bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency and individual severity of arterial blood pressure changes in children and adolescents with attention-deficit/hyperactivity disorder treated with methylphenidate hydrochloride: a prospective non-interventional study
Authors: Busold-Hagenbeck Dorothee , Elmenhorst Julia , Irtel von Brenndorff Christoph , Hilgers Reinhard , Hulpke-Wette Martin
Published: April 2020

Background

Attention-deficit/hyperactivity disorder (ADHD) is a common behavioural disorder in childhood. The psychostimulant methylphenidate hydrochloride (MPH) is one of the major pharmacological options for ADHD. MPH is known to result, on average, in a small increase in arterial blood pressure (BP). However, there are few clinical data regarding theindividualinfluences of MPH on BP among children and adolescents with ADHD. According to the European Union-wide standardised patient information sheet for MPH, BP changes >10 mm Hg compared with baseline values are ‘common’ (ie, ≥1% to <10%) in children and adolescents with ADHD during MPH therapy.

Aim

To investigate the frequency and individual severity of BP changes in children and adolescents with ADHD during the first 6 months of new MPH therapy.

Methods

In this study, 44 (77% male) children and adolescents (mean age (SD) 9.13 (1.86) years) with a diagnosis of ADHD according to the International Classification of Diseases, tenth revision, underwent ambulatory BP monitoring before and during the first 6 months of routine MPH therapy. Exclusion criteria were pre-existing MPH therapy and other medications that potentially influence BP or interfere with MPH. The non-interventional study was conducted prospectively at 10 paediatric cardiology centres in Germany and Austria.

Results

After beginning MPH therapy, 34% of participants (99% CI 15.52% to 52.66%) had BP increases/decreases >10 mm Hg. The mean changes in systolic BP and diastolic BP were 0.87 mm Hg (95% CI -1.75 mm Hg to 3.48 mm Hg) and 1.96 mm Hg (95% CI 0.21 mm Hg to 3.7 mm Hg), respectively. The proportion of participants with initial prehypertension/hypertension was 54.55% .

Conclusions

In our sample with a high baseline rate of prehypertension/hypertension, BP changes >10 mm Hg during MPH therapy were more frequent than those indicated by the patient information sheet. Moreover, individual BP changes, including increases and decreases >10 mm Hg, resulted in a small average BP increase in the sample, thus reflecting neither the severity nor the direction of individual BP changes. Therefore, the frequency and, due to the common use of the arithmetic mean, the individual severity of BP changes during MPH therapy may be underestimated. Further studies without averaging and with larger samples including patients in primary care settings are warranted.
Management of presumptive canine permethrin toxicosis using intravenous lipid emulsion as an adjunctive therapy
Authors: Kopke Matthew A , Yozova Ivayla D
Published: April 2020

A seven‐month‐old Cavalier King Charles spaniel presented with generalised, coarse muscle tremors that progressed to seizure activity, after observed ingestion (licking) of a cleaning product containing permethrin. At the time of presentation, the dog was receiving prednisone as management for masticatory muscle myositis. The dog was treated with symptomatic and supportive therapy in the form of midazolam, dexmedetomidine and intravenous lipid emulsion (ILE). This case details the first reported use of ILE as adjunctive therapy in the successful management of canine permethrin toxicosis. No further tremors or seizure activity, nor any adverse effects were observed following administration of ILE therapy.
Nonparametric and data-driven interpolation of subsurface soil stratigraphy from limited data using multiple point statistics
Authors: Shi Chao , Wang Yu
Published: April 2020

An essential task in many geotechnical projects is delineation of subsurface soil stratigraphy from scatter measurements. Geotechnical engineers often use their knowledge on local geology and interpret soil strata boundaries by linear interpolation of measured data. This usual practice may encounter difficulties when interpreting complex deposits, particularly when measurements are limited. In this study, a novel nonparametric, data-driven method based on multiple point statistics (MPS) is proposed to interpolate subsurface soil stratigraphy from sparse measurements. MPS may be formulated as Bayesian supervised machine learning, which adaptively learns high-order spatial information (e.g., curvilinear features of soil layers) using sparse measurements obtained in a specific site and training image that reflects pre-existing engineering knowledge on similar geological settings. The proposed method is the first ever purely data-driven method (i.e., without using any pre-specified parametric functions) for geotechnical site characterization. The proposed method is illustrated by a simulated example and real data from a reclamation site in Hong Kong. The proposed method not only accurately interpolates the subsurface soil stratigraphy from sparse measurements, but also quantifies uncertainty associated with the interpolation. Effects of governing parameters in the proposed method are explicitly investigated, and parameters appropriate for subsurface soil stratigraphy are identified.
Petrogenesis and geodynamic setting of granitoids at Machangqing Cu–Mo (Au) deposit, western Yangtze craton, southwestern China: constraints from zircon U–Pb and molybdenite Re–Os geochronology, Lu–Hf isotopes, and geochemistry
Authors: Yang Mimi , Zhao Fufeng , Liu Xianfan , Qing Hairuo , Raharimahefa Tsilavo , Duan Wenjing
Published: April 2020

The Machangqing Cu–Mo (Au) deposit is located in the central part of the Jinshajiang – Red River belt in the Sanjiang orogen, which lies across the Qiangtang terrane and western Yangtze craton, southwestern China. Zircon U–Pb dating constrains that the granite porphyry and porphyritic granite emplacements occurred at 35.92 ± 0.31 Ma and 34.92 ± 0.31 Ma, respectively. The Re–Os model ages of molybdenite are 34.94 ± 0.38 Ma. The new ages presented here, along with previously published data in the region, define a short duration of potassic magmatism and mineralization from 37 Ma to 34 Ma in the Jinshajiang – Red River belt. Zircon Ce4+/Ce3+ values of the porphyritic granite and granite porphyry vary from 50.32 to 1579.20 (averaging 481.01) and 33.18 to 1511.80 (averaging 452.98), respectively, and the log(fo2) values vary from –6.66 to −23.86 and −9.88 to −25.18, respectively, which plot within the range of the fayalite–magnetite–quartz buffer curve to the magnetite–hematite buffer curve, indicating an oxidized magma source, which may have facilitated the Cu–Au enrichment. Zircons from granitoids show εHf(t) values ranging from −0.75 to +2.33 and crustal model ages between 0.9 and 1.1 Ga. The features of Lu–Hf isotopes and wide range of Mg#, Cr, and Ni contents imply that the magmas of the Machangqing granitoids were probably derived from partial melting of juvenile lower crust and mixed with some mantle melts. Combined with the features of the Machangqing granitoids, the following evolution process are concluded. During the Cenozoic, the India–Asia continental collision triggered upwelling of hot asthenosphere and underplating of the thickened juvenile lower crust, which caused the formation of mafic and felsic magmas. Those magmas ascended, mixed, crystallized, and formed Machangqing ore-bearing granitoids in an intracontinental extension setting.
A Hybrid Multilingual Fuzzy-Based Approach to the Sentiment Analysis Problem Using SentiWordNet
Authors: Madani Youness , Erritali Mohammed , Bengourram Jamaa , Sailhan Francoise
Published: April 2020

Sentiment Analysis or in particular social network analysis (SNA) is a new research area which is increased explosively. This domain has become a very active research issue in data mining and natural language processing. Sentiment analysis (opinion mining) consists in analyzing and extracting emotions, opinions or attitudes from product’s reviews, movie's reviews, etc., and classify them into classes such as positive, negative and neutral, or extract the degree of importance (polarity). In this paper, we propose a new hybrid approach for classifying tweets into classes based on fuzzy logic and a lexicon based approach using SentiWordnet. Our approach consists in classifying tweets according to three classes: positive, negative or neutral, using SentiWordNet and the fuzzy logic with its three important steps: Fuzzification, Rule Inference/aggregation, and Defuzzification. The dataset of tweets to classify and the result of the classification are stored in the Hadoop Distributed File System (HDFS), and we use the Hadoop MapReduce for the application of our proposal.
The Genetics of Epilepsy
Authors: Perucca Piero , Bahlo Melanie , Berkovic Samuel F.
Published: April 2020

Epilepsy encompasses a group of heterogeneous brain diseases that affect more than 50 million people worldwide. Epilepsy may have discernible structural, infectious, metabolic, and immune etiologies; however, in most people with epilepsy, no obvious cause is identifiable. Based initially on family studies and later on advances in gene sequencing technologies and computational approaches, as well as the establishment of large collaborative initiatives, we now know that genetics plays a much greater role in epilepsy than was previously appreciated. Here, we review the progress in the field of epilepsy genetics and highlight molecular discoveries in the most important epilepsy groups, including those that have been long considered to have a nongenetic cause. We discuss where the field of epilepsy genetics is moving as it enters a new era in which the genetic architecture of common epilepsies is starting to be unraveled.
HDAC6-dependent ciliophagy is involved in ciliary loss and cholangiocarcinoma growth in human cells and murine models
Authors: Peixoto Estanislao , Jin Sujeong , Thelen Kristen , Biswas Aalekhya , Richard Seth , Morleo Manuela , Mansini Adrian , Holtorf Stephanie , Carbone Fabrizia , Pastore Nunzia , Ballabio Andrea , Franco Brunella , Gradilone Sergio A.
Published: April 2020

This work identifies novel targets against primary ciliary disassembly that can lead to new cholangiocarcinoma therapeutic strategies. Furthermore, ciliary loss has been described in different tumors, increasing the significance of our research.
Differences in renal BMAL1 contribution to Na+homeostasis and blood pressure control in male and female mice
Authors: Crislip G. Ryan , Douma Lauren G. , Masten Sarah H. , Cheng Kit-Yan , Lynch I. Jeanette , Johnston Jermaine G. , Barral Dominique , Glasford Krystal B. , Holzworth Meaghan R. , Verlander Jill W. , Wingo Charles S. , Gumz Michelle L.
Published: April 2020

The renal circadian clock has a major influence on the function of the kidney. Aryl hydrocarbon receptor nuclear translocator-like protein 1 [ARNTL; also known as brain and muscle ARNT-like 1 (BMAL1)] is a core clock protein and transcription factor that regulates the expression of nearly half of all genes. Using male and female kidney-specific cadherin BMAL1 knockout (KS-BMAL1 KO) mice, we examined the role of renal distal segment BMAL1 in blood pressure control and solute handling. We confirmed that this mouse model does not express BMAL1 in thick ascending limb, distal convoluted tubule, and collecting duct cells, which are the final locations for solute and fluid regulation. Male KS-BMAL1 KO mice displayed a substantially lower basal systolic blood pressure compared with littermate control mice, yet their circadian rhythm in pressure remained unchanged [male control mice: 127 ± 0.7 mmHg ( n = 4) vs. male KS-BMAL KO mice: 119 ± 2.3 mmHg ( n = 5), P < 0.05]. Female mice, however, did not display a genotype difference in basal systolic blood pressure [female control mice: 120 ± 1.6 mmHg ( n = 5) vs. female KS-BMAL1 KO mice: 119 ± 1.5 mmHg ( n = 7), P = 0.4]. In addition, male KS-BMAL1 KO mice had less Na+retention compared with control mice in response to a K+-restricted diet (15% less following 5 days of treatment). However, there was no genotype difference in Na+handling after a K+-restricted diet in female mice. Furthermore, there was evidence indicating a sex-specific response to K+restriction where female mice reabsorbed less Na+in response to this dietary challenge compared with male mice. We propose that BMAL1 in the distal nephron and collecting duct contributes to blood pressure regulation and Na+handling in a sex-specific manner.
Everolimus-Eluting Biodegradable Abluminal Coating Stent versus Durable Conformal Coating Stent: Termination of the Inflammatory Response Associated with Neointimal Healing in a Porcine Coronary Model
Authors: Mori Masayuki , Sakata Kenji , Yokawa Junichiro , Nakanishi Chiaki , Murai Kota , Okada Hirofumi , Shimojima Masaya , Yoshida Shohei , Yoshioka Kazuaki , Takuwa Yoh , Hayashi Kenshi , Yamagishi Masakazu , Kawashiri Masa-aki
Published: April 2020

Objectives. We evaluated the effect of the different carrier systems on early vascular response through histological analysis and scanning electron microscopy using a porcine model. Background. Although Synergy™ and Promus PREMIER™ share an identical stent material and drug elution (everolimus), they use different drug carrier systems: biodegradable abluminal coating polymer or durable conformal coating polymer, respectively. However, data regarding the impact of the different coating systems on vessel healing are currently limited. Methods. Twelve Synergy™ and Promus PREMIER™ were implanted in 12 swine. Histopathological analysis of the stented segments was performed on the 2nd and 14th days after implantation. Morphometric analysis of the inflammation and intimal fibrin content was also performed. Results. On the 2nd day, neointimal thickness, percentage of neointimal area, and inflammatory and intimal fibrin content scores were not significantly different between the two groups. On the 14th day, the inflammatory and intimal fibrin content scores were significantly lower in Synergy™ versus those observed in Promus PREMIER™. In Synergy™, smooth muscle cells were found and the neointimal layers were smooth. In contrast, inflammatory cells were observed surrounding the struts of Promus PREMIER™. Conclusions. These results demonstrate that termination of reactive inflammation is accelerated after abluminal coating stent versus implantation of conformal coating stent.
Thermally Affected Zone (TAZ) Assessment in Open-Loop Low-Enthalpy Groundwater Heat Pump Systems (GWHPs): Potential of Analytical Solutions
Authors: Gizzi Martina , Taddia Glenda , Abdin Elena Cerino , Russo Stefano Lo
Published: April 2020

Thermal perturbation produced in the subsurface by open-loop groundwater heat pump systems (GWHPs) must be predicted and constantly controlled, especially in the shallow aquifers of more densely urbanized areas, in order to guarantee plants’ long-term sustainable use and to avoid adverse effects on adjacent geothermal systems. Transient conditions in the flow dynamic can be successfully modelled by means of numerical modelling tools. However, for small plants in suitable hydrogeological systems, an alternative tool for predicting the thermally affected zone (TAZ) around the injection well can be found in analytical solutions for steady advective transport in a shallow aquifer. The validity of using steady analytical solutions to predict the TAZ development at the end of two different cooling seasons (2010 and 2016) was tested in the Politecnico di Torino GWHP system (NW Italy). When fixing the constant thermal difference (ΔT) between the injection and abstraction wells at 5°C, results revealed that a rather reliable assessment of the TAZ of Politecnico di Torino GWHPs, in Turin shallow aquifer, can be performed by plotting the cumulative distribution function of the injected discharge rate (Q) and setting 63% as a steady value.
Thumb Interphalangeal Joint Replacement as an Alternative to Joint Fusion
Authors: Grüber Laurence , Kohut Georges , Voser Théa
Published: April 2020

Arthrodesis is the generally accepted treatment for symptomatic osteoarthritis of the interphalangeal (IP) joint of the thumb. For 7 thumbs in 5 patients, an IP joint replacement was offered as a pain alleviating and motion conserving treatment option for osteoarthritis. In these cases, an offlabel use of the SR-PIP prosthesis was performed. All patients did well postoperatively with reasonable pain-free range of motion of the interphalangeal joint except one patient who required further surgeries for recurring joint instability. Radiologically, though, an osteolysis around the stems that could lead to loosening of the prosthesis and progressing periarticular ossifications that might cause a blockage of the joint were observed. IP joint arthroplasty represents a viable option on the short term; however, further studies should be conducted to ensure their long-term sustainability.
Reweighted Covariance Fitting Based on Nonconvex Schatten-p Minimization for Gridless Direction of Arrival Estimation
Authors: Alabideen Lama Zien , Al-Dakkak Oumayma , Khorzom Khaldoun
Published: April 2020

In this paper, we reformulate the gridless direction of arrival (DoA) estimation problem in a novel reweighted covariance fitting (CF) method. The proposed method promotes joint sparsity among different snapshots by means of nonconvex Schatten-p quasi-norm penalty. Furthermore, for more tractable and scalable optimization problem, we apply the unified surrogate for Schatten-p quasi-norm with two-factor matrix norms. Then, a locally convergent iterative reweighted minimization method is derived and solved efficiently via a semidefinite program using the optimization toolbox. Finally, numerical simulations are carried out in the background of unknown nonuniform noise and under the consideration of coprime array (CPA) structure. The results illustrate the superiority of the proposed method in terms of resolution, robustness against nonuniform noise, and correlations of sources, in addition to its applicability in a limited number of snapshots.
Incidence Rate of Type 2 Diabetes Mellitus after Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of 170,139 Women
Authors: Li Zhuyu , Cheng Yunjiu , Wang Dongyu , Chen Haitian , Chen Hanqing , Ming Wai-kit , Wang Zilian
Published: April 2020

Objective. The reported incidence of type 2 diabetes mellitus (T2DM) after gestational diabetes (GDM) varies widely. The purpose of this meta-analysis was to define the incidence rate of T2DM among women with a history of GDM and to examine what might modulate the rate. Research Design and Methods. We searched PubMed and Embase for terms related to T2DM after GDM up to January 2019. Large cohort studies with sample size ≥300 and follow-up duration of at least one year were included. Data from selected studies were extracted, and meta-analysis was performed using the random-effects model. Subgroups analyses were based on the sample size of gestational diabetes, geographic region, maternal age, body-mass index, diagnostic criteria, and duration of follow-up. Results. Twenty-eight studies involving 170,139 women with GDM and 34,627 incident cases of T2DM were identified. The pooled incidence of T2DM after GDM was 26.20 (95% CI, 23.31 to 29.10) per 1000 person-years. Women from Asia and those with older age and higher body mass index seem to experience higher risk of developing T2DM. The incidence rate of T2DM was lowest when applying IADPSG (7.16 per 1000 person-years) to diagnose GDM. The risk of developing T2DM after GDM increased linearly with the duration of follow-up. The increments per year of follow-up were estimated at 9.6‰. The estimated risks for T2DM were 19.72% at 10 years, 29.36% at 20 years, 39.00% at 30 years, 48.64% at 40 years, and 58.27% at 50 years, respectively. Conclusions. The findings of very high incidence of T2DM after GDM add an important insight into the trajectory of the development of T2DM in the long-term postpartum periods, which could provide evidence for consultant and might motivate more women with GDM to screen for T2DM. This trial is registered with PROSPERO identifier CRD42019128980.
Collapse Risk Analysis of Deep Foundation Pits in Metro Stations Using a Fuzzy Bayesian Network and a Fuzzy AHP
Authors: Zhang Guohua , Wang Chengtang , Jiao Yuyong , Wang Hao , Qin Weimin , Chen Wu , Zhong Guoqiang
Published: April 2020

Collapse risk analysis is of great significance for ensuring construction safety in foundation pits. This study proposes a comprehensive methodology for dynamic risk analysis of foundation pit collapse during construction based on a fuzzy Bayesian network (FBN) and a fuzzy analytical hierarchy process (FAHP). Firstly, the potential risk factors contributing to foundation pit collapse are identified based on the results of statistical analysis of foundation pit collapse cases, expert inquiry, and fault tree analysis. Then, a FAHP and improved expert elicitation considering a confidence index are adopted to elicit the probability parameters of the BN. On this basis, quantitative risk reasoning and sensitivity analysis of foundation pit collapse are achieved by means of fuzzy Bayesian inference. Finally, an actual deep foundation pit in a metro station was used to illustrate a specific application of this approach, and the results were in accordance with the field observations and numerical simulation results. The proposed approach can provide effective decision-making support for planners and engineers, which is vital to the prevention and control of the occurrence of the foundation pit collapse accidents.
Theoretical Study on Internal Forces of Primary Support of Tunnel by considering Time Effect
Authors: Yang Zhuangzhi , Wang Yuqing , Song Lin , Wang Xinyu
Published: April 2020

Understanding the internal force distribution and prejudging the weak part of tunnel supporting structure under complicated construction surroundings have become one of the important measures to ensure the safety of tunnel construction. Based on the initial parameter method and field‐monitoring results of surrounding rock pressure, the theory of beam on elastic foundation is employed to derive the analytical solution of primary support internal forces. By combining the monitored data of rock pressure in one tunnel, solution of primary support internal force of a section is back analyzed and weak parts of the primary support are analyzed and evaluated. The results show that, after the tunnel excavation is completed, the internal forces of the primary support of the tunnel arch grow larger over time. When θ > 1.0, the internal forces change greatly. The internal force of the primary support decreased to different extents within 2 days after the primary support was applied and then gradually increased over time. Considering the situationality and changeability of the tunnel construction process, the analytical solution for the primary support internal forces of a multicenter arch tunnel proposed in this paper has a strong feasibility in tunnel construction. The conclusions obtained here could provide theoretical support for the design of supporting structure and the optimization of tunnel construction technology.
Effects on Vaginal Microbiota Restoration and Cervical Epithelialization in Positive HPV Patients Undergoing Vaginal Treatment with Carboxy‐Methyl‐Beta‐Glucan
Authors: Lavitola Giada , Della Corte Luigi , De Rosa Nicoletta , Nappi Carmine , Bifulco Giuseppe
Published: April 2020

Objective. Evaluate the effects of carboxy‐methyl‐beta‐glucan on cervical epithelialization and on the vaginal microbiota in patients with HPV infection or low‐grade cervical preneoplastic lesion (CIN 1). Materials and Methods. Seven‐hundred eighty‐four women with positive HPV tests or diagnosed with CIN 1 were enrolled in a retrospective case‐control study. All the recruited women performed, at baseline and after 6 months, Pap test, HPV test, evaluation of vaginal health according to the Amsel criteria, colposcopy, and punch biopsy. The study population was then divided into 2 groups in relation to the therapy performed during the follow‐up period. Group A performed treatment with vaginal gel based on carboxy‐methyl‐beta‐glucan (1 application/day for 20 days per month for 3 months). Group B was the control group. Results. The patients of group A had a significant improvement in the ectopia pattern and a greater number of cases with metaplasia in the maturation phase with a significant increase in Lugol uptake. In the experimental group, a significant improvement in the pH indices, a negative Swift test and a resolution of the leucorrhoea were observed. A negative result of the 37.1% Pap test and the 39.9% HPV test (vs. 15.2% and 16.5%, respectively) were demonstrated in the treatment group with respect to the control group. A negativization of the colposcopic pictures was observed with a reduction in the amount of CIN 1 found higher in the treatment group. Conclusions. Vaginal therapy based on carboxy‐methyl‐beta‐glucan has been able to improve overall vaginal health; this effect seemed to positively impact the risk of persistence and progression of CIN.
Dynamics of a Stochastic SIRS Epidemic Model with Regime Switching and Specific Functional Response
Authors: Koufi Amine EL , Bennar Abdelkrim , Yousfi Noura
Published: April 2020

The purpose of this work is to investigate the dynamic behaviors of the SIRS epidemic model with nonlinear incident rate under regime switching. We establish the existence of a unique positive solution of our system. Furthermore, we obtain the conditions for the extinction of diseases, and we show the existence of the stationary distribution for our stochastic SIRS model under regime switching. Numerical simulations are employed to illustrate our theoretical analysis.
A Small-Sized Population of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Shows High Stemness Properties and Therapeutic Benefit
Authors: Kim Miyeon , Bae Yun Kyung , Um Soyoun , Kwon Ji Hye , Kim Gee-Hye , Choi Soo Jin , Oh Wonil , Jin Hye Jin
Published: April 2020

Mesenchymal stem cells (MSCs) represent a promising means to promote tissue regeneration. However, the heterogeneity of MSCs impedes their use for regenerative medicine. Further investigation of this phenotype is required to develop cell therapies with improved clinical efficacy. Here, a small-sized population of human umbilical cord blood-derived MSCs (UCB-MSCs) was isolated using a filter and centrifuge system to analyze its stem cell characteristics. Consequently, this population showed higher cell growth and lower senescence. Additionally, it exhibited diverse stem cell properties including differentiation, stemness, and adhesion, as compared to those of the population before isolation. Using cell surface protein array or sorting analysis, both EGFR and CD49f were identified as markers associated with the small-sized population. Accordingly, suppression of these surface proteins abolished the superior characteristics of this population. Moreover, compared to that with large or nonisolated populations, the small-sized population showed greater therapeutic efficacy by promoting the engraftment potential of infused cells and reducing lung damage in an emphysema mouse model. Therefore, the isolation of this small-sized population of UCB-MSCs could be a simple and effective way to enhance the efficacy of cell therapy.
Asymptotic Stability of Neutral Set-Valued Functional Differential Equation by Fixed Point Method
Authors: Bao Junyan , Wang Peiguang
Published: April 2020

This paper studies a class of nonlinear neutral set-valued functional differential equations. The globally asymptotic stability theorem with necessary and sufficient conditions is obtained via the fixed point method. Meanwhile, we give an example to illustrate the obtained result.
Positive Solutions for Elliptic Problems with the Nonlinearity Containing Singularity and Hardy-Sobolev Exponents
Authors: Lan Yong-Yi , Hu Xian , Tang Bi-Yun
Published: April 2020

In this paper, we study multiplicity of positive solutions for a class of semilinear elliptic equations with the nonlinearity containing singularity and Hardy-Sobolev exponents. Using variational methods, we establish the existence and multiplicity of positive solutions for the problem.
Serum Metabolic Profiling Analysis of Gout Patients Treated with Traditional Chinese Medicine Tongfengtai Granules Based on Gas Chromatography‐Mass Spectrometry
Authors: Zhang Jianyong , Pan Hong , Xie Jingjing , Wang Jing , Wang Ruyi , Qiu Xia , Zhong Li , Li Tengyan , Xiao Yuya , Xiao Min , Zhang Yanying , Jia Ertao , Jiang Yubao , Wang Binbin
Published: April 2020

Gout has become a public health problem that seriously threatens human health. Traditional Chinese medicines (TCMs) have a long history of treating gout and have some advantages compared with the conventional medicines. Compound TCM Tongfengtai granules are gradually being used for clinical treatment of gout, but its mechanism is still unclear. The purpose of this study was to explore the metabolic profiling of serum from gout patients before and after treatment with Tongfengtai granules and identify the differential metabolites and related metabolic pathways. A total of 40 gout patients hospitalized in Shenzhen Traditional Chinese Medicine Hospital from 2018 to March 2019 were recruited in the current study, and serum samples from these patients before and after treatment with Tongfengtai granules were collected. Gas chromatography‐mass spectrometry (GC‐MS) assay was used to identify serum metabolites. The OPLS‐DA VIP method was used to screen for potential metabolic biomarkers, and MetaboAnalyst 4.0 was used to identify related metabolic pathways. The result showed that there was a significant difference in the concentrations of six metabolites in the serum after treatment: D‐galactose, lactic acid, 3‐hydroxybutyric acid, D‐pyran (type) glucose, alanine, and L‐isoleucine. Except D‐pyran (type) glucose, the serum concentrations of the other five metabolites were all significantly reduced. Besides, pathway enrichment analysis found that these potential metabolic biomarkers were mainly involved in lactose degradation and the glucose‐alanine cycle. Thus, the serum metabolic profiling of gout patients treated with Tongfengtai granules changed, and the differential metabolites and related metabolic pathways might provide clues for understanding the mechanism of Tongfengtai granules.
Association between Poor Ergophthalmologic Practices and Computer Vision Syndrome among University Administrative Staff in Ghana
Authors: Boadi-Kusi Samuel Bert , Abu Sampson Listowell , Acheampong George Oppong , Adueming Peter Osei-Wusu , Abu Emmanuel Kwasi
Published: April 2020

Aim. The aim of this study was to assess the prevalence of computer vision syndrome (CVS) and its associated ergonomic factors among university administrative staff in Ghana. Methods. A cross-sectional survey was conducted among 200 administrative staff of the University of Cape Coast. The procedure included a self-administered questionnaire, comprehensive ocular health examination, and assessment of computer workstation and lighting conditions. The prevalence of CVS among the subjects and the association between CVS and ergonomic practices were determined. Results. The mean age of the study sample was 31.0 ± 4.7 years, and the majority were males (56.0%). The prevalence of CVS was among 103 (51.5%)participants. Over a third of the respondents used computers for 6 or more hours daily. Significant association was found between CVS and poor ergonomic practices (χ = 15.175, p=0.001). Conclusion. In addition to poor ergonomic office setup, university administrative staff spend several hours behind computer screens leading to the development of CVS. Increased awareness of CVS and adherence to recommended ergonomic practices are necessary to reduce the prevalence of CVS and ultimately enhance work satisfaction and productivity.
A Note on Reverse Minkowski Inequality via Generalized Proportional Fractional Integral Operator with respect to Another Function
Authors: Rashid Saima , Jarad Fahd , Chu Yu-Ming
Published: April 2020

This study reveals new fractional behavior of Minkowski inequality and several other related generalizations in the frame of the newly proposed fractional operators. For this, an efficient technique called generalized proportional fractional integral operator with respect to another function Φ is introduced. This strategy usually arises as a description of the exponential functions in their kernels in terms of another function Φ. The prime purpose of this study is to provide a new fractional technique, which need not use small parameters for finding the approximate solution of fractional coupled systems and eliminate linearization and unrealistic factors. Numerical results represent that the proposed technique is efficient, reliable, and easy to use for a large variety of physical systems. This study shows that a more general proportional fractional operator is very accurate and effective for analysis of the nonlinear behavior of boundary value problems. This study also states that our findings are more convenient and efficient than other available results.
A Proximal Alternating Direction Method of Multipliers with a Substitution Procedure
Authors: Chao Miantao , Zhao Yongxin , Liang Dongying
Published: April 2020

In this paper, we considers the separable convex programming problem with linear constraints. Its objective function is the sum of m individual blocks with nonoverlapping variables and each block consists of two functions: one is smooth convex and the other one is convex. For the general case m≥3, we present a gradient-based alternating direction method of multipliers with a substitution. For the proposed algorithm, we prove its convergence via the analytic framework of contractive-type methods and derive a worst-case O1/t convergence rate in nonergodic sense. Finally, some preliminary numerical results are reported to support the efficiency of the proposed algorithm.
Fatigue Properties Estimation and Life Prediction for Steels under Axial, Torsional, and In‐Phase Loading
Authors: Zhao Ernian , Zhou Qiang , Qu Weilian , Wang Wenming
Published: April 2020

In this study, several estimation methods of fatigue properties based on different monotonic mechanical parameters were first discussed. The advantages and disadvantages of the Hardness Method proposed by Roessle and Fatemi were investigated and improved through the analysis of a total of 92 fatigue test data. A new Segment Fitting Method from Brinell hardness was then proposed for the fatigue properties estimation, and a total of 96 pieces of fatigue test data under axial, torsional, and multiaxial in‐phase loading were collected to verify the applicability of the new proposal. Finally, the prediction accuracy of the new proposal and three exciting estimation methods was compared with the predictions based on the experimental fatigue properties. Based on the results obtained, the newly proposed estimation method has a significant improvement on the relation between fatigue ductility coefficient and Brinell hardness, which consequently improves the fatigue life prediction accuracy with the scatter band of 2, particularly for the materials with low Brinell hardness. The present study can provide a simplified analysis of the preliminary fatigue design of engineering structures.
A Systematic Review of the Mechanisms Underlying Treatment of Gastric Precancerous Lesions by Traditional Chinese Medicine
Authors: Yang Liangjun , Li Jiali , Hu Zhipeng , Fan Xiangzhen , Cai Tiantian , Hengli Zhou  , Pan Huafeng
Published: April 2020

Gastric precancerous lesions (GPLs) are an essential precursor in the occurrence and development of gastric cancer, known to be one of the most common and lethal cancers worldwide. Traditional Chinese medicine (TCM) has a positive prospect for the prevention and therapy of GPL owing to several advantages including a definite curative effect, fewer side effects compared to other treatments, multiple components, and holistic regulation. Despite these characteristic advantages, the mechanisms of TCM in treating GPL have not been fully elucidated. In this review, we summarize the current knowledge with respect to herbal formulations and the therapeutic mechanisms of TCM active ingredients for GPL. This paper elaborates on the mechanisms of TCM underlying the prevention and treatment of GPL, specifically those that are linked to anti‐H. pylori, anti‐inflammation, antiproliferation, proapoptotic, antioxidation, antiglycolytic, and antiangiogenesis effects.
Aptamer‐Conjugated Multifunctional Polymeric Nanoparticles as Cancer‐Targeted, MRI‐Ultrasensitive Drug Delivery Systems for Treatment of Castration‐Resistant Prostate Cancer
Authors: Fang Youqiang , Lin Shaoxiong , Yang Fei , Situ Jie , Lin Shudong , Luo Yun
Published: April 2020

Nanoscopic therapeutic systems that incorporate therapeutic agents, molecular targeting, and imaging capabilities have gained momentum and exhibited significant therapeutic potential. In this study, multifunctional polymeric nanoparticles with controlled drug delivery, cancer‐targeted capability, and efficient magnetic resonance imaging (MRI) contrast characteristics were formulated and applied in the treatment of castration‐resistant prostate cancer (CRPC). The “core‐shell” targeted nanoparticles (NPs) were synthesized by the self‐assembly of a prefunctionalized amphiphilic triblock copolymer composed of poly(lactic‐co‐glycolic‐acid) (PLGA), polyethylene glycol (PEG), and the Wy5a aptamer (Apt), which have been screened for targeting the CRPC cell line PC‐3 by cell‐SELEX technique as described in our previous study. Docetaxel (Dtxl) and a cluster of hydrophobic superparamagnetic iron oxide (SPIO) nanoparticles were simultaneously encapsulated into the targeted nanoparticles. The targeted NPs showed a controlled drug release and an increased contrast‐enhanced MRI capability. The presence of Wy5a on the nanoparticle surface resulted in the cancer‐targeted delivery to PC‐3 cells in vitro and in vivo. In vitro MRI and cytotoxicity studies demonstrated the ultrasensitive MRI and increased cytotoxicity of these targeted NPs. In vivo studies revealed that the targeted NPs exhibited a more efficacious antitumor capability without significant systemic toxicity. Our data suggested that these targeted NPs may be a promising drug delivery system for the efficacious treatment of CRPC.
A Risk Assessment Model for Dam Combining the Probabilistic and the Nonprobabilistic Methods
Authors: Zhu Yantao , Niu Xinqiang , Wang Jimin , Gu Chongshi , Sun Qiang , Li Bo , Huang Lixian
Published: April 2020

The dam reliability study is essential for dam operation safety, regarding the complexity in dam failure causes. The assessment of the dam reliability is now mainly probabilistic or nonprobabilistic. The probabilistic method is usually applied to the cases with sufficient knowledge on dam parameters, while the nonprobabilistic method is suitable for the cases with insufficient knowledge on dam parameters. Since a dam can contain multiple parameters, information abundancy can vary among those parameters, and neither the probabilistic method nor the nonprobabilistic method alone is enough for dam reliability assessment. In this paper, the probabilistic method and nonprobabilistic method are modified based on the adjusted first-order second-moment method and the interval analysis method to suit the dam reliability assessment. Based on characterization on these two methods and the research of the fusion method, the secondary performance function of the dam is constructed, and the construction method of the risk assessment model for dam is proposed. Combined with a case study, this paper contributes to the safe operation of the dam.
p27 as a Transcriptional Regulator: New Roles in Development and Cancer
Authors: Razavipour Seyedeh Fatemeh , Harikumar Kuzhuvelil B. , Slingerland Joyce M.
Published: April 2020

p27 binds and inhibits cyclin-CDK to arrest the cell cycle. p27 also regulates other processes including cell migration and development independent of its cyclin-dependent kinase (CDK) inhibitory action. p27 is an atypical tumor suppressor–deletion or mutational inactivation of the gene encoding p27, CDKN1B, is rare in human cancers. p27 is rarely fully lost in cancers because it can play both tumor suppressive and oncogenic roles. Until recently, the paradigm was that oncogenic deregulation results from either loss of growth restraint due to excess p27 proteolysis or from an oncogenic gain of function through PI3K-mediated C-terminal p27 phosphorylation, which disrupts the cytoskeleton to increase cell motility and metastasis. In cancers, C-terminal phosphorylation alters p27 protein–protein interactions and shifts p27 from CDK inhibitor to oncogene. Recent data indicate p27 regulates transcription and acts as a transcriptional coregulator of cJun. C-terminal p27 phosphorylation increases p27-cJun recruitment to and action on target genes to drive oncogenic pathways and repress differentiation programs. This review focuses on noncanonical, CDK-independent functions of p27 in migration, invasion, development, and gene expression, with emphasis on how transcriptional regulation by p27 illuminates its actions in cancer. A better understanding of how p27-associated transcriptional complexes are regulated might identify new therapeutic targets at the interface between differentiation and growth control.
DGKA Provides Platinum Resistance in Ovarian Cancer Through Activation of c-JUN–WEE1 Signaling
Authors: Li Jie , Pan Chaoyun , Boese Austin C. , Kang JiHoon , Umano Anna D. , Magliocca Kelly R. , Yang Wenqing , Zhang Yu , Lonial Sagar , Jin Lingtao , Kang Sumin
Published: April 2020

Purpose:

Although platinum compounds are the first-line treatment for ovarian cancer, the majority of patients relapse and develop resistance to treatment. However, the mechanism underlying resistance is unclear. The goal of our study is to decipher the mechanism by which a metabolic kinase, diacylglycerol kinase alpha (DGKA), confers platinum resistance in ovarian cancer.

Experimental Design:

Metabolic kinase RNAi synthetic lethal screening was used to identify a cisplatin resistance driver in ovarian cancer. DGKA variants were used to demonstrate the need for DGKA activity in cisplatin resistance. Phospho-proteomic and genomic screens were performed to identify downstream effectors of DGKA. Therapeutic efficacy of targeting DGKA was confirmed and clinical relevance of DGKA signaling was validated using ovarian cancer patient-derived tumors that had different responses to platinum-based therapy.

Results:

We found that platinum resistance was mediated by DGKA and its product, phosphatidic acid (PA), in ovarian cancer. Proteomic and genomic screens revealed that DGKA activates the transcription factor c-JUN and consequently enhances expression of a cell-cycle regulator, WEE1. Mechanistically, PA facilitates c-JUN N-terminal kinase recruitment to c-JUN and its nuclear localization, leading to c-JUN activation upon cisplatin exposure. Pharmacologic inhibition of DGKA sensitized ovarian cancer cells to cisplatin treatment and DGKA–c-JUN–WEE1 signaling positively correlated with platinum resistance in tumors derived from patients with ovarian cancer.

Conclusions:

Our study demonstrates how the DGKA-derived lipid messenger, PA, contributes to cisplatin resistance by intertwining with kinase and transcription networks, and provides preclinical evidence for targeting DGKA as a new strategy in ovarian cancer treatment to battle cisplatin resistance.
Single-Cell Circulating Tumor Cell Analysis Reveals Genomic Instability as a Distinctive Feature of Aggressive Prostate Cancer
Authors: Malihi Paymaneh D. , Graf Ryon P. , Rodriguez Angel , Ramesh Naveen , Lee Jerry , Sutton Ramsay , Jiles Rhett , Ruiz Velasco Carmen , Sei Emi , Kolatkar Anand , Logothetis Christopher , Navin Nicholas E. , Corn Paul , Aparicio Ana M. , Dittamore Ryan , Hicks James , Kuhn Peter , Zurita Amado J.
Published: April 2020

Purpose:

Aggressive variant prostate cancer (AVPC) represents a clinical subset distinguished by therapy resistance and poor prognosis, linked to combined losses of the tumor suppressor genes (TSG) PTEN, RB1, and TP53. Circulating tumor cells (CTC) provide a minimally invasive opportunity for identification and molecular characterization of AVPC. We aimed to evaluate the incidence and clinical significance of compound (2+)TSG losses and genomic instability in prostate cancer CTC, and to expand the set genomic biomarkers relevant to AVPC.

Experimental Design:

Genomic analysis of chromosomal copy-number alterations (CNA) at single-cell resolution was performed in CTC from patients with and without AVPC before initiating chemotherapy with cabazitaxel or cabazitaxel and carboplatin. We evaluated associations between single-CTC genomics and clinical features, progression-free survival, and overall survival.

Results:

A total of 257 individual CTC were sequenced from 47 patients (1–22 CTC/patient). Twenty patients (42.6%) had concurrent 2+TSG losses in at least one CTC in association with poor survival and increased genomic instability, inferred by high large-scale transitions scores. Higher LST in CTC were independent of CTC enumerated, clinically more indicative of aggressive behavior than co-occurring TSG losses, and molecularly associated with gains in chromosomal regions including PTK2, Myc, and NCOA2; increased androgen receptor expression; and BRCA2 loss. In 57 patients with matched cell-free tumor DNA data, CTC were more frequently detectable and evaluable for CNA analysis (in 73.7% vs. 42.1%, respectively).

Conclusions:

Our findings suggest that genomic instability in CTC is a hallmark of advanced prostate cancer aggressiveness, and support single-CTC sequencing as a compelling tool to noninvasively characterize cancer heterogeneity.
Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multicenter Study during the COVID-19 Outbreak
Authors: Dai Mengyuan , Liu Dianbo , Liu Miao , Zhou Fuxiang , Li Guiling , Chen Zhen , Zhang Zhian , You Hua , Wu Meng , Zheng Qichao , Xiong Yong , Xiong Huihua , Wang Chun , Chen Changchun , Xiong Fei , Zhang Yan , Peng Yaqin , Ge Siping , Zhen Bo , Yu Tingting , Wang Ling , Wang Hua , Liu Yu , Chen Yeshan , Mei Junhua , Gao Xiaojia , Li Zhuyan , Gan Lijuan , He Can , Li Zhen , Shi Yuying , Qi Yuwen , Yang Jing , Tenen Daniel G. , Chai Li , Mucci Lorelei A. , Santillana Mauricio , Cai Hongbing
Published: April 2020

The novel COVID-19 outbreak has affected more than 200 countries and territories as of March 2020. Given that patients with cancer are generally more vulnerable to infections, systematic analysis of diverse cohorts of patients with cancer affected by COVID-19 is needed. We performed a multicenter study including 105 patients with cancer and 536 age-matched noncancer patients confirmed with COVID-19. Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes. Patients with hematologic cancer, lung cancer, or with metastatic cancer (stage IV) had the highest frequency of severe events. Patients with nonmetastatic cancer experienced similar frequencies of severe conditions to those observed in patients without cancer. Patients who received surgery had higher risks of having severe events, whereas patients who underwent only radiotherapy did not demonstrate significant differences in severe events when compared with patients without cancer. These findings indicate that patients with cancer appear more vulnerable to SARS-CoV-2 outbreak.

Significance:

Because this is the first large cohort study on this topic, our report will provide much-needed information that will benefit patients with cancer globally. As such, we believe it is extremely important that our study be disseminated widely to alert clinicians and patients.

This article is highlighted in the In This Issue feature, p. 747