bluuebunny/crossref_metadata_2025 huggingface dataset:
Thiamine treatment preserves cardiac function against ischemia injury via maintaining mitochondrial size and ATP levels
Authors: Yamada Yuki , Kusakari Yoichiro , Akaoka Munetoshi , Watanabe Masato , Tanihata Jun , Nishioka Naritomo , Bochimoto Hiroki , Akaike Toru , Tachibana Toshiaki , Minamisawa Susumu
Published: October 2020

We found that treatment with thiamine can have a protective effect on myocardial ischemia. Thiamine likely mediates mitochondrial fission through the inhibition of DRP1 phosphorylation and the preservation of larger-sized mitochondria and ATP concentration, leading to higher cardiac contractility performance during the subsequent reperfusion state.
Anti‐Inflammatory, Barrier‐Protective, and Antiwrinkle Properties of Agastache rugosa Kuntze in Human Epidermal Keratinocytes
Authors: Lee Yoonjin , Lim Hye-Won , Ryu In Wang , Huang Yu-Hua , Park Minsik , Chi Young Min , Lim Chang-Jin
Published: October 2020

This work aimed to assess the skin‐beneficial properties of Agastache rugosa Kuntze, an herbal medication used to treat different types of disorders in traditional folk medicine. The total phenolic compounds and total antiradical, nitrite scavenging, superoxide scavenging, antielastase, and antihyaluronidase activities of a hot water extract of A. rugosa Kuntze leaves (ARE) were spectrophotometrically determined. Intracellular reactive oxygen species (ROS) was fluorometrically quantitated using 2 ′,7 ′‐dichlorodihydrofluorescein diacetate (DCFH‐DA). Inducible nitric oxide synthase (iNOS) and filaggrin were evaluated using Western analysis. Real‐time quantitative RT‐PCR was used to measure filaggrin mRNA. Caspase‐14 activity was determined using a fluorogenic substrate. ARE contained the total phenolic content of 38.9 mg gallic acid equivalent/g extract and exhibited 2,2 ′‐diphenyl‐1‐picrylhydrazyl (DPPH) radical, superoxide radical, and nitrite scavenging activities with the SC50 values of 2.9, 1.4, and 1.7 mg/mL, respectively. ARE exerted suppressive activities on nitric oxide (NO) and ROS levels elevated by lipopolysaccharide (LPS) or tumor necrosis factor‐α (TNF‐α) in HaCaT keratinocytes. It attenuated the LPS‐stimulated expression of iNOS. ARE augmented the UV‐B‐reduced filaggrin expression on both protein and mRNA levels and was capable of upregulating the UV‐B‐reduced caspase‐14 activity. ARE inhibited in vitro elastase and hyaluronidase activities associated with the wrinkling process. ARE, at the concentrations used, did not interfere with the viability of HaCaT keratinocytes. These findings preliminarily imply that the leaves of A. rugosa possess desirable cosmetic potentials, such as anti‐inflammatory, barrier protective, and antiwrinkle activities, which infers their skin healing potentials.
A2AR Antagonists Upregulate Expression of GS and GLAST in Rat Hypoxia Model
Authors: Yu Jun , Yan Yan , Chen Yiye , Zheng Yan , Yu Xiaoyan , Wang Jialu , Wang Yafu , Wang Anken , Kang Xiaoli , Cen Jie , Dong Lingyan , Li Li , Zhao Peiquan
Published: October 2020

Background. The aim of this study was to research the effects of glutamine synthetase (GS) and glutamate aspartate transporter (GLAST) in rat Müller cells and the effects of an adenosine A2AR antagonist (SCH 442416) on GS and GLAST in hypoxia both in vivo and in vitro. Methods. This study used RT‐PCR and Western blotting to quantify the expressions of GS and GLAST under different hypoxic conditions as well as the expressions of GS and GLAST at different drug concentrations. A cell viability assay was used to assess drug toxicity. Results. mRNA and protein expression of GS and GLAST in hypoxia Group 24 h was significantly increased. mRNA and protein expressions of GS and GLAST both increased in Group 1 μM SCH 442416 compared with other groups. One micromolar SCH 442416 could upregulate GS and GLAST’s activity in hypoxia both in vivo and in vitro. Conclusions. Hypoxia activates GS and GLAST in rat retinal Müller cells in a short time in vitro. (2) A2AR antagonists upregulate the activity of GS and GLAST in hypoxia both in vivo and in vitro.
Circulating Irisin Level and Thyroid Dysfunction: A Systematic Review and Meta‐Analysis
Authors: Shan Dan , Zou Li , Liu Xijiao , Cai Yitong , Dong Ruihong , Hu Yayi
Published: October 2020

Both thyroid hormones and irisin have profound influences on the metabolism of the human body. Based on their similarities, several studies have been conducted to explore changes in irisin levels in patients with hypothyroidism and hyperthyroidism. This study was conducted in accordance with the PRISMA statement and the MOOSE reporting guideline. Based on a preregistered protocol (PROSPERO—CRD42019138430), a comprehensive search of eight databases was performed from inception to April 2020. Studies with original data collected from patients with thyroid dysfunction were included. Subgroup analysis was performed based on the different types of clinical manifestations and patient characteristics. The quality of each study and the presence of publication bias were assessed by the Newcastle‐Ottawa score (NOS) and funnel plot with Egger’s test, respectively. A total of 11 studies with 1210 participants were included. Ten studies were identified as high‐quality studies. Pooled analysis indicated decreased irisin levels in patients with hypothyroidism (MD ‐10.37, 95% CI ‐17.81 to ‐2.93). Subgroup analysis revealed an even lower level of irisin in patients with clinical‐type hypothyroidism (MD ‐17.03, 95% CI ‐30.58 to ‐3.49) and hypothyroidism caused by autoimmune disease (MD ‐19.38, 95% CI ‐36.50 to ‐2.26). No differences were found after achieving euthyroid status from levothyroxine treatment in patients with hypothyroidism compared with controls. No differences were found between patients with hyperthyroidism and controls. Correlation analyses revealed a possible negative correlation between irisin and TSH and positive correlations between irisin and both fT3 and fT4. Irisin was correlated with TSH receptor antibodies.
Characterization of Plasmid‐Mediated Quinolone Resistance and Serogroup Distributions of Uropathogenic Escherichia coli among Iranian Kidney Transplant Patients
Authors: Sadeghi Amin , Halaji Mehrdad , Fayyazi Amirhossein , Havaei Seyed Asghar
Published: October 2020

Introduction. Urinary tract infection (UTI) is one of the most frequent infections in kidney transplant patients (KTPs). This infection is mainly caused by uropathogenic Escherichia coli (UPEC). Plasmid‐mediated quinolone resistance (PMQR) was also increasingly identified in UPEC. This study proposed to investigate the frequency of quinolone‐resistance plasmid genes and the O‐antigen serogroup among UPEC isolated from KTPs and non‐KTP with UTI. Methods. Totally, 114 UPEC isolates from 49 KTPs and 65 non‐KTPs patients diagnosed with an UPEC‐associated UTI were obtained from June 2019 to December 2019 at three laboratory centers in Isfahan, Iran. The isolates were confirmed through phenotypic and genotypic methods. Moreover, the antimicrobial susceptibility test to nalidixic acid, ciprofloxacin, norfloxacin, and ofloxacin was performed using a disk diffusion method. The presence of the qnr gene as well as the serogroup distribution was identified using the PCR method. Result. According to data, the distribution of O1, O2, O4, O16, and O25 serogroups were 3.5%, 2.6, 3.5, 3.5, and 20.2%, respectively. Antibiotic susceptibility pattern revealed that the highest and lowest resistance rates were to nalidixic acid (69.3%) and norfloxacin (43.9%), respectively. Also, the frequency of qnrS and qnrB genes were 33.3% and 15.8%, respectively, while none of the isolates was found to be positive for the qnrA gene. There was no significant association between the presence of qnr genes and higher antibiotic resistance. Conclusion. This study recognized that the qnrS gene, O25 serotype, and resistance to nalidixic acid had the highest frequencies in UPEC strains isolated from UTI patients.
Circular RNA circ‐CCAC1 Facilitates Adrenocortical Carcinoma Cell Proliferation, Migration, and Invasion through Regulating the miR‐514a‐5p/C22orf46 Axis
Authors: Li Wei , Liu Rengong , Wei Dongmei , Zhang Wei , Zhang Heyan , Huang Wenjun , Hao Liguo
Published: October 2020

Adrenocortical carcinoma (ACC) is a rare but clinically aggressive endocrine malignancy. Circular RNAs (circRNAs) were found to play key roles in tumorigenesis. In the current study, we aimed to investigate the functions and mechanisms of a novel circRNA, circ‐CCAC1, in ACC cells. circ‐CCAC1 expression levels in ACC tissue specimens and cell lines were evaluated by RT‐qPCR. Kaplan‐Meier analysis was applied to explore the relationship between circ‐CCAC1 and patients’ prognosis. Cell counting kit‐8 (CCK‐8), colony formation, acridine orange/ethidium bromide (AO/EB) double fluorescence staining, and Transwell assays were performed to evaluate the functions of circ‐CCAC1 in ACC cells. Bioinformatics analysis and a dual‐luciferase reporter assay were utilized to explore the mechanisms of circ‐CCAC1. As a result, circ‐CCAC1 was overexpressed in ACC tissue samples and cell lines and correlated with poor prognosis. Gain‐ and loss‐of‐function tests demonstrated that circ‐CCAC1 acted as an oncogene in ACC. What is more, circ‐CCAC1 enhanced C22orf46 expression by sponging miR‐514a‐5p in ACC cells. A rescue assay illustrated that circ‐CCAC1 facilitated ACC progression through miR‐514a‐5p/C22orf46 signaling. To sum up, we identified a novel circRNA, circ‐CCAC1, which may be used as a potential therapeutic target for ACC.
An Intelligent, Secure, and Smart Home Automation System
Authors: Majeed Rizwan , Abdullah Nurul Azma , Ashraf Imran , Zikria Yousaf Bin , Mushtaq Muhammad Faheem , Umer Muhammad
Published: October 2020

The idea of a smart home is getting attention for the last few years. The key challenges in a smart home are intelligent decision making, secure identification, and authentication of the IoT devices, continuous connectivity, data security, and privacy issues. The existing systems are targeting one or two of these issues whereas a smart home automation system that is not only secure but also has intelligent decision making and analytical abilities is the need of time. In this paper, we present a novel idea of a smart home that uses a machine learning algorithm (Support Vector Machine) for intelligent decision making and also uses blockchain technology to ensure identification and authentication of the IoT devices. Emerging blockchain technology plays a vital role by providing a reliable, secure, and decentralized mechanism for identification and authentication of the IoT devices used in the proposed home automation system. Moreover, the SVM classifier is applied to classify the status of devices used in the proposed smart home automation system into one of the two categories, i.e., “ON” and “OFF.” This system is based on Raspberry Pi, 5 V relay circuit, and some sensors. A mobile application is developed using the Android platform. Raspberry Pi acting as the server maintains the database of each appliance. The HTTP web interface and apache server are used for communication among the Android app and Raspberry Pi. The proposed idea is tested in the lab and real life to validate its effectiveness and usefulness. It is also ensured that the hardware and technology used in the proposed idea are cheap, easily available, and replicable. The experimental results highlight its significance and validate the proof of the concept.
Expression of MAPK and PI3K/AKT/mTOR Proteins according to the Chronic Liver Disease Etiology in Hepatocellular Carcinoma
Authors: Diniz Paulo H. C. , Silva Serena D. C. , Vidigal Paula V. T. , Xavier Marcelo A. P. , Lima Cristiano X. , Faria Luciana C. , Ferrari Teresa C. A.
Published: October 2020

Aims. Chronic liver disease (CLD) of different etiologies leads to hepatocellular carcinoma (HCC) by multiple mechanisms that may be translated into clinicopathological differences. We evaluated the tissue expression of the MAPK and PI3K/Akt/mTOR pathway proteins and their association with long-term outcome and other parameters, according to the etiology of the CLD, in HCC patients. Methods. Clinicopathological data from 80 patients who underwent orthotopic liver transplantation for HCC treatment in a Brazilian referral center were compared according to CLD etiology. Event (tumor recurrence or death from any cause) occurrence and event-free survival (EFS) were analyzed. Pathway protein expression was assessed by immunohistochemistry (IHQ) in both tumor and underlying cirrhosis and by RT-PCR in tumor tissue. Results. Strong expression (SE) of KRAS was more frequent in tumors arising from viral (26.8%) than the nonviral group of liver disease (7.7%,

p
=
0.024

) and also than cirrhotic parenchyma (0%,

p
=
0.004

). SE of PI3K was more frequent in tumor than in cirrhosis (

p
=
0.048

,

p
<
0.01

), without differences in its tumor expression among etiologic groups

p
=
0.111

. mRNA of ERK, PI3K, and BRAF was expressed in the tumor, without differences between CLD etiologies, and there was no association with IHQ findings. Older age and microvascular invasion (MIV) were the only parameters independently associated with the event. MIV was also associated with shorter EFS. Conclusions. Hepatitis B and C virus can lead to HCC by different mechanisms compared with nonviral hepatopathy. KRAS and PI3K may have a role in carcinogenesis. The prognostic and therapeutic implications need to be investigated.
Comparisons between Asphalt Pavement Responses under Vehicular Loading and FWD Loading
Authors: Yang Song , Qi Bing , Cao Zhensheng , Zhang Shaoqiang , Cheng Huailei , Yang Ruikang
Published: October 2020

The strain responses of asphalt pavement layer under vehicular loading are different from those under falling weight deflectometer (FWD) loading, due to the discrepancies between the two types of loadings. This research aims to evaluate and compare the asphalt layer responses under vehicular loading and FWD loadings. Two full‐scale asphalt pavement structures, namely, flexible pavement and semirigid pavement, were constructed and instrumented with strain gauges. The strain responses of asphalt layers under vehicular and FWD loadings were measured and analyzed. Except for field measurements, the finite element (FE) models of the experimental pavements were established to simulate the pavement responses under a wide range of loading conditions. Field strain measurements indicate that the asphalt layer strain under vehicular loading increases with the rising temperature roughly in an exponential mode, while it decreases with the rising vehicular speed approximately linearly. The strain pulses in the asphalt layer generated by FWD loading are different from those induced by vehicular loading. The asphalt layer strains generated by FWD loading are close to those induced by low vehicular speed (35 km/h). The results from the FE model imply that the asphalt layer strains under FWD loading and vehicular loading are distributed similarly in the depth profile. For flexible pavement, the position of critical strain shifts gradually from the bottom of the asphalt layer to the mid‐depth of the layer, as the temperature increases. For semirigid pavement, the position of critical strain is always located at the intermediate depth of the asphalt layer, regardless of temperatures.
Optimal Network Defense Strategy Selection Method Based on Evolutionary Network Game
Authors: Liu Xiaohu , Zhang Hengwei , Zhang Yuchen , Shao Lulu
Published: October 2020

The basic hypothesis of evolutionary game theory is that the players in the game possess limited rationality. The interactive behavior of players can be described by a learning mechanism that has theoretical advantages in modeling the network security problem in a real society. The current network security evolutionary game model generally adopts a replicator dynamic learning mechanism and assumes that the interaction between players in the group conforms to the characteristics of uniform mixed distribution. However, in an actual network attack and defense scenario, the players in the game have limited learning capability and can only interact with others within a limited range. To address this, we improved the learning mechanism based on the network topology, established the learning object set based on the learning range of the players, used the Fermi function to calculate the transition probability to the learning object strategy, and employed random noise to describe the degree of irrational influence in the learning process. On this basis, we built an attack and defense evolutionary network game model, analyzed the evolutionary process of attack and defense strategy, solved the evolution equilibrium, and designed a defense strategy selection algorithm. The effectiveness of the model and method is verified by conducting simulation experiments for the transition probability of the players and the evolutionary process of the defense group strategy.
Increased Cytoplasmic CD138 Expression Is Associated with Aggressive Characteristics in Prostate Cancer and Is an Independent Predictor for Biochemical Recurrence
Authors: Kind Simon , Kluth Martina , Hube-Magg Claudia , Möller Katharina , Makrypidi-Fraune Georgia , Lutz Florian , Lennartz Maximilian , Rico Sebastian Dwertmann , Schlomm Thorsten , Heinzer Hans , Höflmayer Doris , Weidemann Sören , Uhlig Ria , Huland Hartwig , Graefen Markus , Bernreuther Christian , Tsourlakis Maria Christina , Minner Sarah , Dum David , Hinsch Andrea , Lübke Andreas M. , Simon Ronald , Sauter Guido , Marx Andreas , Polonski Adam
Published: October 2020

Syndecan‐1 (CD138) is a transmembrane proteoglycan expressed in various normal and malignant tissues. It is of interest due to a possible prognostic effect in tumors and its role as a target for the antibody‐drug conjugate indatuximab ravtansine. Here, we analyzed 17,747 prostate cancers by immunohistochemistry. Membranous and cytoplasmic CD138 staining was separately recorded. In normal prostate glands, CD138 staining was limited to basal cells. In cancers, membranous CD138 positivity was seen in 19.6% and cytoplasmic CD138 staining in 11.2% of 12,851 interpretable cases. A comparison with clinico‐pathological features showed that cytoplasmic CD138 staining was more linked to unfavorable tumor features than membranous staining. Cytoplasmic CD138 immunostaining was associated with high tumor stage (p < 0.0001), high Gleason grade (p < 0.0001), nodal metastases (p < 0.0001), positive surgical margin (p < 0.0001), and biochemical recurrence (p < 0.0001). This also holds true for both V‐ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion positive and ERG fusion negative tumors although the cytoplasmic CD138 expression was markedly more frequent in ERG positive than in ERG negative tumors (p < 0.0001). Comparison with 11 previously analyzed chromosomal deletions identified a conspicuous association between cytoplasmic CD138 expression and 8p deletions (p < 0.0001) suggesting a possible functional interaction of CD138 with one or several 8p genes. Multivariate analysis revealed the cytoplasmic CD138 expression as an independent prognostic parameter in all cancers and in the ERG positive subgroup. In summary, our study indicates the cytoplasmic CD138 expression as a strong and independent predictor of poor prognosis in prostate cancer. Immunohistochemical measurement of CD138 protein may thus—perhaps in combination with other parameters—become clinically useful in the future.
Nonlinear Dynamic Analysis of the Cutting Process of a Nonextensible Composite Boring Bar
Authors: Ma Bole , Ren Yongsheng
Published: October 2020

A nonlinear dynamic analysis of the cutting process of a nonextensible composite cutting bar is presented. The cutting bar is simplified as a cantilever with plane bending. The nonlinearity is mainly originated from the nonextensible assumption, and the material of cutting bar is assumed to be viscoelastic composite, which is described by the Kelvin–Voigt equation. The motion equation of nonlinear chatter of the cutting system is derived based on the Hamilton principle. The partial differential equation of motion is discretized using the Galerkin method to obtain a 1-dof nonlinear ordinary differential equation in a generalized coordinate system. The steady forced response of the cutting system under periodically varying cutting force is approximately solved by the multiscale method. Meanwhile, the effects of parameters such as the geometry of the cutting bar (including length and diameter), damping, the cutting coefficient, the cutting depth, the number of the cutting teeth, the amplitude of the cutting force, and the ply angle on nonlinear lobes and primary resonance curves during the cutting process are investigated using numerical calculations. The results demonstrate that the critical cutting depth is inversely proportional to the aspect ratio of the cutting bar and the cutting force coefficient. Meanwhile, the chatter stability in the milling process can be significantly enhanced by increasing the structural damping. The peak of the primary resonance curve is bent toward the right side. Due to the cubic nonlinearity in the cutting system, primary resonance curves show the characteristics of typical Duffing’s vibrator with hard spring, and jump and multivalue regions appear.
Keratoconus Diagnosis: Validation of a Novel Parameter Set Derived from IOP-Matched Scenario
Authors: Lin Dan , Tian Lei , Zhang Shu , Wang Like , Jie Ying , Zhou Yongjin
Published: October 2020

Purpose. Considering that intraocular pressure (IOP) is an important confounding factor in corneal biomechanical evaluation, the notion of matching IOP should be introduced to eliminate any potential bias. This study aimed to assess the capability of a novel parameter set (NPS) derived from IOP-matched scenario to diagnose keratoconus. Methods. Seventy samples (training set; 35 keratoconus and 35 normal corneas; pairwise matching for IOP) were used to determine NPS by forward logistic regression. A large validation dataset comprising 62 matching samples (31 keratoconus and 31 normal corneas) and 203 unmatching samples (112 keratoconus and 91 normal corneas) was used to evaluate its clinical significance. To further assess its diagnosis capability, NPS was compared with the other two prior biomechanical indexes. Results. NPS was comprised of three biomechanical parameters, namely, DA Ratio Max 1 mm (DRM1), the first applanation time (AT1), and an energy loading parameter (Eload). NPS was successfully applied to the validation dataset, with a higher accuracy of 96.8% and 95.6% in the IOP-matched and -unmatched scenarios, respectively. More surprisingly, accuracy of NPS was 95.5% in the combined validation, an improvement compared to the two prior biomechanical indexes. Conclusions. This is the first study taking IOP bias into consideration to determine a biomechanical parameter set. Our study shows that NPS indeed offers comparable performance in keratoconus diagnosis. Translational Relevance. Determining a parameter set after eliminating the influence from IOP is useful in revealing the essential differences between keratoconus and normal corneas and possibly facilitating further progress in keratoconus diagnosis.
A Derivative-Free Liu–Storey Method for Solving Large-Scale Nonlinear Systems of Equations
Authors: Su Zhenhua , Li Min
Published: October 2020

In this paper, a descent Liu–Storey conjugate gradient method is extended to solve large-scale nonlinear systems of equations. Based on certain assumptions, the global convergence property is obtained with a nonmonotone line search. The proposed method is suitable to solve large-scale problems for the low-storage requirement. Numerical experiment results show that the new method is practically effective.
A Review of Malaysian Herbal Plants and Their Active Constituents with Potential Therapeutic Applications in Sepsis
Authors: Liew Kong Yen , Hafiz Md Faizul , Chong Yi Joong , Harith Hanis Hazeera , Israf Daud Ahmad , Tham Chau Ling
Published: October 2020

Sepsis refers to organ failure due to uncontrolled body immune responses towards infection. The systemic inflammatory response triggered by pathogen‐associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS) from Gram‐negative bacteria, is accompanied by the release of various proinflammatory mediators that can lead to organ damage. The progression to septic shock is even more life‐threatening due to hypotension. Thus, sepsis is a leading cause of death and morbidity globally. However, current therapies are mainly symptomatic treatment and rely on the use of antibiotics. The lack of a specific treatment demands exploration of new drugs. Malaysian herbal plants have a long history of usage for medicinal purposes. A total of 64 Malaysian plants commonly used in the herbal industry have been published in Malaysian Herbal Monograph 2015 and Globinmed website (http://www.globinmed.com/). An extensive bibliographic search in databases such as PubMed, ScienceDirect, and Scopus revealed that seven of these plants have antisepsis properties, as evidenced by the therapeutic effect of their extracts or isolated compounds against sepsis‐associated inflammatory responses or conditions in in vitro or/and in vivo studies. These include Andrographis paniculata, Zingiber officinale, Curcuma longa, Piper nigrum, Syzygium aromaticum, Momordica charantia, and Centella asiatica. Among these, Z. officinale is the most widely studied plant and seems to have the highest potential for future therapeutic applications in sepsis. Although both extracts as well as active constituents from these herbal plants have demonstrated potential antisepsis activity, the activity might be primarily contributed by the active constituent(s) from each of these plants, which are andrographolide (A. paniculata), 6‐gingerol and zingerone (Z. officinale), curcumin (C. longa), piperine and pellitorine (P. nigrum), biflorin (S. aromaticum), and asiaticoside, asiatic acid, and madecassoside (C. asiatica). These active constituents have shown great antisepsis effects, and further investigations into their clinical therapeutic potential may be worthwhile.
Histological Peripheral Margins and Recurrence of Melanoma In Situ Treated with Wide Local Excision
Authors: Moura Francisco S. , Homer Lucy E. , McKirdy Stuart W.
Published: October 2020

Background. The incidence of melanoma in situ (MIS) is increasing faster compared to invasive melanoma. Despite varying international practice, a minimum of 5 mm surgical excision margin is currently recommended in the UK. There is no clear guidance on the minimum histological peripheral clearance margins. Aim. This study compares the histological peripheral clearance margins of MIS using wide local excision (WLE) to the rate of recurrence and progression to invasive disease. Methods. A retrospective single-center review was performed over a 5-year period. Inclusion criteria consisted of MIS diagnosis, ≥16 years of age, and treatment with WLE with curative intent. Those patients with a recurrence of a previous MIS or with a reported focus of invasion/regression were also included. Clinicopathological data and follow-up were recorded. Results. 167 MIS were identified in 155 patients, 80% of which were lentigo maligna subtype. Of patients with completely excised MIS on histology (>0 mm), 9% had recurrence with a median time to recurrence of 36 months. Three (1.8%) cases recurred as invasive disease. Age, MIS site, MIS subtype, and histological evidence of foci of invasion/regression did not predict recurrence nor progression to invasive disease (

p
>
0.05

). The recurrence rate of MIS with a histological excision margin ≤3.0 mm was 13% compared to 3% in those with histology margins of >3.0 mm (

p
=
0.049

). Conclusion. A histological peripheral clearance of at least 3.0 mm is advocated to achieve lower recurrence rates. The follow-up duration should be reviewed due to the median recurrence occurring at 36 months in our cohort. Cumulative work on MIS needs to be collated and completed in a large multicenter study with a long follow-up period.
Ramp Metering for a Distant Downstream Bottleneck Using Reinforcement Learning with Value Function Approximation
Authors: Zhou Yue , Ozbay Kaan , Kachroo Pushkin , Zuo Fan
Published: October 2020

Ramp metering for a bottleneck located far downstream of the ramp is more challenging than for a bottleneck that is near the ramp. This is because under the control of a conventional linear feedback-type ramp metering strategy, when metered traffic from the ramp arrive at the distant downstream bottleneck, the state of the bottleneck may have significantly changed from when it is sampled for computing the metering rate; due to the considerable time, these traffic will have to take to traverse the long distance between the ramp and the bottleneck. As a result of such time-delay effects, significant stability issue can arise. Previous studies have mainly resorted to compensating for the time-delay effects by incorporating predictors of traffic flow evolution into the control systems. This paper presents an alternative approach. The problem of ramp metering for a distant downstream bottleneck is formulated as a Q-learning problem, in which an intelligent ramp meter agent learns a nonlinear optimal ramp metering policy such that the capacity of the distant downstream bottleneck can be fully utilized, but not to be exceeded to cause congestion. The learned policy is in pure feedback form in that only the current state of the environment is needed to determine the optimal metering rate for the current time. No prediction is needed, as anticipation of traffic flow evolution has been instilled into the nonlinear feedback policy via learning. To deal with the intimidating computational cost associated with the multidimensional continuous state space, the value function of actions is approximated by an artificial neural network, rather than a lookup table. The mechanism and development of the approximate value function and how learning of its parameters is integrated into the Q-learning process are well explained. Through experiments, the learned ramp metering policy has demonstrated effectiveness and benign stability and some level of robustness to demand uncertainties.
Numerical Study on Regenerative Cooling Characteristics of Kerosene Scramjets
Authors: Jin Xuan , Shen Chibing , Wu Xianyu
Published: October 2020

The use of kerosene-based regenerative cooling for scramjet has been found widespread attention due to its inherent nature of high energy utilization efficiency and good thermal protection performance. In order to provide a reference for the later design and experiments, three-dimensional turbulence simulations and sensitivity analysis were performed to determine the effects of three operating mode parameters, heat flux, mass flow rate, and outlet pressure, on the regenerative cooling characteristics of kerosene scramjets. A single rectangular-shaped channel for regenerative cooling was assumed. The RNG k-ε turbulence model and kerosene cracking mechanism with single-step global reaction were applied for the supercritical-pressure heat transfer of kerosene flows in the channel. Conclusions can be drawn that as the kerosene temperature rises along the channel, the decrease of fluid density and viscosity contributes to increasing the fluid velocity and heat transfer. When the kerosene temperature is close to the pseudocritical temperature, the pyrolysis reaction results into the rapid increase of fluid velocity. However, the heat transfer deterioration occurs as the specific heat and thermal conductivity experience their turning points. The higher heat flux leads to lower heat transfer coefficient, and the latter stops rising when the wall temperature reaches the pseudocritical temperature. The same rising trend of the heat transfer coefficient is observed under different outlet pressures, but the heat transfer deterioration occurs earlier at smaller outlet pressure for the reason that the corresponding pseudocritical temperature decreases. The heat transfer coefficient increases significantly along with the rise of the mass flow rate, which is mainly attributable to the increase of Reynolds number. Quantitative results indicate that as the main influence factors, the heat flux and mass flow rate are respectively negatively and positively relative to the intensification of heat transfer, but outlet pressure always has little effects on cooling performance.
Adjuvant Fuzheng Huayu Capsule Reduces the Incidence of Hepatocellular Carcinoma in Patients with Hepatitis B‐Caused Cirrhosis
Authors: Shi Ke , Liu Yao , Wang Xiaojing , Li Yuxin , Zhang Qun , Hu Ying , Ran Chongping , Huang Yunyi , Hou Jie , Wang Xianbo
Published: October 2020

Aim. Fuzhenghuayu (FZHY) capsule can inhibit the progression of cirrhosis. This study explored whether FZHY can reduce the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis B‐caused cirrhosis (HBC) undergoing antiviral therapy. Methods. A retrospective review of 842 patients with HBC between 2011 and 2015 was performed, including 270 treated with FZHY combined with nucleos (t) ide analogues (NAs) and 572 with NAs alone. The incidence of HCC was compared between the FZHY (n = 259) and control (n = 259) groups using 1 : 1 propensity score (PS) matching. The incidence of HCC in patients with HBC with different Child‐Turcotte‐Pugh (CTP) classifications and Toronto HCC risk index (THRI) scores was analyzed using Kaplan–Meier curves. Results. The 5‐year cumulative incidence of HCC before and after PS matching was 151 (17.9%) and 86 (16.6%), respectively. In PS‐matched samples, the multivariate Cox proportional‐hazards model indicated that the FZHY group demonstrated a significantly lower risk for HCC than the control group (adjusted hazard ratio [aHR] = 0.32, 95% CI 0.19–0.53 P < 0.001). The risk of HCC diminished with increased duration of FZHY use. The stratified analysis revealed that the FZHY group, regardless of CTP classification, benefited significantly from FZHY therapy. Patients in the medium‐ and high‐THRI risk groups were the dominant population for FZHY. Conclusions. FZHY combined with NAs was associated with a significantly lower risk of HCC than NAs alone in patients with HBC, which supports the integration of FZHY with antiviral treatment into clinical practice.
Seismic Fragility Assessment of Base-Isolated Steel Water Storage Tank
Authors: Zhao Zhuo , Lu Xiaowei , Guo Yu , Zhao Xiaofeng
Published: October 2020

Steel water storage tanks (WSTs) are among the important components of water treatment industry facilities that are expected to remain functional and applicable after strong earthquakes. In this study, the seismic vulnerability of base-isolated steel WST is investigated. A three-dimensional finite element stick model of the targeted tank is created using OpenSees. This model is capable of reproducing convective, impulsive, and rigid responses of fluid-tank systems. Time-history responses of convective displacement, bearing displacement, and base shear force for base-isolated tank subjected to a typical ground motion are compared. Furthermore, time-history analysis based on a suite of 80 ground motions is conducted. The seismic demand models for various responses are established and the most efficient intensity measure (IM) is determined based on the dispersion and coefficient of determination. Seismic fragility curves for different responses are derived for all three damage states using cloud analysis. The results from this study reveal that (i) the convective displacement is significantly greater than bearing displacement; (ii) peak ground displacement (PGD) is the most efficient and sufficient IM for the targeted tank; and (iii) the characteristic of isolation bearing significantly influences the seismic fragilities of convective displacement and bearing displacement and has a little impact on base shear force, which makes the selection of the proper characteristic parameters for isolation bearing very essential. The analysis technique and procedure mentioned above as well as derived insights are of significance to general liquid storage tank system configuration.
Collective Risk Ranking of Highway Segments on the Basis of Severity-Weighted Crash Rates
Authors: Li Dawei , Al-Mahamda Mustafa F. M.
Published: October 2020

This study is intended to focus on the major factors affecting traffic crash rates and severity levels, in addition to identifying crash-prone locations (i.e., black spots) based on the two indicators. The available crash data for different road segments used for the analysis were obtained from the Washington state database provided by the Highway Safety Information System (HSIS) for the years 2006 to 2011. A Random Forest (RF) classifier was used to predict the outcome level of crash severity, while crash rates were predicted by applying RF regressor. Certain features were selected for each model besides the abstraction of new features to check if there are unobserved correlations affecting the independent variables, such as accounting for the number and weight of crashes within 1 km2 area by implementing the Getis-Ord Gi∗ index. Moreover, to calculate the collective risk (CR) score, crash rates were adjusted to incorporate crash severity weights (cost per severity type) and regression-to-the-mean (RTM) bias via Empirical Bayes (EB) method. Finally, segments were ranked according to their CR score.
Seven-Year Analysis of Microbial Keratitis Tendency at an Ophthalmology Department in Poland: A Single-Center Study
Authors: Ulfik Klaudia , Teper Sławomir , Dembski Michał , Nowińska Anna , Wróblewska-Czajka Ewa , Wylęgała Edward
Published: October 2020

This study aimed to analyze the frequency, drug susceptibility, and drug resistance of pathogens causing microbial keratitis (a corneal inflammation) in the Clinical Department of Ophthalmology, Medical University of Silesia, Katowice. Despite intensive treatment, severe inflammation causes irreversible blindness in ∼7% of cases and eye loss (evisceration or enucleation of the eyeball) in ∼1% of cases at our hospital. The choice of a targeted drug depends on the culture result and drug resistance of the microorganism. This was a retrospective observation study. Conjunctival swabs and corneal scrapes were collected between January 1, 2013, and December 31, 2019, in the tertiary reference center for keratitis. The collected data included the type of material received, culture result, and antimicrobial susceptibilities. Of the 2482 samples analyzed, 679 were positive and 1803 were negative. Of the total pathogens isolated, 69.9% were Gram-positive bacteria, 20.8% were Gram-negative bacteria, and 7.1% were fungi. A significant increase in the number of Gram-positive methicillin-resistant Staphylococcus aureus and a partial increase in the number of Gram-negative beta-lactams-resistant bacteria were observed. All fungal species were sensitive to amphotericin B, 82.81% were sensitive to voriconazole, and 56.25% were sensitive to fluconazole. Dual drug therapy (levofloxacin and tobramycin) was the first-line treatment. Drug susceptibility testing of the cultured microorganisms is necessary to initiate targeted treatment. Increased drug resistance was observed in this study. In the present study, most bacteria were sensitive to fluoroquinolones. Ciprofloxacin therapy remains the recommended empirical treatment in microbial keratitis. According to our study, voriconazole remains a first-line antifungal drug, when a fungal infection is suspected.
Effect of Planting Dates and Planting Methods on Water Relations of Wheat
Authors: Meleha Ahmed M. I. , Hassan A. F. , El-Bialy Maha A. , El-Mansoury Mona A. M.
Published: October 2020

Wheat (Triticum aestivum L.) is the uppermost cereal grain crop considered as a major stable food for the Egyptian people. Field experiments were conducted during two consecutive winter seasons of 2017-18 and 2018-19 to study the effect of two planting dates (PD) (20th of November and 20th of December) under four different planting methods (PM) (bed broadcast, flat broadcast, drill at 15 cm, and drill at 25 cm apart rows) on the productivity and water relations of wheat genotype (Egypt 1). The study is intended to assess the water relations for wheat planting dates and planting methods and determine the role of late planting date and planting methods on wheat productivity. Results showed that the values of grain yields and some attributed yields were highly significantly affected by planting dates and methods in the two growing seasons. Planting wheat at the optimal date (20th November) was better than sowing at the late date (20th December) for all values obtained from the studied parameters in both seasons of the study. The bed broadcast planting method gave the highest mean values for all studied parameters except the plant height which was recorded with drilling seeds at a 15 cm planting method in the two growing seasons. The highest values of water applied were recorded with the first date under the borders planting method (PD1M2), while the lowest of Aw recorded was from beds planting method with the second date. The highest mean values for WP were recorded with the bed broadcast planting method.
An Improved Method to Evaluate the Synchronization in Neural Key Exchange Protocol
Authors: Han Yi Liang , Li Yu , Li Zhe , Zhu Shuai Shuai
Published: October 2020

The synchronization between two neural networks by mutual learning can be used to design the neural key exchange protocol. The critical issue is how to evaluate the synchronization without a weight vector. All existing methods have a delay in evaluating the synchronization, which affects the security of the neural key exchange. To evaluate the full synchronization of neural networks more timely and accurately, an improved method for evaluating the synchronization is proposed. First, the frequency that the two networks have the same output in previous steps is used for assessing the degree of them roughly. Second, the hash function is utilized to judge whether the two networks have achieved full synchronization precisely when the degree exceeds a given threshold. The improved method can find the full synchronization between two networks with no information other than the hash value of the weight vector. Compared with other methods, the full synchronization can be detected earlier by two communication partners which adopt the method proposed in this paper. As a result, the successful probability of geometric is reduced. Therefore, the proposed method can enhance the security of the neural exchange protocol.
Potential Molecular Target Prediction and Docking Verification of Hua‐Feng‐Dan in Stroke Based on Network Pharmacology
Authors: Yang Ping , He Haifeng , Xu Shangfu , Liu Ping , Bai Xinyu
Published: October 2020

Objective. Hua‐Feng‐Dan (HFD) is a Chinese medicine for stroke. This study is to predict and verify potential molecular targets and pathways of HFD against stroke using network pharmacology. Methods. The TCMSP database and TCMID were used to search for the active ingredients of HFD, and GeneCards and DrugBank databases were used to search for stroke‐related target genes to construct the “component‐target‐disease” by Cytoscape 3.7.1, which was further filtered by MCODE to build a core network. The STRING database was used to obtain interrelationships by topology and to construct a protein‐protein interaction network. GO and KEGG were carried out through DAVID Bioinformatics. Autodock 4.2 was used for molecular docking. BaseSpace was used to correlate target genes with the GEO database. Results. Based on OB ≥ 30% and DL ≥ 0.18, 42 active ingredients were extracted from HFD, and 107 associated targets were obtained. PPI network and Cytoscape analysis identified 22 key targets. GO analysis suggested 51 cellular biological processes, and KEGG suggested that 60 pathways were related to the antistroke mechanism of HFD, with p53, PI3K‐Akt, and apoptosis signaling pathways being most important for HFD effects. Molecular docking verified interactions between the core target (CASP8, CASP9, MDM2, CYCS, RELA, and CCND1) and the active ingredients (beta‐sitosterol, luteolin, baicalein, and wogonin). The identified gene targets were highly correlated with the GEO biosets, and the stroke‐protection effects of Xuesaitong in the database were verified by identified targets. Conclusion. HFD could regulate the symptoms of stroke through signaling pathways with core targets. This work provided a bioinformatic method to clarify the antistroke mechanism of HFD, and the identified core targets could be valuable to evaluate the antistroke effects of traditional Chinese medicines.
Nonadherence to Antiepileptic Medications and Its Determinants among Epileptic Patients at the University of Gondar Referral Hospital, Gondar, Ethiopia, 2019: An Institutional-Based Cross-Sectional Study
Authors: Tilahun Misganaw , Habte Netsanet , Mekonnen Kenean , Srahbzu Mengesha , Ayelegne Daniel
Published: October 2020

Introduction. Nonadherence to antiepileptic medication is the extent of a patient’s passive failure to follow the prescribed therapeutic regimen. The prevalence and impact of nonadherence to antiepileptic medication are high globally. The main purpose of this study was to assess nonadherence to antiepileptic medications and its associated factors among epileptic patients at the University of Gondar Referral Hospital, Gondar, Ethiopia, 2019. Methods. An institutional-based cross-sectional study was conducted among 365 epileptic patients at the University of Gondar Referral Hospital, who were selected by a systematic random sampling technique. Data were collected by face to face interviews using a structured pretested questionnaire. Data were entered into EPI Info version 7 and then exported to SPSS version 22 for analysis. The data were described by descriptive statistics. Binary logistic regression analysis was used as a model, and variables with a

p

value of less than 0.05 were considered as statistically significant with nonadherence to antiepileptic medications. Results. A total of 356 epileptic patients participated in the study yielding a response rate of 97.5%. The overall prevalence of nonadherence to antiepileptic medications among epileptic patients attending at the University of Gondar Referral Hospital was 38.5% (95% CI: 33.1–43.8). Divorced and/or widowed marital status (AOR: 3.38 (95% CI: 1.54, 7.44)), treatment duration of 3–5 years (AOR = 3.58 (95% CI: 1.38, 9.29)), treatment duration of 5 and above years (AOR: 3.49 (95% CI: 1.53, 7.95)), comorbidity (AOR: 2.42 (95% CI: 1.08, 5.43)), side effects of antiepileptic medications (AOR: 3.36 (95% CI: 1.67, 6.74)), absence of health information (AOR: 1.98 (95% CI: 1.11, 3.52)), epilepsy-related stigma (AOR: 2.81 (95% CI: 1.57, 5.02)), and negative attitude towards antiepileptic medications (AOR: 2.46 (95% CI: 1.36, 4.45)) were significantly associated with nonadherence to antiepileptic medications. Conclusions. Prevalence of nonadherence to antiepileptic medications among epileptic patients at the University of Gondar Referral Hospital was found to be high. Hence, giving health information about epilepsy and its management will help to reduce antiepileptic medications’ nonadherence.