bluuebunny/crossref_metadata_2025 huggingface dataset:
Paediatric Sleep Questionnaire for Obstructive Sleep Apnoea Syndrome Screening: Is Sleep Quality Worthy of Note?
Authors: Panzarella Vera , Giuliana Giovanna , Spinuzza Paola , La Mantia Gaetano , Maniscalco Laura , Pizzo Giuseppe , Matranga Domenica
Published: February 2021

Obstructive sleep apnoea syndrome (OSAS) is the most severe condition on the spectrum of sleep-related breathing disorders (SRBDs). The Paediatric Sleep Questionnaire (PSQ) is one of the most used and validated screening tools, but it lacks the comprehensive assessment of some determinants of OSAS, specifically anamnestic assessment and sleep quality. This study aims to assess the accuracy of some specific items added to the original PSQ, particularly related to the patient’s anamnestic history and to the quality of sleep, for the screening of OSAS in a paediatric population living in Sicily (Italy). Fifteen specific items, divided into “anamnestic” and “related to sleep quality” were added to the original PSQ. The whole questionnaire was administered via a digital form to the parents of children at 4 schools (age range: 3–13 years). For each item, sensitivity and specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated. The highest sensitivity (80.0, 95% CI: 28.4; 99.5), in combination with the highest specificity (61.1, 95% CI: 35.7; 82.7), was found for the Item 32 (“assumption of bizarre or abnormal positions during sleep”). This item was found statistically significant for predicting the occurrence of OSAS in children (p-value ≤0.003). The study demonstrates the accuracy of specific items related to sleep quality disturbance for the preliminary assessment of the disease. Although these results should be validated on a larger sample of subjects, they suggest that including the factors discriminating sleep quality could further increase the efficiency and accuracy of PSQ.
Underwater Acoustic Target Recognition with a Residual Network and the Optimized Feature Extraction Method
Authors: Hong Feng , Liu Chengwei , Guo Lijuan , Chen Feng , Feng Haihong
Published: February 2021

Underwater Acoustic Target Recognition (UATR) remains one of the most challenging tasks in underwater signal processing due to the lack of labeled data acquisition, the impact of the time-space varying intrinsic characteristics, and the interference from other noise sources. Although some deep learning methods have been proven to achieve state-of-the-art accuracy, the accuracy of the recognition task can be improved by designing a Residual Network and optimizing feature extraction. To give a more comprehensive representation of the underwater acoustic signal, we first propose the three-dimensional fusion features along with the data augment strategy of SpecAugment. Afterward, an 18-layer Residual Network (ResNet18), which contains the center loss function with the embedding layer, is designed to train the aggregated features with an adaptable learning rate. The recognition experiments are conducted on the ship-radiated noise dataset from a real environment, and the accuracy results of 94.3% indicate that the proposed method is appropriate for underwater acoustic recognition problems and sufficiently surpasses other classification methods.
WARM: Wearable AR and Tablet-Based Assistant Systems for Bus Maintenance
Authors: Borro Diego , Suescun Ángel , Brazález Alfonso , González José Manuel , Ortega Eloy , González Eduardo
Published: February 2021

This paper shows two developed digital systems as an example of intelligent garage and maintenance that targets the applicability of augmented reality and wearable devices technologies to the maintenance of bus fleets. Both solutions are designed to improve the maintenance process based on verification of tasks checklist. The main contribution of the paper focuses on the implementation of the prototypes in the company’s facilities in an operational environment with real users and address the difficulties inherent in the transfer of a technology to a real work environment, such as a mechanical workshop. The experiments have been conducted in real operation thanks to the involvement of the public transport operator DBUS, which operates public transport buses in the city of Donostia—San Sebastian (Spain). Two solutions have been developed and compared against the traditional process: one based on Tablet and another one based on Microsoft HoloLens. The results show objective metrics (Key Performance Indicators, KPI) as well as subjective metrics based on questionnaires comparing the two technological approaches against the traditional one based on manual work and paper.
Hybrid Metal/Polymer Filaments for Fused Filament Fabrication (FFF) to Print Metal Parts
Authors: Tosto Claudio , Tirillò Jacopo , Sarasini Fabrizio , Cicala Gianluca
Published: February 2021

The exploitation of mechanical properties and customization possibilities of 3D printed metal parts usually come at the cost of complex and expensive equipment. To address this issue, hybrid metal/polymer composite filaments have been studied allowing the printing of metal parts by using the standard Fused Filament Fabrication (FFF) approach. The resulting hybrid metal/polymer part, the so called “green”, can then be transformed into a dense metal part using debinding and sintering cycles. In this work, we investigated the manufacturing and characterization of green and sintered parts obtained by FFF of two commercial hybrid metal/polymer filaments, i.e., the Ultrafuse 316L by BASF and the 17-4 PH by Markforged. The Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectrometry (EDS) analyses of the mesostructure highlighted incomplete raster bonding and voids like those observed in conventional FFF-printed polymeric structures despite the sintering cycle. A significant role in the tensile properties was played by the building orientation, with samples printed flatwise featuring the highest mechanical properties, though lower than those achievable with standard metal additive manufacturing techniques.
More than XRF Mapping: STEAM (Statistically Tailored Elemental Angle Mapper) a Pioneering Analysis Protocol for Pigment Studies
Authors: Orsilli Jacopo , Galli Anna , Bonizzoni Letizia , Caccia Michele
Published: February 2021

Among the possible variants of X-Ray Fluorescence (XRF), applications exploiting scanning Macro-XRF (MA-XRF) are lately widespread as they allow the visualization of the element distribution maintaining a non-destructive approach. The surface is scanned with a focused or collimated X-ray beam of millimeters or less: analyzing the emitted fluorescence radiation, also elements present below the surface contribute to the elemental distribution image obtained, due to the penetrative nature of X-rays. The importance of this method in the investigation of historical paintings is so obvious—as the elemental distribution obtained can reveal hidden sub-surface layers, including changes made by the artist, or restorations, without any damage to the object—that recently specific international conferences have been held. The present paper summarizes the advantages and limitations of using MA-XRF considering it as an imaging technique, in synergy with other hyperspectral methods, or combining it with spot investigations. The most recent applications in the cultural Heritage field are taken into account, demonstrating how obtained 2D-XRF maps can be of great help in the diagnostic applied on Cultural Heritage materials. Moreover, a pioneering analysis protocol based on the Spectral Angle Mapper (SAM) algorithm is presented, unifying the MA-XRF standard approach with punctual XRF, exploiting information from the mapped area as a database to extend the comprehension to data outside the scanned region, and working independently from the acquisition set-up. Experimental application on some reference pigment layers and a painting by Giotto are presented as validation of the proposed method.
Phytotoxic Activity and Growth Inhibitory Substances from Albizia richardiana (Voigt.) King & Prain
Authors: Hossen Kawsar , Iwasaki Arihiro , Suenaga Kiyotake , Kato-Noguchi Hisashi
Published: February 2021

Albizia richardiana, a fast-growing, large deciduous tree belonging to the Fabaceae family, grows well in hot and humid areas but mainly grows in the tropics of the Old World. The medicinal and other uses of Albizia richardiana are well documented, but the phytotoxic effects of this tree have not yet been investigated. We conducted this study to investigate the phytotoxic activity of Albizia richardiana leaves and to identify growth inhibitory substances for controlling weeds in a sustainable way. Aqueous methanol extracts of Albizia richardiana leaves greatly suppressed the growth of cress and barnyard grass seedlings in a concentration- and species-dependent manner. Two phytotoxic substances were separated using several purification steps and characterized through spectral analysis as dehydrovomifoliol and loliolide. Dehydrovomifoliol and loliolide significantly arrested the seedling growth of cress in the concentrations of 0.1 and 0.01 mM, respectively. The extract concentrations needed for 50% growth inhibition (I50 values) of cress seedlings were 3.16–3.01 mM for dehydrovomifoliol and 0.03–0.02 mM for loliolide. The results suggest that these two allelopathic substances might play a vital role in the phytotoxicity of Albizia richardiana leaves.
A Strong Convergence Theorem for Split Null Point Problem and Generalized Mixed Equilibrium Problem in Real Hilbert Spaces
Authors: Oyewole Olawale Kazeem , Mewomo Oluwatosin Temitope
Published: February 2021

In this paper, we study a schematic approximation of solutions of a split null point problem for a finite family of maximal monotone operators in real Hilbert spaces. We propose an iterative algorithm that does not depend on the operator norm which solves the split null point problem and also solves a generalized mixed equilibrium problem. We prove a strong convergence of the proposed algorithm to a common solution of the two problems. We display some numerical examples to illustrate our method. Our result improves some existing results in the literature.
Future Approaches for Treating Chronic Myeloid Leukemia: CRISPR Therapy
Authors: Vuelta Elena , García-Tuñón Ignacio , Hernández-Carabias Patricia , Méndez Lucía , Sánchez-Martín Manuel
Published: February 2021

The constitutively active tyrosine-kinase BCR/ABL1 oncogene plays a key role in human chronic myeloid leukemia development and disease maintenance, and determines most of the features of this leukemia. For this reason, tyrosine-kinase inhibitors are the first-line treatment, offering most patients a life expectancy like that of an equivalent healthy person. However, since the oncogene stays intact, lifelong oral medication is essential, even though this triggers adverse effects in many patients. Furthermore, leukemic stem cells remain quiescent and resistance is observed in approximately 25% of patients. Thus, new therapeutic alternatives are still needed. In this scenario, the interruption/deletion of the oncogenic sequence might be an effective therapeutic option. The emergence of CRISPR (clustered regularly interspaced short palindromic repeats) technology can offer a definitive treatment based on its capacity to induce a specific DNA double strand break. Besides, it has the advantage of providing complete and permanent oncogene knockout, while tyrosine kinase inhibitors (TKIs) only ensure that BCR-ABL1 oncoprotein is inactivated during treatment. CRISPR/Cas9 cuts DNA in a sequence-specific manner making it possible to turn oncogenes off in a way that was not previously feasible in humans. This review describes chronic myeloid leukemia (CML) disease and the main advances in the genome-editing field by which it may be treated in the future.
A Link between Intrahepatic Cholestasis and Genetic Variations in Intracellular Trafficking Regulators
Authors: Li Qinghong , Sun Yue , van IJzendoorn Sven C. D.
Published: February 2021

Intrahepatic cholestasis is characterized by the accumulation of compounds in the serum that are normally secreted by hepatocytes into the bile. Genes associated with familial intrahepatic cholestasis (FIC) include ATP8B1 (FIC1), ABCB11 (FIC2), ABCB4 (FIC3), TJP2 (FIC4), NR1H4 (FIC5) and MYO5B (FIC6). With advanced genome sequencing methodologies, additional mutated genes are rapidly identified in patients presenting with idiopathic FIC. Notably, several of these genes, VPS33B, VIPAS39, SCYL1, and AP1S1, together with MYO5B, are functionally associated with recycling endosomes and/or the Golgi apparatus. These are components of a complex process that controls the sorting and trafficking of proteins, including those involved in bile secretion. These gene variants therefore suggest that defects in intracellular trafficking take a prominent place in FIC. Here we review these FIC-associated trafficking genes and their variants, their contribution to biliary transporter and canalicular protein trafficking, and, when perturbed, to cholestatic liver disease. Published variants for each of these genes have been summarized in table format, providing a convenient reference for those who work in the intrahepatic cholestasis field.
A Modelization of the Propagation of COVID-19 in Regions of Spain and Italy with Evaluation of the Transmission Rates Related to the Intervention Measures
Authors: Nistal Raul , de la Sen Manuel , Gabirondo Jon , Alonso-Quesada Santiago , Garrido Aitor J. , Garrido Izaskun
Published: February 2021

Two discrete mathematical SIR models (Susceptible-Infectious-Recovered) are proposed for modelling the propagation of the SARS-CoV-2 (COVID-19) through Spain and Italy. One of the proposed models is delay-free while the other one considers a delay in the propagation of the infection. The objective is to estimate the transmission, also known as infectivity rate, through time taking into account the infection evolution data supplied by the official health care systems in both countries. Such a parameter is estimated through time at different regional levels and it is seen to be strongly dependent on the intervention measures such as the total (except essential activities) or partial levels of lockdown. Typically, the infectivity rate evolves towards a minimum value under total lockdown and it increases again when the confinement measures are partially or totally removed.
Impact of European Bison Grazing (Bison bonasus (L.)) on Species and Functional Traits of Carabid Beetle Assemblages in Selected Habitats in Poland
Authors: Schwerk Axel , Klich Daniel , Wójtowicz Elżbieta , Olech Wanda
Published: February 2021

Currently we are observing a drastic decline in insect fauna on a large scale. Grazing is regularly used as an ecological method of protecting or restoring special biotopes that are important for species conservation. The European bison (Bison bonasus (L.)) is the largest living wild terrestrial animal in Europe; therefore, a large impact on flora and fauna as a result of its grazing activity can be assumed. There might be potential for implementing conservation measures that employ active grazing. Therefore, a study on a free-ranging European bison population and captive herds in enclosures was carried out in order to determine whether European bison grazing has an impact on carabid beetle assemblages and whether the degree of this impact (if any) depends on the intensity of grazing. No notable influence on numbers of individuals of carabid beetles could be detected, but there was an indication that high-intensity grazing may cause an increase in the number of species. Increased intensity of grazing seems to have only a weak impact on the species assemblage structure, but it has a stronger impact on the composition of functional traits in the assemblage, as demonstrated in particular by the significant impact of captive herds. The stronger relation between grazing intensity and the functional traits of the carabid beetle assemblages than between grazing intensity and assemblage structure indicates that using European bison grazing as a method of ecological engineering in the context of nature conservation may have more potential in regulating properties and functions of the ecosystem than in the conservation of specific species or species assemblages of carabid beetles.
The Role of Cardiolipin as a Scaffold Mitochondrial Phospholipid in Autophagosome Formation: In Vitro Evidence
Authors: Manganelli Valeria , Capozzi Antonella , Recalchi Serena , Riitano Gloria , Mattei Vincenzo , Longo Agostina , Misasi Roberta , Garofalo Tina , Sorice Maurizio
Published: February 2021

Cardiolipin (CL) is a hallmark phospholipid localized within the inner mitochondrial membrane. Upon several mitochondrial stress conditions, CL is translocated to specialized platforms, where it may play a role in signaling events to promote mitophagy and apoptosis. Recent studies characterized the molecular composition of MAM-associated lipid microdomains and their implications in regulating the autophagic process. In this study we analyzed the presence of CL within MAMs following autophagic stimulus and the possible implication of raft-like microdomains enriched in CL as a signaling platform in autophagosome formation. Human 2FTGH fibroblasts and SKNB-E-2 cells were stimulated under nutrient deprivation with HBSS. MAM fraction was obtained by an ultracentrifugation procedure and analyzed by HPTLC immunostaining. CL interactions with mitofusin2 (MFN2), calnexin (CANX) and AMBRA1 were analyzed by scanning confocal microscopy and coimmunoprecipitation. The analysis revealed that CL accumulates in MAMs fractions following autophagic stimulus, where it interacts with MFN2 and CANX. It associates with AMBRA1, which in turn interacts with BECN1 and WIPI1. This study demonstrates that CL is present in MAM fractions following autophagy triggering and interacts with the multimolecular complex (AMBRA1/BECN1/WIPI1) involved in autophagosome formation. It may have both structural and functional implications in the pathophysiology of neurodegenerative disease(s).
Involvement of miR-30a-5p and miR-30d in Endothelial to Mesenchymal Transition and Early Osteogenic Commitment under Inflammatory Stress in HUVEC
Authors: Ciavarella Carmen , Motta Ilenia , Vasuri Francesco , Fittipaldi Silvia , Valente Sabrina , Pollutri Daniela , Ricci Francesca , Gargiulo Mauro , Pasquinelli Gianandrea
Published: February 2021

The endothelial to mesenchymal transition (End–MT) can be associated with vascular calcification, by providing mesengenic progenitors. In this study, we investigated a link between End–MT and the osteogenic process and explored the involvement of miR-30a-5p and miR-30d as potential regulators of these processes. End–MT was induced in Human Umbilical Vein Endothelial Cells (HUVEC) through transforming growth factor-β1 (TGF-β1), TGFβ-3 and tumor necrosis factor-α (TNF-α), for 24 h and 6 days. End–MT mediators, mesenchymal and osteo/chondrogenic markers were analyzed through Real-Time PCR, immunofluorescence, flow cytometry and Western Blot. miR-30a-5p and miR-30d over-expression was carried out in HUVEC to explore their effects on End–MT and osteogenic differentiation. HUVEC at 24 h and 6 days gained mesenchymal morphology markers, including matrix metalloproteinase 9 (MMP-9), SLUG, VIMENTIN and α-smooth muscle actin (α-SMA), and a significant migratory potential, notably with TNF-α. After 6 days, the osteo/chondrogenic markers runt-related transcription factor 2 (RUNX-2) and SRY box transcription factor 9 (SOX-9) were upregulated. At this time point, miR-30a-5p and miR-30d decreased. Over-expression of miR-30a-5p and miR-30d affected End–MT mediators and the osteogenic potency in HUVEC, by reducing SLUG, VIMENTIN and RUNX-2. Our data suggest that End–MT represents a key link between inflammation and vascular calcification. Further, miR-30a-5p and miR-30d can regulate both the End–MT and the osteogenic processes, prompting future studies for exploring their potential use as therapeutic targets or biomarkers in vascular diseases.
The Structure, Activation and Signaling of IRE1 and Its Role in Determining Cell Fate
Authors: Siwecka Natalia , Rozpędek-Kamińska Wioletta , Wawrzynkiewicz Adam , Pytel Dariusz , Diehl J. Alan , Majsterek Ireneusz
Published: February 2021

Inositol-requiring enzyme type 1 (IRE1) is a serine/threonine kinase acting as one of three branches of the Unfolded Protein Response (UPR) signaling pathway, which is activated upon endoplasmic reticulum (ER) stress conditions. It is known to be capable of inducing both pro-survival and pro-apoptotic cellular responses, which are strictly related to numerous human pathologies. Among others, IRE1 activity has been confirmed to be increased in cancer, neurodegeneration, inflammatory and metabolic disorders, which are associated with an accumulation of misfolded proteins within ER lumen and the resulting ER stress conditions. Emerging evidence suggests that genetic or pharmacological modulation of IRE1 may have a significant impact on cell viability, and thus may be a promising step forward towards development of novel therapeutic strategies. In this review, we extensively describe the structural analysis of IRE1 molecule, the molecular dynamics associated with IRE1 activation, and interconnection between it and the other branches of the UPR with regard to its potential use as a therapeutic target. Detailed knowledge of the molecular characteristics of the IRE1 protein and its activation may allow the design of specific kinase or RNase modulators that may act as drug candidates.
Optimisation of an Electrochemical DNA Sensor for Measuring KRAS G12D and G13D Point Mutations in Different Tumour Types
Authors: Attoye Bukola , Baker Matthew J. , Thomson Fiona , Pou Chantevy , Corrigan Damion K.
Published: February 2021

Circulating tumour DNA (ctDNA) is widely used in liquid biopsies due to having a presence in the blood that is typically in proportion to the stage of the cancer and because it may present a quick and practical method of capturing tumour heterogeneity. This paper outlines a simple electrochemical technique adapted towards point-of-care cancer detection and treatment monitoring from biofluids using a label-free detection strategy. The mutations used for analysis were the KRAS G12D and G13D mutations, which are both important in the initiation, progression and drug resistance of many human cancers, leading to a high mortality rate. A low-cost DNA sensor was developed to specifically investigate these common circulating tumour markers. Initially, we report on some developments made in carbon surface pre-treatment and the electrochemical detection scheme which ensure the most sensitive measurement technique is employed. Following pre-treatment of the sensor to ensure homogeneity, DNA probes developed specifically for detection of the KRAS G12D and G13D mutations were immobilized onto low-cost screen printed carbon electrodes using diazonium chemistry and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide coupling. Prior to electrochemical detection, the sensor was functionalised with target DNA amplified by standard and specialist PCR methodologies (6.3% increase). Assay development steps and DNA detection experiments were performed using standard voltammetry techniques. Sensitivity (as low as 0.58 ng/μL) and specificity (>300%) was achieved by detecting mutant KRAS G13D PCR amplicons against a background of wild-type KRAS DNA from the representative cancer sample and our findings give rise to the basis of a simple and very low-cost system for measuring ctDNA biomarkers in patient samples. The current time to receive results from the system was 3.5 h with appreciable scope for optimisation, thus far comparing favourably to the UK National Health Service biopsy service where patients can wait for weeks for biopsy results.
Impacts of Participation in Community-Based Physical Activity Programs on Cognitive Functions of Children and Youth with Neurodevelopmental Disabilities: A Scoping Review
Authors: Gitimoghaddam Mojgan , Vanderloo Leigh M. , Hung Rebecca , Ryce Andrea , McKellin William , Miller Anton , Collet Jean-Paul
Published: February 2021

This review paper aimed to undertake an extensive exploration of the extent, range, and nature of research activities regarding the effect and emerging evidence in the field of physical activity interventions on cognitive development among children and youth (0–17.99 years) with neurodevelopmental disorders (NDD), and to help identify key gaps in research and determine precise research questions for future investigations. To carry out this scoping review, five electronic databases were searched. A total of 12,097 articles were retrieved via search efforts with an additional 93 articles identified from the identified review papers. Sixty articles were eligible for inclusion. The results of this scoping review revealed many positive key cognitive outcomes related to physical activity including, but not limited to: focus, attention, self-control, cognitive process, and alertness. No studies reported a negative association between physical activity and cognitive outcomes. Based on the findings from this scoping review, physical activity appears to have a favorable impact on the cognitive outcomes of children and youth with NDD.
A Densely Connected Multi-Branch 3D Convolutional Neural Network for Motor Imagery EEG Decoding
Authors: Liu Tianjun , Yang Deling
Published: February 2021

Motor imagery (MI) is a classical method of brain–computer interaction (BCI), in which electroencephalogram (EEG) signal features evoked by imaginary body movements are recognized, and relevant information is extracted. Recently, various deep-learning methods are being focused on in finding an easy-to-use EEG representation method that can preserve both temporal information and spatial information. To further utilize the spatial and temporal features of EEG signals, an improved 3D representation of the EEG and a densely connected multi-branch 3D convolutional neural network (dense M3D CNN) for MI classification are introduced in this paper. Specifically, as compared to the original 3D representation, a new padding method is proposed to pad the points without electrodes with the mean of all the EEG signals. Based on this new 3D presentation, a densely connected multi-branch 3D CNN with a novel dense connectivity is proposed for extracting the EEG signal features. Experiments were carried out on the WAY-EEG-GAL and BCI competition IV 2a datasets to verify the performance of this proposed method. The experimental results show that the proposed framework achieves a state-of-the-art performance that significantly outperforms the multi-branch 3D CNN framework, with a 6.208% improvement in the average accuracy for the BCI competition IV 2a datasets and 6.281% improvement in the average accuracy for the WAY-EEG-GAL datasets, with a smaller standard deviation. The results also prove the effectiveness and robustness of the method, along with validating its use in MI-classification tasks.
Metformin and Androgen Receptor-Axis-Targeted (ARAT) Agents Induce Two PARP-1-Dependent Cell Death Pathways in Androgen-Sensitive Human Prostate Cancer Cells
Authors: Xie Yi , Wang Linbo , Khan Mohammad A. , Hamburger Anne W. , Guang Wei , Passaniti Antonino , Munir Kashif , Ross Douglas D. , Dean Michael , Hussain Arif
Published: February 2021

We explored whether the anti-prostate cancer (PC) activity of the androgen receptor-axis-targeted agents (ARATs) abiraterone and enzalutamide is enhanced by metformin. Using complementary biological and molecular approaches, we determined the associated underlying mechanisms in pre-clinical androgen-sensitive PC models. ARATs increased androgren receptors (ARs) in LNCaP and AR/ARv7 (AR variant) in VCaP cells, inhibited cell proliferation in both, and induced poly(ADP-ribose) polymerase-1 (PARP-1) cleavage and death in VCaP but not LNCaP cells. Metformin decreased AR and ARv7 expression and induced cleaved PARP-1-associated death in both cell lines. Metformin with abiraterone or enzalutamide decreased AR and ARv7 expression showed greater inhibition of cell proliferation and greater induction of cell death than single agent treatments. Combination treatments led to increased cleaved PARP-1 and enhanced PARP-1 activity manifested by increases in poly(ADP-ribose) (PAR) and nuclear accumulation of apoptosis inducing factor (AIF). Enhanced annexin V staining occurred in LNCaP cells only with metformin/ARAT combinations, but no caspase 3 recruitment occurred in either cell line. Finally, metformin and metformin/ARAT combinations increased lysosomal permeability resulting in cathepsin G-mediated PARP-1 cleavage and cell death. In conclusion, metformin enhances the efficacy of abiraterone and enzalutamide via two PARP-1-dependent, caspase 3-independent pathways, providing a rationale to evaluate these combinations in castration-sensitive PC.
Integrative Transcriptomic Network Analysis of Butyrate Treated Colorectal Cancer Cells
Authors: Ali Saira R. , Orang Ayla , Marri Shashikanth , McKinnon Ross A. , Meech Robyn , Michael Michael Z.
Published: February 2021

Diet-derived histone deacetylase inhibitor (HDACi), butyrate, alters global acetylation and consequently global gene expression in colorectal cancer (CRC) cells to exert its anticancer effects. Aberrant microRNA (miRNA) expression contributes to CRC development and progression. Butyrate-mediated modulation of microRNA (miRNA) expression remains under-investigated. This study employed a systems biology approach to gain a comprehensive understanding of the complex miRNA-mRNA interactions contributing to the butyrate response in CRC cells. Next-generation sequencing, gene ontology (GO) and pathway enrichment analyses were utilized to reveal the extent of butyrate-mediated gene regulation in CRC cells. Changes in cell proliferation, apoptosis, the cell cycle and gene expression induced by miRNAs and target gene knockdown in CRC cells were assessed. Butyrate induced differential expression of 113 miRNAs and 2447 protein-coding genes in HCT116 cells. Butyrate also altered transcript splicing of 1589 protein-coding genes. GO, and pathway enrichment analyses revealed the cell cycle to be a central target of the butyrate response. Two butyrate-induced miRNAs, miR-139 and miR-542, acted cooperatively with butyrate to induce apoptosis and reduce CRC cell proliferation by regulating target genes, including cell cycle-related EIF4G2 and BIRC5. EIF4G2 RNA interference mimicked the miR-139-mediated reduction in cell proliferation. The cell cycle is a critical pathway involved in the butyrate response of CRC cells. These findings reveal novel roles for miRNAs in the cell cycle-related, anticancer effects of butyrate in CRC cells.
Elucidating the Importance of DOT1L Recruitment in MLL-AF9 Leukemia and Hematopoiesis
Authors: Grigsby Sierrah M. , Friedman Ann , Chase Jennifer , Waas Bridget , Ropa James , Serio Justin , Shen Chenxi , Muntean Andrew G. , Maillard Ivan , Nikolovska-Coleska Zaneta
Published: February 2021

MLL1 (KMT2a) gene rearrangements underlie the pathogenesis of aggressive MLL-driven acute leukemia. AF9, one of the most common MLL-fusion partners, recruits the histone H3K79 methyltransferase DOT1L to MLL target genes, constitutively activating transcription of pro-leukemic targets. DOT1L has emerged as a therapeutic target in patients with MLL-driven leukemia. However, global DOT1L enzymatic inhibition may lead to off-target toxicities in non-leukemic cells that could decrease the therapeutic index of DOT1L inhibitors. To bypass this problem, we developed a novel approach targeting specific protein-protein interactions (PPIs) that mediate DOT1L recruitment to MLL target genes, and compared the effects of enzymatic and PPIs inhibition on leukemic and non-leukemic hematopoiesis. MLL-AF9 cell lines were engineered to carry mutant DOT1L constructs with a defective AF9 interaction site or lacking enzymatic activity. In cell lines expressing a DOT1L mutant with defective AF9 binding, we observed complete disruption of DOT1L recruitment to critical target genes and inhibition of leukemic cell growth. To evaluate the overall impact of DOT1L loss in non-leukemic hematopoiesis, we first assessed the impact of acute Dot1l inactivation in adult mouse bone marrow. We observed a rapid reduction in myeloid progenitor cell numbers within 7 days, followed by a loss of long-term hematopoietic stem cells. Furthermore, WT and PPI-deficient DOT1L mutants but not an enzymatically inactive DOT1L mutant were able to rescue sustained hematopoiesis. These data show that the AF9-DOT1L interaction is dispensable in non-leukemic hematopoiesis. Our findings support targeting of the MLL-AF9–DOT1L interaction as a promising therapeutic strategy that is selectively toxic to MLL-driven leukemic cells.
Highlights of the Nanocatalysis in Organic Chemistry
Authors: Martins Luísa M.D.R.S.
Published: February 2021

Nanocatalysts with superior characteristics regarding activity, selectivity, durability, and recoverability, are envisaged playing a pivotal role to enable a wealth of future applications and contribute to solve current environmental, social, and industrial problems [...]
Treatment Outcomes of Pediatric Acute Myeloid Leukemia in the Yeungnam Region: A Multicenter Retrospective Study of the Study Alliance of Yeungnam Pediatric Hematology–Oncology (SAYPH)
Authors: Lee Jae Min , Yang Eu Jeen , Park Kyung Mi , Lee Young-Ho , Chueh Heewon , Hah Jeong Ok , Park Ji Kyoung , Lim Jae Young , Park Eun Sil , Park Sang Kyu , Kim Heung Sik , Shim Ye Jee , Park Jeong A. , Choi Eun Jin , Lee Kun Soo , Kim Ji Yoon , Lim Young Tak
Published: February 2021

Acute myeloid leukemia (AML) is the second most common pediatric leukemia, with a survival rate of 70%. In this retrospective study, we evaluated the treatment outcomes of pediatric AML among 144 patients diagnosed between 2000 and 2013. After induction, 80.6% of patients achieved complete remission (CR). The 5-year overall survival (OS) and event-free survival (EFS) rates were 58.8 ± 4.2% and 49.8 ± 4.2%, respectively. Based on the response to induction therapy, the 5-year OS was 66.9 ± 5.7% in patients with CR (p < 0.001). Ninety-nine patients with CR after induction therapy were examined, and their 5-year OS and EFS were 66.4 ± 4.9% and 56.3 ± 5.1%, respectively. The 5-year OS rates according to treatment were 59.9 ± 7.4% in the chemotherapy group and 72.3 ± 6.3% in the hematopoietic stem cell transplantation (HSCT) group (p = 0.089). The EFS was 50.1 ± 7.4% in the chemotherapy group and 61.7 ± 6.9% in the HSCT group (p = 0.098). OS and EFS according to cytogenetics were insignificant. Our findings confirmed that the response to induction treatment was important for survival and HSCT had no significant survival benefits compared with those of chemotherapy. Moreover, many early induction deaths under the age of 2 years were observed.
Social and Family Factors as Determinants of Sleep Habits in Japanese Elementary School Children: A Cross-Sectional Study from the Super Shokuiku School Project
Authors: Sawa Satomi , Sekine Michikazu , Yamada Masaaki
Published: February 2021

This study explored the associations of lifestyle, familial, and social factors with sleep habits in 1882 elementary school children, aged 6–13 years, from the Super Shokuiku School Project in January 2016. A survey assessed sex, grade, sleep habits, lifestyle, social background, and parental lifestyle. Bedtime “≥22:00,” wake-up time “≥07:00,” sleep duration “<8 h,” and “daytime sleepiness” were defined as poor sleep habits; correlates were analyzed using logistic regression. Skipping breakfast was consistently significantly associated with poor sleep, especially among children with late wake-up times (adjusted odds ratio 5.45; 95% confidence interval 3.20–9.30). Excessive screen time was associated with late bed and wake-up times. Physical inactivity was significantly associated with daytime sleepiness. Children of mothers with poor lifestyle habits were likely to go to bed late and feel sleepy the next day. Social and family factors were associated with children’s sleep habits. Several behaviors, including skipping breakfast, excessive screen time, and physical inactivity, were associated with poor sleep habits, manifesting as a night-oriented lifestyle. Although a longitudinal study is needed to determine causality, in addition to sleep education for children, sleep education for parents and society at large may be necessary to improve children’s sleep habits.
Vitamin D Status in Children in Greece and Its Relationship with Sunscreen Application
Authors: Feketea Gavriela Maria , Bocsan Ioana Corina , Tsiros Georgios , Voila Panagiota , Stanciu Luminita Aurelia , Zdrenghea Mihnea
Published: February 2021

The aim of this study was to characterize the prevalence and seasonal variation of vitamin D (vit D) deficiency/insufficiency in healthy children and adolescents in Greece, and to explore its relationship with the use of sunscreens. The serum level of 25-hydroxy-vitamin D (25(OH)D) was measured in 376 children and adolescents (184 males and 192 females) with a mean age of 7.6 ± 4.9 years, at different time points over a period of 13 months. The prevalence of low serum 25(OH)D level, including deficiency and insufficiency, was 66.2%. The lowest mean 25(OH)D was observed in the month of January (17.9 ± 6.8 ng/mL) and the highest in September, July, August, and October (34.6 ± 8.7, 33.0 ± 9.4, 30.1 ± 8.2, and 30.1 ± 10.6 ng/mL, respectively). Higher levels of serum 25(OH)D were detected in the children to whom sunscreens had been applied on the beach (p = 0.001) or off the beach (p < 0.001). The subjects with deficiency and insufficiency were significantly older than those with normal levels of 25(OH)D, but no significant differences were demonstrated according to gender. This study emphasizes the high prevalence of low serum levels of 25(OH)D and their seasonal variation in children living in a region characterized by many hours of sunshine. Our data suggest that the real-life use of sunscreens during the summer months allows sufficient sunlight to be received to enable production of vit D at a level adequate to maintain normal serum levels. Vit D supplements should be given to children during the months of lower sun exposure.
Gaze Following and Pupil Dilation as Early Diagnostic Markers of Autism in Toddlers
Authors: Camero Raquel , Martínez Verónica , Gallego Carlos
Published: February 2021

Background: Children with autism spectrum disorder (ASD) show certain characteristics in visual attention. These may generate differences with non-autistic children in the integration of relevant social information to set the basis of communication. Reliable and objective measurement of these characteristics in a language learning context could contribute to a more accurate early diagnosis of ASD. Gaze following and pupil dilation are being studied as possible reliable measures of visual attention for the early detection of ASD. The eye-tracking methodology allows objective measurement of these biomarkers. The aim of this study is to determine whether measurements of gaze following and pupillary dilation in a linguistic interaction task are potential objective biomarkers for the early diagnosis of ASD. Method: A group of 20 children between 17 and 24 months of age, made up of 10 neurotypical children (NT) and 10 children with an increased likelihood of developing ASD were paired together according to chronological age. A human face on a monitor pronounced pseudowords associated with pseudo-objects. Gaze following and pupil dilation were registered during the task These measurements were captured using eye-tracking methodology. Results: Significant statistical differences were found in the time of gaze fixation on the human face and on the object, as well as in the number of gazes. Children with an increased possibility of developing ASD showed a slightly higher pupil dilation than NT children. However, this difference was not statistically significant. Nevertheless, their pupil dilation was uniform throughout the different periods of the task while NT participants showed greater dilation on hearing the pseudoword. Conclusions: The fixing and the duration of gaze, objectively measured by a Tobii eye-tracking system, could be considered as potential biomarkers for early detection of ASD. Additionally, pupil dilation measurement could reflect differential activation patterns during word processing in possible ASD toddlers and NT toddlers.
Patient Centeredness in Orthognathic Surgery
Authors: Vieira Alexandre R. , Prinz Maria C. O.
Published: February 2021

Patient centeredness in planning treatment and research has become paramount. The goal of this report was to describe a complex case in which untreated chronic pain was not properly addressed to reflect on the need to establish alternative protocols for controlling chronic orofacial pain. When a female underwent orthognathic surgery to correct her occlusion, she not only ended up with a worse occlusion, she developed chronic orofacial pain that could not be treated by opioids and only improved after the use of neuropathic medication, and finally disappeared after the use of low-level laser therapy. There is a need to incorporate alternative nonpharmacological approaches to manage chronic pain. Further, what the patient’s goals are for their treatments should be given priority in case of elective procedures.
Oxidation and Microstructural Behaviors of Ni-Based Alloys Strengthened by (Ta, Hf)C Carbides at 1250 °C in Air
Authors: Berthod Patrice , Kane Dame Assane , Aranda Lionel
Published: February 2021

Two alloys based on nickel and designed to be reinforced by MC carbides thanks to the presence of Hf and Ta were produced by casting. They were subjected to 50 h-long isothermal exposure at 1250 °C in synthetic air with thermogravimetric monitoring of the oxidation progress. In the as-cast state, they contain both significant quantities of (Hf,Ta)C carbides. Their verified melting start temperatures, close to 1300 °C, allowed performing the planned oxidation test. The two alloys demonstrated a chromia-forming behavior with limited mass gain rates. However, they also showed a rather low resistance to oxide spallation at cooling, which is in proportion with the Ta/Hf ratio. After 50 h at 1250 °C, the morphology of the carbides had significantly evolved, from their initial script-like shape to a fragmented and coalesced state. The results are promising, but the use of these alloys at 1250 °C needs further improvements on the mechanical level.
Mini-Review Regarding the Applicability of Genome Editing Techniques Developed for Studying Infertility
Authors: Doroftei Bogdan , Ilie Ovidiu-Dumitru , Puiu Maria , Ciobica Alin , Ilea Ciprian
Published: February 2021

Infertility is a highly debated topic today. It has been long hypothesized that infertility has an idiopathic cause, but recent studies demonstrated the existence of a genetic substrate. Fortunately, the methods of editing the human genome proven to be revolutionary. Following research conducted, we identified a total of 21 relevant studies; 14 were performed on mice, 5 on zebrafish and 2 on rats. We concluded that over forty-four genes in total are dispensable for fertility in both sexes without affecting host homeostasis. However, there are genes whose loss-of-function induces moderate to severe phenotypic changes in both sexes. There were situations in which the authors reported infertility, exhibited by the experimental model, or other pathologies such as cryptorchidism, cataracts, or reduced motor activity. Overall, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 are techniques that offer a wide range of possibilities for studying infertility, even to create mutant variants. It can be concluded that ZFNs, TALENs, and CRISPR/Cas9 are crucial tools in biomedical research.
Anatomical Variation and Clinical Diagnosis
Authors: Smith Heather F.
Published: February 2021

In the anatomical sciences, it has long been recognized that the human body displays a range of morphological patterns and arrangements, often termed “anatomical variation” [...]
Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer
Authors: Kurose Sonomi , Nakayama Kentaro , Razia Sultana , Ishikawa Masako , Ishibashi Tomoka , Yamashita Hitomi , Sato Seiya , Sakiyama Asuka , Yoshioka Shinya , Kobayashi Misa , Nakayama Satoru , Otuski Yoshiro , Ishikawa Noriyoshi , Kyo Satoru
Published: February 2021

Malignant transformation of extraovarian endometriosis is rare, with the carcinogenesis mechanism unclear. To clarify the actionable variants of rare-site endometriosis-associated cancer (RSEAC), we performed whole-exome sequencing for the tumor, in two patients. The intestine was affected in both cases, although the histology was that of clear cell carcinoma and undifferentiated carcinoma, respectively. Therefore, the cases were referred to as endometriosis-associated intestinal tumors (EIATs). Actionable variants (all frameshift mutations) were identified in tumor suppressor genes ARID1A, PTEN, and p53; however, no oncogenic variants were identified. Both cases were microsatellite stable. The patient with undifferentiated carcinoma exhibited hypermutator and homologous recombination deficiency phenotypes. The dominant mutation signatures were signature 30 (small subset of breast cancers) and 19 (pilocytic astrocytoma) in patient 1, and signature 5 (small subset of breast cancers) and 3 (breast, ovarian, and pancreatic cancers) in patient 2. Immunohistochemistry revealed positive CD8 and PD-1 expression in both patients; patient 1 also showed positive PDL-1 expression. Our results suggest that RSEAC is associated with variants of tumor suppressor genes as epigenetic alterations. Mutation signature-based whole-exome sequencing could be useful to select an adjuvant chemotherapy regimen. High CD8 and PD-1 expression in RSEAC suggests that immune checkpoint inhibitors are useful for treatment.
Possible Alterations of Local Gravitational Field Inside a Superconductor
Authors: Ummarino Giovanni Alberto , Gallerati Antonio
Published: February 2021

We calculate the possible interaction between a superconductor and the static Earth’s gravitational fields, making use of the gravito-Maxwell formalism combined with the time-dependent Ginzburg–Landau theory. We try to estimate which are the most favorable conditions to enhance the effect, optimizing the superconductor parameters characterizing the chosen sample. We also give a qualitative comparison of the behavior of high–Tc and classical low–Tc superconductors with respect to the gravity/superfluid interplay.
Analysis of the Properties of Fractional Heat Conduction in Porous Electrodes of Lithium-Ion Batteries
Authors: Lu Xin , Li Hui , Chen Ning
Published: February 2021

Research on the heat transfer characteristics of lithium-ion batteries is of great significance to the thermal management system of electric vehicles. The electrodes of lithium-ion batteries are composed of porous materials, and thus the heat conduction of the battery is not a standard form of diffusion. The traditional heat conduction model is not suitable for lithium-ion batteries. In this paper, a fractional heat conduction model is used to study the heat transfer properties of lithium-ion batteries. Firstly, the heat conduction model of the battery is established based on the fractional calculus theory. Then, the temperature characteristic test was carried out to collect the temperature of the battery in various operating environments. Finally, the temperature calculated by the fractional heat conduction model was compared with the measured temperature. The results show that the accuracy of fractional heat conduction model is higher than that of traditional heat conduction model. The fractional heat conduction model can well simulate the transient temperature field of the battery. The fractional heat conduction model can be used to monitor the temperature of the battery, so as to ensure the safety and stability of the battery performance.