bluuebunny/crossref_metadata_2025 huggingface dataset:
Authenticating On-Body Backscatter by Exploiting Propagation Signatures
Authors: Luo Zhiqing , Wang Wei , Xiao Jiang , Huang Qianyi , jiang Tao , Zhang Qian
Published: September 2018

The vision of battery-free communication has made backscatter a compelling technology for on-body wearable and implantable devices. Recent advances have facilitated the communication between backscatter tags and on-body smart devices. These studies have focused on the communication dimension, while the security dimension remains vulnerable. It has been demonstrated that wireless connectivity can be exploited to send unauthorized commands or fake messages that result in device malfunctioning. The key challenge in defending these attacks stems from the minimalist design in backscatter. Thus, in this paper, we explore the feasibility of authenticating an on-body backscatter tag without modifying its signal or protocol. We present SecureScatter, a physical-layer solution that delegates the security of backscatter to an on-body smart device. To this end, we profile the on-body propagation paths of backscatter links, and construct highly sensitive propagation signatures to identify on-body backscatter links. We implement our design in a software radio and evaluate it with different backscatter tags that work at 2.4 GHz and 900 MHz. Results show that our system can identify on-body devices at 93.23% average true positive rate and 3.18% average false positive rate.
Extreme Adaptive Optics
Authors: Guyon Olivier
Published: September 2018

Over the last two decades, several thousand exoplanets have been identified, and their study has become a high scientific priority. Direct imaging of nearby exoplanets and the circumstellar disks in which they form and evolve is challenging due to the high contrast ratio and small angular separation relative to the central star. Exoplanets are typically within 1 arcsec of, and between 4 and 10 orders of magnitude fainter than, the stars they orbit. To meet these challenges, ground-based telescopes must be equipped with extreme adaptive optics (ExAO) systems optimized to acquire high-contrast images of the immediate surrounding of nearby bright stars. Current ExAO systems have the sensitivity to image thermal emission from young massive planets in near-IR, while future systems deployed on Giant Segmented Mirror Telescopes will image starlight reflected by lower-mass rocky planets. Thanks to rapid progress in optical coronagraphy, wavefront control, and data analysis techniques, direct imaging and spectroscopic characterization of habitable exoplanets will be within reach of the next generation of large ground-based telescopes.
The Multiple Levels of Mitonuclear Coregulation
Authors: Isaac R. Stefan , McShane Erik , Churchman L. Stirling
Published: September 2018

Together, the nuclear and mitochondrial genomes encode the oxidative phosphorylation (OXPHOS) complexes that reside in the mitochondrial inner membrane and enable aerobic life. Mitochondria maintain their own genome that is expressed and regulated by factors distinct from their nuclear counterparts. For optimal function, the cell must ensure proper stoichiometric production of OXPHOS subunits by coordinating two physically separated and evolutionarily distinct gene expression systems. Here, we review our current understanding of mitonuclear coregulation primarily at the levels of transcription and translation. Additionally, we discuss other levels of coregulation that may exist but remain largely unexplored, including mRNA modification and stability and posttranslational protein degradation.
The Water Mass Transformation Framework for Ocean Physics and Biogeochemistry
Authors: Groeskamp Sjoerd , Griffies Stephen M. , Iudicone Daniele , Marsh Robert , Nurser A.J. George , Zika Jan D.
Published: September 2018

The water mass transformation (WMT) framework weaves together circulation, thermodynamics, and biogeochemistry into a description of the ocean that complements traditional Eulerian and Lagrangian methods. In so doing, a WMT analysis renders novel insights and predictive capabilities for studies of ocean physics and biogeochemistry. In this review, we describe fundamentals of the WMT framework and illustrate its practical analysis capabilities. We show how it provides a robust methodology to characterize and quantify the impact of physical processes on buoyancy and other thermodynamic fields. We also detail how to extend WMT to insightful analysis of biogeochemical cycles.
Computer Games in Education
Authors: Mayer Richard E.
Published: September 2018

Visionaries offer strong claims for the educational benefits of computer games, but there is a need to test those claims with rigorous scientific research and ground them in evidence-based theories of how people learn. Three genres of game research are ( a) value-added research, which compares the learning outcomes of groups that learn academic material from playing a base version of a game to the outcomes of those playing the same game with one feature added; ( b) cognitive consequences research, which compares improvements in cognitive skills of groups that play an off-the-shelf game to the skill improvements of those who engage in a control activity; and ( c) media comparison research, which compares the learning outcomes of groups that learn academic material in a game to the outcomes of those who learn with conventional media. Value-added research suggests five promising features to include in educational computer games: modality, personalization, pretraining, coaching, and self-explanation. Cognitive consequences research suggests two promising approaches to cognitive training with computer games: using first-person shooter games to train perceptual attention skills and using spatial puzzle games to train two-dimensional mental rotation skills. Media comparison research suggests three promising areas where games may be more effective than conventional media: science, mathematics, and second-language learning. Future research is needed to pinpoint the cognitive, motivational, affective, and social processes that underlie learning with educational computer games.
Neuropathology as a consequence of neonatal ventilation in premature growth-restricted lambs
Authors: Malhotra Atul , Castillo-Melendez Margie , Allison Beth J. , Sutherland Amy E. , Nitsos Ilias , Pham Yen , Alves de Alencar Rocha Anna K. , Fahey Michael C. , Polglase Graeme R. , Jenkin Graham , Miller Suzanne L.
Published: September 2018

Fetal growth restriction (FGR) and prematurity are associated with high risk of brain injury and long-term neurological deficits. FGR infants born preterm are commonly exposed to mechanical ventilation, but it is not known whether ventilation differentially induces brain pathology in FGR infants compared with appropriate for gestational age (AGA) infants. We investigated markers of neuropathology in moderate- to late-preterm FGR lambs, compared with AGA lambs, delivered by caesarean birth and ventilated under standard neonatal conditions for 24 h. FGR was induced by single umbilical artery ligation in fetal sheep at 88-day gestation (term, 150 days). At 125-day gestation, FGR and AGA lambs were delivered, dried, intubated, and commenced on noninjurious ventilation, with surfactant administration at 10 min. A group of unventilated FGR and AGA lambs at the same gestation was also examined. Over 24 h, circulating pH, Po2, and lactate levels were similar between groups. Ventilated FGR lambs had lower cerebral blood flow compared with AGA lambs ( P = 0.01). The brain of ventilated FGR lambs showed neuropathology compared with unventilated FGR, and unventilated and ventilated AGA lambs, with increased apoptosis (caspase-3), blood-brain barrier dysfunction (albumin extravasation), activated microglia (Iba-1), and increased expression of cellular oxidative stress (4-hydroxynonenal). The neuropathologies seen in the ventilated FGR brain were most pronounced in the periventricular and subcortical white matter but also evident in the subventricular zone, cortical gray matter, and hippocampus. Ventilation of preterm FGR lambs increased brain injury compared with AGA preterm lambs and unventilated FGR lambs, mediated via increased vascular permeability, neuroinflammation and oxidative stress.
Proteomic approaches in kidney disease biomarker discovery
Authors: Fenton Robert A.
Published: September 2018

Biomarkers have the potential to greatly facilitate diagnosis and treatment of patients with various forms of kidney disease. State-of-the-art mass spectrometry-based methods possess the capability, on a proteome scale and in an unbiased manner, to detect alterations in protein abundances and/or posttranslational modifications in plasma, urine, or tissue. Such approaches can provide a large, unbiased database to facilitate identification of potential biomarkers. In the diagnosis of kidney diseases, urine is usually a more favorable specimen than plasma and kidney tissue due to its noninvasive collection and simplicity of processing. However, whether analysis of proteins in urine faithfully reflects their changes in the kidney tissue remains unclear. The use of proteomics to analyze kidney tissue samples collected during late-stage kidney diseases has also recently gathered pace. The goal of this minireview is to provide an overview of the proteomic technologies currently applied to studies of kidney and their limitations, present existing kidney and urine proteome databases, and highlight a few applications of such approaches in kidney disease biomarker discovery.
Single-cell responses to three-dimensional structure in a functionally defined patch in macaque area TEO
Authors: Alizadeh Amir-Mohammad , Van Dromme Ilse C. , Janssen Peter
Published: September 2018

Both dorsal and ventral visual pathways harbor several areas sensitive to gradients of binocular disparity (i.e., higher-order disparity). Although a wealth of information exists about disparity processing in early visual (V1, V2, and V3) and end-stage areas, TE in the ventral stream, and the anterior intraparietal area (AIP) in the dorsal stream, little is known about midlevel area TEO in the ventral pathway. We recorded single-unit responses to disparity-defined curved stimuli in a functional magnetic resonance imaging (fMRI) activation elicited by curved surfaces compared with flat surfaces in the macaque area TEO. This fMRI activation contained a small proportion of disparity-selective neurons, with very few of them second-order disparity selective. Overall, this population of TEO neurons did not preserve its three-dimensional structure selectivity across positions in depth, indicating a lack of higher-order disparity selectivity, but showed stronger responses to flat surfaces than to curved surfaces, as predicted by the fMRI experiment. The receptive fields of the responsive TEO cells were relatively small and generally foveal. A linear support vector machine classifier showed that this population of disparity-selective TEO neurons contains reliable information about the sign of curvature and the position in depth of the stimulus.

NEW & NOTEWORTHY We recorded in a part of the macaque area TEO that is activated more by curved surfaces than by flat surfaces at different disparities using the same stimuli. In contrast to previous studies, this functional magnetic resonance imaging-defined patch did not contain a large number of higher-order disparity-selective neurons. However, a linear support vector machine could reliably classify both the sign of the disparity gradient and the position in depth of the stimuli.
Aldosterone and Mineralocorticoid Receptor System in Cardiovascular Physiology and Pathophysiology
Authors: Cannavo Alessandro , Bencivenga Leonardo , Liccardo Daniela , Elia Andrea , Marzano Federica , Gambino Giuseppina , D’Amico Maria Loreta , Perna Claudia , Ferrara Nicola , Rengo Giuseppe , Paolocci Nazareno
Published: September 2018

The mineralocorticoid hormone aldosterone (Aldo) has been intensively studied for its ability to influence both the physiology and pathophysiology of the cardiovascular system. Indeed, although research on Aldo actions for decades has mainly focused on its effects in the kidney, several lines of evidence have now demonstrated that this hormone exerts disparate extrarenal adverse effects, especially in the circulatory system. Accordingly, in the last lusters, a number of studies in preclinical models (in vitro and in vivo) and in humans have established that Aldo, following the interaction with its receptor—the mineralocorticoid receptor (MR)—is able to activate specific intracellular genomic and nongenomic pathways, thus regulating the homeostasis of the cardiovascular system. Importantly, through this mechanism of action, this hormone becomes a crucial regulator of the function and growth of different types of cells, including fibroblasts, cardiomyocytes, and vascular cells. For this main reason, it is plausible that when Aldo is present at high levels in the blood, it profoundly modifies the physiology of these cells, therefore being at the foundation of several cardiovascular disorders, such as heart failure (HF). On these grounds, in this review, we will provide an updated account on the current knowledge concerning Aldo activity in the cardiovascular system and the most recent preclinical studies and clinical trials designed to test better approaches able to counter the hyperactivity of the Aldo/MR signaling pathway in the setting of cardiovascular diseases.
Cost-Effectiveness Analysis for the Treatment of Hyperphosphatemia in Predialysis Patients: Calcium-Based versus Noncalcium-Based Phosphate Binders
Authors: Goh B. L. , Soraya A. , Goh A. , Ang K. L.
Published: September 2018

Background. Hyperphosphatemia in chronic kidney disease (CKD) patients is often treated with calcium carbonate (CaCO3) despite the fact that CaCO3 is associated with increased calcium load and potentially increased cardiovascular risk. Alternative treatments with noncalcium-based phosphate binders do not increase the calcium load but are more costly. This study analyzes the cost-effectiveness of sevelamer versus CaCO3 for the treatment of hyperphosphatemia in stage III-V predialysis CKD patients in Malaysia. Methods. A Markov decision model was adapted to simulate a hypothetical cohort of CKD patients requiring treatment for hyperphosphatemia. Survival was estimated by using efficacy data from the INDEPENDENT-CKD clinical trial. Cost data was obtained from Malaysian studies while health state utilities were derived from literature. Analysis was performed over lifetime duration from the perspective of the Ministry of Health Malaysia with 2013 as reference year. Results. In the base case analysis, sevelamer treatment gained 6.37 life years (5.27 QALY) compared to 4.25 life years (3.54 QALY) with CaCO3. At 3% discount, lifetime costs were RM159,901 ($48,750) and RM77,139 ($23,518) on sevelamer and CaCO3, respectively. Incremental cost-effectiveness (ICER) of sevelamer versus CaCO3 was RM47,679 ($14,536) per QALY, which is less than the WHO threshold of three times GDP per capita (RM99,395) per QALY. Sensitivity analyses, both using scenario sensitivity analysis and probabilistic sensitivity analysis, showed the result to be robust. Conclusions. Our study finds that sevelamer is potentially cost-effective compared to CaCO3, for the treatment of hyperphosphatemia in predialysis CKD III-V. We propose that sevelamer should be an option in the treatment of Malaysian predialysis patients with hyperphosphatemia, particularly those with high calcium load.
Effect of Post-Cam Design for Normal Knee Joint Kinematic, Ligament, and Quadriceps Force in Patient-Specific Posterior-Stabilized Total Knee Arthroplasty by Using Finite Element Analysis
Authors: Koh Yong-Gon , Son Juhyun , Kwon Oh-Ryong , Kwon Sae Kwang , Kang Kyoung-Tak
Published: September 2018

The purpose of this study is to investigate post-cam design via finite element analysis to evaluate the most normal-like knee mechanics. We developed five different three-dimensional computational models of customized posterior-stabilized (PS) total knee arthroplasty (TKA) involving identical surfaces with the exception of the post-cam geometry. They include flat-and-flat, curve-and-curve (concave), curve-and-curve (concave and convex), helical, and asymmetrical post-cam designs. We compared the kinematics, collateral ligament force, and quadriceps force in the customized PS-TKA with five different post-cam designs and conventional PS-TKA to those of a normal knee under deep-knee-bend conditions. The results indicated that femoral rollback in curve-and-curve (concave) post-cam design exhibited the most normal-like knee kinematics, although the internal rotation was the closest to that of a normal knee in the helical post-cam design. The curve-and-curve (concave) post-cam design showed a femoral rollback of 4.4 mm less than the normal knee, and the helical post-cam design showed an internal rotation of 5.6° less than the normal knee. Lateral collateral ligament and quadriceps forces in curve-and-curve (concave) post-cam design, and medial collateral ligament forces in helical post-cam design were the closest to that of a normal knee. The curve-and-curve (concave) post-cam design showed 20% greater lateral collateral ligament force than normal knee, and helical post-cam design showed medial collateral ligament force 14% greater than normal knee. The results revealed the variation in each design that provided the most normal-like biomechanical effect. The present biomechanical data are expected to provide useful information to improve post-cam design to restore normal-like knee mechanics in customized PS-TKA.
Antioxidant and Neuroprotective Properties of Eugenia dysenterica Leaves
Authors: Thomaz Douglas Vieira , Peixoto Luanna Fernandes , de Oliveira Thiago Sardinha , Fajemiroye James Oluwagbamigbe , da Silva Neri Hiasmin Franciely , Xavier Carlos Henrique , Costa Elson Alves , dos Santos Fernanda Cristina Alcantara , de Souza Gil Eric , Ghedini Paulo César
Published: September 2018

Eugenia dysenterica ex DC Mart. (Myrtaceae), popularly known as “cagaita,” is a Brazilian plant rich in polyphenols and other antioxidant compounds. Aiming to evaluate the potential use of cagaita in pathologies involving oxidative stress, such as neurodegenerative disorders, this study investigated its antioxidant potential and neuroprotective effect. Electrochemical approaches and aluminium‐induced neurotoxicity were used to determine respectively in vitro and in vivo antioxidant properties of cagaita. Voltammetric experiments were carried out in a three‐electrode system, whose working electrode consisted of glassy carbon. Male Swiss mice were administered with AlCl3 orally at a dose of 100 mg/kg/day and with cagaita leaf hydroalcoholic extract (CHE) at doses of 10, 100, and 300 mg/kg/day. The redox behavior of CHE presented similar features to that of quercetin, a widely known antioxidant standard. CHE prevented mouse memory impairment which resulted from aluminium intake. In addition, biochemical markers of oxidative stress (catalase, superoxide dismutase activity, and lipid peroxidation) were normalized by CHE treatment. The potential of CHE to prevent aluminium‐induced neurotoxicity was reflected at the microscopic level, through the decrease of the number of eosinophilic necrosis phenotypes seen in treated groups. Moreover, the protective effect of CHE was similar to that of quercetin, which was taken as the standard. These findings showed that the CHE of cagaita leaves has a potential to protect the brain against oxidative‐induced brain damage.
Clostridium difficilePeritonitis: An Emerging Infection in Peritoneal Dialysis Patients
Authors: Chaughtai Saira , Gandhi Bhavika , Chaughtai Zeeshan , Tarina Dana , Hossain Mohammad A. , Asif Arif
Published: September 2018

Recently, the incidence ofClostridium difficile-(C. difficile-) associated infection has increased significantly in hospital and ambulatory care settings in parallel to the increasing use of inappropriate antibiotics. According to the CDC, approximately 83,000 patients who developedC.difficileexperienced at least one recurrence and 29,000 died within 30 days of the initial diagnosis. Patients on dialysis (particularly peritoneal dialysis) are predisposed to this infection due to an inherent immunocompromised state and transmural translocation of the bacteria due to the close association of gastrointestinal tract and peritoneal cavity.C.difficileinfection in peritoneal dialysis patients is problematic from two aspects: (1) because dialysis patients are immunocompromised, the infection can be devastating and (2) infection directly interferes with their renal replacement therapy. In this article, we present a case of peritoneal dialysis (PD)-related peritonitis caused byC. difficile-associated diarrhea and colitis. In this patient, the peritonitis was caused by transmural translocation of the enteric bacteria. While the peritoneal fluid culture did not grow the organism (possibly because of prior empiric broad-spectrum antibiotics use), the positive PCR on stool analysis suggestedC. difficile-related peritonitis, along with the rapid clinical improvement induced byC.difficile-directed therapy (metronidazole) and discontinuation of broad-spectrum antibiotics. The patient was successfully treated with metronidazole without PD catheter removal.C.difficileinfection is common and frequently internists are the first contact with such patients. This article highlightsC.difficileinfection in a PD patient and raises awareness of this infection in dialysis patients.
Damage Diagnosis in 3D Structures Using a Novel Hybrid Multiobjective Optimization and FE Model Updating Framework
Authors: Alkayem Nizar Faisal , Cao Maosen , Ragulskis Minvydas
Published: September 2018

Structural damage detection is a well‐known engineering inverse problem in which the extracting of damage information from the dynamic responses of the structure is considered a complex problem. Within that area, the damage tracking in 3D structures is evaluated as a more complex and difficult task. Swarm intelligence and evolutionary algorithms (EAs) can be well adapted for solving the problem. For this purpose, a hybrid elitist‐guided search combining a multiobjective particle swarm optimization (MOPSO), Lévy flights (LFs), and the technique for the order of preference by similarity to ideal solution (TOPSIS) is evolved in this work. Modal characteristics are employed to develop the objective function by considering two subobjectives, namely, modal strain energy (MSTE) and mode shape (MS) subobjectives. The proposed framework is tested using a well‐known benchmark model. The overall strong performance of the suggested method is maintained even under noisy conditions and in the case of incomplete mode shapes.
Plexin C1 Marks Liver Cancer Cells with Epithelial Phenotype and Is Overexpressed in Hepatocellular Carcinoma
Authors: Odabas Gorkem , Cetin Metin , Turhal Serdar , Baloglu Huseyin , Sayan A. Emre , Yagci Tamer
Published: September 2018

Background and Aims. Hepatocellular carcinoma is an aggressive malignancy of the liver and is ranked as the sixth most common cancer worldwide. There is still room for novel markers to improve the diagnosis and monitoring of HCC. Our observations in cancer databases that PLXNC1 is upregulated in HCC led us to investigate the expression profile of Plexin C1 mRNA and protein in HCC cell lines and tissues. Methods. A recombinant protein encompassing part of the extracellular domain of Plexin C1 was used as an antigen for monoclonal antibody development. Transcript and protein levels of Plexin C1 in HCC cell lines were determined by RT-qPCR and Western blotting, respectively. In vivo evaluation of Plexin C1 expression in HCC tissues was accomplished by immunohistochemistry studies in tissue microarrays. Results. A monoclonal antibody, clone PE4, specific to Plexin C1, was generated. In silico and in vitro analyses revealed a Plexin C1-based clustering of well-differentiated HCC cell lines. Staining of HCC and nontumoral liver tissues with PE4 showed a membrane-localized overexpression of Plexin C1 in tumors (p=0.0118). In addition, this expression was correlated with the histological grades of HCC cases. Conclusions. Plexin C1 distinguishes HCC cells of epithelial characteristics from those with the mesenchymal phenotype. Compared to the nontumoral liver, HCC tissues significantly overexpress Plexin C1. The newly generated PE4 antibody can be evaluated in larger HCC cohorts and might be exploited for the examination of Plexin C1 expression pattern in other epithelial malignancies.
Nesfatin-1/Nucleobindin-2 Is a Potent Prognostic Marker and Enhances Cell Proliferation, Migration, and Invasion in Bladder Cancer
Authors: Liu Guang-Ming , Xu Zi-Qiang , Ma Hong-Shun
Published: September 2018

In recent researches, high expression of nesfatin-1/nucleobindin-2 (NUCB2) is linked to poor prognosis in prostate and colon cancer due to the enhancement in proliferation, migration, and invasion. However, the role of nesfatin-1 in bladder cancer is not clear. In this study, we examined the expression of NUCB2 in bladder cancer using immunohistochemistry and observed that its high expression was associated with recurrence and metastasis. In addition, the transwell assay and wound healing assay showed that cell migration and invasion were decreased with NUCB2 knockdown in T24 and 5637 cells. In vivo, tumor growth and metastasis were inhibited with shRNA treatment in T24 cells. Those results showed that NUCB2 played an important role in bladder cancer and could be considered a potent prognostic factor in bladder cancer.
Performance Assessment of the Mortality in Emergency Department Sepsis Score, Modified Early Warning Score, Rapid Emergency Medicine Score, and Rapid Acute Physiology Score in Predicting Survival Outcomes of Adult Renal Abscess Patients in the Emergency Department
Authors: Chang Su-Han , Hsieh Chiao-Hsuan , Weng Yi-Ming , Hsieh Ming-Shun , Goh Zhong Ning Leonard , Chen Hsien-Yi , Chang Tung , Ng Chip-Jin , Seak Joanna Chen-Yeen , Seak Chen-Ken , Seak Chen-June
Published: September 2018

Background. Renal abscess is a relatively uncommon yet debilitating and potentially fatal disease. There is no clearly defined, objective risk stratification tool available for emergency physicians’ and surgeons’ use in the emergency department (ED) to quickly determine the appropriate management strategy for these patients, despite early intervention having a beneficial impact on survival outcomes. Objective. This case control study evaluates the performance of Mortality in Emergency Department Sepsis Score (MEDS), Modified Early Warning Score (MEWS), Rapid Emergency Medicine Score (REMS), and Rapid Acute Physiology Score (RAPS) in predicting risk of mortality in ED adult patients with renal abscess. This will help emergency physicians, surgeons, and intensivists expedite the time-sensitive decision-making process. Methods. Data from 152 adult patients admitted to the EDs of two training and research hospitals who had undergone a contrast-enhanced computed tomography scan of the abdomen and was diagnosed with renal abscess from January 2011 to December 2015 were analyzed, with the corresponding MEDS, MEWS, REMS, RAPS, and mortality risks calculated. Ability to predict patient mortality was assessed via receiver operating curve analysis and calibration analysis. Results. MEDS was found to be the best performing physiologic scoring system, with sensitivity, specificity, and accuracy of 87.50%, 88.89%, and 88.82%, respectively. Area under receiver operating characteristic curve (AUROC) value was 0.9440, and negative predictive value was 99.22% with a cutoff of 9 points. Conclusion. Our study is the largest of its kind in examining ED patients with renal abscess. MEDS has been demonstrated to be superior to MEWS, REMS, and RAPS in predicting mortality for this patient population. We recommend its use for evaluation of disease severity and risk stratification in these patients, to expedite identification of critically ill patients requiring urgent intervention.
Gene Coexpression Network Comparison via Persistent Homology
Authors: Duman Ali Nabi , Pirim Harun
Published: September 2018

Persistent homology, a topological data analysis (TDA) method, is applied to microarray data sets. Although there are a few papers referring to TDA methods in microarray analysis, the usage of persistent homology in the comparison of several weighted gene coexpression networks (WGCN) was not employed before to the very best of our knowledge. We calculate the persistent homology of weighted networks constructed from 38 Arabidopsis microarray data sets to test the relevance and the success of this approach in distinguishing the stress factors. We quantify multiscale topological features of each network using persistent homology and apply a hierarchical clustering algorithm to the distance matrix whose entries are pairwise bottleneck distance between the networks. The immunoresponses to different stress factors are distinguishable by our method. The networks of similar immunoresponses are found to be close with respect to bottleneck distance indicating the similar topological features of WGCNs. This computationally efficient technique analyzing networks provides a quick test for advanced studies.
Tobacco Carcinogen–Induced Production of GM-CSF Activates CREB to Promote Pancreatic Cancer
Authors: Srinivasan Supriya , Totiger Tulasigeri , Shi Chanjuan , Castellanos Jason , Lamichhane Purushottam , Dosch Austin R. , Messaggio Fanuel , Kashikar Nilesh , Honnenahally Kumaraswamy , Ban Yuguang , Merchant Nipun B. , VanSaun Michael , Nagathihalli Nagaraj S.
Published: September 2018

Although smoking is a significant risk factor for pancreatic ductal adenocarcinoma (PDAC), the molecular mechanisms underlying PDAC development and progression in smokers are still unclear. Here, we show the role of cyclic AMP response element-binding protein (CREB) in the pathogenesis of smoking-induced PDAC. Smokers had significantly higher levels of activated CREB when compared with nonsmokers. Cell lines derived from normal pancreas and pancreatic intraepithelial neoplasm (PanIN) exhibited low baseline pCREB levels compared with PDAC cell lines. Furthermore, elevated CREB expression correlated with reduced survival in patients with PDAC. Depletion of CREB significantly reduced tumor burden after tobacco-specific nitrosamine 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) treatment, suggesting a CREB-dependent contribution to PDAC growth and progression in smokers. Conversely, NNK accelerated PanIN lesion and PDAC formation via GM-CSF–mediated activation of CREB in a PDAC mouse model. CREB inhibition (CREBi) in mice more effectively reduced primary tumor burden compared with control or GM-CSF blockade alone following NNK exposure. GM-CSF played a role in the recruitment of tumor-associated macrophages (TAM) and regulatory T cell (Treg) expansion and promotion, whereas CREBi significantly reduced TAM and Treg populations in NNK-exposed mice. Overall, these results suggest that NNK exposure leads to activation of CREB through GM-CSF, promoting inflammatory and Akt pathways. Direct inhibition of CREB, but not GM-CSF, effectively abrogates these effects and inhibits tumor progression, offering a viable therapeutic strategy for patients with PDAC.

Significance: These findings identify GM-CSF-induced CREB as a driver of pancreatic cancer in smokers and demonstrate the therapeutic potential of targeting CREB to reduce PDAC tumor growth.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/21/6146/F1.large.jpg. Cancer Res; 78(21); 6146–58. ©2018 AACR.
Head-to-Head Comparison of Modified Laparoscopic Pyeloplasty and Robot-Assisted Pyeloplasty for Ureteropelvic Junction Obstruction in China
Authors: Hong Peng , Ding Guangpu , Zhu Dongdong , Yang Kunlin , Pan Jinhong , Li Xuesong , Chen Zhipeng , Zhang Lei , Tang Qi , Hao Han , Zhou Zhansong , Zhou Liqun
Published: September 2018

Objective: To compare the outcomes of modified laparoscopic pyeloplasty (LP) and robot-assisted pyeloplasty (RLP) for ureteropelvic junction obstruction (UPJO) in China patients. Materials and Methods: We retrospectively reviewed the medical records of patients who underwent modified LP and RLP using a transperitoneal laparoscopic approach at 2 different medical institutions between October 2009 and November 2017. Results: Seventy-six patients underwent modified LP and 140 patients underwent RLP. No open conversion occurred. The mean operative time of RLP was shorter than that of modified LP (p = 0.042). For UPJO concomitant with renal calculi, there was no difference in operative time between 2 groups (p = 0.656). With RLP, the operative time for UPJO concomitant with horseshoe was shorter (p = 0.011). In terms of complication rate, there was no significant difference between 2 groups (p = 0.596). The postoperative hospital stay for modified LP was shorter than that for RLP (p < 0.05). The mean follow-up time for modified LP and RLP was 31.79 months and 10.85 months respectively (p < 0.05). The success rate was 96.05 and 97.86% for modified LP and RLP, respectively (p = 0.736). Conclusions: Modified LP and RLP are safe and efficient treatment for UPJO with similar success rates.
The Pubic Diastasis Measurement, a Key Element for the Diagnosis, Management, and Prognosis of the Bladder Exstrophy
Authors: Antomarchi Julie , Moeglin Daniel , Laurichesse Hélène , Combourieu Danièle , Bigi Nicole , Maisonneuve Emeline , Legac Pascale , Althuser Marc , Delotte Jérome , Jouannic Jean-Marie , Bongain André
Published: September 2018

Objective: To demonstrate the feasibility of measuring the fetal pubic diastasis (PD) distance on antenatal ultrasound in normal fetuses and to compare it to fetuses with bladder exstrophy. Methods: Firstly, a prospective multicentric study was conducted to determine the feasibility of the PD ultrasound measurement during the second half of pregnancy. Secondly, data from a single center were used to develop a nomogram for PD values in normal fetuses. Thirdly, retrospective PD measurements were collected from fetuses with bladder exstrophy, diagnosed in seven French Multidisciplinary Centers for Prenatal Diagnosis (MCPDs). Results: Operators from several MCPDs examined 868 fetuses and found that overall PD ultrasound measurement was feasible in 71% of cases and that the ossification of pubic points increased to be always visible from 27 weeks of gestation onward. Performed in a single center by a referring operator on 1,539 fetuses, the feasibility reached 94.74%. Both set of measurements were concordant (mean PD distance value of 5.42 ± 1.8 mm). Interestingly, all 23 fetuses with bladder exstrophy showed a significantly larger PD distance (mean 15.74 ± 3.9 mm). Conclusion: PD measurement in the fetus is feasible and reliable in the second half of gestation and can be used to support the antenatal diagnosis of bladder exstrophy with PD values exceeding 10 mm.
A Kinematic Analysis of Coarticulation Effects on Schwa
Authors: Kim Yunjung , Coalson Geoffrey , Berry Jeffrey
Published: September 2018

Purpose: This study investigated coarticulatory effects on schwa. The purpose was to establish a viable phonetic environment and analysis for future studies of coarticulation, particularly in motor speech disorders. Method: Seven female adults read 2 phrases containing 4 target words in a CVC structure embedded in the carrier phrases, “Put a CVC here” and “Get CVC a puppy.” A 3D electromagnetic articulography system was used to track lingual movements during schwa production. Two indices of coarticulation were employed: (a) tongue position difference between the temporal midpoint (grand mean of each speaker) and the onset/offset of schwa immediately following or preceding a transconsonantal vowel and (b) tongue position differences between the grand mean of each speaker and each utterance repetition, both measured at the temporal midpoint of the schwa. Results: Both measures indicated that schwa is significantly influenced by transconsonantal corner vowels. The magnitude of coarticulation effects on schwa varied among the 4 corner vowels in the order of /i/>/ɑ/ = /æ/>/u/. Conclusion: Findings support the use of schwa in future studies when examining coarticulatory effects in people with and without motor speech disorders. Some methodological issues such as selection of measurement points and speech stimuli are also discussed.
A Survey of Knowledge and Beliefs regarding Autism in Speech-Language Pathologists in India
Authors: Mendonsa Lara Emilia , Tiwari Shivani
Published: September 2018

Background: Speech-language pathologists (SLPs) are significant team members in the identification, assessment, and rehabilitation of children with autism. With a recent upsurge in the number of children with autism, there arises a need to examine SLPs knowledge and skills in identification and intervention of children with autism. Aim: The present study is, thus, a novel attempt aimed to investigate knowledge and belief of SLPs in the assessment and intervention of autism in the Indian context. Method: A total of 219 SLPs participated in a web-based online survey. The study adopted a cross-sectional observational research design. Results: The results of the study showed around 43% of the total SLPs obtained a good score on the knowledge section and 27% received a positive rating for the belief section. Additionally, factors like “educational qualification,” “duration of clinical experience,” and “caseload of children with autism” influenced knowledge and beliefs of SLPs about autism. Conclusion: The study results indicate that SLPs practicing in India show average and below average scores on a questionnaire assessing knowledge and beliefs regarding autism. The study findings have implications towards developing improved training and course structure related to assessment and intervention of children with autism for SLPs practicing in India.
Non-Antibiotic Herbal Therapy (BNO 1045) versus Antibiotic Therapy (Fosfomycin Trometamol) for the Treatment of Acute Lower Uncomplicated Urinary Tract Infections in Women: A Double-Blind, Parallel-Group, Randomized, Multicentre, Non-Inferiority Phase III Trial
Authors: Wagenlehner Florian M. , Abramov-Sommariva Dimitri , Höller Martina , Steindl Hubert , Naber Kurt G.
Published: September 2018

Introduction: This randomized, controlled, Phase III non-inferiority clinical trial aimed to determine whether herbal therapy with Canephron® N (BNO 1045) is non-inferior to fosfomycin trometamol (FT) in treating acute lower uncomplicated urinary tract infections (uUTIs). Materials and Methods: Women aged 18–70 years with typical symptoms of newly diagnosed acute lower uUTIs were randomized to BNO 1045 (n = 325) or FT (n = 334), with corresponding matched placebo. The primary endpoint was the proportion of patients who received additional antibiotics (ABs) to treat uUTIs between Days 1 and 38 ±3. Results: Between Days 1 and 38, 238 (83.5%) patients in the BNO 1045 group and 272 (89.8%) patients in the FT group received no additional ABs. At a 15% non-inferiority margin, BNO 1045 was non-inferior to FT in treating uUTIs (non-AB rate difference: –6.26%; 95% CI –11.99 to –0.53%; 2-sided p = 0.0014). Adverse event rates were similar between groups, with higher rates of gastrointestinal disorders in the FT group and pyelonephritis in the BNO 1045 group. During the trial, no patient died or discontinued due to a treatment-related adverse event. Conclusions: BNO 1045 has the potential to reduce outpatient use of ABs for uUTIs and thus may have a significant impact on antimicrobial stewardship strategies. Trial registration: NCT02639520, EudraCT number 2013-004529-99.
miR-216b Post-Transcriptionally Downregulates Oncogene KRAS and Inhibits Cell Proliferation and Invasion in Clear Cell Renal Cell Carcinoma
Authors: Wang Yan , Dong Daoquan , Jiang Shuqi , Zhang Enpu , Zheng Wenzhong , Mao Longyi , Li Weiqing , Zhou Jingcheng , Fan Longlong , Cheng Ran , Li Zesong , Fang Zhengyu , Gui Yaoting , Li Xianxin
Published: September 2018

Background/Aims: Increasing evidence has shown that miR-216b plays an important role in human cancer progression. However, little is known about the function of miR-216b in renal cell carcinoma. Methods: The expression levels of miR-216b in renal cell carcinoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-216b in renal cell carcinoma proliferation and/or metastasis was examined in vitro and in vivo. The target of miR-216b was identified by a dual-luciferase reporter assay. The expression level of KRAS protein was measured by western blotting. Results: The expression of miR-216b was downregulated in clear cell renal cell carcinoma (ccRCC) cell lines and specimens compared to the adjacent normal tissues. Furthermore, miR-216b can bind to the 3’untranslated region (UTR) of KRAS and inhibit the expression of KRAS through translational repression. The in vitro study revealed that miR-216b attenuated ccRCC cell proliferation and invasion. Furthermore, in vivo study also showed that miR-216b suppressed tumor growth. MiR-216b exerted its tumor suppressor function through inhibiting the KRAS-related MAPK/ERK and PI3K/AKT pathways. Conclusion: Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in ccRCC.
Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers in Human Colon Adenocarcinoma
Authors: Zhang Zhiyuan , Qian Wenwei , Wang Sen , Ji Dongjian , Wang Qingyuan , Li Jie , Peng Wen , Gu Jiou , Hu Tao , Ji Bing , Zhang Yue , Wang Shijia , Sun Yueming
Published: September 2018

Background/Aims: Long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play significant roles in the development of tumors, but the functions of specific lncRNAs and lncRNA-related ceRNA networks have not been fully elucidated for colon adenocarcinoma (COAD). In this study, we aimed to clarify the lncRNA-microRNA (miRNA)-mRNA ceRNA network and potential lncRNA biomarkers in COAD. Methods: We extracted data from The Cancer Genome Atlas (TCGA) and identified COAD-specific mRNAs, miRNAs, and lncRNAs. The biological processes in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed for COAD-specific mRNAs. We then constructed a ceRNA network of COAD-specific mRNAs, miRNAs and lncRNAs and analyzed the correlation between expression patterns and clinical features of the lncRNAs involved. After identifying potential mRNA targets of 4 lncRNAs related to overall survival (OS), we conducted stepwise analysis of these targets through GO and KEGG. Using tissue samples from our own patients, we also verified certain analytical results using quantitative real-time PCR (qRT-PCR). Results: Data from 521 samples (480 tumor tissue and 41 adjacent non-tumor tissue samples) were extracted from TCGA. A total of 258 specific lncRNAs, 206 specific miRNAs, and 1467 specific mRNAs were identified (absolute log2 [fold change] > 2, false discovery rate < 0.01). Analysis of KEGG revealed that specific mRNAs were enriched in cancer-related pathways. The ceRNA network was constructed with 64 lncRNAs, 18 miRNAs, and 42 mRNAs. Among these lncRNAs involved in the network, 3 lncRNAs (LINC00355, HULC, and IGF2-AS) were confirmed to be associated with certain clinical features and 4 lncRNAs (HOTAIR, LINC00355, KCNQ1OT1, and TSSC1-IT1) were found to be negatively linked to OS (log-rank p < 0.05). KEGG showed that the potential mRNA targets of these 4 lncRNAs may be concentrated in the MAPK pathway. Certain results were validated by qRT-PCR. Conclusion: This study providing novel insights into the lncRNA-miRNA-mRNA ceRNA network and reveals potential lncRNA biomarkers in COAD.
Analysis of Oral Microbiota Revealed High Abundance of Prevotella Intermedia in Gout Patients
Authors: Liu Juan , Cui Li , Yan Xinmin , Zhao Xinyuan , Cheng Jinluo , Zhou Lei , Gao Jianbo , Cao Zhong , Ye Xinhua  , Hu Shen
Published: September 2018

Background/Aims: Microbes reside in a number of body sites, including the oral cavity, and are associated with the progression of many systemic diseases. In this study, we aimed to investigate the effects of gout and hyperuricemia (HUA) on the composition of oral microbiomes. Methods: Analysis of the oral microbiota from 12 gout patients, 11 HUA patients, and 19 healthy control subjects was performed using a deep sequencing approach, and validation of significant changes in Prevotella intermedia and Serratia marcescens in new patient cohorts was performed using quantitative PCR (qPCR). Results: Our analysis indicated that both gout and HUA significantly altered the composition of the oral microbiome in patients. Patients with gout or HUA had significantly greater levels of salivary Prevotella intermedia but significantly lower levels of Serratia marcescens than healthy control subjects. Conclusion: We demonstrated the association between the oral microbiome and gout and HUA for the first time. In particular, 16S sequencing and qPCR analysis revealed significantly higher levels of oral Prevotella intermedia in gout/HUA patients, which suggests that these patients might be at risk for the development of periodontitis.
EYA4 Promotes Cell Proliferation Through Downregulation of p27Kip1 in Glioma
Authors: Li Zhaoming , Qiu Ran , Qiu Xia , Tian Tian
Published: September 2018

Background/Aims: Accumulating evidence suggests that Eyes Absent Homologue 4 (EYA4) plays an important role in tumorigenesis and progression of various cancers. However, the role of EYA4 in glioma development is still unclear. Methods: The expression of EYA4 was examined in glioma tissues by immunohistochemistry. Cell viability and apoptosis were analyzed by CCK-8, BrdU assay, and flow cytometry. Results: We found that EYA4 was upregulated in glioma, and its expression was positively correlated with advanced tumor stage. Moreover, higher expression of EYA4 predicted a worse overall survival in patients with glioma. Forced overexpression of EYA4 enhanced glioma cell proliferation, and EYA4 suppressed the expression of p27Kip1 directly in these cells. Furthermore, Six1 was required for EYA4 to suppress the expression of p27Kip1 in glioma. Conclusion: Together, we demonstrate that EYA4 promotes cell proliferation by directly suppressing the expression of p27Kip1 in glioma.