bluuebunny/crossref_metadata_2025 huggingface dataset:
Preconception Risk Factors for Autism Spectrum Disorder—A Pilot Study
Authors: Magdalena Hankus , Beata Kazek , Justyna Paprocka , Agnieszka Kapinos-Gorczyca , Szczepara-Fabian Magdalena , Buczek Agata , Ewa Emich-Widera
Published: May 2020

Autism spectrum disorder (ASD) is a neurodevelopmental disorder of multifactorial etiology. Preconception risk factors are still poorly understood. A survey on preconception risk factors for ASD was conducted among parents of 121 ASD patients aged 3–12 years and parents of 100 healthy children aged 3–12 years. The exclusion criteria were as follows: the presence of associated problems such as intellectual disability, epilepsy or other genetic and neurological diseases. Thirteen parameters were considered, a few among which were conception problems, conception with assisted reproductive techniques, the use and duration of oral contraception, the number of previous pregnancies and miscarriages, time since the previous pregnancy (in months), the history of mental illness in the family (including ASD), other chronic diseases in the mother or father and maternal and paternal treatment in specialist outpatient clinics. Three factors statistically significantly increased the risk of developing ASD: mental illness in the mother/mother’s family (35.54% vs. 16.0%, p = 0.0002), maternal thyroid disease (16.67% vs. 5.0%, p = 0.009) and maternal oral contraception (46.28% vs. 29.0%, p = 0.01). Children of mothers with thyroid disorders or with mental illness in relatives should be closely monitored for ASD. Further studies are warranted to assess a potential effect of oral contraception on the development of offspring.
Hypoxic Roadmap of Glioblastoma—Learning about Directions and Distances in the Brain Tumor Environment
Authors: Bronisz Agnieszka , Salińska Elżbieta , Chiocca E. Antonio , Godlewski Jakub
Published: May 2020

Malignant brain tumor—glioblastoma is not only difficult to treat but also hard to study and model. One of the reasons for these is their heterogeneity, i.e., individual tumors consisting of cancer cells that are unlike each other. Such diverse cells can thrive due to the simultaneous co-evolution of anatomic niches and adaption into zones with distorted homeostasis of oxygen. It dampens cytotoxic and immune therapies as the response depends on the cellular composition and its adaptation to hypoxia. We explored what transcriptome reposition strategies are used by cells in the different areas of the tumor. We created the hypoxic map by differential expression analysis between hypoxic and cellular features using RNA sequencing data cross-referenced with the tumor’s anatomic features (Ivy Glioblastoma Atlas Project). The molecular functions of genes differentially expressed in the hypoxic regions were analyzed by a systematic review of the gene ontology analysis. To put a hypoxic niche signature into a clinical context, we associated the model with patients’ survival datasets (The Cancer Genome Atlas). The most unique class of genes in the hypoxic area of the tumor was associated with the process of autophagy. Both hypoxic and cellular anatomic features were enriched in immune response genes whose, along with autophagy cluster genes, had the power to predict glioblastoma patient survival. Our analysis revealed that transcriptome responsive to hypoxia predicted worse patients’ outcomes by driving tumor cell adaptation to metabolic stress and immune escape.
Identification of Distinct Heterogenic Subtypes and Molecular Signatures Associated with African Ancestry in Triple Negative Breast Cancer Using Quantified Genetic Ancestry Models in Admixed Race Populations
Authors: Davis Melissa , Martini Rachel , Newman Lisa , Elemento Olivier , White Jason , Verma Akanksha , Datta Indrani , Adrianto Indra , Chen Yalei , Gardner Kevin , Kim Hyung-Gyoon , Colomb Windy D. , Eltoum Isam-Eldin , Frost Andra R. , Grizzle William E. , Sboner Andrea , Manne Upender , Yates Clayton
Published: May 2020

Triple negative breast cancers (TNBCs) are molecularly heterogeneous, and the link between their aggressiveness with African ancestry is not established. We investigated primary TNBCs for gene expression among self-reported race (SRR) groups of African American (AA, n = 42) and European American (EA, n = 33) women. RNA sequencing data were analyzed to measure changes in genome-wide expression, and we utilized logistic regressions to identify ancestry-associated gene expression signatures. Using SNVs identified from our RNA sequencing data, global ancestry was estimated. We identified 156 African ancestry-associated genes and found that, compared to SRR, quantitative genetic analysis was a more robust method to identify racial/ethnic-specific genes that were differentially expressed. A subset of African ancestry-specific genes that were upregulated in TNBCs of our AA patients were validated in TCGA data. In AA patients, there was a higher incidence of basal-like two tumors and altered TP53, NFB1, and AKT pathways. The distinct distribution of TNBC subtypes and altered oncologic pathways show that the ethnic variations in TNBCs are driven by shared genetic ancestry. Thus, to appreciate the molecular diversity of TNBCs, tumors from patients of various ancestral origins should be evaluated.
Treatment of Smoldering Multiple Myeloma: Ready for Prime Time?
Authors: Kim E. Bridget , Yee Andrew J. , Raje Noopur
Published: May 2020

The current standard of care for smoldering multiple myeloma (SMM) is observation until there is end-organ involvement. With newer and more effective treatments available, a question that is increasingly asked is whether early intervention in patients with SMM will alter the natural history of their disease. Herein, we review the evolving definition of SMM and risk stratification models. We discuss evidence supporting early intervention for SMM—both as a preventative strategy to delay progression and as an intensive treatment strategy with a goal of potential cure. We highlight ongoing trials and focus on better defining who may require early intervention.
A Preoperative Clinical Risk Score Including C-Reactive Protein Predicts Histological Tumor Characteristics and Patient Survival after Surgery for Sporadic Non-Functional Pancreatic Neuroendocrine Neoplasms: An International Multicenter Cohort Study
Authors: Primavesi Florian , Andreasi Valentina , Hoogwater Frederik J.H. , Partelli Stefano , Wiese Dominik , Heidsma Charlotte , Cardini Benno , Klieser Eckhard , Marsoner Katharina , Fröschl Uwe , Thalhammer Sabine , Fischer Ines , Göbel Georg , Hauer Andreas , Kiesslich Tobias , Ellmerer Philipp , Klug Reinhold , Neureiter Daniel , Wundsam Helwig , Sellner Franz , Kornprat Peter , Függer Reinhold , Öfner Dietmar , Nieveen van Dijkum Elisabeth J.M. , Bartsch Detlef K. , de Kleine Ruben H.J. , Falconi Massimo , Stättner Stefan
Published: May 2020

Background: Oncological survival after resection of pancreatic neuroendocrine neoplasms (panNEN) is highly variable depending on various factors. Risk stratification with preoperatively available parameters could guide decision-making in multidisciplinary treatment concepts. C-reactive Protein (CRP) is linked to inferior survival in several malignancies. This study assesses CRP within a novel risk score predicting histology and outcome after surgery for sporadic non-functional panNENs. Methods: A retrospective multicenter study with national exploration and international validation. CRP and other factors associated with overall survival (OS) were evaluated by multivariable cox-regression to create a clinical risk score (CRS). Predictive values regarding OS, disease-specific survival (DSS), and recurrence-free survival (RFS) were assessed by time-dependent receiver-operating characteristics. Results: Overall, 364 patients were included. Median CRP was significantly higher in patients >60 years, G3, and large tumors. In multivariable analysis, CRP was the strongest preoperative factor for OS in both cohorts. In the combined cohort, CRP (cut-off ≥0.2 mg/dL; hazard-ratio (HR):3.87), metastases (HR:2.80), and primary tumor size ≥3.0 cm (HR:1.83) showed a significant association with OS. A CRS incorporating these variables was associated with postoperative histological grading, T category, nodal positivity, and 90-day morbidity/mortality. Time-dependent area-under-the-curve at 60 months for OS, DSS, and RFS was 69%, 77%, and 67%, respectively (all p < 0.001), and the inclusion of grading further improved the predictive potential (75%, 84%, and 78%, respectively). Conclusions: CRP is a significant marker of unfavorable oncological characteristics in panNENs. The proposed internationally validated CRS predicts histological features and patient survival.
UBQLN2 Promotes the Production of Type I Interferon via the TBK1-IRF3 Pathway
Authors: Chen Tianhong , Zhang Wenjuan , Huang Bo , Chen Xuan , Huang Cao
Published: May 2020

Mutations of Ubiquilin 2 (UBQLN2) or TANK-binding kinase 1 (TBK1) are associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD). However, the mechanisms whereby UBQLN2 or TBK1 mutations lead to ALS and FTD remain unclear. Here, we explored the effect of UBQLN2 on TBK1 in HEK-293T cells or in CRISPR–Cas9-mediated IRF3 and IRF7 knockout (KO) cells. We found an interaction between TBK1 and UBQLN2, which was affected by ALS/FTD-linked mutations in TBK1 or UBQLN2. Co-expression of UBQLN2 with TBK1 elevated the protein level of TBK1 as well as the phosphorylation of TBK1 and IRF3 in a UBQLN2 dose-dependent manner, and this phosphorylation was reduced by mutant UBQLN2. In addition, the cellular production of IFN1 and related pro-inflammatory cytokines was substantially elevated when UBQLN2 and TBK1 were co-expressed, which was also decreased by mutant UBQLN2. Functional assay revealed that mutant UBQLN2 significantly reduced the binding affinity of TBK1 for its partners, including IRF3, (SQSTM1)/p62 and optineurin (OPTN). Moreover, complete loss of IRF3 abolished the induction of IFN1 and related pro-inflammatory cytokines enhanced by UBQLN2 in HEK-293T cells, whereas no significant change in IRF7 knockout cells was observed. Thus, our findings suggest that UBQLN2 promotes IRF3 phosphorylation via TBK1, leading to enhanced IFN1 induction, and also imply that the dysregulated TBK1-IRF3 pathway may play a role in UBQLN2-related neurodegeneration.
The Role of Human γδ T Cells in Anti-Tumor Immunity and Their Potential for Cancer Immunotherapy
Authors: Liu Yuxia , Zhang Cai
Published: May 2020

γδ T cells are a distinct subset of T cells whose T cell receptors consist of γ chains and δ chains, different from conventional αβ T cells. γδ T cells are considered as a member of the innate immunity because of their non-MHC restricted antigen recognition, rapid response to invading pathogens and sense early changes of malignant cells. Upon activation, they can further promote the activation of adaptive immune cells, such as T cells and B cells, by secreting various cytokines. Thus, γδ T cells are regarded as a bridge between innate immunity and acquired immunity. γδ T cells are involved in a variety of immune response processes, including immune defense and immune surveillance against infection and tumorigenesis. γδ T cells recognize multiple tumor-associated antigens or molecules in T cell receptors (TCRs)-dependent and natural killer cell receptors (NKRs)-dependent ways. γδ T cells not only display a direct killing capacity on a variety of tumors, but also exert anti-tumor immune responses indirectly by facilitating the function of other immune cells, such as dendritic cells (DCs), B cells and CD8+ T cells. In this review, we summarize the major subpopulations, the tumor recognition mechanisms, and the anti-tumor effects of human γδ T cells, particularly the potential of γδ T cells for cancer immunotherapy.
Sorting Nexin 27 Regulates the Lysosomal Degradation of Aquaporin-2 Protein in the Kidney Collecting Duct
Authors: Choi Hyo-Jung , Jang Hyo-Ju , Park Euijung , Tingskov Stine Julie , Nørregaard Rikke , Jung Hyun Jun , Kwon Tae-Hwan
Published: May 2020

Sorting nexin 27 (SNX27), a PDZ (Postsynaptic density-95/Discs large/Zonula occludens 1) domain-containing protein, cooperates with a retromer complex, which regulates intracellular trafficking and the abundance of membrane proteins. Since the carboxyl terminus of aquaporin-2 (AQP2c) has a class I PDZ-interacting motif (X-T/S-X-Φ), the role of SNX27 in the regulation of AQP2 was studied. Co-immunoprecipitation assay of the rat kidney demonstrated an interaction of SNX27 with AQP2. Glutathione S-transferase (GST) pull-down assays revealed an interaction of the PDZ domain of SNX27 with AQP2c. Immunocytochemistry of HeLa cells co-transfected with FLAG-SNX27 and hemagglutinin (HA)-AQP2 also revealed co-localization throughout the cytoplasm. When the PDZ domain was deleted, punctate HA-AQP2 labeling was localized in the perinuclear region. The labeling was intensively overlaid by Lysotracker staining but not by GM130 labeling, a cis-Golgi marker. In rat kidneys and primary cultured inner medullary collecting duct cells, the subcellular redistribution of SNX27 was similar to AQP2 under 1-deamino-8-D-arginine vasopressin (dDAVP) stimulation/withdrawal. Cell surface biotinylation assay showed that dDAVP-induced AQP2 translocation to the apical plasma membrane was unaffected after SNX27 knockdown in mpkCCD cells. In contrast, the dDAVP-induced AQP2 protein abundance was significantly attenuated without changes in AQP2 mRNA expression. Moreover, the AQP2 protein abundance was markedly declined during the dDAVP withdrawal period after stimulation under SNX27 knockdown, which was inhibited by lysosome inhibitors. Autophagy was induced after SNX27 knockdown in mpkCCD cells. Lithium-induced nephrogenic diabetes insipidus in rats revealed a significant downregulation of SNX27 in the kidney inner medulla. Taken together, the PDZ domain-containing SNX27 interacts with AQP2 and depletion of SNX27 contributes to the autophagy-lysosomal degradation of AQP2.
Matrix Metalloproteinases as Potential Biomarkers and Therapeutic Targets in Liver Diseases
Authors: Geervliet Eline , Bansal Ruchi
Published: May 2020

Chronic liver diseases, characterized by an excessive accumulation of extracellular matrix (ECM) resulting in scar tissue formation, are a growing health problem causing increasing morbidity and mortality worldwide. Currently, therapeutic options for tissue fibrosis are severely limited, and organ transplantation is the only treatment for the end-stage liver diseases. During liver damage, injured hepatocytes release proinflammatory factors resulting in the recruitment and activation of immune cells that activate quiescent hepatic stellate cells (HSCs). Upon activation, HSCs transdifferentiate into highly proliferative, migratory, contractile and ECM-producing myofibroblasts. The disrupted balance between ECM deposition and degradation leads to the formation of scar tissue referred to as fibrosis. This balance can be restored either by reducing ECM deposition (by inhibition of HSCs activation and proliferation) or enhancing ECM degradation (by increased expression of matrix metalloproteinases (MMPs)). MMPs play an important role in ECM remodeling and represent an interesting target for therapeutic drug discovery. In this review, we present the current knowledge about ECM remodeling and role of the different MMPs in liver diseases. MMP expression patterns in different stages of liver diseases have also been reviewed to determine their role as biomarkers. Finally, we highlight MMPs as promising therapeutic targets for the resolution of liver diseases.
High Prevalence of Novel Beak and Feather Disease Virus in Sympatric Invasive Parakeets Introduced to Spain From Asia and South America
Authors: Morinha Francisco , Carrete Martina , Tella José L. , Blanco Guillermo
Published: May 2020

The psittacine beak and feather disease (PBFD) is a globally widespread infectious bird disease that mainly affects species within the Order Psittaciformes (parrots and allies). The disease is caused by an avian circovirus (the beak and feather disease virus, BFDV), which is highly infectious and can lead to severe consequences in wild and captive populations during an outbreak. Both legal and illegal trading have spread the BFDV around the world, although little is known about its prevalence in invasive parrot populations. Here, we analyze the BFDV prevalence in sympatric invasive populations of rose-ringed (Psittacula krameri) and monk parakeets (Myiopsitta monachus) in Southern Spain. We PCR-screened 110 blood samples (55 individuals from each species) for BFDV and characterized the genotypes of five positives from each species. About 33% of rose-ringed parakeets and 37% of monk parakeets sampled were positive for BFDV, while neither species showed disease symptoms. The circovirus identified is a novel BFDV genotype common to both species, similar to the BFDV genotypes detected in several parrot species kept in captivity in Saudi Arabia, South Africa and China. Our data evidences the importance of an accurate evaluation of avian diseases in wild populations, since invasive parrots may be bringing BFDV without showing any visually detectable clinical sign. Further research on the BFDV prevalence and transmission (individual–individual, captive–wild and wild–captive) in different bird orders and countries is crucial to understand the dynamics of the viral infection and minimize its impact in captive and wild populations.
Weighted Quantile Regression Forests for Bimodal Distribution Modeling: A Loss Given Default Case
Authors: Gostkowski Michał , Gajowniczek Krzysztof
Published: May 2020

Due to various regulations (e.g., the Basel III Accord), banks need to keep a specified amount of capital to reduce the impact of their insolvency. This equity can be calculated using, e.g., the Internal Rating Approach, enabling institutions to develop their own statistical models. In this regard, one of the most important parameters is the loss given default, whose correct estimation may lead to a healthier and riskless allocation of the capital. Unfortunately, since the loss given default distribution is a bimodal application of the modeling methods (e.g., ordinary least squares or regression trees), aiming at predicting the mean value is not enough. Bimodality means that a distribution has two modes and has a large proportion of observations with large distances from the middle of the distribution; therefore, to overcome this fact, more advanced methods are required. To this end, to model the entire loss given default distribution, in this article we present the weighted quantile Regression Forest algorithm, which is an ensemble technique. We evaluate our methodology over a dataset collected by one of the biggest Polish banks. Through our research, we show that weighted quantile Regression Forests outperform “single” state-of-the-art models in terms of their accuracy and the stability.
Novel Models of Image Permutation and Diffusion Based on Perturbed Digital Chaos
Authors: Hoang Thang Manh , Assad Safwan El
Published: May 2020

Most of chaos-based cryptosystems utilize stationary dynamics of chaos for the permutation and diffusion, and many of those are successfully attacked. In this paper, novel models of the image permutation and diffusion are proposed, in which chaotic map is perturbed at bit level on state variables, on control parameters or on both. Amounts of perturbation are initially the coordinate of pixels in the permutation, the value of ciphered word in the diffusion, and then a value extracted from state variables in every iteration. Under the persistent perturbation, dynamics of chaotic map is nonstationary and dependent on the image content. The simulation results and analyses demonstrate the effectiveness of the proposed models by means of the good statistical properties of transformed image obtained after just only a single round.
Battery Electric Vehicle Eco-Cooperative Adaptive Cruise Control in the Vicinity of Signalized Intersections
Authors: Chen Hao , Rakha Hesham A.
Published: May 2020

This study develops a connected eco-driving controller for battery electric vehicles (BEVs), the BEV Eco-Cooperative Adaptive Cruise Control at Intersections (Eco-CACC-I). The developed controller can assist BEVs while traversing signalized intersections with minimal energy consumption. The calculation of the optimal vehicle trajectory is formulated as an optimization problem under the constraints of (1) vehicle acceleration/deceleration behavior, defined by a vehicle dynamics model; (2) vehicle energy consumption behavior, defined by a BEV energy consumption model; and (3) the relationship between vehicle speed, location, and signal timing, defined by vehicle characteristics and signal phase and timing (SPaT) data shared under a connected vehicle environment. The optimal speed trajectory is computed in real-time by the proposed BEV eco-CACC-I controller, so that a BEV can follow the optimal speed while negotiating a signalized intersection. The proposed BEV controller was tested in a case study to investigate its performance under various speed limits, roadway grades, and signal timings. In addition, a comparison of the optimal speed trajectories for BEVs and internal combustion engine vehicles (ICEVs) was conducted to investigate the impact of vehicle engine types on eco-driving solutions. Lastly, the proposed controller was implemented in microscopic traffic simulation software to test its networkwide performance. The test results from an arterial corridor with three signalized intersections demonstrate that the proposed controller can effectively reduce stop-and-go traffic in the vicinity of signalized intersections and that the BEV Eco-CACC-I controller produces average savings of 9.3% in energy consumption and 3.9% in vehicle delays.
Electric Powertrain Topology Analysis and Design for Heavy-Duty Trucks
Authors: Verbruggen Frans J. R. , Silvas Emilia , Hofman Theo
Published: May 2020

Powertrain system design optimization is an unexplored territory for battery electric trucks, which only recently have been seen as a feasible solution for sustainable road transport. To investigate the potential of these vehicles, in this paper, a variety of new battery electric powertrain topologies for heavy-duty trucks is studied. Thereby, topological design considerations are analyzed related to having: (a) a central or distributed drive system (individually-driven wheels); (b) a single or a multi-speed gearbox; and finally, (c) a single or multiple electric machines. For reasons of comparison, each concurrent powertrain topology is optimized using a bilevel optimization framework, incorporating both powertrain components and control design. The results show that the combined choice of powertrain topology and number of gears in the gearbox can result in a 5.6% total-cost-of-ownership variation of the vehicle and can, significantly, influence the optimal sizing of the electric machine(s). The lowest total-cost-of-ownership is achieved by a distributed topology with two electric machines and two two-speed gearboxes. Furthermore, results show that the largest average reduction in total-cost-of-ownership is achieved by choosing a distributed drive over a central drive topology (−1.0%); followed by using a two-speed gearbox over a single speed (−0.6%); and lastly, by using two electric machines over using one for the central drive topologies (−0.3%).
Characteristics of Radioactive Effluent Releases from Pressurized Water Reactors after Permanent Shutdown
Authors: Kang Ji Su , Cheong Jae Hak
Published: May 2020

In order to expand our understanding of the characteristics of radioactive effluent from nuclear power plants under decommissioning, which have not been systematically investigated, a series of source term models of radioactive effluent after permanent shutdown has been established based upon theoretical reasoning on the design and operation features of plants and derived in terms of fifteen arguments. Comprehensive radioactive effluent data have been collected and profiled from twenty-eight decommissioning pressurized water reactors, and annual trends of effluent from each plant have been quantitatively analyzed using Mann-Kendall statistical test. In addition, the characteristics of collected effluent data have been qualitatively interpreted based upon arguments newly proposed in this study. Furthermore, potential decreasing of dilution factor for liquid effluent and its safety implications are identified. The source term models and verified characteristics of radioactive effluent after permanent shutdown developed in this study can be used for establishing more efficient discharge monitoring program for decommissioning authorization.
Assessment of the Operation Process of Wind Power Plant’s Equipment with the Use of an Artificial Neural Network
Authors: Duer Stanisław
Published: May 2020

In this article, a description is presented of simulation investigations concerning the quality of regeneration effects of a technical object in an intelligent system with an artificial neural network. All repairable technical objects used are subject to a cyclic (random) process of damages and repairs in the time of their operation. A reduction of the parameters connected with the use of objects is the fundamental feature of this process. This results in the need of a regeneration (technical maintenance) of this object. Regeneration of an object in an intelligent system with an artificial neural network constitutes an effective approach to this problem. The problem of qualitative assessments of a maintenance process organized in this manner is the focus of this article. For this purpose, a program of simulation investigations is presented. The research program consists of a description of the models of the operation processes of technical objects, determination of the input data to the investigations that are the quantities of the operation time of a technical object being the summary duration time of the regeneration (repairs) and the use of objects and the determination of the indexes of a qualitative assessment of the regeneration of an object in the operation process. The results of the study were justified with an example of simulation investigations concerning the effects of the operation process with the regeneration of a technical object in an intelligent system with an artificial neural network.
Co-Solvent Controllable Engineering of MA0.5FA0.5Pb0.8Sn0.2I3 Lead–Tin Mixed Perovskites for Inverted Perovskite Solar Cells with Improved Stability
Authors: Chen Lung-Chien , Tien Ching-Ho , Jhou Yang-Cheng , Lin Wei-Cheng
Published: May 2020

Use of a lead–tin mixed perovskite is generally considered an effective method to broaden the absorption wavelength of perovskite thin films. However, the preparation of lead–tin mixed perovskites is a major challenge due to the multivalent state of tin and stability in the atmosphere. This study attempted to replace the organic cation and metal elements of perovskites with a relatively thermal stable formamidinium (FA+) and a more environmentally friendly tin element. MA0.5FA0.5Pb0.8Sn0.2I3 lead–tin mixed perovskite thin films were prepared with the one-step spin-coating method. By adjusting the dimethylformamide (DMF):dimethyl sulfoxide (DMSO) concentration ratio of the lead–tin mixed perovskite precursor solution, the surface morphologies, crystallinity, and light-absorbing properties of the films were changed during synthesis to optimize the lead–tin mixed perovskite films as a light-absorbing layer of the inverted perovskite solar cells. The quality of the prepared lead–tin mixed perovskite film was the highest when the ratio of DMF:DMSO = 1:4. The power-conversion efficiency of the perovskite solar cell prepared with the film was 8.05%.
Bolt-Bearing Yield Strength of Three-Layered Cross-Laminated Timber Treated with Phenol Formaldehyde Resin
Authors: Hu Wengang , Zhang Jilei
Published: May 2020

The effect of impregnation treatment of low molecular weight phenol formaldehyde (MWPF) resin on the bolt-bearing yield strength (BBYS) of a three-layered cross-laminated timber (CLT) composed of two face layers of southern pine (Pinus taeda) and one core layer of sweetgum (Liquidambar styraciflua) was investigated together with two additional factors of material type and loading direction. Experimental results indicated that the amount of low MWPF resins penetrating into sweetgum was more than the ones into southern pine. Sweetgum had more uniform distribution of low MWPF resins penetrating longitudinally than southern pine. Impregnation treatment using a low MWPF resin at a concentration of 20% can enhance the BBYS of three-layered CLTs with a 60% increase. The BBYS of a core layer material in three-layered CLTs can significantly alter the overall BBYS of the three-layered CLTs.
A Review of Non-Chemical Weed Control Practices in Christmas Tree Production
Authors: Saha Debalina , Cregg Bert M. , Sidhu Manjot Kaur
Published: May 2020

Weeds interfere with Christmas tree growth at any time and at any stage of production. Growers mostly rely on mechanical mowing and applications of herbicides for weed control in their fields. However, herbicides can be phytotoxic to non-target plants, can cause environment-related issues, and their repeated application can even cause herbicide-resistant weeds. The main objective of this manuscript is to provide a review of non-chemical weed control strategies in Christmas tree production and identify areas where current practices could potentially be improved or in which further research is required. Preventing the introduction of weed seeds requires controlling weeds along farm roads, maintaining clean equipment, and eliminating new weeds before they start seeding. Mowing helps to reduce the number of seeds produced by the weeds and can significantly reduce competition with trees. Shropshire sheep are well suited for grazing Christmas tree plantations as they prefer grazing on grasses and weeds rather than on coniferous trees. Weeds can also be controlled around Christmas trees by mulching. Organic mulch can improve soil moisture, maintain soil temperatures, enhance root establishment and transplant survival, and improve plant establishment and overall growth. Incorporating cover crops into Christmas tree plantations may improve tree growth, quality, and soil fertility and can supplement conventional nitrogen fertilizers. However, if cover crops are not properly managed, they can be highly competitive with the trees. Flaming can cause suppression of many annual weed species but is less effective on larger weeds and needs to be applied with caution. Several insects have been used as biological agents to control selective weed species. However, further research is required to focus on several potential biological agents, different types and depths of mulches, on cover crops types and their competition with different species of Christmas trees and their effects on seedling survival and growth.
Modeling Acoustic Cavitation Using a Pressure-Based Algorithm for Polytropic Fluids
Authors: Denner Fabian , Evrard Fabien , van Wachem Berend
Published: May 2020

A fully coupled pressure-based algorithm and finite-volume framework for the simulation of the acoustic cavitation of bubbles in polytropic gas-liquid systems is proposed. The algorithm is based on a conservative finite-volume discretization with collocated variable arrangement, in which the discretized governing equations are solved in a single linear system of equations for pressure and velocity. Density is described by the polytropic Noble-Abel stiffened-gas model and the interface between the interacting bulk phases is captured by a state-of-the-art algebraic Volume-of-Fluid (VOF) method. The new numerical algorithm is validated using representative test-cases of the interaction of acoustic waves with the gas-liquid interface as well as pressure-driven bubble dynamics in infinite and confined domains, showing excellent agreement of the results obtained with the proposed algorithm compared to linear acoustic theory, the Gilmore model and high-fidelity experiments.
Effect of Moringa oleifera L. Leaf Powder Addition on the Phenolic Bioaccessibility and on In Vitro Starch Digestibility of Durum Wheat Fresh Pasta
Authors: Rocchetti Gabriele , Rizzi Corrado , Pasini Gabriella , Lucini Luigi , Giuberti Gianluca , Simonato Barbara
Published: May 2020

Fresh pasta was formulated by replacing wheat semolina with 0, 5, 10, and 15 g/100 g (w/w) of Moringa oleifera L. leaf powder (MOLP). The samples (i.e., M0, M5, M10, and M15 as a function of the substitution level) were cooked by boiling. The changes in the phenolic bioaccessibility and the in vitro starch digestibility were considered. On the cooked-to-optimum samples, by means of ultra-high-performance liquid chromatography-quadrupole time-of-flight (UHPLC-QTOF) mass spectrometry, 152 polyphenols were putatively annotated with the greatest content recorded for M15 pasta, being 2.19 mg/g dry matter (p < 0.05). Multivariate statistics showed that stigmastanol ferulate (VIP score = 1.22) followed by isomeric forms of kaempferol (VIP scores = 1.19) and other phenolic acids (i.e., schottenol/sitosterol ferulate and 24-methylcholestanol ferulate) were the most affected compounds through the in vitro static digestion process. The inclusion of different levels of MOLP in the recipe increased the slowly digestible starch fractions and decreased the rapidly digestible starch fractions and the starch hydrolysis index of the cooked-to-optimum samples. The present results showed that MOLP could be considered a promising ingredient in fresh pasta formulation.
Molecular Genetics and Pathogenesis of Ehlers–Danlos Syndrome and Related Connective Tissue Disorders
Authors: Ritelli Marco , Colombi Marina
Published: May 2020

Ehlers–Danlos syndromes (EDS) are a group of heritable connective tissue disorders (HCTDs) characterized by a variable degree of skin hyperextensibility, joint hypermobility and tissue fragility. The current EDS classification distinguishes 13 subtypes and 19 different causal genes mainly involved in collagen and extracellular matrix synthesis and maintenance. EDS need to be differentiated from other HCTDs with a variable clinical overlap including Marfan syndrome and related disorders, some types of skeletal dysplasia and cutis laxa. Clinical recognition of EDS is not always straightforward and for a definite diagnosis, molecular testing can be of great assistance, especially in patients with an uncertain phenotype. Currently, the major challenging task in EDS is to unravel the molecular basis of the hypermobile EDS that is the most frequent form, and for which the diagnosis is only clinical in the absence of any definite laboratory test. This EDS subtype, as well as other EDS-reminiscent phenotypes, are currently investigated worldwide to unravel the primary genetic defect and related pathomechanisms. The research articles, case report, and reviews published in this Special Issue focus on different clinical, genetic and molecular aspects of several EDS subtypes and some related disorders, offering novel findings and future research and nosological perspectives.
Haplotype-Based Genome-Wide Association Study and Identification of Candidate Genes Associated with Carcass Traits in Hanwoo Cattle
Authors: Srivastava Swati , Srikanth Krishnamoorthy , Won Sohyoung , Son Ju-Hwan , Park Jong-Eun , Park Woncheoul , Chai Han-Ha , Lim Dajeong
Published: May 2020

Hanwoo, is the most popular native beef cattle in South Korea. Due to its extensive popularity, research is ongoing to enhance its carcass quality and marbling traits. In this study we conducted a haplotype-based genome-wide association study (GWAS) by constructing haplotype blocks by three methods: number of single nucleotide polymorphisms (SNPs) in a haplotype block (nsnp), length of genomic region in kb (Len) and linkage disequilibrium (LD). Significant haplotype blocks and genes associated with them were identified for carcass traits such as BFT (back fat thickness), EMA (eye Muscle area), CWT (carcass weight) and MS (marbling score). Gene-set enrichment analysis and functional annotation of genes in the significantly-associated loci revealed candidate genes, including PLCB1 and PLCB4 present on BTA13, coding for phospholipases, which might be important candidates for increasing fat deposition due to their role in lipid metabolism and adipogenesis. CEL (carboxyl ester lipase), a bile-salt activated lipase, responsible for lipid catabolic process was also identified within the significantly-associated haplotype block on BTA11. The results were validated in a different Hanwoo population. The genes and pathways identified in this study may serve as good candidates for improving carcass traits in Hanwoo cattle.
rps3 as a Candidate Mitochondrial Gene for the Molecular Identification of Species from the Colletotrichum acutatum Species Complex
Authors: Pszczółkowska Agnieszka , Androsiuk Piotr , Jastrzębski Jan Paweł , Paukszto Łukasz , Okorski Adam
Published: May 2020

Colletotrichum species form one of the most economically significant groups of pathogenic fungi and lead to significant losses in the production of major crops—in particular, fruits, vegetables, ornamental plants, shrubs, and trees. Members of the genus Colletotrichum cause anthracnose disease in many plants. Due to their considerable variation, these fungi have been widely investigated in genetic studies as model organisms. Here, we report the complete mitochondrial genome sequences of four Colletotrichum species (C. fioriniae, C. lupini, C. salicis, and C. tamarilloi). The reported circular mitogenomes range from 30,020 (C. fioriniae) to 36,554 bp (C. lupini) in size and have identical sets of genes, including 15 protein-coding genes, two ribosomal RNA genes, and 29 tRNA genes. All four mitogenomes are characterized by a rather poor repetitive sequence content with only forward repeat representatives and a low number of microsatellites. The topology of the phylogenetic tree reflects the systematic positions of the studied species, with representatives of each Colletotrichum species complex gathered in one clade. A comparative analysis reveals consistency in the gene composition and order of Colletotrichum mitogenomes, although some highly divergent regions are also identified, like the rps3 gene which appears as a source of potential diagnostic markers for all studied Colletotrichum species.
Hearts—A New International Open Access Journal for Cardiology, Cardiac and Vascular Surgery
Authors: Thielmann Matthias
Published: May 2020

As an international and multidisciplinary peer-reviewed open access journal for all areas of cardiology and cardiovascular surgery, Hearts has now been founded to publish original research, reviews, position papers and guideline documents, letters, ‘how to do’ reports, and rapid communications [...]
A Multiscale Evaluation of the Coupling Relationship between Urban Land and Carbon Emissions: A Case Study of Chongqing, China
Authors: Li Chuanlong , Li Yuanqing , Shi Kaifang , Yang Qingyuan
Published: May 2020

Exploring the coupling relationship between urban land and carbon emissions (CE) is one of the important premises for coordinating the urban development and the ecological environment. Due to the influence of the scale effect, a systematic evaluation of the CE at different scales will help to develop more reasonable strategies for low-carbon urban planning. However, corresponding studies are still lacking. Hence, two administrative scales (e.g., region and county) in Chongqing were selected as experimental objects to compare and analyze the CE at different scales using the spatiotemporal coupling and coupling coordination models. The results show that urban land and carbon emissions presented a significant growth trend in Chongqing at different scales from 2000 to 2015. The strength of the spatiotemporal coupling relationship between urban land and total carbon emissions gradually increased with increasing scale. At the regional scale, the high coupling coordination between urban land and total carbon emissions was mainly concentrated in the urban functional development region. Additionally, the high coupling coordination between urban land and carbon emission intensity (OI) was still located in the counties within the metropolitan region of Chongqing, but the low OI was mainly distributed in the counties in the northeastern and southeastern regions of Chongqing at the county level. This study illustrates the multiscale trend of CE and suggests differentiated urban land and carbon emission reduction policies for controlling urban land sprawl and reducing carbon emissions.
The Expression and Polymorphism of Entry Machinery for COVID-19 in Human: Juxtaposing Population Groups, Gender, and Different Tissues
Authors: Darbani Behrooz
Published: May 2020

(1) Background: Combating viral disease outbreaks has doubtlessly been one of the major public health challenges for the 21st century. (2) Methods: The host entry machinery required for COVID-19 (SARS-CoV-2) infection was examined for the gene expression profiles and polymorphism. (3) Results: Lung, kidney, small intestine, and salivary glands were among the tissues which expressed the entry machinery coding genes Ace2, Tmprss2, CtsB, and CtsL. The genes had no significant expression changes between males and females. The four human population groups of Europeans, Africans, Asians, and Americans had specific and also a common pool of rare variants for the X-linked locus of ACE2 receptor. Several specific and common ACE2 variants including S19P, I21T/V, E23K, A25T, K26R, T27A, E35D/K, E37K, Y50F, N51D/S, M62V, N64K, K68E, F72V, E75G, M82I, T92I, Q102P, G220S, H239Q, G326E, E329G, G352V, D355N, H378R, Q388L, P389H, E467K, H505R, R514G/*, and Y515C were of the utmost importance to the viral entry and infection. The variants of S19P, I21T, K26R, T27A, E37K, N51D, N64K, K68E, F72V, M82I, G326E, H378R, Q388L, and P389H also had significant differences in frequencies among the population groups. Most interestingly, the analyses revealed that more than half of the variants can exist in males, i.e., as hemizygous. (4) Conclusions: The rare variants of human ACE2 seem to be one of the determinant factors associated with fitness in the battle against SARS viruses. The hemizygous viral-entry booster variants of ACE2 describe the higher SARS-CoV-2 mortality rate in males. This is also supported by the lack of gender bias for the gene expression profiles of entry machinery. A personalized medicine strategy is conceived for isolating high-risk individuals in epidemic circumstances.
Targeting Actomyosin Contractility Suppresses Malignant Phenotypes of Acute Myeloid Leukemia Cells
Authors: Chang Fengjiao , Kong So Jung , Wang Lele , Choi Beom K. , Lee Hyewon , Kim Chan , Kim Jin Man , Park Kyungpyo
Published: May 2020

Actomyosin-mediated contractility is required for the majority of force-driven cellular events such as cell division, adhesion, and migration. Under pathological conditions, the role of actomyosin contractility in malignant phenotypes of various solid tumors has been extensively discussed, but the pathophysiological relevance in hematopoietic malignancies has yet to be elucidated. In this study, we found enhanced actomyosin contractility in diverse acute myeloid leukemia (AML) cell lines represented by highly expressed non-muscle myosin heavy chain A (NMIIA) and increased phosphorylation of the myosin regulatory light chain. Genetic and pharmacological inhibition of actomyosin contractility induced multivalent malignancy- suppressive effects in AML cells. In this context, perturbed actomyosin contractility enhances AML cell apoptosis through cytokinesis failure and aryl hydrocarbon receptor activation. Moreover, leukemic oncogenes were downregulated by the YAP/TAZ-mediated mechanotransduction pathway. Our results provide a theoretical background for targeting actomyosin contractility to suppress the malignancy of AML cells.
Nutrients and Porphyria: An Intriguing Crosstalk
Authors: Di Pierro Elena , Granata Francesca
Published: May 2020

Porphyria refers to a group of fascinating diseases from a metabolic and nutritional standpoint as it provides an example of how metabolic manipulation can be used for therapeutic purposes. It is characterized by defects in heme synthesis, particularly in the erythrocytes and liver. Specific enzymes involved in heme biosynthesis directly depend on adequate levels of vitamins and minerals in the tissues. Moreover, micronutrients that are required for producing succinyl CoA and other intermediates in the Krebs (TCA) cycle are indirectly necessary for heme metabolism. This review summarizes articles that describe the nutritional status, supplements intake, and dietary practices of patients affected by porphyria, paying special attention to the therapeutic use of nutrients that may help or hinder this group of diseases.
CX3CR1-Targeted PLGA Nanoparticles Reduce Microglia Activation and Pain Behavior in Rats with Spinal Nerve Ligation
Authors: Noh Chan , Shin Hyo Jung , Lee Seounghun , Kim Song I , Kim Yoon-Hee , Lee Won Hyung , Kim Dong Woon , Lee Sun Yeul , Ko Young Kwon
Published: May 2020

Activation of CX3CR1 in microglia plays an important role in the development of neuropathic pain. Here, we investigated whether neuropathic pain could be attenuated in spinal nerve ligation (SNL)-induced rats by reducing microglial activation through the use of poly(D,L-lactic-co-glycolic acid) (PLGA)-encapsulated CX3CR1 small-interfering RNA (siRNA) nanoparticles. After confirming the efficacy and specificity of CX3CR1 siRNA, as evidenced by its anti-inflammatory effects in lipopolysaccharide-stimulated BV2 cells in vitro, PLGA-encapsulated CX3CR1 siRNA nanoparticles were synthesized by sonication using the conventional double emulsion (W/O/W) method and administered intrathecally into SNL rats. CX3CR1 siRNA-treated rats exhibited significant reductions in the activation of microglia in the spinal dorsal horn and a downregulation of proinflammatory mediators, as well as a significant attenuation of mechanical allodynia. These data indicate that the PLGA-encapsulated CX3CR1 siRNA nanoparticles effectively reduce neuropathic pain in SNL-induced rats by reducing microglial activity and the expression of proinflammatory mediators. Therefore, we believe that PLGA-encapsulated CX3CR1 siRNA nanoparticles represent a valuable new treatment option for neuropathic pain.
Characterizing the Nature of Probability-Based Proof Number Search: A Case Study in the Othello and Connect Four Games
Authors: Primanita Anggina , Khalid Mohd Nor Akmal , Iida Hiroyuki
Published: May 2020

Variants of best-first search algorithms and their expansions have continuously been introduced to solve challenging problems. The probability-based proof number search (PPNS) is a best-first search algorithm that can be used to solve positions in AND/OR game tree structures. It combines information from explored (based on winning status) and unexplored (through Monte Carlo simulation) nodes from a game tree using an indicator called the probability-based proof number (PPN). In this study, PPNS is employed to solve randomly generated positions in Connect Four and Othello, in which the results are compared with the two well-known best-first search algorithms (proof number search (PNS) and Monte Carlo proof number search). Adopting a simple improvement parameter in PPNS reduces the number of nodes that need to be explored by up to 57%. Moreover, further observation showed the varying importance of information from explored and unexplored nodes in which PPNS relies critically on the combination of such information in earlier stages of the Othello game. Discussion and insights from these findings are provided where the potential future works are briefly described.