bluuebunny/crossref_metadata_2025 huggingface dataset:
A First Glimpse of the Mexican Fruit Fly Anastrepha ludens (Diptera: Tephritidae) Antenna Morphology and Proteome in Response to a Proteinaceous Attractant
Authors: Ruiz-May Eliel , Altúzar-Molina Alma , Elizalde-Contreras José M. , Arellano-de los Santos Jiovanny , Monribot-Villanueva Juan , Guillén Larissa , Vázquez-Rosas-Landa Mirna , Ibarra-Laclette Enrique , Ramírez-Vázquez Mónica , Ortega Rafael , Aluja Martín
Published: October 2020

Anastrepha ludens is a key pest of mangoes and citrus from Texas to Costa Rica but the mechanisms of odorant perception in this species are poorly understood. Detection of volatiles in insects occurs mainly in the antenna, where molecules penetrate sensillum pores and link to soluble proteins in the hemolymph until reaching specific odor receptors that trigger signal transduction and lead to behavioral responses. Scrutinizing the molecular foundation of odorant perception in A. ludens is necessary to improve biorational management strategies against this pest. After exposing adults of three maturity stages to a proteinaceous attractant, we studied antennal morphology and comparative proteomic profiles using nano-LC-MS/MS with tandem mass tags combined with synchronous precursor selection (SPS)-MS3. Antennas from newly emerged flies exhibited dense agglomerations of olfactory sensory neurons. We discovered 4618 unique proteins in the antennas of A. ludens and identified some associated with odor signaling, including odorant-binding and calcium signaling related proteins, the odorant receptor co-receptor (Orco), and putative odorant-degrading enzymes. Antennas of sexually immature flies exhibited the most upregulation of odor perception proteins compared to mature flies exposed to the attractant. This is the first report where critical molecular players are linked to the odor perception mechanism of A. ludens.
Vitamin B3-Based Biologically Active Compounds as Inhibitors of Human Cholinesterases
Authors: Zandona Antonio , Lihtar Gabriela , Maraković Nikola , Miš Katarina , Bušić Valentina , Gašo-Sokač Dajana , Pirkmajer Sergej , Katalinić Maja
Published: October 2020

We evaluated the potential of nine vitamin B3 scaffold-based derivatives as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors, as a starting point for the development of novel drugs for treating disorders with cholinergic neurotransmission-linked pathology. As the results indicate, all compounds reversibly inhibited both enzymes in the micromolar range pointing to the preference of AChE over BChE for binding the tested derivatives. Molecular docking studies revealed the importance of interactions with AChE active site residues Tyr337 and Tyr124, which dictated most of the observed differences. The most potent inhibitor of both enzymes with Ki of 4 μM for AChE and 8 μM for BChE was the nicotinamide derivative 1-(4′-phenylphenacyl)-3-carbamoylpyridinium bromide. Such a result places it within the range of several currently studied novel cholinesterase inhibitors. Cytotoxicity profiling did not classify this compound as highly toxic, but the induced effects on cells should not be neglected in any future detailed studies and when considering this scaffold for drug development.
PD-L1 Influences Cell Spreading, Migration and Invasion in Head and Neck Cancer Cells
Authors: Eichberger Jonas , Schulz Daniela , Pscheidl Kristian , Fiedler Mathias , Reichert Torsten Eugen , Bauer Richard Josef , Ettl Tobias
Published: October 2020

The programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis blockade has been implemented in advanced-stage tumor therapy for various entities, including head and neck squamous cell carcinoma (HNSCC). Despite a promising tumor response in a subgroup of HNSCC patients, the majority suffer from disease progression. PD-L1 is known to influence several intrinsic mechanisms in cancer cells, such as proliferation, apoptosis, migration and invasion. Here, we modulated PD-L1 expression in three HNSCC cell lines with differential intrinsic PD-L1 expression. In addition to an alteration in the epithelial-to-mesenchymal transition (EMT) marker expression, we observed PD-L1-dependent cell spreading, migration and invasion in a spheroid spreading assay on four different coatings (poly-L-lysine, collagen type I, fibronectin and Matrigel®) and a chemotactic transwell migration/invasion assay. Furthermore, the overexpression of PD-L1 led to increased gene expression and small interfering ribonucleic acid (siRNA) knockdown and decreased gene expression of Rho-GTPases and related proteins in a RT2 Profiler™ PCR Array. Rac1 and Rho-GTPase pulldown assays revealed a change in the activation state concordantly with PD-L1 expression. In summary, our results suggest a major role for PD-L1 in favoring cell motility, including cell spreading, migration and invasion. This is presumably caused by altered N-cadherin expression and changes in the activation states of small Rho-GTPases Rho and Rac1.
p53 Immunohistochemical Patterns in HPV-Independent Squamous Cell Carcinomas of the Vulva and the Associated Skin Lesions: A Study of 779 Cases
Authors: Rakislova Natalia , Alemany Laia , Clavero Omar , Saco Adela , Torné Aureli , del Pino Marta , Munmany Meritxell , Rodrigo-Calvo Maria , Guerrero José , Marimon Lorena , Vega Naiara , Quirós Beatriz , Lloveras Belen , Ribera-Cortada Inmaculada , Alejo Maria , Pawlita Michael , Quint Wim , de Sanjose Silvia , Ordi Jaume ,   VVAP Study Group
Published: October 2020

Human papillomavirus (HPV)-independent vulvar squamous cell carcinomas (VSCC) and its precursors frequently harbour TP53 mutations. Recently, six p53 immunohistochemical (IHC) patterns have been defined, which have shown strong correlation with TP53 mutation status. However, few studies have applied this new six-pattern framework and none of them exhaustively compared p53 IHC positivity and patterns between invasive VSCC and adjacent skin lesion. We performed p53 IHC in a series of 779 HPV-independent VSCC with adjacent skin and evaluated the IHC slides following the newly described classification. Some 74.1% invasive VSCC showed abnormal p53 IHC staining. A skin lesion was identified in 450 cases (57.8%), including 254 intraepithelial precursors and 196 inflammatory/reactive lesions. Two hundred and ten of 450 (47%) VSCC with associated skin lesions showed an abnormal p53 IHC stain, with an identical staining pattern between the VSCC and the adjacent skin lesion in 80% of the cases. A total of 144/450 (32%) VSCC showed wild-type p53 IHC both in the invasive VSCC and adjacent skin lesion. Finally, 96/450 (21%) VSCC showed p53 IHC abnormal staining in the invasive VSCC but a wild-type p53 staining in the skin lesion. Most of the discordant cases (70/96; 73%) showed adjacent inflammatory lesions. In conclusion, the p53 IHC staining and pattern are usually identical in the VSCC and the intraepithelial precursor.
Correction: Ueoka, I., et al. Autism Spectrum Disorder-Related Syndromes: Modeling with Drosophila and Rodents. Int. J. Mol. Sci. 2019, 20, 4071
Authors: Ueoka Ibuki , Pham Hang Thi Nguyet , Matsumoto Kinzo , Yamaguchi Masamitsu
Published: October 2020

The author wishes to make the following correction to this paper [...]
KV11.1, NaV1.5, and CaV1.2 Transporter Proteins as Antitarget for Drug Cardiotoxicity
Authors: Kowalska Magdalena , Nowaczyk Jacek , Nowaczyk Alicja
Published: October 2020

Safety assessment of pharmaceuticals is a rapidly developing area of pharmacy and medicine. The new advanced guidelines for testing the toxicity of compounds require specialized tools that provide information on the tested drug in a quick and reliable way. Ion channels represent the third-largest target. As mentioned in the literature, ion channels are an indispensable part of the heart’s work. In this paper the most important information concerning the guidelines for cardiotoxicity testing and the way the tests are conducted has been collected. Attention has been focused on the role of selected ion channels in this process.
Genetic Susceptibility and Protein Expression of Extracellular Matrix Turnover-Related Genes in Oral Submucous Fibrosis
Authors: Cheng Ru-Hsiu , Wang Yi-Ping , Chang Julia Yu-Fong , Pan Yu-Hwa , Chang Mei-Chi , Jeng Jiiang-Huei
Published: October 2020

Betel quid (BQ) chewing increased the risk of oral cancer and oral submucous fibrosis (OSMF), an oral premalignant disorder (OPMD) with malignant transformation potential. BQ components such as areca nut (AN), trauma by coarse AN fiber, catechin, copper, alkaloids, stimulated reactive oxygen species (ROS), inflammation and cytotoxicity are suggested to be the contributing factors. They may induce tissue inflammation, proliferation of fibroblasts and collagen deposition, myofibroblast differentiation and contraction, collagen cross-links and inhibit collagen phagocytosis, finally leading to the development of OSMF and oral cancer. These events are mediated by BQ components-induced changes of extracellular matrix (ECM) turnover via regulation of TGF-β1, plasminogen activator inhibitor-1 (PAI-1), cystatin, lysyl oxidase (LOX) and tissue inhibitors of metalloproteinases (TIMPs) and metalloproteinases (MMPs). Genetic susceptibility is also involved in these disease processes. Further understanding the molecular mechanisms of BQ-induced OSMF and oral cancer can be helpful for future disease prevention and treatment.
Protective Role of St. John’s Wort and Its Components Hyperforin and Hypericin against Diabetes through Inhibition of Inflammatory Signaling: Evidence from In Vitro and In Vivo Studies
Authors: Novelli Michela , Masiello Pellegrino , Beffy Pascale , Menegazzi Marta
Published: October 2020

Diabetes mellitus is a very common chronic disease with progressively increasing prevalence. Besides the well-known autoimmune and inflammatory pathogenesis of type 1 diabetes, in many people, metabolic changes and inappropriate lifestyle favor a subtle chronic inflammatory state that contributes to development of insulin resistance and progressive loss of β-cell function and mass, eventually resulting in metabolic syndrome or overt type 2 diabetes. In this paper, we review the anti-inflammatory effects of the extract of Hypericum perforatum L. (St. John’s wort, SJW) and its main active ingredients firstly in representative pathological situations on inflammatory basis and then in pancreatic β cells and in obese or diabetic animal models. The simultaneous and long-lasting inhibition of signal transducer and activator of transcription (STAT)-1, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPKs)/c-jun N-terminal kinase (JNK) signaling pathways involved in pro-inflammatory cytokine-induced β-cell dysfunction/death and insulin resistance make SJW particularly suitable for both preventive and therapeutic use in metabolic diseases. Hindrance of inflammatory cytokine signaling is likely dependent on the hyperforin content of SJW extract, but recent data reveal that hypericin can also exert relevant protective effects, mediated by activation of the cyclic adenosine monophosphate (cAMP)/protein kinase cAMP-dependent (PKA)/adenosine monophosphate activated protein kinase (AMPK) pathway, against high-fat-diet-induced metabolic abnormalities. Actually, the mechanisms of action of the two main components of SJW appear complementary, strengthening the efficacy of the plant extract. Careful quantitative analysis of SJW components and suitable dosage, with monitoring of possible drug–drug interaction in a context of remarkable tolerability, are easily achievable pre-requisites for forthcoming clinical applications.
Hypoxia Regulates DPP4 Expression, Proteolytic Inactivation, and Shedding from Ovarian Cancer Cells
Authors: Moffitt Laura R. , Bilandzic Maree , Wilson Amy L. , Chen Yiqian , Gorrell Mark D. , Oehler Martin K. , Plebanski Magdalena , Stephens Andrew N.
Published: October 2020

The treatment of ovarian cancer has not significantly changed in decades and it remains one of the most lethal malignancies in women. The serine protease dipeptidyl peptidase 4 (DPP4) plays key roles in metabolism and immunity, and its expression has been associated with either pro- or anti-tumour effects in multiple tumour types. In this study, we provide the first evidence that DPP4 expression and enzyme activity are uncoupled under hypoxic conditions in ovarian cancer cells. Whilst we identified strong up-regulation of DPP4 mRNA expression under hypoxic growth, the specific activity of secreted DPP4 was paradoxically decreased. Further investigation revealed matrix metalloproteinases (MMP)-dependent inactivation and proteolytic shedding of DPP4 from the cell surface, mediated by at least MMP10 and MMP13. This is the first report of uncoupled DPP4 expression and activity in ovarian cancer cells, and suggests a previously unrecognized, cell- and tissue-type-dependent mechanism for the regulation of DPP4 in solid tumours. Further studies are necessary to identify the functional consequences of DPP4 processing and its potential prognostic or therapeutic value.
Assessment of NK Cell Activity Based on NK Cell-Specific Receptor Synergy in Peripheral Blood Mononuclear Cells and Whole Blood
Authors: Kim Jung Min , Yi Eunbi , Cho Hyungwoo , Choi Woo Seon , Ko Dae-Hyun , Yoon Dok Hyun , Hwang Sang-Hyun , Kim Hun Sik
Published: October 2020

Natural killer (NK) cells are cytotoxic innate lymphocytes endowed with a unique ability to kill a broad spectrum of cancer and virus-infected cells. Given their key contribution to diverse diseases, the measurement of NK cell activity (NKA) has been used to estimate disease prognosis or the effect of therapeutic treatment. Currently, NKA assays are primarily based on cumbersome procedures related to careful labeling and handling of target cells and/or NK cells, and they require a rapid isolation of peripheral blood mononuclear cells (PBMCs) which often necessitates a large amount of blood. Here, we developed an ELISA-based whole blood (WB) NKA assay involving engineered target cells (P815-ULBP1+CD48) providing defined and synergistic stimulation for NK cells via NKG2D and 2B4. WB collected from healthy donors (HDs) and patients with multiple myeloma (MM) was stimulated with P815-ULBP1+CD48 cells combined with IL-2. Thereafter, it utilized the serum concentrations of granzyme B and IFN-γ originating in NK cells as independent and complementary indicators of NKA. This WB NKA assay demonstrated that MM patients exhibit a significantly lower NKA than HDs following stimulation with P815-ULBP1+CD48 cells and had a good correlation with the commonly used flow cytometry-based PBMC NKA assay. Moreover, the use of P815-ULBP1+CD48 cells in relation to assessing the levels of NKG2D and 2B4 receptors on NK cells facilitated the mechanistic study and led to the identification of TGF-β1 as a potential mediator of compromised NKA in MM. Thus, our proposed WB NKA assay facilitates the reliable measurement of NKA and holds promise for further development as both a clinical and research tool.
Molecular Mechanisms of Central Nervous System Axonal Regeneration and Remyelination: A Review
Authors: Uyeda Akiko , Muramatsu Rieko
Published: October 2020

Central nervous system (CNS) injury, including stroke, spinal cord injury, and traumatic brain injury, causes severe neurological symptoms such as sensory and motor deficits. Currently, there is no effective therapeutic method to restore neurological function because the adult CNS has limited capacity to regenerate after injury. Many efforts have been made to understand the molecular and cellular mechanisms underlying CNS regeneration and to establish novel therapeutic methods based on these mechanisms, with a variety of strategies including cell transplantation, modulation of cell intrinsic molecular mechanisms, and therapeutic targeting of the pathological nature of the extracellular environment in CNS injury. In this review, we will focus on the mechanisms that regulate CNS regeneration, highlighting the history, recent efforts, and questions left unanswered in this field.
Advances in Understanding TKS4 and TKS5: Molecular Scaffolds Regulating Cellular Processes from Podosome and Invadopodium Formation to Differentiation and Tissue Homeostasis
Authors: Kudlik Gyöngyi , Takács Tamás , Radnai László , Kurilla Anita , Szeder Bálint , Koprivanacz Kitti , Merő Balázs L. , Buday László , Vas Virag
Published: October 2020

Scaffold proteins are typically thought of as multi-domain “bridging molecules.” They serve as crucial regulators of key signaling events by simultaneously binding multiple participants involved in specific signaling pathways. In the case of epidermal growth factor (EGF)-epidermal growth factor receptor (EGFR) binding, the activated EGFR contacts cytosolic SRC tyrosine-kinase, which then becomes activated. This process leads to the phosphorylation of SRC-substrates, including the tyrosine kinase substrates (TKS) scaffold proteins. The TKS proteins serve as a platform for the recruitment of key players in EGFR signal transduction, promoting cell spreading and migration. The TKS4 and the TKS5 scaffold proteins are tyrosine kinase substrates with four or five SH3 domains, respectively. Their structural features allow them to recruit and bind a variety of signaling proteins and to anchor them to the cytoplasmic surface of the cell membrane. Until recently, TKS4 and TKS5 had been recognized for their involvement in cellular motility, reactive oxygen species-dependent processes, and embryonic development, among others. However, a number of novel functions have been discovered for these molecules in recent years. In this review, we attempt to cover the diverse nature of the TKS molecules by discussing their structure, regulation by SRC kinase, relevant signaling pathways, and interaction partners, as well as their involvement in cellular processes, including migration, invasion, differentiation, and adipose tissue and bone homeostasis. We also describe related pathologies and the established mouse models.
Cell Wall Composition as a Marker of the Reprogramming of the Cell Fate on the Example of a Daucus carota (L.) Hypocotyl in Which Somatic Embryogenesis Was Induced
Authors: Kuczak Michał , Kurczyńska Ewa
Published: October 2020

Changes in the composition of the cell walls are postulated to accompany changes in the cell’s fate. We check whether there is a relationship between the presence of selected pectic, arabinogalactan proteins (AGPs), and extensins epitopes and changes in cell reprogramming in order to answer the question of whether they can be markers accompanying changes of cell fate. Selected antibodies were used for spatio-temporal immunolocalization of wall components during the induction of somatic embryogenesis. Based on the obtained results, it can be concluded that (1) the LM6 (pectic), LM2 (AGPs) epitopes are positive markers, but the LM5, LM19 (pectic), JIM8, JIM13 (AGPs) epitopes are negative markers of cells reprogramming to the meristematic/pluripotent state; (2) the LM8 (pectic), JIM8, JIM13, LM2 (AGPs) and JIM11 (extensin) epitopes are positive markers, but LM6 (pectic) epitope is negative marker of cells undergoing detachment; (3) JIM4 (AGPs) is a positive marker, but LM5 (pectic), JIM8, JIM13, LM2 (AGPs) are negative markers for pericycle cells on the xylem pole; (4) LM19, LM20 (pectic), JIM13, LM2 (AGPs) are constitutive wall components, but LM6, LM8 (pectic), JIM4, JIM8, JIM16 (AGPs), JIM11, JIM12 and JIM20 (extensins) are not constitutive wall components; (5) the extensins do not contribute to the cell reprogramming.
Cooperative Interaction of Janthinobacterium sp. SLB01 and Flavobacterium sp. SLB02 in the Diseased Sponge Lubomirskia baicalensis
Authors: Petrushin Ivan , Belikov Sergei , Chernogor Lubov
Published: October 2020

Endemic freshwater sponges (demosponges, Lubomirskiidae) dominate in Lake Baikal, Central Siberia, Russia. These sponges are multicellular filter-feeding animals that represent a complex consortium of many species of eukaryotes and prokaryotes. In recent years, mass disease and death of Lubomirskia baicalensis has been a significant problem in Lake Baikal. The etiology and ecology of these events remain unknown. Bacteria from the families Flavobacteriaceae and Oxalobacteraceae dominate the microbiomes of diseased sponges. Both species are opportunistic pathogens common in freshwater ecosystems. The aim of our study was to analyze the genomes of strains Janthinobacterium sp. SLB01 and Flavobacterium sp. SLB02, isolated from diseased sponges to identify the reasons for their joint dominance. Janthinobacterium sp. SLB01 attacks other cells using a type VI secretion system and suppresses gram-positive bacteria with violacein, and regulates its own activity via quorum sensing. It produces floc and strong biofilm by exopolysaccharide biosynthesis and PEP-CTERM/XrtA protein expression. Flavobacterium sp. SLB02 utilizes the fragments of cell walls produced by polysaccharides. These two strains have a marked difference in carbohydrate acquisition. We described a possible means of joint occupation of the ecological niche in the freshwater sponge microbial community. This study expands the understanding of the symbiotic relationship of microorganisms with freshwater Baikal sponges.
Therapeutic Potential of Repeated Intravenous Transplantation of Human Adipose-Derived Stem Cells in Subchronic MPTP-Induced Parkinson’s Disease Mouse Model
Authors: Park Hyunjun , Chang Keun-A
Published: October 2020

Parkinson’s disease (PD) is the second most common neurodegenerative disease, which is clinically and pathologically characterized by motor dysfunction and the loss of dopaminergic neurons in the substantia nigra, respectively. PD treatment with stem cells has long been studied by researchers; however, no adequate treatment strategy has been established. The results of studies so far have suggested that stem cell transplantation can be an effective treatment for PD. However, PD is a progressively deteriorating neurodegenerative disease that requires long-term treatment, and this has been insufficiently studied. Thus, we aimed to investigate the therapeutic potential of human adipose-derived stem cells (hASC) for repeated vein transplantation over long-term in an animal model of PD. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice, hASCs were administered on the tail vein six times at two-week intervals. After the last injection of hASCs, motor function significantly improved. The number of dopaminergic neurons present in the nigrostriatal pathway was recovered using hASC transplantation. Moreover, the administration of hASC restored altered dopamine transporter expression and increased neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF), in the striatum. Overall, this study suggests that repeated intravenous transplantation of hASC may exert therapeutic effects on PD by restoring BDNF and GDNF expressions, protecting dopaminergic neurons, and maintaining the nigrostriatal pathway.
Processed Eggshell Membrane Powder Is a Promising Biomaterial for Use in Tissue Engineering
Authors: Rønning Sissel B. , Berg Ragnhild S. , Høst Vibeke , Veiseth-Kent Eva , Wilhelmsen Christian R. , Haugen Eirik , Suso Henri-Pierre , Barham Paul , Schmidt Ralf , Pedersen Mona E.
Published: October 2020

The purpose of this study was to investigate the tissue regenerating and biomechanical properties of processed eggshell membrane powder (PEP) for use in 3D-scaffolds. PEP is a low-cost, natural biomaterial with beneficial bioactive properties. Most importantly, this material is available as a by-product of the chicken egg processing (breaking) industry on a large scale, and it could have potential as a low-cost ingredient for therapeutic scaffolds. Scaffolds consisting of collagen alone and collagen combined with PEP were produced and analyzed for their mechanical properties and the growth of primary fibroblasts and skeletal muscle cells. Mechanical testing revealed that a PEP/collagen-based scaffold increased the mechanical hardness of the scaffold compared with a pure collagen scaffold. Scanning electron microscopy (SEM) demonstrated an interconnected porous structure for both scaffolds, and that the PEP was evenly distributed in dense clusters within the scaffold. Fibroblast and skeletal muscle cells attached, were viable and able to proliferate for 1 and 2 weeks in both scaffolds. The cell types retained their phenotypic properties expressing phenotype markers of fibroblasts (TE7, alpha-smooth muscle actin) and skeletal muscle (CD56) visualized by immunostaining. mRNA expression of the skeletal muscle markers myoD, myogenin, and fibroblasts marker (SMA) together with extracellular matrix components supported viable phenotypes and matrix-producing cells in both types of scaffolds. In conclusion, PEP is a promising low-cost, natural biomaterial for use in combination with collagen as a scaffold for 3D-tissue engineering to improve the mechanical properties and promote cellular adhesion and growth of regenerating cells.
Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis
Authors: Watts Deepika , Gaete Diana , Rodriguez Diego , Hoogewijs David , Rauner Martina , Sormendi Sundary , Wielockx Ben
Published: October 2020

Erythropoiesis is a complex process driving the production of red blood cells. During homeostasis, adult erythropoiesis takes place in the bone marrow and is tightly controlled by erythropoietin (EPO), a central hormone mainly produced in renal EPO-producing cells. The expression of EPO is strictly regulated by local changes in oxygen partial pressure (pO2) as under-deprived oxygen (hypoxia); the transcription factor hypoxia-inducible factor-2 induces EPO. However, erythropoiesis regulation extends beyond the well-established hypoxia-inducible factor (HIF)–EPO axis and involves processes modulated by other hypoxia pathway proteins (HPPs), including proteins involved in iron metabolism. The importance of a number of these factors is evident as their altered expression has been associated with various anemia-related disorders, including chronic kidney disease. Eventually, our emerging understanding of HPPs and their regulatory feedback will be instrumental in developing specific therapies for anemic patients and beyond.
Understanding the Blockchain Oracle Problem: A Call for Action
Authors: Caldarelli Giulio
Published: October 2020

Scarce and niche in the literature just a few years ago, the blockchain topic is now the main subject in conference papers and books. However, the hype generated by the technology and its potential implications for real-world applications is flawed by many misconceptions about how it works and how it is implemented, creating faulty thinking or overly optimistic expectations. Too often, characteristics such as immutability, transparency, and censorship resistance, which mainly belong to the bitcoin blockchain, are sought in regular blockchains, whose potential is barely comparable. Furthermore, critical aspects such as oracles and their role in smart contracts receive few literature contributions, leaving results and theoretical implications highly questionable. This literature review of the latest papers in the field aims to give clarity to the blockchain oracle problem by discussing its effects in some of the most promising real-world applications. The analysis supports the view that the more trusted a system is, the less the oracle problem impacts.
Not All Slugs Are the Same: Variation in Growth and Development of the Slug Deroceras reticulatum
Authors: Shirley Mark , Howlett Sally , Port Gordon
Published: October 2020

Models to forecast slug populations make assumptions about growth and mortality in response to environmental factors. To refine these models, the growth trajectories and survival of Deroceras reticulatum, a worldwide pest, hatching in spring and autumn were compared at three rearing temperatures (ambient, 12 °C and 15 °C). Deroceras reticulatum reared under identical conditions showed great variation in growth and strong bimodality in growth rates. At all rearing temperatures, growth was influenced by hatching season; in all cases, fast growers dominated in autumn and slow growers dominated in spring. Survival was influenced by hatching season: autumn-born slugs survived better at ambient temperatures, but spring-born slugs had better survival at 15 °C. Deroceras reticulatum may be partitioned into ”slow growers” and ”fast growers”. Fast growers responded to warmer conditions, growing to large sizes. Slow growers, in contrast, gained weight at comparable rates to ambient reared slugs, regardless of the elevated constant temperatures. The peaks of slug activity in autumn and spring are possibly not distinct generations as some slugs may mature early/late and slip into the alternative cohort. Rather, the observed autumn and spring peaks in slug numbers may be a response of a mixed-age population to the favourable environmental conditions at that time.
Toxorhynchites Species: A Review of Current Knowledge
Authors: Donald Claire L. , Siriyasatien Padet , Kohl Alain
Published: October 2020

The increasing global incidence of mosquito-borne infections is driving a need for effective control methods. Vector populations have expanded their geographical ranges, while increasing resistance to chemical insecticides and a lack of effective treatments or vaccines has meant that the development of vector control methods is essential in the fight against mosquito-transmitted diseases. This review will focus on Toxorhynchites, a non-hematophagous mosquito genus which is a natural predator of vector species and may be exploited as a biological control agent. Their effectiveness in this role has been strongly debated for many years and early trials have been marred by misinformation and incomplete descriptions. Here, we draw together current knowledge of the general biology of Toxorhynchites and discuss how this updated information will benefit their role in an integrated vector management program.
Effects of Lethal Bronzing Disease, Palm Height, and Temperature on Abundance and Monitoring of Haplaxius crudus
Authors: Mou De-Fen , Lee Chih-Chung , Hahn Philip G. , Soto Noemi , Humphries Alessandra R. , Helmick Ericka E. , Bahder Brian W.
Published: October 2020

Insect vector feeding preference and behavior play important roles in pathogen transmission, especially for pathogens that solely rely on insect vector transmission. This study aims to examine the effects of the 16SrIV-D phytoplasma, the causal agent of lethal bronzing (LB) disease of palms, on associated auchenorrhynchan insects. The numbers of auchenorrhynchans collected during weekly surveys during a yearlong study using yellow sticky traps were analyzed. The cumulative number of H. crudus was 4.5 times greater on phytoplasma-infected relative to non-infected palms. Other auchenorrhynchans showed no difference between phytoplasma-infected and non-infected palms or were greater on non-infected rather than on infected palms. Furthermore, we examined the effects of LB, palm height, temperature, and the interactive effects of these factors on H. crudus abundance. When the palms were infected with LB, at low temperature, H. crudus was more abundant on shorter than taller palms; however, H. crudus was more abundant on taller than shorter palms at the median and higher temperatures. These results may indicate that H. crudus prefers LB-infected palms over non-infected palms. The interactive effects of LB, palm heights, and temperature further suggest that vector monitoring and disease management should be optimized according to seasonal variation in temperature.
Self- and Parent-Reported Psychological Symptoms in Young Cancer Survivors and Control Peers: Results from a Clinical Center
Authors: Barone Rita , Gulisano Mariangela , Cannata Emanuela , Padalino Sara , Saia Federica , Maugeri Nicoletta , Pettinato Fabio , Lo Nigro Luca , Casabona Antonino , Russo Giovanna , Di Cataldo Andrea , Rizzo Renata
Published: October 2020

Pediatric cancer survivors are at increased risk for psychological distress. We sought to understand the severity and symptoms’ co-occurrence among pediatric survivors compared to controls by rating both self- and parent-reported symptomatology. Forty survivors (22 males; mean age at study time: 12.9 years) participated in the study. Most survivors (85%) had a diagnosis of acute lymphoblastic leukemia. Seventy-nine healthy controls with the same age and gender distribution as the patients were included. A standardized assessment of psychological functioning was conducted by self- and parent-reported symptoms evaluations. The self-reported anxious symptom severity was significantly higher in survivors. A significantly higher proportion of survivors compared to controls had clinically significant anxiety, depression, and combined anxiety symptoms (i.e., social anxiety, separation anxiety, or physical symptoms). In both study groups, the self-reported emotional and somatic symptoms were significantly associated. The multi-informant assessments of the psychological symptoms revealed distinct associations between the child- and parent-reported symptoms in the survivors’ group: the survivors’ self-reports of depressive symptoms, somatic symptoms, and functional impairment were significantly correlated with the parent reports of child behavioral concerns, somatic complaints, and functional impairment, respectively. Conclusion: Self-reported symptoms showed similar comorbidity profiles in survivors and control peers. The multi-informant assessments detected differences in the association of self- and parent-reported symptoms between the survivor and control groups. The present study showed that multi-informant assessment is critical to understanding symptom profiles and to informing intervention with particular regard to parental participation and support.
In Vivo Quantification of Myocardial Amyloid Deposits in Patients with Suspected Transthyretin-Related Amyloidosis (ATTR)
Authors: Wollenweber Tim , Rettl Rene , Kretschmer-Chott Elisabeth , Rasul Sazan , Kulterer Oana , Rainer Eva , Raidl Markus , Schaffarich Michael P. , Matschitsch Sabrina , Stadler Michael , Traub-Weidinger Tatjana , Beiztke Dietrich , Loewe Christian , Duca Franz , Mascherbauer Julia , Bonderman Diana , Hacker Marcus
Published: October 2020

Background: Current diagnosis of Transthyretin-related Amyloidosis (ATTR) using bone scintigraphy is primarily based on visual scoring and semi-quantitative indices. With the introduction of new potential life-prolonging drugs for ATTR, a more precise quantification of myocardial amyloid burden is desirable for improved response prediction and therapy monitoring. Methods: At first, quantification experiments using an anthropomorphic thorax phantom were performed. Second, 32 patients underwent both planar whole body [99mTc]- 3,3-Diphosphono-1,2-Propanodicarboxylic Acid (DPD)-scintigraphy and quantitative Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) of the thorax. SPECT/CT standardized myocardial uptake values SUVpeak and SUVpeak normalized to bone uptake (nSUVpeak) were determined. Results: Phantom measurements showed a strong linear relationship between the activity in the myocardial insert and the measured activity (r = 0.9998, p = 0.01), but the measured activity was systematically underestimated by approximately 30%. Receiver operating characteristics (ROC) analysis revealed a 100% sensitivity and specificity at a cut-off of 3.1 for SUVpeak for the differentiation of both patient groups. Conclusion: SUV quantification of ATTR amyloid burden is feasible using novel SPECT/CT technology. With a SUVpeak cut-off of 3.1, patients with Perugini grade 2 and 3 could be clearly separated from those with Perugini grade 0 and 1. Besides ATTR diagnostics, quantification of amyloid deposits could potentially be used for therapy monitoring and prognostication in patients with cardiac ATTR.
Reply to Comment on Nogueira, P.J., et al. “The Role of Health Preconditions on COVID-19 Deaths in Portugal: Evidence from Surveillance Data of the First 20293 Infection Cases”. J. Clin. Med. 2020, 9, 2368
Authors: Nogueira Paulo Jorge , de Araújo Nobre Miguel , Costa Andreia , Ribeiro Ruy M. , Furtado Cristina , Bacelar Nicolau Leonor , Camarinha Catarina , Luís Márcia , Abrantes Ricardo , Carneiro António Vaz
Published: October 2020

We thank Costa-Santos C [...]
The Oral Glucose Tolerance Test—Is It Time for a Change?—A Literature Review with an Emphasis on Pregnancy
Authors: Bogdanet Delia , O’Shea Paula , Lyons Claire , Shafat Amir , Dunne Fidelma
Published: October 2020

Globally, gestational diabetes (GDM) is increasing at an alarming rate. This increase is linked to the rise in obesity rates among women of reproductive age. GDM poses a major global health problem due to the related micro- and macro-vascular complications of subsequent Type 2 diabetes and the impact on the future health of generations through the long-term impact of GDM on both mothers and their infants. Therefore, correctly identifying subjects as having GDM is of utmost importance. The oral glucose tolerance test (OGTT) has been the mainstay for diagnosing gestational diabetes for decades. However, this test is deeply flawed. In this review, we explore a history of the OGTT, its reproducibility and the many factors that can impact its results with an emphasis on pregnancy.
Comprehensive Gene Analysis of IgG4-Related Ophthalmic Disease Using RNA Sequencing
Authors: Asakage Masaki , Usui Yoshihiko , Nezu Naoya , Shimizu Hiroyuki , Tsubota Kinya , Umazume Kazuhiko , Yamakawa Naoyuki , Umezu Tomohiro , Suwanai Hirotsugu , Kuroda Masahiko , Goto Hiroshi
Published: October 2020

High-throughput RNA sequencing (RNA-seq) uses massive parallel sequencing technology, allowing the unbiased analysis of genome-wide transcription levels and tumor mutation status. Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) is a fibroinflammatory disease characterized by the enlargement of the ocular adnexal tissues. We analyzed RNA expression levels via RNA-seq in the biopsy specimens of three patients diagnosed with IgG4-ROD. Mucosa-associated lymphoid tissue (MALT) lymphoma, reactive lymphoid hyperplasia (RLH), normal lacrimal gland tissue, and adjacent adipose tissue were used as the controls (n = 3 each). RNA-seq was performed using the NextSeq 500 system, and genes with |fold change| ≥ 2 and p < 0.05 relative to the controls were defined as differentially expressed genes (DEGs) in IgG4-ROD. To validate the results of RNA-seq, real-time polymerase chain reaction (PCR) was performed in 30 IgG4-ROD and 30 orbital MALT lymphoma tissue samples. RNA-seq identified 35 up-regulated genes, including matrix metallopeptidase 12 (MMP12) and secreted phosphoprotein 1 (SPP1), in IgG4-ROD tissues when compared to all the controls. Many pathways related to the immune system were included when compared to all the controls. Expressions of MMP12 and SPP1 in IgG4-ROD tissues were confirmed by real-time PCR and immunohistochemistry. In conclusion, we identified novel DEGs, including those associated with extracellular matrix degradation, fibrosis, and inflammation, in IgG4-ROD biopsy specimens. These data provide new insights into molecular pathogenetic mechanisms and may contribute to the development of new biomarkers for diagnosis and molecular targeted drugs.
Anatomical Considerations for Endovascular Intervention for Extracranial Carotid Disease: A Review of the Literature and Recommended Guidelines
Authors: Scullen Tyler , Mathkour Mansour , Carr Christopher , Wang Arthur , Amenta Peter S. , Nerva John D. , Dumont Aaron S.
Published: October 2020

Patient selection for endovascular intervention in extracranial carotid disease is centered on vascular anatomy. We review anatomical considerations for non-traumatic disease and offer guidelines in patient selection and management. We conducted a systematic literature review without meta-analysis for studies involving anatomical considerations in extracranial carotid intervention for non-traumatic disease. Anatomical considerations discussed included aortic arch variants, degree of vessel stenosis, angulation, tortuosity, and anomalous origins, and atheromatous plaque morphology, composition, and location. Available literature suggests that anatomical risks of morbidity are largely secondary to increased procedural times and difficulties in intervention system delivery. We recommend the prioritization of endovascular techniques on an individual basis in cases where accessible systems and surgeon familiarity provide an acceptable likelihood of rapid access and device deployment.
The Relationship between Suicide and Oxidative Stress in a Group of Psychiatric Inpatients
Authors: Koweszko Tytus , Gierus Jacek , Zalewska Anna , Maciejczyk Mateusz , Waszkiewicz Napoleon , Szulc Agata
Published: October 2020

Diagnosis of suicide risk is a clinical challenge requiring an interdisciplinary therapeutic approach. Except for psychological explanation of the suicidal mechanism, there is evidence that it is associated with brain chemistry disturbances as oxidative stress. The objective of this study was to explore the role of oxidative stress components in suicidality comparing subjects at different stages of suicide. The study included psychiatric inpatients aged 18–64 (n = 48) with different psychiatric diagnoses. Blood specimens were collected from subjects and tested for oxidative stress biomarkers: superoxide dismutase (SOD), dityrozine (DT), oxidative stress index (OSI), glutathione peroxidase (GPx), total antioxidant capacity (TAC trolox), ferric reducing ability of plasma (FRAP), total oxidant status (TOS), catalase (CAT), advanced glycoxidation end products (AGE), NADPH oxidase (NOX), and advanced oxidation protein products (AOPP). The Columbia Severity Suicide Scale (C-SSRS) was used for suicidality assessment. Subjects with a history of suicide ideations over the last three months had significantly higher levels of NOX, AOPP, and OSI. There was no significant relationship to any oxidative stress component levels either with a history of suicide behaviors or with suicide attempts over the last three months. The levels of NOX and AOPP were both positively correlated to the intensity of suicidal thoughts. Moreover, there was a positive correlation between a number of suicide attempts during a lifetime with AGE and DT and negative with CAT. Similarly, the subjects with a history of suicide attempts had significantly higher AGE and DT levels and lower CAT values. The study confirmed that oxidative stress plays an important role in the pathophysiology of suicide and specific oxidative stress measures vary in suicidal and non-suicidal psychiatric inpatients.
Impact of Timely Public Health Measures on Kidney Transplantation in Austria during the SARS-CoV-2 Outbreak—A Nationwide Analysis
Authors: Watschinger Bruno , Watschinger Clara , Reindl-Schwaighofer Roman , Meyer Elias L. , Deak Andras T. , Hammer Tamara , Eigner Manfred , Sprenger-Mähr Hannelore , Schneeberger Stefan , Cejka Daniel , Mayer Gert , Oberbauer Rainer , Rosenkranz Alexander R. , Kerschbaum Julia
Published: October 2020

SARS-CoV-2 led to considerable morbidity/mortality worldwide and tremendously impacted on daily life. Strict lockdown measures were implemented early to contain the viral outbreak in Austria. Massive changes in organizational structures of healthcare facilities followed with unclear implications on the care of non-COVID-19-affected patients. We studied the nationwide impact of COVID-19 on kidney transplantation in Austria during the first six months of 2020. Concurrent with general lockdown measures, all kidney transplant activity was suspended from 13 March to 9 April. Nevertheless, between January and June, total transplant (p = 0.48) and procured donor organ numbers (p = 0.6) did not differ significantly from earlier years. Ten (0.18%) of 5512 prevalent Austrian kidney transplant recipients were diagnosed with SARS-CoV-2. The case fatality rate (one death; 10%) in renal transplant patients was less than in other countries but higher than in Austria’s general population (2.4%). We conclude that early and strict general lockdown measures imposed by the government allowed an early, however cautious, re-opening of Austrian transplant programs and played a crucial role for the favorable outcomes of SARS-CoV-2 in Austrian kidney transplant patients. Even though it may be uncertain whether similar results may be obtainable in other countries, the findings may support early intervention strategies during similar episodes in the future.
Multicenter Study of Intense Pulsed Light for Patients with Refractory Aqueous-Deficient Dry Eye Accompanied by Mild Meibomian Gland Dysfunction
Authors: Arita Reiko , Fukuoka Shima , Mizoguchi Takanori , Morishige Naoyuki
Published: October 2020

Aqueous-deficient dry eye (ADDE) and meibomian gland dysfunction (MGD) can be refractory to therapy. Intense pulsed light (IPL) was recently introduced as an effective treatment for MGD. We here evaluated the efficacy of IPL combined with MG expression (MGX) compared with MGX alone (n = 23 and 20, respectively) for patients with refractory ADDE with mild MGD at three sites. Symptom score, visual acuity (VA), noninvasive breakup time (NIBUT) and lipid layer thickness (LLT) of the tear film, lid margin abnormalities, fluorescein BUT (FBUT), fluorescein staining, tear meniscus height (TMH), meibum grade, meiboscore, and Schirmer’s test value were assessed at baseline and 1 and 3 months after treatment. LLT, plugging, vascularity, FBUT and NIBUT were improved only in the IPL-MGX group at three months compared with baseline. All parameters with the exception of VA, meiboscore, TMH, Schirmer’s test value were also improved in the IPL-MGX group compared with the control group at three months, as was VA in patients with central corneal epitheliopathy. Although IPL-MGX does not affect aqueous layer, the induced improvement in quality and quantity of the lipid layer may increase tear film stability and ameliorate symptoms not only for evaporative dry eye but for ADDE.
Comparison of the Effects of Sugammadex, Neostigmine, and Pyridostigmine on Postoperative Nausea and Vomiting: A Propensity Matched Study of Five Hospitals
Authors: Kim Jong Ho , Lim Man-Sup , Choi Jun Woo , Kim Haewon , Kwon Young-Suk , Lee Jae Jun
Published: October 2020

Thus far, few studies have compared the effects of sugammadex and cholinesterase inhibitors on postoperative nausea and vomiting (PONV), and the results have been controversial. Here, we compared the effects of sugammadex, neostigmine, and pyridostigmine on PONV by means of a five hospital analysis with propensity score matching. We analyzed adults aged ≥ 18 years who underwent general anesthesia between January 2014 and December 2019. Following propensity score matching, 7793 patients were included in each of the neostigmine and sugammadex matched patient groups (absolute standardized difference (ASD), 0.01–0.07), and 10,197 patients were included in each of the pyridostigmine and sugammadex matched patient groups (ASD, 0.01–0.02), while 19,377 patients were included in each of the pyridostigmine and neostigmine matched patient groups. (ASD, 0.01–0.19). The odds of PONV were low in the sugammadex group (odds ratio, 0.65; 95% confidence interval, 0.59–0.72; p < 0.0001) and pyridostigmine group (odds ratio, 0.22; 95% confidence interval, 0.20–0.24; p < 0.0001) compared to the neostigmine group, while there was no difference between sugammadex and pyridostigmine (odds ratio, 0.95; 95% confidence interval, 0.86–1.04; p = 0.281). Therefore, sugammadex and pyridostigmine may lower the incidence of PONV compared to neostigmine in patients undergoing general anesthesia.