bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Autotaxin and Lysophosphatidic Acid Receptor 5 Attenuates Neuroinflammation in LPS-Activated BV-2 Microglia and a Mouse Endotoxemia Model
Authors: Joshi Lisha , Plastira Ioanna , Bernhart Eva , Reicher Helga , Triebl Alexander , Köfeler Harald C. , Sattler Wolfgang
Published: August 2021

Increasing evidence suggests that systemic inflammation triggers a neuroinflammatory response that involves sustained microglia activation. This response has deleterious consequences on memory and learning capability in experimental animal models and in patients. However, the mechanisms connecting systemic inflammation and microglia activation remain poorly understood. Here, we identify the autotaxin (ATX)/lysophosphatidic acid (LPA)/LPA-receptor axis as a potential pharmacological target to modulate the LPS-mediated neuroinflammatory response in vitro (the murine BV-2 microglia cell line) and in vivo (C57BL/6J mice receiving a single i.p. LPS injection). In LPS-stimulated (20 ng/mL) BV-2 cells, we observed increased phosphorylation of transcription factors (STAT1, p65, and c-Jun) that are known to induce a proinflammatory microglia phenotype. LPS upregulated ATX, TLR4, and COX2 expression, amplified NO production, increased neurotoxicity of microglia conditioned medium, and augmented cyto-/chemokine concentrations in the cellular supernatants. PF8380 (a type I ATX inhibitor, used at 10 and 1 µM) and AS2717638 (an LPA5 antagonist, used at 1 and 0.1 µM) attenuated these proinflammatory responses, at non-toxic concentrations, in BV-2 cells. In vivo, we demonstrate accumulation of PF8380 in the mouse brain and an accompanying decrease in LPA concentrations. In vivo, co-injection of LPS (5 mg/kg body weight) and PF8380 (30 mg/kg body weight), or LPS/AS2717638 (10 mg/kg body weight), significantly attenuated LPS-induced iNOS, TNFα, IL-1β, IL-6, and CXCL2 mRNA expression in the mouse brain. On the protein level, PF8380 and AS2717638 significantly reduced TLR4, Iba1, GFAP and COX2 expression, as compared to LPS-only injected animals. In terms of the communication between systemic inflammation and neuroinflammation, both inhibitors significantly attenuated LPS-mediated systemic TNFα and IL-6 synthesis, while IL-1β was only reduced by PF8380. Inhibition of ATX and LPA5 may thus provide an opportunity to protect the brain from the toxic effects that are provoked by systemic endotoxemia.
Biological Aspects of Selected Myokines in Skeletal Muscle: Focus on Aging
Authors: Mancinelli Rosa , Checcaglini Franco , Coscia Francesco , Gigliotti Paola , Fulle Stefania , Fanò-Illic Giorgio
Published: August 2021

In the last decade, clear evidence has emerged that the cellular components of skeletal muscle are important sites for the release of proteins and peptides called “myokines”, suggesting that skeletal muscle plays the role of a secretory organ. After their secretion by muscles, these factors serve many biological functions, including the exertion of complex autocrine, paracrine and/or endocrine effects. In sum, myokines affect complex multi-organ processes, such as skeletal muscle trophism, metabolism, angiogenesis and immunological response to different physiological (physical activity, aging, etc.) or pathological states (cachexia, dysmetabolic conditions, chronic inflammation, etc.). The aim of this review is to describe in detail a number of myokines that are, to varying degrees, involved in skeletal muscle aging processes and belong to the group of proteins present in the functional environment surrounding the muscle cell known as the “Niche”. The particular myokines described are those that, acting both from within the cell and in an autocrine manner, have a defined relationship with the modulation of oxidative stress in muscle cells (mature or stem) involved in the regulatory (metabolic or regenerative) processes of muscle aging. Myostatin, IGF-1, NGF, S100 and irisin are examples of specific myokines that have peculiar features in their mechanisms of action. In particular, the potential role of one of the most recently characterized myokines—irisin, directly linked to an active lifestyle—in reducing if not reversing senescence-induced oxidative damage is discussed in terms of its possible application as an agent able to counteract the deleterious effects of muscle aging.
Quantitative Assessment of Point-of-Care 3D-Printed Patient-Specific Polyetheretherketone (PEEK) Cranial Implants
Authors: Sharma Neha , Aghlmandi Soheila , Dalcanale Federico , Seiler Daniel , Zeilhofer Hans-Florian , Honigmann Philipp , Thieringer Florian M.
Published: August 2021

Recent advancements in medical imaging, virtual surgical planning (VSP), and three-dimensional (3D) printing have potentially changed how today’s craniomaxillofacial surgeons use patient information for customized treatments. Over the years, polyetheretherketone (PEEK) has emerged as the biomaterial of choice to reconstruct craniofacial defects. With advancements in additive manufacturing (AM) systems, prospects for the point-of-care (POC) 3D printing of PEEK patient-specific implants (PSIs) have emerged. Consequently, investigating the clinical reliability of POC-manufactured PEEK implants has become a necessary endeavor. Therefore, this paper aims to provide a quantitative assessment of POC-manufactured, 3D-printed PEEK PSIs for cranial reconstruction through characterization of the geometrical, morphological, and biomechanical aspects of the in-hospital 3D-printed PEEK cranial implants. The study results revealed that the printed customized cranial implants had high dimensional accuracy and repeatability, displaying clinically acceptable morphologic similarity concerning fit and contours continuity. From a biomechanical standpoint, it was noticed that the tested implants had variable peak load values with discrete fracture patterns and failed at a mean (SD) peak load of 798.38 ± 211.45 N. In conclusion, the results of this preclinical study are in line with cranial implant expectations; however, specific attributes have scope for further improvements.
EphB4 as a Novel Target for the EGFR-Independent Suppressive Effects of Osimertinib on Cell Cycle Progression in Non-Small Cell Lung Cancer
Authors: Nanamiya Ren , Saito-Koyama Ryoko , Miki Yasuhiro , Inoue Chihiro , Asavasupreechar Teeranut , Abe Jiro , Sato Ikuro , Sasano Hironobu
Published: August 2021

Osimertinib is the latest generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor used for patients with EGFR-mutated non-small cell lung cancer (NSCLC). We aimed to explore the novel mechanisms of osimertinib by particularly focusing on EGFR-independent effects, which have not been well characterized. We explored the EGFR-independent effects of osimertinib on cell proliferation using NSCLC cell lines, an antibody array analysis, and the association between the action of osimertinib and the ephrin receptor B4 (EphB4). We also studied the clinicopathological significance of EphB4 in 84 lung adenocarcinoma patients. Osimertinib exerted significant inhibitory effects on cell growth and cell cycle progression by promoting the phosphorylation of p53 and p21 and decreasing cyclin D1 expression independently of EGFR. EphB4 was significantly suppressed by osimertinib and promoted cell growth and sensitivity to osimertinib. The EphB4 status in carcinoma cells was positively correlated with tumor size, T factor, and Ki-67 labeling index in all patients and was associated with poor relapse-free survival in EGFR mutation-positive patients. EphB4 is associated with the EGFR-independent suppressive effects of osimertinib on cell cycle and with a poor clinical outcome. Osimertinib can exert significant growth inhibitory effects in EGFR-mutated NSCLC patients with a high EphB4 status.
Mitochondria-Induced Immune Response as a Trigger for Neurodegeneration: A Pathogen from Within
Authors: Luna-Sánchez Marta , Bianchi Patrizia , Quintana Albert
Published: August 2021

Symbiosis between the mitochondrion and the ancestor of the eukaryotic cell allowed cellular complexity and supported life. Mitochondria have specialized in many key functions ensuring cell homeostasis and survival. Thus, proper communication between mitochondria and cell nucleus is paramount for cellular health. However, due to their archaebacterial origin, mitochondria possess a high immunogenic potential. Indeed, mitochondria have been identified as an intracellular source of molecules that can elicit cellular responses to pathogens. Compromised mitochondrial integrity leads to release of mitochondrial content into the cytosol, which triggers an unwanted cellular immune response. Mitochondrial nucleic acids (mtDNA and mtRNA) can interact with the same cytoplasmic sensors that are specialized in recognizing genetic material from pathogens. High-energy demanding cells, such as neurons, are highly affected by deficits in mitochondrial function. Notably, mitochondrial dysfunction, neurodegeneration, and chronic inflammation are concurrent events in many severe debilitating disorders. Interestingly in this context of pathology, increasing number of studies have detected immune-activating mtDNA and mtRNA that induce an aberrant production of pro-inflammatory cytokines and interferon effectors. Thus, this review provides new insights on mitochondria-driven inflammation as a potential therapeutic target for neurodegenerative and primary mitochondrial diseases.
Global Lysine Acetylome Analysis of LPS-Stimulated HepG2 Cells Identified Hyperacetylation of PKM2 as a Metabolic Regulator in Sepsis
Authors: Na Ann-Yae , Paudel Sanjita , Choi Soyoung , Lee Jun Hyung , Kim Min-Sik , Bae Jong-Sup , Lee Sangkyu
Published: August 2021

Sepsis-induced liver dysfunction (SILD) is a common event and is strongly associated with mortality. Establishing a causative link between protein post-translational modification and diseases is challenging. We studied the relationship among lysine acetylation (Kac), sirtuin (SIRTs), and the factors involved in SILD, which was induced in LPS-stimulated HepG2 cells. Protein hyperacetylation was observed according to SIRTs reduction after LPS treatment for 24 h. We identified 1449 Kac sites based on comparative acetylome analysis and quantified 1086 Kac sites on 410 proteins for acetylation. Interestingly, the upregulated Kac proteins are enriched in glycolysis/gluconeogenesis pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) category. Among the proteins in the glycolysis pathway, hyperacetylation, a key regulator of lactate level in sepsis, was observed at three pyruvate kinase M2 (PKM2) sites. Hyperacetylation of PKM2 induced an increase in its activity, consequently increasing the lactate concentration. In conclusion, this study is the first to conduct global profiling of Kac, suggesting that the Kac mechanism of PKM2 in glycolysis is associated with sepsis. Moreover, it helps to further understand the systematic information regarding hyperacetylation during the sepsis process.
Insights into the Mechanisms of Heat Priming and Thermotolerance in Tobacco Pollen
Authors: Mareri Lavinia , Faleri Claudia , Aloisi Iris , Parrotta Luigi , Del Duca Stefano , Cai Giampiero
Published: August 2021

Global warming leads to a progressive rise in environmental temperature. Plants, as sessile organisms, are threatened by these changes; the male gametophyte is extremely sensitive to high temperature and its ability to preserve its physiological status under heat stress is known as acquired thermotolerance. This latter can be achieved by exposing plant to a sub-lethal temperature (priming) or to a progressive increase in temperature. The present research aims to investigate the effects of heat priming on the functioning of tobacco pollen grains. In addition to evaluating basic physiological parameters (e.g., pollen viability, germination and pollen tube length), several aspects related to a correct pollen functioning were considered. Calcium (Ca2+) level, reactive oxygen species (ROS) and related antioxidant systems were investigated, also to the organization of actin filaments and cytoskeletal protein such as tubulin (including tyrosinated and acetylated isoforms) and actin. We also focused on sucrose synthase (Sus), a key metabolic enzyme and on the content of main soluble sugars, including UDP-glucose. Results here obtained showed that a pre-exposure to sub-lethal temperatures can positively enhance pollen performance by altering its metabolism. This can have a considerable impact, especially from the point of view of breeding strategies aimed at improving crop species.
Repair Mechanisms of the Neurovascular Unit after Ischemic Stroke with a Focus on VEGF
Authors: Moon Sunhong , Chang Mi-Sook , Koh Seong-Ho , Choi Yoon Kyung
Published: August 2021

The functional neural circuits are partially repaired after an ischemic stroke in the central nervous system (CNS). In the CNS, neurovascular units, including neurons, endothelial cells, astrocytes, pericytes, microglia, and oligodendrocytes maintain homeostasis; however, these cellular networks are damaged after an ischemic stroke. The present review discusses the repair potential of stem cells (i.e., mesenchymal stem cells, endothelial precursor cells, and neural stem cells) and gaseous molecules (i.e., nitric oxide and carbon monoxide) with respect to neuroprotection in the acute phase and regeneration in the late phase after an ischemic stroke. Commonly shared molecular mechanisms in the neurovascular unit are associated with the vascular endothelial growth factor (VEGF) and its related factors. Stem cells and gaseous molecules may exert therapeutic effects by diminishing VEGF-mediated vascular leakage and facilitating VEGF-mediated regenerative capacity. This review presents an in-depth discussion of the regeneration ability by which endogenous neural stem cells and endothelial cells produce neurons and vessels capable of replacing injured neurons and vessels in the CNS.
Modeling Neuroimmune Interactions in Human Subjects and Animal Models to Predict Subtype-Specific Multidrug Treatments for Gulf War Illness
Authors: Carrera Arias Francisco J. , Aenlle Kristina , Abreu Maria , Holschbach Mary A. , Michalovicz Lindsay T. , Kelly Kimberly A. , Klimas Nancy , O’Callaghan James P. , Craddock Travis J. A.
Published: August 2021

Gulf War Illness (GWI) is a persistent chronic neuroinflammatory illness exacerbated by external stressors and characterized by fatigue, musculoskeletal pain, cognitive, and neurological problems linked to underlying immunological dysfunction for which there is no known treatment. As the immune system and the brain communicate through several signaling pathways, including the hypothalamic–pituitary–adrenal (HPA) axis, it underlies many of the behavioral and physiological responses to stressors via blood-borne mediators, such as cytokines, chemokines, and hormones. Signaling by these molecules is mediated by the semipermeable blood–brain barrier (BBB) made up of a monocellular layer forming an integral part of the neuroimmune axis. BBB permeability can be altered and even diminished by both external factors (e.g., chemical agents) and internal conditions (e.g., acute or chronic stress, or cross-signaling from the hypothalamic–pituitary–gonadal (HPG) axis). Such a complex network of regulatory interactions that possess feed-forward and feedback connections can have multiple response dynamics that may include several stable homeostatic states beyond normal health. Here we compare immune and hormone measures in the blood of human clinical samples and mouse models of Gulf War Illness (GWI) subtyped by exposure to traumatic stress for subtyping this complex illness. We do this via constructing a detailed logic model of HPA–HPG–Immune regulatory behavior that also considers signaling pathways across the BBB to neuronal–glial interactions within the brain. We apply conditional interactions to model the effects of changes in BBB permeability. Several stable states are identified in the system beyond typical health. Following alignment of the human and mouse blood profiles in the context of the model, mouse brain sample measures were used to infer the neuroinflammatory state in human GWI and perform treatment simulations using a genetic algorithm to optimize the Monte Carlo simulations of the putative treatment strategies aimed at returning the ill system back to health. We identify several ideal multi-intervention strategies and potential drug candidates that may be used to treat chronic neuroinflammation in GWI.
Chitin-Derived AVR-48 Prevents Experimental Bronchopulmonary Dysplasia (BPD) and BPD-Associated Pulmonary Hypertension in Newborn Mice
Authors: Das Pragnya , Acharya Suchismita , Prahaladan Varsha M. , Kumova Ogan K. , Malaeb Shadi , Behera Sumita , Agarwal Beamon , Christensen Dale J. , Carey Alison J. , Bhandari Vineet
Published: August 2021

Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity and a key contributor to the large health care burden associated with prematurity, longer hospital stays, higher hospital costs, and frequent re-hospitalizations of affected patients through the first year of life and increased resource utilization throughout childhood. This disease is associated with abnormal pulmonary function that may lead to BPD-associated pulmonary hypertension (PH), a major contributor to neonatal mortality and morbidity. In the absence of any definitive treatment options, this life-threatening disease is associated with high resource utilization during and after neonatal intensive care unit (NICU) stay. The goal of this study was to test the safety and efficacy of a small molecule derivative of chitin, AVR-48, as prophylactic therapy for preventing experimental BPD in a mouse model. Two doses of AVR-48 were delivered either intranasally (0.11 mg/kg), intraperitoneally (10 mg/kg), or intravenously (IV) (10 mg/kg) to newborn mouse pups on postnatal day (P)2 and P4. The outcomes were assessed by measuring total inflammatory cells in the broncho-alveolar lavage fluid (BALF), chord length, septal thickness, and radial alveolar counts of the alveoli, Fulton’s Index (for PH), cell proliferation and cell death by immunostaining, and markers of inflammation by Western blotting and ELISA. The bioavailability and safety of the drug were assessed by pharmacokinetic and toxicity studies in both neonatal mice and rat pups (P3-P5). Following AVR-48 treatment, alveolar simplification was improved, as evident from chord length, septal thickness, and radial alveolar counts; total inflammatory cells were decreased in the BALF; Fulton’s Index was decreased and lung inflammation and cell death were decreased, while angiogenesis and cell proliferation were increased. AVR-48 was found to be safe and the no-observed-adverse-effect level (NOAEL) in rat pups was determined to be 100 mg/kg when delivered via IV dosing with a 20-fold safety margin. With no reported toxicity and with a shorter half-life, AVR-48 is able to reverse the worsening cardiopulmonary phenotype of experimental BPD and BPD-PH, compared to controls, thus positioning it as a future drug candidate.
Ngn3-Positive Cells Arise from Pancreatic Duct Cells
Authors: Kimura-Nakajima Chiemi , Sakaguchi Kousuke , Hatano Yoshiko , Matsumoto Masahito , Okazaki Yasushi , Tanaka Keisuke , Yamane Takumi , Oishi Yuichi , Kamimoto Kenji , Iwatsuki Ken
Published: August 2021

The production of pancreatic β cells is the most challenging step for curing diabetes using next-generation treatments. Adult pancreatic endocrine cells are thought to be maintained by the self-duplication of differentiated cells, and pancreatic endocrine neogenesis can only be observed when the tissue is severely damaged. Experimentally, this can be performed using a method named partial duct ligation (PDL). As the success rate of PDL surgery is low because of difficulties in identifying the pancreatic duct, we previously proposed a method for fluorescently labeling the duct in live animals. Using this method, we performed PDL on neurogenin3 (Ngn3)-GFP transgenic mice to determine the origin of endocrine precursor cells and evaluate their potential to differentiate into multiple cell types. Ngn3-activated cells, which were marked with GFP, appeared after PDL operation. Because some GFP-positive cells were aligned proximally to the duct, we hypothesized that Ngn3-positive cells arise from the pancreatic duct. Therefore, we next developed an in vitro pancreatic duct culture system using Ngn3-GFP mice and examined whether Ngn3-positive cells emerge from this duct. We observed GFP expressions in ductal organoid cultures. GFP expressions were correlated with Ngn3 expressions and endocrine cell lineage markers. Interestingly, tuft cell markers were also correlated with GFP expressions. Our results demonstrate that in adult mice, Ngn3-positive endocrine precursor cells arise from the pancreatic ducts both in vivo and in vitro experiments indicating that the pancreatic duct could be a potential donor for therapeutic use.
Graph Theoretical Methods and Workflows for Searching and Annotation of RNA Tertiary Base Motifs and Substructures
Authors: Emrizal Reeki , Hamdani Hazrina Yusof , Firdaus-Raih Mohd
Published: August 2021

The increasing number and complexity of structures containing RNA chains in the Protein Data Bank (PDB) have led to the need for automated structure annotation methods to replace or complement expert visual curation. This is especially true when searching for tertiary base motifs and substructures. Such base arrangements and motifs have diverse roles that range from contributions to structural stability to more direct involvement in the molecule’s functions, such as the sites for ligand binding and catalytic activity. We review the utility of computational approaches in annotating RNA tertiary base motifs in a dataset of PDB structures, particularly the use of graph theoretical algorithms that can search for such base motifs and annotate them or find and annotate clusters of hydrogen-bond-connected bases. We also demonstrate how such graph theoretical algorithms can be integrated into a workflow that allows for functional analysis and comparisons of base arrangements and sub-structures, such as those involved in ligand binding. The capacity to carry out such automatic curations has led to the discovery of novel motifs and can give new context to known motifs as well as enable the rapid compilation of RNA 3D motifs into a database.
ABCB1 Does Not Require the Side-Chain Hydrogen-Bond Donors Gln347, Gln725, Gln990 to Confer Cellular Resistance to the Anticancer Drug Taxol
Authors: Sasitharan Keerthana , Iqbal Hamzah Asad , Bifsa Foteini , Olszewska Aleksandra , Linton Kenneth J.
Published: August 2021

The multidrug efflux transporter ABCB1 is clinically important for drug absorption and distribution and can be a determinant of chemotherapy failure. Recent structure data shows that three glutamines donate hydrogen bonds to coordinate taxol in the drug binding pocket. This is consistent with earlier drug structure-activity relationships that implicated the importance of hydrogen bonds in drug recognition by ABCB1. By replacing the glutamines with alanines we have tested whether any, or all, of Gln347, Gln725, and Gln990 are important for the transport of three different drug classes. Flow cytometric transport assays show that Q347A and Q990A act synergistically to reduce transport of Calcein-AM, BODIPY-verapamil, and OREGON GREEN-taxol bisacetate but the magnitude of the effect was dependent on the test drug and no combination of mutations completely abrogated function. Surprisingly, Q725A mutants generally improved transport of Calcein-AM and BODIPY-verapamil, suggesting that engagement of the wild-type Gln725 in a hydrogen bond is inhibitory for the transport mechanism. To test transport of unmodified taxol, stable expression of Q347/725A and the triple mutant was engineered and shown to confer equivalent resistance to the drug as the wild-type transporter, further indicating that none of these potential hydrogen bonds between transporter and transport substrate are critical for the function of ABCB1. The implications of the data for plasticity of the drug binding pocket are discussed.
The Simple Method of Preparation of Highly Carboxylated Bacterial Cellulose with Ni- and Mg-Ferrite-Based Versatile Magnetic Carrier for Enzyme Immobilization
Authors: Drozd Radosław , Szymańska Magdalena , Przygrodzka Katarzyna , Hoppe Jakub , Leniec Grzegorz , Kowalska Urszula
Published: August 2021

The bacterial cellulose (BC) is a versatile biopolymer of microbial origin characterized by high purity and unusual water and material properties. However, the native BC contains a low number of functional groups, which significantly limits its further application. The main goal of its effective modification is to use methods that allow the unusual properties of BC to be retained and the desired functional group to be efficiently introduced. In the present study, the new magnetic carrier based on functionalized citric acid (CA) bacterial cellulose was developed and tested to support critical industrial enzymes such as lipase B from Candida antarctica and phospholipase A from Aspergillus oryzae. The applied method allowed BC to be effectively modified by citric acid and a sufficient number of carboxylic groups to be introduced, up to 3.6 mmol of COOH per gram of dry mass of the prepared carrier. The DSC and TGA analyses revealed carrier stability at operational temperatures in the range of 20 °C to 100 °C and substantially influenced the amount of the introduced carboxyl groups on carrier properties. Both enzymes’ immobilization significantly improves their thermal stability at 60 °C without a significant thermal and pH optima effect. The analyzed enzymes showed good operational stability with a significant residual activity after ten cycles of repeated uses. The new magnetic carrier based on highly carboxylated bacterial cellulose has a high application capability as matrix for immobilization the various enzymes of industrial interest.
Adaptive Combined Channel-Network Coding for Cooperative Relay Aided Cognitive Radio Networks
Authors: AbuZeid Mohamed S. , Fahmy Yasmine A. , El-Soudani Magdy S.
Published: August 2021

Cognitive radio (CR) is one of the emerging technologies for 4G/5G applications. Cooperative relay communications and network coding are some techniques that helped in enhancing the CR applications. This paper considers a primary broadcasting system for multimedia video streaming applications that broadcasts data to the primary users and to an aiding cooperative relay CR secondary system. The cooperative overlay secondary system can use many error control coding techniques for point-to-point data retransmissions such as channel coding, network coding, and combined coding techniques to enhance the system performance under variable channel conditions. This work proposes a novel adaptive combined channel network coding (AC2NC) technique for data retransmissions. The new AC2NC first analyses the channel feedback information and then selects the best retransmission coding technique based on the targeted bandwidth or transmission time optimization. This is instead of using a single static channel or network coding technique with dynamic channel conditions. The proposed AC2NC improves the system throughput, decreases the retransmission time, and avails more spectrum access opportunities for the secondary system’s own data transmissions. The AC2NC relative bandwidth and time saving opportunities for CR users can exceed 90% under certain channel conditions versus some static coding techniques.
A Digital Thesaurus of Ethnic Groups in the Mekong River Basin
Authors: Chansanam Wirapong , Kwiecien Kanyarat , Buranarach Marut , Tuamsuk Kulthida
Published: August 2021

This research was aimed at constructing a thesaurus of the ethnic groups in the Mekong River Basin that is a compilation of controlled vocabularies of both Thai and English language, with a digital platform that enables semantic search and linked open data. The research method involved four steps: (1) organization of knowledge content; (2) construction of the thesaurus; (3) development of a digital thesaurus platform; and (4) evaluation. The concepts and theories used in the research comprised knowledge organization, thesaurus construction, digital platform development, and system evaluation. The tool for developing the digital thesaurus was the Tematres web application. The research results are: (1) there are 4273 principle words related to the ethnic groups that have been compiled and classified by the terms for each of the eight deep levels, 2596 were found to have hierarchical relationships, and 6858 had associative relationships; (2) the digital thesaurus platform was able to manage the controlled vocabularies related to the Mekong ethnic groups by storing both Thai and English vocabularies. When retrieved, the vocabulary, details of the broader term, narrow term, related term, cross reference, and scope note are displayed. Thus, semantic search is viable through applications, linked open data technology, and web services.
Efficacy of Anystis baccarum against Foxglove Aphids, Aulacorthum solani, in Laboratory and Small-Scale Greenhouse Trials
Authors: Saito Taro , Brownbridge Michael
Published: August 2021

A generalist predatory mite, Anystis baccarum (L.), has been identified as a key predator of small, soft-bodied pest species in various agroecosystems around the world. The foxglove aphid Aulacorthum solani (Keltenbach) is a new problematic pest in Canadian greenhouses. Laboratory colonies of A. baccarum were established and its predatory efficacy against A. solani was assessed. In laboratory trials, A. baccarum ate approximately one adult aphid or seven first instar aphids in 24 h. In a greenhouse bench trial on sweet peppers with the free-flying aphid parasitoid, Aphidius ervi Haliday, the population dynamics of A. solani in the presence or absence of A. baccarum was evaluated. Although the parasitoid alone successfully eradicated A. solani, when A. baccarum were present on the plants, the aphid population was eradicated more rapidly. Fruit yield was also 15% higher from plants where A. baccarum was released than the control (without A. baccarum). Furthermore, plants were naturally infested by Frankliniella occidentalis (Pergande) during the trial, which caused visible feeding damage to the fruits. Anystis baccarum also predates on thrips and thrips’ feeding damage to the fruits was reduced on plants where A. baccarum was released. Anystis baccarum was able to establish in sweet peppers and was determined to be complementary to the current practice of using A. ervi for the biological control of A. solani.
Ruling Out Coronavirus Disease 2019 in Patients with Pneumonia: The Role of Blood Cell Count and Lung Ultrasound
Authors: Biolo Gianni , Fiotti Nicola , Cominotto Franco , Di Girolamo Filippo Giorgio , Panizon Emiliano , Altamura Nicola , Casarsa Chiara , Pipoli Alessandro , Giordano Mauro , Torelli Lucio , Mearelli Filippo , Vinci Pierandrea
Published: August 2021

Coronavirus disease 2019 (COVID-19) is characterized by a distinctive blood leucocyte pattern and B-lines on lung ultrasound (LUS) as marker of alveolar-interstitial syndrome. We aimed to evaluate the accuracy of blood leucocyte count alone or in combination with LUS for COVID-19 diagnosis. We retrospectively enrolled consecutive patients diagnosed with community acquired pneumonia (CAP) at hospital admission to derive and validate cutoff values for blood cell count that could be predictive of COVID-19 before confirmation by the nucleic acid amplification test (NAAT). Cutoff values, generated and confirmed in inception (41/115, positive/negative patients) and validation (100/180, positive/negative patients) cohorts, were ≤17 and ≤10 cells/mm3 for basophils and eosinophils, respectively. Basophils and/or eosinophils below cutoff were associated with sensitivity of 98% (95%CI, 94–100) and negative likelihood ratio of 0.04 (95%CI, 0.01–0.11). In a subgroup of 265 subjects, the sensitivity of B-line on LUS was 15% lower (p < 0.001) than that of basophils and/or eosinophils below cutoff. The combination of B-lines with basophils and eosinophils below cutoff was associated with a moderate increase of the positive likelihood ratio: 5.0 (95%CI, 3.2–7.7). In conclusion, basophil and eosinophil counts above the generated cutoff virtually rule out COVID-19 in patients with CAP. Our findings can help optimize patient triage pending the NAAT results.
Periodontal Behavior and Patient Satisfaction of Anterior Teeth Restored with Single Zirconia Crowns Using a Biologically Oriented Preparation Technique: A 6-Year Prospective Clinical Study
Authors: Serra-Pastor Blanca , Bustamante-Hernández Naia , Fons-Font Antonio , Fernanda Solá-Ruíz María , Revilla-León Marta , Agustín-Panadero Rubén
Published: August 2021

Objectives. The aim of this study was to analyze the behavior of the periodontal tissues around teeth in the anterior region when restored with zirconia single crowns, using a biologically oriented preparation technique (BOPT), over a 6-year follow-up. Methods. The study investigated tooth-supported single crowns in the anterior region that were fabricated with a zirconia core and feldspathic ceramic covering, in 34 patients. Follow-up analysis took place annually for 6 years, assessing periodontal responses by evaluating the following variables: plaque index (PI); probing depth (PD); gingival index (GI); gingival thickness adjacent to the restoration; and stability of the gingival margin (MS). Any (biological and mechanical) complications were also recorded, as well as the patients’ satisfaction with the treatment. Results. After 6 years’ follow-up, a low mean plaque index was obtained, probing depth was stable, and gingival thickness and margin stability had increased. Complications (biological and mechanical) did not present a statistically significant incidence and a crown survival rate of 97.2% was achieved. Patients’ satisfaction obtained a mean VAS score of 9.04 under 10. Conclusion. Teeth that are prepared with BOPT in the anterior region present good periodontal behavior around the restored teeth, particularly in terms of the stability of the gingival margin and increased gingival thickness. Single crowns prepared with BOPT obtain an excellent clinical survival rate, as well as a high score in patients’ satisfaction after 6 years.
Optimizing Care for Adults with Congenital Heart Disease: Results of a Conjoint Analysis Based on a Nationwide Sample of Patients Included in the German National Register
Authors: Lammers Astrid E. , Helm Paul C. , Bauer Ulrike M. , van Huelsen Ann-Kathrin , Schneider Helmut , Baumgartner Helmut , Diller Gerhard-Paul
Published: August 2021

(1) Background: Congenital heart disease (CHD) requires lifelong specialized care. Failure to follow up and gaps in care are common in this group and lead to increased morbidity/mortality. We evaluated patients’ perceived needs and expectations regarding specialized care using state-of-the-art statistical and market research techniques based on a nationwide sample of CHD patients. (2) Methods: A random sample of adults with CHD registered in the German National Register for Congenital Heart Defects were invited to answer an adaptive online questionnaire based on the conjoint analysis (CA) technique. CA determines the relative importance of various aspects of health care provision and allows individuals to trade between characteristics, thus recognizing limited resources. (3) Results: 637 patients participated (mean age 33.8 ± 12.6 years; 55.6% female; disease complexity: simple defect 12.6%, moderate complexity 40.3%, complex CHD 40.2%) in the analysis. Patients assigned the highest relative importance to aspects of patient–physician communication, physician qualifications, waiting time, medical care, and medical equipment. Comfort-related aspects such as driving time or hotel aspects of care received much lower scores. We identified four well-defined clusters of patients with differing expectation patterns: (i) time sensitive patients; (ii) excellence seeking patients; (iii) continuity seekers, and (iv) support seeking patients. (4) Conclusions: Adult CHD patients rank effective patient–physician interaction and communication as the most important factors. As we identified significant heterogeneity between CHD patients, centers should cater for individual preferences and integrate individual needs into treatment plans to prevent failure to follow up and ensure patient compliance.
The Quality of Medical Care in the Conditions of the COVID-19 Pandemic, with Particular Emphasis on the Access to Primary Healthcare and the Effectiveness of Treatment in Poland
Authors: Kludacz-Alessandri Magdalena , Walczak Renata , Hawrysz Liliana , Korneta Piotr
Published: August 2021

Health has a significant influence on the quality of life of a society. The COVID-19 pandemic has forced many countries to implement restrictive measures to prevent its wider spread, including, inter alia, the introduction of remote healthcare in the form of teleconsultations. Therefore, there is the question of how such a change affects the quality of treatment and the primary healthcare of patients during the COVID-19 pandemic. The article aims to examine patient satisfaction with the access to primary healthcare and the effectiveness of treatment in a condition of remote medical care caused by the COVID-19 pandemic. We also analyse the impact of access to primary healthcare on the treatment effectiveness. Patient satisfaction was measured using a questionnaire assessing the quality of primary medical care. Of the 36 items studied, seven were related to the accessibility dimension and four were related to the treatment effectiveness dimension. Our results suggest that the treatment effectiveness and the access to primary healthcare services during the COVID-19 pandemic through telemedicine are quite highly rated by patients. Hence, further implementation of telemedicine in primary healthcare should improve the quality of lives of the wide society. We have also identified the access to primary healthcare has a considerable impact on the treatment effectiveness. Therefore, we recommend increasing the contact between patients and GPs via telemedicine under lockdown conditions.
Efficacy of Statin Treatment According to Baseline Renal Function in Korean Patients with Acute Myocardial Infarction Not Requiring Dialysis Undergoing Newer-Generation Drug-Eluting Stent Implantation
Authors: Kim Yong Hoon , Her Ae-Young , Jeong Myung Ho , Kim Byeong-Keuk , Hong Sung-Jin , Kim Seunghwan , Ahn Chul-Min , Kim Jung-Sun , Ko Young-Guk , Choi Donghoon , Hong Myeong-Ki , Jang Yangsoo
Published: August 2021

We investigated the 2-year efficacy of statin treatment according to baseline renal function in patients with acute myocardial infarction (AMI) not requiring dialysis undergoing newer-generation drug-eluting stent (DES) implantation. A total of 18,875 AMI patients were classified into group A (statin users, n = 16,055) and group B (statin nonusers, n = 2820). According to the baseline estimated glomerular filtration rate (eGFR; ≥90, 60–89, 30–59 and <30 mL/min/1.73 m2), these two groups were sub-classified into groups A1, A2, A3 and A4 and groups B1, B2, B3 and B4. The major adverse cardiac events (MACE), defined as all-cause death, recurrent MI (re-MI) and any repeat revascularization, were evaluated. The MACE (group A1 vs. B1, p = 0.002; group A2 vs. B2, p = 0.007; group A3 vs. B3, p < 0.001; group A4 vs. B4, p < 0.001), all-cause death (p = 0.006, p < 0.001, p < 0.001, p < 0.001, respectively) and cardiac death (p = 0.004, p < 0.001, p < 0.001, p < 0.001, respectively) rates were significantly higher in statin nonusers than those in statin users. Despite the beneficial effects of statin treatment, the MACE (group A1 vs. A2 vs. A3 vs. A4: 5.2%, 6.4%, 10.1% and 18.5%, respectively), all-cause mortality (0.9%, 1.8%, 4.6% and 12.9%, respectively) and cardiac death (0.4%, 1.0%, 2.6% and 6.8%, respectively) rates were significantly increased as eGFR decreased in group A. These results may be related to the peculiar characteristics of chronic kidney disease, including increased vascular calcification and traditional or nontraditional cardiovascular risk factors. In the era of newer-generation DESs, although statin treatment was effective in reducing mortality, this beneficial effect was diminished in accordance with the deterioration of baseline renal function.
A Green Prospective for Learned Post-Processing in Sparse-View Tomographic Reconstruction
Authors: Morotti Elena , Evangelista Davide , Loli Piccolomini Elena
Published: August 2021

Deep Learning is developing interesting tools that are of great interest for inverse imaging applications. In this work, we consider a medical imaging reconstruction task from subsampled measurements, which is an active research field where Convolutional Neural Networks have already revealed their great potential. However, the commonly used architectures are very deep and, hence, prone to overfitting and unfeasible for clinical usages. Inspired by the ideas of the green AI literature, we propose a shallow neural network to perform efficient Learned Post-Processing on images roughly reconstructed by the filtered backprojection algorithm. The results show that the proposed inexpensive network computes images of comparable (or even higher) quality in about one-fourth of time and is more robust than the widely used and very deep ResUNet for tomographic reconstructions from sparse-view protocols.
Fungal Taxa Responsible for Mucormycosis/“Black Fungus” among COVID-19 Patients in India
Authors: Divakar Pradeep K.
Published: August 2021

Mucormycosis is caused by fungi belonging to the order Mucorales. The term “Black Fungus” has been widely applied to human pathogenic Mucorales in India. They mainly infect the sinuses and brain, lungs, stomach and intestines, and skin. While this has been considered a rare disease, thousands of cases have been reported during the second wave of COVID-19 in India, between the months of April and June 2021. Hitherto, more than 45,374 cases and over 4300 deaths have been reported among COVID-19 patients across India from April 2021 to July 21, 2021. Though the mortality rate is estimated to be 50%, it could be above 90% if left untreated. In India, Rhizopus arrhizus has been related to be the most common species to cause human mucormycosis, followed by Apophysomyces variabilis, Rhizopus microsporus, and R. homothallicus. Accurate sample identification of human pathogenic Mucorales species is challenging especially due to the frequent lack of diagnostic morphological features. Traditionally, the culture-based approach has been extensively used to isolate and characterize human pathogenic Mucorales. However, this may not be an appropriate approach to objectively isolate and characterize all species, as the germination and growth of fungal spores are highly dependent on culture media and environmental conditions. Therefore, a robust approach to the accurate and rapid identification of human pathogenic Mucorales species is a prerequisite. The metagenomic approach comprehensively sequences and analyzes all genetic material in a complex biological sample and, consequently, this could be an appropriate approach to objectively characterize human pathogenic Mucorales taxa without the need for in vitro culture. The precise identification of the species will not only be useful for the correct diagnosis of this disease, but also for the development of antifungal drugs specific for each species. Accurate and rapid species identification is desperately needed to save lives in the mucormycosis outbreak among COVID-19 patients in India and neighboring countries.
A Putative Lignin Copper Oxidase from Trichoderma reesei
Authors: Daou Mariane , Bisotto Alexandra , Haon Mireille , Oliveira Correia Lydie , Cottyn Betty , Drula Elodie , Garajová Soňa , Bertrand Emmanuel , Record Eric , Navarro David , Raouche Sana , Baumberger Stéphanie , Faulds Craig B.
Published: August 2021

The ability of Trichoderma reesei, a fungus widely used for the commercial production of hemicellulases and cellulases, to grow and modify technical soda lignin was investigated. By quantifying fungal genomic DNA, T. reesei showed growth and sporulation in solid and liquid cultures containing lignin alone. The analysis of released soluble lignin and residual insoluble lignin was indicative of enzymatic oxidative conversion of phenolic lignin side chains and the modification of lignin structure by cleaving the β-O-4 linkages. The results also showed that polymerization reactions were taking place. A proteomic analysis conducted to investigate secreted proteins at days 3, 7, and 14 of growth revealed the presence of five auxiliary activity (AA) enzymes in the secretome: AA6, AA9, two AA3 enzymes), and the only copper radical oxidase encoded in the genome of T. reesei. This enzyme was heterologously produced and characterized, and its activity on lignin-derived molecules was investigated. Phylogenetic characterization demonstrated that this enzyme belonged to the AA5_1 family, which includes characterized glyoxal oxidases. However, the enzyme displayed overlapping physicochemical and catalytic properties across the AA5 family. The enzyme was remarkably stable at high pH and oxidized both, alcohols and aldehydes with preference to the alcohol group. It was also active on lignin-derived phenolic molecules as well as simple carbohydrates. HPSEC and LC-MS analyses on the reactions of the produced protein on lignin dimers (SS ββ, SS βO4 and GG β5) uncovered the polymerizing activity of this enzyme, which was accordingly named lignin copper oxidase (TrLOx). Polymers of up 10 units were formed by hydroxy group oxidation and radical formation. The activations of lignin molecules by TrLOx along with the co-secretion of this enzyme with reductases and FAD flavoproteins oxidoreductases during growth on lignin suggest a synergistic mechanism for lignin breakdown.
Batrachochytrium salamandrivorans Threat to the Iberian Urodele Hotspot
Authors: Bosch Jaime , Martel An , Sopniewski Jarrod , Thumsová Barbora , Ayres Cesar , Scheele Ben C. , Velo-Antón Guillermo , Pasmans Frank
Published: August 2021

The recent introduction of the chytrid fungus Batrachochytrium salamandrivorans into northeastern Spain threatens salamander diversity on the Iberian Peninsula. We assessed the current epidemiological situation with extensive field sampling of urodele populations. We then sought to delineate priority regions and identify conservation units for the Iberian Peninsula by estimating the susceptibility of Iberian urodeles using laboratory experiments, evidence from mortality events in nature and captivity and inference from phylogeny. None of the 1395 field samples, collected between 2015 and 2021 were positive for Bsal and no Bsal-associated mortality events were recorded, in contrast to the confirmed occurrence of Bsal outbreak previously described in 2018. We classified five of eleven Iberian urodele species as highly susceptible, predicting elevated mortality and population declines following potential Bsal emergence in the wild, five species as intermediately susceptible with variable disease outcomes and one species as resistant to disease and mortality. We identified the six conservation units (i.e., species or lineages within species) at highest risk and propose priority areas for active disease surveillance and field biosecurity measures. The magnitude of the disease threat identified here emphasizes the need for region-tailored disease abatement plans that couple active disease surveillance to rapid and drastic actions.