bluuebunny/crossref_metadata_2025 huggingface dataset:
A Gene Signature Derived from the Loss of CDKN1A (p21) Is Associated with CMS4 Colorectal Cancer
Authors: Bueno-Fortes Santiago , Muenzner Julienne K. , Berral-Gonzalez Alberto , Hampel Chuanpit , Lindner Pablo , Berninger Alexandra , Huebner Kerstin , Kunze Philipp , Bäuerle Tobias , Erlenbach-Wuensch Katharina , Sánchez-Santos José Manuel , Hartmann Arndt , De Las Rivas Javier , Schneider-Stock Regine
Published: December 2021

The epithelial–mesenchymal transition (EMT) is associated with tumor aggressiveness and increased invasion, migration, metastasis, angiogenesis, and drug resistance. Although the HCT116 p21-/- cell line is well known for its EMT-associated phenotype, with high Vimentin and low E-cadherin protein levels, the gene signature of this rather intermediate EMT-like cell line has not been determined so far. In this work, we present a robust molecular and bioinformatics analysis, to reveal the associated gene expression profile and its correlation with different types of colorectal cancer tumors. We compared the quantitative signature obtained with the NanoString platform with the expression profiles of colorectal cancer (CRC) Consensus Molecular Subtypes (CMS) as identified, and validated the results in a large independent cohort of human tumor samples. The expression signature derived from the p21-/- cells showed consistent and reliable numbers of upregulated and downregulated genes, as evaluated with two machine learning methods against the four CRC subtypes (i.e., CMS1, 2, 3, and 4). High concordance was found between the upregulated gene signature of HCT116 p21-/- cells and the signature of the CMS4 mesenchymal subtype. At the same time, the upregulated gene signature of the native HCT116 cells was similar to that of CMS1. Using a multivariate Cox regression model to analyze the survival data in the CRC tumor cohort, we selected genes that have a predictive risk power (with a significant gene risk incidence score). A set of genes of the mesenchymal signature was proven to be significantly associated with poor survival, specifically in the CMS4 CRC human cohort. We suggest that the gene signature of HCT116 p21-/- cells could be a suitable metric for mechanistic studies regarding the CMS4 signature and its functional consequences in CRC. Moreover, this model could help to discover the molecular mechanisms of intermediate EMT, which is known to be associated with extraordinarily high stemness and drug resistance.
CO2 Reduction to Valuable Chemicals on TiO2-Carbon Photocatalysts Deposited on Silica Cloth
Authors: Morawski Antoni , Ćmielewska Katarzyna , Witkowski Kordian , Kusiak-Nejman Ewelina , Pełech Iwona , Staciwa Piotr , Ekiert Ewa , Sibera Daniel , Wanag Agnieszka , Gano Marcin , Narkiewicz Urszula
Published: December 2021

A new photocatalyst for CO2 reduction has been presented. The photocatalyst was prepared from a combination of a commercial P25 with a mesopore structure and carbon spheres with a microporous structure with high CO2 adsorption capacity. Then, the obtained hybrid TiO2-carbon sphere photocatalysts were deposited on a glass fiber fabric. The combined TiO2-carbon spheres/silica cloth photocatalysts showed higher efficiency in the two-electron CO2 reduction towards CO than in the eight-electron reaction to methane. The 0.5 g graphitic carbon spheres combined with 1 g of TiO2 P25 resulted in almost 100% selectivity to CO. From a practical point of view, this is promising as it economically eliminates the need to separate CO from the gas mixture after the reaction, which also contains CH4 and H2.
Analysis of TCR Repertoire by High-Throughput Sequencing Indicates the Feature of T Cell Immune Response after SARS-CoV-2 Infection
Authors: Wang Yifan , Duan Fugang , Zhu Zhu , Yu Meng , Jia Xiaodong , Dai Hui , Wang Pingzhang , Qiu Xiaoyan , Lu Yinying , Huang Jing
Published: December 2021

Coronavirus disease 2019 (COVID-19) is a global infectious disease caused by the SARS-CoV-2 coronavirus. T cells play an essential role in the body’s fighting against the virus invasion, and the T cell receptor (TCR) is crucial in T cell-mediated virus recognition and clearance. However, little has been known about the features of T cell response in convalescent COVID-19 patients. In this study, using 5′RACE technology and PacBio sequencing, we analyzed the TCR repertoire of COVID-19 patients after recovery for 2 weeks and 6 months compared with the healthy donors. The TCR clustering and CDR3 annotation were exploited to discover groups of patient-specific TCR clonotypes with potential SARS-CoV-2 antigen specificities. We first identified CD4+ and CD8+ T cell clones with certain clonal expansion after infection, and then observed the preferential recombination usage of V(D) J gene segments in CD4+ and CD8+ T cells of COVID-19 patients with different convalescent stages. More important, the TRBV6-5-TRBD2-TRBJ2-7 combination with high frequency was shared between CD4+ T and CD8+ T cells of different COVID-19 patients. Finally, we found the dominant characteristic motifs of the CDR3 sequence between recovered COVID-19 and healthy control. Our study provides novel insights on TCR in COVID-19 with different convalescent phases, contributing to our understanding of the immune response induced by SARS-CoV-2.
High Throughput Small Molecule Screen for Reactivation of FMR1 in Fragile X Syndrome Human Neural Cells
Authors: Hunt Jack F. V. , Li Meng , Risgaard Ryan , Ananiev Gene E. , Wildman Scott , Zhang Fan , Bugni Tim S. , Zhao Xinyu , Bhattacharyya Anita
Published: December 2021

Fragile X syndrome (FXS) is the most common inherited cause of autism and intellectual disability. The majority of FXS cases are caused by transcriptional repression of the FMR1 gene due to epigenetic changes that are not recapitulated in current animal disease models. FXS patient induced pluripotent stem cell (iPSC)-derived gene edited reporter cell lines enable novel strategies to discover reactivators of FMR1 expression in human cells on a much larger scale than previously possible. Here, we describe the workflow using FXS iPSC-derived neural cell lines to conduct a massive, unbiased screen for small molecule activators of the FMR1 gene. The proof-of-principle methodology demonstrates the utility of human stem-cell-based methodology for the untargeted discovery of reactivators of the human FMR1 gene that can be applied to other diseases.
Biochemical, Biophysical and Functional Characterization of an Insoluble Iron Containing Hepcidin–Ferritin Chimeric Monomer Assembled Together with Human Ferritin H/L Chains at Different Molar Ratios
Authors: Boumaiza Mohamed , Fhoula Imene , Carmona Fernando , Poli Maura , Asperti Michela , Gianoncelli Alessandra , Bertuzzi Michela , Arosio Paolo , Marzouki Mohamed Nejib
Published: December 2021

Hepcidin and ferritin are key proteins of iron homeostasis in mammals. In this study, we characterize a chimera by fusing camel hepcidin to a human ferritin H-chain to verify if it retained the properties of the two proteins. The construct (HepcH) is expressed in E. coli in an insoluble and iron-containing form. To characterize it, the product was incubated with ascorbic acid and TCEP to reduce and solubilize the iron, which was quantified with ferrozine. HepcH bound approximately five times more iron than the wild type human ferritin, due to the presence of the hepcidin moiety. To obtain a soluble and stable product, the chimera was denatured and renatured together with different amounts of L-ferritin of the H-chain in order to produce 24-shell heteropolymers with different subunit proportions. They were analyzed by denaturing and non-denaturing PAGE and by mass spectroscopy. At the 1:5 ratio of HepcH to H- or L-ferritin, a stable and soluble molecule was obtained. Its biological activity was verified by its ability to both bind specifically cell lines that express ferroportin and to promote ferroportin degradation. This chimeric molecule showed the ability to bind both mouse J774 macrophage cells, as well as human HepG2 cells, via the hepcidin–ferroportin axis. We conclude that the chimera retains the properties of both hepcidin and ferritin and might be exploited for drug delivery.
Push-Pull Heterocyclic Dyes Based on Pyrrole and Thiophene: Synthesis and Evaluation of Their Optical, Redox and Photovoltaic Properties
Authors: Fernandes Sara S. M. , Castro Maria Cidália R. , Ivanou Dzmitry , Mendes Adélio , Raposo Maria Manuela M.
Published: December 2021

Three heterocyclic dyes were synthesized having in mind the changes in the photovoltaic, optical and redox properties by functionalization of 5-aryl-thieno[3,2-b]thiophene, 5-arylthiophene and bis-methylpyrrolylthiophene π-bridges with different donor, acceptor/anchoring groups. Knoevenagel condensation of the aldehyde precursors with 2-cyanoacetic acid was used to prepare the donor-acceptor functionalized heterocyclic molecules. These organic metal-free dyes are constituted by thieno[3,2-b]thiophene, arylthiophene, bis-methylpyrrolylthiophene, spacers and one or two cyanoacetic acid acceptor groups and different electron donor groups (alkoxyl, and pyrrole electron-rich heterocycle). The evaluation of the redox, optical and photovoltaic properties of these compounds indicate that 5-aryl-thieno[3,2-b]thiophene-based dye functionalized with an ethoxyl electron donor and a cyanoacetic acid electron acceptor group/anchoring moiety displays as sensitizer for DSSCs the best conversion efficiency (2.21%). It is mainly assigned to the higher molar extinction coefficient, long π-conjugation of the heterocyclic system, higher oxidation potential and strong electron donating capacity of the ethoxyl group compared to the pirrolyl moiety.
Detection of Microorganisms in Body Fluids via MTT-PMS Assay
Authors: Chen Cheng-Han , Tsao Yu-Ting , Yeh Po-Ting , Liao Yu-Hsiang , Lee Yi-Tzu , Liao Wan-Ting , Wang Yung-Chih , Shen Ching-Fen , Cheng Chao-Min
Published: December 2021

Early detection of microorganisms is essential for the management of infectious diseases. However, this is challenging, as traditional culture methods are labor-intensive and time-consuming. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-phenazine methosulfate (MTT-PMS) assay has been used to evaluate the metabolic activity in live cells and can thus be used for detecting living microorganisms. With the addition of NaOH and Tris-EDTA, the same approach can be accelerated (within 15 min) and used for the quick detection of common bacterial pathogens. The assay results can be evaluated colorimetrically or semi-quantitatively. Here, the quick detection by MTT-PMS assay was further investigated. The assay had a detection limit of approximately 104 CFU/mL. In clinical evaluations, we used the MTT-PMS assay to detect clinical samples and bacteriuria (>105 CFU/mL). The negative predictive value of the MTT-PMS assay for determining bacteriuria was 79.59% but was 100% when the interference of abnormal blood was excluded. Thus, the MTT-PMS assay might be a potential “rule-out” tool for bacterial detection in clinical samples, at a cost of approximately USD 1 per test. Owing to its low cost, rapid results, and easy-to-use characteristics, the MTT-PMS assay may be a potential tool for microorganism detection.
“What Is Hidden behind the Mask?” Facial Emotion Recognition at the Time of COVID-19 Pandemic in Cognitively Normal Multiple Sclerosis Patients
Authors: Ziccardi Stefano , Crescenzo Francesco , Calabrese Massimiliano
Published: December 2021

Social cognition deficits have been described in people with multiple sclerosis (PwMS), even in absence of a global cognitive impairment, affecting predominantly the ability to adequately process emotions from human faces. The COVID-19 pandemic has forced people to wear face masks that might interfere with facial emotion recognition. Therefore, in the present study, we aimed at investigating the ability of emotion recognition in PwMS from faces wearing masks. We enrolled a total of 42 cognitively normal relapsing–remitting PwMS and a matched group of 20 healthy controls (HCs). Participants underwent a facial emotion recognition task in which they had to recognize from faces wearing or not surgical masks which of the six basic emotions (happiness, anger, fear, sadness, surprise, disgust) was presented. Results showed that face masks negatively affected emotion recognition in all participants (p < 0.001); in particular, PwMS showed a global worse accuracy than HCs (p = 0.005), mainly driven by the “no masked” (p = 0.021) than the “masked” (p = 0.064) condition. Considering individual emotions, PwMS showed a selective impairment in the recognition of fear, compared with HCs, in both the conditions investigated (“masked”: p = 0.023; “no masked”: p = 0.016). Face masks affected negatively also response times (p < 0.001); in particular, PwMS were globally hastier than HCs (p = 0.024), especially in the “masked” condition (p = 0.013). Furthermore, a detailed characterization of the performance of PwMS and HCs in terms of accuracy and response speed was proposed. Results from the present study showed the effect of face masks on the ability to process facial emotions in PwMS, compared with HCs. Healthcare professionals working with PwMS at the time of the COVID-19 outbreak should take into consideration this effect in their clinical practice. Implications in the everyday life of PwMS are also discussed.
MNCD: A New Tool for Classifying Parkinson’s Disease in Daily Clinical Practice
Authors: Santos García Diego , Álvarez Sauco María , Calopa Matilde , Carrillo Fátima , Escamilla Sevilla Francisco , Freire Eric , García Ramos Rocío , Kulisevsky Jaime , Gómez Esteban Juan Carlos , Legarda Inés , Luquín María Rosario Isabel , Castrillo Juan Carlos Martínez , Martínez-Martin Pablo , Martínez-Torres Irene , Mir Pablo , Ignacio Ángel Sesar
Published: December 2021

Background and objective: Parkinson’s disease (PD) is a clinically heterogeneous disorder in which the symptoms and prognosis can be very different among patients. We propose a new simple classification to identify key symptoms and staging in PD. Patients and Methods: Sixteen movement disorders specialists from Spain participated in this project. The classification was consensually approved after a discussion and review process from June to October 2021. The TNM classification and the National Institutes of Health Stroke Scale (NIHSS) were considered as models in the design. Results: The classification was named MNCD and included 4 major axes: (1) motor symptoms; (2) non-motor symptoms; (3) cognition; (4) dependency for activities of daily living (ADL). Motor axis included 4 sub-axes: (1) motor fluctuations; (2) dyskinesia; (3) axial symptoms; (4) tremor. Four other sub-axes were included in the non-motor axis: (1) neuropsychiatric symptoms; (2) autonomic dysfunction; (3) sleep disturbances and fatigue; (4) pain and sensory disorders. According to the MNCD, 5 stages were considered, from stage 1 (no disabling motor or non-motor symptoms with normal cognition and independency for ADL) to 5 (dementia and dependency for basic ADL). Conclusions: A new simple classification of PD is proposed. The MNCD classification includes 4 major axes and 5 stages to identify key symptoms and monitor the evolution of the disease in patients with PD. It is necessary to apply this proof of concept in a properly designed study.
A Multimodal Approach for the Risk Prediction of Intensive Care and Mortality in Patients with COVID-19
Authors: Pezoulas Vasileios C. , Kourou Konstantina D. , Papaloukas Costas , Triantafyllia Vassiliki , Lampropoulou Vicky , Siouti Eleni , Papadaki Maria , Salagianni Maria , Koukaki Evangelia , Rovina Nikoletta , Koutsoukou Antonia , Andreakos Evangelos , Fotiadis Dimitrios I.
Published: December 2021

Background: Although several studies have been launched towards the prediction of risk factors for mortality and admission in the intensive care unit (ICU) in COVID-19, none of them focuses on the development of explainable AI models to define an ICU scoring index using dynamically associated biological markers. Methods: We propose a multimodal approach which combines explainable AI models with dynamic modeling methods to shed light into the clinical features of COVID-19. Dynamic Bayesian networks were used to seek associations among cytokines across four time intervals after hospitalization. Explainable gradient boosting trees were trained to predict the risk for ICU admission and mortality towards the development of an ICU scoring index. Results: Our results highlight LDH, IL-6, IL-8, Cr, number of monocytes, lymphocyte count, TNF as risk predictors for ICU admission and survival along with LDH, age, CRP, Cr, WBC, lymphocyte count for mortality in the ICU, with prediction accuracy 0.79 and 0.81, respectively. These risk factors were combined with dynamically associated biological markers to develop an ICU scoring index with accuracy 0.9. Conclusions: to our knowledge, this is the first multimodal and explainable AI model which quantifies the risk of intensive care with accuracy up to 0.9 across multiple timepoints.
Virtual Validation of an Automated Lane-Keeping System with an Extended Operational Design Domain
Authors: Weissensteiner Patrick , Stettinger Georg , Rumetshofer Johannes , Watzenig Daniel
Published: December 2021

Virtual testing using simulation will play a significant role in future safety validation procedures for automated driving systems, as it provides the needed scalability for executing a scenario-based assessment approach. This article combines multiple essential aspects that are necessary for the virtual validation of such systems. First, a general framework that contains the vital subsystems needed for virtual validation is introduced. Secondly, the interfaces between the subsystems are explored. Additionally, the concept of model fidelities is presented and extended towards all relevant subsystems. For an automated lane-keeping system with two different definitions of an operational design domain, all relevant subsystems are defined and integrated into an overall simulation framework. The resulting difference between both operational design domains is the occurrence of lateral manoeuvres, leading to greater demands of the fidelity of the vehicle dynamics model. The simulation results support the initial assumption that by extending the operation domain, the requirements for all subsystems are subject to adaption. As an essential aspect of harmonising virtual validation frameworks, the article identifies four separate layers and their corresponding parameters. In particular, the tool-specific co-simulation capability layer is critical, as it enables model exchange through consistently defined interfaces and reduces the integration effort. The introduction of this layered architecture for virtual validation frameworks enables further cross-domain collaboration.
Fire Detection Method in Smart City Environments Using a Deep-Learning-Based Approach
Authors: Avazov Kuldoshbay , Mukhiddinov Mukhriddin , Makhmudov Fazliddin , Cho Young Im
Published: December 2021

In the construction of new smart cities, traditional fire-detection systems can be replaced with vision-based systems to establish fire safety in society using emerging technologies, such as digital cameras, computer vision, artificial intelligence, and deep learning. In this study, we developed a fire detector that accurately detects even small sparks and sounds an alarm within 8 s of a fire outbreak. A novel convolutional neural network was developed to detect fire regions using an enhanced You Only Look Once (YOLO) v4network. Based on the improved YOLOv4 algorithm, we adapted the network to operate on the Banana Pi M3 board using only three layers. Initially, we examined the originalYOLOv4 approach to determine the accuracy of predictions of candidate fire regions. However, the anticipated results were not observed after several experiments involving this approach to detect fire accidents. We improved the traditional YOLOv4 network by increasing the size of the training dataset based on data augmentation techniques for the real-time monitoring of fire disasters. By modifying the network structure through automatic color augmentation, reducing parameters, etc., the proposed method successfully detected and notified the incidence of disastrous fires with a high speed and accuracy in different weather environments—sunny or cloudy, day or night. Experimental results revealed that the proposed method can be used successfully for the protection of smart cities and in monitoring fires in urban areas. Finally, we compared the performance of our method with that of recently reported fire-detection approaches employing widely used performance matrices to test the fire classification results achieved.
Enabling Processing Power Scalability with Internet of Things (IoT) Clusters
Authors: Coelho Jorge , Nogueira Luís
Published: December 2021

Internet of things (IoT) devices play a crucial role in the design of state-of-the-art infrastructures, with an increasing demand to support more complex services and applications. However, IoT devices are known for having limited computational capacities. Traditional approaches used to offload applications to the cloud to ease the burden on end-user devices, at the expense of a greater latency and increased network traffic. Our goal is to optimize the use of IoT devices, particularly those being underutilized. In this paper, we propose a pragmatic solution, built upon the Erlang programming language, that allows a group of IoT devices to collectively execute services, using their spare resources with minimal interference, and achieving a level of performance that otherwise would not be met by individual execution.
Caffe2Unity: Immersive Visualization and Interpretation of Deep Neural Networks
Authors: Aamir Aisha , Tamosiunaite Minija , Wörgötter Florentin
Published: December 2021

Deep neural networks (DNNs) dominate many tasks in the computer vision domain, but it is still difficult to understand and interpret the information contained within these networks. To gain better insight into how a network learns and operates, there is a strong need to visualize these complex structures, and this remains an important research direction. In this paper, we address the problem of how the interactive display of DNNs in a virtual reality (VR) setup can be used for general understanding and architectural assessment. We compiled a static library as a plugin for the Caffe framework in the Unity gaming engine. We used routines from this plugin to create and visualize a VR-based AlexNet architecture for an image classification task. Our layered interactive model allows the user to freely navigate back and forth within the network during visual exploration. To make the DNN model even more accessible, the user can select certain connections to understand the activity flow at a particular neuron. Our VR setup also allows users to hide the activation maps/filters or even interactively occlude certain features in an image in real-time. Furthermore, we added an interpretation module and reframed the Shapley values to give a deeper understanding of the different layers. Thus, this novel tool offers more direct access to network structures and results, and its immersive operation is especially instructive for both novices and experts in the field of DNNs.
Watt-Level Ka-Band Integrated Doherty Power Amplifiers: Technologies and Power Combination Strategies Invited Paper
Authors: Piacibello Anna , Camarchia Vittorio
Published: December 2021

This paper discusses some of the design choices underlying the development of watt-level integrated Doherty power amplifiers in the K and Ka band, focusing on compound semiconductor technologies. The key aspect of on-chip power combination is discussed, presenting and comparing some of the possible alternatives. Then, the impact on the achievable bandwidth and performance of different parameters is quantified, adopting an approximate analysis, which focuses on the Doherty output combiner and allows estimating the non-linear performance of the amplifier thanks to some simplifying assumptions, without requiring a full, non-linear model of the active devices. Two sample GaAs and GaN technologies are compared first, considering parameters that are representative of the currently available commercial processes, and then several power combination strategies are analyzed, adopting the GaN technology, which is currently the only one that allows achieving the power levels required by the applications directly on chip. Finally, some hints as to the impact of the output parasitic effects of the transistors on the presented analysis are given.
Efficiency Evaluation of the Dual System Power Inverter for On-Grid Photovoltaic System
Authors: Vaicys Jonas , Norkevicius Povilas , Baronas Arturas , Gudzius Saulius , Jonaitis Audrius , Peftitsis Dimosthenis
Published: December 2021

The implementation of a dual electric system that is capable of operating with either constant current and variable voltage, or constant voltage and variable current appliances, is one of the possible options to solve low-intensity stochastic energy utilization problems from renewable energy sources. This research paper analyzes the potential benefit of a novel three-phase dual system power inverter over the conventional inverter used in a solar power plant. The concept of such a power inverter is explained, and the digital twin model is created in a MATLAB Simulink environment. The efficiency characteristic of the simulated inverter is compared to the efficiency characteristic of a real conventional inverter. A standalone data logging system and an additional data acquisition system were used to collect and process data from the real inverter. Comparison of the digital twin inverter and the real conventional inverter shows the potential benefit of this novel inverter technology. It is shown that the novel inverter can operate in a wider range of DC input power. The potential economic benefit is also presented and discussed in the paper.
Risk of Secondary Household Transmission of COVID-19 from Health Care Workers in a Hospital in Spain
Authors: Remón-Berrade Miren , Guillen-Aguinaga Sara , Sarrate-Adot Isabel , Garcia-Garcia Maria Pilar , Lerga-Berruezo Maria del Carmen , Guillen-Aguinaga Laura , Guillen-Grima Francisco
Published: December 2021

Background: Hospital health care workers are at high risk of developing COVID-19 and transmitting the disease to their family upon returning home; the aim here is to estimate the secondary attack rate of COVID-19 in household contacts of health care workers and their transmission risk factors. Material and Methods: COVID-19 cases in the health care workers of an academic hospital in Pamplona, Spain, from 2 March to 26 May 2020, were followed up. The secondary attack rate (SAR) was estimated from cases in household contacts of index cases and their risk factors by Poisson regression. Results: 89 index cases were studied from 99 notified cases in health care workers (89.0%), excluding secondary cases or those who lived alone. Forty-six secondary cases confirmed by the laboratory were found among 326 household contacts, a secondary attack rate of 14.11% (95% CI 10.75–18.31), and 33 household contacts with acute infection symptoms without microbiologic confirmation 10.12% (95% CI 7.30–13.87). Considering all the cases, the secondary attack rate was 27.3 (95% CI 22.75–32.38). Risk factors were the gender and profession of the index case, the number of people living in the household, and the number of persons per bedroom. When the index case health worker used a single room, it had a protective effect, with an incidence rate ratio (IRR) of 0.493 (95% CI 0.246–0.985); Conclusions: The secondary attack rate found among household contacts of health care workers is high. The preventive isolation of health care workers in individual rooms in their house may reduce the transmission in their families.
Correction: Lippe et al. Estimating Global Forest-Based Employment. Forests 2021, 12, 1219
Authors: Lippe Rattiya Suddeephong , Cui Shannon , Schweinle Jörg
Published: December 2021

In the original publication [...]
Overexpression of CpWRKY75 from Chimonanthus praecox Promotes Flowering Time in Transgenic Arabidopsis
Authors: Huang Renwei , Sui Shunzhao , Liu Huamin , Li Mingyang , Liu Daofeng
Published: December 2021

WRKY transcription factors play critical roles in the physiological processes of plants. Although the roles of WRKYs have been characterized in some model plants, their roles in woody plants, especially wintersweet (Chimonanthus praecox), are largely unclear. In this study, a wintersweet WRKY gene named CpWRKY75 belonging to group IIc was isolated and its characteristics were identified. CpWRKY75 is a nucleus-localized protein, and exhibited no transcriptional activation activity in yeast. CpWRKY75 was highly expressed in flowers at different bloom stages. Ectopic expression of CpWRKY75 significantly promoted the flowering time of transgenic Arabidopsis (Arabidopsis thaliana), as determined by the rosette leaf number and first flower open time. The expression levels of flowering-related genes were quantified by qRT-PCR, and the results suggested that CpWRKY75 had obvious influence on the expression level of MICRORNA156C (MIR156C), SQUAMOSA PROMOTER BINDING PROTEIN-LIKE3 (SPL3) and SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 9 (SPL9), FLOWERING LOCUS T (FT), LEAFY (LFY), SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1), APETALA1 (AP1), CAULIFLOWER (CAL), and FRUITFULL (FUL). These results suggest that CpWRKY75 might have a flowering time regulation function, and additionally provide a new gene resource for the genetic engineering of woody flowering plants.
Fine Mapping of the Mouse Ath28 Locus Yields Three Atherosclerosis Modifying Sub-Regions
Authors: Han Juying , Ritchey Brian , Opoku Emmanuel , Smith Jonathan D.
Published: December 2021

A mouse strain intercross between Apoe−/− AKR/J and DBA/2J mice identified three replicated atherosclerosis quantitative trait loci (QTLs). Our objective was to fine map mouse atherosclerosis modifier genes within a genomic region known to affect lesion development in apoE-deficient (Apoe−/−) mice. We dissected the Ath28 QTL on the distal end of chromosome 2 by breeding a panel of congenic strains and measuring aortic root lesion area in 16-week-old male and female mice fed regular laboratory diets. The parental congenic strain contained ~9.65 Mb of AKR/J DNA from chromosome 2 on the DBA/2J genetic background, which had lesions 55% and 47% smaller than female and male DBA/2J mice, respectively (p < 0.001). Seven additional congenic lines identified three separate regions associated with the lesion area, named Ath28.1, Ath28.2, and Ath28.3, where the AKR/J alleles were atherosclerosis-protective for two regions and atherosclerosis-promoting for the other region. These results were replicated in both sexes, and in combined analysis after adjusting for sex. The congenic lines did not greatly impact total and HDL cholesterol levels or body weight. Bioinformatic analyses identified all coding and non-coding genes in the Ath28.1 sub-region, as well as strain sequence differences that may be impactful. Even within a <10 Mb region of the mouse genome, evidence supports the presence of at least three atherosclerosis modifier genes that differ between the AKR/J and DBA/2J mouse strains, supporting the polygenic nature of atherosclerosis susceptibility.
Integrated Runoff-Storm Surge Flood Hazard Mapping Associated with Tropical Cyclones in the Suburbs of La Paz, Baja California Sur, México
Authors: Imaz-Lamadrid Miguel Angel , Wurl Jobst , Ramos-Velázquez Ernesto , Rodríguez-Trasviña Jaqueline
Published: December 2021

Floods are amongst the most frequent and destructive type of disaster, causing significant damage to communities. Globally, there is an increasing trend in the damage caused by floods generated by several factors. Flooding is characterized by the overflow of water onto dry land. Tropical cyclones generate floods due to excess water in rivers and streams and storm surges; however, the hazard of both phenomena is presented separately. In this research we present a methodology for the estimation of flood hazards related to tropical cyclones, integrating runoff and storm surge floods. As a case study, we selected the south-western suburbs of the city of La Paz, the capital of the state of Baja California Sur in northwest Mexico. The city has experienced in recent years an expansion of the urban area. In addition, there is an infrastructure of great importance such as the transpeninsular highway that connects the capital with the north of the state, as well as the international airport. Our results indicate that urban areas, agricultural lands, as well as the air force base, airport, and portions of the transpeninsular highway are in hazardous flood areas, making necessary to reduce the exposure and vulnerability to these tropical cyclone-related events. A resulting map was effective in defining those areas that would be exposed to flooding in the face of the impact of tropical cyclones and considering climate change scenarios, which represents an invaluable source of information for society and decision-makers for comprehensive risk management and disaster prevention.
Vibration Analyses of a Gantry Structure by Mobile Phone Digital Image Correlation and Interferometric Radar
Authors: Mugnai Francesco , Cosentino Antonio , Mazzanti Paolo , Tucci Grazia
Published: December 2021

The study presents results from applying the Real Aperture Radar interferometry technique and Digital Image Correlation through a mobile phone camera to identify static and dynamic deformations of a gantry during surveying operations on the Michelangelo’s David at the Galleria dell’Accademia di Firenze Museum in Florence. The statue has considerable size and reaches an elevation of more than seven meters on its pedestal. An ad-hoc gantry was designed and deployed, given the cramped operating area around the statue. The scanner had a stability control system that forbid surveying in instrument movements. However, considering the unicity of the survey and its rare occurrence, the previous survey had been carried out in the year 2000; verifying stability and recording deformations is a crucial task, and necessary for validation. As the gantry does not have an on-board stability sensor, and considering the hi-survey accuracy requested, a redundant, contactless, remote monitoring system of the gantry and the statue stability was chosen to guarantee the maximum freedom of movement around the David to avoid any interference during scanning operations. Thanks to the TInRAR technique, the gantry and the statue were monitored with an accuracy of 0.01 mm. At the same time, a Digital Image Correlation analysis was performed on the gantry, which can be considered a Multi-Degree-Of-Freedom (MDOF) system, to accurately calculate the vibration frequency and amplitude. A comparison between TInRAR and DIC results reported substantial accordance in detecting gantry’s oscillating frequencies; a predominant oscillation frequency of 1.33 Hz was identified on the gantry structure by TinSAR and DIC analysis.
Correction: Hayakawa et al. Lithosphere–Atmosphere–Ionosphere Coupling Effects Based on Multiparameter Precursor Observations for February–March 2021 Earthquakes (M~7) in the Offshore of Tohoku Area of Japan. Geosciences 2021, 11, 481
Authors: Hayakawa Masashi , Izutsu Jun , Schekotov Alexander , Yang Shih-Sian , Solovieva Maria , Budilova Ekaterina
Published: December 2021

The authors would like to make the following corrections to this paper [...]
Senescence-Mediated Redox Imbalance in Liver and Kidney: Antioxidant Rejuvenating Potential of Green Tea Extract
Authors: Hsu Yu-Wen , Chen Wen-Kang , Tsai Chia-Fang
Published: December 2021

This study investigates the catechin composition and protective effect of green tea extract on senescence-mediated redox imbalance in the livers and kidneys of aged mice. The results showed that the seven catechins in the green tea extract analyzed in this study could be completely separated within 30 min and the main components of catechins in green tea extract were EGCG, EGC and ECG. In terms of the anti-senescence effects of green tea extract, green tea extract supplementation at doses of 125, 625 and 1250 mg/kg for 4 weeks significantly alleviated the senescence-mediated redox imbalance, as exhibited from significantly (p < 0.05) reduced thiobarbituric acid-reactive substances (TBARS) and protein carbonyls levels in the serum, and increased glutathione (GSH) and total thiols contents in the plasma. Additionally, hepatic and renal protein carbonyls levels were significantly diminished (p < 0.05) and the activities of superoxide dismutase (SOD), catalase, glucose-6-phosphate dehydrogenase (G6PD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd) in the liver and kidney were remarkably elevated (p < 0.05). Overall, these results clearly show that green tea extract exhibits extremely potent protective effects against senescence-mediated redox imbalance in the livers and kidneys of mice by inhibiting oxidative damage of lipids and proteins and increasing the activities of antioxidant enzymes in organs.
A Web-Based Geoinformation System for Heritage Management and Geovisualisation in Cantón Nabón (Ecuador)
Authors: Collado Angel , Mora-Navarro Gaspar , Heras Verónica , Lerma José Luis
Published: December 2021

Since ancient times, human beings have been interested in knowing their environment in order to make the right decisions in territorial management. The spatial component is a feature of great importance in the assets that surround us. Heritage geoinformation is a convenient and effective way for management, protection and safeguarding of cultural and natural heritage. For optimal compliance, it is nowadays indispensable to rely on the use of new web technologies and geomatics knowledge that allow the documentation, visualisation, monitoring and management of heritage. Therefore, the main objective of this article is to develop a web-based cultural heritage management system in Cantón Nabón, Ecuador, as a case study. The system, consisting of a web-based geoportal accessible to the whole society, will allow consulting the geolocalised heritage information of the study area on a virtual map, as well as 3D geovisualisation in an interactive web viewer. The integrated system, once implemented, will take into consideration the preventive conservation cycle in the heritage field, highlighting, in Spanish, the creation of the heritage data models according to ISO21127:2014.
Hybrid Metaheuristic-Based Spatial Modeling and Analysis of Logistics Distribution Center
Authors: Khairunissa Maryam , Lee Hyunsoo
Published: December 2021

The location analysis of logistics distribution centers is one of the most critical issues in large-scale supply chains. While a number of algorithms and applications have been provided for this end, comparatively fewer investigations have been made into the integration of geographical information. This study proposes logistic distribution center location analysis that considers current geographic and embedded information gathered from a geographic information system (GIS). After reviewing the GIS, the decision variables and parameters are estimated using spatial analysis. These variables and parameters are utilized during mathematical problem-based analysis stage. While a number of existing algorithms have been proposed, this study applies a hybrid metaheuristic algorithm integrating particle swarm optimization (PSO) and genetic algorithm (GA). Using the proposed method, a more realistic mathematical model is established and solved for accurate analysis of logistics performance. To demonstrate the effectiveness of the proposed method, Korea Post distribution centers were considered in South Korea. Through tests with several real-world scenarios, it is proven experimentally that the proposed solution is more effective than existing PSO variations.
Human iPSC-Derived Astrocytes: A Powerful Tool to Study Primary Astrocyte Dysfunction in the Pathogenesis of Rare Leukodystrophies
Authors: Lanciotti Angela , Brignone Maria Stefania , Macioce Pompeo , Visentin Sergio , Ambrosini Elena
Published: December 2021

Astrocytes are very versatile cells, endowed with multitasking capacities to ensure brain homeostasis maintenance from brain development to adult life. It has become increasingly evident that astrocytes play a central role in many central nervous system pathologies, not only as regulators of defensive responses against brain insults but also as primary culprits of the disease onset and progression. This is particularly evident in some rare leukodystrophies (LDs) where white matter/myelin deterioration is due to primary astrocyte dysfunctions. Understanding the molecular defects causing these LDs may help clarify astrocyte contribution to myelin formation/maintenance and favor the identification of possible therapeutic targets for LDs and other CNS demyelinating diseases. To date, the pathogenic mechanisms of these LDs are poorly known due to the rarity of the pathological tissue and the failure of the animal models to fully recapitulate the human diseases. Thus, the development of human induced pluripotent stem cells (hiPSC) from patient fibroblasts and their differentiation into astrocytes is a promising approach to overcome these issues. In this review, we discuss the primary role of astrocytes in LD pathogenesis, the experimental models currently available and the advantages, future evolutions, perspectives, and limitations of hiPSC to study pathologies implying astrocyte dysfunctions.
The Protective Effects of Lactoferrin on Aflatoxin M1-Induced Compromised Intestinal Integrity
Authors: Gao Ya-Nan , Li Song-Li , Yang Xue , Wang Jia-Qi , Zheng Nan
Published: December 2021

Aflatoxin M1 (AFM1), the only toxin with maximum residue levels in milk, has adverse effects on the intestinal barrier, resulting in intestinal inflammatory disease. Lactoferrin (LF), one of the important bioactive proteins in milk, performs multiple biological functions, but knowledge of the protective effects of LF on the compromised intestinal barrier induced by AFM1 has not been investigated. In the present study, results using Balb/C mice and differentiated Caco-2 cells showed that LF intervention decreased AFM1-induced increased intestinal permeability, improved the protein expression of claudin-3, occludin and ZO-1, and repaired the injured intestinal barrier. The transcriptome and proteome were used to clarify the underlying mechanisms. It was found that LF reduced the intestinal barrier dysfunction caused by AFM1 and was associated with intestinal cell survival related pathways, such as cell cycle, apoptosis and MAPK signaling pathway and intestinal integrity related pathways including endocytosis, tight junction, adherens junction and gap junction. The cross-omics analysis suggested that insulin receptor (INSR), cytoplasmic FMR1 interacting protein 2 (CYFIP2), dedicator of cytokinesis 1 (DOCK1) and ribonucleotide reductase regulatory subunit M2 (RRM2) were the potential key regulators as LF repaired the compromised intestinal barrier. These findings indicated that LF may be an alternative treatment for the compromised intestinal barrier induced by AFM1.
Characterization of Mutations Causing CYP21A2 Deficiency in Brazilian and Portuguese Populations
Authors: Prado Mayara J. , Singh Shripriya , Ligabue-Braun Rodrigo , Meneghetti Bruna V. , Rispoli Thaiane , Kopacek Cristiane , Monteiro Karina , Zaha Arnaldo , Rossetti Maria L. R. , Pandey Amit V.
Published: December 2021

Deficiency of 21-hydroxylase enzyme (CYP21A2) represents 90% of cases in congenital adrenal hyperplasia (CAH), an autosomal recessive disease caused by defects in cortisol biosynthesis. Computational prediction and functional studies are often the only way to classify variants to understand the links to disease-causing effects. Here we investigated the pathogenicity of uncharacterized variants in the CYP21A2 gene reported in Brazilian and Portuguese populations. Physicochemical alterations, residue conservation, and effect on protein structure were accessed by computational analysis. The enzymatic performance was obtained by functional assay with the wild-type and mutant CYP21A2 proteins expressed in HEK293 cells. Computational analysis showed that p.W202R, p.E352V, and p.R484L have severely impaired the protein structure, while p.P35L, p.L199P, and p.P433L have moderate effects. The p.W202R, p.E352V, p.P433L, and p.R484L variants showed residual 21OH activity consistent with the simple virilizing phenotype. The p.P35L and p.L199P variants showed partial 21OH efficiency associated with the non-classical phenotype. Additionally, p.W202R, p.E352V, and p.R484L also modified the protein expression level. We have determined how the selected CYP21A2 gene mutations affect the 21OH activity through structural and activity alteration contributing to the future diagnosis and management of CYP21A2 deficiency.
Organizational E-Readiness for the Digital Transformation of Primary Healthcare Providers during the COVID-19 Pandemic in Poland
Authors: Kruszyńska-Fischbach Agnieszka , Sysko-Romańczuk Sylwia , Rafalik Mateusz , Walczak Renata , Kludacz-Alessandri Magdalena
Published: December 2021

The COVID-19 pandemic has forced many countries to implement a variety of restrictive measures to prevent it from spreading more widely, including the introduction of medical teleconsultations and the use of various tools in the field of inpatient telemedicine care. Digital technologies provide a wide range of treatment options for patients, and at the same time pose a number of organizational challenges for medical entities. Therefore, the question arises of whether organizations are ready to use modern telemedicine tools during the COVID-19 pandemic. The aim of this article is to examine two factors that impact the level of organizational e-readiness for digital transformation in Polish primary healthcare providers (PHC). The first factor comprises operational capabilities, which are the sum of valuable, scarce, unique, and irreplaceable resources and the ability to use them. The second factor comprises technological capabilities, which determine the adoption and usage of innovative technologies. Contrary to the commonly analyzed impacts of technology on operational capabilities, we state the reverse hypothesis. The verification confirms the significant influence of operational capabilities on technological capabilities. The research is conducted using a questionnaire covering organizational e-readiness for digital transformation prepared by the authors. Out of the 32 items examined, four are related to the operational capabilities and four to the technological capabilities. The result of our evaluation shows that: (i) a basic set of four variables can effectively measure the dimensions of OC, namely the degree of agility, level of process integration, quality of resources, and quality of cooperation; (ii) a basic set of three variables can effectively measure the dimensions of TC, namely adoption and usage of technologies, customer interaction, and process automation; (iii) the empirical results show that OC is on a higher level than TC in Polish PHCs; (iv) the assessment of the relationship between OC and TC reveals a significant influence of operational capabilities on technological capabilities with a structural coefficient of 0.697. We recommend increasing the level of technological capability in PHC providers in order to improve the contact between patients and general practitioners (GPs) via telemedicine in lockdown conditions.