bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a 17-Plex of Penta- and Tetra-Nucleotide Microsatellites for DNA Profiling and Paternity Testing in Horses
Authors: Luttman Andrea M. , Komine Misa , Thaiwong Tuddow , Carpenter Tyler , Ewart Susan L. , Kiupel Matti , Langohr Ingeborg M. , Venta Patrick J.
Published: April 2022

Tetranucleotide and pentanucleotide short tandem repeat (hereafter termed tetraSTR and pentaSTR) polymorphisms have properties that make them desirable for DNA profiling and paternity testing. However, certain species, such as the horse, have far fewer tetraSTRs than other species and for this reason dinucleotide STRs (diSTRs) have become the standard for DNA profiling in horses, despite being less desirable for technical reasons. During our testing of a series of candidate genes as potentially underlying a heritable condition characterized by megaesophagus in the Friesian horse breed, we found that good tetraSTRs do exist in horses but, as expected, at a much lower frequency than in other species, e.g., dogs and humans. Using a series of efficient methods developed in our laboratory for the production of multiplexed tetraSTRs in other species, we identified a set of tetra- and pentaSTRs that we developed into a 17-plex panel for the horse, plus a sex-identifying marker near the amelogenin gene. These markers were tested in 128 horses representing 16 breeds as well as crossbred horses, and we found that these markers have useful genetic variability. Average observed heterozygosities (Ho) ranged from 0.53 to 0.89 for the individual markers (0.66 average Ho for all markers), and 0.62-0.82 for expected heterozygosity (He) within breeds (0.72 average He for all markers). The probability of identity (PI) within breeds for which 10 or more samples were available was at least 1.1 x 10−11, and the PI among siblings (PIsib) was 1.5 x 10−5. Stutter was ≤ 11% (average stutter for all markers combined was 6.9%) compared to the more than 30% typically seen with diSTRs. We predict that it will be possible to develop accurate allelic ladders for this multiplex panel that will make cross-laboratory comparisons easier and will also improve DNA profiling accuracy. Although we were only able to exclude candidate genes for Friesian horse megaesophagus with no unexcluded genes that are possibly causative at this point in time, the study helped us to refine the methods used to develop better tetraSTR multiplexed panels for species such as the horse that have a low frequency of tetraSTRs.
Optimization of Geostationary Orbit Transfers via Combined Chemical–Electric Propulsion
Authors: Yang Shihai , Xu Bo , Li Xin
Published: April 2022

For geostationary orbit transfers, a long duration is required using electric propulsion and a large propellant mass is needed with chemical propulsion. Hybrid transfers can achieve a balance between the fuel consumption and transfer time. In this paper, a trajectory optimization method is proposed for time-fixed minimum-fuel orbital transfer with combined chemical–electric propulsion. The necessary conditions and transversality conditions related to impulsive burns are derived theoretically with Pontryagin’s maximum principle. The long-duration geostationary orbit transfer is a many-revolution transfer, and is solved with the homotopic approach from the short-duration transfer problem. The variation in fuel consumption with transfer time is nearly linear, and the variation in the magnitude of impulsive burn is exponential. A simple model is presented for the estimation of fuel consumption and magnitude of impulsive burn with given transfer time, specific impulse of propulsion system and low-thrust magnitude.
The Novel-miR-659/SPP1 Interaction Regulates Fat Deposition in Castrated Male Pigs
Authors: Xiao Lianmei , Xu Qiao , Liu Ximing , Chan Shuheng , Luo Yabiao , He Shuaihan , Fang Meiying
Published: April 2022

Castration is usually used to remove boar taint in commercial pork production, but the adipose accumulation was increased excessively, which affected the meat quality of pigs. Based on our previous study, secreted phosphoprotein 1 (SPP1) was significantly differentially expressed between castrated and intact male pigs. However, the role of SPP1 in regulating adipose growth and fat storage caused by castration is unknown. In this study, SPP1 was identified to inhibit adipogenesis by the expression of adipogenic markers PPARγ and FABP4 as well as Oil red staining assay during differentiation of porcine bone marrow mesenchymal stem cells (pBMSCs). Subsequently, testosterone was used to treat pBMSCs to simulate the androgen status of intact pigs. Compared with the control groups without testosterone, the SPP1 expression in the testosterone group was markedly increased in the late stage of pBMSCs differentiation. Furthermore, novel-miR-659 was predicted by TargetScan and miRDB to target SPP1 and verified through a dual-luciferase reporter assay. Oil Red O staining assay indicated that novel-miR-659 overexpression significantly promoted adipogenesis, whereas novel-miR-659 inhibition suppressed adipogenesis. The expressions of adipogenic markers PPARγ and FABP4 showed the same tendency. Taken together, our study found that the targeted interaction between novel-miR-659 and SPP1 is involved in regulation of fat deposition in castrated male pigs.
Genetic Diversity of Porcine Circovirus Types 2 and 3 in Wild Boar in Italy
Authors: Fanelli Angela , Pellegrini Francesco , Camero Michele , Catella Cristiana , Buonavoglia Domenico , Fusco Giovanna , Martella Vito , Lanave Gianvito
Published: April 2022

Porcine circovirus (PCV) infection is associated with relevant economic impact to the pig industry. To date, four species of PCV (PCV1 to 4) have been identified but only PCV2 has been associated firmly with disease in pigs. The objective of this study was to assess the prevalence of PCV2 and PCV3 in the wild boar population in Basilicata region, Southern Italy, since this region is characterized by large forested and rural areas and the anthropic pressure is lower than in other Italian regions. Liver samples from 82 hunted wild boar were collected in 2021 from 3 different hunting districts. Sixty (73%, 95%CI: 63–82) samples tested positive for PCVs by quantitative PCR. In detail, 22 (27%, 95%CI: 18–37) were positive for PCV2, 58 (71%, 95%CI: 60–79) for PCV3, and 20 (24.4%, 95%CI 16–35) for both PCV2 and PCV3. On genome sequencing, different types and sub-types of PCV2 and PCV3 were identified, remarking a genetic diversity and hinting to a global circulation for the identified PCV strains. Overall, the high prevalence suggests that PCV2 and PCV3 infections are endemic in the wild boar population, posing risks for semi-intensive and free-range pig farming, typical of this region, due to contact with PCV-infected wild boar.
Lemon Balm and Corn Silk Mixture Alleviates Metabolic Disorders Caused by a High-Fat Diet
Authors: Cho Il-Je , Shin Joung-Hoon , Choi Beom-Rak , Park Hye-Rim , Park Jeong-Eun , Hong Seong-Hwa , Kwon Young-Sam , Oh Won-Seok , Ku Sae-Kwang
Published: April 2022

We recently reported that varying combination ratios of lemon balm (Mellissa officinalis L.) and corn silk extracts (Stigma of Zea mays L. fruit) could reduce the obesity caused by a high-fat diet (HFD). The present study investigated the dose-dependent effect of a 1:1 (w:w) mixture of lemon balm and corn silk extracts (M-LB/CS) on HFD-mediated metabolic disorders and compared the effect with metformin. Oral administration of 50–200 mg/kg of M-LB/CS for 84 days significantly inhibited HFD-induced body weight gain, adipocyte hypertrophy, and lipogenic gene induction without affecting food consumption in mice. Biochemical analyses showed that M-LB/CS blocked abnormal lipid accumulation in the blood by escalating fecal lipid excretion. In addition, M-LB/CS prevented HFD-mediated pancreatic atrophy, decreased the number of insulin- and glucagon-immunoreactive cells, and inhibited increases in glycated hemoglobin, glucose, and insulin. Moreover, M-LB/CS also reduced hepatic injury, lipid accumulation, gluconeogenesis, and lipid peroxidation in parallel with the induction of AMP-activated protein kinase and antioxidant enzymes. Furthermore, M-LB/CS protected the kidney by inhibiting tubular vacuolation and reducing serum creatinine and blood urea nitrogen levels. The prophylactic effect of 100 mg/kg M-LB/CS-administration was comparable to that of metformin. Therefore, M-LB/CS may be an alternative option for managing obesity and its related metabolic disorders.
Digital versus Conventional Workflow in Oral Rehabilitations: Current Status
Authors: Cortes Arthur Rodriguez Gonzalez
Published: April 2022

In recent years, computer-aided design and computer-aided manufacturing (CAD-CAM) technology has developed along with its applications in dentistry, including several new techniques that are used in oral rehabilitation applications [...]
Unsupervised Segmentation in NSCLC: How to Map the Output of Unsupervised Segmentation to Meaningful Histological Labels by Linear Combination?
Authors: Weis Cleo-Aron , Weihrauch Kian R. , Kriegsmann Katharina , Kriegsmann Mark
Published: April 2022

Background: Segmentation is, in many Pathomics projects, an initial step. Usually, in supervised settings, well-annotated and large datasets are required. Regarding the rarity of such datasets, unsupervised learning concepts appear to be a potential solution. Against this background, we tested for a small dataset on lung cancer tissue microarrays (TMA) if a model (i) first can be in a previously published unsupervised setting and (ii) secondly can be modified and retrained to produce meaningful labels, and (iii) we finally compared this approach to standard segmentation models. Methods: (ad i) First, a convolutional neuronal network (CNN) segmentation model is trained in an unsupervised fashion, as recently described by Kanezaki et al. (ad ii) Second, the model is modified by adding a remapping block and is retrained on an annotated dataset in a supervised setting. (ad iii) Third, the segmentation results are compared to standard segmentation models trained on the same dataset. Results: (ad i–ii) By adding an additional mapping-block layer and by retraining, models previously trained in an unsupervised manner can produce meaningful labels. (ad iii) The segmentation quality is inferior to standard segmentation models trained on the same dataset. Conclusions: Unsupervised training in combination with subsequent supervised training offers for histological images here no benefit.
Remote-Controlled Method with Force and Visual Assists Based on Time to Collision for Mobile Robot
Authors: Masaki Ryo , Kobayashi Masato , Motoi Naoki
Published: April 2022

Various remote-controlled methods have been developed to improve operability using force or visual assists; however, using only force or visual assists may deteriorate the operability or safety performance. Therefore, a remote-controlled method with both force and visual assists is proposed to improve the operability while maintaining safety performance. The proposed remote-controlled system consists of a wheeled mobile robot, control device, and monitor. The force assist is generated using the time to collision (TTC), which is the predicted time of collision of the mobile robot against an obstacle. This force assist is applied to the operator using a control device to achieve collision avoidance. Using a visual assist, a predicted trajectory for the mobile robot based on the TTC is generated. For operability improvement, this predicted trajectory with color gradation is shown on the monitor. In summary, the achievement of operability improvement while maintaining safety performance is confirmed from experimental results using the proposed method.
Quenching Efficiency of Quantum Dots Conjugated to Lipid Bilayers on Graphene Oxide Evaluated by Fluorescence Single Particle Tracking
Authors: Okamoto Yoshiaki , Iwasa Seiji , Tero Ryugo
Published: April 2022

A single particle observation of quantum dots (QDs) was performed on lipid bilayers formed on graphene oxide (GO). The long-range fluorescence quenching of GO has been applied to biosensing for various biomolecules. We demonstrated the single particle observation of a QD on supported lipid bilayers in this study, aiming to detect the quenching efficiency of lipid and protein molecules in a lipid bilayer by fluorescence single particle tacking (SPT). A single lipid bilayer or double lipid bilayers were formed on GO flakes deposited on a thermally oxidized silicon substrate by the vesicle fusion method. The QDs were conjugated on the lipid bilayers, and single particle images of the QDs were obtained under the quenching effect of GO. The quenching efficiency of a single QD was evaluated from the fluorescence intensities on the regions with and without GO. The quenching efficiency reflecting the layer numbers of the lipid bilayers was obtained.
Perception of Urban Leftover Spaces: A Comparative Study of Built Environment and Non-Built Environment Participants
Authors: Azhar Jasim , Gjerde Morten , Vale Brenda , Asif Muhammad
Published: April 2022

The built environment, urban processes, and experience all work together to create the spatial environment of a city. Many urban spaces, especially those that appear to be ‘leftover’, do not reflect a set concept but are constantly questioned and recreated. Recognizing leftover spaces in an urban environment is an important aspect of the urban redevelopment process. Researchers have highlighted the difficulties, circumstances, and relevance of making good use of leftover space. To accomplish environmental and social benefits, these places can be created, changed, and incorporated into the main urban fabric; however, there is a scarcity of knowledge on how to go about constructing such environments. This study explores the visual perception of two groups of people, those with knowledge of the built environment and those with other educational backgrounds regarding leftover spaces in Wellington City. The research, which employs a mixed approach, consists of three studies, beginning with a visual preference study to better understand human perceptions, which might lead to better design solutions. The second study looked at differences in design preferences across the built environment and non-built environment participants. Finally, individuals from the built and non-built environments participants were invited to a focus group discussion for study three. To summarize, the findings demonstrated that adding vegetation is a crucial design feature. The findings refute the hypotheses of non-built environment specialists have different design perceptions for a built environment.
Heart Rate Variability Analysis for Seizure Detection in Neonatal Intensive Care Units
Authors: Olmi Benedetta , Manfredi Claudia , Frassineti Lorenzo , Dani Carlo , Lori Silvia , Bertini Giovanna , Cossu Cesarina , Bastianelli Maria , Gabbanini Simonetta , Lanatà Antonio
Published: April 2022

In Neonatal Intensive Care Units (NICUs), the early detection of neonatal seizures is of utmost importance for a timely clinical intervention. Over the years, several neonatal seizure detection systems were proposed to detect neonatal seizures automatically and speed up seizure diagnosis, most based on the EEG signal analysis. Recently, research has focused on other possible seizure markers, such as electrocardiography (ECG). This work proposes an ECG-based NSD system to investigate the usefulness of heart rate variability (HRV) analysis to detect neonatal seizures in the NICUs. HRV analysis is performed considering time-domain, frequency-domain, entropy and multiscale entropy features. The performance is evaluated on a dataset of ECG signals from 51 full-term babies, 29 seizure-free. The proposed system gives results comparable to those reported in the literature: Area Under the Receiver Operating Characteristic Curve = 62%, Sensitivity = 47%, Specificity = 67%. Moreover, the system’s performance is evaluated in a real clinical environment, inevitably affected by several artefacts. To the best of our knowledge, our study proposes for the first time a multi-feature ECG-based NSD system that also offers a comparative analysis between babies suffering from seizures and seizure-free ones.
Investigation of the Molecular Mechanisms of the Eukaryotic Cytochrome-c Maturation System
Authors: Silva Ana V. , Firmino Maria O. , Costa Nazua L. , Louro Ricardo O. , Paquete Catarina M.
Published: April 2022

Cytochromes-c are ubiquitous heme proteins with enormous impact at the cellular level, being key players in metabolic processes such as electron transfer chains and apoptosis. The assembly of these proteins requires maturation systems that catalyse the formation of the covalent thioether bond between two cysteine residues and the vinyl groups of the heme. System III is the maturation system present in Eukaryotes, designated CcHL or HCCS. This System requires a specific amino acid sequence in the apocytochrome to be recognized as a substrate and for heme insertion. To explore the recognition mechanisms of CcHL, the bacterial tetraheme cytochrome STC from Shewanella oneidensis MR-1, which is not a native substrate for System III, was mutated to be identified as a substrate. The results obtained show that it is possible to convert a bacterial cytochrome as a substrate by CcHL, but the presence of the recognition sequence is not the only factor that induces the maturation of a holocytochrome by System III. The location of this sequence in the polypeptide also plays a role in the maturation of the c-type cytochrome. Furthermore, CcHL appears to be able to catalyse the binding of only one heme per polypeptide chain, being unable to assemble multiheme cytochromes c, in contrast with bacterial maturation systems.
DNMT3B System Dysregulation Contributes to the Hypomethylated State in Ischaemic Human Hearts
Authors: Tarazón Estefanía , Pérez-Carrillo Lorena , Giménez-Escamilla Isaac , García-Manzanares María , Martínez-Dolz Luis , Portolés Manuel , Roselló-Lletí Esther
Published: April 2022

A controversial understanding of the state of the DNA methylation machinery exists in ischaemic cardiomyopathy (ICM). Moreover, its relationship to other epigenetic alterations is incomplete. Therefore, we carried out an in-depth study of the DNA methylation process in human cardiac tissue. We showed a dysregulation of the DNA methylation machinery accordingly with the genome-wide hypomethylation that we observed: specifically, an overexpression of main genes involved in the elimination of methyl groups (TET1, SMUG1), and underexpression of molecules implicated in the maintenance of methylation (MBD2, UHRF1). By contrast, we found DNMT3B upregulation, a key molecule in the addition of methyl residues in DNA, and an underexpression of miR-133a-3p, an inhibitor of DNMT3B transcription. However, we found many relevant alterations that would counteract the upregulation observed, such as the overexpression of TRAF6, responsible for Dnmt3b degradation. Furthermore, we showed that molecules regulating Dnmts activity were altered; specifically, SAM/SAH ratio reduction. All these results are in concordance with the Dnmts normal function that we show. Our analysis revealed genome-wide hypomethylation along with dysregulation in the mechanisms of addition, elimination and maintenance of methyl groups in the DNA of ICM. We describe relevant alterations in the DNMT3B system, which promote a normal Dnmt3b function despite its upregulation.
Recent Advances in Microfluidic Platform for Physical and Immunological Detection and Capture of Circulating Tumor Cells
Authors: Bhat Mahesh Padmalaya , Thendral Venkatachalam , Uthappa Uluvangada Thammaiah , Lee Kyeong-Hwan , Kigga Madhuprasad , Altalhi Tariq , Kurkuri Mahaveer D. , Kant Krishna
Published: April 2022

CTCs (circulating tumor cells) are well-known for their use in clinical trials for tumor diagnosis. Capturing and isolating these CTCs from whole blood samples has enormous benefits in cancer diagnosis and treatment. In general, various approaches are being used to separate malignant cells, including immunomagnets, macroscale filters, centrifuges, dielectrophoresis, and immunological approaches. These procedures, on the other hand, are time-consuming and necessitate multiple high-level operational protocols. In addition, considering their low efficiency and throughput, the processes of capturing and isolating CTCs face tremendous challenges. Meanwhile, recent advances in microfluidic devices promise unprecedented advantages for capturing and isolating CTCs with greater efficiency, sensitivity, selectivity and accuracy. In this regard, this review article focuses primarily on the various fabrication methodologies involved in microfluidic devices and techniques specifically used to capture and isolate CTCs using various physical and biological methods as well as their conceptual ideas, advantages and disadvantages.
Nitrogen Removal Characteristics of a Cold-Tolerant Aerobic Denitrification Bacterium, Pseudomonas sp. 41
Authors: Lv Pengyi , Wei Bohui , Ma Wenkai , Luo Xiao
Published: April 2022

Nitrogen pollution of surface water is the main cause of water eutrophication, and is considered a worldwide challenge in surface water treatment. Currently, the total nitrogen (TN) content in the effluent of wastewater treatment plants (WWTPs) is still high at low winter temperatures, mainly as a result of the incomplete removal of nitrate (NO3−-N). In this research, a novel aerobic denitrifier identified as Pseudomonas sp. 41 was isolated from municipal activated sludge; this strain could rapidly degrade a high concentration of NO3−-N at low temperature. Strain 41 completely converted 100 mg/L NO3−-N in 48 h at 15 °C, and the maximum removal rate reached 4.0 mg/L/h. The functional genes napA, nirS, norB and nosZ were successfully amplified, which provided a theoretical support for the aerobic denitrification capacity of strain 41. In particular, the results of denitrification experiments showed that strain 41 could perform aerobic denitrification under the catalysis of NAP. Nitrogen balance analysis revealed that strain 41 degraded NO3−-N mainly through assimilation (52.35%) and aerobic denitrification (44.02%), and combined with the gene amplification results, the nitrate metabolism pathway of strain 41 was proposed. Single-factor experiments confirmed that strain 41 possessed the best nitrogen removal performance under the conditions of sodium citrate as carbon source, C/N ratio 10, pH 8, temperature 15–30 °C and rotation speed 120 rpm. Meanwhile, the bioaugmentation test manifested that the immobilized strain 41 remarkably improved the denitrification efficiency and shortened the reaction time in the treatment of synthetic wastewater.
Peroxymonosulfate Activation by Photoelectroactive Nanohybrid Filter towards Effective Micropollutant Decontamination
Authors: Zhao Wenchang , Dai Yuling , Zheng Wentian , Liu Yanbiao
Published: April 2022

Herein, we report and demonstrate a photoelectrochemical filtration system that enables the effective decontamination of micropollutants from water. The key to this system was a photoelectric–active nanohybrid filter consisting of a carbon nanotube (CNT) and MIL–101(Fe). Various advanced characterization techniques were employed to obtain detailed information on the microstructure, morphology, and defect states of the nanohybrid filter. The results suggest that both radical and nonradical pathways collectively contributed to the degradation of antibiotic tetracycline, a model refractory micropollutant. The underlying working mechanism was proposed based on solid experimental evidences. This study provides new insights into the effective removal of micropollutants from water by integrating state–of–the–art advanced oxidation and microfiltration techniques.
Depletion of the Origin Recognition Complex Subunits Delays Aging in Budding Yeast
Authors: Stępień Karolina , Skoneczna Adrianna , Kula-Maximenko Monika , Jurczyk Łukasz , Mołoń Mateusz
Published: April 2022

Precise DNA replication is pivotal for ensuring the accurate inheritance of genetic information. To avoid genetic instability, each DNA fragment needs to be amplified only once per cell cycle. DNA replication in eukaryotes starts with the binding of the origin recognition complex (ORC) to the origins of DNA replication. The genes encoding ORC subunits have been conserved across eukaryotic evolution and are essential for the initiation of DNA replication. In this study, we conducted an extensive physiological and aging-dependent analysis of heterozygous cells lacking one copy of ORC genes in the BY4743 background. Cells with only one copy of the ORC genes showed a significant decrease in the level of ORC mRNA, a delay in the G1 phase of the cell cycle, and an extended doubling time. Here, we also show that the reducing the levels of Orc1-6 proteins significantly extends both the budding and average chronological lifespans. Heterozygous ORC/orcΔ and wild-type diploid cells easily undergo haploidization during chronological aging. This ploidy shift might be related to nutrient starvation or the inability to survive under stress conditions. A Raman spectroscopy analysis helped us to strengthen the hypothesis of the importance of lipid metabolism and homeostasis in aging.
Development and Experimental Validation of Regularized Machine Learning Models Detecting New, Structurally Distinct Activators of PXR
Authors: Hirte Steffen , Burk Oliver , Tahir Ammar , Schwab Matthias , Windshügel Björn , Kirchmair Johannes
Published: April 2022

The pregnane X receptor (PXR) regulates the metabolism of many xenobiotic and endobiotic substances. In consequence, PXR decreases the efficacy of many small-molecule drugs and induces drug-drug interactions. The prediction of PXR activators with theoretical approaches such as machine learning (ML) proves challenging due to the ligand promiscuity of PXR, which is related to its large and flexible binding pocket. In this work we demonstrate, by the example of random forest models and support vector machines, that classifiers generated following classical training procedures often fail to predict PXR activity for compounds that are dissimilar from those in the training set. We present a novel regularization technique that penalizes the gap between a model’s training and validation performance. On a challenging test set, this technique led to improvements in Matthew correlation coefficients (MCCs) by up to 0.21. Using these regularized ML models, we selected 31 compounds that are structurally distinct from known PXR ligands for experimental validation. Twelve of them were confirmed as active in the cellular PXR ligand-binding domain assembly assay and more hits were identified during follow-up studies. Comprehensive analysis of key features of PXR biology conducted for three representative hits confirmed their ability to activate the PXR.
Comprehensive Characterization of Platelet-Enriched MicroRNAs as Biomarkers of Platelet Activation
Authors: Krammer Teresa L. , Zeibig Stephan , Schrottmaier Waltraud C. , Pirabe Anita , Goebel Silvia , Diendorfer Andreas B. , Holthoff Hans-Peter , Assinger Alice , Hackl Matthias
Published: April 2022

Dysregulation of platelet function is causally connected to thrombus formation and cardiovascular diseases. Therefore, assessing platelet reactivity is crucial. However, current platelet function tests come with pitfalls, limiting clinical use. Plasma miRNA signatures have been suggested as novel biomarkers for predicting/diagnosing cardiovascular diseases and monitoring antiplatelet therapy. Here, we provide results from a comprehensive study on the feasibility of using circulatory platelet miRNAs as surrogate markers of platelet activation. We performed small RNA-Seq on different blood cell types to confirm known and identify novel platelet-enriched miRNAs and validated a panel of 16 miRNAs using RT-qPCR. To identify the main carrier of these blood-based platelet miRNAs, we enriched and analyzed distinct microvesicle populations. Platelets were stimulated with GPVI and P2Y12 agonists in vitro to monitor the release of the selected miRNAs following activation. Finally, the miRNA panel was also measured in plasma from mice undergoing the Folts intervention (recurrent thrombus formation in the carotid artery). Applying an unbiased bioinformatics-supported workflow to our NGS data, we were able to confirm a panel of previously established miRNA biomarker candidates and identify three new candidates (i.e., miR-199a-3p, miR-151a-5p, and miR-148b-3p). Basal levels of platelet-derived miRNAs in plasma were mainly complexed with proteins, not extracellular vesicles. We show that changes in miRNA levels due to platelet activation are detectable using RT-qPCR. In addition, we highlight limitations of studying the in vitro release of miRNAs from platelets. In vivo thrombosis resulted in significant elevations of platelet-derived miRNA levels in mice. In conclusion, we provide in-depth evidence that activated platelets release miRNAs, resulting in measurable changes in circulatory miRNA levels, rendering them promising biomarker candidates.
Proteomics and Metabolomics Profiling of Platelets and Plasma Mediators of Thrombo-Inflammation in Gestational Hypertension and Preeclampsia
Authors: de Almeida Luiz Gustavo N. , Young Daniel , Chow Lorraine , Nicholas Joshua , Lee Adrienne , Poon Man-Chiu , Dufour Antoine , Agbani Ejaife O.
Published: April 2022

Platelets may be pivotal mediators of the thrombotic and coagulopathic complications of preeclampsia (PE), linking inflammation and thrombosis with endothelial and vascular dysfunction. Both PE and gestational hypertension (GH) fall within the spectrum of hypertensive complications of pregnancy, with GH being a risk factor for preeclampsia. However, it is unclear what biomarkers distinguish PE from GH. Using a discovery size cohort, we aimed to characterize specific plasma and platelet thrombo-inflammatory drivers indicative of PE and differentiate PE from GH. We performed multiplex immunoassays, platelet and plasma quantitative proteomics and metabolomics of PE patients, comparing with non-pregnant (NP), healthy pregnant controls (PC) and GH participants. The expression pattern of plasma proteins and metabolites in PE/GH platelets was distinct from that of NP and PC. Whilst procoagulation in PC may be fibrinogen driven, inter-alpha-trypsin inhibitors ITIH2 and ITIH3 are likely mediators of thrombo-inflammation in GH and PE, and fibronectin and S100A8/9 may be major procoagulant agonists in PE only. Also enriched in PE were CCL1 and CCL27 plasma cytokines, and the platelet leucine-rich repeat-containing protein 27 and 42 (LRRC27/42), whose effects on platelets were explored using STRING analysis. Through protein-protein interactions analysis, we generated a new hypothesis for platelets’ contribution to the thrombo-inflammatory states of preeclampsia.
NUP133 Controls Nuclear Pore Assembly, Transcriptome Composition, and Cytoskeleton Regulation in Podocytes
Authors: Rogg Manuel , Maier Jasmin I. , Ehle Markus , Sammarco Alena , Schilling Oliver , Werner Martin , Schell Christoph
Published: April 2022

Steroid-resistant nephrotic syndrome (SRNS) frequently leads to end-stage renal disease, ultimately requiring kidney replacement therapies. SRNS is often caused by hereditary monogenic mutations, specifically affecting specialized epithelial cells (podocytes) of the glomerular filtration barrier. Mutations in several components of the nuclear pore complex, including NUP133 and NUP107, have been recently identified to cause hereditary SRNS. However, underlying pathomechanisms, eliciting podocyte-specific manifestations of these nucleoporopathies, remained largely elusive. Here, we generated an in vitro model of NUP133-linked nucleoporopathies using CRISPR/Cas9-mediated genome editing in human podocytes. Transcriptome, nuclear pore assembly, and cytoskeleton regulation of NUP133 loss-of-function, mutant, and wild-type podocytes were analyzed. Loss of NUP133 translated into a disruption of the nuclear pore, alterations of the podocyte-specific transcriptome, and impaired cellular protrusion generation. Surprisingly, comparative analysis of the described SRNS-related NUP133 mutations revealed only mild defects. Am impaired protein interaction in the Y-complex and decrease of NUP133 protein levels might be the primary and unifying consequence of mutant variants, leading to a partial loss-of-function phenotype and disease manifestation in susceptible cell types, such as podocytes.
Preliminary Exploration of the Red Pigment from Scytalidium cuboideum as a Cellulosic Pulp Colorant
Authors: Stone Derek W. , Vega Gutierrez Sarath M. , Walsh Zielle M. , Robinson Seri C.
Published: April 2022

Pollution from the international dye industry continues to be a global problem. Biotechnology offers new options, including a closer look at select wood decay fungi to replace inorganic dyes. The pigments produced by a small group of soft rotting fungi are generally naphthoquinonic and remarkably stable. From this group, the dramada crystals, produced by Scytalidium cuboideum, are of particular interest. To test the application of this pigment as a natural colorant of cellulosic pulps, four different bleached pulps were selected (one hardwood, three softwood), in three different mediums (acetone, ethanol, and DI water). The pigment generated a significant change of color, but there was no significant difference in color intensity based on the solvent carrier. These preliminary results are promising as they open the door for further exploration of applications of fungal pigments in the paper industry. Once these pigments can be reliably grown, they will offer a sustainable organic alternative to polluting inorganic dyestuffs and help reduce the toxic effluent released into the soil and waterways.
Highly Sensitive Detection of Carbaryl Pesticides Using Potentiometric Biosensor with Nanocomposite Ag/r-Graphene Oxide/Chitosan Immobilized Acetylcholinesterase Enzyme
Authors: Mashuni Mashuni , Ritonga Halimahtussaddiyah , Jahiding M. , Rubak Bonni , Hamid Fitri Handayani
Published: April 2022

Novel, sensitive, selective, efficient and portable electrochemical biosensors are needed to detect residual contaminants of the pesticide 1-naphthyl methylcarbamate (carbaryl) in the environment, food, and essential biological fluids. In this work, a study of nanocomposite-based Ag reduced graphene oxide (rGO) and chitosan (CS) that optimise surface conditions for immobilisation of acetylcholinesterase (AChE) enzyme to improve the performance of catalytic biosensors is examined. The Ag/rGO/CS nanocomposite membrane was used to determine carbaryl pesticide using a potentiometer transducer. The AChE enzyme-based biosensor exhibits a good affinity for acetylthiocholine chloride (ATCl). It can catalyse the hydrolysis of ATCl with a potential value of 197.06 mV, which is then oxidised to produce a detectable and rapid response. Under optimal conditions, the biosensor detected carbaryl pesticide at concentrations in the linear range of 1.0 × 10−8 to 1.0 μg mL−1 with a limit of detection (LoD) of 1.0 × 10−9 μg mL−1. The developed biosensor exhibits a wide working concentration range, detection at low concentrations, high sensitivity, acceptable stability, reproducibility and simple fabrication, thus providing a promising tool for pesticide residue analysis.
Sleep Studies for Clinical Indications during the First Year of Life: Infants Are Not Small Children
Authors: Kaditis Athanasios , Gozal David
Published: April 2022

In a previous issue of Children, Guyon et al [...]
Neuralgic Amyotrophy with Concomitant Hereditary Neuropathy with Liability to Pressure Palsy as a Cause of Dropped Shoulder in a Child after Human Papillomavirus Vaccination: A Case Report
Authors: Ahn Hye-Chan , Kim Do-Hoon , Cho Chul-Hyun , Byun Jun-Chul , Cho Jang-Hyuk
Published: April 2022

Hereditary neuropathy with liability to pressure palsy (HNPP) makes nerves increasingly susceptible to mechanical pressure at entrapment sites. Neuralgic amyotrophy (NA) can cause sudden regional weakness following events to which the patient is immunologically predisposed, such as vaccination. However, NA related to human papilloma virus (HPV) vaccination is seldom reported. We describe the case of a child with NA as the cause of a dropped shoulder following the administration of the HPV vaccine. Underlying asymptomatic HNPP was confirmed in this patient based on the electrodiagnostic findings and genetic analysis. We speculate that HPV vaccination elicited an immune-mediated inflammatory response, resulting in NA. Our patient with pre-existing HNPP might be vulnerable to the occurrence of an immune-mediated NA, which caused the dropped shoulder.
CRISPR/Cas9 Screening for Identification of Genes Required for the Growth of Ovarian Clear Cell Carcinoma Cells
Authors: Kawabata Ayako , Hayashi Tomoatsu , Akasu-Nagayoshi Yoko , Yamada Ai , Shimizu Naomi , Yokota Naoko , Nakato Ryuichiro , Shirahige Katsuhiko , Okamoto Aikou , Akiyama Tetsu
Published: April 2022

Epithelial ovarian cancer is classified into four major histological subtypes: serous, clear cell, endometrioid and mucinous. Ovarian clear cell carcinoma (OCCC) responds poorly to conventional chemotherapies and shows poor prognosis. Thus, there is a need to develop new drugs for the treatment of OCCC. In this study, we performed CRISPR/Cas9 screens against OCCC cell lines and identified candidate genes important for their proliferation. We found that quite different genes are required for the growth of ARID1A and PIK3CA mutant and wild-type OCCC cell lines, respectively. Furthermore, we found that the epigenetic regulator KDM2A and the translation regulator PAIP1 may play important roles in the growth of ARID1A and PIK3CA mutant, but not wild-type, OCCC cells. The results of our CRISPR/Cas9 screening may be useful in elucidating the molecular mechanism of OCCC tumorigenesis and in developing OCCC-targeted drugs.
Hot Corrosion Behavior of Arc-Sprayed NiCrB and NiCrTi Coatings with Different Oxide Contents
Authors: Wang Xu , He Dingyong , Zhou Zheng , Shao Wei , Guo Xingye , Wang Guohong
Published: April 2022

In this study, newly developed NiCrB and conventional NiCrTi coatings were produced by arc spraying using compressed air and nitrogen as atomization gases. In this way, four coatings with different oxide contents were produced. The coatings were investigated in terms of their phase compositions, oxygen contents, and microstructures. The results showed that the oxygen contents in coatings were pronouncedly reduced by nitrogen-atomized compared to air-atomized. The oxygen contents in the nitrogen-atomized coatings were about one-fourth of those in the corresponding air-atomized coatings, respectively. No significant oxide phases were observed in the XRD patterns of the nitrogen-atomized coatings. Moreover, the corrosion behavior of the coatings was studied using a hot corrosion test in molten Na2SO4-10 wt.% NaCl salt at T = 800 °C. All coatings were significantly corroded under this test condition. However, NiCrB coatings exhibited higher corrosion resistance than NiCrTi coatings. The NiCrB and NiCrTi coatings prepared by nitrogen atomization corroded more severely in the initial stage than the corresponding coatings prepared by air atomization. The NiCrB coating with air-atomized showed the best corrosion resistance due to the low chromium content and the addition of boron.
Color Dependence Analysis in a CNN-Based Computer-Aided Diagnosis System for Middle and External Ear Diseases
Authors: Viscaino Michelle , Talamilla Matias , Maass Juan Cristóbal , Henríquez Pablo , Délano Paul H. , Auat Cheein Cecilia , Auat Cheein Fernando
Published: April 2022

Artificial intelligence-assisted otologic diagnosis has been of growing interest in the scientific community, where middle and external ear disorders are the most frequent diseases in daily ENT practice. There are some efforts focused on reducing medical errors and enhancing physician capabilities using conventional artificial vision systems. However, approaches with multispectral analysis have not yet been addressed. Tissues of the tympanic membrane possess optical properties that define their characteristics in specific light spectra. This work explores color wavelengths dependence in a model that classifies four middle and external ear conditions: normal, chronic otitis media, otitis media with effusion, and earwax plug. The model is constructed under a computer-aided diagnosis system that uses a convolutional neural network architecture. We trained several models using different single-channel images by taking each color wavelength separately. The results showed that a single green channel model achieves the best overall performance in terms of accuracy (92%), sensitivity (85%), specificity (95%), precision (86%), and F1-score (85%). Our findings can be a suitable alternative for artificial intelligence diagnosis systems compared to the 50% of overall misdiagnosis of a non-specialist physician.
The Role of Epigenetic and Biological Biomarkers in the Diagnosis of Periodontal Disease: A Systematic Review Approach
Authors: Faulkner Erin , Mensah Adelaide , Rodgers Aoife M. , McMullan Lyndsey R. , Courtenay Aaron J.
Published: April 2022

The aim of this systemic review was to collate and analyze existing data from published literature sources to identify the current understanding of the role of epigenetic and biological biomarkers in periodontal disease and diagnostics. A comprehensive searching strategy was undertaken in Embase, Medline, The Dentistry and Oral Sciences and CINAHL databases. Grey literature searching strategies were also employed. Articles published in the English language between 2017–2020 were included. A total of 1014 studies were returned of which 15 studies were included. All included articles were cross-sectional, case–control studies. Relevant data were extracted according to various demographic and methodological factors including cohort size, oral biofluid sampled, number of examiners, smoking status and reported outcomes. A measure of the biomarker levels and corresponding significance were documented where possible. This review identified that exRNA has the greatest diagnostic potential, with four biomarkers (SPRR1A, lnc-TET3-2:1, FAM25A, CRCT1) displaying sensitivity of >71% and specificity of 100% in the assessed samples (p < 0.001) for gingivitis. This work also identifies the need for a unified approach to future research to draw meaningful comparison. Further investigations are warranted to definitively validate exRNA data and for the development of an exRNA-specific point-of-care diagnostic test.
An Examination of Practice-Based Virtual Simulations and Pre-Service Mathematics Teaching Efficacy and Outcome Expectancy
Authors: Davis Trina J. , Merchant Zahira , Kwok Oi-Man
Published: April 2022

Authentic practice in pedagogical approaches is essential for preparing teachers to design effective learning experiences that foster student engagement during this digital era. There is an opportunity to explore novel and effective designs of virtual experiences that may augment or better prepare preservice teachers for field placements in physical classrooms. We proffer that virtual classroom simulations can and should be further explored and leveraged, now more than ever. In this paper, we examined a model of the impact of perceptual variables on instructional effectiveness that can enhance teaching efficacy and outcome expectancy when preservice teachers engage in practice teaching experiences in a virtual classroom simulation. The relationships between perceptual variables (presence, instructional time, and engagement) and teaching efficacy and outcome expectancy, as they relate to instructional effectiveness, were analyzed using the structural equation modeling approach. The results supported all of the hypothesized relationships. For example, presence and instructional time strongly and positively influenced engagement. Engagement was strongly related to instructional effectiveness. Instructional effectiveness was strongly and positively related to teaching self-efficacy, as well as outcome expectancy. The results support that virtual world classroom simulations can be an effective space for practice teaching for prospective mathematics teachers. Furthermore, this study provides insights for teacher educators, developers, and instructional designers interested in designing and utilizing practice-based simulations.
The Application of Improved Harmony Search Algorithm to Multi-UAV Task Assignment
Authors: Cui Yujuan , Dong Wenhan , Hu Duoxiu , Liu Haibo
Published: April 2022

In this work, aiming at the problem of cooperative task assignment for multiple unmanned aerial vehicles (UAVs) in actual combat, battlefield tasks are divided into reconnaissance tasks, strike tasks and evaluation tasks, and a cooperative task-assignment model for multiple UAVs is built. Meanwhile, heterogeneous UAV-load constraints and mission-cost constraints are introduced, the UAVs and their constraints are analyzed and the mathematical model is established. The exploration performance and convergence performance of the harmony search algorithm are analyzed theoretically, and the more general formulas of exploration performance and convergence performance are proved. Based on theoretical analysis, an algorithm called opposition-based learning parameter-adjusting harmony search is proposed. Using the algorithm to test the functions of different properties, the value range of key control parameters of the algorithm is given. Finally, four algorithms are used to simulate and solve the assignment problem, which verifies the effectiveness of the task-assignment model and the excellence of the designed algorithm. Simulation results show that while ensuring proper assignment, the proposed algorithm is very effective for the multi-objective optimization of heterogeneous UAV-cooperation mission planning with multiple constraints.
Piecewise Iterative Extrapolation Method for Bandlimited Signal
Authors: Zhang Yusi , Sha Xuejun , Fang Xiaojie , Lin Xu
Published: April 2022

In some high spectrally efficient communication structures, the Gerchberg-Papoulis extrapolation algorithm can be used to reconstruct nonorthogonal signals. However, the extrapolation efficiency and accuracy degrades when the energy of known signal is small or the iterative filter bandwidth is large. Focused on these drawbacks, a piecewise iterative extrapolation method is proposed to extrapolate bandlimited signals with higher extrapolation efficiency and accuracy. In this paper, the amplitude change of the unknown part over iterations is analyzed and the feasibility of the proposed extrapolation method is discussed. Numerical simulation shows the accuracy superiority of proposed method with the frequency offset compared to the GP algorithm with fixed computational complexity. Besides, the feasibility of the proposed method is verified in fractional Fourier domain with performance advantages.