bluuebunny/crossref_metadata_2025 huggingface dataset:
Currently Applied Molecular Assays for Identifying ESR1 Mutations in Patients with Advanced Breast Cancer
Authors: Lee Nuri , Park Min-Jeong , Song Wonkeun , Jeon Kibum , Jeong Seri
Published: November 2020

Approximately 70% of breast cancers, the leading cause of cancer-related mortality worldwide, are positive for the estrogen receptor (ER). Treatment of patients with luminal subtypes is mainly based on endocrine therapy. However, ER positivity is reduced and ESR1 mutations play an important role in resistance to endocrine therapy, leading to advanced breast cancer. Various methodologies for the detection of ESR1 mutations have been developed, and the most commonly used method is next-generation sequencing (NGS)-based assays (50.0%) followed by droplet digital PCR (ddPCR) (45.5%). Regarding the sample type, tissue (50.0%) was more frequently used than plasma (27.3%). However, plasma (46.2%) became the most used method in 2016–2019, in contrast to 2012–2015 (22.2%). In 2016–2019, ddPCR (61.5%), rather than NGS (30.8%), became a more popular method than it was in 2012–2015. The easy accessibility, non-invasiveness, and demonstrated usefulness with high sensitivity of ddPCR using plasma have changed the trends. When using these assays, there should be a comprehensive understanding of the principles, advantages, vulnerability, and precautions for interpretation. In the future, advanced NGS platforms and modified ddPCR will benefit patients by facilitating treatment decisions efficiently based on information regarding ESR1 mutations.
Repositioned Drugs for Chagas Disease Unveiled via Structure-Based Drug Repositioning
Authors: Adasme Melissa F. , Bolz Sarah Naomi , Adelmann Lauren , Salentin Sebastian , Haupt V. Joachim , Moreno-Rodríguez Adriana , Nogueda-Torres Benjamín , Castillo-Campos Verónica , Yepez-Mulia Lilián , De Fuentes-Vicente José A. , Rivera Gildardo , Schroeder Michael
Published: November 2020

Chagas disease, caused by the parasite Trypanosoma cruzi, affects millions of people in South America. The current treatments are limited, have severe side effects, and are only partially effective. Drug repositioning, defined as finding new indications for already approved drugs, has the potential to provide new therapeutic options for Chagas. In this work, we conducted a structure-based drug repositioning approach with over 130,000 3D protein structures to identify drugs that bind therapeutic Chagas targets and thus represent potential new Chagas treatments. The screening yielded over 500 molecules as hits, out of which 38 drugs were prioritized following a rigorous filtering process. About half of the latter were already known to have trypanocidal activity, while the others are novel to Chagas disease. Three of the new drug candidates—ciprofloxacin, naproxen, and folic acid—showed a growth inhibitory activity in the micromolar range when tested ex vivo on T. cruzi trypomastigotes, validating the prediction. We show that our drug repositioning approach is able to pinpoint relevant drug candidates at a fraction of the time and cost of a conventional screening. Furthermore, our results demonstrate the power and potential of structure-based drug repositioning in the context of neglected tropical diseases where the pharmaceutical industry has little financial interest in the development of new drugs.
Generation of an Oncolytic Herpes Simplex Viral Vector Completely Retargeted to the GDNF Receptor GFRα1 for Specific Infection of Breast Cancer Cells
Authors: Hall Bonnie L. , Leronni Daniela , Miyagawa Yoshitaka , Goins William F. , Glorioso Joseph C. , Cohen Justus B.
Published: November 2020

Oncolytic herpes simplex viruses (oHSV) are under development for the treatment of a variety of human cancers, including breast cancer, a leading cause of cancer mortality among women worldwide. Here we report the design of a fully retargeted oHSV for preferential infection of breast cancer cells through virus recognition of GFRα1, the cellular receptor for glial cell-derived neurotrophic factor (GDNF). GFRα1 displays a limited expression profile in normal adult tissue, but is upregulated in a subset of breast cancers. We generated a recombinant HSV expressing a completely retargeted glycoprotein D (gD), the viral attachment/entry protein, that incorporates pre-pro-GDNF in place of the signal peptide and HVEM binding domain of gD and contains a deletion of amino acid 38 to eliminate nectin-1 binding. We show that GFRα1 is necessary and sufficient for infection by the purified recombinant virus. Moreover, this virus enters and spreads in GFRα1-positive breast cancer cells in vitro and caused tumor regression upon intratumoral injection in vivo. Given the heterogeneity observed between and within individual breast cancers at the molecular level, these results expand our ability to deliver oHSV to specific tumors and suggest opportunities to enhance drug or viral treatments aimed at other receptors.
Pro-Resolving Lipid Mediator Resolvin E1 Mitigates the Progress of Diethylnitrosamine-Induced Liver Fibrosis in Sprague-Dawley Rats by Attenuating Fibrogenesis and Restricting Proliferation
Authors: Rodríguez Maria José , Herrera Francisca , Donoso Wendy , Castillo Iván , Orrego Roxana , González Daniel R. , Zúñiga-Hernández Jessica
Published: November 2020

Liver fibrosis is a complex process associated to most types of chronic liver disease, which is characterized by a disturbance of hepatic tissue architecture and the excessive accumulation of extracellular matrix. Resolvin E1 (RvE1) is a representative member of the eicosapentaenoic omega-3 lipid derivatives, and is a drug candidate of the growing family of endogenous resolvins. Considering the aforementioned, the main objective of this study was to analyze the hepatoprotective effect of RvE1 in a rat model of liver fibrosis. Male Sprague-Dawley rats received diethylnitrosamine (DEN, 70 mg/mg body weight intraperitoneally (i.p)) as an inductor of liver fibrosis once weekly and RvE1(100 ng/body weight i.p) twice weekly for four weeks. RvE1 suppressed the alterations induced by DEN, normalizing the levels of alanine aminotransferase (ALT), albumin, and lactate dehydrogenase (LDH), and ameliorated DEN injury by decreasing the architecture distortion, inflammatory infiltration, necrotic areas, and microsteatosis. RvE1 also limited DEN-induced proliferation through a decrease in Ki67-positive cells and cyclin D1 protein expression, which is related to an increase of the levels of cleaved caspase-3. Interestingly, we found that RvE1 promotes higher nuclear translocation of nuclear factor κB (NF-κB)p65 than DEN. RvE1 also increased the levels of nuclear the nuclear factor erythroid 2–related factor 2 (Nrf2), but with no antioxidant effect, measured as an increase in glutathione disulfide (GSSG) and a decrease in the ratio of glutathione (GSH)/GSSG. Taken together, these results suggest that RvE1 modulates the fibrogenesis, steatosis, and cell proliferation in a model of DEN induced fibrosis.
Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs)
Authors: Luo Yuxiang , Li Huilin
Published: November 2020

Class I histone deacetylases (HDACs) are promising targets for epigenetic therapies for a range of diseases such as cancers, inflammations, infections and neurological diseases. Although six HDAC inhibitors are now licensed for clinical treatments, they are all pan-inhibitors with little or no HDAC isoform selectivity, exhibiting undesirable side effects. A major issue with the currently available HDAC inhibitors is that they have limited specificity and target multiple deacetylases. Except for HDAC8, Class I HDACs (1, 2 and 3) are recruited to large multiprotein complexes to function. Therefore, there are rising needs to develop new, hopefully, therapeutically efficacious HDAC inhibitors with isoform or complex selectivity. Here, upon the introduction of the structures of Class I HDACs and their complexes, we provide an up-to-date overview of the structure-based discovery of Class I HDAC inhibitors, including pan-, isoform-selective and complex-specific inhibitors, aiming to provide an insight into the discovery of additional HDAC inhibitors with greater selectivity, specificity and therapeutic utility.
Flow Cytometry: From Experimental Design to Its Application in the Diagnosis and Monitoring of Respiratory Diseases
Authors: Flores-Gonzalez Julio , Cancino-Díaz Juan Carlos , Chavez-Galan Leslie
Published: November 2020

Recent advances in the field of flow cytometry (FCM) have highlighted the importance of incorporating it as a basic analysis tool in laboratories. FCM not only allows the identification of cell subpopulations by detecting the expression of molecules in the cell membrane or cytoplasm, but it can also quantify and identify soluble molecules. The proper functioning of the FCM requires six fundamental systems, from those related to the transport of events to the systems dedicated to the analysis of information. In this review, we have identified the main considerations that every FCM user must know for an optimal antibody panel design, the quality systems that must govern the FCM protocols to guarantee reproducible results in research or clinical laboratories. Finally, we have introduced the current evidence that highlights the relevance of FCM in the investigation and clinical diagnosis of respiratory diseases, establishing important advances in the basic and clinical study of diseases as old as Tuberculosis along with the recent proposals for the monitoring and classification of patients infected with the new SARS-CoV2 virus.
Phytochemical Molecules from the Decarboxylation of Gomphrenins in Violet Gomphrena globosa L.—Floral Infusions from Functional Food
Authors: Drobnicka Natalia , Sutor Katarzyna , Kumorkiewicz-Jamro Agnieszka , Spórna-Kucab Aneta , Antonik Michał , Dziedzic Ewa , Świergosz Tomasz , Ortyl Joanna , Wybraniec Sławomir
Published: November 2020

Herein, the generation of decarboxylated derivatives of gomphrenin pigments exhibiting potential health-promoting properties and the kinetics of their extraction during tea brewing from the purple flowers of Gomphrena globosa L. in aqueous and aqueous citric acid solutions were investigated. Time-dependent concentration monitoring of natural gomphrenins and their tentative identification was carried out by LC-DAD-ESI-MS/MS. The high content of acylated gomphrenins and their principal decarboxylation products, 2-, 15-, 17-decarboxy-gomphrenins, along with minor levels of their bidecarboxylated derivatives, were reported in the infusions. The identification was supported by the determination of molecular formulas of the extracted pigments by liquid chromatography coupled with high-resolution mass spectrometry (LCMS-IT-TOF). The influence of plant matrix on gomphrenins’ stability and generation of their derivatives, including the extraction kinetics, was determined by studying the concentration profiles in the primary and diluted infusions. Isolated and purified acylated gomphrenins from the same plant material were used for the preliminary determination of their decarboxylated derivatives. The acylated gomphrenins were found to be more stable than nonacylated ones. Citric acid addition had a degradative influence on natural gomphrenins mainly during the longer tea brewing process (above 15 min); however, the presence of plant matrix significantly increased the stability for betacyanins’ identification.
Recent Advances in Zinc Oxide Nanostructures with Antimicrobial Activities
Authors: Li Yuchao , Liao Chengzhu , Tjong Sie Chin
Published: November 2020

This article reviews the recent developments in the synthesis, antibacterial activity, and visible-light photocatalytic bacterial inactivation of nano-zinc oxide. Polycrystalline wurtzite ZnO nanostructures with a hexagonal lattice having different shapes can be synthesized by means of vapor-, liquid-, and solid-phase processing techniques. Among these, ZnO hierarchical nanostructures prepared from the liquid phase route are commonly used for antimicrobial activity. In particular, plant extract-mediated biosynthesis is a single step process for preparing nano-ZnO without using surfactants and toxic chemicals. The phytochemical molecules of natural plant extracts are attractive agents for reducing and stabilizing zinc ions of zinc salt precursors to form green ZnO nanostructures. The peel extracts of certain citrus fruits like grapefruits, lemons and oranges, acting as excellent chelating agents for zinc ions. Furthermore, phytochemicals of the plant extracts capped on ZnO nanomaterials are very effective for killing various bacterial strains, leading to low minimum inhibitory concentration (MIC) values. Bioactive phytocompounds from green ZnO also inhibit hemolysis of Staphylococcus aureus infected red blood cells and inflammatory activity of mammalian immune system. In general, three mechanisms have been adopted to explain bactericidal activity of ZnO nanomaterials, including direct contact killing, reactive oxygen species (ROS) production, and released zinc ion inactivation. These toxic effects lead to the destruction of bacterial membrane, denaturation of enzyme, inhibition of cellular respiration and deoxyribonucleic acid replication, causing leakage of the cytoplasmic content and eventual cell death. Meanwhile, antimicrobial activity of doped and modified ZnO nanomaterials under visible light can be attributed to photogeneration of ROS on their surfaces. Thus particular attention is paid to the design and synthesis of visible light-activated ZnO photocatalysts with antibacterial properties
Notch Signaling Regulation in Autoinflammatory Diseases
Authors: Gratton Rossella , Tricarico Paola Maura , d'Adamo Adamo Pio , Bianco Anna Monica , Moura Ronald , Agrelli Almerinda , Brandão Lucas , Zupin Luisa , Crovella Sergio
Published: November 2020

Notch pathway is a highly conserved intracellular signaling route that modulates a vast variety of cellular processes including proliferation, differentiation, migration, cell fate and death. Recently, the presence of a strict crosstalk between Notch signaling and inflammation has been described, although the precise molecular mechanisms underlying this interplay have not yet been fully unravelled. Disruptions in Notch cascade, due both to direct mutations and/or to an altered regulation in the core components of Notch signaling, might lead to hypo- or hyperactivation of Notch target genes and signaling molecules, ultimately contributing to the onset of autoinflammatory diseases. To date, alterations in Notch signaling have been reported as associated with three autoinflammatory disorders, therefore, suggesting a possible role of Notch in the pathogenesis of the following diseases: hidradenitis suppurativa (HS), Behçet disease (BD), and giant cell arteritis (GCA). In this review, we aim at better characterizing the interplay between Notch and autoinflammatory diseases, trying to identify the role of this signaling route in the context of these disorders.
LncRNAs in Ovarian Cancer Progression, Metastasis, and Main Pathways: ceRNA and Alternative Mechanisms
Authors: Braga Eleonora A. , Fridman Marina V. , Moscovtsev Alexey A. , Filippova Elena A. , Dmitriev Alexey A. , Kushlinskii Nikolay E.
Published: November 2020

Ovarian cancer (OvCa) develops asymptomatically until it reaches the advanced stages with metastasis, chemoresistance, and poor prognosis. Our review focuses on the analysis of regulatory long non-coding RNAs (lncRNAs) competing with protein-coding mRNAs for binding to miRNAs according to the model of competitive endogenous RNA (ceRNA) in OvCa. Analysis of publications showed that most lncRNAs acting as ceRNAs participate in OvCa progression: migration, invasion, epithelial-mesenchymal transition (EMT), and metastasis. More than 30 lncRNAs turned out to be predictors of survival and/or response to therapy in patients with OvCa. For a number of oncogenic (CCAT1, HOTAIR, NEAT1, and TUG1 among others) and some suppressive lncRNAs, several lncRNA/miRNA/mRNA axes were identified, which revealed various functions for each of them. Our review also considers examples of alternative mechanisms of actions for lncRNAs besides being ceRNAs, including binding directly to mRNA or protein, and some of them (DANCR, GAS5, MALAT1, and UCA1 among others) act by both mechanisms depending on the target protein. A systematic analysis based on the data from literature and Panther or KEGG (Kyoto Encyclopedia of Genes and Genomes) databases showed that a significant part of lncRNAs affects the key pathways involved in OvCa metastasis, EMT, and chemoresistance.
Site-Specific Phosphorylation of Histone H1.4 Is Associated with Transcription Activation
Authors: Saha Ankita , Seward Christopher H. , Stubbs Lisa , Mizzen Craig A.
Published: November 2020

Core histone variants, such as H2A.X and H3.3, serve specialized roles in chromatin processes that depend on the genomic distributions and amino acid sequence differences of the variant proteins. Modifications of these variants alter interactions with other chromatin components and thus the protein’s functions. These inferences add to the growing arsenal of evidence against the older generic view of those linker histones as redundant repressors. Furthermore, certain modifications of specific H1 variants can confer distinct roles. On the one hand, it has been reported that the phosphorylation of H1 results in its release from chromatin and the subsequent transcription of HIV-1 genes. On the other hand, recent evidence indicates that phosphorylated H1 may in fact be associated with active promoters. This conflict suggests that different H1 isoforms and modified versions of these variants are not redundant when together but may play distinct functional roles. Here, we provide the first genome-wide evidence that when phosphorylated, the H1.4 variant remains associated with active promoters and may even play a role in transcription activation. Using novel, highly specific antibodies, we generated the first genome-wide view of the H1.4 isoform phosphorylated at serine 187 (pS187-H1.4) in estradiol-inducible MCF7 cells. We observe that pS187-H1.4 is enriched primarily at the transcription start sites (TSSs) of genes activated by estradiol treatment and depleted from those that are repressed. We also show that pS187-H1.4 associates with ‘early estrogen response’ genes and stably interacts with RNAPII. Based on the observations presented here, we propose that phosphorylation at S187 by CDK9 represents an early event required for gene activation. This event may also be involved in the release of promoter-proximal polymerases to begin elongation by interacting directly with the polymerase or other parts of the transcription machinery. Although we focused on estrogen-responsive genes, taking into account previous evidence of H1.4′s enrichment of promoters of pluripotency genes, and its involvement with rDNA activation, we propose that H1.4 phosphorylation for gene activation may be a more global observation.
GLP-2 Prevents Neuronal and Glial Changes in the Distal Colon of Mice Chronically Treated with Cisplatin
Authors: Nardini Patrizia , Pini Alessandro , Bessard Anne , Duchalais Emilie , Niccolai Elena , Neunlist Michel , Vannucchi Maria Giuliana
Published: November 2020

Cisplatin is a chemotherapeutic agent widely used for the treatment of solid cancers. Its administration is commonly associated with acute and chronic gastrointestinal dysfunctions, likely related to mucosal and enteric nervous system (ENS) injuries, respectively. Glucagon-like peptide-2 (GLP-2) is a pleiotropic hormone exerting trophic/reparative activities on the intestine, via antiapoptotic and pro-proliferating pathways, to guarantee mucosal integrity, energy absorption and motility. Further, it possesses anti-inflammatory properties. Presently, cisplatin acute and chronic damages and GLP-2 protective effects were investigated in the mouse distal colon using histological, immunohistochemical and biochemical techniques. The mice received cisplatin and the degradation-resistant GLP-2 analog ([Gly2]GLP-2) for 4 weeks. Cisplatin-treated mice showed mucosal damage, inflammation, IL-1β and IL-10 increase; decreased number of total neurons, ChAT- and nNOS-immunoreactive (IR) neurons; loss of SOX-10-IR cells and reduced expression of GFAP- and S100β-glial markers in the myenteric plexus. [Gly2]GLP-2 co-treatment partially prevented mucosal damage and counteracted the increase in cytokines and the loss of nNOS-IR and SOX-10-IR cells but not that of ChAT-IR neurons. Our data demonstrate that cisplatin causes mucosal injuries, neuropathy and gliopathy and that [Gly2]GLP-2 prevents these injuries, partially reducing mucosal inflammation and inducing ENS remodeling. Hence, this analog could represent an effective strategy to overcome colonic injures induced by cisplatin.
5′ Untranslated Region Elements Show High Abundance and Great Variability in Homologous ABCA Subfamily Genes
Authors: Dvorak Pavel , Hlavac Viktor , Soucek Pavel
Published: November 2020

The 12 members of the ABCA subfamily in humans are known for their ability to transport cholesterol and its derivatives, vitamins, and xenobiotics across biomembranes. Several ABCA genes are causatively linked to inborn diseases, and the role in cancer progression and metastasis is studied intensively. The regulation of translation initiation is implicated as the major mechanism in the processes of post-transcriptional modifications determining final protein levels. In the current bioinformatics study, we mapped the features of the 5′ untranslated regions (5′UTR) known to have the potential to regulate translation, such as the length of 5′UTRs, upstream ATG codons, upstream open-reading frames, introns, RNA G-quadruplex-forming sequences, stem loops, and Kozak consensus motifs, in the DNA sequences of all members of the subfamily. Subsequently, the conservation of the features, correlations among them, ribosome profiling data as well as protein levels in normal human tissues were examined. The 5′UTRs of ABCA genes contain above-average numbers of upstream ATGs, open-reading frames and introns, as well as conserved ones, and these elements probably play important biological roles in this subfamily, unlike RG4s. Although we found significant correlations among the features, we did not find any correlation between the numbers of 5′UTR features and protein tissue distribution and expression scores. We showed the existence of single nucleotide variants in relation to the 5′UTR features experimentally in a cohort of 105 breast cancer patients. 5′UTR features presumably prepare a complex playground, in which the other elements such as RNA binding proteins and non-coding RNAs play the major role in the fine-tuning of protein expression.
Humanities: The Outlier of Research Assessments
Authors: Doğan Güleda , Taşkın Zehra
Published: November 2020

Commercial bibliometric databases, and the quantitative indicators presented by them, are widely used for research assessment purposes, which is not fair for the humanities. The humanities are different from all other areas by nature in many aspects. This study aimed to show the extent of the difference in terms of five size-independent bibliometric indicators, based on citations and collaborations. We used categorical InCites data (1980–2020) to compare six main Organisation for Economic Co-operation and Development (OECD) subject areas, and the 45,987 sources of humanities, to make a comparison for subareas of the humanities. Results showed that the humanities are statistically different from all other areas, including social sciences, with high effect sizes in terms of the five indicators taken into consideration. Besides that, all the subareas of the humanities differ from each other. This main finding indicates that the humanities do not need new indicators for quantitative evaluation, but different approaches for assessment, such as bottom-up approaches.
Transcriptomics-Based Approach Identifies Spinosad-Associated Targets in the Colorado Potato Beetle, Leptinotarsa decemlineata
Authors: Bastarache Pierre , Wajnberg Gabriel , Dumas Pascal , Chacko Simi , Lacroix Jacynthe , Crapoulet Nicolas , Moffat Chandra E. , Morin Pier
Published: November 2020

The Colorado potato beetle Leptinotarsa decemlineata is an insect pest that threatens potato crops globally. The primary method to control its damage on potato plants is the use of insecticides, including imidacloprid, chlorantraniliprole and spinosad. However, insecticide resistance has been frequently observed in Colorado potato beetles. The molecular targets and the basis of resistance to imidacloprid and chlorantraniliprole have both been previously quantified. This work was undertaken with the overarching goal of better characterizing the molecular changes associated with spinosad exposure in this insect pest. Next-generation sequencing was conducted to identify transcripts that were differentially expressed between Colorado potato beetles exposed to spinosad versus control insects. Results showed several transcripts that exhibit different expression levels between the two conditions, including ones coding for venom carboxylesterase-6, chitinase 10, juvenile hormone esterase and multidrug resistance-associated protein 4. In addition, several microRNAs, such as miR-12-3p and miR-750-3p, were also modulated in the investigated conditions. Overall, this work reveals a molecular footprint underlying spinosad response in Colorado potato beetles and provides novel leads that could be targeted as part of RNAi-based approaches to control this insect pest.
Hidden Host Mortality from an Introduced Parasitoid: Conventional and Molecular Evaluation of Non-Target Risk
Authors: Hepler James R. , Athey Kacie , Enicks David , Abram Paul K. , Gariepy Tara D. , Talamas Elijah J. , Beers Elizabeth
Published: November 2020

Hidden trophic interactions are important in understanding food web ecology and evaluating the ecological risks and benefits associated with the introduction of exotic natural enemies in classical biological control programs. Although non-target risk is typically evaluated based on evidence of successful parasitism, parasitoid-induced host mortality not resulting in visible evidence of parasitism (i.e., nonreproductive effects) is often overlooked. The adventive establishment of Trissolcus japonicus, an exotic parasitoid of the introduced stink bug Halyomorpha halys, provides an opportunity to investigate the total impact of this parasitoid on target and non-target hosts in the field. We developed a new methodology to measure nonreproductive effects in this system, involving a species-specific diagnostic PCR assay for T. japonicus. We applied this methodology to field-deployed eggs of four pentatomid species, coupled with traditional rearing techniques. Nonreproductive effects were responsible for the mortality of an additional 5.6% of H. halys eggs due to T. japonicus, and were even more substantial in some of the non-target species (5.4–43.2%). The observed hidden mortality of native non-target species from an introduced parasitoid could change predictions about direct and indirect ecological interactions and the efficacy of biological control of the target pest.
Invasive Agricultural Pest Drosophila suzukii (Diptera, Drosophilidae) Appeared in the Russian Caucasus
Authors: Bieńkowski Andrzej O. , Orlova-Bienkowskaja Marina J.
Published: November 2020

Spotted-wing drosophila Drosophila suzukii (Matsumura) is one of the most important invasive pests of fruit and wine production worldwide. This species feeds on Prunus spp., Rubus spp., Fragaria spp. (Rosaceae), Vaccinium spp. (Ericaceae), Vitis spp. (Vitaceae), and other soft fruits. It causes significant damage because, unlike most other Drosophila species, it oviposits and feeds on healthy fruits. Drosophila suzukii is a quarantine pest that is included on the European and Mediterranean Plant Protection Organization (EPPO) A2 List. This species is native to East Asia and has been rapidly spreading through Europe since 2008. Herein, we report the first records of D. suzukii in European Russia. In 2017 and 2020, we placed baited traps in different districts of the resort city of Sochi (Black sea Coast of the Caucasus, Krasnodar Territory, Russia). Three specimens of D. suzukii were collected in June 2017, two specimens in September 2017, and 44 specimens in September 2020. Specimens were identified by the typical female ovipositor, spotted wings of the males, and other morphological characters. Krasnodar Territory is one of the main fruit-producing regions of Russia. Therefore, populations of this pest should be monitored and measures to minimize economic damage should be taken.
Regulation of Skin Barrier Function via Competition between AHR Axis versus IL-13/IL-4‒JAK‒STAT6/STAT3 Axis: Pathogenic and Therapeutic Implications in Atopic Dermatitis
Authors: Furue Masutaka
Published: November 2020

Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction, and chronic pruritus. As the anti-interleukin-4 (IL-4) receptor α antibody dupilumab improves all three cardinal features of AD, the type 2 cytokines IL-4 and especially IL-13 have been indicated to have pathogenic significance in AD. Accumulating evidence has shown that the skin barrier function is regulated via competition between the aryl hydrocarbon receptor (AHR) axis (up-regulation of barrier) and the IL-13/IL-4‒JAK‒STAT6/STAT3 axis (down-regulation of barrier). This latter axis also induces oxidative stress, which exacerbates inflammation. Conventional and recently developed agents for treating AD such as steroid, calcineurin inhibitors, cyclosporine, dupilumab, and JAK inhibitors inhibit the IL-13/IL-4‒JAK‒STAT6/STAT3 axis, while older remedies such as coal tar and glyteer are antioxidative AHR agonists. In this article, I summarize the pathogenic and therapeutic implications of the IL-13/IL-4‒JAK‒STAT6/STAT3 axis and the AHR axis in AD.
Pregnancy and Childbirth in the COVID-19 Era—The Course of Disease and Maternal–Fetal Transmission
Authors: Mazur-Bialy Agnieszka Irena , Kołomańska-Bogucka Daria , Tim Sabina , Opławski Marcin
Published: November 2020

From the beginning of the Coronavirus Disease 2019 (COVID-19) pandemic, special attention has been paid to pregnant women and to monitoring comorbidities, such as gestational diabetes and hypertension, which could increase their risk of disease and death. The purpose of this review is to synthesize the available knowledge on the course of COVID-19 in pregnant women as well as the risk of maternal–fetal transmission. The study indicated that the course of COVID-19 is worse in pregnant women who are more often admitted to intensive care units or who require mechanical ventilation than nonpregnant women with COVID-19. Some symptoms, such as dyspnea and cough, were similar to those observed in nonpregnant women, but fever, headache, muscle aches, chills, and diarrhea were less frequent. A study revealed that premature delivery and cesarean section were more common in pregnant women diagnosed with COVID-19. In addition, recent studies confirm the possibility of intrauterine maternal–fetal transmission by positive genetic tests and the presence of IgM in newborns just after delivery; at the moment, the probability of transmission through mother’s milk is inconclusive. Considering all the above, a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is an important factor that threatens the health and life of both the mother and the fetus, but further studies are still needed.
The Management of Children with Cancer during the COVID-19 Pandemic: A Rapid Review
Authors: Amicucci Matteo , Mastronuzzi Angela , Ciaralli Italo , Piccioni Federico , Schiopu Andreea Cristina , Tiozzo Emanuela , Gawronski Orsola , Biagioli Valentina , Dall’Oglio Immacolata
Published: November 2020

Despite the fact that cancer patients seem to be at a higher risk of being infected with SARS-CoV-2, limited data are available in the pediatric oncology setting. A systematic rapid review was conducted to analyze scientific literature regarding the management, interventions, and strategies adopted to prevent the spread of COVID-19 in the pediatric cancer population. Our search on PubMed, Scopus, Cochrane, and EMBASE databases yielded 505 articles. After removing duplicates, 21 articles were included. Articles focused on infection prevention (n = 19; 90.5%), management (n = 18; 85.7%), overall management of specific treatments for cancer (n = 13; 61.9%), and education (n = 7; 33.3%). The interventions adopted to prevent the spread of COVID-19 were similar across organizations and in line with general recommendations. Most of them reported interventions that could be used as valid strategies for similar emergencies. The strategies included limiting the risk of contagion by restricting access to the wards and implementing hygiene measures, the identification of separate pathways for the management of patients suspected or confirmed to be infected with COVID-19, the postponement of people accessing the hospital for non-urgent or unnecessary tests or medical examinations, and the preventive screening of patients before chemotherapy treatment or transplantation of hematopoietic stem cells. It is necessary to identify key indicators in order to better evaluate the effectiveness of the interventions implemented over time. A summary of the recommendations is provided.
Assessing the Effectiveness of Pirfenidone in Idiopathic Pulmonary Fibrosis: Long-Term, Real-World Data from European IPF Registry (eurIPFreg)
Authors: Krauss Ekaterina , Tello Silke , Wilhelm Jochen , Schmidt Johanna , Stoehr Mark , Seeger Werner , Dartsch Ruth , Crestani Bruno , Guenther Andreas
Published: November 2020

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic pulmonary disease with rising incidence. In this study the effectiveness of pirfenidone, as measured by longitudinal change in individual slope of forced vital capacity (FVC) prior to and after initiating pirfenidone treatment, was evaluated in IPF patients recruited into the European registry for idiopathic pulmonary fibrosis (eurIPFreg). Secondary variables were the evaluation of the change in individual slope of diffusion capacity of the lungs for carbon monoxide (DLco), the Borg dyspnea scale, and six-minute walking distance (6MWD), as well as survival analyses. Results: Data of 122 eurIPFreg patients, who had at least two pulmonary function tests (PFTs) prior to or under treatment with pirfenidone, were analyzed by calculating slope-changes. The global analysis revealed an average slope change of +1.48 ± 0.28 (% per annum (p.a)) after start of treatment (p < 0.001), reflecting a reduction in annual FVC decline of approx. 50% under pirfenidone; it also showed a reduction in DLco, and increase in 6MWD (both p < 0.0001), as well as a flattening of the Borg dyspnea scale (p = 0.02). The median survival under treatment was 4.82 years. Patients with a more restrictive disease (FVC < 80% pred.), with a rapid progression (FVC decline >10% pred. p.a.), previous smokers and patients > 60 years of age seemed to profit more from pirfenidone treatment. Conclusions: We report the effectiveness of pirfenidone in a European “real world” IPF cohort with outcome data extending up to 9 years. Global analyses demonstrated a positive effect of pirfenidone on the decline of the lung function over time. Survival was dependent on Gender–Age–Physiology (GAP) score and age prior to therapy.
Improvement of Gait after 4 Weeks of Wearable Focal Muscle Vibration Therapy for Individuals with Diabetic Peripheral Neuropathy
Authors: Rippetoe Josiah , Wang Hongwu , James Shirley A. , Dionne Carol , Block Bethany , Beckner Matthew
Published: November 2020

People with diabetic peripheral neuropathy (DPN) experience lower quality of life caused by associated balance, posture, and gait impairments. While focal muscle vibration (FMV) has been associated with improvements in gait performance in individuals with neurological disorders, little is known about its effectiveness in patients with DPN. The purpose of this study was to investigate the effect of FMV on gait outcomes in patients with DPN. The authors randomized 23 participants into three FMV intervention groups depending upon the delivery of vibration. Participants applied wearable FMV to the bilateral quadriceps, gastrocnemius, and tibialis anterior, 10 min per muscle, three times per week over a four-week period. Spatiotemporal, kinematic, and kinetic gait parameters at baseline and post-intervention were calculated and analyzed. Gait speed, cadence, stride time, left and right stance time, duration of double limb support, and left and right knee flexor moments significantly improved after four weeks of FMV. Trends toward significant improvements were noted in maximum left and right knee flexion. Results indicate that FMV therapy was associated with improvements in gait parameters in individuals with DPN, warranting expanded study of FMV therapy for long-term gait performance improvement in these individuals.
Uterus Preservation in Case of Vaginal Prolapse Surgery Acts as a Protector against Postoperative Urinary Retention
Authors: Bekos Christine , Morgenbesser Raffaela , Kölbl Heinz , Husslein Heinrich , Umek Wolfgang , Bodner Klaus , Bodner-Adler Barbara
Published: November 2020

Background: The aim of this study was to identify clinical risk factors for increased post-void residual (PVR) volumes in patients undergoing vaginal prolapse surgery and to find out whether uterus preservation or prolapse hysterectomy influences the incidence of postoperative urinary retention. Methods: This retrospective study included women who presented with pelvic organ prolapse (POP) and planned prolapse surgery between January 2017 and July 2019. PVR was assessed postoperatively and increased amounts were defined as incomplete voiding with residual urine volume greater than 150 mL. Results: Increased PVR at the first postoperative day occurred in 31.8% (56/176). Body mass index (BMI) was significantly lower in patients with increased PVR after pelvic floor surgery compared to patients with normal PVR amounts (p = 0.040). Furthermore, during multiple logistic regression analysis, low BMI (p = 0.009) as well as prolapse hysterectomy (p = 0.032) turned out to be the strongest risk factors associated with increased PVR volume. Conclusion: This is the first study identifying prolapse hysterectomy as an independent risk factor for increased PVR after surgical prolapse repair. Our results might be helpful in counseling patients prior to surgery and underline the option of uterus preservation during prolapse surgery in selected cases.
Overcoming the Use of Mechanical Restraints in Psychiatry: A New Challenge in the Everyday Clinical Practice at the Time of COVID-19
Authors: De Berardis Domenico , Ventriglio Antonio , Fornaro Michele , Vellante Federica , Martinotti Giovanni , Fraticelli Silvia , Di Giannantonio Massimo
Published: November 2020

Restraining interventions, which comprise physical (PR) and mechanical restraint (MR), have a long history in mental health services [...]
Exploring the Role of Caffeine Use in Adult-ADHD Symptom Severity of US Army Soldiers
Authors: Cipollone Giada , Gehrman Philip , Manni Corrado , Pallucchini Alessandro , Maremmani Angelo , Palagini Laura , Perugi Giulio , Maremmani Icro
Published: November 2020

There is a growing trend of using energy drinks and caffeinated beverages to improve cognitive performance that is widespread and well-studied among children and teenagers with Attention Deficit Hyperactive Disorder (ADHD), but little is known about adult ADHD (A-ADHD). As a consequence, the use of highly caffeinated drinks and their impact on ADHD symptoms are poorly understood. This is especially true in populations where A-ADHD and the use of these beverages are largely represented, such as in military samples. From the All Army Study (AAS) of the Army Study to Assess Risk and Resilience in Service members (STARRS) data, 1,239 A-ADHD soldiers and 17,674 peers without any psychiatric comorbidity were selected. The two groups were compared on: (1) the presence of substance use disorder (SUD) diagnosis both over their lifetime and in the previous 30 days; (2) patterns of alcohol and caffeine use using chi-square analyses. Lastly, the relationship between substance use and severity of A-ADHD symptoms was assessed using Pearson’s correlations. Soldiers with a diagnosis of A-ADHD had a higher prevalence of SUD diagnosis compared to their peers without psychiatric comorbidity. They also tended to use more alcohol, caffeine pills, energy drinks, and other caffeinated drinks. Alcohol use was positively correlated with A-ADHD symptoms; on the contrary, energy drinks, caffeine pills and other caffeinated drinks showed negative correlations with some aspects of A-ADHD symptomatology. The use of caffeinated compounds appears to be increased among military soldiers with ADHD, and they may help reducing A-ADHD symptoms and improve cognitive performance. These results suggest a possible role for caffeine as a potential pharmacological tool in the treatment of adult ADHD.
Enhanced Mechanical Properties of Carbon Nanotube/Aluminum Composites Fabricated by Powder Metallurgical and Repeated Hot-Rolling Techniques
Authors: Tsukamoto Hideaki
Published: November 2020

This research aimed to fabricate lightweight and high-strength carbon nanotube (CNT)/aluminum (Al) composites by powder metallurgical and repeated hot-rolling techniques. The fabrication was conducted in three steps: (1) CNT dispersion, (2) preparation of CNT/Al compacts by powder metallurgical slurry methods, and (3) strengthening and refining of CNT/Al composites by repeated hot rolling. The processes of dispersion of CNTs were carried out with dimethylacetamide as a solvent and potassium carbonate as a dispersing agent, which is an inorganic salt, under ultrasonic sonication conditions. Effect of sonication time on dispersion states and mechanical properties was also examined.
Contrary to the Conclusions Stated in the Paper, Only Dry Fat-Free Mass Was Different between Groups upon Reanalysis. Comment on: “Intermittent Energy Restriction Attenuates the Loss of Fat-Free Mass in Resistance Trained Individuals. A Randomized Controlled Trial”
Authors: Peos Jackson , Brown Andrew W. , Vorland Colby J. , Allison David B. , Sainsbury Amanda
Published: November 2020

Campbell and colleagues recently published a randomised controlled trial investigating the effects of diets involving intermittent energy restriction versus continuous energy restriction on changes in body composition and resting metabolic rate (RMR) in resistance-trained adults[...]
Financial Analysis of Automated Container Terminal Capacity from the Perspective of Terminal Operating Company
Authors: Park Nam Kyu , An Yohan
Published: November 2020

This study examines the financially feasibility of the proper terminal capacity by each berth size of the automatic container terminal (ACT) from the perspective of Terminal Operating Company (TOC). ACT is a highly productive and eco-friendly port facility, but it requires a lot of capital investment. Thus, the investment of ACT should consider the TOC’s operating profit preservation to determine the proper terminal capacity. In this study, we attempt to conduct financial analysis using the net present value method and estimate breakeven handling volume of five berth sizes (nine, five, four, three, and two berths). In particular, as the aim of this study is to propose a capacity model of ACT, the model must be able to adapt to a variety of situations reflecting the number of berths and financial discount rate. The case study focused on the new port of Busan, introducing ACT. As a result, the breakeven terminal capacity changes from 560,421 TEU of the 9-berth model to 633,102 TEU of the 2-berth model, applying a 4.5% standard discount ratio. In a sensitivity test considering the change in discount rate and the size of the berth at the same time, the net present value (NPV) has a positive value at the level of at least 550,000 TEU (nine berths and 3.5% discount rate) and up to 650,000 TEU (two berths and 5.5% discount rate). The method of optimizing financial efficiency by analyzing the appropriate loading capacity will be an important support tool in decision-making by providing the analysis results and reasonable information obtained during the analysis process to the TOC, the main stakeholder in the adoption of ACT.
Long-Term SARS-CoV-2 Infection Associated with Viral Dissemination in Different Body Fluids Including Bile in Two Patients with Acute Cholecystitis
Authors: Scutari Rossana , Piermatteo Lorenzo , Manuelli Matteo Ciancio , Iannetta Marco , Salpini Romina , Bertoli Ada , Alteri Claudia , Saccomandi Patrizia , Bellocchi Maria Concetta , Malagnino Vincenzo , Teti Elisabetta , Sforza Daniele , Siragusa Leandro , Grande Michele , Sarmati Loredana , Svicher Valentina , Andreoni Massimo , Ceccherini-Silberstein Francesca
Published: November 2020

Our study aimed to investigate the kinetics of SARS-CoV-2 RNA in bile and in different body fluids of two SARS-CoV-2 positive patients with acute cholecystitis by innovative droplet digital PCR (ddPCR) assays. For each patient, nasopharyngeal- and rectal swabs, bile, urine, and plasma samples were collected at different time points for SARS-CoV-2 RNA quantification by two ddPCR assays. For both patients, ddPCR revealed persistent and prolonged detection of viral RNA in the nasopharyngeal swab despite triple-negative or single-positive results by qRT-PCR. In Patient 1, SARS-CoV-2 RNA dropped more rapidly in bile and rectal-swab and declined slowly in nasopharyngeal swab and plasma, becoming undetectable in all compartments 97 days after symptoms started. Conversely, in patient 2, SARS-CoV-2 RNA was detected, even if at low copies, in all body samples (with the exception of urine) up to 75 days after the onset of symptoms. This study highlights that SARS-CoV-2 RNA can persist for a prolonged time in respiratory samples and in several biological samples despite negativity to qRT-PCR, supporting SARS-CoV-2’s ability to provoke persistent and disseminated infection and therefore to contribute to extra-pulmonary clinical manifestations.
Joule Heating-Induced Carbon Fibers for Flexible Fiber Supercapacitor Electrodes
Authors: Kang Jin Gu , Wang Gang , Kim Sung-Kon
Published: November 2020

Microscale fiber-based supercapacitors have become increasingly important for the needs of flexible, wearable, and lightweight portable electronics. Fiber electrodes without pre-existing cores enable a wider selection of materials and geometries than is possible through core-containing electrodes. The carbonization of fibrous precursors using an electrically driven route, different from a conventional high-temperature process, is particularly promising for achieving this structure. Here, we present a facile and low-cost process for producing high-performance microfiber supercapacitor electrodes based on carbonaceous materials without cores. Fibrous carbon nanotubes-agarose composite hydrogels, formed by an extrusion process, are converted to a composite fiber consisting of carbon nanotubes (CNTs) surrounded by an amorphous carbon (aC) matrix via Joule heating. When assembled into symmetrical two-electrode cells, the composite fiber (aC-CNTs) supercapacitor electrodes deliver a volumetric capacitance of 5.1 F cm−3 even at a high current density of 118 mA cm−3. Based on electrochemical impedance spectroscopy analysis, it is revealed that high electrochemical properties are attributed to fast response kinetics with a characteristic time constant of 2.5 s. The aC-CNTs fiber electrodes exhibit a 94% capacitance retention at 14 mA cm−3 for at least 10,000 charge-discharge cycles even when deformed (90° bend), which is essentially the same as that (96%) when not deformed. The aC-CNTs fiber electrodes also demonstrate excellent storage performance under mechanical deformation—for example, 1000 bending-straightening cycles.