bluuebunny/crossref_metadata_2025 huggingface dataset:
Eclipsing Systems with Pulsating Components (Types β Cep, δ Sct, γ Dor or Red Giant) in the Era of High-Accuracy Space Data
Authors: Lampens Patricia
Published: April 2021

Eclipsing systems are essential objects for understanding the properties of stars and stellar systems. Eclipsing systems with pulsating components are furthermore advantageous because they provide accurate constraints on the component properties, as well as a complementary method for pulsation mode determination, crucial for precise asteroseismology. The outcome of space missions aiming at delivering high-accuracy light curves for many thousands of stars in search of planetary systems has also generated new insights in the field of variable stars and revived the interest of binary systems in general. The detection of eclipsing systems with pulsating components has particularly benefitted from this, and progress in this field is growing fast. In this review, we showcase some of the recent results obtained from studies of eclipsing systems with pulsating components based on data acquired by the space missions Kepler or TESS. We consider different system configurations including semi-detached eclipsing binaries in (near-)circular orbits, a (near-)circular and non-synchronized eclipsing binary with a chemically peculiar component, eclipsing binaries showing the heartbeat phenomenon, as well as detached, eccentric double-lined systems. All display one or more pulsating component(s). Among the great variety of known classes of pulsating stars, we discuss unevolved or slightly evolved pulsators of spectral type B, A or F and red giants with solar-like oscillations. Some systems exhibit additional phenomena such as tidal effects, angular momentum transfer, (occasional) mass transfer between the components and/or magnetic activity. How these phenomena and the orbital changes affect the different types of pulsations excited in one or more components, offers a new window of opportunity to better understand the physics of pulsations.
Telemonitoring in the Covid-19 Era: The Tuscany Region Experience
Authors: Panicacci Silvia , Donati Massimiliano , Lubrano Alberto , Vianello Annamaria , Ruiu Alessio , Melani Luca , Tomei Antonella , Fanucci Luca
Published: April 2021

Covid-19 has brought many difficulties in the management of infected and high-risk patients. Telemedicine platforms can really help in this situation, since they allow remotely monitoring Covid-19 patients, reducing the risk for the doctors, without decreasing the efficiency of the therapies and while alleviating patients’ mental issues. In this paper, we present the entire architecture and the experience of using the Tel.Te.Covid19 telemedicine platform. Projected for the treatment of chronic diseases, it has been technologically updated for the management of Covid-19 patients with the support of a group of doctors in the territory when the pandemic arrived, introducing new sensors and functionalities (e.g., the familiar use and video calls). In Tuscany (Central Italy), during the first wave of outbreak, a model for enrolling patients was created and tested. Because of the positive results, the latter has been then adopted in the second current wave. The Tel.Te.Covid19 platform has been used by 40 among general practitioners and doctors of continuity care and about 180 symptomatic patients since March 2020. Both patients and doctors have good opinion of the platform, and no hospitalisations or deaths occurred for the monitored patients, reducing also the impact on the National Healthcare System.
The Epidemiology of Hip and Knee Primary and Revision Arthroplasties during the COVID-19 Pandemic
Authors: Kazubski Krystian , Tomczyk Łukasz , Kopczyński Bartosz , Morasiewicz Piotr
Published: April 2021

Background: The purpose of this study was to provide a comprehensive assessment of the impact of the COVID-19 pandemic on the epidemiology of primary and revision arthroplasties of the hip and knee joint. Methods: This study compared the data on knee and hip arthroplasty procedures from 2 hospitals (primary and revision) conducted in two periods: the period of the COVID-19 pandemic in Poland (from 4 March 2020 to 15 October 2020) and the corresponding period prior to the pandemic (from 4 March 2019 to 15 October 2019). We compared the epidemiological data, demographic data, and hospital stay duration data from these two periods. Results: Our analysis demonstrated that the total number of hip arthroplasties conducted in 2020 decreased by 26% in comparison with 2019. In the case of knee arthroplasties, the total number of procedures in the evaluated period in 2020 decreased by 44%. Our study also showed that the mean time of hospital stay for orthopedic patients following hip or knee arthroplasty was 22.87% shorter. The female-to-male patient ratio decreased between the analyzed periods, and this was 22.96% lower during the pandemic. Conclusion: The COVID-19 pandemic in these two hospitals in Poland led to reduced numbers of hip and knee replacement procedures, shorter hospital stays, and a decreased female-to-male patient ratio. The mean age of patients undergoing hip or knee arthroplasty remained unchanged during the national lockdown with respect to the pre-pandemic figure.
Generalized Joint Hypermobility and Anxiety in Adolescents and Young Adults, the Impact on Physical and Psychosocial Functioning
Authors: de Vries Janneke , Verbunt Jeanine , Stubbe Janine , Visser Bart , Ramaekers Stephan , Calders Patrick , Engelbert Raoul
Published: April 2021

The purpose of this study was to study the association between the presence of generalized joint hypermobility (GJH) and anxiety within a non-clinical high performing group of adolescents and young adults. Second, to study the impact of GJH and/or anxiety on physical and psychosocial functioning, 168 adolescents and young adults (mean (SD) age 20 (2.9)) were screened. Joint (hyper)mobility, anxiety, and physical and psychosocial functioning were measured. In 48.8% of all high performing adolescents and young adults, GJH was present, whereas 60% had symptoms of anxiety. Linear models controlled for confounders showed that adolescents and young adults with GJH and anxiety had decreased workload (ß (95%CI) −0.43 (−0.8 to −0.08), p-value 0.02), increased fatigue (ß (95%CI) 12.97 (6.3–19.5), p-value < 0.01), and a higher level of pain catastrophizing (ß (95%CI) 4.5 (0.5–8.6), p-value 0.03). Adolescents and young adults with only anxiety had increased fatigue (ß (95%CI) 11 (4.9–19.5). In adolescents and young adults with GJH alone, no impact on physical and psychosocial functioning was found. Adolescents and young adults with the combination of GJH and anxiety were significantly more impaired, showing decreased physical and psychosocial functioning with decreased workload, increased fatigue, and pain catastrophizing. Presence of GJH alone had no negative impact on physical and psychosocial functioning. This study confirms the association between GJH and anxiety, but especially emphasizes the disabling role of anxiety. Screening for anxiety is relevant in adolescents and young adults with GJH and might influence tailored interventions.
Deep Understanding of Urban Dynamics from Imprint Urban Toponymic Data Using a Spatial–Temporal–Semantic Analysis Approach
Authors: Chen Yurong , Zhang Feng , Li Xinba , Zhang Chuanrong , Chen Ninghua , Du Zhenhong , Liu Renyi , Wang Bo
Published: April 2021

Urban land use is constantly changing via human activities. These changes are recorded by imprint data. Traditionally, urban dynamics studies focus on two-dimensional spatiotemporal analysis. Based on our best knowledge, there is no study in the literature that uses imprint data for better understanding urban dynamics. In this research, we propose a spatial–temporal–semantic triple analytical framework to better understand urban dynamics by making full use of the imprint data, toponyms. The framework includes a text classification method and geographical analysis methods to understand urban dynamics in depth. Based on the inherent temporal and spatial information, we enrich semantic information with street names to explain urban dynamics in multiple dimensions. Taking Hangzhou city as an example, we used street names to reproduce the city changes over the past century. The results obtained through analysis of street names may accurately reflect the real development process of Hangzhou. This research demonstrates that imprint data left by urban development may play a pivotal role in better understanding urban dynamics.
Towards Measuring Shape Similarity of Polygons Based on Multiscale Features and Grid Context Descriptors
Authors: Fan Hongchao , Zhao Zhiyao , Li Wenwen
Published: April 2021

In spatial analysis applications, measuring the shape similarity of polygons is crucial for polygonal object retrieval and shape clustering. As a complex cognition process, measuring shape similarity should involve finding the difference between polygons, as objects in observation, in terms of visual perception and the differences of the regions, boundaries, and structures formed by the polygons from a mathematical point of view. In existing approaches, the shape similarity of polygons is calculated by only comparing their mathematical characteristics while not taking human perception into consideration. Aiming to solve this problem, we use the features of context and texture of polygons, since they are basic visual perception elements, to fit the cognition purpose. In this paper, we propose a contour diffusion method for the similarity measurement of polygons. By converting a polygon into a grid representation, the contour feature is represented as a multiscale statistic feature, and the region feature is transformed into condensed grid of context features. Instead of treating shape similarity as a distance between two representations of polygons, the proposed method observes similarity as a correlation between textures extracted by shape features. The experiments show that the accuracy of the proposed method is superior to that of the turning function and Fourier descriptor.
Transcriptome and MiRNAomics Analyses Identify Genes Associated with Cytoplasmic Male Sterility in Cotton (Gossypium hirsutum L.)
Authors: Li Min , Chen Li , Khan Aziz , Kong Xiangjun , Khan Muhammad Rabnawaz , Rao Muhammad Junaid , Wang Jibin , Wang Lingqiang , Zhou Ruiyang
Published: April 2021

Cytoplasmic male sterility (CMS) is important for large-scale hybrid seed production. Rearrangements in the mitochondrial DNA (mtDNA) for the cotton (Gossypium hirsutum L.) CMS line J4A were responsible for pollen abortion. However, the expression patterns of nuclear genes associated with pollen abortion and the molecular basis of CMS for J4A are unknown, and were the objectives of this study by comparing J4A with the J4B maintainer line. Cytological evaluation of J4A anthers showed that microspore abortion occurs during meiosis preventing pollen development. Changes in enzyme activity of mitochondrial respiratory chain complex IV and mitochondrial respiratory chain complex V and the content of ribosomal protein and ATP during anther abortion were observed for J4A suggesting insufficient synthesis of ATP hindered pollen production. Additionally, levels of sucrose, starch, soluble sugar, and fructose were significantly altered in J4A during the meiosis stage, suggesting reduced sugar metabolism contributed to sterility. Transcriptome and miRNAomics analyses identified 4461 differentially expressed mRNAs (DEGs) and 26 differentially expressed microRNAs (DEMIs). Pathway enrichment analysis indicated that the DEMIs were associated with starch and sugar metabolism. Six deduced target gene regulatory pairs that may participate in CMS were identified, ghi-MIR7484-10/mitogen-activated protein kinase kinase 6 (MAPKK6), ghi-undef-156/agamous-like MADS-box protein AGL19 (AGL19), ghi-MIR171-1-22/SNF1-related protein kinase regulatory subunit gamma-1 and protein trichome birefringence-like 38, and ghi-MIR156-(8/36)/WRKY transcription factor 28 (WRKY28). Overall, a putative CMS mechanism involving mitochondrial dysfunction, the ghi-MIR7484-10/MAPKK6 network, and reduced glucose metabolism was suggested, and ghi-MIR7484-10/MAPKK6 may be related to abnormal microspore meiosis and induction of excessive sucrose accumulation in anthers.
Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases
Authors: Salman Mootaz M. , Al-Obaidi Zaid , Kitchen Philip , Loreto Andrea , Bill Roslyn M. , Wade-Martins Richard
Published: April 2021

Neurodegenerative diseases (NDs) including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease are incurable and affect millions of people worldwide. The development of treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number of ligands that could be screened in biological assays, reducing the cost, time, and effort required to develop new drugs. In this review, we provide an introduction to CADD and examine the progress in applying CADD and other molecular docking studies to NDs. We provide an updated overview of potential therapeutic targets for various NDs and discuss some of the advantages and disadvantages of these tools.
The Potential of Calcium/Phosphate Containing MAO Implanted in Bone Tissue Regeneration and Biological Characteristics
Authors: Jian Shun-Yi , Aktug Salim Levent , Huang Hsuan-Ti , Ho Cheng-Jung , Lin Sung-Yen , Chen Chung-Hwan , Wang Min-Wen , Tseng Chun-Chieh
Published: April 2021

Micro arc oxidation (MAO) is a prominent surface treatment to form bioceramic coating layers with beneficial physical, chemical, and biological properties on the metal substrates for biomaterial applications. In this study, MAO treatment has been performed to modify the surface characteristics of AZ31 Mg alloy to enhance the biocompatibility and corrosion resistance for implant applications by using an electrolytic mixture of Ca3(PO4)2 and C10H16N2O8 (EDTA) in the solutions. For this purpose, the calcium phosphate (Ca-P) containing thin film was successfully fabricated on the surface of the implant material. After in-vivo implantation into the rabbit bone for four weeks, the apparent growth of soft tissues and bone healing effects have been documented. The morphology, microstructure, chemical composition, and phase structures of the coating were identified by SEM, XPS, and XRD. The corrosion resistance of the coating was analyzed by polarization and salt spray test. The coatings consist of Ca-P compounds continuously have proliferation activity and show better corrosion resistance and lower roughness in comparison to mere MAO coated AZ31. The corrosion current density decreased to approximately 2.81 × 10−7 A/cm2 and roughness was reduced to 0.622 μm. Thus, based on the results, it was anticipated that the development of degradable materials and implants would be feasible using this method. This study aims to fabricate MAO coatings for orthopedic magnesium implants that can enhance bioactivity, biocompatibility, and prevent additional surgery and implant-related infections to be used in clinical applications.
Detecting the Mechanism behind the Transition from Fixed Two-Dimensional Patterned Sika Deer (Cervus nippon) Dermal Papilla Cells to Three-Dimensional Pattern
Authors: Wei Guanning , Sun Hongmei , Wei Haijun , Qin Tao , Yang Yifeng , Xu Xiaohong , Zhao Shoujing
Published: April 2021

The hair follicle dermal papilla is critical for hair generation and de novo regeneration. When cultured in vitro, dermal papilla cells from different species demonstrate two distinguishable growth patterns under the conventional culture condition: a self-aggregative three dimensional spheroidal (3D) cell pattern and a two dimensional (2D) monolayer cell pattern, correlating with different hair inducing properties. Whether the loss of self-aggregative behavior relates to species-specific differences or the improper culture condition remains unclear. Can the fixed 2D patterned dermal papilla cells recover the self-aggregative behavior and 3D pattern also remains undetected. Here, we successfully constructed the two growth patterns using sika deer (Cervus nippon) dermal papilla cells and proved it was the culture condition that determined the dermal papilla growth pattern. The two growth patterns could transit mutually as the culture condition was exchanged. The fixed 2D patterned sika deer dermal papilla cells could recover the self-aggregative behavior and transit back to 3D pattern, accompanied by the restoration of hair inducing capability when the culture condition was changed. In addition, the global gene expressions during the transition from 2D pattern to 3D pattern were compared to detect the potential regulating genes and pathways involved in the recovery of 3D pattern and hair inducing capability.
Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters
Authors: Ciscato Francesco , Ferrone Lavinia , Masgras Ionica , Laquatra Claudio , Rasola Andrea
Published: April 2021

Hexokinases are a family of ubiquitous exose-phosphorylating enzymes that prime glucose for intracellular utilization. Hexokinase 2 (HK2) is the most active isozyme of the family, mainly expressed in insulin-sensitive tissues. HK2 induction in most neoplastic cells contributes to their metabolic rewiring towards aerobic glycolysis, and its genetic ablation inhibits malignant growth in mouse models. HK2 can dock to mitochondria, where it performs additional functions in autophagy regulation and cell death inhibition that are independent of its enzymatic activity. The recent definition of HK2 localization to contact points between mitochondria and endoplasmic reticulum called Mitochondria Associated Membranes (MAMs) has unveiled a novel HK2 role in regulating intracellular Ca2+ fluxes. Here, we propose that HK2 localization in MAMs of tumor cells is key in sustaining neoplastic progression, as it acts as an intersection node between metabolic and survival pathways. Disrupting these functions by targeting HK2 subcellular localization can constitute a promising anti-tumor strategy.
Immune-Associated Proteins Are Enriched in Lung Tissue-Derived Extracellular Vesicles during Allergen-Induced Eosinophilic Airway Inflammation
Authors: Lässer Cecilia , Kishino Yasunari , Park Kyong-su , Shelke Ganesh Vilas , Karimi Nasibeh , Suzuki Shintaro , Hovhannisyan Lilit , Rådinger Madeleine , Lötvall Jan
Published: April 2021

Studying the proteomes of tissue-derived extracellular vesicles (EVs) can lead to the identification of biomarkers of disease and can provide a better understanding of cell-to-cell communication in both healthy and diseased tissue. The aim of this study was to apply our previously established tissue-derived EV isolation protocol to mouse lungs in order to determine the changes in the proteomes of lung tissue-derived EVs during allergen-induced eosinophilic airway inflammation. A mouse model for allergic airway inflammation was used by sensitizing the mice intraperitoneal with ovalbumin (OVA), and one week after the final sensitization, the mice were challenged intranasal with OVA or PBS. The animals were sacrificed 24 h after the final challenge, and their lungs were removed and sliced into smaller pieces that were incubated in culture media with DNase I and Collagenase D for 30 min at 37 °C. Vesicles were isolated from the medium by ultracentrifugation and bottom-loaded iodixanol density cushions, and the proteomes were determined using quantitative mass spectrometry. More EVs were present in the lungs of the OVA-challenged mice compared to the PBS-challenged control mice. In total, 4510 proteins were quantified in all samples. Among them, over 1000 proteins were significantly altered (fold change >2), with 614 proteins being increased and 425 proteins being decreased in the EVs from OVA-challenged mice compared to EVs from PBS-challenged animals. The associated cellular components and biological processes were analyzed for the altered EV proteins, and the proteins enriched during allergen-induced airway inflammation were mainly associated with gene ontology (GO) terms related to immune responses. In conclusion, EVs can be isolated from mouse lung tissue, and the EVs’ proteomes undergo changes in response to allergen-induced airway inflammation. This suggests that the composition of lung-derived EVs is altered in diseases associated with inflammation of the lung, which may have implications in type-2 driven eosinophilic asthma pathogenesis.
Phenotypic and Functional Consequences of PLT Binding to Monocytes and Its Association with Clinical Features in SLE
Authors: Mariscal Anaís , Zamora Carlos , Magallares Berta , Salman-Monte Tarek Carlos , Ortiz Mª Àngels , Díaz-Torné Cesar , Castellví Iván , Corominas Héctor , Vidal Silvia
Published: April 2021

Platelets (PLTs) can modulate the immune system through the release of soluble mediators or through interaction with immune cells. Monocytes are the main immune cells that bind with PLTs, and this interaction is increased in several inflammatory and autoimmune conditions, including systemic lupus erythematosus (SLE). Our aim was to characterize the phenotypic and functional consequences of PLT binding to monocytes in healthy donors (HD) and in SLE and to relate it to the pathogenesis of SLE. We analyzed the phenotypic and functional features of monocytes with non-activated and activated bound PLTs by flow cytometry. We observed that monocytes with bound PLTs and especially those with activated PLTs have an up-regulated HLA-DR, CD86, CD54, CD16 and CD64 expression. Monocytes with bound PLTs also have an increased capacity for phagocytosis, though not for efferocytosis. In addition, monocytes with bound PLTs have increased IL-10, but not TNF-α, secretion. The altered phenotypic and functional features are comparable in SLE and HD monocytes and in bound PLTs. However, the percentages of monocytes with bound PLTs are significantly higher in SLE patients and are associated with undetectable levels of anti-dsDNA antibodies and hematuria, and with normal C3 and albumin/creatinine levels. Our results suggest that PLTs have a modulatory influence on monocytes and that this effect may be highlighted by an increased binding of PLTs to monocytes in autoimmune conditions.
Protective Effects of a Lutein Ester Prodrug, Lutein Diglutaric Acid, against H2O2-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells
Authors: Muangnoi Chawanphat , Phumsuay Rianthong , Jongjitphisut Nattapong , Waikasikorn Pasin , Sangsawat Monsin , Rashatasakhon Paitoon , Paraoan Luminita , Rojsitthisak Pornchai
Published: April 2021

Oxidative stress-induced cell damage and death of the retinal pigmented epithelium (RPE), a polarized monolayer that maintains retinal health and homeostasis, lead to the development of age-related macular degeneration (AMD). Several studies show that the naturally occurring antioxidant Lutein (Lut) can protect RPE cells from oxidative stress. However, the poor solubility and low oral bioavailability limit the potential of Lut as a therapeutic agent. In this study, lutein diglutaric acid (Lut-DG), a prodrug of Lut, was synthesized and its ability to protect human ARPE-19 cells from oxidative stress was tested compared to Lut. Both Lut and Lut-DG significantly decreased H2O2-induced reactive oxygen species (ROS) production and protected RPE cells from oxidative stress-induced death. Moreover, the immunoblotting analysis indicated that both drugs exerted their protective effects by modulating phosphorylated MAPKs (p38, ERK1/2 and SAPK/JNK) and downstream molecules Bax, Bcl-2 and Cytochrome c. In addition, the enzymatic antioxidants glutathione peroxidase (GPx) and catalase (CAT) and non-enzymatic antioxidant glutathione (GSH) were enhanced in cells treated with Lut and Lut-DG. In all cases, Lut-DG was more effective than its parent drug against oxidative stress-induced damage to RPE cells. These findings highlight Lut-DG as a more potent compound than Lut with the protective effects against oxidative stress in RPE cells through the modulation of key MAPKs, apoptotic and antioxidant molecular pathways.
Screening for Interacting Proteins with Peptide Biomarker of Blood–Brain Barrier Alteration under Inflammatory Conditions
Authors: Vargas-Sanchez Karina , Losada-Barragán Monica , Mogilevskaya Maria , Novoa-Herrán Susana , Medina Yehidi , Buendía-Atencio Cristian , Lorett-Velásquez Vaneza , Martínez-Bernal Jessica , Gonzalez-Reyes Rodrigo E. , Ramírez David , Petry Klaus G.
Published: April 2021

Neurodegenerative diseases are characterized by increased permeability of the blood–brain barrier (BBB) due to alterations in cellular and structural components of the neurovascular unit, particularly in association with neuroinflammation. A previous screening study of peptide ligands to identify molecular alterations of the BBB in neuroinflammation by phage-display, revealed that phage clone 88 presented specific binding affinity to endothelial cells under inflammatory conditions in vivo and in vitro. Here, we aimed to identify the possible target receptor of the peptide ligand 88 expressed under inflammatory conditions. A cross-link test between phage-peptide-88 with IL-1β-stimulated human hCMEC cells, followed by mass spectrometry analysis, was used to identify the target of peptide-88. We modeled the epitope–receptor molecular interaction between peptide-88 and its target by using docking simulations. Three proteins were selected as potential target candidates and tested in enzyme-linked immunosorbent assays with peptide-88: fibronectin, laminin subunit α5 and laminin subunit β-1. Among them, only laminin subunit β-1 presented measurable interaction with peptide-88. Peptide-88 showed specific interaction with laminin subunit β-1, highlighting its importance as a potential biomarker of the laminin changes that may occur at the BBB endothelial cells under pathological inflammation conditions.
Lost-in-Translation of Metabolic Effects of Inorganic Nitrate in Type 2 Diabetes: Is Ascorbic Acid the Answer?
Authors: Bahadoran Zahra , Mirmiran Parvin , Kashfi Khosrow , Ghasemi Asghar
Published: April 2021

Beneficial metabolic effects of inorganic nitrate (NO3−) and nitrite (NO2−) in type 2 diabetes mellitus (T2DM) have been documented in animal experiments; however, this is not the case for humans. Although it has remained an open question, the redox environment affecting the conversion of NO3− to NO2− and then to NO is suggested as a potential reason for this lost-in-translation. Ascorbic acid (AA) has a critical role in the gastric conversion of NO2− to NO following ingestion of NO3−. In contrast to AA-synthesizing species like rats, the lack of ability to synthesize AA and a lower AA body pool and plasma concentrations may partly explain why humans with T2DM do not benefit from NO3−/NO2− supplementation. Rats also have higher AA concentrations in their stomach tissue and gastric juice that can significantly potentiate gastric NO2−-to-NO conversion. Here, we hypothesized that the lack of beneficial metabolic effects of inorganic NO3− in patients with T2DM may be at least in part attributed to species differences in AA metabolism and also abnormal metabolism of AA in patients with T2DM. If this hypothesis is proved to be correct, then patients with T2DM may need supplementation of AA to attain the beneficial metabolic effects of inorganic NO3− therapy.
Effects of TGF-β1 Receptor Inhibitor GW788388 on the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells
Authors: Lho Yunmee , Do Jun-Young , Heo Jung-Yoon , Kim A-Young , Kim Sang-Woon , Kang Seok-Hui
Published: April 2021

We investigated the effectiveness of the transforming growth factor beta-1 (TGF-β) receptor inhibitor GW788388 on the epithelial to mesenchymal transition (EMT) using human peritoneal mesothelial cells (HPMCs) and examined the effectiveness of GW788388 on the peritoneal membrane using a peritoneal fibrosis mouse model. HPMCs were treated with TGF-β with or without GW788388. Animal experiments were conducted on male C57/BL6 mice. Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate. GW788388 was administered by once-daily oral gavage. The morphological change, cell migration, and invasion resulted from TGF-β treatment, but these changes were attenuated by cotreatment with GW788388. TGF-β-treated HPMCs decreased the level of the epithelial cell marker and increased the levels of the mesenchymal cell markers. Cotreatment with GW788388 reversed these changes. Phosphorylated Smad2 and Smad3 protein levels were stimulated with TGF-β and the change was attenuated by cotreatment with GW788388. For the peritoneal fibrosis mice, thickness and collagen deposition of parietal peritoneum was increased, but this change was attenuated by cotreatment with GW788388. GW788388, an orally available potent TGF-β receptor type 1 inhibitor, effectively attenuated TGF-β-induced EMT in HPMCs. Cotreatment with GW788388 improved peritoneal thickness and fibrosis, and recovered peritoneal membrane function in a peritoneal fibrosis mouse model.
Identification of Novel Toxin Genes from the Stinging Nettle Caterpillar Parasa lepida (Cramer, 1799): Insights into the Evolution of Lepidoptera Toxins
Authors: Mitpuangchon Natrada , Nualcharoen Kwan , Boonrotpong Singtoe , Engsontia Patamarerk
Published: April 2021

Many animal species can produce venom for defense, predation, and competition. The venom usually contains diverse peptide and protein toxins, including neurotoxins, proteolytic enzymes, protease inhibitors, and allergens. Some drugs for cancer, neurological disorders, and analgesics were developed based on animal toxin structures and functions. Several caterpillar species possess venoms that cause varying effects on humans both locally and systemically. However, toxins from only a few species have been investigated, limiting the full understanding of the Lepidoptera toxin diversity and evolution. We used the RNA-seq technique to identify toxin genes from the stinging nettle caterpillar, Parasa lepida (Cramer, 1799). We constructed a transcriptome from caterpillar urticating hairs and reported 34,968 unique transcripts. Using our toxin gene annotation pipeline, we identified 168 candidate toxin genes, including protease inhibitors, proteolytic enzymes, and allergens. The 21 P. lepida novel Knottin-like peptides, which do not show sequence similarity to any known peptide, have predicted 3D structures similar to tarantula, scorpion, and cone snail neurotoxins. We highlighted the importance of convergent evolution in the Lepidoptera toxin evolution and the possible mechanisms. This study opens a new path to understanding the hidden diversity of Lepidoptera toxins, which could be a fruitful source for developing new drugs.
Using Data Mining and Network Analysis to Infer Arboviral Dynamics: The Case of Mosquito-Borne Flaviviruses Reported in Mexico
Authors: Sotomayor-Bonilla Jesús , Callejo-Canal Enrique Del , González-Salazar Constantino , Suzán Gerardo , Stephens Christopher R.
Published: April 2021

Given the significant impact of mosquito-borne flaviviruses (MBFVs) on both human and animal health, predicting their dynamics and understanding their transmission cycle is of the utmost importance. Usually, predictions about the distribution of priority pathogens, such as Dengue, Yellow fever, West Nile Virus and St. Louis encephalitis, relate abiotic elements to simple biotic components, such as a single causal agent. Furthermore, focusing on single pathogens neglects the possibility of interactions and the existence of common elements in the transmission cycles of multiple pathogens. A necessary, but not sufficient, condition that a mosquito be a vector of a MBFV is that it co-occurs with hosts of the pathogen. We therefore use a recently developed modeling framework, based on co-occurrence data, to infer potential biotic interactions between those mosquito and mammal species which have previously been identified as vectors or confirmed positives of at least one of the considered MBFVs. We thus create models for predicting the relative importance of mosquito species as potential vectors for each pathogen, and also for all pathogens together, using the known vectors to validate the models. We infer that various mosquito species are likely to be significant vectors, even though they have not currently been identified as such, and are likely to harbor multiple pathogens, again validating the predictions with known results. Besides the above “niche-based” viewpoint we also consider an assemblage-based analysis, wherein we use a community-identification algorithm to identify those mosquito and/or mammal species that form assemblages by dint of their significant degree of co-occurrence. The most cohesive assemblage includes important primary vectors, such as A. aegypti, A. albopictus, C. quinquefasciatus, C. pipiens and mammals with abundant populations that are well-adapted to human environments, such as the white-tailed deer (Odocoileus virginianus), peccary (Tayassu pecari), opossum (Didelphis marsupialis) and bats (Artibeus lituratus and Sturnira lilium). Our results suggest that this assemblage has an important role in the transmission dynamics of this viral group viewed as a complex multi-pathogen-vector-host system. By including biotic risk factors our approach also modifies the geographical risk profiles of the spatial distribution of MBFVs in Mexico relative to a consideration of only abiotic niche variables.
Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia
Authors: Inaba Hiroto , Pui Ching-Hon
Published: April 2021

The outcomes of pediatric acute lymphoblastic leukemia (ALL) have improved remarkably during the last five decades. Such improvements were made possible by the incorporation of new diagnostic technologies, the effective administration of conventional chemotherapeutic agents, and the provision of better supportive care. With the 5-year survival rates now exceeding 90% in high-income countries, the goal for the next decade is to improve survival further toward 100% and to minimize treatment-related adverse effects. Based on genome-wide analyses, especially RNA-sequencing analyses, ALL can be classified into more than 20 B-lineage subtypes and more than 10 T-lineage subtypes with prognostic and therapeutic implications. Response to treatment is another critical prognostic factor, and detailed analysis of minimal residual disease can detect levels as low as one ALL cell among 1 million total cells. Such detailed analysis can facilitate the rational use of molecular targeted therapy and immunotherapy, which have emerged as new treatment strategies that can replace or reduce the use of conventional chemotherapy.
Impact of Isolated High Home Systolic Blood Pressure and Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus: A 5-Year Prospective Cohort Study
Authors: Kitagawa Nobuko , Kitagawa Noriyuki , Ushigome Emi , Ushigome Hidetaka , Yokota Isao , Nakanishi Naoko , Hamaguchi Masahide , Asano Mai , Yamazaki Masahiro , Fukui Michiaki
Published: April 2021

Background: A previous 2-year cohort study has shown that isolated high home systolic blood pressure (IH-HSBP) may increase the risk of diabetic nephropathy, using normal HBP as a reference. However, this association has not been previously assessed in the medium to long term. Methods: This prospective 5-year cohort study of 424 patients, with normal or mildly increased albuminuria, investigated the effect of IH-HSBP on the risk of diabetic nephropathy in patients with type 2 diabetes mellitus. Diabetic nephropathy was defined as an advancement from normal or mildly increased albuminuira to moderate or severely increased albuminuria. Results: Among 424 patients, 75 developed diabetic nephropathy during the study period. The adjusted odds ratio for developing diabetic nephropathy given IH-HSBP was 2.39 (95% confidence interval, 1.15–4.96, p = 0.02). The odds ratio for developing nephropathy in patients with IH-HSBP younger than 65 years was higher than that in patients with IH-HSBP older than 65 years. Conclusion: IH-HSBP was associated with an increased risk of diabetic nephropathy among type 2 diabetes mellitus patients with normal or mildly increased albuminuria in the medium to long term. The results support and strengthen previous reports. These findings suggest that IH-HSBP might be a useful marker in disease prognostication.
Right Ventricular Volume and Function Assessment in Congenital Heart Disease Using CMR Compressed-Sensing Real-Time Cine Imaging
Authors: Longère Benjamin , Pagniez Julien , Coisne Augustin , Farah Hedi , Schmidt Michaela , Forman Christoph , Silvestri Valentina , Simeone Arianna , Gkizas Christos V , Hennicaux Justin , Cheasty Emma , Toupin Solenn , Montaigne David , Pontana François
Published: April 2021

Background and objective: To evaluate the reliability of compressed-sensing (CS) real-time single-breath-hold cine imaging for quantification of right ventricular (RV) function and volumes in congenital heart disease (CHD) patients in comparison with the standard multi-breath-hold technique. Methods: Sixty-one consecutive CHD patients (mean age = 22.2 ± 9.0 (SD) years) were prospectively evaluated during either the initial work-up or after repair. For each patient, two series of cine images were acquired: first, the reference segmented multi-breath-hold steady-state free-precession sequence (SSFPref), including a short-axis stack, one four-chamber slice, and one long-axis slice; then, an additional real-time compressed-sensing single-breath-hold sequence (CSrt) providing the same slices. Two radiologists independently assessed the image quality and RV volumes for both techniques, which were compared using the Wilcoxon test and paired Student’s t test, Bland–Altman, and linear regression analyses. The visualization of wall-motion disorders and tricuspid-regurgitation-related signal voids were also analyzed. Results: The mean acquisition time for CSrt was 22.4 ± 6.2 (SD) s (95% CI: 20.8–23.9 s) versus 442.2 ± 89.9 (SD) s (95% CI: 419.2–465.2 s) for SSFPref (p < 0.001). The image quality of CSrt was diagnostic in all examinations and was mostly rated as good (n = 49/61; 80.3%). There was a high correlation between SSFPref and CSrt images regarding RV ejection fraction (49.8 ± 7.8 (SD)% (95% CI: 47.8–51.8%) versus 48.7 ± 8.6 (SD)% (95% CI: 46.5–50.9%), respectively; r = 0.94) and RV end-diastolic volume (192.9 ± 60.1 (SD) mL (95% CI: 177.5–208.3 mL) versus 194.9 ± 62.1 (SD) mL (95% CI: 179.0–210.8 mL), respectively; r = 0.98). In CSrt images, tricuspid-regurgitation and wall-motion disorder visualization was good (area under receiver operating characteristic curve (AUC) = 0.87) and excellent (AUC = 1), respectively. Conclusions: Compressed-sensing real-time cine imaging enables, in one breath hold, an accurate assessment of RV function and volumes in CHD patients in comparison with standard SSFPref, allowing a substantial improvement in time efficiency.
Saliva Gene Promoter Hypermethylation as a Biomarker in Oral Cancer
Authors: Rapado-González Óscar , López-Cedrún José Luis , López-López Rafael , Rodríguez-Ces Ana María , Suárez-Cunqueiro María Mercedes
Published: April 2021

Oral carcinogenesis is a multistep process characterized by a summation of multiple genetic and epigenetic alterations in key regulatory genes. The silencing of genes by aberrant promoter hypermethylation is thought to be an important epigenetic event in cancer development and progression which has great potential as a biomarker for early diagnosis, tumor molecular subtyping, prognosis, monitoring, and therapy. Aberrant DNA methylation has been detected in different liquid biopsies, which may represent a potential alternative to solid biopsies. The detection of methylated genes in saliva may have clinical application for noninvasive oral cancer screening and early diagnosis. Here, we review the current evidence on gene promoter hypermethylation in saliva.
Application of Métier-Based Approaches for Spatial Planning and Management: A Case Study on a Mixed Trawl Fishery in Taiwan
Authors: Lee Yi-Jou , Su Nan-Jay , Lee Hung-Tai , Hsu William Wei-Yuan , Liao Cheng-Hsin
Published: April 2021

Mixed fisheries refer to fishing activities that catch more than one species simultaneously, and a species may be fished using different gear. A trawl fishery shares these features to exploit multiple species simultaneously, with diverse fishing gear and strategies. The situation becomes more complex when interactions among fleet dynamics, fishing activities, and fishery resources are involved and influence each other. Information regarding the operational patterns may be hidden in a set of long-term big data. This study aims to investigate the fishery structure and fleet dynamics of trawl fisheries in Taiwan for spatial planning and management, based on a long-term dataset from a management system that collects information by using voyage data recorders (VDR) and dockside observers. We applied a two-step data mining process with a clustering algorithm to classify the main groups of fishery resources and then identified 18 catch métiers based on catch composition. The target species, operation pattern, and fishing season were determined for each métier, and associated with the relevant fishery resources and the fishing gear used. Additionally, fishing effects on target species were estimated using information on fishing grounds and trajectories from VDR. The métier-based approach was successfully applied to define the six major fishery resources targeted by trawlers. We examined the key features of fishing activity associated with catch composition and spatial-temporal fishing metrics, which could be used to provide suggestions for the spatial planning and management of the mixed trawl fishery in the offshore waters of Taiwan.
High-Throughput Detection of Multiple miRNAs and Methylated DNA by Droplet Digital PCR
Authors: Li Ning , Dhilipkannah Pushpa , Jiang Feng
Published: April 2021

Altered miRNA expression and DNA methylation have highly active and diverse roles in carcinogenesis. Simultaneous detection of the molecular aberrations may have a synergistic effect on the diagnosis of malignancies. Herein, we develop a high-throughput assay for detecting multiple miRNAs and DNA methylation using droplet digital PCR (ddPCR) coupled with a 96-microwell plate. The microplate-based ddPCR could absolutely and reproducibly quantify 15 miRNAs and 14 DNA methylation sites with a high sensitivity (one copy/µL and 0.1%, respectively). Analyzing sputum and plasma of 40 lung cancer patients and 36 cancer-free smokers by this approach identified an integrated biomarker panel consisting of two sputum miRNAs (miRs-31-5p and 210-3p), one sputum DNA methylation (RASSF1A), and two plasma miRNAs (miR-21-5p and 126) for the diagnosis of lung cancer with higher sensitivity and specificity compared with a single type of biomarker. The diagnostic value of the integrated biomarker panel for the early detection of lung cancer was confirmed in a different cohort of 36 lung cancer patients and 39 cancer-free smokers. The high-throughput assay for quantification of multiple molecular aberrations across sputum and plasma could improve the early detection of lung cancer.
A System for Monitoring Acoustics to Supplement an Animal Welfare Plan for Bottlenose Dolphins
Authors: Jones Brittany L. , Oswald Michael , Tufano Samantha , Baird Mark , Mulsow Jason , Ridgway Sam H.
Published: April 2021

Animal sounds are commonly used by humans to infer information about their motivations and their health, yet, acoustic data is an underutilized welfare biomarker especially for aquatic animals. Here, we describe an acoustic monitoring system that is being implemented at the U.S. Navy Marine Mammal Program where dolphins live in groups in ocean enclosures in San Diego Bay. A four-element bottom mounted hydrophone array is used to continuously record, detect and localize acoustic detections from this focal group. Software provides users an automated comparison of the current acoustic behavior to group historical data which can be used to identify periods of normal, healthy thriving dolphins, and allows rare instances of deviations from typical behavior to stand out. Variations in a group or individual’s call rates can be correlated with independent veterinary examinations and behavioral observations in order to better assess dolphin health and welfare. Additionally, the monitoring system identifies time periods in which a sound source from San Diego Bay is of high-enough amplitude that the received level at our array is considered a potential concern for the focal animals. These time stamps can be used to identify and potentially mitigate exposures to acoustic sources that may otherwise not be obvious to human listeners. We hope this application inspires zoos and aquaria to innovate and create ways to incorporate acoustic information into their own animal welfare management programs.
Understanding the Driving Forces and Actors of Land Change Due to Forestry and Agricultural Practices in Sumatra and Kalimantan: A Systematic Review
Authors: Juniyanti Lila , Purnomo Herry , Kartodihardjo Hariadi , Prasetyo Lilik Budi
Published: April 2021

Indonesia has experienced one of the world’s greatest dynamic land changes due to forestry and agricultural practices. Understanding the drivers behind these land changes remains challenging, partly because landscape research is spread across many domains and disciplines. We provide a systematic review of 91 studies that identify the causes and land change actors across Sumatra and Kalimantan. Our review shows that oil palm expansion is the most prominent (65 studies) among multiple direct causes of land change. We determined that property rights are the most prominent issue (31 studies) among the multiple underlying causes of land change. Distinct combinations of mainly economic, institutional, political, and social underlying drivers determine land change, rather than single key drivers. Our review also shows that central and district governments as decision-making actors are prominent (69 studies) among multiple land change actors. Our systematic review indicates knowledge gaps that can be filled by clarifying the identification and role of actors in land change.
Review of Rotor Balancing Methods
Authors: Li Liqing , Cao Shuqian , Li Jing , Nie Rimin , Hou Lanlan
Published: April 2021

This review is dedicated to balancing methods that are used to solve the rotor-balancing problem. To ensure a stable operation over an operating speed range, it is necessary to balance a rotor. The traditional methods, including the influence coefficient method (ICM) and the modal balancing method (MBM) are introduced, and the research progress, operation steps, advantages and disadvantages of these methods are elaborated. The classification of new balancing methods is reviewed. Readers are expected to obtain an overview of the research progress of existing balancing methods and the directions for future studies.
Stabilization of Stochastic Differential Equations Driven by G-Brownian Motion with Aperiodically Intermittent Control
Authors: Duan Pengju
Published: April 2021

The paper is devoted to studying the exponential stability of a mild solution of stochastic differential equations driven by G-Brownian motion with an aperiodically intermittent control. The aperiodically intermittent control is added into the drift coefficients, when intermittent intervals and coefficients satisfy suitable conditions; by use of the G-Lyapunov function, the p-th exponential stability is obtained. Finally, an example is given to illustrate the availability of the obtained results.