bluuebunny/crossref_metadata_2025 huggingface dataset:
Eugenol-Induced Autophagy and Apoptosis in Breast Cancer Cells via PI3K/AKT/FOXO3a Pathway Inhibition
Authors: Abdullah Mashan L. , Al-Shabanah Othman , Hassan Zeinab K. , Hafez Mohamed M.
Published: August 2021

The use of natural compounds is promising in approaches to prevent and treat cancer. The long-term application of most currently employed chemotherapy techniques has toxic side effects. Eugenol, a phenolic phytochemical extracted from certain essential oils, has an anti-cancer effect. The modulation of autophagy can promote either the survival or apoptosis of cancer cells. Triple-negative (MDA-MB-231) and HER2 positive (SK-BR-3) breast cancer cell lines were treated with different doses of eugenol. Apoptosis was detected by a flow-cytometry technique, while autophagy was detected by acridine orange. Real-time PCR and Western blot assays were applied to investigate the effect of eugenol on the gene and protein expression levels of autophagy and apoptotic genes. Treating cells with different concentrations of eugenol significantly inhibited cell proliferation. The protein levels of AKT serine/threonine kinase 1 (AKT), forkhead box O3 (FOXO3a), cyclin dependent kinase inhibitor 1A (p21), cyclin-dependent kinase inhibitor (p27), and Caspase-3 and -9 increased significantly in Eugenol-treated cells. Eugenol also induced autophagy by upregulating the expression levels of microtubule-associated protein 1 light chain 3 (LC3) and downregulating the expression of nucleoporin 62 (NU p62). Eugenol is a promising natural anti-cancer agent against triple-negative and HER2-positive breast cancer. It appears to work by targeting the caspase pathway and by inducing autophagic cell death.
Evidence for the Role of CYP51A and Xenobiotic Detoxification in Differential Sensitivity to Azole Fungicides in Boxwood Blight Pathogens
Authors: Stravoravdis Stefanos , Marra Robert E. , LeBlanc Nicholas R. , Crouch Jo Anne , Hulvey Jonathan P.
Published: August 2021

Boxwood blight, a fungal disease of ornamental plants (Buxus spp.), is caused by two sister species, Calonectria pseudonaviculata (Cps) and C. henricotiae (Che). Compared to Cps, Che is documented to display reduced sensitivity to fungicides, including the azole class of antifungals, which block synthesis of a key fungal membrane component, ergosterol. A previous study reported an ergosterol biosynthesis gene in Cps, CYP51A, to be a pseudogene, and RNA-Seq data confirm that a functional CYP51A is expressed only in Che. The lack of additional ergosterol biosynthesis genes showing significant differential expression suggests that the functional CYP51A in Che could contribute to reduced azole sensitivity when compared to Cps. RNA-Seq and bioinformatic analyses found that following azole treatment, 55 genes in Cps, belonging to diverse pathways, displayed a significant decrease in expression. Putative xenobiotic detoxification genes overexpressed in tetraconazole-treated Che encoded predicted monooxygenase and oxidoreductase enzymes. In summary, expression of a functional CYP51A gene and overexpression of predicted xenobiotic detoxification genes appear likely to contribute to differential fungicide sensitivity in these two sister taxa.
Interplay between Hepatitis E Virus and Host Cell Pattern Recognition Receptors
Authors: Devhare Pradip , Madiyal Mridula , Mukhopadhyay Chiranjay , Shetty Shiran , Shastry Shamee
Published: August 2021

Hepatitis E virus (HEV) usually causes self-limiting acute hepatitis, but the disease can become chronic in immunocompromised individuals. HEV infection in pregnant women is reported to cause up to 30% mortality, especially in the third trimester. Additionally, extrahepatic manifestations like neuronal and renal diseases and pancreatitis are also reported during the course of HEV infection. The mechanism of HEV pathogenesis remains poorly understood. Innate immunity is the first line of defense triggered within minutes to hours after the first pathogenic insult. Growing evidence based on reverse genetics systems, in vitro cell culture models, and representative studies in animal models including non-human primates, has implicated the role of the host’s innate immune response during HEV infection. HEV persists in presence of interferons (IFNs) plausibly by evading cellular antiviral defense. This review summarizes our current understanding of recognizing HEV-associated molecular patterns by host cell Pattern Recognition Receptors (PRRs) in eliciting innate immune response during HEV infection as well as mechanisms of virus-mediated immune evasion.
Anti-Inflammatory Fibronectin-AgNP for Regulation of Biological Performance and Endothelial Differentiation Ability of Mesenchymal Stem Cells
Authors: Hung Huey-Shan , Chang Kai-Bo , Tang Cheng-Ming , Ku Tian-Ren , Kung Mei-Lang , Yu Alex Yang-Hao , Shen Chiung-Chyi , Yang Yi-Chin , Hsieh Hsien-Hsu , Hsu Shan-hui
Published: August 2021

The engineering of vascular regeneration still involves barriers that need to be conquered. In the current study, a novel nanocomposite comprising of fibronectin (denoted as FN) and a small amount of silver nanoparticles (AgNP, ~15.1, ~30.2 or ~75.5 ppm) was developed and its biological function and biocompatibility in Wharton’s jelly-derived mesenchymal stem cells (MSCs) and rat models was investigated. The surface morphology as well as chemical composition for pure FN and the FN-AgNP nanocomposites incorporating various amounts of AgNP were firstly characterized by atomic force microscopy (AFM), UV-Visible spectroscopy (UV-Vis), and Fourier-transform infrared spectroscopy (FTIR). Among the nanocomposites, FN-AgNP with 30.2 ppm silver nanoparticles demonstrated the best biocompatibility as assessed through intracellular ROS production, proliferation of MSCs, and monocytes activation. The expression levels of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, were also examined. FN-AgNP 30.2 ppm significantly inhibited pro-inflammatory cytokine expression compared to other materials, indicating superior performance of anti-immune response. Mechanistically, FN-AgNP 30.2 ppm significantly induced greater expression of vascular endothelial growth factor (VEGF) and stromal-cell derived factor-1 alpha (SDF-1α) and promoted the migration of MSCs through matrix metalloproteinase (MMP) signaling pathway. Besides, in vitro and in vivo studies indicated that FN-AgNP 30.2 ppm stimulated greater protein expressions of CD31 and von Willebrand Factor (vWF) as well as facilitated better endothelialization capacity than other materials. Furthermore, the histological tissue examination revealed the lowest capsule formation and collagen deposition in rat subcutaneous implantation of FN-AgNP 30.2 ppm. In conclusion, FN-AgNP nanocomposites may facilitate the migration and proliferation of MSCs, induce endothelial cell differentiation, and attenuate immune response. These finding also suggests that FN-AgNP may be a potential anti-inflammatory surface modification strategy for vascular biomaterials.
Lipid Cubic Mesophases Combined with Superparamagnetic Iron Oxide Nanoparticles: A Hybrid Multifunctional Platform with Tunable Magnetic Properties for Nanomedical Applications
Authors: Caselli Lucrezia , Mendozza Marco , Muzzi Beatrice , Toti Alessandra , Montis Costanza , Mello Tommaso , Di Cesare Mannelli Lorenzo , Ghelardini Carla , Sangregorio Claudio , Berti Debora
Published: August 2021

Hybrid materials composed of superparamagnetic iron oxide nanoparticles (SPIONs) and lipid self-assemblies possess considerable applicative potential in the biomedical field, specifically, for drug/nutrient delivery. Recently, we showed that SPIONs-doped lipid cubic liquid crystals undergo a cubic-to-hexagonal phase transition under the action of temperature or of an alternating magnetic field (AMF). This transition triggers the release of drugs embedded in the lipid scaffold or in the water channels. In this contribution, we address this phenomenon in depth, to fully elucidate the structural details and optimize the design of hybrid multifunctional carriers for drug delivery. Combining small-angle X-ray scattering (SAXS) with a magnetic characterization, we find that, in bulk lipid cubic phases, the cubic-to-hexagonal transition determines the magnetic response of SPIONs. We then extend the investigation from bulk liquid-crystalline phases to colloidal dispersions, i.e., to lipid/SPIONs nanoparticles with cubic internal structure (“magnetocubosomes”). Through Synchrotron SAXS, we monitor the structural response of magnetocubosomes while exposed to an AMF: the magnetic energy, converted into heat by SPIONs, activates the cubic-to-hexagonal transition, and can thus be used as a remote stimulus to spike drug release “on-demand”. In addition, we show that the AMF-induced phase transition in magnetocubosomes steers the realignment of SPIONs into linear string assemblies and connect this effect with the change in their magnetic properties, observed at the bulk level. Finally, we assess the internalization ability and cytotoxicity of magnetocubosomes in vitro on HT29 adenocarcinoma cancer cells, in order to test the applicability of these smart carriers in drug delivery applications.
Identification and Validation of Esophageal Squamous Cell Carcinoma Targets for Fluorescence Molecular Endoscopy
Authors: Zhao Xiaojuan , Huang Qingfeng , Koller Marjory , Linssen Matthijs D. , Hooghiemstra Wouter T. R. , de Jongh Steven J. , van Vugt Marcel A. T. M. , Fehrmann Rudolf S. N. , Li Enmin , Nagengast Wouter B.
Published: August 2021

Dysplasia and intramucosal esophageal squamous cell carcinoma (ESCC) frequently go unnoticed with white-light endoscopy and, therefore, progress to invasive tumors. If suitable targets are available, fluorescence molecular endoscopy might be promising to improve early detection. Microarray expression data of patient-derived normal esophagus (n = 120) and ESCC samples (n = 118) were analyzed by functional genomic mRNA (FGmRNA) profiling to predict target upregulation on protein levels. The predicted top 60 upregulated genes were prioritized based on literature and immunohistochemistry (IHC) validation to select the most promising targets for fluorescent imaging. By IHC, GLUT1 showed significantly higher expression in ESCC tissue (30 patients) compared to the normal esophagus adjacent to the tumor (27 patients) (p < 0.001). Ex vivo imaging of GLUT1 with the 2-DG 800CW tracer showed that the mean fluorescence intensity in ESCC (n = 17) and high-grade dysplasia (HGD, n = 13) is higher (p < 0.05) compared to that in low-grade dysplasia (LGD) (n = 7) and to the normal esophagus adjacent to the tumor (n = 5). The sensitivity and specificity of 2-DG 800CW to detect HGD and ESCC is 80% and 83%, respectively (ROC = 0.85). We identified and validated GLUT1 as a promising molecular imaging target and demonstrated that fluorescent imaging after topical application of 2-DG 800CW can differentiate HGD and ESCC from LGD and normal esophagus.
Molecular Basis of Endometriosis and Endometrial Cancer: Current Knowledge and Future Perspectives
Authors: Terzic Milan , Aimagambetova Gulzhanat , Kunz Jeannette , Bapayeva Gauri , Aitbayeva Botagoz , Terzic Sanja , Laganà Antonio Simone
Published: August 2021

The human endometrium is a unique tissue undergoing important changes through the menstrual cycle. Under the exposure of different risk factors in a woman’s lifetime, normal endometrial tissue can give rise to multiple pathologic conditions, including endometriosis and endometrial cancer. Etiology and pathophysiologic changes behind such conditions remain largely unclear. This review summarizes the current knowledge of the pathophysiology of endometriosis and its potential role in the development of endometrial cancer from a molecular perspective. A better understanding of the molecular basis of endometriosis and its role in the development of endometrial pathology will improve the approach to clinical management.
Identification of Activated Protein Kinase Cα (PKCα) in the Urine of Orthotopic Bladder Cancer Xenograft Model as a Potential Biomarker for the Diagnosis of Bladder Cancer
Authors: Kawano Takahito , Tachibana Yoko , Inokuchi Junichi , Kang Jeong-Hun , Murata Masaharu , Eto Masatoshi
Published: August 2021

Bladder cancer has a high recurrence rate; therefore, frequent and effective monitoring is essential for disease management. Cystoscopy is considered the gold standard for the diagnosis and continuous monitoring of bladder cancer. However, cystoscopy is invasive and relatively expensive. Thus, there is a need for non-invasive, relatively inexpensive urinary biomarker-based diagnoses of bladder cancer. This study aimed to investigate the presence of activated protein kinase Cα (PKCα) in urine samples and the possibility of PKCα as a urinary biomarker for bladder cancer diagnosis. Activated PKCα was found to be present at higher levels in bladder cancer tissues than in normal bladder tissues. Furthermore, high levels of activated PKCα were observed in urine samples collected from orthotopic xenograft mice carrying human bladder cancer cells compared to urine samples from normal mice. These results suggest that activated PKCα can be used as a urinary biomarker to diagnose bladder cancer. To the best of our knowledge, this is the first report describing the presence of activated PKCα in the urine of orthotopic xenograft mice.
Cripto-1 as a Key Factor in Tumor Progression, Epithelial to Mesenchymal Transition and Cancer Stem Cells
Authors: Arnouk Hilal , Yum Gloria , Shah Dean
Published: August 2021

Cripto-1 is an essential protein for human development that plays a key role in the early phase of gastrulation in the differentiation of an embryo as well as assists with wound healing processes. Importantly, Cripto-1 induces epithelial to mesenchymal transition to turn fixed epithelial cells into a more mobile mesenchymal phenotype through the downregulation of epithelial adhesion molecules such as E-cadherin, occludins, and claudins, and the upregulation of mesenchymal, mobile proteins, such as N-cadherin, Snail, and Slug. Consequently, Cripto-1’s role in inducing EMT to promote cell motility is beneficial in embryogenesis, but detrimental in the formation, progression and metastasis of malignant tumors. Indeed, Cripto-1 is found to be upregulated in most cancers, such as breast, lung, gastrointestinal, hepatic, renal, cervical, ovarian, prostate, and skin cancers. Through its role in EMT, Cripto-1 can remodel cancer cells to enable them to travel through the extracellular matrix as well as blood and lymphatic vessels to metastasize to different organs. Additionally, Cripto-1 promotes the survival of cancer stem cells, which can lead to relapse in cancer patients.
Doxorubicin-Induced Autophagolysosome Formation Is Partly Prevented by Mitochondrial ROS Elimination in DOX-Resistant Breast Cancer Cells
Authors: Ahmadpour Seyedeh Tayebeh , Desquiret-Dumas Valérie , Yikilmaz Ulku , Dartier Julie , Domingo Isabelle , Wetterwald Celine , Orre Charlotte , Gueguen Naïg , Brisson Lucie , Mahéo Karine , Dumas Jean-François
Published: August 2021

Since its discovery, mitophagy has been viewed as a protective mechanism used by cancer cells to prevent the induction of mitochondrial apoptosis. Most cancer treatments directly or indirectly cause mitochondrial dysfunction in order to trigger signals for cell death. Elimination of these dysfunctional mitochondria by mitophagy could thus prevent the initiation of the apoptotic cascade. In breast cancer patients, resistance to doxorubicin (DOX), one of the most widely used cancer drugs, is an important cause of poor clinical outcomes. However, the role played by mitophagy in the context of DOX resistance in breast cancer cells is not well understood. We therefore tried to determine whether an increase in mitophagic flux was associated with the resistance of breast cancer cells to DOX. Our first objective was to explore whether DOX-resistant breast cancer cells were characterized by conditions that favor mitophagy induction. We next tried to determine whether mitophagic flux was increased in DOX-resistant cells in response to DOX treatment. For this purpose, the parental (MCF-7) and DOX-resistant (MCF-7dox) breast cancer cell lines were used. Our results show that mitochondrial reactive oxygen species (ROS) production and hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression are higher in MCF-7dox in a basal condition compared to MCF-7, suggesting DOX-resistant breast cancer cells are prone to stimuli to induce a mitophagy-related event. Our results also showed that, in response to DOX, autophagolysosome formation is induced in DOX-resistant breast cancer cells. This mitophagic step following DOX treatment seems to be partly due to mitochondrial ROS production as autophagolysosome formation is moderately decreased by the mitochondrial antioxidant mitoTEMPO.
(20S) Ginsenoside Rh2 Inhibits STAT3/VEGF Signaling by Targeting Annexin A2
Authors: Wang Yu-Shi , Chen Chen , Zhang Shi-Yin , Li Yang , Jin Ying-Hua
Published: August 2021

Signal transducers and activators of transcription 3 (STAT3) acts as a transcriptional signal transducer, converting cytokine stimulation into specific gene expression. In tumor cells, aberrant activation of the tyrosine kinase pathway leads to excessive and continuous activation of STAT3, which provides further signals for tumor cell growth and surrounding angiogenesis. In this process, the tumor-associated protein Annexin A2 interacts with STAT3 and promotes Tyr705 phosphorylation and STAT3 transcriptional activation. In this study, we found that (20S) ginsenoside Rh2 (G-Rh2), a natural compound inhibitor of Annexin A2, inhibited STAT3 activity in HepG2 cells. (20S) G-Rh2 interfered with the interaction between Annexin A2 and STAT3, and inhibited Tyr705 phosphorylation and subsequent transcriptional activity. The inhibitory activity of STAT3 leaded to the negative regulation of the four VEGFs, which significantly reduced the enhanced growth and migration ability of HUVECs in co-culture system. In addition, (20S)G-Rh2 failed to inhibit STAT3 activity in cells overexpressing (20S)G-Rh2 binding-deficient Annexin A2-K301A mutant, further proving Annexin A2-mediated inhibition of STAT3 by (20S)G-Rh2. These results indicate that (20S)G-Rh2 is a potent inhibitor of STAT3, predicting the potential activity of (20S)G-Rh2 in targeted therapy applications.
Gibberellins Inhibit Flavonoid Biosynthesis and Promote Nitrogen Metabolism in Medicago truncatula
Authors: Sun Hao , Cui Huiting , Zhang Jiaju , Kang Junmei , Wang Zhen , Li Mingna , Yi Fengyan , Yang Qingchuan , Long Ruicai
Published: August 2021

Bioactive gibberellic acids (GAs) are diterpenoid plant hormones that are biosynthesized through complex pathways and control various aspects of growth and development. Although GA biosynthesis has been intensively studied, the downstream metabolic pathways regulated by GAs have remained largely unexplored. We investigated Tnt1 retrotransposon insertion mutant lines of Medicago truncatula with a dwarf phenotype by forward and reverse genetics screening and phylogenetic, molecular, biochemical, proteomic and metabolomic analyses. Three Tnt1 retrotransposon insertion mutant lines of the gibberellin 3-beta-dioxygenase 1 gene (GA3ox1) with a dwarf phenotype were identified, in which the synthesis of GAs (GA3 and GA4) was inhibited. Phenotypic analysis revealed that plant height, root and petiole length of ga3ox1 mutants were shorter than those of the wild type (Medicago truncatula ecotype R108). Leaf size was also much smaller in ga3ox1 mutants than that in wild-type R108, which is probably due to cell-size diminution instead of a decrease in cell number. Proteomic and metabolomic analyses of ga3ox1/R108 leaves revealed that in the ga3ox1 mutant, flavonoid isoflavonoid biosynthesis was significantly up-regulated, while nitrogen metabolism was down-regulated. Additionally, we further demonstrated that flavonoid and isoflavonoid biosynthesis was induced by prohexadione calcium, an inhibitor of GA3ox enzyme, and inhibited by exogenous GA3. In contrast, nitrogen metabolism was promoted by exogenous GA3 but inhibited by prohexadione calcium. The results of this study further demonstrated that GAs play critical roles in positively regulating nitrogen metabolism and transport and negatively regulating flavonoid biosynthesis through GA-mediated signaling pathways in leaves.
Development, Diversity, and Death of MGE-Derived Cortical Interneurons
Authors: Williams Rhîannan H. , Riedemann Therese
Published: August 2021

In the mammalian brain, cortical interneurons (INs) are a highly diverse group of cells. A key neurophysiological question concerns how each class of INs contributes to cortical circuit function and whether specific roles can be attributed to a selective cell type. To address this question, researchers are integrating knowledge derived from transcriptomic, histological, electrophysiological, developmental, and functional experiments to extensively characterise the different classes of INs. Our hope is that such knowledge permits the selective targeting of cell types for therapeutic endeavours. This review will focus on two of the main types of INs, namely the parvalbumin (PV+) or somatostatin (SOM+)-containing cells, and summarise the research to date on these classes.
Histone Deacetylase 3 Regulates Adipocyte Phenotype at Early Stages of Differentiation
Authors: Cricrí Dalma , Coppi Lara , Pedretti Silvia , Mitro Nico , Caruso Donatella , De Fabiani Emma , Crestani Maurizio
Published: August 2021

Obesity is a condition characterized by uncontrolled expansion of adipose tissue mass resulting in pathological weight gain. Histone deacetylases (HDACs) have emerged as crucial players in epigenetic regulation of adipocyte metabolism. Previously, we demonstrated that selective inhibition of class I HDACs improves white adipocyte functionality and promotes the browning phenotype of murine mesenchymal stem cells (MSCs) C3H/10T1/2 differentiated to adipocytes. These effects were also observed in db/db and diet induced obesity mouse models and in mice with adipose-selective inactivation of HDAC3, a member of class I HDACs. The molecular basis of class I HDACs action in adipose tissue is not deeply characterized and it is not known whether the effects of their inhibition are exerted on adipocyte precursors or mature adipocytes. Therefore, the aim of the present work was to explore the molecular mechanism of class I HDAC action in adipocytes by evaluating the effects of HDAC3-specific silencing at different stages of differentiation. HDAC3 was silenced in C3H/10T1/2 MSCs at different stages of differentiation to adipocytes. shRNA targeting HDAC3 was used to generate the knock-down model. Proper HDAC3 silencing was assessed by measuring both mRNA and protein levels of mouse HDAC3 via qPCR and western blot, respectively. Mitochondrial DNA content and gene expression were quantified via qPCR. HDAC3 silencing at the beginning of differentiation enhanced adipocyte functionality by amplifying the expression of genes regulating differentiation, oxidative metabolism, browning and mitochondrial activity, starting from 72 h after induction of differentiation and silencing. Insulin signaling was enhanced as demonstrated by increased AKT phosphorylation following HDAC3 silencing. Mitochondrial content/density did not change, while the increased expression of the transcriptional co-activator Ppargc1b suggests the observed phenotype was related to enhanced mitochondrial activity, which was confirmed by increased maximal respiration and proton leak linked to reduced coupling efficiency. Moreover, the expression of pro-inflammatory markers increased with HDAC3 early silencing. To the contrary, no differences in terms of gene expression were found when HDAC3 silencing occurred in terminally differentiated adipocyte. Our data demonstrated that early epigenetic events mediated by class I HDAC inhibition/silencing are crucial to commit adipocyte precursors towards the above-mentioned metabolic phenotype. Moreover, our data suggest that these effects are exerted on adipocyte precursors.
Overexpression of Tropomyosin Isoform Tpm3.1 Does Not Alter Synaptic Function in Hippocampal Neurons
Authors: Chaichim Chanchanok , Tomanic Tamara , Stefen Holly , Paric Esmeralda , Gamaroff Lucy , Suchowerska Alexandra K. , Gunning Peter W. , Ke Yazi D. , Fath Thomas , Power John
Published: August 2021

Tropomyosin (Tpm) has been regarded as the master regulator of actin dynamics. Tpms regulate the binding of the various proteins involved in restructuring actin. The actin cytoskeleton is the predominant cytoskeletal structure in dendritic spines. Its regulation is critical for spine formation and long-term activity-dependent changes in synaptic strength. The Tpm isoform Tpm3.1 is enriched in dendritic spines, but its role in regulating the synapse structure and function is not known. To determine the role of Tpm3.1, we studied the synapse structure and function of cultured hippocampal neurons from transgenic mice overexpressing Tpm3.1. We recorded hippocampal field excitatory postsynaptic potentials (fEPSPs) from brain slices to examine if Tpm3.1 overexpression alters long-term synaptic plasticity. Tpm3.1-overexpressing cultured neurons did not show a significantly altered dendritic spine morphology or synaptic activity. Similarly, we did not observe altered synaptic transmission or plasticity in brain slices. Furthermore, expression of Tpm3.1 at the postsynaptic compartment does not increase the local F-actin levels. The results suggest that although Tpm3.1 localises to dendritic spines in cultured hippocampal neurons, it does not have any apparent impact on dendritic spine morphology or function. This is contrary to the functional role of Tpm3.1 previously observed at the tip of growing neurites, where it increases the F-actin levels and impacts growth cone dynamics.
Phenotypic Characterization of Immortalized Chondrocytes from a Desbuquois Dysplasia Type 1 Mouse Model: A Tool for Studying Defects in Glycosaminoglycan Biosynthesis
Authors: Gramegna Tota Chiara , Valenti Beatrice , Forlino Antonella , Rossi Antonio , Paganini Chiara
Published: August 2021

The complexity of skeletal pathologies makes use of in vivo models essential to elucidate the pathogenesis of the diseases; nevertheless, chondrocyte and osteoblast cell lines provide relevant information on the underlying disease mechanisms. Due to the limitations of primary chondrocytes, immortalized cells represent a unique tool to overcome this problem since they grow very easily for several passages. However, in the immortalization procedure the cells might lose the original phenotype; thus, these cell lines should be deeply characterized before their use. We immortalized primary chondrocytes from a Cant1 knock-out mouse, an animal model of Desbuquois dysplasia type 1, with a plasmid expressing the SV40 large and small T antigen. This cell line, based on morphological and biochemical parameters, showed preservation of the chondrocyte phenotype. In addition reduced proteoglycan synthesis and oversulfation of glycosaminoglycan chains were demonstrated, as already observed in primary chondrocytes from the Cant1 knock-out mouse. In conclusion, immortalized Cant1 knock-out chondrocytes maintained the disease phenotype observed in primary cells validating the in vitro model and providing an additional tool to further study the proteoglycan biosynthesis defect. The same approach might be extended to other cartilage disorders.
Pharmaco-Magnetic Resonance as a Tool for Monitoring the Medication-Related Effects in the Brain May Provide Potential Biomarkers for Psychotic Disorders
Authors: Aryutova Katrin , Stoyanov Drozdstoy
Published: August 2021

The neurodegenerative and neurodevelopmental hypotheses represent the basic etiological framework for the origin of schizophrenia. Additionally, the dopamine hypothesis, adopted more than two decades ago, has repeatedly asserted the position of dopamine as a pathobiochemical substrate through the action of psychostimulants and neuroleptics on the mesolimbic and mesocortical systems, giving insight into the origin of positive and negative schizophrenic symptoms. Meanwhile, cognitive impairments in schizophrenia remain incompletely understood but are thought to be present during all stages of the disease, as well as in the prodromal, interictal and residual phases. On the other hand, observations on the effects of NMDA antagonists, such as ketamine and phencyclidine, reveal that hypoglutamatergic neurotransmission causes not only positive and negative but also cognitive schizophrenic symptoms. This review aims to summarize the different hypotheses about the origin of psychoses and to identify the optimal neuroimaging method that can serve to unite them in an integral etiological framework. We systematically searched Google scholar (with no concern to the date published) to identify studies investigating the etiology of schizophrenia, with a focus on impaired central neurotransmission. The complex interaction between the dopamine and glutamate neurotransmitter systems provides the long-needed etiological concept, which combines the neurodegenerative hypothesis with the hypothesis of impaired neurodevelopment in schizophrenia. Pharmaco-magnetic resonance imaging is a neuroimaging method that can provide a translation of scientific knowledge about the neural networks and the disruptions in and between different brain regions, into clinically applicable and effective therapeutic results in the management of severe psychotic disorders.
Recurrence of a Mediastinal Germ-Cell Tumor as a Somatic-Type Malignancy: A Complex Case Report
Authors: Hulsker Caroline C. C. , Kranendonk Mariëtte E. G. , Eleveld Thomas F. , Gillis Ad J. M. , van de Ven Cornelis P. , van Eijkelenburg Natasha K. A. , van der Kaaij Niels P. , van der Steeg Alida F. W. , Looijenga Leendert H. J.
Published: August 2021

Background and case: An adolescent male presented with a second mediastinal tumor 1.5 years after treatment of a proven malignant germ-cell tumor in that location. The differential diagnosis included a recurrent germ-cell tumor or a non-germ cell malignancy. Serum tumor markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) were negative. The first biopsy was not informative, and the second biopsy gave a broad differential diagnosis including secondary non-germ cell malignancy using histology and immunohistochemistry. DNA methylation profiling, RNA sequencing, and targeted microRNA371a-3p profiling was subsequently performed, without a supportive result. After resection of the tumor the definitive diagnosis yielded two secondary non-germ cell malignancies in the form of a leiomyosarcoma and a solitary neuro endocrine carcinoma (NEC). In spite of the differences between the molecular profiles of the initial germ-cell tumor, the leiomyosarcoma and large-cell NEC are clonally related, as determined by the presence of identical chromosomal breakpoints. The copy number profiles suggest an initial polyploidization step, followed by various independent chromosomal gains and losses. This case demonstrates that germ-cell tumors must be evaluated carefully, including molecularly, in which the non-germ cell malignancy is negative for miR-371a-3p, both in tissue as well as in serum, in contrast to the primary tumor. We conclude that the patient presented with a primary type II mediastinal GCT and, a year and a half later, followed by a leiomyosarcoma and a large-cell NEC presenting as two secondary somatic-type malignancies clonally related to the original GCT. Conclusions: Malignant germ-cell tumors are known to recur as a somatic-type malignancy in very rare cases. This case report illustrates the challenges faced in defining the nature and clonality of the secondary somatic-type malignancies.
Comparing the Appetitive Learning Performance of Six European Honeybee Subspecies in a Common Apiary
Authors: Scheiner Ricarda , Lim Kayun , Meixner Marina D. , Gabel Martin S.
Published: August 2021

The Western honeybee (Apis mellifera L.) is one of the most widespread insects with numerous subspecies in its native range. How far adaptation to local habitats has affected the cognitive skills of the different subspecies is an intriguing question that we investigate in this study. Naturally mated queens of the following five subspecies from different parts of Europe were transferred to Southern Germany: A. m. iberiensis from Portugal, A. m. mellifera from Belgium, A. m. macedonica from Greece, A. m. ligustica from Italy, and A. m. ruttneri from Malta. We also included the local subspecies A. m. carnica in our study. New colonies were built up in a common apiary where the respective queens were introduced. Worker offspring from the different subspecies were compared in classical olfactory learning performance using the proboscis extension response. Prior to conditioning, we measured individual sucrose responsiveness to investigate whether possible differences in learning performances were due to differential responsiveness to the sugar water reward. Most subspecies did not differ in their appetitive learning performance. However, foragers of the Iberian honeybee, A. m. iberiensis, performed significantly more poorly, despite having a similar sucrose responsiveness. We discuss possible causes for the poor performance of the Iberian honeybees, which may have been shaped by adaptation to the local habitat.
Sex-Specific Impacts of Exercise on Cardiovascular Remodeling
Authors: Islam Rifat A. , Khalsa Siri Sham S. , Vyas Arpita K. , Rahimian Roshanak
Published: August 2021

Cardiovascular diseases (CVD) remain the leading cause of death in men and women. Biological sex plays a major role in cardiovascular physiology and pathological cardiovascular remodeling. Traditionally, pathological remodeling of cardiovascular system refers to the molecular, cellular, and morphological changes that result from insults, such as myocardial infarction or hypertension. Regular exercise training is known to induce physiological cardiovascular remodeling and beneficial functional adaptation of the cardiovascular apparatus. However, impact of exercise-induced cardiovascular remodeling and functional adaptation varies between males and females. This review aims to compare and contrast sex-specific manifestations of exercise-induced cardiovascular remodeling and functional adaptation. Specifically, we review (1) sex disparities in cardiovascular function, (2) influence of biological sex on exercise-induced cardiovascular remodeling and functional adaptation, and (3) sex-specific impacts of various types, intensities, and durations of exercise training on cardiovascular apparatus. The review highlights both animal and human studies in order to give an all-encompassing view of the exercise-induced sex differences in cardiovascular system and addresses the gaps in knowledge in the field.
Hyperspectral Imaging and Machine Perfusion in Solid Organ Transplantation: Clinical Potentials of Combining Two Novel Technologies
Authors: Fodor Margot , Hofmann Julia , Lanser Lukas , Otarashvili Giorgi , Pühringer Marlene , Hautz Theresa , Sucher Robert , Schneeberger Stefan
Published: August 2021

Organ transplantation survival rates have continued to improve over the last decades, mostly due to reduction of mortality early after transplantation. The advancement of the field is facilitating a liberalization of the access to organ transplantation with more patients with higher risk profile being added to the waiting list. At the same time, the persisting organ shortage fosters strategies to rescue organs of marginal donors. In this regard, hypothermic and normothermic machine perfusion are recognized as one of the most important developments in the modern era. Owing to these developments, novel non-invasive tools for the assessment of organ quality are on the horizon. Hyperspectral imaging represents a potentially suitable method capable of evaluating tissue morphology and organ perfusion prior to transplantation. Considering the changing environment, we here discuss the hypothetical combination of organ machine perfusion and hyperspectral imaging as a prospective feasibility concept in organ transplantation.
Characteristics of Optic Disc and Visual Field Changes in Patients with Thyroid-Associated Orbitopathy and Open-Angle Glaucoma
Authors: Hsu Chih-Kang , Yao Hsin-Yu , Lin Che-Min , Chang Hsu-Chieh , Lu Da-Wen , Chen Yi-Hao , Chien Ke-Hung
Published: August 2021

This study aimed to characterize the changes in the visual field (VF) patterns and disc morphology of patients with thyroid-associated orbitopathy (TAO) and open-angle glaucoma (OAG). A retrospective review of the medical records at the Tri-Service General Hospital in Taiwan identified 396 eyes of 198 patients with thyroid-associated glaucoma. A final follow-up of VF examination in 140 eyes revealed 114 eyes with VF defects, indicating disease progression. The characteristics of and changes in disc morphology, optical coherence tomography findings, and VF defects were statistically analyzed. The most common VF defects at the initial diagnosis and the end of the follow-up period were inferior partial arcuate (17%) and paracentral (15%) defects, respectively. The most common VF defect in patients with unspecific disc signs was an unspecific scotoma (13%). The most common optic disc feature was disc cupping (51%), followed by parapapillary atrophy (48%). The most frequent location of nerve fiber layer thinning was the inferotemporal region (48%). VF defects showed a significantly more pronounced progression in the non-nerve fiber bundle group than in the nerve fiber bundle group (p < 0.001). This study details the characteristics and progression of disc morphology and VF defects in patients with TAO and OAG.
A Changing Perspective for Treatment of Chronic Kidney Disease
Authors: Garibotto Giacomo
Published: August 2021

Chronic kidney disease (CKD) is now an enormous worldwide health problem [...]
Bioactive Calcium Phosphate-Based Composites for Bone Regeneration
Authors: Tavoni Marta , Dapporto Massimiliano , Tampieri Anna , Sprio Simone
Published: August 2021

Calcium phosphates (CaPs) are widely accepted biomaterials able to promote the regeneration of bone tissue. However, the regeneration of critical-sized bone defects has been considered challenging, and the development of bioceramics exhibiting enhanced bioactivity, bioresorbability and mechanical performance is highly demanded. In this respect, the tuning of their chemical composition, crystal size and morphology have been the matter of intense research in the last decades, including the preparation of composites. The development of effective bioceramic composite scaffolds relies on effective manufacturing techniques able to control the final multi-scale porosity of the devices, relevant to ensure osteointegration and bio-competent mechanical performance. In this context, the present work provides an overview about the reported strategies to develop and optimize bioceramics, while also highlighting future perspectives in the development of bioactive ceramic composites for bone tissue regeneration.
Continuity in general practice as predictor of mortality, acute hospitalisation, and use of out-of-hours care: a registry-based observational study in Norway
Authors: Sandvik Hogne , Hetlevik Øystein , Blinkenberg Jesper , Hunskaar Steinar
Published: August 2021

Background

Continuity, usually considered a quality aspect of primary care, is under pressure in Norway, and elsewhere.

Aim

To analyse the association between longitudinal continuity with a named regular general practitioner (RGP) and use of out-of-hours (OOH) services, acute hospital admission, and mortality.

Design and setting

Registry-based observational study in Norway covering 4 552 978 Norwegians listed with their RGPs.

Method

Duration of RGP–patient relationship was used as explanatory variable for the use of OOH services, acute hospital admission, and mortality in 2018. Several patient-related and RGP-related covariates were included in the analyses by individual linking to high-quality national registries. Duration of RGP–patient relationship was categorised as 1, 2–3, 4–5, 6–10, 11–15, or >15 years. Results are given as adjusted odds ratio (OR) with 95% confidence intervals (CI) resulting from multilevel logistic regression analyses.

Results

Compared with a 1-year RGP–patient relationship, the OR for use of OOH services decreased gradually from 0.87 (95% CI = 0.86 to 0.88) after 2–3 years’ duration to 0.70 (95% CI = 0.69 to 0.71) after >15 years. OR for acute hospital admission decreased gradually from 0.88 (95% CI = 0.86 to 0.90) after 2–3 years’ duration to 0.72 (95% CI = 0.70 to 0.73) after >15 years. OR for dying decreased gradually from 0.92 (95% CI = 0.86 to 0.98) after 2–3 years’ duration, to 0.75 (95% CI = 0.70 to 0.80) after an RGP–patient relationship of >15 years.

Conclusion

Length of RGP–patient relationship is significantly associated with lower use of OOH services, fewer acute hospital admissions, and lower mortality. The presence of a dose–response relationship between continuity and these outcomes indicates that the associations are causal.
Dimensional Speech Emotion Recognition from Acoustic and Text Features using Recurrent Neural Networks
Authors:   Sepuluh NopemberInstitute of Technology, Surabaya, Indonesia, Tris Atmaja Bagus , Elbarougy Reda ,   Damietta University, New Damietta, Egypt, Akagi Masato ,   Japan Advanced Institute of Science of Technology, Nomi, Japan
Published: August 2021

Emotion can be inferred from tonal and verbal information, where both features can be extracted from speech. While most researchers conducted studies on categorical emotion recognition from a single modality, this research presents a dimensional emotion recognition combining acoustic and text features. A number of 31 acoustic features are extracted from speech, while word vector is used as text features. The initial result on single modality emotion recognition can be used as a cue to combine both features with improving the recognition result. The latter result shows that a combination of acoustic and text features decreases the error of dimensional emotion score prediction by about 5% from the acoustic system and 1% from the text system. This smallest error is achieved by combining the text system with Long Short-Term Memory (LSTM) networks and acoustic systems with bidirectional LSTM networks and concatenated both systems with dense networks
SWOT Analysis of Lending Platform from Blockchain Technology Perspectives
Authors:   INSA Lyon, LIRIS, UMR5205, France, Uriawan Wisnu
Published: August 2021

Blockchain Technology become phenomenal issue in the world, emerging with bitcoin and IoT. It had been implemented in many areas in human activity. Advantages of blockchain technology is distributed ledger where resources distributed to all member in network. Loans or credit as part of human activity in their life. When we need cash for a major expense, it might be tempting to borrow from a payday lender or max out a credit card or similar, but you have other options that will not harm your credit or put you in a cycle of debt, even if your credit record is not all that great. Collateral loans could be a way to borrow the money as you need. One of which is the lending platform. Blockchain technology has been implemented in many lending platforms, but there are still any weaknesses that can be refined and optimized. Tool of analysis is SWOT, describes of four analysis, as follow: Strength, Weakness, Opportunity and Threats. This paper purpose to analyzed lending platform measured by look for the weaknesses variable and how to optimize that system performance that can improve for helping people in lending process. In addition, the result of this analysis can use for enhancement recommendation the system based on the weaknesses are found and opportunity for make a lending platform robust
Modeling Traffic Flows with Fluid Flow Model
Authors:   Department of Information Technology,Institut Teknologi Harapan Bangsa, Jl. DipatiukurNo. 80-84, Bandung, Indonesia, Setiawan Suryadjaja Paulus , Hutagalung Maclaurin ,   Department of Information Technology,Institut Teknologi Harapan Bangsa, Jl. DipatiukurNo. 80-84, Bandung, Indonesia, Yoseph Sutarto Herman ,   Department of Information Technology,Institut Teknologi Harapan Bangsa, Jl. DipatiukurNo. 80-84, Bandung, Indonesia
Published: August 2021

This Research presents a macroscopic model of traffic flow as the basis for making Intelligent Transportation System (ITS). The data used for modeling is The number of passing vehicles per three minutes. The traffic flow model created in The form of Fluid Flow Model (FFM). The parameters in The model are obtained by mixture Gaussian distribution approach. The distribution consists of two Gaussian distributions, each representing the mode of traffic flow. In The distribution, intermode shifting process is illustrated by the first-order Markov chain process. The parameters values are estimated using The Expectation-maximization (EM) algorithm. After The required parameter values are obtained, traffic flow is estimated using the Observation and transition-basedmost likely estimates Tracking Particle Filter (OTPF). To Examine the accuracy of the model has been made, the model estimation results are compared with the actual traffic flow data. Traffic flow data is collected on Monday 20 September 2017 at 06.00 to 10.00 on DipatiukurRoad, Bandung. The proposed model has accuracy with MAPE value below 10%, or falls into highly accurate categories
Diagnosis of COVID-19 Using Chest X-ray
Authors:   Noida Institute of Engineering and Technology, Malik Sumit , Singh Shivendra , Mohan Singh Narendra , Panwar Naman
Published: August 2021

Covid-19 is also a wide spreading infective agent disease that infects humans. A clinical study of COVID-19 infected patients has shown that these kinds of patients are square measure principally infected from a respiratory organ infection when come in contact with this disease. Chest xray (i.e., radiography) a less complicated imaging technique for identification respiratory organ connected issues. Deep learning is that the foremost undefeated technique of machine learning, that provides helpful analysis to review an oversize quantity of chest x-ray pictures which may critically impact on screening of Covid-19. Throughout this work, we have taken the PA read of chest x-ray scans for covid-19 affected patients conjointly as healthy patients. We have used deep learning-based CNN models and compared their performance. We have equate ResNeXt models and inspect their precision to investigate the model presentation, 6432 chest x-ray scans samples square measure collected from the Kaggle repository. This work solely core on potential ways of cluster covid-19 infected patients.
Virtual Voting System
Authors:   Department of Information Technology, Noida Institute of Engineering and Technology, Greater Noida, India, Kumar Gaurav , Gupta Smriti , Agarwal Divya , Tiwari Astha
Published: August 2021

India's voting system plays an important role in Indian Democracy. The existing system is offline and has certain weaknesses. In recent years, the spread of covid19, inefficient rural voters, people far from their place of birth, paper waste affecting nature, budgets that should be used for development, invisible fraud, waste of human labor, have been recorded and can be avoided by the virtual voting system. The research aims to supply an easy and secure electoral system in India. The method used descriptive qualitative. The results indicate that a virtual voting system is environmentally friendly and is considered a resource-saving way for the election. It is because minimizes errors and increases voter participation through convenient virtual voting. In conclusion, a virtual voting system can develop an Aadhar based advanced Electronic Voting Machine (EVM), which helps in a free and fair way of conducting elections