bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge Graphs for COVID-19: An Exploratory Review of the Current Landscape
Authors: Chatterjee Avishek , Nardi Cosimo , Oberije Cary , Lambin Philippe
Published: April 2021

Background: Searching through the COVID-19 research literature to gain actionable clinical insight is a formidable task, even for experts. The usefulness of this corpus in terms of improving patient care is tied to the ability to see the big picture that emerges when the studies are seen in conjunction rather than in isolation. When the answer to a search query requires linking together multiple pieces of information across documents, simple keyword searches are insufficient. To answer such complex information needs, an innovative artificial intelligence (AI) technology named a knowledge graph (KG) could prove to be effective. Methods: We conducted an exploratory literature review of KG applications in the context of COVID-19. The search term used was “covid-19 knowledge graph”. In addition to PubMed, the first five pages of search results for Google Scholar and Google were considered for inclusion. Google Scholar was used to include non-peer-reviewed or non-indexed articles such as pre-prints and conference proceedings. Google was used to identify companies or consortiums active in this domain that have not published any literature, peer-reviewed or otherwise. Results: Our search yielded 34 results on PubMed and 50 results each on Google and Google Scholar. We found KGs being used for facilitating literature search, drug repurposing, clinical trial mapping, and risk factor analysis. Conclusions: Our synopses of these works make a compelling case for the utility of this nascent field of research.
Long Term Sediment Modification Effects after Applications of P Inactivation Method in Meromictic Lake (Starodworskie Lake, Olsztyn Lakeland, Poland)
Authors: Augustyniak Renata , Tandyrak Renata , Łopata Michał , Grochowska Jolanta
Published: April 2021

Lake restoration is a part of geoengineering, which is a useful tool for landscape management. The phosphorus inactivation method is one of the most popular lake restoration methods. Using chemical compounds for P binding is leading to the creation of sediment “active layer”, which should show higher P adsorption abilities, compared to non-modified sediment. Howewer, it provides rather little information, how long the modified sediment remains active, and whether it is effective in continuous P binding. Lake meromixis is not commonly observed phenomenon, and sediment located in monimolimnion area is subjected long term anoxia. Therefore, observation of “active layer” in a meromictic lake can give very important data about durability of restoration effects. The object of our study was meromictic Starodworskie Lake (5.57 ha, max. depth 24.5 m), located in Olsztyn Lakeland, Poland. In the past the analyzed lake was subjected to various restoration methods, and phosphorus inactivation method by alum use (1994–1995) was the last used treatment type. The mixing regime of this lake had changed from bradimictic (before and during restoration time) into durable meromictic (post-restoration period). The research made two decades after implementing of P inactivation showed the presence of “active” sediment layer 10–15 cm below sediment surface. This sediment layer showed much higher content of P bound to aluminum, compared to surficial sediment layer. P binding molar ratio was assessed and amounted to 16.1 straightly after restoration and 6.1 after 21 years. This fraction amounts were higher that the values noted before restoration (ca. 358% higher than in 1994) and during restoration (ca. 86% higher than in 1995), which was probably the effect of continuous phosphorus adsorption by “active layer” in post-restoration period.
DUAL-tDCS Treatment over the Temporo-Parietal Cortex Enhances Writing Skills: First Evidence from Chronic Post-Stroke Aphasia
Authors: Pisano Francesca , Caltagirone Carlo , Incoccia Chiara , Marangolo Paola
Published: April 2021

The learning of writing skills involves the re-engagement of previously established independent procedures. Indeed, the writing deficit an adult may acquire after left hemispheric brain injury is caused by either an impairment to the lexical route, which processes words as a whole, to the sublexical procedure based on phoneme-to-grapheme conversion rules, or to both procedures. To date, several approaches have been proposed for writing disorders, among which, interventions aimed at restoring the sub-lexical procedure were successful in cases of severe agraphia. In a randomized double-blind crossover design, fourteen chronic Italian post-stroke aphasics underwent dual transcranial direct current stimulation (tDCS) (20 min, 2 mA) with anodal and cathodal current simultaneously placed over the left and right temporo-parietal cortex, respectively. Two different conditions were considered: (1) real, and (2) sham, while performing a writing task. Each experimental condition was performed for ten workdays over two weeks. After real stimulation, a greater amelioration in writing with respect to the sham was found. Relevantly, these effects generalized to different language tasks not directly treated. This evidence suggests, for the first time, that dual tDCS associated with training is efficacious for severe agraphia. Our results confirm the critical role of the temporo-parietal cortex in writing skills.
The State of Starch/Hydroxyapatite Composite Scaffold in Bone Tissue Engineering with Consideration for Dielectric Measurement as an Alternative Characterization Technique
Authors: Mohd Roslan Mohd Riza , Mohd Kamal Nadhiya Liyana , Abdul Khalid Muhammad Farid , Mohd Nasir Nashrul Fazli , Cheng Ee Meng , Beh Chong You , Tan Joo Shun , Mohamed Mohd Shamzi
Published: April 2021

Hydroxyapatite (HA) has been widely used as a scaffold in tissue engineering. HA possesses high mechanical stress and exhibits particularly excellent biocompatibility owing to its similarity to natural bone. Nonetheless, this ceramic scaffold has limited applications due to its apparent brittleness. Therefore, this had presented some difficulties when shaping implants out of HA and for sustaining a high mechanical load. Fortunately, these drawbacks can be improved by combining HA with other biomaterials. Starch was heavily considered for biomedical device applications in favor of its low cost, wide availability, and biocompatibility properties that complement HA. This review provides an insight into starch/HA composites used in the fabrication of bone tissue scaffolds and numerous factors that influence the scaffold properties. Moreover, an alternative characterization of scaffolds via dielectric and free space measurement as a potential contactless and nondestructive measurement method is also highlighted.
Extended Residual-State Creep Test and Its Application for Landslide Stability Assessment
Authors: Bhat Deepak R. , Kozubal Janusz V. , Tankiewicz Matylda
Published: April 2021

This paper contains the results of a newly developed residual-state creep test performed to determine the behavior of a selected geomaterial in the context of reactivated landslides. Soil and rock creep is a time-dependent phenomenon in which a deformation occurs under constant stress. Based on the examination results, it was found that the tested clayey material (from Kobe, Japan) shows tertiary creep behavior only under shear stress higher than the residual strength condition and primary and secondary creep behavior under shear stress lower or equal to the residual strength condition. Based on the data, a model for predicting the critical or failure time is introduced. The study traces the development of the limit state based on the contact model corresponding to Blair’s body. The time to occurrence of the conditions necessary for unlimited creep on the surface is estimated. As long-term precipitation and infiltrating water in the area of the landslides are identified as the key phenomena initiating collapse, the work focuses on the prediction of landslides with identified surfaces of potential damage as a result of changes in the saturation state. The procedure outlined is applied to a case study and considerations as to when the necessary safety work should be carried out are presented.
A Hybrid Strategic Oscillation with Path Relinking Algorithm for the Multiobjective k-Balanced Center Location Problem
Authors: Sánchez-Oro Jesús , López-Sánchez Ana D. , Martínez-Gavara Anna , Hernández-Díaz Alfredo G. , Duarte Abraham
Published: April 2021

This paper presents a hybridization of Strategic Oscillation with Path Relinking to provide a set of high-quality nondominated solutions for the Multiobjective k-Balanced Center Location problem. The considered location problem seeks to locate k out of m facilities in order to serve n demand points, minimizing the maximum distance between any demand point and its closest facility while balancing the workload among the facilities. An extensive computational experimentation is carried out to compare the performance of our proposal, including the best method found in the state-of-the-art as well as traditional multiobjective evolutionary algorithms.
Resolving Long-Standing Uncertainty about the Clinical Efficacy of Transcutaneous Electrical Nerve Stimulation (TENS) to Relieve Pain: A Comprehensive Review of Factors Influencing Outcome
Authors: Johnson Mark I.
Published: April 2021

Pain is managed using a biopsychosocial approach and pharmacological and non-pharmacological treatments. Transcutaneous electrical nerve stimulation (TENS) is a technique whereby pulsed electrical currents are administered through the intact surface of the skin with the intention of alleviating pain, akin to ‘electrically rubbing pain away’. Despite over 50 years of published research, uncertainty about the clinical efficacy of TENS remains. The purpose of this comprehensive review is to critically appraise clinical research on TENS to inform future strategies to resolve the ‘efficacy-impasse’. The principles and practices of TENS are described to provide context for readers unfamiliar with TENS treatment. The findings of systematic reviews evaluating TENS are described from a historical perspective to provide context for a critical evaluation of factors influencing the outcomes of randomized controlled trials (RCTs); including sample populations, outcome measures, TENS techniques, and comparator interventions. Three possibilities are offered to resolve the impasse. Firstly, to conduct large multi-centered RCTs using an enriched enrolment with randomized withdrawal design, that incorporates a ‘run-in phase’ to screen for potential TENS responders and to optimise TENS treatment according to individual need. Secondly, to meta-analyze published RCT data, irrespective of type of pain, to determine whether TENS reduces the intensity of pain during stimulation, and to include a detailed assessment of levels of certainty and precision. Thirdly, to concede that it may be impossible to determine efficacy due to insurmountable methodological, logistical and financial challenges. The consequences to clinicians, policy makers and funders of this third scenario are discussed. I argue that patients will continue to use TENS irrespective of the views of clinicians, policy makers, funders or guideline panel recommendations, because TENS is readily available without prescription; TENS generates a pleasant sensory experience that is similar to easing pain using warming and cooling techniques; and technological developments such as smart wearable TENS devices will improve usability in the future. Thus, research is needed on how best to integrate TENS into existing pain management strategies by analyzing data of TENS usage by expert-patients in real-world settings.
Lipidomics-Based Comparison of Molecular Compositions of Green, Yellow, and Red Bell Peppers
Authors: Sutliff Aimee K. , Saint-Cyr Martine , Hendricks Audrey E. , Chen Samuel S. , Doenges Katrina A. , Quinn Kevin , Westcott Jamie , Tang Minghua , Borengasser Sarah J. , Reisdorph Richard M. , Campbell Wayne W. , Krebs Nancy F. , Reisdorph Nichole A.
Published: April 2021

Identifying and annotating the molecular composition of individual foods will improve scientific understanding of how foods impact human health and how much variation exists in the molecular composition of foods of the same species. The complexity of this task includes distinct varieties and variations in natural occurring pigments of foods. Lipidomics, a sub-field of metabolomics, has emerged as an effective tool to help decipher the molecular composition of foods. For this proof-of-principle research, we determined the lipidomic profiles of green, yellow and red bell peppers (Capsicum annuum) using liquid chromatography mass spectrometry and a novel tool for automated annotation of compounds following database searches. Among 23 samples analyzed from 6 peppers (2 green, 1 yellow, and 3 red), over 8000 lipid compounds were detected with 315 compounds (106 annotated) found in all three colors. Assessments of relationships between these compounds and pepper color, using linear mixed effects regression and false discovery rate (<0.05) statistical adjustment, revealed 11 compounds differing by color. The compound most strongly associated with color was the carotenoid, β-cryptoxanthin (p-value = 7.4 × 10−5; FDR adjusted p-value = 0.0080). These results support lipidomics as a viable analytical technique to identify molecular compounds that can be used for unique characterization of foods.
Biosensing Near the Exceptional Point Based on Resonant Optical Tunneling Effect
Authors: Liu Yang , Yan Pengyun , Liu Feng , Jian Aoqun , Sang Shengbo
Published: April 2021

Inspired by exceptional point (EP) sensing in non-Hermitian systems, in this work, a label-free biosensor for detecting low-concentration analytes is proposed, via a special multilayer structure: a resonant optical tunneling resonator. Due to the square root topology near the exceptional point, a recognized target analyte perturbs the system deviated from the exceptional point, leading to resolvable modes splitting in the transmission spectrum. The performance of the designed sensor is analyzed by the coupled-mode theory and transfer matrix method, separately. Here, the simulation results demonstrate that the obtained sensitivity is 17,120 nm/imaginary part unit of refractive index (IP) and the theoretical detection limit is 4.2 × 10−8 IP (regarding carcinoembryonic antigen (CEA), the minimum detection value is 1.78 ng). Instead of the typical diffusion manner, the liquid sample is loaded by convection, which can considerably improve the efficiency of sample capture and shorten the response time of the sensor. The sketched sensor may find potential application in the fields of biomedical detection, environment protection, and drinking water safety.
The Influence of Wire Speed on Phase Transitions and Residual Stress in Single Crystal Silicon Wafers Sawn by Resin Bonded Diamond Wire Saw
Authors: Liu Tengyun , Ge Peiqi , Bi Wenbo
Published: April 2021

Lower warp is required for the single crystal silicon wafers sawn by a fixed diamond wire saw with the thinness of a silicon wafer. The residual stress in the surface layer of the silicon wafer is the primary reason for warp, which is generated by the phase transitions, elastic-plastic deformation, and non-uniform distribution of thermal energy during wire sawing. In this paper, an experiment of multi-wire sawing single crystal silicon is carried out, and the Raman spectra technique is used to detect the phase transitions and residual stress in the surface layer of the silicon wafers. Three different wire speeds are used to study the effect of wire speed on phase transition and residual stress of the silicon wafers. The experimental results indicate that amorphous silicon is generated during resin bonded diamond wire sawing, of which the Raman peaks are at 178.9 cm−1 and 468.5 cm−1. The ratio of the amorphous silicon surface area and the surface area of a single crystal silicon, and the depth of amorphous silicon layer increases with the increasing of wire speed. This indicates that more amorphous silicon is generated. There is both compressive stress and tensile stress on the surface layer of the silicon wafer. The residual tensile stress is between 0 and 200 MPa, and the compressive stress is between 0 and 300 MPa for the experimental results of this paper. Moreover, the residual stress increases with the increase of wire speed, indicating more amorphous silicon generated as well.
4E Interacting Protein as a Potential Novel Drug Target for Nucleoside Analogues in Trypanosoma brucei
Authors: Mabille Dorien , Cardoso Santos Camila , Hendrickx Rik , Claes Mathieu , Takac Peter , Clayton Christine , Hendrickx Sarah , Hulpia Fabian , Maes Louis , Van Calenbergh Serge , Caljon Guy
Published: April 2021

Human African trypanosomiasis is a neglected parasitic disease for which the current treatment options are quite limited. Trypanosomes are not able to synthesize purines de novo and thus solely depend on purine salvage from the host environment. This characteristic makes players of the purine salvage pathway putative drug targets. The activity of known nucleoside analogues such as tubercidin and cordycepin led to the development of a series of C7-substituted nucleoside analogues. Here, we use RNA interference (RNAi) libraries to gain insight into the mode-of-action of these novel nucleoside analogues. Whole-genome RNAi screening revealed the involvement of adenosine kinase and 4E interacting protein into the mode-of-action of certain antitrypanosomal nucleoside analogues. Using RNAi lines and gene-deficient parasites, 4E interacting protein was found to be essential for parasite growth and infectivity in the vertebrate host. The essential nature of this gene product and involvement in the activity of certain nucleoside analogues indicates that it represents a potential novel drug target.
Amygdalin: Toxicity, Anticancer Activity and Analytical Procedures for Its Determination in Plant Seeds
Authors: Jaszczak-Wilke Ewa , Polkowska Żaneta , Koprowski Marek , Owsianik Krzysztof , Mitchell Alyson E. , Bałczewski Piotr
Published: April 2021

Amygdalin (d-Mandelonitrile 6-O-β-d-glucosido-β-d-glucoside) is a natural cyanogenic glycoside occurring in the seeds of some edible plants, such as bitter almonds and peaches. It is a medically interesting but controversial compound as it has anticancer activity on one hand and can be toxic via enzymatic degradation and production of hydrogen cyanide on the other hand. Despite numerous contributions on cancer cell lines, the clinical evidence for the anticancer activity of amygdalin is not fully confirmed. Moreover, high dose exposures to amygdalin can produce cyanide toxicity. The aim of this review is to present the current state of knowledge on the sources, toxicity and anticancer properties of amygdalin, and analytical methods for its determination in plant seeds.
Chemical Structure and Biological Activity of Humic Substances Define Their Role as Plant Growth Promoters
Authors: Nardi Serenella , Schiavon Michela , Francioso Ornella
Published: April 2021

Humic substances (HS) are dominant components of soil organic matter and are recognized as natural, effective growth promoters to be used in sustainable agriculture. In recent years, many efforts have been made to get insights on the relationship between HS chemical structure and their biological activity in plants using combinatory approaches. Relevant results highlight the existence of key functional groups in HS that might trigger positive local and systemic physiological responses via a complex network of hormone-like signaling pathways. The biological activity of HS finely relies on their dosage, origin, molecular size, degree of hydrophobicity and aromaticity, and spatial distribution of hydrophilic and hydrophobic domains. The molecular size of HS also impacts their mode of action in plants, as low molecular size HS can enter the root cells and directly elicit intracellular signals, while high molecular size HS bind to external cell receptors to induce molecular responses. Main targets of HS in plants are nutrient transporters, plasma membrane H+-ATPases, hormone routes, genes/enzymes involved in nitrogen assimilation, cell division, and development. This review aims to give a detailed survey of the mechanisms associated to the growth regulatory functions of HS in view of their use in sustainable technologies.
Alpha-Glucosidase Inhibitory Diterpenes from Euphorbia antiquorum Growing in Vietnam
Authors: Tran Cong-Luan , Dao Thi-Bich-Ngoc , Tran Thanh-Nha , Mai Dinh-Tri , Tran Thi-Minh-Dinh , Tran Nguyen-Minh-An , Dang Van-Son , Vo Thi-Xuyen , Duong Thuc-Huy , Sichaem Jirapast
Published: April 2021

Bioactive-guided phytochemical investigation of Euphorbia antiquorum L. growing in Vietnam led to the isolation of five ent-atisanes, one seco-ent-atisane, and one lathyrane (ingol-type). The structures were elucidated as ent-1α,3α,16β,17-tetrahydroxyatisane (1), ethyl ent-3,4-seco-4,16β,17-trihydroxyatisane-3-carboxylate (2), ent-atisane-3-oxo-16β,17-acetonide (3), ent-3α-acetoxy-16β,17-dihydroxyatisane (4), ent-16β,17-dihydroxyatisane-3-one (5), calliterpenone (6), and ingol 12-acetate (7). Their chemical structures were unambiguously determined by analysis of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and high resolution mass spectrometry, as well as by comparison with literature data. Among them, 1 is a new compound while 2 is an ethylated artifact of ent-3,4-seco-4,16β,17-trihydroxyatisane-3-carboxylic acid, a new compound. Isolates were evaluated for alpha-glucosidase inhibition. Compound 3 showed the most significant inhibitory activity against alpha-glucosidase with an IC50 value of 69.62 µM. Further study on mechanism underlying yeast alpha-glucosidase inhibition indicated that 3 could retard the enzyme function by noncompetitive.
Cholinergic Signaling, Neural Excitability, and Epilepsy
Authors: Wang Yu , Tan Bei , Wang Yi , Chen Zhong
Published: April 2021

Epilepsy is a common brain disorder characterized by recurrent epileptic seizures with neuronal hyperexcitability. Apart from the classical imbalance between excitatory glutamatergic transmission and inhibitory γ-aminobutyric acidergic transmission, cumulative evidence suggest that cholinergic signaling is crucially involved in the modulation of neural excitability and epilepsy. In this review, we briefly describe the distribution of cholinergic neurons, muscarinic, and nicotinic receptors in the central nervous system and their relationship with neural excitability. Then, we summarize the findings from experimental and clinical research on the role of cholinergic signaling in epilepsy. Furthermore, we provide some perspectives on future investigation to reveal the precise role of the cholinergic system in epilepsy.
Extraction of Tropical Fruit Peels and Development of HPMC Film Containing the Extracts as an Active Antibacterial Packaging Material
Authors: Chaiwarit Tanpong , Kantrong Nutthapong , Sommano Sarana Rose , Rachtanapun Pornchai , Junmahasathien Taepin , Kumpugdee-Vollrath Mont , Jantrawut Pensak
Published: April 2021

In recent years, instead of the use of chemical substances, alternative substances, especially plant extracts, have been characterized for an active packaging of antibacterial elements. In this study, the peels of mangosteen (Garcinia mangostana), rambutan (Nephelium lappaceum), and mango (Mangifera indica) were extracted to obtain bioactive compound by microwave-assisted extraction (MAE) and maceration with water, ethanol 95% and water–ethanol (40:60%). All extracts contained phenolics and flavonoids. However, mangosteen peel extracted by MAE and maceration with water/ethanol (MT-MAE-W/E and MT-Ma-W/E, respectively) contained higher phenolic and flavonoid contents, and exhibited greater antibacterial activity against Staphylococcus aureus and Escherichia coli. Thus, both extracts were analyzed by liquid chromatograph-mass spectrometer (LC-MS) analysis, α-mangostin conferring antibacterial property was found in both extracts. The MT-MAE-W/E and MT-Ma-W/E films exhibited 30.22 ± 2.14 and 30.60 ± 2.83 mm of growth inhibition zones against S. aureus and 26.50 ± 1.60 and 26.93 ± 3.92 mm of growth inhibition zones against E. coli. These clear zones were wider than its crude extract approximately 3 times, possibly because the film formulation enhanced antibacterial activity with sustained release of active compound. Thus, the mangosteen extracts have potential to be used as an antibacterial compound in active packaging.
Magnetic ZnO Crystal Nanoparticle Growth on Reduced Graphene Oxide for Enhanced Photocatalytic Performance under Visible Light Irradiation
Authors: Elshypany Rania , Selim Hanaa , Zakaria K. , Moustafa Ahmed H. , Sadeek Sadeek A. , Sharaa S.I. , Raynaud Patrice , Nada Amr A.
Published: April 2021

Magnetite zinc oxide (MZ) (Fe3O4/ZnO) with different ratios of reduced graphene oxide (rGO) was synthesized using the solid-state method. The structural and optical properties of the nanocomposites were analyzed using transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR), ultraviolet–visible diffuse reflectance spectroscopy (UV–Vis/DRS), and photoluminescence (PL) spectrophotometry. In particular, the analyses show higher photocatalytic movement for crystalline nanocomposite (MZG) than MZ and ZnO nanoparticles. The photocatalytic degradation of methylene blue (MB) with crystalline ZnO for 1.5 h under visible light was 12%. By contrast, the photocatalytic activity for MZG was more than 98.5%. The superior photocatalytic activity of the crystalline nanocomposite was detected to be due to the synergistic effect between magnetite and zinc oxide in the presence of reduced graphene oxide. Moreover, the fabricated nanocomposite had high electron–hole stability. The crystalline nanocomposite was stable when the material was used several times.
Biocatalysis in the Chemistry of Lupane Triterpenoids
Authors: Bachořík Jan , Urban Milan
Published: April 2021

Pentacyclic triterpenes are important representatives of natural products that exhibit a wide variety of biological activities. These activities suggest that these compounds may represent potential medicines for the treatment of cancer and viral, bacterial, or protozoal infections. Naturally occurring triterpenes usually have several drawbacks, such as limited activity and insufficient solubility and bioavailability; therefore, they need to be modified to obtain compounds suitable for drug development. Modifications can be achieved either by methods of standard organic synthesis or with the use of biocatalysts, such as enzymes or enzyme systems within living organisms. In most cases, these modifications result in the preparation of esters, amides, saponins, or sugar conjugates. Notably, while standard organic synthesis has been heavily used and developed, the use of the latter methodology has been rather limited, but it appears that biocatalysis has recently sparked considerably wider interest within the scientific community. Among triterpenes, derivatives of lupane play important roles. This review therefore summarizes the natural occurrence and sources of lupane triterpenoids, their biosynthesis, and semisynthetic methods that may be used for the production of betulinic acid from abundant and inexpensive betulin. Most importantly, this article compares chemical transformations of lupane triterpenoids with analogous reactions performed by biocatalysts and highlights a large space for the future development of biocatalysis in this field. The results of this study may serve as a summary of the current state of research and demonstrate the potential of the method in future applications.
The Role of Polymeric Coatings for a Safe-by-Design Development of Biomedical Gold Nanoparticles Assessed in Zebrafish Embryo
Authors: Floris Pamela , Garbujo Stefania , Rolla Gabriele , Giustra Marco , Salvioni Lucia , Catelani Tiziano , Colombo Miriam , Mantecca Paride , Fiandra Luisa
Published: April 2021

In the biomedical field, gold nanoparticles (GNPs) have attracted the attention of the scientific community thanks to their high potential in both diagnostic and therapeutic applications. The extensive use of GNPs led researchers to investigate their toxicity, identifying stability, size, shape, and surface charge as key properties determining their impact on biological systems, with possible strategies defined to reduce it according to a Safe-by-Design (SbD) approach. The purpose of the present work was to analyze the toxicity of GNPs of various sizes and with different coating polymers on the developing vertebrate model, zebrafish. In particular, increasing concentrations (from 0.001 to 1 nM) of 6 or 15 nm poly-(isobutylene-alt-maleic anhydride)-graft-dodecyl polymer (PMA)- or polyethylene glycol (PEG)-coated GNPs were tested on zebrafish embryos using the fish embryo test (FET). While GNP@PMA did not exert significant toxicity on zebrafish embryos, GNP@PEG induced a significant inhibition of embryo viability, a delay of hatching (with the smaller size NPs), and a higher incidence of malformations, in terms of tail morphology and eye development. Transmission electron microscope analysis evidenced that the more negatively charged GNP@PMA was sequestered by the positive charges of chorion proteins, with a consequent reduction in the amount of NPs able to reach the developing embryo and exert toxicological activity. The mild toxic response observed on embryos directly exposed to GNP@PMA suggest that these NPs are promising in terms of SbD development of gold-based biomedical nanodevices. On the other hand, the almost neutral GNP@PEG, which did not interact with the chorion surface and was free to cross chorion pores, significantly impacted the developing zebrafish. The present study raises concerns about the safety of PEGylated gold nanoparticles and contributes to the debated issue of the free use of this nanotool in medicine and nano-biotechnologies.
The Combination of Berberine, Tocotrienols and Coffee Extracts Improves Metabolic Profile and Liver Steatosis by the Modulation of Gut Microbiota and Hepatic miR-122 and miR-34a Expression in Mice
Authors: Cossiga Valentina , Lembo Vincenzo , Nigro Cecilia , Mirra Paola , Miele Claudia , D’Argenio Valeria , Leone Alessia , Mazzone Giovanna , Veneruso Iolanda , Guido Maria , Beguinot Francesco , Caporaso Nicola , Morisco Filomena
Published: April 2021

Non-alcoholic-fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora, on the development of obesity, hepatic steatosis, insulin-resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR-122 and miR-34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E-mice showed lower body weight (p < 0.01), amelioration of insulin-sensitivity (p = 0.021), total cholesterol (p = 0.014), low-density-lipoprotein-cholesterol (p < 0.001), alanine-aminotransferase (p = 0.038) and hepatic steatosis compared to HFD-mice. While a decrease of hepatic miR-122 and increase of miR-34a were observed in HFD-mice compared to SD-mice, both these miRNAs had similar levels to SD-mice in HFD+E-mice. Moreover, a different microbial composition was found between SD- and HFD-mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD-induced NAFLD by the modulation of miR-122, miR-34a and gut microbiome.
The INTER-ACT E-Health Supported Lifestyle Intervention Improves Postpartum Food Intake and Eating Behavior, but Not Physical Activity and Sedentary Behavior—A Randomized Controlled Trial
Authors: Bijlholt Margriet , Ameye Lieveke , Van Uytsel Hanne , Devlieger Roland , Bogaerts Annick
Published: April 2021

Unhealthy postpartum lifestyle is related to long-term adverse psychological, metabolic and cardiovascular health outcomes as well as to complications in the next pregnancy. Especially women with preceding excessive gestational weight gain are at risk. This paper aims to evaluate the effect of the postpartum phase of the INTER-ACT randomized controlled trial (RCT) on food intake, eating behavior, physical activity and sedentary time at the end of the intervention (six months postpartum) and at six-months follow-up (12 months postpartum). The study population comprised women with excessive gestational weight gain in the preceding pregnancy. The lifestyle intervention combined a smartphone application with four face-to-face coaching sessions between six weeks and six months postpartum. After the intervention, restrained eating score was 1 point higher (95% CI 0.5, 1.5; p < 0.001), uncontrolled eating score was 1 point lower (95% CI −1.9, −0.2; p = 0.02) and energy intake was 69 kcal lower (95% CI −123, −15; p = 0.01) in the intervention group compared to the control group. The differences were no longer statistically significant at follow-up. No significant effects on emotional eating, physical activity and sedentary behavior were found. In conclusion, the postpartum phase of the INTER-ACT RCT was effective in improving nutrition-related outcomes, however, these improvements could not be sustained at follow-up. ClinicalTrials.gov identifier: NCT02989142.
Role of Dietary Habits in the Prevention of Diverticular Disease Complications: A Systematic Review
Authors: Carabotti Marilia , Falangone Francesca , Cuomo Rosario , Annibale Bruno
Published: April 2021

Recent evidence showed that dietary habits play a role as risk factors for the development of diverticular complications. This systematic review aims to assess the effect of dietary habits in the prevention of diverticula complications (i.e., acute diverticulitis and diverticula bleeding) in patients with diverticula disease. PubMed and Scopus databases were searched up to 19 January 2021, 330 records were identified, and 8 articles met the eligibility criteria and were subjected to data extraction. The quality of the studies was evaluated by the Newcastle-Ottawa quality assessment form. No study meets the criteria for being a high-quality study. A high intake of fiber was associated to a decreased risk of diverticulitis or hospitalization due to diverticular disease, with a protective effect for fruits and cereal fiber, but not for vegetable fiber; whereas, a high red meat consumption and a generally Western dietary pattern were associated with an increased risk of diverticulitis. Alcohol use seemed to be associated to diverticular bleeding, but not to recurrent diverticulitis or diverticular complications. Further high-quality studies are needed to better define these associations. It is mandatory to ascertain the role of dietary habits for the development of recurrent acute diverticulitis and diverticular bleeding.
Pre-Exercise Carbohydrate or Protein Ingestion Influences Substrate Oxidation but Not Performance or Hunger Compared with Cycling in the Fasted State
Authors: Rothschild Jeffrey A. , Kilding Andrew E. , Broome Sophie C. , Stewart Tom , Cronin John B. , Plews Daniel J.
Published: April 2021

Nutritional intake can influence exercise metabolism and performance, but there is a lack of research comparing protein-rich pre-exercise meals with endurance exercise performed both in the fasted state and following a carbohydrate-rich breakfast. The purpose of this study was to determine the effects of three pre-exercise nutrition strategies on metabolism and exercise capacity during cycling. On three occasions, seventeen trained male cyclists (VO2peak 62.2 ± 5.8 mL·kg−1·min−1, 31.2 ± 12.4 years, 74.8 ± 9.6 kg) performed twenty minutes of submaximal cycling (4 × 5 min stages at 60%, 80%, and 100% of ventilatory threshold (VT), and 20% of the difference between power at the VT and peak power), followed by 3 × 3 min intervals at 80% peak aerobic power and 3 × 3 min intervals at maximal effort, 30 min after consuming a carbohydrate-rich meal (CARB; 1 g/kg CHO), a protein-rich meal (PROTEIN; 0.45 g/kg protein + 0.24 g/kg fat), or water (FASTED), in a randomized and counter-balanced order. Fat oxidation was lower for CARB compared with FASTED at and below the VT, and compared with PROTEIN at 60% VT. There were no differences between trials for average power during high-intensity intervals (367 ± 51 W, p = 0.516). Oxidative stress (F2-Isoprostanes), perceived exertion, and hunger were not different between trials. Overall, exercising in the overnight-fasted state increased fat oxidation during submaximal exercise compared with exercise following a CHO-rich breakfast, and pre-exercise protein ingestion allowed similarly high levels of fat oxidation. There were no differences in perceived exertion, hunger, or performance, and we provide novel data showing no influence of pre-exercise nutrition ingestion on exercise-induced oxidative stress.
Hypomagnesemia Is a Risk Factor for Infections after Kidney Transplantation: A Retrospective Cohort Analysis
Authors: Odler Balazs , Deak Andras T. , Pregartner Gudrun , Riedl Regina , Bozic Jasmin , Trummer Christian , Prenner Anna , Söllinger Lukas , Krall Marcell , Höflechner Lukas , Hebesberger Carina , Boxler Matias S. , Berghold Andrea , Schemmer Peter , Pilz Stefan , Rosenkranz Alexander R.
Published: April 2021

Introduction: Magnesium (Mg2+) deficiency is a common finding in the early phase after kidney transplantation (KT) and has been linked to immune dysfunction and infections. Data on the association of hypomagnesemia and the rate of infections in kidney transplant recipients (KTRs) are sparse. Methods: We conducted a single-center retrospective cohort study of KTRs transplanted between 2005 and 2015. Laboratory data, including serum Mg2+ (median time of the Mg2+ measurement from KT: 29 days), rate of infections including mainly urinary tract infections (UTI), and common transplant-related viral infections (CMV, polyoma, EBV) in the early phase after KT were recorded. The primary outcome was the incidence of infections within one year after KT, while secondary outcomes were hospitalization due to infection, incidence rates of long-term (up to two years) infections, and all-cause mortality. Results: We enrolled 376 KTRs of whom 229 patients (60.9%) suffered from Mg2+ deficiency defined as a serum Mg2+ < 0.7 mmol/L. A significantly higher incidence rate of UTIs and viral infections was observed in patients with versus without Mg2+ deficiency during the first year after KT (58.5% vs. 47.6%, p = 0.039 and 69.9% vs. 51.7%, p < 0.001). After adjustment for potential confounders, serum Mg2+ deficiency remained an independent predictor of both UTIs and viral infections (odds ratio (OR): 1.73, 95% CI: 1.04–2.86, p = 0.035 and OR: 2.05, 95% CI: 1.23–3.41, p = 0.006). No group differences according to Mg2+ status in hospitalizations due to infections and infection incidence rates in the 12–24 months post-transplant were observed. In the Cox regression analysis, Mg2+ deficiency was not significantly associated with all-cause mortality (HR: 1.15, 95% CI: 0.70–1.89, p = 0.577). Conclusions: KTRs suffering from Mg2+ deficiency are at increased risk of UTIs and viral infections in the first year after KT. Interventional studies investigating the effect of Mg2+ supplementation on Mg2+ deficiency and viral infections in KTRs are needed.
Cytomegalovirus Disease in Renal Transplanted Patients: Prevalence, Determining Factors, and Influence on Graft and Patients Outcomes
Authors: Alfieri Carlo Maria , Molinari Paolo , Gandolfo Mariateresa , Campise Mariarosaria , Cresseri Donata , Regalia Anna , Favi Evaldo , Li Min , Ikehata Masami , Delbue Serena , Messa Piergiorgio
Published: April 2021

The prevalence and the factors related to cytomegalovirus (CMV) disease (CMVd) during the 1st year of renal transplantation (RTx) and the relationship between CMVd and early and long-term graft and RTx-patient (RTx-p) survival were evaluated. In 505 RTx-p, followed up for 8(5–11) years, data were recorded after 1-(T1) and 12-(T12) months of RTx. CMVd was defined either by CMV replication without clinical signs of disease (CMVr, 43%), or CMV replication with signs of disease (CMVs, 57%). During the 1st year of RTx, 45% of RTx-p had CMVd (CMVd+). CMVd+ patients were older than CMVd− patients. Female gender and Donor CMV-IgG+ (CMV IgG−D+)/recipient IgG- (CMV IgG−R-) status were more prevalent in CMVd+. At T1, CMVd+ had lower albumin, haemoglobin, and higher uric-acid and reactive C-protein than CMVd− and, at T1 and T12, received more steroids. Albumin-T1 was the unique factor in determining CMVd+, maintaining its significance also after the inclusion of IgG−D+/IgG−R− status to the model. CMVs had higher prevalence of CMV IgG-D+/IgG-R- than CMVr. CMVd, CMVr, and CMVs had no impact on graft loss (11% of RTx-p) and RTx-p death (8% of RTx-p). CMVd is highly prevalent during the 1st year of RTx. Albumin-T1 influences CMVd insurgence. CMVd did not impact on RTx and RTx-p loss.
Hybrid Atypical Enteropathogenic and Extraintestinal Escherichia coli (aEPEC/ExPEC) BA1250 Strain: A Draft Genome
Authors: Munhoz Danielle D. , Santos Fernanda F. , Mitsunari Thais , Schüroff Paulo A. , Elias Waldir P. , Carvalho Eneas , Piazza Roxane M. F.
Published: April 2021

Diarrheagenic Escherichia coli is the major bacterial etiological agent of severe diarrhea and a major concern of public health. These pathogens have acquired genetic characteristics from other pathotypes, leading to unusual and singular genetic combinations, known as hybrid strains and may be more virulent due to a set of virulence factors from more than one pathotype. One of the possible combinations is with extraintestinal E. coli (ExPEC), a leading cause of urinary tract infection, often lethal after entering the bloodstream and atypical enteropathogenic E. coli (aEPEC), responsible for death of thousands of people every year, mainly children under five years old. Here we report the draft genome of a strain originally classified as aEPEC (BA1250) isolated from feces of a child with acute diarrhea. Phylogenetic analysis indicates that BA1250 genome content is genetically closer to E. coli strains that cause extraintestinal infections, other than intestinal infections. A deeper analysis showed that in fact this is a hybrid strain, due to the presence of a set of genes typically characteristic of ExPEC. These genomic findings expand our knowledge about aEPEC heterogeneity allowing further studies concerning E. coli pathogenicity and may be a source for future comparative studies, virulence characteristics, and evolutionary biology.
A Meta-Analysis of the Analgesic Efficacy of Single-Doses of Ibuprofen Compared to Traditional Non-Opioid Analgesics Following Third Molar Surgery
Authors: Franco-de la Torre Lorenzo , Figueroa-Fernández Norma Patricia , Franco-González Diana Laura , Alonso-Castro Ángel Josabad , Rivera-Luna Federico , Isiordia-Espinoza Mario Alberto
Published: April 2021

The purpose of this systematic review was to determine the analgesic efficacy and adverse effects of ibuprofen in comparison with other traditional non-opioid analgesics after third molar surgery. A total of 17 full texts were identified in PubMed and assessed using the Cochrane Collaboration’s risk of bias tool by two independent researchers. The sum of pain intensity differences, total pain relief, the overall evaluation, the number of patients requiring rescue analgesics, and adverse effects were collected. Data were analyzed using the Review Manager Software 5.3. for Windows. A total of 15 articles met the criteria. The qualitative and quantitative analysis showed that ibuprofen is more effective to relieve post-operative dental pain than acetaminophen, meclofenamate, aceclofenac, bromfenac, and aspirin. Moreover, ibuprofen and traditional non-steroidal anti-inflammatory drugs have a similar safety profile. In conclusion, ibuprofen 400 mg appears to have good analgesic efficacy and a safety profile similar to other traditional non-steroidal anti-inflammatory drugs after third molar surgery.
3D Bioprinting of Functional Skin Substitutes: From Current Achievements to Future Goals
Authors: Manita Paula Gabriela , Garcia-Orue Itxaso , Santos-Vizcaino Edorta , Hernandez Rosa Maria , Igartua Manoli
Published: April 2021

The aim of this review is to present 3D bioprinting of skin substitutes as an efficient approach of managing skin injuries. From a clinical point of view, classic treatments only provide physical protection from the environment, and existing engineered scaffolds, albeit acting as a physical support for cells, fail to overcome needs, such as neovascularisation. In the present work, the basic principles of bioprinting, together with the most popular approaches and choices of biomaterials for 3D-printed skin construct production, are explained, as well as the main advantages over other production methods. Moreover, the development of this technology is described in a chronological manner through examples of relevant experimental work in the last two decades: from the pioneers Lee et al. to the latest advances and different innovative strategies carried out lately to overcome the well-known challenges in tissue engineering of skin. In general, this technology has a huge potential to offer, although a multidisciplinary effort is required to optimise designs, biomaterials and production processes.
Proteomic Identification and Meta-Analysis in Salvia hispanica RNA-Seq de novo Assemblies
Authors: Klein Ashwil , Husselmann Lizex H. H. , Williams Achmat , Bell Liam , Cooper Bret , Ragar Brent , Tabb David L.
Published: April 2021

While proteomics has demonstrated its value for model organisms and for organisms with mature genome sequence annotations, proteomics has been of less value in nonmodel organisms that are unaccompanied by genome sequence annotations. This project sought to determine the value of RNA-Seq experiments as a basis for establishing a set of protein sequences to represent a nonmodel organism, in this case, the pseudocereal chia. Assembling four publicly available chia RNA-Seq datasets produced transcript sequence sets with a high BUSCO completeness, though the number of transcript sequences and Trinity “genes” varied considerably among them. After six-frame translation, ProteinOrtho detected substantial numbers of orthologs among other species within the taxonomic order Lamiales. These protein sequence databases demonstrated a good identification efficiency for three different LC-MS/MS proteomics experiments, though a seed proteome showed considerable variability in the identification of peptides based on seed protein sequence inclusion. If a proteomics experiment emphasizes a particular tissue, an RNA-Seq experiment incorporating that same tissue is more likely to support a database search identification of that proteome.