bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperpolarized 13C Magnetic Resonance Spectroscopic Imaging of Pyruvate Metabolism in Murine Breast Cancer Models of Different Metastatic Potential
Authors: Macdonald Erin B. , Begovatz Paul , Barton Gregory P. , Erickson-Bhatt Sarah , Inman David R. , Cox Benjamin L. , Eliceiri Kevin W. , Strigel Roberta M. , Ponik Suzanne M. , Fain Sean B.
Published: April 2021

This study uses dynamic hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopic imaging (MRSI) to estimate differences in glycolytic metabolism between highly metastatic (4T1, n = 7) and metastatically dormant (4T07, n = 7) murine breast cancer models. The apparent conversion rate of pyruvate-to-lactate (kPL) and lactate-to-pyruvate area-under-the-curve ratio (AUCL/P) were estimated from the metabolite images and compared with biochemical metabolic measures and immunohistochemistry (IHC). A non-significant trend of increasing kPL (p = 0.17) and AUCL/P (p = 0.11) from 4T07 to 4T1 tumors was observed. No significant differences in tumor IHC lactate dehydrogenase-A (LDHA), monocarboxylate transporter-1 (MCT1), cluster of differentiation 31 (CD31), and hypoxia inducible factor-α (HIF-1α), tumor lactate-dehydrogenase (LDH) activity, or blood lactate or glucose levels were found between the two tumor lines. However, AUCL/P was significantly correlated with tumor LDH activity (ρspearman = 0.621, p = 0.027) and blood glucose levels (ρspearman = −0.474, p = 0.042). kPL displayed a similar, non-significant trend for LDH activity (ρspearman = 0.480, p = 0.114) and blood glucose levels (ρspearman = −0.414, p = 0.088). Neither kPL nor AUCL/P were significantly correlated with blood lactate levels or tumor LDHA or MCT1. The significant positive correlation between AUCL/P and tumor LDH activity indicates the potential of AUCL/P as a biomarker of glycolytic metabolism in breast cancer models. However, the lack of a significant difference between in vivo tumor metabolism for the two models suggest similar pyruvate-to-lactate conversion despite differing metastatic potential.
Preliminary Results of CitraVes™ Effects on Low Density Lipoprotein Cholesterol and Waist Circumference in Healthy Subjects after 12 Weeks: A Pilot Open-Label Study
Authors: Raimondo Stefania , Nikolic Dragana , Conigliaro Alice , Giavaresi Gianluca , Lo Sasso Bruna , Giglio Rosaria Vincenza , Chianetta Roberta , Manno Mauro , Raccosta Samuele , Corleone Valeria , Ferrante Giovanni , Citarrella Roberto , Rizzo Manfredi , De Leo Giacomo , Ciaccio Marcello , Montalto Giuseppe , Alessandro Riccardo
Published: April 2021

Appropriate monitoring and control of modifiable risk factors, such as the level of low-density lipoprotein cholesterol (LDL-C) and other types of dyslipidemia, have an important role in the prevention of cardiovascular diseases (CVD). Recently, various nutraceuticals with lipid-lowering effects have gained attention. In addition to the plant-derived bioactive compounds, recent studies suggested that plant cells are able to release small lipoproteic structures named extracellular vesicles (EVs). The interaction between EVs and mammalian cells could lead to beneficial effects through anti-inflammatory and antioxidant activities. The present study aimed to assess the safety of the new patented plant-based product citraVes™, containing extracellular vesicles (EVs) from Citrus limon (L.) Osbeck juice, and to investigate its ability to modulate different CV risk factors in healthy subjects. A cohort of 20 healthy volunteers was recruited in a prospective open-label study. All participants received the supplement in a spray-dried formulation at a stable dose of 1000 mg/day for 3 months. Anthropometric and hematobiochemical parameters were analyzed at the baseline and after the follow-up period of 1 and 3 months. We observed that the supplement has an effect on two key factors of cardiometabolic risk in healthy subjects. A significant change in waist circumference was found in women after 4 (85.4 [79.9, 91.0] cm, p < 0.005) and 12 (85.0 [80.0, 90.0] cm, p < 0.0005) weeks, when compared to the baseline value (87.6 [81.7, 93.6] cm). No difference was found in men (baseline: 100.3 [95.4, 105.2] cm; 4 weeks: 102.0 [95.7, 108.3] cm; 12 weeks: 100.0 [95.3, 104.7] cm). The level of LDL-C was significantly lower at 12 weeks versus 4 weeks (p = 0.0064). Our study evaluated, for the first time, the effects of a natural product containing plant-derived EVs on modifiable risk factors in healthy volunteers. The results support the use of EV extracts to manage cardiometabolic risk factors successfully.
Simulation-Based and Experimental Investigation of Micro End Mills with Wiper Geometry
Authors: Platt Timo , Meijer Alexander , Merhofe Torben , Biermann Dirk
Published: April 2021

One of the major advantages of micromachining is the high achievable surface quality at highly flexible capabilities in terms of the machining of workpieces with complex geometric properties. Unfortunately, finishing operations often result in extensive process times due to the dependency of the resulting surface topography on the cutting parameter, e.g., the feed per tooth, fz. To overcome this dependency, special tool shapes, called wipers, have proven themselves in the field of turning. This paper presents the transfer of such tool shapes to solid carbide milling tools for micromachining. In this context, a material removal simulation (MRS) was used to investigate promising wiper geometries for micro end mills (d = 1 mm). Through experimental validation of the results, the surface topography, the resulting process forces, and tendencies in the residual stress state were investigated, machining the hot work tool steel (AISI H11). The surface-related results show a high agreement and thus the potential of MRS for tool development. Deviations from the experimental data for large wipers could be attributed to the non-modeled tool deflections, friction, and plastic deformations. Furthermore, a slight geometry-dependent increase in cutting forces and compressive stresses were observed, while a significant reduction in roughness up to 84% and favorable topography conditions were achieved by adjusting wipers and cutting parameters.
Mutation Signatures and In Silico Docking of Novel SARS-CoV-2 Variants of Concern
Authors: Shahhosseini Nariman , Babuadze George , Wong Gary , Kobinger Gary
Published: April 2021

One year since the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China, several variants of concern (VOC) have appeared around the world, with some variants seeming to pose a greater thread to public health due to enhanced transmissibility or infectivity. This study provides a framework for molecular characterization of novel VOC and investigates the effect of mutations on the binding affinity of the receptor-binding domain (RBD) to human angiotensin-converting enzyme 2 (hACE2) using in silico approach. Notable nonsynonymous mutations in RBD of VOC include the E484K and K417N/T that can be seen in South African and Brazilian variants, and N501Y and D614G that can be seen in all VOC. Phylogenetic analyses demonstrated that although the UK-VOC and the BR-VOC fell in the clade GR, they have different mutation signatures, implying an independent evolutionary pathway. The same is true about SA-VOC and COH-VOC felling in clade GH, but different mutation signatures. Combining molecular interaction modeling and the free energy of binding (FEB) calculations for VOC, it can be assumed that the mutation N501Y has the highest binding affinity in RBD for all VOC, followed by E484K (only for BR-VOC), which favors the formation of a stable complex. However, mutations at the residue K417N/T are shown to reduce the binding affinity. Once vaccination has started, there will be selective pressure that would be in favor of the emergence of novel variants capable of escaping the immune system. Therefore, genomic surveillance should be enhanced to find and monitor new emerging SARS-CoV-2 variants before they become a public health concern.
Ecophysiological Features Shape the Distribution of Prophages and CRISPR in Sulfate Reducing Prokaryotes
Authors: Orellana Roberto , Arancibia Alejandra , Badilla Leonardo , Acosta Jonathan , Arancibia Gabriela , Escar Rodrigo , Ferrada Gustavo , Seeger Michael
Published: April 2021

Sulfate reducing prokaryotes (SRP) are a phylogenetically and physiologically diverse group of microorganisms that use sulfate as an electron acceptor. SRP have long been recognized as key players of the carbon and sulfur cycles, and more recently, they have been identified to play a relevant role as part of syntrophic and symbiotic relations and the human microbiome. Despite their environmental relevance, there is a poor understanding about the prevalence of prophages and CRISPR arrays and how their distribution and dynamic affect the ecological role of SRP. We addressed this question by analyzing the results of a comprehensive survey of prophages and CRISPR in a total of 91 genomes of SRP with several genotypic, phenotypic, and physiological traits, including genome size, cell volume, minimum doubling time, cell wall, and habitat, among others. Our analysis discovered 81 prophages in 51 strains, representing the 56% of the total evaluated strains. Prophages are non-uniformly distributed across the SRP phylogeny, where prophage-rich lineages belonged to Desulfovibrionaceae and Peptococcaceae. Furthermore, our study found 160 CRISPR arrays in 71 SRP, which is more abundant and widely spread than previously expected. Although there is no correlation between presence and abundance of prophages and CRISPR arrays at the strain level, our analysis showed that there is a directly proportional relation between cellular volumes and number of prophages per cell. This result suggests that there is an additional selective pressure for strains with smaller cells to get rid of foreign DNA, such as prophages, but not CRISPR, due to less availability of cellular resources. Analysis of the prophage genes encoding viral structural proteins reported that 44% of SRP prophages are classified as Myoviridae, and comparative analysis showed high level of homology, but not synteny, among prophages belonging to the Family Desulfovibrionaceae. We further recovered viral-like particles and structures that resemble outer membrane vesicles from D. vulgaris str. Hildenborough. The results of this study improved the current understanding of dynamic interactions between prophages and CRISPR with their hosts in both cultured and hitherto-uncultured SRP strains, and how their distribution affects the microbial community dynamics in several sulfidogenic natural and engineered environments.
Complementary Use of Magnetometric Measurements for Geochemical Investigation of Light REE Concentration in Anthropogenically Polluted Soils
Authors: Fabijańczyk Piotr , Zawadzki Jarosław
Published: April 2021

The purpose of this study was to use fast geophysical measurements of soil magnetic susceptibility (κ) as supplementary data for chemical measurements of selected light rare earth elements (REEs) in soil. In order to ensure diversity in soil conditions, anthropogenic conditions and types of land use, seven areas were selected, all located in regions subjected to past or present industrial pollution. Magnetometric parameters were measured using a selected magnetic sensor that was specially designed for measurements of soil cores and were used to classify collected soil cores into six distinctive types. The analysis of REEs concentrations in soil was carried out taking into account the grouping of collected soil samples based on the type of study area (open, forested and mountain), and additionally on the measured magnetometric parameters of collected soil cores. A use of magnetometric measurements provided different, but complementary to chemical measurements information, which allowed to obtain deeper insight on REEs concentrations in soils in studied areas.
Upper Jurassic Bedded Limestones and Early Diagenetic Dolomitized Limestones in the Light of Mineralogical, Geochemical and Sedimentological Studies; Kraków Area, Poland
Authors: Krajewski Marcin , Olchowy Piotr
Published: April 2021

This paper describes and analyzes the Upper Jurassic (Lower Kimmeridgian) succession exposed in the Zakrzówek Horst, located in the Kraków area. Three distinguished facies types FT 1-FT 3 comprise several limestone varieties: sponge-microbial, pelitic-bioclastic, and partly dolomitized detrital-bioclastic. Their sedimentary environments varied from relatively deeper, attaining storm-wave base, to more shallower, probably close to normal-wave base. Characteristic features of limestones are changes in contents of CaCO3 and insoluble residuum as well as porosity values in vertical transitional zones between facies types. The investigated facies types differ in sediment porosity dependent on development of limestones and its susceptibility to mechanical compaction during the early diagenesis. The studied limestones show high CaCO3 contents and minor insoluble residuum contents comprising quartz, chalcedony and clay minerals. No distinct variability occurs in contents of magnesium, silica, alumina and iron accumulated in clay minerals, iron oxides and oxyhydroxides, as well as in the amounts of amorphous silica. Early diagenetic dolomites, which occur locally within the limestones, were unrelated to fracture systems as possible pathways responsible for transfer of solutions rich in Mg2+ ions. The possible source of Mg2+ ions might have been the pore solutions, which migrated from compacted basinal bedded facies towards reef facies or the grain-supported bedded facies developed in the adjacent areas. Microscopic studies revealed dedolomitization at the surfaces and in the inner parts of dolomite crystals. In many cases, dolomite crystals were replaced by calcite forming pseudomorphs.
Synthesis, Biomacromolecular Interactions, Photodynamic NO Releasing and Cellular Imaging of Two [RuCl(qn)(Lbpy)(NO)]X Complexes
Authors: Song Luna , Bai Hehe , Liu Chenyang , Gong Wenjun , Wang Ai , Wang Li , Zhao Yi , Zhao Xuan , Wang Hongfei
Published: April 2021

Two light-activated NO donors [RuCl(qn)(Lbpy)(NO)]X with 8-hydroxyquinoline (qn) and 2,2′-bipyridine derivatives (Lbpy) as co-ligands were synthesized (Lbpy1 = 4,4′-dicarboxyl-2,2′-dipyridine, X = Cl− and Lbpy2 = 4,4′-dimethoxycarbonyl-2,2′-dipyridine, X = NO3−), and characterized using ultraviolet–visible (UV-vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (1H NMR), elemental analysis and electrospray ionization mass spectrometry (ESI-MS) spectra. The [RuCl(qn)(Lbpy2)(NO)]NO3 complex was crystallized and exhibited distorted octahedral geometry, in which the Ru–N(O) bond length was 1.752(6) Å and the Ru–N–O angle was 177.6(6)°. Time-resolved FT-IR and electron paramagnetic resonance (EPR) spectra were used to confirm the photoactivated NO release of the complexes. The binding constant (Kb) of two complexes with human serum albumin (HSA) and DNA were quantitatively evaluated using fluorescence spectroscopy, Ru-Lbpy1 (Kb~106 with HSA and ~104 with DNA) had higher affinity than Ru-Lbpy2. The interactions between the complexes and HSA were investigated using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) and EPR spectra. HSA can be used as a carrier to facilitate the release of NO from the complexes upon photoirradiation. The confocal imaging of photo-induced NO release in living cells was successfully observed with a fluorescent NO probe. Moreover, the photocleavage of pBR322 DNA for the complexes and the effect of different Lbpy substituted groups in the complexes on their reactivity were analyzed.
The Effect of a New Glucose–Methotrexate Conjugate on Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma Cell Lines
Authors: Woźniak Marta , Makuch Sebastian , Pastuch-Gawołek Gabriela , Wiśniewski Jerzy , Szeja Wiesław , Nowak Martyna , Krawczyk Monika , Agrawal Siddarth
Published: April 2021

Patients with hematologic malignancies require intensive therapies, including high-dose chemotherapy. Antimetabolite–methotrexate (MTX) has been used for many years in the treatment of leukemia and in lymphoma patients. However, the lack of MTX specificity causes a significant risk of morbidity, mortality, and severe side effects that impairs the quality of patients’ life. Therefore, novel targeted therapies based on the malignant cells’ common traits have become an essential treatment strategy. Glucose transporters have been found to be overexpressed in neoplastic cells, including hematologic malignancies. In this study, we biologically evaluated a novel glucose–methotrexate conjugate (Glu–MTX) in comparison to a free MTX. The research aimed to assess the effectiveness of Glu–MTX on chosen human lymphoma and leukemia cell lines. Cell cytotoxicity was verified by MTT viability test and flow cytometry. Moreover, the cell cycle and cellular uptake of Glu–MTX were evaluated. Our study reveals that conjugation of methotrexate with glucose significantly increases drug uptake and results in similar cytotoxicity of the synthesized compound. Although the finding has been confined to in vitro studies, our observations shed light on a potential therapeutic approach that increases the selectivity of chemotherapeutics and can improve leukemia and lymphoma patients’ outcomes.
Pressurized-Liquid Extraction as an Efficient Method for Valorization of Thymus serpyllum Herbal Dust towards Sustainable Production of Antioxidants
Authors: Mrkonjić Živan , Rakić Dušan , Kaplan Muammer , Teslić Nemanja , Zeković Zoran , Pavlić Branimir
Published: April 2021

The aim of this study was to valorize Thymus serpyllum herbal dust, a particular fraction distinguished as an industrial waste from filter-tea production. Pressurized liquid extraction (PLE) was used with the aim of overcoming certain obstacles of conventional extraction techniques in terms of shortening extraction time, reducing solvent consumption and energy costs, using “green” solvents and obtaining high yield and quality products. In order to optimize PLE of T. serpyllum herbal dust, the preliminary screening of the independent variables in order to define the most influential parameters and their domain was done first. After the screening, the optimization study using the face-centered central composite experimental design (CCD) with response surface methodology (RSM) was implemented. Additionally, taking into account the high awareness of the positive influence of antioxidants on the human health and associating it with high content of polyphenolic compounds in various members of Lamiaceae family, PLE has proven to be a great approach for antioxidants recovery from T. serpyllum herbal dust.
Microbial Sensing and Removal of Heavy Metals: Bioelectrochemical Detection and Removal of Chromium(VI) and Cadmium(II)
Authors: Alfadaly Reham A. , Elsayed Ashraf , Hassan Rabeay Y. A. , Noureldeen Ahmed , Darwish Hadeer , Gebreil Ahmed S.
Published: April 2021

The presence of inorganic pollutants such as Cadmium(II) and Chromium(VI) could destroy our environment and ecosystem. To overcome this problem, much attention was directed to microbial technology, whereas some microorganisms could resist the toxic effects and decrease pollutants concentration while the microbial viability is sustained. Therefore, we built up a complementary strategy to study the biofilm formation of isolated strains under the stress of heavy metals. As target resistive organisms, Rhizobium-MAP7 and Rhodotorula ALT72 were identified. However, Pontoea agglumerans strains were exploited as the susceptible organism to the heavy metal exposure. Among the methods of sensing and analysis, bioelectrochemical measurements showed the most effective tools to study the susceptibility and resistivity to the heavy metals. The tested Rhizobium strain showed higher ability of removal of heavy metals and more resistive to metals ions since its cell viability was not strongly inhibited by the toxic metal ions over various concentrations. On the other hand, electrochemically active biofilm exhibited higher bioelectrochemical signals in presence of heavy metals ions. So by using the two strains, especially Rhizobium-MAP7, the detection and removal of heavy metals Cr(VI) and Cd(II) is highly supported and recommended.
Effect of Process Conditions and Colloidal Properties of Cellulose Nanocrystals Suspensions on the Production of Hydrogel Beads
Authors: Ferrari Nicola , Maestri Cecilia Ada , Bettotti Paolo , Grassi Mario , Abrami Michela , Scarpa Marina
Published: April 2021

The influence of the physical, rheological, and process parameters on the cellulose nanocrystal (CNC) drops before and after external gelation in a CaCl2 solution was investigated. The dominant role of the CNC’s colloidal suspension properties, such as the viscous force, inertial, and surface tension forces in the fluid dynamics was quantitatively evaluated in the formation of drops and jellified beads. The similarity and difference between the behavior of carbohydrate polymers and rod-like crystallites such as CNC were enlightened. Pump-driven and centrifugally-driven external gelation approaches were followed to obtain CNC hydrogel beads with tunable size and regular shape. A superior morphological control—that is, a more regular shape and smaller dimension of the beads—were obtained by centrifugal force-driven gelation. These results suggest that even by using a simple set-up and a low-speed centrifuge device, the extrusion of a colloidal solution through a small nozzle under a centrifugal field is an efficient approach for the production of CNC hydrogel beads with good reproducibility, control over the bead morphology and size monodispersion.
Microfluidics for Peptidomics, Proteomics, and Cell Analysis
Authors: Vitorino Rui , Guedes Sofia , da Costa João Pinto , Kašička Václav
Published: April 2021

Microfluidics is the advanced microtechnology of fluid manipulation in channels with at least one dimension in the range of 1–100 microns. Microfluidic technology offers a growing number of tools for manipulating small volumes of fluid to control chemical, biological, and physical processes relevant to separation, analysis, and detection. Currently, microfluidic devices play an important role in many biological, chemical, physical, biotechnological and engineering applications. There are numerous ways to fabricate the necessary microchannels and integrate them into microfluidic platforms. In peptidomics and proteomics, microfluidics is often used in combination with mass spectrometric (MS) analysis. This review provides an overview of using microfluidic systems for peptidomics, proteomics and cell analysis. The application of microfluidics in combination with MS detection and other novel techniques to answer clinical questions is also discussed in the context of disease diagnosis and therapy. Recent developments and applications of capillary and microchip (electro)separation methods in proteomic and peptidomic analysis are summarized. The state of the art of microchip platforms for cell sorting and single-cell analysis is also discussed. Advances in detection methods are reported, and new applications in proteomics and peptidomics, quality control of peptide and protein pharmaceuticals, analysis of proteins and peptides in biomatrices and determination of their physicochemical parameters are highlighted.
Global Analysis of RNA-Dependent RNA Polymerase-Dependent Small RNAs Reveals New Substrates and Functions for These Proteins and SGS3 in Arabidopsis
Authors: Hua Xia , Berkowitz Nathan D. , Willmann Matthew R. , Yu Xiang , Lyons Eric , Gregory Brian D.
Published: April 2021

RNA silencing pathways control eukaryotic gene expression transcriptionally or posttranscriptionally in a sequence-specific manner. In RNA silencing, the production of double-stranded RNA (dsRNA) gives rise to various classes of 20–24 nucleotide (nt) small RNAs (smRNAs). In Arabidopsis thaliana, smRNAs are often derived from long dsRNA molecules synthesized by one of the six genomically encoded RNA-dependent RNA Polymerase (RDR) proteins. However, the full complement of the RDR-dependent smRNAs and functions that these proteins and their RNA-binding cofactors play in plant RNA silencing has not been fully uncovered. To address this gap, we performed a global genomic analysis of all six RDRs and two of their cofactors to find new substrates for RDRs and targets of the resulting RDR-derived siRNAs to uncover new functions for these proteins in plants. Based on these analyses, we identified substrates for the three RDRγ clade proteins (RDR3–5), which had not been well-characterized previously. We also identified new substrates for the other three RDRs (RDR1, RDR2, and RDR6) as well as the RDR2 cofactor RNA-directed DNA methylation 12 (RDM12) and the RDR6 cofactor suppressor of gene silencing 3 (SGS3). These findings revealed that the target substrates of SGS3 are not limited to those solely utilized by RDR6, but that this protein seems to be a more general cofactor for the RDR family of proteins. Additionally, we found that RDR6 and SGS3 are involved in the production of smRNAs that target transcripts related to abiotic stresses, including water deprivation, salt stress, and ABA response, and as expected the levels of these mRNAs are increased in rdr6 and sgs3 mutant plants. Correspondingly, plants that lack these proteins (rdr6 and sgs3 mutants) are hypersensitive to ABA treatment, tolerant to high levels of PEG8000, and have a higher survival rate under salt treatment in comparison to wild-type plants. In total, our analyses have provided an extremely data-rich resource for uncovering new functions of RDR-dependent RNA silencing in plants, while also revealing a previously unexplored link between the RDR6/SGS3-dependent pathway and plant abiotic stress responses.
Publisher’s Note: Resumed Publication of Neuroglia by MDPI
Authors: Arranz Marcos
Published: April 2021

Since the launch of the first journal Molecules [...]
Associations between Family-Based Stress and Dietary Inflammatory Potential among Families with Preschool-Aged Children
Authors: Hruska Valerie , Shivappa Nitin , Hébert James R. , Duncan Alison M. , Haines Jess , Ma David W. L.
Published: April 2021

Chronic stress is known to influence dietary choices, and stressed families often report poorer diet quality; however, little is known about how family-based stress is linked with dietary patterns that promote inflammation. This study investigated associations between family-based stress and the inflammatory potential of the diet among preschool-aged children and their parents. Parents (n = 212 mothers, n = 146 fathers) and children (n = 130 girls, n = 123 boys; aged 18 months to 5 years) from 241 families participating in the Guelph Family Health Study were included in the analyses. Parents reported levels of parenting distress, depressive symptoms, household chaos, and family functioning. The inflammatory potential of parents’ and children’s diets was quantified using the Dietary Inflammatory Index (DII®), adjusted for total energy intake (i.e., the E-DIITM). E-DII scores were regressed onto family stress using generalized estimating equations to account for shared variance among family clusters. Compared to those in homes with low chaos, parents in chaotic homes had significantly more proinflammatory dietary profiles (β = 0.973; 95% CI: 0.321, 1.624, p = 0.003). Similarly, compared to those in well-functioning families, parents in dysfunctional families had significantly more proinflammatory dietary profiles (β = 0.967; 95% CI: 0.173, 1.761, p = 0.02). No significant associations were found between parents’ E-DII scores and parenting distress or depressive symptoms, nor were any associations found for children’s E-DII scores. Results were not found to differ between males and females. Parents in chaotic or dysfunctional family environments may be at increased risk of chronic disease due to proinflammatory dietary profiles. Children’s dietary inflammatory profiles were not directly associated with family stress; however, indirect connections through family food-related behaviours may exist. Future research should prioritize elucidating these mechanisms.
Dietary Essential Amino Acid Restriction Promotes Hyperdipsia via Hepatic FGF21
Authors: Rusu Patricia M. , Chan Andrea Y. , Heikenwalder Mathias , Müller Oliver J. , Rose Adam J.
Published: April 2021

Prior studies have reported that dietary protein dilution (DPD) or amino acid dilution promotes heightened water intake (i.e., hyperdipsia) however, the exact dietary requirements and the mechanism responsible for this effect are still unknown. Here, we show that dietary amino acid (AA) restriction is sufficient and required to drive hyperdipsia during DPD. Our studies demonstrate that particularly dietary essential AA (EAA) restriction, but not non-EAA, is responsible for the hyperdipsic effect of total dietary AA restriction (DAR). Additionally, by using diets with varying amounts of individual EAA under constant total AA supply, we demonstrate that restriction of threonine (Thr) or tryptophan (Trp) is mandatory and sufficient for the effects of DAR on hyperdipsia and that liver-derived fibroblast growth factor 21 (FGF21) is required for this hyperdipsic effect. Strikingly, artificially introducing Thr de novo biosynthesis in hepatocytes reversed hyperdipsia during DAR. In summary, our results show that the DPD effects on hyperdipsia are induced by the deprivation of Thr and Trp, and in turn, via liver/hepatocyte-derived FGF21.
Foods, Nutrients and Dietary Patterns in Relation to Irrational Beliefs and Related Psychological Disorders: The ATTICA Epidemiological Study
Authors: Vassou Christina , Yannakoulia Mary , Georgousopoulou Ekavi N. , Pitsavos Christos , Cropley Mark , Panagiotakos Demosthenes B.
Published: April 2021

We explored the differences in dietary habits and dietary patterns between individuals characterized by irrational beliefs with no or low anxiety and depressive symptoms and individuals characterized by irrational beliefs with high anxiety and depressive symptomatology. Within the context of the ATTICA cohort study (2002–2012), 853 participants without evidence of cardiovascular disease (453 men (45 ± 13 years) and 400 women (44 ± 18 years)) underwent mental health assessment through the irrational beliefs inventory (IBI), the Zung self-rating depression scale (ZDRS) and the state–trait anxiety inventory (STAI). Demographic characteristics, a thorough medical history, dietary behaviour and other lifestyle behaviours were also evaluated and analysed using factor analysis. Five main factors related to dietary patterns were extracted for the high-IBI/low-STAI group of participants (explaining the 63% of the total variation in consumption), whereas four factors were extracted for the high-IBI/high-STAI participants, the high-IBI/low-ZDRS participants and the high-IBI/high-ZDRS participants, explaining 53%, 54% and 54% of the total variation, respectively. A Western-type dietary pattern was the most dominant factor for individuals reporting irrational beliefs and anxiety or depressive symptomatology. The high refined carbohydrates and fats dietary pattern was the most dominant factor for individuals with irrational beliefs but without psychopathology. Linear regression analysis showed that irrational beliefs, in combination with anxiety or depression, age, sex and BMI, were important predictors of adherence to the Mediterranean diet. Dietary habits interact with irrational beliefs and, in association with the consequent psychological disorders, are associated with overall diet, and presumably may affect the health status of individuals.
Safety and Efficacy of Sodium and Potassium Arachidonic Acid Salts in the Young Pig
Authors: Hahn Kaylee , Hardimon Joseph R. , Caskey Doug , Jost Douglas A. , Roady Patrick J. , Brenna J. Thomas , Dilger Ryan N.
Published: April 2021

Arachidonic acid (ARA; 20:4n6) and docosahexaenoic acid (DHA; 22:6n3) are polyunsaturated fatty acids (FA) naturally present in breast milk and added to most North American infant formulas (IF). We investigated the safety and efficacy of novel sodium and potassium salts of arachidonic acid as bioequivalent to support tissue levels of ARA comparable to the parent oil; M. alpina oil (Na-ARA and K-ARA) and including a Na-DHA group. Pigs of both sexes were randomized to one of five dietary treatments (n = 16 per treatment; 8 male and 8 female) from postnatal day 2 to 23. ARA and DHA were included as either triglyceride (TG) or salt. Target dietary ARA/DHA concentrations as percent of total FA by weight were as follows: TT (0.47 TG/0.32 TG), NaT (0.47 Na-salt/0.32 TG), KT (0.47 K-salt/0.32 TG), and Na0 (0.47 Na-salt/0.00), NaNa (0.47 Na-salt/0.32 Na-salt). The primary outcome in this study was bioequivalence of ARA brain accretion. Growth performance; blood and tissue fatty acid levels; liver histology; complete blood cell counts; and serum chemistries were all evaluated. Overall, diets containing test sources of ARA and DHA did not affect growth performance; liver histology; or substantially influence hematological outcomes as compared with TT. The results confirm that the use of Na and K salt forms of ARA yield bioequivalent ARA accretion in the cerebral cortex and retinal tissue compared to TG-ARA. These findings confirm that use of Na-ARA and K-ARA salts in the young pig was safe and nutritionally bioequivalent to TG-ARA for critical neural tissues.
Obesity and Ideal Cardiovascular Health: Results from the My Research Legacy Study
Authors: Leopold Jane A. , Antman Elliott M.
Published: April 2021

Obesity is associated with increased risk for cardiovascular diseases compared to normal-weight and overweight status. We hypothesized that obese subjects would have lower ideal cardiovascular health than normal-weight and overweight subjects, but a subset among the obese would have a favorable cardiovascular health profile. Differences in ideal cardiovascular health between normal-weight (n = 523), overweight (n = 378), and obese (n = 660) subjects were examined using data from the Life’s Simple 7 survey and digital health devices. Obese participants were more likely to have prevalent cardiovascular disease, diabetes mellitus, hypertension, and hypercholesterolemia compared to normal weight and overweight (all p < 0.01). Life’s Simple 7 Health Scores, a measure of ideal cardiovascular health, were lower in obese than in normal-weight and overweight groups (5.6 ± 1.2 vs. 8.0 ± 1.1 vs. 6.8 ± 1.1, p < 0.01). A subset of obese with ideal cardiovascular health scores was identified (n = 103). Compared to obese with non-ideal health scores (n = 557), these individuals were more likely to have ideal cardiovascular risk factor status, diet, and exercise profiles. These findings indicate that there is heterogeneity among obese persons and suggest that an assessment of cardiovascular health factors and behaviors can identify areas for intervention beyond weight reduction alone to optimize cardiovascular health.
Improving the Solubilization and Bioavailability of Arbidol Hydrochloride by the Preparation of Binary and Ternary β-Cyclodextrin Complexes with Poloxamer 188
Authors: Anwer Md. Khalid , Iqbal Muzaffar , Ahmed Mohammad Muqtader , Aldawsari Mohammed F. , Ansari Mohd Nazam , Ezzeldin Essam , Khalil Nasr Y. , Ali Raisuddin
Published: April 2021

In the current study, the effect of poloxamer 188 on the complexation efficiency and dissolution of arbidol hydrochloride (ADL), a broad-spectrum antiviral agent, with β-cyclodextrin (β-CD) was investigated. Phase solubility studies confirmed a stoichiometry of a 1:1 ratio for both ADL:β-CD and ADL/β-CD with a 1% poloxamer 188 system with an AL type of phase solubility curve. The stability constants (K1:1) calculated from the AL type diagram were 550 M-1 and 2134 M-1 for AD:β-CD and ADL/β-CD with 1% poloxamer 188, respectively. The binary ADL/β-CD and ternary ADL/β-CD with 1% poloxamer 188 complexes were prepared by kneading and a solvent evaporation method and were characterized by aqueous solubility, FTIR, PXRD, DSC and SEM in vitro studies. The solubility (13.1 fold) and release of ADL were markedly improved in kneaded ternary ADL/β-CD with 1% poloxamer 188 (KDB). The binding affinity of ADL and β-CD was confirmed by 1H NMR and 2D ROSEY studies. The ternary complex (KDB) was further subjected for in vivo pharmacokinetic studies in rats and a significant improvement in the bioavailability (2.17 fold) was observed in comparison with pure ADL. Therefore, it can be concluded that the solubilization and bioavailability of ADL can be remarkably increased by ADL/β-CD complexation in the presence of a third component, poloxamer 188.
Preparation of Topical Itraconazole with Enhanced Skin/Nail Permeability and In Vivo Antifungal Efficacy against Superficial Mycosis
Authors: Subedi Laxman , Song Seung-Yub , Jha Saurav Kumar , Lee Sung-Ho , Pangeni Rudra , Koo Kyo-Tan , Kim Beum Joon , Cho Seung-Sik , Park Jin Woo
Published: April 2021

In this study, a stable and highly skin-permeable topical delivery system for itraconazole (ITZ) was designed to provide effective treatment against superficial mycosis. Herein, ITZ was incorporated into a solution composed of ethanol, benzyl alcohol, hydrochloric acid, Transcutol P, and cyclomethicone as a delivery vehicle, solubilizer, protonating agent, permeation enhancer, and spreading agent, respectively. At 72 h, the optimal topical ITZ formulation (ITZ–TF#11) exhibited 135% enhanced skin permeability, which led to increases in drug deposition in the stratum corneum, epidermis, and dermis of 479%, 739%, and 2024%, respectively, compared with the deposition of 1% ITZ in ethanol (control). Moreover, on day 7, ITZ–TF#11 demonstrated 2.09- and 2.30-fold enhanced nail flux and drug deposition, compared with the control. At a dose of 40 mg/kg/day, ITZ–TF#11 showed 323% greater lesion recovery, a 165% lower mean erythema severity score, and a 37% lower mean logarithm of viable fungal cells in skin in the treated area, compared with mice that received oral ITZ at the same dose. Overall, the findings imply that ITZ–TF#11 is a superior alternative to oral ITZ for treatment of superficial mycosis.
Advances in Twin-Screw Granulation Processing
Authors: Nandi Uttom , Trivedi Vivek , Ross Steven A. , Douroumis Dennis
Published: April 2021

Twin-screw granulation (TSG) is a pharmaceutical process that has gained increased interest from the pharmaceutical industry for its potential for the development of oral dosage forms. The technology has evolved rapidly due to the flexibility of the equipment design, the selection of the process variables and the wide range of processed materials. Most importantly, TSG offers the benefits of both batch and continuous manufacturing for pharmaceutical products, accompanied by excellent process control, high product quality which can be achieved through the implementation of Quality by Design (QbD) approaches and the integration of Process Analytical Tools (PAT). Here, we present basic concepts of the various twin-screw granulation techniques and present in detail their advantages and disadvantages. In addition, we discuss the detail of the instrumentation used for TSG and how the critical processing paraments (CPP) affect the critical quality attributes (CQA) of the produced granules. Finally, we present recent advances in TSG continuous manufacturing including the paradigms of modelling of continuous granulation process, QbD approaches coupled with PAT monitoring for granule optimization and process understanding.
Double Blind Peer-Review in Philosophies
Authors: Schroeder Marcin J. , Aloè Carla
Published: April 2021

Peer-review has become increasingly important to the way scholarly journals assess whether a manuscript is suitable for publication [...]
Improved Measurements of the Physical Properties of Oriental Lacquers Using Atomic Force Microscopy and a Nanoindenter
Authors: Yu Hye Hyun , Lim Jung-Ah , Lee Kang-Bong , Lee Yeonhee
Published: April 2021

Researchers have widely investigated Oriental lacquers to identify the chemical composition and have elucidated corresponding polymerization mechanisms using rigorous analytical techniques. However, researchers generally test the physical properties of Oriental lacquers by conventional methods that are perhaps overly simplistic. Here, we propose accurate and quantitative methods for evaluating the physical properties of Korean, Vietnamese, and Myanmarese lacquer films using atomic force microscopy (AFM), a nanoindenter, and a 90° peel tester. We obtained surface images of the lacquers in accordance with drying time using scanning electron microscopy and AFM. The Korean lacquer film exhibited fast hardening speed, enhanced hardness, and strong adhesion strength compared with the other lacquers, although the Myanmarese lacquer film had a smoother surface than the Korean lacquer film. We used our characterization approach for evaluating a mixed Korean/Myanmarese (50/50 w/w) lacquer. Our proposed measurement techniques for Oriental lacquer films provided results that agreed with qualitative results from conventional tests. Force–distance curves in AFM and force–displacement with nanoindenter for Oriental lacquer films showed more accurate and quantitative data on the mechanical properties. Thus, researchers will find our approach useful when they optimize the chemical compositions and improve the physical properties of Oriental lacquer films for industrial applications.
Asphalt Incorporation with Ethylene Vinyl Acetate (EVA) Copolymer and Natural Rubber (NR) Thermoplastic Vulcanizates (TPVs): Effects of TPV Gel Content on Physical and Rheological Properties
Authors: Kunanusont Nappaphan , Sangpetngam Boonchai , Somwangthanaroj Anongnat
Published: April 2021

Plastic waste has been incorporated with asphalt to improve the physical properties of asphalt and alleviate the increasing trend of plastic waste being introduced into the environment. However, plastic waste comes in different types such as thermoplastic or thermoset, which results in varied properties of polymer modified asphalt (PMA). In this work, four thermoplastic vulcanizates (TPVs) were prepared using different peroxide concentrations to produce four formulations of gel content (with varying extent of crosslinked part) in order to imitate the variation of plastic waste. All four TPVs were then mixed with asphalt at 5 wt% thus producing four formulations of PMA, which went through physical, rheological, and storage stability assessments. PMA with higher gel content possessed lower penetration and higher softening temperature, indicating physically harder appearance of PMA. Superpave parameters remained unchanged among different gel content PMA at temperatures of 64, 70, and 76 °C. PMA with any level of gel content had lower Brookfield viscosity than PMA without gel content at a temperature of 135 °C. Higher gel content resulted in shorter storage stability measured with greater different softening temperatures between top and bottom layers of PMA after 5 days of 163 °C storage. This study shows that asphalt with thermoset plastic waste is harder and easier to pave, thus making the non-recycling thermoset plastic waste more useful and friendly to the environment.
Effects of Ignition Timing on Combustion Characteristics of a Gasoline Direct Injection Engine with Added Compressed Natural Gas under Partial Load Conditions
Authors: Zhang Peng , Ni Jimin , Shi Xiuyong , Yin Sheng , Zhang Dezheng
Published: April 2021

The gasoline/natural gas dual-fuel combustion mode has been found to have unique advantages in combustion. The ignition timing has a significant impact on the combustion characteristics of gasoline engines. Thus, here we study the combustion characteristics of gasoline/natural gas dual-fuel combustion mode to determine the details of their respective advantages under cooperative combustion. A direct-injection turbocharged gasoline engine was modified, and an engine experimental platform was built for the coordinated control of gasoline direct-injection and natural gas port injection. A low-speed and low-load operating point was selected, and the in-cylinder pressure, heat release rate, pressure rise rate, combustion temperature, ignition delay, and combustion duration under the coordinated combustion of gasoline and natural gas dual fuel at the ignition moment were studied through bench tests among other typical combustion parameters. The results show that with the increase of the ignition advance angle, the maximum cylinder pressure, heat release rate, pressure rise rate, and maximum combustion temperature increase. The ignition advance angle is 28°CA-BTDC, and PES40 has the best fuel synergy effect and the best power performance improvement. The effect of the advance of the ignition advance angle on the ignition delay and the combustion duration reaches the peak at 20°CA-BTDC–22°CA-BTDC, and the improvement of the two periods is more significant at PES60.
Associations between Cognitive Concepts of Self and Emotional Facial Expressions with an Emphasis on Emotion Awareness
Authors: Walla Peter , Mavratzakis Aimee
Published: April 2021

Recognising our own and others’ emotions is vital for healthy social development. The aim of the current study was to determine how emotions related to the self or to another influence behavioural expressions of emotion. Facial electromyography (EMG) was used to record spontaneous facial muscle activity in nineteen participants while they passively viewed negative, positive and neutral emotional pictures during three blocks of referential instructions. Each participant imagined themself, another person or no one experiencing the emotional scenario, with the priming words “You”, “Him” or “None” presented before each picture for the respective block of instructions. Emotion awareness (EA) was also recorded using the TAS-20 alexithymia questionnaire. Corrugator supercilii (cs) muscle activity increased significantly between 500 and 1000 ms post stimulus onset during negative and neutral picture presentations, regardless of ownership. Independent of emotion, cs activity was greatest during the “no one” task and lowest during the “self” task from less than 250 to 1000 ms. Interestingly, the degree of cs activation during referential tasks was further modulated by EA. Low EA corresponded to significantly stronger cs activity overall compared with high EA, and this effect was even more pronounced during the “no one” task. The findings suggest that cognitive processes related to the perception of emotion ownership can influence spontaneous facial muscle activity, but that a greater degree of integration between higher cognitive and lower affective levels of information may interrupt or suppress these behavioural expressions of emotion.
Desorption of Implanted Deuterium in Heavy Ion-Irradiated Zry-2
Authors: Watanabe Hideo , Saita Yoshiki , Takahashi Katsuhito , Yasunaga Kazufumi
Published: April 2021

To understand the degradation behavior of light water reactor (LWR) fuel-cladding tubes under neutron irradiation, a detailed mechanism of hydrogen pickup related to the point defect formation (i.e., a-component and c-component dislocation loops) and to the dissolution of precipitates must be elucidated. In this study, 3.2 MeV Ni3+ ion irradiation was conducted on Zircaloy-2 samples at room temperature. Thermal desorption spectroscopy is used to evaluate the deuterium desorption with and without Ni3+ ion irradiation. A conventional transmission electron microscope and a spherical aberration-corrected high-resolution analytical electron microscope are used to observe the microstructure. The experimental results indicate that radiation-induced dislocation loops and hydrides form in Zircaloy-2 and act as major trapping sites at lower (400–600 °C) and higher (700–900 °C)-temperature regions, respectively. These results show that the detailed microstructural changes related to the hydrogen pickup at the defect sinks formed by irradiation are necessary for the degradation of LWR fuel-cladding tubes during operation.