bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic performance of a qPCR for Leishmania on stained cytological specimens and on filter paper impressions obtained from cutaneous lesions suggestive of canine leishmaniosis
Authors: Lima Tatiana , Martínez‐Sogues Laura , Montserrat‐Sangrà Sara , Solano‐Gallego Laia , Ordeix Laura
Published: May 2019

Background

Detection of Leishmania in cutaneous lesions is possible by visualization of amastigotes. Detection of Leishmania DNA by PCR presents greater sensitivity, and PCR has been used to diagnose cutaneous leishmaniosis in humans using noninvasive clinical specimens.

Objectives

Study I: to determine if Leishmania DNA could be efficiently extracted and amplified from archived Diff‐Quik®‐stained slides of cytological specimens from canine cutaneous lesions. Study II: to evaluate the diagnostic performance of a Leishmania‐quantitative (q)PCR on stained cytological specimens and on filter paper impressions (FPI) obtained from cutaneous lesions suggestive of canine leishmaniosis (CanL).

Animals

Samples from cutaneous lesions of 54 dogs.

Methods and materials

Study I: Leishmania‐qPCR was performed on 19 glass slides (from nine dogs) with cytologically visible amastigotes. Fifteen slides with no visible amastigotes, obtained from 12 dogs seronegative for Leishmania by ELISA, served as controls. Study II: Leishmania‐qPCR was performed on glass slides and FPI from cutaneous lesions compatible with clinical leishmaniosis in 33 dogs.

Results

Study I: all slides with visible amastigotes had positive qPCR, whereas all control slides yielded negative results. Study II: of 13 dogs definitively diagnosed with clinical leishmaniosis, eight had visible amastigotes on cytology, whereas Leishmania‐qPCR was positive on 11 glass slides and 13 FPI. Leishmaniosis was ruled out by standard methods in 20 dogs, four of which yielded positive qPCR on FPI and/or glass slides.

Conclusions and clinical importance

Leishmania‐DNA can be detected efficiently by qPCR from cutaneous cytological specimens and FPI to diagnose Leishmania infection in dogs with cutaneous lesions suggestive of CanL.
Application of precedence constrained travelling salesman problem model for tool path optimization in CNC milling machines
Authors: Kucukoglu Ilker , Gunduz Tulin , Balkancioglu Fatma , Topal Emine Chousein , Sayim Oznur
Published: May 2019

In this study, a tool path optimization problem in Computer Numerical Control (CNC) milling machines is considered to increase the operational efficiency rates of a company. In this context, tool path optimization problem of the company is formulated based on the precedence constrained travelling salesman problem (PCTSP), where the general form of the TSP model is extended by taking the precedence of the tool operations into account. The objective of the model is to minimize total idle and unnecessary times of the tools for internal operations. To solve the considered problem, a recent optimization algorithm, called Satin Bowerbird Optimizer (SBO), is used. Since the SBO is first introduced for the global optimization problems, the original version of the SBO is modified for the PCTSP with discretization and local search procedures. In computational studies, first, the performance of the proposed algorithm is tested on a well-known PCTSP benchmark problems by comparing the proposed algorithm against two recently proposed meta-heuristic approaches. Results of the comparisons show that the proposed algorithm outperforms the other two competitive algorithms by finding better results. Then, the proposed algorithm is carried out to optimize the hole drilling processes of three different products produced by the company. For this case, with up to 4.05% improvement on the operational times was provided for the real-life problem of the company. As a consequence, it should be noted that the proposed solution approach for the tool path optimization is capable of providing considerable time reductions on the CNC internal operations for the company.
Reflection and transmission characteristics of Lamb waves at an adhesive lap joint of plates
Authors: Mori Naoki , Kusaka Takayuki
Published: May 2019

The reflection and transmission characteristics of Lamb waves at an adhesive single lap joint of plates are examined theoretically by the hybrid finite element method. The adhesive joint is modeled by a linear spring-type interface, which is characterized by normal and tangential stiffnesses. For the incidence of the lowest-order antisymmetric (A0) Lamb mode in a low frequency range, it is shown that the reflection and transmission coefficients of the A0 mode take local maxima and minima at multiple frequencies. This behavior results from the interference of waves originating from the lowest-order antisymmetric guided wave mode in the overlap region. The peak frequencies of the transmission coefficient increase monotonically with increasing tangential stiffness, but are almost invariant with the normal stiffness of the adhesive joint. Furthermore, time-domain numerical simulation using the finite element method is carried out to discuss the theoretical results. As a result, for the A0 mode incidence, the reflection and transmission waveforms of the A0 mode from the lap joint are found to show long-oscillation tails. The spectral analysis for the obtained waveforms shows that these tails are necessary to identify the frequencies at which the reflection and transmission coefficients take local maxima and minima.
Too close not to encyst: Polycystic kidney disease and interorganellar contact sites
Authors: Lorenzi Isotta , Scorrano Luca
Published: May 2019

Polycystic kidney disease is a disorder of increased mitochondria-ER communication (Kuo
et al.
, in 7 May 2019 issue).
KRAS
G12C
inhibition produces a driver-limited state revealing collateral dependencies
Authors: Lou Kevin , Steri Veronica , Ge Alex Y. , Hwang Y. Christina , Yogodzinski Christopher H. , Shkedi Arielle R. , Choi Alex L. M. , Mitchell Dominique C. , Swaney Danielle L. , Hann Byron , Gordan John D. , Shokat Kevan M. , Gilbert Luke A.
Published: May 2019

Functional genomics reveals paths to enhancing combination therapies in KRAS-mutant cancers.
Cystic Fibrosis and Pseudomonas aeruginosa: the Host-Microbe Interface
Authors: Malhotra Sankalp , Hayes Don , Wozniak Daniel J.
Published: May 2019

In human pathophysiology, the clash between microbial infection and host immunity contributes to multiple diseases. Cystic fibrosis (CF) is a classical example of this phenomenon, wherein a dysfunctional, hyperinflammatory immune response combined with chronic pulmonary infections wreak havoc upon the airway, leading to a disease course of substantial morbidity and shortened life span.
Simple point of care continuous positive airway pressure delivery device (Jain-CPAP)
Authors: Jain Ashish , DiBlasi Robert M , Devgan Veena , Kumari Nisha , Kalra Kunal
Published: May 2019

Objective

To describe the effective pressure and FiO2delivery to a realistic spontaneously breathing lung model using a novel, simple, inexpensive neonatal non-invasive bubble continuous positive airway pressure (CPAP) device.

Methods

This experimental bench study was conducted at Bench Testing Laboratory at a Children’s Hospital. A realistic 3D anatomic airway model of a 28-week preterm neonate was affixed to the ASL5000 Test Lung to simulate spontaneous breathing with lung mechanics that are specific to a preterm neonate. The assembly was constructed on site using easily available nasal prongs, paediatric infusion set with a graduated chamber, three-way stop cocks and oxygen tubing. The adult nasal prong was used as cannulae. However, this assembly had the limitation of the lack of humidification and inability to deliver graduated oxygen. This assembly was attached to the anatomic airway with nasal prongs. Pressure and FiO2were measured from within the lung model at different flow settings and recorded for 10 breaths.

Results

There was a linear increase in the mean pressure in the 10 recorded breaths as oxygen flows were increased.

Conclusions

Our nasal CPAP is a simple device, as it can be easily assembled at the point of care using simple, affordable supplies by the healthcare providers and can benefit the newborns with respiratory distress in the resource constraint settings.
Screening and assessment tools for early detection of malnutrition in hospitalised children: a systematic review of validation studies
Authors: Klanjsek Petra , Pajnkihar Majda , Marcun Varda Natasa , Povalej Brzan Petra
Published: May 2019

Objective

The aim of the present study was to identify all currently available screening and assessment tools for detection of malnutrition in hospitalised children, and to identify the most useful tools on the basis of published validation studies.

Design

Systematic review.

Data sources

PubMed, CINAHL and MEDLINE were searched up to October 2017.

Eligibility criteria for selecting studies

Studies in English that reported sensitivity, specificity and positive/negative predictive values (PPVs/NPVs) in the paediatric population were eligible for inclusion.

Data extraction and synthesis

Two authors independently screened all of the studies identified, and extracted the data. The methodological qualities of the studies included were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool.

Results

The 26 validation studies that met the inclusion criteria for this systematic review used eight screening and three assessment tools. The number of participants varied from 32 to 14 477. There was considerable variability in the chosen reference standards, which prevented direct comparisons of the predictive performances of the tools. Anthropometric measurements were used as reference standards in 16 of the identified studies, and full nutritional assessment in 5. The Pediatric Yorkhill Malnutrition Score (PYMS) screening tool performed better than Screening Tool for the Assessment of Malnutrition and Screening Tool for Risk On Nutritional status and Growth when compared in terms of anthropometric measurements, especially for body mass index (Se=90.9, Sp=81.9) and triceps skinfold thickness (Se=80.0, Sp=75.0). However, low PPVs indicated the problem of overprediction of positive cases, which was typical for all of the studies that used anthropometric measurements as the reference standard.

Conclusions

This systematic review identifies the need for definition of the gold standard for validation of screening tools. Anthropometry measurements using WHO or Centers for Disease Control and Prevention growth charts should be considered as the possible reference standard in future validation studies. We would recommend the use of PYMS for hospitalised paediatric patients without chronic conditions, in combination with full nutritional assessment.

PROSPERO registration number

CRD42017077477.
EBN perspectives: care of the older person
Authors: Barrett David , Green Laura
Published: May 2019

EBN Perspectives brings together key issues from the commentaries in one of our nursing topic themes.
Response of growth, yield, and quality of edible-podded snow peas to supplemental LED lighting during winter greenhouse production
Authors: Kong Yun , Zheng Youbin
Published: May 2019

The occurrence of low natural light levels during winter months is a major limiting factor for greenhouse plant production in northern regions. To determine the effects of supplemental lighting (SL) on winter greenhouse production of pea pods, plant growth, pod yield, and quality were investigated under SL at a photosynthetic photon flux density (PPFD) of 50, 80, 110, and 140 μmol m−2 s−1, plus a no-SL control treatment, inside a Canadian greenhouse from January to March. Light-emitting diodes with a red-to-blue PPFD ratio of 4:1 and a 16 h photoperiod were used for the lighting treatments. During the trial period, the average natural daily light integral (DLI) inside the greenhouse was 6.6 mol m−2 d−1 and the average daily temperature was around 13 °C. Compared with the control, SL treatments increased pod yield and promoted plant growth, as demonstrated by faster main stem extension and greater aerial biomass. Also, total pod yield (g plant−1 or no. plant−1) and some growth traits (e.g., stem diameter, branch number, leaf thickness, and leaf chlorophyll content) were proportional to supplemental PPFD within the range of 0–140 μmol m−2 s−1. However, SL levels of 50–80 μmol m−2 s−1, corresponding to a total (natural + supplemental) DLI of 9.4–11.1 mol m−2 d−1, resulted in the best pod quality based on evaluations of individual fresh mass, length, soluble solids content, succulence, and firmness. Therefore, a total DLI ranging between 9.4 and 11.1 mol m−2 d−1 can be recommended as a target light level for greenhouse production of pea pods using SL under winter environment conditions.
The μ+μ− collider to sensitivity estimates on the magnetic and electric dipole moments of the tau-lepton
Authors: Köksal M. , Billur A. A. , Gutiérrez-Rodríguez A. , Hernández-Ruíz M. A.
Published: May 2019

Using the effective Lagrangian formalism, the anomalous magnetic and electric dipole moments of the tau-lepton in the [Formula: see text] process are investigated with the future muon collider where [Formula: see text], 3 and 6 TeV. In addition, the bounds at the 95% confidence level on the dipole moments of the tau-lepton are estimated using different integrated luminosities. It is shown that the [Formula: see text] process leads to a remarkable improvement in the existing experimental bounds on the anomalous magnetic and electric dipole moments of the tau-lepton [Formula: see text] and [Formula: see text] at 95% C.L. for [Formula: see text], [Formula: see text] and [Formula: see text].
Dietary Fuels in Athletic Performance
Authors: Fritzen Andreas Mæchel , Lundsgaard Anne-Marie , Kiens Bente
Published: May 2019

Focusing on daily nutrition is important for athletes to perform and adapt optimally to exercise training. The major roles of an athlete's daily diet are to supply the substrates needed to cover the energy demands for exercise, to ensure quick recovery between exercise bouts, to optimize adaptations to exercise training, and to stay healthy. The major energy substrates for exercising skeletal muscles are carbohydrate and fat stores. Optimizing the timing and type of energy intake and the amount of dietary macronutrients is essential to ensure peak training and competition performance, and these strategies play important roles in modulating skeletal muscle adaptations to endurance and resistance training. In this review, recent advances in nutritional strategies designed to optimize exercise-induced adaptations in skeletal muscle are discussed, with an emphasis on mechanistic approaches, by describing the physiological mechanisms that provide the basis for different nutrition regimens.
Beyond Calories: The New Economics of Nutrition
Authors: Finaret Amelia B. , Masters William A.
Published: May 2019

The economics of human nutrition has changed greatly in recent years as researchers have moved beyond supply and demand of specific foods and total calories to functional aspects of diet quality, such as nutrient composition, sustainability, and a variety of credence attributes. New kinds of data and methods allow researchers to focus on beneficial or harmful attributes of dietary patterns and the cost-effectiveness of interventions aimed at improving health through diet. This review describes some of the recent literature in nutrition economics and its implications for food policy around the world. The new economics of nutrition is benefiting from a strong foundation in the behavioral and social sciences, building on evidence from the natural and health sciences to address fundamental aspects of human well-being and sustainable development.
New Zealand Building Project Cost and Its Influential Factors: A Structural Equation Modelling Approach
Authors: Zhao Linlin , Wang Bill , Mbachu Jasper , Liu Zhansheng
Published: May 2019

Construction industry significantly contributes to New Zealand’s economic development. However, the delivery of construction projects is usually plagued by cost overruns, which turn potentially successful projects into money‐losing ventures, resulting in various other unexpected negative impacts. The objectives of the study were to identify, classify, and assess the impacts of the factors affecting project cost in New Zealand. The proposed research model was examined with structural equation modelling. Recognising the lack of a systematic approach for assessing the influencing factors associated with project cost, this study identified 30 influencing factors from various sources and quantified their relative impacts. The research data were gathered through a questionnaire survey circulated across New Zealand construction industry. A total of 283 responses were received, with a 37% response rate. A model was developed for testing the relationship between project cost and the influential factors. The proposed research model was examined with structural equation modelling (SEM). According to the results of the analysis, market and industry conditions factor has the most significant effect on project cost, while regulatory regime is the second‐most significant influencing factor, followed by key stakeholders’ perspectives. The findings can improve project cost performance through the identification and evaluation of the cost‐influencing factors. The results of such analysis enable industry professionals to better understand cost‐related risks in the complex environment.
Classification and Statistical Trend Analysis in Detecting Glaucomatous Visual Field Progression
Authors: Valente Cristiana , D’Alessandro Elisa , Iester Michele
Published: May 2019

Aim. To evaluate the agreement between different methods in detection of glaucomatous visual field progression using two classification-based methods and four statistical approaches based on trend analysis. Methods. This is a retrospective and longitudinal study. Twenty Caucasian patients (mean age 73.8 ± 13.43 years) with open-angle glaucoma were recruited in the study. Each visual field was assessed by Humphrey Field Analyzer, program SITA standard 30-2 or 24-2 (Carl Zeiss Meditec, Inc., Dublin, CA). Full threshold strategy was also accepted for baseline tests. Progression was analyzed by using Hodapp–Parrish–Anderson classification and the Advanced Glaucoma Intervention Study visual field defect score. For the statistical analysis, linear regression (r2) was calculated for mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI), and when it was significant, each series of visual field was considered progressive. We also used Progressor to look for a significant progression of each visual field series. The agreement between methods, based on statistical analysis and classification, was evaluated using a weighted kappa statistic. Results. Thirty-eight visual field series were analyzed. The mean follow-up time was 6.2 ± 1.53 years (mean ± standard deviation). At baseline, the mean MD was −7.34 ± 7.18 dB; at the end of the follow-up, the mean MD was −9.25 ± 8.65 dB; this difference was statistically significant (p<0.001). The agreement to detect progression was fair between all methods based on statistical analysis and classification except for PSD r2. A substantial agreement (κ = 0.698 ± 0.126) was found between MD r2 and VFI r2. With the use of all the statistical analysis, there was a better time-saving. Conclusions. The best agreement to detect progression was found between MD r2 and VFI r2. VFI r2 showed the best agreement with all the other methods. GPA2 can help ophthalmologists to detect glaucoma progression and to help in treatment decisions. PSD r2 was the worse method to detect progression.
Medical Diagnostic Tests: A Review of Test Anatomy, Phases, and Statistical Treatment of Data
Authors: Bolboacă Sorana D.
Published: May 2019

Diagnostic tests are approaches used in clinical practice to identify with high accuracy the disease of a particular patient and thus to provide early and proper treatment. Reporting high-quality results of diagnostic tests, for both basic and advanced methods, is solely the responsibility of the authors. Despite the existence of recommendation and standards regarding the content or format of statistical aspects, the quality of what and how the statistic is reported when a diagnostic test is assessed varied from excellent to very poor. This article briefly reviews the steps in the evaluation of a diagnostic test from the anatomy, to the role in clinical practice, and to the statistical methods used to show their performances. The statistical approaches are linked with the phase, clinical question, and objective and are accompanied by examples. More details are provided for phase I and II studies while the statistical treatment of phase III and IV is just briefly presented. Several free online resources useful in the calculation of some statistics are also given.
Epistasis‐Based Basis Estimation Method for Simplifying the Problem Space of an Evolutionary Search in Binary Representation
Authors: Lee Junghwan , Kim Yong-Hyuk
Published: May 2019

An evolutionary search space can be smoothly transformed via a suitable change of basis; however, it can be difficult to determine an appropriate basis. In this paper, a method is proposed to select an optimum basis can be used to simplify an evolutionary search space in a binary encoding scheme. The basis search method is based on a genetic algorithm and the fitness evaluation is based on the epistasis, which is an indicator of the complexity of a genetic algorithm. Two tests were conducted to validate the proposed method when applied to two different evolutionary search problems. The first searched for an appropriate basis to apply, while the second searched for a solution to the test problem. The results obtained after the identified basis had been applied were compared to those with the original basis, and it was found that the proposed method provided superior results.
Exosomes Modulate the Viral Replication and Host Immune Responses in HBV Infection
Authors: Li Shuang , Li Shilin , Wu Shaobo , Chen Limin
Published: May 2019

Although current diagnosis and treatment of hepatitis B virus (HBV) infection can maintain viral suppression, new therapies need to be invented to sustain off-treatment virologic suppression and reduce side effects. Exosomes act as intercellular communicators to facilitate direct transfer of proteins, lipids, and nucleic acids between cells in vitro and in vivo. Pioneering work has demonstrated that exosomal cargos changed markedly during HBV infection. An improved understanding of the functions of exosomes during HBV infection could lead to a powerful new strategy for preventing and treating HBV. In this review, we point out the role of exosomes in HBV infection: (1) exosomes could directly participate in HBV replication; (2) exosomes modulate immune response during HBV infections; (3) exosomal RNAs and proteins might be selected as novel biomarkers for the diagnosis of HBV infections; and (4) exosomes can also be designed as vaccines.
Systematic Review with Meta-Analysis: Fecal Calprotectin as a Surrogate Marker for Predicting Relapse in Adults with Ulcerative Colitis
Authors: Li Jiajia , Zhao Xiaojing , Li Xueting , Lu Meijiao , Zhang Hongjie
Published: May 2019

The clinical course of ulcerative colitis (UC) is featured by remission and relapse, which remains unpredictable. Recent studies revealed that fecal calprotectin (FC) could predict clinical relapse for UC patients in remission, which has not yet been well accepted. To detect the predictive value of FC for clinical relapse in adult UC patients based on updated literature, we carried out a comprehensive electronic search of PubMed, Web of Science, Embase, and the Cochrane Library to identify all eligible studies. Diagnostic accuracy including pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and pooled area under the receiver operating characteristic (AUROC) was calculated using a random effects model. Heterogeneity across studies was assessed by the I2 metric. Sources of heterogeneity were detected using subgroup analysis. Metaregression was used to test potential factors correlated to DOR. Publication bias was assessed using Deek’s funnel plots. In our study, 14 articles enrolling a total of 1110 participants were finally included, and all articles underwent a quality assessment. Pooled sensitivity, specificity, PLR, and NLR with 95% confidence intervals (CIs) were 0.75 (95% CI: 0.70–0.79), 0.77 (95% CI: 0.74–0.80), 3.45 (95% CI: 2.31–5.14), and 0.37 (95% CI: 0.28–0.49) respectively. The area under the summary receiver operating characteristic (sROC) curve was 0.82, and the diagnostic odds ratio was 10.54 (95% CI: 6.16–18.02). Our study suggested that FC is useful in predicting clinical relapse for adult UC patients in remission as a simple and noninvasive marker.
Behavior of an Innovative Square Composite Column Made of Four Steel Tubes at the Corners and Corrugated Steel Batten Plates on all Sides
Authors: Wang Chengquan , Yun Zou , Kang Jinxin , Zhou Yuan , Chen Ming , Wu Yichao
Published: May 2019

Steel‐concrete composite (SCC) columns have widely been applied in modern construction industry owing to the composite action between the concrete and the steel. The benefits of SCC columns can be further achieved if the confinement effect of concrete is applied. Therefore, this paper presents an innovative square steel‐concrete composite (ISSCC) column made of four steel tubes at the corners and corrugated steel batten plates on all sides. Through the experimental and finite element (FE) numerical simulation calculations, the axial compression performance and seismic performance of the ISSCC column were discussed, and the FE model was verified through experimental results. The seismic performance of the ISSCC column was compared and analyzed with reinforced concrete column under different axial compression ratios. The research showed that FE models can accurately simulate the deformation, stress, and failure states of the ISSCC column under axial pressure and horizontal low cyclic load. Furthermore, the ISSCC column performed good ductility and energy dissipation capacity, and the seismic performance index was better than the reinforced concrete column and had better seismic performance. The results of this study can provide reference for the design and development of the new composite column.
Multiobjective Optimal Control for Hydraulic Turbine Governing System Based on an Improved MOGWO Algorithm
Authors: Xia Xin , Ji Jie , Li Chao-shun , Xue Xiaoming , Wang Xiaolu , Zhang Chu
Published: May 2019

Hydraulic turbine governing system (HTGS) is essential equipment which regulates frequency and power of the power grids. In previous studies, optimal control of HTGS is always aiming at one single operation condition. The variation of operation conditions of HTGS is seldom considered. In this paper, multiobjective optimal function is proposed for HTGS under multiple operation conditions. In order to optimize the solution to the multiobjective problems, a novel multiobjective grey wolf optimizer algorithm with searching factor (sMOGWO) is also proposed with two improvements: adding searching step to search more no‐domain solutions nearby the wolves and adjusting control parameters to keep exploration ability in later period. At first, the searching ability of the sMOGWO has been verified on several UF test problems by statistical analysis. And then, the sMOGWO is applied to optimize the solutions of the multiobjective problems of HTGS, while different algorithms are employed for comparison. The experimental results indicate that the sMOGWO is more effective algorithm and improves the control quality of the HTGS under multiple operation conditions.
Noncanonical IFN Signaling, Steroids, and STATs: A Probable Role of V-ATPase
Authors: Johnson Howard M. , Noon-Song Ezra , Ahmed Chulbul M.
Published: May 2019

A small group of only seven transcription factors known as STATs (signal transducer and activator of transcription) are considered to be canonical determinants of specific gene activation for a plethora of ligand/receptor systems. The activation of STATs involves a family of four tyrosine kinases called JAK kinases. JAK1 and JAK2 activate STAT1 in the cytoplasm at the heterodimeric gamma interferon (IFNγ) receptor, while JAK1 and TYK2 activate STAT1 and STAT2 at the type I IFN heterodimeric receptor. The same STATs and JAKs are also involved in signaling by functionally different cytokines, growth factors, and hormones. Related to this, IFNγ-activated STAT1 binds to the IFNγ-activated sequence (GAS) element, but so do other STATs that are not involved in IFNγsignaling. Activated JAKs such as JAK2 and TYK2 are also involved in the epigenetics of nucleosome unwrapping for exposure of DNA to transcription. Furthermore, activated JAKs and STATs appear to function coordinately for specific gene activation. These complex events have not been addressed in canonical STAT signaling. Additionally, the function of noncoding enhancer RNAs, including their role in enhancer/promoter interaction is not addressed in the canonical STAT signaling model. In this perspective, we show that JAK/STAT signaling, involving membrane receptors, is essentially a variation of cytoplasmic nuclear receptor signaling. Focusing on IFN signaling, we showed that ligand, IFN receptor, the JAKs, and the STATs all undergo endocytosis and ATP-dependent nuclear translocation to promoters of genes specifically activated by IFNs. We argue here that the vacuolar ATPase (V-ATPase) proton pump probably plays a key role in endosomal membrane crossing by IFNs for receptor cytoplasmic binding. Signaling of nuclear receptors such as those of estrogen and dihydrotestosterone provides templates for making sense of the specificity of gene activation by closely related cytokines, which has implications for lymphocyte phenotypes.
Mechanisms of Compound Kushen Injection for the Treatment of Lung Cancer Based on Network Pharmacology
Authors: Meng Ziqi , Liu Xinkui , Wu Jiarui , Zhou Wei , Wang Kaihuan , Jing Zhiwei , Liu Shuyu , Ni Mengwei , Zhang Xiaomeng
Published: May 2019

Background. Compound Kushen Injection (CKI) is a Chinese patent drug that shows good efficacy in treating lung cancer (LC). However, its underlying mechanisms need to be further clarified.Methods. In this study, we adopted a network pharmacology method to gather compounds, predict targets, construct networks, and analyze biological functions and pathways. Moreover, molecular docking simulation was employed to assess the binding potential of selected target-compound pairs.Results. Four networks were established, including the compound-putative target network, protein-protein interaction (PPI) network of LC targets, compound-LC target network, and herb-compound-target-pathway network. Network analysis showed that 8 targets (CHRNA3, DRD2, PRKCA, CDK1, CDK2, CHRNA5, MMP1, and MMP9) may be the therapeutic targets of CKI in LC. In addition, molecular docking simulation indicated that CHRNA3, DRD2, PRKCA, CDK1, CDK2, MMP1, and MMP9 had good binding activity with the corresponding compounds. Furthermore, enrichment analysis indicated that CKI might exert a therapeutic role in LC by regulating some important pathways, namely, pathways in cancer, proteoglycans in cancer, PI3K-Akt signaling pathway, non-small-cell lung cancer, and small cell lung cancer.Conclusions. This study validated and predicted the mechanism of CKI in treating LC. Additionally, this study provides a good foundation for further experimental studies and promotes the reasonable application of CKI in the clinical treatment of LC.
Impairment in Theory of Mind in Parkinson’s Disease Is Explained by Deficits in Inhibition
Authors: Foley Jennifer A. , Lancaster Claire , Poznyak Elena , Borejko Olga , Niven Elaine , Foltynie Thomas , Abrahams Sharon , Cipolotti Lisa
Published: May 2019

Objective. Several studies have reported that people with Parkinson’s disease (PD) perform poorly on tests of ‘Theory of Mind’ (ToM), suggesting impairment in the ability to understand and infer other people’s thoughts and feelings. However, few studies have sought to separate the processes involved in social reasoning from those involved in managing the inhibitory demands on these tests. In this study, we investigated the contribution of inhibition to ToM performance in PD. Methods. 18 PD patients and 22 age-matched healthy controls performed a ToM test that separates the ability to infer someone else’s perspective from the ability to inhibit one’s own. Participants also completed a battery of standard measures of social and executive functioning, including measures of inhibition. Results. The PD patients performed worse on the ToM test only when the inhibitory demands were high. When the level of inhibition required was reduced, there were no significant group differences. Furthermore, executive impairments in PD patients were limited to measures of inhibition, with disadvantages associated with poorer ToM performance in this group. Conclusions. This study provides convincing evidence that the apparent impairment observed on ToM tests in PD is explained by deficits in inhibition.
Abnormal Expression of DICER1 Leads to Dysregulation of Inflammatory Effectors in Human Synoviocytes
Authors: Jiang Congshan , Xu Jing , Zhu Wenhua , Cai Yongsong , Wang Si , Guo Yuanxu , Xu Ke , Geng Manman , Hussain Nazim , Han Yan , Zhang Fujun , Ning Qilan , Meng Liesu , Lu Shemin
Published: May 2019

Dysregulation of multiple microRNAs widely takes place during rheumatoid arthritis (RA) and experimental arthritides. This study is performed to explore the possible mechanism underlying DICER1 deficiency-mediated inflammation in human synoviocytes SW982. Firstly, RNAi of DICER1 led to increased COX2, MMP3, and MMP13 protein production, while DICER1 overexpression could reduce MMP13 expression. Secondly, the increase of IL-8 and decrease of TGF-β1 and TIMP1 were determined in the supernatant derived from DICER1 siRNA-treated cells, while DICER1 overexpression was found capable to reverse this effect. Ingenuity pathway analysis (IPA) software predicted that the Dicer1 deficiency-induced dysregulated cytokines in synoviocytes could possibly lead to the inflammatory disorders in the synovial tissue. Moreover, DICER1 deficiency could also reduce apoptosis, while DICER1 overexpression was found to decrease the proliferation and enhance apoptosis. In addition, DICER1 deficiency could lower the expression of multiple RA-related miRNAs such as miR-155. Meanwhile, DICER1 overexpression could rescue their low expression levels. And then, gain or loss of miR-155 function could regulate the protein levels of MMP3 and MMP13. These results indicated that DICER1 might play its role through regulating its downstream RA-related miRNAs. Our data demonstrated that DICER1 deficiency could cause multiple proinflammatory events in human synoviocytes SW982. This mechanism study might provide the possible target molecule to modify the inflammatory destruction and overproliferation in synoviocytes.
Effects of Food Environments and Eating Environments on Consumers’ Food Consumption Volume
Authors: Kuo Su-Hui , Lin Hung-Chou
Published: May 2019

Even though the influences of eating environments and the food environments on consumption have been discussed, little has been done to examine whether the food environments would be influenced by the eating environments. For example, the size of plate has been proved to have impact on consumers’ consumption volume; it is still unknown whether the eating environment would interact with the food environment and in turn influences consumers’ consumption volume. This research explores the underlying mechanisms how consumers are influenced by the size of bowl when they consume food. In addition, eating environments are also incorporated to discuss their effects on the relationship between bowl size and consumers’ consumption volume. The results indicate people who receive a large bowl with large chopsticks exhibit greater food consumption than those who receive a small bowl with small chopsticks. However, when people use tableware inconsistently, they exhibit similar food consumption. Under bright illumination, people given large bowls with large chopsticks exhibit greater food consumption than those given small bowls with small chopsticks; however, when people use inconsistently sized tableware, they exhibit similar food consumption. Under dim illumination, no significant differences in food consumption amount are evident in association with bowl and chopstick sizes.
Site Measurement and Study of Vertical Freezing Wall Temperatures of a Large‐Diameter Shield Tunnel
Authors: Hu Jun , Liu Wenbo , Pan Yutao , Zeng Hui
Published: May 2019

When a large‐diameter shield tunnel boring machine enters or exits a tunnel, the newly exposed tunnel face is prone to instability and water seepage. In order to prevent collapse of the tunnel face, local ground improvement can be used until the permanent tunnel lining can be installed. The tunnel launching project of the Nanjing Metro Line 10 cross‐river tunnel had a high stability requirement for the entry and exit phases. To this end, this project used a combination of cement treatment and ground freezing methods. In this project, field measurement of the vertical freezing improvement of the large‐diameter shield tunnel was carried out. The temperature distribution and ground surface deformation of the vertical frozen soil wall at the end of the tunnel during the active freezing and maintenance freezing periods were analyzed in detail. The result shows that the surface settlement and seepage were successfully controlled by the combined cement treatment and ground freezing. On the other hand, the combination of cement treatment and ground freezing helps to control the freezing‐induced heaving. The hydration heat in improved ground leads to an increase in ground temperature and this leads to additional freezing duration. It was examined that the frozen soil wall and the enclosure structure were in a good cementation condition. These measured values provide guidance on the timing of the shield departure. The project results confirmed that instability and water permeation did not occur in the tunnel face during the subsequent excavation.
Tissue Inhibitor of Metalloproteinase-2 Polymorphisms and Risk for HIV-Associated Neurocognitive Disorder
Authors: Singh HariOm , Jadhav Sushma , Samani Dharmesh , Nain Sumitra
Published: May 2019

The imbalance between MMPs and TIMPs is associated with the HIV dissemination tissue damage pathology neurodegenerative disorders, including HAND. Genetic variations in theTIMPgene may modulate the neurocognitive disorder in HIV patients. Hence, we evaluated the genetic variants ofTIMP-2 (-418G/C, 303G/A) gene with the risk of HAND. Genotyping ofTIMP-2 polymorphism was performed in 50 patients with HAND, 100 no HAND, and 154 healthy controls by PCR-RFLP.TIMP-2-418GC and 303AA genotypes represented a predominant risk for HAND severity (OR=1.55,P=0.30;OR=4.58,P=0.24). The variant -418CC genotype, -418A allele, had exhibited a significant risk for the acquisition of HAND (OR=12.55,P=0.026;OR=2.66,P=0.004).TIMP-2303GA, 303AA genotype, and 303A allele evinced a higher risk for HAND severity (OR=1.82,P=0.14;OR=1.70,P=0.63; andOR=1.68,P=0.12). In HIV patients,TIMP-2-418CC genotype and -418C allele significantly occurred in comparison to healthy controls (OR=10.10,P=0.006;OR=2.02,P=0.009). In the intermediate and early HIV disease stage,TIMP-2-418CC genotype was significantly increased compared with healthy controls (11.1% vs. 1.3%,OR=14.63,P=0.01; 16.9% vs. 1.3%,OR=14.51,P=0.002). In patients with HAND among tobacco and alcohol users,TIMP-2-418CC genotype displayed a risk for HAND severity (OR=3.96,P=0.26;OR=4.83,P=0.19). On multivariate logistic regression,TIMP-2303AA genotype, advanced stage, and gender had a risk for HAND severity (OR=28.98,P=0.02;OR=2.35,P=0.070; andOR=2.36,P=0.04). In conclusion,TIMP-2-418G/C polymorphism independently, along with alcohol and tobacco, may have an impact on the acquisition of HAND and its severity.TIMP-2303G/A polymorphism bare a risk for HAND severity.
Active Vitamin D and Vitamin D Receptor Help Prevent High Glucose Induced Oxidative Stress of Renal Tubular Cells via AKT/UCP2 Signaling Pathway
Authors: Zhu XiaoJuan , Wu ShengHua , Guo HanCheng
Published: May 2019

Background. It has been documented that vitamin D supplementation showed an improvement of symptoms of diabetic nephropathy; however, the underlying mechanisms remain unknown. We here tested the hypothesis that active vitamin D is able to up-regulate AKT/UCP2 signaling to alleviate oxidative stress of renal tubular cell line HK2.Methods. There are eight groups in the present study: normal glucose, osmotic control (5.5 mmol/L D-glucose+24.5 mmol/L D-mannitol), NAC control (30 mmol/L D-glucose + 1.0 mmol/L N-Methylcysteine), high glucose, high glucose+VD, high glucose (HG)+VD+siVDR, HG+VD+AKT inhibitor (AI), and high glucose+VD+UCP2 inhibitor (Gelipin). Concentration of superoxide dismutase (SOD) and malondialdehyde (MDA) was analyzed by ELISA. Reactive oxygen species (ROS), mitochondrial membrane potential and apoptosis were measured by flow cytometry. JC-1 was evaluated by flow cytometry. The presence of VDR, AKT, and UCP2 in HK cells was assessed using RT-PCR and western blot analyses.Results. VD administration significantly upregulated the SOD activation and downregulated MDA levels compared to HG group. siVDR, AKT inhibitor, and UCP2 inhibitor significantly suppressed the activation of SOD and increased the expression of MDA compared to VD group. ROS generation and apoptosis of HK2 cells in HG+VD group were significantly lower than those in HG, HG+VD+siVDR, HG+VD+AI, and HG+VD+Gelipin group. ΔΨm in HG+VD group was obviously higher than those in HG, HG+VD+siVDR, HG+VD+AI, and HG+VD+Gelipin group. Decreased mRNA and protein levels of VDR, p-AKT, and UCP2 were observed in HG+VD+siVDR, HG+VD+AI, and HG+VD+Gelipin group compared to those in HG+VD group.Conclusions. siVDR, AKT inhibitor, and UCP2 inhibitor elevated the ROS and apoptosis of HK2 cells while attenuating the mitochondrial membrane potential, suggesting that vitamin D protects renal tubular cell from high glucose by AKT/UCP2 signaling pathway.
Whole-Exome Sequencing Identified a De Novo Mutation of Junction Plakoglobin (p.R577C) in a Chinese Patient with Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Liu Lv , Chen Chan , Li YaLi , Yu Rong
Published: May 2019

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare and potentially life-threatening disorder of the heart. The clinical spectrum of ARVC includes myocyte loss and fibro-fatty tissue replacement. With the progress of ARVC, the patient can present serious ventricular arrhythmias, heart failure, and even sudden cardiac death. Previous studies have demonstrated that desmosomes and intermediate junctions play a crucial role in the generation and development of ARVC. In this study, we enrolled a Chinese patient with suspicious ARVC. The patient suffered from right ventricular enlargement and less thickening of right ventricular wall. ECG record showed an epsilon wave. However, there was no obvious symptom in his parents. After whole-exome sequencing and data filtering, we identified a de novo mutation (c.1729C>T/p.R577C) of junction plakoglobin (JUP) in this patient. Bioinformatics programs predicted that this mutation was deleterious. Western blot revealed that, compared to cells transfected with WT plasmids, the expressions of desmoglein 2 (DSG2) and Connexin 43 were decreased overtly in cells transfected with the mutant plasmid. Previous studies have proven that the reduction of DSG2 and Connexin 43 may disturb the stability of desmosomes. In this research, we reported a novel de novo mutation (c.1729C>T/p.R577C) of JUP in a Chinese patient with suspicious ARVC. Functional research further confirmed the pathogenicity of this novel mutation. Our study expanded the spectrum of JUP mutations and may contribute to the genetic diagnosis and counseling of patients with ARVC.
Monthly Attenuation Prediction for Asphalt Pavement Performance by Using GM (1, 1) Model
Authors: Tang Limin , Xiao Duyang
Published: May 2019

Due to the uncertainty and variability of various factors affecting the pavement performance, the change in pavement performance cannot be completely determined. In addition, this uncertainty is not accurately reflected by the pavement performance prediction model. In particular, the gray GM (1, 1) model is very suitable due to it is ability to better predict the existing situation of a domestic asphalt pavement along with the actual performance of a road surface of the “small sample, poor information” gray system. In this regard, the gray GM (1, 1) model is being increasingly used to forecast the performance of an asphalt pavement. When a gray GM (1, 1) model is used to predict the performance of an asphalt pavement, the condition number of the GM (1, 1) model matrix is too large, which, in turn, leads to the deviation of calculation and even wrong results in some cases. This study analyzed the reason for a large condition number of the GM (1, 1) model matrix. Combined with the numerical characteristics of the pavement condition index (PCI) and pavement quality index (PQI), this study focused on the annual, monthly, and daily attenuations of PCI and PQI to the condition number of the GM (1, 1) model matrix. Accordingly, we propose a method to forecast the performance of an asphalt pavement using the monthly attenuation of PCI and PQI. The PCI and PQI in Hunan Province in recent years have been predicted, and the findings reveal that the prediction GM (1, 1) model for the monthly attenuation of PCI and PQI not only effectively lowered the condition number of the matrix but also ensured that the relative error was small.
Automatic System for Detection and Positioning of Impacts in Metals Based on Arduino
Authors: Morón Carlos , Ferrández Daniel , Saiz Pablo , Morón Alberto
Published: May 2019

This work presents a new application to detect vibrations in metallic structures based on low‐cost sensors compatible with the Arduino platform that enables identification of points where the impact is produced, in order to facilitate inspection. If the impact is produced on a metal bar, the energy introduced in the system is spread through the material in the form of vibration. Thus, using standardized construction steel rods B500SD that can be considered homogeneous along entire section, it was possible to detect where the impact is produced, measuring delays of propagation of acoustic wave throughout the material. For that, it was necessary to place the accelerometers at the ends of the structure that enables an automatic and efficient way to determine the moment and the position of the impact. Hypothesis of supported beam was taken into consideration, obtaining for distances of 0.1 and 0.9 m with delay times of 500 μs.
Effective Cancer Genotyping—Many Means to One End
Authors: Meador Catherine B. , Oxnard Geoffrey R.
Published: May 2019

Precision cancer medicine requires effective genotyping of every patient's tumor to optimally design treatment plans. Despite its imperfect sensitivity, the rapidity and convenience of cell-free DNA sequencing makes it an essential complement to tumor genotyping, which, when used appropriately, can aid the pursuit of effective genotyping for all patients.

See related article by Leighl et al., p. 4691