bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the Brain Development in Newborns by Information-Based Analysis of Electroencephalography (EEG) Signal
Authors: Namazi Hamidreza
Published: July 2020

In this paper, we employ the information theory to analyze the development of brain as the newborn ages. We compute the Shannon entropy of Electroencephalography (EEG) signal during sleep for 10 groups of newborns who are aged 36 weeks to 45 weeks (first to the last group). Based on the obtained results, EEG signals for newborns in 36 weeks have the lowest information content, whereas EEG signals for newborns in 45 weeks show the greatest information content. Therefore, we concluded that the information content of EEG signal increases as the age of newborn increases. Th result of statistical analysis demonstrated that the influence of increment of age of newborn on the variations of informant content of their EEG signals was significant.
The trailing terms ideal
Authors: Ben Amor Faten , Yengui Ihsen
Published: July 2020

In this paper, we address the following question: for a nonzero finitely generated ideal [Formula: see text] of a multivariate polynomial ring [Formula: see text] over a coherent ring [Formula: see text], fixing a monomial order [Formula: see text] on [Formula: see text], is the trailing terms ideal [Formula: see text] of [Formula: see text] (that is, the ideal generated by the trailing terms of the nonzero polynomials in [Formula: see text]) finitely generated? We show that while [Formula: see text] can be nonfinitely generated, it is always countably generated when the monomial order is Noetherian (graded monomial orders as instances).
Cyclic and cyclic controlled quantum teleportation in a high-dimension system
Authors: Wu Fan , Bai Ming-Qiang , Zhang Yu-Chun , Liu Ren-Ju , Mo Zhi-Wen
Published: July 2020

In this paper, two schemes for cyclic quantum teleportation (CQT) and cyclic controlled quantum teleportation (CCQT) in a high-dimension system are proposed. In the first scheme, three distant agents, Alice, Bob and Charlie, are not only the senders but also the receivers, and via the six-qutrit entangled state as the quantum channel, Alice can transfer her quantum information to Bob, at the same time, Bob can transfer his quantum information to Charlie and Charlie can transfer his quantum information to Alice. While for the second scheme, there is one controller David, and only with the help of him can the teleportation be accomplished via the seven-qutrit entangled state as the quantum channel. These schemes can be generalized to realize the teleportation with [Formula: see text] agents. Furthermore, the resource consumption and feasibility of the schemes are investigated at the end of the paper.
Between a Rock and a Hard Place: The Dilemmas of Middle Powers
Authors: JOB BRIAN L.
Published: July 2020

“Middle powers,” variously defined, have served relevant and significant roles in the post-WWII regional and global orders, facilitated by structural conditions of “long peace” among great powers and proactive leadership by and among creative middle powers. Within the complex Asia-Pacific security order, “middle powers” such as Australia, Canada, and South Korea have had the “space” to engage the non-like minded and advance multilateralism with security guarantees from the US. However, Beijing and Washington today are eliminating this space and its associated choices for middle-power diplomacy by increasingly characterizing their rivalry as a confrontation of “existential threats” between incompatible “civilizations” and securitizing trade and technology. China and the US are each selectively ignoring or purposely eroding key aspects of a rules-based international order. This paper highlights the dilemmas of South Korea, Australia, and Canada, middle powers who have found themselves individually and collectively “stuck” facing contradictory global and regional policy choices.
Ground models; a brief overview
Authors: Norbury David
Published: July 2020

The background to the presence of ground models in ground investigation practice is outlined. Ground models are not new but have been more widely and explicitly used since Fookes’ First Glossop Lecture in 1997. Most authors identify that a ground model is both necessary and beneficial, although they use a variety of alternative terms, and also present a range of views as to what should be included in a ground model. The literature on this variety of approaches is reviewed to suggest a consensus. In parallel, developments have led to the use of ground models being called for in the British (just published) and European Standards (currently in preparation). These explicit requirements in normative Standards will require that the geology, in the form of the ground model, will become an explicit and integral element of the whole process of the ground investigation and design and construction in the ground. The paper reviews the background to ground models, their suggested content and the significance of their presence in the latest Standards.

Thematic collection:
This article is part of the Ground models in engineering geology and hydrogeology collection available at:
https://www.lyellcollection.org/cc/Ground-models-in-engineering-geology-and-hydrogeology
Flood-generated hyperpycnal delta front sands of the Brora Arenaceous Formation (upper Callovian–middle Oxfordian) of the Inner Moray Firth, Scotland, record the onset of rifting
Authors: Surlyk Finn , Bruhn Rikke
Published: July 2020

Sandstones of the Middle–Upper Jurassic Brora Arenaceous Formation of the Inner Moray Firth, NE Scotland have hitherto been interpreted as representing coastal, tidally-influenced bars. The formation is exposed close to the northern basin-bounding Helmsdale Fault, and the middle member of the formation, the Clynelish Quarry Sandstone, consists of thick, mainly structureless sandstone beds with wavy, commonly amalgamated boundaries. It also includes sandstone bodies with sigmoidal clinothems, erosional surfaces and backset beds. Rich marine faunas dominated by bivalves and ammonites occur at a few levels, whereas trace fossils are rare or absent. The Clynelish Quarry Sandstone is here reinterpreted as reflecting deposition by hyperpycnal sandy density flows in flood-generated marine, subaqueous, delta-scale clinoforms and lobes in front of local mountain streams. The reinterpretation of these sandstones implies the presence of a tectonically controlled, relatively steep basin margin along the line of the Helmsdale Fault. The Brora Arenaceous Formation thus dates the onset of Jurassic rifting in the Inner Moray Firth to the latest Callovian rather than the late Oxfordian as previously interpreted from seismic data.
Archean granitoids of India: windows into early Earth tectonics – an introduction
Authors: Dey Sukanta , Moyen Jean-François
Published: July 2020

Granitoids form the dominant component of Archean cratons. They are generated by partial melting of diverse crustal and mantle sources and subsequent differentiation of the primary magmas, and are formed through a variety of geodynamic processes. Granitoids, therefore, are important archives for early Earth lithospheric evolution. Peninsular India comprises five cratonic blocks bordered by mobile belts. The cratons that stabilized during the Paleoarchean–Mesoarchean (Singhbhum and Western Dharwar) recorded mostly diapirism or sagduction tectonics. Conversely, cratons that stabilized during the late Neoarchean (Eastern Dharwar, Bundelkhand, Bastar and Aravalli) show evidence consistent with terrane accretion–collision in a convergent setting. Thus, the Indian cratons provide testimony to a transition from a dominantly pre-plate tectonic regime in the Paleoarchean–Mesoarchean to a plate-tectonic-like regime in the late Neoarchean. Despite this diversity, all five cratons had a similar petrological evolution with a long period (250–850 myr) of episodic tonalite–trondhjemite–granodiorite (TTG) magmatism followed by a shorter period (30–100 myr) of granitoid diversification (sanukitoid, K-rich anatectic granite and A-type granite) with signatures of input from both mantle and crust. The contributions of this Special Publication cover diverse granitoid-related themes, highlighting the potential of Indian cratons in addressing global issues of Archean crustal evolution.
Learning Distance Metrics from Probabilistic Information
Authors: Huai Mengdi , Miao Chenglin , Li Yaliang , Suo Qiuling , Su Lu , Zhang Aidong
Published: July 2020

The goal of metric learning is to learn a good distance metric that can capture the relationships among instances, and its importance has long been recognized in many fields. An implicit assumption in the traditional settings of metric learning is that the associated labels of the instances are deterministic. However, in many real-world applications, the associated labels come naturally with probabilities instead of deterministic values, which makes it difficult for the existing metric-learning methods to work well in these applications. To address this challenge, in this article, we study how to effectively learn the distance metric from datasets that contain probabilistic information, and then propose several novel metric-learning mechanisms for two types of probabilistic labels, i.e., the instance-wise probabilistic label and the group-wise probabilistic label. Compared with the existing metric-learning methods, our proposed mechanisms are capable of learning distance metrics directly from the probabilistic labels with high accuracy. We also theoretically analyze the proposed mechanisms and conduct extensive experiments on real-world datasets to verify the desirable properties of these mechanisms.
PREASC
Authors: Goli Mehran , Drechsler Rolf
Published: July 2020

The increasing functionality of electronic systems due to the constant evolution of the market requirements makes the non-functional aspects of such systems (e.g., energy consumption, area overhead, or performance) a major concern in the design process. Approximate computing is a promising way to optimize these criteria by trading accuracy within acceptable limits. Since the cost of applying significant structural changes to a given design increases with the stage of development, the optimization solution needs to be incorporated into the design as early as possible. For the early design entry, modeling hardware at the
Electronic System Level
(ESL) using the SystemC language is nowadays widely used in the industry. To apply approximation techniques to optimize a given SystemC design, designers need to know which parts of the design can be approximated. However, identifying these parts is a crucial and non-trivial starting point of approximate computing, as the incorrect detection of even one critical part as resilient may result in an unacceptable output. This usually requires a significant programming effort by designers, especially when exploring the design space manually.

In this article, we present PREASC, a fully automated framework to identify the resilience portions of a given SystemC design. PREASC is based on a combination of static and dynamic analysis methods along with regression analysis techniques (a fast machine learning method providing an accurate function estimation). Once the resilient portions are identified, an approximation degree analysis is performed to determine the maximum error rate that each resilient portion can tolerate. Subsequently, the maximum number of resilient portions that can be approximated at the same time are reported to designers at different granularity levels. The effectiveness of our approach is evaluated using several standard SystemC benchmarks from various domains.
The impact of using virtual patients in preclinical pharmacology teaching
Authors: Nicolaou Persoulla A. , El Saifi Mamoun
Published: July 2020

To reduce medication errors, medical educators must nurture the early development of rational and safe prescribing. Teaching pharmacology is challenging because it requires knowledge integration across disciplines, including physiology and pathology. Traditionally, pharmacology has been taught using lecture-based learning, which conveys consistent information but may promote passive learning. Virtual patients (VPs) have been used more recently to promote active learning, mainly in clinical years. Conversely, the use of VPs in preclinical disciplines, including pharmacology, is not well described. The objective was to investigate the potential benefits of combining traditional teaching with VPs in preclinical pharmacology teaching. All year 3 medical students (2 cohorts), enrolled in the Systematic Pharmacology I course (lectures: 3 h weekly; tutorial: 1 h weekly), were invited to participate in this naturalistic, prospective study. During tutorials, students were taught using case-based discussion and single-best-answer questions (control) in four tutorials and VPs (experimental) in the remaining six tutorials. The impact of VPs was assessed by 1) performance in written examinations, and 2) student satisfaction/perceptions, using a validated, modified questionnaire. Examination performance related to teaching in VP-based tutorials was significantly improved, compared with traditional tutorials. The level of difficulty of control and experimental assessment items was comparable, as determined by the Angoff method. Facilitation of learning was higher in VP tutorials, while a no-harm effect was noted on knowledge acquisition/maintenance, authenticity of learning, and disadvantages of learning. VPs may be effectively integrated in preclinical pharmacology teaching, with benefits on pharmacological knowledge and facilitation of learning.
Self-directed learning: assessment of students’ abilities and their perspective
Authors: Bhandari Bharti , Chopra Deepti , Singh Kavita
Published: July 2020

The introduction of Competency-Based Medical Education Curriculum in India has endorsed many new concepts, like foundation course, self-directed learning (SDL), early clinical exposure, etc. Emphasis is being given to active teaching-learning approaches. One such approach is SDL. SDL is an active learning approach in which the students are responsible for their own learning outcome, with teacher acting as a facilitator of learning. A medical graduate, being a lifelong learner, should inculcate the habit of SDL. In the present study, the SDL abilities of first year Bachelor of Medicine, Bachelor of Surgery students were assessed using a questionnaire. Based on their experience, students were also asked about the prerequisites of SDL, how it can be promoted, and their expectations from the teachers. Students scored high in most of the SDL skills. However, they felt they need improvement in time management. Furthermore, the students are required to develop their interpersonal communication skills, and they also find it difficult to express messages effectively in oral presentations. Most of the students felt they need help in finding the correct learning resources. According to them, the students should be focused, motivated and stress-free, have time management skills, and be able to search learning resources for successful implementation of SDL. They felt that events that encourage active participation by students, if organized at regular intervals, could promote SDL. Some felt that evaluation of SDL would motivate them to take it seriously. According to the students, teacher should act as a facilitator, a mentor, as well as an evaluator.
The role of endothelial autocrine NRG1/ERBB4 signaling in cardiac remodeling
Authors: Dugaucquier Lindsey , Feyen Eline , Mateiu Ligia , Bruyns Tine Anne Marie , De Keulenaer Gilles W. , Segers Vincent F. M.
Published: July 2020

The role of NRG1/ERBB signaling in endothelial cells is not completely understood. Our study contributes to the understanding of spatiotemporal heterogeneity of myocardial autocrine and paracrine responses following cardiac injury and shows a role of endothelial autocrine NRG1/ERBB4 signaling in the modulation of hypertrophic and fibrotic responses during early cardiac remodeling.
Dilated cardiomyopathy mutations in thin-filament regulatory proteins reduce contractility, suppress systolic Ca2+, and activate NFAT and Akt signaling
Authors: Robinson Paul , Sparrow Alexander J. , Patel Suketu , Malinowska Marta , Reilly Svetlana N. , Zhang Yin-Hua , Casadei Barbara , Watkins Hugh , Redwood Charles
Published: July 2020

Dilated cardiomyopathy (DCM) is a frequently occurring cardiac disorder with a degree of genetic inheritance. We have found that DCM mutations in proteins that regulate the contractile machinery cause alterations to contraction, calcium-handling, and some new signaling pathways that provide stimuli for disease development. We have used guinea pig cells that recapitulate human calcium-handling and introduced the mutations using adenovirus gene transduction to look at the initial triggers of disease before remodeling.
Inhibition of ERRαAggravates Sepsis-Induced Acute Lung Injury in Rats via Provoking Inflammation and Oxidative Stress
Authors: Xia Wenfang , Pan Zhou , Zhang Huanming , Zhou Qingshan , Liu Yu
Published: July 2020

Inflammation and oxidative stress are critical pathologies that contribute to sepsis-induced acute lung injury (ALI). This study investigated the regulatory role of estrogen-related receptor alpha (ERRα) in an experimental model of sepsis-induced ALI.In vivo, a cecal ligation and puncture- (CLP-) induced ALI model was established in anesthetized rats. Animals were then randomly assigned to receive an intraperitoneal injection of vehicle or ERRαinverse agonist (XCT-790, 2.5 mg/kg). Administration of XCT-790 significantly aggravated a sepsis-induced increase in pathological damage of lung tissues, lung endothelial permeability, myeloperoxidase (MPO) activity in lung tissues, production of serum inflammatory factors, and inflammatory cell accumulation in bronchoalveolar lavage fluid. In addition, XCT-790 treatment exacerbated a CLP-induced decrease in lung superoxide dismutase and an increase in lung malondialdehyde levels.In vitro, the exposure of rat pulmonary microvascular endothelial cells (PMVECs) to lipopolysaccharide (LPS) resulted in increased endothelial permeability and reduced expression of tight junction protein ZO-1, Occludin, JAM-A, and adherens junction protein VE-cadherin, which were further deteriorated by knockdown of ERRα. In addition, LPS-triggered inflammatory factor production and increase in the expression of phosphorylated IκBαand NF-κB p65 were also exacerbated by silencing ERRαgene. Meanwhile, knockdown of ERRαdramatically promoted LPS-activated mitochondrial reactive oxygen species production and LPS-induced downregulation of Sirt3 protein levels in rat PMVECs. Taken together, our present study provides evidences that ERRαfunctions as a novel negative modulator of sepsis-induced ALI in rats. The underlying mechanisms responsible for ERRα-elicited effects are largely dependent on the regulation of inflammatory response and oxidative stress.
The Dissolved Oxygen Sensor Design Based on Ultrasonic Self-Adaption and Self-Cleaning
Authors: Xiao Zhong , Wang Jingtong , Yi Chen , Wang Zairong , Wang Liang
Published: July 2020

Dissolved oxygen sensor is the key of dissolved oxygen measurement and it is usually implemented by electrochemical method, which measures dissolved oxygen content by the diffusion rate of molecular oxygen through film. However, the film on the electrochemical sensor probe is most likely to be blocked up by the waterborne contaminant, which may reduce the service life of the sensor and the indirect influence on the sensor’s current. This is caused by changes of water temperature, which may lead to the decline in the accuracy of the sensor’s output. This paper suggests a new method to implement the intelligent dissolved oxygen sensor. Our method mainly aims at ultrasonic automatic cleaning, automatic adjustment, and adaptation for the changes of temperature, which can not only regularly clean the dissolved oxygen sensor probe but also automatically calibrate the instruments based on the changes of temperature by combining software and hardware. The experiments show that the ultrasonic cleaning technology can not only increase the service life of the sensor by cleaning the film on the probe safely and effectively but also improve the accuracy of the sensor’s output. Our method also has the advantages of simple structure, high accuracy of measurement, long service life, convenience, and stability, which is suitable for application and popularization.
Adiabatic Temperature Rise Test of Cemented Sand and Gravel (CSG) and Its Application to Temperature Stress Prediction of CSG Dam
Authors: Jiang Minmin , Cai Xin , Guo Xingwen , Liu Qinghui , Zhang Tianye
Published: July 2020

An adiabatic temperature rise test of cemented sand and gravel (CSG) is conducted, a model for temperature rising of CSG is proposed, and its application to temperature stress prediction of CSG dam is presented. Adiabatic temperature rise tests are first conducted to investigate the temperature rise properties of CSG material with different cementing agent contents. The results demonstrate that the hydration reaction time is longer for CSG material with higher cementing agent content, and a linear relationship is presented between cementing agent contents and final value of adiabatic temperature rise. Then, a calculation model considering different cementing agent contents is developed based on the regression analysis of the test data. The proposed model is implanted into the ANSYS software platform for predictions of temperature distributions and stress fields of a typical CSG dam. The results show that the distributions of temperature and temperature stress are similar to those of roller compacted concrete (RCC) dam. Due to the high temperature stress at the long intermittent surface and downstream surface of the dam, the thermal insulation measures on the surface of the dam should be considered in the CSG dam with high cementing agent contents and in the severe cold environment. Therefore, it cannot be generally considered that the temperature control of the CSG dam does not need to be considered, and it should be determined according to the specific working conditions.
Dentists Are at a Higher Risk for Oral Helicobacter pylori Infection
Authors: Liu Qian , Zhang Yunhan , Xu Chunmei , Chen Boran , Xu Hao , Cao Yangpei , Guo Tingwei , Gao Yuan , Zhou Zhou , Zhou Xuedong , Xu Xin , He Jinzhi
Published: July 2020

Oral cavity has been taken as one of the major reservoirs for Helicobacter pylori, the bacteria responsible for gastric infection and cancers. Dentists are frequently exposed to saliva; thus, theoretically, they are at a higher risk for oral H. pylori infection. In the present study, to test this hypothesis and to find out the potential factors associated with the increased risk, a cross‐sectional study was carried out on a large scale of dentists (N = 90) and nondentist controls (N = 110). By using nested polymerase chain reaction to amplify a specific DNA fragment of H. pylori, we found 7.27% of saliva samples from the nondentist group and 16.67% of saliva samples from the dentist group were oral H. pylori positive, and the difference between groups was statistically significant (χ2 = 4.292, p = 0.038). Importantly, however, after stratifying enrolled subjects with factors which might interfere with the comparison of H. pylori detection rate between groups, we still observed a higher H. pylori frequency in the dentists than that in the controls in subgroups, including those with good individual hygiene, healthy lifestyle, and physical condition, as well as those living with families to be gastric disease free and not sharing meals with H. pylori‐positive persons, respectively. Moreover, the frequency of clinical practice per week of the investigated dentists was closely associated with an oral H. pylori infection risk. Our data indicates that dentists are at a higher risk for H. pylori infection, and intensive attention needs to be paid on this issue.
Ganoderma lucidum Prevents Cisplatin-Induced Nephrotoxicity through Inhibition of Epidermal Growth Factor Receptor Signaling and Autophagy-Mediated Apoptosis
Authors: Mahran Yasmen F. , Hassan Hanan M.
Published: July 2020

Background. Cisplatin (cis-diaminedichloroplatinum, CDDP) is a broad-spectrum antineoplastic agent. However, CDDP has been blamed for its nephrotoxicity, which is the main dose-limiting adverse effect. Ganoderma lucidum (GL), a medicinal mushroom, has antioxidant and inflammatory activities. Therefore, this study is aimed at finding out the potential nephroprotection of GL against CDDP-induced nephrotoxicity in rats and the possible molecular mechanisms including the EGFR downstream signaling, apoptosis, and autophagy. Methods. Rats were given GL (500 mg/kg) for 10 days and a single injection of CDDP (12 mg/kg, i.p). Results. Nephrotoxicity was evidenced by a significant increase in renal indices and oxidative stress markers. Additionally, CDDP showed a plethora of inflammatory and apoptotic responses as evidenced by a profound increase of HMGB-1, NF-κB, and caspase-3 expressions, whereas administration of GL significantly improved all these indices as well as the histopathological insults. Renal expression of EGFR showed a similar trend after GL administration. Furthermore, activation of autophagy protein, LC3 II, was found to be involved in GL-mediated nephroprotection correlated with the downregulation of apoptotic signaling, caspase-3 and terminal deoxynucleotidyl transferase (TDT) renal expressions. Conclusion. These results suggest that GL might have improved CDDP-induced nephrotoxicity through antioxidant, anti-inflammatory, and autophagy-mediated apoptosis mechanisms and that inhibition of EGFR signaling might be involved in nephroprotection.
Fuzzy Fixed Point Results in F-Metric Spaces with Applications
Authors: Alansari Monairah , Mohammed Shehu Shagari , Azam Akbar
Published: July 2020

In this paper, some concepts of F-metric spaces are used to study a few fuzzy fixed point theorems. Consequently, corresponding fixed point theorems of multivalued and single-valued mappings are discussed. Moreover, one of our obtained results is applied to establish some conditions for existence of solutions of fuzzy Cauchy problems. It is hoped that the established ideas in this work will awake new research directions in fuzzy fixed point theory and related hybrid models in the framework of F-metric spaces.
Nutritional Status of Children and Its Associated Factors in Selected Earthquake-Affected VDCs of Gorkha District, Nepal
Authors: Shrestha Asmita , Bhusal Chet Kant , Shrestha Binjwala , Bhattarai Kiran Dev
Published: July 2020

Background. Malnutrition is a major public health problem and most enveloping cause of morbidity and mortality among children and adolescents throughout the world. This study was aimed at assessing the nutritional status and associated factors among 6-10-year-old children in selected earthquake-affected areas of Gorkha district, Nepal. Methods. A community-based cross-sectional study among 420 mothers having children of age groups 6-10 years (with anthropometric measurement among children) was conducted using a mixed method in selected earthquake-affected areas of Gorkha district, Nepal, from October 2015 to April 2016. Gorkha was selected purposively from 14 earthquake-affected districts. Two village development committees were selected randomly among 6 having severe impact. Randomly, 5 wards were selected from each of the 2 village development committees. As the sample was 420, 42 children were selected randomly from every ward. Result. Among the 420 children, 31.9% were underweight, 51.9% were stunted, and 2.9% were wasted after the earthquake. Children who were more prone to being underweight were the following: male children (RR=1.34 95% CI: 1.01-1.78) and children from illiterate mothers (RR=2.49, 95% CI: 1.85-3.36), illiterate fathers (RR=1.73, 95% CI: 1.32-2.27), and homemaker mothers (RR=0.28, 95% CI: 0.20-0.38); children whose families were using nonimproved sources of water (RR=2.60, 95% CI: 1.07-6.60); and households having food insecurity (RR=12.97, 95% CI: 3.29-51.18). Similarly, children of illiterate fathers (RR=1.67, 95% CI: 1.41-1.97), children of illiterate mothers (RR=2.32, 95% CI: 1.91-2.83), children of homemaker mothers (RR=0.59, 95% CI: 0.49-0.70), children whose family were using treated water (RR=0.32, 95% CI: 0.15-0.67), and children from food insecure households (RR=10.52, CI: 4.05-27.33) were found to be stunted. After adjustment, children from households consuming nonimproved water were 6 times more likely (OR=6.75; 95% CI: 1.59-28.62) to be wasted. Conclusion. Illiterate mothers, illiterate fathers, mothers engaged in occupation other than household work, and food insecure households were found to be independent predictors of underweight and stunting. Nonimproved source of drinking water was found to be independent predictors of wasting.
Iterative Positive Solutions to a Coupled Hadamard-Type Fractional Differential System on Infinite Domain with the Multistrip and Multipoint Mixed Boundary Conditions
Authors: Du Xinran , Meng Yuan , Pang Huihui
Published: July 2020

This paper is devoted to the existence of positive solutions for a nonlinear coupled Hadamard fractional differential system, with multistrip and multipoint mixed boundary conditions on an infinite interval. Based on the Arzelá-Ascoli theorem, we establish an important lemma to prove the complete continuity of operators on the infinite interval. Using the monotone iterative technique, the existence criteria for positive extremal solutions can be acquired, and an example is given to illustrate the feasibility of the above study as well.
Antioxidant Effects and Cytoprotective Potentials of Herbal Tea against H2O2‐Induced Oxidative Damage by Activating Heme Oxygenase1 Pathway
Authors: Zhang Ke-Xin , Tan Jian-Bin , Xie Cheng-Liang , Zheng Rong-Bo , Huang Xiao-Dan , Zhang Meng-Meng , Zhao Min
Published: July 2020

Herbal tea with antioxidant ingredients has gained increasing attention in the field of functional foods due to their amelioration potential in aging‐related diseases. Wanglaoji herbal tea (WHT) is a kind of traditional beverage made from herbal materials. This study was performed to investigate its antioxidant activity and identify its protective effect on a H2O2‐induced cell damage model. In this study, we identified six kinds of phenolic acids with antioxidant activity in WHT, among which rosmarinic acid had the highest content and the highest contribution ratio to the antioxidant activity of WHT. Moreover, compared with the H2O2‐induced damage group, the WHT treatment group can significantly increase the viability of cells and decrease the ratio of senescence‐associated β‐galactosidase‐positive cells, intracellular malondialdehyde levels, and the percentage of G1 phase. Furthermore, enrichment analysis of differentially expressed genes revealed that heme oxygenase1 (HMOX1) was a key gene for protective effect of WHT on oxidative stress‐induced cell damage. Thus, WHT exerted protective effects not only by scavenging reactive oxygen species but also by inducing the expression of cytoprotective genes by activating the HMOX1 pathway, which showed that WHT had a potential of promoting health by reducing oxidative stress‐induced cell damage.
Comparison of Repeated Fluid-Air Exchange and Passive Drainage for Removing Residual Emulsified Silicone Oil Droplets
Authors: Yu Jian , Zong Yuan , Tan Ye , Jiang Chunhui , Xu Gezhi
Published: July 2020

Purpose. To compare the efficacy of passive drainage (PD) and repeated fluid-air (FA) exchange for removing emulsified silicone oil (SO) droplets. Methods. Twenty rhegmatogenous retinal detachment (RRD) patients who underwent primary pars plana vitrectomy (PPV) with SO tamponade were randomly and evenly divided into two groups for PD and FA exchange. Once the bulk of SO was removed, the first 2 mL of the washout fluid was collected, and then, another 2 mL of the washout fluid was collected after PD or FA exchange. The size and number of SO droplets in the washout fluid were measured using a Coulter counter (Multisizer 3, Beckman Coulter, Indianapolis, IN, USA). The efficiencies of FA exchange and PD for removing emulsified SO were compared. Results. The number of SO droplets decreased significantly after FA exchange and PD. The decrease in the number of droplets was statistically significant for larger droplets (>4 µm) with PD and for all droplet sizes with FA exchange. The decrease in the number of SO droplets of <4 μm was significantly greater with FA exchange than with PD. However, at the end of the procedure, the overall number and size distribution of SO droplets were similar for both procedures. Conclusions. PD and FA exchange reduced the number of residual emulsified SO droplets after SO tamponade efficiently. FA exchange may have some advantages over PD in removing small droplets.
Successful Percutaneous Coronary Intervention Using Intravascular Ultrasound-Guided Rewiring Technique in a Case of Spontaneous Coronary Artery Dissection Involving Left Main Bifurcation
Authors: Numasawa Yohei , Yokokura Souichi , Hitomi Yasuhiro , Imaeda Shohei , Tanaka Makoto , Tabei Ryota , Kodaira Masaki
Published: July 2020

We herein describe a 49-year-old woman without significant cardiovascular risk factors who was transferred to our hospital with sudden onset of chest pain. The patient was diagnosed with non-ST-elevation acute myocardial infarction, and coronary angiography revealed a dissection at the proximal site of the left anterior descending artery (LAD) extending from the left main trunk (LMT) suggestive of spontaneous coronary artery dissection (SCAD). Because coronary flow was impaired after contrast injection and the patient had chest pain with ST elevation, urgent percutaneous coronary intervention was performed. The first guide wire was initially introduced from the LMT to the distal LAD, but intravascular ultrasound (IVUS) imaging revealed that the guide wire had passed through the true lumen of the left coronary artery ostium, false lumen at the ostium of the left circumflex artery, and true lumen of the distal LAD. We then reinserted another guide wire using an IVUS-guided rewiring technique from the true lumen of the LMT to the distal LAD. Finally, a drug-eluting stent was deployed to cover the dissected segment, and final coronary angiography revealed acceptable results with a patent left circumflex artery. This case report highlights that physicians should consider SCAD among the differential diagnoses in patients presenting with acute coronary syndrome, particularly in young women. In the present case, IVUS played a pivotal role in not only detecting the arterial dissection but also correctly introducing the guide wire into the true lumen.
A Serum Protein Classifier Identifying Patients with Advanced Non–Small Cell Lung Cancer Who Derive Clinical Benefit from Treatment with Immune Checkpoint Inhibitors
Authors: Muller Mirte , Hummelink Karlijn , Hurkmans Daan P. , Niemeijer Anna-Larissa N. , Monkhorst Kim , Roder Joanna , Oliveira Carlos , Roder Heinrich , Aerts Joachim G. , Smit Egbert F.
Published: July 2020

Purpose:

Pretreatment selection of patients with non–small cell lung cancer (NSCLC) who would derive clinical benefit from treatment with immune checkpoint inhibitors (CPIs) would fulfill an unmet clinical need by reducing unnecessary toxicities from treatment and result in substantial health care savings.

Experimental Design:

In a retrospective study, mass spectrometry (MS)-based proteomic analysis was performed on pretreatment sera derived from patients with advanced NSCLC treated with nivolumab as part of routine clinical care (n = 289). Machine learning combined spectral and clinical data to stratify patients into three groups with good (“sensitive”), intermediate, and poor (“resistant”) outcomes following treatment in the second-line setting. The test was applied to three independent patient cohorts and its biology was investigated using protein set enrichment analyses (PSEA).

Results:

A signature consisting of 274 MS features derived from a development set of 116 patients was associated with progression-free survival (PFS) and overall survival (OS) across two validation cohorts (N = 98 and N = 75). In pooled analysis, significantly better OS was demonstrated for “sensitive” relative to “not sensitive” patients treated with nivolumab; HR, 0.58 (95% confidence interval, 0.38–0–87; P = 0.009). There was no significant association with clinical factors including PD-L1 expression, available from 133 of 289 patients. The test demonstrated no significant association with PFS or OS in a historical cohort (n = 68) of second-line NSCLC patients treated with docetaxel. PSEA revealed proteomic classification to be significantly associated with complement and wound-healing cascades.

Conclusions:

This serum-derived protein signature successfully stratified outcomes in cohorts of patients with advanced NSCLC treated with second-line PD-1 CPIs and deserves further prospective study.
Defining an Optimal Dual-Targeted CAR T-cell Therapy Approach Simultaneously Targeting BCMA and GPRC5D to Prevent BCMA Escape–Driven Relapse in Multiple Myeloma
Authors: Fernández de Larrea Carlos , Staehr Mette , Lopez Andrea V. , Ng Khong Y. , Chen Yunxin , Godfrey William D. , Purdon Terence J. , Ponomarev Vladimir , Wendel Hans-Guido , Brentjens Renier J. , Smith Eric L.
Published: July 2020

Chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma targeting B-cell maturation antigen (TNFRSF17; BCMA) induces high overall response rates; however, relapse occurs commonly. A reservoir of multiple myeloma cells lacking sufficient BCMA surface expression (antigen escape) may be implicated in relapse. We demonstrate that simultaneous targeting of an additional antigen—here, G protein-coupled receptor class-C group-5 member-D (GPRC5D)—can prevent BCMA escape–mediated relapse in a model of multiple myeloma. To identify an optimal approach, we compare subtherapeutic doses of different forms of dual-targeted cellular therapy. These include; (i) parallel-produced and pooled mono-targeted CAR T cells, (ii) bicistronic constructs expressing distinct CARs from a single vector, and (iii) a dual-scFv “single-stalk” CAR design. When targeting BCMA-negative disease, bicistronic and pooled approaches had the highest efficacy, whereas for dual-antigen–expressing disease, the bicistronic approach was more efficacious than the pooled approach. Mechanistically, expressing two CARs on a single cell enhanced the strength of CAR T-cell/target cell interactions.

Significance:

Myeloma frequently relapses post-CAR T-cell therapy; antigen escape–mediated relapse can be mitigated with upfront dual-targeting (BCMA/GPRC5D). A bicistronic vector encoding two CARs avoids the challenge of parallel manufacturing separate CAR T-cell products, while providing superior efficacy; this dual-targeted approach may enhance the durability of responses to cellular therapy for myeloma.

See related commentary by Simon and Riddell, p. 130.

This article is highlighted in the In This Issue feature, p. 127
Significance of Neutrophil Gelatinase-Associated Lipocalin as a Biomarker for the Diagnosis of Diabetic Kidney Disease: A Systematic Review and Meta-Analysis
Authors: He Peng , Bai Ming , Hu Jin-ping , Dong Chen , Sun Shiren , Huang Chen
Published: July 2020

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising marker for the diagnosis of diabetic kidney disease (DKD), but its utility is currently debated. This meta-analysis aims to evaluate the diagnostic value of NGAL for DKD. Method: MEDLINE, Embase, ­Cochrane Library, CNKI, and CBM databases were searched up to April 13, 2019. In bivariate random-effect models, the diagnostic performance of NGAL for DKD was assessed using pooled estimates of sensitivity, specificity, likelihood ratio, diagnostic odds ratio, and hierarchical summary receiver-operating characteristic analysis. Results: Nineteen studies were eligible for the meta-analysis. Serum NGAL had a pooled sensitivity and specificity of 0.79 (95% confidence intervals [CI] 0.60–0.91) and 0.87 (0.75–0.93) (7 studies, 1,238 patients). The pooled positive likelihood ratio (LR+) and negative likelihood ratio (LR–) were 5.97 (3.03–11.76) and 0.24 (0.11–0.51). For urine NGAL, the pooled sensitivity, specificity, LR+, and LR– were 0.85 (0.74–0.91), 0.74 (0.57–0.86), 3.26 (1.87–5.67), and 0.21 (0.12–0.35), respectively (10 studies, 1,369 patients). The pooled sensitivity and specificity for kidney disease in normoalbuminuric patients with diabetes was 0.90 (0.82–0.95) and 0.97 (0.90–0.99) for both serum NGAL and 0.94 (0.87–0.98) and 0.90 (0.81–0.96) for urine NGAL (4 studies, 221 patients). NGAL appeared to perform similarly in subgroup analysis. Conclusion: The meta-analysis has shown that NGAL may be useful for DKD classification and also has a potential diagnostic value for normoalbuminuric kidney disease. Large-scale prospective studies are required to clarify its role in the diagnosis and risk stratification of patients with DKD.
Anxiety Mediates the Relationship between Psychotic-Like Experiences and Social Functioning in the General Population
Authors: Deng Wisteria Y. , Grove Tyler , Deldin Patricia
Published: July 2020

Introduction: Within the psychosis continuum that includes schizophrenia (SZ) at the severe end and the general population at the mild end, anxiety may negatively impact social functioning more than psychosis or psychotic-like experiences (PLE). This claim is supported by previous reports that show anxiety mediates the relationship between psychosis and social functioning in SZ, suggesting anxiety is critical to social functioning in SZ. Yet no studies have examined a similar relationship in the general population, and this is important because people with PLE are at a significantly higher risk for developing full-blown psychosis. Methods: Similar to those with SZ, we predicted heightened anxiety would mediate the relationship between PLE, as measured by The ­Oxford-Liverpool Inventory of Feelings and Experiences, and social functioning, as measured by Social Adjustment Scale – Self-Report, in the general population. Results: Indeed, the current study showed that the relationship between PLE and social functioning was mediated by anxiety (z = 7.81, p < 0.001) within an unselected crowdsourcing sample representative of the general population (Amazon M-Turk; n = 197, mean age 32.38 years). Conclusion: Taken together with previous reports, the current findings suggest that anxiety is a functionally relevant dimension across the psychosis continuum and improving anxiety may improve social functioning across this continuum.
Complex Gait Is Related to Cognitive Functioning in Older People: A Cross-Sectional Study Providing an Innovative Test
Authors: Latorre Román Pedro Ángel , Muñoz Jiménez Marcos , Salas Sánchez Jesús , Consuegra González Pedro , Moreno del Castillo Rafael , Herrador Sánchez Julio A. , López Ivanco María del Amor , Linares Jiménez Claudia , Navas Morales Juan Francisco , Párraga Montilla Juan Antonio
Published: July 2020

Background: Many studies have demonstrated an inverse relationship between gait performance and cognitive impairment. The main purposes of this study were: (1) to design and validate a complex gait test (CGT) in older people, (2) to analyze the effects of age and sex on CGT, and (3) to analyze the association between CGT performance and physical functioning and cognitive measures. Methods: A total of 279 older people (60–97 years) were analyzed in 2019. Fitness tests, gait performance, and several cognitive measures such asthe Trail-Walking Test and Montreal Cognitive Assessment were used. Results: The CGT reported adequate reliability and validity parameters. In the test-retest analysis, the intra-class correlation coefficient was 0.868 (p < 0.001). There was a significant correlation between the CGT and Trail-Walking Test (r = 0.592; p < 0.001). The linear regression analysis showed that the CGT was associated with the Montreal Cognitive Assessment (R2 = 0.357; p =0.001). The binary logistic regression analysis revealed that a high CGT score was a risk factor for mild cognitive impairment (odds ratio 1.201, 95% CI 1.081–1.334; p = 0.001). The ROC curve of the mild cognitive impairment was predicted by the CGT performance (area under the curve = 0.768, 95% CI 0.647–0.889; p < 0.001), reaching the cut-off point at 20.25 s. Conclusions: The CGT showed good reliability and validity and may serve as a potential biomarker in mild cognitive impairment prediction in older adults aged 60–97 years.
Maternal Poppy Seed Tea Ingestion and Ensuing Neonatal Abstinence Syndrome
Authors: Garcia Melissa Rae , Swortwood Madeleine J. , Aune Christine Nicole , Ahmad Kaashif Aqeeb
Published: July 2020

The incidence of neonatal abstinence syndrome has been rising in the USA. Nonpharmacological treatments resulting in similar withdrawal states in the newborn have also been described. We report an infant with neonatal abstinence syndrome born to a mother with daily poppy seed tea ingestion for the self-treatment of nausea. A sample of poppy seed tea was replicated using the mother’s self-reported recipe. The sample was analyzed using liquid chromatography tandem mass spectrometry. This recipe produced a result of approximately 7.8 mg of morphine per serving which she reported to have drank 5–6 days per week, for an estimated 7 months during the course of her pregnancy.
Spondias mombin L. decoction utilization as antiseptic in cats submitted to castration
Authors: Dantas Thalles D’avila Pires Dutra , Feijó Francisco Marlon Carneiro , Alves Nilza Dutra , Rodrigues Gardênia Silvana De Oliveira , Santos Caio Sérgio dos , Soares Waleska Nayane Costa , Santos Paula Vivian Feitosa dos , Medeiros Letícia Cely Vieira de
Published: July 2020

This survey evaluated mombin leaves (Spondias mombin L.) decoction efficiency as an antiseptic during post-surgery period on cats submitted to orchiectomy and ovariosalpingohisterectomy. For this purpose, 45 castrated mongrels cats were divided into three groups, the first group as a positive control using 0.5% chlorhexidine-alcohol solution, the second a negative control group using sterile distilled water and, finally, the test group using mombin leaves decocted with a concentration of 100 mg/mL. All animals, independent of age and sex, had visibly healed in most cases in a similar time. Animals treated with mombin leaves decoction presented a significant reduction of bacterial growth. In addition, the animals treated in the test group had better surgical wound healing. All isolated bacterial strains presented inhibition halo for chlorhexidine and for Spondias mombin L. Thus, the decoction of Spondias mombin L. leaves proved antiseptic efficacy in the surgical wounds of cats submitted to orchiectomy and ovariosalpingohisterectomy.