bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncertainty Modeling of a Modified SEIR Epidemic Model for COVID-19
Authors: Wang Yanjin , Wang Pei , Zhang Shudao , Pan Hao
Published: August 2022

Based on SEIR (susceptible–exposed–infectious–removed) epidemic model, we propose a modified epidemic mathematical model to describe the spread of the coronavirus disease 2019 (COVID-19) epidemic in Wuhan, China. Using public data, the uncertainty parameters of the proposed model for COVID-19 in Wuhan were calibrated. The uncertainty of the control basic reproduction number was studied with the posterior probability density function of the uncertainty model parameters. The mathematical model was used to inverse deduce the earliest start date of COVID-19 infection in Wuhan with consideration of the lack of information for the initial conditions of the model. The result of the uncertainty analysis of the model is in line with the observed data for COVID-19 in Wuhan, China. The numerical results show that the modified mathematical model could model the spread of COVID-19 epidemics.
Soft-Tissue, Rare Earth Element, and Molecular Analyses of Dreadnoughtus schrani, an Exceptionally Complete Titanosaur from Argentina
Authors: Schroeter Elena R. , Ullmann Paul V. , Macauley Kyle , Ash Richard D. , Zheng Wenxia , Schweitzer Mary H. , Lacovara Kenneth J.
Published: August 2022

Evidence that organic material preserves in deep time (>1 Ma) has been reported using a wide variety of analytical techniques. However, the comprehensive geochemical data that could aid in building robust hypotheses for how soft-tissues persist over millions of years are lacking from most paleomolecular reports. Here, we analyze the molecular preservation and taphonomic history of the Dreadnougtus schrani holotype (MPM-PV 1156) at both macroscopic and microscopic levels. We review the stratigraphy, depositional setting, and physical taphonomy of the D. schrani skeletal assemblage, and extensively characterize the preservation and taphonomic history of the humerus at a micro-scale via: (1) histological analysis (structural integrity) and X-ray diffraction (exogenous mineral content); (2) laser ablation-inductively coupled plasma mass spectrometry (analyses of rare earth element content throughout cortex); (3) demineralization and optical microscopy (soft-tissue microstructures); (4) in situ and in-solution immunological assays (presence of endogenous protein). Our data show the D. schrani holotype preserves soft-tissue microstructures and remnants of endogenous bone protein. Further, it was exposed to LREE-enriched groundwaters and weakly-oxidizing conditions after burial, but experienced negligible further chemical alteration after early-diagenetic fossilization. These findings support previous hypotheses that fossils that display low trace element uptake are favorable targets for paleomolecular analyses.
Soft Tissue and Biomolecular Preservation in Vertebrate Fossils from Glauconitic, Shallow Marine Sediments of the Hornerstown Formation, Edelman Fossil Park, New Jersey
Authors: Voegele Kristyn K. , Boles Zachary M. , Ullmann Paul V. , Schroeter Elena R. , Zheng Wenxia , Lacovara Kenneth J.
Published: August 2022

Endogenous biomolecules and soft tissues are known to persist in the fossil record. To date, these discoveries derive from a limited number of preservational environments, (e.g., fluvial channels and floodplains), and fossils from less common depositional environments have been largely unexplored. We conducted paleomolecular analyses of shallow marine vertebrate fossils from the Cretaceous–Paleogene Hornerstown Formation, an 80–90% glauconitic greensand from Jean and Ric Edelman Fossil Park in Mantua Township, NJ. Twelve samples were demineralized and found to yield products morphologically consistent with vertebrate osteocytes, blood vessels, and bone matrix. Specimens from these deposits that are dark in color exhibit excellent histological preservation and yielded a greater recovery of cells and soft tissues, whereas lighter-colored specimens exhibit poor histology and few to no cells/soft tissues. Additionally, a well-preserved femur of the marine crocodilian Thoracosaurus was found to have retained endogenous collagen I by immunofluorescence and enzyme-linked immunosorbent assays. Our results thus not only corroborate previous findings that soft tissue and biomolecular recovery from fossils preserved in marine environments are possible but also expand the range of depositional environments documented to preserve endogenous biomolecules, thus broadening the suite of geologic strata that may be fruitful to examine in future paleomolecular studies.
Picrotoxin Delineates Different Transport Configurations for Malate and γ Aminobutyric Acid through TaALMT1
Authors: Ramesh Sunita A. , Long Yu , Dashtbani-Roozbehani Abolfazl , Gilliham Matthew , Brown Melissa H. , Tyerman Stephen D.
Published: August 2022

Plant-derived pharmacological agents have been used extensively to dissect the structure–function relationships of mammalian GABA receptors and ion channels. Picrotoxin is a non-competitive antagonist of mammalian GABAA receptors. Here, we report that picrotoxin inhibits the anion (malate) efflux mediated by wheat (Triticum aestivum) ALMT1 but has no effect on GABA transport. The EC50 for inhibition was 0.14 nM and 0.18 nM when the ALMTs were expressed in tobacco BY2 cells and in Xenopus oocytes, respectively. Patch clamping of the oocyte plasma membrane expressing wheat ALMT1 showed that picrotoxin inhibited malate currents from both sides of the membrane. These results demonstrate that picrotoxin inhibits anion efflux effectively and can be used as a new inhibitor to study the ion fluxes mediated by ALMT proteins that allow either GABA or anion transport.
Calcium Binds to Transthyretin with Low Affinity
Authors: Cantarutti Cristina , Mimmi Maria Chiara , Verona Guglielmo , Mandaliti Walter , Taylor Graham W. , Mangione P. Patrizia , Giorgetti Sofia , Bellotti Vittorio , Corazza Alessandra
Published: August 2022

The plasma protein transthyretin (TTR), a transporter for thyroid hormones and retinol in plasma and cerebrospinal fluid, is responsible for the second most common type of systemic (ATTR) amyloidosis either in its wild type form or as a result of destabilizing genetic mutations that increase its aggregation propensity. The association between free calcium ions (Ca2+) and TTR is still debated, although recent work seems to suggest that calcium induces structural destabilization of TTR and promotes its aggregation at non-physiological low pH in vitro. We apply high-resolution NMR spectroscopy to investigate calcium binding to TTR showing the formation of labile interactions, which leave the native structure of TTR substantially unaltered. The effect of calcium binding on TTR-enhanced aggregation is also assessed at physiological pH through the mechano-enzymatic mechanism. Our results indicate that, even if the binding is weak, about 7% of TTR is likely to be Ca2+-bound in vivo and therefore more aggregation prone as we have shown that this interaction is able to increase the protein susceptibility to the proteolytic cleavage that leads to aggregation at physiological pH. These events, even if involving a minority of circulating TTR, may be relevant for ATTR, a pathology that takes several decades to develop.
Recent Progress in the Discovery and Development of Monoclonal Antibodies against Viral Infections
Authors: Mokhtary Pardis , Pourhashem Zeinab , Mehrizi Akram Abouei , Sala Claudia , Rappuoli Rino
Published: August 2022

Monoclonal antibodies (mAbs), the new revolutionary class of medications, are fast becoming tools against various diseases thanks to a unique structure and function that allow them to bind highly specific targets or receptors. These specialized proteins can be produced in large quantities via the hybridoma technique introduced in 1975 or by means of modern technologies. Additional methods have been developed to generate mAbs with new biological properties such as humanized, chimeric, or murine. The inclusion of mAbs in therapeutic regimens is a major medical advance and will hopefully lead to significant improvements in infectious disease management. Since the first therapeutic mAb, muromonab-CD3, was approved by the U.S. Food and Drug Administration (FDA) in 1986, the list of approved mAbs and their clinical indications and applications have been proliferating. New technologies have been developed to modify the structure of mAbs, thereby increasing efficacy and improving delivery routes. Gene delivery technologies, such as non-viral synthetic plasmid DNA and messenger RNA vectors (DMabs or mRNA-encoded mAbs), built to express tailored mAb genes, might help overcome some of the challenges of mAb therapy, including production restrictions, cold-chain storage, transportation requirements, and expensive manufacturing and distribution processes. This paper reviews some of the recent developments in mAb discovery against viral infections and illustrates how mAbs can help to combat viral diseases and outbreaks.
Cannabinoids—Perspectives for Individual Treatment in Selected Patients: Analysis of the Case Series
Authors: Graczyk Michał , Lewandowska Agata Anna , Melnyczok Piotr , Zgliński Adam , Łukowicz Małgorzata
Published: August 2022

Cannabinoids can be successfully used in the treatment of many symptoms and diseases; however, most often they are not the drugs of first choice. They can be added to the primary therapy, which can improve its effectiveness, or be introduced as the basic treatment when the conventional methods have failed. Small clinical trials and case reports prove the benefits of applying medicinal cannabis in various indications; however, clinical trials in larger groups of patients are scarce and often controversial. Due to limited scientific evidence, it is essential to conduct further experimental trials. Understanding the role of endocannabinoids, as well as the composition of cannabis containing both phytocannabinoids and terpenes plays an important role in their clinical use. The clinical effects of cannabinoids depend, among other things, on the activity of the endocannabinoid system, the proportion of phytocannabinoids, such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and the dosage used. The article discusses the role of phytocannabinoids and the potential of using them in different clinical cases in patients suffering from chronic pain, opioid dependence, depression and migraine, who did not respond to the conventional therapeutic methods. In each of the presented cases, the implementation of cannabinoids altered the course of the disease and resulted in symptom relief. Every decision to introduce cannabinoids to the treatment should be made individually with careful attention paid to details. Additionally, it is worth taking care of good clinical communication and education so that the implemented therapy is safe, effective and properly perceived by the patient.
CAG Repeat Instability in the Peripheral and Central Nervous System of Transgenic Huntington’s Disease Monkeys
Authors: Cho In K. , Clever Faye , Hong Gordon , Chan Anthony W. S.
Published: August 2022

Huntington’s Disease (HD) is an autosomal dominant disease that results in severe neurodegeneration with no cure. HD is caused by the expanded CAG trinucleotide repeat (TNR) on the Huntingtin gene (HTT). Although the somatic and germline expansion of the CAG repeats has been well-documented, the underlying mechanisms had not been fully delineated. Increased CAG repeat length is associated with a more severe phenotype, greater TNR instability, and earlier age of onset. The direct relationship between CAG repeat length and molecular pathogenesis makes TNR instability a useful measure of symptom severity and tissue susceptibility. Thus, we examined the tissue-specific TNR instability of transgenic nonhuman primate models of Huntington’s disease. Our data show a similar profile of CAG repeat expansion in both rHD1 and rHD7, where high instability was observed in testis, liver, caudate, and putamen. CAG repeat expansion was observed in all tissue samples, and tissue- and CAG repeat size-dependent expansion was observed. Correlation analysis of CAG repeat expansion and the gene expression profile of four genes in different tissues, clusterin (CLU), transferrin (TF), ribosomal protein lateral stalk subunit P1 (RPLP1), and ribosomal protein L13a (RPL13A), showed a strong correlation with CAG repeat instability. Overall, our data, along with previously published studies, can be used for studying the biology of CAG repeat instability and identifying new therapeutic targets.
Optimized Design of a Tuned Mass Damper Inerter (TMDI) Applied to Circular Section Members of Transmission Towers
Authors: Bian Yongfei , Liu Xinpeng , Sun Yi , Zhong Yongli
Published: August 2022

Wind loads can cause significant vibrations in circular section members, resulting in serious structural hazards. In order to control the vibration of the structure and mitigate the hazards, this study investigates the optimal design and carries out a performance evaluation of a tuned mass damper inerter (TMDI) designed for the vibration control of circular section members in structures. The TMDI system is a novel vibration reduction device that utilizes an inerter based on a tuned mass damper (TMD). The main structure is a simplified Euler beam made up of circular section members, and the mass of the TMDI is coupled to the main structure by a spring and damper, as well as to the ground via an inerter. The optimization objectives are to minimize the displacement variance and maximize the energy dissipation index (EDI), and two different optimization schemes are designed. In addition to the comparative analysis of the results obtained from the different optimization schemes, a sensitivity analysis of the design parameters is also performed, and the results show that TMDI not only effectively reduces the additional mass but also has better vibration control performance and robustness than the TMD.
Knockdown of CKAP2 Inhibits Proliferation, Migration, and Aggregate Formation in Aggressive Breast Cancer
Authors: dos Santos Alexsandro , Ouellete Geneviève , Diorio Caroline , Elowe Sabine , Durocher Francine
Published: August 2022

Loss of mitotic regulation is commonly observed in cancer and is a major cause of whole-chromosome aneuploidy. The identification of genes that play a role in the proper progression of mitosis can help us to understand the development and evolution of this disease. Here, we generated a list of proteins implicated in mitosis that we used to probe a patient-derived breast cancer (BC) continuum gene-expression dataset generated by our group by human transcriptome analysis of breast lesions of varying aggressiveness (from normal to invasive). We identified cytoskeleton-associated protein 2 (CKAP2) as an important mitotic regulator in invasive BC. The results showed that CKAP2 is overexpressed in invasive BC tumors when compared with normal tissues, and highly expressed in all BC subtypes. Higher expression of CKAP2 is also related to a worse prognosis in overall survival and relapse-free survival in estrogen receptor (ER)-positive and human epidermal growth factor receptor type 2 (HER2)-negative BC patients. Knockdown of CKAP2 in SKBR3 cells impaired cell proliferation and cell migration and reduced aggregate formation in a 3D culture. Our results show the important role of CKAP2 in BC tumorigenesis, and its potential utility as a prognostic marker in BC.
Salvage Nodal Radiotherapy as Metastasis-Directed Therapy for Oligorecurrent Prostate Cancer Detected by Positron Emission Tomography Shows Favorable Outcome in Long-Term Follow-Up
Authors: Tamihardja Jörg , Zehner Leonie , Hartrampf Philipp , Lisowski Dominik , Kneitz Susanne , Cirsi Sinan , Razinskas Gary , Flentje Michael , Polat Bülent
Published: August 2022

Background: The study aimed to access the long-term outcome of salvage nodal radiotherapy (SNRT) in oligorecurrent prostate cancer. Methods: A total of 95 consecutive patients received SNRT for pelvic and/or extrapelvic nodal recurrence after prostate-specific membrane antigen (PSMA) or choline PET from 2010 to 2021. SNRT was applied as external beam radiotherapy with simultaneous integrated boost up to a median total dose of 62.9 Gy (EQD21.5Gy) to the recurrent lymph node metastases. The outcome was analyzed by cumulative incidence functions with death as the competing risk. Fine–Gray regression analyses were performed to estimate the relative hazards of the outcome parameters. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation utilized Common Toxicity Criteria for Adverse Events (v5.0). The results are as follows: the median follow-up was 47.1 months. The five-year biochemical progression rate (95% CI) was 50.1% (35.7–62.9%). Concomitant androgen deprivation therapy (ADT) was adminstered in 60.0% of the patients. The five-year biochemical progression rate was 75.0% (42.0–90.9%) without ADT versus 35.3% (19.6–51.4%) with ADT (p = 0.003). The cumulative five-year late grade 3 GU toxicity rate was 2.1%. No late grade 3 GI toxicity occured. Conclusions: Metastasis-directed therapy through SNRT for PET-staged oligorecurrent prostate cancer demonstrated a favorable long-term oncologic outcome. Omittance of ADT led to an increased biochemical progression.
Induction of Bystander and Abscopal Effects after Electroporation-Based Treatments
Authors: Ruzgys Paulius , Navickaitė Diana , Palepšienė Rūta , Uždavinytė Dovilė , Barauskaitė Neringa , Novickij Vitalij , Girkontaitė Irutė , Šitkauskienė Brigita , Šatkauskas Saulius
Published: August 2022

Electroporation-based antitumor therapies, including bleomycin electrotransfer, calcium electroporation, and irreversible electroporation, are very effective on directly treated tumors, but have no or low effect on distal nodules. In this study, we aimed to investigate the abscopal effect following calcium electroporation and bleomycin electrotransfer and to find out the effect of the increase of IL-2 serum concentration by muscle transfection. The bystander effect was analyzed in in vitro studies on 4T1tumor cells, while abscopal effect was investigated in an in vivo setting using Balb/c mice bearing 4T1 tumors. ELISA was used to monitor IL-2 serum concentration. We showed that, similarly to cell treatment with bleomycin electrotransfer, the bystander effect occurs also following calcium electroporation and that these effects can be combined. Combination of these treatments also resulted in the enhancement of the abscopal effect in vivo. Since these treatments resulted in an increase of IL-2 serum concentration only in mice bearing one but not two tumors, we increased IL-2 serum concentration by muscle transfection. Although this did not enhance the abscopal effect of combined tumor treatment using calcium electroporation and bleomycin electrotransfer, boosting of IL-2 serum concentration had a significant inhibitory effect on directly treated tumors.
High-Efficiency Oxygen Reduction to Hydrogen Peroxide Catalyzed by Oxidized Mo2TiC2 MXene
Authors: Li Ge , Zhou Bin , Wang Ping , He Miao , Fang Zhao , Yuan Xilin , Wang Weiwei , Sun Xiaohua , Li Zhenxing
Published: August 2022

The two-electron oxygen reduction reaction (2e−ORR) pathway electrochemical synthesis to H2O2 has the advantages of low investment and environmental protection and is considered to be a promising green method. Herein, the oxidized Mo2TiC2 MXene (O-Mo2TiC2) was successfully synthesized by a facile hydrothermal method as an electrocatalyst in electrocatalytic H2O2 production. The O-Mo2TiC2 achieved the 90% of H2O2 selectivity and 0.72 V vs. RHE of the onset potential. Moreover, O-Mo2TiC2 showed high charge transfer ability and long-term stable working ability of 40 h. This significantly enhanced electrocatalytic H2O2 production capacity is assigned the oxidation treatment of Mo2TiC2 MXene to generate more oxygen-containing groups in O-Mo2TiC2. This work provides a promising catalyst candidate for the electrochemical synthesis of H2O2.
Identification, Quantification, and Characterization of HIV-1 Reservoirs in the Human Brain
Authors: Donoso Maribel , D’Amico Daniela , Valdebenito Silvana , Hernandez Cristian A. , Prideaux Brendan , Eugenin Eliseo A.
Published: August 2022

The major barrier to cure HIV infection is the early generation and extended survival of HIV reservoirs in the circulation and tissues. Currently, the techniques used to detect and quantify HIV reservoirs are mostly based on blood-based assays; however, it has become evident that viral reservoirs remain in tissues. Our study describes a novel multi-component imaging method (HIV DNA, mRNA, and viral proteins in the same assay) to identify, quantify, and characterize viral reservoirs in tissues and blood products obtained from HIV-infected individuals even when systemic replication is undetectable. In the human brains of HIV-infected individuals under ART, we identified that microglia/macrophages and a small population of astrocytes are the main cells with integrated HIV DNA. Only half of the cells with integrated HIV DNA expressed viral mRNA, and one-third expressed viral proteins. Surprisingly, we identified residual HIV-p24, gp120, nef, vpr, and tat protein expression and accumulation in uninfected cells around HIV-infected cells suggesting local synthesis, secretion, and bystander uptake. In conclusion, our data show that ART reduces the size of the brain’s HIV reservoirs; however, local/chronic viral protein secretion still occurs, indicating that the brain is still a major anatomical target to cure HIV infection.
Quantitative Acetylomics Uncover Acetylation-Mediated Pathway Changes Following Histone Deacetylase Inhibition in Anaplastic Large Cell Lymphoma
Authors: Zrimšek Maša , Kuchaříková Hana , Draganić Kristina , Dobrovolná Pavlína , Heiss Spornberger Verena , Winkelmayer Lisa , Hassler Melanie , Lochmanová Gabriela , Zdráhal Zbyněk , Egger Gerda
Published: August 2022

Histone deacetylases (HDACs) target acetylated lysine residues in histone and non-histone proteins. HDACs are implicated in the regulation of genomic stability, cell cycle, cell death and differentiation and thus critically involved in tumorigenesis. Further, HDACs regulate T-cell development and HDAC inhibitors (HDACis) have been approved for clinical use in some T-cell malignancies. Still, the exact targets and mechanisms of HDAC inhibition in cancer are understudied. We isolated tumor cell lines from a transgenic mouse model of anaplastic large cell lymphoma (ALCL), a rare T-cell lymphoma, and abrogated HDAC activity by treatment with the HDACis Vorinostat and Entinostat or Cre-mediated deletion of Hdac1. Changes in overall protein expression as well as histone and protein acetylation were measured following Hdac1 deletion or pharmacological inhibition using label-free liquid chromatography mass spectrometry (LC-MS/MS). We found changes in overall protein abundance and increased acetylation of histones and non-histone proteins, many of which were newly discovered and associated with major metabolic and DNA damage pathways. For non-histone acetylation, we mapped a total of 1204 acetylated peptides corresponding to 603 proteins, including chromatin modifying proteins and transcription factors. Hyperacetylated proteins were involved in processes such as transcription, RNA metabolism and DNA damage repair (DDR). The DDR pathway was majorly affected by hyperacetylation following HDAC inhibition. This included acetylation of H2AX, PARP1 and previously unrecognized acetylation sites in TP53BP1. Our data provide a comprehensive view of the targets of HDAC inhibition in malignant T cells with general applicability and could have translational impact for the treatment of ALCL with HDACis alone or in combination therapies.
Nuclear Receptor Atlases of Choroidal Tissues Reveal Candidate Receptors Associated with Age-Related Macular Degeneration
Authors: Peavey Jeremy , Parmar Vipul M. , Malek Goldis
Published: August 2022

The choroid is a vulnerable tissue site in the eye, impacted in several blinding diseases including age related macular degeneration (AMD), which is the leading cause of central vision loss in the aging population. Choroidal thinning and choriocapillary dropout are features of the early form of AMD, and endothelial dysfunction and vascular changes are primary characteristics of the neovascular clinical sub-type of AMD. Given the importance, the choroidal endothelium and outer vasculature play in supporting visual function, a better understanding of baseline choroidal signaling pathways engaged in tissue and cellular homeostasis is needed. Nuclear receptors are a large family of transcription factors responsible for maintaining various cellular processes during development, aging and disease. Herein we developed a comprehensive nuclear receptor atlas of human choroidal endothelial cells and freshly isolated choroidal tissue by examining the expression levels of all members of this transcription family using quantitative real time PCR. Given the close relationship between the choroid and retinal pigment epithelium (RPE), this data was cross-referenced with the expression profile of nuclear receptors in human RPE cells, to discover potential overlap versus cell-specific nuclear receptor expression. Finally, to identify candidate receptors that may participate in the pathobiology of AMD, we cataloged nuclear receptor expression in a murine model of wet AMD, from which we discovered a subset of nuclear receptors differentially regulated following neovascularization. Overall, these databases serve as useful resources establishing the influence of nuclear receptor signaling pathways on the outer vascular tissue of the eye, while providing a list of receptors, for more focused investigations in the future, to determine their suitability as potential therapeutic targets for diseases, in which the choroid is affected.
Modeling MEN1 with Patient-Origin iPSCs Reveals GLP-1R Mediated Hypersecretion of Insulin
Authors: Cheng Ziqi , Guo Dongsheng , Ruzi Aynisahan , Pan Tingcai , You Kai , Chen Yan , Huang Xinping , Zhang Jiaye , Yang Fan , Niu Lizhi , Xu Kecheng , Li Yin-Xiong
Published: August 2022

Multiple endocrine neoplasia type 1 (MEN1) is an inherited disease caused by mutations in the MEN1 gene encoding a nuclear protein menin. Among those different endocrine tumors of MEN1, the pancreatic neuroendocrine tumors (PNETs) are life-threatening and frequently implicated. Since there are uncertainties in genotype and phenotype relationship and there are species differences between humans and mice, it is worth it to replenish the mice model with human cell resources. Here, we tested whether the patient-origin induced pluripotent stem cell (iPSC) lines could phenocopy some defects of MEN1. In vitro β-cell differentiation revealed that the percentage of insulin-positive cells and insulin secretion were increased by at least two-fold in MEN1-iPSC derived cells, which was mainly resulted from significantly higher proliferative activities in the pancreatic progenitor stage (Day 7–13). This scenario was paralleled with increased expressions of prohormone convertase1/3 (PC1/3), glucagon-like peptide-1 (GLP-1), GLP-1R, and factors in the phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway, and the GLP-1R was mainly expressed in β-like cells. Blockages of either GLP-1R or PI3K significantly reduced the percentages of insulin-positive cells and hypersecretion of insulin in MEN1-derived cells. Furthermore, in transplantation of different stages of MEN1-derived cells into immune-deficient mice, only those β-like cells produced tumors that mimicked the features of the PNETs from the original patient. To the best of our knowledge, this was the first case using patient-origin iPSCs modeling most phenotypes of MEN1, and the results suggested that GLP-1R may be a potential therapeutic target for MEN1-related hyperinsulinemia.
Correction: Stoll et al. Impact of HLA-B27 and Disease Status on the Gut Microbiome of the Offspring of Ankylosing Spondylitis Patients. Children 2022, 9, 569
Authors: Stoll Matthew L. , DeQuattro Kimberly , Li Zhixiu , Sawhney Henna , Weiss Pamela F. , Nigrovic Peter A. , Wright Tracey B. , Schikler Kenneth , Edelheit Barbara , Morrow Casey D. , Reveille John D. , Brown Matthew A. , Gensler Lianne S.
Published: August 2022

The authors wish to make the following correction to this paper [...]
Comparison of the UEscope Video Laryngoscope with the Traditional Direct Laryngoscope in Neonates and Infants: A Randomized Clinical Trial
Authors: Chae Min-Suk , Chung Jae-Hee , Shim Jung-Woo , Park Jae-Sik , Bae Jin-Hoon , Lee Hyung-Mook
Published: August 2022

The role of video laryngoscopy in adults is well established, but its role in children is still inconclusive. Previous studies on the UEscope in pediatric patients with difficult airways showed that it could reduce the time to intubation (TTI) compared to a conventional direct laryngoscope. The main objective of the current study was to investigate if the use of the UEscope could reduce the TTI in neonates and infants. Forty patients under 12 months old were recruited from a single tertiary hospital from March 2020 to September 2021 and were randomly assigned to the direct laryngoscope group (n = 19, neonates = 4, infants = 15) or UEscope group (n = 21, neonates = 6, infants = 15). Although the quality of glottic view was comparable in both groups, the TTI was significantly lower in the UEscope group in both the “intention-to-treat” (–19.34 s, 95% confidence interval = –28.82 to –1.75, p = 0.0144) and “as treated” (–11.24 s, 95% confidence interval: –21.73 to 0, p = 0.0488) analyses. The UEscope may be a better choice for tracheal intubation than conventional direct laryngoscope in neonates and infants.
Liraglutide Exerts Protective Effects by Downregulation of PPARγ, ACSL1 and SREBP-1c in Huh7 Cell Culture Models of Non-Alcoholic Steatosis and Drug-Induced Steatosis
Authors: Omanovic Kolaric Tea , Kizivat Tomislav , Mihaljevic Vjera , Zjalic Milorad , Bilic-Curcic Ines , Kuna Lucija , Smolic Robert , Vcev Aleksandar , Wu George Y. , Smolic Martina
Published: August 2022

(1) Background: With the aging of the population and polypharmacy encountered in the elderly, drug-induced steatosis (DIS) has become frequent cause of non-alcoholic steatosis (NAS). Indeed, NAS and DIS may co-exist, making the ability to distinguish between the entities ever more important. The aim of our study was to study cell culture models of NAS and DIS and determine the effects of liraglutide (LIRA) in those models. (2) Methods: Huh7 cells were treated with oleic acid (OA), or amiodarone (AMD) to establish models of NAS and DIS, respectively. Cells were treated with LIRA and cell viability was assessed by MTT, lipid accumulation by Oil-Red-O staining and triglyceride assay, and intracellular signals involved in hepatosteatosis were quantitated by RT-PCR. (3) Results: After exposure to various OA and AMD concentrations, those that achieved 80% of cells viabilities were used in further experiments to establish NAS and DIS models using 0.5 mM OA and 20 µM AMD, respectively. In both models, LIRA increased cell viability (p < 0.01). Lipid accumulation was increased in both models, with microsteatotic pattern in DIS, and macrosteatotic pattern in NAS which corresponds to greater triglyceride accumulation in latter. LIRA ameliorated these changes (p < 0.001), and downregulated expression of lipogenic ACSL1, PPARγ, and SREBP-1c pathways in the liver (p < 0.01) (4) Conclusions: LIRA ameliorates hepatocyte steatosis in Huh7 cell culture models of NAS and DIS.
Test and Mesoscopic Analysis of Chloride Ion Diffusion of High-Performance-Concrete with Fly Ash and Silica Fume
Authors: Tang Huang , Yang Yiming , Peng Jianxin , Liu Peng , Zhang Jianren
Published: August 2022

High performance concrete (HPC) is a kind of concrete with mineral admixtures, which has better resistance ability to chloride ions diffusion than ordinary concrete. In the present study, the authors carried out a chloride ion diffusion experiment for the HPC with fly ash and silica fume. The influence of the water–binder ratio (W/B), binary (Portland cement–Fly ash (PC-FS) and Portland cement–Silica fume (PC-SF) and ternary (Portland cement–Fly ash–Silica fume (PC-FA-SF)) combinations on the concrete compressive strength and chloride ion diffusion was investigated. It was found that the compressive strength of normal concrete and HPC increase with the decrease in the W/B, the ratio of W/B deceasing value to strength increasing value for normal concrete is 0.74, and for the HPC is 0.20, so the influence of the W/B on the concrete strength for normal concrete was obviously more than the HPC. The influence of the contents of the SF or FA on developing the concrete strength was limited. The concrete compressive strength of ternary combination specimens decreases with the increase in FA or SF when the content of the other mineral admixture SF or FA remained unchanged. The ternary combination was more efficient in prohibiting chlorides ingress insider the specimens than the binary combination. The mesoscopic simulation and the tested value of the chloride ion under the same depth was close, the average ratio of simulation value to tested value was 0.91. The aggregate shape and distribution also had a negligible influence on chloride diffusivity in the HPC, but the chloride ion concentration increased with the increase in aggregate size.
Impact of Throughflow and Coriolis Force on the Onset of Double-Diffusive Convection with Internal Heat Source
Authors: Rafeek Kallu Vetty Muhammed , Reddy Gudala Janardhana , Ragoju Ravi , Reddy Gundlapally Shiva Kumar , Sheremet Mikhail A.
Published: August 2022

The present research examines the joint influence of throughflow and Coriolis force on the onset of double-diffusive convection with an internal heat source modelled by Darcy’s law. The BVP4C routine in MATLAB R2020a is used to solve the eigenvalue problem numerically. Critical Rayleigh numbers are obtained for designated values of governing parameters. The effect of the internal heat source parameter, Taylor number, Darcy number, and Peclet number on the system’s stability is investigated. The internal heat source parameter has a destabilizing influence on the system, according to our findings. The reason behind this observation is that the presence of an internal heat source in the porous medium may cause more molecular diffusion inside the medium. The Taylor number, on the other hand, stabilizes the system for both upward and downward throughflow because rotation introduces vorticity into the fluid. Thus, the fluid moves with higher velocity in horizontal planes. The velocity of the fluid perpendicular to the planes reduces as a result of this motion. Thus, the onset of convection is delayed.
MgB2 Thin Films Fabricated by Pulsed Laser Deposition Using Nd:YAG Laser in an In Situ Two-Step Process
Authors: Ozaki Toshinori , Kikukawa Satoshi , Tanaka Rika , Yamamoto Akiyasu , Tsuruta Akihiro , Tsuchiya Yuji
Published: August 2022

Magnesium diboride (MgB2) thin films on r-cut sapphire (r-Al2O3) single crystals were fabricated by a precursor, which was obtained at room temperature via a pulsed laser deposition (PLD) method using a Nd:YAG laser, and an in situ postannealing process. The onset superconducting transition, Tconset, and zero-resistivity transition, Tczero, were observed at 33.6 and 31.7 K, respectively, in the MgB2 thin films prepared by a Mg-rich target with a ratio of Mg:B = 3:2. The critical current density, Jc, calculated from magnetization measurements reached up to 0.9 × 106 A cm−2 at 20 K and 0 T. The broad angular Jc peak was found at 28 K when the magnetic fields were applied in a direction parallel to the film surface (θ = 90°). This could be indicative of the granular structure with randomly oriented grains. Our results demonstrate that this process is a promising candidate for the fabrication of MgB2 superconducting devices.
In Vitro and Ex Vivo Mechanistic Understanding and Clinical Evidence of a Novel Anti-Wrinkle Technology in Single-Arm, Monocentric, Open-Label Observational Studies
Authors: Bhardwaj Vinay , Namkoong Jin , Tartar Océane , Diaz Isabel , Mao Junhong , Wu Joanna
Published: August 2022

Skin aging is a biological process leading to visible skin alterations. The mechanism of action, clinical efficacy and tolerance of a novel anti-wrinkle technology were evaluated in two skin care products formulated for different skin types. Two single-arm monocentric, open-label observational clinical studies, which were 56 days long, evaluated a cream-gel (n = 30) and a cream (n = 33) on the face and neck. Morphometric analyses of five types of wrinkles were performed at 0, 7, 28 and 56 days. Structural changes in extracellular matrix (ECM) including collagen, elastin and hyaluronic acid (HA) were visualized and quantified by histochemical imaging after daily treatment of skin explants for 6 days. Protein and gene expression related to barrier and hydration were analyzed using ELISA and qRT-PCR, respectively, in a reconstituted human skin model treated daily for 48 h. A decrease in wrinkle dimensions was found in the majority of parameters after 28 days of treatment. Collagen, elastin, HA, procollagen type I, hyaluronan synthases, HAS2 and HAS3 were all stimulated. Based on significant and consistent changes in our investigations, we conclude that the underlying mechanism of action of the novel anti-wrinkle technology could be the remodeling of dermal ECM, and both the test formulations were efficacious and well tolerated.
Individual Evaluation of the Common Extensor Tendon and Lateral Collateral Ligament Improves the Severity Diagnostic Accuracy of Magnetic Resonance Imaging for Lateral Epicondylitis
Authors: Ikeda Kazuhiro , Ogawa Takeshi , Ikumi Akira , Yoshii Yuichi , Kohyama Sho , Ikeda Reimi , Yamazaki Masashi
Published: August 2022

The effectiveness of magnetic resonance imaging for diagnosing lateral epicondylitis severity is controversial. We aimed to verify whether individual evaluations of the common extensor tendon and lateral collateral ligament would improve the severity diagnostic accuracy of magnetic resonance imaging for lateral epicondylitis. We obtained coronal images of the lateral elbow in three groups: healthy, clinically mild, and clinically severe. We used our scoring system for evaluation using combined and individual methods. We developed the receiver operating characteristic curve for diagnosis using the scores of the healthy and mild groups and that for severity diagnosis using the scores of the mild and severe groups. The scores, in decreasing value, were those of the severe, mild, and healthy groups, with a significant difference in both methods. The curve for diagnosis showed an area under the curve of 0.85 for the combined evaluation and 0.89 for the individual evaluation, without a significant difference between the methods (p = 0.23). The curve for severity diagnosis showed an area under the curve of 0.69 for combined and 0.81 for individual evaluation, with a significant difference between the methods (p = 0.046). Individual evaluation of the common extensor tendon and lateral collateral ligament improved the severity diagnostic accuracy of lateral epicondylitis.
Classification Scheme of Heating Risk during MRI Scans on Patients with Orthopaedic Prostheses
Authors: Clementi Valeria , Zanovello Umberto , Arduino Alessandro , Ancarani Cristina , Baruffaldi Fabio , Bordini Barbara , Chiampi Mario , Zilberti Luca , Bottauscio Oriano
Published: August 2022

Due to the large variety of possible clinical scenarios, a reliable heating-risk assessment is not straightforward when patients with arthroplasty undergo MRI scans. This paper proposes a simple procedure to estimate the thermal effects induced in patients with hip, knee, or shoulder arthroplasty during MRI exams. The most representative clinical scenarios were identified by a preliminary frequency analysis, based on clinical service databases, collecting MRI exams of 11,658 implant carrier patients. The thermal effects produced by radiofrequency and switching gradient fields were investigated through 588 numerical simulations performed on an ASTM-like phantom, considering four prostheses, two static field values, seven MR sequences, and seven regions of imaging. The risk assessment was inspired by standards for radiofrequency fields and by scientific studies for gradient fields. Three risk tiers were defined for the radiofrequency, in terms of whole-body and local SAR averages, and for GC fields, in terms of temperature elevation. Only 50 out of 588 scenarios require some caution to be managed. Results showed that the whole-body SAR is not a self-reliant safety parameter for patients with metallic implants. The proposed numerical procedure can be easily extended to any other scenario, including the use of detailed anatomical models.
Association of Handgrip Strength with Diabetes Mellitus in Korean Adults According to Sex
Authors: Lee Sung-Bum , Moon Ji-Eun , Kim Jong-Koo
Published: August 2022

Diabetes mellitus (DM) is known to lead to many diseases such as cardiovascular disease and chronic kidney diseases. Therefore, it is essential to find diagnostic tools to prevent DM. This study aimed to find the association between handgrip strength and the prevalence of diabetes mellitus (DM) in Korean adults with respect to sex and menopause. A total of 26,536 participants (12,247 men, 6977 premenopausal women, and 7312 postmenopausal women) aged >19 years were recruited. The study population was divided into quartiles of relative handgrip strength. Logistic regression was used to analyse the association between relative handgrip strength and the prevalence of DM. Compared with the lowest quartile, the odds ratio (95% confidence interval (CI)) the prevalence of DM for the fourth quartile (Q4) was 0.57 (0.43–0.75) after adjusting for confounding factors in men; 0.33 (0.14–0.75), premenopausal women; and 0.82 (0.63–1.07), postmenopausal women. The prevalence of DM decreased as relative handgrip strength increased. This inverse association was more significant in men and premenopausal women than that in postmenopausal women.
Development and Initial Validation of the Safety Training Engagement Scale (STE-S)
Authors: Mariani Marco Giovanni , Petruzziello Gerardo , Vignoli Michela , Guglielmi Dina
Published: August 2022

Safety training promotes safety at work, in particular through the use of engaging methods. This study introduces a newly developed measure of individual engagement in safety training, and aims to analyze the psychometric proprieties of the scale. The safety training engagement scale (STE) consists of five items pertaining to the trainee’s dedication and absorption in a safety training session. Two studies are carried out to analyze the validity of the scale. The first study focuses on the construct (internal) validity, to examine the scale’s internal consistency and dimensional structure. The second study seeks to provide further evidence for construct validity by testing the external validity of the scale. The sample consists of 913 (study 1) and 133 (study 2) participants in safety training programs in the field of the chemical industry who were invited to fill the STE scale after attending a safety training course. The results provide support to affirm the validity and reliability of the scale. The discussion describes the implication and the limitations of using the STE scale in practical safety training programs, and outlines recommendations for research to improve the scale’s robustness.
Seamless Capable PV Power Generation System without Battery Storage for Rural Residential Load
Authors: Chankaya Mukul , Hussain Ikhlaq , Malik Hasmat , Ahmad Aijaz , Alotaibi Majed A. , Márquez Fausto Pedro García
Published: August 2022

The presented system is a three-phase three-wire (3P–3W), seamless, capable, dual-stage PV power generation system without battery storage for rural residential loads to ensure a continuous power supply during the daytime. This system effortlessly shifts from the grid-connected (GC) mode to the standalone (SA) mode when the grid utility is unavailable. During the GC mode, a voltage source converter (VSC) is regulated by the polynomial zero-attracting least mean square (PZA-LMS) algorithm-based current control scheme. During the GC mode, the power balance is achieved at the point of common coupling (PCC) by exchanging active power with the grid, whereas the VSC delivers reactive power. Considering the low efficiency of PV power generation systems, an incremental conductance (InC)-based maximum power point tracking (MPPT) algorithm is necessary for the maximum power extraction out of a PV array. During the unavailability of the grid, the presented system operates in the SA mode, when the load is delivered with PV power only via VSC. Considering the high cost of the battery storage system (BSS), bi-directional converter, and charge control circuitry incurred by rural consumers, they were omitted from the system. Without a BSS, the InC-based MPPT is executed in the derated mode, extracting the PV power to exactly match the load demand. Without derated PV power generation operation, the load may be damaged due to excess PV power flow to the load end or the load may remain underpowered, leading to load shedding or complete disconnection. A synchronous reference frame (SRF)-based voltage control scheme is responsible for the VSC control during the SA operation of the system. The presented system performance was observed and found satisfactory during the irradiation variation, load balancing, islanding, and re-synchronization of the grid. The presented system was found to carry out harmonics suppression and active and reactive power balance at the PCC during both the GC and SA modes. The grid’s total harmonics distortion (THD) levels were shown to be kept below 5% as per the IEEE 519 standard in the GC mode.
Preliminary Experimental Research on the Influence of Counterbalance Valves on the Operation of a Heavy Hydraulic Manipulator during Long-Range Straight-Line Movement
Authors: Łopatka Marian Janusz , Krogul Piotr , Rubiec Arkadiusz , Przybysz Mirosław
Published: August 2022

The effective use of robotic manipulators is particularly important when carrying out hazardous tasks. Often, for this type of mission, manipulators equipped with a hydraulic drive system are used, and their work results primarily from the implementation of precise movements through their effectors. In heavy manipulators, limiting the uncontrolled movement resulting from high inertia and relatively low stiffness has an impact on the improvement of the control precision. Therefore, the paper presents experimental studies that allow the assessment of the impact of the use of counterbalance valves on the precision and dynamics of a manipulator with a hydrostatic drive system. The tests were carried out for a wide range of effector velocities along a horizontal trajectory, on the basis of which, it was found that it was possible to improve the precision and dynamics of the work of such manipulators due to the precision of the trajectory and pressures in the drive system.
Waste Heat Recovery from Air Using Porous Media and Conversion to Electricity
Authors: Donoso-García Pablo , Henríquez-Vargas Luis , Huerta Esteban
Published: August 2022

This paper presents a numerical study of waste heat recovery from a fluid stream using thermoelectric devices. The system consisted of a square section duct with spherical porous media placed in its central region. Hot air circulates continuously through the duct and exchanges energy with the solid matrix and subsequently with the thermoelectric modules. The mathematical model of the system was solved using ANSYS/FLUENT software, requiring the implementation of user-defined functions (UDFs) and user-defined scalars (UDS) regarding porous media and thermoelectric generation modelling. From the simulations carried out, global efficiency and electrical power values were obtained in the range of [0.11–4.51] [%] and [0.01–12.77] [W], respectively. Furthermore, for the set of variables analysed, it was observed that the performance of the system is favoured by an increase in the fluid inlet temperature and speed, as well as by a higher external heat transfer coefficient.