bluuebunny/crossref_metadata_2025 huggingface dataset:
The Proteasome Inhibitor Bortezomib Induces Apoptosis and Activation in Gel-Filtered Human Platelets
Authors: Ghansah Harriet , Debreceni Ildikó Beke , Fejes Zsolt , Nagy Béla , Kappelmayer János
Published: August 2021

Bortezomib (BTZ) has demonstrated its efficacy in several hematological disorders and has been associated with thrombocytopenia. There is controversy about the effect of BTZ on human platelets, so we set out to determine its effect on various types of platelet samples. Human platelets were investigated in platelet-rich plasma (PRP) and as gel-filtered platelets (GFPs). Mitochondrial inner membrane potential depolarization and phosphatidylserine (PS) and P-selectin expression levels were studied by flow cytometry, while thrombin generation was measured by a fluorescent method. In PRP, BTZ caused negligible PS expression after 60 min of treatment. However, in GFPs, PS expression was dose- and time-dependently increased in the BTZ-treated groups, as was P-selectin. The percentage of depolarized cells was also higher after BTZ pretreatment at both time points. Peak thrombin and velocity index increased significantly even with the lowest BTZ concentration (p = 0.0019; p = 0.0032) whereas time to peak and start tail parameters decreased (p = 0.0007; p = 0.0034). The difference between PRP and GFP results can be attributed to the presence of plasma proteins in PRP, as the PS-stimulating effect of BTZ could be attenuated by supplementing GFPs with purified human albumin. Overall, BTZ induces a procoagulant platelet phenotype in an experimental setting devoid of plasma proteins.
Role of β-Adrenergic Receptors and Estrogen in Cardiac Repair after Myocardial Infarction: An Overview
Authors: Matarrese Paola , Maccari Sonia , Vona Rosa , Gambardella Lucrezia , Stati Tonino , Marano Giuseppe
Published: August 2021

Acute myocardial infarction (MI) is associated with an intense inflammatory response that is critical for cardiac repair but is also involved in the pathogenesis of adverse cardiac remodeling, i.e., the set of size, geometry, and structure changes that represent the structural substrate for the development of post-MI heart failure. Deciphering the pathophysiological mechanisms underlying cardiac repair after MI is, therefore, critical to favorably regulate cardiac wound repair and to prevent development of heart failure. Catecholamines and estrogen play an active role in regulating the inflammatory response in the infarcted area. For example, stress-induced catecholamines alter recruitment and trafficking of leukocytes to the heart. Additionally, estrogen affects rate of cardiac rupture during the acute phase of MI, as well as infarct size and survival in animal models of MI. In this review, we will summarize the role of β-adrenergic receptors and estrogen in cardiac repair after infarction in preclinical studies.
iBitter-Fuse: A Novel Sequence-Based Bitter Peptide Predictor by Fusing Multi-View Features
Authors: Charoenkwan Phasit , Nantasenamat Chanin , Hasan Md. Mehedi , Moni Mohammad Ali , Lio’ Pietro , Shoombuatong Watshara
Published: August 2021

Accurate identification of bitter peptides is of great importance for better understanding their biochemical and biophysical properties. To date, machine learning-based methods have become effective approaches for providing a good avenue for identifying potential bitter peptides from large-scale protein datasets. Although few machine learning-based predictors have been developed for identifying the bitterness of peptides, their prediction performances could be improved. In this study, we developed a new predictor (named iBitter-Fuse) for achieving more accurate identification of bitter peptides. In the proposed iBitter-Fuse, we have integrated a variety of feature encoding schemes for providing sufficient information from different aspects, namely consisting of compositional information and physicochemical properties. To enhance the predictive performance, the customized genetic algorithm utilizing self-assessment-report (GA-SAR) was employed for identifying informative features followed by inputting optimal ones into a support vector machine (SVM)-based classifier for developing the final model (iBitter-Fuse). Benchmarking experiments based on both 10-fold cross-validation and independent tests indicated that the iBitter-Fuse was able to achieve more accurate performance as compared to state-of-the-art methods. To facilitate the high-throughput identification of bitter peptides, the iBitter-Fuse web server was established and made freely available online. It is anticipated that the iBitter-Fuse will be a useful tool for aiding the discovery and de novo design of bitter peptides.
Effects of Primary Mast Cell Disease on Hemostasis and Erythropoiesis
Authors: Seidel Holger , Hertfelder Hans-Jörg , Oldenburg Johannes , Kruppenbacher Johannes P. , Afrin Lawrence B. , Molderings Gerhard J.
Published: August 2021

Mast cell disease is an epigenetically and genetically determined disease entity with very diverse clinical manifestations in potentially every system and tissue due to inap pro priate release of variable subsets of mast cell mediators together with accumulation of either morphologically normal or altered mast cells. Easy bruising, excessive bleeding, and aberrancies of erythropoiesis can frequently be observed in patients with mast cell disease. A thorough history, including a family history, will guide the appropriate work-up, and laboratory evaluations may provide clues to diagnosis. In recent years, our understanding of the involvement of coagulation and anticoagulant pathways, the fibrinolytic system, and erythropoiesis in the pathophysiology of mast cell disease has increased considerably. This review summarizes current knowledge of the impact of the disturbed hemostatic and erythropoietic balance in patients with mast cell disease and describes options of treatment.
The CB2 Receptor as a Novel Therapeutic Target for Epilepsy Treatment
Authors: Ji Xiaoyu , Zeng Yang , Wu Jie
Published: August 2021

Epilepsy is characterized by repeated spontaneous bursts of neuronal hyperactivity and high synchronization in the central nervous system. It seriously affects the quality of life of epileptic patients, and nearly 30% of individuals are refractory to treatment of antiseizure drugs. Therefore, there is an urgent need to develop new drugs to manage and control refractory epilepsy. Cannabinoid ligands, including selective cannabinoid receptor subtype (CB1 or CB2 receptor) ligands and non-selective cannabinoid (synthetic and endogenous) ligands, may serve as novel candidates for this need. Cannabinoid appears to regulate seizure activity in the brain through the activation of CB1 and CB2 cannabinoid receptors (CB1R and CB2R). An abundant series of cannabinoid analogues have been tested in various animal models, including the rat pilocarpine model of acquired epilepsy, a pentylenetetrazol model of myoclonic seizures in mice, and a penicillin-induced model of epileptiform activity in the rats. The accumulating lines of evidence show that cannabinoid ligands exhibit significant benefits to control seizure activity in different epileptic models. In this review, we summarize the relationship between brain CB2 receptors and seizures and emphasize the potential mechanisms of their therapeutic effects involving the influences of neurons, astrocytes, and microglia cells. The unique features of CB2Rs, such as lower expression levels under physiological conditions and high inducibility under epileptic conditions, make it an important target for future research on drug-resistant epilepsy.
“Molecular Masks” for ACE2 to Effectively and Safely Block SARS-CoV-2 Virus Entry
Authors: Shukla Satya , Cho Kwang , Rustagi Vineeta , Gao Xiang , Fu Xinping , Zhang Shaun , Guo Bin , Udugamasooriya D.
Published: August 2021

Coronavirus Disease 2019 (COVID-19) remains a global health crisis, despite the development and success of vaccines in certain countries. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, uses its spike protein to bind to the human cell surface receptor angiotensin-converting enzyme 2 (ACE2), which allows the virus to enter the human body. Using our unique cell screening technology, we identified two ACE2-binding peptoid compounds and developed dimeric derivatives (ACE2P1D1 and ACE2P2D1) that effectively blocked spike protein-ACE2 interaction, resulting in the inhibition of SARS-CoV-2 pseudovirus entry into human cells. ACE2P1D1 and ACE2P2D1 also blocked infection by a D614G mutant pseudovirus. More importantly, these compounds do not decrease ACE2 expression nor its enzyme activity (which is important in normal blood pressure regulation), suggesting safe applicability in humans
The Structural Characterization and Antipathogenic Activities of Quinoin, a Type 1 Ribosome-Inactivating Protein from Quinoa Seeds
Authors: Ragucci Sara , Bulgari Daniela , Landi Nicola , Russo Rosita , Clemente Angela , Valletta Mariangela , Chambery Angela , Gobbi Emanuela , Faoro Franco , Di Maro Antimo
Published: August 2021

Quinoin is a type 1 ribosome-inactivating protein (RIP) we previously isolated from the seeds of pseudocereal quinoa (Chenopodium quinoa) and is known as a functional food for its beneficial effects on human health. As the presence of RIPs in edible plants could be potentially risky, here we further characterised biochemically the protein (complete amino acid sequence, homologies/differences with other RIPs and three-dimensional homology modeling) and explored its possible defensive role against pathogens. Quinoin consists of 254 amino acid residues, without cysteinyl residues. As demonstrated by similarities and homology modeling, quinoin preserves the amino acid residues of the active site (Tyr75, Tyr122, Glu177, Arg180, Phe181 and Trp206; quinoin numbering) and the RIP-fold characteristic of RIPs. The polypeptide chain of quinoin contains two N-glycosylation sites at Asn115 and Asp231, the second of which appears to be linked to sugars. Moreover, by comparative MALDI-TOF tryptic peptide mapping, two differently glycosylated forms of quinoin, named pre-quinoin-1 and pre-quinoin-2 (~0.11 mg/100 g and ~0.85 mg/100 g of seeds, respectively) were characterised. Finally, quinoin possesses: (i) strong antiviral activity, both in vitro and in vivo towards Tobacco Necrosis Virus (TNV); (ii) a growth inhibition effect on the bacterial pathogens of plants; and (iii) a slight antifungal effect against two Cryphonectria parasitica strains.
C-Type Natriuretic Peptide Ameliorates Vascular Injury and Improves Neurological Outcomes in Neonatal Hypoxic-Ischemic Brain Injury in Mice
Authors: Shen Guofang , Hu Shirley , Zhao Zhen , Zhang Lubo , Ma Qingyi
Published: August 2021

C-type natriuretic peptide (CNP) is an important vascular regulator that is present in the brain. Our previous study demonstrated the innate neuroprotectant role of CNP in the neonatal brain after hypoxic-ischemic (HI) insults. In this study, we further explored the role of CNP in cerebrovascular pathology using both in vivo and in vitro models. In a neonatal mouse HI brain injury model, we found that intracerebroventricular administration of recombinant CNP dose-dependently reduces brain infarct size. CNP significantly decreases brain edema and immunoglobulin G (IgG) extravasation into the brain tissue, suggesting a vasculoprotective effect of CNP. Moreover, in primary brain microvascular endothelial cells (BMECs), CNP dose-dependently protects BMEC survival and monolayer integrity against oxygen-glucose deprivation (OGD). The vasculoprotective effect of CNP is mediated by its innate receptors NPR2 and NPR3, in that inhibition of either NPR2 or NPR3 counteracts the protective effect of CNP on IgG leakage after HI insult and BMEC survival under OGD. Of importance, CNP significantly ameliorates brain atrophy and improves neurological deficits after HI insults. Altogether, the present study indicates that recombinant CNP exerts vascular protection in neonatal HI brain injury via its innate receptors, suggesting a potential therapeutic target for the treatment of neonatal HI brain injury.
Aflatoxin Exposure during Early Life Is Associated with Differential DNA Methylation in Two-Year-Old Gambian Children
Authors: Ghantous Akram , Novoloaca Alexei , Bouaoun Liacine , Cuenin Cyrille , Cros Marie-Pierre , Xu Ya , Hernandez-Vargas Hector , Darboe Momodou K. , Prentice Andrew M. , Moore Sophie E. , Gong Yun Yun , Herceg Zdenko , Routledge Michael N.
Published: August 2021

Background: DNA methylation is an epigenetic control mechanism that may be altered by environmental exposures. We have previously reported that in utero exposure to the mycotoxin and liver carcinogen aflatoxin B1 from the maternal diet, as measured using biomarkers in the mothers’ blood, was associated with differential DNA methylation in white blood cells of 6-month-old infants from The Gambia. Methods: Here we examined aflatoxin B1-associated differential DNA methylation in white blood cells of 24-month-old children from the same population (n = 244), in relation to the child’s dietary exposure assessed using aflatoxin albumin biomarkers in blood samples collected at 6, 12 and 18 months of age. HM450 BeadChip arrays were used to assess DNA methylation, with data compared to aflatoxin albumin adduct levels using two approaches; a continuous model comparing aflatoxin adducts measured in samples collected at 18 months to DNA methylation at 24 months, and a categorical time-dose model that took into account aflatoxin adduct levels at 6, 12 and 18 months, for comparison to DNA methylation at 24 months. Results: Geometric mean (95% confidence intervals) for aflatoxin albumin levels were 3.78 (3.29, 4.34) at 6 months, 25.1 (21.67, 29.13) at 12 months and 49.48 (43.34, 56.49) at 18 months of age. A number of differentially methylated CpG positions and regions were associated with aflatoxin exposure, some of which affected gene expression. Pathway analysis highlighted effects on genes involved with with inflammatory, signalling and growth pathways. Conclusions: This study provides further evidence that exposure to aflatoxin in early childhood may impact on DNA methylation.
The Role of Mutant p63 in Female Fertility
Authors: Luan Yi , Xu Pauline , Yu Seok-Yeong , Kim So-Youn
Published: August 2021

The transcription factor p63, one of the p53 family members, plays an essential role in regulating maternal reproduction and genomic integrity as well as epidermal development. TP63 (human)/Trp63 (mouse) produces multiple isoforms: TAp63 and ΔNp63, which possess a different N-terminus depending on two different promoters, and p63a, p63b, p63g, p63δ, and p63ε as products of alternative splicing at the C-terminus. TAp63 expression turns on in the nuclei of primordial germ cells in females and is maintained mainly in the oocyte nuclei of immature follicles. It has been established that TAp63 is the genomic guardian in oocytes of the female ovaries and plays a central role in determining the oocyte fate upon oocyte damage. Lately, there is increasing evidence that TP63 mutations are connected with female infertility, including isolated premature ovarian insufficiency (POI) and syndromic POI. Here, we review the biological functions of p63 in females and discuss the consequences of p63 mutations, which result in infertility in human patients.
Adiponectin and Asthma: Knowns, Unknowns and Controversies
Authors: Otelea Marina Ruxandra , Arghir Oana Cristina , Zugravu Corina , Rascu Agripina
Published: August 2021

Adiponectin is an adipokine associated with the healthy obese phenotype. Adiponectin increases insulin sensitivity and has cardio and vascular protection actions. Studies related to adiponectin, a modulator of the innate and acquired immunity response, have suggested a role of this molecule in asthma. Studies based on various asthma animal models and on the key cells involved in the allergic response have provided important insights about this relation. Some of them indicated protection and others reversed the balance towards negative effects. Many of them described the cellular pathways activated by adiponectin, which are potentially beneficial for asthma prevention or for reduction in the risk of exacerbations. However, conclusive proofs about their efficiency still need to be provided. In this article, we will, briefly, present the general actions of adiponectin and the epidemiological studies supporting the relation with asthma. The main focus of the current review is on the mechanisms of adiponectin and the impact on the pathobiology of asthma. From this perspective, we will provide arguments for and against the positive influence of this molecule in asthma, also indicating the controversies and sketching out the potential directions of research to complete the picture.
Understanding Starch Metabolism in Pea Seeds towards Tailoring Functionality for Value-Added Utilization
Authors: Yu Bianyun , Xiang Daoquan , Mahfuz Humaira , Patterson Nii , Bing Dengjin
Published: August 2021

Starch is the most abundant storage carbohydrate and a major component in pea seeds, accounting for about 50% of dry seed weight. As a by-product of pea protein processing, current uses for pea starch are limited to low-value, commodity markets. The globally growing demand for pea protein poses a great challenge for the pea fractionation industry to develop new markets for starch valorization. However, there exist gaps in our understanding of the genetic mechanism underlying starch metabolism, and its relationship with physicochemical and functional properties, which is a prerequisite for targeted tailoring functionality and innovative applications of starch. This review outlines the understanding of starch metabolism with a particular focus on peas and highlights the knowledge of pea starch granule structure and its relationship with functional properties, and industrial applications. Using the currently available pea genetics and genomics knowledge and breakthroughs in omics technologies, we discuss the perspectives and possible avenues to advance our understanding of starch metabolism in peas at an unprecedented level, to ultimately enable the molecular design of multi-functional native pea starch and to create value-added utilization.
Simple and Rapid Method for Wogonin Preparation and Its Biotransformation
Authors: Tronina Tomasz , Mrozowska Monika , Bartmańska Agnieszka , Popłoński Jarosław , Sordon Sandra , Huszcza Ewa
Published: August 2021

Wogonin is one of the most active flavonoids from Scutellaria baicalensis Georgi (baikal skullcap), widely used in traditional Chinese medicine. It exhibits a broad spectrum of health-promoting and therapeutic activities. Together with baicalein, it is considered to be the one of main active ingredients of Chinese medicines for the management of COVID-19. However, therapeutic use of wogonin may be limited due to low market availability connected with its low content in baikal skullcap and lack of efficient preparative methods for obtaining this compound. Although the amount of wogonin in skullcap root often does not exceed 0.5%, this material is rich in wogonin glucuronide, which may be used as a substrate for wogonin production. In the present study, a rapid, simple, cheap and effective method of wogonin and baicalein preparation, which provides gram quantities of both flavonoids, is proposed. The obtained wogonin was used as a substrate for biotransformation. Thirty-six microorganisms were tested in screening studies. The most efficient were used in enlarged scale transformations to determine metabolism of this xenobiotic. The major phase I metabolism product was 4′-hydroxywogonin—a rare flavonoid which exhibits anticancer activity—whereas phase II metabolism products were glucosides of wogonin. The present studies complement and extend the knowledge on the effect of substitution of A- and B-ring on the regioselective glycosylation of flavonoids catalyzed by microorganisms.
GPCR Partners as Cancer Driver Genes: Association with PH-Signal Proteins in a Distinctive Signaling Network
Authors: Nag Jeetendra Kumar , Malka Hodaya , Appasamy Priyanga , Sedley Shoshana , Bar-Shavit Rachel
Published: August 2021

The essential role of G-protein coupled receptors (GPCRs) in tumor growth is recognized, yet a GPCR based drug in cancer is rare. Understanding the molecular path of a tumor driver gene may lead to the design and development of an effective drug. For example, in members of protease-activated receptor (PAR) family (e.g., PAR1 and PAR2), a novel PH-binding motif is allocated as critical for tumor growth. Animal models have indicated the generation of large tumors in the presence of PAR1 or PAR2 oncogenes. These tumors showed effective inhibition when the PH-binding motif was either modified or were inhibited by a specific inhibitor targeted to the PH-binding motif. In the second part of the review we discuss several aspects of some cardinal GPCRs in tumor angiogenesis.
Mitochondrial Dysfunction in Vascular Wall Cells and Its Role in Atherosclerosis
Authors: Salnikova Diana , Orekhova Varvara , Grechko Andrey , Starodubova Antonina , Bezsonov Evgeny , Popkova Tatyana , Orekhov Alexander
Published: August 2021

Altered mitochondrial function is currently recognized as an important factor in atherosclerosis initiation and progression. Mitochondrial dysfunction can be caused by mitochondrial DNA (mtDNA) mutations, which can be inherited or spontaneously acquired in various organs and tissues, having more or less profound effects depending on the tissue energy status. Arterial wall cells are among the most vulnerable to mitochondrial dysfunction due to their barrier and metabolic functions. In atherosclerosis, mitochondria cause alteration of cellular metabolism and respiration and are known to produce excessive amounts of reactive oxygen species (ROS) resulting in oxidative stress. These processes are involved in vascular disease and chronic inflammation associated with atherosclerosis. Currently, the list of known mtDNA mutations associated with human pathologies is growing, and many of the identified mtDNA variants are being tested as disease markers. Alleviation of oxidative stress and inflammation appears to be promising for atherosclerosis treatment. In this review, we discuss the role of mitochondrial dysfunction in atherosclerosis development, focusing on the key cell types of the arterial wall involved in the pathological processes. Accumulation of mtDNA mutations in isolated arterial wall cells, such as endothelial cells, may contribute to the development of local inflammatory process that helps explaining the focal distribution of atherosclerotic plaques on the arterial wall surface. We also discuss antioxidant and anti-inflammatory approaches that can potentially reduce the impact of mitochondrial dysfunction.
Macrophage Motility in Wound Healing Is Regulated by HIF-1α via S1P Signaling
Authors: Hutami Islamy Rahma , Izawa Takashi , Khurel-Ochir Tsendsuren , Sakamaki Takuma , Iwasa Akihiko , Tanaka Eiji
Published: August 2021

Accumulating evidence indicates that the molecular pathways mediating wound healing induce cell migration and localization of cytokines to sites of injury. Macrophages are immune cells that sense and actively respond to disturbances in tissue homeostasis by initiating, and subsequently resolving, inflammation. Hypoxic conditions generated at a wound site also strongly recruit macrophages and affect their function. Hypoxia inducible factor (HIF)-1α is a transcription factor that contributes to both glycolysis and the induction of inflammatory genes, while also being critical for macrophage activation. For the latter, HIF-1α regulates sphingosine 1-phosphate (S1P) to affect the migration, activation, differentiation, and polarization of macrophages. Recently, S1P and HIF-1α have received much attention, and various studies have been performed to investigate their roles in initiating and resolving inflammation via macrophages. It is hypothesized that the HIF-1α/S1P/S1P receptor axis is an important determinant of macrophage function under inflammatory conditions and during disease pathogenesis. Therefore, in this review, biological regulation of monocytes/macrophages in response to circulating HIF-1α is summarized, including signaling by S1P/S1P receptors, which have essential roles in wound healing.
SAG-DTA: Prediction of Drug–Target Affinity Using Self-Attention Graph Network
Authors: Zhang Shugang , Jiang Mingjian , Wang Shuang , Wang Xiaofeng , Wei Zhiqiang , Li Zhen
Published: August 2021

The prediction of drug–target affinity (DTA) is a crucial step for drug screening and discovery. In this study, a new graph-based prediction model named SAG-DTA (self-attention graph drug–target affinity) was implemented. Unlike previous graph-based methods, the proposed model utilized self-attention mechanisms on the drug molecular graph to obtain effective representations of drugs for DTA prediction. Features of each atom node in the molecular graph were weighted using an attention score before being aggregated as molecule representation. Various self-attention scoring methods were compared in this study. In addition, two pooing architectures, namely, global and hierarchical architectures, were presented and evaluated on benchmark datasets. Results of comparative experiments on both regression and binary classification tasks showed that SAG-DTA was superior to previous sequence-based or other graph-based methods and exhibited good generalization ability.
Goal-Driven Visual Question Generation from Radiology Images
Authors: Sarrouti Mourad , Ben Abacha Asma , Demner-Fushman Dina
Published: August 2021

Visual Question Generation (VQG) from images is a rising research topic in both fields of natural language processing and computer vision. Although there are some recent efforts towards generating questions from images in the open domain, the VQG task in the medical domain has not been well-studied so far due to the lack of labeled data. In this paper, we introduce a goal-driven VQG approach for radiology images called VQGRaD that generates questions targeting specific image aspects such as modality and abnormality. In particular, we study generating natural language questions based on the visual content of the image and on additional information such as the image caption and the question category. VQGRaD encodes the dense vectors of different inputs into two latent spaces, which allows generating, for a specific question category, relevant questions about the images, with or without their captions. We also explore the impact of domain knowledge incorporation (e.g., medical entities and semantic types) and data augmentation techniques on visual question generation in the medical domain. Experiments performed on the VQA-RAD dataset of clinical visual questions showed that VQGRaD achieves 61.86% BLEU score and outperforms strong baselines. We also performed a blinded human evaluation of the grammaticality, fluency, and relevance of the generated questions. The human evaluation demonstrated the better quality of VQGRaD outputs and showed that incorporating medical entities improves the quality of the generated questions. Using the test data and evaluation process of the ImageCLEF 2020 VQA-Med challenge, we found that relying on the proposed data augmentation technique to generate new training samples by applying different kinds of transformations, can mitigate the lack of data, avoid overfitting, and bring a substantial improvement in medical VQG.
Crumb Rubber in Concrete—The Barriers for Application in the Construction Industry
Authors: Kara De Maeijer Patricia , Craeye Bart , Blom Johan , Bervoets Lieven
Published: August 2021

This state-of-the-art review was aimed to conduct a comprehensive literature survey to summarize experiences of crumb rubber (CR) application in concrete within the last 30 years. It shows that certain gaps prevent obtaining a coherent overview of both mechanical behaviour and environmental impact of crumb rubber concrete (CRC) to object to the stereotypes which prevent to use of CR in concrete in the construction industry. Currently, four major barriers can be distinguished for a successful CR application in the concrete industry: (1) the cost of CR recycling, (2) mechanical properties reduction, (3) insufficient research about leaching criteria and ecotoxicological risks and (4) recyclability of CRC. The application of CR in concrete has certainly its advantages and in general cannot be ignored by the construction industry. CR can be applied, for example, as an alternative material to replace natural aggregates and CRC can be used as recycled concrete aggregates (RCA) in the future. A certain diversity for the CR application can be introduced in a more efficient way when surface treatment and concrete mix design optimization are properly developed for each type of CR application in concrete for possible field applications. The role of CRC should not be limited to structures that are less dependent on strength.
Comparing the Cost of Rigid and Flexible Aircraft Pavements Using a Parametric Whole of Life Cost Analysis
Authors: White Greg
Published: August 2021

The construction and maintenance costs, as well as the residual value, were calculated for structurally equivalent rigid and flexible airfield pavements, for a range of typical commercial aircraft, as well as a range for typical subgrade conditions. Whole of life cost analysis was performed for a range of analysis periods, from 40 years to 100 years. For the standard 40-year analysis period and a residual value based on rigid pavement reconstruction, the rigid pavements had a 40% to 105% higher whole of life cost than equivalent flexible pavements, although this comparison is limited to the pavement compositions and material cost rates adopted. However, longer analysis periods had a significant impact on the relative whole of life cost, although the rigid pavements always had a higher cost than the flexible pavements. The assumed condition of the rigid pavement at the end of the design life was the most influential factor, with a 60-year service life resulting in the rigid pavements having a lower whole of life cost than the flexible pavements, but assuming a requirement for expedient rigid pavement reconstruction resulted in the rigid pavements costing approximately 4–6 times the cost of the flexible pavements over the 40-year analysis period.
Changes in Eyelid Pressure and Dry Eye Status after Orbital Decompression in Thyroid Eye Disease
Authors: Takahashi Yasuhiro , Vaidya Aric , Kakizaki Hirohiko
Published: August 2021

The aim of this prospective observational study was to examine changes in eyelid pressure and dry eye status after orbital decompression in thyroid eye disease (TED). In 16 patients (29 sides), upper eyelid pressure at plateau phase and maximum pressure were measured. TED status was evaluated through the Hertel exophthalmometric value and margin reflex distance (MRD)-1 and 2. Dry eye status was quantified through corneal fluorescein staining, tear break-up time, Schirmer test I results, meibomian gland dysfunction (MGD), tear meniscus height, and superior limbic keratoconjunctivitis (SLK). Patients were classified into two groups: patients with decreased eyelid pressure (Group 1) and those with elevated pressure (Group 2). Consequently, neither the maximum upper eyelid pressure nor pressure at plateau phase significantly changed after surgery (p > 0.050). Some parameters about MGD improved after surgery, but the other parameters on dry eye, MGD, and SLK worsened or did not change. MRD-1 decreased more (p = 0.028), and the ratio of patients in whom SLK improved after surgery was larger in Group 1 (p = 0.030). These results indicate that upper eyelid pressure tends to decrease postoperatively in patients with a high upper eyelid position, resulting in improvement of SLK.
Social Distancing during COVID-19 Pandemic among Inflammatory Bowel Disease Patients
Authors: Łodyga Michał , Maciejewska Katarzyna , Eder Piotr , Waszak Katarzyna , Stawczyk-Eder Kamila , Dobrowolska Agnieszka , Kaczka Aleksandra , Gąsiorowska Anita , Stępień-Wrochna Beata , Cicha Małgorzata , Rydzewska Grażyna
Published: August 2021

(1) Background: Social distancing rules have been widely introduced in the fight against the coronavirus disease 2019 (COVID-19) pandemic. So far, the effectiveness of these methods has not been assessed in the group of inflammatory bowel disease (IBD) patients. (2) Methods: The study included 473 patients with IBD who made 1180 hospital visits from 1 May to 30 September 2020. During each visit, the patients completed a five-step, progressive scale that was developed to assess the degree of social isolation. In parallel, other demographic data were collected and the concentrations of anti-severe acute respiratory coronavirus 2 (SARS-CoV-2) IgG and IgM+IgA antibodies were measured using the ELISA method. (3) Results: The study found a significant correlation between the degree of social distancing and the presence of anti-SARS-CoV-2 antibodies in the groups with the lowest degree of isolation (3 to 5). (4) Conclusions: Maintaining social distancing is an effective method for reducing the spread of SARS-CoV-2 virus among IBD patients.
Application of a Global Multiparameter Scoring System for the Prenatal Prediction of Coarctation of the Aorta
Authors: Gómez-Montes Enery , Herraiz García Ignacio , Escribano Abad David , Rodríguez Calvo Jesús , Villalaín González Cecilia , Galindo Izquierdo Alberto
Published: August 2021

To assess prospectively the capability of our previously reported global multiparameter scoring system to predict coarctation of the aorta (CoAo) in fetuses with cardiac asymmetry, we applied and analyzed the performance of our scoring system in predicting postnatal CoAo in fetuses undergoing prenatal echocardiographic assessment because of cardiac asymmetry between 2011 and 2021, and we determined the cut-off points of the score with the best balance between specificity and sensitivity, and of maximum sensitivity and specificity. CoAo was confirmed in 39/179 newborns (21.8%). We found a significantly higher probability of CoAo in fetuses with CoAo than in cases without CoAo (84.2 ± 18.2% vs. 26.0 ± 28.6%, p < 0.001). The AUC of the ROC of the score was 0.93 (95% CI 0.89–0.97). The cut-off value with the best balance between specificity and sensitivity was a predicted risk of ≥53% (sensitivity 92.3% and specificity 80.0%). The cut-off point of maximum sensitivity was ≥35% (sensitivity 100% and specificity 72.9%), and that of maximum specificity was ≥96% (sensitivity 43.6% and specificity 96.4%). In none of the fetuses with a probability of CoAo < 35% was this condition confirmed after birth. This occurred in 102 fetuses in the whole study population (57%) and in 84 of the 111 in whom CoAo was suspected beyond 28 weeks (75.7%). This multiparameter score allows an adequate discrimination between fetuses without CoAo and those with CoAo, reducing the false positive diagnoses in cardiac asymmetry.
Influence of Chronic Ocular Hypertension on Emmetropia: Refractive, Structural and Functional Study in Two Rat Models
Authors: Mendez-Martinez Silvia , Martínez-Rincón Teresa , Subias Manuel , Pablo Luis E. , García-Herranz David , Feijoo Julian García , Bravo-Osuna Irene , Herrero-Vanrell Rocío , Garcia-Martin Elena , Rodrigo María J.
Published: August 2021

Chronic ocular hypertension (OHT) influences on refraction in youth and causes glaucoma in adulthood. However, the origin of the responsible mechanism is unclear. This study analyzes the effect of mild-moderate chronic OHT on refraction and neuroretina (structure and function) in young-adult Long-Evans rats using optical coherence tomography and electroretinography over 24 weeks. Data from 260 eyes were retrospectively analyzed in two cohorts: an ocular normotension (ONT) cohort (<20 mmHg) and an OHT cohort (>20 mmHg), in which OHT was induced either by sclerosing the episcleral veins (ES group) or by injecting microspheres into the anterior chamber. A trend toward emmetropia was found in both cohorts over time, though it was more pronounced in the OHT cohort (p < 0.001), especially in the ES group (p = 0.001) and males. IOP and refraction were negatively correlated at week 24 (p = 0.010). The OHT cohort showed early thickening in outer retinal sectors (p < 0.050) and the retinal nerve fiber layer, which later thinned. Electroretinography demonstrated early supranormal amplitudes and faster latencies that later declined. Chronic OHT accelerates emmetropia in Long–Evans rat eyes towards slowly progressive myopia, with an initial increase in structure and function that reversed over time.
Dataset Growth in Medical Image Analysis Research
Authors: Kiryati Nahum , Landau Yuval
Published: August 2021

Medical image analysis research requires medical image datasets. Nevertheless, due to various impediments, researchers have been described as “data starved”. We hypothesize that implicit evolving community standards require researchers to use ever-growing datasets. In Phase I of this research, we scanned the MICCAI (Medical Image Computing and Computer-Assisted Intervention) conference proceedings from 2011 to 2018. We identified 907 papers involving human MRI, CT or fMRI datasets and extracted their sizes. The median dataset size had grown by 3–10 times from 2011 to 2018, depending on imaging modality. Statistical analysis revealed exponential growth of the geometric mean dataset size with an annual growth of 21% for MRI, 24% for CT and 31% for fMRI. Thereupon, we had issued a forecast for dataset sizes in MICCAI 2019 well before the conference. In Phase II of this research, we examined the MICCAI 2019 proceedings and analyzed 308 relevant papers. The MICCAI 2019 statistics compare well with the forecast. The revised annual growth rates of the geometric mean dataset size are 27% for MRI, 30% for CT and 32% for fMRI. We predict the respective dataset sizes in the MICCAI 2020 conference (that we have not yet analyzed) and the future MICCAI 2021 conference.
The Synergy of Arbuscular Mycorrhizal Fungi and Exogenous Abscisic Acid Benefits Robinia pseudoacacia L. Growth through Altering the Distribution of Zn and Endogenous Abscisic Acid
Authors: Lou Xiao , Zhang Xiangyu , Zhang Yu , Tang Ming
Published: August 2021

The simultaneous effects of arbuscular mycorrhizal (AM) fungi and abscisic acid (ABA) on the tolerance of plants to heavy metal (HM) remain unclear. A pot experiment was carried out to clarify the effects of simultaneous applications of AM fungi and ABA on plant growth, Zn accumulation, endogenous ABA contents, proline metabolism, and the oxidative injury of black locust (Robinia pseudoacacia L.) exposed to excess Zn stress. The results suggested that exogenously applied ABA positively enhanced AM colonization, and that the growth of plants only with AM fungi was improved by ABA application. Under Zn stress, AM inoculation and ABA application increased the ABA content in the root/leaf (increased by 48–172% and 92%, respectively) and Zn content in the root/shoot (increased by 63–152% and 61%, respectively) in AM plants, but no similar trends were observed in NM plants. Additionally, exogenous ABA addition increased the proline contents of NM roots concomitantly with the activities of the related synthases, whereas it reduced the proline contents and the activity of Δ1-pyrroline-5-carboxylate synthetase in AM roots. Under Zn stress, AM inoculation and ABA application decreased H2O2 contents and the production rate of O2, to varying degrees. Furthermore, in the roots exposed to Zn stress, AM inoculation augmented the activities of SOD, CAT, POD and APX, and exogenously applied ABA increased the activities of SOD and POD. Overall, AM inoculation combined with ABA application might be beneficial to the survival of black locust under Zn stress by improving AM symbiosis, inhibiting the transport of Zn from the roots to the shoots, increasing the distribution of ABA in roots, and stimulating antioxidant defense systems.
Screening of Mood Symptoms Using MMPI-2-RF Scales: An Application of Machine Learning Techniques
Authors: Kim Sunhae , Lee Hye-Kyung , Lee Kounseok
Published: August 2021

(1) Background: The MMPI-2-RF is the most widely used and most researched test among the tools for assessing psychopathology, and previous studies have established its validity. Mood disorders are the most common mental disorders worldwide; they present difficulties in early detection, go undiagnosed in many cases, and have a poor prognosis. (2) Methods: We analyzed a total of 8645 participants. We used the PHQ-9 to evaluate depressive symptoms and the MDQ to evaluate hypomanic symptoms. We used the 10 MMPI-2 Restructured Form scales and 23 Specific Problems scales for the MMPI-2-RF as predictors. We performed machine learning analysis using the k-nearest neighbor classification, linear discriminant analysis, and random forest classification. (3) Results: Through the machine learning technique, depressive symptoms were predicted with an AUC of 0.634–0.767, and the corresponding value range for hypomanic symptoms was 0.770–0.840. When using RCd to predict depressive symptoms, the AUC was 0.807, but this value was 0.840 when using linear discriminant classification. When predicting hypomanic symptoms with RC9, the AUC was 0.704, but this value was 0.767 when using the linear discriminant method. (4) Conclusions: Using machine learning analysis, we defined that participants’ mood symptoms could be classified and predicted better than when using the Restructured Clinical scales.
Misfit? The Use of Metrics in Innovation
Authors: de Jong Ilse Svensson
Published: August 2021

Measuring innovation is a challenging but essential task to improve business performance. To tackle this task, key performance indicators (KPIs) can be used to measure and monitor innovation. The objective of this study is to explore how KPIs, designed for measuring innovation, are used in practice. To achieve this objective, the author draws upon literature on business performance in accounting and innovation, yet moves away from the functional view. Instead, the author focuses explicitly on how organizational members, through their use of KPIs in innovation, make sense of conflicting interpretations and integrate them into their practices. A qualitative in-depth case study was conducted at the innovation department of an organization in the process industry that operates production sites and sales organizations worldwide. In total, 28 interviews and complementary observations were undertaken at several organizational levels (multi-level). The empirical evidence suggests that strategic change, attributed to commoditization, affects the predetermined KPIs in use. Notably, these KPIs in innovation are used, despite their poor fit to innovation subject to commoditization. From a relational perspective, this study indicates that in innovation, KPIs are usually complemented by or supplemented with other information, as stand-alone KPIs exhibit a significant degree of incompleteness. In contrast to conventional studies in innovation and management accounting, this study explores the use of key performance indicators (KPIs) in innovation from an interpretative perspective. This perspective advances our understanding of the actual use of KPIs and uncovers the complexity of accounting and innovation, which involve numerous angles and organizational levels. Practically, the findings of this study will inform managers in innovation about the use of KPIs in innovation and the challenges individual organizational members face when using them. In innovation, KPIs appear to be subjective and used in unintended ways. Thus, understanding how KPIs are used in innovation is a game of reading between the lines, and these KPIs can be regarded as misfits.
Impact of the LACKS of Fusion Induced by Additive Manufacturing on the Lubrication of a Gear Flank
Authors: Concli Franco , Della Torre Augusto
Published: August 2021

Additive Manufacturing (AM) is becoming a more and more widespread technology. Its capability to produce complex geometries opens new design possibilities. Despite the big efforts made by the scientific community for improving the AM processes, this technology still has some limitations, mainly related to the achievable surface quality. It is known that AM technologies promote the formation of LACKS of fusion inside the material. In some cases, the external surfaces are finished with traditional machining. This is the case of AM-produced gears. While the grinding operation aims to reduce the surface roughness, the presence of porosities just below the surface of the wrought component, could lead, after grinding, to the exposure of those porosities leading to a pitted surface. This phenomenon is surely not beneficial in terms of structural resistance, but can help the lubrication promoting the clinging of the lubricant to the surface. The aim of this paper is to study this effect. Micro-Computer-Tomography (μ-CT) analyses were performed on a 17-4 PH Stainless Steel (SS) produced via Selective Laser Melting (SLM). The real geometry of the pores was reproduced virtually and analyzed by means of multiphase CFD analyses in the presence of centrifugal effects.
Determination of the Actual Stress–Strain Diagram for Undermatching Welded Joint Using DIC and FEM
Authors: Milošević Nenad Zoran , Sedmak Aleksandar Stojan , Bakić Gordana Miodrag , Lazić Vukić , Milošević Miloš , Mladenović Goran , Maslarević Aleksandar
Published: August 2021

This paper presents new methodology for determining the actual stress–strain diagram based on analytical equations, in combination with numerical and experimental data. The first step was to use the 3D digital image correlation (DIC) to estimate true stress–strain diagram by replacing common analytical expression for contraction with measured values. Next step was to estimate the stress concentration by using a new methodology, based on recently introduced analytical expressions and numerical verification by the finite element method (FEM), to obtain actual stress–strain diagrams, as named in this paper. The essence of new methodology is to introduce stress concentration factor into the procedure of actual stress evaluation. New methodology is then applied to determine actual stress–strain diagrams for two undermatched welded joints with different rectangular cross-section and groove shapes, made of martensitic steels X10 CrMoVNb 9-1 and Armox 500T. Results indicated that new methodology is a general one, since it is not dependent on welded joint material and geometry.
The Effect of Prestressing and Temperature on Tensile Strength of Basalt Fiber-Reinforced Plywood
Authors: Lohmus Rynno , Kallakas Heikko , Tuhkanen Eero , Gulik Volodymyr , Kiisk Madis , Saal Kristjan , Kalamees Targo
Published: August 2021

The reinforcement of plywood is demonstrated by laminating pretensioned basalt fibers between veneer sheets, to fabricate so-called prestressed plywood. Belt type basalt fibers bearing a specific adhesion promoting silane sizing were aligned between veneer sheets with 20 mm spacing and were pretensioned at 150 N. Three-layer plywood samples were prepared and tested for tensile strength at room temperature and at 150 °C. The room temperature tensile tests revealed a 35% increase in tensile strength for prestressed plywood compared to that of the conventional specimen. The reinforcement effect deteriorated at 150 °C but was restored upon cooling to room temperature. The deterioration is attributed to the weakening of bonding between the basalt fibers and phenolic resin matrix at elevated temperatures due to the softening of the resin.