bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronic Circular Dichroism of the Cas9 Protein and gRNA:Cas9 Ribonucleoprotein Complex
Authors: Halat Monika , Klimek-Chodacka Magdalena , Orleanska Jagoda , Baranska Malgorzata , Baranski Rafal
Published: March 2021

The Streptococcus pyogenes Cas9 protein (SpCas9), a component of CRISPR-based immune system in microbes, has become commonly utilized for genome editing. This nuclease forms a ribonucleoprotein (RNP) complex with guide RNA (gRNA) which induces Cas9 structural changes and triggers its cleavage activity. Here, electronic circular dichroism (ECD) spectroscopy was used to confirm the RNP formation and to determine its individual components. The ECD spectra had characteristic features differentiating Cas9 and gRNA, the former showed a negative/positive profile with maxima located at 221, 209 and 196 nm, while the latter revealed positive/negative/positive/negative pattern with bands observed at 266, 242, 222 and 209 nm, respectively. For the first time, the experimental ECD spectrum of the gRNA:Cas9 RNP complex is presented. It exhibits a bisignate positive/negative ECD couplet with maxima at 273 and 235 nm, and it differs significantly from individual spectrum of each RNP components. Additionally, the Cas9 protein and RNP complex retained biological activity after ECD measurements and they were able to bind and cleave DNA in vitro. Hence, we conclude that ECD spectroscopy can be considered as a quick and non-destructive method of monitoring conformational changes of the Cas9 protein as a result of Cas9 and gRNA interaction, and identification of the gRNA:Cas9 RNP complex.
m5U54 tRNA Hypomodification by Lack of TRMT2A Drives the Generation of tRNA-Derived Small RNAs
Authors: Pereira Marisa , Ribeiro Diana R. , Pinheiro Miguel M. , Ferreira Margarida , Kellner Stefanie , Soares Ana R.
Published: March 2021

Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation to gene expression control and cellular stress response. Recent evidence indicates that tsRNAs are also modified, however, the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. The tRNA methyltransferase TRMT2A catalyzes this modification, but its biological role remains mostly unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification and tsRNA formation. More specifically, m5U54 hypomodification is followed by overexpression of the ribonuclease angiogenin (ANG) that cleaves tRNAs near the anticodon, resulting in accumulation of 5′tRNA-derived stress-induced RNAs (5′tiRNAs), namely 5′tiRNA-GlyGCC and 5′tiRNA-GluCTC, among others. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tiRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tiRNA formation in mammalian cells. These results establish a link between tRNA hypomethylation and ANG-dependent tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.
Genetic Deletion of Trace-Amine Associated Receptor 9 (TAAR9) in Rats Leads to Decreased Blood Cholesterol Levels
Authors: Murtazina Ramilya Z. , Zhukov Ilya S. , Korenkova Olga M. , Popova Elena A. , Kuvarzin Savelii R. , Efimova Evgeniya V. , Kubarskaya Larisa G. , Batotsyrenova Ekaterina G. , Zolotoverkhaya Ekaterina A. , Vaganova Anastasia N. , Apryatin Sergey A. , Alenina Natalia V. , Gainetdinov Raul R.
Published: March 2021

In the last two decades, interest has grown significantly in the investigation of the role of trace amines and their receptors in mammalian physiology and pathology. Trace amine-associated receptor 9 (TAAR9) is one of the least studied members of this receptor family with unidentified endogenous ligands and an unknown role in the central nervous system and periphery. In this study, we generated two new TAAR9 knockout (TAAR9-KO) rat strains by CRISPR-Cas9 technology as in vivo models to evaluate the role of TAAR9 in mammalian physiology. In these mutant rats, we performed a comparative analysis of a number of hematological and biochemical parameters in the blood. Particularly, we carried out a complete blood count, erythrocyte osmotic fragility test, and screening of a panel of basic biochemical parameters. No significant alterations in any of the hematological and most biochemical parameters were found between mutant and WT rats. However, biochemical studies revealed a significant decrease in total and low-density lipoprotein cholesterol levels in the blood of both strains of TAAR9-KO rats. Such role of TAAR9 in cholesterol regulation not only brings a new understanding of mechanisms and biological pathways of lipid exchange but also provides a new potential drug target for disorders involving cholesterol-related pathology, such as atherosclerosis.
Maternal and Postnatal High Linoleic Acid Diet Impacts Lipid Metabolism in Adult Rat Offspring in a Sex-Specific Manner
Authors: Shrestha Nirajan , Vidimce Josif , Holland Olivia J. , Cuffe James S. M. , Beck Belinda R. , Perkins Anthony V. , McAinch Andrew J. , Hryciw Deanne H.
Published: March 2021

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is essential for fetal growth and development. We aimed to investigate the effect of maternal and postnatal high LA (HLA) diet on plasma FA composition, plasma and hepatic lipids and genes involved in lipid metabolism in the liver of adult offspring. Female rats were fed with low LA (LLA; 1.44% LA) or HLA (6.21% LA) diets for 10 weeks before pregnancy, and during gestation/lactation. Offspring were weaned at postnatal day 25 (PN25), fed either LLA or HLA diets and sacrificed at PN180. Postnatal HLA diet decreased circulating total n-3 PUFA and alpha-linolenic acid (ALA), while increased total n-6 PUFA, LA and arachidonic acid (AA) in both male and female offspring. Maternal HLA diet increased circulating leptin in female offspring, but not in males. Maternal HLA diet decreased circulating adiponectin in males. Postnatal HLA diet significantly decreased aspartate transaminase (AST) in females and downregulated total cholesterol, HDL-cholesterol and triglycerides in the plasma of males. Maternal HLA diet downregulated the hepatic mRNA expression of Hmgcr in both male and female offspring and decreased the hepatic mRNA expression of Cpt1a and Acox1 in females. Both maternal and postnatal HLA diet decreased hepatic mRNA expression of Cyp27a1 in females. Postnatal diet significantly altered circulating fatty acid concentrations, with sex-specific differences in genes that control lipid metabolism in the adult offspring following exposure to high LA diet in utero.
6-Azauridine Induces Autophagy-Mediated Cell Death via a p53- and AMPK-Dependent Pathway
Authors: Cha Yeo-Eun , Park Rackhyun , Jang Minsu , Park Yea-In , Yamamoto Ayane , Oh Won Keun , Lee Eun-Ju , Park Junsoo
Published: March 2021

6-Azauridine (6-AZA), a pyrimidine nucleoside analogue, is known to exhibit both antitumor and antiviral activities. Although 6-AZA was discovered more than 60 years ago, the cellular effects of this compound are yet to be elucidated. Here, we report that 6-AZA regulates autophagy-mediated cell death in various human cancer cells, where 6-AZA treatment activates autophagic flux through the activation of lysosomal function. Furthermore, 6-AZA exhibited cytotoxicity in all cancer cells studied, although the mechanisms of action were diverse. In H460 cells, 6-AZA treatment induced apoptosis, and the extent of the latter could be reduced by treatment with chloroquine (CQ), a lysosomal inhibitor. However, 6-AZA treatment resulted in cell cycle arrest in H1299 cells, which could not be reversed by CQ. The cytotoxicity associated with 6-AZA treatment could be linearly correlated to the degree of autophagy-mediated cell death. In addition, we demonstrated that the cytotoxic effect of 6-AZA was dependent on AMPK and p53. These results collectively indicate that autophagy-mediated cell death triggered by 6-AZA contributes to its antitumor effect.
The Time Has Come to Explore Plasma Biomarkers in Genetic Cardiomyopathies
Authors: Stege Nienke M. , de Boer Rudolf A. , van den Berg Maarten P. , Silljé Herman H. W.
Published: March 2021

For patients with hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM), screening for pathogenic variants has become standard clinical practice. Genetic cascade screening also allows the identification of relatives that carry the same mutation as the proband, but disease onset and severity in mutation carriers often remains uncertain. Early detection of disease onset may allow timely treatment before irreversible changes are present. Although plasma biomarkers may aid in the prediction of disease onset, monitoring relies predominantly on identifying early clinical symptoms, on imaging techniques like echocardiography (Echo) and cardiac magnetic resonance imaging (CMR), and on (ambulatory) electrocardiography (electrocardiograms (ECGs)). In contrast to most other cardiac diseases, which are explained by a combination of risk factors and comorbidities, genetic cardiomyopathies have a clear primary genetically defined cardiac background. Cardiomyopathy cohorts could therefore have excellent value in biomarker studies and in distinguishing biomarkers related to the primary cardiac disease from those related to extracardiac, secondary organ dysfunction. Despite this advantage, biomarker investigations in cardiomyopathies are still limited, most likely due to the limited number of carriers in the past. Here, we discuss not only the potential use of established plasma biomarkers, including natriuretic peptides and troponins, but also the use of novel biomarkers, such as cardiac autoantibodies in genetic cardiomyopathy, and discuss how we can gauge biomarker studies in cardiomyopathy cohorts for heart failure at large.
Implication of EZH2 in the Pro-Proliferative and Apoptosis-Resistant Phenotype of Pulmonary Artery Smooth Muscle Cells in PAH: A Transcriptomic and Proteomic Approach
Authors: Habbout Karima , Omura Junichi , Awada Charifa , Bourgeois Alice , Grobs Yann , Krishna Vinod , Breuils-Bonnet Sandra , Tremblay Eve , Mkannez Ghada , Martineau Sandra , Nadeau Valérie , Roux-Dalvai Florence , Orcholski Mark , Jeyaseelan Jey , Gutstein David , Potus François , Provencher Steeve , Bonnet Sébastien , Paulin Roxane , Boucherat Olivier
Published: March 2021

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by a sustained elevation of pulmonary artery (PA) pressure, right ventricular failure, and premature death. Enhanced proliferation and resistance to apoptosis (as seen in cancer cells) of PA smooth muscle cells (PASMCs) is a major pathological hallmark contributing to pulmonary vascular remodeling in PAH, for which current therapies have only limited effects. Emerging evidence points toward a critical role for Enhancer of Zeste Homolog 2 (EZH2) in cancer cell proliferation and survival. However, its role in PAH remains largely unknown. The aim of this study was to determine whether EZH2 represents a new factor critically involved in the abnormal phenotype of PAH-PASMCs. We found that EZH2 is overexpressed in human lung tissues and isolated PASMCs from PAH patients compared to controls as well as in two animal models mimicking the disease. Through loss- and gain-of-function approaches, we showed that EZH2 promotes PAH-PASMC proliferation and survival. By combining quantitative transcriptomic and proteomic approaches in PAH-PASMCs subjected or not to EZH2 knockdown, we found that inhibition of EZH2 downregulates many factors involved in cell-cycle progression, including E2F targets, and contributes to maintain energy production. Notably, we found that EZH2 promotes expression of several nuclear-encoded components of the mitochondrial translation machinery and tricarboxylic acid cycle genes. Overall, this study provides evidence that, by overexpressing EZH2, PAH-PASMCs remove the physiological breaks that normally restrain their proliferation and susceptibility to apoptosis and suggests that EZH2 or downstream factors may serve as therapeutic targets to combat pulmonary vascular remodeling.
Diabetes during Pregnancy: A Maternal Disease Complicating the Course of Pregnancy with Long-Term Deleterious Effects on the Offspring. A Clinical Review
Authors: Ornoy Asher , Becker Maria , Weinstein-Fudim Liza , Ergaz Zivanit
Published: March 2021

In spite of the huge progress in the treatment of diabetes mellitus, we are still in the situation that both pregestational (PGDM) and gestational diabetes (GDM) impose an additional risk to the embryo, fetus, and course of pregnancy. PGDM may increase the rate of congenital malformations, especially cardiac, nervous system, musculoskeletal system, and limbs. PGDM may interfere with fetal growth, often causing macrosomia, but in the presence of severe maternal complications, especially nephropathy, it may inhibit fetal growth. PGDM may also induce a variety of perinatal complications such as stillbirth and perinatal death, cardiomyopathy, respiratory morbidity, and perinatal asphyxia. GDM that generally develops in the second half of pregnancy induces similar but generally less severe complications. Their severity is higher with earlier onset of GDM and inversely correlated with the degree of glycemic control. Early initiation of GDM might even cause some increase in the rate of congenital malformations. Both PGDM and GDM may cause various motor and behavioral neurodevelopmental problems, including an increased incidence of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Most complications are reduced in incidence and severity with the improvement in diabetic control. Mechanisms of diabetic-induced damage in pregnancy are related to maternal and fetal hyperglycemia, enhanced oxidative stress, epigenetic changes, and other, less defined, pathogenic mechanisms.
Glyphosate and AMPA Induce Alterations in Expression of Genes Involved in Chromatin Architecture in Human Peripheral Blood Mononuclear Cells (In Vitro)
Authors: Woźniak Ewelina , Reszka Edyta , Jabłońska Ewa , Michałowicz Jaromir , Huras Bogumiła , Bukowska Bożena
Published: March 2021

We have determined the effect of glyphosate and aminomethylphosphonic acid (AMPA) on expression of genes involved in chromatin architecture in human peripheral blood mononuclear cells (PBMCs). The cells were incubated with glyphosate and AMPA in the concentrations ranging from 0.5 to 100 μM and from 0.5, to 250 μM, respectively. The expression profile of the following genes by quantitative Real-Time PCR was evaluated: Genes involved in the DNA methylation (DNMT1, DNMT3A) and DNA demethylation process (TET3) and those involved in chromatin remodeling: genes involved in the modification of histone methylation (EHMT1, EHMT2) and genes involved in the modification of histone deacetylation (HDAC3, HDAC5). Gene profiling showed that glyphosate changed the expression of DNMT1, DMNT3A, and HDAC3, while AMPA changed the expression of DNMT1 and HDAC3. The results also revealed that glyphosate at lower concentrations than AMPA upregulated the expression of the tested genes. Both compounds studied altered expression of genes, which are characteristic for the regulation of transcriptionally inactive chromatin. However, the unknown activity of many other proteins involved in chromatin structure regulation prevents to carry out an unambiguous evaluation of the effect of tested xenobiotics on the studied process. Undoubtedly, we have observed that glyphosate and AMPA affect epigenetic processes that regulate chromatin architecture.
CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus
Authors: Sampani Erasmia , Daikidou Dimitra-Vasilia , Lioulios George , Xochelli Aliki , Mitsoglou Zoi , Nikolaidou Vasiliki , Dimitriadis Chrysostomos , Fylaktou Asimina , Papagianni Aikaterini , Stangou Maria
Published: March 2021

Background: End-stage renal disease (ESRD) is associated with alterations in T-cell immunity, including increased CD28null and reduced regulatory T cells (Tregs). However, whether immune disturbances are due to ESRD or primary disease is not yet clear. As diabetes mellitus is the leading cause of ESRD, we evaluated its impact on the immune profile of ESRD patients. Methods: CD28null, Tregs, and natural killer cells were initially analyzed by flow cytometry in 30 predialysis ESRD patients due to diabetes (DM), 30 non-DM (NDM), and 25 healthy controls. Measurements were repeated after 6 months on hemodialysis (HD) or peritoneal dialysis (CAPD). Results: The percentage of CD4 + CD28null cells, CD8 + CD28null cells, and Tregs showed significant differences in DM, NDM, and controls; mean rank 33.71 vs. 25.68 vs. 18.88, p = 0.006, 37.79 vs. 28.82 vs. 17.08, p = 0.008, and 20.79 vs. 26.12 vs. 41.33, p = 0.001, respectively. DM vs. NDM had increased CD4 + CD28null and CD8 + CD28null cells, 11.5% (1.5%–24%) vs. 4.1% (0–42.3%), p = 0.02 and 61.3% (24%–76%) vs. 43% (5.7%–85%), p = 0.04, respectively. After 6 months on HD but not CAPD, DM showed a significant further increase in CD4 + CD28null cells, from 30 (14–100) to 52.7 (15–203), p = 0.02; and CD8 + CD28null cells, from 137 (56–275) to 266 (103–456), p = 0.01. Conclusions: Diabetes mellitus affects T-cell subtypes even at predialysis stage, though changes become more prominent after commencement on HD.
Psoriasis: Pathogenesis, Comorbidities, and Therapy Updated
Authors: Kanda Naoko
Published: March 2021

Psoriasis is a chronic inflammatory skin disease characterized by IL-17-dominant abnormal innate and acquired immunity, and the hyperproliferation and aberrant differentiation of epidermal keratinocytes, and comorbid arthritis or cardiometabolic diseases. This Special Issue presented updated information on pathogenesis, comorbidities, and therapy of psoriasis. The pathogenesis of psoriasis may involve the dysfunction of indoleamine 2,3-dioxygenase 2 or of UBA domain containing 1-mediated regulation of CARD14/CARMA2sh. The blood cells of psoriasis patients showed the enhanced oxidative stress/autophagy flux and decreased 20S proteasome activity. Elafin, clusterin, or selenoprotein P may act as biomarkers for psoriasis and comorbid metabolic diseases. The proteomic profile of psoriasis lesions showed the dysfunction of dermal fibroblasts; up-regulation of proinflammatory factors and signal transduction or down-regulation of structural molecules. The skin inflammation in psoriasis may populate certain gut bacteria, such as Staphylococcus aureus and Streptococcus danieliae, which worsen the skin inflammation in turn. The psoriasis-associated pruritus may be caused by immune, nervous, or vascular mechanisms. In addition to current oral treatments and biologics, a new treatment option for psoriasis is now being developed, such as retinoic-acid-receptor-related orphan nuclear receptor γt inhibitors, IL-36 receptor antagonist, or aryl hydrocarbon receptor agonist. Antimicrobial peptides and innate immune cells, involved in the pathogenesis of psoriasis, may be novel therapeutic targets. The pathomechanisms and responses to drugs in collagen diseases are partially shared with and partially different from those in psoriasis. Certain nutrients can exacerbate or regulate the progress of psoriasis. The articles in this Special Issue will encourage attractive approaches to psoriasis by future researchers.
Novel (Phenothiazinyl)Vinyl-Pyridinium Dyes and Their Potential Applications as Cellular Staining Agents
Authors: Stoean Bianca , Rugina Dumitrita , Focsan Monica , Craciun Ana-Maria , Nistor Mǎdǎlina , Lovasz Tamas , Turza Alexandru , Porumb Ioan-Dan , Gál Emese , Cristea Castelia , Silaghi-Dumitrescu Luminita , Astilean Simion , Gaina Luiza Ioana
Published: March 2021

We report here the synthesis and structural characterization of novel cationic (phenothiazinyl)vinyl-pyridinium (PVP) dyes, together with optical (absorption/emission) properties and their potential applicability as fluorescent labels. Convective heating, ultrasound irradiation and mechanochemical synthesis were considered as alternative synthetic methodologies proficient for overcoming drawbacks such as long reaction time, nonsatisfactory yields or solvent requirements in the synthesis of novel dye (E)-1-(3-chloropropyl)-4-(2-(10-methyl-10H-phenothiazin-3-yl)vinyl)pyridin-1-ium bromide 3d and its N-alkyl-2-methylpyridinium precursor 1c. The trans geometry of the newly synthesized (E)-4-(2-(7-bromo-10-ethyl-10H-phenothiazin-3-yl)vinyl)-1-methylpyridin-1-ium iodide 3b and (E)-1-methyl-4-(2-(10-methyl-10H-phenothiazin-3-yl)vinyl)pyridin-1-ium tetrafluoroborate 3a′ was confirmed by single crystal X-ray diffraction. A negative solvatochromism of the dyes in polar solvents was highlighted by UV-Vis spectroscopy and explanatory insights were supported by molecular modeling which suggested a better stabilization of the lowest unoccupied molecular orbitals (LUMO). The photostability of the dye 3b was investigated by irradiation at 365 nm in different solvents, while the steady-state and time-resolved fluorescence properties of dye 3b and 3a′ in solid state were evaluated under one-photon excitation at 485 nm. The in vitro cytotoxicity of the new PVP dyes on B16-F10 melanoma cells was evaluated by WST-1 assay, while their intracellular localization was assessed by epi-fluorescence conventional microscopy imaging as well as one- and two-photon excited confocal fluorescence lifetime imaging microscopy (FLIM). PVP dyes displayed low cytotoxicity, good internalization inside melanoma cells and intense fluorescence emission inside the B16-F10 murine melanoma cells, making them suitable staining agents for imaging applications.
Hylotelephium spectabile, a New Host for Carnation Tortrix Moth (Cacoecimorpha pronubana) and Molecular Characterization in Greece
Authors: Simoglou Konstantinos B. , Avtzis Dimitrios N. , Baixeras Joaquín , Sarigkoli Ioanna , Roditakis Emmanouil
Published: March 2021

Cacoecimorpha pronubana (Hübner) (Lepidoptera, Tortricidae) is a highly polyphagous pest of a wide range of crop and ornamental plants. It is of Mediterranean origin and widespread in European and Mediterranean Plant Protection Organization (EPPO) region. For the first time, infestations of Hylotelephium spectabile (Boreau) Ohba (syn.: Sedum spectabile Boreau) (Saxifragales, Crassulaceae) ornamental plants by C. pronubana larvae, in private gardens in urban area of Drama, Greece, were found. Species identification was conducted based on morphology of female genitalia. In addition, due to reports on occurrence of cryptic C. pronubana species within Europe, DNA barcoding was carried out to determine the molecular status of the pest. This communication reports a new host of C. pronubana and places the Greek pest population along with European species clade.
Systemic Inflammatory Parameters in Patients with Elderly-Onset Rheumatoid Arthritis (EORA) and Young-Onset Rheumatoid Arthritis (YORA)—An Observational Study
Authors: Targońska-Stępniak Bożena , Grzechnik Krzysztof , Kolarz Katarzyna , Gągoł Danuta , Majdan Maria
Published: March 2021

Background: Rheumatoid arthritis (RA) occurs more often in elderly individuals. Elderly onset RA (EORA) (onset > 60 years) encompasses a specific subset of patients if compared with young onset RA (YORA) (onset at a younger age). There is a need to define reliable, simple markers to properly assess the inflammatory activity of RA. Hematological markers of systemic inflammation (Platelet-To-Lymphocyte (PLR) and Neutrophil-To-Lymphocyte (NLR) ratios) are novel measures of the inflammatory response. The goal of the study was to analyze the course of EORA vs. YORA patients and to assess associations between systemic and clinical disease activity markers, including PLR and NLR, in different subsets of patients. PLR and NLR have not previously been assessed in EORA and YORA. Methods: The study group consisted of 113 consecutive patients (63 EORA and 50 YORA). The following assessments were performed: joint counts, Disease Activity Score (DAS28), complete blood cell counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Results: EORA was characterized by significantly higher disease activity markers (conventional inflammatory and clinical), a lower rate of remission or low disease activity, and less frequent use of biological drugs and glucocorticoids. The NLR and PLR were positively correlated with disease activity markers. The PLR was significantly lower in EORA compared with in YORA. Conclusion: EORA and YORA patients differed significantly. In EORA, conventional disease activity markers were higher, the PLR was significantly lower.
The Impact of the COVID-19 Pandemic on Psychological Health and Insomnia among People with Chronic Diseases
Authors: Wańkowicz Paweł , Szylińska Aleksandra , Rotter Iwona
Published: March 2021

The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic highlighted the serious problems of health care systems but also threatened the mental and physical health of patients worldwide. The goal of this study was to assess psychological health and insomnia in people with chronic diseases in the time of elevated stress associated with the pandemic. The study involved 879 people from Zachodniopomorskie province in Poland. Each participant provided basic demographic data, data on symptoms of insomnia, depression, anxiety and information on concomitant diseases such as hypertension, diabetes mellitus, coronary heart disease, heart failure, dyslipidemia, chronic obstructive pulmonary disease, Hashimoto’s disease and smoking cigarettes. Chronic diseases included in this study showed a strong correlation between Hashimoto’s disease and increase scores according to the Insomnia Severity Index (ISI, r = 0.797, p < 0.001), the Generalized Anxiety Disorder scale (GAD-7, r = 0.766, p < 0.001) and the Patient Health Questionnaire (PHQ-9, r = 0.767, p < 0.001). After the results were corrected for age, gender, diagnosed hypertension, dyslipidemia and cigarette smoking, it was confirmed that the diagnosis of Hashimoto’s disease was associated with an increased risk of anxiety (odds ratio (OR) = 2.225; p < 0.001), depression (OR = 2.518; p < 0.001) and insomnia (OR = 3.530; p < 0.001). Our study showed that during the SARS-CoV-2 pandemic patients with Hashimoto’s disease show a higher risk of insomnia, anxiety and depression.
Relapsed Mantle Cell Lymphoma: Current Management, Recent Progress, and Future Directions
Authors: Bond David A , Martin Peter , Maddocks Kami J
Published: March 2021

The increasing number of approved therapies for relapsed mantle cell lymphoma (MCL) provides patients effective treatment options, with increasing complexity in prioritization and sequencing of these therapies. Chemo-immunotherapy remains widely used as frontline MCL treatment with multiple targeted therapies available for relapsed disease. The Bruton’s tyrosine kinase inhibitors (BTKi) ibrutinib, acalabrutinib, and zanubrutinib achieve objective responses in the majority of patients as single agent therapy for relapsed MCL, but differ with regard to toxicity profile and dosing schedule. Lenalidomide and bortezomib are likewise approved for relapsed MCL and are active as monotherapy or in combination with other agents. Venetoclax has been used off-label for the treatment of relapsed and refractory MCL, however data are lacking regarding the efficacy of this approach particularly following BTKi treatment. Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapies have emerged as highly effective therapy for relapsed MCL, with the CAR-T treatment brexucabtagene autoleucel now approved for relapsed MCL. In this review the authors summarize evidence to date for currently approved MCL treatments for relapsed disease including sequencing of therapies, and discuss future directions including combination treatment strategies and new therapies under investigation.
Conceptual Model for Using Imidazoline Derivative Solutions in Pulpal Management
Authors: Jones Robert S.
Published: March 2021

Alpha-adrenergic agonists, such as the Imidazoline derivatives (ImDs) of oxymetazoline and xylometazoline, are highly effective hemostatic agents. ImDs have not been widely used in dentistry but their use in medicine, specifically in ophthalmology and otolaryngology, warrants consideration for pulpal hemostasis. This review presents dental healthcare professionals with an overview of ImDs in medicine. ImD solutions have the potential to be more effective and biocompatible than existing topical hemostatic compounds in pulpal management. Through a comprehensive analysis of the pharmacology of ImDs and the microphysiology of hemostasis regulation in oral tissues, a conceptual model of pulpal management by ImD solutions is presented.
Degenerative Cervical Myelopathy: Insights into Its Pathobiology and Molecular Mechanisms
Authors: Tu Ji , Vargas Castillo Jose , Das Abhirup , Diwan Ashish D.
Published: March 2021

Degenerative cervical myelopathy (DCM), earlier referred to as cervical spondylotic myelopathy (CSM), is the most common and serious neurological disorder in the elderly population caused by chronic progressive compression or irritation of the spinal cord in the neck. The clinical features of DCM include localised neck pain and functional impairment of motor function in the arms, fingers and hands. If left untreated, this can lead to significant and permanent nerve damage including paralysis and death. Despite recent advancements in understanding the DCM pathology, prognosis remains poor and little is known about the molecular mechanisms underlying its pathogenesis. Moreover, there is scant evidence for the best treatment suitable for DCM patients. Decompressive surgery remains the most effective long-term treatment for this pathology, although the decision of when to perform such a procedure remains challenging. Given the fact that the aged population in the world is continuously increasing, DCM is posing a formidable challenge that needs urgent attention. Here, in this comprehensive review, we discuss the current knowledge of DCM pathology, including epidemiology, diagnosis, natural history, pathophysiology, risk factors, molecular features and treatment options. In addition to describing different scoring and classification systems used by clinicians in diagnosing DCM, we also highlight how advanced imaging techniques are being used to study the disease process. Last but not the least, we discuss several molecular underpinnings of DCM aetiology, including the cells involved and the pathways and molecules that are hallmarks of this disease.
Morphological Description of Frontal EEG Interictal and Ictal Discharges in an Adult Cohort of 175 Patients
Authors: García-López Beatriz , Sueiras-Gil María , Gómez-Menéndez Ana Isabel , Vázquez-Sánchez Fernando , Lloria-Gil María Carmen , González-Bernal Jerónimo J. , González-Santos Josefa , Santamaría-Pelaéz Mirian , Soto-Cámara Raúl , Wesenberg Kjaer Troels
Published: March 2021

Clinical and electroencephalogram (EEG) features in frontal lobe epilepsy (FLE) vary considerably among patients, making the diagnosis a challenge. The objective of this study was to describe interictal and ictal EEG activity, identifying variables that could help to differentiate and diagnose frontal lobe epilepsy cases. A prospective cross-sectional study from patients with frontal interictal epileptiform discharges (IED) referred to the Vall d’Hebron University Hospital (Barcelona, Spain) after a clinical event compatible with epileptic seizures was designed. The interictal and ictal activity were analyzed to provide a detailed EEG description of the cases, using different statistical analyses. The morphological seizure pattern at the ictal onset remained globally unchanged over time in seizures arising from the frontal lobe for each patient. Isolated sharp waves were the most frequent waveforms in the expression of IED. Frontal lobe seizures are frequently short and sometimes appear grouped in clusters within the same recording. Often the ictal expression of the electrical activity in frontal lobe seizure is subtle and challenging to interpret. A description of the main findings is summarized to identify seizures arising from the frontal lobe and avoid false negatives findings in EEG interpretations.
Transition Metal Oxides and Their Composites for Photocatalytic Dye Degradation
Authors: Ahuja Preety , Ujjain Sanjeev Kumar , Kanojia Rajni , Attri Pankaj
Published: March 2021

Transition metal oxides (TMO) and their carbon composites have become a glittering upcoming material science candidate. Their interesting properties, such as their meticulous morphology, plentiful availability, flexible surface chemistry along with outstanding mechanical, thermal, and optical properties make them ideal for efficient photocatalytic dye degradation. An extensive range of TMO, and their carbon composites are reviewed highlighting the progression and opportunities for the photocatalytic degradation of dyes. Here, we concisely describe the numerous techniques to extend the optical absorption of these TMOs involving dye sensitization, metal doping, etc. Besides this, an overview of all aspects of dye degradation along with the prevailing challenges for future utilization and development of such nanocomposites towards highly efficient dye degradation system are also reported.
The Resilient Recurrent Behavior of Mediterranean Semi-Arid Complex Adaptive Landscapes
Authors: Petrosillo Irene , Valente Donatella , Mulder Christian , Li Bai-Lian , Jones K. Bruce , Zurlini Giovanni
Published: March 2021

Growing external pressures from human activities and climate change can exacerbate desertification, compromising the livelihoods of more than 25% of the world’s population. The dryland mosaic is defined by land covers that do not behave similarly, and the identification of their recurring or irregular changes over time is crucial, especially in areas susceptible to become desertified. To this aim, the methodological approach of this research is based on the integration of non-linear data analysis techniques, such as recurrence plots (RPs) and recurrence quantification analysis (RQA), applied to the Enhanced Vegetation Index (EVI), which is a functional ecological proxy of above ground net primary production. The research exploits the recurring change detected in vegetation cover over time to gauge the predictable (resilient) behavior of the EVI as well as its chaoticity in a semi-arid Mediterranean region (Apulia, Italy). Interestingly, the results have shown the spatial rendering of recurrence variables, confirming the well-known hot spots of soil degradation and desertification taking place in the region, which are characterized by greater EVI chaoticity, but they have also identified new potential candidate sites. As a result, the susceptibility to land degradation, as measured by the EVI-RQA approach, can help in measuring land desertification with evident operational benefits for landscape planning. The novelty of the research lies in the spatially explicit identification of resilient and less resilient areas to desertification that can support the definition of more targeted interventions and conservation priorities for better planning and sustainable management of Mediterranean drylands.
Bioengineering Solution to Prevent Rainfall-Induced Slope Failures in Tropical Soil
Authors: Patil Ujwalkumar Dashrath , Shelton III Austin J. , Aquino Edriel
Published: March 2021

This paper presents test results of comprehensive laboratory and field-testing program efforts for the development of bioengineering solutions such as growing vegetation for protection of slopes from erosion and landslides in a tropical environmental setting. Saturated shear strength of soil was determined using direct shear tests and unsaturated soil properties, such as soil water retention curve (SWRC), were obtained using a computer-controlled hydraulic property analyzer (HYROP) system as well as a WP4C instrument. Climate data were obtained via field instrumentation and appropriate vegetation data were assumed to perform a finite element method-based transient seepage analysis and coupled slope stability analysis to test the potential of tropical hillslope to fail with and without vegetation over a period of one month. Results show that the factor of safety (FOS) for test slope considering case (a) the rainfall and bare ground, case (b) no rainfall with vegetation, and case (c) rainfall with vegetation were found to be 1.630, 1.763, and 1.650, respectively. Although FOS is marginally improved during storm events due to consideration of vegetation as compared to bare slope, this improvement in FOS is much pronounced during antecedent rainfall (i.e., long duration and small intensity) up to the first 26 days of analysis before the storm event (i.e., high intensity and short duration rainfall), which occurs on 27th day and can be instrumental in preventing slope failures. Similarly, the negative pore water pressure (i.e., matric suction) in the top layer is reduced for case (a) from −260 kPa to −40 kPa, increased for case (b) from −260 kPa to −320 kPa, and decreased for case (c) from −260 kPa to −60 kPa. The practical application of these findings is more applicable to the engineered slopes with vegetation during the dry season when the slope is more stable due to high FOS which, however, will need careful watering just to keep them healthy but prevent complete loss of developed matric suction resulting from root water uptake (RWU). In addition, the small improvement in FOS due to matric suction induced from RWU could play a key role in keeping the slope just stable during extreme storm events especially, when FOS of the bare slope is close to 1. To the best knowledge of the authors this is the first documented geotechnical study, using the tropical soil of Guam, which considers the hydro-mechanical effect of RWU-induced matric suction in slope stability analysis in a tropical setting.
Impact of Power Transformer Oil-Temperature on the Measurement Uncertainty of All-Acoustic Non-Iterative Partial Discharge Location
Authors: Polužanski Vladimir , Kartalović Nenad , Nikolić Boško
Published: March 2021

In this paper, the influence of the variation in transformer oil temperature on the accuracy of the all-acoustic non-iterative method for partial discharge location in a power transformer is researched. The research can improve power transformers’ testing and monitoring, particularly given the large transformer oil temperature variations during real-time monitoring. The research is based on quantifying the contribution of oil temperature to the standard combined measurement uncertainty of the non-iterative algorithm by using analytical, statistical, and Monte Carlo methods. The contribution can be quantified and controlled. The contribution varied significantly with different mutual placements of partial discharge and acoustic sensors. The correlation between the contribution and the mean distance between partial discharge and acoustic sensors was observed. Based on these findings, the procedure to quantify and control the contribution in practice was proposed. The procedure considers the specificity of the method’s mathematical model (the assumption that the oil temperature is constant), the non-iterative algorithm’s nonlinearity, and the large variations in transformer oil temperature. Existing studies did not consider the significant effect of the oil temperature on the combined measurement uncertainty of partial discharge location influenced by those phenomena. The research is limited to partial discharge located in the transformer oil.
Solution Synthesis of Cubic Spinel Mn–Ni–Cu–O Thermistor Powder
Authors: Le Duc Thang , Ju Heongkyu
Published: March 2021

Toward the development of NTCR thermistors, nanocrystalline Mn–Ni–Cu–O powder was synthesized from a mixed chloride aqueous solution by a simple co-precipitation method.The introduction of an oxidizing agent (H2O2) into the solution led to the partial oxidation of Mn2+ ions into Mn3+ ions, which enabled the collected powder to be well crystallized at 650 °C. Such a low calcining temperature resulted in fine particles with a mean size of 60 nm, which significantly promoted densification of the resulting ceramics. As a result, a dense and homogenous microstructure with a relative density up to 97.2% was achieved for pellets sintered at 1100 °C. Furthermore, these sintered ceramics exhibited a room temperature resistivity (ρ25) of 67 Ω·cmand a thermistor constant (B25/85) of 2843 K, which make them suitable for use in industrial thermistors. In addition, electrical stability was greatly improved when the ceramics were prepared by a new two-step sintering method. The results suggest that the co-precipitation route with the introduction of H2O2 is suitable for the fabrication of cubic spinel thermistor nanopowders.
Diffusion of Shape Stabilized PEG-SiO2 as a Driver for Producing Thermoregulating Facing Bricks
Authors: Serrano Angel , Borreguero Ana M. , Iglesias Isabel , Acosta Anselmo , Rodríguez Juan F. , Carmona Manuel
Published: March 2021

A novel form-stable phase-change material (PCM) based on facing bricks was developed by incorporating thermoregulating PEG-SiO2, synthetized by sol-gel method and based on polyethylene glycol as phase-change material and silica as stabilizer compound. The PEG-SiO2 in its liquid form (sol) is firstly adsorbed inside the porous brick and lastly stabilized (gel) by controlling its gelation time, obtaining form-stable PCMs with PEG-SiO2 contents within 15–110 wt.%. Kinetic adsorption curves of the sol into bricks having different porosities as well as maximum adsorption capacities were obtained. The effective diffusion coefficients (Deff) were estimated by means of Fick’s second law, it being possible to predict the adsorption of sol PEG-SiO2 by the brick as function of its porosity and the free diffusion coefficient. Finally, form-stable PCMs demonstrated an improvement in their thermal energy storage capacity (up to 338%), these materials being capable of buffering the indoor temperature during an entire operational day
Selective Deposition of Hard Boron-Carbon Microstructures on Silicon
Authors: Samudrala Gopi , Chakrabarty Kallol , Baker Paul A. , Tucker Bernabe S. , Vohra Yogesh K. , Catledge Shane A.
Published: March 2021

Boron-rich B-C compounds with high hardness have been recently synthesized by the chemical vapor deposition (CVD) method. In this paper, we present our successful efforts in the selective growth of microstructures of boron-carbon compounds on silicon substrates. This was achieved by combining microfabrication techniques such as maskless lithography and sputter deposition with the CVD technique. Our characterization studies on these B-C microstructures showed that they maintain structural and mechanical properties similar to that of their thin-film counterparts. The methodology presented here paves the way for the development of microstructures for microelectromechanical system (MEMS) applications which require custom hardness and strength properties. These hard B-C microstructures are an excellent choice as support structures in MEMS-based devices.
Experimental and Numerical Investigation in Directed Energy Deposition for Component Repair
Authors: Li Lan , Zhang Xinchang , Liou Frank
Published: March 2021

Directed energy deposition (DED) has been widely used for component repair. In the repair process, the surface defects are machined to a groove or slot and then refilled. The sidewall inclination angle of the groove geometry has been recognized to have a considerable impact on the mechanical properties of repaired parts. The objective of this work was to investigate the feasibility of repairing various V-shaped defects with both experiments and modeling. At first, the repair volume was defined by scanning the defective zone. Then, the repair volume was sliced to generate the repair toolpath. After that, the DED process was used to deposit Ti6Al4V powder on the damaged plates with two different slot geometries. Mechanical properties of the repaired parts were evaluated by microstructure analysis and tensile test. Testing of the repaired parts showed excellent bonding between the deposits and base materials with the triangular slot repair. 3D finite element analysis (FEA) models based on sequentially coupled thermo-mechanical field analysis were developed to simulate the corresponding repair process. Thermal histories of the substrate on the repair sample were measured to calibrate the 3D coupled thermo-mechanical model. The temperature measurements showed very good verification with the predicted temperature results. After that, the validated model was used to predict the residual stresses and distortions in the parts. Predicted deformation and stress results can guide the evaluation of the repair quality.
Numerical Simulation and Experimental Study on Compound Casting of Layered Aluminum Matrix Composite Brake Drum
Authors: Zheng Hansen , Zhang Zhifeng , Bai Yuelong
Published: March 2021

The requirements of high-strength, wear-resistance and lightweight of brake drums have been continually increasing in recent years and any specific aluminum alloy or particle-reinforced aluminum matrix composites may not satisfy all the demands. Combining dissimilar materials to play their respective advantages is a solution to this problem. In this study, a compound casting method was used to combine solid SiCp/A357 composite and a liquid 7050 aluminum alloy to prepare an aluminum matrix composite with a layered structure. The ProCAST numerical simulation software was used to predict the heat transfer in compound casting process and guide the preheating temperature of the wear-resistant ring in the experiment. An Optical Microscope (OM) and Scanning Electron Microscope (SEM) were used to observe microstructures around the solid–liquid bonding interface, the element distribution and phase component of which were analyzed by Energy Dispersive Spectroscopy (EDS) and mechanical properties were evaluated by microhardness and shear tests. The results showed that the interface of the layered aluminum matrix composite prepared by this method achieved complete metallurgical bonding and a transition zone formed on the solid surface. After T6 heat treatment, the average shear strength of the interface increased from 19.8 MPa to 33.8 MPa.
Nitric-Acid Oxidized Single-Walled Carbon Nanohorns as a Potential Material for Bio-Applications—Toxicity and Hemocompatibility Studies
Authors: Zieba Wojciech , Czarnecka Joanna , Rusak Tomasz , Zieba Monika , Terzyk Artur P.
Published: March 2021

The results of in vitro studies of single-walled carbon nanohorn (SWCNH) oxidized materials’ cytotoxicity obtained by the cell membrane integrity (Neutral Red Uptake (NRU)) and metabolic activity (by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)) on A549 and human dermal fibroblasts (HDF) cell lines are presented. We also present hemocompatibility studies on human and porcine blood, and an erythrocyte concentrate to prove that the obtained samples will not interfere with blood components. Characterization of the materials is supplemented by ζ-potential measurements, Transmission Electron Microscope (TEM) imaging, and thermogravimetric studies (TG). The presented results show the correlation between the specific surface area of materials and the platelet aggregation, when the ID/IG ratio determined from Raman spectra correlates with hemoglobin release from the erythrocytes (in whole blood testing). A plausible mechanism explaining the observed correlations is given. The cytotoxicity and hemocompatibility studies prove that the studied materials are acceptable for use in biomedical applications, especially a sample SWCNH-ox-1.5 with the best application potential.