bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting the DEAD-Box RNA Helicase eIF4A with Rocaglates—A Pan-Antiviral Strategy for Minimizing the Impact of Future RNA Virus Pandemics
Authors: Taroncher-Oldenburg Gaspar , Müller Christin , Obermann Wiebke , Ziebuhr John , Hartmann Roland K. , Grünweller Arnold
Published: March 2021

The increase in pandemics caused by RNA viruses of zoonotic origin highlights the urgent need for broad-spectrum antivirals against novel and re-emerging RNA viruses. Broad-spectrum antivirals could be deployed as first-line interventions during an outbreak while virus-specific drugs and vaccines are developed and rolled out. Viruses depend on the host’s protein synthesis machinery for replication. Several natural compounds that target the cellular DEAD-box RNA helicase eIF4A, a key component of the eukaryotic translation initiation complex eIF4F, have emerged as potential broad-spectrum antivirals. Rocaglates, a group of flavaglines of plant origin that clamp mRNAs with highly structured 5′ untranslated regions (5′UTRs) onto the surface of eIF4A through specific stacking interactions, exhibit the largest selectivity and potential therapeutic indices among all known eIF4A inhibitors. Their unique mechanism of action limits the inhibitory effect of rocaglates to the translation of eIF4A-dependent viral mRNAs and a minor fraction of host mRNAs exhibiting stable RNA secondary structures and/or polypurine sequence stretches in their 5′UTRs, resulting in minimal potential toxic side effects. Maintaining a favorable safety profile while inducing efficient inhibition of a broad spectrum of RNA viruses makes rocaglates into primary candidates for further development as pan-antiviral therapeutics.
The ldhA Gene Encoding Fermentative l-Lactate Dehydrogenase in Corynebacterium Glutamicum Is Positively Regulated by the Global Regulator GlxR
Authors: Toyoda Koichi , Inui Masayuki
Published: March 2021

Bacterial metabolism shifts from aerobic respiration to fermentation at the transition from exponential to stationary growth phases in response to limited oxygen availability. Corynebacterium glutamicum, a Gram-positive, facultative aerobic bacterium used for industrial amino acid production, excretes l-lactate, acetate, and succinate as fermentation products. The ldhA gene encoding l-lactate dehydrogenase is solely responsible for l-lactate production. Its expression is repressed at the exponential phase and prominently induced at the transition phase. ldhA is transcriptionally repressed by the sugar-phosphate-responsive regulator SugR and l-lactate-responsive regulator LldR. Although ldhA expression is derepressed even at the exponential phase in the sugR and lldR double deletion mutant, a further increase in its expression is still observed at the stationary phase, implicating the action of additional transcription regulators. In this study, involvement of the cAMP receptor protein-type global regulator GlxR in the regulation of ldhA expression was investigated. The GlxR-binding site found in the ldhA promoter was modified to inhibit or enhance binding of GlxR. The ldhA promoter activity and expression of ldhA were altered in proportion to the binding affinity of GlxR. Similarly, l-lactate production was also affected by the binding site modification. Thus, GlxR was demonstrated to act as a transcriptional activator of ldhA.
Young at Gut—Turning Back the Clock with the Gut Microbiome
Authors: Narasimhan Harish , Ren Clarissa C. , Deshpande Sharvari , Sylvia Kristyn E.
Published: March 2021

Over the past century, we have witnessed an increase in life-expectancy due to public health measures; however, we have also seen an increase in susceptibility to chronic disease and frailty. Microbiome dysfunction may be linked to many of the conditions that increase in prevalence with age, including type 2 diabetes, cardiovascular disease, Alzheimer’s disease, and cancer, suggesting the need for further research on these connections. Moreover, because both non-modifiable (e.g., age, sex, genetics) and environmental (e.g., diet, infection) factors can influence the microbiome, there are vast opportunities for the use of interventions related to the microbiome to promote lifespan and healthspan in aging populations. To understand the mechanisms mediating many of the interventions discussed in this review, we also provide an overview of the gut microbiome’s relationships with the immune system, aging, and the brain. Importantly, we explore how inflammageing (low-grade chronic inflammation that often develops with age), systemic inflammation, and senescent cells may arise from and relate to the gut microbiome. Furthermore, we explore in detail the complex gut–brain axis and the evidence surrounding how gut dysbiosis may be implicated in several age-associated neurodegenerative diseases. We also examine current research on potential interventions for healthspan and lifespan as they relate to the changes taking place in the microbiome during aging; and we begin to explore how the reduction in senescent cells and senescence-associated secretory phenotype (SASP) interplay with the microbiome during the aging process and highlight avenues for further research in this area.
Stratigraphic Variations of Fe–Mn Micronodules and Implications for the Formation of Extremely REY-Rich Mud in the Western North Pacific Ocean
Authors: Yasukawa Kazutaka , Kino Satoshi , Ohta Junichiro , Azami Keishiro , Tanaka Erika , Mimura Kazuhide , Fujinaga Koichiro , Nakamura Kentaro , Kato Yasuhiro
Published: March 2021

The origin of deep-sea sediments in the western North Pacific Ocean, which are significantly enriched in rare-earth elements and yttrium (REY), and its paleoceanographic implications have been poorly constrained. Here, we investigated stratigraphic variations in the chemical compositions and textures of ferromanganese (Fe–Mn) micronodules separated from western North Pacific sediments. The characteristics of the micronodules of an extremely REY-rich mud layer vary from almost purely diagenetic to relatively hydrogenetic. This indicates the abundant supply of organic matter to the sediment together with fish debris that accumulates REY at the onset of the REY-enrichment of the mud, followed by the exposure of the seafloor to oxic water masses during the latter half of the formation of the REY-rich mud. These results support a previously proposed formation mechanism based on which enhanced bottom water currents caused pelagic fish proliferation via the upwelling of nutrients and fish debris was physically sorted and selectively accumulated on the seafloor. After the main REY-enrichment, the micronodules exhibit varying diagenetic signatures, suggesting changes in the bottom current intensities after the main REY-enrichment. However, the bulk REY contents do not increase. This implies that a sufficient increase in the fish productivity is an essential factor affecting the formation of REY-rich mud.
A Mero-Plesiotype Series of Vanadates, Arsenates, and Phosphates with Blocks Based on Densely Packed Octahedral Layers as Repeating Modules
Authors: Yakubovich Olga , Kiriukhina Galina
Published: March 2021

The family of layered vanadates, arsenates, and phosphates is discussed in terms of a modular concept. The group includes minerals vésignéite and bayldonite, and a number of synthetic analogous and modifications which are not isotypic, but their crystal structures comprise similar blocks (modules) consisting of a central octahedral layer filled by atoms of d elements (Mn, Ni, Cu, or Co) and adjacent [VO4], [AsO4], or [PO4] tetrahedra. The octahedral layers are based on the close-packing of oxygen atoms. Within these layers having the same anionic substructure, the number and distribution of octahedral voids are different. In the crystal structures of compounds participating in the polysomatic series, these blocks alternate with various other structural fragments. These circumstances define the row of structurally-related vanadates, arsenates, and phosphates as a mero-plesiotype series. Most of the series members exhibit magnetic properties, representing two-dimensional antiferromagnets or frustrated magnets.
Selected Elements in the Soils Covering Mass Graves from World Wars I and II in Southeastern Poland
Authors: Żychowski Józef
Published: March 2021

This study evaluates the reasons for the different content of eight selected elements, Cu, Pb, Zn, S, K, Na, Ca and P, in the upper sections of soil profiles covering mass graves in southeastern Poland. The burial sites include 18 mass graves from World Wars I and II, an active parish cemetery, an old kirkut (Jewish cemetery) and, as a comparative site, a forest nursery. Chemical analyses were carried out using atomic absorption spectroscopy. Among the elements were P and Ca, which dominate in the soils covering the burial sites from World War II. Higher amounts of the elements analysed were found at sites where many people were buried in a small area. The burial sites dug in pure sand revealed a lower content of the elements analysed, particularly Ca and P. In places where human ashes were scattered, Ca and P prevailed. The comparative site, a wet forest margin, is characterized by low levels of S and relatively higher amounts of Ca and P. In the soils covering World War I graves P, in particular, prevails over Zn, Pb and Cu. Differences in the concentrations of the elements studied depend on the type and age of the burial site, the type of soil, the slope gradient and water content prevailing at the site and the proximity to mass graves and cemeteries found close to each other.
Adsorption Studies of Waterborne Trihalomethanes Using Modified Polysaccharide Adsorbents
Authors: Guo Rui , Bharadwaj Lalita , Wilson Lee D.
Published: March 2021

The adsorptive removal of trihalomethanes (THMs) from spiked water samples was evaluated with a series of modified polysaccharide adsorbents that contain β-cylodextrin or chitosan. The uptake properties of these biodegradable polymer adsorbents were evaluated with a mixture of THMs in aqueous solution. Gas chromatography employing a direct aqueous injection (DAI) method with electrolytic conductivity detection enabled quantification of THMs in water at 295 K and at pH 6.5. The adsorption isotherms for the polymer-THMs was evaluated using the Sips model, where the monolayer adsorption capacities ranged between 0.04 and 1.07 mmol THMs/g for respective component THMs. Unique adsorption characteristics were observed that vary according to the polymer structure, composition, and surface chemical properties. The modified polysaccharide adsorbents display variable molecular recognition and selectivity toward component THMs in the mixed systems according to the molecular size and polarizability of the adsorbates.
Enzymatically Extracted Apple Pectin Possesses Antioxidant and Antitumor Activity
Authors: Wikiera Agnieszka , Grabacka Maja , Byczyński Łukasz , Stodolak Bożena , Mika Magdalena
Published: March 2021

The biological activity of apple pectin extracted conventionally or enzymatically using endo-xylanase and endo-cellulase, was tested in vitro. The analyses were performerd in tetraplicates and the statistical significance of the differences were assessed using ANOVA, Tukey post hoc and LSD (the least significant difference) tests. Multivariate regression analysis was applied to determine the structural components that have a crucial importance for antioxidant and antitumor properties of pectins. The pectins extracted by enzymes contained up to four times more ferulic acid and showed twice as great ability to neutralize free radicals and Fe(III) reduction. The antiradical potential positively correlated with phenols, fucose and rhamnose content. In the assays performed on HT-29 human adenocarcinoma and B16F10 melanoma cell cultures, the “green” pectins, contrary to acid isolated ones, exhibited remarkable anti-neoplastic potential while being nontoxic to nontransformed L929 cell line. The pectins in the dose of 1 mg/mL were capable of inhibiting adhesion (max 23.1%), proliferation (max 40.4%), invasion (max 76.9%) and anchorage-independent growth (max 90%) of HT-29 cells (significance level p < 0.001). These pectin preparations were slightly less active towards B16F10 cells. The enzyme-isolated apple pectins may be useful as a functional food additive and an ingredient of the ointment formulas for post-surgical melanoma treatment.
The Complex Structure of Protein AaLpxC from Aquifex aeolicus with ACHN-975 Molecule Suggests an Inhibitory Mechanism at Atomic-Level against Gram-Negative Bacteria
Authors: Fan Shuai , Li Danyang , Yan Maocai , Feng Xiao , Lv Guangxin , Wu Guangteng , Jin Yuanyuan , Wang Yucheng , Yang Zhaoyong
Published: March 2021

New drugs with novel antibacterial targets for Gram-negative bacterial pathogens are desperately needed. The protein LpxC is a vital enzyme for the biosynthesis of lipid A, an outer membrane component of Gram-negative bacterial pathogens. The ACHN-975 molecule has high enzymatic inhibitory capacity against the infectious diseases, which are caused by multidrug-resistant bacteria, but clinical research was halted because of its inflammatory response in previous studies. In this work, the structure of the recombinant UDP-3-O-(R-3-hydroxymyristol)-N-acetylglucosamine deacetylase from Aquifex aeolicus in complex with ACHN-975 was determined to a resolution at 1.21 Å. According to the solved complex structure, ACHN-975 was docked into the AaLpxC’s active site, which occupied the site of AaLpxC substrate. Hydroxamate group of ACHN-975 forms five-valenced coordination with resides His74, His226, Asp230, and the long chain part of ACHN-975 containing the rigid alkynyl groups docked in further to interact with the hydrophobic area of AaLpxC. We employed isothermal titration calorimetry for the measurement of affinity between AaLpxC mutants and ACHN-975, and the results manifest the key residues (His74, Thr179, Tyr212, His226, Asp230 and His253) for interaction. The determined AaLpxC crystal structure in complex with ACHN-975 is expected to serve as a guidance and basis for the design and optimization of molecular structures of ACHN-975 analogues to develop novel drug candidates against Gram-negative bacteria.
One-Pot Synthesis of Novel Multisubstituted 1-Alkoxyindoles
Authors: Kim Ye Eun , Cho Hyunsung , Lim Yoo Jin , Kim Chorong , Lee Sang Hyup
Published: March 2021

Studies on a one-pot synthesis of novel multisubstituted 1-alkoxyindoles 1 and their mechanistic investigations are presented. The synthesis of 1 was successfully achieved through consecutive four step reactions from substrates 2. The substrates 2, prepared through a two-step synthetic sequence, underwent three consecutive reactions of nitro reduction, intramolecular condensation, and nucleophilic 1,5-addition to provide the intermediates, 1-hydroxyindoles 8, which then were alkylated in situ with alkyl halide to afford the novel target products 1. We optimized the reaction conditions for 1 focusing on the alkylation step, along with the consideration of formation of intermediates 8. The optimized condition was SnCl2·2H2O (3.3 eq) and alcohols (R1OH, 2.0 eq) for 1–2 h at 40 °C and then, base (10 eq) and alkyl halides (R2Y, 2.0 eq) for 1–4 h at 25–50 °C. Notably, all four step reactions were performed in one-pot to give 1 in good to modest yields. Furthermore, the mechanistic aspects were also discussed regarding the reaction pathways and the formation of side products. The significance lies in development of efficient one-pot reactions and in generation of new 1-alkoxyindoles.
Effect of Viscosity on the Formation of Porous Polydimethylsiloxane for Wearable Device Applications
Authors: Baek Dong-Hyun , Jung Hachul , Kim Jeong Hun , Park Young Wook , Kim Dae Wook , Kim Ho Seob , Ahn Seungjoon , Kim Young-Jin
Published: March 2021

Medical devices, which enhance the quality of life, have experienced a gradual increase in demand. Various research groups have attempted to incorporate soft materials such as skin into wearable devices. We developed a stretchable substrate with high elasticity by forming a porous structure on polydimethylsiloxane (PDMS). To optimize the porous structure, we propose a manufacturing process that utilizes a high-pressure steam with different viscosities (400, 800, 2100, and 3000 cP) of an uncured PDMS solution. The proposed method simplifies the manufacturing of porous structures and is cost-effective compared to other technologies. Porous structures of various viscosities were formed, and their electrical and mechanical properties evaluated. Porous PDMS (3000 cP) was formed in a sponge-like three-dimensional porous structure, compared to PDMS formed by other viscosities. The elongation of porous PDMS (3000 cP) was increased by up to 30%, and the relative resistance changed to less than 1000 times with the maximum strain test. The relative resistance increased the initial resistance (R0) by approximately 10 times during the 1500-times repeated cycling tests with 30% strain. As a result, patch-type wearable devices based on soft materials can provide an innovative platform that can connect with the human skin for robotics applications and for continuous health monitoring.
Reduced Graphene Oxide Inserted into PEDOT:PSS Layer to Enhance the Electrical Behaviour of Light-Emitting Diodes
Authors: Rodríguez-Mas Fernando , Ferrer Juan Carlos , Alonso José Luis , Fernández de Ávila Susana , Valiente David
Published: March 2021

In this study, poly(9-vinylcarbazole) (PVK)-based LEDs doped with reduced graphene oxide (rGO) and cadmium sulphide (CdS) nanocrystals were fabricated by spin-coating. The hybrid LED structure was a layer sequence of glass/indium tin oxide (ITO)/PEDOT:PSS|rGO/PVK/Al. rGO was included in the poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) layer due to its energy bands being close to PEDOT:PSS bands, and the possibility of using water for dispersing both polymer and flakes. Optical properties such as photoluminescence and UV-Vis absorption were not affected by the addition of rGO to the PEDOT:PSS solution. However, PVK-based LEDs with rGO showed increased current density compared to those without rGO in the hole transporting layer. Higher electroluminescence intensities were observed for rGO-enriched LEDs, although the shape of the spectrum was not modified. LEDs including CdS nanocrystals in the poly(9-vinylcarbazole) emissive layer did not show such dependence on the rGO presence. Though the addition of rGO to PEDOT:PSS still produces a slightly higher current density in CdS doped LEDs, this growth is no longer proportional to the rGO load.
Green Synthesis of Iron Nanoparticles Using Green Tea and Its Removal of Hexavalent Chromium
Authors: Hao Runqin , Li Dong , Zhang Jie , Jiao Tifeng
Published: March 2021

Chromium (VI) is a ubiquitous groundwater contaminant and it is dangerous to both ecological and human health. Iron nanoparticles (nFe) have a large specific surface area and they are highly efficient in removing chromium (VI) from aqueous solution. However, since the traditional reductive synthesis of nFe is relatively expensive and often causes secondary pollution, it is necessary to develop a low-cost green synthetic method using plant extracts. Synthetic conditions are important for obtaining highly active chromium-removing nanomaterials. In this paper, a green tea extract was used to prepare nFe and the effects of synthetic conditions on subsequent remediation performance were investigated. The optimal conditions included a green tea extract/Fe2+ ratio of 1:2 (91.6%), a green tea extract temperature of 353 K (88.3%) and a synthetic temperature of 298 K (88.1%). Advanced material characterization techniques, including XPS, SEM-EDS, TEM, and Brunauer–Emmett–Teller (BET) confirmed that the average particle size was between 50–80 nm, with a specific surface area of 42.25 m2·g−1. Furthermore nFe had a core-shell structure, where Fe (0) constituted the core and a shell was composed of iron oxide. Finally, a mechanism for synthesizing nFe by green tea extract was proposed, providing a theoretical basis for optimized synthetic conditions for preparing nFe when using green tea extract.
Antibacterial Activity of Positively and Negatively Charged Hematite (α-Fe2O3) Nanoparticles to Escherichia coli, Staphylococcus aureus and Vibrio fischeri
Authors: Vihodceva Svetlana , Šutka Andris , Sihtmäe Mariliis , Rosenberg Merilin , Otsus Maarja , Kurvet Imbi , Smits Krisjanis , Bikse Liga , Kahru Anne , Kasemets Kaja
Published: March 2021

In the current study, the antibacterial activity of positively and negatively charged spherical hematite (α-Fe2O3) nanoparticles (NPs) with primary size of 45 and 70 nm was evaluated against clinically relevant bacteria Escherichia coli (gram-negative) and Staphylococcus aureus (gram-positive) as well as against naturally bioluminescent bacteria Vibrio fischeri (an ecotoxicological model organism). α-Fe2O3 NPs were synthesized using a simple green hydrothermal method and the surface charge was altered via citrate coating. To minimize the interference of testing environment with NP’s physic-chemical properties, E. coli and S. aureus were exposed to NPs in deionized water for 30 min and 24 h, covering concentrations from 1 to 1000 mg/L. The growth inhibition was evaluated following the postexposure colony-forming ability of bacteria on toxicant-free agar plates. The positively charged α-Fe2O3 at concentrations from 100 mg/L upwards showed inhibitory activity towards E. coli already after 30 min of contact. Extending the exposure to 24 h caused total inhibition of growth at 100 mg/L. Bactericidal activity of positively charged hematite NPs against S. aureus was not observed up to 1000 mg/L. Differently from positively charged hematite NPs, negatively charged citrate-coated α-Fe2O3 NPs did not exhibit any antibacterial activity against E. coli and S. aureus even at 1000 mg/L. Confocal laser scanning microscopy and flow cytometer analysis showed that bacteria were more tightly associated with positively charged α-Fe2O3 NPs than with negatively charged citrate-coated α-Fe2O3 NPs. Moreover, the observed associations were more evident in the case of E. coli than S. aureus, being coherent with the toxicity results. Vibrio fischeri bioluminescence inhibition assays (exposure medium 2% NaCl) and colony forming ability on agar plates showed no (eco)toxicity of α-Fe2O3 (EC50 and MBC > 1000 mg/L).
Effects of Annealing Temperature on the Oxygen Evolution Reaction Activity of Copper–Cobalt Oxide Nanosheets
Authors: Kim Geul Han , Park Yoo Sei , Yang Juchan , Jang Myeong Je , Jeong Jaehoon , Lee Ji-Hoon , Park Han-Saem , Park Yong Ho , Choi Sung Mook , Lee Jooyoung
Published: March 2021

Developing high performance, highly stable, and low-cost electrodes for the oxygen evolution reaction (OER) is challenging in water electrolysis technology. However, Ir- and Ru-based OER catalysts with high OER efficiency are difficult to commercialize as precious metal-based catalysts. Therefore, the study of OER catalysts, which are replaced by non-precious metals and have high activity and stability, are necessary. In this study, a copper–cobalt oxide nanosheet (CCO) electrode was synthesized by the electrodeposition of copper–cobalt hydroxide (CCOH) on Ni foam followed by annealing. The CCOH was annealed at various temperatures, and the structure changed to that of CCO at temperatures above 250 °C. In addition, it was observed that the nanosheets agglomerated when annealed at 300 °C. The CCO electrode annealed at 250 °C had a high surface area and efficient electron conduction pathways as a result of the direct growth on the Ni foam. Thus, the prepared CCO electrode exhibited enhanced OER activity (1.6 V at 261 mA/cm2) compared to those of CCOH (1.6 V at 144 mA/cm2), Co3O4 (1.6 V at 39 mA/cm2), and commercial IrO2 (1.6 V at 14 mA/cm2) electrodes. The optimized catalyst also showed high activity and stability under high pH conditions, demonstrating its potential as a low cost, highly efficient OER electrode material.
Investigation on the Mass Distribution and Chemical Compositions of Various Ionic Liquids-Extracted Coal Fragments and Their Effects on the Electrochemical Performance of Coal-Derived Carbon Nanofibers (CCNFs)
Authors: Tan Shuai , Kraus Theodore , Helling Mitchell , Mignon Rudolph , Basile Franco , Li-Oakey Katie
Published: March 2021

Coal-derived carbon nanofibers (CCNFs) have been recently found to be a promising and low-cost electrode material for high-performance supercapacitors. However, the knowledge gap still exists between holistic understanding of coal precursors derived from different solvents and resulting CCNFs’ properties, prohibiting further optimization of their electrochemical performance. In this paper, assisted by laser desorption/ionization (LDI) and gas chromatography–mass spectrometry (GC–MS) technologies, a systematic study was performed to holistically characterize mass distribution and chemical composition of coal precursors derived from various ionic liquids (ILs) as extractants. Sequentially, X-ray photoelectron spectroscopy (XPS) revealed that the differences in chemical properties of various coal products significantly affected the surface oxygen concentrations and certain species distributions on the CCNFs, which, in turn, determined the electrochemical performances of CCNFs as electrode materials. We report that the CCNF that was produced by an oxygen-rich coal fragment from C6mimCl ionic liquid extraction showed the highest concentrations of quinone and ester groups on the surface. Consequentially, C6mimCl-CCNF achieved the highest specific capacitance and lowest ion diffusion resistance. Finally, a symmetric carbon/carbon supercapacitor fabricated with such CCNF as electrode delivered an energy density of 21.1 Wh/kg at the power density of 0.6 kW/kg, which is comparable to commercial active carbon supercapacitors.
Indwelling Device-Associated Biofilms in Critically Ill Cancer Patients—Study Protocol
Authors: Lungu Olguta , Grigoras Ioana , Dorneanu Olivia Simona , Lunca Catalina , Vremera Teodora , Copacianu Stefania Brandusa , Ivanov Iuliu , Iancu Luminita Smaranda
Published: March 2021

Health care-associated infections are a leading cause of inpatient complications. Rapid pathogen detection/identification is a major challenge in sepsis management that highly influences the successful outcome. The current standard of microorganism identification relies on bacterial growth in culture, which has several limitations. Gene sequencing research has developed culture-independent techniques for microorganism identification, with the aim to improve etiological diagnosis and, therefore, to change sepsis outcome. A prospective, observational, non-interventional, single-center study was designed that assesses biofilm-associated pathogens in a specific subpopulation of septic critically ill cancer patients. Indwelling device samples will be collected in septic patients at the moment of the removal of the arterial catheter, central venous catheter, endotracheal tube and urinary catheter. Concomitantly, clinical data regarding 4 sites (nasal, pharyngeal, rectal and skin) of pathogen colonization at the time of hospital/intensive care admission will be collected. The present study aims to offer new insights into biofilm-associated infections and to evaluate the infection caused by catheter-specific and patient-specific biofilm-associated pathogens in association with the extent of colonization. The analysis relies on the two following detection/identification techniques: standard microbiological method and next generation sequencing (NGS). Retrospectively, the study will estimate the clinical value of the NGS-based detection and its virtual potential in changing patient management and outcome, notably in the subjects with missing sepsis source or lack of response to anti-infective treatment.
New Epidemiological Aspects of Animal Leishmaniosis in Europe: The Role of Vertebrate Hosts Other Than Dogs
Authors: Cardoso Luís , Schallig Henk , Persichetti Maria Flaminia , Pennisi Maria Grazia
Published: March 2021

Infection with Leishmania parasites can lead to severe disease in humans and dogs, which act as a reservoir in zoonotic transmission. An increasing number of reports suggest that leishmaniosis is not restricted to dogs, but also affects many other mammalian and avian species. Consequently, this expands the potential reservoir and is of great public and veterinary health concern. The present study reviews, based on a comprehensive search of scientific literature published from 1 January 2001 to 31 December 2020, the currently available information on animal leishmaniosis in vertebrates in Europe, other than dogs and humans. This review provides an exhaustive list of mammals and birds in which infections with or exposure to Leishmania parasites have been detected in European countries. Most cases are reported from the Mediterranean region. Domestic animals, in particular cats, pose a concern because of close contact with humans. The wildlife reservoir is less likely to contribute to zoonotic transmission, with the exception of hares. This potentially large reservoir needs to be taken into account when developing control measures for zoonotic leishmaniosis. From a veterinary point of view, it is important that veterinarians are better aware of leishmaniosis and trained in its management.
Exposure to Leptospira spp. and Associated Risk Factors in the Human, Cattle and Dog Populations in Bhutan
Authors: Dreyfus Anou , Ruf Marie-Thérèse , Mayer-Scholl Anne , Zitzl Theresa , Loosli Nadine , Bier Nadja Seyhan , Hiereth Stephanie , Ulrich Sebastian , Poppert Sven , Straubinger Reinhard K. , Stenos John , Tshokey Tshokey
Published: March 2021

Leptospirosis is a neglected worldwide zoonotic bacterial disease with a high prevalence in subtropical and tropical countries. The prevalence of Leptospira spp. in humans, cattle and dogs is unknown in Bhutan. Therefore, we sought to find out whether humans, cattle or dogs had been infected in the past with leptospires by measuring antibodies in the serum. We therefore collected blood from 864 humans ≥13 years of age, 130 bovines and 84 dogs from different rural and urban areas in Bhutan and tested the serum for antibodies specific for leptospires with a screening of enzyme-linked immunosorbent assays (ELISA) and a confirmatory microscopic agglutination test (MAT). In humans, 17.6% were seropositive by ELISA and 1.6% by MAT. The seropositivity was stronger in bovines (36.9%) and dogs (47.6%). “Having had a fever recently” (OR 5.2, p = 0.004), “working for the military” (OR 26.6, p = 0.028) and “being unemployed” (OR 12.9, p = 0.041) (reference category = housemaker) were statistically significantly associated with seropositivity when controlled for the effects of other risk factors. However, due to the small number of positive test results, the findings on risk factors should be interpreted with caution. Based on the serogroups found in the three species, dogs could be a source of infection for humans, or dogs and humans are exposed to the same environmental risk factors Clinical leptospirosis in humans and domestic animals should be investigated by testing blood and urine for the presence of leptospires by molecular methods (qPCR).
Impact of Annual Albendazole versus Four-Monthly Test-and-Treat Approach of Intestinal Parasites on Children Growth—A Longitudinal Four-Arm Randomized Parallel Trial during Two Years of a Community Follow-Up in Bengo, Angola
Authors: Gasparinho Carolina , Kanjungo Aguinaldo , Zage Félix , Clemente Isabel , Santos-Reis Ana , Brito Miguel , Sousa-Figueiredo José Carlos , Fortes Filomeno , Gonçalves Luzia
Published: March 2021

Malnutrition and intestinal parasites continue to have serious impacts on growth and cognitive development of children in Angola. A longitudinal four-arm randomized parallel trial was conducted to investigate if deworming with a single annual dose of albendazole (annual-ALB) or a four-monthly test-and-treat (4TT) intestinal parasites approach at individual or household levels improve nutritional outcomes of pre-school children in Bengo province. Children with intestinal parasites (n = 121) were randomly assigned (1:1:1:1) to arm A1: annual-ALB*individual level; A2: annual-ALB*household level; A3: 4TT*individual; and A4: 4TT*household level. At baseline, 4, 8, 12, 16, 20, and 24 months of follow-up, growth was assessed by height, weight, height-for-age, weight-for-height, weight-for-age, and mid-upper arm circumference. Intention-to-treat analysis was done using non-parametric approach, mixed effect models, and generalized estimating equations (GEE). Initially, 57% and 26% of the children were infected by Giardia lamblia and Ascaris lumbricoides, respectively. This study did not show that a 4TT intestinal parasites approach results on better growth outcomes of children (height, weight, HAZ, WAZ, WHZ and MUACZ) when compared with annual ALB, with exception of height and WHZ using GEE model at 5% level. Positive temporal effects on most nutrition outcomes were observed. Implementing a longitudinal study in a poor setting is challenging and larger sample sizes and ‘pure and clean’ data are difficult to obtain. Nevertheless, learned lessons from this intensive study may contribute to future scientific research and to tailor multidisciplinary approaches to minimize malnutrition and infections in resource-poor countries.
One Health Approach to Zoonotic Parasites: Molecular Detection of Intestinal Protozoans in an Urban Population of Norway Rats, Rattus norvegicus, in Barcelona, Spain
Authors: Galán-Puchades María Teresa , Trelis María , Sáez-Durán Sandra , Cifre Susana , Gosálvez Carla , Sanxis-Furió Joan , Pascual Jordi , Bueno-Marí Rubén , Franco Sandra , Peracho Víctor , Montalvo Tomás , Fuentes Màrius Vicent
Published: March 2021

Rattus norvegicus, the brown or Norway rat, is the most abundant mammal after humans in urban areas, where they live in close proximity to people. Among rodent-borne diseases, the reservoir role of Norway rats of zoonotic parasites in cities has practically been ignored. Considering the parasitic diseases in the One Health approach, we intended to identify and quantify the zoonotic intestinal protozoans (ZIP) in an urban population of R. norvegicus in the city of Barcelona, Spain. We studied the presence of ZIP in 100 rats trapped in parks (n = 15) as well as in the city’s sewage system (n = 85) in the winter of 2016/17. The protozoans were molecularly identified by means of a multiplex PCR (AllplexTM Gastrointestinal Panel-Parasite Assay). We also investigated the presence of co-infections among the species found. Four ZIP were identified, presenting significant prevalences in sewers, specifically Blastocystis (83.5%), Giardia duodenalis (37.7%), Cryptosporidium spp. (34.1%), and Dientamoeba fragilis (14.1%). Several co-infections among the detected ZIP were also detected. The reservoir role of ZIP that Norway rats play in cities as well as the role rats may play as sentinels of zoonotic parasites affecting humans in urban areas are strongly backed up by our findings. The increasing worldwide urbanization, climate change, and the COVID-19 pandemic are factors that are producing an increase in human–rat interactions. Our results should be considered a warning to the authorities to intensify rat control and surveillance in public health interventions.
Staphylococcus aureus in Intensive Pig Production in South Africa: Antibiotic Resistance, Virulence Determinants, and Clonality
Authors: Sineke Ncomeka , Asante Jonathan , Amoako Daniel Gyamfi , Abia Akebe Luther King , Perrett Keith , Bester Linda A. , Essack Sabiha Y.
Published: March 2021

Although Staphylococcus aureus is a major threat to the veterinary, agricultural, and public health sectors because of its zoonotic potential, studies on its molecular characterisation in intensive animal production are rare. We phenotypically and genotypically characterised antibiotic-resistant S. aureus in intensive pig production in South Africa, using the farm-to-fork approach. Samples (n = 461) were collected from the farm, transport vehicles, and the abattoir using the World Health Organisation on Integrated Surveillance of Antimicrobial Resistance (WHO-AGISAR) sampling protocol. Bacteria were isolated using selective media and identified using biochemical tests and polymerase chain reaction (PCR). Phenotypic resistance was determined using the disk diffusion method. Selected resistance and virulence genes were investigated using PCR. Clonality among the isolates was determined using the repetitive element sequence-PCR. In all, 333 presumptive staphylococcal isolates were obtained, with 141/333 (42.3%) identified as staphylococci biochemically. Ninety-seven (97; 68.8%) were confirmed as S. aureus using PCR, 52.6% of which were identified as methicillin-resistant S. aureus (MRSA) through the mecA gene. All the 97 S. aureus isolates (100%) were resistant to at least one of the antibiotics tested, with the highest resistance observed against erythromycin and clindamycin (84.50% each), and the lowest observed against amikacin (2.10%); 82.47% (80/97) were multidrug-resistant with an average multiple antibiotic resistance index of 0.50. Most of the phenotypically resistant isolates carried at least one of the corresponding resistance genes tested, ermC being the most detected. hla was the most detected virulence gene (38.14%) and etb was the least (1.03%). Genetic fingerprinting revealed diverse MRSA isolates along the farm-to-fork continuum, the major REP types consisting of isolates from different sources suggesting a potential transmission along the continuum. Resistance to antibiotics used as growth promoters was evidenced by the high prevalence of MDR isolates with elevated multiple antibiotic resistance indices >0.2, specifically at the farm, indicating exposure to high antibiotic use environments, necessitating antibiotic stewardship and proper infection control measures in pig husbandry and intensive pig production.
Low Crystallinity of Poly(3-Hydroxybutyrate-co-3-Hydroxyvalerate) Bioproduction by Hot Spring Cyanobacterium Cyanosarcina sp. AARL T020
Authors: Chotchindakun Kittipat , Pathom-Aree Wasu , Dumri Kanchana , Ruangsuriya Jetsada , Pumas Chayakorn , Pekkoh Jeeraporn
Published: March 2021

The poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) derived from cyanobacteria is an environmentally friendly biodegradable polymer. The low yield of PHBV’s production is the main hindrance to its sustainable production, and the manipulation of PHBV production processes could potentially overcome this obstacle. The present research investigated evolutionarily divergent cyanobacteria obtained from local environments of Thailand. Among the strains tested, Cyanosarcina sp. AARL T020, a hot spring cyanobacterium, showed a high rate of PHBV accumulation with a fascinating 3-hydroxyvalerate mole fraction. A two-stage cultivation strategy with sole organic carbon supplementation was successful in maximizing cyanobacterial PHBV production. The use of an optimized medium in the first stage of cultivation provided a 4.9-fold increase in biomass production. Subsequently, the addition of levulinic acid in the second stage of cultivation can induce significant biomass and PHBV production. With this strategy, the final biomass production and PHBV productivity were increased by 6.5 and 73.2 fold, respectively. The GC-MS, FTIR, and NMR analyses confirmed that the obtained PHBV consisted of two subunits of 3-hydroxyvaryrate and 3-hydroxybutyrate. Interestingly, the cyanobacterial PHBV contained a very high 3-hydroxyvalerate mole fraction (94%) exhibiting a low degree of crystallinity and expanding in processability window, which could be applied to polymers for desirable advanced applications.
Drug Carriers: Classification, Administration, Release Profiles, and Industrial Approach
Authors: Trucillo Paolo
Published: March 2021

This work is aimed at providing a description of the complex world of drug carriers, starting from the description of this particular market in terms of revenue. Then, a brief overview of several types of conventional and innovative drug carrier systems has been included. The types of administration routes were also analyzed, with a critical and qualitative comment on drug release kinetics and drug profile shapes. Carriers were classified according to their ability to provide a prolonged and targeted release. The concept of the therapeutic window has been presented, providing advantages of having pulsed drug release to avoid side effects to target tissues. A critical comment on the use of conventional and innovative techniques for the production of drug carriers by large industrial companies has been proposed. As a final attempt for this work, an overall unique schematization of a drug carrier production process has been added, highlighting the necessity to create a strong double link among world-requested versatility of drug carriers for human applications and the newly developed industrial processes.
PAT for Continuous Chromatography Integrated into Continuous Manufacturing of Biologics towards Autonomous Operation
Authors: Vetter Florian Lukas , Zobel-Roos Steffen , Strube Jochen
Published: March 2021

This study proposes a reliable inline PAT concept for the simultaneous monitoring of different product components after chromatography. The feed for purification consisted of four main components, IgG monomer, dimer, and two lower molecular weight components of 4.4 kDa and 1 kDa molecular weight. The proposed measurement setup consists of a UV–VIS diode-array detector and a fluorescence detector. Applying this system, a R2 of 0.93 for the target component, a R2 of 0.67 for the dimer, a R2 of 0.91 for the first side component and a R2 of 0.93 for the second side component is achieved. Root mean square error for IgG monomer was 0.027 g/L, for dimer 0.0047 g/L, for side component 1 0.016 g/L and for the side component 2 0.014 g/L. The proposed measurement concept tracked component concentration reliably down to 0.05 g/L. Zero-point fluctuations were kept within a standard deviation of 0.018 g/L for samples with no IgG concentration but with side components present, allowing a reliable detection of the target component. The main reason inline concentration measurements have not been established yet, is the false-positive measurement of target components when side components are present. This problem was eliminated using the combination of fluorescence and UV–VIS data for the test system. The use of this measurement system is simulated for the test system, allowing an automatic fraction cut at 0.05 g/L. In this simulation a consistent yield of >99% was achieved. Process disturbances for processed feed volume, feed purity and feed IgG concentration can be compensated with this setup. Compared to a timed process control, yield can be increased by up to 12.5%, if unexpected process disturbances occur.
In Vitro Studies to Assess the α-Glucosidase Inhibitory Activity and Insulin Secretion Effect of Isorhamnetin 3-O-Glucoside and Quercetin 3-O-Glucoside Isolated from Salicornia herbacea
Authors: Lee Dahae , Park Jun , Lee Sanghyun , Kang Ki
Published: March 2021

In this study, we examined the effect of ethanolic extract of Salicornia herbacea (ESH), isorhamnetin 3-O-glucoside (I3G), quercetin 3-O-glucoside (Q3G), quercetin, and isorhamnetin on α-glucosidase activity and glucose-stimulated insulin secretion (GSIS) in insulin-secreting rat insulinoma (INS-1) cells. A portion of the ethyl acetate fraction of ESH was chromatographed on a silica gel by a gradient elution with chloroform and methanol to provide Q3G and I3G. ESH, Q3G, and quercetin inhibited α-glucosidase activity, and quercetin (IC50 value was 29.47 ± 3.36 μM) inhibited the activity more effectively than Q3G. We further demonstrated that ESH, Q3G, quercetin, I3G, and isorhamnetin promote GSIS in INS-1 pancreatic β-cells without inducing cytotoxicity. Among them, I3G was the most effective in enhancing GSIS. I3G enhanced the phosphorylation of total extracellular signal-regulated kinase (ERK), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, and activated pancreatic and duodenal homeobox-1 (PDX-1), which are associated with insulin secretion and β-cell function. As components of ESH, Q3G has the potential to regulate blood glucose by inhibiting α-glucosidase activity, and I3G enhances the insulin secretion, but its bioavailability should be considered in determining biological importance.
Alleviating Class Imbalance in Actuarial Applications Using Generative Adversarial Networks
Authors: Ngwenduna Kwanda Sydwell , Mbuvha Rendani
Published: March 2021

To build adequate predictive models, a substantial amount of data is desirable. However, when expanding to new or unexplored territories, this required level of information is rarely always available. To build such models, actuaries often have to: procure data from local providers, use limited unsuitable industry and public research, or rely on extrapolations from other better-known markets. Another common pathology when applying machine learning techniques in actuarial domains is the prevalence of imbalanced classes where risk events of interest, such as mortality and fraud, are under-represented in data. In this work, we show how an implicit model using the Generative Adversarial Network (GAN) can alleviate these problems through the generation of adequate quality data from very limited or highly imbalanced samples. We provide an introduction to GANs and how they are used to synthesize data that accurately enhance the data resolution of very infrequent events and improve model robustness. Overall, we show a significant superiority of GANs for boosting predictive models when compared to competing approaches on benchmark data sets. This work offers numerous of contributions to actuaries with applications to inter alia new sample creation, data augmentation, boosting predictive models, anomaly detection, and missing data imputation.
Liminality and Child Labour: Experiences of School Aged Working Children with Implications for Community Education in Africa
Authors: Chukwudeh Okechukwu Stephen , Oduaran Akpovire
Published: March 2021

Background: Liminality brings confusion among children as they cannot progress to the next stage of life, neither could they regress to their previous state of events. The situation is precarious for socioeconomic deprived children in Africa as it cast aspersion on their career, health and well-being. The study, therefore, examines the experiences’ of children who were supposed to be in school but were observed working at the informal market space in Africa. Methods: Qualitative data was collected through referral and non-discriminative snowballing. Fourty-eight participants (48-KII 2, IDI 10, FGD 6–6 person per group, total 36) from Aleshinloye and Bodija markets in Southwest Nigeria were included in the study. Results: Parental poverty, poor education facilities, peer influence, and the frequent strike by education institutions (pre-tertiary and tertiary) were implicated for the prevalence of child labour in the informal market space in Southwest Nigeria. Conclusions: The negative consequences of the liminality stage far outweigh the positive. Therefore, there is a need for conscientious efforts by community leaders, parents, and relevant stakeholders in the society to eradicate snags within the liminality of children’s education in order to curb child labour. This is necessary to achieve the sustainable development goals by 2030.