bluuebunny/crossref_metadata_2025 huggingface dataset:
Wind‐Induced Vibration Response of an Inspection Vehicle for Main Cables Based on Computer Simulation
Authors: Zhang Lu , Wang Shaohua , Guo Peng , Wang Qunsheng
Published: October 2019

This paper presents a simulation approach based on the finite element method (FEM) to analyze the wind‐induced vibration response of an inspection vehicle for main cables. First, two finite element (FE) models of a suspension bridge and a main cable‐inspection vehicle coupled system are established using MIDAS Civil software and ANSYS software, respectively. Second, the mean wind speed distribution characteristics at a bridge site are analyzed, and the wind field is simulated based on the spectral representation method (SRM). Third, a modal analysis and a wind‐induced vibration response transient analysis of the suspension bridge FE model are completed. Fourth, the vibration characteristics of the inspection vehicle are analyzed by applying fluctuating wind conditions and main cable vibration displacements in the main cable‐inspection vehicle coupled FE model. Finally, based on the ISO2631‐1‐1997 standard, a vehicle ride comfort evaluation is performed. The results of the suspension bridge FE modal analysis are in good accordance with those of the experimental modal test. The effects of the working height, number of nonworking compressing wheels, and number of nonworking driving wheels during driving are discussed. When the average wind speed is less than 13.3 m/s, the maximum total weighted root mean square acceleration (av) is 0.1646 m/s2 and the vehicle ride comfort level is classified as “not uncomfortable.” This approach provides a foundation for the design and application of inspection vehicles.
Urinary Metabolomics Study of the Intervention Effect of Hypoglycemic Decoction on Type 2 Diabetes Mellitus Rats Model
Authors: Pan Lin-Lin , Sun Qi-Hui , Liu Gui-Rong , Guo Jia-Yin
Published: October 2019

The hypoglycemic decoction (HD) is a traditional Chinese medicine (TCM) preparation for the treatment of diabetes mellitus (DM), with a remarkable therapeutic effect. However, its mechanism of action is still unclear at the metabolic level. In this study, the biochemical markers from type 2 DM (T2DM) rats, induced by a high-sugar and high-fat diet combined with streptozotocin (STZ), were detected. The metabolomics-based analysis using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was conducted to evaluate urine samples from control, model, metformin, and HD groups. After oral administration of HD for 28 days, the general state, weight, fasting blood glucose (FBG), blood lipid level, oral glucose tolerance test (OGTT), fasting insulin (FINS), insulin sensitivity index (ISI), and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly improved (P<0.01). The western blotting showed that HD can enhance the protein expression of glucose transporter 4 (GLUT4) and adenosine monophosphate-activated protein kinase (AMPK). The metabolomics results revealed that after treatment with HD, the levels of L-carnitine, 1-methyladenosine, 1-methylhistamine, and 3-indoleacrylic acid were upregulated and the levels of riboflavin, phenylalanine, atrolactic acid, 2-oxoglutarate, citrate, isocitrate, cortisol, and glucose were downregulated. The main mechanism may be closely related to the regulation of the tricarboxylic acid (TCA) cycle, phenylalanine metabolism, glyoxylate metabolism, and dicarboxylate metabolism. Additionally, it was also found that HD can regulate the protein expression of GLUT4 and AMPK to interfere with TCA cycle and carbohydrate metabolism to treat T2DM.
The Stability Evaluation of Shaft during Drastic Drawdown Dewatering of Alluvium
Authors: Du Mingze , Xu Yanchun , Duan Heng , Li Wen
Published: October 2019

The hydrophobicity of the aquifer at the bottom of the porous alluvium will affect the stability of the shaft. According to the changes of water level and the compressive amount of alluvium, we can evaluate the shaft stability and predict the shaft failure. In this work, the simulation model of the auxiliary shaft in the Zhuxianzhuang Coal Mine is generated by using the Nsdc software to evaluate the stability of the shaft during drastic drawdown dewatering. Based on the measured hydrophobic compression ratio in an adjacent coal mine, the compressive amounts of the strata near the main and auxiliary shafts in the Zhuxianzhuang Coal Mine are predicted under the condition of drastic drawdown dewatering, which will be 249.69 mm and 302.75 mm, respectively. It is more likely that the shaft wall may fracture in the 15th day (fourth load level) under the condition of drastic drawdown dewatering. The formation compressive amount near the auxiliary shaft is approximately 320 mm, which is close to the measured predicted value. At the same time, the Fisher discriminant model is established, and it is predicted that the state of the main and auxiliary shafts will be failure under the conditions of drastic drawdown dewatering in the Zhuxianzhuang Coal Mine. Based on the simulating results, the technical means of using the ground grouting for early prevention and control is proposed.
Synergistic Effects of Human Platelet-Rich Plasma Combined with Adipose-Derived Stem Cells on Healing in a Mouse Pressure Injury Model
Authors: Liu Zhiyuan , Xiao Shune , Tao Kerong , Li Hai , Jin Wenhu , Wei Zairong , Wang Dali , Deng Chengliang
Published: October 2019

Pressure injury (PI) affects quality of life and results in economic and social burdens. Local transplantation of human adipose-derived stem cells (ASCs) is considered an effective treatment. However, ASC suspension alone is vulnerable to the immune system and results in a shortened cell survival. There is increasing evidence of a synergistic effect of platelet-rich plasma (PRP) combined with ASCs on wound healing. This study investigated the effectiveness, synergy, and mechanism of wound healing following local injection of PRP combined with ASCs in a rodent PI model. PRP or ASCs alone were the control intervention. Wound healing, inflammatory infiltration, collagen deposition, angiogenesis, neurogenesis, and cell homing were investigated. PI healing was promoted by the synergistic effects of PRP combined with ASCs. The combination was more effective than ASCs alone for modulating inflammation, increasing collagen deposition, angiogenesis, neurogenesis, and the persistence of the injected ASCs. These data provide a theoretical foundation for the clinical administration of ASCs combined with PRP in PI healing and skin regeneration.
A New Design Method for PI‐PD Control of Unstable Fractional‐Order System with Time Delay
Authors: Zheng Min , Huang Tao , Zhang Guangfeng
Published: October 2019

In this paper, a practical PI‐PD controller parameter tuning method is proposed, which uses the incenter of the triangle and the Fermat point of the convex polygon to optimize the PI‐PD controller. Combined with the stability boundary locus method, the PI‐PD controller parameters that can ensure stability for the unstable fractional‐order system with time delay are obtained. Firstly, the parameters of the inner‐loop PD controller are determined by the centre coordinates of the CSR in the kd − kf plane. Secondly, a new graphical method is used to calculate the parameters of the PI controller, in which Fermat points in the CSR of (kp − ki) plane are selected. Furthermore, the method is extended to uncertain systems, and the PI‐PD controller parameters are obtained by using the proposed method through common stable region of all stable regions. The proposed graphical method not only ensures the stability of the closed‐loop system but also avoids the complicated optimization calculations. The superior control performance of this method is illustrated by simulation.
Master‐Slave Synchronization of Chaotic Φ6 Duffing Oscillators by Linear State Error Feedback Control
Authors: Ding Ke
Published: October 2019

This paper is concerned with master‐slave synchronization of chaotic Φ6 Duffing oscillators by using linear state error feedback control. Compared with some existing methods and results, this paper estimates the bound of the first trajectory (variable) of the controlled slave system and uses this bound to derive synchronization criteria for two chaotic Φ6 Duffing oscillators. The effectiveness of synchronization criteria is illustrated by three simulation examples.
Design Criterion and a Technical Approach for the Controlled Seismic Behavior of Continuous Girder Bridges
Authors: Gao Hao , Song Yanchen , Wang Junjie , Liu Huijie
Published: October 2019

Seismic design involving “fuse components” between the superstructure and substructure can improve the seismic performance of continuous girder bridges during strong earthquakes by ensuring an elastic working state. The mechanical properties of the “fuse components” directly affect the seismic behavior of continuous girder bridges, and many theoretical and experimental studies of isolation devices to achieve the controlled seismic behavior of continuous girder bridges have been carried out, and some devices are in use in large‐scale construction projects. However, there is a lack of evidence from structures that have been subject to earthquakes. Test results show that the shear behavior of isolation bearings is unpredictable and the friction behavior is uncontrollable. Further, limiting devices often suffer from an insufficient deformation capacity and have large space requirements. Therefore, we propose a new type of spherical steel bearing and two kinds of large‐stroke steel damping devices with different space requirements. The full‐scale test results reveal that the bearing has strong controllability with respect to shearing, stable friction behavior after fracture, and little unpredictability in the friction‐based processes. Furthermore, the large‐stroke steel damping device shows a full hysteresis curve and excellent energy dissipation characteristics. Finally, using a continuous girder bridge as an example and combined with the results of mechanical tests, the effectiveness of the controlled design criterion was verified using numerical simulations. The calculated results show that, compared with conventional fixed bearings, the shear and bending moments are decreased by 60% and 53%, respectively, and the ratio of both the shear and bending moment response of the pier bottom to its capacity is less than 0.5. However, the ratio of the maximum deformation of the damper to its capacity is only 0.28, and the residual displacement is 0.01 m. Therefore, an alternative scheme is provided for postearthquake maintenance and replacement.
The Spatiotemporal Pattern of the Aerosol Optical Depth (AOD) on the Canopies of Various Forest Types in the Exurban National Park: A Case in Ningbo City, Eastern China
Authors: Chi Yufeng , Zuo Shudi , Ren Yin , Chen Kaichao
Published: October 2019

The spatiotemporal distribution pattern of the aerosol optical depth (AOD) is influenced by many environmental factors, such as meteorological condition changes, atmospheric pollution, and topographic changes. Understanding the relationship between the vegetation land cover and the AOD would favor the improvement of forest ecosystem services. This quantitative research integrated remote sensing and ground survey data and used spatial statistical methods to explore the drivers that influence the AOD of the exurban national forest park and analyze the differences between various forest types. The driver analysis was carried out in the hot (Z ≥ 1.64) and cold (Z ≤ −1.64) spots of AOD in 2010 and 2017. Our results showed that (1) the forest type was proved to be the main factor contributing to the AOD pattern and (2) from 2010 to 2017, the average growth rate of broad-leaved forest, coniferous forest, bamboo, and shrub in hot spots was significantly higher than that in cold spots, while there was no significant difference in the mixed forest. The average growth rate of biomass densities of bamboo, coniferous forest, and mixed forest were higher than that of the shrub and broad-leaved forest. These findings provided the guidance for the rational allocation of tree species to increase the biomass and improve the ecosystem service values of forest parks.
Experimental and Numerical Studies on Rock Cutting with Saw Blade and Conical Pick Combined Cutting Method
Authors: Lu Zhenguo , Zeng Qingliang , Wang Zhiwen , Li Xu , Gao Kuidong
Published: October 2019

In the rock cutting process, conical pick wear is often encountered. In order to restrain this condition, a saw blades and conical pick combined cutting method was put forward. Saw blades were employed to slit the rock for increasing the free surface, and then the conical pick was used to break the rock. To research the cutting performance of the new cutting method, the corresponding experimental device and a three‐dimensional finite element model are established. In order to obtain crack propagation and fragment separation and to study the fracture process of the rock plate, a damage constative model and failure mechanism were combined in the numerical model. The mechanical tests were carried out to achieve the mechanical parameters of the rock. To investigate different parameters affecting rock plate cutting performance, experiments with different compressive strengths, physical parameters, and cutting depths were carried out. Moreover, the confining pressures affecting the cutting performance were adopted to simulate deep mining conditions. The experimental results demonstrated that the peak cutting force shows the exponential positive correlation with compressive strength, thickness of the rock plate, and cutting depth of the conical pick, and exhibits the exponential positive correlation with rock plate height and width. Besides, the numerical simulation results show that peak cutting force and confining pressure have a binomial relationship.
The Use of Succinylcholine in Brugada Syndrome: A Case Report and Discussion of Literature
Authors: de Wolf Marcus M. , Rus Nellie M. , Beljaars Guus H. , Tan Hanno L.
Published: October 2019

We describe a patient with a major depression and a newly discovered Brugada syndrome, who was successfully treated with 35 electroconvulsive therapy sessions using succinylcholine as muscle relaxant. We discuss the use of succinylcholine in patients with Brugada syndrome.
Identification of Two DNMT3A Mutations Compromising Protein Stability and Methylation Capacity in Acute Myeloid Leukemia
Authors: Bruno Samantha , Bochicchio Maria Teresa , Franchini Eugenia , Padella Antonella , Marconi Giovanni , Ghelli Luserna di Rorà Andrea , Venturi Claudia , Raffini Maddalena , Prisinzano Giovanna , Ferrari Anna , Bandini Lorenza , Robustelli Valentina , Pazzaglia Martina , Fontana Maria Chiara , Sartor Chiara , Abbenante Maria Chiara , Papayannidis Cristina , Soverini Simona , Ottaviani Emanuela , Simonetti Giorgia , Martinelli Giovanni
Published: October 2019

Somatic mutations of DNMT3A occur in about 20% of acute myeloid leukemia (AML) patients. They mostly consist in heterozygous missense mutations targeting a hotspot site at R882 codon, which exhibit a dominant negative effect and are associated with high myeloblast count, advanced age, and poor prognosis. Other types of mutations such as truncations, insertions, or single-nucleotide deletion also affect the DNMT3A gene, though with lower frequency. The present study aimed to characterize two DNMT3A gene mutations identified by next-generation sequencing (NGS), through analysis of protein stability and DNA methylation status at CpG islands. The first mutation was a single-nucleotide variant of DNMT3A at exon 20 causing a premature STOP codon (c.2385G > A; p.Trp795∗; NM_022552.4). The DNMT3A mutation load increased from 4.5% to 38.2% during guadecitabine treatment, with a dominant negative effect on CpG methylation and on protein expression. The second mutation was a novel insertion of 35 nucleotides in exon 22 of DNMT3A (NM_022552.4) that introduced a STOP codon too, after the amino acid Glu863 caused by a frameshift insertion (c.2586_2587insTCATGAATGAGAAAGAGGACATCTTATGGTGCACT; p. Thr862_Glu863fsins). The mutation, which was associated with reduced DNMT3A expression and CpG methylation, persisted at relapse with minor changes in the methylation profile and at protein level. Our data highlight the need to better understand the consequences of DNMT3A mutations other than R882 substitutions in the leukemogenic process in order to tailor patient treatments, thus avoiding therapeutic resistance and disease relapse.
Protein Binding Characteristics of the Principal Green Tea Catechins: A QCM Study Comparing Crude Extract to Pure EGCG
Authors: Ali Elsadig E. , Elmakki Mohamed O. , Gavette Miranda L. , Doyle Brian J. , Timpe Shannon J.
Published: October 2019

Label-free detection methods such as the quartz crystal microbalance (QCM) are well suited to the analysis of molecular interactions in complex mixtures such as crude botanical extracts. In the present study, the binding characteristics of epigallocatechin gallate (EGCG) and crude green tea extract solutions to bovine serum albumin (BSA) have been investigated. The adsorbed mass levels onto BSA-functionalized surfaces were measured at various solution concentrations. Langmuir and Freundlich isotherms were used to model the adsorption data. The Langmuir isotherm better described the adsorption behavior with correlations of 0.68 and 0.70 for the EGCG and the crude extract solutions, respectively. The better fit of the Langmuir model indicates that adsorption occurs homogeneously and that aggregation is negligible. The mass saturation is estimated to be 58% higher for the crude green tea solution as compared to the pure EGCG solution (7.9 ng/cm2 for green tea and 5 ng/cm2 for EGCG). The increased adsorption for the crude extract indicates that the additional tea chemical constituents are binding to alternate sites on the protein molecule and that competitive binding is a nondominant effect. However, a reduced adsorption rate for the crude extract was also observed, indicating some presence of competitive mechanisms. The results demonstrate the utility of the QCM for the analysis of protein binding in crude mixtures as well as pure compounds.
Influential Node Identification in Command and Control Networks Based on Integral k-Shell
Authors: Wang Yunming , Chen Bo , Li Weidong , Zhang Duoping
Published: October 2019

Influential nodes act as a hub for information transmission in a command and control network. The identification of influential nodes in a network of this nature is a significant and challenging task; however, it is necessary if the invulnerability of the network is to be increased. The existing k-shell method is problematic in that it features a coarse sorting granularity and does not consider the local centrality of nodes. Thus, the degree of accuracy with which the influential nodes can be identified is relatively low. This motivates us to propose a method based on an integral k-shell to identify the influential nodes in a command and control network. This new method takes both the global and local information of nodes into account, introduces the historical k-shell and a 2-order neighboring degree, and refines the k-shell decomposition process in a network. Simulation analysis is carried out from two perspectives: to determine the impact on network performance when influential nodes are removed and to obtain the correlation between the integral k-shell value and its propagation value. The simulation results show that the integral k-shell method, which employs an algorithm of lower complexity, accurately identifies the influence of those nodes with the same k-shell values. Furthermore, the method significantly improves the accuracy with which the influential nodes can be identified.
Seasonal Variations of Phosphorus Species in the Overlying and Pore Waters of the Tuohe River, China
Authors: Xu Qing , Yu Xiaoping , Guo Yafei , Deng Tianlong , Chen Yu-Wei , Belzile Nelson
Published: October 2019

Overlying sediment and pore waters were collected in summer and winter at upstream (Jintang) and downstream (Neijiang) sites of the Tuohe River, which is one of the five largest tributaries of the Yangtze River in China. Phosphorus species, including soluble reactive phosphorus (SRP), soluble unreactive phosphorus (SUP), and total dissolved phosphorus (TDP), and some diagenetic constituents including dissolved Fe(II), Mn(II), and sulfide in overlying and pore waters, were measured systematically. The seasonal variations and vertical distributions of phosphorus species in overlying and pore waters at both sampling sites were obtained to elucidate some aspects of the transport and transformations of phosphorus. Based on the profiles of pore and overlying waters as well as the TDN/TDP data during an algal bloom in 2007, it was clearly demonstrated that phosphorus was the main factor limiting the phytoplankton growth in the Tuohe River.
Evaluation of the Bioactivities of Rumex crispus L. Leaves and Root Extracts Using Toxicity, Antimicrobial, and Antiparasitic Assays
Authors: Idris Oladayo Amed , Wintola Olubunmi Abosede , Afolayan Anthony Jide
Published: October 2019

Traditional folks in different parts of the world use Rumex crispus L. for the treatment of microbial infections, malaria, and sleeping sickness in the form of decoction or tincture. In the search for a natural alternative remedy, this study aimed to evaluate the antimicrobial, antitrypanosomal, and antiplasmodial efficacy and the toxicity of R. crispus extracts. Antimicrobial potency of the extracts was evaluated using the agar dilution method to determine the minimum inhibitory concentration (MIC). The antitrypanosomal activity of the extracts was evaluated with the Trypanosoma brucei brucei model while the antimalaria potency was tested using Plasmodium falciparum 3D7 strain. Toxicity was then tested with brine shrimp assay and cytotoxicity (HeLa cells). The acetone extract of the root (RT-ACE) reveals the highest antimicrobial potency with the lowest MIC value of <1.562 mg/mL for all bacteria strains and also showed high potent against fungi. RT-ACE (IC50: 13 μg/mL) and methanol extract of the leaf (LF-MEE; IC50: 15 μg/mL) show a strong inhibition of P. falciparum. The ethanol extract of the root (RT-ETE: IC50: 9.7 μg/mL) reveals the highest inhibition of T.b. brucei parasite. RT-ETE and RT-ACE were found to have the highest toxicity in brine shrimp lethality assay (BSLA) and cytotoxicity which correlates in the two assays. This research revealed Rumex crispus has potency against microorganisms, Trypanosoma, and Plasmodium and could be a potential source for the treatment of these diseases.
Experimental Study of Thermal Effect of Lacquer Coating for PV-Trombe Wall System Combined with Phase Change Material in Summer
Authors: Luo Chenglong , Zou Wu , Sun Dan , Xu Lijie , Ji Jie , Liao Mengyin
Published: October 2019

This paper proposes a novel PV-Trombe wall system combined with phase-change material, which is named as PV-PCM-Trombe system. The work mainly experimentally studies the effectiveness and characteristics of using phase change materials to improve the overheating problem of PV-Trombe wall in summer. Through experiments, the photoelectric performance of the system using phase-change board surfaces with and without a matte black paint lacquer are compared; moreover, the influence on thermal environment of building is evaluated. The results indicate the PV-PCM-Trombe wall system shows an effective cooling effect on PV cell in both experiments and that the surface lacquer coating treatment of PCM plates affects little the photoelectric performance of the system and can reduce the working temperature of PV cell.
TF-343 Alleviates Diesel Exhaust Particulate-Induced Lung Inflammation via Modulation of Nuclear Factor-κB Signaling
Authors: Kim Dong Im , Song Mi-Kyung , Kim Seon-Hee , Park Chan Young , Lee Kyuhong
Published: October 2019

Inhalation of diesel exhaust particulate (DEP) causes oxidative stress-induced lung inflammation. This study investigated the protective effects of TF-343, an antioxidant and anti-inflammatory agent, in mouse and cellular models of DEP-induced lung inflammation as well as the underlying molecular mechanisms. Mice were intratracheally instilled with DEP or vehicle (0.05% Tween 80 in saline). TF-343 was orally administered for 3 weeks. Cell counts and histological analysis of lung tissue showed that DEP exposure increased the infiltration of neutrophils and macrophages in the peribronchial/perivascular/interstitial regions, with macrophages harboring black pigments observed in alveoli. TF-343 pretreatment reduced lung inflammation caused by DEP exposure. In an in vitro study using alveolar macrophages (AMs), DEP exposure reduced cell viability and increased the levels of intracellular reactive oxygen species and inflammatory genes (IL-1β, inhibitor of nuclear factor- (NF-) κB (IκB), and Toll-like receptor 4), effects that were reduced by TF-343. A western blot analysis showed that the IκB degradation-induced increase in NF-κB nuclear localization caused by DEP was reversed by TF-343. In conclusion, TF-343 reduces DEP-induced lung inflammation by suppressing NF-κB signaling and may protect against adverse respiratory effects caused by DEP exposure.
An Online Degradation Feature Extraction Technique for Shore Bridge Gearbox Based on Morphological Fractal Dimension and Sliding Window Weibull Fitting
Authors: Sun Dejian , Wang Bing , Hu Xiong , Wang Wei
Published: October 2019

Shore bridge and other port cranes have some working condition characters including high speed, heavy load, and large impact. In order to solve the degradation feature extraction issue of hoisting mechanism gearbox, an online degradation feature extraction technique based on morphological fractal dimension and sliding window Weibull fitting is proposed. Firstly, taking the vibration energy spectrum collecting from the gearbox as the online data source, the fractal dimension of the vibration energy spectrum during an analysis period is calculated and a fractal evolution curve is obtained. A three‐parameter Weibull fitting on the fractal curve within a sliding window after setting the window’s width and step size is performed. The scale parameter of the Weibull fitting model is introduced as the performance degradation feature. The effectiveness of the technique is verified by the full‐life vibration data of hoisting gearbox from Shanghai Port Group. The results show that the morphological fractal dimension is able to describe the fractal complexity of the vibration energy spectrum. The scale parameter of Weibull distribution is able to reflect the performance degradation trend of fractal curve smoothly, which lays a theoretical foundation for further solving the problem of online health assessment.
Common and Rare Sequence Variants Influencing Tumor Biomarkers in Blood
Authors: Olafsson Sigurgeir , Alexandersson Kristjan F. , Gizurarson Johann G.K. , Hauksdottir Katrin , Gunnarsson Orvar , Olafsson Karl , Gudmundsson Julius , Stacey Simon N. , Sveinbjornsson Gardar , Saemundsdottir Jona , Bjornsson Einar S. , Olafsson Sigurdur , Bjornsson Sigurdur , Orvar Kjartan B. , Vikingsson Arnor , Geirsson Arni J. , Arinbjarnarson Sturla , Bjornsdottir Gyda , Thorgeirsson Thorgeir E. , Sigurdsson Snaevar , Halldorsson Gisli H. , Magnusson Olafur T. , Masson Gisli , Holm Hilma , Jonsdottir Ingileif , Sigurdardottir Olof , Eyjolfsson Gudmundur I. , Olafsson Isleifur , Sulem Patrick , Thorsteinsdottir Unnur , Jonsson Thorvaldur , Rafnar Thorunn , Gudbjartsson Daniel F. , Stefansson Kari
Published: October 2019

Background:

Alpha-fetoprotein (AFP), cancer antigens 15.3, 19.9, and 125, carcinoembryonic antigen, and alkaline phosphatase (ALP) are widely measured in attempts to detect cancer and to monitor treatment response. However, due to lack of sensitivity and specificity, their utility is debated. The serum levels of these markers are affected by a number of nonmalignant factors, including genotype. Thus, it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects.

Methods:

We performed genome-wide association studies of serum levels of AFP (N = 22,686), carcinoembryonic antigen (N = 22,309), cancer antigens 15.3 (N = 7,107), 19.9 (N = 9,945), and 125 (N = 9,824), and ALP (N = 162,774). We also examined the correlations between levels of these biomarkers and the presence of cancer, using data from a nationwide cancer registry.

Results:

We report a total of 84 associations of 79 sequence variants with levels of the six biomarkers, explaining between 2.3% and 42.3% of the phenotypic variance. Among the 79 variants, 22 are cis (in- or near the gene encoding the biomarker), 18 have minor allele frequency less than 1%, 31 are coding variants, and 7 are associated with gene expression in whole blood. We also find multiple conditions associated with higher biomarker levels.

Conclusions:

Our results provide insights into the genetic contribution to diversity in concentration of tumor biomarkers in blood.

Impact:

Genetic correction of biomarker values could improve prediction algorithms and decision-making based on these biomarkers.
Comparative Effectiveness of Two Interventions to Increase Colorectal Cancer Screening for Those at Increased Risk Based on Family History: Results of a Randomized Trial
Authors: Paskett Electra D. , Bernardo Brittany M. , Young Gregory S. , Katz Mira L. , Reiter Paul L. , Tatum Cathy M. , Oliveri Jill M. , DeGraffinreid Cecilia R. , Gray Darrell Mason , Pearlman Rachel , Hampel Heather
Published: October 2019

Background:

First-degree relatives (FDR) of patients with colorectal cancer are at risk for colorectal cancer, but may not be up to date with colorectal cancer screening. We sought to determine whether a one-time recommendation about needing colorectal cancer screening using patient navigation (PN) was better than just receiving the recommendation only.

Methods:

Participants were FDRs of patients with Lynch syndrome–negative colorectal cancer from participating Ohio hospitals. FDRs from 259 families were randomized to a website intervention (528 individuals), which included a survey and personal colorectal cancer screening recommendation, while those from 254 families were randomized to the website plus telephonic PN intervention (515 individuals). Primary outcome was adherence to the personal screening recommendation (to get screened or not to get screened) received from the website. Secondary outcomes examined who benefited from adding PN.

Results:

At the end of the 14-month follow-up, 78.6% of participants were adherent to their recommendation for colorectal cancer screening with adherence similar between arms (P = 0.14). Among those who received a recommendation to have a colonoscopy immediately, the website plus PN intervention significantly increased the odds of receiving screening, compared with the website intervention (OR: 2.98; 95% confidence interval, 1.68–5.28).

Conclusions:

Addition of PN to a website intervention did not improve adherence to a colorectal cancer screening recommendation overall; however, the addition of PN was more effective in increasing adherence among FDRs who needed screening immediately.

Impact:

These findings provide important information as to when the additional costs of PN are needed to assure colorectal cancer screening among those at high risk for colorectal cancer.
Hemodynamic Changes Associated with Mydriatic Eye Drop Administration in Anesthetized Pediatric Patients
Authors: Arslan-Carlon Vittoria , Walline Maria C. , Seier Kenneth , Tan Kay See , Abramson David H.
Published: October 2019

Background: Dilating eye drops are routinely used in pediatric retinoblastoma patients during anesthetized ophthalmologic exams. Information on the systemic effects of ocular mydriatics, especially in anesthetized pediatric patients, is limited. Objective: The primary aim of this study was to analyze hemodynamic changes during mydriatic eye drop administration in anesthetized pediatric patients. Methods: A retrospective chart review was performed for pediatric retinoblastoma patients who underwent MRI with anesthesia. Baseline blood pressure (BP) and heart rate (HR) were charted for each patient at induction. HR and mean arterial pressure (MAP) measurements were recorded at 5, 10, 15, 30, and 45 min after eye drop administration. Secondarily, we included data from 15 patients who received dilating eye drops while under sevoflurane general anesthetic. All patients were dilated with phenylephrine 2.5 or 10% (depending on age) and tropicamide 1%. Results: The final analysis included 176 anesthesia encounters. The results demonstrate no statistically significant deviation of more than 20% from baseline for either HR or MAP. Additionally, we did not detect any difference between patients who were anesthetized with propofol versus sevoflurane. Conclusions: We did not observe significant hemodynamic instability with administration of dilating eye drops during propofol anesthesia.
TRIAP1 Inhibition Activates the Cytochrome c/Apaf-1/Caspase-9 Signaling Pathway to Enhance Human Ovarian Cancer Sensitivity to Cisplatin
Authors: Zhang Tian-Mei
Published: October 2019

Objective: To investigate whether TRIAP1inhibition affects the ovarian cancer cell resistance to cisplatin (DDP) via the Cyt c/Apaf-1/caspase-9 pathway by in vitro and in vivo experiments. Methods: CCK8 assay was performed to find out how treatment with both TRIAP1 siRNA and DDP affects the cell viability of SKOV3 cells and DDP-resistant human ovarian carcinoma cell line SKOV3/DDP. SKOV3/DDP cells were transfected with control siRNA or TRIAP1 siRNA before 24 h of treatment with DDP (5 μg/mL). Flow cytometry was employed to detect cell apoptosis and Western blot to examine the expressions of Cyt c/Apaf-1/caspase-9 pathway-related proteins. SKOV3/DDP cells transfected with control siRNA or TRIAP1 siRNA were subcutaneously injected into BALB/c-nu/nu nude mice followed by the intraperitoneal injection of DDP (4 mg/kg). Cyt c/Apaf-1/caspase-9 pathway in transplanted tumors was detected by immunohistochemistry. Results: TRIAP1 expression declined in SKOV3 cells when compared with SKOV3/DDP cells. The proliferation rate was lower in SKOV3/DDP cells transfected with TRIAP1 siRNA combined with treatment of DDP (1, 2, 4, 6, 8, 16, 32 μg/mL) than in those transfected with control siRNA. Moreover, the TRIAP1 siRNA group had an increased SKOV3/DDP cell apoptosis rate with the activation of the Cyt c/Apaf-1/caspase-9 pathway. During DDP treatment, nude mice in TRIAP1 siRNA group had slower growth and smaller size of transplanted tumor than those in control siRNA group, with increased expression of Cyt c, Apaf-1, and caspase-9. Conclusion: TRIAP1 inhibition may enhance the sensitivity of SKOV3/DDP cells to cisplatin via activation of the Cyt c/Apaf-1/caspase-9 pathway.
Imaging Predictors for Nonsentinel Lymph Node Metastases in Breast Cancer Patients
Authors: Cong Yizi , Wang Suxia , Zou Haidong , Zhu Shiguang , Wang Xingmiao , Cao Jianqiao , Wang Ji , Liu Yanqing , Qiao Guangdong
Published: October 2019

Background: The relationship between imaging features and nonsentinel lymph node (NSLN) metastasis is not clear. Objectives: To determine whether imaging features could predict NSLN metastasis in sentinel lymph node (SLN)-positive breast cancer patients and to provide new clues for avoiding unnecessary axillary lymph node dissection. Method: 171 patients with clinically negative axillary lymph nodes and a pathologically positive SLN were recruited between January 2007 and January 2014. According to the Breast Imaging Reporting and Data System (BI-RADS), the effects of clinicopathological factors, especially imaging features, on NSLN metastases were assessed by univariate and multivariate statistical analyses. Results: The average number of dissected SLNs was 2.11 (range, 1–6); 56 of the 171 (32.75%) patients exhibited NSLN metastases. In univariate analysis, tumor size, number of positive SLNs, ratio of positive SLNs, mammographic mass margins, ultrasonographic mass margins, and ultrasonographic vascularity were significantly correlated with NSLN involvement. Furthermore, through multivariate analysis, tumor size, number of positive SLNs, mammographic mass margins, and ultrasonographic vascularity were still independent predictors of NSLN involvement. Additionally, in SLN-positive patients, number of positive SLNs and ultrasonographic vascularity could also predict the tumor burden in NSLN. Conclusions: In addition to tumor size and the number of positive SLNs, mammographic mass margins and ultrasonographic vascularity were also independent predictors of NSLN metastases in SLN-positive patients of breast cancer. The number of positive SLNs and ultrasonographic vascularity could also predict the tumor burden in NSLN.
The Ability of Different Scoring Systems to Predict Mortality in Chronic Obstructive Pulmonary Disease Patients: A Prospective Cohort Study
Authors: Kim Joohae , Lee Chang-Hoon , Hwang Seung-Sik , Kim Deog-Kyeom , Yoon Ho Il , Lee Sang Haak , Kim Ki Uk , Kim Eun Kyung , Kim Tae-Hyung , Lee Ji-Hyun , Oh Yeon-Mok , Lee Sang-Do
Published: October 2019

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality, therefore the prediction of mortality in COPD patients is crucial. In the current study, the abilities of different categorization systems to predict mortality in stable COPD patients from a prospective cohort were compared. Methods: The ability to predict mortality was compared in terms of discrimination by Harrell’s C (HC) index and calibration using graphical comparison among the GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2011, GOLD 2017, GOLD grade, BODE (BMI, Airflow Obstruction, Dyspnea, Exercise), updated BODE, BODEx (BMI, Airflow Obstruction, Dyspnea, Exacerbation), e-BODE (Exacerbation and BODE), ADO (Age, Dyspnea, Airflow Obstruction), COPD prognostic index (CPI), and simplified/optimized B-AE-D (BMI, Acute Exacerbation, Dyspnea) indexes. Results: The study included 520 patients, of whom 63 died during a median 40-month follow-up period. Combined prediction systems exhibited higher discrimination properties than single predictors. The CPI exhibited the highest with a HC of 0.768, followed by the simplified B-AE-D (HC 0.761), ADO (HC 0.760), and optimized B-AE-D (HC 0.756). The BODE and its variants other than the ADO exhibited relatively lower HCs (0.656–0.705), and GOLD exhibited the lowest discrimination ability among the combined indices (HCs 0.628–0.637). Subjective symptom questionnaires such as the modified Medical Research Council (mMRC) scale (HC 0.693) and SGRQ (HC 0.679) exhibited the highest ability to predict mortality among the single indices. Conclusion: The ADO, simplified B-AE-D, optimized B-AE-D, and GOLD 2017 exhibited good calibration properties, but the CPI did not. The simplified and optimized B-AE-Ds and the ADO index had good discrimination and calibration properties for the prediction of mortality in stable COPD patients.
Neoadjuvant Chemotherapy for Locally Advanced T4 Colon Cancer: A Nationwide Propensity-Score Matched Cohort Analysis
Authors: de Gooyer Jan-Marie , Verstegen Marlies G. , ’t Lam-Boer Jorine , Radema Sandra A. , Verhoeven Rob H.A. , Verhoef Cornelis , Schreinemakers Jennifer M.J. , de Wilt Johannes H.W.
Published: October 2019

Introduction: Neoadjuvant chemotherapy (CT) for locally advanced colon cancer (LACC) could potentially lead to tumor shrinkage, eradication of micrometastases, and prevention of tumor cell shedding during surgery. This retrospective study investigates the surgical and oncological outcomes of preoperative CT for LACC. Methods: Using the Netherlands Cancer Registry, data of patients with stage II or III colon cancer, diagnosed between 2008 and 2016 was collected. A propensity score matching (PSM; 1:2) was performed and compared patients with clinical tumor (cT) 4 colon cancer who were treated with neoadjuvant CT to patients with cT4 colon cancer treated with adjuvant CT (Fig. 1). Results: A total of 192 patients treated with neoadjuvant CT were compared to 1,954 patients that received adjuvant CT. After PSM, 149 patients in the neoadjuvant group were compared to 298 patients in the control group. No significant differences were found in baseline characteristics after PSM. After neoadjuvant CT, a significant response was observed in 13 (9%) patients with 5 (4%) patients showing a complete response. Complete resection margins (R0) were achieved in 77% in the neoadjuvant group versus 86% in the adjuvant treated group (p = 0.037). Significantly less tumor positive lymph nodes were found in the neoadjuvant group (median 0 vs. 2, p < 0.001). Major complication rates and 5-year overall survival did not differ between both groups (67–65%, p = 0.87). Conclusion: Neoadjuvant CT seems safe and feasible with similar long-term survival compared to patients who are treated with adjuvant CT.
The Sound and Face of Others: Vocal Priming Effects on Facial Emotion Processing in Posttraumatic Stress Disorder
Authors: Schneider Isabella , Bertsch Katja , Izurieta Hidalgo Natalie A. , Müller Laura E. , Defiebre Nadine , Herpertz Sabine C.
Published: October 2019

Introduction: Facial expressions and vocal intonation are key signals in the communication of emotions. Individuals with posttraumatic stress disorder (PTSD) are known to show an impaired perception of facial emotions. So far, research on multimodal emotional stimuli or the priming effects on emotion processing has been absent in PTSD. Therefore, we conducted a study to investigate the influence of vocal priming on facial emotion processing and classification in PTSD using electroencephalography. Methods: Twenty-one women with PTSD compared to 28 healthy women were asked to classify emotion-morphed faces with predominantly angry, ambiguous, or predominantly happy expressions primed by either an angry or a happy voice. Responses and reaction times as well as the N170, a component reflecting configural face processing, were analyzed. Results: Patients with PTSD were slower in classifying emotional faces that were primed by either an angry or happy voice compared to the healthy controls (HCs; η2 = 0.14). Additionally, patients with PTSD were faster in classifying facial expressions after angry compared to happy vocal primes (η2 = 0.14). HCs did not show this effect. Correlation analyses revealed positive associations between emotion (dys-)regulation and reaction times in patients with PTSD but not in HCs (r = 0.64–0.76). Furthermore, patients with PTSD showed greater N170 amplitudes for predominantly angry and ambiguous faces than HCs (η2 = 0.07). Conclusion: Data suggest that patients with PTSD experience more difficulties when processing complex social stimuli than HCs. The altered processing of complex social-emotional signals could amplify PTSD symptoms, thus qualifying as an explicit therapy target.
Assessment of Exudative Activity of Choroidal Neovascularization in Age-Related Macular Degeneration by OCT Angiography
Authors: von der Emde Leon , Thiele Sarah , Pfau Maximilian , Nadal Jennifer , Meyer Johanna , Möller Philipp T. , Schmid Matthias , Fleckenstein Monika , Holz Frank G. , Schmitz-Valckenberg Steffen
Published: October 2019

Purpose: Based on exudative activity, choroidal neovascularization (CNV) in age-related macular degeneration (AMD) can be classified as “active” aCNV, pretherapied “silent” sCNV (i.e., a treatment-free interval >12 weeks), or treatment-naïve “quiescent” qCNV. We evaluated the qualitative and quantitative optical coherence tomography angiography (OCTA) features of these CNV subgroups. Methods: The presence of small-caliber vessels, peripheral arcades, and a ­perilesional OCTA signal attenuation as well as values for vessel length, density, and branching index were evaluated for each CNV network in a 6 × 6 mm OCTA scan pattern. Results: Fifty-one eyes of 51 patients with AMD (age 75.9 ± 7.5 years; 20 males [39.2%]) were included. The qCNV subgroup (n = 8) showed the highest prevalence of qualitative and quantitative values for OCTA activity criteria, reaching significance with regard to small-caliber vessels (p = 0.003), peripheral arcades (p = 0.039), vessel length (p = 0.020), and branching index (p < 0.001) when compared to the aCNV (n = 32) and sCNV (n = 11) subgroups. Qualitative criteria were inversely associated with the number of previous anti-VEGF injections (each p < 0.03), while quantitative metrics also suggested lower values. Conclusions: These findings suggest that OCTA may be supportive in the phenotypical differentiation of CNV lesions secondary to AMD, while the assessed structural changes appeared to be more indicative of previously administered anti-VEGF therapy than current exudative activity.
Ultrafiltration Rate Effects Declines in Residual Kidney Function in Hemodialysis Patients
Authors: Lee Yuji , Okuda Yusuke , Sy John , Kim Sung Rok , Obi Yoshitsugu , Kovesdy Csaba P. , Rhee Connie M. , Streja Elani , Kalantar-Zadeh Kamyar
Published: October 2019

Background: High ultrafiltration rate (UFR) has been associated with increased mortality in hemodialysis (HD) patients. However, the impact of UFR on decline of residual kidney function (RKF) has not been elucidated among patients receiving conventional HD. Methods: We performed a retrospective cohort study of 7,753 patients who initiated conventional HD from 2007 to 2011 and survived the first year of dialysis with baseline UFR and renal urea clearance (KRU) data at baseline and 1 year (5th patient-quarter). The primary exposure was average UFR at the 1st patient-quarter from dialysis initiation (<4, 4 to <6, 6 to <9, 9 to <13, and ≥13 mL/h/kg). Decline in RKF was defined as the percent change in KRU and decline in urine output during the first year after initiation of dialysis. We used a logistic regression model for rapid decline in RKF and a linear regression model for change in urine volume. Results: In our HD cohort, mean baseline UFR was 7.0 ± 3.1 mL/h/kg, and median (interquartile range) baseline KRU was 3.5 (2.1–5.3) mL/min/1.73 m2. There was a graded association between UFR and a rapid decline in RKF; the expanded case mix-adjusted ORs and 95% CIs were 1.21 (1.04–1.40), 1.34 (1.16–1.55), 1.73 (1.46–2.04), and 1.93 (1.48–2.52) for baseline UFR 4 to <6, 6 to <9, 9 to <13, and ≥13  mL/h/kg, respectively (reference: <4 mL/h/kg). KRU trajectories showed a greater KRU decline over time in higher UFR categories. Higher UFR was also associated with a greater decline in urine output after 1 year. Conclusion: Higher UFR was associated with a rapid decline in RKF among conventional HD patients. Further clinical trials are needed to elucidate a causal effect of UFR on RKF among HD patients.