bluuebunny/crossref_metadata_2025 huggingface dataset:
Approximations of an Equilibrium Problem without Prior Knowledge of Lipschitz Constants in Hilbert Spaces with Applications
Authors: Khanpanuk Chainarong , Pakkaranang Nuttapol , Wairojjana Nopparat , Pholasa Nattawut
Published: April 2021

The objective of this paper is to introduce an iterative method with the addition of an inertial term to solve equilibrium problems in a real Hilbert space. The proposed iterative scheme is based on the Mann-type iterative scheme and the extragradient method. By imposing certain mild conditions on a bifunction, the corresponding theorem of strong convergence in real Hilbert space is well-established. The proposed method has the advantage of requiring no knowledge of Lipschitz-type constants. The applications of our results to solve particular classes of equilibrium problems is presented. Numerical results are established to validate the proposed method’s efficiency and to compare it to other methods in the literature.
CoreValve vs. Sapien 3 Transcatheter Aortic Valve Replacement: A Finite Element Analysis Study
Authors: Nappi Francesco , Mazzocchi Laura , Spadaccio Cristiano , Attias David , Timofeva Irina , Macron Laurent , Iervolino Adelaide , Morganti Simone , Auricchio Ferdinando
Published: April 2021

Aim: to investigate the factors implied in the development of postoperative complications in both self-expandable and balloon-expandable transcatheter heart valves by means of finite element analysis (FEA). Materials and methods: FEA was integrated into CT scans to investigate two cases of postoperative device failure for valve thrombosis after the successful implantation of a CoreValve and a Sapien 3 valve. Data were then compared with two patients who had undergone uncomplicated transcatheter heart valve replacement (TAVR) with the same types of valves. Results: Computational biomechanical modeling showed calcifications persisting after device expansion, not visible on the CT scan. These calcifications determined geometrical distortion and elliptical deformation of the valve predisposing to hemodynamic disturbances and potential thrombosis. Increased regional stress was also identified in correspondence to the areas of distortion with the associated paravalvular leak. Conclusion: the use of FEA as an adjunct to preoperative imaging might assist patient selection and procedure planning as well as help in the detection and prevention of TAVR complications.
Extracellular Vesicles as Promising Carriers in Drug Delivery: Considerations from a Cell Biologist’s Perspective
Authors: Pedrioli Giona , Piovesana Ester , Vacchi Elena , Balbi Carolina
Published: April 2021

The use of extracellular vesicles as cell-free therapy is a promising approach currently investigated in several disease models. The intrinsic capacity of extracellular vesicles to encapsulate macromolecules within their lipid bilayer membrane-bound lumen is a characteristic exploited in drug delivery to transport active pharmaceutical ingredients. Besides their role as biological nanocarriers, extracellular vesicles have a specific tropism towards target cells, which is a key aspect in precision medicine. However, the little knowledge of the mechanisms governing the release of a cargo macromolecule in recipient cells and the Good Manufacturing Practice (GMP) grade scale-up manufacturing of extracellular vesicles are currently slowing their application as drug delivery nanocarriers. In this review, we summarize, from a cell biologist’s perspective, the main evidence supporting the role of extracellular vesicles as promising carriers in drug delivery, and we report five key considerations that merit further investigation before translating Extracellular Vesicles (EVs) to clinical applications.
Comprehensive Transcriptome Analysis of mRNA Expression Patterns of Early Embryo Development in Goat under Hypoxic and Normoxic Conditions
Authors: Wan Yongjie , Li Dongxu , Deng Mingtian , Liu Zifei , Liu Liang , Wang Feng
Published: April 2021

It has been reported that hypoxic environments were more suitable for the in vitro development of mammalian embryos, but the underlying mechanisms were still unclear. In the present study, RNA-seq was performed to compare 8-cell-stage and blastocyst-stage goat embryos under hypoxic and normoxic conditions; zygotes were checked at 72 and 168 h to 8-cell stage (L8C) and blastocyst stage (LM) in hypoxic conditions and 8-cell stage (H8C) and blastocyst stage (HM) in normoxic conditions. In the H8C and L8C groups, 399 DEGs were identified, including 348 up- and 51 down-regulated DEGs. In the HM and LM groups, 1710 DEGs were identified, including 1516 up- and 194 down-regulated DEGs. The expression levels of zygotic genes, transcription factors, and maternal genes, such as WEE2, GDF9, HSP70.1, BTG4, and UBE2S showed significant changes. Functional enrichment analysis indicated that these DEGs were mainly related to biological processes and function regulation. In addition, combined with the pathway–gene interaction network and protein–protein interaction network, twenty-two of the hub genes were identified and they are mainly involved in energy metabolism, immune stress response, cell cycle, receptor binding, and signal transduction pathways. The present study provides comprehensive insights into the effects of oxidative stress on early embryo development in goats.
Biocompatible Platinum Nanoclusters Prepared Using Bitter Gourd Polysaccharide for Colorimetric Detection of Ascorbic Acid
Authors: Liu Kai , Zhao Yu , Zhang Lu , He Mengmeng , Lin Weifeng , Sun Haotian , Liu Zhiwei , Hu Jie , Wang Longgang
Published: April 2021

Ascorbic acid is an organic compound with antioxidant properties that can protect the human body from the threat of free radicals. Therefore, it is important to detect the existence and measure the concentration of ascorbic acid to regulate its content in the human body. In this work, we prepared bitter gourd polysaccharide (BGP)-stabilized platinum nanoclusters (Pt-BGP NCs) by reacting BGP with K2PtCl4. Pt-BGP NCs and catalyzed the decomposition of H2O2 to generate •OH radicals, which could oxidize TMB to form oxidized TMB (oxTMB), indicating their peroxidase-like properties. The kinetics followed the Michaelis–Menten equation. Furthermore, the colorimetric detection of ascorbic acid using Pt-BGP NCs showed high selectivity and a low detection limit of 0.191 μM. The accuracy of real sample detection using Pt-BGP NCs was as high as 98.9%. More importantly, Pt-BGP NCs had high cell biocompatibility and extremely low hemolysis rate due to the component of BGP. In summary, the prepared Pt-BGP NCs with reductive activity and good biocompatibility have good application prospects in colorimetric detection of ascorbic acid.
MicroRNA Expression in Extracellular Vesicles from Nasal Lavage Fluid in Chronic Rhinosinusitis
Authors: Cha Seungbin , Seo Eun-Hye , Lee Seung , Kim Kyung , Oh Chung-Sik , Moon Jong-Seok , Kim Jin
Published: April 2021

Extracellular vesicles (EVs) are nanovesicles of endocytic origin released by cells and found in human bodily fluids. EVs contain both mRNA and microRNA (miRNA), which can be shuttled between cells, indicating their role in cell communication. This study investigated whether nasal secretions contain EVs and whether these EVs contain RNA. EVs were isolated from nasal lavage fluid (NLF) using sequential centrifugation. EVs were characterized and EV sizes were identified by transmission electron microscopy (TEM). In addition, EV miRNA expression was different in the chronic rhinosinusitis without nasal polyp (CRSsNP) and chronic rhinosinusitis with nasal polyp (CRSwNP) groups. The Kyoto encyclopedia gene and genome database (KEGG) database was used to identify pathways associated with changed miRNAs in each analysis group. Twelve miRNAs were differentially expressed in NLF-EVs of CRS patients versus HCs. In addition, eight miRNAs were differentially expressed in NLF-EVs of CRSwNP versus CRSsNP patients. The mucin-type O-glycan biosynthesis was a high-ranked predicted pathway in CRS patients versus healthy controls (HCs), and the Transforming growth factor beta (TGF-β) signaling pathway was a high-ranked predicted pathway in CRSwNP versus CRSsNP patients. We demonstrated the presence of and differences in NLF-EV miRNAs between CRS patients and HCs. These findings open up a broad and novel area of research on CRS pathophysiology as driven by miRNA cell communication.
Neurophysiological Mechanisms Underlying Cortical Hyper-Excitability in Amyotrophic Lateral Sclerosis: A Review
Authors: Pradhan Jonu , Bellingham Mark C.
Published: April 2021

Amyotrophic lateral sclerosis (ALS) is a progressive neuromotor disease characterized by the loss of upper and lower motor neurons (MNs), resulting in muscle paralysis and death. Early cortical hyper-excitability is a common pathological process observed clinically and in animal disease models. Although the mechanisms that underlie cortical hyper-excitability are not completely understood, the molecular and cellular mechanisms that cause enhanced neuronal intrinsic excitability and changes in excitatory and inhibitory synaptic activity are starting to emerge. Here, we review the evidence for an anterograde glutamatergic excitotoxic process, leading to cortical hyper-excitability via intrinsic cellular and synaptic mechanisms and for the role of interneurons in establishing disinhibition in clinical and experimental settings. Understanding the mechanisms that lead to these complex pathological processes will likely produce key insights towards developing novel therapeutic strategies to rescue upper MNs, thus alleviating the impact of this fatal disease.
Use of PET Imaging in Neuro-Oncological Surgery
Authors: Holzgreve Adrien , Albert Nathalie L. , Galldiks Norbert , Suchorska Bogdana
Published: April 2021

This review provides an overview of current applications and perspectives of PET imaging in neuro-oncological surgery. The past and future of PET imaging in the management of patients with glioma and brain metastases are elucidated with an emphasis on amino acid tracers, such as O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET). The thematic scope includes surgical resection planning, prognostication, non-invasive prediction of molecular tumor characteristics, depiction of intratumoral heterogeneity, response assessment, differentiation between tumor progression and treatment-related changes, and emerging new tracers. Furthermore, the role of PET using specific somatostatin receptor ligands for the management of patients with meningioma is discussed. Further advances in neuro-oncological imaging can be expected from promising new techniques, such as hybrid PET/MR scanners and the implementation of artificial intelligence methods, such as radiomics.
Gene Regulation Network Analysis on Human Prostate Orthografts Highlights a Potential Role for the JMJD6 Regulon in Clinical Prostate Cancer
Authors: Cangiano Mario , Grudniewska Magda , Salji Mark J. , Nykter Matti , Jenster Guido , Urbanucci Alfonso , Granchi Zoraide , Janssen Bart , Hamilton Graham , Leung Hing Y. , Beumer Inès J.
Published: April 2021

Background: Prostate cancer (PCa) is the second most common tumour diagnosed in men. Tumoral heterogeneity in PCa creates a significant challenge to develop robust prognostic markers and novel targets for therapy. An analysis of gene regulatory networks (GRNs) in PCa may provide insight into progressive PCa. Herein, we exploited a graph-based enrichment score to integrate data from GRNs identified in preclinical prostate orthografts and differentially expressed genes in clinical resected PCa. We identified active regulons (transcriptional regulators and their targeted genes) associated with PCa recurrence following radical prostatectomy. Methods: The expression of known transcription factors and co-factors was analysed in a panel of prostate orthografts (n = 18). We searched for genes (as part of individual GRNs) predicted to be regulated by the highest number of transcriptional factors. Using differentially expressed gene analysis (on a per sample basis) coupled with gene graph enrichment analysis, we identified candidate genes and associated GRNs in PCa within the UTA cohort, with the most enriched regulon being JMJD6, which was further validated in two additional cohorts, namely EMC and ICGC cohorts. Cox regression analysis was performed to evaluate the association of the JMJD6 regulon activity with disease-free survival time in the three clinical cohorts as well as compared to three published prognostic gene signatures (TMCC11, BROMO-10 and HYPOXIA-28). Results: 1308 regulons were correlated to transcriptomic data from the three clinical prostatectomy cohorts. The JMJD6 regulon was identified as the top enriched regulon in the UTA cohort and again validated in the EMC cohort as the top-ranking regulon. In both UTA and EMC cohorts, the JMJD6 regulon was significantly associated with cancer recurrence. Active JMJD6 regulon also correlated with disease recurrence in the ICGC cohort. Furthermore, Kaplan–Meier analysis confirmed shorter time to recurrence in patients with active JMJD6 regulon for all three clinical cohorts (UTA, EMC and ICGC), which was not the case for three published prognostic gene signatures (TMCC11, BROMO-10 and HYPOXIA-28). In multivariate analysis, the JMJD6 regulon status significantly predicted disease recurrence in the UTA and EMC, but not ICGC datasets, while none of the three published signatures significantly prognosticate for cancer recurrence. Conclusions: We have characterised gene regulatory networks from preclinical prostate orthografts and applied transcriptomic data from three clinical cohorts to evaluate the prognostic potential of the JMJD6 regulon.
Identification of CRYAB+ KCNN3+ SOX9+ Astrocyte-Like and EGFR+ PDGFRA+ OLIG1+ Oligodendrocyte-Like Tumoral Cells in Diffuse IDH1-Mutant Gliomas and Implication of NOTCH1 Signalling in Their Genesis
Authors: Augustus Meera , Pineau Donovan , Aimond Franck , Azar Safa , Lecca Davide , Scamps Frédérique , Muxel Sophie , Darlix Amélie , Ritchie William , Gozé Catherine , Rigau Valérie , Duffau Hugues , Hugnot Jean-Philippe
Published: April 2021

Diffuse grade II IDH-mutant gliomas are slow-growing brain tumors that progress into high-grade gliomas. They present intratumoral cell heterogeneity, and no reliable markers are available to distinguish the different cell subtypes. The molecular mechanisms underlying the formation of this cell diversity is also ill-defined. Here, we report that SOX9 and OLIG1 transcription factors, which specifically label astrocytes and oligodendrocytes in the normal brain, revealed the presence of two largely nonoverlapping tumoral populations in IDH1-mutant oligodendrogliomas and astrocytomas. Astrocyte-like SOX9+ cells additionally stained for APOE, CRYAB, ID4, KCNN3, while oligodendrocyte-like OLIG1+ cells stained for ASCL1, EGFR, IDH1, PDGFRA, PTPRZ1, SOX4, and SOX8. GPR17, an oligodendrocytic marker, was expressed by both cells. These two subpopulations appear to have distinct BMP, NOTCH1, and MAPK active pathways as stainings for BMP4, HEY1, HEY2, p-SMAD1/5 and p-ERK were higher in SOX9+ cells. We used primary cultures and a new cell line to explore the influence of NOTCH1 activation and BMP treatment on the IDH1-mutant glioma cell phenotype. This revealed that NOTCH1 globally reduced oligodendrocytic markers and IDH1 expression while upregulating APOE, CRYAB, HEY1/2, and an electrophysiologically-active Ca2+-activated apamin-sensitive K+ channel (KCNN3/SK3). This was accompanied by a reduction in proliferation. Similar effects of NOTCH1 activation were observed in nontumoral human oligodendrocytic cells, which additionally induced strong SOX9 expression. BMP treatment reduced OLIG1/2 expression and strongly upregulated CRYAB and NOGGIN, a negative regulator of BMP. The presence of astrocyte-like SOX9+ and oligodendrocyte-like OLIG1+ cells in grade II IDH1-mutant gliomas raises new questions about their role in the pathology.
Prognostic Factors and Current Treatment Strategies for Renal Cell Carcinoma Metastatic to the Brain: An Overview
Authors: Internò Valeria , De Santis Pierluigi , Stefania Stucci Luigia , Rudà Roberta , Tucci Marco , Soffietti Riccardo , Porta Camillo
Published: April 2021

Renal cell carcinoma (RCC) is one of primary cancers that frequently metastasize to the brain. Brain metastasis derived from RCC has the propensity of intratumoral hemorrhage and relatively massive surrounding edema. Moreover, it confers a grim prognosis in a great percentage of cases with a median overall survical (mOS) around 10 months. The well-recognized prognostic factors for brain metastatic renal cell carcinoma (BMRCC) are Karnofsky Performance Status (KPS), the number of brain metastasis (BM), the presence of a sarcomatoid component and the presence of extracranial metastasis. Therapeutic strategies are multimodal and include surgical resection, radiotherapy, such as stereotactic radiosurgery due to the radioresistance of RCC and systemic strategies with tyrosin kinase inhibitors (TKI) or Immune checkpoint inhibitors (ICI) whose efficacy is not well-established in this setting of patients due to their exclusion from most clinical trials. To date, in case of positive prognostic factors and after performing local radical therapies, such as complete resection of BM or stereotactic radiosurgery (SRS), the outcome of these patients significantly improves, up to 33 months in some patients. As a consequence, tailored clinical trials designed for BMRCC are needed to define the correct treatment strategy even in this poor prognostic subgroup of patients.
Genomic Correlates of DNA Damage in Breast Cancer Subtypes
Authors: Cabañas Morafraile Esther , Pérez-Peña Javier , Fuentes-Antrás Jesús , Manzano Aránzazu , Pérez-Segura Pedro , Pandiella Atanasio , Galán-Moya Eva M. , Ocaña Alberto
Published: April 2021

Among the described druggable vulnerabilities, acting on the DNA repair mechanism has gained momentum, with the approval of PARP inhibitors in several indications, including breast cancer. However, beyond the mere presence of BRCA1/BRCA2 mutations, the identification of additional biomarkers that would help to select tumors with an extreme dependence on DNA repair machinery would help to stratify therapeutic decisions. Gene set enrichment analyses (GSEA) using public datasets evaluating expression values between normal breast tissue and breast cancer identified a set of upregulated genes. Genes included in different pathways, such as ATM/ATR, BARD1, and Fanconi Anemia, which are involved in the DNA damage response, were selected and confirmed using molecular alterations data contained at cBioportal. Nineteen genes from these gene sets were identified to be amplified and upregulated in breast cancer but only five of them NBN, PRKDC, RFWD2, UBE2T, and YWHAZ meet criteria in all breast cancer molecular subtypes. Correlation of the selected genes with prognosis (relapse free survival, RFS, and overall survival, OS) was performed using the KM Plotter Online Tool. In last place, we selected the best signature of genes within this process whose upregulation can be indicative of a more aggressive phenotype and linked with worse outcome. In summary, we identify genomic correlates within DNA damage pathway associated with prognosis in breast cancer.
Prognostic Role of Plasma PD-1, PD-L1, pan-BTN3As and BTN3A1 in Patients Affected by Metastatic Gastrointestinal Stromal Tumors: Can Immune Checkpoints Act as a Sentinel for Short-Term Survival?
Authors: Fanale Daniele , Incorvaia Lorena , Badalamenti Giuseppe , De Luca Ida , Algeri Laura , Bonasera Annalisa , Corsini Lidia Rita , Brando Chiara , Russo Antonio , Iovanna Juan Lucio , Bazan Viviana
Published: April 2021

Gastrointestinal stromal tumors (GISTs) represent 1% of all primary gastrointestinal tumors. Immune surveillance is often overcome by cancer cells due to the activation of immunoregulatory molecules such as programmed death protein (PD-1) and its ligand PD-L1, and butyrophilin sub-family 3A/CD277 receptors (BTN3A). Because several studies demonstrated that tumor PD-1 and PD-L1 expression may have a prominent prognostic function, this investigation aimed to discover if soluble forms of these molecules may be useful in predicting survival of metastatic GIST (mGIST) patients. Through specific ad hoc developed ELISA assays not yet available on the market, the circulating PD-1, PD-L1, BTN3A1, and pan-BTN3As levels were examined in 30 c-KIT exon 11-mutated mGIST patients, prior to imatinib therapy. Using specific thresholds derived by ROC analysis, we found that high baseline levels of sPD-1 (>8.1 ng/mL), sPD-L1 (>0.7 ng/mL), sBTN3A1 (>7.0 ng/mL), and pan-BTN3As (>5.0 ng/mL) were correlated with shorter progression-free survival (PFS) and poor prognosis. Contrariwise, subjects with lower plasma concentrations exhibited a median PFS about 20 months longer than to the earlier. Finally, an additional multivariate analysis revealed that circulating levels of sPD-L1 ≤ 0.7 ng/mL and pan-sBTN3As ≤ 5.0 ng/mL, and the absence of KIT exon 11 deletions or delins at codons 557 and/or 558 were associated with a longer PFS in mGIST patients. Our investigation, for the first time, revealed that evaluating the plasma concentration of some immune checkpoints may help prognosticate survival in mGIST patients, suggesting their potential use as prognostic biomarkers beyond the presence of KIT exon 11 Del or Delins at codons 557/558.
Development of a microRNA Panel for Classification of Abnormal Mammograms for Breast Cancer
Authors: Zou Ruiyang , Loke Sau Yeen , Tan Veronique Kiak-Mien , Quek Swee Tian , Jagmohan Pooja , Tang Yew Chung , Madhukumar Preetha , Tan Benita Kiat-Tee , Yong Wei Sean , Sim Yirong , Lim Sue Zann , Png Eunice , Lee Shu Yun Sherylyn , Chan Mun Yew Patrick , Ho Teng Swan Juliana , Khoo Boon Kheng James , Wong Su Lin Jill , Thng Choon Hua , Chong Bee Kiang , Teo Yik Ying , Too Heng-Phon , Hartman Mikael , Tan Ngiap Chuan , Tan Ern Yu , Lee Soo Chin , Zhou Lihan , Lee Ann Siew Gek
Published: April 2021

Mammography is extensively used for breast cancer screening but has high false-positive rates. Here, prospectively collected blood samples were used to identify circulating microRNA (miRNA) biomarkers to discriminate between malignant and benign breast lesions among women with abnormal mammograms. The Discovery cohort comprised 72 patients with breast cancer and 197 patients with benign breast lesions, while the Validation cohort had 73 and 196 cancer and benign cases, respectively. Absolute expression levels of 324 miRNAs were determined using RT-qPCR. miRNA biomarker panels were identified by: (1) determining differential expression between malignant and benign breast lesions, (2) focusing on top differentially expressed miRNAs, and (3) building panels from an unbiased search among all expressed miRNAs. Two-fold cross-validation incorporating a feature selection algorithm and logistic regression was performed. A six-miRNA biomarker panel identified by the third strategy, had an area under the curve (AUC) of 0.785 and 0.774 in the Discovery and Validation cohorts, respectively, and an AUC of 0.881 when differentiating between cases versus those with benign lesions or healthy individuals with normal mammograms. Biomarker panel scores increased with tumor size, stage and number of lymph nodes involved. Our work demonstrates that circulating miRNA signatures can potentially be used with mammography to differentiate between patients with malignant and benign breast lesions.
Cancer-Associated Fibroblast-Derived IL-6 Determines Unfavorable Prognosis in Cholangiocarcinoma by Affecting Autophagy-Associated Chemoresponse
Authors: Thongchot Suyanee , Vidoni Chiara , Ferraresi Alessandra , Loilome Watcharin , Khuntikeo Narong , Sangkhamanon Sakkarn , Titapun Attapol , Isidoro Ciro , Namwat Nisana
Published: April 2021

Background: Interleukin-6 (IL-6) released by cancer-associated fibroblasts (CAFs) has been shown to associate with the malignant behavior of cholangiocarcinoma (CCA). Here, we aimed to validate with clinical and molecular data the hypothesis that CAF infiltration and release of IL-6 predict poor prognosis in CCA patients following dysregulation of autophagy in cancer cells. Methods: Stromal IL-6 and cancer-cell-associated autophagy proteins LC3 and p62 were assayed by Tissue MicroArray immunohistochemistry and their expression correlated with overall survival (OS) in a cohort of 70 CCA patients. The 5-FU cytotoxicity and autophagy were determined in CCA cells cultured with CAF-conditioned medium. Results: We show that patients bearing a CCA with low production of stromal IL-6 and active autophagy flux in the cancer cells have the best prognosis and this correlates with a more effective response to post-operative chemotherapy. A similar trend was observed in CCA patients from the TCGA database. In vitro genetic manipulation of IL-6 production by primary CAFs isolated from human CCA showed that IL-6 impairs the autophagy-associated apoptotic response to 5-FU in human CCA cells. Stromal IL-6 inhibition of autophagy in cancer cells was confirmed in an animal model of CCA. Conclusion: Our data support a therapeutic strategy that includes autophagy-enhancing drugs along with adjuvants limiting the stromal inflammation (i.e., the secretion of IL-6) to improve the survival of CCA patients.
The Catalytic Oxidation of Formaldehyde by FeOx-MnO2-CeO2 Catalyst: Effect of Iron Modification
Authors: Dong Yaxin , Su Chenguang , Liu Kai , Wang Haomeng , Zheng Zheng , Zhao Wei , Lu Suhong
Published: April 2021

A series of FeOx-MnO2-CeO2 catalysts were synthesized by the surfactant-templated coprecipitation method and applied for HCHO removal. The influence of Fe/Mn/Ce molar ratio on the catalytic performance was investigated, and the FeOx-MnO2-CeO2 catalyst exhibited excellent catalytic activity, with complete HCHO conversion at low temperatures (40 °C) when the molar ratio of Fe/Mn/Ce was 2/5/5. The catalysts were characterized by N2 adsorption and desorption, XRD, H2-TPR, O2-TPD and XPS techniques to illustrate their structure–activity relationships. The result revealed that the introduction of FeOx into MnO2-CeO2 formed a strong interaction between FeOx-MnO2-CeO2, which facilitated the improved dispersion of MnO2-CeO2, subsequently increasing the surface area and aiding pore development. This promotion effect of Fe enhanced the reducibility and produced abundant surface-active oxygen. In addition, a great number of Oα is beneficial to the intermediate decomposition, whereas the existence of Ce3+ favors the formation of oxygen vacancies on the surface of the catalyst, all of which contributed to HCHO oxidation at low temperatures.
Drosophila O-GlcNAcase Mutants Reveal an Expanded Glycoproteome and Novel Growth and Longevity Phenotypes
Authors: Akan Ilhan , Halim Adnan , Vakhrushev Sergey Y. , Clausen Henrik , Hanover John A.
Published: April 2021

The reversible posttranslational O-GlcNAc modification of serine or threonine residues of intracellular proteins is involved in many cellular events from signaling cascades to epigenetic and transcriptional regulation. O-GlcNAcylation is a conserved nutrient-dependent process involving two enzymes, with O-GlcNAc transferase (OGT) adding O-GlcNAc and with O-GlcNAcase (OGA) removing it in a manner that’s protein- and context-dependent. O-GlcNAcylation is essential for epigenetic regulation of gene expression through its action on Polycomb and Trithorax and COMPASS complexes. However, the important role of O-GlcNAc in adult life and health span has been largely unexplored, mainly due the lack of available model systems. Cataloging the O-GlcNAc proteome has proven useful in understanding the biology of this modification in vivo. In this study, we leveraged a recently developed oga knockout fly mutant to identify the O-GlcNAcylated proteins in adult Drosophilamelanogaster. The adult O-GlcNAc proteome revealed many proteins related to cell and organismal growth, development, differentiation, and epigenetics. We identified many O-GlcNAcylated proteins that play a role in increased growth and decreased longevity, including HCF, SIN3A, LOLA, KISMET, ATX2, SHOT, and FOXO. Interestingly, oga mutant flies are larger and have a shorter life span compared to wild type flies, suggesting increased O-GlcNAc results in increased growth. Our results suggest that O-GlcNAc alters the function of many proteins related to transcription, epigenetic modification and signaling pathways that regulate growth rate and longevity. Therefore, our findings highlight the importance of O-GlcNAc in growth and life span in adult Drosophila.
Post-Translational Modification Networks of Contractile and Cellular Stress Response Proteins in Bladder Ischemia
Authors: Yang Jing-Hua , Choi Han-Pil , Yang Annie , Azad Roya , Chen Fengmei , Liu Zhangsuo , Azadzoi Kazem M.
Published: April 2021

Molecular mechanisms underlying bladder dysfunction in ischemia, particularly at the protein and protein modification levels and downstream pathways, remain largely unknown. Here we describe a comparison of protein sequence variations in the ischemic and normal bladder tissues by measuring the mass differences of the coding amino acids and actual residues crossing the proteome. A large number of nonzero delta masses (11,056) were detected, spanning over 1295 protein residues. Clustering analysis identified 12 delta mass clusters that were significantly dysregulated, involving 30 upregulated (R2 > 0.5, ratio > 2, p < 0.05) and 33 downregulated (R2 > 0.5, ratio < −2, p < 0.05) proteins in bladder ischemia. These protein residues had different mass weights from those of the standard coding amino acids, suggesting the formation of non-coded amino acid (ncAA) residues in bladder ischemia. Pathway, gene ontology, and protein–protein interaction network analyses of these ischemia-associated delta-mass containing proteins indicated that ischemia provoked several amino acid variations, potentially post-translational modifications, in the contractile proteins and stress response molecules in the bladder. Accumulation of ncAAs may be a novel biomarker of smooth muscle dysfunction, with diagnostic potential for bladder dysfunction. Our data suggest that systematic assessment of global protein modifications may be crucial to the characterization of ischemic conditions in general and the pathomechanism of bladder dysfunction in ischemia.
DNMT3B Is an Oxygen-Sensitive De Novo Methylase in Human Mesenchymal Stem Cells
Authors: Dogan Fatma , Aljumaily Rakad M Kh , Kitchen Mark , Forsyth Nicholas R.
Published: April 2021

The application of physiological oxygen (physoxia) concentrations is becoming increasingly commonplace within a mammalian stem cell culture. Human mesenchymal stem cells (hMSCs) attract widespread interest for clinical application due to their unique immunomodulatory, multi-lineage potential, and regenerative capacities. Descriptions of the impact of physoxia on global DNA methylation patterns in hMSCs and the activity of enzymatic machinery responsible for its regulation remain limited. Human bone marrow-derived mesenchymal stem cells (BM-hMSCs, passage 1) isolated in reduced oxygen conditions displayed an upregulation of SOX2 in reduced oxygen conditions vs. air oxygen (21% O2, AO), while no change was noted for either OCT-4 or NANOG. DNA methylation marks 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) showed decreases in 2% O2 environment (workstation) (2% WKS). DNMT3B (DNA methyltransferase 3B) and TET1 (Ten-eleven translocation enzyme 1) displayed reduced transcription in physoxia. Consistent with transcriptional downregulation, we noted increased promoter methylation levels of DNMT3B in 2% WKS accompanied by reduced DNMT3B and TET1 protein expression. Finally, a decrease in HIF1A (Hypoxia-inducible factor 1A) gene expression in 2% WKS environment correlated with protein levels, while HIF2A was significantly higher in physoxia correlated with protein expression levels vs. AO. Together, these data have demonstrated, for the first time, that global 5mC, 5hmC, and DNMT3B are oxygen-sensitive in hMSCs. Further insights into the appropriate epigenetic regulation within hMSCs may enable increased safety and efficacy development within the therapeutic ambitions.
The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions
Authors: Robert Jérôme , Osto Elena , von Eckardstein Arnold
Published: April 2021

The vascular endothelium serves as a barrier between the intravascular and extravascular compartments. High-density lipoproteins (HDL) have two kinds of interactions with this barrier. First, bloodborne HDL must pass the endothelium to access extravascular tissues, for example the arterial wall or the brain, to mediate cholesterol efflux from macrophages and other cells or exert other functions. To complete reverse cholesterol transport, HDL must even pass the endothelium a second time to re-enter circulation via the lymphatics. Transendothelial HDL transport is a regulated process involving scavenger receptor SR-BI, endothelial lipase, and ATP binding cassette transporters A1 and G1. Second, HDL helps to maintain the integrity of the endothelial barrier by (i) promoting junction closure as well as (ii) repair by stimulating the proliferation and migration of endothelial cells and their progenitor cells, and by preventing (iii) loss of glycocalix, (iv) apoptosis, as well as (v) transmigration of inflammatory cells. Additional vasoprotective functions of HDL include (vi) the induction of nitric oxide (NO) production and (vii) the inhibition of reactive oxygen species (ROS) production. These vasoprotective functions are exerted by the interactions of HDL particles with SR-BI as well as specific agonists carried by HDL, notably sphingosine-1-phophate (S1P), with their specific cellular counterparts, e.g., S1P receptors. Various diseases modify the protein and lipid composition and thereby the endothelial functionality of HDL. Thorough understanding of the structure–function relationships underlying the multiple interactions of HDL with endothelial cells is expected to elucidate new targets and strategies for the treatment or prevention of various diseases.
Optical Constant and Conformality Analysis of SiO2 Thin Films Deposited on Linear Array Microstructure Substrate by PECVD
Authors: Pan Yongqiang , Liu Huan , Wang Zhuoman , Jia Jinmei , Zhao Jijie
Published: April 2021

SiO2 thin films are deposited by radio frequency (RF) plasma-enhanced chemical vapor deposition (PECVD) technique using SiH4 and N2O as precursor gases. The stoichiometry of SiO2 thin films is determined by the X-ray photoelectron spectroscopy (XPS), and the optical constant n and k are obtained by using variable angle spectroscopic ellipsometer (VASE) in the spectral range 380–1600 nm. The refractive index and extinction coefficient of the deposited SiO2 thin films at 500 nm are 1.464 and 0.0069, respectively. The deposition rate of SiO2 thin films is controlled by changing the reaction pressure. The effects of deposition rate, film thickness, and microstructure size on the conformality of SiO2 thin films are studied. The conformality of SiO2 thin films increases from 0.68 to 0.91, with the increase of deposition rate of the SiO2 thin film from 20.84 to 41.92 nm/min. The conformality of SiO2 thin films decreases with the increase of film thickness, and the higher the step height, the smaller the conformality of SiO2 thin films.
Effect of Chitosan/Nano-TiO2 Composite Coating on the Postharvest Quality of Blueberry Fruit
Authors: Xing Yage , Yang Shuang , Xu Qinglian , Xu Lin , Zhu Dan , Li Xuanlin , Shui Yuru , Liu Xiaocui , Bi Xiufang
Published: April 2021

Blueberries are a rich source of health-promoting compounds such as vitamins and anthocyanins and show a high antioxidant capacity. Thus, considerable commercial and scientific interest exists in prolonging its postharvest life to meet the year-round demand for this fruit. In this investigation, the effect of a chitosan-based edible coating, as well as a chitosan-based edible coating containing nanosized titanium dioxide particles (CTS-TiO2), on the postharvest quality of blueberry fruit quality was evaluated during storage at 0 °C. The blueberries were treated with a chitosan coating (CTS) and a CTS-TiO2 composite, respectively. The most suitable chitosan and nano-TiO2 fraction concentrations to be incorporated in the coating formulation were prepared based on the wettability of the corresponding coating solutions. Changes in firmness, total soluble solids (TSS), titratable acidity (TA), ascorbic acid (VC), malondialdehyde (MDA), polyphenol oxidase (PPO), and peroxidase (POD) activities, anthocyanins, flavonoids, total phenolic content, and microbiological analysis were measured and compared. This combined treatment prevented product corruption. Compared with CTS, the CTS-TiO2 composite coating application effectively slowed down the decrease in firmness, TSS, VC, and TA in the blueberries. Additionally, changes in the total polyphenol, anthocyanin, and flavonoid contents and the antioxidant capacity of CTS-TiO2 composite coating blueberry fruits were delayed. Therefore, these results indicated that the chitosan/nano-TiO2 composite coating could maintain the nutrient composition of blueberries while playing a significant role in preserving the quality of fruit at 0 °C.
Colocation for SLAM-Tracked VR Headsets with Hand Tracking
Authors: Reimer Dennis , Podkosova Iana , Scherzer Daniel , Kaufmann Hannes
Published: April 2021

In colocated multi-user Virtual Reality applications, relative user positions in the virtual environment need to match their relative positions in the physical tracking space. A mismatch between virtual and real relative user positions might lead to harmful events such as physical user collisions. This paper examines three calibration methods that enable colocated Virtual Reality scenarios for SLAM-tracked head-mounted displays without the need for an external tracking system. Two of these methods—fixed-point calibration and marked-based calibration—have been described in previous research; the third method that uses hand tracking capabilities of head-mounted displays is novel. We evaluated the accuracy of these three methods in an experimental procedure with two colocated Oculus Quest devices. The results of the evaluation show that our novel hand tracking-based calibration method provides better accuracy and consistency while at the same time being easy to execute. The paper further discusses the potential of all evaluated calibration methods.
Fast Predictive Model of Crystallographic Texture Evolution in Metal Additive Manufacturing
Authors: Lei Yucong , Ghayoor Milad , Pasebani Somayeh , Tabei Ali
Published: April 2021

This communication introduces a fast material- and process-agnostic modeling approach, not reported in the open literature, that is calibrated for predicting the evolution of texture in metal additive manufacturing of stainless steel 304L as a function of a process parameter, namely the laser scanning speed. The outputs of the model are compared against independent validation experiments for the same material system and show excellent consistency. The model also predicts a trend in the change of texture intensity as a function of the process parameter. The major novelty and strength of this work is the model’s speed and extremely light computational load. The model’s calibrations and predictions were carried out in 9.2 s on a typical desktop computer.
Thermophysical Properties of Cement Mortar Containing Waste Glass Powder
Authors: Nasry Oumaima , Samaouali Abderrahim , Belarouf Sara , Moufakkir Abdelkrim , Sghiouri El Idrissi Hanane , Soulami Houda , El Rhaffari Younes , Hraita Mohamed , Fertahi Saïf Ed Dîn , Hafidi-Alaoui Adil
Published: April 2021

This study aims to provide a thermophysical characterization of a new economical and green mortar. This material is characterized by partially replacing the cement with recycled soda lime glass. The cement was partially substituted (10, 20, 30, 40, 50 and 60% in weight) by glass powder with a water/cement ratio of 0.4. The glass powder and four of the seven samples were analyzed using a scanning electron microscope (SEM). The thermophysical properties, such as thermal conductivity and volumetric specific heat, were experimentally measured in both dry and wet (water saturated) states. These properties were determined as a function of the glass powder percentage by using a CT-Meter at different temperatures (20 °C, 30 °C, 40 °C and 50 °C) in a temperature-controlled box. The results show that the thermophysical parameters decreased linearly when 60% glass powder was added to cement mortar: 37% for thermal conductivity, 18% for volumetric specific heat and 22% for thermal diffusivity. The density of the mortar also decreased by about 11% in dry state and 5% in wet state. The use of waste glass powder as a cement replacement affects the thermophysical properties of cement mortar due to its porosity as compared with the control mortar. The results indicate that thermal conductivity and volumetric specific heat increases with temperature increase and/or the substitution rate decrease. Therefore, the addition of waste glass powder can significantly affect the thermophysical properties of ordinary cement mortar.
Penguins Strike Back: A Report on the Unusual Case of Adélie Penguin (Pygoscelis adeliae) Attacks on South Polar Skua Nests Distant from the Breeding Colony
Authors: Kim Youmin , Kim Jong-U , Chung Hosung , Oh Yeon-Soo , Oh Young-Geun , Kim Jeong-Hoon
Published: April 2021

Colonial seabirds use various methods to defend their nests from predators [...]
State-of-the-Art Methods and Emerging Fluid Biomarkers in the Diagnostics of Dementia—A Short Review and Diagnostic Algorithm
Authors: Solje Eino , Benussi Alberto , Buratti Emanuele , Remes Anne M. , Haapasalo Annakaisa , Borroni Barbara
Published: April 2021

The most common neurodegenerative dementias include Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). The correct etiology-based diagnosis is pivotal for clinical management of these diseases as well as for the suitable timing and choosing the accurate disease-modifying therapies when these become available. Enzyme-linked immunosorbent assay (ELISA)-based methods, detecting altered levels of cerebrospinal fluid (CSF) Tau, phosphorylated Tau, and Aβ-42 in AD, allowed the wide use of this set of biomarkers in clinical practice. These analyses demonstrate a high diagnostic accuracy in AD but suffer from a relatively restricted usefulness due to invasiveness and lack of prognostic value. In recent years, the development of novel advanced techniques has offered new state-of-the-art opportunities in biomarker discovery. These include single molecule array technology (SIMOA), a tool for non-invasive analysis of ultra-low levels of central nervous system-derived molecules from biofluids, such as CSF or blood, and real-time quaking (RT-QuIC), developed to analyze misfolded proteins. In the present review, we describe the history of methods used in the fluid biomarker analyses of dementia, discuss specific emerging biomarkers with translational potential for clinical use, and suggest an algorithm for the use of new non-invasive blood biomarkers in clinical practice.
Prediction of Hypertension Outcomes Based on Gain Sequence Forward Tabu Search Feature Selection and XGBoost
Authors: Chang Wenbing , Ji Xinpeng , Xiao Yiyong , Zhang Yue , Chen Bang , Liu Houxiang , Zhou Shenghan
Published: April 2021

For patients with hypertension, serious complications, such as myocardial infarction, a common cause of heart failure, occurs in the late stage of hypertension. Hypertension outcomes can lead to complications, including death. Hypertension outcomes threaten patients’ lives and need to be predicted. In our research, we reviewed the hypertension medical data from a tertiary-grade A class hospital in Beijing, and established a hypertension outcome prediction model with the machine learning theory. We first proposed a gain sequence forward tabu search feature selection (GSFTS-FS) method, which can search the optimal combination of medical variables that affect hypertension outcomes. Based on this, the XGBoost algorithm established a prediction model because of its good stability. We verified the proposed method by comparing other commonly used models in similar works. The proposed GSFTS-FS improved the performance by about 10%. The proposed prediction method has the best performance and its AUC value, accuracy, F1 value, and recall of 10-fold cross-validation were 0.96. 0.95, 0.88, and 0.82, respectively. It also performed well on test datasets with 0.92, 0.94, 0.87, and 0.80 for AUC, accuracy, F1, and recall, respectively. Therefore, the XGBoost with GSFTS-FS can accurately and effectively predict the occurrence of outcomes for patients with hypertension, and can provide guidance for doctors in clinical diagnoses and medical decision-making.
Liver Fibrosis and Steatosis in Alström Syndrome: A Genetic Model for Metabolic Syndrome
Authors: Bettini Silvia , Bombonato Giancarlo , Dassie Francesca , Favaretto Francesca , Piffer Luca , Bizzotto Paola , Busetto Luca , Chemello Liliana , Senzolo Marco , Merkel Carlo , Angeli Paolo , Vettor Roberto , Milan Gabriella , Maffei Pietro
Published: April 2021

Alström syndrome (ALMS) is an ultra-rare monogenic disease characterized by insulin resistance, multi-organ fibrosis, obesity, type 2 diabetes mellitus (T2DM), and hypertriglyceridemia with high and early incidence of non-alcoholic fatty liver disease (NAFLD). We evaluated liver fibrosis quantifying liver stiffness (LS) by shear wave elastography (SWE) and steatosis using ultrasound sonographic (US) liver/kidney ratios (L/K) in 18 patients with ALMS and 25 controls, and analyzed the contribution of metabolic and genetic alterations in NAFLD progression. We also genetically characterized patients. LS and L/K values were significantly higher in patients compared with in controls (p < 0.001 versus p = 0.013). In patients, LS correlated with the Fibrosis-4 Index and age, while L/K was associated with triglyceride levels. LS showed an increasing trend in patients with metabolic comorbidities and displayed a significant correlation with waist circumference, the homeostasis model assessment, and glycated hemoglobin A1c. SWE and US represent promising tools to accurately evaluate early liver fibrosis and steatosis in adults and children with ALMS during follow-up. We described a new pathogenic variant of exon 8 in ALMS1. Patients with ALMS displayed enhanced steatosis, an early increased age-dependent LS that is associated with obesity and T2DM but also linked to genetic alterations, suggesting that ALMS1 could be involved in liver fibrogenesis.
Progressive Traffic-Oriented Resource Management for Reducing Network Congestion in Edge Computing
Authors: Kim Won-Suk
Published: April 2021

Edge computing can deliver network services with low latency and real-time processing by providing cloud services at the network edge. Edge computing has a number of advantages such as low latency, locality, and network traffic distribution, but the associated resource management has become a significant challenge because of its inherent hierarchical, distributed, and heterogeneous nature. Various cloud-based network services such as crowd sensing, hierarchical deep learning systems, and cloud gaming each have their own traffic patterns and computing requirements. To provide a satisfactory user experience for these services, resource management that comprehensively considers service diversity, client usage patterns, and network performance indicators is required. In this study, an algorithm that simultaneously considers computing resources and network traffic load when deploying servers that provide edge services is proposed. The proposed algorithm generates candidate deployments based on factors that affect traffic load, such as the number of servers, server location, and client mapping according to service characteristics and usage. A final deployment plan is then established using a partial vector bin packing scheme that considers both the generated traffic and computing resources in the network. The proposed algorithm is evaluated using several simulations that consider actual network service and device characteristics.