bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Transport Link Density on Conductivity If Junctions and/or Links Are Blocked
Authors: Aleshkin Anton
Published: June 2021

This paper examines some approaches to modeling and managing traffic flows in modern megapolises and proposes using the methods and approaches of the percolation theory. The author sets the task of determining the properties of the transport network (percolation threshold) when designing such networks, based on the calculation of network parameters (average number of connections per crossroads, road network density). Particular attention is paid to the planarity and nonplanarity of the road transport network. Algorithms for building a planar random network (for modeling purposes) and calculating the percolation thresholds in the resulting network model are proposed. The article analyzes the resulting percolation thresholds for road networks with different relationship densities per crossroad and analyzes the effect of network density on the percolation threshold for these structures. This dependence is specified mathematically, which allows predicting the qualitative characteristics of road network structures (percolation thresholds) in their design. The conclusion shows how the change in the planar characteristics of the road network (with adding interchanges to it) can improve its quality characteristics, i.e., its overall capacity.
Fire Risk Sub-Module Assessment under Solvency II. Calculating the Highest Risk Exposure
Authors: Badal-Valero Elena , Coll-Serrano Vicente , Segura-Gisbert Jorge
Published: June 2021

The European Directive 2009/138 of Solvency II requires adopting a new approach based on risk, applying a standard formula as a market proxy in which the risk profile of insurers is fundamental. This study focuses on the fire risk sub-module, framed within the man-made catastrophe risk module, for which the regulations require the calculation of the highest concentration of risks that make up the portfolio of an insurance company within a radius of 200 m. However, the regulations do not indicate a specific methodology. This study proposes a procedure consisting of calculating the cluster with the highest risk and identifying this on a map. The results can be applied immediately by any insurance company, covered under the Solvency II regulations, to determine their maximum exposure to the catastrophic man-made risk of fire, instantly providing them with the necessary input for calibration of the solvency capital requirement.
Demand Subsidy versus Production Regulation: Development of New Energy Vehicles in a Competitive Environment
Authors: Wang Zixuan , Li Xiuzhang
Published: June 2021

In the competitive market environment, the growth of new energy vehicles (NEVs) faces many obstacles. Demand subsidy or production regulation-related policies are widely used to promote the development of NEVs. A comparative analysis of the effects of the two types of policies on the competitive vehicle market requires further study. To fill this gap, we investigate which type of policy is more preferable from the perspective of the social planner. In this paper, we construct a Stackelberg game with a welfare-maximizing social planner and two profit-maximizing manufacturers producing NEVs and fuel vehicles (FVs), respectively. Interestingly, although both types of policies can increase the quantity of NEVs, demand subsidy also promotes the growth of total vehicles at the same time; in contrast, production regulation reduces the total vehicles. Moreover, compared with the benchmark that no policy intervention, demand subsidy generally improves social welfare, while production regulation improves social welfare only with high consumer preference for NEVs. Nevertheless, production regulation always has a positive impact on the environment, whereas demand subsidy may have a positive impact only when the NEV is very environment friendly. The numerical results show that consumer environmental preferences and the regulation of environmental impact determine which type of policy dominates the other.
Critical Tetramine Poisoning after Sea Snail Ingestion in a Patient on Peritoneal Dialysis: A Case Report
Authors: Yeo In-Hwan , Lim Jeong-Hoon
Published: June 2021

Tetramine in gastropods can cause poisoning symptoms with various side effects. Most of these symptoms are mild and spontaneously resolved due to the rapid excretion of tetramine through the kidneys; however, patients with kidney dysfunction can present severe symptoms. A 48-year-old woman with end-stage kidney disease due to diabetic nephropathy and undergoing peritoneal dialysis (PD) visited our emergency department (ED) with complaints of general weakness, vomiting, and shortness of breath after ingesting some sea snails. On ED arrival, she was in a respiratory failure state; therefore, invasive mechanical ventilation was immediately initiated. Chest radiography showed diffuse severe pulmonary edema and her vital signs fluctuated; thus, continuous renal replacement therapy (CRRT) was initiated at the intensive care unit to treat tetramine intoxication and control volume status. Her condition gradually improved, and she was successfully weaned from mechanical ventilation on the 5th day of admission and moved to the general ward on the 10th day. CRRT was switched to PD. She fully recovered and was discharged on the 15th day of admission. Therefore, clinicians should explain the risk associated with gastropod ingestion to patients with kidney dysfunction and recognize that the clinical course of tetramine toxicity can be critical.
Wear and Rolling Contact Fatigue Analysis of AISI 52100 Bearing Steel in Presence of Additivated Lubricants
Authors: Bhaumik Shubrajit , Paleu Viorel
Published: June 2021

Tribological properties of lithium potassium titanate (PT), molybdenum disulphide, and tungsten disulphide-dispersed mineral oil (MO) were investigated. The sample containing 2 wt.% WS2 exhibited the lowest coefficient of friction. However, the wear scar diameters of the additivated samples were very narrow. Extreme pressure properties of mineral oil were enhanced with the addition of additives. The rolling contact fatigue results exhibited better fatigue life of the balls in MoS2 and PT-dispersed MO. Surface characterization of the balls indicated more pitting on the balls of the MO and WS2-dispersed MO as compared to MoS2 and PT, indicating a stable film in the case of MoS2 and PT, which was confirmed by the presence of additives on ball surfaces by Raman spectrograph. The results of extended rolling contact fatigue tests proved that PT-added mineral oil provided the highest life cycles of the tested balls, followed by MoS2 and WS2-added mineral oil; thus, indicating PT as a plausible alternative to MoS2 and WS2.
What Is the Metabolic Amplification of Insulin Secretion and Is It (Still) Relevant?
Authors: Rustenbeck Ingo , Schulze Torben , Morsi Mai , Alshafei Mohammed , Panten Uwe
Published: June 2021

The pancreatic beta-cell transduces the availability of nutrients into the secretion of insulin. While this process is extensively modified by hormones and neurotransmitters, it is the availability of nutrients, above all glucose, which sets the process of insulin synthesis and secretion in motion. The central role of the mitochondria in this process was identified decades ago, but how changes in mitochondrial activity are coupled to the exocytosis of insulin granules is still incompletely understood. The identification of ATP-sensitive K+-channels provided the link between the level of adenine nucleotides and the electrical activity of the beta cell, but the depolarization-induced Ca2+-influx into the beta cells, although necessary for stimulated secretion, is not sufficient to generate the secretion pattern as produced by glucose and other nutrient secretagogues. The metabolic amplification of insulin secretion is thus the sequence of events that enables the secretory response to a nutrient secretagogue to exceed the secretory response to a purely depolarizing stimulus and is thus of prime importance. Since the cataplerotic export of mitochondrial metabolites is involved in this signaling, an orienting overview on the topic of nutrient secretagogues beyond glucose is included. Their judicious use may help to define better the nature of the signals and their mechanism of action.
Insufficient Anthrax Lethal Toxin Neutralization Is Associated with Antibody Subclass and Domain Specificity in the Plasma of Anthrax-Vaccinated Individuals
Authors: Smith Kenneth , Garman Lori , Norris Kathleen , Muther Jennifer , Duke Angie , Engler Renata J. M. , Nelson Michael R. , Collins Limone C. , Spooner Christina , Guthridge Carla , James Judith A.
Published: June 2021

Anthrax vaccine adsorbed (AVA) is a significant line of defense against bioterrorist attack from Bacillus anthracis spores. However, in a subset of individuals, this vaccine may produce a suboptimal quantity of anti-protective antigen (PA), antibodies that are poorly neutralizing, and/or antibody titers that wane over time, necessitating annual boosters. To study individuals with such poor responses, we examine the properties of anti-PA in a subset of vaccinated individuals that make significant quantities of antibody but are still unable to neutralize toxin. In this cohort, characterized by poorly neutralizing antibody, we find that increased IgG4 to IgG1 subclass ratios, low antibody avidity, and insufficient antibody targeting domain 4 associate with improper neutralization. Thus, future vaccines and vaccination schedules should be formulated to improve these deficiencies.
An Assessment of the Lolium perenne (Perennial Ryegrass) Seedborne Microbiome across Cultivars, Time, and Biogeography: Implications for Microbiome Breeding
Authors: Tannenbaum Ian , Rodoni Brendan , Spangenberg German , Mann Ross , Sawbridge Tim
Published: June 2021

Research into the bacterial component of the seed microbiome has been intensifying, with the aim of understanding its structure and potential for exploitation. We previously studied the intergenerational seed microbiome of one cultivar of perennial ryegrass with and without one strain of the commercially deployed fungal endophyte Epichloë festucae var. lolii. The work described here expands on our previous study by exploring the bacterial seed microbiome of different commercial cultivar/Epichloë festucae var. lolii combinations in collections of single seeds from the harvest year 2016. In this dataset, a cultivar effect could be seen between the seed microbiomes from cultivars Alto and Trojan. The bacterial component of the seed microbiome from pooled seeds from a single cultivar/E. festucae var. lolii combination harvested from 13 seed production farms around Canterbury in the year 2018 was also studied. This dataset allows the effect of different production locations on the bacterial seed microbiome to be examined. By comparing the two sets of data, bacteria from the genera Pantoea, Pseudomonas, Duganella, Massilia, and an unknown Enterobacteriaceae were observed to be in common. This core bacterial microbiome was stable over time but could be affected by supplemental taxa derived from the growth environment of the parental plant; differing microbiomes were seen between different seed production farms. By comparison to a collection of bacterial isolates, we demonstrated that many of the members of the core microbiome were culturable. This allows for the possibility of exploiting these microbes in the future.
Modulation of Serotonin Receptors in Neurodevelopmental Disorders: Focus on 5-HT7 Receptor
Authors: Lee Jieon , Avramets Diana , Jeon Byungsun , Choo Hyunah
Published: June 2021

Since neurodevelopmental disorders (NDDs) influence more than 3% of children worldwide, there has been intense investigation to understand the etiology of disorders and develop treatments. Although there are drugs such as aripiprazole, risperidone, and lurasidone, these medications are not cures for the disorders and can only help people feel better or alleviate their symptoms. Thus, it is required to discover therapeutic targets in order to find the ultimate treatments of neurodevelopmental disorders. It is suggested that abnormal neuronal morphology in the neurodevelopment process is a main cause of NDDs, in which the serotonergic system is emerging as playing a crucial role. From this point of view, we noticed the correlation between serotonin receptor subtype 7 (5-HT7R) and NDDs including autism spectrum disorder (ASD), fragile X syndrome (FXS), and Rett syndrome (RTT). 5-HT7R modulators improved altered behaviors in animal models and also affected neuronal morphology via the 5-HT7R/G12 signaling pathway. Through the investigation of recent studies, it is suggested that 5-HT7R could be a potential therapeutic target for the treatment of NDDs.
Anti-Inflammatory, Antiallergic, and COVID-19 Main Protease (Mpro) Inhibitory Activities of Butenolides from a Marine-Derived Fungus Aspergillus terreus
Authors: Uras Ibrahim Seyda , Ebada Sherif S. , Korinek Michal , Albohy Amgad , Abdulrazik Basma S. , Wang Yi-Hsuan , Chen Bing-Hung , Horng Jim-Tong , Lin Wenhan , Hwang Tsong-Long , Konuklugil Belma
Published: June 2021

In December 2020, the U.K. authorities reported to the World Health Organization (WHO) that a new COVID-19 variant, considered to be a variant under investigation from December 2020 (VUI-202012/01), was identified through viral genomic sequencing. Although several other mutants were previously reported, VUI-202012/01 proved to be about 70% more transmissible. Hence, the usefulness and effectiveness of the newly U.S. Food and Drug Administration (FDA)-approved COVID-19 vaccines against these new variants are doubtfully questioned. As a result of these unexpected mutants from COVID-19 and due to lack of time, much research interest is directed toward assessing secondary metabolites as potential candidates for developing lead pharmaceuticals. In this study, a marine-derived fungus Aspergillus terreus was investigated, affording two butenolide derivatives, butyrolactones I (1) and III (2), a meroterpenoid, terretonin (3), and 4-hydroxy-3-(3-methylbut-2-enyl)benzaldehyde (4). Chemical structures were unambiguously determined based on mass spectrometry and extensive 1D/2D NMR analyses experiments. Compounds (1–4) were assessed for their in vitro anti-inflammatory, antiallergic, and in silico COVID-19 main protease (Mpro) and elastase inhibitory activities. Among the tested compounds, only 1 revealed significant activities comparable to or even more potent than respective standard drugs, which makes butyrolactone I (1) a potential lead entity for developing a new remedy to treat and/or control the currently devastating and deadly effects of COVID-19 pandemic and elastase-related inflammatory complications.
[3 + n] Cycloaddition Reactions: A Milestone Approach for Elaborating Pyridazine of Potential Interest in Medicinal Chemistry and Optoelectronics
Authors: Amariucai-Mantu Dorina , Mangalagiu Violeta , Mangalagiu Ionel I.
Published: June 2021

During the last few decades, pyridazine derivatives have emerged as privileged structures in heterocyclic chemistry, both because of their excellent chemistry and because of their potential applications in medicinal chemistry and optoelectronics. This review is focused on the recent advances in [3 + n] cycloaddition reactions in the pyridazine series as well as their medicinal chemistry and optoelectronic applications over the last ten years. The stereochemistry and regiochemistry of the cycloaddition reactions are discussed. Applications in optoelectronics (in particular, as fluorescent materials and sensors) and medicinal chemistry (in particular, antimicrobials and anticancer) are also reviewed.
A Comparative Study of Antimicrobial and Antioxidant Activities of Plant Essential Oils and Extracts as Candidate Ingredients for Edible Coatings to Control Decay in ‘Wonderful’ Pomegranate
Authors: Kawhena Tatenda Gift , Opara Umezuruike Linus , Fawole Olaniyi Amos
Published: June 2021

This study determined the antimicrobial and antioxidant activity of lemongrass (LO), thyme (TO), and oregano (OO) essential oils and ethanolic extracts of pomegranate peel (PPE) and grape pomace (GPE) as candidate ingredients for edible coatings. Antifungal effects against Botrytis cinerea and Penicillium spp. were tested using paper disc and well diffusion methods. Radical scavenging activity (RSA) was evaluated using 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid assays. Gas chromatography-mass spectrometry analysis identified limonene (16.59%), α-citral (27.45%), β-citral (27.43%), thymol (33.31%), paracymene (43.26%), 1,8-cineole (17.53%), and trans-caryphellene (60.84%) as major compounds of the essential oils. From both paper disc and well diffusion methods, LO recorded the widest zone of inhibition against tested microbes (B. cinerea and Penicillium spp.). The minimum inhibitory concentrations of LO against B. cinerea and Penicillium spp., were 15 µL/mL and 30 µL/mL, respectively. The highest (69.95%) and lowest (1.64%) RSA at 1 mg/mL were recorded for PPE and OO. Application of sodium alginate and chitosan-based coatings formulated with LO (15 or 30 µL/mL) completely inhibited spore germination and reduced the decay severity of ‘Wonderful’ pomegranate. Lemongrass oil proved to be a potential antifungal agent for edible coatings developed to extend shelf life of ‘Wonderful’ pomegranate.
Nanoceria Prevents Glucose-Induced Protein Glycation in Eye Lens Cells
Authors: Hanafy Belal I. , Cave Gareth W. V. , Barnett Yvonne , Pierscionek Barbara K.
Published: June 2021

Cerium oxide nanoparticles (nanoceria) are generally known for their recyclable antioxidative properties making them an appealing biomaterial for protecting against physiological and pathological age-related changes that are caused by reactive oxygen species (ROS). Cataract is one such pathology that has been associated with oxidation and glycation of the lens proteins (crystallins) leading to aggregation and opacification. A novel coated nanoceria formulation has been previously shown to enter the human lens epithelial cells (HLECs) and protect them from oxidative stress induced by hydrogen peroxide (H2O2). In this work, the mechanism of nanoceria uptake in HLECs is studied and multiple anti-cataractogenic properties are assessed in vitro. Our results show that the nanoceria provide multiple beneficial actions to delay cataract progression by (1) acting as a catalase mimetic in cells with inhibited catalase, (2) improving reduced to oxidised glutathione ratio (GSH/GSSG) in HLECs, and (3) inhibiting the non-enzymatic glucose-induced glycation of the chaperone lens protein α-crystallin. Given the multifactorial nature of cataract progression, the varied actions of nanoceria render them promising candidates for potential non-surgical therapeutic treatment.
Knockout or Knock-in? A Truncated D2 Receptor Protein Is Expressed in the Brain of Functional D2 Receptor Knockout Mice
Authors: Sánchez Natalia , Olivares-Costa Montserrat , González Marcela P , Munita Roberto , Escobar Angélica P , Meza Rodrigo , Herrera-Rojas Mauricio , Albornoz Jessica , Merello Gianluca , Andrés María E
Published: June 2021

Null mice for the dopamine D2 receptor (D2R) have been instrumental in understanding the function of this protein. For our research, we obtained the functional D2R knockout mouse strain described initially in 1997. Surprisingly, our biochemical characterization showed that this mouse strain is not a true knockout. We determined by sequence analysis of the rapid 3′ amplification of cDNA ends that functional D2R knockout mice express transcripts that lack only the eighth exon. Furthermore, immunofluorescence assays showed a D2R-like protein in the brain of functional D2R knockout mice. We verified by immunofluorescence that the recombinant truncated D2R is expressed in HEK293T cells, showing intracellular localization, colocalizing in the Golgi apparatus and the endoplasmic reticulum, but with less presence in the Golgi apparatus compared to the native D2R. As previously reported, functional D2R knockout mice are hypoactive and insensitive to the D2R agonist quinpirole. Concordantly, microdialysis studies confirmed that functional D2R knockout mice have lower extracellular dopamine levels in the striatum than the native mice. In conclusion, functional D2R knockout mice express transcripts that lead to a truncated D2R protein lacking from the sixth transmembrane domain to the C-terminus. We share these findings to avoid future confusion and the community considers this mouse strain in D2R traffic and protein–protein interaction studies.
“Aggressive” Feeding of Very Preterm Neonates and Body Mass Index at School Age
Authors: Gounaris Antonios , Sokou Rozeta , Theodoraki Martha , Gounari Eleni , Panagiotounakou Polytimi , Antonogeorgos George , Ioakeimidis Georgios , Parastatidou Stavroula , Konstantinidi Aikaterini , Grivea Ioanna N.
Published: June 2021

Introduction: The effects of “aggressive” neonatal feeding policies of very preterm neonates (VPN) and the risk of metabolic syndrome later in life remain questionable. We aimed to evaluate the effect of our “aggressive” nutrition policies of VPN during hospitalisation on body mass index (BMI) at ages 2 and 8 years. Materials and Methods: Eighty four VPN, who received “aggressive” nutrition during hospitalisation in an effort to minimise postnatal growth restriction (PGR) (group A), and 62 term neonates, as controls (group B), were enrolled in the study. Group A was further divided in four subgroups depending on the type (A1: fortified expressed breast milk and preterm formula; A2: exclusively preterm formula) and quantity of milk received (A3: maximum feeds 180–210 mL/kg/day; A4: maximum feeds 210 and up to 260 mL/kg/day). BMI was calculated at ages 2 and 8 years and plotted on the centile charts. Results: There was no significant difference in BMI between groups A and B at 2 and 8 years, respectively, in both absolute BMI values and their centile chart distribution. There was no significant difference in BMI at 2 and 8 years either between subgroups A1 and A2 or between subgroups A3 and A4. Conclusions: “Aggressive” and individualised feeding policy for VPN did not affect the BMI and obesity rates at ages of 2 and 8 years in our study population. The type and quantity of milk feeds had no impact on their BMI at school age. Further larger studies are needed to confirm our results.
The Probiotic Strain H. alvei HA4597® Improves Weight Loss in Overweight Subjects under Moderate Hypocaloric Diet: A Proof-of-Concept, Multicenter Randomized, Double-Blind Placebo-Controlled Study
Authors: Déchelotte Pierre , Breton Jonathan , Trotin-Picolo Clémentine , Grube Barbara , Erlenbeck Constantin , Bothe Gordana , Fetissov Sergueï O. , Lambert Grégory
Published: June 2021

Background: Increasing evidence supports the role of the gut microbiota in the control of body weight and feeding behavior. Moreover, recent studies have reported that the probiotic strain Hafnia alvei HA4597® (HA), which produces the satietogenic peptide ClpB mimicking the effect of alpha-MSH, reduced weight gain and adiposity in rodent models of obesity. Methods: To investigate the clinical efficacy of HA, 236 overweight subjects were included, after written informed consent, in a 12-week prospective, double-blind, randomized study. All subjects received standardized counselling for a −20% hypocaloric diet and were asked to maintain their usual physical activity. Subjects of the HA group received two capsules per day providing 100 billion bacteria per day and subjects in the Placebo (P) group received two placebo capsules. The primary endpoint was the percentage of subjects achieving a weight loss of at least 3% after 12 weeks. Intention-to-treat statistical analysis was performed using exact-Fischer, Mann-Whitney and paired-Wilcoxon tests as appropriate. Results: In the HA group, significantly more subjects (+33%) met the primary endpoint than in the P group (54.9 vs. 41.4%, p = 0.048). In the HA group, an increased feeling of fullness (p = 0.009) and a greater loss of hip circumference (p < 0.001) at 12 weeks were also observed. Fasting glycemia at 12 weeks was significantly lower (p < 0.05) in the HA compared to P group. Clinical and biological tolerance was good in both groups. Conclusions: A 12-week treatment with the probiotic strain H. alvei HA4597® significantly improves weight loss, feeling of fullness and reduction of hip circumference in overweight subjects following moderate hypocaloric diet. These data support the use of H. alvei HA4597® in the global management of excess weight.
Do Lifestyle Interventions in Pregnant Women with Overweight or Obesity Have an Effect on Neonatal Adiposity? A Systematic Review with Meta-Analysis
Authors: Baroni Naiara F. , Baldoni Nayara R. , Alves Geisa C. S. , Crivellenti Lívia C. , Braga Giordana C. , Sartorelli Daniela S.
Published: June 2021

Excessive body fat at birth is a risk factor for the development of childhood obesity. The aim of the present systematic review with meta-analysis was to evaluate the effect of lifestyle interventions in pregnant women with overweight or obesity on neonatal adiposity. The PubMed, Embase, Web of Science, Scopus, and LILACS databases were used as information sources. Original articles from randomized clinical trials of lifestyle intervention studies on pregnant women with excessive body weight and the effect on neonatal adiposity were considered eligible. The risk of bias was assessed using Cochrane criteria. The meta-analysis was calculated using the inverse variance for continuous data expressed as mean difference (MD), using the random effect model with a 95% confidence interval (CI). The outcomes were submitted to the GRADE evaluation. Of 2877 studies, four were included in the qualitative and quantitative synthesis (n = 1494). All studies were conducted in developed countries, with three including pregnant women with overweight or obesity, and one only pregnant women with obesity. The interventions had no effect on neonatal adiposity [Heterogeneity = 56%, MD = −0.21, CI = (−0.92, 0.50)] with low confidence in the evidence, according to GRADE. Studies are needed in low- and medium-developed countries with different ethnic-racial populations. PROSPERO (CRD42020152489).
Efficacy of a Multi-Strain Probiotic Formulation in Pediatric Populations: A Comprehensive Review of Clinical Studies
Authors: Tremblay Annie , Xu Xiaoyu , Colee James , Tompkins Thomas A.
Published: June 2021

A probiotic formulation combining Lactobacillus helveticus Rosell®-52, Bifidobacterium infantis Rosell®-33, and Bifidobacterium bifidum Rosell®-71 with fructooligosaccharides, first commercialized in China, has been sold in over 28 countries since 2002. Clinical studies with this blend of strains were conducted mainly in pediatric populations, and most were published in non-English journals. This comprehensive review summarizes the clinical studies in infants and children to evaluate the efficacy of this probiotic for pediatric indications. Literature searches for pediatric studies on Biostime® or Probiokid® (non-commercial name) in 6 international and Chinese databases identified 28 studies, which were classified by indications. Twelve studies show that the probiotic significantly increases the efficacy of standard diarrhea treatment regardless of etiology, reducing the risk of unresolved diarrhea (RR 0.31 [0.23; 0.42]; p < 0.0001) by 69%. In eight studies, the probiotic enhanced immune defenses, assessed by levels of various immune competence and mucosal immunity markers (six studies), and reduced the incidence of common infections (two studies). The probiotic improved iron deficiency anemia treatment efficacy (three studies), reducing the risk of unresolved anemia by 49% (RR 0.51 [0.28; 0.92]; p = 0.0263) and significantly reducing treatment side effects by 47% (RR 0.53 [0.37; 0.77]; p = 0.0009). Other studies support further investigation into this probiotic for oral candidiasis, eczema, feeding intolerance in premature babies, or hyperbilirubinemia in newborns.
Hepatitis C Virus Glycan-Dependent Interactions and the Potential for Novel Preventative Strategies
Authors: LeBlanc Emmanuelle V. , Kim Youjin , Capicciotti Chantelle J. , Colpitts Che C.
Published: June 2021

Chronic hepatitis C virus (HCV) infections continue to be a major contributor to liver disease worldwide. HCV treatment has become highly effective, yet there are still no vaccines or prophylactic strategies available to prevent infection and allow effective management of the global HCV burden. Glycan-dependent interactions are crucial to many aspects of the highly complex HCV entry process, and also modulate immune evasion. This review provides an overview of the roles of viral and cellular glycans in HCV infection and highlights glycan-focused advances in the development of entry inhibitors and vaccines to effectively prevent HCV infection.
Unusual Presentation of Feline Leprosy Caused by Mycobacterium lepraemurium in the Alpine Region
Authors: Ghielmetti Giovanni , Schmitt Sarah , Friedel Ute , Guscetti Franco , Walser-Reinhardt Ladina
Published: June 2021

A 9-year-old cat was referred with multiple, raised, ulcerative and non-ulcerative nodules in the periocular area, sclera and ear-base region, and on the ventral aspect of the tongue. In addition, a progressive ulcerative skin nodule on the tail was observed. Fine-needle aspirations of multiple nodules from the eyelid and sclera revealed the presence of histiocytes with numerous acid-fast intracellular bacilli. The replication of slowly growing mycobacteria in liquid media was detected from biopsied nodules after three months of incubation. The molecular characterization of the isolate identified Mycobacterium (M.) lepraemurium as the cause of the infection. The cat was treated with a combination of surgical excision and a four-week course of antimicrobial therapy including rifampicin combined with clarithromycin. This is an unusual manifestation of feline leprosy and the first molecularly confirmed M. lepraemurium infection in a cat with ocular involvement in Europe. The successful combination of a surgical and antimycobacterial treatment regimen is reported.
Evaluation of a Novel CLIA Monotest Assay for the Detection of Anti-Hepatitis E Virus-IgG and IgM: A Retrospective Comparison with a Line Blot and an ELISA
Authors: Dichtl Karl , Zimmermann Julia , Koeppel Martin B. , Böhm Stephan , Osterman Andreas
Published: June 2021

Despite the increasing relevance of Hepatitis E, an emerging disease endemic in developing and with increasing numbers of sporadic cases in industrialized countries, commercial tests are mainly based on batch oriented serological assays. In this retrospective study, we compared a line immunoassay (LIA; recomLine HEV, Mikrogen) and an ELISA (EIA; Anti-Hepatitis E Virus ELISA, Euroimmun) with a novel chemoluminescence immunoassay in a monotest format (CLIA; Hepatitis E VirClia, Vircell). Twenty sera of PCR proven cases of hepatitis E and 68 blood samples serologically pre-characterized were included. Applying the WHO reference standard, the CLIA demonstrated the highest analytical sensitivity for IgG and IgM. The combinations of CLIA/EIA (IgG and IgM) and CLIA/LIA (IgG) measurements showed substantial correlation. Compared to overall antibody detection (seropositivity in ≥2 assays), CLIA correlation was excellent, outperforming LIA (IgM) and EIA (IgG and IgM). Minor IgM cross reactivity in samples of patients with acute EBV infection was observed in all three assays. The CLIA showed good performance in diagnostic samples compared to established LIA and EIA assays. Due to its ready-to-use monotest format, the CLIA allows simple, time- and cost-effective handling of single samples. These qualities make the assay suitable for diagnostics, especially in the emergency setting and for low-throughput laboratories.
Molecular Characterization of German Acinetobacter baumannii Isolates and Multilocus Sequence Typing (MLST) Analysis Based on WGS Reveals Novel STs
Authors: Wareth Gamal , Linde Jörg , Hammer Philipp , Splettstoesser Wolf D. , Pletz Mathias W. , Neubauer Heinrich , Sprague Lisa D.
Published: June 2021

Acinetobacter baumannii (A. baumannii) is a major cause of severe nosocomial infections worldwide. The emergence of infections associated with A. baumannii poses a significant health risk in Germany. A. baumannii is part of the ACB complex and is difficult to distinguish from other species phenotypically, necessitating its reliable identification. The current study analyzed 89 A. baumannii strains from human and non-human origins by matrix-assisted laser desorption/ionization (MALDI–TOF) and PCR detection of intrinsic blaOXA-51-like carbapenemase, blaOXA-23-like, blaOXA-24-like, blaOXA-58-like, and ISAba 1 genes. Whole-genome sequencing (WGS) was applied for species confirmation and strain type determination. Combining the molecular detection of the intrinsic blaOXA-51-like carbapenemase gene together with MALDI–TOF with a score value of >2.300 proved to be a suitable tool for A. baumannii identification. WGS data for all of the sequenced strains confirmed the identity of all A. baumannii strains. The Pasteur scheme successfully assigned 79.7% of the strains into distinct STs, while the Oxford scheme succeeded in allocating only 42.7% of isolates. Multilocus sequence typing (MLST) analysis based on the Pasteur scheme identified 16 STs. ST/241 was the most prevalent in samples from non-human origin, whereas ST/2 was predominant in human samples. Furthermore, eight isolates of non-human origin were allocated to seven new STs (ST/1410, ST/1414, ST/1416, ST/1417, ST/1418, ST/1419, and ST/1421). Ten isolates from non-human origin could not be typed since new alleles were observed in the loci Pas_cpn60, Pas_rpoB, and Pas_gltA. MLST analysis based on the Pasteur scheme was more appropriate than the Oxford scheme for the current group of A. baumannii.
Elucidating the Local Transmission Dynamics of Highly Pathogenic Avian Influenza H5N6 in the Republic of Korea by Integrating Phylogenetic Information
Authors: Yoo Dae-Sung , Chun Byungchul , Min Kyung-Duk , Lim Jun-Sik , Moon Oun-Kyoung , Lee Kwang-Nyeong
Published: June 2021

Highly pathogenic avian influenza (HPAI) virus is one of the most virulent and infectious pathogens of poultry. As a response to HPAI epidemics, veterinary authorities implement preemptive depopulation as a controlling strategy. However, mass culling within a uniform radius of the infection site can result in unnecessary depopulation. Therefore, it is useful to quantify the transmission distance from infected premises (IPs) before determining the optimal area for preemptive depopulation. Accordingly, we analyzed the transmission risk within spatiotemporal clusters of IPs using transmission kernel estimates derived from phylogenetic clustering information on 311 HPAI H5N6 IPs identified during the 2016–2017 epidemic, Republic of Korea. Subsequently, we explored the impact of varying the culling radius on the local transmission of HPAI given the transmission risk estimates. The domestic duck farm density was positively associated with higher transmissibility. Ring culling over a radius of 3 km may be effective for areas with high dense duck holdings, but this approach does not appear to significantly reduce the risk for local transmission in areas with chicken farms. This study provides the first estimation of the local transmission dynamics of HPAI in the Republic of Korea as well as insight into determining an effective ring culling radius.
Description and Analysis of Cytokine Storm in Registered COVID-19 Clinical Trials: A Systematic Review
Authors: Eljaaly Khalid , Malibary Husam , Alsulami Shaimaa , Albanji Muradi , Badawi Mazen , Al-Tawfiq Jaffar A.
Published: June 2021

The purpose of this systematic review was to describe the characteristics of clinical trials that focused on COVID-19 patients with cytokine release syndrome (CRS) and the variability in CRS definitions. Two authors independently searched three clinical trial registries and included interventional clinical trials on COVID-19 hospitalized patients that required at least one elevated inflammatory biomarker. Relevant data, including the type and cutoff of the measured biomarker, oxygen/respiratory criteria, fever, radiologic criteria, and medications, were summarized. A total of 47 clinical trials were included. The included studies considered the following criteria: oxygen/respiratory criteria in 42 trials (89%), radiologic criteria in 29 trials (62%), and fever in 6 trials (18%). Serum ferritin was measured in 35 trials (74%), CRP in 34 trials (72%), D-dimer in 26 trials (55%), LDH in 24 trials (51%), lymphocyte count in 14 trials (30%), and IL-6 in 8 trials (17%). The cutoff values were variable for the included biomarkers. The most commonly used medications were tocilizumab, in 15 trials (32%), and anakinra in 10 trials (24.4%). This systematic review found high variability in CRS definitions and associated biomarker cutoff values in COVID-19 clinical trials. We call for a standardized definition of CRS, especially in COVID-19 patients.
New Quality-Range-Setting Method Based on Between- and Within-Batch Variability for Biosimilarity Assessment
Authors: Oliva Alexis , Llabrés Matías
Published: June 2021

Analytical biosimilarity assessment relies on two implicit conditions. First, the analytical method must meet a set of requirements known as fit for intended use related to trueness and precision. Second, the manufacture of the reference drug product must be under statistical quality control; i.e., the between-batch variability is not larger than the expected within-batch variability. In addition, the quality range (QR) method is based on one sample per batch to avoid biased standard deviations in unbalanced studies. This, together with the small number of reference drug product batches, leads to highly variable QR bounds. In this paper, we propose to set the QR bounds from variance components estimated using a two-level nested linear model, accounting for between- and within-batch variances of the reference drug product. In this way, the standard deviation used to set QR is equal to the square root of the sum of between-batch variance plus the within-batch variance estimated by the maximum likelihood method. The process of this method, which we call QRML, is as follows. First, the condition of statistical quality control of the manufacture process is tested. Second, confidence intervals for QR bounds lead to an analysis of the reliability of the biosimilarity assessment. Third, after analyzing the molecular weight and dimer content of seven batches of a commercial bevacizumab drug product, we concluded that the QRML method was more reliable than QR.
Inherent and Stress-Induced Responses of Fine Root Morphology and Anatomy in Commercial Grapevine Rootstocks with Contrasting Drought Resistance
Authors: Reingwirtz Idan , Uretsky Jake , Cuneo Italo F. , Knipfer Thorsten , Reyes Clarissa , Walker M. Andrew , McElrone Andrew J.
Published: June 2021

Some grapevine rootstocks perform better than others during and after drought events, yet it is not clear how inherent and stress-induced differences in root morphology and anatomy along the length of fine roots are involved in these responses. Using a variety of growing conditions and plant materials, we observed significant differences in root diameter, specific root length (SRL) and root diameter distribution between two commonly used commercial grapevine rootstocks: Richter 110 (110R; drought resistant) and Millardet et de Grasset 101-14 (101-14Mgt; drought sensitive). The 110R consistently showed greater root diameters with smaller SRL and proportion of root length comprised of fine lateral roots. The 110R also exhibited significantly greater distance from tip to nearest lateral, longer white root length, and larger proportion of root length that is white under drought stress. Mapping of fine root cortical lacunae showed similar patterns between the rootstocks; mechanical failure of cortical cells was common in the maturation zone, limited near the root tip, and increased with drought stress for both genotypes; however, lacuna formed under wetter soil conditions in 110R. Results suggest that drought resistance in grapevine rootstocks is associated with thick, limitedly branched roots with a larger proportion of white-functional roots that tend to form lacuna under more mild water deficit, all of which likely favor continued resource acquisition at depth.
Topical Gynura procumbens as a Novel Therapeutic Improves Wound Healing in Diabetic Mice
Authors: Sutthammikorn Nutda , Supajatura Volaluck , Yue Hainan , Takahashi Miho , Chansakaow Sunee , Nakano Nobuhiro , Song Pu , Ogawa Takasuke , Ikeda Shigaku , Okumura Ko , Ogawa Hideoki , Niyonsaba François
Published: June 2021

Nonhealing wounds are major socioeconomic challenges to healthcare systems worldwide. Therefore, there is a substantially unmet need to develop new drugs for wound healing. Gynura procumbens, a herb found in Southeast Asia, may be an effective therapeutic for nonhealing diabetic wounds. The aim of this study was to evaluate the efficacy of G. procumbens on wound healing in the diabetic milieu. G. procumbens extract was obtained using 95% ethanol and its components were determined by thin layer chromatography. Diabetes was induced in mice using streptozotocin. We found that G. procumbens extract contained stigmasterol, kaempferol and quercetin compounds. Topical application of G. procumbens on the wounded skin of diabetic mice accelerated wound healing and induced the expression of angiogenin, epidermal growth factor, fibroblast growth factor, transforming growth factor and vascular endothelial growth factor. Furthermore, G. procumbens promoted in vitro wound healing and enhanced the migration and/or proliferation of human endothelial cells, fibroblasts, keratinocytes and mast cells cultured in diabetic conditions. Finally, G. procumbens promoted vascular formation in the diabetic mice. To the best of our knowledge, this is the first study that evaluates in vivo wound healing activities of G. procumbens and activation of cells involved in wound healing process in diabetic conditions. The findings that G. procumbens accelerates wound healing and activates cells involved in the wound healing process suggest that G. procumbens might be an effective alternative therapeutic option for nonhealing diabetic wounds.
Quality Attributes and Storage of Tomato Fruits as Affected by an Eco-Friendly, Essential Oil-Based Product
Authors: Xylia Panayiota , Ioannou Irene , Chrysargyris Antonios , Stavrinides Menelaos C. , Tzortzakis Nikolaos
Published: June 2021

The preservation of fresh produce quality is a major aim in the food industry since consumers demand safe and of high nutritional value products. In recent decades there has been a turn towards the use of eco-friendly, natural products (i.e., essential oils-EOs) in an attempt to reduce chemical-based sanitizing agents (i.e., chlorine and chlorine-based agents). The aim of this study was to evaluate the efficacy of an eco-friendly product (EP—based on rosemary and eucalyptus essential oils) and two different application methods (vapor and dipping) on the quality attributes of tomato fruits throughout storage at 11 °C and 90% relative humidity for 14 days. The results indicated that overall, the EP was able to maintain the quality of tomato fruits. Dipping application was found to affect less the quality attributes of tomato, such as titratable acidity, ripening index and antioxidant activity compared to the vapor application method. Vapor application of 0.4% EP increased fruit’s antioxidant activity, whereas tomatoes dipped in EP solution presented decreased damage index (hydrogen peroxide and lipid peroxidation levels), activating enzymes antioxidant capacity (catalases and peroxidases). Moreover, higher EP concentration (up to 0.8%) resulted in a less acceptable product compared to lower concentration (0.4%). Overall, the results from the present study suggest that the investigated EP can be used for the preservation of fresh produce instead of the current commercial sanitizing agent (chlorine); however, the method of application and conditions of application must be further assessed for every commodity tested.
The Importance of Synthesis and Characterization of Biomedical Materials for the Current State of Medicine and Dentistry
Authors: Dobrzański Leszek A. , Dobrzańska-Danikiewicz Anna D. , Dobrzański Lech B. , Dobrzańska Joanna
Published: June 2021

From time immemorial to the present day, health has been considered to be of the highest value [...]
Feasibility Analyses of Real-Time Detection of Wildlife Using UAV-Derived Thermal and RGB Images
Authors: Lee Seunghyeon , Song Youngkeun , Kil Sung-Ho
Published: June 2021

Wildlife monitoring is carried out for diverse reasons, and monitoring methods have gradually advanced through technological development. Direct field investigations have been replaced by remote monitoring methods, and unmanned aerial vehicles (UAVs) have recently become the most important tool for wildlife monitoring. Many previous studies on detecting wild animals have used RGB images acquired from UAVs, with most of the analyses depending on machine learning–deep learning (ML–DL) methods. These methods provide relatively accurate results, and when thermal sensors are used as a supplement, even more accurate detection results can be obtained through complementation with RGB images. However, because most previous analyses were based on ML–DL methods, a lot of time was required to generate training data and train detection models. This drawback makes ML–DL methods unsuitable for real-time detection in the field. To compensate for the disadvantages of the previous methods, this paper proposes a real-time animal detection method that generates a total of six applicable input images depending on the context and uses them for detection. The proposed method is based on the Sobel edge algorithm, which is simple but can detect edges quickly based on change values. The method can detect animals in a single image without training data. The fastest detection time per image was 0.033 s, and all frames of a thermal video could be analyzed. Furthermore, because of the synchronization of the properties of the thermal and RGB images, the performance of the method was above average in comparison with previous studies. With target images acquired at heights below 100 m, the maximum detection precision and detection recall of the most accurate input image were 0.804 and 0.699, respectively. However, the low resolution of the thermal sensor and its shooting height limitation were hindrances to wildlife detection. The aim of future research will be to develop a detection method that can improve these shortcomings.