bluuebunny/crossref_metadata_2025 huggingface dataset:
Draft Sequencing Crested Wheatgrass Chromosomes Identified Evolutionary Structural Changes and Genes and Facilitated the Development of SSR Markers
Authors: Zwyrtková Jana , Blavet Nicolas , Doležalová Alžběta , Cápal Petr , Said Mahmoud , Molnár István , Vrána Jan , Doležel Jaroslav , Hřibová Eva
Published: March 2022

Crested wheatgrass (Agropyron cristatum), a wild relative of wheat, is an attractive source of genes and alleles for their improvement. Its wider use is hampered by limited knowledge of its complex genome. In this work, individual chromosomes were purified by flow sorting, and DNA shotgun sequencing was performed. The annotation of chromosome-specific sequences characterized the DNA-repeat content and led to the identification of genic sequences. Among them, genic sequences homologous to genes conferring plant disease resistance and involved in plant tolerance to biotic and abiotic stress were identified. Genes belonging to the important groups for breeders involved in different functional categories were found. The analysis of the DNA-repeat content identified a new LTR element, Agrocen, which is enriched in centromeric regions. The colocalization of the element with the centromeric histone H3 variant CENH3 suggested its functional role in the grass centromere. Finally, 159 polymorphic simple-sequence-repeat (SSR) markers were identified, with 72 of them being chromosome- or chromosome-arm-specific, 16 mapping to more than one chromosome, and 71 mapping to all the Agropyron chromosomes. The markers were used to characterize orthologous relationships between A. cristatum and common wheat that will facilitate the introgression breeding of wheat using A. cristatum.
The Hematopoietic TALE-Code Shows Normal Activity of IRX1 in Myeloid Progenitors and Reveals Ectopic Expression of IRX3 and IRX5 in Acute Myeloid Leukemia
Authors: Nagel Stefan , Pommerenke Claudia , Meyer Corinna , MacLeod Roderick A. F.
Published: March 2022

Homeobox genes encode transcription factors that control basic developmental decisions. Knowledge of their hematopoietic activities casts light on normal and malignant immune cell development. Recently, we constructed the so-called lymphoid TALE-code that codifies expression patterns of all active TALE class homeobox genes in early hematopoiesis and lymphopoiesis. Here, we present the corresponding myeloid TALE-code to extend this gene signature, covering the entire hematopoietic system. The collective data showed expression patterns for eleven TALE homeobox genes and highlighted the exclusive expression of IRX1 in megakaryocyte-erythroid progenitors (MEPs), implicating this TALE class member in a specific myeloid differentiation process. Analysis of public profiling data from acute myeloid leukemia (AML) patients revealed aberrant activity of IRX1 in addition to IRX3 and IRX5, indicating an oncogenic role for these TALE homeobox genes when deregulated. Screening of RNA-seq data from 100 leukemia/lymphoma cell lines showed overexpression of IRX1, IRX3, and IRX5 in megakaryoblastic and myelomonocytic AML cell lines, chosen as suitable models for studying the regulation and function of these homeo-oncogenes. Genomic copy number analysis of IRX-positive cell lines demonstrated chromosomal amplification of the neighboring IRX3 and IRX5 genes at position 16q12 in MEGAL, underlying their overexpression in this cell line model. Comparative gene expression analysis of these cell lines revealed candidate upstream factors and target genes, namely the co-expression of GATA1 and GATA2 together with IRX1, and of BMP2 and HOXA10 with IRX3/IRX5. Subsequent knockdown and stimulation experiments in AML cell lines confirmed their activating impact in the corresponding IRX gene expression. Furthermore, we demonstrated that IRX1 activated KLF1 and TAL1, while IRX3 inhibited GATA1, GATA2, and FST. Accordingly, we propose that these regulatory relationships may represent major physiological and oncogenic activities of IRX factors in normal and malignant myeloid differentiation, respectively. Finally, the established myeloid TALE-code is a useful tool for evaluating TALE homeobox gene activities in AML.
Regulation of ABCA1 by AMD-Associated Genetic Variants and Hypoxia in iPSC-RPE
Authors: Peters Florian , Ebner Lynn J. A. , Atac David , Maggi Jordi , Berger Wolfgang , den Hollander Anneke I. , Grimm Christian
Published: March 2022

Age-related macular degeneration (AMD) is a progressive disease of the macula characterized by atrophy of the retinal pigment epithelium (RPE) and photoreceptor degeneration, leading to severe vision loss at advanced stages in the elderly population. Impaired reverse cholesterol transport (RCT) as well as intracellular lipid accumulation in the RPE are implicated in AMD pathogenesis. Here, we focus on ATP-binding cassette transporter A1 (ABCA1), a major cholesterol transport protein in the RPE, and analyze conditions that lead to ABCA1 dysregulation in induced pluripotent stem cell (iPSC)-derived RPE cells (iRPEs). Our results indicate that the risk-conferring alleles rs1883025 (C) and rs2740488 (A) in ABCA1 are associated with increased ABCA1 mRNA and protein levels and reduced efficiency of cholesterol efflux from the RPE. Hypoxia, an environmental risk factor for AMD, reduced expression of ABCA1 and increased intracellular lipid accumulation. Treatment with a liver X receptor (LXR) agonist led to an increase in ABCA1 expression and reduced lipid accumulation. Our data strengthen the homeostatic role of cholesterol efflux in the RPE and suggest that increasing cellular cholesterol export by stimulating ABCA1 expression might lessen lipid load, improving RPE survival and reducing the risk of developing AMD.
Pediatric Brain Tumors: Signatures from the Intact Proteome
Authors: Rossetti Diana Valeria , Inserra Ilaria , Nesticò Alessia , Vincenzoni Federica , Iavarone Federica , Messana Irene , Castagnola Massimo , Massimi Luca , Tamburrini Gianpiero , Caldarelli Massimo , Desiderio Claudia
Published: March 2022

The present investigation aimed to explore the intact proteome of tissues of pediatric brain tumors of different WHO grades and localizations, including medulloblastoma, pilocytic astrocytoma, and glioblastoma, in comparison with the available data on ependymoma, to contribute to the understanding of the molecular mechanisms underlying the onset and progression of these pathologies. Tissues have been homogenized in acidic water–acetonitrile solutions containing proteases inhibitors and analyzed by LC–high resolution MS for proteomic characterization and label-free relative quantitation. Tandem MS spectra have been analyzed by either manual inspection or software elaboration, followed by experimental/theoretical MS fragmentation data comparison by bioinformatic tools. Statistically significant differences in protein/peptide levels between the different tumor histotypes have been evaluated by ANOVA test and Tukey’s post-hoc test, considering a p-value > 0.05 as significant. Together with intact protein and peptide chains, in the range of molecular mass of 1.3–22.8 kDa, several naturally occurring fragments from major proteins, peptides, and proteoforms have been also identified, some exhibiting proper biological activities. Protein and peptide sequencing allowed for the identification of different post-translational modifications, with acetylations, oxidations, citrullinations, deamidations, and C-terminal truncations being the most frequently characterized. C-terminal truncations, lacking from two to four amino acid residues, particularly characterizing the β-thymosin peptides and ubiquitin, showed a different modulation in the diverse tumors studied. With respect to the other tumors, medulloblastoma, the most frequent malignant brain tumor of the pediatric age, was characterized by higher levels of thymosin β4 and β10 peptides, the latter and its des-IS form particularly marking this histotype. The distribution pattern of the C-terminal truncated forms was also different in glioblastoma, particularly underlying gender differences, according to the definition of male and female glioblastoma as biologically distinct diseases. Glioblastoma was also distinguished for the peculiar identification of the truncated form of the α-hemoglobin chain, lacking the C-terminal arginine, and exhibiting oxygen-binding and vasoconstrictive properties different from the intact form. The proteomic characterization of the undigested proteome, following the top-down approach, was challenging to originally investigate the post-translational events that differently characterize pediatric brain tumors. This study provides a contribution to elucidate the molecular profiles of the solid tumors most frequently affecting the pediatric age, and which are characterized by different grades of aggressiveness and localization.
Zimbro (Juniperus communis L.) as a Promising Source of Bioactive Compounds and Biomedical Activities: A Review on Recent Trends
Authors: Gonçalves Ana , Flores-Félix José , Coutinho Paula , Alves Gilberto , Silva Luís
Published: March 2022

Plant-derived products and their extracted compounds have been used in folk medicine since early times. Zimbro or common juniper (Juniperus communis) is traditionally used to treat renal suppression, acute and chronic cystitis, bladder catarrh, albuminuria, leucorrhea, and amenorrhea. These uses are mainly attributed to its bioactive composition, which is very rich in phenolics, terpenoids, organic acids, alkaloids, and volatile compounds. In the last few years, several studies have analyzed the huge potential of this evergreen shrub, describing a wide range of activities with relevance in different biomedical discipline areas, namely antimicrobial potential against human pathogens and foodborne microorganisms, notorious antioxidant and anti-inflammatory activities, antidiabetic, antihypercholesterolemic and antihyperlipidemic effects, and neuroprotective action, as well as antiproliferative ability against cancer cells and the ability to activate inductive hepato-, renal- and gastroprotective mechanisms. Owing to these promising activities, extracts and bioactive compounds of juniper could be useful for the development of new pharmacological applications in the treatment of several acute and chronic human diseases.
A Homologous Recombination System to Generate Epitope-Tagged Target Genes in Chaetomium thermophilum: A Genetic Approach to Investigate Native Thermostable Proteins
Authors: Kellner Nikola , Griesel Sabine , Hurt Ed
Published: March 2022

Chaetomium thermophilum is an attractive eukaryotic model organism which, due to its unusually high temperature tolerance (optimal growth at 50–52 °C), has a thermostable proteome that can be exploited for biochemical, structural and biotechnological applications. Site directed gene manipulation for the expression of labeled target genes is a desirable approach to study the structure and function of thermostable proteins and their organization in complexes, which has not been established for this thermophile yet. Here, we describe the development of a homologous recombination system to epitope-tag chromosomal genes of interest in Chaetomium thermophilum with the goal to exploit the derived thermostable fusion proteins for tandem-affinity purification. This genetic approach was facilitated by the engineering of suitable strains, in which factors of the non-homologous end-joining pathway were deleted, thereby improving the efficiency of homologous integration at specific gene loci. Following this strategy, we could demonstrate that gene tagging via homologous recombination improved the yield of purified bait proteins and co-precipitated factors, paving the way for related studies in fundamental research and industrial applications.
Chronic Cardiotoxicity Assays Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs)
Authors: Narkar Akshay , Willard James M. , Blinova Ksenia
Published: March 2022

Cardiomyocytes (CMs) differentiated from human induced pluripotent stem cells (hiPSCs) are increasingly used in cardiac safety assessment, disease modeling and regenerative medicine. A vast majority of cardiotoxicity studies in the past have tested acute effects of compounds and drugs; however, these studies lack information on the morphological or physiological responses that may occur after prolonged exposure to a cardiotoxic compound. In this review, we focus on recent advances in chronic cardiotoxicity assays using hiPSC-CMs. We summarize recently published literature on hiPSC-CMs assays applied to chronic cardiotoxicity induced by anticancer agents, as well as non-cancer classes of drugs, including antibiotics, anti-hepatitis C virus (HCV) and antidiabetic drugs. We then review publications on the implementation of hiPSC-CMs-based assays to investigate the effects of non-pharmaceutical cardiotoxicants, such as environmental chemicals or chronic alcohol consumption. We also highlight studies demonstrating the chronic effects of smoking and implementation of hiPSC-CMs to perform genomic screens and metabolomics-based biomarker assay development. The acceptance and wide implementation of hiPSC-CMs-based assays for chronic cardiotoxicity assessment will require multi-site standardization of assay protocols, chronic cardiac maturity marker reproducibility, time points optimization, minimal cellular variation (commercial vs. lab reprogrammed), stringent and matched controls and close clinical setting resemblance. A comprehensive investigation of long-term repeated exposure-induced effects on both the structure and function of cardiomyocytes can provide mechanistic insights and recapitulate drug and environmental cardiotoxicity.
Preventing Bacterial Translocation in Patients with Leaky Gut Syndrome: Nutrition and Pharmacological Treatment Options
Authors: Twardowska Agata , Makaro Adam , Binienda Agata , Fichna Jakub , Salaga Maciej
Published: March 2022

Leaky gut syndrome is a medical condition characterized by intestinal hyperpermeability. Since the intestinal barrier is one of the essential components maintaining homeostasis along the gastrointestinal tract, loss of its integrity due to changes in bacterial composition, decreased expression levels of tight junction proteins, and increased concentration of pro-inflammatory cytokines may lead to intestinal hyperpermeability followed by the development of gastrointestinal and non-gastrointestinal diseases. Translocation of microorganisms and their toxic metabolites beyond the gastrointestinal tract is one of the fallouts of the leaky gut syndrome. The presence of intestinal bacteria in sterile tissues and distant organs may cause damage due to chronic inflammation and progression of disorders, including inflammatory bowel diseases, liver cirrhosis, and acute pancreatitis. Currently, there are no medical guidelines for the treatment or prevention of bacterial translocation in patients with the leaky gut syndrome; however, several studies suggest that dietary intervention can improve barrier function and restrict bacteria invasion. This review contains current literature data concerning the influence of diet, dietary supplements, probiotics, and drugs on intestinal permeability and bacterial translocation.
The mRubyFT Protein, Genetically Encoded Blue-to-Red Fluorescent Timer
Authors: Subach Oksana M. , Tashkeev Aleksandr , Vlaskina Anna V. , Petrenko Dmitry E. , Gaivoronskii Filipp A. , Nikolaeva Alena Y. , Ivashkina Olga I. , Anokhin Konstantin V. , Popov Vladimir O. , Boyko Konstantin M. , Subach Fedor V.
Published: March 2022

Genetically encoded monomeric blue-to-red fluorescent timers (mFTs) change their fluorescent color over time. mCherry-derived mFTs were used for the tracking of the protein age, visualization of the protein trafficking, and labeling of engram cells. However, the brightness of the blue and red forms of mFTs are 2–3- and 5–7-fold dimmer compared to the brightness of the enhanced green fluorescent protein (EGFP). To address this limitation, we developed a blue-to-red fluorescent timer, named mRubyFT, derived from the bright mRuby2 red fluorescent protein. The blue form of mRubyFT reached its maximum at 5.7 h and completely transformed into the red form that had a maturation half-time of 15 h. Blue and red forms of purified mRubyFT were 4.1-fold brighter and 1.3-fold dimmer than the respective forms of the mCherry-derived Fast-FT timer in vitro. When expressed in mammalian cells, both forms of mRubyFT were 1.3-fold brighter than the respective forms of Fast-FT. The violet light-induced blue-to-red photoconversion was 4.2-fold less efficient in the case of mRubyFT timer compared to the same photoconversion of the Fast-FT timer. The timer behavior of mRubyFT was confirmed in mammalian cells. The monomeric properties of mRubyFT allowed the labeling and confocal imaging of cytoskeleton proteins in live mammalian cells. The X-ray structure of the red form of mRubyFT at 1.5 Å resolution was obtained and analyzed. The role of the residues from the chromophore surrounding was studied using site-directed mutagenesis.
Structural Plasticity Is a Feature of Rheostat Positions in the Human Na+/Taurocholate Cotransporting Polypeptide (NTCP)
Authors: Ruggiero Melissa J. , Malhotra Shipra , Fenton Aron W. , Swint-Kruse Liskin , Karanicolas John , Hagenbuch Bruno
Published: March 2022

In the Na+/taurocholate cotransporting polypeptide (NTCP), the clinically relevant S267F polymorphism occurs at a “rheostat position”. That is, amino acid substitutions at this position (“S267X”) lead to a wide range of functional outcomes. This result was particularly striking because molecular models predicted the S267X side chains are buried, and thus, usually expected to be less tolerant of substitutions. To assess whether structural tolerance to buried substitutions is widespread in NTCP, here we used Rosetta to model all 19 potential substitutions at another 13 buried positions. Again, only subtle changes in the calculated stabilities and structures were predicted. Calculations were experimentally validated for 19 variants at codon 271 (“N271X”). Results showed near wildtype expression and rheostatic modulation of substrate transport, implicating N271 as a rheostat position. Notably, each N271X substitution showed a similar effect on the transport of three different substrates and thus did not alter substrate specificity. This differs from S267X, which altered both transport kinetics and specificity. As both transport and specificity may change during protein evolution, the recognition of such rheostat positions may be important for evolutionary studies. We further propose that the presence of rheostat positions is facilitated by local plasticity within the protein structure. Finally, we note that identifying rheostat positions may advance efforts to predict new biomedically relevant missense variants in NTCP and other membrane transport proteins.
Tumor-Mediated Neutrophil Polarization and Therapeutic Implications
Authors: Raftopoulou Sofia , Valadez-Cosmes Paulina , Mihalic Zala Nikita , Schicho Rudolf , Kargl Julia
Published: March 2022

Neutrophils are immune cells with reported phenotypic and functional plasticity. Tumor-associated neutrophils display many roles during cancer progression. Several tumor microenvironment (TME)-derived factors orchestrate neutrophil release from the bone marrow, recruitment and functional polarization, while simultaneously neutrophils are active stimulators of the TME by secreting factors that affect immune interactions and subsequently tumor progression. Successful immunotherapies for many cancer types and stages depend on the targeting of tumor-infiltrating lymphocytes. Neutrophils impact the success of immunotherapies, such as immune checkpoint blockade therapies, by displaying lymphocyte suppressive properties. The identification and characterization of distinct neutrophil subpopulations or polarization states with pro- and antitumor phenotypes and the identification of the major TME-derived factors of neutrophil polarization would allow us to harness the full potential of neutrophils as complementary targets in anticancer precision therapies.
Characterization of a Novel Aspect of Tissue Scarring Following Experimental Spinal Cord Injury and the Implantation of Bioengineered Type-I Collagen Scaffolds in the Adult Rat: Involvement of Perineurial-like Cells?
Authors: Altinova Haktan , Achenbach Pascal , Palm Moniek , Katona Istvan , Hermans Emmanuel , Clusmann Hans , Weis Joachim , Brook Gary Anthony
Published: March 2022

Numerous intervention strategies have been developed to promote functional tissue repair following experimental spinal cord injury (SCI), including the bridging of lesion-induced cystic cavities with bioengineered scaffolds. Integration between such implanted scaffolds and the lesioned host spinal cord is critical for supporting regenerative growth, but only moderate-to-low degrees of success have been reported. Light and electron microscopy were employed to better characterise the fibroadhesive scarring process taking place after implantation of a longitudinally microstructured type-I collagen scaffold into unilateral mid-cervical resection injuries of the adult rat spinal cord. At long survival times (10 weeks post-surgery), sheets of tightly packed cells (of uniform morphology) could be seen lining the inner surface of the repaired dura mater of lesion-only control animals, as well as forming a barrier along the implant–host interface of the scaffold-implanted animals. The highly uniform ultrastructural features of these scarring cells and their anatomical continuity with the local, reactive spinal nerve roots strongly suggest their identity to be perineurial-like cells. This novel aspect of the cellular composition of reactive spinal cord tissue highlights the increasingly complex nature of fibroadhesive scarring involved in traumatic injury, and particularly in response to the implantation of bioengineered collagen scaffolds.
Application of the Generalized Thurstone Method for Evaluations of Sports Tournaments’ Results
Authors: Orbán-Mihálykó Éva , Mihálykó Csaba , Gyarmati László
Published: March 2022

Due to the non-played matches on the grounds of COVID-19 pandemics, the usual evaluation of the results of tournaments is biased. Matches won by default may cause unrealistic results. In this paper, an expedient method, the generalization of Thurstone method for more than two options, is applied. It is able to evaluate the results of the played matches without requiring equal matches’ numbers. This method takes the strength of the opposer into consideration as well. We apply the method for evaluating Handball Champions’ League’s results. We illustrate that it efficiently predicts the results in the future.
Molybdenum Oxide Nanoparticle Aggregates Grown by Chemical Vapor Transport
Authors: Choi Yun-Hyuk
Published: March 2022

In this study, the advanced chemical vapor transport (CVT) method in combination with the quenching effect is introduced for creating molybdenum oxide nanoparticle arrays, composed of the hierarchical structure of fine nanoparticles (NPs), which are vertically grown with a homogeneous coverage on the individual carbon fibers of carbon fiber paper (CFP) substrates. The obtained molybdenum oxide NPs hold a metastable high-temperature γ-Mo4O11 phase along with a stable α-MoO3 phase by the quenching effect. Furthermore, such a quenching effect forms thinner and smaller nanoparticle aggregates by suppressing the growth and coalescence of primary particles. The molybdenum oxide nanoparticle aggregates are prepared using two different types of precursors: MoO3 and a 1:1 (mol/mol) mixture of MoO3 and activated carbon. The results characterized using X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy show that the relative amount of α-MoO3 to γ-Mo4O11 within the prepared NPs is dependent on the precursor type; a lower amount of α-MoO3 to γ-Mo4O11 is obtained in the NPs prepared using the mixed precursor of MoO3 and carbon. This processing–structure landscape study can serve as the groundwork for the development of high-performance nanomaterials in various electronic and catalytic applications.
Characteristics of Vibrating Fluidization and Transportation for Al2O3 Powder
Authors: Ogata Koichiro , Harada Tsutomu , Kawahara Hideo , Tokumaru Kazuki , Abe Riho , Mitani Eiji , Mitani Koji
Published: March 2022

This study focused on the vibrating fluidized-bed-type powder feeder used in HVAF thermal spraying equipment. This feeder has been used in thermal spraying equipment and industrial applications. However, particulate materials’ flow mechanism and stable transport characteristics have not been fully understood. This study experimentally investigated the fluidization characteristics, powder dispersion state, and powder transportation characteristics of Al2O3 particles during vertical vibration fluidization. The material used was Al2O3 particles of 2.9 μm and 3808 kg/m3, classified as the group C particles in the Geldart diagram. As experimental conditions, the fluidized air velocity to the bottom of the powder bed and the vibration intensity in the vertical direction changed. The critical fluidization air velocity was defined to evaluate the generating powder flow by vertical vibrating fluidization. As a result, good fluidization of the powder bed of Al2O3 was obtained by the vertical vibration, as well as an airflow that was higher than the critical fluidization air velocity. Regarding powder transportation characteristics, it was clarified that the fluidized air velocity at the bottom of the powder dispersion vessel and the pressure difference from the powder dispersion vessel to the transportation part significantly affect the mass flow rate.
Interfacial Deposition of Titanium Dioxide at the Polarized Liquid–Liquid Interface
Authors: Kowalewska Karolina , Sipa Karolina , Burnat Barbara , Skrzypek Sławomira , Poltorak Lukasz
Published: March 2022

The interfacial polycondensation of titanium dioxide was studied at the bare and fiberglass membrane supported polarized liquid–liquid interface (LLI). Titanium dioxide synthesis was derived from the titanium (IV) tetrabutoxide (initially dissolved in the 1,2-dichloroethane) interfacial hydrolysis followed by its condensation. Experimental parameters, such as the pH of the aqueous phase and the influence of titanium alkoxide concentration in the organic phase on the electrochemical signal and material morphology, were investigated. The latter was achieved with fiberglass membranes used as the LLI support during TiO2 interfacial deposition. Cyclic voltammetry was used for the in situ studies, whereas scanning electron microscopy, energy-dispersive X-ray spectroscopy, and infrared spectroscopy were used during ex situ examination. The interfacial polycondensation reaction could be studied using electrified LLI and resulted in the material being a TiO2 film alone or film decorated with particles.
Characterization of Microstructure, Phase Composition, and Mechanical Behavior of Ballistic Steels
Authors: Khan Waseem , Tufail Muhammad , Chandio Ali Dad
Published: March 2022

For the protection of civil and military armored vehicles, advanced steels are used, due to their outstanding mechanical properties, high ballistic performance, ease of manufacturing and low cost. However, after retrofitting, weight is the prominent issue. In this regard, several strategies are being proposed, which include the surface engineering of either low-thickness ballistic steels or conventional steels, in addition to new alloys and composites. Therefore, to better understand the response of such materials under various stimuli, the existing state of the art ballistic steels was utilized in this study. The aim of this study was to better understand the existing materials and their corrosion behavior. Therefore, in this connection, two thicknesses were selected, i.e., thin (6.7–7.0 mm) and thick (13.0–15.0 mm), henceforth termed as low thickness (LT) and high thickness (HT), respectively. This was followed by characterization using tensile, Charpy, micro-Vickers, nanoindentation, XRD, SEM-EDS and corrosion tests. Microstructurally, the LT samples only exhibited ε-carbide precipitates, whereas the HT samples contained both ε-carbides and Mo2C (molybdenum carbides). However, both samples were found to be tempered martensite with a lath morphology. Moreover, higher hardness, and lower elastic modulus and stiffness were noticed in the HT samples compared with their LT counterparts. Fractured surfaces of both of these alloys were also examined, wherein a ductile mode of fracturing was observed. Further, a corrosion study was also carried out in brine solution. The results showed a higher corrosion rate in the HT samples than that of their LT counterparts. An extensive discussion is presented in light of the observed findings.
Hypokalemia in Diabetes Mellitus Setting
Authors: Coregliano-Ring Lucas , Goia-Nishide Kleber , Rangel Érika Bevilaqua
Published: March 2022

Diabetes mellitus is a public health problem that affects millions of people worldwide regardless of age, sex, and ethnicity. Electrolyte disturbances may occur as a consequence of disease progression or its treatment, in particular potassium disorders. The prevalence of hypokalemia in diabetic individuals over 55 years of age is up to 1.2%. In patients with acute complications of diabetes, such as diabetic ketoacidosis, this prevalence is even higher. Potassium disorders, either hypokalemia or hyperkalemia, have been associated with increased all-cause mortality in diabetic individuals, especially in those with associated comorbidities, such as heart failure and chronic kidney disease. In this article, we discuss the main conditions for the onset of hypokalemia in diabetic individuals, briefly review the pathophysiology of acute complications of diabetes mellitus and their association with hypokalemia, the main signs, symptoms, and laboratory parameters for the diagnosis of hypokalemia, and the management of one of the most common electrolyte disturbances in clinical practice.
Publics’ Perceptions of Community Pharmacists and Satisfaction with Pharmacy Services in Al-Madinah City, Saudi Arabia: A Cross Sectional Study
Authors: El-Kholy Amal A. , Abdelaal Khaled , Alqhtani Hussain , Abdel-Wahab Basel A. , Abdel-Latif Mohamed M. M.
Published: March 2022

Background and Objectives: Pharmacists play a major role in serving patients and delivering pharmaceutical services to the community. It is unclear whether the public fully appreciates what pharmacists can do as key health care providers. This study aims to examine public perceptions of community pharmacists and levels of satisfaction with pharmacy services. Materials and Methods: A cross-sectional study was conducted on a randomly selected sample population (n = 1000) in Saudi Arabia over a period of six months from January through June 2019. A 40-item, structured, self-administered questionnaire was used, comprised of questions on the demographics characteristics of the respondents and their satisfaction with pharmacy services. Descriptive statistics were used to analyze the data. Results: The response rate of the survey was 76.92%. Public opinions were influenced by pharmacists’ availability and knowledge, service promptness, and counseling services. Overall, 80.5% of respondents agreed that community pharmacists treat them with respect. Doctors were identified as the preferred source of drug therapy consultation by 58.7% and pharmacists by 41.29%. About 72.8% of respondents agreed that pharmacists provided them with clear instructions about medication use, and 70.2% trusted pharmacists’ opinions about medications. About 62.5% of respondents expressed satisfaction with pharmacists, and 64.8% with pharmacy services. Conclusions: Customers’ opinions were influenced by pharmacists’ availability and knowledge, pharmacy service promptness, pharmacy location, waiting area, medication knowledge, and counseling. However, the public was greatly satisfied with community pharmacists’ professionalism and pharmaceutical services. This positive perception provides an opportunity for pharmacists to extend their roles as healthcare professionals.
MALDI-TOF/MS Analysis of Non-Invasive Human Urine and Saliva Samples for the Identification of New Cancer Biomarkers
Authors: Zambonin Carlo , Aresta Antonella
Published: March 2022

Cancer represents a group of heterogeneous diseases that are a leading global cause of death. Even though mortality has decreased in the past thirty years for different reasons, most patients are still diagnosed at the advanced stage, with limited therapeutic choices and poor outcomes. Moreover, the majority of cancers are detected using invasive painful methods, such as endoscopic biopsy, making the development of non-invasive or minimally invasive methods for the discovery and fast detection of specific biomarkers a crucial need. Among body fluids, a valuable non-invasive alternative to tissue biopsy, the most accessible and least invasive are undoubtedly urine and saliva. They are easily retrievable complex fluids containing a large variety of endogenous compounds that may provide information on the physiological condition of the body. The combined analysis of these fluids with matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF/MS), a reliable and easy-to-use instrumentation that provides information with relatively simple sample pretreatments, could represent the ideal option to rapidly achieve fast early stage diagnosis of tumors and their real-time monitoring. On this basis, the present review summarizes the recently reported applications relevant to the MALDI analysis of human urine and saliva samples.
Combined Analytical Study on Chemical Transformations and Detoxification of Model Phenolic Pollutants during Various Advanced Oxidation Treatment Processes
Authors: Kravos Aleksander , Žgajnar Gotvajn Andreja , Lavrenčič Štangar Urška , Malinović Borislav N. , Prosen Helena
Published: March 2022

Advanced oxidation processes (AOPs) have been introduced to deal with different types of water pollution. They cause effective chemical destruction of pollutants, yet leading to a mixture of transformation by-products, rather than complete mineralization. Therefore, the aim of our study was to understand complex degradation processes induced by different AOPs from chemical and ecotoxicological point of view. Phenol, 2,4-dichlorophenol, and pentachlorophenol were used as model pollutants since they are still common industrial chemicals and thus encountered in the aquatic environment. A comprehensive study of efficiency of several AOPs was undertaken by using instrumental analyses along with ecotoxicological assessment. Four approaches were compared: ozonation, photocatalytic oxidation with immobilized nitrogen-doped TiO2 thin films, the sequence of both, as well as electrooxidation on boron-doped diamond (BDD) and mixed metal oxide (MMO) anodes. The monitored parameters were: removal of target phenols, dechlorination, transformation products, and ecotoxicological impact. Therefore, HPLC–DAD, GC–MS, UHPLC–MS/MS, ion chromatography, and 48 h inhibition tests on Daphnia magna were applied. In addition, pH and total organic carbon (TOC) were measured. Results show that ozonation provides by far the most suitable pattern of degradation accompanied by rapid detoxification. In contrast, photocatalysis was found to be slow and mild, marked by the accumulation of aromatic products. Preozonation reinforces the photocatalytic process. Regarding the electrooxidations, BDD is more effective than MMO, while the degradation pattern and transformation products formed depend on supporting electrolyte.
Reactive Oxygen Species: Angels and Demons in the Life of a Neuron
Authors: Biswas Kasturi , Alexander Kellianne , Francis Michael M.
Published: March 2022

Reactive oxygen species (ROS) have emerged as regulators of key processes supporting neuronal growth, function, and plasticity across lifespan. At normal physiological levels, ROS perform important roles as secondary messengers in diverse molecular processes such as regulating neuronal differentiation, polarization, synapse maturation, and neurotransmission. In contrast, high levels of ROS are toxic and can ultimately lead to cell death. Excitable cells, such as neurons, often require high levels of metabolic activity to perform their functions. As a consequence, these cells are more likely to produce high levels of ROS, potentially enhancing their susceptibility to oxidative damage. In addition, because neurons are generally post-mitotic, they may be subject to accumulating oxidative damage. Thus, maintaining tight control over ROS concentration in the nervous system is essential for proper neuronal development and function. We are developing a more complete understanding of the cellular and molecular mechanisms for control of ROS in these processes. This review focuses on ROS regulation of the developmental and functional properties of neurons, highlighting recent in vivo studies. We also discuss the current evidence linking oxidative damage to pathological conditions associated with neurodevelopmental and neurodegenerative disorders.
A Consistency Model for Identifying the Effects of n-3 and n-6 Fatty Acids on Lipoproteins in Dialysis Patients
Authors: Chang Ke-Yu , Chen Yi-Chun , Yeh Shu-Ching , Kao Chih-Chin , Cheng Chung-Yi , Kang Yi-No , Huang Chih-Wei
Published: March 2022

Numerous randomized controlled trials (RCTs) and meta-analyses have assessed the effects of supplemental dietary polyunsaturated fatty acids (PUFAs) on levels of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) and the LDL/HDL ratio in patients receiving renal replacement therapy (RRT). However, results are ambiguous due to mixed reports of various nutrients used in the intervention group. We performed a network meta-analysis of RCTs to assess the effects of PUFAs on lipid profiles in patients undergoing RRT. RCTs performed before November 2021 were gathered from three databases. The means, standard deviations and the number of cases for each arm were independently extracted by two authors to form a network meta-analysis of LDL and HDL levels and the LDL/HDL ratio in a random effects model. Twenty-eight RCTs (n = 2017 subjects) were included in this study. The pooled results revealed that the combination of omega-3 fatty acids (n-3) and omega-6 fatty acids (n-6) produced significantly lower LDL (standardized mean difference (SMD) = −1.43, 95% confidence interval: −2.28 to −0.57) than the placebo. Both n-3 fatty acids (SMD = 0.78) and the combination of n-3 + n-6 (SMD = 1.09) benefited HDL significantly compared with placebo. Moreover, n-3 alone also exhibited a significantly lower LDL/HDL ratio than placebo. Collectively, PUFAs seem to be adequate nutrients for controlling lipoproteins in patients undergoing RRT. Specifically, n-3 + n-6 supplementation improved LDL levels, while n-3 improved HDL levels and the LDL/HDL ratio. However, our data provide limited information on specific dosages of PUFAs to form a concrete recommendation.
Online and Blended Learning Courses for Healthcare Professionals and Policymakers on Patients’ Perspectives on Medicine: A Project Report
Authors: Jacobsen Ramune , Almarsdóttir Anna Birna , Cantarero-Arevalo Lourdes , Granås Anne Gerd , Hansen Johanne M. , Henman Martin C. , Jacobsen Solveig N. , Kaae Susanne , Nørgaard Lotte S. , Taxis Katja , Sporrong Sofia K.
Published: March 2022

In order for healthcare professionals to better engage with patients, they need to understand and integrate the perspectives of patients into their daily work. In this project, we developed two courses for healthcare professionals on patients’ perspectives on medicine. One course was an online course that introduced the patients’ perspectives on medicine and explained its importance for healthcare and health policy. The second course was a blended learning course, consisting of online modules and face-to-face webinars, which specified how to explore patients’ perspectives in qualitative interviews, and how to develop implementation plans. Patients participated in the development, execution, and evaluation of both courses. Overall, more than 2000 healthcare professionals enrolled in the first course and, in just over a year, 191 participants completed the online course; 57 healthcare professionals registered in the second blended learning course and six participants completed both components of the course. The relevance of knowledge gained was positively evaluated. Participants especially appreciated the participation of patients. Based on the feedback, the second blended learning course was adapted to run online and both courses continue to be freely available to all interested healthcare professionals on the Coursera platform.
From Prolepsis to Hyperraising
Authors: Lohninger Magdalena , Kovač Iva , Wurmbrand Susanne
Published: March 2022

Case, agreement, and A-movement dependencies across finite clause boundaries, such as Hyperraising (to subject or object) or Long-Distance Case or Agreement [LDA], are available in many typologically diverse languages. The research on such dependencies typically distinguishes between cross-linguistically restricted true A-dependencies across finite clauses, and generally available binding-like A′-dependencies as found in Prolepsis. In this paper, we investigate both types of configurations in parallel and refer to this as the A-domain. Since the diagnostics to distinguish A-configurations vary across languages and often cannot be compared directly, we define four characteristic properties: (A) whether the construction is restricted by matrix predicate selection, (B) whether movement in the embedded clause is involved, (C) whether the dependency shows locality restrictions (in particular, A-Minimality), and (D) whether there are semantic restrictions on the relevant DP. By combining different values of the characteristic properties, we show, differently from previous approaches, that the A-domain does not simply consist of two types of configurations, but that the empirical landscape represents a continuum of five A-constructions. We suggest a theoretical implementation of our empirical findings, which is built on a predicational relator phrase above the embedded CP and propose that, in some of the constructions, these two projections fuse into one. We employ a minimalist probing approach which relies on differences in the base-generated position of the relevant DP (matrix clause, high in the embedded clause, argument position in the embedded clause), differences in the feature composition of the embedded C (a plain A′-head, or a bundled predicational C head involving composite A/A′ probes), a composite probe hierarchy yielding three types of feature-dependencies of composite probes, and, resulting from that, different probing mechanisms (conjunctive satisfaction, dependent satisfaction, and independent satisfaction). Lastly, this paper also contributes methodological tools for disentangling constructions of the A-domain.
Antioxidant Capacity Determination of Hungarian-, Slovak-, and Polish-Origin Goldenrod Honeys
Authors: Czigle Szilvia , Filep Rita , Balažová Ema , Szentgyörgyi Hajnalka , Balázs Viktória Lilla , Kocsis Marianna , Purger Dragica , Papp Nóra , Farkas Ágnes
Published: March 2022

The goldenrod (Solidago) species are flowering plants that produce nectar and can be the sources of unifloral honeys. S. canadensis and S. gigantea are native to North America and invasive in several European countries, while S. virgaurea is native to Europe. The aim of this work was to determine and compare the antioxidant capacity of goldenrod honeys collected in three central European countries (Hungary, Poland, and Slovakia), from three locations within each country. The botanical origin of each honey sample was checked with melissopalynological analysis. Color intensity was determined using the Pfund scale. The antioxidant activity was determined with different spectrophotometric methods (DPPH, ABTS, and FRAP). The content of total polyphenols, flavonoids, and phenolic acids was quantified using spectrophotometric methods. The highest radical-scavenging activity was identified for Hungarian samples with all three antioxidant capacity assays. Medium antioxidant activity was described for Slovak samples. The DPPH and ABTS assays discriminated Polish honeys with the lowest antioxidant activity. The highest flavonoid and phenolic acid content was detected in Hungarian and Slovak honeys, while the lowest values were measured in Polish samples. Our study shows that the antioxidant capacity of unifloral goldenrod honeys can be different in various countries of origin, correlating with color intensity and polyphenol content.
Impact of DC Transient Disturbances on Harmonic Performance of Voltage Transformers for AC Railway Applications
Authors: Letizia Palma Sara , Signorino Davide , Crotti Gabriella
Published: March 2022

This paper analyzes the impact of typical DC transient events occurring in railway grids on the frequency performance of instrument transformers (ITs) installed onboard trains and in AC substations for power quality (PQ) applications. PQ monitoring in railway systems is an issue of great interest because it plays a key role in the improvement of energy efficiency. The measurement chain for the PQ measurements, at 15 kV at 16.7 Hz and 25 kV at 50/60 Hz, commonly includes ITs to scale the voltage to levels fitting the input of the measurement units. Nevertheless, the behavior of ITs in the presence of PQ phenomena represents an open issue from a normative point of view, even for those installed in conventional AC power supply systems. In this context, the paper presents a possible definition of DC transient disturbances test waveforms, a measurement procedure, and a setup to assess the impact of these disturbances on the harmonic performances of ITs for railway systems. Preliminary experimental tests carried out on two commercial ITs under wide ranges of variation for the amplitude and the time duration of DC disturbances show that, in some cases, the error introduced in harmonic measurements can exceed 100%.
An Innovative Malaxer Equipped with SCADA Platform for Improving Extra Virgin Olive Oil Quality
Authors: Vallone Mariangela , Aiello Giuseppe , Bono Filippa , De Pasquale Claudio , Presti Giovanni , Catania Pietro
Published: March 2022

Agriculture 4.0 is gaining more attention, and all companies are thinking about innovating machines to increase income and improve the quality of the final products. In the agro-food sector, there is space for innovation, as it is far behind the industrial sector. This paper reports an industrial-scale study on the application of an innovative system for the extraction of Sicilian EVOO (extra virgin olive oil) to improve both process management and the quality of the product. Based on previous studies, the authors suggested an innovative machine equipped with a SCADA (supervisory control and data acquisition system) for oxygen and process duration monitoring and control. The objective of the research was thus to discuss the development of a SCADA platform applied to the malaxer and the establishment of an optimized approach to control the main process parameters for obtaining high-quality EVOO. The SCADA system application in the EVOO extraction process allowed a qualitative improvement of the Sicilian EVOO of Nocellara del Belice and Cerasuola cultivars. The use of the innovative system made it possible to increase the values of tocopherols (by about 25%) in Cerasuola cultivar and total phenol content (by about 30%) in Nocellara del Belice cultivar EVOOs.