bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of the Enrichment of Circulating Tumor Cells for Downstream Phenotypic Analysis in Patients with Non-Small Cell Lung Cancer Treated with Anti-PD-1 Immunotherapy
Authors: Papadaki Maria A , Sotiriou Afroditi I , Vasilopoulou Christina , Filika Maria , Aggouraki Despoina , Tsoulfas Panormitis G , Apostolopoulou Christina A , Rounis Konstantinos , Mavroudis Dimitrios , Agelaki Sofia
Published: June 2020

The current study aimed at the optimization of circulating tumor cell (CTC) enrichment for downstream protein expression analyses in non-small cell lung cancer (NSCLC) to serve as a tool for the investigation of immune checkpoints in real time. Different enrichment approaches—ficoll density, erythrolysis, their combination with magnetic separation, ISET, and Parsortix—were compared in spiking experiments using the A549, H1975, and SKMES-1 NSCLC cell lines. The most efficient methods were tested in patients (n = 15) receiving immunotherapy targeting programmed cell death-1 (PD-1). Samples were immunofluorescently stained for a) cytokeratins (CK)/epithelial cell adhesion molecule (EpCAM)/leukocyte common antigen (CD45), and b) CK/programmed cell death ligand-1 (PD-L1)/ indoleamine-2,3-dioxygenase (IDO). Ficoll, ISET, and Parsortix presented the highest yields and compatibility with phenotypic analysis; however, at the patient level, they provided discordant CTC positivity (13%, 33%, and 60% of patients, respectively) and enriched for distinct CTC populations. IDO and PD-L1 were expressed in 44% and 33% and co-expressed in 19% of CTCs. CTC detection was associated with progressive disease (PD) (p = 0.006), reduced progression-free survival PFS (p = 0.007), and increased risk of relapse (hazard ratio; HR: 10.733; p = 0.026). IDO-positive CTCs were associated with shorter PFS (p = 0.039) and overall survival OS (p = 0.021) and increased risk of death (HR: 5.462; p = 0.039). The current study indicates that CTC analysis according to distinct immune checkpoints is feasible and may provide valuable biomarkers to monitor NSCLC patients treated with anti-PD-1 agents.
Personalised Dosimetry in Radioembolisation for HCC: Impact on Clinical Outcome and on Trial Design
Authors: Garin Etienne , Palard Xavier , Rolland Yan
Published: June 2020

Selective internal radiation therapy (SIRT) of hepatocellular carcinoma (HCC) has been used for many years, usually without any specific dosimetry endpoint. Despite good clinical results in early phase studies or in cohort studies, three randomized trials in locally advanced HCC available failed to demonstrate any improvement of overall overall survival (OS) in comparison with sorafenib. In recent years, many studies have evaluated the dosimetry of SIRT using either a simulation-based dosimetry (macroaggregated albumin (MAA)-based) or a post-therapy-based one (90Y-based). The goal of this review is to present the dosimetry concept, tools available, its limitations, and main clinical results described for HCC patients treated with 90Y-loaded resin or glass microspheres. With MAA-based dosimetry, the threshold tumor doses allowing for a response were between 100 and 210 Gy for resin microspheres and between 205 and 257 Gy for glass microspheres. The significant impact of the tumor dose on OS was reported with both devices. The correlation between 90Y-based dosimetry and response was also reported. Regarding the safety, preliminary results are available for both products but with a larger range of normal liver doses values correlated with liver toxicities due to numerous confounding factors. Based on those results, international expert group recommendations for personalized dosimetry have been provided for both devices. The clinical impact of personalized dosimetry has been recently confirmed in a multicenter randomized study demonstrating a doubling of the response rate and an OS of 150% while using personalized dosimetry. Even if technical dosimetry improvements are still under investigation, the use of personalized dosimetry has to be generalized for both clinical practice and trial design.
New Use for Old Drugs: The Protective Effect of Risperidone on Colorectal Cancer
Authors: Chen Vincent Chin-Hung , Hsieh Yi-Hsuan , Lin Tzu-Chin , Lu Mong-Liang , Liao Yin-To , Yang Yao-Hsu , Hsu Tsai-Ching , Stewart Robert , Weng Jun-Cheng , Lee Min-Jing , Chiu Wei-Che , Tzang Bor-Show
Published: June 2020

(1) Background: The potential of old drugs in novel indications is being greatly valued. We propose a triple-model study involving population-based, cell, and animal studies to investigate the effects of risperidone, a type of second-generation antipsychotic (SGA) drug, on colorectal cancer. (2) Methods: We used data from Taiwan’s National Health Insurance Research Database between 1997 and 2013 to compare 101,989 patients with colorectal cancer and 101,989 controls. Conditional logistic regression analyses were used to explore the association between SGA exposure and the risk of colorectal cancer. The following bench studies were performed to evaluate the findings of the population-based study. (3) Results: We found that SGAs had been less commonly used in colorectal cancer patients than in controls. The colorectal cancer risk was reduced with an increase in the cumulative defined daily dose (cDDD) of SGAs. The adjusted odds ratio of antipsychotic use for cDDD days was 0.32 (95% CI: 0.25–0.42). Risperidone exhibited the most prominent tumor inhibition effect in a cell screen study. Bench data revealed that risperidone significantly induced apoptosis and elevated intracellular ROS in human SW480 cells and suppressed the proliferation of the xenografted SW480 tumor in nude mice. (4) Conclusion: This triple-model study demonstrates the association between risperidone usage and a lower risk of colorectal cancer.
Management of Drug Resistance in Mantle Cell Lymphoma
Authors: Roué Gaël , Sola Brigitte
Published: June 2020

Mantle cell lymphoma (MCL) is a rare but aggressive B-cell hemopathy characterized by the translocation t(11;14)(q13;q32) that leads to the overexpression of the cell cycle regulatory protein cyclin D1. This translocation is the initial event of the lymphomagenesis, but tumor cells can acquire additional alterations allowing the progression of the disease with a more aggressive phenotype and a tight dependency on microenvironment signaling. To date, the chemotherapeutic-based standard care is largely inefficient and despite the recent advent of different targeted therapies including proteasome inhibitors, immunomodulatory drugs, tyrosine kinase inhibitors, relapses are frequent and are generally related to a dismal prognosis. As a result, MCL remains an incurable disease. In this review, we will present the molecular mechanisms of drug resistance learned from both preclinical and clinical experiences in MCL, detailing the main tumor intrinsic processes and signaling pathways associated to therapeutic drug escape. We will also discuss the possibility to counteract the acquisition of drug refractoriness through the design of more efficient strategies, with an emphasis on the most recent combination approaches.
Circulating Tumor DNA as a Novel Biomarker Optimizing Chemotherapy for Colorectal Cancer
Authors: Osumi Hiroki , Shinozaki Eiji , Yamaguchi Kensei
Published: June 2020

Liquid biopsy is a minimally invasive method for detecting soluble factors, including circulating tumor DNA (ctDNA), in body fluids. ctDNA carrying tumor-specific genetic or epigenetic alterations is released into circulation from tumor cells. ctDNA in the plasma contains somatic mutations that have occurred in the tumor, and reflects tumor progression and therapeutic effects promptly and accurately. Furthermore, ctDNA is useful for early detection of recurrence and estimation of prognosis and may be utilized for diagnosis and personalized medicine for treatment selection. Thus, in the near future, it will be possible to select the most appropriate treatment based on real-time genetic information using ctDNA.
Quantitative Analysis of Differential Expression of HOX Genes in Multiple Cancers
Authors: Adato Orit , Orenstein Yaron , Kopolovic Juri , Juven-Gershon Tamar , Unger Ron
Published: June 2020

Transcription factors encoded by Homeobox (HOX) genes play numerous key functions during early embryonic development and differentiation. Multiple reports have shown that mis-regulation of HOX gene expression plays key roles in the development of cancers. Their expression levels in cancers tend to differ based on tissue and tumor type. Here, we performed a comprehensive analysis comparing HOX gene expression in different cancer types, obtained from The Cancer Genome Atlas (TCGA), with matched healthy tissues, obtained from Genotype-Tissue Expression (GTEx). We identified and quantified differential expression patterns that confirmed previously identified expression changes and highlighted new differential expression signatures. We discovered differential expression patterns that are in line with patient survival data. This comprehensive and quantitative analysis provides a global picture of HOX genes’ differential expression patterns in different cancer types.
Sorafenib Resistance in Hepatocellular Carcinoma: The Relevance of Genetic Heterogeneity
Authors: Cabral Loraine Kay D. , Tiribelli Claudio , Sukowati Caecilia H. C.
Published: June 2020

Despite advances in biomedicine, the incidence and the mortality of hepatocellular carcinoma (HCC) remain high. The majority of HCC cases are diagnosed in later stages leading to the less than optimal outcome of the treatments. Molecular targeted therapy with sorafenib, a dual-target inhibitor targeting the serine-threonine kinase Raf and the tyrosine kinases VEGFR/PDGFR, is at present the main treatment for advanced-stage HCC, either in a single or combinatory regimen. However, it was observed in a large number of patients that its effectiveness is hampered by drug resistance. HCC is highly heterogeneous, within the tumor and among individuals, and this influences disease progression, classification, prognosis, and naturally cellular susceptibility to drug resistance. This review aims to provide an insight on how HCC heterogeneity influences the different primary mechanisms of chemoresistance against sorafenib including reduced drug intake, enhanced drug efflux, intracellular drug metabolism, alteration of molecular targets, activation/inactivation of signaling pathways, changes in the DNA repair machinery, and negative balance between apoptosis and survival of the cancer cells. The diverse variants, mutations, and polymorphisms in molecules and their association with drug response can be a helpful tool in treatment decision making. Accordingly, the existence of heterogeneous biomarkers in the tumor must be considered to strengthen multi-target strategies in patient-tailored treatment.
Low Prevalence of HER2-Positive Breast Carcinomas among Screening Detected Breast Cancers
Authors: López-García M. Ángeles , Carretero-Barrio Irene , Pérez-Míes Belén , Chiva Miguel , Castilla Carolina , Vieites Begoña , Palacios José
Published: June 2020

Conflicting results have been reported regarding the prevalence of screen-detected human epidermal growth factor receptor 2 (HER2)-positive breast carcinomas and non-screen detected HER2-positive breast carcinomas. To address this issue, we evaluated the prevalence of HER2-positive breast carcinomas in two independent regional screening programs in Spain. The clinicopathologic and immunohistochemical characteristics of 479 (306 and 173) screen-detected breast carcinomas and 819 (479 and 340) non-screen-detected breast carcinomas diagnosed in women between 50 and 69-year-olds were compared. The prevalence of HER2-positive breast carcinomas was 8.8% and 6.4% in the two series of screen-detected tumors, compared with 16.4% and 13% in non-screen-detected carcinomas. These differences were statistically significant. This lower prevalence of HER2-positive in-screen-detected breast carcinomas was observed in both hormone receptor positive (luminal HER2) and hormone-receptor-negative (HER2 enriched) tumors. In addition, a lower prevalence of triple-negative and a higher prevalence of luminal-A breast carcinomas was observed in screen-detected tumors. Moreover, a literature review pointed out important differences in subrogate molecular types in screen-detected breast carcinomas among reported series, mainly due to study design, technical issues and racial differences.
The Deubiquitinase USP4 Stabilizes Twist1 Protein to Promote Lung Cancer Cell Stemness
Authors: Li Fengtian , Hu Qingyong , He Tao , Xu Jing , Yi Yong , Xie Siyi , Ding Liangping , Fu Mengyuan , Guo Rongtian , Xiao Zhi-Xiong Jim , Niu Mengmeng
Published: June 2020

Lung cancer stem cells (CSCs) play a pivotal role in tumor development, drug resistance, metastasis and recurrence of lung cancer. Thus, it is of great importance to study the mechanism by which CSCs are regulated. In this study, we demonstrate that the deubiquitinase USP4 is critically important in promoting lung cancer stemness. Silencing of USP4 leads to reduction of Oct4 and Sox2 expression, decreased CD133+ cell population and inhibition of tumorsphere formation. Conversely, ectopic expression of USP4 significantly enhances lung cancer cell stemness, which is effectively rescued by simultaneous silencing of Twist1. Mechanistically, we identified USP4 as a novel deubiquitinase of Twist1. USP4 binds to, deubiquitinates and stabilizes Twist1 protein. Furthermore, we show that USP4 expression is elevated in human lung cancer specimens and is positively correlated with Twist1 expression. High expression of USP4/Twist1 is associated with poor clinical outcomes of lung cancer patients. Together, this study highlights an important role for USP4 in lung cancer stemness and suggests USP4 as a potential target for lung cancer diagnosis and treatment.
Use of a Luciferase-Expressing Orthotopic Rat Brain Tumor Model to Optimize a Targeted Irradiation Strategy for Efficacy Testing with Temozolomide
Authors: Mowday Alexandra M. , Lieuwes Natasja G. , Biemans Rianne , Marcus Damiënne , Rezaeifar Behzad , Reniers Brigitte , Verhaegen Frank , Theys Jan , Dubois Ludwig J.
Published: June 2020

Glioblastoma multiforme (GBM) is a common and aggressive malignant brain cancer with a mean survival time of approximately 15 months after initial diagnosis. Currently, the standard-of-care (SOC) treatment for this disease consists of radiotherapy (RT) with concomitant and adjuvant temozolomide (TMZ). We sought to develop an orthotopic preclinical model of GBM and to optimize a protocol for non-invasive monitoring of tumor growth, allowing for determination of the efficacy of SOC therapy using a targeted RT strategy combined with TMZ. A strong correlation (r = 0.80) was observed between contrast-enhanced (CE)-CT-based volume quantification and bioluminescent (BLI)-integrated image intensity when monitoring tumor growth, allowing for BLI imaging as a substitute for CE-CT. An optimized parallel-opposed single-angle RT beam plan delivered on average 96% of the expected RT dose (20, 30 or 60 Gy) to the tumor. Normal tissue on the ipsilateral and contralateral sides of the brain were spared 84% and 99% of the expected dose, respectively. An increase in median survival time was demonstrated for all SOC regimens compared to untreated controls (average 5.2 days, p < 0.05), but treatment was not curative, suggesting the need for novel treatment options to increase therapeutic efficacy.
Current Strategies for Treating NSCLC: From Biological Mechanisms to Clinical Treatment
Authors: Li Junnan , Kwok Hang
Published: June 2020

The identification of specific epidermal growth factor receptor (EGFR)-activating mutations heralded a breakthrough in non-small-cell lung cancer (NSCLC) treatments, with the subsequent development of EGFR-tyrosine kinase inhibitor (TKIs) becoming the first-line therapy for patients harboring EGFR mutations. However, acquired resistance to EGFR-TKIs inevitably occurs in patients following initial TKI treatment, leading to disease progression. Various mechanisms are behind the acquired resistance, and mainly include (1) target gene modification, (2) alternative parallel pathway activation, (3) downstream pathway activation, and (4) histological/phenotypic transformation. Approaches to combat the acquired resistance have been investigated according to these mechanisms. Newer generations of TKIs have been developed to target the secondary/tertiary EGFR mutations in patients with acquired resistance. In addition, combination therapies have been developed as another promising strategy to overcome acquired resistance through the activation of other signaling pathways. Thus, in this review, we summarize the mechanisms for acquired resistance and focus on the potential corresponding therapeutic strategies for acquired resistance.
Biotransformation of Phytosterols to Androst-1,4-Diene-3,17-Dione by Mycobacterium sp. ZFZ Expressing 3-Ketosteroid-Δ1-Dehydrogenase
Authors: Liu Xiangcen , Zhang Ruijie , Bao Zhiwei , Yuan Chenyang , Cao Huijin , Shi Jiping , Sun Junsong , Zhang Baoguo
Published: June 2020

As an important hormone drug intermediate, androst-1,4-diene-3,17-dione can be bio-converted from phytosterols. However, separation and purification in the downstream process are very difficult due to the similarity in structure and physiological characteristics between ADD and androstenedione (AD). This phenomenon was correlated to the insufficient enzyme activity of 3-ketosteroid-Δ1-dehydrogenase (KSDD), which specifically catalyzes the C1,2 dehydrogenation of AD. In order to obtain a highly purified ADD from phytosterols, the dehydrogenation effect of different kinds of KSDDs and the transcription effect of four promoter sequences on ksdd were analyzed in Mycobacterium sp. ZFZ (ZFZ), the cell host that transform phytosterols to AD in the oil-aqueous system. A tandem KSDD expression cassette containing strain ZFZ-2111 yielded 2.06 ± 0.09 g L−1 ADD, with a molar ratio of ADD/AD at 41.47:1.00 in 120 h. In waste cooking oil-aqueous media, the proportion of ADD in the fermentation by ZFZ-2111 was 92%. The present study provides a reliable theoretical basis for the step-by-step transformation of phytosterols to ADD.
Understanding the Photo- and Electro-Carboxylation of o-Methylbenzophenone with Carbon Dioxide
Authors: Tian Keyi , Chen Ruonan , Xu Jiafang , Yang Ge , Xu Xintong , Zhang Yanhua
Published: June 2020

The lack of understanding of the radical reaction mechanism of Carbon dioxide (CO2) in photo- and electro-catalysis results in the development of such applications far behind the traditional synthesis methods. Using methylbenzophenone as the model, we clarify and compare the photo-enolization/Diels−Alder (PEDA) mechanism for photo-carboxylation and the two-step single-electron reduction pathway for electro-carboxylation with CO2 through careful control experiments. The regioselective carboxylation products, o-acylphenylacetic acid and α-hydroxycarboxylic acid are obtained, respectively, in photo- and electro-chemistry systems. On the basis of understanding the mechanism, a one-pot step-by-step dicarboxylation of o-methylbenzophenone is designed and conducted. Both the experimental results and related density functional theory (DFT) calculation verify the feasibility of the possible pathway in which electro-carboxylation is conducted right after photo-carboxylation in one vessel. This synthesis approach may provide a mild, eco-friendly strategy for the production of polycarboxylic acids in industry.
Bioalcohol Reforming: An Overview of the Recent Advances for the Enhancement of Catalyst Stability
Authors: Palma Vincenzo , Ruocco Concetta , Cortese Marta , Martino Marco
Published: June 2020

The growing demand for energy production highlights the shortage of traditional resources and the related environmental issues. The adoption of bioalcohols (i.e., alcohols produced from biomass or biological routes) is progressively becoming an interesting approach that is used to restrict the consumption of fossil fuels. Bioethanol, biomethanol, bioglycerol, and other bioalcohols (propanol and butanol) represent attractive feedstocks for catalytic reforming and production of hydrogen, which is considered the fuel of the future. Different processes are already available, including steam reforming, oxidative reforming, dry reforming, and aqueous-phase reforming. Achieving the desired hydrogen selectivity is one of the main challenges, due to the occurrence of side reactions that cause coke formation and catalyst deactivation. The aims of this review are related to the critical identification of the formation of carbon roots and the deactivation of catalysts in bioalcohol reforming reactions. Furthermore, attention is focused on the strategies used to improve the durability and stability of the catalysts, with particular attention paid to the innovative formulations developed over the last 5 years.
Covalent Functionalization of Nanodiamonds by Ruthenium Porphyrin, and Their Catalytic Activity in the Cyclopropanation Reaction of Olefins
Authors: Lorecchio Chiara , Tamburri Emanuela , Lazzarini Laura , Orlanducci Silvia , Zanoni Robertino , Tagliatesta Pietro
Published: June 2020

Detonation nanodiamonds (DNDs) were functionalized by ruthenium porphyrins and used as catalysts in the cyclopropanation reaction of olefins. The heterogeneous catalyst was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and XPS (X-ray photoelectron spectroscopy). The XPS was used to control the binding of the ruthenium porphyrin to the DNDs’ surface. This catalyst was used in the cyclopropanation reactions of simple olefins and was reused with no loss of activity in four consecutive cycles, after recovering each time by simple centrifugation.
Editorial: Special Issue on “Emerging Trends in TiO2 Photocatalysis and Applications”
Authors: Do Trong-On , Mohan Sakar
Published: June 2020

It is not an exaggerated fact that the semiconductor titanium dioxide (TiO2) has been evolved as a prototypical material to understand the photocatalytic process and has been demonstrated for various photocatalytic applications such as pollutants degradation, water splitting, heavy metal reduction, CO2 conversion, N2 fixation, bacterial disinfection, etc [...]
Glycerol Dehydration to Acrolein over Supported Vanadyl Orthophosphates Catalysts
Authors: Ruoppolo Giovanna , Landi Gianluca , Di Benedetto Almerinda
Published: June 2020

Biodiesel has been identified as one of the notable options for at least complementing conventional fuels. From a transesterification reaction, crude glycerol is produced as the main by-product. Given the difficultly in upgrading to high-grade glycerin and glycerol market saturation, alternative routes to more value-added products have aroused significant interest. In this work, we proposed supported vanadyl orthophosphates (VOP) as catalysts for the glycerol dehydration to acrolein. VOP supported on γ-Al2O3, TiO2, and ZrO2 were prepared, characterized by inductively coupled plasma mass spectrometry (ICP-MS), X-ray diffraction (XRD), N2 physisorption and temperature-programmed desorption of ammonia (NH3-TPD), and tested under different operating conditions. All the samples showed low coke formation in the presence of molecular oxygen in the feed. Acrolein is the main condensable product, with carbon balance being satisfactory under most operating conditions. VOP supported onto alumina provided the best catalytic performance, due to a good balance between the acid (weak and medium acid sites) and redox sites, thereby appearing as a good candidate for glycerol dehydration to acrolein.
MiRNA Profiling in Plasma Neural-Derived Small Extracellular Vesicles from Patients with Alzheimer’s Disease
Authors: Serpente Maria , Fenoglio Chiara , D’Anca Marianna , Arcaro Marina , Sorrentino Federica , Visconte Caterina , Arighi Andrea , Fumagalli Giorgio G. , Porretti Laura , Cattaneo Alessandra , Ciani Miriam , Zanardini Roberta , Benussi Luisa , Ghidoni Roberta , Scarpini Elio , Galimberti Daniela
Published: June 2020

Small extracellular vesicles (EVs) are able to pass from the central nervous system (CNS) into peripheral blood and contain molecule markers of their parental origin. The aim of our study was to isolate and characterize total and neural-derived small EVs (NDEVs) and their micro RNA (miRNA) cargo in Alzheimer’s disease (AD) patients. Small NDEVs were isolated from plasma in a population consisting of 40 AD patients and 40 healthy subjects (CTRLs) using high throughput Advanced TaqMan miRNA OpenArrays®, which enables the simultaneous determination of 754 miRNAs. MiR-23a-3p, miR-223-3p, miR-100-3p and miR-190-5p showed a significant dysregulation in small NDEVs from AD patients as compared with controls (1.16 ± 0.49 versus 7.54 ± 2.5, p = 0.026; 9.32 ± 2.27 versus 0.66 ± 0.18, p <0.0001; 0.069 ± 0.01 versus 0.5 ± 0.1, p < 0.0001 and 2.9 ± 1.2 versus 1.93 ± 0.9, p < 0.05, respectively). A further validation analysis confirmed that miR-23a-3p, miR-223-3p and miR-190a-5p levels in small NDEVs from AD patients were significantly upregulated as compared with controls (p = 0.008; p = 0.016; p = 0.003, respectively) whereas miR-100-3p levels were significantly downregulated (p = 0.008). This is the first study that carries out the comparison between total plasma small EV population and NDEVs, demonstrating the presence of a specific AD NDEV miRNA signature.
Valproic Acid Significantly Improves CRISPR/Cas9-Mediated Gene Editing
Authors: Park Hanseul , Shin Jaein , Choi Hwan , Cho Byounggook , Kim Jongpil
Published: June 2020

The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has emerged as a powerful technology, with the potential to generate transgenic animals. Particularly, efficient and precise genetic editing with CRISPR/Cas9 offers immense prospects in various biotechnological applications. Here, we report that the histone deacetylase inhibitor valproic acid (VPA) significantly increases the efficiency of CRISPR/Cas9-mediated gene editing in mouse embryonic stem cells and embryos. This effect may be caused through globally enhanced chromatin accessibility, as indicate by histone hyperacetylation. Taken together, our results suggest that VPA can be used to increase the efficacy of CRISPR/Cas9 in generating transgenic systems.
Ablation of Vitamin D Signaling Compromises Cerebrovascular Adaptation to Carotid Artery Occlusion in Mice
Authors: Pál Éva , Hricisák László , Lékai Ágnes , Nagy Dorina , Fülöp Ágnes , Erben Reinhold G. , Várbíró Szabolcs , Sándor Péter , Benyó Zoltán
Published: June 2020

Vitamin D insufficiency has been associated with increased incidence and severity of cerebrovascular disorders. We analyzed the impact of impaired vitamin D signaling on the anatomical and functional aspects of cerebrovascular adaptation to unilateral carotid artery occlusion (CAO), a common consequence of atherosclerosis and cause of ischemic stroke. Cerebrocortical blood flow (CoBF) showed a significantly increased drop and delayed recovery after CAO in mice carrying a functionally inactive vitamin D receptor (VDR) with the most sustained perfusion deficit in the temporal cortex. To identify the cause(s) for this altered adaptation, the extent of compensatory blood flow increase in the contralateral carotid artery and the morphology of pial collaterals between the anterior and middle cerebral arteries were determined. Whereas VDR deficiency had no significant influence on the contralateral carotid arterial blood flow increase, it was associated with decreased number and increased tortuosity of pial anastomoses resulting in unfavorable changes of the intracranial collateral circulation. These results indicate that VDR deficiency compromises the cerebrovascular adaptation to CAO with the most sustained consequences in the temporal cortex. The dysregulation can be attributed to the altered development and function of pial collateral circulation whereas extracranial vessels may not be impaired.
Assessment of Seasonal Winter Temperature Forecast Errors in the RegCM Model over Northern Vietnam
Authors: Vo Van Hoa , Du Duc Tien , Mai Khanh Hung , Robert Hole Lars , Tran Anh Duc , Luong Thi Thanh Huyen , Dang Dinh Quan
Published: June 2020

This study verified the seasonal six-month forecasts for winter temperatures for northern Vietnam in 1998–2018 using a regional climate model (RegCM4) with the boundary conditions of the climate forecast system Version 2 (CFSv2) from the National Centers for Environmental Prediction (NCEP). First, different physical schemes (land-surface process, cumulus, and radiation parameterizations) in RegCM4 were applied to generate 12 single forecasts. Second, the simple ensemble forecasts were generated through the combinations of those different physical formulations. Three subclimate regions (R1, R2, R3) of northern Vietnam were separately tested with surface observations and a reanalysis dataset (Japanese 55-year reanalysis (JRA55)). The highest sensitivity to the mean monthly temperature forecasts was shown by the land-surface parameterizations (the biosphere−atmosphere transfer scheme (BATS) and community land model version 4.5 (CLM)). The BATS forecast groups tended to provide forecasts with lower temperatures than the actual observations, while the CLM forecast groups tended to overestimate the temperatures. The forecast errors from single forecasts could be clearly reduced with ensemble mean forecasts, but ensemble spreads were less than those root-mean-square errors (RMSEs). This indicated that the ensemble forecast was underdispersed and that the direct forecast from RegCM4 needed more postprocessing.
Etching Characteristics of SixNy Film on Textured Single Crystalline Silicon Surface Using Ar/CF4 and He/CF4 Surface-Discharge Plasma
Authors: Hamada Toshiyuki , Masuda Shunsuke , Nishida Kazuki , Yamamoto Soma
Published: June 2020

In this study, we investigated the characteristics of electrode grooves formed by etching silicon nitride (SixNy) films using surface-discharge plasma under Ar/CF4 and He/CF4 gases on the basis of differences in the widths of the electrode grooves etched on the SixNy film. The widths of the grooves etched using Ar as the carrier gas were narrower than those etched using He, and the etching speed achieved using Ar was higher than that achieved using He. Furthermore, the electrode groove created by surface-discharge plasma gradually widened as etching time and applied voltage increased.
Gas Technique of Simultaneous Borocarburizing of Armco Iron Using Trimethyl Borate
Authors: Makuch Natalia , Dziarski Piotr , Kulka Michał
Published: June 2020

The gas boriding process is an appropriate technique used for increasing the hardness and wear resistance of iron and steels. However, the boron halides (e.g., BCl3, BF3) are rarely used as a boron source during gas boriding in industry due to the toxic character of these reagents. The possibility of the use of organic compounds as a boron source in plasma assisted processes was the instigation to determine the possibility of applying these agents for gas boriding. In the present work trimethyl borate was used as an organic boron source. The use of a N2–H2–B(CH3O)3 atmosphere ensured the appropriate conditions for the simultaneous gas borocarburizing of Armco iron. The process was carried out at 1223 K (950 °C) for 2 h. The produced layer consisted of two zones: an outer zone containing a diffusion of boron atoms and an inner zone containing a diffusion of carbon atoms, under the outer zone. Due to the reduction of trimethyl borate with hydrogen, free atoms of carbon were released for the gas atmosphere. Therefore, there existed favorable conditions for carburizing. Unfortunately, the formation of a carburized layer was the reason for the difficult diffusion of boron atoms. As a consequence, the boron diffusion front was hindered, and the outer boride layer was relatively thin (ca. 7.8 µm). The boride layer contained only Fe2B phase, which was characterized by high hardness in the range from 1103 HV0.01 to 1546 HV0.01. The presence of iron borides in the outer layer was also the reason for increased wear resistance in comparison with untreated Armco iron.
DFT Investigation on the Electronic, Magnetic, Mechanical Properties and Strain Effects of the Quaternary Compound Cu2FeSnS4
Authors: Bai Jing , Ji Jiaying , Hao Liyu , Yang Tie , Tan Xingwen
Published: June 2020

The electronic, magnetic and mechanical properties of the quaternary compound Cu2FeSnS4 have been investigated with first principle calculations. Its half-metallicity has been identified with spin polarized band structures and its magnetic origination is caused by the strong spin splitting effect in the d orbitals of Fe atoms. The total magnetic moment of 4 μB is mainly contributed by the Fe atoms and the spatial distribution of the magnetic spin density and charge density difference have also been examined. Moreover, several mechanical properties of Cu2FeSnS4 have been derived and its mechanical stability is also verified. The directional dependent Young’s modulus exhibits relatively small anisotropy yet the shear modulus shows strong directional anisotropy. At last, the tetragonal strain effects have been evaluated and their impact on the electronic and magnetic properties are provided. Results show the total magnetic moment stays almost unchanged while the half-metallicity can only be maintained under relatively small variations for both strains. This study can provide comprehensive information about the various properties of Cu2FeSnS4 compound and serve as a helpful reference for its future applications.
The Dynamic State of a Pseudo-Crystalline Structure of B42 Molecules
Authors: Bubenchikov Alexey , Bubenchikov Mikhail , Mamontov Dmitriy
Published: June 2020

In this paper, we have developed a mathematical model of the dynamics of molecular structures arising from an approach using B42 molecules. The model is based on equations that determine the motion of the centers of mass of the molecules in question, and equations for the projections of the moments of quantities of motion of these particles on the axes associated with them. The thermal motions of boron atoms within each individual molecule are calculated using a bond-ordered potential. The intermolecular interactions of atoms have a potential that appears to coincide with that of free atoms. However, the interaction parameters differ. The obtained columns of molecular disks for B42 are stable structures. We determine the characteristic vibration amplitudes and rotation frequency of the molecules in question.
Cereal Straw Mulching in Strawberry—A Facilitator of Plant Visits by Edaphic Predatory Mites at Night?
Authors: Neves Esteca Fernanda de Cássia , Trandem Nina , Klingen Ingeborg , Cruz Santos Jandir , Delalibera Júnior Italo , de Moraes Gilberto José
Published: June 2020

In Norway, strawberry producers use cereal straw mulching to prevent berries from contacting the soil and to control weeds. We hypothesized that organic matter such as straw mulch also favors the maintenance of predatory mites which visit strawberry plants at nighttime. We compared mite diversity in cereal straw exposed for different periods in strawberry fields and evaluated their possible migration to plants in two experiments with potted plants in 2019. An ‘Early season’ experiment compared no mulching (T1), oat straw mulch exposed in field since 2018 (T2), or 2017 (T3), while a ‘Mid-season’ experiment compared no mulching (T1), barley straw mulch from 2018 (T2), or a mix from 2017 and 2018 (T3). To provide edaphic predatory mites with a potential source of food, all plants were infested with two-spotted spider mite (Tetranychus urticae Koch). Results suggested that straw mulch facilitates the prevalence of predatory mites in strawberry fields. Most predatory mite visits were at night, confirming our initial hypothesis. Predominant nocturnal mites on leaves belonged to Melicharidae (Proctolaelaps sp.) (‘Early season’, T2), Blattisociidae (Lasioseius sp.) (‘Early and Mid-season’, T3) and Phytoseiidae (‘Mid-season’, T2). Parasitus consanguineus Oudemans & Voigts was the predominant species (‘Early season’, T3) at the base of plants. Anystidae were diurnal visitors only (‘Mid-season’, T2). Future studies should evaluate the predation potential of Proctolaelaps sp. and Lasioseius sp. on two-spotted spider mite and other strawberry pests.
Ecosystem Engineers in the World Coasts: Case Studies and Conceptual Linkages
Authors: Gutiérrez Jorge L.
Published: June 2020

Research on physical ecosystem engineering—i.e., the structural modification of environments by organisms—has flourished during the last two decades. At present, the importance of physical ecosystem engineers for the biodiversity and the functioning of ecosystems is well recognized by scientists. This Special Issue contains fifteen papers that illustrate the diversity of physical ecosystem engineering processes that occur in the world coastal habitats—from coastal dunes to the shallow subtidal zone. It includes 2 reviews comparing ecosystem engineering attributes and impacts across taxa and 13 case studies that inform our general understanding of the variation in engineering impacts, compound engineering effects, novel engineering interactions, and engineered structural legacies.
Changes in the Abundance of Danish Orchids over the Past 30 Years
Authors: Damgaard Christian , Moeslund Jesper Erenskjold , Wind Peter
Published: June 2020

Orchid abundance data collected over the past 30 years (1987–2016) from 440 sites within the National Orchid Monitoring Program were analyzed to quantify the population trends of orchids in Denmark, and the underlying reasons for the observed population trends were analyzed and discussed. Of the 45 monitored Danish orchids, 20 showed a significant decrease in abundance over the past 30 years (16, if only orchids with at least 50 observations each were selected), thus corroborating the previous observations of declining orchid abundances at the European scale. Generally, there was a significant negative effect of overgrowing with tall-growing herbs and shrubs on the abundance of Danish orchids, mainly caused by change of farming practices, as extensive management, such as grazing or mowing of light-open grassland areas, has decreased.
Development of a Nucleic Acid Lateral Flow Immunoassay for the Detection of Human Polyomavirus BK
Authors: Huang Yi-Huei , Yu Kuan-Yi , Huang Shou-Ping , Chuang Hui-Wen , Lin Wen-Zhi , Cherng Juin-Hong , Hung Yao-Wen , Yeh Ming-Kung , Hong Po-Da , Liu Cheng-Che
Published: June 2020

The BK virus (BKV) is an emerging pathogen in immunocompromised individuals and widespread in the human population. Polymerase chain reaction is a simple and highly sensitive method for detecting BKV, but it is time consuming and requires expensive instruments and expert judgment. The lateral flow assay, a rapid, low-cost, minimal-labor, and easy-to-use diagnostic method, was successfully applied for pathogen detection. In this study, we used oligonucleotide probes to develop a simple and rapid sandwich-type lateral flow immunoassay for detecting BKV DNA within 45 minutes. The detection limit for the synthetic single-stranded DNA was 5 nM. The specificity study showed no cross-reactivity with other polyomaviruses, such as JC virus and simian virus 40. For the Escherichia coli containing BKV plasmid cultured samples, the sensitivity was determined to be 107 copies/mL. The approach offers great potential for BKV detection of various target analytes in point-of-care settings.
Pathogenic PSEN1 Thr119Ile Mutation in Two Korean Patients with Early-Onset Alzheimer’s Disease
Authors: Bagyinszky Eva , Lee Hyon , Pyun Jung Min , Suh Jeewon , Kang Min Ju , Vo Van Giau , An Seong Soo A. , Park Kee Hyung , Kim SangYun
Published: June 2020

We report a probable pathogenic Thr119Ile mutation in presenilin-1 (PSEN1) in two unrelated Korean patients, diagnosed with early onset Alzheimer’s disease (EOAD). The first patient presented with memory decline when she was 64 years old. Magnetic resonance imaging (MRI) scans showed diffuse atrophy in the fronto-parietal regions. In addition, 18F-fludeoxyglucose positron emission tomography (FDG-PET) showed reduced tracer uptake in the parietal and temporal cortices, bilaterally. The second patient developed memory dysfunction at the age of 49, and his mother was also affected. Amyloid positron emission tomography (PET) was positive, but MRI scans did not reveal any atrophy. Targeted NGS and Sanger sequencing identified a heterozygous C to T exchange in PSEN1 exon 5 (c.356C>T), resulting in a p.Thr119Ile mutation. The mutation is located in the conserved HL-I loop, where several Alzheimer’s disease (AD) related mutations have been described. Structure analyses suggested that Thr119Ile mutation may result in a significant change inside conservative loop. Additional in vitro studies are needed to estimate the role of the PSEN1 Thr119Ile in AD disease progression.
5G-Enabled Security Scenarios for Unmanned Aircraft: Experimentation in Urban Environment
Authors: Ferro Erina , Gennaro Claudio , Nordio Alessandro , Paonessa Fabio , Vairo Claudio , Virone Giuseppe , Argentieri Arturo , Berton Andrea , Bragagnini Andrea
Published: June 2020

The telecommunication industry has seen rapid growth in the last few decades. This trend has been fostered by the diffusion of wireless communication technologies. In the city of Matera, Italy (European capital of culture 2019), two applications of 5G for public security have been tested by using an aerial drone: the recognition of objects and people in a crowded city and the detection of radio-frequency jammers. This article describes the experiments and the results obtained.
Network Rewiring in the r-K Plane
Authors: Bertotti Maria Letizia , Modanese Giovanni
Published: June 2020

We generate correlated scale-free networks in the configuration model through a new rewiring algorithm that allows one to tune the Newman assortativity coefficient r and the average degree of the nearest neighbors K (in the range − 1 ≤ r ≤ 1 , K ≥ ⟨ k ⟩ ). At each attempted rewiring step, local variations Δ r and Δ K are computed and then the step is accepted according to a standard Metropolis probability exp ( ± Δ r / T ) , where T is a variable temperature. We prove a general relation between Δ r and Δ K , thus finding a connection between two variables that have very different definitions and topological meaning. We describe rewiring trajectories in the r-K plane and explore the limits of maximally assortative and disassortative networks, including the case of small minimum degree ( k m i n ≥ 1 ), which has previously not been considered. The size of the giant component and the entropy of the network are monitored in the rewiring. The average number of second neighbors in the branching approximation z ¯ 2 , B is proven to be constant in the rewiring, and independent from the correlations for Markovian networks. As a function of the degree, however, the number of second neighbors gives useful information on the network connectivity and is also monitored.
A Deep Learning Approach for Segmentation of Red Blood Cell Images and Malaria Detection
Authors: Delgado-Ortet Maria , Molina Angel , Alférez Santiago , Rodellar José , Merino Anna
Published: June 2020

Malaria is an endemic life-threating disease caused by the unicellular protozoan parasites of the genus Plasmodium. Confirming the presence of parasites early in all malaria cases ensures species-specific antimalarial treatment, reducing the mortality rate, and points to other illnesses in negative cases. However, the gold standard remains the light microscopy of May-Grünwald–Giemsa (MGG)-stained thin and thick peripheral blood (PB) films. This is a time-consuming procedure, dependent on a pathologist’s skills, meaning that healthcare providers may encounter difficulty in diagnosing malaria in places where it is not endemic. This work presents a novel three-stage pipeline to (1) segment erythrocytes, (2) crop and mask them, and (3) classify them into malaria infected or not. The first and third steps involved the design, training, validation and testing of a Segmentation Neural Network and a Convolutional Neural Network from scratch using a Graphic Processing Unit. Segmentation achieved a global accuracy of 93.72% over the test set and the specificity for malaria detection in red blood cells (RBCs) was 87.04%. This work shows the potential that deep learning has in the digital pathology field and opens the way for future improvements, as well as for broadening the use of the created networks.
Beam-Reconfigurable Multi-Antenna System with Beam-Combining Technology for UAV-to-Everything Communications
Authors: Choi Yu-Seong , Park Jeong-Su , Lee Wang-Sang
Published: June 2020

This paper proposes a beam-reconfigurable antenna for unmanned aerial vehicles (UAVs) with wide beam coverage by applying beam-combining technology to multiple antennas with different beam patterns. The proposed multi-antenna system consists of a circular patch antenna and a low-profile printed meandered monopole antenna. For beam combining, a coplanar waveguide with ground (CPW-G) structure feeding network is proposed, and it consists of two input ports, a 90° hybrid coupler, a microstrip 90° phase delay line, and a single-pole double-throw (SPDT) switch. It performs the role of power distribution and phase adjustment, and synthesizes the broad-side beam of the monopole antenna and the end-fire beam of the patch antenna to form the directive broadside beams in four different directions. The proposed antenna system operates at 5–5.5 GHz which covers both UAV ground control frequencies (5.03–5.09 GHz) and UAV mission frequencies (5.091–5.150 GHz). The peak gain, total efficiency, and half-power beamwidth (HPBW) of the antenna system are approximately 5.8 dBi, 76%, 145° in the elevation plane, and 360° in the azimuth plane respectively. Its electrical size and weight are λ 0 × λ 0 × 0.21 λ 0 at 5.09 GHz and 19.2 g, respectively.
Side-Information-Aided Preprocessing Scheme for Deep-Learning Classifier in Fingerprint-Based Indoor Positioning
Authors: Liu Yue , Sinha Rashmi Sharan , Liu Shu-Zhi , Hwang Seung-Hoon
Published: June 2020

Deep-learning classifiers can effectively improve the accuracy of fingerprint-based indoor positioning. During fingerprint database construction, all received signal strength indicators from each access point are combined without any distinction. Therefore, the database is created and utilised for deep-learning models. Meanwhile, side information regarding specific conditions may help characterise the data features for the deep-learning classifier and improve the accuracy of indoor positioning. Herein, a side-information-aided preprocessing scheme for deep-learning classifiers is proposed in a dynamic environment, where several groups of different databases are constructed for training multiple classifiers. Therefore, appropriate databases can be employed to effectively improve positioning accuracies. Specifically, two kinds of side information, namely time (morning/afternoon) and direction (forward/backward), are considered when collecting the received signal strength indicator. Simulations and experiments are performed with the deep-learning classifier trained on four different databases. Moreover, these are compared with conventional results from the combined database. The results show that the side-information-aided preprocessing scheme allows better success probability than the conventional method. With two margins, the proposed scheme has 6.55% and 5.8% improved performances for simulations and experiments compared to the conventional scheme. Additionally, the proposed scheme, with time as the side information, obtains a higher success probability when the positioning accuracy requirement is loose with larger margin. With direction as the side information, the proposed scheme shows better performance for high positioning precision requirements. Thus, side information such as time or direction is advantageous for preprocessing data in deep-learning classifiers for fingerprint-based indoor positioning.