bluuebunny/crossref_metadata_2025 huggingface dataset:
Plant-Based Biosynthesis of Copper/Copper Oxide Nanoparticles: An Update on Their Applications in Biomedicine, Mechanisms, and Toxicity
Authors: Letchumanan Devanthiran , Sok Sophia P. M. , Ibrahim Suriani , Nagoor Noor Hasima , Arshad Norhafiza Mohd
Published: April 2021

Plants are rich in phytoconstituent biomolecules that served as a good source of medicine. More recently, they have been employed in synthesizing metal/metal oxide nanoparticles (NPs) due to their capping and reducing properties. This green synthesis approach is environmentally friendly and allows the production of the desired NPs in different sizes and shapes by manipulating parameters during the synthesis process. The most commonly used metals and oxides are gold (Au), silver (Ag), and copper (Cu). Among these, Cu is a relatively low-cost metal that is more cost-effective than Au and Ag. In this review, we present an overview and current update of plant-mediated Cu/copper oxide (CuO) NPs, including their synthesis, medicinal applications, and mechanisms. Furthermore, the toxic effects of these NPs and their efficacy compared to commercial NPs are reviewed. This review provides an insight into the potential of developing plant-based Cu/CuO NPs as a therapeutic agent for various diseases in the future.
Extremely Thermostabilizing Core Mutations in Coiled-Coil Mimetic Proteins of HIV-1 gp41 Produce Diverse Effects on Target Binding but Do Not Affect Their Inhibitory Activity
Authors: Cano-Muñoz Mario , Cesaro Samuele , Morel Bertrand , Lucas Julie , Moog Christiane , Conejero-Lara Francisco
Published: April 2021

A promising strategy to neutralize HIV-1 is to target the gp41 spike subunit to block membrane fusion with the cell. We previously designed a series of single-chain proteins (named covNHR) that mimic the trimeric coiled-coil structure of the gp41 N-terminal heptad repeat (NHR) region and potently inhibit HIV-1 cell infection by avidly binding the complementary C-terminal heptad repeat (CHR) region. These proteins constitute excellent tools to understand the structural and thermodynamic features of this therapeutically important interaction. Gp41, as with many coiled-coil proteins, contains in core positions of the NHR trimer several highly conserved, buried polar residues, the role of which in gp41 structure and function is unclear. Here we produced three covNHR mutants by substituting each triad of polar residues for the canonical isoleucine. The mutants preserve their helical structure and show an extremely increased thermal stability. However, increased hydrophobicity enhances their self-association. Calorimetric analyses show a marked influence of mutations on the binding thermodynamics of CHR-derived peptides. The mutations do not affect however the in vitro HIV-1 inhibitory activity of the proteins. The results support a role of buried core polar residues in maintaining structural uniqueness and promoting an energetic coupling between conformational stability and NHR–CHR binding.
Relationship between Sensory Alterations and Repetitive Behaviours in Children with Autism Spectrum Disorders: A Parents’ Questionnaire Based Study
Authors: Fetta Anna , Carati Elisa , Moneti Laura , Pignataro Veronica , Angotti Marida , Bardasi Maria Chiara , Cordelli Duccio Maria , Franzoni Emilio , Parmeggiani Antonia
Published: April 2021

The relationship between sensory profile and repetitive behaviours in autism spectrum disorder (ASD) has long been known. However, there is no consensus on the type of relationship that exists between them. This monocentric retrospective–prospective observational study aimed (a) to detect a clinical correlation between the severity of repetitive behaviours and the alterations of sensory profile in a sample of 50 children diagnosed with ASD; (b) to evaluate how different patterns of stereotypies and sensory alterations correlate with each other and with the main clinical–instrumental variables in the same sample. We enrolled 29 children in the retrospective phase of the study and 21 in the prospective phase. The Repetitive Behaviour Scale-Revised (RBS-R) and the Short Sensory Profile (SSP) were administered to the caregivers, and clinical–instrumental data were collected. SSP and RBS-R total scores directly correlated with a high significance rate. Among the subscales, the strongest correlations involved “Visual/Auditory Sensitivity”, related to “Stereotyped Behaviour” and “Sameness Behaviour”. “Under-Responsive/Seeks Sensation” related to “Stereotyped Behaviour”. Sex and intellectual disability significantly influenced both the stereotypies and the sensory alterations of the examined population. In conclusion, this study provides new insights into the relationship between sensory alterations and repetitive behaviours in ASD children by using direct medical observation and parent observation.
Condition Assessment Framework for Facility Management Based on Fuzzy Sets Theory
Authors: Besiktepe Deniz , Ozbek Mehmet E. , Atadero Rebecca A.
Published: April 2021

Condition information is essential to develop effective facility management (FM) strategies. Visual inspections and walk-through surveys are common practices of condition assessment (CA), generally resulting in qualitative and subjective outcomes such as “poor”, “good”, etc. Furthermore, limited resources of the FM process demand that CA practices be efficient. Given these, the purpose of this study is to develop a resource efficient quantitative CA framework that can be less subjective in establishing a condition rating. The condition variables of the study—mean time between failures, age-based obsolescence, facility condition index, occupant feedback, and preventive maintenance cycle—are identified through different sources, such as a computerized maintenance management system, expert opinions, occupants, and industry standards. These variables provide proxy measures for determining the condition of equipment with the implementation example for heating, ventilating, and air conditioning equipment. Fuzzy sets theory is utilized to obtain a quantitative condition rating while minimizing subjectivity, as fuzzy sets theory deals with imprecise, uncertain, and ambiguous judgments with membership relations. The proposed CA framework does not require additional resources, and the obtained condition rating value supports decision-making for building maintenance management and strategic planning in FM, with a comprehensive and less subjective understanding of condition.
Review of Design of Collective Housing in the 21st Century
Authors: Hernández Falagán David
Published: April 2021

This essay proposes a review of current trends in the design of collective housing projects. The method for the review is based on the observation of certain conditions of contemporary society that show an immediate influence on new habitat patterns. The concepts of uncertainty, scarcity and contingency are the catalysts for the observation, and conditions that provoke new diffuse scenarios for residential buildings. The concept of diffuse dwelling is identified here as the conjunction of three factors: non-permanent coexistence models, residential adaptation of the built environment, and non-hierarchical typological patterns. The review proposes a qualitative analysis questionnaire for the recognition of significant projects of this new residential paradigm. By tracing the EU Mies Award Archive, various examples have been identified that allow us to recognize common characteristics. The result of the analysis reveals how these parameters define a new paradigm in the design of collective housing based on collectivity, constructive resilience, and a new value of domesticity.
A G316A Polymorphism in the Ornithine Decarboxylase Gene Promoter Modulates MYCN-Driven Childhood Neuroblastoma
Authors: Gamble Laura D. , Purgato Stefania , Henderson Michelle J. , Di Giacomo Simone , Russell Amanda J. , Pigini Paolo , Murray Jayne , Valli Emanuele , Milazzo Giorgio , Giorgi Federico M. , Cowley Mark , Ashton Lesley J. , Bhalshankar Jaydutt , Schleiermacher Gudrun , Rihani Ali , Van Maerken Tom , Vandesompele Jo , Speleman Frank , Versteeg Rogier , Koster Jan , Eggert Angelika , Noguera Rosa , Stallings Raymond L. , Tonini Gian Paolo , Fong Kwun , Vaksman Zalman , Diskin Sharon J. , Maris John M. , London Wendy B. , Marshall Glenn M. , Ziegler David S. , Hogarty Michael D. , Perini Giovanni , Norris Murray D. , Haber Michelle
Published: April 2021

Ornithine decarboxylase (ODC1), a critical regulatory enzyme in polyamine biosynthesis, is a direct transcriptional target of MYCN, amplification of which is a powerful marker of aggressive neuroblastoma. A single nucleotide polymorphism (SNP), G316A, within the first intron of ODC1, results in genotypes wildtype GG, and variants AG/AA. CRISPR-cas9 technology was used to investigate the effects of AG clones from wildtype MYCN-amplified SK-N-BE(2)-C cells and the effect of the SNP on MYCN binding, and promoter activity was investigated using EMSA and luciferase assays. AG clones exhibited decreased ODC1 expression, growth rates, and histone acetylation and increased sensitivity to ODC1 inhibition. MYCN was a stronger transcriptional regulator of the ODC1 promoter containing the G allele, and preferentially bound the G allele over the A. Two neuroblastoma cohorts were used to investigate the clinical impact of the SNP. In the study cohort, the minor AA genotype was associated with improved survival, while poor prognosis was associated with the GG genotype and AG/GG genotypes in MYCN-amplified and non-amplified patients, respectively. These effects were lost in the GWAS cohort. We have demonstrated that the ODC1 G316A polymorphism has functional significance in neuroblastoma and is subject to allele-specific regulation by the MYCN oncoprotein.
Functional Characterization of Circulating Tumor Cells (CTCs) from Metastatic ER+/HER2− Breast Cancer Reveals Dependence on HER2 and FOXM1 for Endocrine Therapy Resistance and Tumor Cell Survival: Implications for Treatment of ER+/HER2− Breast Cancer
Authors: Roßwag Sven , Cotarelo Cristina L. , Pantel Klaus , Riethdorf Sabine , Sleeman Jonathan P. , Schmidt Marcus , Thaler Sonja
Published: April 2021

Mechanisms of acquired endocrine resistance and late recurrence in patients with ER+/HER2− breast cancer are complex and not fully understood. Here, we evaluated mechanisms of acquired resistance in circulating tumor cells (CTCs) from an ER+/HER2− breast cancer patient who initially responded but later progressed under endocrine treatment. We found a switch from ERα-dependent to HER2-dependent and ERα-independent expression of FOXM1, which may enable disseminated ER+/HER2− cells to re-initiate tumor cell growth and metastasis formation in the presence of endocrine treatment. Our results also suggest a role for HER2 in resistance, even in ER+ breast cancer cells that have neither HER2 amplification nor activating HER2 mutations. We found that NFkB signaling sustains HER2 and FOXM1 expression in CTCs in the presence of ERα inhibitors. Inhibition of NFkB signaling blocked expression of HER2 and FOXM1 in the CTCs, and induced apoptosis. Thus, targeting of NFkB and FOXM1 might be an efficient therapeutic approach to prevent late recurrence and to treat endocrine resistance. Collectively our data show that CTCs from patients with endocrine resistance allow mechanisms of acquired endocrine resistance to be delineated, and can be used to test potential drug regimens for combatting resistance.
The Leloir Cycle in Glioblastoma: Galactose Scavenging and Metabolic Remodeling
Authors: Sharpe Martyn A. , Ijare Omkar B. , Baskin David S. , Baskin Alexandra M. , Baskin Brianna N. , Pichumani Kumar
Published: April 2021

Background: Glioblastoma (GBM) can use metabolic fuels other than glucose (Glc). The ability of GBM to use galactose (Gal) as a fuel via the Leloir pathway is investigated. Methods: Gene transcript data were accessed to determine the association between expression of genes of the Leloir pathway and patient outcomes. Growth studies were performed on five primary patient-derived GBM cultures using Glc-free media supplemented with Gal. The role of Glut3/Glut14 in sugar import was investigated using antibody inhibition of hexose transport. A specific inhibitor of GALK1 (Cpd36) was used to inhibit Gal catabolism. Gal metabolism was examined using proton, carbon and phosphorous NMR spectroscopy, with 13C-labeled Glc and Gal as tracers. Results: Data analysis from published databases revealed that elevated levels of mRNA transcripts of SLC2A3 (Glut3), SLC2A14 (Glut14) and key Leloir pathway enzymes correlate with poor patient outcomes. GBM cultures proliferated when grown solely on Gal in Glc-free media and switching Glc-grown GBM cells into Gal-enriched/Glc-free media produced elevated levels of Glut3 and/or Glut14 enzymes. The 13C NMR-based metabolic flux analysis demonstrated a fully functional Leloir pathway and elevated pentose phosphate pathway activity for efficient Gal metabolism in GBM cells. Conclusion: Expression of Glut3 and/or Glut14 together with the enzymes of the Leloir pathway allows GBM to transport and metabolize Gal at physiological glucose concentrations, providing GBM cells with an alternate energy source. The presence of this pathway in GBM and its selective targeting may provide new treatment strategies.
Octreotide and Pasireotide Combination Treatment in Somatotroph Tumor Cells: Predominant Role of SST2 in Mediating Ligand Effects
Authors: Amarù Jessica , Barbieri Federica , Arvigo Marica , Solari Agnese , Bajetto Adriana , Nista Federica , Campana Claudia , Gaggero Gabriele , Prior Alessandro , Criminelli Rossi Diego , Zona Gianluigi , Ferone Diego , Florio Tullio , Gatto Federico
Published: April 2021

First-generation somatostatin receptor ligands (fg-SRLs), such as octreotide (OCT), represent the first-line medical therapy in acromegaly. Fg-SRLs show a preferential binding affinity for somatostatin receptor subtype-2 (SST2), while the second-generation ligand, pasireotide (PAS), has high affinity for multiple SSTs (SST5 > SST2 > SST3 > SST1). Whether PAS acts via SST2 in somatotroph tumors, or through other SSTs (e.g., SST5), is a matter of debate. In this light, the combined treatment OCT+PAS could result in additive/synergistic effects. We evaluated the efficacy of OCT and PAS (alone and in combination) on growth hormone (GH) secretion in primary cultures from human somatotroph tumors, as well as on cell proliferation, intracellular signaling and receptor trafficking in the rat GH4C1 cell line. The results confirmed the superimposable efficacy of OCT and PAS in reducing GH secretion (primary cultures), cell proliferation, cAMP accumulation and intracellular [Ca2+] increase (GH4C1 cells), without any additive effect observed for OCT+PAS. In GH4C1 cells, co-incubation with a SST2-selective antagonist reversed the inhibitory effect of OCT and PAS on cell proliferation and cAMP accumulation, while both compounds resulted in a robust internalization of SST2 (but not SST5). In conclusion, OCT and PAS seem to act mainly through SST2 in somatotroph tumor cells in vitro, without inducing any additive/synergistic effect when tested in combination.
Serum Dickkopf-1 in Combined with CA 19-9 as a Biomarker of Intrahepatic Cholangiocarcinoma
Authors: Kim Si-Young , Lee Hee-Seung , Bang Seung-Min , Han Dai-Hoon , Hwang Ho-Kyoung , Choi Gi-Hong , Chung Moon-Jae , Kim Seung-Up
Published: April 2021

Dickkopf-related protein 1 (DKK-1) has a diagnostic and prognostic value in various malignant tumors. We investigated the diagnostic and prognostic performance of DKK-1 in combination with carbohydrate antigen 19-9 (CA 19-9) in cholangiocarcinoma (CCC) patients. Serum DKK-1 levels were measured using enzyme-linked immunosorbent assay. The receiver operating characteristic (ROC) curve, area under ROC (AUROC) analyses, Kaplan–Meier method, and Cox proportional hazard model were used to evaluate the diagnostic and prognostic performance of DKK-1 in combination with CA 19-9. We checked DKK-1 levels in 356 CCC patients and found that DKK-1 was significantly elevated only in 79 intrahepatic CCC (ICC) patients compared to controls (340.5 vs. 249.8 pg/mL, p = 0.002). The optimal cutoff level of DKK-1 used to identify ICC patients was 258.0 pg/mL (AUROC = 0.637, sensitivity = 59.5%, specificity = 56.9%, positive predictive value (PPV) = 40.5%, negative predictive value (NPV) = 74.0%, positive likelihood ratio (LR) = 1.38, and negative LR = 0.71). Using this cutoff, 47 (59.5%) patients were correctly diagnosed with ICC. DKK-1 in combination with CA 19-9 showed a better diagnostic performance (AUROC = 0.793, sensitivity = 74.7%, specificity = 56.3%, PPV = 45.7, NPV = 81.8, positive LR = 1.71, and negative LR = 0.45) than CA 19-9 alone. The low DKK-1 and CA 19-9 expression group had a significantly longer overall survival (OS) than the high expression group (p = 0.006). The higher level of DKK-1 and CA 19-9 was independently associated with shorter OS (hazard ratio = 3.077, 95% confidence interval 1.389–6.819, p = 0.006). The diagnostic and prognostic performance of DKK-1 in combination with CA 19-9 might be better than those of CA 19-9 alone in ICC patients.
Identification of a Candidate Gene Set Signature for the Risk of Progression in IgM MGUS to Smoldering/Symptomatic Waldenström Macroglobulinemia (WM) by a Comparative Transcriptome Analysis of B Cells and Plasma Cells
Authors: Trojani Alessandra , Di Camillo Barbara , Bossi Luca Emanuele , Leuzzi Livia , Greco Antonino , Tedeschi Alessandra , Frustaci Anna Maria , Deodato Marina , Zamprogna Giulia , Beghini Alessandro , Cairoli Roberto
Published: April 2021

Waldenström Macroglobulinemia (WM) is a B-cell lymphoma characterized by the precursor condition IgM monoclonal gammopathies of undetermined significance (IgM MGUS). We performed a gene expression profiling study to compare the transcriptome signatures of bone marrow (BM) B-cells and plasma cells of 36 WM patients, 13 IgM MGUS cases, and 7 healthy subjects used as controls (CTRLs) by Affymetrix microarray. We determined 2038 differentially expressed genes (DEGs) in CD19+ cells and 29 DEGs genes in CD138+ cells, respectively. The DEGs identified in B-cells were associated with KEGG pathways, mainly involved in hematopoietic cell lineage antigens, cell adhesion/focal adhesion/transmembrane proteins, adherens junctions, Wnt-signaling pathway, BCR-signaling pathway, calcium signaling pathway, complement/coagulation cascade, platelet activation, cytokine-cytokine receptor interactions, and signaling pathways responsible for cell cycle, apoptosis, proliferation and survival. In conclusion, we showed the deregulation of groups of genes belonging to KEGG pathways in the comparison among WM vs. IgM MGUS vs. CTRLs in B-cells. Interestingly, a small set of genes in B-cells displayed a common transcriptome expression profile between WM and IgM MGUS compared to CTRLs, suggesting its possible role in the risk of transformation of IgM MGUS to WM.
Two Novel, Flavin-Dependent Halogenases from the Bacterial Consortia of Botryococcus braunii Catalyze Mono- and Dibromination
Authors: Neubauer Pia R. , Blifernez-Klassen Olga , Pfaff Lara , Ismail Mohamed , Kruse Olaf , Sewald Norbert
Published: April 2021

Halogen substituents often lead to a profound effect on the biological activity of organic compounds. Flavin-dependent halogenases offer the possibility of regioselective halogenation at non-activated carbon atoms, while employing only halide salts and molecular oxygen. However, low enzyme activity, instability, and narrow substrate scope compromise the use of enzymatic halogenation as an economical and environmentally friendly process. To overcome these drawbacks, it is of tremendous interest to identify novel halogenases with high enzymatic activity and novel substrate scopes. Previously, Neubauer et al. developed a new hidden Markov model (pHMM) based on the PFAM tryptophan halogenase model, and identified 254 complete and partial putative flavin-dependent halogenase genes in eleven metagenomic data sets. In the present study, the pHMM was used to screen the bacterial associates of the Botryococcus braunii consortia (PRJEB21978), leading to the identification of several putative, flavin-dependent halogenase genes. Two of these new halogenase genes were found in one gene cluster of the Botryococcus braunii symbiont Sphingomonas sp. In vitro activity tests revealed that both heterologously expressed enzymes are active flavin-dependent halogenases able to halogenate indole and indole derivatives, as well as phenol derivatives, while preferring bromination over chlorination. Interestingly, SpH1 catalyses only monohalogenation, while SpH2 can catalyse both mono- and dihalogenation for some substrates.
Chemogenetic Activation of CX3CR1-Expressing Spinal Microglia Using Gq-DREADD Elicits Mechanical Allodynia in Male Mice
Authors: Saika Fumihiro , Matsuzaki Shinsuke , Kishioka Shiroh , Kiguchi Norikazu
Published: April 2021

It is important to investigate the sex-dependent roles of microglia in pain hypersensitivity as reactive microglia within the spinal dorsal horn (DH) have been reported to be pivotal in neuropathic pain induction in male rodents upon nerve injury. Here, we aimed at determining the role of sex differences in the behavioral and functional outcomes of the chemogenetic activation of spinal microglia using Gq-designer receptors exclusively activated by designer drugs (Gq-DREADD) driven by the microglia-specific Cx3cr1 promoter. CAG-LSL-human Gq-coupled M3 muscarinic receptors (hM3Dq)-DREADD mice were crossed with CX3C chemokine receptor 1 (CX3CR1)-Cre mice, and immunohistochemistry images revealed that hM3Dq was selectively expressed on Iba1+ microglia, but not on astrocytes and neurons. Intrathecal (i.t.) administration of clozapine-N-oxide (CNO) elicited mechanical allodynia exclusively in male mice. Furthermore, the reactive microglia-dominant molecules that contributed to pain hypersensitivity in CX3CR1-hM3Dq were upregulated in mice of both sexes. The degree of upregulation was greater in male than in female mice. Depletion of spinal microglia using pexidartinib (PLX3397), a colony stimulating factor-1 receptor inhibitor, alleviated the male CX3CR1-hM3Dq mice from pain hypersensitivity and compromised the expression of inflammatory molecules. Thus, the chemogenetic activation of spinal microglia resulted in pain hypersensitivity in male mice, suggesting the sex-dependent molecular aspects of spinal microglia in the regulation of pain.
Cardiac Computed Tomography Radiomics for the Non-Invasive Assessment of Coronary Inflammation
Authors: Cheng Kevin , Lin Andrew , Yuvaraj Jeremy , Nicholls Stephen J. , Wong Dennis T.L.
Published: April 2021

Radiomics, via the extraction of quantitative information from conventional radiologic images, can identify imperceptible imaging biomarkers that can advance the characterization of coronary plaques and the surrounding adipose tissue. Such an approach can unravel the underlying pathophysiology of atherosclerosis which has the potential to aid diagnostic, prognostic and, therapeutic decision making. Several studies have demonstrated that radiomic analysis can characterize coronary atherosclerotic plaques with a level of accuracy comparable, if not superior, to current conventional qualitative and quantitative image analysis. While there are many milestones still to be reached before radiomics can be integrated into current clinical practice, such techniques hold great promise for improving the imaging phenotyping of coronary artery disease.
Climate Aridity and the Geographical Shift of Olive Trees in a Mediterranean Northern Region
Authors: Rodrigo-Comino Jesús , Salvia Rosanna , Quaranta Giovanni , Cudlín Pavel , Salvati Luca , Gimenez-Morera Antonio
Published: April 2021

Climate change leverages landscape transformations and exerts variable pressure on natural environments and rural systems. Earlier studies outlined how Mediterranean Europe has become a global hotspot of climate warming and land use change. The present work assumes the olive tree, a typical Mediterranean crop, as a candidate bioclimatic indicator, delineating the latent impact of climate aridity on traditional cropping systems at the northern range of the biogeographical distribution of the olive tree. Since the olive tree follows a well-defined latitude gradient with a progressive decline in both frequency and density moving toward the north, we considered Italy as an appropriate case to investigate how climate change may (directly or indirectly) influence the spatial distribution of this crop. By adopting an exploratory approach grounded in the quali-quantitative analysis of official statistics, the present study investigates long-term changes over time in the spatial distribution of the olive tree surface area in Northern Italy, a region traditionally considered outside the ecological range of the species because of unsuitable climate conditions. Olive tree cultivated areas increased in Northern Italy, especially in flat districts and upland areas, while they decreased in Central and Southern Italy under optimal climate conditions, mostly because of land abandonment. The most intense expansion of the olive tree surface area in Italy was observed in the northern region between 1992 and 2000 and corresponded with the intensification of winter droughts during the late 1980s and the early 1990s and local warming since the mid-1980s. Assuming the intrinsic role of farmers in the expansion of the olive tree into the suboptimal land of Northern Italy, the empirical results of our study suggest how climate aridity and local warming may underlie the shift toward the north in the geographical range of the olive tree in the Mediterranean Basin. We finally discussed the implications of the olive range shift as a part of a possible landscape scenario for a more arid future.
Evaluation of Damage Process of a Coating by Using Nonlinear Ultrasonic Method
Authors: Xu Chunguang , He Lei , Zhou Shiyuan , Xiao Dingguo , Ma Pengzhi
Published: April 2021

During the service or external loading of the surface coating, the damage accumulation may develop in the coating or at the interface between the substrate and the coating, but it is difficult to measure directly in the early stage, so the acoustic nonlinear parameters are used as the early damage index of the coating. In this paper, the nonlinear wave motion equation is solved by the perturbation method and the new relationship between the relative ratio of second-order parameter and third-order parameter was derived. The nonlinear ultrasonic testing system is used to detect received signals during tensile testing of for the specimen with Al2O3 coatings. It is found that when the stress is less than 260 MPa, the appearance of the coating has no obvious change, but the nonlinear coefficients measured by the experiment increase with the increase of the tensile stress. By comparing the curves of nonlinear coefficients and stress respectively, the fluctuation of curves the second-order nonlinear coefficient A2 and the relative nonlinear coefficient β′ to stress is relatively small, and close to the linear relationship with the tensile stress, which indicates that the two parameters of the specimen with Al2O3 coatings are more sensitive to the bonding conditions, and can be used as an evaluation method to track the coating damage.
A Brief Review on the Sensor Measurement Solutions for the Ten-Meter Walk Test
Authors: Pires Ivan Miguel , Lopes Eurico , Villasana María Vanessa , Garcia Nuno M. , Zdravevski Eftim , Ponciano Vasco
Published: April 2021

The wide-spread use of wearables and the adoption of the Internet of Things (IoT) paradigm provide an opportunity to use mobile-device sensors for medical applications. Sensors available in the commonly used devices may inspire innovative solutions for physiotherapy striving for accurate and early identification of various pathologies. An essential and reliable performance measure is the ten-meter walk test, which is employed to determine functional mobility, gait, and vestibular function. Sensor-based approaches can identify the various test phases and their segmented duration, among other parameters. The measurement parameter primarily used is related to the tests’ duration, and after identifying patterns, a variety of physical treatments can be recommended. This paper reviews multiple studies focusing on automated measurements of the ten-meter walk test with different sensors. Most of the analyzed studies measure similar parameters as traditional methods, such as velocity, duration, and other involuntary and dangerous patients’ movements after stroke. That provides an opportunity to measure different parameters that can be later fed into machine learning models for analyzing more complex patterns.
Improvement for Interfacial Microstructure and Mechanical Properties of Ti3SiC2/Cu Joint Brazed by Ag-Cu-Ti Filler with Copper Mesh
Authors: Chen Haiyan , Nai Xin , Zhao Shuai , Lu Decai , Shen Zhikang , Li Wenya , Cao Jian
Published: April 2021

Ti3SiC2 ceramic and copper were successfully vacuum brazed using Ag-Cu-Ti filler and Ag-Cu-Ti filler with copper mesh, respectively. In this study, the effects of copper mesh and brazing parameters on the interface microstructure and mechanical properties of the joints were systematically studied. The results revealed that the typical interfacial microstructure of joint was Ti3SiC2 ceramic/Ti5Si3 + TiC + Ti2Cu + Ti3Cu/Ag (s, s) + Cu (s, s)/eutectic Ag-Cu + TiSiCu/Cu. A maximum shear strength of joint obtained at a brazing temperature of 870 °C and a holding time of 10 min can reached up to 66.3 ± 1.2 MPa, which was 34.7% higher than that without copper mesh. The improvement of mechanical property was attributed to the extraordinary plasticity of copper mesh, which reduced the residual stress caused by the difference in the coefficient of thermal expansion at the interface of joints. As the brazing temperature and holding time further increased, the shear strength of joints decreased due to the excessively thick reaction layer of intermetallic compounds.
Solid-State Dehydration Mechanism of Diclofenac Sodium Salt Hydrates
Authors: Oyama Hironaga , Miyamoto Takashi , Sekine Akiko , Nugrahani Ilma , Uekusa Hidehiro
Published: April 2021

Salt formation is a useful technique for improving the solubility of active pharmaceutical ingredients (APIs). For instance, a nonsteroidal anti-inflammatory drug, diclofenac (DIC), is used in a sodium salt form, and it has been reported to form several hydrate forms. However, the crystal structure of the anhydrous form of diclofenac sodium (DIC-Na) and the structural relationship among the anhydrate and hydrated forms have not yet been revealed. In this study, DIC-Na anhydrate was analyzed using single-crystal X-ray diffraction (XRD). To determine the solid-state dehydration/hydration mechanism of DIC-Na hydrates based on both the present and previously reported crystal structures (4.75-hydrate and 3.5-hydrate), additional experiments including simultaneous powder XRD and differential scanning calorimetry, thermogravimetry, dynamic vapor sorption measurements, and a comparison of the crystal structures were performed. The dehydration of the 4.75-hydrate form was found to occur in two steps. During the first step, only water molecules that were not coordinated to Na+ ions were lost, which led to the formation of the 3.5-hydrate while retaining alternating layered structures. The subsequent dehydration step into the anhydrous phase accompanied a substantial structural reconstruction. This study elucidated the complete landscape of the dehydration/hydration transformation of DIC-Na for the first time through a crystal structure investigation. These findings contribute to understanding the mechanism underlying these dehydration/hydration phenomena and the physicochemical properties of pharmaceutical crystals.
Disturbance Effects on Spatial Autocorrelation in Biodiversity: An Overview and a Call for Study
Authors: Biswas Shekhar , Xiang Jingyin , Li Hui
Published: April 2021

The spatially autocorrelated patterns of biodiversity can be an important determinant of ecological processes, functions and delivery of services across spatial scales. Therefore, understanding disturbance effects on spatial autocorrelation in biodiversity is crucial for conservation and restoration planning but remains unclear. In a survey of disturbance versus spatial patterns of biodiversity literature from forests, grasslands and savannah ecosystems, we found that habitat disturbances generally reduce the spatial autocorrelation in species diversity on average by 15.5% and reduce its range (the distance up to which autocorrelation prevails) by 21.4%, in part, due to disturbance-driven changes in environmental conditions, dispersal, species interactions, or a combination of these processes. The observed effect of disturbance, however, varied markedly among the scale of disturbance (patch-scale versus habitat-scale). Surprisingly, few studies have examined disturbance effects on the spatial patterns of functional diversity, and the overall effect was non-significant. Despite major knowledge gaps in certain areas, our analysis offers a much-needed initial insights into the disturbance-driven changes in the spatial patterns of biodiversity, thereby setting the ground for informed discussion on conservation and promotion of spatial heterogeneity in managing natural systems under a changing world.
Atypical Granulomatosis with Polyangiitis Presenting with Meibomitis, Scleritis, Uveitis and Papillary Bladder Tumor: A Case Report and Literature Review
Authors: Kojima Takashi , Dogru Murat , Shimizu Eisuke , Yazu Hiroyuki , Takahashi Aya , Shimazaki Jun
Published: April 2021

Granulomatosis with polyangiitis (GPA) presents with a variety of systemic findings, sometimes with ocular findings initially, but is often difficult to diagnose at an early stage. An 85-year-old male had complaints of ocular dryness and redness and was diagnosed with meibomian gland dysfunction with meibomitis. Despite an initial treatment with topical steroid and antibiotics, the meibomitis did not improve and the left eye developed scleritis and iridocyclitis. The patient was administered topical mydriatics and oral steroids. During follow-up, the patient developed left hearing difficulty and reported a darker urine. Urinalysis revealed microscopic hematuria. A blood test showed an elevated erythrocyte sedimentation rate, positivity for perinuclear anti-neutorophil cytoplasmic antibody, and elevations in blood urea nitrogen and serum creatinine. Nasal mucosal biopsy showed a non-necrotizing granulomatous inflammation. Renal biopsy revealed focal glomerulosclerosis. Cystoscopy and bladder wash followed by a planned transurethral resection revealed atypical cells and apical papillary tumors which were resected. Iridocyclitis and scleritis responded well to oral prednisolone with 0.1% topical betamethasone and prednisolone ointment. The patient is tumor free with no recurrences 24 months after resection. GPA may present atypically with meibomian gland dysfunction without showing representative clinical findings. Early detection and treatment are essential for visual recovery.
The Prognostic Value of White-Matter Selective Double Inversion Recovery MRI Sequence in Multiple Sclerosis: An Exploratory Study
Authors: Crescenzo Francesco , Marastoni Damiano , Pisani Anna Isabella , Tamanti Agnese , Dapor Caterina , Colombi Annalisa , Brillo Alessandro , Magliozzi Roberta , Pizzini Francesca Benedetta , Castellaro Marco , Calabrese Massimiliano
Published: April 2021

Using a white-matter selective double inversion recovery sequence (WM-DIR) that suppresses both grey matter (GM) and cerebrospinal fluid (CSF) signals, some white matter (WM) lesions appear surrounded by a dark rim. These dark rim lesions (DRLs) seem to be specific for multiple sclerosis (MS). They could be of great usefulness in clinical practice, proving to increase the MRI diagnostic criteria specificity. The aims of this study are the identification of DRLs on 1.5 T MRI, the exploration of the relationship between DRLs and disease course, the characterization of DRLs with respect to perilesional normal-appearing WM using magnetization transfer imaging, and the investigation of possible differences in the underlying tissue properties by assessing WM-DIR images obtained at 3.0 T MRI. DRLs are frequent in primary progressive MS (PPMS) patients. Amongst relapsing-remitting MS (RRMS) patients, DRLs are associated with a high risk of the disease worsening and secondary progressive MS (SPMS) conversion after 15 years. The mean magnetization transfer ratio (MTR) of DRLs is significantly different from the lesion without the dark rim, suggesting that DRLs correspond to more destructive lesions.
Deep Active Learning for Automatic Segmentation of Maxillary Sinus Lesions Using a Convolutional Neural Network
Authors: Jung Seok-Ki , Lim Ho-Kyung , Lee Seungjun , Cho Yongwon , Song In-Seok
Published: April 2021

The aim of this study was to segment the maxillary sinus into the maxillary bone, air, and lesion, and to evaluate its accuracy by comparing and analyzing the results performed by the experts. We randomly selected 83 cases of deep active learning. Our active learning framework consists of three steps. This framework adds new volumes per step to improve the performance of the model with limited training datasets, while inferring automatically using the model trained in the previous step. We determined the effect of active learning on cone-beam computed tomography (CBCT) volumes of dental with our customized 3D nnU-Net in all three steps. The dice similarity coefficients (DSCs) at each stage of air were 0.920 ± 0.17, 0.925 ± 0.16, and 0.930 ± 0.16, respectively. The DSCs at each stage of the lesion were 0.770 ± 0.18, 0.750 ± 0.19, and 0.760 ± 0.18, respectively. The time consumed by the convolutional neural network (CNN) assisted and manually modified segmentation decreased by approximately 493.2 s for 30 scans in the second step, and by approximately 362.7 s for 76 scans in the last step. In conclusion, this study demonstrates that a deep active learning framework can alleviate annotation efforts and costs by efficiently training on limited CBCT datasets.
Non-Alcoholic Fatty Liver Disease and Cardiovascular Comorbidities: Pathophysiological Links, Diagnosis, and Therapeutic Management
Authors: Jichitu Alexandra , Bungau Simona , Stanescu Ana Maria Alexandra , Vesa Cosmin Mihai , Toma Mirela Marioara , Bustea Cristiana , Iurciuc Stela , Rus Marius , Bacalbasa Nicolae , Diaconu Camelia Cristina
Published: April 2021

Non-alcoholic fatty liver disease (NAFLD) has a growing prevalence in recent years. Its association with cardiovascular disease has been intensively studied, and certain correlations have been identified. The connection between these two entities has lately aroused interest regarding therapeutic management. In order to find the best therapeutic options, a detailed understanding of the pathophysiology that links (NAFLD) to cardiovascular comorbidities is needed. This review focuses on the pathogenic mechanisms that are behind these two diseases and on the therapeutic management available at this time.
Hair Cortisol Concentrations Are Associated with Dental Anxiety during Pregnancy
Authors: Viitaniemi Hilja , Suominen Auli , Karlsson Linnea , Mustonen Paula , Kortesluoma Susanna , Rantavuori Kari , Rodrigues Ana João , Coimbra Bárbara , Karlsson Hasse , Lahti Satu
Published: April 2021

Dental anxiety (DA) and hair cortisol concentrations (HCC) are associated with psychological symptoms and vary during pregnancy. We aimed to examine the association between HCC and DA at two points of pregnancy. Participants were pregnant mothers (n = 533) drawn from the FinnBrain Birth Cohort Study donating a hair sample at gestational week (gwk) 24 (n = 442) and/or at delivery (n = 176) and completed questionnaires on DA. Two groups, HCC1 and HCC2, treated as separate in the analyses, were formed according to the hair sample donation time i.e., gwk24 and delivery. 85 subjects were included in both groups. MDAS, EPDS, and SCL-90 were used to measure DA, depressive and anxiety symptoms, respectively, at gwk14 for the HCC1 group and gwk34 for the HCC2 group. The association between DA and HCC was studied with a binary logistic regression model, adjusted for anxiety and depressive symptoms, age, BMI, and smoking status. Individuals with high DA had lower HCC levels at gwk24 (OR = 0.548; 95% CI = 0.35–0.86; p = 0.009), but the association was not statistically significant at the delivery (OR = 0.611; 95% CI = 0.28–1.33; p = 0.216). The independent association between HCC and DA in pregnant women suggests that long-term cortisol levels could play a role in the endogenous etiology of DA. Further studies are however, needed.
A Survey of Function Analysis and Applied Dynamic Equations on Hybrid Time Scales
Authors: Wang Chao , Agarwal Ravi P.
Published: April 2021

As an effective tool to unify discrete and continuous analysis, time scale calculus have been widely applied to study dynamic systems in both theoretical and practical aspects. In addition to such a classical role of unification, the dynamic equations on time scales have their own unique features which the difference and differential equations do not possess and these advantages have been highlighted in describing some complicated dynamical behavior in the hybrid time process. In this review article, we conduct a survey of abstract analysis and applied dynamic equations on hybrid time scales, some recent main results and the related developments on hybrid time scales will be reported and the future research related to this research field is discussed. The results presented in this article can be extended and generalized to study both pure mathematical analysis and real applications such as mathematical physics, biological dynamical models and neural networks, etc.
A Graph-Transformational Approach to Swarm Computation
Authors: Abdenebaoui Larbi , Kreowski Hans-Jörg , Kuske Sabine
Published: April 2021

In this paper, we propose a graph-transformational approach to swarm computation that is flexible enough to cover various existing notions of swarms and swarm computation, and it provides a mathematical basis for the analysis of swarms with respect to their correct behavior and efficiency. A graph transformational swarm consists of members of some kinds. They are modeled by graph transformation units providing rules and control conditions to specify the capability of members and kinds. The swarm members act on an environment—represented by a graph—by applying their rules in parallel. Moreover, a swarm has a cooperation condition to coordinate the simultaneous actions of the swarm members and two graph class expressions to specify the initial environments on one hand and to fix the goal on the other hand. Semantically, a swarm runs from an initial environment to one that fulfills the goal by a sequence of simultaneous actions of all its members. As main results, we show that cellular automata and particle swarms can be simulated by graph-transformational swarms. Moreover, we give an illustrative example of a simple ant colony the ants of which forage for food choosing their tracks randomly based on pheromone trails.
Achieving the Sustainable Development Goals through Company Staff Vocational Training—The Case of the Federal Institute for Vocational Education and Training (BIBB) INEBB Project
Authors: Lambini Cosmas Kombat , Goeschl Angelina , Wäsch Max , Wittau Martin
Published: April 2021

Education for sustainable development (ESD) plays a significant role in achieving the 17 Sustainable Development Goals (SDGs) and simultaneously tackling the current global ecological challenges. Integration of ESD in Vocational Education and Training (VET) offers opportunities for private sector actors to contribute to reaching these global goals. The dual structure of business-integrated training in Germany further exemplifies a business case and the numerous opportunities available to private companies for engaging with the SDG framework. This briefing paper highlighted available evidence from the ESD literature on VET skills development in advancing the SDGs. Outcomes from best practices were based on the tried-and-tested länder—federal states—piloted vocational training of the Federal Institute for Vocational Education and Training (BIBB) INEBB1 project (INEBB), demonstrating the conditions necessary for vocational education training in sustainability and plausible transfer mechanism within companies. These conditions included (1) the application of deductive concepts, (2) the establishment of blended-learning platforms (place-based and digital), and (3) the adaptation of the criteria and contents from the German Sustainability Codex (DNK) in curriculums designed for the training. This innovative vocational course and certification as specialist training for sustainable development was a model case in bringing the SDGs closer to German companies’ vocational education. INEBB2 sought to upscale applicable and task-based instructions from the experimented model project INEBB1 within different companies through regional, lateral, and vertical transfer strands. The INEBB project model in the review suggested there was a need for further empirical work and policy discourse on educational transfer research in the framework of VET for sustainable development. The INEBB project model integrated the new standard occupational profile items of the environmental protection and the sustainability and digitalised world of work across occupational competencies in the German dual system of vocational education and training that will come into force in August 2021 for all 326 dual training professions.
Handwritten Character Recognition on Android for Basic Education Using Convolutional Neural Network
Authors: Zin Thi Thi , Thant Shin , Pwint Moe Zet , Ogino Tsugunobu
Published: April 2021

An international initiative called Education for All (EFA) aims to create an environment in which everyone in the world can get an education. Especially in developing countries, many children lack access to a quality education. Therefore, we propose an offline self-learning application to learn written English and basic calculation for primary level students. It can also be used as a supplement for teachers to make the learning environment more interactive and interesting. In our proposed system, handwritten characters or words written on tablets were saved as input images. Then, we performed character segmentation by using our proposed character segmentation methods. For the character recognition, the Convolutional Neural Network (CNN) was used for recognizing segmented characters. For building our own dataset, handwritten data were collected from primary level students in developing countries. The network model was trained on a high-end machine to reduce the workload on the Android tablet. Various types of classifiers (digit and special characters, uppercase letters, lowercase letters, etc.) were created in order to reduce the incorrect classification. According to our experimental results, the proposed system achieved 95.6% on the 1000 randomly selected words and 98.7% for each character.