bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of the Coordination between Healthcare and Educational Personnel on the Health and Inclusion of Children and Adolescents with Rare Diseases
Authors: Verger Sebastià , Negre Francisca , Fernández-Hawrylak María , Paz-Lourido Berta
Published: June 2021

Rare diseases produce multiple impacts for the people who suffer from them, but they also have repercussions for their families, education and healthcare. The objective of this study is to analyze the coordination between healthcare and education professionals who intervene with children and adolescents with rare diseases. It is a qualitative study designed with a critical paradigm, and it was carried out through focus group discussions. A total of 50 people participated in the study, including healthcare professionals, teachers and families. The results suggest that poor communication and coordination negatively impact minors with rare diseases, placing an extra burden on their families, who take on an intermediary role in communication. Participants in the study recognized coordination as an area for improvement as it can compromise equitable social and health services and inclusive education. Other measures must also be put into action at the public administration level not only to establish protocols for intersectoral coordination, but also to increase the knowledge and awareness of staff involved in health and education interventions for children with rare diseases.
A Spatially Highly Resolved Ground Mounted and Rooftop Potential Analysis for Photovoltaics in Austria
Authors: Mikovits Christian , Schauppenlehner Thomas , Scherhaufer Patrick , Schmidt Johannes , Schmalzl Lilia , Dworzak Veronika , Hampl Nina , Sposato Robert Gennaro
Published: June 2021

Austria aims to meet 100% of its electricity demand from domestic renewable sources by 2030 which means, that an additional 27 TWh/a of renewable electricity generation are required, thereof 11 TWh/a from photovoltaic. While some federal states and municipalities released a solar rooftop cadastre, there is lacking knowledge on the estimation of the potential of both, ground mounted installations and rooftop modules, on a national level with a high spatial resolution. As a first, in this work data on agricultural land-use is combined with highly resolved data on buildings on a national level. Our results show significant differences between urban and rural areas, as well as between the Alpine regions and the Prealpine- and Easter Plain areas. Rooftop potential concentrates in the big urban areas, but also in densely populated areas in Lower- and Upper Austria, Styria and the Rhine valley of Vorarlberg. The ground mounted photovoltaic potential is highest in Eastern Austria. This potential is geographically consistent with the demand and allows for a production close to the consumer. In theory, the goal of meeting 11 TWh/a in 2030 can be achieved solely with the rooftop PV potential. However, considering the necessary installation efforts, the associated costs of small and dispersed production units and finally the inherent uncertainty with respect to the willingness of tens of thousands of individual households to install PV systems, installing the necessary solar PV on buildings alone is constrained.
Atorvastatin Modulates Bile Acid Homeostasis in Mice with Diet-Induced Nonalcoholic Steatohepatitis
Authors: Lastuvkova Hana , Faradonbeh Fatemeh Alaei , Schreiberova Jolana , Hroch Milos , Mokry Jaroslav , Faistova Hana , Nova Zuzana , Hyspler Radomír , Igreja Sa Ivone Cristina , Nachtigal Petr , Stefela Alzbeta , Pavek Petr , Micuda Stanislav
Published: June 2021

Bile acids (BA) play a significant role in the pathophysiology of nonalcoholic steatohepatitis (NASH). The present study evaluates the modulation of bile acid metabolomics by atorvastatin, a cholesterol-lowering agent commonly used to treat cardiovascular complications accompanying NASH. NASH was induced in mice by 24 weeks of consuming a high–saturated fat, high-fructose, and high-cholesterol diet (F), with atorvastatin administered orally (20 mg/kg/day) during the last three weeks. Biochemical and histological analyses confirmed the effectiveness of the F diet in inducing NASH. Untreated NASH animals had significantly reduced biliary secretion of BA and increased fecal excretion of BA via decreased apical sodium-dependent bile salt transporter (Asbt)-mediated reabsorption. Atorvastatin decreased liver steatosis and inflammation in NASH animals consistently with a reduction in crucial lipogenic enzyme stearoyl–coenzyme A (CoA) desaturase-1 and nuclear factor kappa light chain enhancer of activated B-cell pro-inflammatory signaling, respectively. In this group, atorvastatin also uniformly enhanced plasma concentration, biliary secretion and fecal excretion of the secondary BA, deoxycholic acid (DCA). However, in the chow diet–fed animals, atorvastatin decreased plasma concentrations of BA, and reduced BA biliary secretions. These changes stemmed primarily from the increased fecal excretion of BA resulting from the reduced Asbt-mediated BA reabsorption in the ileum and suppression of synthesis in the liver. In conclusion, our results reveal that atorvastatin significantly modulates BA metabolomics by altering their intestinal processing and liver synthesis in control and NASH mice.
Inhibition of P2X7 Purinergic Receptor Ameliorates Fibromyalgia Syndrome by Suppressing NLRP3 Pathway
Authors: D’Amico Ramona , Fusco Roberta , Siracusa Rosalba , Impellizzeri Daniela , Peritore Alessio Filippo , Gugliandolo Enrico , Interdonato Livia , Sforza Andrea Maria , Crupi Rosalia , Cuzzocrea Salvatore , Genovese Tiziana , Cordaro Marika , Di Paola Rosanna
Published: June 2021

Fibromyalgia is a chronic condition characterized by persistent widespread pain that significantly reduces quality of life in patients. The purinergic P2X7 receptor (P2X7R) seems to be involved in different pain states and neuroinflammation. The purpose of this study is to investigate the positive effects of P2X7R inhibition by the antagonist Brilliant Blue G (BBG) in a rat model of reserpine-induced fibromyalgia. Sprague–Dawley male rats were injected with 1 mg/kg of reserpine for three consecutive days. Later, animals were administered BBG (50 mg/kg) intraperitoneally for seven days. Reserpine injections induced a significant increase in pain pro-inflammatory mediators as well as a significant increase in neuroinflammation. Chronic pain, in turn, led to depressive-like symptoms and reduced neurogenesis. Blockage of P2X7R by BBG administrations is able to attenuate the behavioral deficits, pain mediators and microglial activation induced by reserpine injection. Additionally, BBG prevents NLRP3 inflammasome activation and consequently the release of active interleukin (IL)-1 and IL-18, involved in the activation of nociceptors. In conclusion, these results suggest that inhibition of P2X7R should be further investigated to develop a potential approach for the management of fibromyalgia.
Exploring the Interaction of Curaxin CBL0137 with G-Quadruplex DNA Oligomers
Authors: Dallavalle Sabrina , Mattio Luce M. , Artali Roberto , Musso Loana , Aviñó Anna , Fàbrega Carme , Eritja Ramon , Gargallo Raimundo , Mazzini Stefania
Published: June 2021

Curaxins and especially the second-generation derivative curaxin CBL0137 have important antitumor activities in multiple cancers such as glioblastoma, melanoma and others. Although most of the authors suggest that their mechanism of action comes from the activation of p53 and inactivation of NF-kB by targeting FACT, there is evidence supporting the involvement of DNA binding in their antitumor activity. In this work, the DNA binding properties of curaxin CBL0137 with model quadruplex DNA oligomers were studied by 1H NMR, CD, fluorescence and molecular modeling. We provided molecular details of the interaction of curaxin with two G-quadruplex structures, the single repeat of human telomere d(TTAGGGT)4 and the c-myc promoter Pu22 sequence. We also performed 1H and 31P NMR experiments were also performed in order to investigate the interaction with duplex DNA models. Our data support the hypothesis that the interaction of curaxin with G-quadruplex may provide a novel insight into the DNA-binding properties of CBL0137, and it will be helpful for the design of novel selective DNA-targeting curaxin analogues.
Nonalcoholic Fatty Liver Disease (NAFLD) as Model of Gut–Liver Axis Interaction: From Pathophysiology to Potential Target of Treatment for Personalized Therapy
Authors: Fianchi Francesca , Liguori Antonio , Gasbarrini Antonio , Grieco Antonio , Miele Luca
Published: June 2021

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide, affecting both adults and children and will result, in the near future, as the leading cause of end-stage liver disease. Indeed, its prevalence is rapidly increasing, and NAFLD is becoming a major public health concern. For this reason, great efforts are needed to identify its pathogenetic factors and new therapeutic approaches. In the past decade, enormous advances understanding the gut–liver axis―the complex network of cross-talking between the gut, microbiome and liver through the portal circulation―have elucidated its role as one of the main actors in the pathogenesis of NAFLD. Indeed, evidence shows that gut microbiota is involved in the development and progression of liver steatosis, inflammation and fibrosis seen in the context of NAFLD, as well as in the process of hepatocarcinogenesis. As a result, gut microbiota is currently emerging as a non-invasive biomarker for the diagnosis of disease and for the assessment of its severity. Additionally, to its enormous diagnostic potential, gut microbiota is currently studied as a therapeutic target in NAFLD: several different approaches targeting the gut homeostasis such as antibiotics, prebiotics, probiotics, symbiotics, adsorbents, bariatric surgery and fecal microbiota transplantation are emerging as promising therapeutic options.
New Structural Perspectives in G Protein-Coupled Receptor-Mediated Src Family Kinase Activation
Authors: Berndt Sandra , Liebscher Ines
Published: June 2021

Src family kinases (SFKs) are key regulators of cell proliferation, differentiation, and survival. The expression of these non-receptor tyrosine kinases is strongly correlated with cancer development and tumor progression. Thus, this family of proteins serves as an attractive drug target. The activation of SFKs can occur via multiple signaling pathways, yet many of them are poorly understood. Here, we summarize the current knowledge on G protein-coupled receptor (GPCR)-mediated regulation of SFKs, which is of considerable interest because GPCRs are among the most widely used pharmaceutical targets. This type of activation can occur through a direct interaction between the two proteins or be allosterically regulated by arrestins and G proteins. We postulate that a rearrangement of binding motifs within the active conformation of arrestin-3 mediates Src regulation by comparison of available crystal structures. Therefore, we hypothesize a potentially different activation mechanism compared to arrestin-2. Furthermore, we discuss the probable direct regulation of SFK by GPCRs and investigate the intracellular domains of exemplary GPCRs with conserved polyproline binding motifs that might serve as scaffolding domains to allow such a direct interaction. Large intracellular domains in GPCRs are often understudied and, in general, not much is known of their contribution to different signaling pathways. The suggested direct interaction between a GPCR and a SFK could allow for a potential immediate allosteric regulation of SFKs by GPCRs and thereby unravel a novel mechanism of SFK signaling. This overview will help to identify new GPCR–SFK interactions, which could serve to explain biological functions or be used to modulate downstream effectors.
The Functional Consequences of the Novel Ribosomal Pausing Site in SARS-CoV-2 Spike Glycoprotein RNA
Authors: Postnikova Olga A. , Uppal Sheetal , Huang Weiliang , Kane Maureen A. , Villasmil Rafael , Rogozin Igor B. , Poliakov Eugenia , Redmond T. Michael
Published: June 2021

The SARS-CoV-2 Spike glycoprotein (S protein) acquired a unique new 4 amino acid -PRRA- insertion sequence at amino acid residues (aa) 681–684 that forms a new furin cleavage site in S protein as well as several new glycosylation sites. We studied various statistical properties of the -PRRA- insertion at the RNA level (CCUCGGCGGGCA). The nucleotide composition and codon usage of this sequence are different from the rest of the SARS-CoV-2 genome. One of such features is two tandem CGG codons, although the CGG codon is the rarest codon in the SARS-CoV-2 genome. This suggests that the insertion sequence could cause ribosome pausing as the result of these rare codons. Due to population variants, the Nextstrain divergence measure of the CCU codon is extremely large. We cannot exclude that this divergence might affect host immune responses/effectiveness of SARS-CoV-2 vaccines, possibilities awaiting further investigation. Our experimental studies show that the expression level of original RNA sequence “wildtype” spike protein is much lower than for codon-optimized spike protein in all studied cell lines. Interestingly, the original spike sequence produces a higher titer of pseudoviral particles and a higher level of infection. Further mutagenesis experiments suggest that this dual-effect insert, comprised of a combination of overlapping translation pausing and furin sites, has allowed SARS-CoV-2 to infect its new host (human) more readily. This underlines the importance of ribosome pausing to allow efficient regulation of protein expression and also of cotranslational subdomain folding.
The Role of Sphingolipids in Cancer Immunotherapy
Authors: Giussani Paola , Prinetti Alessandro , Tringali Cristina
Published: June 2021

Immunotherapy is now considered an innovative and strong strategy to beat metastatic, drug-resistant, or relapsing tumours. It is based on the manipulation of several mechanisms involved in the complex interplay between cancer cells and immune system that culminates in a form of immune-tolerance of tumour cells, favouring their expansion. Current immunotherapies are devoted enforcing the immune response against cancer cells and are represented by approaches employing vaccines, monoclonal antibodies, interleukins, checkpoint inhibitors, and chimeric antigen receptor (CAR)-T cells. Despite the undoubted potency of these treatments in some malignancies, many issues are being investigated to amplify the potential of application and to avoid side effects. In this review, we discuss how sphingolipids are involved in interactions between cancer cells and the immune system and how knowledge in this topic could be employed to enhance the efficacy of different immunotherapy approaches. In particular, we explore the following aspects: how sphingolipids are pivotal components of plasma membranes and could modulate the functionality of surface receptors expressed also by immune cells and thus their functionality; how sphingolipids are related to the release of bioactive mediators, sphingosine 1-phosphate, and ceramide that could significantly affect lymphocyte egress and migration toward the tumour milieu, in addition regulating key pathways needed to activate immune cells; given the renowned capability of altering sphingolipid expression and metabolism shown by cancer cells, how it is possible to employ sphingolipids as antigen targets.
Cardiac Biomarkers and Autoantibodies in Endurance Athletes: Potential Similarities with Arrhythmogenic Cardiomyopathy Pathogenic Mechanisms
Authors: Stadiotti Ilaria , Lippi Melania , Maione Angela Serena , Compagnucci Paolo , Andreini Daniele , Casella Michela , Pompilio Giulio , Sommariva Elena
Published: June 2021

The “Extreme Exercise Hypothesis” states that when individuals perform training beyond the ideal exercise dose, a decline in the beneficial effects of physical activity occurs. This is due to significant changes in myocardial structure and function, such as hemodynamic alterations, cardiac chamber enlargement and hypertrophy, myocardial inflammation, oxidative stress, fibrosis, and conduction changes. In addition, an increased amount of circulating biomarkers of exercise-induced damage has been reported. Although these changes are often reversible, long-lasting cardiac damage may develop after years of intense physical exercise. Since several features of the athlete’s heart overlap with arrhythmogenic cardiomyopathy (ACM), the syndrome of “exercise-induced ACM” has been postulated. Thus, the distinction between ACM and the athlete’s heart may be challenging. Recently, an autoimmune mechanism has been discovered in ACM patients linked to their characteristic junctional impairment. Since cardiac junctions are similarly impaired by intense physical activity due to the strong myocardial stretching, we propose in the present work the novel hypothesis of an autoimmune response in endurance athletes. This investigation may deepen the knowledge about the pathological remodeling and relative activated mechanisms induced by intense endurance exercise, potentially improving the early recognition of whom is actually at risk.
MUC16 Is Overexpressed in Idiopathic Pulmonary Fibrosis and Induces Fibrotic Responses Mediated by Transforming Growth Factor-β1 Canonical Pathway
Authors: Ballester Beatriz , Milara Javier , Montero Paula , Cortijo Julio
Published: June 2021

Several transmembrane mucins have demonstrated that they contribute intracellularly to induce fibrotic processes. The extracellular domain of MUC16 is considered as a biomarker for disease progression and death in IPF patients. However, there is no evidence regarding the signalling capabilities of MUC16 that contribute to IPF development. Here, we demonstrate that MUC16 was overexpressed in the lung tissue of IPF patients (n = 20) compared with healthy subjects (n = 17) and localised in fibroblasts and hyperplastic alveolar type II cells. Repression of MUC16 expression by siRNA-MUC16 transfection inhibited the TGF-β1-induced fibrotic processes such as mesenchymal/ myofibroblast transformations of alveolar type II A549 cells and lung fibroblasts, as well as fibroblast proliferation. SiRNA-MUC16 transfection also decreased the TGF-β1-induced SMAD3 phosphorylation, thus inhibiting the Smad Binding Element activation. Immunoprecipitation assays and confocal immunofluorescence showed the formation of a protein complex between MUC16/p-SMAD3 in the cell membrane after TGF-β1 stimulation. This study shows that MUC16 is overexpressed in IPF and collaborates with the TGF-β1 canonical pathway to induce fibrotic processes. Therefore, direct or indirect targeting of MUC16 could be a potential drug target for human IPF.
Ras Isoforms from Lab Benches to Lives—What Are We Missing and How Far Are We?
Authors: Nair Arathi , Kubatzky Katharina F. , Saha Bhaskar
Published: June 2021

The central protein in the oncogenic circuitry is the Ras GTPase that has been under intense scrutiny for the last four decades. From its discovery as a viral oncogene and its non-oncogenic contribution to crucial cellular functioning, an elaborate genetic, structural, and functional map of Ras is being created for its therapeutic targeting. Despite decades of research, there still exist lacunae in our understanding of Ras. The complexity of the Ras functioning is further exemplified by the fact that the three canonical Ras genes encode for four protein isoforms (H-Ras, K-Ras4A, K-Ras4B, and N-Ras). Contrary to the initial assessment that the H-, K-, and N-Ras isoforms are functionally similar, emerging data are uncovering crucial differences between them. These Ras isoforms exhibit not only cell-type and context-dependent functions but also activator and effector specificities on activation by the same receptor. Preferential localization of H-, K-, and N-Ras in different microdomains of the plasma membrane and cellular organelles like Golgi, endoplasmic reticulum, mitochondria, and endosome adds a new dimension to isoform-specific signaling and diverse functions. Herein, we review isoform-specific properties of Ras GTPase and highlight the importance of considering these towards generating effective isoform-specific therapies in the future.
Ergosta-7, 9 (11), 22-trien-3β-ol Interferes with LPS Docking to LBP, CD14, and TLR4/MD-2 Co-Receptors to Attenuate the NF-κB Inflammatory Pathway In Vitro and Drosophila
Authors: Hsieh Wen-Tsong , Hsu Min-Hsien , Lin Wen-Jen , Xiao Yi-Cheng , Lyu Ping-Chiang , Liu Yi-Chung , Lin Wei-Yong , Kuo Yueh-Hsiung , Chung Jing-Gung
Published: June 2021

Ergosta-7, 9 (11), 22-trien-3β-ol (EK100) was isolated from Cordyceps militaris, which has been used as a traditional anti-inflammatory medicine. EK100 has been reported to attenuate inflammatory diseases, but its anti-inflammatory mechanism is still unclear. We were the first to investigate the effect of EK100 on the Toll-like receptor 4 (TLR4)/nuclear factor of the κ light chain enhancer of B cells (NF-κB) signaling in the lipopolysaccharide (LPS)-stimulated RAW264.7 cells and the green fluorescent protein (GFP)-labeled NF-κB reporter gene of Drosophila. EK100 suppressed the release of the cytokine and attenuated the mRNA and protein expression of pro-inflammatory mediators. EK100 inhibited the inhibitor kappa B (IκB)/NF-κB signaling pathway. EK100 also inhibited phosphatidylinositol-3-kinase (PI3K)/Protein kinase B (Akt) signal transduction. Moreover, EK100 interfered with LPS docking to the LPS-binding protein (LBP), transferred to the cluster of differentiation 14 (CD14), and bonded to TLR4/myeloid differentiation-2 (MD-2) co-receptors. Compared with the TLR4 antagonist, resatorvid (CLI-095), and dexamethasone (Dexa), EK100 suppressed the TLR4/AKT signaling pathway. In addition, we also confirmed that EK100 attenuated the GFP-labeled NF-κB reporter gene expression in Drosophila. In summary, EK100 might alter LPS docking to LBP, CD14, and TLR4/MD-2 co-receptors, and then it suppresses the TLR4/NF-κB inflammatory pathway in LPS-stimulated RAW264.7 cells and Drosophila.
Free Radicals and ROS Induce Protein Denaturation by UV Photostability Assay
Authors: Ruzza Paolo , Honisch Claudia , Hussain Rohanah , Siligardi Giuliano
Published: June 2021

Oxidative stress, photo-oxidation, and photosensitizers are activated by UV irradiation and are affecting the photo-stability of proteins. Understanding the mechanisms that govern protein photo-stability is essential for its control enabling enhancement or reduction. Currently, two major mechanisms for protein denaturation induced by UV irradiation are available: one generated by the local heating of water molecules bound to the proteins and the other by the formation of reactive free radicals. To discriminate which is the likely or dominant mechanism we have studied the effects of thermal and UV denaturation of aqueous protein solutions with and without DHR-123 as fluorogenic probe using circular dichroism (CD), synchrotron radiation circular dichroism (SRCD), and fluorescence spectroscopies. The results indicated that the mechanism of protein denaturation induced by VUV and far-UV irradiation were mediated by the formation of reactive free radicals (FR) and reactive oxygen species (ROS). The development at Diamond B23 beamline for SRCD of a novel protein UV photo-stability assay based on consecutive repeated CD measurements in the far-UV (180–250 nm) region has been successfully used to assess and characterize the photo-stability of protein formulations and ligand binding interactions, in particular for ligand molecules devoid of significant UV absorption.
The Role of Processed Aloe vera Gel in Intestinal Tight Junction: An In Vivo and In Vitro Study
Authors: Le Phan Thu Han , Park Se Yong , Jung Hyun Jin , Kim Min Woo , Cho Eunae , Shim Kyu-Suk , Shin Eunju , Yoon Jin-Ha , Maeng Han-Joo , Kang Ju-Hee , Oh Seung Hyun
Published: June 2021

Leaky gut is a condition of increased paracellular permeability of the intestine due to compromised tight junction barriers. In recent years, this affliction has drawn the attention of scientists from different fields, as a myriad of studies prosecuted it to be the silent culprit of various immune diseases. Due to various controversies surrounding its culpability in the clinic, approaches to leaky gut are restricted in maintaining a healthy lifestyle, avoiding irritating factors, and practicing alternative medicine, including the consumption of supplements. In the current study, we investigate the tight junction-modulating effects of processed Aloe vera gel (PAG), comprising 5–400-kD polysaccharides as the main components. Our results show that oral treatment of 143 mg/kg PAG daily for 10 days improves the age-related leaky gut condition in old mice, by reducing their individual urinal lactulose/mannitol (L/M) ratio. In concordance with in vivo experiments, PAG treatment at dose 400 μg/mL accelerated the polarization process of Caco-2 monolayers. The underlying mechanism was attributed to enhancement in the expression of intestinal tight junction-associated scaffold protein zonula occludens (ZO)-1 at the translation level. This was induced by activation of the MAPK/ERK signaling pathway, which inhibits the translation repressor 4E-BP1. In conclusion, we propose that consuming PAG as a complementary food has the potential to benefit high-risk patients.
The Impact of Chronic Heart Failure on Retinal Vessel Density Assessed by Optical Coherence Tomography Angiography in Children with Dilated Cardiomyopathy
Authors: Rakusiewicz Klaudia , Kanigowska Krystyna , Hautz Wojciech , Ziółkowska Lidia
Published: June 2021

(1) Introduction: The aim of this study is to assess retinal vessel density (VD) in the superficial capillary plexus layer (SP) and deep capillary plexus layer (DP) in children with chronic heart failure (CHF) in the course of dilated cardiomyopathy (DCM) using optical coherence tomography angiography (OCTA). (2) Methods: Thirty children with CHF due to DCM lasting more than six months, with an enlarged left ventricle and impaired left ventricular systolic function (left ventricular ejection fraction (LVEF) ≤ 55%), were enrolled to have both their eyes assessed for this study. Mean age of the children was 9.9 ± 3.57 years. The control group consisted of an additional 30 children without CHF (mean age 11.27 ± 3.33 years) matched for age and gender against the study group. All participants underwent transthoracic echocardiography to measure LVEF using Simpson method. Blood serum was tested for N-terminal-pro-brain natriuretic peptide (NT-proBNP) marker value. All children underwent OCTA with evaluation of the foveal avascular zone (FAZ), whole superficial vessel density (wsVD), foveal superficial vessel density (fsVD), parafoveal superficial vessel density (psVD), whole deep vessel density (wdVD), foveal deep vessel density (fdVD), parafoveal deep vessel density (pdVD), whole thickness (WT), foveal thickness (FT), and parafoveal thickness (PFT). (3) Results: Retinal VD in SP was significantly lower in children with CHF as compared to the controls. The following SP parameters in the study group were statistically significantly lower than these same measurements for the control group. Details, with study group findings quantified first, include wsVD (46.2% vs. 49.83%, p < 0.05), fsVD (18.07% vs. 24.15%, p < 0.05), and psVD (49.24% vs. 52.51%, p < 0.05). The WT (311.03 micrometers (μm) vs. 323.55 μm, p < 0.05), FT (244.57 μm vs. 256.98 μm, p < 0.05), and PFT (320.63 μm vs. 332.02 μm, p < 0.05). No significant differences in DP retinal VD were found between the two groups. No statistically significant differences in the FAZ were found. The fsVD and FT were correlated with biometry and the age of the study participants. There was a correlation between FAZ and FT (p < 0.001). There were no correlations between retinal VD in both plexuses and refractive error, sex, NT-proBNP, and LVEF. (4) Conclusions: In children with CHF in the course of DCM as compared to the control group, significantly decreased retinal VD in SP was observed. The results of our study indicate that measurements of the OCTA may be a useful diagnostic method in children with chronic heart failure, but it is necessary to conduct further studies in larger groups of participants and long-term observation of these patients.
Endocarditis in Liver Transplant Recipients: A Systematic Review
Authors: Ioannou Petros , Alexakis Konstantinos , Kofteridis Diamantis P
Published: June 2021

Infective Endocarditis (IE) is associated with significant mortality. Interestingly, IE in patients with liver transplantation has not been adequately described. The aim of this review was to systematically review all published cases of IE in liver transplant recipients and describe their epidemiology, microbiology, clinical characteristics, treatment and outcomes. A systematic review of PubMed, Scopus and Cochrane Library (through 2 January 2021) for studies providing epidemiological, clinical, microbiological, treatment data and outcomes of IE in liver transplant recipients was conducted. A total of 39 studies, containing data for 62 patients, were included in the analysis. The most common causative pathogens were gram-positive microorganisms in 69.4%, fungi in 25.8%, and gram-negative microorganisms in 9.7% of cases, while in 9.3% IE was culture-negative. The aortic valve was the most commonly infected valve followed by mitral, tricuspid and the pulmonary valve. Aminoglycosides, vancomycin and aminopenicillins were the most commonly used antimicrobials, and surgical management was performed in half of the cases. Clinical cure was noted in 57.4%, while overall mortality was 43.5%. To conclude, this systematic review thoroughly describes IE in liver transplant recipients and provides information on epidemiology, clinical presentation, treatment and outcomes.
A Double-Blind Crossover RCT Analyzing Technical and Clinical Performance of Monolithic ZrO2 Implant Fixed Dental Prostheses (iFDP) in Three Different Digital Workflows
Authors: Gintaute Aiste , Weber Karin , Zitzmann Nicola U. , Brägger Urs , Ferrari Marco , Joda Tim
Published: June 2021

This double-blind randomized controlled trial with a crossover design analyzed the technical and clinical performance of three-unit monolithic ZrO2 implant-fixed dental prostheses (iFDPs), prepared using two complete digital workflows (Test-1, Test-2) and one mixed analog–digital workflow (Control). Each of the 20 study patients received three iFDPs, resulting in 60 restorations for analysis. The quality of the restorations was assessed by analyzing laboratory cross-mounting and calculating the chairside adjustment time required during fitting. All iFDPs could be produced successfully with all three workflows. The highest cross-mounting success rate was observed for the original pairing iFDP/model of the Control group. Overall, 60% of iFDPs prepared with Test-1 workflow did not require chairside adjustment compared with 50% for Test-2 and 30% for Controls. The mean total chairside adjustment time, as the sum of interproximal, pontic, and occlusal corrections was 2.59 ± 2.51 min (Control), 2.88 ± 2.86 min (Test-1), and 3.87 ± 3.02 min (Test-2). All tested workflows were feasible for treatment with iFDPs in posterior sites on a soft tissue level type implant system. For clinical routine, it has to be considered that chairside adjustments may be necessary, at least in every second patient, independent on the workflow used.
Retrospective Monocentric Clinical Study on Male Infertility: Comparison between Two Different Therapeutic Schemes Using Follicle-Stimulating Hormone
Authors: Condorelli Rosita A. , Cannarella Rossella , Crafa Andrea , Barbagallo Federica , Mongioì Laura M. , Aversa Antonio , Greco Emanuela , Calogero Aldo E. , La Vignera Sandro
Published: June 2021

Follicle-stimulating hormone (FSH) is a therapeutic option in patients with idiopathic oligozoospermia and normal FSH serum levels. However, few studies have evaluated which dose of FSH is more effective. The aim of this study was to compare the clinical efficacy of the two most frequently used FSH treatment regimens: 75 IU daily vs. 150 IU three times a week. Patients were retrospectively assigned to two groups. The first group (n = 24) was prescribed highly purified FSH (hpFSH) 75 IU/daily (Group A), and the second group (n = 24) was prescribed hpFSH 150 IU three times a week (Group B) for three months. Before and after treatment, each patient underwent semen analysis, evaluation of the percentage of DNA-fragmented spermatozoa, assessment of testicular volume (by ultrasonography), and measurement of FSH and total testosterone (TT) serum levels. Treatment with hpFSH significantly improved conventional sperm parameters. In detail, sperm concentration increased significantly after treatment only in Group A, whereas total sperm count, percentage of spermatozoa with progressive motility, normal morphology, or alive improved significantly in both groups. Interestingly, the percentage of sperm DNA fragmentation decreased significantly in both groups after treatment with hpFSH. FSH serum levels were expectably higher at the end of the treatment than before hpFSH was administered to both groups. Remarkably, TT serum levels only increased significantly in Group A. Finally, testicular volume was significantly higher in Group A after treatment, while it did not change significantly compared to baseline in Group B. The percentage of FSH responders did not differ significantly between the two groups (8/24 vs. 6/24). The daily administration of hpFSH 75 IU seems more effective than using 150 IU three times a week. However, this therapeutic scheme implies a higher number of injections and slightly higher costs.
Twenty Years of GH Treatment in Adults with Prader-Willi Syndrome
Authors: Sjöström Anna , Höybye Charlotte
Published: June 2021

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder. In adults, the syndrome is characterised by muscular hypotonia, a different body composition with more body fat than muscle mass, hyperphagia, behavioural problems, and cognitive dysfunction. Endocrine deficiencies are common, including growth hormone (GH) deficiency. Here, we present data from a cross-sectional study in adults with PWS with a focus on the long-term safety of GH treatment. A total of 22 patients (14 men) were treated with GH for a median of 20 years. Data on body composition, hormones, and metabolic parameters were retrieved from the patients’ medical records. The median age was 27 years. The median GH dose was 0.5 mg/day. Insulin-like growth factor 1 (IGF-I) and blood lipids were normal, while fasting glucose and HbA1c were slightly elevated in three men with diabetes. Fat mass was less than fat free mass in all, though this was less pronounced in women. GH treatment did not negatively affect the metabolic profile, and none developed cardiovascular diseases or cancer. All adults on long-term GH treatment had a normal body composition and our results indicate that treatment was safe. However, PWS is a complex, multisystemic disease and continuous, individual considerations are required during GH treatment, especially in patients with risk factors for adverse effects.
Areas of Interest and Attitudes towards the Pharmacological Treatment of Attention Deficit Hyperactivity Disorder: Thematic and Quantitative Analysis Using Twitter
Authors: Alvarez-Mon Miguel Angel , de Anta Laura , Llavero-Valero Maria , Lahera Guillermo , Ortega Miguel A. , Soutullo Cesar , Quintero Javier , Asunsolo del Barco Angel , Alvarez-Mon Melchor
Published: June 2021

We focused on tweets containing hashtags related to ADHD pharmacotherapy between 20 September and 31 October 2019. Tweets were classified as to whether they described medical issues or not. Tweets with medical content were classified according to the topic they referred to: side effects, efficacy, or adherence. Furthermore, we classified any links included within a tweet as either scientific or non-scientific. We created a dataset of 6568 tweets: 4949 (75.4%) related to stimulants, 605 (9.2%) to non-stimulants and 1014 (15.4%) to alpha-2 agonists. Next, we manually analyzed 1810 tweets. In the end, 481 (48%) of the tweets in the stimulant group, 218 (71.9%) in the non-stimulant group and 162 (31.9%) in the alpha agonist group were considered classifiable. Stimulants accumulated the majority of tweets. Notably, the content that generated the highest frequency of tweets was that related to treatment efficacy, with alpha-2 agonist-related tweets accumulating the highest proportion of positive consideration. We found the highest percentages of tweets with scientific links in those posts related to alpha-2 agonists. Stimulant-related tweets obtained the highest proportion of likes and were the most disseminated within the Twitter community. Understanding the public view of these medications is necessary to design promotional strategies aimed at the appropriate population.
Serum Amyloid Beta42 Is Not Eliminated by the Cirrhotic Liver: A Pilot Study
Authors: Wiest Reiner , Weiss Thomas S. , Danielyan Lusine , Buechler Christa
Published: June 2021

Amyloid-beta (Aβ) deposition in the brain is the main pathological hallmark of Alzheimer disease. Peripheral clearance of Aβ may possibly also lower brain levels. Recent evidence suggested that hepatic clearance of Aβ42 is impaired in liver cirrhosis. To further test this hypothesis, serum Aβ42 was measured by ELISA in portal venous serum (PVS), systemic venous serum (SVS), and hepatic venous serum (HVS) of 20 patients with liver cirrhosis. Mean Aβ42 level was 24.7 ± 20.4 pg/mL in PVS, 21.2 ± 16.7 pg/mL in HVS, and 19.2 ± 11.7 pg/mL in SVS. Similar levels in the three blood compartments suggested that the cirrhotic liver does not clear Aβ42. Aβ42 was neither associated with the model of end-stage liver disease score nor the Child–Pugh score. Patients with abnormal creatinine or bilirubin levels or prolonged prothrombin time did not display higher Aβ42 levels. Patients with massive ascites and patients with large varices had serum Aβ42 levels similar to patients without these complications. Serum Aβ42 was negatively associated with connective tissue growth factor levels (r = −0.580, p = 0.007) and a protective role of Aβ42 in fibrogenesis was already described. Diabetic patients with liver cirrhosis had higher Aβ42 levels (p = 0.069 for PVS, p = 0.047 for HVS and p = 0.181 for SVS), which is in accordance with previous reports. Present analysis showed that the cirrhotic liver does not eliminate Aβ42. Further studies are needed to explore the association of liver cirrhosis, Aβ42 levels, and cognitive dysfunction.
Eotaxins and Their Receptor as Biomarkers of Colorectal Cancer
Authors: Zajkowska Monika , Kulczyńska-Przybik Agnieszka , Dulewicz Maciej , Safiejko Kamil , Juchimiuk Marcin , Konopko Marzena , Kozłowski Leszek , Mroczko Barbara
Published: June 2021

Colorectal cancer (CRC) is one of the most common malignancies. Despite the availability of diagnostic tests, an increasing number of new cases is observed. That is why it is very important to search new markers that would show high diagnostic utility. Therefore, we made an attempt to assess the usefulness of eotaxins, as there are few studies that investigate their significance, in patients with CRC. The study included 80 subjects (CRC patients and healthy volunteers). Serum concentrations of all eotaxins were measured using a multiplexing method (Luminex), while CCR3 was measured by immunoenzymatic assay (ELISA). CRP levels were determined by immunoturbidimetry and classical tumor marker levels (CEA and CA 19-9) and were measured using chemiluminescent microparticle immunoassay (CMIA). The highest usefulness among the proteins tested showed CCR3. Its concentrations were significantly higher in the CRC group than in healthy controls. The diagnostic sensitivity, specificity, positive and negative predictive value, and the area under the ROC curve (AUC) of CCR3 were higher than those of CA 19-9. The maximum values for sensitivity, negative predictive value, and AUC were obtained for a combination of CCR3 and CRP. Our findings suggest the potential usefulness of CCR3 in the diagnosis of CRC, especially in combination with CRP or CEA.
Effects of a Home-Based Lifestyle Intervention Program on Cardiometabolic Health in Breast Cancer Survivors during the COVID-19 Lockdown
Authors: Natalucci Valentina , Marini Carlo Ferri , Flori Marco , Pietropaolo Francesca , Lucertini Francesco , Annibalini Giosuè , Vallorani Luciana , Sisti Davide , Saltarelli Roberta , Villarini Anna , Monaldi Silvia , Barocci Simone , Catalano Vincenzo , Rocchi Marco Bruno Luigi , Benelli Piero , Stocchi Vilberto , Barbieri Elena , Emili Rita
Published: June 2021

This study aimed to evaluate the cardiometabolic effects of a home-based lifestyle intervention (LI) in breast cancer survivors (BCSs) during the COVID-19 lockdown. In total, 30 BCSs (women; stages 0–II; non-metastatic; aged 53.5 ± 7.6 years; non-physically active; normal left ventricular systolic function) with a risk factor for recurrence underwent a 3-month LI based on nutrition and exercise. Anthropometrics, Mediterranean diet adherence, physical activity level (PAL), cardiorespiratory fitness (VO2max), echocardiographic parameters, heart rate variability (average standard deviation of NN intervals (ASDNN/5 min) and 24 h very- (24 hVLF) and low-frequency (24 hLF)), and metabolic, endocrine, and inflammatory serum biomarkers (glycemia, insulin resistance, progesterone, testosterone, and high-sensitivity C-reactive protein (hs-CRP)) were evaluated before (T0) and after (T1) the LI. After the LI, there were improvements in: body mass index (kg/m2: T0 = 26.0 ± 5.0, T1 = 25.5 ± 4.7; p = 0.035); diet (Mediet score: T0 = 6.9 ± 2.3, T1 = 8.8 ± 2.2; p < 0.001); PAL (MET-min/week: T0 = 647 ± 547, T1 = 1043 ± 564; p < 0.001); VO2max (mL·min−1·kg−1: T0 = 30.5 ± 5.8, T1 = 33.4 ± 6.8; p < 0.001); signs of diastolic dysfunction (participants: T0 = 15, T1 = 10; p = 0.007); AS-DNN/5 min (ms: T0 = 50.6 ± 14.4, T1 = 55.3 ± 16.7; p = 0.032); 24 hLF (ms2: T0 = 589 ± 391, T1 = 732 ± 542; p = 0.014); glycemia (mg/dL: T0 = 100.8 ± 11.4, T1 = 91.7 ± 11.0; p < 0.001); insulin resistance (HOMA-IR score: T0 = 2.07 ± 1.54, T1 = 1.53 ± 1.11; p = 0.005); testosterone (ng/mL: T0 = 0.34 ± 0.27, T1 = 0.24 ± 0.20; p = 0.003); hs-CRP (mg/L: T0 = 2.18 ± 2.14, T1 = 1.75 ± 1.74; p = 0.027). The other parameters did not change. Despite the home-confinement, LI based on exercise and nutrition improved cardiometabolic health in BCSs.
Audit Committee Characteristics and Quality of Financial Information: The Role of the Internal Information Environment and Political Connections
Authors: Namakavarani Omid , Daryaei Abbas , Askarany Davood , Askary Saeed
Published: June 2021

This study explores the relationship between audit committee characteristics and accounting information quality by justifying the role of the internal information environment and political connections under the theocracy state of Iran with syncretic politics. Using panel data of 558 firms from the Tehran Stock Exchange (TSE) for 2011–2016, we rank firms using Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) and entropy method for determination of the weight of evaluating indicators. The firms are positioned into high- to low-level political connections, and two proxies for audit committee characteristics are used: independence of audit committee and financial knowledge. Furthermore, three proxies are used for an internal information environment: earning announcement speed, the accuracy of earning forecasting and lack of financial restatements. Our findings show that there is a significant and positive relationship between the audit committee and financial information quality characteristics in high-level political connections, as well as between financial knowledge and financial information quality. Furthermore, the findings of this study suggest that the application of political economy theories could be appropriate for more inquiry.
Gender Difference in Architectural and Mechanical Properties of Medial Gastrocnemius–Achilles Tendon Unit In Vivo
Authors: Deng Liqin , Zhang Xini , Xiao Songlin , Wang Baofeng , Fu Weijie
Published: June 2021

This study aims to explore whether gender differences exist in the architectural and mechanical properties of the medial gastrocnemius–Achilles tendon unit (gMTU) in vivo. Thirty-six healthy male and female adults without training experience and regular exercise habits were recruited. The architectural and mechanical properties of the gMTU were measured via an ultrasonography system and MyotonPRO, respectively. Independent t-tests were utilized to quantify the gender difference in the architectural and mechanical properties of the gMTU. In terms of architectural properties, the medial gastrocnemius (MG)’s pennation angle and thickness were greater in males than in females, whereas no substantial gender difference was observed in the MG’s fascicle length; the males possessed Achilles tendons (ATs) with a longer length and a greater cross-sectional area than females. In terms of mechanical properties, the MG’s vertical stiffness was lower and the MG’s logarithmic decrement was greater in females than in males. Both genders had no remarkable difference in the AT’s vertical stiffness and logarithmic decrement. Gender differences of individuals without training experience and regular exercise habits exist in the architectural and mechanical properties of the gMTU in vivo. The MG’s force-producing capacities, ankle torque, mechanical efficiency and peak power were higher in males than in females. The load-resisting capacities of AT were greater and the MG strain was lesser in males than in females. These findings suggest that males have better physical fitness, speed and performance in power-based sports events than females from the perspective of morphology and biomechanics.
Multiscale Models for Fibril Formation: Rare Events Methods, Microkinetic Models, and Population Balances
Authors: Shayesteh Zadeh Armin , Peters Baron
Published: June 2021

Amyloid fibrils are thought to grow by a two-step dock-lock mechanism. However, previous simulations of fibril formation (i) overlook the bi-molecular nature of the docking step and obtain rates with first-order units, or (ii) superimpose the docked and locked states when computing the potential of mean force for association and thereby muddle the docking and locking steps. Here, we developed a simple microkinetic model with separate locking and docking steps and with the appropriate concentration dependences for each step. We constructed a simple model comprised of chiral dumbbells that retains qualitative aspects of fibril formation. We used rare events methods to predict separate docking and locking rate constants for the model. The rate constants were embedded in the microkinetic model, with the microkinetic model embedded in a population balance model for “bottom-up” multiscale fibril growth rate predictions. These were compared to “top-down” results using simulation data with the same model and multiscale framework to obtain maximum likelihood estimates of the separate lock and dock rate constants. We used the same procedures to extract separate docking and locking rate constants from experimental fibril growth data. Our multiscale strategy, embedding rate theories, and kinetic models in conservation laws should help to extract docking and locking rate constants from experimental data or long molecular simulations with correct units and without compromising the molecular description.