bluuebunny/crossref_metadata_2025 huggingface dataset:
Peroxisomal ABC Transporters: An Update
Authors: Tawbeh Ali , Gondcaille Catherine , Trompier Doriane , Savary Stéphane
Published: June 2021

ATP-binding cassette (ABC) transporters constitute one of the largest superfamilies of conserved proteins from bacteria to mammals. In humans, three members of this family are expressed in the peroxisomal membrane and belong to the subfamily D: ABCD1 (ALDP), ABCD2 (ALDRP), and ABCD3 (PMP70). These half-transporters must dimerize to form a functional transporter, but they are thought to exist primarily as tetramers. They possess overlapping but specific substrate specificity, allowing the transport of various lipids into the peroxisomal matrix. The defects of ABCD1 and ABCD3 are responsible for two genetic disorders called X-linked adrenoleukodystrophy and congenital bile acid synthesis defect 5, respectively. In addition to their role in peroxisome metabolism, it has recently been proposed that peroxisomal ABC transporters participate in cell signaling and cell control, particularly in cancer. This review presents an overview of the knowledge on the structure, function, and mechanisms involving these proteins and their link to pathologies. We summarize the different in vitro and in vivo models existing across the species to study peroxisomal ABC transporters and the consequences of their defects. Finally, an overview of the known and possible interactome involving these proteins, which reveal putative and unexpected new functions, is shown and discussed.
In Silico and In Vitro Analyses Validate Human MicroRNAs Targeting the SARS-CoV-2 3′-UTR
Authors: Barreda-Manso María Asunción , Nieto-Díaz Manuel , Soto Altea , Muñoz-Galdeano Teresa , Reigada David , Maza Rodrigo M.
Published: June 2021

COVID-19 pandemic is caused by betacoronavirus SARS-CoV-2. The genome of this virus is composed of a single strand of RNA with 5′ and 3′-UTR flanking a region of protein-coding ORFs closely resembling cells’ mRNAs. MicroRNAs are endogenous post-transcriptional regulators that target mRNA to modulate protein expression and mediate cellular functions, including antiviral defense. In the present study, we carried out a bioinformatics screening to search for endogenous human microRNAs targeting the 3′-UTR of SARS-CoV-2. Results from the computational techniques allowed us to identify 10 potential candidates. The capacity of 3 of them, together with hsa-miR-138-5p, to target the SARS-CoV-2 3′-UTR was validated in vitro by gene reporter assays. Available information indicates that two of these microRNAs, namely, hsa-miR-3941 and hsa-miR-138-5p, combine effective targeting of SARS-CoV-2 genome with complementary antiviral or protective effects in the host cells that make them potential candidates for therapeutic treatment of most, if not all, COVID-19 variants known to date. All information obtained while conducting the present analysis is available at Open Science Framework repository.
Carnosic Acid Attenuates an Early Increase in ROS Levels during Adipocyte Differentiation by Suppressing Translation of Nox4 and Inducing Translation of Antioxidant Enzymes
Authors: Lee Dae-Kun , Jang Hae-Dong
Published: June 2021

The objective of this study was to investigate molecular mechanisms underlying the ability of carnosic acid to attenuate an early increase in reactive oxygen species (ROS) levels during MDI-induced adipocyte differentiation. The levels of superoxide anion and ROS were determined using dihydroethidium (DHE) and 2′-7′-dichlorofluorescin diacetate (DCFH-DA), respectively. Both superoxide anion and ROS levels peaked on the second day of differentiation. They were suppressed by carnosic acid. Carnosic acid attenuates the translation of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 4 (Nox4), p47phox, and p22phox, and the phosphorylation of nuclear factor-kappa B (NF-κB) and NF-κB inhibitor (IkBa). The translocation of NF-κB into the nucleus was also decreased by carnosic acid. In addition, carnosic acid increased the translation of heme oxygenase-1 (HO-1), γ–glutamylcysteine synthetase (γ-GCSc), and glutathione S-transferase (GST) and both the translation and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Taken together, these results indicate that carnosic acid could down-regulate ROS level in an early stage of MPI-induced adipocyte differentiation by attenuating ROS generation through suppression of NF-κB-mediated translation of Nox4 enzyme and increasing ROS neutralization through induction of Nrf2-mediated translation of phase II antioxidant enzymes such as HO-1, γ-GCS, and GST, leading to its anti-adipogenetic effect.
Characteristics of Ventricular Electrophysiological Substrates in Metabolic Mice Treated with Empagliflozin
Authors: Jhuo Shih-Jie , Liu I-Hsin , Tasi Wei-Chung , Chou Te-Wu , Lin Yi-Hsiung , Wu Bin-Nan , Lee Kun-Tai , Lai Wen-Ter
Published: June 2021

Empagliflozin (EMPA) is a sodium–glucose transporter 2 (SGLT2) inhibitor that functions as a new-generation glucose-lowering agent and has been proven to be beneficial for patients with cardiovascular diseases. However, the possible benefits and mechanisms of its antiarrhythmic effects in cardiac tissue have not yet been reported. In this study, we elucidated the possible antiarrhythmic effects and mechanisms of EMPA treatment in cardiac tissues of metabolic syndrome (MS) mice. A total of 20 C57BL/6J mice (age: 8 weeks) were divided into four groups: (1) control group, mice fed a standard chow for 16 weeks; (2) MS group, mice fed a high-fat diet for 16 weeks; (3) EMPA group, mice fed a high-fat diet for 12 weeks and administered EMPA at 10 mg/kg daily for the following 4 weeks; and (4) glibenclamide (GLI) group, mice fed a high-fat diet for 12 weeks and administered GLI at 0.6 mg/kg daily for the following 4 weeks. All mice were sacrificed after 16 weeks of feeding. The parameters of electrocardiography (ECG), echocardiography, and the effective refractory period (ERP) of the left ventricle were recorded. The histological characteristics of cardiac tissue, including connexin (Cx) expression and fibrotic areas, were also evaluated. Compared with the MS group, the ECG QT interval in the EMPA group was significantly shorter (57.06 ± 3.43 ms vs. 50.00 ± 2.62 ms, p = 0.011). The ERP of the left ventricle was also significantly shorter in the EMPA group than that in the GLI group (20.00 ± 10.00 ms vs. 60.00 ± 10.00 ms, p = 0.001). The expression of Cx40 and Cx43 in ventricular tissue was significantly lower in the MS group than in the control group. However, the downregulation of Cx40 and Cx43 was significantly attenuated in the EMPA group compared with the MS and GLI groups. The fibrotic areas of ventricular tissue were also fewer in the EMPA group than that in the MS group. In this study, the ECG QT interval in the EMPA group was shorter than that in the MS group. Compared with the MS group, the EMPA group exhibited significant attenuation of downregulated connexin expression and significantly fewer fibrotic areas in ventricles. These results may provide evidence of possible antiarrhythmic effects of EMPA.
Molecular Pathogenesis of Pulmonary Fibrosis, with Focus on Pathways Related to TGF-β and the Ubiquitin-Proteasome Pathway
Authors: Inui Naoki , Sakai Satoshi , Kitagawa Masatoshi
Published: June 2021

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. During the past decade, novel pathogenic mechanisms of IPF have been elucidated that have shifted the concept of IPF from an inflammatory-driven to an epithelial-driven disease. Dysregulated repair responses induced by recurrent epithelial cell damage and excessive extracellular matrix accumulation result in pulmonary fibrosis. Although there is currently no curative therapy for IPF, two medications, pirfenidone and nintedanib, have been introduced based on understanding the pathogenesis of the disease. In this review, we discuss advances in understanding IPF pathogenesis, highlighting epithelial–mesenchymal transition (EMT), the ubiquitin-proteasome system, and endothelial cells. TGF-β is a central regulator involved in EMT and pulmonary fibrosis. HECT-, RING finger-, and U-box-type E3 ubiquitin ligases regulate TGF-β-Smad pathway-mediated EMT via the ubiquitin-proteasome pathway. p27 degradation mediated by the SCF-type E3 ligase, Skp2, contributes to the progression of pulmonary fibrosis by promotion of either mesenchymal fibroblast proliferation, EMT, or both. In addition to fibroblasts as key effector cells in myofibroblast differentiation and extracellular matrix deposition, endothelial cells also play a role in the processes of IPF. Endothelial cells can transform into myofibroblasts; therefore, endothelial–mesenchymal transition can be another source of myofibroblasts.
Docking-Based 3D-QSAR Studies for 1,3,4-oxadiazol-2-one Derivatives as FAAH Inhibitors
Authors: Zięba Agata , Laitinen Tuomo , Patel Jayendra Z. , Poso Antti , Kaczor Agnieszka A.
Published: June 2021

This work aimed to construct 3D-QSAR CoMFA and CoMSIA models for a series of 31 FAAH inhibitors, containing the 1,3,4-oxadiazol-2-one moiety. The obtained models were characterized by good statistical parameters: CoMFA Q2 = 0.61, R2 = 0.98; CoMSIA Q2 = 0.64, R2 = 0.93. The CoMFA model field contributions were 54.1% and 45.9% for steric and electrostatic fields, respectively. In the CoMSIA model, electrostatic, steric, hydrogen bond donor, and hydrogen acceptor properties were equal to 34.6%, 23.9%, 23.4%, and 18.0%, respectively. These models were validated by applying the leave-one-out technique, the seven-element test set (CoMFA r2test-set = 0.91; CoMSIA r2test-set = 0.91), a progressive scrambling test, and external validation criteria developed by Golbraikh and Tropsha (CoMFA r20 = 0.98, k = 0.95; CoMSIA r20 = 0.98, k = 0.89). As the statistical significance of the obtained model was confirmed, the results of the CoMFA and CoMSIA field calculation were mapped onto the enzyme binding site. It gave us the opportunity to discuss the structure–activity relationship based on the ligand–enzyme interactions. In particular, examination of the electrostatic properties of the established CoMFA model revealed fields that correspond to the regions where electropositive substituents are not desired, e.g., in the neighborhood of the 1,3,4-oxadiazol-2-one moiety. This highlights the importance of heterocycle, a highly electronegative moiety in this area of each ligand. Examination of hydrogen bond donor and acceptor properties contour maps revealed several spots where the implementation of another hydrogen-bond-donating moiety will positively impact molecules’ binding affinity, e.g., in the neighborhood of the 1,3,4-oxadiazol-2-one ring. On the other hand, there is a large isopleth that refers to the favorable H-bond properties close to the terminal phenoxy group of a ligand, which means that, generally speaking, H-bond acceptors are desired in this area.
Neurobiology of Cancer: Introduction of New Drugs in the Treatment and Prevention of Cancer
Authors: Mravec Boris
Published: June 2021

Research on the neurobiology of cancer, which lies at the border of neuroscience and oncology, has elucidated the mechanisms and pathways that enable the nervous system to modulate processes associated with cancer initiation and progression. This research has also shown that several drugs which modulate interactions between the nervous system and the tumor micro- and macroenvironments significantly reduced the progression of cancer in animal models. Encouraging results were also provided by prospective clinical trials investigating the effect of drugs that reduce adrenergic signaling on the course of cancer in oncological patients. Moreover, it has been shown that reducing adrenergic signaling might also reduce the incidence of cancer in animal models, as well as in humans. However, even if many experimental and clinical findings have confirmed the preventive and therapeutic potential of drugs that reduce the stimulatory effect of the nervous system on processes related to cancer initiation and progression, several questions remain unanswered. Therefore, the aim of this review is to critically evaluate the efficiency of these drugs and to discuss questions that need to be answered before their introduction into conventional cancer treatment and prevention.
The Emerging Roles of Chromogranins and Derived Polypeptides in Atherosclerosis, Diabetes, and Coronary Heart Disease
Authors: Watanabe Takuya
Published: June 2021

Chromogranin A (CgA), B (CgB), and C (CgC), the family members of the granin glycoproteins, are associated with diabetes. These proteins are abundantly expressed in neurons, endocrine, and neuroendocrine cells. They are also present in other areas of the body. Patients with diabetic retinopathy have higher levels of CgA, CgB, and CgC in the vitreous humor. In addition, type 1 diabetic patients have high CgA and low CgB levels in the circulating blood. Plasma CgA levels are increased in patients with hypertension, coronary heart disease, and heart failure. CgA is the precursor to several functional peptides, including catestatin, vasostatin-1, vasostatin-2, pancreastatin, chromofungin, and many others. Catestatin, vasostain-1, and vasostatin-2 suppress the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in human vascular endothelial cells. Catestatin and vasostatin-1 suppress oxidized low-density lipoprotein-induced foam cell formation in human macrophages. Catestatin and vasostatin-2, but not vasostatin-1, suppress the proliferation and these three peptides suppress the migration in human vascular smooth muscles. Chronic infusion of catestatin, vasostatin-1, or vasostatin-2 suppresses the development of atherosclerosis of the aorta in apolipoprotein E-deficient mice. Catestatin, vasostatin-1, vasostatin-2, and chromofungin protect ischemia/reperfusion-induced myocardial dysfunction in rats. Since pancreastatin inhibits insulin secretion from pancreatic β-cells, and regulates glucose metabolism in liver and adipose tissues, pancreastatin inhibitor peptide-8 (PSTi8) improves insulin resistance and glucose homeostasis. Catestatin stimulates therapeutic angiogenesis in the mouse hind limb ischemia model. Gene therapy with secretoneurin, a CgC-derived peptide, stimulates postischemic neovascularization in apolipoprotein E-deficient mice and streptozotocin-induced diabetic mice, and improves diabetic neuropathy in db/db mice. Therefore, CgA is a biomarker for atherosclerosis, diabetes, hypertension, and coronary heart disease. CgA- and CgC--derived polypeptides provide the therapeutic target for atherosclerosis and ischemia-induced tissue damages. PSTi8 is useful in the treatment of diabetes.
Pro- and Antiangiogenic Factors in Gliomas: Implications for Novel Therapeutic Possibilities
Authors: Groblewska Magdalena , Mroczko Barbara
Published: June 2021

Angiogenesis, a complex, multistep process of forming new blood vessels, plays crucial role in normal development, embryogenesis, and wound healing. Malignant tumors characterized by increased proliferation also require new vasculature to provide an adequate supply of oxygen and nutrients for developing tumor. Gliomas are among the most frequent primary tumors of the central nervous system (CNS), characterized by increased new vessel formation. The processes of neoangiogenesis, necessary for glioma development, are mediated by numerous growth factors, cytokines, chemokines and other proteins. In contrast to other solid tumors, some biological conditions, such as the blood–brain barrier and the unique interplay between immune microenvironment and tumor, represent significant challenges in glioma therapy. Therefore, the objective of the study was to present the role of various proangiogenic factors in glioma angiogenesis as well as the differences between normal and tumoral angiogenesis. Another goal was to present novel therapeutic options in oncology approaches. We performed a thorough search via the PubMed database. In this paper we describe various proangiogenic factors in glioma vasculature development. The presented paper also reviews various antiangiogenic factors necessary in maintaining equilibrium between pro- and antiangiogenic processes. Furthermore, we present some novel possibilities of antiangiogenic therapy in this type of tumors.
Aged Mice Devoid of the M3 Muscarinic Acetylcholine Receptor Develop Mild Dry Eye Disease
Authors: Musayeva Aytan , Jiang Subao , Ruan Yue , Zadeh Jenia Kouchek , Chronopoulos Panagiotis , Pfeiffer Norbert , Müller Werner E.G. , Ackermann Maximilian , Xia Ning , Li Huige , Gericke Adrian
Published: June 2021

The parasympathetic nervous system is critically involved in the regulation of tear secretion by activating muscarinic acetylcholine receptors. Hence, various animal models targeting parasympathetic signaling have been developed to induce dry eye disease (DED). However, the muscarinic receptor subtype (M1–M5) mediating tear secretion remains to be determined. This study was conducted to test the hypothesis that the M3 receptor subtype regulates tear secretion and to evaluate the ocular surface phenotype of mice with targeted disruption of the M3 receptor (M3R−/−). The experimental techniques included quantification of tear production, fluorescein staining of the ocular surface, environmental scanning electron microscopy, assessment of proliferating cells in the corneal epithelium and of goblet cells in the conjunctiva, quantification of mRNA for inflammatory cytokines and prooxidant redox enzymes and quantification of reactive oxygen species. Tear volume was reduced in M3R−/− mice compared to age-matched controls at the age of 3 months and 15 months, respectively. This was associated with mild corneal epitheliopathy in the 15-month-old but not in the 3-month-old M3R−/− mice. M3R−/− mice at the age of 15 months also displayed changes in corneal epithelial cell texture, reduced conjunctival goblet cell density, oxidative stress and elevated mRNA expression levels for inflammatory cytokines and prooxidant redox enzymes. The findings suggest that the M3 receptor plays a pivotal role in tear production and its absence leads to ocular surface changes typical for DED at advanced age.
TRPV1: Role in Skin and Skin Diseases and Potential Target for Improving Wound Healing
Authors: Bagood Michelle D. , Isseroff R. Rivkah
Published: June 2021

Skin is innervated by a multitude of sensory nerves that are important to the function of this barrier tissue in homeostasis and injury. The role of innervation and neuromediators has been previously reviewed so here we focus on the role of the transient receptor potential cation channel, subfamily V member 1 (TRPV1) in wound healing, with the intent of targeting it in treatment of non-healing wounds. TRPV1 structure and function as well as the outcomes of TRPV1-targeted therapies utilized in several diseases and tissues are summarized. In skin, keratinocytes, sebocytes, nociceptors, and several immune cells express TRPV1, making it an attractive focus area for treating wounds. Many intrinsic and extrinsic factors confound the function and targeting of TRPV1 and may lead to adverse or off-target effects. Therefore, a better understanding of what is known about the role of TRPV1 in skin and wound healing will inform future therapies to treat impaired and chronic wounds to improve healing.
Short-Term Effect of a Low-Protein High-Carbohydrate Diet on Mature Female and Male, and Neomale Rainbow Trout
Authors: Favalier Nathan , Véron Vincent , Marchand Michael , Surget Anne , Maunas Patrick , Turonnet Nicolas , Panserat Stéphane , Marandel Lucie
Published: June 2021

Rainbow trout are considered as a poor user of dietary carbohydrates, displaying persistent postprandial hyperglycaemia when fed a diet containing high amounts of carbohydrates. While this phenotype is well-described in juveniles, less attention was given to broodstock. Our objective was to assess for the first time the short-term consequences of feeding mature female and male, and neomale trout with a low-protein high-carbohydrate diet on glucose and lipid metabolism. Fish were fed for two days with a diet containing either no or 32% of carbohydrates. We analysed plasma metabolites, mRNA levels and enzymatic activities of glycolysis, gluconeogenesis, de novo lipogenesis and β-oxidation in the liver. Results demonstrated that the glucose and lipid metabolism were regulated by the nutritional status in all sexes, irrespective of the carbohydrate intake. These data point out that carbohydrate intake during a short period (5 meals) at 8 °C did not induce specific metabolic changes in broodstock. Finally, we demonstrated, for the first time, sex differences regarding the consequences of two days of feeding on glucose and lipid metabolism.
Nucleic Acid Testing of SARS-CoV-2
Authors: Yoo Hee Min , Kim Il-Hwan , Kim Seil
Published: June 2021

The coronavirus disease 2019 (COVID-19) has caused a large global outbreak. It is accordingly important to develop accurate and rapid diagnostic methods. The polymerase chain reaction (PCR)-based method including reverse transcription-polymerase chain reaction (RT-PCR) is the most widely used assay for the detection of SARS-CoV-2 RNA. Along with the RT-PCR method, digital PCR has emerged as a powerful tool to quantify nucleic acid of the virus with high accuracy and sensitivity. Non-PCR based techniques such as reverse transcription loop-mediated isothermal amplification (RT-LAMP) and reverse transcription recombinase polymerase amplification (RT-RPA) are considered to be rapid and simple nucleic acid detection methods and were reviewed in this paper. Non-conventional molecular diagnostic methods including next-generation sequencing (NGS), CRISPR-based assays and nanotechnology are improving the accuracy and sensitivity of COVID-19 diagnosis. In this review, we also focus on standardization of SARS-CoV-2 nucleic acid testing and the activity of the National Metrology Institutes (NMIs) and highlight resources such as reference materials (RM) that provide the values of specified properties. Finally, we summarize the useful resources for convenient COVID-19 molecular diagnostics.
Evidence of the CH···O HydrogenBonding in Imidazolium-Based Ionic Liquids from Far-Infrared Spectroscopy Measurements and DFT Calculations
Authors: Palumbo Oriele , Cimini Adriano , Trequattrini Francesco , Brubach Jean-Blaise , Roy Pascale , Paolone Annalisa
Published: June 2021

Knowledge of all the intermolecular forces occurring in ionic liquids (ILs) is essential to master their properties. Aiming at investigating the weaker hydrogen bonding in aprotic liquids, the present work combined computational study and far-infrared spectroscopy on four imidazolium-based ILs with different anions. The DFT calculations of the ionic couples, using the ωB97X-D functional and considering both the empirical dispersion corrections and the presence of a polar solvent, show that, for all samples, the lowest energy configurations of the ion pair present H atoms, directly bound to C atoms of the cation and close to O atoms of the anion, capable of creating moderate to weak hydrogen bonding with anions. For the liquids containing anions of higher bonding ability, the absorption curves generated from the calculated vibrational frequencies and intensities show absorption bands between 100 and 125 cm−1 corresponding to the stretching of the hydrogen bond. These indications are in complete agreement with the presently reported temperature dependence of the far-infrared spectrum, where the stretching modes of the hydrogen bonding are detected only for samples presenting a moderate interaction and become particularly prominent at low temperatures. Moreover, from the analysis of the infrared spectra, the occurrence of various phase transitions as a function of temperature was detected, and the difference in the average energy between the H-bonded and the dispersion-governed molecular configurations was evaluated.
Plasma Proteomic Analysis in Morquio A Disease
Authors: Álvarez José V. , Bravo Susana B. , Chantada-Vázquez María Pilar , Barbosa-Gouveia Sofía , Colón Cristóbal , López-Suarez Olalla , Tomatsu Shunji , Otero-Espinar Francisco J. , Couce María L.
Published: June 2021

Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal disease caused by mutations in the gene encoding the enzymeN-acetylgalactosamine-6-sulfate sulfatase (GALNS), and is characterized by systemic skeletal dysplasia due to excessive storage of keratan sulfate (KS) and chondroitin-6-sulfate in chondrocytes. Although improvements in the activity of daily living and endurance tests have been achieved with enzyme replacement therapy (ERT) with recombinant human GALNS, recovery of bone lesions and bone growth in MPS IVA has not been demonstrated to date. Moreover, no correlation has been described between therapeutic efficacy and urine levels of KS, which accumulates in MPS IVA patients. The objective of this study was to assess the validity of potential biomarkers proposed by other authors and to identify new biomarkers. To identify candidate biomarkers of this disease, we analyzed plasma samples from healthy controls (n=6) and from untreated (n=8) and ERT-treated (n=5, sampled before and after treatment) MPS IVA patients using both qualitative and quantitative proteomics analyses. The qualitative proteomics approach analyzed the proteomic profile of the different study groups. In the quantitative analysis, we identified/quantified 215 proteins after comparing healthy control untreated, ERT-treated MPSIVA patients. We selected a group of proteins that were dysregulated in MPS IVA patients. We identified four potential protein biomarkers, all of which may influence bone and cartilage metabolism: fetuin-A, vitronectin, alpha-1antitrypsin, and clusterin. Further studies of cartilage and bone samples from MPS IVA patients will be required to verify the validity of these proteins as potential biomarkers of MPS IVA.
Coping Strategies by University Students in Response to COVID-19: Differences between Community and Clinical Groups
Authors: López-Ramos Víctor-María , León-del-Barco Benito , Mendo-Lázaro Santiago , Polo-del-Río María-Isabel
Published: June 2021

Last year, the COVID-19 pandemic had severe consequences on the health and well-being of millions of people. Different studies try to identify the main effects that the crisis and several lockdowns have had on the citizens’ mental health. This research analyses the coping strategies generated by students from a community group and a clinical group in response to this crisis, using the Coping Responses Inventory—Adult Form (CRI-A) by Moos with a sample of 1074 students of Universidad de Extremadura. Multivariate analysis and receiver operating characteristic curve analysis have been carried out, revealing, amongst other things, a greater predisposition of the clinical sample towards factors such as seeking guidance and support, cognitive avoidance or emotional discharge. Results show that students with prior mental health problems perform an unhealthy coping response based on avoidance strategies. This group of students suffers a double source of distress and anxiety, one derived from their prior psychopathologic problems and the stress of the lockdown and another one originating from an inefficient coping response, which makes coping strategies raise levels of distress and anxiety.
Role of Glucose-Lowering Medications in Erectile Dysfunction
Authors: Cignarelli Angelo , Genchi Valentina Annamaria , D’Oria Rossella , Giordano Fiorella , Caruso Irene , Perrini Sebastio , Natalicchio Annalisa , Laviola Luigi , Giorgino Francesco
Published: June 2021

Erectile dysfunction (ED) is a long-term complication of type 2 diabetes (T2D) widely known to affect the quality of life. Several aspects of altered metabolism in individuals with T2D may help to compromise the penile vasculature structure and functions, thus exacerbating the imbalance between smooth muscle contractility and relaxation. Among these, advanced glycation end-products and reactive oxygen species derived from a hyperglycaemic state are known to accelerate endothelial dysfunction by lowering nitric oxide bioavailability, the essential stimulus of relaxation. Although several studies have explained the pathogenetic mechanisms involved in the generation of erectile failure, few studies to date have described the efficacy of glucose-lowering medications in the restoration of normal sexual activity. Herein, we will present current knowledge about the main starters of the pathophysiology of diabetic ED and explore the role of different anti-diabetes therapies in the potential remission of ED, highlighting specific pathways whose activation or inhibition could be fundamental for sexual care in a diabetes setting.
Efficacy and Safety of Hydroxychloroquine for Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis
Authors: Hernandez Adrian V. , Phan Mi T. , Rocco Jonathon , Pasupuleti Vinay , Barboza Joshuan J. , Piscoya Alejandro , Roman Yuani M. , White Charles M.
Published: June 2021

We systematically reviewed the efficacy and safety of hydroxychloroquine as treatment for hospitalized COVID-19. Randomized controlled trials (RCTs) evaluating hydroxychloroquine as treatment for hospitalized COVID-19 patients were searched until 2nd of December 2020. Primary outcomes were all-cause mortality, need of mechanical ventilation, need of non-invasive ventilation, ICU admission and oxygen support at 14 and 30 days. Secondary outcomes were clinical recovery and worsening, discharge, radiological progression of pneumonia, virologic clearance, serious adverse events (SAE) and adverse events. Inverse variance random effects meta-analyses were performed. Thirteen RCTs (n=18,540) were included. Hydroxychloroquine total doses ranged between 2000 and 12,400 mg; treatment durations were from 5 to 16 days and follow up times between 5 and 30 days. Compared to controls, hydroxychloroquine non-significantly increased mortality at 14 days (RR 1.07, 95%CI 0.92–1.25) or 30 days (RR 1.08, 95%CI 1.00–1.16). Hydroxychloroquine did not affect other primary or secondary outcomes, except SAEs that were significantly higher than the control (RR 1.24, 95%CI 1.05–1.46). Eleven RCTs had high or some concerns of bias. Subgroup analyses were consistent with main analyses. Hydroxychloroquine was not efficacious for treating hospitalized COVID-19 patients and caused more severe adverse events. Hydroxychloroquine should not be recommended as treatment for hospitalized COVID-19 patients.
Treatment of Fetal Arrhythmias
Authors: Veduta Alina , Panaitescu Anca Maria , Ciobanu Anca Marina , Neculcea Diana , Popescu Mihaela Roxana , Peltecu Gheorghe , Cavoretto Paolo
Published: June 2021

Fetal arrhythmias are mostly benign and transient. However, some of them are associated with structural defects or can cause heart failure, fetal hydrops, and can lead to intrauterine death. The analysis of fetal heart rhythm is based on ultrasound (M-mode and Doppler echocardiography). Irregular rhythm due to atrial ectopic beats is the most common type of fetal arrhythmia and is generally benign. Tachyarrhythmias are diagnosed when the fetal heart rate is persistently above 180 beats per minute (bpm). The most common fetal tachyarrhythmias are paroxysmal supraventricular tachycardia and atrial flutter. Most fetal tachycardias can be terminated or controlled by transplacental or direct administration of anti-arrhythmic drugs. Fetal bradycardia is diagnosed when the fetal heart rate is slower than 110 bpm. Persistent bradycardia outside labor or in the absence of placental pathology is mostly due to atrioventricular (AV) block. Approximately half of fetal heart blocks are in cases with structural heart defects, and AV block in cases with structurally normal heart is often caused by maternal anti-Ro/SSA antibodies. The efficacy of prenatal treatment for fetal AV block is limited. Our review aims to provide a practical guide for the diagnosis and management of common fetal arrythmias, from the joint perspective of the fetal medicine specialist and the cardiologist.
Disturbances in White Matter Integrity in the Ultra-High-Risk Psychosis State—A Systematic Review
Authors: Waszczuk Katarzyna , Rek-Owodziń Katarzyna , Tyburski Ernest , Mak Monika , Misiak Błażej , Samochowiec Jerzy
Published: June 2021

Schizophrenia is a severe and disabling mental illness whose etiology still remains unclear. The available literature indicates that there exist white matter (WM) abnormalities in people with schizophrenia spectrum disorders. Recent developments in modern neuroimaging methods have enabled the identification of the structure, morphology, and function of the underlying WM fibers in vivo. The purpose of this paper is to review the existing evidence about WM abnormalities in individuals at ultra-high risk of psychosis (UHR) with the use of diffusion tensor imaging (DTI) available from the National Center for Biotechnology Information PubMed (Medline) and Health Source: Nursing/Academic Edition databases. Of 358 relevant articles identified, 25 papers published in the years 2008–2020 were ultimately included in the review. Most of them supported the presence of subtle aberrations in WM in UHR individuals, especially in the superior longitudinal fasciculus (SLF), the inferior longitudinal fasciculus (ILF), and the inferior fronto-occipital fasciculus (IFOF). These alterations may therefore be considered a promising neurobiological marker for the risk of psychosis. However, due to methodological discrepancies and the relative scarcity of evidence, further investigation is called for, especially into connectome analysis in UHR patients.
Will New Drugs Replace Transplants for Chronic Lymphocytic Leukaemia?
Authors: Yang Shenmiao , Huang Xiaojun , Gale Robert Peter
Published: June 2021

Transplants have been used to treat chronic lymphocytic leukemia (CLL) for more than 35 years. Use has been restricted to <1 percent of highly selected persons typically failing concurrent conventional therapies. As therapies of CLL have evolved, so have indications for transplantation and transplant techniques. The data that we review indicate that transplants can result in long-term leukemia-free survival in some persons but are associated with substantial transplant-related morbidity and mortality. We discuss the mechanisms underlying the anti-leukemia effects of transplants including drugs, ionizing radiations, immune-mediated mechanisms and/or a combination. We discuss prognostic and predicative covariates for transplant outcomes. Importantly, we consider whether there is presently a role of transplants in CLL and who, if anyone, is an appropriate candidate in the context of new drugs.
Clinical Differences between COVID-19 and a COVID-Like Syndrome
Authors: Di Micco Pierpaolo , Camporese Giuseppe , Russo Vincenzo , Cardillo Giuseppe , Imbalzano Egidio , Tufano Antonella , Bernardi Enrico , Fontanella Andrea
Published: June 2021

COVID-19 is an infection due to SARS-CoV-2; this virus has been identified as the cause of the present pandemic. Several typical characteristics are present in this infection, in particular pneumonia with possible lung failure, but atypical clinical presentations are being described daily by physicians around the world. Ground-glass opacities with pneumonia are the most common and dangerous presentations of the COVID-19 disease, and they are usually associated with positive nasopharyngeal swab (NPS) tests with detectable SARS-CoV-2 viral RNA. Compared to the general population, hospital workers have been at a greater risk of infection ever since the first patients were hospitalized. However, hospital workers have also been reported as having COVID-like symptoms despite repeated negative swab tests but having tested positive for SARS-CoV-2 antibodies with serological tests. We can postulate that a COVID-like syndrome is possible, in particular in hospital workers, that is characterized by symptoms similar to those of COVID-19, but with repeated negative nasopharyngeal swabs. These repeated negative NSPs make the difference in daily clinical management with people that experienced a single false negative nasopharyngeal swab; furthermore, a clear clinical differentiation of these situations is still lacking in the literature. For this reason, here, we report our main findings from a cohort of patients with a COVID-like syndrome compared to a similar group affected by typical COVID-19.
Visceral Artery Aneurysms Embolization and Other Interventional Options: State of the Art and New Perspectives
Authors: Venturini Massimo , Piacentino Filippo , Coppola Andrea , Bettoni Valeria , Macchi Edoardo , De Marchi Giuseppe , Curti Marco , Ossola Christian , Marra Paolo , Palmisano Anna , Cappelli Alberta , Basile Antonio , Golfieri Rita , Cobelli Francesco De , Piffaretti Gabriele , Tozzi Matteo , Carcano Giulio , Fontana Federico
Published: June 2021

Visceral artery aneurysms (VAAs) are rare, usually asymptomatic and incidentally discovered during a routine radiological examination. Shared guidelines suggest their treatment in the following conditions: VAAs with diameter larger than 2 cm, or 3 times exceeding the target artery; VAAs with a progressive growth of at least 0.5 cm per year; symptomatic or ruptured VAAs. Endovascular treatment, less burdened by morbidity and mortality than surgery, is generally the preferred option. Selection of the best strategy depends on the visceral artery involved, aneurysm characteristics, the clinical scenario and the operator’s experience. Tortuosity of VAAs almost always makes embolization the only technically feasible option. The present narrative review reports state of the art and new perspectives on the main endovascular and other interventional options in the treatment of VAAs. Embolization techniques and materials, use of covered and flow-diverting stents and percutaneous approaches are accurately analyzed based on the current literature. Visceral artery-related considerations and targeted approaches are also provided and discussed.
Effectiveness of Topical Anesthetics in Pain Management for Dermal Injuries: A Systematic Review
Authors: Navarro-Rodriguez Juan Manuel , Suarez-Serrano Carmen , Martin-Valero Rocio , Marcen-Roman Yolanda , de-la-Casa-Almeida Maria
Published: June 2021

The treatment of dermal injuries is associated with pain in both adult and pediatric populations. We reviewed traditional treatments for controlling the pain of these lesions, such as infiltrated local anesthetics and topical local anesthetics. The objective of this review was to elucidate the efficacy of topical anesthetics in reducing the pain of dermal injuries, as well as the efficacy of topical anesthetics versus other anesthetics, or versus a placebo. Methodology: a systematic review was carried out by searching Medline (PubMED), Scopus, Cinahl, Cochrane, Lilacs, and ENFISPO for randomized clinical trials on the control of pain in dermal lesions through the use of topical anesthetics, versus a placebo or versus another anesthetic. Results: twelve randomized clinical trials with a total of 952 patients were included. Seven studies analyzed the efficacy of topical anesthetics compared to a placebo, and six of them observed statistically significant differences in favor of the experimental group. Five studies analyzed the efficacy of topical anesthetics compared to other anesthetics or sedatives; three of them observed statistically significant differences in favor of the experimental group, and two found no difference between the anesthetics analyzed. Conclusion: topical anesthesia is a useful method for pain control, is safe compared to other traditional methods, and offers a satisfactory form of pain relief in relation to infiltration anesthesia and compared to placebo.
New Perspectives in the Antimicrobial Activity of the Amphibian Temporin B: Peptide Analogs Are Effective Inhibitors of Candida albicans Growth
Authors: Kakar Anant , Holzknecht Jeanett , Dubrac Sandrine , Gelmi Maria Luisa , Romanelli Alessandra , Marx Florentine
Published: June 2021

Temporin B (TB) is a short, positively charged peptide secreted by the granular glands of the European frog Rana temporaria. While the antibacterial and antiviral efficacy of TB and some of its improved analogs are well documented, nothing is known about their antifungal potency so far. We dedicated this study to characterize the antifungal potential of the TB analog TB_KKG6K and the newly designed D-Lys_TB_KKG6K, the latter having the L-lysines replaced by the chiral counterpart D-lysines to improve its proteolytic stability. Both peptides inhibited the growth of opportunistic human pathogenic yeasts and killed planktonic and sessile cells of the most prevalent human pathogen, Candida albicans. The anti-yeast efficacy of the peptides coincided with the induction of intracellular reactive oxygen species. Their thermal, cation, pH and serum tolerance were similar, while the proteolytic stability of D-Lys_TB_KKG6K was superior to that of its template peptide. Importantly, both peptides lacked hemolytic activity and showed minimal in vitro cytotoxicity in primary human keratinocytes. The tolerance of both peptides in a reconstructed human epidermis model further supports their potential for topical application. Our results open up an exciting field of research for new anti-Candida therapeutic options based on amphibian TB analogs.
Quantitative Analysis of Factors Influencing Spatial Distribution of Soil Erosion Based on Geo-Detector Model under Diverse Geomorphological Types
Authors: Zhao Yonghua , Liu Li , Kang Shuaizhi , Ao Yong , Han Lei , Ma Chaoqun
Published: June 2021

The Loess Plateau of China suffers from severe erosion, which results in a great variety of economic and ecological problems. For scientific control of soil erosion, the key questions urgently to be addressed in this paper are: (1) Which are the driving factors under diverse geomorphological types? (2) Do these driving factors operate independently or by interacting? (3) Which zones under diverse geomorphological types suffer from severe erosion and need more attention? In this paper, the RUSLE model was applied here to demonstrate the spatio-temporal variations in soil erosion from 2010 to 2017 in Yan’an City, and the Geo-detector model proved to be a useful tool to solve the questions mentioned above. The results showed that the average erosion modulus in Yan’an City decreased by 1927.36 t/km2·a from 2010 to 2017. The intensity of soil erosion in the northern Baota District, central Ganquan County, Luochuan County, Ansai County, and Zhidan County decreased to varying degrees. The effect size of driving factors affecting soil erosion varied significantly in diverse geomorphological types. The effect size of interaction between land-use types and vegetation coverage, land-use types and slope, slope and precipitation was higher than that of a single factor. High-risk zones with severe erosion were closer to cultivated land and forest land with steep slopes (>25°) in the mid-elevation hills of Yan’an City. Additionally, based on the specificity of the study area, the Geo-detector model performed better in a relatively flat region, and factors with macroscopic spatial distributions weaken its explanatory power on soil erosion on a regional scale. Based on data selection, data of different accuracy sparked the issue of “data coupling”, which led to the enormous deviation of model results in mid-elevation plains. Results from our analysis provide insights for a more ecologically sound development of Yan’an City and provide references for the scientific use of the Geo-detector model.
Selection of Independent Variables for Crop Yield Prediction Using Artificial Neural Network Models with Remote Sensing Data
Authors: Hara Patryk , Piekutowska Magdalena , Niedbała Gniewko
Published: June 2021

Knowing the expected crop yield in the current growing season provides valuable information for farmers, policy makers, and food processing plants. One of the main benefits of using reliable forecasting tools is generating more income from grown crops. Information on the amount of crop yielding before harvesting helps to guide the adoption of an appropriate strategy for managing agricultural products. The difficulty in creating forecasting models is related to the appropriate selection of independent variables. Their proper selection requires a perfect knowledge of the research object. The following article presents and discusses the most commonly used independent variables in agricultural crop yield prediction modeling based on artificial neural networks (ANNs). Particular attention is paid to environmental variables, such as climatic data, air temperature, total precipitation, insolation, and soil parameters. The possibility of using plant productivity indices and vegetation indices, which are valuable predictors obtained due to the application of remote sensing techniques, are analyzed in detail. The paper emphasizes that the increasingly common use of remote sensing and photogrammetric tools enables the development of precision agriculture. In addition, some limitations in the application of certain input variables are specified, as well as further possibilities for the development of non-linear modeling, using artificial neural networks as a tool supporting the practical use of and improvement in precision farming techniques.
“No Entry into New South Wales”: COVID-19 and the Historic and Contemporary Trajectories of the Effects of Border Closures on an Australian Cross-Border Community
Authors: Spennemann Dirk H. R.
Published: June 2021

Given its intensity, rapid spread, geographic reach and multiple waves of infections, the COVID-19 pandemic of 2020/21 became a major global disruptor with a truly cross-sectoral impact, surpassing even the 1918/19 influenza epidemic. Public health measures designed to contain the spread of the disease saw the cessation of international travel as well as the establishment of border closures between and within countries. The social and economic impact was considerable. This paper examines the effects of the public health measures of “ring-fencing” and of prolonged closures of the state border between New South Wales and Victoria (Australia), placing the events of 2020/21 into the context of the historic and contemporary trajectories of the border between the two states. It shows that while border closures as public-health measures had occurred in the past, their social and economic impact had been comparatively negligible due to low cross-border community integration. Concerted efforts since the mid-1970s have led to effective and close integration of employment and services, with over a quarter of the resident population of the two border towns commuting daily across the state lines. As a result, border closures and state-based lockdown directives caused significant social disruption and considerable economic cost to families and the community as a whole. One of the lessons of the 2020/21 pandemic will be to either re-evaluate the wisdom of a close social and economic integration of border communities, which would be a backwards step, or to future-proof these communities by developing strategies, effectively public health management plans, to avoid a repeat when the next pandemic strikes.