bluuebunny/crossref_metadata_2025 huggingface dataset:
CRISPR Co-Editing Strategy for Scarless Homology-Directed Genome Editing
Authors: Reuven Nina , Adler Julia , Myers Nadav , Shaul Yosef
Published: April 2021

The clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 has revolutionized genome editing by providing a simple and robust means to cleave specific genomic sequences. However, introducing templated changes at the targeted site usually requires homology-directed repair (HDR), active in only a small subset of cells in culture. To enrich for HDR-dependent edited cells, we employed a co-editing strategy, editing a gene of interest (GOI) concomitantly with rescuing an endogenous pre-made temperature-sensitive (ts) mutation. By using the repair of the ts mutation as a selectable marker, the selection is “scarless” since editing restores the wild-type (wt) sequence. As proof of principle, we used HEK293 and HeLa cells with a ts mutation in the essential TAF1 gene. CRISPR co-editing of TAF1ts and a GOI resulted in up to 90% of the temperature-resistant cells bearing the desired mutation in the GOI. We used this system to insert large cassettes encoded by plasmid donors and smaller changes encoded by single-stranded oligonucleotide donors (ssODN). Of note, among the genes we edited was the introduction of a T35A mutation in the proteasome subunit PSMB6, which eliminates its caspase-like activity. The edited cells showed a specific reduction in this activity, demonstrating this system’s utility in generating cell lines with biologically relevant mutations in endogenous genes. This approach offers a rapid, efficient, and scarless method for selecting genome-edited cells requiring HDR.
Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level
Authors: Al Rihani Sweilem B. , Darakjian Lucy I. , Deodhar Malavika , Dow Pamela , Turgeon Jacques , Michaud Veronique
Published: April 2021

The blood–brain barrier (BBB) is a highly selective and restrictive semipermeable network of cells and blood vessel constituents. All components of the neurovascular unit give to the BBB its crucial and protective function, i.e., to regulate homeostasis in the central nervous system (CNS) by removing substances from the endothelial compartment and supplying the brain with nutrients and other endogenous compounds. Many transporters have been identified that play a role in maintaining BBB integrity and homeostasis. As such, the restrictive nature of the BBB provides an obstacle for drug delivery to the CNS. Nevertheless, according to their physicochemical or pharmacological properties, drugs may reach the CNS by passive diffusion or be subjected to putative influx and/or efflux through BBB membrane transporters, allowing or limiting their distribution to the CNS. Drug transporters functionally expressed on various compartments of the BBB involve numerous proteins from either the ATP-binding cassette (ABC) or the solute carrier (SLC) superfamilies. Pathophysiological stressors, age, and age-associated disorders may alter the expression level and functionality of transporter protein elements that modulate drug distribution and accumulation into the brain, namely, drug efficacy and toxicity. This review focuses and sheds light on the influence of inflammatory conditions and diseases such as Alzheimer’s disease, epilepsy, and stroke on the expression and functionality of the BBB drug transporters, the consequential modulation of drug distribution to the brain, and their impact on drug efficacy and toxicity.
Application of Upstream Open Reading Frames (uORFs) Editing for the Development of Stress-Tolerant Crops
Authors: Um Taeyoung , Park Taehyeon , Shim Jae Sung , Kim Youn Shic , Lee Gang-Seob , Choi Ik-Young , Kim Ju-Kon , Seo Jun Sung , Park Soo Chul
Published: April 2021

Global population growth and climate change are posing increasing challenges to the production of a stable crop supply using current agricultural practices. The generation of genetically modified (GM) crops has contributed to improving crop stress tolerance and productivity; however, many regulations are still in place that limit their commercialization. Recently, alternative biotechnology-based strategies, such as gene-edited (GE) crops, have been in the spotlight. Gene-editing technology, based on the clustered regularly interspaced short palindromic repeats (CRISPR) platform, has emerged as a revolutionary tool for targeted gene mutation, and has received attention as a game changer in the global biotechnology market. Here, we briefly introduce the concept of upstream open reading frames (uORFs) editing, which allows for control of the translation of downstream ORFs, and outline the potential for enhancing target gene expression by mutating uORFs. We discuss the current status of developing stress-tolerant crops, and discuss uORF targets associated with salt stress-responsive genes in rice that have already been verified by transgenic research. Finally, we overview the strategy for developing GE crops using uORF editing via the CRISPR-Cas9 system. A case is therefore made that the mutation of uORFs represents an efficient method for developing GE crops and an expansion of the scope of application of genome editing technology.
Mechanically Strong Polyurethane Composites Reinforced with Montmorillonite-Modified Sage Filler (Salvia officinalis L.)
Authors: Członka Sylwia , Kairytė Agnė , Miedzińska Karolina , Strąkowska Anna , Adamus-Włodarczyk Agnieszka
Published: April 2021

Rigid polyurethane (PUR) foams reinforced with 1, 2, and 5 wt.% of salvia filler (SO filler) and montmorillonite-modified salvia filler (MMT-modified SO filler) were produced in the following study. The impact of 1, 2, and 5 wt.% of SO filler and MMT-modified SO filler on the morphological, chemical, and mechanical properties of PUR composites were examined. In both cases, the addition of 1 and 2 wt.% of SO fillers resulted in the synthesis of PUR composites with improved physicomechanical properties, while the addition of 5 wt.% of SO fillers resulted in the formation of PUR composites with a less uniform structure and, therefore, some deterioration in their physicomechanical performances. Moreover, the results showed that the modification of SO filler with MMT improved the interphase compatibility between filler surface and PUR matrix. Therefore, such reinforced PUR composites were characterized by a well-developed closed-cell structure and improved mechanical, thermal, and flame-retardant performances. For example, when compared with reference foam, the addition of 2 wt.% of MMT-modified SO filler resulted in the formation of PUR composites with greater mechanical properties (compressive strength, flexural strength) and improved dynamic-mechanical properties (storage modulus). The PUR composites were characterized by better thermal stability as well as improved flame retardancy—e.g., decreased peak rate of heat release (pHRR), reduced total smoke release (TSR), and increased limiting oxygen index (LOI).
Positive Effects of Oral Antibiotic Administration in Murine Chronic Graft-Versus-Host Disease
Authors: Sato Shinri , Shimizu Eisuke , He Jingliang , Ogawa Mamoru , Asai Kazuki , Yazu Hiroyuki , Rusch Robert , Yamane Mio , Yang Fan , Fukuda Shinji , Kawakami Yutaka , Tsubota Kazuo , Ogawa Yoko
Published: April 2021

Chronic graft-versus-host disease (cGVHD) is one of the most frequent complications experienced after allogeneic hematopoietic stem cell transplantation. Reportedly, dysbiosis and severe damage to the microbiome are also closely associated with GVHD. Herein, we aimed to elucidate the positive and negative effects of the administration of various antibiotics in a murine model of cGVHD. For allogeneic bone marrow transplantation (allo-BMT), bone marrow from B10.D2 mice were transplanted in BALB/c mice to induce cGVHD. The cGVHD mice were orally administered ampicillin, gentamicin (GM), fradiomycin, vancomycin, or the solvent vehicle (control group). Among the antibiotic-treated mice, the systemic cGVHD phenotypes and ocular cGVHD manifestations were suppressed significantly in GM-treated mice compared to that in control mice. Inflammatory cell infiltration and fibrosis in cGVHD-targeted organs were significantly attenuated in GM-treated mice. Although regulatory T cells were retained at greater levels in GM-treated mice, there were significantly fewer Th17 cells and interleukin (IL)-6-producing macrophages in cGVHD-targeted organs in these mice. Collectively, our results revealed that orally administered GM may exert positive effects in a cGVHD mouse model.
High-Fat Diet Leads to Reduced Protein O-GlcNAcylation and Mitochondrial Defects Promoting the Development of Alzheimer’s Disease Signatures
Authors: Zuliani Ilaria , Lanzillotta Chiara , Tramutola Antonella , Barone Eugenio , Perluigi Marzia , Rinaldo Serena , Paone Alessio , Cutruzzolà Francesca , Bellanti Francesco , Spinelli Matteo , Natale Francesca , Fusco Salvatore , Grassi Claudio , Di Domenico Fabio
Published: April 2021

The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer’s disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-fat diet (HFD) is known to foster metabolic dysregulation and insulin resistance in the brain and such effects have been associated with the reduction of cognitive performances. Remarkably, a significant role in HFD-related cognitive decline might be played by aberrant protein O-GlcNAcylation by triggering the development of AD signature and mitochondrial impairment. Our data support the impairment of total protein O-GlcNAcylation profile both in the brain of mice subjected to a 6-week high-fat-diet (HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling and reduced mitochondrial activity), which promoted the dysregulation of the hexosamine biosynthetic pathway (HBP) flux, through the AMPK-driven reduction of GFAT1 activation. Further, we observed that a HFD induced the selective impairment of O-GlcNAcylated-tau and of O-GlcNAcylated-Complex I subunit NDUFB8, thus resulting in tau toxicity and reduced respiratory chain functionality respectively, highlighting the involvement of this posttranslational modification in the neurodegenerative process.
Changes in Bacterial Endophyte Community Following Aspergillus flavus Infection in Resistant and Susceptible Maize Kernels
Authors: Majumdar Rajtilak , Kandel Shyam L. , Cary Jeffrey W. , Rajasekaran Kanniah
Published: April 2021

Aspergillus flavus (A. flavus)-mediated aflatoxin contamination in maize is a major global economic and health concern. As A. flavus is an opportunistic seed pathogen, the identification of factors contributing to kernel resistance will be of great importance in the development of novel mitigation strategies. Using V3–V4 bacterial rRNA sequencing and seeds of A. flavus-resistant maize breeding lines TZAR102 and MI82 and a susceptible line, SC212, we investigated kernel-specific changes in bacterial endophytes during infection. A total of 81 bacterial genera belonging to 10 phyla were detected. Bacteria belonging to the phylum Tenericutes comprised 86–99% of the detected phyla, followed by Proteobacteria (14%) and others (<5%) that changed with treatments and/or genotypes. Higher basal levels (without infection) of Streptomyces and Microbacterium in TZAR102 and increases in the abundance of Stenotrophomonas and Sphingomonas in MI82 following infection may suggest their role in resistance. Functional profiling of bacteria using 16S rRNA sequencing data revealed the presence of bacteria associated with the production of putative type II polyketides and sesquiterpenoids in the resistant vs. susceptible lines. Future characterization of endophytes predicted to possess antifungal/ anti-aflatoxigenic properties will aid in their development as effective biocontrol agents or microbiome markers for maize aflatoxin resistance.
Association of TaD14-4D, a Gene Involved in Strigolactone Signaling, with Yield Contributing Traits in Wheat
Authors: Liu Ruifang , Hou Jian , Li Huifang , Xu Ping , Zhang Zhengbin , Zhang Xueyong
Published: April 2021

Tillering is a crucial agronomic trait of wheat; it determines yield and plant architecture. Strigolactones (SLs) have been reported to inhibit plant branching. D14, a receptor of SLs, has been described to affect tillering in rice, yet it has seldomly been studied in wheat. In this study, three TaD14 homoeologous genes, TaD14-4A, TaD14-4B, and TaD14-4D, were identified. TaD14-4A, TaD14-4B, and TaD14-4D were constitutively expressed, and TaD14-4D had a higher expression level in most tissues. TaD14 proteins were localized in both cytoplasm and nucleus. An SNP and a 22 bp insertion/deletion (Indel) at the exon regions of TaD14-4D were detected, forming three haplotypes, namely 4D-HapI, 4D-HapII, and 4D-HapIII. Due to the frameshift mutation in the coding region of 4D-HapII, the interaction of 4D-HapII with TaMAX2 and TaD53 was blocked, which led to the blocking of SL signal transduction. Based on the two variation sites, two molecular markers, namely dCAPS-250 and Indel-747, were developed. Association analysis suggested that haplotypes of TaD14-4D were associated with effective tillering number (ETN) and thousand kernel weight (TKW) simultaneously in four environments. The favorable haplotype 4D-HapIII underwent positive selection in global wheat breeding. This study provides insights into understanding the function of natural variations of TaD14-4D and develops two useful molecular markers for wheat breeding.
Uptake of MicroRNAs from Exosome-Like Nanovesicles of Edible Plant Juice by Rat Enterocytes
Authors: Ito Yuko , Taniguchi Kohei , Kuranaga Yuki , Eid Nabil , Inomata Yosuke , Lee Sang-Woong , Uchiyama Kazuhisa
Published: April 2021

MicroRNAs (miRNAs) are small RNAs present in extracellular vesicles (EVs) that, when transferred to a target cell, affect its biological functions. Plant miRNAs regulate the expression of certain mammalian genes. Here, we characterized EVs in fruit and vegetable juice, and their miRNA cargo, and investigated whether such miRNA-containing EVs could be taken up by mammalian enterocytes in vitro. Using filtration and ultra-centrifugation methods, EVs were purified from commercially available and manually squeezed plant juice. EV morphological features and subcellular localization were analyzed using the NanoSight tracking system and electron microscopy. Plant EV miRNA levels were evaluated using quantitative reverse transcription PCR. For the in vitro EV uptake experiments, rat intestinal epithelial cells (IEC6) were used. Plant EVs shared morphological features with mammalian EVs and contained miR156a-5p, miR166a-3p, and miR168a-5p. EVs were present in the cell sap-filled central vacuoles and were taken up by IEC6 cells. Edible plant cells produce EVs that contain various miRNAs and release them into the central vacuole. The exogenous plant EVs are taken up by mammalian enterocytes in vitro. These findings suggest the possibility that exogenous plant miRNAs carried by EVs can be absorbed via the gastrointestinal tract.
CHOP Pro-Apoptotic Transcriptional Program in Response to ER Stress Is Hacked by Zika Virus
Authors: Turpin Jonathan , El-Safadi Daed , Lebeau Grégorie , Frumence Etienne , Desprès Philippe , Viranaïcken Wildriss , Krejbich-Trotot Pascale
Published: April 2021

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus considered as a threat to human health due to large epidemics and serious clinical outcomes such as microcephaly in new-borns. Like all flaviviruses, ZIKV relies on the cellular machinery to complete its viral cycle, with the endoplasmic reticulum (ER) being the critical site of viral replication factories. The sudden high protein load in the ER induces an ER stress to which the cell responds with an appropriate unfolded protein response (UPR) in an attempt to restore its disturbed homeostasis. When the restoration fails, the cell signalling leads to a programmed cell death by apoptosis with the upregulation of the UPR-induced C/EBP homologous protein (CHOP) which acts as the main trigger for this fatal outcome. Our previous studies have shown the ability of ZIKV to manipulate various cellular responses in order to optimize virus production. ZIKV is able to delay apoptosis to its benefit and although ER stress is induced, the UPR is not complete. Here we discovered that ZIKV impairs the expression of CHOP/DDIT3, the main factor responsible of ER-stress driven apoptosis. Surprisingly, the mechanism does not take place at the transcriptional level but at the translational level.
Editorial for Special Issue Indoor Navigation in Smart Cities
Authors: Motta Gianmario
Published: April 2021

The lifecycle of indoor navigation includes various phases [...]
Synthesis of a Ru(II) Complex with a Naphthoquinone-Annelated Imidazole Ligand Exhibiting Proton-Responsive Redox and Luminescent Behavior
Authors: Shiga Takuya , Tachibana Minami , Oshio Hiroki , Nihei Masayuki
Published: April 2021

A mononuclear ruthenium complex, [RuII(L)(bpy)2](PF6), with a naphthoquinone-annelated imidazole ligand HL (2-(pyridin-2-yl)-1H-naphtho[2,3-d]imidazole-4,9-dione) was synthesized and structurally characterized. Electrochemical study reveals that the Ru complex shows four reversible redox waves at +0.98 V, −1.13 V, −1.53 V, and −1.71 V versus SCE in acetonitrile, which are assigned to Ru(II)/Ru(III), L−/L•2−, and two bpy/bpy•− redox couples, respectively. The redox potential of Ru(II)/Ru(III) was positively shifted upon the addition of trifluoromethanesulfonic acid due to protonation of the L− moiety, leading to stabilization of the Ru 4d orbital. In UV-vis absorption measurements for the Ru complex in acetonitrile, a metal-to-ligand charge transfer (MLCT) band was observed at 476 nm, which was shifted to 450 nm by protonation, which might be due to a decrease in the electron delocalization and stabilization of the π orbitals in L−. The blue shift of the MLCT band by protonation was associated with a shift of an emission band from 774 nm to 620 nm, which could be caused by the decreased electronic delocalization in the MLCT excited state. These electrochemical and spectroscopic changes were reversible for the protonation/deprotonation stimuli.
Association of Prolonged Fluoroscopy Time with Procedural Success of Percutaneous Coronary Intervention for Stable Coronary Artery Disease with and without Chronic Total Occlusion
Authors: Tajti Peter , Ayoub Mohamed , Nuehrenberg Thomas , Ferenc Miroslaw , Behnes Michael , Buettner Heinz Joachim , Neumann Franz-Josef , Mashayekhi Kambis
Published: April 2021

Background: In percutaneous coronary interventions (PCI), the impact of prolonged fluoroscopy time (FT) on procedural outcomes is poorly studied. Methods and Results: We analyzed the outcomes of 12,538 consecutive elective PCIs. The primary endpoint was procedure failure (PF), the composite of technical failure, and adverse in-hospital events including all-cause death, myocardial infarction, stroke, and target vessel revascularization (MACCE), as well as pericardial tamponade. We stratified the procedures as PCI for chronic total occlusion (CTO, n = 2720) and PCI for non-CTO (n = 9818). Logistic regression demonstrated a significant association between fluoroscopy time and procedural failure with a significant interaction with PCI type (both p < 0.001). The odds ratios (OR) of procedural failure for a 10-min increment in FT were 1.15 (confidence interval (CI) 95% 1.12–1.18, p < 0.001) in non-CTO PCI and 1.05 (CI 95% 1.03–1.06, p < 0.001) in CTO PCI. The optimal cut-point for prediction of PF was 21.1 min in non-CTO PCI (procedural success in 98.4% versus 95.3%, adjusted OR for PF 2.79 (CI 95% 1.93–4.04), p < 0.001) and 41 min in CTO PCI (procedural success in 92.3% versus 83.8%, adjusted OR for PF 2.18 (CI 95% 1.64–2.94), p < 0.001). In CTO PCI, the increase in PF with FT was largely driven by technical failure (adjusted OR 2.25 (CI 95% 1.65–3.10), p < 0.001), whereas in non-CTO PCI, it was driven by major complications (adjusted OR 2.94 (CI 95% 1.93–4.53), p < 0.001). Conclusions: Prolonged FT is strongly associated with procedural failure in both non-CTO and CTO PCI. In CTO PCI, this relation is shifted towards longer FT. The mechanisms of procedural failure differ between CTO and non-CTO PCI.
Predictive Periodontitis: The Most Promising Salivary Biomarkers for Early Diagnosis of Periodontitis
Authors: Cafiero Carlo , Spagnuolo Gianrico , Marenzi Gaetano , Martuscelli Ranieri , Colamaio Michele , Leuci Stefania
Published: April 2021

The primary cause of tooth loss in the industrialized world is periodontitis, a bacterial anaerobic infection whose pathogenesis is characterized by composite immune response. At present, the diagnose of periodontitis is made by a complete status check of the patient’s periodontal health; full-mouth plaque score, full-mouth bleeding score, probing depth, clinical attachment level, bleeding on probing, recessions, mobility, and migration are evaluated in order to provides a clear picture of the periodontal conditions of a single patient. Chair-side diagnostic tests based on whole saliva could be routinely used by periodontists for a very early diagnosis of periodontitis, monitoring, prognosis, and management of periodontal patients by biomarker detection, whose diagnostic validity is related to sensitivity and specificity. Recent paper reviews and meta-analyses have focused on five promising host derived biomarkers as candidate for early diagnosis of periodontitis: MMP-8 (Metalloproteinase-8), MIP-1α (Macrophage inflammatory protein-1 alpha), IL-1 β (Interleukin-1 beta), IL-6 (Interleukin-6), and HB (Hemoglobin), and their combinations. Chair-side Lab-on-a-chip (LOC) technology may soon become an important part of efforts to detect such biomarkers in saliva medium to improve worldwide periodontal health in developed nations as well as in underserved communities and poor countries. Their applications in preventive and predictive medicine is now fundamental, and is aimed at the early detection of risk factors or the presence or evolution of the disease, and in personalized medicine, which aims to identify tailor-made treatments for individual patients. The aim of the present paper is to be informative about host derived periodontal biomarkers and, in particular, we intend to report information about the most important immune response derived biomarkers and Hemoglobin as candidates to be routinely utilized in order to obtain a chair-side early diagnosis of periodontal disease.
GT-Repeat Polymorphism in the HO-1 Gene Promoter Is Associated with Risk of Liver Cancer: A Follow-Up Study from Arseniasis-Endemic Areas in Taiwan
Authors: Wu Meei-Maan , Hsieh Fang-I , Hsu Ling-I , Lee Te-Chang , Chiou Hung-Yi , Chen Chien-Jen
Published: April 2021

The induction of heme oxygenase-1 (HO-1) has been shown to have therapeutic potential in experimental models of hepatitis and liver fibrosis, which are closely related to liver cancer. In humans, HO-1 induction is transcriptionally modulated by the length of a GT-repeat [(GT)n] in the promoter region. We aimed to investigate the effect of HO-1 (GT)n variants on liver cancer in a human population. We determined the HO-1 genotype in 1153 study subjects and examined their association with liver cancer risk during a 15.9-year follow-up. Allelic polymorphisms were classified as short [S, <27 (GT)n] or long [L, ≥27 (GT)n]. Newly developed cancer cases were identified through linkage to the National Cancer Registry of Taiwan. Multivariate Cox regression analysis was used to evaluate the effect of the HO-1 (GT)n variants. Alpha-fetoprotein (AFP) and cirrhosis history were also examined. The S/S genotype was found to be significantly associated with liver cancer risk, compared to the L/S and L/L genotypes. The S/S genotype group also had a higher percentage of subjects with abnormal AFP levels than other groups. There were significant percentages of cirrhosis among groups who carried S-alleles. Our findings indicate that short (GT)n variants in the HO-1 gene may confer susceptibility to rather than protection from liver cirrhosis/cancer.
Prior Neurosurgery Decreases fMRI Estimates of Language Laterality in Patients with Gliomas within Anterior Language Sites
Authors: Połczyńska Monika M. , Ding Bryan , Dang Bianca H. , Cavanagh Lucia
Published: April 2021

The impact of previous surgery on the assessment of language dominance with preoperative fMRI remains inconclusive in patients with recurrent brain tumors. Samples in this retrospective study included 17 patients with prior brain surgery and 21 patients without prior surgery (38 patients total; mean age 43.2, SD = 11.9; 18 females; seven left-handed). All the patients were left language dominant, as determined clinically. The two samples were matched on 10 known confounds, including, for example, tumor laterality and location (all tumors affected Brodmann areas 44/45/47). We calculated fMRI language dominance with laterality indices using a whole-brain and region of interest approach (ROI; Broca’s and Wernicke’s area). Patients with prior surgery had decreased fMRI language dominance (p = 0.03) with more activity in the right hemisphere (p = 0.03) than patients without surgery. Patients with prior brain surgery did not display less language activity in the left hemisphere than patients without surgery. These results were replicated using an ROI approach in the affected Broca’s area. Further, we observed no differences between our samples in the unaffected Wernicke’s area. In sum, prior brain surgery affecting Broca’s area could be a confounding factor that needs to be considered when evaluating fMRI language dominance.
Headache Is Associated with Low Systolic Blood Pressure and Psychosocial Problems in German Adolescents: Results from the Population-Based German KiGGS Study
Authors: Córdova Melissa A. Centeno , Stausberg Daniela , Wang Biyao , Becker Andreas , Rothenberger Aribert , Herrmann-Lingen Christoph , Meyer Thomas , Staab Julia
Published: April 2021

Studies have reported controversial results on the relationship between headache and blood pressure. The aim of this post hoc study was twofold: first, to further investigate this relationship and, second, to assess the impact of psychosocial factors on this association in a population-based study of German children and adolescents. The analysis was conducted on study participants aged between 11 and 17 years (n = 5221, weighted from the total study cohort) from the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Health-related quality of life was assessed by self- and parent-rated German-language KINDL-R questionnaires (Children’s Quality of Life Questionnaire), while mental problems were analyzed using the Strengths and Difficulties Questionnaire (SDQ). Our findings confirmed that blood pressure was significantly lower in adolescents reporting episodes of headache than in those without headache (114.0 ± 10.2 mmHg vs. 115.5 ± 11.0 mmHg, p < 0.001). Logistic regression models adjusted to sex, age, body mass index, contraceptive use, and serum magnesium concentration demonstrated that headache was significantly associated with self-rated KINDL-R (Exp(B) = 0.96, 95% confidence interval (95% Cl) = 0.96–0.97, p < 0.001), parent-rated KINDL-R (Exp(B) = 0.97, 95% CI = 0.96–0.98, p < 0.001), as well as self-rated SDQ (Exp(B) = 1.08, 95% CI = 1.07–1.10, p < 0.001), and parent-rated SDQ (Exp(B) = 1.05, 95% CI = 1.04–1.06, p < 0.001). There was evidence that quality of life and mental problems mediated the effect of blood pressure on headache, as revealed by mediation models. Our results from the nationwide, representative KiGGS survey showed that low blood pressure is a significant predictor of headache, independent of quality of life and mental problems. However, these psychosocial factors may mediate the effect of blood pressure on headache in a still unknown manner.
Classification of Dental Radiographs Using Deep Learning
Authors: Cejudo Jose E. , Chaurasia Akhilanand , Feldberg Ben , Krois Joachim , Schwendicke Falk
Published: April 2021

Objectives: To retrospectively assess radiographic data and to prospectively classify radiographs (namely, panoramic, bitewing, periapical, and cephalometric images), we compared three deep learning architectures for their classification performance. Methods: Our dataset consisted of 31,288 panoramic, 43,598 periapical, 14,326 bitewing, and 1176 cephalometric radiographs from two centers (Berlin/Germany; Lucknow/India). For a subset of images L (32,381 images), image classifications were available and manually validated by an expert. The remaining subset of images U was iteratively annotated using active learning, with ResNet-34 being trained on L, least confidence informative sampling being performed on U, and the most uncertain image classifications from U being reviewed by a human expert and iteratively used for re-training. We then employed a baseline convolutional neural networks (CNN), a residual network (another ResNet-34, pretrained on ImageNet), and a capsule network (CapsNet) for classification. Early stopping was used to prevent overfitting. Evaluation of the model performances followed stratified k-fold cross-validation. Gradient-weighted Class Activation Mapping (Grad-CAM) was used to provide visualizations of the weighted activations maps. Results: All three models showed high accuracy (>98%) with significantly higher accuracy, F1-score, precision, and sensitivity of ResNet than baseline CNN and CapsNet (p < 0.05). Specificity was not significantly different. ResNet achieved the best performance at small variance and fastest convergence. Misclassification was most common between bitewings and periapicals. For bitewings, model activation was most notable in the inter-arch space for periapicals interdentally, for panoramics on bony structures of maxilla and mandible, and for cephalometrics on the viscerocranium. Conclusions: Regardless of the models, high classification accuracies were achieved. Image features considered for classification were consistent with expert reasoning.
A Comprehensive Review of Deep-Learning-Based Methods for Image Forensics
Authors: Castillo Camacho Ivan , Wang Kai
Published: April 2021

Seeing is not believing anymore. Different techniques have brought to our fingertips the ability to modify an image. As the difficulty of using such techniques decreases, lowering the necessity of specialized knowledge has been the focus for companies who create and sell these tools. Furthermore, image forgeries are presently so realistic that it becomes difficult for the naked eye to differentiate between fake and real media. This can bring different problems, from misleading public opinion to the usage of doctored proof in court. For these reasons, it is important to have tools that can help us discern the truth. This paper presents a comprehensive literature review of the image forensics techniques with a special focus on deep-learning-based methods. In this review, we cover a broad range of image forensics problems including the detection of routine image manipulations, detection of intentional image falsifications, camera identification, classification of computer graphics images and detection of emerging Deepfake images. With this review it can be observed that even if image forgeries are becoming easy to create, there are several options to detect each kind of them. A review of different image databases and an overview of anti-forensic methods are also presented. Finally, we suggest some future working directions that the research community could consider to tackle in a more effective way the spread of doctored images.
Progressive Secret Sharing with Adaptive Priority and Perfect Reconstruction
Authors: Prasetyo Heri , Hsia Chih-Hsien , Wicaksono Hari Prayuda Alim
Published: April 2021

A new technique for progressive visual secret sharing (PVSS) with adaptive priority weight is proposed in this paper. This approach employs the bitwise and eXclusive-OR (XOR) based approaches for generating a set of shared images from a single secret image. It effectively overcomes the former scheme limitation on dealing with an odd number of stacked or collected shared images in the recovery process. The presented technique works well when the number of stacked shared images is odd or even. As documented in experimental results, the proposed method offers good results over binary, grayscale, and color images with a perfectly reconstructed secret image. In addition, the performance of the proposed method is also supported with theoretical analysis showing its lossless ability to recover the secret image. However, it can be considered as a strong substitutive candidate for implementing a PVSS system.
Orbital Ultrasonic Welding of Ti-Fittings to CFRP-Tubes
Authors: Liesegang Moritz , Arweiler Sophie , Beck Tilmann , Balle Frank
Published: April 2021

Hybrid structures are important for the automotive and aeronautical industry as they have the potential to reduce vehicle or aircraft weight and to improve fuel efficiency. Continuous ultrasonic metal welding is a promising technique for hydraulic applications in aircraft to realise tubular metal/fiber reinforced polymer (FRP) hybrids. Fluid proof connections between dissimilar components can be joined by continuous welding seams. Tubular metal/FRP hybrids, produced by a new advanced variant of ultrasonic metal welding, are investigated as a potential substitute for metallic hydraulic tubes. The oscillating welding system moves around the tubular joining partners to generate a sealed orbital connection. Homogeneous joint quality is required to assure the requested component strength. Therefore, the amplitude of sonotrode displacement and the welding force are controlled to keep the induced welding energy constant and the joint quality uniform. High mechanical strength is required for a safe application in the 5000 psi hydraulic system of current and future aircraft concepts. For this study metal injection molded (MIM) titanium fittings (TiAl6V4) and carbon fiber reinforced PEEK (CF-PEEK) tubes were investigated. Process parameters for metal/FRP hybrid joining were evaluated considering their mechanical and technological properties, as well as the microstructure of the hybrid interfacial area. The entire joining area of tubular joining partners has to be in close contact before welding to assure a continuous tight joint. Hence, the titanium fitting is thermally shrunk onto the CFRP tube before ultrasonic welding. The presented orbital ultrasonic welding technology was developed for prospective industrial use and future applications of ultrasonically welded tubular multi-material-components.
Examining Perceptual Differences in Maritime Safety Climate: A Case Study of Korean Seafarers
Authors: Jung Min
Published: April 2021

To ensure ship safety, safety culture is a critical factor in the organization of shipping companies. The safety climate has been evaluated to determine the level of a particular group’s safety culture. This study investigated South Korean seafarers’ safety culture awareness to compare whether there are differences between those who work on ships engaged in domestic and international voyages. In the latter, reinforced international regulations are applied. A questionnaire survey was conducted with 261 Korean seafarers using seven indicators representing the safety climate used in the aviation and maritime fields. Results showed that seafarers engaged in ocean-going navigation had a higher awareness of management involvement, organizational commitment, learning, and reporting systems, which yielded more positive effects than those engaged in domestic navigation. However, this did not significantly affect communication or employee empowerment. The survey methodology in this study can be used as an effective measure to assess the maritime safety climate; thus, it is possible to prepare policies and educational programs aimed at improving maritime safety.
Mycotic Keratitis—A Global Threat from the Filamentous Fungi
Authors: Hoffman Jeremy J. , Burton Matthew J. , Leck Astrid
Published: April 2021

Mycotic or fungal keratitis (FK) is a sight-threatening disease, caused by infection of the cornea by filamentous fungi or yeasts. In tropical, low and middle-income countries, it accounts for the majority of cases of microbial keratitis (MK). Filamentous fungi, in particular Fusarium spp., the aspergilli and dematiaceous fungi, are responsible for the greatest burden of disease. The predominant risk factor for filamentous fungal keratitis is trauma, typically with organic, plant-based material. In developed countries, contact lens wear and related products are frequently implicated as risk factors, and have been linked to global outbreaks of Fusarium keratitis in the recent past. In 2020, the incidence of FK was estimated to be over 1 million cases per year, and there is significant geographical variation; accounting for less than 1% of cases of MK in some European countries to over 80% in parts of south and south-east Asia. The proportion of MK cases is inversely correlated to distance from the equator and there is emerging evidence that the incidence of FK may be increasing. Diagnosing FK is challenging; accurate diagnosis relies on reliable microscopy and culture, aided by adjunctive tools such as in vivo confocal microscopy or PCR. Unfortunately, these facilities are infrequently available in areas most in need. Current topical antifungals are not very effective; infections can progress despite prompt treatment. Antifungal drops are often unavailable. When available, natamycin is usually first-line treatment. However, infections may progress to perforation in ~25% of cases. Future work needs to be directed at addressing these challenges and unmet needs. This review discusses the epidemiology, clinical features, diagnosis, management and aetiology of FK.
Next-Generation Sequencing Identifies Potential Actionable Targets in Paediatric Sarcomas
Authors: Juan Ribelles Antonio , Gargallo Pablo , Berlanga Pablo , Segura Vanessa , Yáñez Yania , Juan Bárbara , Salom Marta , Llavador Margarita , Font de Mora Jaime , Castel Victoria , Cañete Adela
Published: April 2021

Background: Bone and soft-tissue sarcomas represent 13% of all paediatric malignancies. International contributions to introduce next-generation sequencing (NGS) approaches into clinical application are currently developing. We present the results from the Precision Medicine program for children with sarcomas at a reference centre. Results: Samples of 70 paediatric sarcomas were processed for histopathological analysis, reverse transcriptase polymerase chain reaction (RT-PCR) and next-generation sequencing (NGS) with a consensus gene panel. Pathogenic alterations were reported and, if existing, targeted recommendations were translated to the clinic. Seventy paediatric patients with sarcomas from 10 centres were studied. Median age was 11.5 years (range 1–18). Twenty-two (31%) had at least one pathogenic alteration by NGS. Thirty pathogenic mutations in 18 different genes were detected amongst the 22 patients. The most frequent alterations were found in TP53, followed by FGFR4 and CTNNB1. Combining all biological studies, 18 actionable variants were detected and six patients received targeted treatment observing a disease control rate of 78%. Extrapolating the results to the whole cohort, 23% of the patients would obtain clinical benefit from this approach. Conclusions: Paediatric sarcomas have a different genomic landscape when compared to adult cohorts. Incorporating NGS targets into paediatric sarcomas’ therapy is feasible and allows personalized treatments with clinical benefit in the relapse setting.
Portfolio Optimalization on Digital Currency Market
Authors: Mazanec Jaroslav
Published: April 2021

Virtual currency represents a specific technological innovation on financial markets. Bitcoin and other cryptocurrencies are popular alternatives to traditional cash and investment. We indicate a research gap in the literature review. We find out that current research focused rarely on portfolio diversification using bibliographic analysis in VOSviewer. We think that portfolio diversification is extremely important on the crypto market for most investors because virtual currencies are very risky compared to traditional assets. The primary aim is to construct an optimal portfolio consisting of several cryptocurrencies without traditional assets using a modern theory portfolio. The total sample consists of 16 virtual currencies from 1 October 2017 to 13 January 2020. We mainly obtain historical data on the daily close price of cryptocurrencies from Yahoo Finance. The results show that the optimal portfolio using Markowitz approach consists of Cardano, Binance Coin, and Bitcoin. In addition, virtual currencies are moderately Correlated, with the exception of Tether based on correlation analysis. The high correlation is dangerous for cryptocurrency in portfolio diversification. However, Tether is an atypical virtual currency compared to other cryptocurrencies.
Correlative Coordination and Variable Subject–Verb Agreement in German
Authors: Felser Claudia , Jessen Anna
Published: April 2021

Coordinated subjects often show variable number agreement with the finite verb, but linguistic approaches to this phenomenon have rarely been informed by systematically collected data. We report the results from three experiments investigating German speakers’ agreement preferences with complex subjects joined by the correlative conjunctions sowohl…als auch (‘both…and’), weder…noch (‘neither…nor’) or entweder…oder (‘either…or’). We examine to what extent conjunction type and a conjunct’s relative proximity to the verb affect the acceptability and processibility of singular vs. plural agreement. Experiment 1 was an untimed acceptability rating task, Experiment 2 a timed sentence completion task, and Experiment 3 was a self-paced reading task. Taken together, our results show that number agreement with correlative coordination in German is primarily determined by a default constraint triggering plural agreement, which interacts with linear order and semantic factors. Semantic differences between conjunctions only affected speakers’ agreement preferences in the absence of processing pressure but not their initial agreement computation. The combined results from our offline and online experimental measures of German speakers’ agreement preferences suggest that the constraints under investigation do not only differ in their relative weighting but also in their relative timing during agreement computation.
Bisphenol A, Bisphenol F, and Bisphenol S: The Bad and the Ugly. Where Is the Good?
Authors: Fouyet Sophie , Olivier Elodie , Leproux Pascale , Dutot Mélody , Rat Patrice
Published: April 2021

Background: Bisphenol A (BPA), a reprotoxic and endocrine-disrupting chemical, has been substituted by alternative bisphenols such as bisphenol F (BPF) and bisphenol S (BPS) in the plastic industry. Despite their detection in placenta and amniotic fluids, the effects of bisphenols on human placental cells have not been characterized. Our objective was to explore in vitro and to compare the toxicity of BPA to its substitutes BPF and BPS to highlight their potential risks for placenta and then pregnancy. Methods: Human placenta cells (JEG-Tox cells) were incubated with BPA, BPF, and BPS for 72 h. Cell viability, cell death, and degenerative P2X7 receptor and caspases activation, and chromatin condensation were assessed using microplate cytometry and fluorescence microscopy. Results: Incubation with BPA, BPF, or BPS was associated with P2X7 receptor activation and chromatin condensation. BPA and BPF induced more caspase-1, caspase-9, and caspase-3 activation than BPS. Only BPF enhanced caspase-8 activity. Conclusions: BPA, BPF, and BPS are all toxic to human placental cells, with the P2X7 receptor being a common key element. BPA substitution by BPF and BPS does not appear to be a safe alternative for human health, particularly for pregnant women and their fetuses.
Analysis of Friction in Total Knee Prosthesis during a Standard Gait Cycle
Authors: Ranuša Matúš , Wimmer Markus A. , Fullam Spencer , Vrbka Martin , Křupka Ivan
Published: April 2021

Total knee arthroplasty is on the rise worldwide. Despite its success, revision surgeries are also increasing. According to the American Joint Replacement Registry 2020, 3.3% of revision surgeries are due to wear, and 24.2% are due to mechanical loosening. The combination of shear stresses and wear particles occurring at the bone/implant interface can lead to local osteolysis. Although the shear stresses are partially driven by joint friction, relatively little is known about the evolution of the coefficient of friction (CoF) during a gait cycle in total knee replacement. Here we describe the CoF during a gait cycle and investigate its association with kinematics (slide–roll-ratio), applied load, and relative velocity. The artificial knee was simulated by cobalt–chromium condyle on a flat ultra-high-molecular-weight polyethylene (UHMWPE) tibial plateau, lubricated by either water or proteinaceous solution. We found that the CoF is not a constant but fluctuates between the values close to 0 and 0.15. Cross-correlation suggested that this is primarily an effect of the slide–roll ratio and the contact pressure. There was no difference in the CoF between water and proteinaceous solution. Knowledge about the CoF behavior during a gait cycle will help to increase the accuracy of future computational models of total knee replacement.
UV-Visible Spectrophotometer for Distinguishing Oxidation Time of Engine Oil
Authors: Holland Torrey , Abdul-Munaim Ali Mazin , Mandrell Christopher , Karunanithy Robinson , Watson Dennis G. , Sivakumar Poopalasingam
Published: April 2021

Samples of gasoline engine oil (SAE 5W20) that had been exposed to various oxidation times were inspected with a UV-Visible (UV-Vis) spectrophotometer to select the best wavelengths and wavelength ranges for distinguishing oxidation times. Engine oil samples were subjected to different thermal oxidation periods of 0, 24, 48, 72, 96, 120, and 144 hours, resulting in a range of total base number (TBN) levels. Each wavelength (190.5 – 849.5 nm) and selected wavelength ranges were evaluated to determine the wavelength or wavelength ranges that could best distinguish among all oxidation times. The best wavelengths and wavelength ranges were analyzed with linear regression to determine the best wavelength or range to predict oxidation time.