bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent Human KIT Receptor Signaling Disposes Murine Placenta to Premature Differentiation Resulting in Severely Disrupted Placental Structure and Functionality
Authors: Kaiser Franziska , Hartweg Julia , Jansky Selina , Pelusi Natalie , Kubaczka Caroline , Sharma Neha , Nitsche Dominik , Langkabel Jan , Schorle Hubert
Published: August 2020

Activating mutations in the human KIT receptor is known to drive severe hematopoietic disorders and tumor formation spanning various entities. The most common mutation is the substitution of aspartic acid at position 816 to valine (D816V), rendering the receptor constitutively active independent of ligand binding. As the role of the KIT receptor in placental signaling cascades is poorly understood, we analyzed the impact of KITD816V expression on placental development using a humanized mouse model. Placentas from KITD816V animals present with a grossly changed morphology, displaying a reduction in labyrinth and spongiotrophoblast layer and an increase in the Parietal Trophoblast Giant Cell (P-TGC) layer. Elevated differentiation to P-TGCs was accompanied with reduced differentiation to other Trophoblast Giant Cell (TGC) subtypes and by severe decrease in proliferation. The embryos display growth retardation and die in utero. KITD816V-trophoblast stem cells (TSC) differentiate much faster compared to wild type (WT) controls. In undifferentiated KITD816V-TSCs, levels of Phosphorylated Extracellular-signal Regulated Kinase (P-ERK) and Phosphorylated Protein Kinase B (P-AKT) are comparable to wildtype cultures differentiating for 3–6 days. Accordingly, P-TGC markers Placental Lactogen 1 (PL1) and Proliferin (PLF) are upregulated as well. The results reveal that KIT signaling orchestrates the fine-tuned differentiation of the placenta, with special emphasis on P-TGC differentiation. Appropriate control of KIT receptor action is therefore essential for placental development and nourishment of the embryo.
Localization of the Elastic Proteins in the Flight Muscle of Manduca sexta
Authors: Gong Henry , Ma Weikang , Chen Shaoshuai , Wang Geng , Khairallah Ramzi , Irving Thomas
Published: August 2020

The flight muscle of Manduca sexta (DLM1) is an emerging model system for biophysical studies of muscle contraction. Unlike the well-studied indirect flight muscle of Lethocerus and Drosophila, the DLM1 of Manduca is a synchronous muscle, as are the vertebrate cardiac and skeletal muscles. Very little has been published regarding the ultrastructure and protein composition of this muscle. Previous studies have demonstrated that DLM1 express two projectin isoform, two kettin isoforms, and two large Salimus (Sls) isoforms. Such large Sls isoforms have not been observed in the asynchronous flight muscles of Lethocerus and Drosophila. The spatial localization of these proteins was unknown. Here, immuno-localization was used to show that the N-termini of projectin and Salimus are inserted into the Z-band. Projectin spans across the I-band, and the C-terminus is attached to the thick filament in the A-band. The C-terminus of Sls was also located in the A-band. Using confocal microscopy and experimental force-length curves, thin filament lengths were estimated as ~1.5 µm and thick filament lengths were measured as ~2.5 µm. This structural information may help provide an interpretive framework for future studies using this muscle system.
Emerging Role of Extracellular Vesicles in Embryo–Maternal Communication throughout Implantation Processes
Authors: Nakamura Keigo , Kusama Kazuya , Suda Yoshihito , Fujiwara Hiroshi , Hori Masatoshi , Imakawa Kazuhiko
Published: August 2020

In ruminants, the establishment of proper conceptus–endometrial communication is essential for conceptus implantation and subsequent successful placentation. Accumulated evidence supports the idea that extracellular vesicles (EVs) present in uterine lumen are involved in conceptus–endometrial interactions during the preimplantation period. EVs make up a new field of intercellular communicators, which transport a variety of bioactive molecules, including soluble and membrane-bound proteins, lipids, DNA, and RNAs. EVs thus regulate gene expression and elicit biological effects including increased cell proliferation, migration, and adhesion in recipient cells. Uterine EVs are interactive and coordinate with ovarian progesterone (P4), trophectoderm-derived interferon tau (IFNT) and/or prostaglandins (PGs) in the physiological or pathological microenvironment. In this review, we will focus on intrauterine EVs in embryo–maternal interactions during the early stage of pregnancy, especially the implantation period in ruminant ungulates.
Exploring the Potential of Mesenchymal Stem Cell-Based Therapy in Mouse Models of Vascular Cognitive Impairment
Authors: Lee Na Kyung , Kim Hyeongseop , Chang Jong Wook , Jang Hyemin , Kim Hunnyun , Yang Jehoon , Kim Jeyun , Son Jeong Pyo , Na Duk L.
Published: August 2020

Closely linked to Alzheimer’s disease (AD), the pathological spectrum of vascular cognitive impairment (VCI) is known to be wide and complex. Considering that multiple instead of a single targeting approach is considered a treatment option for such complicated diseases, the multifaceted aspects of mesenchymal stem cells (MSCs) make them a suitable candidate to tackle the heterogeneity of VCI. MSCs were delivered via the intracerebroventricular (ICV) route in mice that were subjected to VCI by carotid artery stenosis. VCI was induced in C57BL6/J mice wild type (C57VCI) mice by applying a combination of ameroid constrictors and microcoils, while ameroid constrictors alone were bilaterally applied to 5xFAD (transgenic AD mouse model) mice (5xVCI). Compared to the controls (minimal essential medium (MEM)-injected C57VCI mice), changes in spatial working memory were not noted in the MSC-injected C57VCI mice, and unexpectedly, the mortality rate was higher. In contrast, compared to the MEM-injected 5xVCI mice, mortality was not observed, and the spatial working memory was also improved in MSC-injected 5xVCI mice. Disease progression of the VCI-induced mice seems to be affected by the method of carotid artery stenosis and due to this heterogeneity, various factors must be considered to maximize the therapeutic benefits exerted by MSCs. Factors, such as the optimal MSC injection time point, cell concentration, sacrifice time point, and immunogenicity of the transplanted cells, must all be adequately addressed so that MSCs can be appropriately and effectively used as a treatment option for VCI.
Surfactin as a Green Agent Controlling the Growth of Porous Calcite Microstructures
Authors: Bastrzyk Anna , Fiedot-Toboła Marta , Maniak Halina , Polowczyk Izabela , Płaza Grażyna
Published: August 2020

This study presents a new, simple way to obtain mesoporous calcite structures via a green method using an eco-friendly surface-active compound, surfactin, as a controlling agent. The effects of synthesis time and surfactin concentration were investigated. The obtained structures were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) coupled with gas mass spectrometry (QMS) analysis. The experimental data showed that surfactin molecules significantly changed the morphology of the calcite crystals, roughening and deforming the surface and creating a greater specific surface area, even at low biosurfactant concentrations (10 ppm). The size of the crystals was reduced, and the zeta potential value of calcium carbonate was more negative when more biosurfactant was added. The XRD data revealed that the biomolecules were incorporated into the crystals and slowed the transformation of vaterite into calcite. It has been shown that as long as vaterite is present in the medium, the calcite surface will be less deformed. The strong influence of surfactin molecules on the crystal growth of calcium carbonate was due to the interaction of surfactin molecules with free calcium ions in the solution as well as the biomolecules adsorption at the formed crystal surface. The role of micelles in crystal growth was examined, and the mechanism of mesoporous calcium carbonate formation was presented.
Impact of Nucleic Acid Sequencing on Viroid Biology
Authors: Adkar-Purushothama Charith Raj , Perreault Jean-Pierre
Published: August 2020

The early 1970s marked two breakthroughs in the field of biology: (i) The development of nucleotide sequencing technology; and, (ii) the discovery of the viroids. The first DNA sequences were obtained by two-dimensional chromatography which was later replaced by sequencing using electrophoresis technique. The subsequent development of fluorescence-based sequencing method which made DNA sequencing not only easier, but many orders of magnitude faster. The knowledge of DNA sequences has become an indispensable tool for both basic and applied research. It has shed light biology of viroids, the highly structured, circular, single-stranded non-coding RNA molecules that infect numerous economically important plants. Our understanding of viroid molecular biology and biochemistry has been intimately associated with the evolution of nucleic acid sequencing technologies. With the development of the next-generation sequence method, viroid research exponentially progressed, notably in the areas of the molecular mechanisms of viroids and viroid diseases, viroid pathogenesis, viroid quasi-species, viroid adaptability, and viroid–host interactions, to name a few examples. In this review, the progress in the understanding of viroid biology in conjunction with the improvements in nucleotide sequencing technology is summarized. The future of viroid research with respect to the use of third-generation sequencing technology is also briefly envisaged.
Cytotoxic Effects of Cannabinoids on Human HT-29 Colorectal Adenocarcinoma Cells: Different Mechanisms of THC, CBD, and CB83
Authors: Cerretani Daniela , Collodel Giulia , Brizzi Antonella , Fiaschi Anna Ida , Menchiari Andrea , Moretti Elena , Moltoni Laura , Micheli Lucia
Published: August 2020

In this study, we investigated the effects of exposition to IC50 dose for 24 h of a new synthetic cannabinoid (CB83) and of phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on HT-29 colorectal carcinoma cells. Cell viability and proliferative activity evaluated using the MTT, lactate dehydrogenase (LDH), and CyQUANT assays showed that cell viability was significantly affected when CB83, THC, and CBD were administered to cells. The results obtained showed that the reduced glutathione/oxidized glutathione ratio was significantly reduced in the cells exposed to CBD and significantly increased in the cells treated with the CB83 when compared to the controls. CBD treatment causes a significant increase in malondialdehyde content. The catalase activity was significantly reduced in HT-29 cells after incubation with CB83, THC, and CBD. The activities of glutathione reductase and glutathione peroxidase were significantly increased in cells exposed to THC and significantly decreased in those treated with CBD. The ascorbic acid content was significantly reduced in cells exposed to CB83, THC, and CBD. The ultrastructural investigation by TEM highlighted a significantly increased percentage of cells apoptotic and necrotic after CB83 exposition. The Annexin V-Propidium Iodide assay showed a significantly increased percentage of cells apoptotic after CB83 exposition and necrotic cells after CBD and THC exposition. Our results proved that only CBD induced oxidative stress in HT-29 colorectal carcinoma cells via CB receptor-independent mechanisms and that CB83 caused a mainly CB2 receptor-mediated antiproliferative effect comparable to 5-Fuorouracil, which is still the mainstay drug in protocols for colorectal cancer.
An EPR Study on the Interaction between the Cu(I) Metal Binding Domains of ATP7B and the Atox1 Metallochaperone
Authors: Zaccak Michael , Qasem Zena , Gevorkyan-Airapetov Lada , Ruthstein Sharon
Published: August 2020

Copper’s essentiality and toxicity mean it requires a sophisticated regulation system for its acquisition, cellular distribution and excretion, which until now has remained elusive. Herein, we applied continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) spectroscopy in solution to resolve the copper trafficking mechanism in humans, by considering the route travelled by Cu(I) from the metallochaperone Atox1 to the metal binding domains of ATP7B. Our study revealed that Cu(I) is most likely mediated by the binding of the Atox1 monomer to metal binding domain 1 (MBD1) and MBD4 of ATP7B in the final part of its extraction pathway, while the other MBDs mediate this interaction and participate in copper transfer between the various MBDs to the ATP7B membrane domain. This research also proposes that MBD1-3 and MBD4-6 act as two independent units.
Orally Administered Exosomes Suppress Mouse Delayed-Type Hypersensitivity by Delivering miRNA-150 to Antigen-Primed Macrophage APC Targeted by Exosome-Surface Anti-Peptide Antibody Light Chains
Authors: Nazimek Katarzyna , Bryniarski Krzysztof , Ptak Wlodzimierz , Groot Kormelink Tom , Askenase Philip
Published: August 2020

We previously discovered suppressor T cell-derived, antigen (Ag)-specific exosomes inhibiting mouse hapten-induced contact sensitivity effector T cells by targeting antigen-presenting cells (APCs). These suppressive exosomes acted Ag-specifically due to a coating of antibody free light chains (FLC) from Ag-activated B1a cells. Current studies are aimed at determining if similar immune tolerance could be induced in cutaneous delayed-type hypersensitivity (DTH) to the protein Ag (ovalbumin, OVA). Intravenous administration of a high dose of OVA-coupled, syngeneic erythrocytes similarly induced CD3+CD8+ suppressor T cells producing suppressive, miRNA-150-carrying exosomes, also coated with B1a cell-derived, OVA-specific FLC. Simultaneously, OVA-immunized B1a cells produced an exosome subpopulation, originally coated with Ag-specific FLC, that could be rendered suppressive by in vitro association with miRNA-150. Importantly, miRNA-150-carrying exosomes from both suppressor T cells and B1a cells efficiently induced prolonged DTH suppression after single systemic administration into actively immunized mice, with the strongest effect observed after oral treatment. Current studies also showed that OVA-specific FLC on suppressive exosomes bind OVA peptides suggesting that exosome-coating FLC target APCs by binding to peptide-Ag-major histocompatibility complexes. This renders APCs capable of inhibiting DTH effector T cells. Thus, our studies describe a novel immune tolerance mechanism mediated by FLC-coated, Ag-specific, miRNA-150-carrying exosomes that act on the APC and are particularly effective after oral administration.
The N-Terminal Region of Soybean PM1 Protein Protects Liposomes during Freeze-Thaw
Authors: Chen Liyi , Sun Yajun , Liu Yun , Zou Yongdong , Huang Jianzi , Zheng Yizhi , Liu Guobao
Published: August 2020

Late embryogenesis abundant (LEA) group 1 (LEA_1) proteins are intrinsically disordered proteins (IDPs) that play important roles in protecting plants from abiotic stress. Their protective function, at a molecular level, has not yet been fully elucidated, but several studies suggest their involvement in membrane stabilization under stress conditions. In this paper, the soybean LEA_1 protein PM1 and its truncated forms (PM1-N: N-terminal half; PM1-C: C-terminal half) were tested for the ability to protect liposomes against damage induced by freeze-thaw stress. Turbidity measurement and light microscopy showed that full-length PM1 and PM1-N, but not PM1-C, can prevent freeze-thaw-induced aggregation of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) liposomes and native thylakoid membranes, isolated from spinach leaves (Spinacia oleracea). Particle size distribution analysis by dynamic light scattering (DLS) further confirmed that PM1 and PM1-N can prevent liposome aggregation during freeze-thaw. Furthermore, PM1 or PM1-N could significantly inhibit membrane fusion of liposomes, but not reduce the leakage of their contents following freezing stress. The results of proteolytic digestion and circular dichroism experiments suggest that PM1 and PM1-N proteins bind mainly on the surface of the POPC liposome. We propose that, through its N-terminal region, PM1 functions as a membrane-stabilizing protein during abiotic stress, and might inhibit membrane fusion and aggregation of vesicles or other endomembrane structures within the plant cell.
Inhibition of Colony-Stimulating Factor 1 Receptor by PLX3397 Prevents Amyloid Beta Pathology and Rescues Dopaminergic Signaling in Aging 5xFAD Mice
Authors: Son Yeonghoon , Jeong Ye Ji , Shin Na-Rae , Oh Se Jong , Nam Kyung Rok , Choi Hyung-Do , Choi Jae Yong , Lee Hae-June
Published: August 2020

Alzheimer’s disease (AD) is a progressive neurodegenerative disease. In this study, to investigate the effect of microglial elimination on AD progression, we administered PLX3397, a selective colony-stimulating factor 1 receptor inhibitor, to the mouse model of AD (5xFAD mice). Amyloid-beta (Aβ) deposition and amyloid precursor protein (APP), carboxyl-terminal fragment β, ionized calcium-binding adaptor molecule 1, synaptophysin, and postsynaptic density (PSD)-95 levels were evaluated in the cortex and hippocampus. In addition, the receptor density changes in dopamine D2 receptor (D2R) and metabotropic glutamate receptor 5 were evaluated using positron emission tomography (PET). D2R, tyrosine hydroxylase (TH), and dopamine transporter (DAT) levels were analyzed in the brains of Tg (5xFAD) mice using immunohistochemistry. PLX3397 administration significantly decreased Aβ deposition following microglial depletion in the cortex and hippocampus of Tg mice. In the neuro-PET studies, the binding values for D2R in the Tg mice were lower than those in the wild type mice; however, after PLX3397 treatment, the binding dramatically increased. PLX3397 administration also reversed the changes in synaptophysin and PSD-95 expression in the brain. Furthermore, the D2R and TH expression in the brains of Tg mice was significantly lower than that in the wild type; however, after PLX3397 administration, the D2R and TH levels were significantly higher than those in untreated Tg mice. Thus, our findings show that administering PLX3397 to aged 5xFAD mice could prevent amyloid pathology, concomitant with the rescue of dopaminergic signaling, suggesting that targeting microglia may serve as a useful therapeutic option for neurodegenerative diseases, including AD.
Real Gas Models in Coupled Algorithms Numerical Recipes and Thermophysical Relations
Authors: Hanimann Lucian , Mangani Luca , Casartelli Ernesto , Vogt Damian , Darwish Marwan
Published: August 2020

In the majority of compressible flow CFD simulations, the standard ideal gas state equation is accurate enough. However, there is a range of applications where the deviations from the ideal gas behaviour is significant enough that performance predictions are no longer valid and more accurate models are needed. While a considerable amount of the literature has been written about the application of real gas state equations in CFD simulations, there is much less information on the numerical issues involved in the actual implementation of such models. The aim of this article is to present a robust implementation of real gas flow physics in an in-house, coupled, pressure-based solver, and highlight the main difference that arises as compared to standard ideal gas model. The consistency of the developed iterative procedures is demonstrated by first comparing against results obtained with a framework using perfect gas simplifications. The generality of the developed framework is tested by using the parameters from two different real gas state equations, namely the IAPWS-97 and the cubic state equations state equations. The highly polynomial IAPWS-97 formulation for water is applied to a transonic nozzle case where steam is expanded at transonic conditions until phase transition occurs. The cubic state equations are applied to a two stage radial compressor setup. Results are compared in terms of accuracy with a commercial code and measurement data. Results are also compared against simulations using the ideal gas model, highlighting the limitations of the later model. Finally, the effects of the real gas formulations on computational time are compared with results obtained using the ideal gas model.
DNA Barcoding: A Reliable Method for the Identification of Thrips Species (Thysanoptera, Thripidae) Collected on Sticky Traps in Onion Fields
Authors: Marullo Rita , Mercati Francesco , Vono Gregorio
Published: August 2020

Several thrips species (Insecta, Thysanoptera) are globally known as important crop pests and vectors of viral diseases, but their identification is difficult because of their small body size and inconspicuous morphological differences. Sequencing variation in the mitochondrial cytochrome c oxidase I (COI) region has been proven to be useful for the identification of species of many groups of insect pests. Here, DNA barcoding has been used to identify thrips species collected with the use of sticky traps placed in an open onion field. A total of 238 thrips specimens were analyzed, 151 of which could be identified to species and 27 to genera belonging to the family Thripidae. Fifty-one specimens could not be assigned to any genus, with the closest BLAST match in the GenBank queries being below 98%, whilst six specimens were not recognized as Thysanoptera. The results indicate that, although there are a few pest thrips species not yet barcoded, most of the species that may cause damage to crops in Europe are represented in GenBank and other databases, enabling correct identification. Additionally, DNA barcoding can be considered a valuable alternative to the classic morphology method for identification of major thrips species.
Lethal and Sublethal Effects of Chlorpyrifos on Biological Traits and Feeding of the Aphidophagous Predator Harmonia axyridis
Authors: Rasheed Muhammad Asim , Khan Muhammad Musa , Hafeez Muhammad , Zhao Jing , Islam Yasir , Ali Shahzaib , Ur-Rehman Shakeel , e-Hani Um , Zhou Xingmiao
Published: August 2020

Except of pest control, insecticides have shown adverse effects on natural enemies as well. Thus, risk assessment of pesticides for biological control agents is critical for effective use in integrated pest management (IPM) schemes. In the present study, the lethal and sublethal effects of chlorpyrifos, a commonly used insecticide that may negatively affect biological control agents, were evaluated on a non-target predator, the Asian ladybeetle Harmonia axyridis. Previous studies have reported on lethal concentrations, but the effects of sublethal concentrations remain unclear. Lethal and sublethal concentrations of chlorpyrifos were applied to third instar larvae of H. axyridis, and different growth and developmental parameters were measured. Treatment with LC10 (4.62 mg a.i. L−1) significantly shortened the developmental period of third instar larvae, whereas it significantly prolonged those of fourth instar larvae and pupa. Treatment with LC30 (9.59 mg a.i. L−1) significantly increased the larval and pupal developmental period compared with that of the control, whereas feeding potential, female fecundity, and adult longevity significantly decreased after LC10 and LC30 treatment. The pre-oviposition period significantly increased compared with that of the control. Population growth parameters, the finite (λ) and intrinsic rate of increase (r) and the net reproductive rate (R0), decreased following exposure to sublethal concentrations of chlorpyrifos. According to the results, the use of chlorpyrifos in IPM schemes requires further research because even sublethal concentrations of this insecticide were harmful to H. axyridis population growth.
Current Distribution and Diagnostic Features of Two Potentially Invasive Asian Buprestid Species: Agrilus mali Matsumura and A. fleischeri Obenberger (Coleoptera: Buprestidae)
Authors: Volkovitsh Mark G. , Kovalev Alexey V. , Orlova-Bienkowskaja Marina J.
Published: August 2020

Our goal is to analyze the known geographical ranges and diagnostic features of two potentially invasive Asian buprestid species: the quarantine apple tree pest, Agrilus mali Matsumura, and the poplar pest A. fleischeri Obenberger. Based on the examination of museum collections and literature sources, we compiled comprehensive databases of records of the exact collecting sites for both species and generated detailed maps of their ranges. There are 51 documented localities for A. mali in the Russian Far East and East Siberia, Mongolia, China, and the Korean peninsula, and there are 53 documented localities for A. fleischeri in the Far East and Siberia, Kazakhstan, Mongolia, China, and Japan. No evidence of the presence of A. mali in Japan was found. Outbreak sites of A. mali in Xinjiang in the 2000s most likely represent the newly forming invasion areas; their proximity to the wild apple stands in the Kazakh part of the Tien Shan is a direct threat to Kazakhstan and adjacent countries. Sites damaged by A. fleischeri in Liaoning are situated within its native range; the outbreaks were likely triggered by the switch from indigenous to introduced poplars. This situation is similar to the early stages of emerald ash borer (Agrilus planipennis Fairmaire) invasion.
Novel Input for Designing Patient-Tailored Pulmonary Rehabilitation: Telemonitoring Physical Activity as a Vital Sign—SMARTREAB Study
Authors: Santos Catarina Duarte , das Neves Rui César , Ribeiro Ruy M. , Caneiras Cátia , Rodrigues Fátima , Spruit Martijn A. , Bárbara Cristina
Published: August 2020

Physical inactivity may be a consequence of chronic diseases but also a potential modifiable risk factor. Therefore, it should be clinically assessed as a vital sign of patients’ general physical condition prior to any exercise-based intervention. This cross-sectional study describes physical activity in the daily life of 100 chronic respiratory patients before pulmonary rehabilitation, comparing subjective and objective measures. The assessment combined the International Physical Activity Questionnaire (IPAQ) and 4-day accelerometer and oximeter telemonitoring with SMARTREAB technology, assessing heart rate, transcutaneous oxygen saturation and activity-related energy expenditure by metabolic equivalent of task (MET). According to IPAQ, 49% of patients had a moderate level of physical activity in daily life (PADL), a weekly mean level of 2844 ± 2925 MET.min/week, and a mean sedentary time of 5.8 ± 2.7 h/day. Alongside this, SMARTREAB telemonitoring assessed maximum activity ranging from 1.51 to 4.64 METs, with 99.6% daytime spent on PADL below 3 METs and 93% of patients with daily desaturation episodes. Regardless of the self-reported IPAQ, patients spend at least 70% of daytime on PADL below 2 METs. SMARTREAB was demonstrated to be an innovative methodology to measure PADL as a vital sign, combining oximetry with accelerometry, crossmatched with qualitative patient data, providing important input for designing patient-tailored pulmonary rehabilitation.
Pachydrusen in Fellow Eyes Predict Response to Aflibercept Monotherapy in Patients with Polypoidal Choroidal Vasculopathy
Authors: Fukuda Yoshiko , Sakurada Yoichi , Sugiyama Atsushi , Yoneyama Seigo , Matsubara Mio , Kikushima Wataru , Tanabe Naohiko , Parikh Ravi , Kashiwagi Kenji
Published: August 2020

We investigated whether responses to as-needed intravitreal aflibercept injections (IAIs) for polypoidal choroidal vasculopathy (PCV) differed among patients based upon drusen characteristics in fellow eyes. 110 eyes from 110 patients with PCV received 3 monthly IAI and thereafter Pro re nata (PRN) IAI over 12 months. Patients were classified into 4 groups depending on fellow eye findings. Group 1 (n = 16): pachydrusen; Group 2 (n = 45): no drusen; Group 3 (n = 35): soft drusen; Group4 (n = 14) PCV/scarring. Best-corrected visual acuity improved at 12 months in all groups, but not significantly in Group 1 and Group 4; however, visual improvement was similar among the groups after adjusting baseline confounders. Group 1 had a significantly lower percentage of eyes needing retreatment (all p < 0.001; Group 1: 16.7%; Group 2: 50.8%; Group 3: 80%; Group 4: 85.7%). The mean number of retreatments was least in Group 1 among the groups (all p-value < 0.003; Group 1: 0.50 ± 1.32; Group 2: 1.73 ± 2.08; Group 3:2.71 ± 1.99; Group 3: 2.71 ± 2.16). Patients with pachydrusen in fellow eyes were less likely to require additional IAI following the loading dose and may be ideal candidates for aflibercept monotherapy in their first year.
Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies
Authors: Kleinfinger Pascale , Lohmann Laurence , Luscan Armelle , Trost Detlef , Bidat Laurent , Debarge Véronique , Castaigne Vanina , Senat Marie-Victoire , Brechard Marie-Pierre , Guilbaud Lucie , Le Guyader Gwenaël , Satre Véronique , Laurichesse Delmas Hélène , Lallaoui Hakima , Manca-Pellissier Marie-Christine , Boughalem Aicha , Valduga Mylene , Hodeib Farah , Benachi Alexandra , Costa Jean Marc
Published: August 2020

Atypical fetal chromosomal anomalies are more frequent than previously recognized and can affect fetal development. We propose a screening strategy for a genome-wide non-invasive prenatal test (NIPT) to detect these atypical chromosomal anomalies (ACAs). Two sample cohorts were tested. Assay performances were determined using Cohort A, which consisted of 192 biobanked plasma samples—42 with ACAs, and 150 without. The rate of additional invasive diagnostic procedures was determined using Cohort B, which consisted of 3097 pregnant women referred for routine NIPT. Of the 192 samples in Cohort A, there were four initial test failures and six discordant calls; overall sensitivity was 88.1% (37/42; CI 75.00–94.81) and specificity was 99.3% (145/146; CI 96.22–99.88). In Cohort B, there were 90 first-pass failures (2.9%). The rate of positive results indicating an anomaly was 1.2% (36/3007) and 0.57% (17/3007) when limited to significant unbalanced chromosomal anomalies and trisomies 8, 9, 12, 14, 15, 16, and 22. These results show that genome-wide NIPT can screen for ACAs with an acceptable sensitivity and a small increase in invasive testing, particularly for women with increased risk following maternal serum screening and by limiting screening to structural anomalies and the most clinically meaningful trisomies.
Differential Diagnosis and Management of Diarrhea in Patients with Neuroendocrine Tumors
Authors: Pusceddu Sara , Rossi Roberta Elisa , Torchio Martina , Prinzi Natalie , Niger Monica , Coppa Jorgelina , Giacomelli Luca , Sacco Rodolfo , Facciorusso Antonio , Corti Francesca , Raimondi Alessandra , Prisciandaro Michele , Colombo Elena , Beninato Teresa , Del Vecchio Marta , Milione Massimo , Di Bartolomeo Maria , de Braud Filippo
Published: August 2020

Diarrhea is a recurrent symptom in patients with neuroendocrine tumors (NETs) and can represent different etiologies; thus, differential diagnosis is challenging. This paper distinguishes the different causes of chronic diarrhea in patients with gastroenteropancreatic NETs, with the aim to identify the most appropriate therapeutic approach. Underlying causes of diarrhea can be multifactorial, including not only diarrhea that is related to specific hormonal hypersecretory syndromes, but also diarrhea that is secondary to the following: extensive surgery which can cause pancreatic exocrine insufficiency or short bowel syndrome, treatment with somatostatin analogs or other antineoplastic agents, and bile acid malabsorption. After initial management of diarrhea with general treatments (dietary modification, use of antidiarrheals), a proper differential diagnosis is necessary to treat patients with specific etiology-driven therapeutic approaches, such as somatostatin analogs, pancreatic enzyme replacement therapy, and tryptophan hydroxylase inhibitors. In conclusion, NETs should be considered in the differential diagnosis of patients suffering from chronic diarrhea, after the exclusion of more common etiologies. Furthermore, physicians should keep in mind that several different etiologies might be responsible for diarrhea occurrence in NET patients. A prompt diagnosis of the actual cause of diarrhea is necessary to guide the treatment and a multidisciplinary approach is mandatory.
Chronic Kidney Disease and Its Impact on a Prothrombotic State in Patients with Atrial Fibrillation
Authors: Matusik Paweł T. , Heleniak Zbigniew , Papuga-Szela Elżbieta , Plens Krzysztof , Lelakowski Jacek , Undas Anetta
Published: August 2020

It is unclear whether chronic kidney disease (CKD) increases thromboembolism in atrial fibrillation (AF). We conducted a retrospective cross-sectional analysis of 502 non-anticoagulated AF patients (median age, 66 (60–73) years, median CHA2DS2-VASc score, 3.0 (2.0–4.0)) with an estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m2. Endogenous thrombin potential (ETP), clot permeability (Ks), and clot lysis time (CLT), among others, were determined. Patients with stage 4 CKD (n = 87; 17.3%) had higher ETP and prolonged CLT compared with those with stage 3 CKD. In patients with stages 3 to 4 CKD (n = 180; 35.9%) N-terminal pro-B-type natriuretic peptide predicted low Ks (the lowest quartile, odds ratio [OR] per 100 pg/mL: 1.03, 95% confidence interval [CI]: 1.01–1.06) and prolonged CLT (the top quartile, OR per 100 pg/mL: 1.05, 95% CI: 1.02–1.08), but not high ETP. In the whole cohort, after adjustment for CHA2DS2-VASc score, stage 4 CKD, but not stage 3 CKD, predicted high ETP (OR: 9.06; 95% CI: 4.44−18.46) and prolonged CLT (OR: 3.58; 95% CI: 1.76–7.28), but not low Ks. compared to the reference eGFR category. This study is the first to demonstrate the prothrombotic and antifibrinolytic alterations in AF patients with stage 4 CKD, but not stage 3 CKD irrespective of clinical stroke risk factors.
Translating Evidence from Clonal Hematopoiesis to Cardiovascular Disease: A Systematic Review
Authors: Papa Veronica , Marracino Luisa , Fortini Francesca , Rizzo Paola , Campo Gianluca , Vaccarezza Mauro , Vieceli Dalla Sega Francesco
Published: August 2020

Some random mutations can confer a selective advantage to a hematopoietic stem cell. As a result, mutated hematopoietic stem cells can give rise to a significant proportion of mutated clones of blood cells. This event is known as “clonal hematopoiesis.” Clonal hematopoiesis is closely associated with age, and carriers show an increased risk of developing blood cancers. Clonal hematopoiesis of indeterminate potential is defined by the presence of clones carrying a mutation associated with a blood neoplasm without obvious hematological malignancies. Unexpectedly, in recent years, it has emerged that clonal hematopoiesis of indeterminate potential carriers also have an increased risk of developing cardiovascular disease. Mechanisms linking clonal hematopoiesis of indeterminate potential to cardiovascular disease are only partially known. Findings in animal models indicate that clonal hematopoiesis of indeterminate potential-related mutations amplify inflammatory responses. Consistently, clinical studies have revealed that clonal hematopoiesis of indeterminate potential carriers display increased levels of inflammatory markers. In this review, we describe progress in our understanding of clonal hematopoiesis in the context of cancer, and we discuss the most recent findings linking clonal hematopoiesis of indeterminate potential and cardiovascular diseases.
Recycling Waste Tires into Ground Tire Rubber (GTR)/Rubber Compounds: A Review
Authors: Fazli Ali , Rodrigue Denis
Published: August 2020

Recycling and recovery of waste tires is a serious environmental problem since vulcanized rubbers require several years to degrade naturally and remain for long periods of time in the environment. This is associated to a complex three dimensional (3D) crosslinked structure and the presence of a high number of different additives inside a tire formulation. Most end-of-life tires are discarded as waste in landfills taking space or incinerated for energy recovery, especially for highly degraded rubber wastes. All these options are no longer acceptable for the environment and circular economy. However, a great deal of progress has been made on the sustainability of waste tires via recycling as this material has high potential being a source of valuable raw materials. Extensive researches were performed on using these end-of-life tires as fillers in civil engineering applications (concrete and asphalt), as well as blending with polymeric matrices (thermoplastics, thermosets or virgin rubber). Several grinding technologies, such as ambient, wet or cryogenic processes, are widely used for downsizing waste tires and converting them into ground tire rubber (GTR) with a larger specific surface area. Here, a focus is made on the use of GTR as a partial replacement in virgin rubber compounds. The paper also presents a review of the possible physical and chemical surface treatments to improve the GTR adhesion and interaction with different matrices, including rubber regeneration processes such as thermomechanical, microwave, ultrasonic and thermochemical producing regenerated tire rubber (RTR). This review also includes a detailed discussion on the effect of GTR/RTR particle size, concentration and crosslinking level on the curing, rheological, mechanical, aging, thermal, dynamic mechanical and swelling properties of rubber compounds. Finally, a conclusion on the current situation is provided with openings for future works.
Measuring Fiber Length in the Core and Shell Regions of Injection Molded Long Fiber-Reinforced Thermoplastic Plaques
Authors: Senior Abrahán Bechara , Osswald Tim
Published: August 2020

Long fiber-reinforced thermoplastics are an attractive design option for many industries due to their excellent mechanical properties and processability. Processing of these materials has a significant influence on their microstructure, which controls the properties of the final part. The microstructure is characterized by the fibers’ orientation, length, and concentration. Many characterization methods can capture the fiber orientation and concentration changes through the thickness in injection molded parts, but not the changes in fiber length. In this study, a technique for measuring fiber length in the core and shell regions of molded parts was proposed, experimentally verified, and used on injection molded 20 wt.% glass fiber-reinforced polypropylene plaques. The measured fiber length in the core was 50% higher than in the shell region. Comparison with simulation results shows disagreement in the shape of the through-thickness fiber length profile. Stiffness predictions show that the through-thickness changes in fiber length have little impact on the longitudinal and transverse Young’s modulus.
Effect of Novel Antibacterial Composites on Bacterial Biofilms
Authors: Yaghmoor Rayan B. , Xia Wendy , Ashley Paul , Allan Elaine , Young Anne M.
Published: August 2020

Continuing cariogenic bacterial growth demineralizing dentine beneath a composite filling is the most common cause of tooth restoration failure. Novel composites with antibacterial polylysine (PLS) (0, 4, 6, or 8 wt%) in its filler phase were therefore produced. Remineralising monocalcium phosphate was also included at double the PLS weight. Antibacterial studies involved set composite disc placement in 1% sucrose-supplemented broth containing Streptococcus mutans (UA159). Relative surface bacterial biofilm mass (n = 4) after 24 h was determined by crystal violet-binding. Live/dead bacteria and biofilm thickness (n = 3) were assessed using confocal laser scanning microscopy (CLSM). To understand results and model possible in vivo benefits, cumulative PLS release from discs into water (n = 3) was determined by a ninhydrin assay. Results showed biofilm mass and thickness decreased linearly by 28% and 33%, respectively, upon increasing PLS from 0% to 8%. With 4, 6, and 8 wt% PLS, respectively, biofilm dead bacterial percentages and PLS release at 24 h were 20%, 60%, and 80% and 85, 163, and 241 μg/disc. Furthermore, initial PLS release was proportional to the square root of time and levelled after 1, 2, and 3 months at 13%, 28%, and 42%. This suggested diffusion controlled release from water-exposed composite surface layers of 65, 140, and 210 μm thickness, respectively. In conclusion, increasing PLS release initially in any gaps under the restoration to kill residual bacteria or longer-term following composite/tooth interface damage might help prevent recurrent caries.
Novel CaF2 Nanocomposites with Antibacterial Function and Fluoride and Calcium Ion Release to Inhibit Oral Biofilm and Protect Teeth
Authors: Mitwalli Heba , Balhaddad Abdulrahman A. , AlSahafi Rashed , Oates Thomas W. , Melo Mary Anne S. , Xu Hockin H. K. , Weir Michael D.
Published: August 2020

(1) Background: The objective of this study was to develop a novel dental nanocomposite containing dimethylaminohexadecyl methacrylate (DMAHDM), 2-methacryloyloxyethyl phosphorylcholine (MPC), and nanoparticles of calcium fluoride (nCaF2) for preventing recurrent caries via antibacterial, protein repellent and fluoride releasing capabilities. (2) Methods: Composites were made by adding 3% MPC, 3% DMAHDM and 15% nCaF2 into bisphenol A glycidyl dimethacrylate (Bis-GMA) and triethylene glycol dimethacrylate (TEGDMA) (denoted BT). Calcium and fluoride ion releases were evaluated. Biofilms of human saliva were assessed. (3) Results: nCaF2+DMAHDM+MPC composite had the lowest biofilm colony forming units (CFU) and the greatest ion release; however, its mechanical properties were lower than commercial control composite (p < 0.05). nCaF2+DMAHDM composite had similarly potent biofilm reduction, with mechanical properties matching commercial control composite (p > 0.05). Fluoride and calcium ion releases from nCaF2+DMAHDM were much more than commercial composite. Biofilm CFU on composite was reduced by 4 logs (n = 9, p < 0.05). Biofilm metabolic activity and lactic acid were also substantially reduced by nCaF2+DMAHDM, compared to commercial control composite (p < 0.05). (4) Conclusions: The novel nanocomposite nCaF2+DMAHDM achieved strong antibacterial and ion release capabilities, without compromising the mechanical properties. This bioactive nanocomposite is promising to reduce biofilm acid production, inhibit recurrent caries, and increase restoration longevity.
Drug Use among Nursing Home Residents in Denmark for Drugs Having Pharmacogenomics Based (PGx) Dosing Guidelines: Potential for Preemptive PGx Testing
Authors: Vermehren Charlotte , Søgaard Nielsen Regitze , Jørgensen Steffen , Drastrup Anne Mette , Westergaard Niels
Published: August 2020

Background: Polypharmacy is most prevalent among the elderly population and in particular among nursing home residents. The frequency of the use of drugs with pharmacogenomics (PGx)-based dosing guidelines for CYP2D6, CYP2C9, CYP2C19 and SLCO1B1 were measured among nursing home residents in the Capital Region of Denmark as well as drug–drug interactions. The aim was to evaluate the potential of applying PGx-test as a supportive tool in medication reviews. Methods: Drug use among nursing home residents during 2017–2018 in the Capital Region of Copenhagen, for drugs with PGx-based dosing guidelines available through the PharmGKB website, were measured. Drug–drug interactions were scored in severity by using drug interaction checkers. Results: The number of residents using drugs with PGx-based actionable dosing guidelines (AG) were 119 out of 141 residents (84.3%). Of these 119 residents, 87 residents used drugs with AG for CYP2C19, 47 residents for CYP2D6, and 42 residents for SLCO1B1. In addition, 30 residents used two drugs with an AG for CYP2C19, and for CYP2D6, it was only seven residents. The most used drugs with AG were clopidogrel (42), pantoprazole (32), simvastatin (30), metoprolol (25), and citalopram (24). The most frequent drug interactions found with warnings were combinations of proton pump inhibitors and clopidogrel underscoring the potential for phenoconversion. Conclusion: this study clearly showed that the majority of the nursing home residents were exposed to drugs or drug combinations for which there exist PGx-based AG. This indeed supports the notion of accessing and accounting for not only drug–gene but also drug–drug–gene interactions as a supplement to medication review.
30 Years of Land Cover Change in Connecticut, USA: A Case Study of Long-Term Research, Dissemination of Results, and Their Use in Land Use Planning and Natural Resource Conservation
Authors: Arnold Chester , Wilson Emily , Hurd James , Civco Daniel
Published: August 2020

Remotely sensed land cover data can be a tremendous resource to land use decision makers, yet there is often a disconnect between the worlds of remote sensing and local government. The Connecticut’s Changing Landscape project is focused on bridging this gap. The project analyzes changes to the state’s landscape using Landsat-derived 30-m land cover and cross-correlation analysis. It includes seven dates spanning 30 years, from 1985 to 2015. During this period an additional 4.7 percent of the state was converted to development-related land covers, with corresponding losses to forest and agricultural land. New development was for the most part in attenuated patterns rather than concentrated near existing developed areas. Additional land cover analyses were conducted of agricultural areas, riparian corridors, core forest, and watershed imperviousness, to more closely examine issues of sustainability. Particular care is taken to make research findings accessible, understandable, and usable for the public through traditional outreach methods, and increasingly through internet mapping technology. As a result, the project has become a widely used resource informing the work of state, regional and local governments, nonprofit organizations, and researchers. A more concerted effort to integrate research and outreach is needed to ensure that land cover research has an impact on issues of land use and sustainability.
Hybrid Decision-Making Evaluation for Future Scenarios of Cultural Ecosystem Services
Authors: Peng Li-Pei , Wang Wei-Ming
Published: August 2020

In the face of rapid urbanization and globalization, the continual loss of rural landscapes is occurring globally because of declining rural industries, abandoned farmlands and aging local populations. These problems highlight the versatility and diverse values of cultural ecosystem services (CES) to provide feasible responses for rural landscapes. To utilize CES and ensure the sustainability of rural landscapes in Taiwan, this study combined multiple-criteria decision analysis (MCDA) and a development evaluation structure that can effectively address interdependent factors for practical application. This study presents the importance of different evaluation compositions with clear weights. The results indicated that the “global technotopia” scenario is the highest priority, followed by the “Satoyama–Satoumi renaissance” scenario, and the other two.