bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel 2-Stage Fractional Runge–Kutta Method for a Time-Fractional Logistic Growth Model
Authors: Arshad Muhammad Sarmad , Baleanu Dumitru , Riaz Muhammad Bilal , Abbas Muhammad
Published: June 2020

In this paper, the fractional Euler method has been studied, and the derivation of the novel 2-stage fractional Runge–Kutta (FRK) method has been presented. The proposed fractional numerical method has been implemented to find the solution of fractional differential equations. The proposed novel method will be helpful to derive the higher-order family of fractional Runge–Kutta methods. The nonlinear fractional Logistic Growth Model is solved and analyzed. The numerical results and graphs of the examples demonstrate the effectiveness of the method.
Mesenchymal Stem Cell-Based Therapy for Allergic Rhinitis
Authors: Sun Liwei , Sha Jichao , Meng Cuida , Zhu Dongdong
Published: June 2020

Allergic rhinitis (AR) is a prevalent disorder that causes a significant and often underestimated health burden for individuals and society. The current drug treatment cannot essentially deal with the regulation of the allergic reaction, while the allergic symptoms could be alleviated. Mesenchymal stem cells (MSCs) bear a variety of properties, such as the ability to differentiate into various cell lineages, to secrete soluble factors crucial for cell survival and proliferation, to migrate to the exact site of injury, and to modulate the immune response. Clinical studies have been extensively conducted in MSCs as the models for varieties of diseases such as neurological diseases. Due to their immunomodulatory properties, the MSCs have gradually been believed to become one of the promising strategies for AR treatments although so far the MSCs-mediated treatment for AR is still at animal experiments stage. Fully understanding the roles and mechanisms of MSCs immunomodulatory effects serves as the prerequisite that will be beneficial to the application of MSCs-based AR clinical treatment methods. In this review article, we highlighted the recent research advances and give a brief perspective in the future study of the MSCs-mediated therapeutic application in AR treatments.
Reduction in Serum High-Sensitivity C-Reactive Protein Favors Kidney Outcomes in Patients with Impaired Fasting Glucose or Diabetes
Authors: Liu Lili , Gao Bixia , Wang Jinwei , Yang Chao , Wu Shouling , Wu Yuntao , Chen Shuohua , Li Qiuyun , Zhang Huifen , Wang Guodong , Chen Min , Zhao Ming-hui , Zhang Luxia
Published: June 2020

Objective. We aimed to evaluate whether the reduction in serum high-sensitivity C-reactive protein (hs-CRP) favors kidney outcomes. Methods. This study was a subanalysis including patients with impaired fasting glucose or diabetes of the Kailuan cohort study. The predictor was based on two consecutive visits of hs-CRP levels in 2006 and 2008. A total of 3924 patients with hs-CRP≥3 mg/L in 2006 were divided into two groups according to whether the levels of hs-CRP were reduced in 2008: Group 1: no reduction: hs-CRP≥3 mg/L in 2008; Group 2: reduction: hs-CRP<3 mg/L in 2008. Kidney outcomes include kidney function decline and development and progression of proteinuria and were followed up until the end of 2015. Results. There were 3905, 2049, and 493 patients included into our analysis for the outcomes of kidney function decline and the development and progression of proteinuria, respectively. A total of 398, 297, and 47 events occurred after 5 years of follow-up, respectively. Cox regression revealed that patients with reduction in hs-CRP have lower risk of kidney function decline (HR 0.71, 95% CI 0.57-0.89, and P=0.002) and development of proteinuria (0.77, 0.61-0.99, and P=0.038) after controlling for potential confounders as compared to those with no reduction in hs-CRP levels. Conclusions. Reduction in serum hs-CRP levels favors kidney outcomes in patients with impaired fasting glucose or diabetes.
Optimization of Maximum Routing Hop Count Parameter Based on Vehicle Density for VANET
Authors: Pei Zhonghui , Chen Wei , Zheng Hongjiang , Du Luyao
Published: June 2020

Vehicular Ad Hoc Network (VANET) is the basic technology of intelligent transportation systems for providing reliable and real-time communications between vehicles and vehicles or roadside units. In order to improve the communication quality of VANET, this paper studies the effects of different maximum routing hop count parameters on the performance of the network under different vehicle densities. We establish the mathematical models of node connectivity probability and the packet delivery ratio by using the Poisson distribution model. And the maximum routing hop count selection algorithm (MRHSA) is proposed based on the theoretical model established in the paper. The simulation experiments and statistical analysis on packet delivery ratio, throughput, and end-to-end delay are performed under the straight road and urban road scenes, supported by the Vehicle in Network Simulation (Veins). The results show that the maximum routing hop count parameter is an important impact factor on the communication quality of the network. It is found that MRSHA proposed in this paper can improve the packet delivery ratio by about 9.1% at most in straight road scenarios, which indicates that MRHSA will contribute to the improvement of the communication quality of VANET.
Numerical Estimation of Material Properties in the Electrohydraulic Forming Process Based on a Kriging Surrogate Model
Authors: Woo Mina , Lee Kyunghoon , Song Woojin , Kang Beomsoo , Kim Jeong
Published: June 2020

High-speed forming processes, such as electrohydraulic forming, have recently attracted attention with the development of forming technology. However, because the high-speed operation (above 100 m/s) raises safety concerns, most experiments are conducted in a closed die, which hides the forming process. Therefore, the experimental process can only be observed in a numerical simulation with accurate material properties. The conventional quasistatic material properties are improper for high-speed forming simulations with high strain rates (>102 s−1). In this study, the material properties of Al 6061-T6, which reflect the deformation behavior in the high-strain-rate region, were investigated in a numerical approach based on a reduced order model and a surrogate model in which the numerical results resemble the experimental results. The strain rate effect on the material was determined by the Cowper–Symonds constitutive equation, and two strain rate parameters were predicted. The surrogate model takes two material parameters as inputs and outputs a weighting coefficient calculated by the reduced order model. The surrogate model is based on the Kriging method to reduce the simulation cost. Next, the optimal material parameters that minimize the error between the surrogate model and the experiments are estimated by nonlinear least-squares optimization using a genetic algorithm and the constructed surrogate model. The predicted optimal parameters were verified by comparing the results of the experiment, numerical simulation, and surrogate model.
Endoplasmic Reticulum Stress Regulates Scleral Remodeling in a Guinea Pig Model of Form-Deprivation Myopia
Authors: Zhu Chengcheng , Chen Qingzhong , Yuan Ying , Li Min , Ke Bilian
Published: June 2020

Purpose. This study aimed to investigate the role of endoplasmic reticulum (ER) stress in scleral remodeling in a guinea pig model of form-deprivation myopia (FDM). Methods. Guinea pigs were form deprived to induce myopia. ER ultrastructural changes in the sclera were examined by transmission electron microscopy (TEM). The protein levels of ER stress chaperones, including GRP78, CHOP, and calreticulin (CRT), were analyzed by western blotting at 24 hours, 1 week, and 4 weeks of FD. Scleral fibroblasts from guinea pigs were cultured and exposed to the ER stress inducer tunicamycin (TM) or the ER stress inhibitor 4-phenylbutyric acid (4-PBA). CRT was knocked down by lentivirus-mediated CRT shRNA transfection. The expression levels of GRP78, CHOP, TGF-β1, and COL1A1 were analyzed by qRT-PCR or western blotting. Results. The sclera of FDM eyes exhibited swollen and distended ER at 4 weeks, as well as significantly increased protein expression of GRP78 and CRT at 1 week and 4 weeks, compared to the sclera of the control eyes. In vitro, TM induced ER stress in scleral fibroblasts, which was suppressed by 4-PBA. The mRNA expression of TGF-β1 and COL1A1 was upregulated after TM stimulation for 24 hours, but downregulated for 48 hours. Additionally, change of TGF-β1 and COL1A1 transcription induced by TM was suppressed by CRT knockdown. Conclusions. ER stress was an important modulator which could influence the expression of the scleral collagen. CRT might be a new target for the intervention of the FDM scleral remodeling process.
Cognitive Protective Mechanism of Crocin Pretreatment in Rat Submitted to Acute High‐Altitude Hypoxia Exposure
Authors: Zhang Xiaoyan , Zhang Xianjun , Dang Zhancui , Su Shanshan , Li Zhanqiang , Lu Dianxiang
Published: June 2020

Inadequate oxygen availability at high altitude leads to oxidative stress, resulting in hippocampal neurodegeneration and memory impairment. In our previous study, we found that the cognitive dysfunction occurred when male SD rat was rapidly exposed to 4200 m of high altitude for 3 days. And we also found that crocin showed a cognitive protective effect under hypoxia by regulating SIRT1/PGC‐1α pathways in rat’s hippocampus. In this article, focused on factors related to SIRT1/PGC‐1α pathways, we proposed to further elucidate crocin’s pharmacological mechanism. Adult male Sprague‐Dawley rats were randomly divided into five groups: control group, hypoxia group (rats were rapidly transported to high altitude of 4200 m for 72 h), and crocins+hypoxia groups (pretreatment with crocin of 25, 50, and 100 mg/kg/d for 3 days). The learning and memory ability was tested by Morris water maze analysis. Hippocampal histopathological changes were observed by HE staining and Nissl staining. The expression of NRF1, TFAM, Bcl‐2, Bax, and caspase‐3 was detected by immunohistochemistry, RT‐PCR, and western blotting test. The contents of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSHPx) were detected by the TBA, WST, and colorimetry method. Neuronal apoptosis was observed by TUNEL staining. After crocin pretreatment, the traveled distance was significantly reduced and the percentage of time in the target quadrant was significantly increased tested by Morris water maze. And neuronal damage in the hippocampus was also significantly ameliorated based on HE staining and Nissl staining. Furthermore, in hippocampus tissue, mitochondrial biosynthesis‐related factors of NRF1, TFAM expression was increased; oxidative stress factors of SOD, GSH, and GSHPx expression level were increased, and MDA and glutathione disulfide (GSSG) level were decreased; antiapoptotic protein Bcl‐2 expression was increased, and proapoptotic proteins Bax and caspase‐3 expression were decreased, with a manner of crocin dose dependent. Therefore, the cognitive protective mechanism of crocin in rat under acute hypoxia was related to promoting mitochondrial biosynthesis, ameliorating oxidative stress injury, and decreasing neuronal apoptosis.
Quantitative Research and Characterization of the Loess Microstructure in the Bai Lu Tableland, Shaanxi Province, China
Authors: Deng Longsheng , Fan Wen , Liu Shaopeng , Chang Yupeng , Dai Yan , Li Yubo
Published: June 2020

Loess is a special geotechnical material with strong structural properties, and the microstructural characteristics of loess significantly influence its macroscopic physical features, mechanical properties, and catastrophic behavior. In this paper, serial samples were extracted from the continuous loess and paleosol strata of the Bai Lu tableland; with these samples, the optical microscopy‐based serial sectioning method was adopted to study the quantitative characterization and variation in the loess microstructure. Three‐dimensional characteristics and quantitative parameters of the particles, pores, and throats of the loess were obtained. The results indicate that the volume, Eq‐Radius, and major‐minor axis ratio of the loess particles satisfy third‐order, third‐order, and second‐order Gaussian distributions, respectively. The Eq‐Radius of the loess pores and throats satisfies a first‐order Gaussian distribution, and the throat channel length satisfies a gamma distribution. With increasing stratum depth, the particles become more flattened, the throat radii become larger and the pore channels become slenderer. The variation in fitting parameters and the correlations between the macrophysical and mechanical properties of loess were then explored. The study of the microstructure of loess contributes to a better understanding of the catastrophic behavior of loess and the physical mechanism of geologic hazards in this area.
Association between Oral Health Status and Diabetic Nephropathy-Related Indices in Japanese Middle-Aged Men
Authors: Yoshioka Masami , Okamoto Yoshifumi , Murata Masahiro , Fukui Makoto , Yanagisawa Shizuko , Shirayama Yasuhiko , Nagai Kojiro , Hinode Daisuke
Published: June 2020

Oral health status is known to be associated with lifestyle-related diseases such as diabetes and chronic kidney disease. In Japan, around 40% of hemodialysis cases are patients with diabetic nephropathy. The aim of this study was to clarify the association between oral health status and diabetic nephropathy-related indices in Japanese middle-aged men. Sixty-six men (age range: 55–64 years) with ≥20 remaining teeth and who received public medical checkups and oral examinations were enrolled. We examined correlations of age, body mass index, HbA1c, HDL-C, LDL-C, neutral fat, serum creatinine, and the estimated glomerular filtration rate (eGFR) with the number of remaining teeth or the community periodontal index (CPI) score (periodontal pocket<4 mm: 0, 4–6 mm: 1, ≥6 mm: 2). A positive correlation between the CPI score and serum creatinine and a negative correlation between CPI score and eGFR (Spearman’s rank correlation coefficient, r=0.459, p<0.01, and r=−0.460, p<0.01, respectively) were observed. The mean eGFR in the CPI score 0 group was significantly higher than that in the CPI score 1/2 group (82.6 vs. 70.7, Student’s t-test, p<0.01). Logistic regression analysis using eGFR as a dependent variable and age, CPI score, body mass index, HbA1c, and neutral fat as independent variables suggested that low eGFR (<60) could be attributed to CPI score (OR=3.169, 95% CI: 1.031–9.742, p=0.044). These results suggest a possible association between periodontal status and renal function in Japanese middle-aged men. Periodontal condition is controlled by oral prophylaxis, and periodontal disease and chronic kidney disease have some common risk factors. Thus, periodontal management can contribute to the prevention of severe chronic kidney disease.
Pentraxin 3 (PTX-3) Levels in Bronchoalveolar Lavage Fluid as a Lung Cancer Biomarker
Authors: Hu Tinghua , Qiao LiBang , Li Hong , Ren Hui , Ning Qian , Zhou Hong , Chen Xue , Sun Zhongmin , Shen Liangrong
Published: June 2020

In this study, we investigated the utility of pentraxin 3 (PTX-3) in bronchoalveolar lavage fluid (BALF) as lung cancer (LCa) diagnostic. A total of 89 LCa patients and 84 non-LCa patients who received bronchoscopy in the First Affiliated Hospital of Xi’an Jiaotong University from December 2014 to February 2015 were enrolled. LCa was subdivided according to pathological type (scale, gland, and small cell lung cancer). BALF samples were obtained during bronchoscopy and PTX-3 levels assayed by ELISA. t-tests, Mann-Whitney, and Kruskal-Wallis tests were performed for the comparison of PTX-3 levels between the different groups. Correlation analysis and receiver operating characteristic (ROC) analysis were used to analyze clinical data. The levels of PTX-3 increased in the LCa groups. PTX-3 levels were higher in the small cell lung cancer (SCLC) compared to non-small-cell lung cancer (NSCLC) groups. In LCa patients, obstructive pneumonia could upregulate the expression of PTX-3 in BALF. The area under the ROC curve of PTX-3 in BALF during LCa diagnosis, SCLC, and LCa with obstructive pneumonia was 0.949 (p≤0.001), 0.672 (p<0.05), and 0.838 (p<0.01), respectively. In conclusion, PTX-3 in BALF has a potential value as an LCa biomarker, particularly in cases of SCLC and LCa with obstructive pneumonia.
Existence of Solutions for Fractional Differential Equations with p-Laplacian Operator and Integral Boundary Conditions
Authors: Xie Jingli , Duan Lijing
Published: June 2020

In this paper, we investigate a class of integral boundary value problems of fractional differential equations with a p-Laplacian operator. Existence of solutions is obtained by using the fixed point theorem, and an example is given to show the applicability of our main result.
Roles and Clinical Applications of Exosomes in Cardiovascular Disease
Authors: Guo Dong , Xu Yuerong , Ding Jian , Dong Jiaying , Jia Ning , Li Yan , Zhang Mingming
Published: June 2020

Despite substantial improvements in therapeutic strategies, cardiovascular disease (CVD) is still among the leading causes of mortality and morbidity worldwide. Exosomes, extracellular vesicles with a lipid bilayer membrane of endosomal origin, have been the focus of a large body of research in CVD. Exosomes not only serve as carriers for signal molecules responsible for intercellular and interorgan communication underlying CVD pathophysiology but also are bioactive agents which are partly responsible for the therapeutic effect of stem cell therapy of CVD. We here review recent insights gained into the role of exosomes in apoptosis, hypertrophy, angiogenesis, fibrosis, and inflammation in CVD pathophysiology and progression and the application and mechanisms of exosomes as therapeutic agents for CVD.
Finite Element Modeling of Slip Insert Geometric Grip Optimization for Oil Well Drill Pipes
Authors: Tang Liping , Guo Baolin , Zhu Xiaohua
Published: June 2020

Drilling is being used to access ever-deeper oil and gas reservoirs, thereby presenting various challenges to the design and operation of down-hole tools. Slip inserts are suspension devices that are used to lower the drill pipe into the borehole and lift it to the wellhead, and their performance determines the extended depth of the borehole. In this paper, based on the field and laboratory test of the slip system, parameter sensitivity analysis is applied to the performance of a slip insert to guide the design of the latter. First, a mechanical model is developed of the drill pipe with the slip insert acting on it, and the stress acting on the drill pipe is analyzed theoretically by regarding the drill pipe as a thick-walled cylinder. Next, a numerical model is established to investigate how the slip-insert structure influences the drill-pipe stress, wherein the drill-pipe diameter is 5″ and the axial load is 180 tons. Finally, the results of a series of numerical simulations are presented. For the present slip insert and drill pipe, the optimum slip-insert parameter values are a front-rake angle of 70°, a back-rake angle of 30°, a tooth height of 2 mm, and zero chamfer.
Coupled Vibration Behavior of Hot Rolling Mill Rolls under Multinonlinear Effects
Authors: Peng Rongrong , Zhang Xingzhong , Shi Peiming
Published: June 2020

A coupled vibration model of hot rolling mill rolls under multiple nonlinear effects is established by considering the nonlinear spring force produced by the hydraulic cylinder, the nonlinear friction between the work rolls, the dynamic variation of rolling force, and the effect of external excitation as well as according to the structural constraints of a four-high hot rolling mill in the vertical and horizontal directions. The amplitude-frequency response equation of rolling mill rolls is determined by using a multiple-scale approximation method. Furthermore, use of actual data for simulation indicates that the internal resonance is the main cause of coupling vibration of the rolling mill rolls. In addition, changes in the movement displacement of the hydraulic cylinder and the coupling parameters strongly affect the coupling system of the rolling mill rolls. Finally, the study of the dynamic bifurcation characteristics of the rolling mill rolls indicates that, with varying external excitation amplitude, the vibration of rolls alternates between periodic motion, period-doubling motion, and chaotic motion in both vertical and horizontal directions. This is one of the reasons for the appearance of periodic light and dark stripes on the strip surface. Furthermore, the range of the external excitation amplitude (F0) at which the rolling mill roll system vibrates violently, that is, 5.68e5 N < F0 < 5.84e5 N and F0 > 6.12e5 N, must be avoided. The research results can provide a theoretical reference for further exploration of the coupling vibration mechanism of hot rolling mills.
Targeting MEF2D-fusion Oncogenic Transcriptional Circuitries in B-cell Precursor Acute Lymphoblastic Leukemia
Authors: Tsuzuki Shinobu , Yasuda Takahiko , Kojima Shinya , Kawazu Masahito , Akahane Koshi , Inukai Takeshi , Imaizumi Masue , Morishita Takanobu , Miyamura Koichi , Ueno Toshihide , Karnan Sivasundaram , Ota Akinobu , Hyodo Toshinori , Konishi Hiroyuki , Sanada Masashi , Nagai Hirokazu , Horibe Keizo , Tomita Akihiro , Suzuki Kyogo , Muramatsu Hideki , Takahashi Yoshiyuki , Miyazaki Yasushi , Matsumura Itaru , Kiyoi Hitoshi , Hosokawa Yoshitaka , Mano Hiroyuki , Hayakawa Fumihiko
Published: June 2020

The cellular context that integrates gene expression, signaling, and metabolism dictates the oncogenic behavior and shapes the treatment responses in distinct cancer types. Although chimeric fusion proteins involving transcription factors (TF) are hallmarks of many types of acute lymphoblastic leukemia (ALL), therapeutically targeting the fusion proteins is a challenge. In this work, we characterize the core regulatory circuitry (CRC; interconnected autoregulatory loops of TFs) of B-ALL involving MEF2D-fusions and identify MEF2D-fusion and SREBF1 TFs as crucial CRC components. By gene silencing and pharmacologic perturbation, we reveal that the CRC integrates the pre-B-cell receptor (BCR) and lipid metabolism to maintain itself and govern malignant phenotypes. Small-molecule inhibitors of pre-BCR signaling and lipid biosynthesis disrupt the CRC and silence the MEF2D fusion in cell culture and show therapeutic efficacy in xenografted mice. Therefore, pharmacologic disruption of CRC presents a potential therapeutic strategy to target fusion protein–driven leukemia.

Significance:

Cancer type–specific gene expression is governed by transcription factors involved in a highly interconnected autoregulatory loop called CRC. Here, we characterized fusion protein–driven CRC and identified its pharmacologic vulnerabilities, opening therapeutic avenues to indirectly target fusion-driven leukemia by disrupting its CRC.

See related commentary by Sadras and Müschen, p. 18.

This article is highlighted in the In This Issue feature, p. 5
Genomic Characterization of HIV-Associated Plasmablastic Lymphoma Identifies Pervasive Mutations in the JAK–STAT Pathway
Authors: Liu Zhaoqi , Filip Ioan , Gomez Karen , Engelbrecht Dewaldt , Meer Shabnum , Lalloo Pooja N. , Patel Pareen , Perner Yvonne , Zhao Junfei , Wang Jiguang , Pasqualucci Laura , Rabadan Raul , Willem Pascale
Published: June 2020

Plasmablastic lymphoma (PBL) is an aggressive B-cell non-Hodgkin lymphoma associated with immunodeficiency in the context of human immunodeficiency virus (HIV) infection or iatrogenic immunosuppression. While a rare disease in general, the incidence is dramatically increased in regions of the world with high HIV prevalence. The molecular pathogenesis of this disease is poorly characterized. Here, we defined the genomic features of PBL in a cohort of 110 patients from South Africa (15 by whole-exome sequencing and 95 by deep targeted sequencing). We identified recurrent mutations in genes of the JAK–STAT signaling pathway, including STAT3 (42%), JAK1 (14%), and SOCS1 (10%), leading to its constitutive activation. Moreover, 24% of cases harbored gain-of-function mutations in RAS family members (NRAS and KRAS). Comparative analysis with other B-cell malignancies uncovered PBL-specific somatic mutations and transcriptional programs. We also found recurrent copy number gains encompassing the CD44 gene (37%), which encodes for a cell surface receptor involved in lymphocyte activation and homing, and was found expressed at high levels in all tested cases, independent of genetic alterations. These findings have implications for the understanding of the pathogenesis of this disease and the development of personalized medicine approaches.

Significance:

Plasmablastic lymphoma is a poorly studied and extremely aggressive tumor. Here we define the genomic landscape of this lymphoma in HIV-positive individuals from South Africa and identify pervasive mutations in JAK–STAT3 and RAS–MAPK signaling pathways. These data offer a genomic framework for the design of improved treatment strategies targeting these circuits.

See related commentary by Küppers, p. 23.

This article is highlighted in the In This Issue feature, p. 5
Probable Creutzfeldt-Jakob Disease Presenting Dementia and Urinary Retention
Authors: Aiba Yosuke , Sakakibara Ryuji , Iimura Ayako , Inoue Chiaki , Terayama Keiichiro , Suzuki Keiko , Katsuragawa Shuichi , Tateno Fuyuki , Ogata Tsuyoshi
Published: June 2020

We describe the case of an 80-year-old woman with probable Creutzfeldt-Jakob disease (CJD) presenting dementia and urinary retention. Although the number of patients previously examined, including ours, is small for conclusion, provided that other etiologies of urinary retention are carefully excluded, urinary retention seems to become a feature in CJD, presumably reflecting spinal cord pathology in CJD. Physicians are advised to evaluate pelvic floor function in CJD particularly by checking post-void residuals.
Exercise Capacity and Ventricular Remodeling After Transcatheter Ventricular Septal Defect Closure in Asymptomatic or Minimally Symptomatic Adolescents and Adults
Authors: Chen Chun-An , Wang Jou-Kou , Lin Ming-Tai , Chiu Hsin-Hui , Hsu Jui-Yu , Lin Shu-Man , Chang Ya-Mei , Chiu Shuenn-Nan , Lu Chun-Wei , Wu Mei-Hwan , Yang Ming-Chun
Published: June 2020

Background:

Transcatheter ventricular septal defect (VSD) closure is a safe and efficacious alternative to surgery. However, its benefits in asymptomatic or minimally symptomatic patients remain unknown.

Methods:

Sixty patients with VSD aged 12 to 60 years underwent cardiopulmonary exercise test and echocardiography 1 day before transcatheter VSD closure and 6 months after intervention (closure group). Thirty patients who did not receive the intervention underwent the same evaluations over 6 months (observation group).

Results:

No significant change in exercise function was observed after VSD closure, except for increased peak oxygen (O
2
) pulse (absolute increase: 0.4±1.4 mL/beat). Left ventricular end-diastolic dimension and mitral peak early filling velocity-to-early diastolic annular velocity ratio decreased (absolute decrease: 0.3±0.6 cm and 0.7±1.9, respectively). Despite unchanged overall peak O
2
consumption, 33% of closure group patients exhibited clinically significant improvements in peak O
2
consumption (>10% increase relative to baseline). This was not related to the pulmonary flow-to-systemic flow ratio or baseline exercise capacity. By contrast, all exercise function parameters deteriorated significantly in the observation group. Subgroup analysis revealed that patients with a baseline left ventricular end-diastolic dimension
Z
score of >2 exhibited a significantly greater improvement in peak O
2
consumption, peak O
2
pulse, and oxygen uptake efficiency slope than did the observation group.

Conclusions:

Compared with conservative management, transcatheter VSD closure prevents deterioration in exercise capacity and promotes left ventricular reverse remodeling in asymptomatic or minimally symptomatic patients. These benefits are most prominent in patients whose left ventricular end-diastolic dimension
Z
score before intervention is >2, irrespective of baseline peak O
2
consumption and pulmonary flow/systemic flow ratio.

Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT03127748.
Trimethylamine-N-Oxide Promotes Age-Related Vascular Oxidative Stress and Endothelial Dysfunction in Mice and Healthy Humans
Authors: Brunt Vienna E. , Gioscia-Ryan Rachel A. , Casso Abigail G. , VanDongen Nicholas S. , Ziemba Brian P. , Sapinsley Zachary J. , Richey James J. , Zigler Melanie C. , Neilson Andrew P. , Davy Kevin P. , Seals Douglas R.
Published: June 2020

Age-related vascular endothelial dysfunction is a major antecedent to cardiovascular diseases. We investigated whether increased circulating levels of the gut microbiome-generated metabolite trimethylamine-N-oxide induces endothelial dysfunction with aging. In healthy humans, plasma trimethylamine-N-oxide was higher in middle-aged/older (64±7 years) versus young (22±2 years) adults (6.5±0.7 versus 1.6±0.2 µmol/L) and inversely related to brachial artery flow-mediated dilation (
r

2

=0.29,
P
<0.00001). In young mice, 6 months of dietary supplementation with trimethylamine-N-oxide induced an aging-like impairment in carotid artery endothelium-dependent dilation to acetylcholine versus control feeding (peak dilation: 79±3% versus 95±3%,
P
<0.01). This impairment was accompanied by increased vascular nitrotyrosine, a marker of oxidative stress, and reversed by the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl. Trimethylamine-N-oxide supplementation also reduced activation of endothelial nitric oxide synthase and impaired nitric oxide-mediated dilation, as assessed with the nitric oxide synthase inhibitor L-NAME (N
G
-nitro-L-arginine methyl ester). Acute incubation of carotid arteries with trimethylamine-N-oxide recapitulated these events. Next, treatment with 3,3-dimethyl-1-butanol for 8 to 10 weeks to suppress trimethylamine-N-oxide selectively improved endothelium-dependent dilation in old mice to young levels (peak: 90±2%) by normalizing vascular superoxide production, restoring nitric oxide-mediated dilation, and ameliorating superoxide-related suppression of endothelium-dependent dilation. Lastly, among healthy middle-aged/older adults, higher plasma trimethylamine-N-oxide was associated with greater nitrotyrosine abundance in biopsied endothelial cells, and infusion of the antioxidant ascorbic acid restored flow-mediated dilation to young levels, indicating tonic oxidative stress-related suppression of endothelial function with higher circulating trimethylamine-N-oxide. Using multiple experimental approaches in mice and humans, we demonstrate a clear role of trimethylamine-N-oxide in promoting age-related endothelial dysfunction via oxidative stress, which may have implications for prevention of cardiovascular diseases.
Mineralocorticoid Receptor Antagonists for Hypertension Management in Advanced Chronic Kidney Disease
Authors: Bakris George , Yang Y. Fred , Pitt Bertram
Published: June 2020

Spironolactone, a steroidal mineralocorticoid receptor antagonist, is recommended as add-on therapy for treatment-resistant/uncontrolled hypertension. However, caution is advised in patients with advanced chronic kidney disease (CKD) due to an increased risk for hyperkalemia. KBP-5074 is a nonsteroidal mineralocorticoid receptor antagonist under investigation for the treatment of treatment-resistant and uncontrolled hypertension in patients with moderate-to-severe CKD. BLOCK-CKD is a phase 2, international, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of KBP-5074, on top of current therapy, in patients with stage 3B/4 CKD (estimated glomerular filtration rate ≥15 and ≤44 mL/[min·1.73 m
2
]) and resistant hypertension (trough cuff seated systolic blood pressure ≥140 mm Hg, despite treatment with maximally tolerated doses of 2 or more antihypertensive medicines with complementary mechanisms). Patients (n=240) will be randomized 1:1:1 to once-daily treatment with KBP-5074 0.25 mg, KBP-5074 0.5 mg, or placebo, stratified by estimated glomerular filtration rate (≥30 versus <30 mL/[min·1.73 m
2
]) and systolic blood pressure (≥160 versus <160 mm Hg). Approximately 30% of enrolled patients should have an estimated glomerular filtration rate of 15 to 29 mL/(min·1.73 m
2
). The primary efficacy analysis is the change in trough cuff seated systolic blood pressure from baseline to day 84 for the KBP-5074 doses compared with placebo. Changes in urinary albumin-creatinine ratio will be assessed along with changes in serum potassium/incidence of hyperkalemia and changes in estimated glomerular filtration rate and serum creatinine. BLOCK-CKD will determine whether the addition of KBP-5074 will effectively lower blood pressure without an increased risk of hyperkalemia in patients who are not candidates for steroidal mineralocorticoid receptor antagonists due to advanced CKD.

Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT 03574363.
The results of external quality assessment programme on urine leukocyte and erythrocyte counting in Poland
Authors: Ćwiklińska Agnieszka , Kortas-Stempak Barbara , Jankowski Maciej , Bednarczuk Gabriela , Fijałkowska Aleksandra , Kuchta Agnieszka , Kowalski Robert
Published: June 2020

Introduction:
Urine particle analysis is an important diagnostic tool. The aim of this study was to evaluate the quality of urine leukocyte (WBC) and
erythrocyte (RBC) counting results obtained with manual and automated methods in Polish laboratories participating in the international external
quality assessment (EQA) programme.

Materials and methods:
1400 WBC and RBC counting results were obtained from 183 laboratories in EQA surveys organised by Labquality (Helsinki,
Finland) from 2017 to 2019. The between-laboratory coefficient of variation (CV), the percentage difference between the laboratories' results and
target values (Q-score (%)), as well as modified Youden plots were analysed.

Results:
For automated method groups, the medians of inter-laboratory CVs varied from 14% to 33% for WBC counting and from 10% to 39% for
RBC counting. For manual method groups, the medians of CV varied from 53% to 71% (WBC) and from 55% to 70% (RBC), and they were significantly
higher, in comparison to CVs for most automated method groups (P < 0.001). The highest percentage of results outside the target limits
(36%) and the highest range of Q-score (%) (from - 93% to 706%) were observed for laboratories which participated in the surveys for the first or
second time. The percentage of deviating results and the ranges of Q-score decreased with an increased frequency of laboratories’ participation in
the surveys.

Conclusions:
The quality of manual methods of urine WBC and RBC counting is unsatisfactory. There is an urgent need to take actions to improve
laboratories’ performance and to increase harmonisation of the results.
Quality improvement project: Reducing non-conformities of the samples for haemostasis testing in a secondary healthcare centre through the nurses’ education in phlebotomy
Authors: Banković Radovanović Patricija
Published: June 2020

Introduction: Poor compliance to the current guidelines and lack of knowledge among nurses about proper blood sampling is set as the study hypothesis. Here is presented a quality improvement project with following aims: a) to identify the most prevalent non-conformity of the samples for haemostasis testing, b) to identify the cause of sample non-conformity, c) to perform corrective action(s) and d) to assess the effectiveness of the corrective action(s). Materials and methods: The rate of non-conformity of samples collected for haemostasis tests was established for hospital wards with inpatients. Phlebotomy practice was audited throughout anonymous questionnaire among hospital’s nurses who perform phlebotomy. Education about blood sampling was performed as a 1-hour lecture in different small groups each working day within one month. Education effectiveness was assessed through the evaluation of sample quality and is considered effective if more than half of the hospital wards significantly reduced their sample non-conformities rate. Results: Clotted sample constituted 84% of sample non-conformities. The questionnaire revealed nurses’ poor knowledge in phlebotomy. There was no difference in nurses’ knowledge regarding the level of education or work experience. Reduction in sample non-conformities was observed in 7 out of 9 wards 4 months after education; this improvement was statistically significant for 5 wards. Conclusion: Clotted sample as the most prevalent non-conformity of the samples for haemostasis testing is caused by the lack of knowledge of the nurses in several parts of the phlebotomy process. Specific education of the motivated personnel in small groups was successful and long-term effective.
A Discrete-Time Neurodynamic Approach to Sparsity-Constrained Nonnegative Matrix Factorization
Authors: Li Xinqi , Wang Jun , Kwong Sam
Published: June 2020

Sparsity is a desirable property in many nonnegative matrix factorization (NMF) applications. Although some level of sparseness of NMF solutions can be achieved by using regularization, the resulting sparsity depends highly on the regularization parameter to be valued in an ad hoc way. In this letter we formulate sparse NMF as a mixed-integer optimization problem with sparsity as binary constraints. A discrete-time projection neural network is developed for solving the formulated problem. Sufficient conditions for its stability and convergence are analytically characterized by using Lyapunov's method. Experimental results on sparse feature extraction are discussed to substantiate the superiority of this approach to extracting highly sparse features.
Can the plant immune system be activated against animal parasites such as nematodes?
Authors: Molinari Sergio
Published: June 2020

Plants have an immune system that can be exerted by every cell against a vast array of pathogens and parasites. This immune system has several levels of specialisation. A first level induces a general basal defence, after which specific pathogen-associated molecular patterns (PAMPs) are recognised by plant receptors. Normally, this basal defence is overcome by specialised pests by secreting specific effectors that suppress this first line of defence. Plant-parasitic nematodes have been found to secrete several such effectors through amphid and cuticle secretions or directly into the cells through their stylets. Many studies carried out on endoparasitic sedentary nematodes (ESN), in particular, reported the suppression of plant defence, especially in terms of down-regulation of the genes involved in salicylic acid (SA)-mediated defence, in the very first stages of plant-nematode interaction. However, plants can be immunised or primed against nematode attacks. Immunised plants respond to nematode infection more rapidly and efficiently and let a minor number of invasive juveniles become sedentary, develop to gravid females and reproduce. Immunisation of plants can be achieved by pre-treatments with chemicals that are functional analogues of the phytohormones that mediate defence reactions, such as salicylic acid (SA). Moreover, plants provided with the beneficial microorganisms commonly present in a healthy rhizosphere, such as arbuscular mycorrhizal fungi or opportunistic symbiotic fungi, have been found to be immunised against ESN. Immunisation is mainly mediated by up-regulation of SA-dependent defence genes, such as pathogenesis-related genes (PR-genes). Immunisation is systemic and can also work against herbivorous insects.
Macro and microcharacters reveal a new species of Dichanthelium (Poaceae, Panicoideae) endemic to sandy soils of the Chapada Diamantina, Bahia, northeastern Brazil

Authors: MATOS ANDREZA O. , CARNEIRO JOSEANE S. , OLIVEIRA IASMIN L. C. , LEITE KELLY R. B. , SILVA CHRISTIAN , OLIVEIRA REYJANE P.
Published: June 2020

Dichanthelium is a genus belonging to the family Poaceae, included in the subfamily Panicoideae. It is widely distributed on the American continent, from Canada to Argentina. In Brazil, several species are endemic, mainly to the Chapada Diamantina, the Bahian portion of the Espinhaço range. One of them, D. cumbucana, has a problematic circumscription. During the preparation of a taxonomic account of Dichanthelium for Bahia, we found some specimens from Morro do Chapéu, a municipality of the northern portion of Chapada Diamantina, to be similar to D. cumbucana, but with distinguishing features. After morphological, anatomical and scanning electron microscopy (SEM) analyses, we found significant differences in the vegetative and reproductive characters of these specimens. Based on these data, we consider these specimens to be part of an independent taxon, herein described as the new species D. arenicola, which is only known from areas of sandy soils associated with “campo rupestre” vegetation. We also provide illustrations, data on habitat and distribution, as well as a conservation status assessment for the new species.
Pinnularia sikkimensis sp. nov. (Bacillariophyceae), from Eastern Himalayas and its distribution in Southeast Asia

Authors: DAS SUDIPTA KUMAR , RADHAKRISHNAN CHERAN , KULIKOVSKIY MAXIM , GLUSHCHENKO ANTON , KOCIOLEK JOHN PATRICK , Balasubramanian Karthick
Published: June 2020

A new species of Pinnularia is described from a stream from Sikkim, India, falls under Eastern Himalayas biodiversity hotspot. Features that help make this species distinctive include having triundulate margin, a broad, central fascia, a central depression, and oppositely-deflected external distal raphe fissures. Pinnularia sikkimensis sp. nov. is compared with its morphologically similar species, such as Pinnularia nodosa, P. biceps, P. grunowii, P. septentrionalis, P. graciloides var. jogensis and P. ferrophila. The taxon is also recorded from two stream sites in Vietnam suggesting a wide distribution across Southeast Asia. In addition to the description of the new species, a checklist of endemic Pinnularia taxa from India is also presented.
A new endemic Vincetoxicum (Apocynaceae) in the Eastern Cape, and a conspectus of the genus for South Africa

Authors: MEVE ULRICH , HEIDUK ANNEMARIE , LIEDE-SCHUMANN SIGRID
Published: June 2020

A new species is described in African Vincetoxicum (incl. Tylophora), and the present status of Vincetoxicum in South Africa is recapitulated. The new species, here described as Vincetoxicum stylesii, is a twining forest dweller known so far only from the Dwesa-Cwebe Nature Reserve in the Eastern Cape Province of South Africa. Due to its isolated phylogenetic position at the very base of Vincetoxicum, and to its rarity, it is to be regarded as a relict species. With the new species, the genus includes ten species in South Africa when adopting the here also proposed new synonymy for Vincetoxicum simianum (in V. cordatum) and V. badium var. latifolium (in V. umbelliferum); six of the species are endemic.
The near demise of Marlierea: moving last species to correct genera and notes on three incertae saedis taxa (Myrtaceae, Myrteae, Myrciinae)

Authors: SANTOS MATHEUS F. , STADNIK ALINE , PROENÇA CAROLYN E. B. , SOBRAL MARCOS
Published: June 2020

Recent phylogenetic and taxonomic studies resulted in the synonymization of Marlierea into Myrcia. This paper aims to transfer the last Marlierea species to their correct genera, which include not only taxa belonging to Myrcia, but also to Eugenia, Plinia and Siphoneugena. Five new combinations are proposed: Eugenia choriophylla, based on Marlierea choriophylla; Myrcia resupinata, based on Myrtus resupinata; Plinia parvifolia, based on Marlierea parvifolia; Plinia sessiliflora, based on Marlierea sessiliflora; and Siphoneugena martinellii, based on Marlierea martinellii. Two new names are proposed: Myrcia rufopilosa, replacing Myrtus rufa; and Myrcia sintenisiana, replacing Marlierea sintenisii. A new synonym is proposed, Marlierea cordata under Eugenia hirta. Three names, Marlierea capitata, Marlierea involucrata and Marlierea occhionii remain as incertae saedis, and, additionally, we have listed two nomina nuda referenced in the literature as Marlierea.
Typification of the names of three species of Carex (Cyperaceae)—proposed by Francis Boott

Authors: GHOSH ASOK , MALLICK TANMOY
Published: June 2020

Recent studies on nomenclatural revision showed that the name of three species of Carex L. (Cyperaceae; confined to Central and Eastern Himalayas) have not yet typified. We proposed the lectotypes for three names applied for the first time by Francis Boott in Illustration of the genus Carex (1858, 1862): Carex decora Boott, Carex pulchra Boott, and Carex vesiculosa Boott. The basic aim of the present study is to stabilize the binomen with the original materials and to locate the typous of the name for future correspondence.
Typification of Euphorbia candelabrum (Euphorbiaceae) and associated names

Authors: FIGUEIREDO ESTRELA , SMITH GIDEON F.
Published: June 2020

The valid publication of the name Euphorbia candelabrum Welwitsch (1855: 328) or E. candelabrum Welwitsch (1856: 251) (Euphorbiaceae) is subject to a request for a binding decision, which, following Art. 38.4 of the International Code of Nomenclature for algae, fungi, and plants (or Shenzhen Code, see Turland et al. 2018), provides the only means of permanently settling different views on the issue. As some typifications of associated names have not previously been effectively done, the following names are effectively typified here: E. candelabrum Trémaux ex Kotschy (1857: 169), E. venefica Trémaux ex Kotschy (1857: 173), and E. similis Berger (1907: 69). The type citation for E. conspicua Brown (1912: 600) is clarified. The nomenclatural status and type citations for E. confertiflora Volkens (1899: 266) and E. reinhardtii Volkens (1899: 263) are elucidated. These two names were not based on the same type and they are therefore not homotypic. Euphorbia confertiflora is a legitimate name.
First record of the genus Vailimia Kammerer, 2006 from India, with the description of two new species (Araneae: Salticidae: Plexippina)
Authors: BASUMATARY PARIS , CALEB JOHN T.D. , DAS SANGEETA , JANGID ASHISH KUMAR , KALITA JATIN , BRAHMA DULUR
Published: June 2020

The genus Vailimia Kammerer, 2006 is recorded for the first time from India. Two new species, Vailimia ajmerensis Caleb & Jangid sp. nov. (♂), and V. jharbari Basumatary, Caleb & Das sp. nov. (♂♀), are described and illustrated in detail. Presently, the genus is known only by the males, which means that the female of V. jharbari described herein is the first female known in the genus.
A new species of Clidicus in East Malaysia (Coleoptera, Staphylinidae, Scydmaeninae)
Authors: JAŁOSZYŃSKI PAWEŁ
Published: June 2020

A new species of Clidicini ant-like stone beetles, Clidicus mawarensis sp. n., is described and illustrated. The holotype male was collected in East Malaysia (Borneo: Sabah); the new species belongs to a group of large-bodied Clidicus, and shows similarities to C. ganglbaueri Reitter; the male has unusually complex structures of the aedeagal apical region.
A review of the leafhopper genus Pseudosubhimalus Ghauri (Hemiptera: Cicadellidae: Deltocephalinae) with description of a new species from Pakistan
Authors: NAVEED HASSAN , SHAH BISMILLAH , ZHANG YALIN
Published: June 2020

A new species of the leafhopper genus Pseudosubhimalus Ghauri (Cicadellidae: Deltocephalinae: Cicadulini), Pseudosubhimalus pakistanicus sp. n., is described from Khyber Pakhtunkhwa Province, Pakistan. Figures for habitus and genitalic characters are given for this new species and newly recorded species from Pakistan. A key to all the known species of the genus Pseudosubhimalus is provided.