bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of a Hyperelastic 3D Printed Scaffold for Mesenchymal Stem Cell-Based Fabrication of a Bizonal Tendon Enthesis-like Construct
Authors: Gottardi Riccardo , Moeller Kim , Di Gesù Roberto , Tuan Rocky S. , van Griensven Martijn , Balmayor Elizabeth R.
Published: March 2021

After surgical tendon repair, the tendon-to-bone enthesis often does not regenerate, which leads to high numbers of rupture recurrences. To remedy this, tissue engineering techniques are being pursued to strengthen the interface and improve regeneration. In this study, we used hyperelastic biphasic 3D printed PLGA scaffolds with aligned pores at the tendon side and random pores at the bone side to mimic the native insertion side. In an attempt to recreate the enthesis, the scaffolds were seeded with adult human mesenchymal stem cells and then cultured in dual fluidic bioreactors, which allows the separate in-flow of tenogenic and chondrogenic differentiation media. MTS assay confirmed the ability of cells to proliferate in dual-flow bioreactors at similar levels to tissue culture plate. Hematoxylin-eosin staining confirmed a compact cell layer entrapped within newly deposited extracellular matrix attached to the scaffolds’ fibers and between the porous cavities, that increased with culture time. After 7, 14, and 21 days, samples were collected and analyzed by qRT-PCR and GAG production. Cultured constructs in dual fluidic bioreactors differentiate regionally toward a tenogenic or chondrogenic fate dependent on exposure to the corresponding differentiation medium. SOX9 gene expression was upregulated (up to 50-fold compared to control) in both compartments, with a more marked upregulation in the cartilaginous portion of the scaffold, By day 21, the cartilage matrix marker, collage II, and the tendon specific marker, tenomodulin, were found to be highly upregulated in the cartilaginous and tendinous portions of the construct, respectively. In addition, GAG production in the treated constructs (serum-free) matched that in control constructs exposed to 10% fetal bovine serum, confirming the support of functional matrix formation in this system. In summary, our findings have validated this dual fluidic system as a potential platform to form the tendon enthesis, and will be optimized in future studies to achieve the fabrication of distinctly biphasic constructs.
Outer Membrane Vesicles of Gram-Negative Bacteria: An Outlook on Biogenesis
Authors: Avila-Calderón Eric Daniel , Ruiz-Palma María del Socorro , Aguilera-Arreola Ma. Guadalupe , Velázquez-Guadarrama Norma , Ruiz Enrico A. , Gomez-Lunar Zulema , Witonsky Sharon , Contreras-Rodríguez Araceli
Published: March 2021

Outer membrane vesicles (OMVs) from Gram-negative bacteria were first described more than 50 years ago. However, the molecular mechanisms involved in biogenesis began to be studied only in the last few decades. Presently, the biogenesis and molecular mechanisms for their release are not completely known. This review covers the most recent information on cellular components involved in OMV biogenesis, such as lipoproteins and outer membrane proteins, lipopolysaccharide, phospholipids, quorum-sensing molecules, and flagella.
Mitochondrial 13513G>A Mutation With Low Mutant Load Presenting as Isolated Leber's Hereditary Optic Neuropathy Assessed by Next Generation Sequencing
Authors: Sun Chuan-bin , Bai Hai-xia , Xu Dan-ni , Xiao Qing , Liu Zhe
Published: March 2021

Objective: Mitochondrial 13513G>A mutation presenting as isolated Leber's hereditary optic neuropathy (LHON) without any extraocular pathology has not been reported in literature. We herein evaluate the clinical characteristics and heteroplasmy of m.13513G>A mutation manifesting as isolated LHON.

Methods: Seven members of a Chinese family were enrolled in this study. All subjects underwent detailed systemic and ophthalmic examinations. Mitochondrial DNA in their blood was assessed by targeted PCR amplifications, next generation sequencing (NGS), and pyrosequencing. One hundred of blood samples from ethnic-matched healthy volunteers were tested by NGS and pyrosequencing as normal controls.

Results: Isolated LHON without any other ocular or extraocular pathology was identified in a 16 year old patient in this family. Heteroplasmic m.13513G>A mutation was detected by NGS of the full mtDNA genome in the patient with mutant load of 33.56%, and of 26% 3 months and 3 years after the onset of LHON, respectively. No m.13513G>A mutation was detected in all his relatives by NGS. Pyrosequencing revealed the mutant load of m.13513G>A mutation of the LHON patient, his mother, father and sister were 22.4, 1.9, 0, and 0%, respectively. None of 100 healthy control subjects was detected to harbor m.13513G>A mutation either by NGS or by pyrosequencing of the full mt DNA genome.

Conclusions: We first report m.13513G>A mutation with low mutant load presenting as isolated LHON. NGS of the full mitochondrial DNA genome is highly recommended for LHON suspects when targeted PCR amplification for main primary point mutations of LHON was negative.
Transcutaneous Auricular Neurostimulation (tAN): A Novel Adjuvant Treatment in Neonatal Opioid Withdrawal Syndrome
Authors: Jenkins Dorothea D. , Khodaparast Navid , O’Leary Georgia H. , Washburn Stephanie N. , Covalin Alejandro , Badran Bashar W.
Published: March 2021

Maternal opioid use during pregnancy is a growing national problem and can lead to newborns developing neonatal opioid withdrawal syndrome (NOWS) soon after birth. Recent data demonstrates that nearly every 15 min a baby is born in the United States suffering from NOWS. The primary treatment for NOWS is opioid replacement therapy, commonly oral morphine, which has neurotoxic effects on the developing brain. There is an urgent need for non-opioid treatments for NOWS. Transcutaneous auricular neurostimulation (tAN), a novel and non-invasive form of electrostimulation, may serve as a promising alternative to morphine. tAN is delivered via a multichannel earpiece electrode worn on and around the left ear, targeting two cranial nerves—the vagus and trigeminal nerves. Prior research suggests that auricular neurostimulation exerts an anxiolytic effect on the body by releasing endogenous opioids and reduces withdrawal symptoms in adults actively withdrawing from opioids. In this first-in-human prospective, open-label trial, we investigated tAN as an adjuvant to morphine therapy in eight infants >33 weeks gestational age suffering from NOWS and receiving oral morphine treatment. Infants received tAN for 30 min 1 h before receiving a morphine dose. tAN was delivered at 0.1 mA below perception intensity at two different nerve targets on the ear: Region 1, the auricular branch of the vagus nerve; and Region 2, the auriculotemporal nerve. tAN was delivered up to four times daily for a maximum of 12 days. The primary outcome measures were safety [heart rate monitoring, Neonatal Infant Pain Scale (NIPS), and skin irritation] and morphine length of treatment (LOT). tAN was well-tolerated and resulted in no unanticipated adverse events. Comparing to the national average of 23 days, the average oral morphine LOT was 13.3 days (median 9 days) and the average LOT after tAN initiation was 7 days (median 6 days). These preliminary data suggest that tAN is safe and may serve as a promising alternative adjuvant for treating NOWS and reducing the amount of time an infant receives oral morphine.
Dysregulation of MicroRNAs and PIWI-Interacting RNAs in a Caenorhabditis elegans Parkinson’s Disease Model Overexpressing Human α-Synuclein and Influence of tdp-1
Authors: Shen Linjing , Wang Changliang , Chen Liang , Wong Garry
Published: March 2021

MicroRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) regulate gene expression and biological processes through specific genetic and epigenetic mechanisms. Recent studies have described a dysregulation of small non-coding RNAs in Parkinson’s disease (PD) tissues but have been limited in scope. Here, we extend these studies by comparing the dysregulation of both miRNAs and piRNAs from transgenic Caenorhabditis elegans (C. elegans) nematodes overexpressing pan-neuronally human α-synuclein wild-type (WT) (HASNWT OX) or mutant (HASNA53T OX). We observed 32 miRNAs and 112 piRNAs dysregulated in HASNA53T OX compared with WT. Genetic crosses of HASNA53T OX PD animal models with tdp-1 null mutants, the C. elegans ortholog of TDP-43, an RNA-binding protein aggregated in frontal temporal lobar degeneration, improved their behavioral deficits and changed the number of dysregulated miRNAs to 11 and piRNAs to none. Neuronal function-related genes T28F4.5, C34F6.1, C05C10.3, camt-1, and F54D10.3 were predicted to be targeted by cel-miR-1018, cel-miR-355-5p (C34F6.1 and C05C10.3), cel-miR-800-3p, and 21ur-1581 accordingly. This study provides a molecular landscape of small non-coding RNA dysregulation in an animal model that provides insight into the epigenetic changes, molecular processes, and interactions that occur during PD-associated neurodegenerative disorders.
The Association of Meat Intake With All-Cause Mortality and Acute Myocardial Infarction Is Age-Dependent in Patients With Stable Angina Pectoris
Authors: Matre Åslaug O. , Van Parys Anthea , Olsen Thomas , Haugsgjerd Teresa R. , Baravelli Carl M. , Nygård Ottar , Dierkes Jutta , Lysne Vegard
Published: March 2021

Background: Red and processed meat intake have been associated with increased risk of morbidity and mortality, and a restricted intake is encouraged in patients with cardiovascular disease. However, evidence on the association between total meat intake and clinical outcomes in this patient group is lacking.

Objectives: To investigate the association between total meat intake and risk of all-cause mortality, acute myocardial infarction, cancer, and gastrointestinal cancer in patients with stable angina pectoris. We also investigated whether age modified these associations.

Materials and Methods: This prospective cohort study consisted of 1,929 patients (80% male, mean age 62 years) with stable angina pectoris from the Western Norway B-Vitamin Intervention Trial. Dietary assessment was performed by the administration of a semi-quantitative food frequency questionnaire. Cox proportional hazards models were used to investigate the association between a relative increase in total meat intake and the outcomes of interest.

Results: The association per 50 g/1,000 kcal higher intake of total meat with morbidity and mortality were generally inconclusive but indicated an increased risk of acute myocardial infarction [HR: 1.26 (95% CI: 0.98, 1.61)] and gastrointestinal cancer [1.23 (0.70, 2.16)]. However, we observed a clear effect modification by age, where total meat intake was associated with an increased risk of mortality and acute myocardial infarction among younger individuals, but an attenuation, and even reversal of the risk association with increasing age.

Conclusion: Our findings support the current dietary guidelines emphasizing a restricted meat intake in cardiovascular disease patients but highlights the need for further research on the association between meat intake and health outcomes in elderly populations. Future studies should investigate different types of meat separately in other CVD-cohorts, in different age-groups, as well as in the general population.
Biomarkers for Immunotherapy of Oral Squamous Cell Carcinoma: Current Status and Challenges
Authors: Almangush Alhadi , Leivo Ilmo , Mäkitie Antti A.
Published: March 2021

Oral squamous cell carcinoma (OSCC) forms a major health problem in many countries. For several decades the management of OSCC consisted of surgery with or without radiotherapy or chemoradiotherapy. Aiming to increase survival rate, recent research has underlined the significance of harnessing the immune response in treatment of many cancers. The promising finding of checkpoint inhibitors as a weapon for targeting metastatic melanoma was a key event in the development of immunotherapy. Furthermore, clinical trials have recently proven inhibitor of PD-1 for treatment of recurrent/metastatic head and neck cancer. However, some challenges (including patient selection) are presented in the era of immunotherapy. In this mini-review we discuss the emergence of immunotherapy for OSCC and the recently introduced biomarkers of this therapeutic strategy. Immune biomarkers and their prognostic perspectives for selecting patients who may benefit from immunotherapy are addressed. In addition, possible use of such biomarkers to assess the response to this new treatment modality of OSCC will also be discussed.
Case Report: Enfortumab Vedotin for Metastatic Urothelial Carcinoma: A Case Series on the Clinical and Histopathologic Spectrum of Adverse Cutaneous Reactions From Fatal Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis to Dermal Hypersensitivity Reaction
Authors: Viscuse Paul V. , Marques-Piubelli Mario L. , Heberton Meghan M. , Parra Edwin Roger , Shah Amishi Y. , Siefker-Radtke Arlene , Gao Jianjun , Goswami Sangeeta , Ivan Doina , Curry Jonathan L. , Campbell Matthew T.
Published: March 2021

Enfortumab vedotin is a Nectin-4 directed antibody-drug conjugate approved in metastatic urothelial carcinoma following progression on a platinum-containing chemotherapy and immune checkpoint blockade. On-target dermatologic toxicity may occur from Nectin-4 expression in the skin. We highlight a case of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis following enfortumab infusions that was ultimately fatal. The second case describes an erythema multiforme-like rash with interface dermatitis related to enfortumab. Dermatologic findings, immunohistochemistry studies, and immune profiling are detailed. These cases demonstrate the potentially catastrophic outcomes in some patients treated with enfortumab. Patients must be monitored for cutaneous toxicities with early involvement of dermatology and dermatopathology.
Photodynamic Therapy as an Alternative Therapeutic Tool in Functionally Inoperable Oral and Oropharyngeal Carcinoma: A Single Tertiary Center Retrospective Cohort Analysis
Authors: Lambert Arnaud , Nees Lotte , Nuyts Sandra , Clement Paul , Meulemans Jeroen , Delaere Pierre , Vander Poorten Vincent
Published: March 2021

Background: Head and neck cancer is typically treated with surgery, radiotherapy, chemoradiation, or a combination of these treatments. This study aims to retrospectively analyse oncological outcomes, adverse events and toxicity of treatment with temoporfin-mediated photodynamic therapy at a single tertiary referral center. More specifically, in a selected group of patients with otherwise (functionally) inoperable oral or oropharyngeal head and neck squamous cell carcinoma.

Methods: Twenty-six consecutive patients who received photodynamic therapy for oral or oropharyngeal squamous cell carcinoma from January 2002 until July 2019 at the University Hospitals Leuven were included. These were (1) patients with an accessible recurrent or new primary tumor in an extensively treated area of the head and neck, not suitable for standard treatment, or (2) patients that were judged medically unfit to undergo standard treatment modalities.

Results: Complete tumor response immediately after PDT was obtained in 76.9% of cases. During follow-up, a proportion of CR patients did recur, to reach recurrence-free rates at six months, one year and two years of 60.6%, 48.5% and 32.3%. Local control at the PDT treated area was 42.3% with a median recurrence free interval time of 9 months. Recurrence-free interval was statistically more favorable for oropharyngeal squamous cell carcinoma (with or without oral cavity extension) in comparison to oral cavity squamous cell carcinoma alone (p < 0.001). During a median follow-up period of 27 months, we report new tumor activity in 80.8% of patients. Median overall and disease-specific survival time was 31 and 34 months, respectively. Most reported adverse events were pain after treatment and facial edema. At the end of follow-up, swallowing and upper airway functionality were preserved in 76.9 and 95.7% of patients, respectively.

Conclusion: Photodynamic therapy is a valuable treatment option in highly selected patients with oral and/or oropharyngeal (functionally) inoperable head and neck squamous cell carcinoma. Treatment with this alternative modality can induce durable local control in an important fraction of treated patients, with an acceptable toxicity profile.
Identification of Potential Diagnostic Gene Targets for Pediatric Sepsis Based on Bioinformatics and Machine Learning
Authors: Qiao Ying , Zhang Bo , Liu Ying
Published: March 2021

Purpose: To develop a comprehensive differential expression gene profile as well as a prediction model based on the expression analysis of pediatric sepsis specimens.

Methods: In this study, compared with control specimens, a total of 708 differentially expressed genes in pediatric sepsis (case–control at a ratio of 1:3) were identified, including 507 up-regulated and 201 down-regulated ones. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes indicated the close interaction between neutrophil activation, neutrophil degranulation, hematopoietic cell lineage, Staphylococcus aureus infection, and periodontitis. Meanwhile, the results also suggested a significant difference for 16 kinds of immune cell compositions between two sample sets. The two potential selected biomarkers (MMP and MPO) had been validated in septic children patients by the ELISA method.

Conclusion: This study identified two potential hub gene biomarkers and established a differentially expressed genes-based prediction model for pediatric sepsis, which provided a valuable reference for future clinical research.
Lower Leg Fractures in Children and Adolescents—Comparison of Conservative vs. ECMES Treatment
Authors: Weber Birte , Kalbitz Miriam , Baur Meike , Braun Christian Karl , Zwingmann Jörn , Pressmar Jochen
Published: March 2021

Background: Lower leg fractures are one of the most common fractures in pediatric age. In general, treatment of lower leg fractures is predominantly non-operative, requiring clinical and radiological controls. Nevertheless, it can be observed that in recent years tibial shaft fractures have increasingly been treated surgically. The aim of the present study is to investigate treatment strategies in the context of different fracture types of the lower leg.

Methods: In this retrospective chart review, we analyzed 168 children with a diaphyseal fracture of the lower leg admitted to a trauma center between 2005 and 2017. The fractures were classified according to the AO Pediatric Comprehensive Classification of Long Bone Fractures (AO-PCCF).

Results: The frequency of fractures based on the AO-PCCF classification was as follows: Simple oblique fracture of the tibia (43.5%, n = 73), hereof 32 toddler's fractures, multifragmentary oblique fracture of the tibia in 14.3% (n = 24) and simple oblique fracture of both, tibia and fibula in 18 patients (10.7%). Most pediatric fractures were treated conservatively by cast (n = 125). Thirty-seven patients received an ECMES, whereas 3 patients were treated with an external fixator and also 3 fractures were stabilized by plate osteosynthesis. Conservatively treated patients were significantly younger (mean age 6.0) compared to patients treated with ECMES (mean age 10.2) or plate osteosynthesis (PO)/external fixator (EF) (mean age 11.3), even if toddler's fractures (mean age 2.0) are excluded (mean age 7.4). There was no difference in time to full weight-bearing, hospitalization of patients treated with ECMES compared to conservative therapy although ECMES-treated fractures show more instability. The consolidation time was significantly higher in ECMES treated patients compared to conservative therapy.

Conclusion: Pediatric patients (≤4 years) with lower leg fractures most often showed simple oblique fractures of the tibia, half of them toddler's fractures, which were treated predominantly by conservative therapy. All in all, the consolidation time was longer in intramedullary nailing (ECMES) than in conservative therapy. Nevertheless, time to full weight bearing and duration of cast was the same in both groups, even though ECMES treated fractures show more instability.
Novel Gross Deletion Mutations in NTRK1 Gene Associated With Congenital Insensitivity to Pain With Anhidrosis
Authors: Li Lulu , Jia Chao , Tang Yue , Kong Yuanyuan , Xia Yaofang , Ma Li
Published: March 2021

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare inherited autosomal recessive disorder characterized by insensitivity to noxious stimuli, anhidrosis, recurrent fever, and intellectual disability. CIPA is mainly caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1). This study aims to identify pathogenic mutations underlying CIPA in two unrelated Chinese families.

Methods: DNA was extracted from blood samples of patients and their available family members and subjected to whole exome sequencing (WES). Real-time PCR (qPCR), Gap-PCR, and Sanger sequencing were applied to verify the identified variants.

Result: We found novel compound gross deletion mutations [exon1-6 del (g.1-1258_10169del); exon5-7 del (g.6995_11999del)] of NTRK1 (MIM 191315) gene in family 1 and the compound heterozygous mutations [c.851-33T>A; exon5-7 del (g.6995_11999del)] in family 2. Interestingly, we discovered the intragenic novel gross deletion [exon5-7 del (g.6995_11999del)] mediated by recombination between Alu elements.

Conclusions: The present study highlights two rare gross deletion mutations in the NTRK1 gene associated with CIPA in two unrelated Chinese families. The deletion of exon1-6 (g.1-1258_10169del) is thought to be the largest NTRK1 deletion reported to date. Our findings expand the mutation spectrum of NTRK1 mutations in the Chinese and could be useful for prenatal interventions and more precise pharmacological treatments to patients. WES conducted in our study is a convenient and useful tool for clinical diagnosis of CIPA and other associated disorders.
Small Molecule Cjoc42 Improves Chemo-Sensitivity and Increases Levels of Tumor Suppressor Proteins in Hepatoblastoma Cells and in Mice by Inhibiting Oncogene Gankyrin
Authors: D’Souza Amber M. , Cast Ashley , Kumbaji Meenasri , Rivas Maria , Gulati Ruhi , Johnston Michael , Smithrud David , Geller James , Timchenko Nikolai
Published: March 2021

Objective: Relapsed hepatoblastoma (HBL) and upfront hepatocellular carcinoma (HCC) are notoriously chemoresistant tumors associated with poor outcomes. Gankyrin (Gank) is a known oncogene that is overexpressed in pediatric liver cancer and implicated in chemo-resistance. The goal of this study was to evaluate if the Gank-tumor suppressor axis is activated in chemoresistant hepatoblastoma patients and examine if an inhibitor of Gank, Cjoc42, might improve the chemosensitivity of cancer cells.

Methods: Expression of Gank and its downstream targets were examined in fresh human HBL samples using immunostaining, QRT-PCR, and Western Blot. Cancer cells, Huh6 (human HBL) and Hepa1c1c7 (mouse HCC) were treated with Cjoc42 and with Cjoc42 in combination with cisplatin or doxorubicin. Cell proliferation, apoptosis, and chemoresistance were examined. To examine activities of Cjoc42 in vivo, mice were treated with different doses of Cjoc42, and biological activities of Gank and cytotoxicity of Cjoc42 were tested.

Results: Elevation of Gank and Gank-mediated elimination of TSPs are observed in patients with minimal necrosis after chemotherapy and relapsed disease. The treatment of Huh6 and Hepa1c1c7 with Cjoc42 was not cytotoxic; however, in combination with cisplatin or doxorubicin, Cjoc42 caused a significant increase in cytotoxicity compared to chemotherapy alone with increased apoptosis. Examination of Cjoc42 in WT mice showed that Cjoc42 is well tolerated without systemic toxicity, and levels of tumor suppressors CUGBP1, Rb, p53, C/EBPα, and HNF4α are increased by blocking their Gank-dependent degradation.

Conclusions: Our work shows that Cjoc42 might be a promising adjunct to chemotherapy for the treatment of severe pediatric liver cancer and presents mechanisms by which Cjoc42 increases chemo-sensitivity.
1,2,3,4,6-Pentagalloyl Glucose, a RBD-ACE2 Binding Inhibitor to Prevent SARS-CoV-2 Infection
Authors: Chen Rui Hong , Yang Li Jun , Hamdoun Sami , Chung Sookja Kim , Lam Christopher Wai-kei , Zhang Kai Xi , Guo Xiaoling , Xia Chenglai , Law Betty Yuen Kwan , Wong Vincent Kam Wai
Published: March 2021

The outbreak of SARS-CoV-2 virus caused more than 80,155,187 confirmed COVID-19 cases worldwide, which has posed a serious threat to global public health and the economy. The development of vaccines and discovery of novel drugs for COVID-19 are urgently needed. Although the FDA-approved SARS-CoV-2 vaccines has been launched in many countries recently, the strength of safety, stringent storage condition and the possibly short-term immunized efficacy remain as the major challenges in the popularity and recognition of using vaccines against SARS-CoV-2. With the spike-receptor binding domain (RBD) of SARS-CoV-2 being responsible for binding to human angiotensin-converting enzyme 2 receptor (hACE2), ACE2 is identified as the receptor for the entry and viral infection of SARS-CoV-2. In this study, molecular docking and biolayer interferometry (BLI) binding assay were adopted to determine the direct molecular interactions between natural small-molecule, 1,2,3,4,6-Pentagalloyl glucose (PGG) and the spike-RBD of the SARS-CoV-2. Our results showed that PGG preferentially binds to a pocket that contains residues Glu 340 to Lys 356 of spike-RBD with a relatively low binding energy of -8 kcal/mol. BLI assay further confirmed that PGG exhibits a relatively strong binding affinity to SARS-CoV-2-RBD protein in comparison to hACE2. In addition, both ELISA and immunocytochemistry assay proved that PGG blocks SARS-CoV-2-RBD binding to hACE2 dose dependently in cellular level. Notably, PGG was confirmed to abolish the infectious property of RBD-pseudotyped lentivirus in hACE2 overexpressing HEK293 cells, which mimicked the entry of wild type SARS-CoV-2 virus in human host cells. Finally, maximal tolerated dose (MTD) studies revealed that up to 200 mg/kg/day of PGG was confirmed orally safe in mice. Our findings suggest that PGG may be a safe and potential antiviral agent against the COVID-19 by blockade the fusion of SARS-CoV-2 spike-RBD to hACE2 receptors. Therefore, PGG may be considered as a safe and natural antiviral agent for its possible preventive application in daily anti-virus hygienic products such as a disinfectant spray or face mask.
Characterization of Crystalline CsPbBr3 Perovksite Dosimeters for Clinical Radiotherapy
Authors: Bruzzi Mara , Talamonti Cinzia
Published: March 2021

Lead halide perovskite CsPbBr3 is a wide-gap semiconductor material potentially very attractive for next generations of real-time monitors and particle detectors in high-energy physics. Here, we present the first characterization of crystalline CsPbBr3 point dosimeters with submillimeter size, under 6 MV X-photon beams used in clinical radiotherapy. Current response of the devices proved to be promising in terms of fast rise and decay times, of the same order of the X-ray beam onset and offset ones; absence of polarization effects; reproducibility to repeated irradiations; and linearity of the collected charge as a function of the absorbed dose. Comparing the measured sensitivity with the theoretical one, a charge collection distance of about 100 μm has been evaluated, of the same order of the linear dimensions of crystallites within the samples, suggesting that recombination centers are mainly placed at grain boundaries. A much higher sensitivity per unit area measured with crystalline CsPbBr3 as compared with drop-casted ones can be explained in terms of a less disordered crystalline structure. This work opens the way to CsPbBr3 point dosimeters, with linear dimensions meeting the strict spatial resolution constraints for bidimensional dose mapping required in clinical radiotherapy.
Life Satisfaction, Positive Affect, and Sleep Impairment in Masters Athletes: Modulation by Age, Sex, and Exercise Type
Authors: Wooten Savannah V. , Mittag Uwe , Alvero Cruz José Ramón , Stray-Gundersen Sten , Hoffmann Fabian , Michély Sarah , Möstl Stefan , Sies Wolfram , Mulder Edwin , Rauschendorfer Philipp , Chilibeck Philip D. , Rittweger Jörn , Tanaka Hirofumi
Published: March 2021

Introduction

The masters athlete has been proposed as a model of successful aging. Research studies investigating psychological outlook in older athletes have primarily addressed negative affects including depression, anxiety, and stress. The impact of lifelong exercise on positive affect and life satisfaction as well as sleep impairment that could impact on these psychological states is largely unknown.

Methods

A series of questionnaires (general life satisfaction, positive affect, and sleep-related impairment) were administered to 240 masters athletes participating in the World Masters Athletics Championships. Total raw scores were converted into T scores for comparison with the general population. Meaningful difference was defined by the PROMIS® as one-half standard deviation from the centering sample.

Results

Meaningful differences were observed for improved general life satisfaction and reduced sleep impairment for all masters athletes. Positive affect did not reach the meaningful difference threshold. No significant sex differences were found for any of the questionnaires (all p > 0.05). Similarly, no significant differences were found between endurance, sprint, and strength/power sports for general life satisfaction (p = 0.18), positive affect (p = 0.46), and sleep impairment (p = 0.77). In general, life satisfaction increased with age (r = 0.15, p = 0.02), and sleep impairment trended towards reduction with age (r = −0.13, p = 0.05). Positive affect demonstrated no correlation with age (r = 0.09, p = 0.18).

Conclusion

This study demonstrates that the lifestyles of masters athletes contribute to improved general life satisfaction and reduced sleep impairment but not improved positive affect. The beneficial effects were observed irrespective of age, gender, and sporting types.
Evolution and Functional Divergence of SUN Genes in Plants
Authors: Yuan Li , Pan Jingwen , Zhu Shouhong , Li Yan , Yao Jinbo , Li Qiulin , Fang Shengtao , Liu Chunyan , Wang Xinyu , Li Bei , Chen Wei , Zhang Yongshan
Published: March 2021

SUN-domain containing proteins are crucial nuclear membrane proteins involved in a plethora of biological functions, including meiosis, nuclear morphology, and embryonic development, but their evolutionary history and functional divergence are obscure. In all, 216 SUN proteins from protists, fungi, and plants were divided into two monophyletic clades (Cter-SUN and Mid-SUN). We performed comprehensive evolutionary analyses, investigating the characteristics of different subfamilies in plants. Mid-SUNs further evolved into two subgroups, SUN3 and SUN5, before the emergence of the ancestor of angiosperms, while Cter-SUNs retained one subfamily of SUN1. The two clades were distinct from each other in the conserved residues of the SUN domain, the TM motif, and exon/intron structures. The gene losses occurred with equal frequency between these two clades, but duplication events of Mid-SUNs were more frequent. In cotton, SUN3 proteins are primarily expressed in petals and stamens and are moderately expressed in other tissues, whereas SUN5 proteins are specifically expressed in mature pollen. Virus-induced knock-down and the CRISPR/Cas9-mediated knockout ofGbSUN5both showed higher ratios of aborted seeds, although pollen viability remained normal. Our results indicated divergence of biological function between SUN3 and SUN5, and that SUN5 plays an important role in reproductive development.
The Importance of Nature Exposure and Physical Activity for Psychological Health and Stress Perception: Evidence From the First Lockdown Period During the Coronavirus Pandemic 2020 in France and Germany
Authors: Javelle Florian , Laborde Sylvain , Hosang Thomas Jean , Metcalfe Alan James , Zimmer Philipp
Published: March 2021

Objective: This cross-sectional questionnaire-based study aims to compare physical activity and nature exposure levels between people living in France and Germany during the lockdown. Furthermore, the secondary aim is to observe the relationship between perceived stress, psychological health, physical activity, and nature exposure in Germany and France during the coronavirus disease 2019 (COVID-19)-related lockdown of April/May 2020.

Methods: The study includes 419 participants who have completed the Perceived Stress Scale 10, the World Health Organization Quality of Life-BREF, the Godin-Shephard Leisure-Time Physical Activity Questionnaire, the modified Nature Exposure Scale, and complementary questions related to the lockdown period from April 19 to May 11, 2020. Multiple regression models were constructed to evaluate the relationship of nature exposure and physical exercise with overall stress perception and psychological health in France and Germany when considering a broad range of covariates.

Results: Exposure to nature during the lockdown (ηp2 = 0.034, p < 0.001), amount of physical activity ηp2 = 0.014, p < 0.001), and psychological health (ηp2 = 0.041, p < 0.001) were greater in German compared with French participants. Godin Index and Nature Exposure Scale total score were both inversely correlated to stress perception and positively correlated to psychological health. The stress and psychological health regression models explained 10% of the results' variance. Physical activity (Godin Index) was a significant for both models. Nature Exposure Scale total score was a significant predictor only for psychological health. When including all significant covariates, the regression models explained 30.7% for the perceived stress and 42.1% for the psychological health total overall variance.

Conclusion: Physical activity and nature exposure are significant predictors of psychological health. Even though both variables are associated with stress perception, only physical activity is a significant predictor of stress perception. Our results suggest that physical activity and nature exposure were key factors to go through the lockdown period in France and Germany.
Attentional Bias to High-Calorie Food in Binge Eaters With High Shape/Weight Concern
Authors: Seo Chai Lee , Lee Jang-Han
Published: March 2021

Individuals with high shape/weight concern (SWC) place disproportionate emphasis on shape and weight in evaluating their self-worth, making them more vulnerable to body-related cues. Binge eaters (BE), who are obsessed with devouring high-calorie foods, would show severe symptomatology, especially when they have clinically high SWC. The present study attempted to elucidate how SWC influences binging based on attentional patterns toward high-calorie food cues. A total of 120 participants were selected and divided into four groups: (1) BE with high SWC, (2) BE with low SWC, (3) healthy controls (HC) with high SWC, and (4) HC with low SWC. BE and SWC status were respectively determined using the Eating Disorder Diagnostic Scale (DSM-5) and the Eating Disorder Examination Questionnaire. All participants completed the same free-viewing task, measuring initial fixation latency and total fixation duration. BE with high SWC showed attentional bias toward high-calorie food cues in terms of significantly faster initial fixation latency and longer total fixation duration, whereas BE with low SWC and the HC groups did not show any differences. The results revealed that SWC level makes unique contributions to BE's initial orienting bias toward and difficulty disengaging from high-calorie food cues. This may indicate that BE with high SWC merely worry about eating high-calorie food in a cognitive way, but not controlling actual binging behavior. The current study of attentional bias elucidated the role of SWC as a potential maintenance factor of being concerned and binging in BE.
German Farmers’ Attitudes on Adopting Autonomous Field Robots: An Empirical Survey
Authors: Rübcke von Veltheim Friedrich , Heise Heinke
Published: March 2021

Agricultural production methods in Europe are increasingly subject to public criticism from which many farmers suffer. This applies, among other areas, to the widespread use of pesticides. Autonomous field robots (AFR), as the next stage of agricultural automation, have the potential to farm more intensively and, at the same time, in a more environmentally friendly way. However, a certain skepticism towards autonomous systems is suspected among farmers. Whether farmers adopt a technology depends largely on their uncertainty about the consequences of its use and the resulting attitude on the adoption. In order to quantify the attitude on adopting AFR in Germany and to identify possible group differences within the population, 490 German farmers were surveyed using an online questionnaire, which is based on an extended version of the Unified Theory of Acceptance and Use of Technology (UTAUT). In the subsequent cluster analysis, the statements inquiring the intention to use AFR served as cluster-forming variables. As a result, three groups (“open-minded AFR supporters”, “convinced AFR adopters”, “reserved AFR interested”) could be identified according to their response behavior. Despite existing group differences, an overall attitude in favor of autonomous field robots was observed. The results complement the existing research with a further empirical study and provide interesting starting points for further analysis, field robot manufacturers, and political decision makers.
Multi-Objective Instance Weighting-Based Deep Transfer Learning Network for Intelligent Fault Diagnosis
Authors: Lee Kihoon , Han Soonyoung , Pham Van Huan , Cho Seungyon , Choi Hae-Jin , Lee Jiwoong , Noh Inwoong , Lee Sang Won
Published: March 2021

Fault diagnosis is a top-priority task for the health management of manufacturing processes. Deep learning-based methods are widely used to secure high fault diagnosis accuracy. Actually, it is difficult and expensive to collect large-scale data in industrial fields. Several prerequisite problems can be solved using transfer learning for fault diagnosis. Data from the source domain that are different but related to the target domain are used to increase the diagnosis performance of the target domain. However, a negative transfer occurs that degrades diagnosis performance due to the transfer when the discrepancy between and within domains is large. A multi-objective instance weighting-based transfer learning network is proposed to solve this problem and successfully applied to fault diagnosis. The proposed method uses a newly devised multi-objective instance weight to deal with practical situations where domain discrepancy is large. It adjusts the influence of the domain data on model training through two theoretically different indicators. Knowledge transfer is performed differentially by sorting instances similar to the target domain in terms of distribution with useful information for the target task. This domain optimization process maximizes the performance of transfer learning. A case study using an industrial robot and spot-welding testbed is conducted to verify the effectiveness of the proposed technique. The performance and applicability of transfer learning in the proposed method are observed in detail through the same case study as the actual industrial field for comparison. The diagnostic accuracy and robustness are high, even when few data are used. Thus, the proposed technique is a promising tool that can be used for successful fault diagnosis.
Construction of DNA Biosensors for Mercury (II) Ion Detection Based on Enzyme-Driven Signal Amplification Strategy
Authors: Wang Shuchang
Published: March 2021

Mercury ion (Hg2+) is a well-known toxic heavy metal ion. It is harmful for human health even at low concentrations in the environment. Therefore, it is very important to measure the level of Hg2+. Many methods, reviewed in several papers, have been established on DNA biosensors for detecting Hg2+. However, few reviews on the strategy of enzyme-driven signal amplification have been reported. In this paper, we reviewed this topic by dividing the enzymes into nucleases and DNAzymes according to their chemical nature. Initially, we introduce the nucleases including Exo III, Exo I, Nickase, DSN, and DNase I. In this section, the Exo III-driven signal amplification strategy was described in detail. Because Hg2+ can help ssDNA fold into dsDNA by T-Hg-T, and the substrate of Exo III is dsDNA, Exo III can be used to design Hg2+ biosensor very flexibly. Then, the DNAzyme-assisted signal amplification strategies were reviewed in three categories, including UO22+-specific DNAzymes, Cu2+-specific DNAzymes and Mg2+-specific DNAzymes. In this section, the Mg2+-specific DNAzyme was introduced in detail, because this DNAzyme has highly catalytic activity, and Mg2+ is very common ion which is not harmful to the environment. Finally, the challenges and future perspectives were discussed.
Research on a Multi-Parameter Fusion Prediction Model of Pressure Relief Gas Concentration Based on RNN
Authors: Song Shuang , Li Shugang , Zhang Tianjun , Ma Li , Pan Shaobo , Gao Lu
Published: March 2021

The effective prediction of gas concentration and the reasonable formulation of corresponding safety measures have important significance for improving the level of coal mine safety. To improve the accuracy of gas concentration prediction and enhance the applicability of the models, this paper starts with actual coal mine production monitoring data, improves the accuracy of gas concentration prediction through multi-parameter fusion prediction, and constructs a recurrent neural network (RNN)-based multi-parameter fusion prediction of coal face gas concentration. We determined the performance evaluation index of the model’s prediction method; used the grid search method to optimize the hyperparameters of the batch size; and used the number of neurons, the learning rate, the discard ratio, the network depth, and the early stopping method to prevent overfitting. The gas concentration prediction models—based on RNN and PSO-SVR and PSO-Adam-BP neural networks—were compared and analyzed experimentally with the mean absolute percentage error (MAPE) as the performance evaluation index. The result show that using the grid search method to adjust the batch size, the number of neurons, the learning rate, the discard ratio, and the network depth can effectively find the optimal hyperparameter combination. The training error can be reduced to 0.0195. Therefore, Adam’s optimized RNN gas concentration prediction model had higher accuracy and stability than the BP neural network and SVR. During training, the mean absolute error (MAE) could be reduced to 0.0573, and the root mean squared error (RMSE) could be reduced to 0.0167; however, the MAPE could be reduced to 0.3384% during prediction. The RNN gas concentration prediction model and parameter optimization method based on Adam optimization can effectively predict gas concentration. This method shows high accuracy in the prediction of gas concentration time series and can be used as a reference model for predicting mine gas concentration.
Analysis of Aeroacoustic Properties of the Local Radial Point Interpolation Cumulant Lattice Boltzmann Method
Authors: Gorakifard Mohsen , Salueña Clara , Cuesta Ildefonso , Far Ehsan Kian
Published: March 2021

The lattice Boltzmann method (LBM) has recently been used to simulate wave propagation, one of the challenging aspects of wind turbine modeling and simulation. However, standard LB methods suffer from the instability that occurs at low viscosities and from its characteristic lattice uniformity, which results in issues of accuracy and computational efficiency following mesh refinement. The local radial point interpolation cumulant lattice Boltzmann method (LRPIC-LBM) is proposed in this paper to overcome these shortcomings. The LB equation is divided into collision and streaming steps. The collision step is modeled by the cumulant method, one of the stable LB methods at low viscosities. In addition, the streaming step, which is naturally a pure advection equation, is discretized in time and space using the Lax–Wendroff scheme and the local radial point interpolation method (RPIM), a mesh free method. We describe the propagation of planar acoustic waves, including the temporal decay of a standing plane wave and the spatial decay of a planar acoustic pulse. The analysis of these specific benchmark problems has yielded qualitative and quantitative data on acoustic dispersion and dissipation, and their deviation from analytical results demonstrates the accuracy of the method. We found that the LRPIC-LBM replicates the analytical results for different viscosities, and the errors of the fundamental acoustic properties are negligible, even for quite low resolutions. Thus, this method may constitute a useful platform for effectively predicting complex engineering problems such as wind turbine simulations, without parameter dependencies such as the number of points per wavelength Nppw and resolution σ or the detrimental effect caused by the use of coarse grids found in other accurate and stable LB models.
Examination of Selected Physicochemical Properties of Biodiesel after Electron Beam Sterilization in Flow System
Authors: Grabowski Paweł , Jarosiński Przemysław
Published: March 2021

The problem of microbial growth in fuels, especially biofuels, is a very important issue. Water is a necessity for microbial growth to occur. Unfortunately, it is very hard to exclude all water from fuel systems during daily operations, especially when biodiesel is added to the fuel mix. The aim of this work was to investigate the impact of ionizing radiation on selected properties of fatty acids methyl esters in order to evaluate the possibility of using irradiation techniques to sterilize biodiesel and its blends. Ionizing radiation influences the chemical composition of biodiesel samples containing especially unsaturated bonds. Irradiation was performed in a specially designed flow system. The tested parameters were compared with the normative values from the ISO 14214 standard. Density, kinematic viscosity, flash point, water content and cold filter plugging point as a macroscopic parameters do not change despite their irradiation with ionizing radiation. Change was observed in microscopic parameters as oxidation stability and esters content. During irradiation, Rapeseed Methyl Ester (RME) samples formed oxidation products, which lower the oxidative stability. It was observed that, for esters content, requirements of the standard could be met in the case of using very small doses. In the case of RME samples saturated with water, the changes in the ester concentration were smaller, but the resulting products decreased the oxidation stability. Sterilization fatty acids methyl esters (FAME) was observed with the use of e beam radiation is to apply very low doses (up to 2 kGy) in a flow system without adding water. Sterilization FAME saturated by water requires the use of higher doses of radiation, which adversely affects the oxidative stability.