance phase. BCR‐TKA demonstrated no statistical significant differences in anterior–posterior translation as well as varus rotation, when compared to normal healthy knees during the stance phase. However, sagittal plane motion and tibiofemoral articular contact characteristics including pivoting patterns were not fully restored in BCR TKA patients during gait, suggesting that BCR TKA does not restore native tibiofemoral articular contact kinematics. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1929–1937, 2019
Monitoring ecosystem service change in the City of Shenzhen by the use of high‐resolution remotely sensed imagery and deep learning
Authors: Huang Xin , Han Xiaopeng , Ma Song , Lin Tianjia , Gong Jianya
Published: May 2019

Information concerning land‐use change is imperative for improving conservation policies that promote sustainable land development. However, to date, most of the previous studies have largely focused on the use of coarse‐ or moderate‐resolution data, with which it may not be possible to identify the land‐use classes in urban environments. Due to the improved spatial details, high‐resolution (HR) remote sensing imagery provides us with an opportunity for the semantic interpretation of urban landscapes. Therefore, in this study, we took the City of Shenzhen (1997 km2) in China as an example to assess the detailed land‐use change and its effect on ecosystem services (ESs), based on HR satellite data from 2005 to 2017. In particular, deep learning was used to obtain accurate land‐use maps, because this technique is able to model the hierarchical representations of features and can thus effectively characterize urban scenes. The results revealed the following findings: (a) The overall accuracy of the proposed approach was 96.9% and 97.1% for 2005 and 2017, respectively, outperforming state‐of‐the‐art semantic classification models; (b) residential and commercial areas in Shenzhen increased dramatically over the study period by 10,416 and 9,168 ha, at the expense of ecological land; (c) supply capacity of the ecosystem decreased by 13.7%, but demand for ESs showed an increase of 23.5%. By courtesy of HR images, detailed land‐use changes and the associated ESs can be monitored, which facilitates the in‐depth understanding of urban environmental systems.
Scaled boundary finite element method for compressible and nearly incompressible elasticity over arbitrary polytopes
Authors: Aladurthi Lakshmi Narasimha Pramod , Natarajan Sundararajan , Ooi Ean Tat , Song Chongmin
Published: May 2019

In this paper, a purely displacement‐based formulation is presented within the framework of the scaled boundary finite element method to model compressible and nearly incompressible materials. A selective reduced integration technique combined with an analytical treatment in the nearly incompressible limit is employed to alleviate volumetric locking. The stiffness matrix is computed by solving the scaled boundary finite element equation. The salient feature of the proposed technique is that it neither requires a stabilization parameter nor adds additional degrees of freedom to handle volumetric locking. The efficiency and the robustness of the proposed approach is demonstrated by solving various numerical examples in two and three dimensions.