bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Possible Mechanism and Drug Targets of Huang‐Qi‐Gui‐Zhi‐Wu‐Wu Decoction for the Treatment of Chemotherapy‐Induced Peripheral Neuropathy on Network Pharmacology
Authors: Gu Jia-lin , Wei Guo-li , Ma Yu-zhu , Zhang Jin-zhi , Ji Yi , Li Ling-chang , Yu Jia-lin , Hu Can-hong , Huo Jie-ge
Published: November 2020

Chemotherapy‐induced peripheral neuropathy (CIPN) is a common side effect of anticancer treatment, which may influence its successful completion. The Huang‐Qi‐Gui‐Zhi‐Wu‐Wu decoction (HQGZWWD) has been widely used to treat CIPN in China although the pharmacological mechanisms involved have not been clarified. Using the network pharmacology approach, this study investigated the potential pathogenesis of CIPN and the therapeutic mechanisms exerted by the HQGZWWD herbal formula in CIPN. The targets of HQGZWWD were identified using traditional Chinese medicine (TCM) databases (TCMSP and ETCM) and prediction platforms (PharmMapper and TargetNet), and the genes of CIPN were collected by DisGeNET, GeneCards, and literature search. The common target interaction network between herbal formula and diseases was constructed by using Cytoscape. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to reveal the mechanism and efficacy of HQGZWWD in the treatment of CIPN. A total of 153 CIPN‐related genes were screened, and a protein‐protein interaction (PPI) network with 96 nodes and 424 edges was constructed. Sixty‐three active components were retrieved from HQGZWWD, with a herb‐composite compound‐target network including 748 nodes and 5448 edges. Forty‐one targets belong to the above two networks. The analysis of network results and literature review shows that the main pathological processes of CIPN may be the inflammatory response and nerve injury, and HQGZWWD plays a therapeutic role in CIPN by regulating inflammatory response and repairing nerve injury, thus verifying the reliable efficacy of this herbal formula. In addition, we found two new potential therapeutic targets (CDK7 and GSTM2) warranting further investigation. This study fully illustrates that TCM has the characteristics of a multicompound, multitarget, and multipathway treatment, which is of great significance to study the curative effect of herbal formulations.
A Goal Programming Approach to Nurse Scheduling with Individual Preference Satisfaction
Authors: Rerkjirattikal Pavinee , Huynh Van-Nam , Olapiriyakul Sun , Supnithi Thepchai
Published: November 2020

The use of scheduling optimization tools is essential in creating an efficient nurse shift-rotation schedule. A well-designed nurse scheduling technique can improve nurses’ job satisfaction and their intention to stay. This study develops a goal programming approach to nurse scheduling that simultaneously considers workload fairness and individual preferences on working shift and day off assignments. A case study of an operating room at a hospital in Thailand is used to illustrate the model capabilities for solving an actual nurse scheduling problem. The job satisfaction factors defined based on an interview and questionnaire survey are integrated into the model. When compared against the manual scheduling result, the optimal schedules can be implemented to improve the nurse’s perception of fairness and preference satisfaction. The analysis of fairness and multiple individual preferences based on a case study investigation is the main contribution of this study.
Chemical Composition and Evaluation of the α‐Glucosidase Inhibitory and Cytotoxic Properties of Marine Algae Ulva intestinalis, Halimeda macroloba, and Sargassum ilicifolium
Authors: Nazarudin Muhammad Farhan , Isha Azizul , Mastuki Siti Nurulhuda , Ain Nooraini Mohd. , Mohd Ikhsan Natrah Fatin , Abidin Atifa Zainal , Aliyu-Paiko Mohammed
Published: November 2020

Seaweed has tremendous potentials as an alternative source of high‐quality food products that have attracted research in recent times, due to their abundance and diversity. In the present study, three selected seaweed species commonly found in the Malaysian Peninsular, Ulva intestinalis, Halimeda macroloba, and Sargassum ilicifolium, were subjected to preliminary chemical screening and evaluated for α‐glucosidase inhibitory and cytotoxic activities against five cancer cell lines. Chemical composition of U. intestinalis, H. macroloba, and S. ilicifolium methanolic extracts was evaluated by Gas Chromatography‐Mass Spectrometry (GC‐MS) analysis. Our results revealed the highest total carotenoids (162.00 μg g−1 DW), chlorophyll a (313.09 ± 2.53 μg g−1 DW), and chlorophyll b (292.52 ± 8.84 μg g−1 DW) concentrations in U. intestinalis. In the α‐glucosidase inhibitory activity, S. ilicifolium demonstrated the lowest efficacy with an IC50 value of 38.491 ppm compared to other species of seaweed. H. macroloba extract, on the other hand, was found to be the most cytotoxic toward MCF‐7 and HT 29 cells with IC50 of 37.25 ± 0.58 and 21.32 ± 0.25 μg/mL, respectively, compared to other cell lines evaluated. Furthermore, H. macroloba extract was also found to be less toxic to normal cell (3T3) with IC50 of 48.80 ± 0.11 μg/mL. U. intestinalis extract exhibited the highest cytotoxicity toward Hep G2 cells with IC50 of 23.21 ± 0.11 μg/mL, whereas S. ilicifolium was less toxic to MDA‐ MB231 cell with IC50 of 25.23 ± 0.11 μg/mL. Subsequently, the GC‐MS analysis of the methanolic extracts of these seaweed samples led to the identification of 27 metabolites in U. intestinalis, 22 metabolites in H. macroloba, and 24 metabolites in S. ilicifolium. Taken together, the results of this present study indicated that all the seaweed species evaluated are good seaweed candidates that exhibit potential for cultivation as functional food sources for human consumption and need to be promoted.
Antiaging Property and Mechanism of Phase‐Change Asphalt with PEG as an Additive
Authors: Wang Huiru , Wang Yanmin , Li Xian , Chen Min , Wu Yanling , Sun Cuicui , Wang Xiaoning
Published: November 2020

In this study, phase‐change asphalt was prepared with polyethylene glycol (PEG‐1000) as a modifier. The short‐ and long‐term antiaging performances were characterized by rolling‐thin‐film‐oven (RTFOT) and pressure‐aging vessel (PAV) tests, respectively. The functional groups and “bee structures” of PEG‐modified asphalt and base asphalt were characterized by Fourier transform infrared absorption spectroscopy (FTIR) and atomic force microscopy (AFM). The research results indicate that the additive of PEG can improve the high‐temperature, temperature sensitivity, and the antiaging properties of asphalt. The FTIR reveals that only physical blending and no chemical reaction occurs between PEG and asphalt. AFM topography indicates that smaller “bee structures” appear on the surface of PEG‐modified asphalt and these structures do not change during aging.
Global Dynamics of a Generalized SIRS Epidemic Model with Constant Immigration
Authors: Cui Qianqian , Du Qinghui , Wang Li
Published: November 2020

In this paper, we discuss the global dynamics of a general susceptible-infected-recovered-susceptible (SIRS) epidemic model. By using LaSalle’s invariance principle and Lyapunov direct method, the global stability of equilibria is completely established. If there is no input of infectious individuals, the dynamical behaviors completely depend on the basic reproduction number. If there exists input of infectious individuals, the unique equilibrium of model is endemic equilibrium and is globally asymptotically stable. Once one place has imported a disease case, then it may become outbreak after that. Numerical simulations are presented to expound and complement our theoretical conclusions.
Oral Rehabilitation Using Noninvasive Restorative Approach for Late Mixed Dentition of Preterm Birth Child with Amelogenesis Imperfecta
Authors: Alazmah Abdulfatah
Published: November 2020

Preterm birth children comprise about 6% of live births around the world. It is known that premature children exhibit oral anomalies that could affect the function and/or appearance of their dentition in addition to their medical needs. A diagnosis of amelogenesis imperfecta (AI) can present a challenge for both the patient and the treating clinician. This can be more complicated in the case of child treatment, where cooperation and some of the treatment modalities for adults can not be considered. Conventional management of such children is not possible due to the ongoing process of growth and development and the ability of the child to cope with the extensive and lengthy treatment procedure. This article highlights a minimally invasive method for managing AI using adhesive and full-coverage restoration that requires no tooth preparation; this allows the structural integrity of the teeth to be maintained, along with their vitality. As a result, the child will have teeth with better function and aesthetic, to improve eating, appearance, and self-confidence.
An Efficient Deployment Model for Maximizing Coverage of Heterogeneous Wireless Sensor Network Based on Harmony Search Algorithm
Authors: Al-Fuhaidi Belal , Mohsen Abdulqader M. , Ghazi Abdulkhabeer , Yousef Walid M.
Published: November 2020

Due to the increase of Wireless Sensor Network (WSN) technologies demand, the optimal sensor node deployment is considered as one of the most important factors that directly affect the network coverage. Most researches in WSNs that solved the problem of coverage in homogeneous and heterogeneous cases are suffering from many drawbacks such as consumed energy and high cost. In this paper, we propose an efficient deployment model based on probabilistic sensing model (PSM) and harmony search algorithm (HSA) to achieve the balance between the network coverage performance and the network cost in a heterogeneous wireless sensor network (HEWSN). The HSA is used for deployment optimization of HEWSN nodes which makes a balance between the coverage and financial cost. The PSM is used to solve the overlapping problem among the sensors. The performance of the proposed model is analyzed in terms of coverage ratio and cost evaluations. The simulation results showed the capability of the proposed heterogeneous deployment model to achieve maximum coverage and a minimum number of sensors compared to homogeneous deployment. Furthermore, a comparative study with a meta-heuristic genetic-based algorithm in HEWSN has also been conducted, and its results confirm the superiority of the proposed model.
A New Presentation: Aphallia, Vesicoureteral Reflux, Rectovesical Fistula, and Adrenal Insufficiency
Authors: El Qadiry R. , Lalaoui A. , Nassih H. , Bourrahouat A. , Ait Sab I.
Published: November 2020

Aphallia or penile agenesis is a rare congenital malformation with an estimated incidence rate of 1 in 10 to 30 million births. More than half of aphallia cases have associated anomalies including caudal axis, cardiovascular, genitourinary, and gastrointestinal anomalies. The penile agenesis associated with adrenal insufficiency has never been reported in an infant. We report a rare case of a newborn that was diagnosed as a case of aphallia with vesicorectal fistula and vesicoureteral reflux, complicated by adrenal insufficiency with salt-wasting crisis.
Coupled Hydraulic-Thermal Modelling and Related Numerical Analysis on Rock Fractures
Authors: Pan Yongjian , Wang Huajun , Liu Qiang
Published: November 2020

Hydraulic-thermal coupling is a key problem in rock mass engineering, especially in the disposal of nuclear wastes in deep rock mass. To accurately describe the coupling action of rock mass when under the interaction of hydraulic stress and thermal, the hydraulic-thermal coupling solving methods were proposed in this paper; in addition, the corresponding hydraulic-thermal coupling program FRHT3D was complied. Consequently, the numerical simulation was performed, it can be concluded that the flow speed is faster when the coupling effect is considered at the unstable seepage stage, and the seepage coupling solution is larger than that of uncoupling. Furthermore, when the coupling effects are considered, the permeable water head solution is much larger than that of the uncoupling solution at the unstable seepage stage. The proposed hydraulic-thermal coupling solving methods and programs can be applied to rock mass engineering practice.
FEA Simulation of the Biomechanical Structure Overload in the University Campus Planting
Authors: Dounar Stanislau , Iakimovitch Alexandre , Mishchanka Katsiaryna , Jakubowski Andrzej , Chybowski Leszek
Published: November 2020

Research of breakage of the chestnut tree branch on the planting of university campus is provided. Collapse is caused by a severe accidental wind gust. Due to collapse in the student environment, the investigation has additional methodical value for the teaching of FEA simulation. The model includes roots, trunk, branch, and conditional crown, where the trunk-branch junction is steady enough. The load-bearing system of tree is taken as an example of an effective bionic design. The branch has grown with the implementation of the idea of “equal-strength console”—the change of sections along the branch provides constant stress level and near uniform dispensation of their without stress concentrators. Static simulation of the tree loading is provided both in the linear formulation and in the geometrically nonlinear one. It is proved that in the trunk-branch junction area the stresses are twice lower than the branch itself, and it is not the place for fracture. For the given wind pressure, the work stress in the branch has exceeded twice the allowable level under bending with some torsion. In such construction (of the tree), the breakage could happen even in the perfect branch condition due to her severe overloading.
Feature Guided CNN for Baby’s Facial Expression Recognition
Authors: Lin Qing , He Ruili , Jiang Peihe
Published: November 2020

State-of-the-art facial expression methods outperform human beings, especially, thanks to the success of convolutional neural networks (CNNs). However, most of the existing works focus mainly on analyzing an adult’s face and ignore the important problems: how can we recognize facial expression from a baby’s face image and how difficult is it? In this paper, we first introduce a new face image database, named BabyExp, which contains 12,000 images from babies younger than two years old, and each image is with one of three facial expressions (i.e., happy, sad, and normal). To the best of our knowledge, the proposed dataset is the first baby face dataset for analyzing a baby’s face image, which is complementary to the existing adult face datasets and can shed some light on exploring baby face analysis. We also propose a feature guided CNN method with a new loss function, called distance loss, to optimize interclass distance. In order to facilitate further research, we provide the benchmark of expression recognition on the BabyExp dataset. Experimental results show that the proposed network achieves the recognition accuracy of 87.90% on BabyExp.
Approximation by Parametric Extension of Szász-Mirakjan-Kantorovich Operators Involving the Appell Polynomials
Authors: Nasiruzzaman Md. , Aljohani A. F.
Published: November 2020

The purpose of this article is to introduce a Kantorovich variant of Szász-Mirakjan operators by including the Dunkl analogue involving the Appell polynomials, namely, the Szász-Mirakjan-Jakimovski-Leviatan-type positive linear operators. We study the global approximation in terms of uniform modulus of smoothness and calculate the local direct theorems of the rate of convergence with the help of Lipschitz-type maximal functions in weighted space. Furthermore, the Voronovskaja-type approximation theorems of this new operator are also presented.
Dynamic Transitions in Neuronal Network Firing Sustained by Abnormal Astrocyte Feedback
Authors: Yu Yangyang , Yuan Zhixuan , Fan Yongchen , Li Jiajia , Wu Ying
Published: November 2020

Astrocytes play a crucial role in neuronal firing activity. Their abnormal state may lead to the pathological transition of neuronal firing patterns and even induce seizures. However, there is still little evidence explaining how the astrocyte network modulates seizures caused by structural abnormalities, such as gliosis. To explore the role of gliosis of the astrocyte network in epileptic seizures, we first established a direct astrocyte feedback neuronal network model on the basis of the hippocampal CA3 neuron-astrocyte model to simulate the condition of gliosis when astrocyte processes swell and the feedback to neurons increases in an abnormal state. We analyzed the firing pattern transitions of the neuronal network when astrocyte feedback starts to change via increases in both astrocyte feedback intensity and the connection probability of astrocytes to neurons in the network. The results show that as the connection probability and astrocyte feedback intensity increase, neuronal firing transforms from a nonepileptic synchronous firing state to an asynchronous firing state, and when astrocyte feedback starts to become abnormal, seizure-like firing becomes more severe and synchronized; meanwhile, the synchronization area continues to expand and eventually transforms into long-term seizure-like synchronous firing. Therefore, our results prove that astrocyte feedback can regulate the firing of the neuronal network, and when the astrocyte network develops gliosis, there will be an increase in the induction rate of epileptic seizures.
Identification of Circulating lncRNA Expression Profiles in Patients with Atrial Fibrillation
Authors: Ruan Zhong-bao , Wang Fei , Gongben Bing-di , Chen Ge-cai , Zhu Li
Published: November 2020

Purpose. To investigate the expression profiles of long noncoding RNAs (lncRNAs) in patients with atrial fibrillation (AF). Methods. The peripheral blood monocytes of a total of 20 patients with AF and 20 healthy subjects were collected for gene chip technology to detect differentially expressed lncRNAs from 2017.01 to 2017.08. Reverse transcription polymerase chain reaction (RT-PCR) was applied for further verification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify the functions of differentially expressed genes and related pathways. Results. There were 19 lncRNAs differentially expressed (

FC
≥
2

,

P
<
0.05

), of which 6 were upregulated and 13 were downregulated. Two of three upregulated lncRNAs (

P
=
0.014

and 0.006 for HNRNPU-AS1 and LINC00861, respectively) and two of three downregulated lncRNAs (

P
=
0.028

and 0.032 for RP11-443B7.3 and CTD-2616J11.14, respectively) were randomly confirmed by RT-PCR and showed a significantly different expression with the RNA-seq results. GO analysis showed that differentially expressed genes enriched in differentially expressed transcripts in biological process were mainly involved in metabolic process, catabolic process, and biosynthetic process. Differentially expressed transcripts in cellular component were mainly involved in nuclear lumen, organelle lumen, and cytoplasm. Differentially expressed transcripts in molecular function were mainly involved in protein binding, RNA binding, and molecular function. KEGG enrichment pathway analysis showed that some of the enrichment pathways associated with differentially expressed lncRNAs include calcium signaling pathway, NF-kappa B signaling pathway, cytokine-cytokine receptor interaction, and Toll-like receptor signaling pathway. HNRNPU-AS1 was the highest positive correlated lncRNA in the networks. Conclusions. The expression of lncRNA in peripheral blood of AF patients is different from that of normal people. The physiological functions of these differentially expressed lncRNAs may be related to the pathogenesis of AF, which provide experimental basis and new therapeutic target for prognosis and treatment of patients with AF. HNRNPU-AS1 may play an important role in the pathophysiology and mechanisms of AF.
Broad Learning Enhanced 1H-MRS for Early Diagnosis of Neuropsychiatric Systemic Lupus Erythematosus
Authors: Li Yan , Ge Zuhao , Zhang Zhiyan , Shen Zhiwei , Wang Yukai , Zhou Teng , Wu Renhua
Published: November 2020

In this paper, we explore the potential of using the multivoxel proton magnetic resonance spectroscopy (1H-MRS) to diagnose neuropsychiatric systemic lupus erythematosus (NPSLE) with the assistance of a support vector machine broad learning system (BL-SVM). We retrospectively analysed 23 confirmed patients and 16 healthy controls, who underwent a 3.0 T magnetic resonance imaging (MRI) sequence with multivoxel 1H-MRS in our hospitals. One hundred and seventeen metabolic features were extracted from the multivoxel 1H-MRS image. Thirty-three metabolic features selected by the Mann-Whitney

U

test were considered to have a statistically significant difference (

p
<
0.05

). However, the best accuracy achieved by conventional statistical methods using these 33 metabolic features was only 77%. We turned to develop a support vector machine broad learning system (BL-SVM) to quantitatively analyse the metabolic features from 1H-MRS. Although not all the individual features manifested statistics significantly, the BL-SVM could still learn to distinguish the NPSLE from the healthy controls. The area under the receiver operating characteristic curve (AUC), the sensitivity, and the specificity of our BL-SVM in predicting NPSLE were 95%, 95.8%, and 93%, respectively, by 3-fold cross-validation. We consequently conclude that the proposed system effectively and efficiently working on limited and noisy samples may brighten a noinvasive in vivo instrument for early diagnosis of NPSLE.
Transcranial Doppler for Early Prediction of Cognitive Impairment after Aneurysmal Subarachnoid Hemorrhage and the Associated Clinical Biomarkers
Authors: Esmael Ahmed , Belal Tamer , Eltoukhy Khaled
Published: November 2020

Background and Aim. Cognitive impairment after aneurysmal subarachnoid hemorrhage (aSAH) stays under investigation. This study is aimed at predicting the cognitive impairment by transcranial Doppler (TCD) and detecting the associated clinical biomarkers of impaired cognition after aSAH after 3 months from the onset. Methods. Prospective study included 40 cases with acute aSAH. Initial evaluation by Glasgow Coma Scale (GCS) and the severity of aSAH was detected by both the clinical Hunt and Hess and radiological Fisher’s grading scales. TCD was done for all patients five times within 10 days measuring the mean flow velocities (MFVs) of cerebral arteries. At the 3-month follow-up, patients were classified into two groups according to Montreal Cognitive Assessment (MoCA) scale: the first group was 31 cases (77.5%) with intact cognitive functions and the other group was 9 cases (22.5%) with impaired cognition. Results. Patients with impaired cognitive functions showed significantly lower mean GCS (

p
=
0.03

), significantly higher mean Hunt and Hess scale grades (

p
=
0.04

), significantly higher mean diabetes mellitus (DM) (

p
=
0.03

), significantly higher mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) (

p
=
0.02

and

p
=
0.005

, respectively), and significantly higher MFVs measured within the first 10 days. The patients with cognitive impairment were accompanied by a higher incidence of hydrocephalus (

p
=
0.01

) and a higher incidence of delayed cerebral ischemia (DCI) (

p
<
0.001

). Logistic regression analysis detected that

MFV
≥
86
 
 
cm
/
s

in the middle cerebral artery (MCA),

MFV
≥
68
 
 
cm
/
s

in the anterior cerebral artery (ACA), and

MFV
≥
45
 
 
cm
/
s

in the posterior cerebral artery (PCA) were significantly associated with increased risk of cognitive impairment. Conclusion. Cognitive impairment after the 3-month follow-up phase in aSAH patients was 22.5%. Acute hydrocephalus and DCI are highly associated with poor cognitive function in aSAH. Increased MFV is a strong predictor for poor cognitive function in aSAH. This trial is registered with NCT04329208.
Synthesis and Characterization of Gallium Oxide/Tin Oxide Nanostructures via Horizontal Vapor Phase Growth Technique for Potential Power Electronics Application
Authors: Bernardino Lester D. , Santos Gil Nonato C.
Published: November 2020

The monoclinic β‐gallium oxide (Ga2O3) was viewed as a potential candidate for power electronics due to its excellent material properties. However, its undoped form makes it highly resistive. The Ga2O3/SnO2 nanostructures were synthesized effectively via the horizontal vapor phase growth (HVPG) technique without the use of a magnetic field. Different concentrations of Ga2O3 and SnO2 were varied to analyze and describe the surface morphology and elemental composition of the samples using the scanning electron microscopy (SEM) and energy‐dispersive X‐ray (EDX) spectroscopy, respectively. Meanwhile, the polytype of the Ga2O3 was confirmed through the Fourier transform infrared (FTIR) spectroscopy. The current‐voltage (I–V) characteristics were established using a Keithley 2450 source meter. The resistivity was determined using the van der Pauw technique. The mobility and carrier concentration was done through the Hall effect measurements at room temperature using a 0.30‐Tesla magnet. It was observed that there was an increase in the size of the nanostructures, and more globules appeared after the concentration of SnO2 was increased. It was proven that the drop in the resistivity of Ga2O3 was due to the presence of SnO2. The data gathered were supported by the Raman peak located at 662 cm−1, attributed to the high conductivity of β‐Ga2O3. However, the ε‐polytype was verified to appear as a result of adding SnO2. All the samples were considered as n‐type semiconductors. High mobility, low power loss, and low specific on‐resistance were attained by the highest concentration of SnO2. Hence, it was clinched as the optimal n‐type Ga2O3/SnO2 concentration and recommended to be a potential substrate for power electronics application.
Glutamine-Directed Migration of Cancer-Activated Fibroblasts Facilitates Epithelial Tumor Invasion
Authors: Mestre-Farrera Aida , Bruch-Oms Marina , Peña Raúl , Rodríguez-Morató José , Alba-Castellón Lorena , Comerma Laura , Quintela-Fandino Miguel , Duñach Mireia , Baulida Josep , Pozo Óscar J. , García de Herreros Antonio
Published: November 2020

Tumors are complex tissues composed of transformed epithelial cells as well as cancer-activated fibroblasts (CAF) that facilitate epithelial tumor cell invasion. We show here that CAFs and other mesenchymal cells rely much more on glutamine than epithelial tumor cells; consequently, they are more sensitive to inhibition of glutaminase. Glutamine dependence drove CAF migration toward this amino acid when cultured in low glutamine conditions. CAFs also invaded a Matrigel matrix following a glutamine concentration gradient and enhanced the invasion of tumor cells when both cells were cocultured. Accordingly, glutamine directed invasion of xenografted tumors in immunocompromised mice. Stimulation of glutamine-driven epithelial tumor invasion by fibroblasts required previous CAF activation, which involved the TGFβ/Snail1 signaling axis. CAFs moving toward Gln presented a polarized Akt2 distribution that was modulated by the Gln-dependent activity of TRAF6 and p62 in the migrating front, and depletion of these proteins prevented Akt2 polarization and Gln-driven CAF invasion. Our results demonstrate that glutamine deprivation promotes CAF migration and invasion, which in turn facilitates the movement of tumor epithelial cells toward nutrient-rich territories. These results provide a novel molecular mechanism for how metabolic stress enhances invasion and metastasis.

Significance:

Cancer-associated fibroblasts migrate and invade toward free glutamine and facilitate invasion of tumor epithelial cells, accounting for their movement away from the hostile conditions of the tumor towards nutrient-rich adjacent tissues.
Clinical Evaluation of DNA Ploidy for the Triage of HPV-Positive Chinese Women During Cervical Cancer Screening
Authors: Cang Wei , Li Qing , Gu Liying , Hong Zubei , Hu Yuan , Di Wen , Qiu Lihua
Published: November 2020

Quantification of DNA aneuploidy has great potential as a prognostic marker of cervical precancerous lesions. We aim to evaluate the performance of DNA ploidy analysis for the triage of HPV-positive women. 523 HPV-positive women ages 25–64 undergoing HPV and pap cytology testing with valid cervical biopsies in Renji Hospital were enrolled in a prospective observational study from June 2018 to June 2019. The clinical performances of DNA ploidy, with or without HPV16/18 genotyping, were evaluated for all HPV-positive women to detect histologic high-grade squamous intraepithelial lesion or worse (HSIL+). For HSIL+ detection, DNA ploidy had statistically higher specificity (83.89%) than Pap cytology (75.50%, P = 0.002) and HPV16/18 genotyping (77.92%, P = 0.023). Although the sensitivity of DNA ploidy (58.57%) remained similar with pap cytology (65.71%, P = 0.461) and HPV16/18 genotyping (55.71%, P = 0.734). A comparable sensitivity (84.29% vs. 84.29%, P = 1.000) and a higher specificity (66.00% vs. 58.94%, P < 0.001) compared with combination with Pap cytology. DNA ploidy triage strategy required fewer colposcopies per detection of HSIL+ compared with pap cytologic testing, with a 13.1% (34 of 258) reduction of colposcopies compared with routine triage strategy of HPV screening with Pap cytologic testing. HPV16/18-negative women with negative DNA ploidy results had the lowest risk of HSIL+ among HPV-positive women (3.55%). Automated DNA ploidy analysis, alone or in combination with HPV16/18 genotyping, shows the potential as a triage strategy of cervical cancer screening for HPV-positive women.

Prevention Relevance:

Results from this study indicate that DNA ploidy analysis has good performance in early detection of high-grade precancerous and cancerous lesions of the cervix. This strategy could be used in the triage of HPV-positive women in cervical cancer screening.
KIR3DL3 Is an Inhibitory Receptor for HHLA2 that Mediates an Alternative Immunoinhibitory Pathway to PD1
Authors: Bhatt Rupal S. , Berjis Abdulla , Konge Julie C. , Mahoney Kathleen M. , Klee Alyssa N. , Freeman Samuel S. , Chen Chun-Hau , Jegede Opeyemi A. , Catalano Paul J. , Pignon Jean-Christophe , Sticco-Ivins Maura , Zhu Baogong , Hua Ping , Soden Jo , Zhu Jie , McDermott David F. , Arulanandam Antonio R. , Signoretti Sabina , Freeman Gordon J.
Published: November 2020

Blockade of the PD1 pathway is a broadly effective cancer therapy, but additional immune-inhibitory pathways contribute to tumor immune evasion. HERV–H LTR-associating 2 (HHLA2; also known as B7H5 and B7H7) is a member of the B7 family of immunoregulatory ligands that mediates costimulatory effects through its interaction with the CD28 family member transmembrane and immunoglobulin domain containing 2 (TMIGD2). However, HHLA2 has also been known to have inhibitory effects on T cells. Here, we report that we have identified killer cell immunoglobulin-like receptor, three immunoglobulin domains and long cytoplasmic tail 3 (KIR3DL3) as an inhibitory receptor for HHLA2 in T cells and natural killer (NK) cells and have generated HHLA2 and KIR3DL3 antibodies that block the immune-inhibitory activity of HHLA2, preserving the costimulatory signal. It is known that HHLA2 is frequently expressed in several tumor types, including clear cell renal cell carcinoma (ccRCC). We found that HHLA2 expression was nonoverlapping with PDL1 expression in ccRCC, suggesting that HHLA2 mediates a mechanism of tumor immune evasion that is independent from PDL1. Blockade of both the PD1 and KIR3DL3 pathways may be a more effective way to reverse tumor immune evasion.

See related Spotlight on p. 128
Efficacy of Probiotic Milk for Caries Regression in Preschool Children: A Multicenter Randomized Controlled Trial
Authors: Piwat Supatcharin , Teanpaisan Rawee , Manmontri Chanika , Wattanarat Onnida , Pahumunto Nuntiya , Makeudom Anupong , Krisanaprakornkit Suttichai , Nirunsittirat Areerat
Published: November 2020

This multicenter double-blind randomized controlled trial aimed to determine the efficacy of daily or triweekly consumption of reconstituted milk powder, containing Lactobacillus paracaseiSD1, in preschool children for caries prevention. A 6-month intervention was conducted in 487 children (aged 37.6 ± 9.2 months) with ≤4 decayed teeth from 8 childcare centers. Using stratified block randomization, participants were randomly allocated into 3 groups, comprising: (1) daily probiotic, receiving probiotic milk once daily, (2) triweekly probiotic, randomly receiving probiotic milk 3 days a week and the placebo milk for the remaining 4 days, and (3) placebo, receiving milk without probiotics. Each tooth surface was assessed for caries status using the modified Nyvad criteria at baseline (T0), 6 (T6) and 12 (T12) months after T0. Study outcomes were caries transition, including caries progression and regression during the T0–T6, T6–T12 and T0–T12 periods. Negative binomial regression with a generalized linear model was used to estimate the caries outcomes, which were reported as incidence rate ratios (IRRs) and 95% confidence intervals (CIs). At baseline, caries prevalence and mean decayed surfaces were 81.9% and 7.29 ± 7.60, respectively. Three groups were balanced at baseline with an overall dropout rate of 25.2%. After adjusting for age, sex, and the number of noncavitated and cavitated caries at baseline, a decreased caries risk during T0–T6 was shown in both the daily and triweekly probiotic groups (adjusted IRR 0.83, 95% CI 0.72–0.96 in both groups) and during T0–T12 (adjusted IRR 0.84, 95% CI 0.76–0.94, and adjusted IRR 0.86, 95% CI 0.76–0.96, respectively) compared to the placebo group. In contrast, significantly increased regressive surfaces were demonstrated during T0–T6 by adjusted IRR 1.76 (95% CI 1.25–2.48) and 2.01 (95% CI 1.42–2.85) and during T0–T12 by adjusted IRR 1.98 (95% CI 1.50–2.61) and 1.92 (95% CI 1.45–2.55) for the daily and triweekly groups, respectively. In conclusion, probiotic milk consumption either daily or triweekly can modestly prevent new caries, but considerably reverse carious lesions, suggesting that a daily or triweekly dose interval is sufficient to reverse carious lesions.
An Emphasis on Screening to Detect Liver Cirrhosis and Hepatocellular Carcinoma in Patients Having Undergone the Fontan Procedure in Early Childhood
Authors: Madala Samragnyi , MacDougall Kira , Polavarapu Abhishek , Gurala Dinesh , Gumaste Vivek , Morvillo Gerard
Published: November 2020

The Fontan procedure is a surgical procedure for patients with single-ventricle anatomy that results in the flow of systemic venous blood to the lungs without passing through a ventricle. Before the 1970s, most children with single-ventricle anatomy failed to survive into adulthood. With the introduction of the Fontan procedure, and its many modifications, the survival rate of these patients improved exponentially. With patients surviving longer, complications from this procedure are being documented for the first time. Cardiovascular complications are expected early on and are well studied. More serious are the non-cardiovascular complications in patients who survive into adulthood. The biggest entity is Fontan-associated liver disease (FALD) which needs thorough monitoring to screen for hepatocellular carcinoma (HCC). FALD includes chronic passive congestion, liver cirrhosis, and HCC. Once cirrhosis develops, monitoring with annual liver function tests, AFP, and abdominal ultrasonography need to occur to screen for HCC. Patients may need to be evaluated for combined heart-liver transplantation. Strict guidelines need to be developed for monitoring and surveillance of these patients to prevent late-stage complications. Herein, we report a unique case of FALD in a young female presenting two decades after the procedure with variceal bleeding.
Ontogenetic Shifts in Brain Size and Brain Organization of the Atlantic Sharpnose Shark, Rhizoprionodon terraenovae
Authors: Laforest Krista V. , Peele Emily E. , Yopak Kara E.
Published: November 2020

Throughout an animal’s life, species may occupy different environments and exhibit distinct life stages, known as ontogenetic shifts. The life histories of most sharks (class: Chondrichthyes) are characterized by these ontogenetic shifts, which can be defined by changes in habitat and diet as well as behavioral changes at the onset of sexual maturity. In addition, fishes experience indeterminate growth, whereby the brain and body grow throughout the organism’s life. Despite a presupposed lifelong neurogenesis in sharks, very little work has been done on ontogenetic changes in the brain, which may be informative about functional shifts in sensory and behavioral specializations. This study quantified changes in brain-body scaling and the scaling of six major brain regions (olfactory bulbs, telencephalon, diencephalon, optic tectum, cerebellum, and medulla oblongata) throughout ontogeny in the Atlantic sharpnose shark, Rhizoprio­nodon terraenovae. As documented in other fishes, brain size increased significantly with body mass throughout ontogeny in this species, with the steepest period of growth in early life. The telencephalon, diencephalon, optic tectum, and medulla oblongata scaled with negative allometry against the rest of the brain throughout ontogeny. However, notably, the olfactory bulbs and cerebellum scaled hyperallometrically to the rest of the brain, whereby these structures enlarged disproportionately as this species matured. Changes in the relative size of the olfactory bulbs throughout ontogeny may reflect an increased reliance on olfaction at later life history stages in R. terraenovae, while changes in the relative size of the cerebellum throughout ontogeny may be indicative of the ability to capture faster prey or an increase in migratory nature as this species moves to offshore habitats, associated with the onset of sexual maturity.
Challenges in Urology during the COVID-19 Pandemic
Authors: Jin Peng , Park Hyusim , Jung Sungyong , Kim Jayoung
Published: November 2020

The COVID-19 pandemic has caused a global health threat. This disease has brought about huge changes in the priorities of medical and surgical procedures. This short review article summarizes several test methods for COVID-19 that are currently being used or under development. This paper also introduces the corresponding changes in the diagnosis and treatment of urological diseases during the COVID-19 pandemic. We further discuss the potential impacts of the pandemic on urology, including the outpatient setting, clinical work, teaching, and research.
Unique Metastatic Patterns in Neuroendocrine Neoplasms of Different Primary Origin
Authors: Hermans Bregtje C.M. , de Vos-Geelen Judith , Derks Jules L. , Latten Loes , Liem Ing Han , van der Zwan Jan Maarten , Speel Ernst-Jan M. , Dercksen M. Wouter , Dingemans Anne-Marie C.
Published: November 2020

Introduction: Neuroendocrine neoplasms (NEN) can originate in different organs, for example, the gastroenteral tract (GE), pancreas (Pan), or lungs (L). Our aim was to examine metastatic patterns for patients with NEN of various primary origins with a special focus on brain metastases to indicate utility for screening. Methods: All NEN patients except for small cell lung cancer registered in the Netherlands Cancer Registry from 2008 to 2018 were selected. Metastatic patterns at initial diagnosis for NEN with different primary origins were compared. In a subcohort of patients from 2 referral hospitals (2014–2019), additional information on, for example, development of metastases after initial presentation was available. Results: In the nationwide cohort, 4,768/11,120 (43%) patients had metastatic disease at diagnosis (GE: 1,504/4,710 [32%]; Pan: 489/1,150 [43%]; and L: 1,230/2,978 [41%]). For GE- and Pan-NEN, the most prevalent metastatic site was the liver (25 and 39%), followed by distant lymph nodes (8 and 8%), whereas only few patients with brain metastases were identified (0% in both). In contrast, for L-NEN, prevalence of metastases in the liver (19%), brain (9%), lung (7%), and bone (14%) was more equal. In the reference network cohort, slightly more NEN patients had metastatic disease (260/539, 48%) and similar metastatic patterns were observed. Conclusion: Almost half of NEN patients were diagnosed with synchronous metastatic disease. L-NEN have a unique metastatic pattern compared to GE- and Pan-NEN. Remarkably, an important part of L-NEN metastases was in the brain, whereas brain metastases were almost absent in GE- and Pan-NEN, indicating utility of screening in L-NEN.
Unveiling a new taxonomy in education field
Authors: Aripin Muhamad Afzamiman , Hamzah R. , Setya P. , Hisham M. H. M. , Ishar M. I. Mohd
Published: November 2020

Taxonomy is a set of hierarchical models that is applied to classify educational learning goals or objectives into a certain level of complexity. Many models have been developed and implemented to suit the educational settings of schools or educational institutions around the world. Realising the importance of educational taxonomy, the purpose of this paper is to explore the function and role of the taxonomy framework used in education, especially through the lens of Bloom, Anderson and SOLO’s (Structure of the Observed Learning Outcome) framework. In addition, this concept paper also aims to formulate a more holistic alternative taxonomy based on the concept of Syed Muhammad Naquib Al-Attas. Research on Bloom, Anderson and SOLO’s taxonomies is not intended to deny the role and contribution of existing taxonomies, but to provide an alternative and space in creating a balanced system of cognitive classification of students through teaching and learning as well as in the evaluation system.
Perspectives on the challenges of leadership in schools to improve student learning systems
Authors: Taufik Ali , Istiarsono Zen
Published: November 2020

This study is an analysis of the challenges of leaders in schools to improve learning systems, trying to do an analysis of the six aspects of analysis during the study. The main contribution of this research is related to how to deal with challenges in improving learning systems in schools that have so far faced challenges and obstacles, and these need to be analyzed and solutions. This study uses a qualitative method with a case study model, because this researcher is a case that must be disclosed and found a solution, looking at the gap between quality, performance and leadership in several schools that are the object of research and this research lasted for several years. four months (18 weeks), the time is indeed quite short, but researchers try to use this time effectively to produce something useful. In this case involving eight school leaders, as participants, the results of the application of the six aspects of indicators were able to improve teacher performance and from changes in the learning system as well. can be significantly improved as evidenced by the results of evaluating student learning, this research does indeed need to be deepened comprehensively. The author measures the success rate of these indicators by using a cluster system (individually intervening) individually either for the principal or when assessing students, so the writer can see the improvement.
The role of entrepreneurial intention in predicting vocational high school students’ employability
Authors: Tentama Fatwa , Yusantri Sabrina
Published: November 2020

One of the factors that contribute to the level of employability is entrepreneurial intention. This study discusses the role of entrepreneurial intentions on students' employability. The population in this study was all students of grade XII of Vocational High School Koperasi Yogyakarta, Indonesia, consisting of 141 students. The sample in this study was 86 students. The sample selection was done by randomizing using a cluster random sampling technique. Methods of data collection used in this study are scales, employability scale, and entrepreneurial intentions scale. Analysis of the data used in this study is the product-moment analysis technique. The results of data analysis showed the correlation between entrepreneurial intentions and employability where r = 0.339 with p = 0.001 (p < 0.01), which showed a very significant positive correlation between the two variables at the research site. It means that the level of employability can be predicted based on entrepreneurial intention. The entrepreneurial intention contributed 11.5% to employability, and the remaining 88.5% can be influenced by other variables.
Teaching challenges on the use of storytelling in elementary science lessons
Authors: Haji Matamit Hajah Nuruljannah , Roslan Roslinawati , Shahrill Masitah , Said Hardimah Mohd
Published: November 2020

This study investigated the use of storytelling in teaching elementary science on the topic of ‘Sense Organs’ at the Grade 1 level. A total of 21 students from one of the elementary schools in Brunei Darussalam participated in the study. The qualitative analyses of the observations and video recordings resulted in the classifications of the challenges faced when storytelling was used in the lessons. The four identified categories were the language aspect, development aspect, external challenges and existing knowledge. These categories were then used to investigate further any aspect that would develop the challenges into the teaching and learning of science using storytelling. Despite identifying the challenges in using storytelling in teaching science, storytelling may enhance the students’ understanding of science concepts.
Role of gamification in classroom teaching: Pre-service teachers’ view
Authors: Mee Mee Rita Wong , Tengku Shahdan Tengku Shahrom , Ismail Md Rosli , Abd Ghani Khatipah , Pek Lim Seong , Von Wong Yee , Woo Adelaide , Rao Yugeshineey Subba
Published: November 2020

Planning a creative learning environment is not an easy task. Teachers prefer to teach traditionally in chalk-and-talk approach during language teaching. However, this does not fit learners of the 21st Century as they prefer game-like activities instead of pen-and-paper lessons. Hence, the introduction of gamification in classroom would result in immediate enthusiasm and curiosity, which leads to the learners’ willingness to learn. Gamification prepares learners to be active and take responsibility upon their own learning. Lessons filled with fun games are believed to be more effective in producing a positive outcome as learners are motivated to play more although they do not realise the fact that they are learning subconsciously. This study aimed to explore views of 33 pre-service teachers in using gamification in language teaching during their 16-week internship at local primary schools around Selangor, Malaysia. A quantitative survey research method was used by administering a set of questionnaires at the end of their internship. The data collected was then analysed and presented in the form of tables. The results showed that integrating gamification into language learning improved learners’ creative, critical and problem-solving skills. Thus, interesting and engaging activities spark learners’ interest in language learning subconsciously.