bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of the Duration and Timing of Data Collection on Accelerometer-Measured Physical Activity, Sedentary Time and Associated Insulin Resistance
Authors: Sjöros Tanja , Vähä-Ypyä Henri , Laine Saara , Garthwaite Taru , Löyttyniemi Eliisa , Sievänen Harri , Kalliokoski Kari K. , Knuuti Juhani , Vasankari Tommi , Heinonen Ilkka H. A.
Published: May 2021

Accelerometry is a commonly used method to determine physical activity in clinical studies, but the duration and timing of measurement have seldom been addressed. We aimed to evaluate possible changes in the measured outcomes and associations with insulin resistance during four weeks of accelerometry data collection. This study included 143 participants (median age of 59 (IQR9) years; mean BMI of 30.7 (SD4) kg/m2; 41 men). Sedentary and standing time, breaks in sedentary time, and different intensities of physical activity were measured with hip-worn accelerometers. Differences in the accelerometer-based results between weeks 1, 2, 3 and 4 were analyzed by mixed models, differences during winter and summer by two-way ANOVA, and the associations between insulin resistance and cumulative means of accelerometer results during weeks 1 to 4 by linear models. Mean accelerometry duration was 24 (SD3) days. Sedentary time decreased after three weeks of measurement. More physical activity was measured during summer compared to winter. The associations between insulin resistance and sedentary behavior and light physical activity were non-significant after the first week of measurement, but the associations turned significant in two to three weeks. If the purpose of data collection is to reveal associations between accelerometer-measured outcomes and tenuous health outcomes, such as insulin sensitivity, data collection for at least three weeks may be needed.
Structure-Level 3D Building Model Encoding Method for Progressive Transmission
Authors: Dong Jiwei , Tan Junzhong , Zhao Qiang , He Lixia , Li Sirui , She Jiangfeng
Published: May 2021

Progressive encoding and transmission, i.e., a crucial technical foundation of 3D Web Geographic Information Systems (WebGIS), addresses the contradiction between massive 3D building data and limited network transmission capacity. Most progressive encoding algorithms, taking vertices, edges or triangles as encoding units, may break the inherent geometric and topological characteristics of 3D building models. Thus, a novel 3D building model encoding method that can maintain the internal characteristics is proposed, which can be used for high-efficiency progressive transmission. With this method, each building is decomposed into three types of fundamental structures: main structure, independent structure and attached structure. A structural topology graph (STG) was constructed based on the connections among structures. Guided by STG, one or more structures were wrapped as the smallest incremental transmission unit, denoted as transmission node. When requested, the real-time position of viewpoint, orientation and visual importance of nodes are used to pick up expected nodes for responding. The results confirm that the proposed method can better maintain the geometric and topological characteristics while encoding 3D building models. While serving for transmission, the proposed method not only effectively reduces the transmission load, but also provides users with a better consistency experience on the building appearance at different simplification levels.
Identifying Users’ Requirements for Emergency Mapping Team Operations in Small Island Developing States: Caribbean Perspective
Authors: Rosario Michel Gregorio , Manzano Aybar Fernando , Neris Guzmán Leris , Villalta Calderón Christian , Durán Teodoro Jiménez , Crompvoets Joep
Published: May 2021

Small Island Developing States (SIDS) increasingly face natural hazards that overwhelm their capacity to generate and share spatial-information to reduce human–economic losses. Under such circumstances, the emergency mapping team (EMT) enables a common operational picture of the impacted communities. This paper aims to identify user requirements for EMT operations in the Caribbean and, based on those findings, improve the level of preparedness to deliver information-services that contribute to disaster risk management in the region. The results are built upon a case-study and a survey targeted for technical personnel responsible for emergency mapping in three Caribbean states: the Dominican Republic, Saint Lucia and Sint Maarten. Our findings revealed five user requirements for EMT operations: institutional arrangements, implementation of a Cloud-based spatial data infrastructure, linking community stakeholders, partnerships and capacity building. This study provides the foundation for future EMT developments in the Caribbean region and in others SIDS with similar settings in the world.
Cord Blood T Cells Expressing High and Low PKCζ Levels Develop into Cells with a Propensity to Display Th1 and Th9 Cytokine Profiles, Respectively
Authors: Perveen Khalida , Quach Alex , McPhee Andrew , Prescott Susan L. , Barry Simon C. , Hii Charles S. , Ferrante Antonio
Published: May 2021

Low Protein Kinase C zeta (PKCζ) levels in cord blood T cells (CBTC) have been shown to correlate with the development of allergic sensitization in childhood. However, little is known about the mechanisms responsible. We have examined the relationship between the expression of different levels of PKCζ in CBTC and their development into mature T cell cytokine producers that relate to allergy or anti-allergy promoting cells. Maturation of naïve CBTC was initiated with anti-CD3/-CD28 antibodies and recombinant human interleukin-2 (rhIL-2). To stimulate lymphocyte proliferation and cytokine production the cells were treated with Phytohaemagglutinin (PHA) and Phorbol myristate acetate (PMA). Irrespective of the PKCζ levels expressed, immature CBTC showed no difference in lymphocyte proliferation and the production of T helper 2 (Th2) cytokine interleukin-4 (IL-4) and Th1 cytokine, interferon-gamma (IFN-γ), and influenced neither their maturation from CD45RA+ to CD45RO+ cells nor cell viability/apoptosis. However, upon maturation the low PKCζ expressing cells produced low levels of the Th1 cytokines, IFN-γ, IL-2 and tumour necrosis factor-alpha (TNF), no changes to levels of the Th2 cytokines, IL-4, IL-5 and IL-13, and an increase in the Th9 cytokine, IL-9. Other cytokines, lymphotoxin-α (LT-α), IL-10, IL-17, IL-21, IL-22 and Transforming growth factor-beta (TGF-β) were not significantly different. The findings support the view that low CBTC PKCζ levels relate to the increased risk of developing allergic diseases.
Extracellular Vesicles in Synovial Fluid from Rheumatoid Arthritis Patients Contain miRNAs with Capacity to Modulate Inflammation
Authors: Foers Andrew D. , Garnham Alexandra L. , Chatfield Simon , Smyth Gordon K. , Cheng Lesley , Hill Andrew F. , Wicks Ian P. , Pang Ken C.
Published: May 2021

In rheumatoid arthritis (RA), extracellular vesicles (EVs) are associated with both the propagation and attenuation of joint inflammation and destruction. However, the specific EV content responsible for these processes is largely unknown. Investigations into identifying EV content are confounded by the challenges in obtaining high-quality EV preparations from synovial fluid. Implementing a size exclusion chromatography-based method of EV isolation, coupled with small RNA sequencing, we accurately characterised EV miRNAs in synovial fluid obtained from RA patients and investigated the differences between joints with high- and low-grade inflammation. Synovial fluid was obtained from the joints of 12 RA patients and, based on leukocyte counts, classified as either high (n = 7)- or low (n = 5)-grade inflammation. Using size exclusion chromatography, EVs were purified and small RNA was extracted and sequenced on a NextSeq 500. Sequencing reads were aligned to miRBase v21, and differences in miRNA profiles between RA patients with high- and low-grade joint inflammation were analysed. In total, 1972 distinct miRNAs were identified from RA synovial fluid EVs. miRNAs with less than five reads in fewer than five patients were filtered out, leaving 318 miRNAs for analysis. Analysis of the most abundant miRNAs suggested that they negatively regulate multiple genes relevant to inflammation, including signal transducer and activator of transcription 3 (STAT3), which lies downstream of IL-6 and has a pro-inflammatory role in RA. Synovial fluid from joints with high-grade inflammation contained 3.5-fold more EV miRNA per mL of synovial fluid (p = 0.0017). Seventy-eight EV miRNAs were differentially expressed between RA joints with high- and low-grade inflammation, and pathway analysis revealed that their target genes were commonly involved a variety of processes, including cellular apoptosis, proliferation and migration. Of the 49 miRNAs that were elevated in joints with high-grade inflammation, pathway analysis revealed that genes involved in cytokine-mediated signalling pathways were significantly enriched targets. In contrast, genes associated with reactive oxygen species signalling were significantly enriched as targets of the 29 miRNAs elevated in joints with low-grade inflammation. Our study identified an abundance of EV miRNAs from the synovial fluid of RA patients with the potential to modulate inflammation. In doing so, we defined potential mechanisms by which synovial fluid EVs may contribute to RA pathophysiology.
Cholinergic Modulation of Neuroinflammation: Focus on α7 Nicotinic Receptor
Authors: Piovesana Roberta , Salazar Intriago Michael Sebastian , Dini Luciana , Tata Ada Maria
Published: May 2021

All nervous system pathologies (e.g., neurodegenerative/demyelinating diseases and brain tumours) develop neuroinflammation, a beneficial process during pathological events, aimed at removing damaged cells, toxic agents, and/or pathogens. Unfortunately, excessive inflammation frequently occurs during nervous system disorders, becoming a detrimental event capable of enhancing neurons and myelinating glial cell impairment, rather than improving their survival and activity. Consequently, targeting the neuroinflammation could be relevant for reducing brain injury and rescuing neuronal and glial cell functions. Several studies have highlighted the role of acetylcholine and its receptors in the regulation of central and peripheral inflammation. In particular, α7 nicotinic receptor has been described as one of the main regulators of the “brain cholinergic anti-inflammatory pathway”. Its expression in astrocytes and microglial cells and the ability to modulate anti-inflammatory cytokines make this receptor a new interesting therapeutic target for neuroinflammation regulation. In this review, we summarize the distribution and physiological functions of the α7 nicotinic receptor in glial cells (astrocytes and microglia) and its role in the modulation of neuroinflammation. Moreover, we explore how its altered expression and function contribute to the development of different neurological pathologies and exacerbate neuroinflammatory processes.
Low-Cost Biobased Coatings for AM60 Magnesium Alloys for Food Contact and Harsh Environment Applications
Authors: Mangolini Beatrice , Lopresti Mattia , Conterosito Eleonora , Rombolà Giuseppe , Palin Luca , Gianotti Valentina , Milanesio Marco
Published: May 2021

Low-cost, environmentally friendly and easily applicable coating for Mg alloys, able to resist in real world conditions, are studied. Coatings already used for other metals (aluminum, steel) and never tested on Mg alloy for its different surface and reactivity were deposited on AM60 magnesium alloys to facilitate their technological applications, also in presence of chemically aggressive conditions. A biobased PA11 powder coating was compared to synthetic silicon-based and polyester coatings, producing lab scale samples, probed by drop deposition tests and dipping in increasingly aggressive, salty, basic and acid solutions, at RT and at higher temperatures. Coatings were analyzed by SEM/EDX to assess their morphology and compositions, by optical and IR-ATR microscopy analyses, before and after the drop tests. Migration analyses from the samples were performed by immersion tests using food simulants followed by ICP-OES analysis of the recovered simulant to explore applications also in the food contact field. A 30 μm thick white lacquer and a 120 μm PA11 coating resulted the best solutions. The thinner siliconic and lacquer coatings, appearing brittle and thin in the SEM analysis, failed some drop and/or dipping test, with damages especially at the edges. The larger thickness is thus the unique solution for edgy or pointy samples. Finally, coffee cups in AM60 alloy were produced, as real word prototypes, with the best performing coatings and tested for both migration by dipping, simulating also real world aging (2 h in acetic acid at 70° and 24 h in hot coffee at 60 °C): PA11 resulted stable in all the tests and no migration of toxic metals was observed, resulting a promising candidate for many real world application in chemically aggressive environments and also food and beverage related applications.
Bis-Pyrene Photo-Switch Open- and Closed-Form Differently Bind to ds-DNA, ds-RNA and Serum Albumin and Reveal Light-Induced Bioactivity
Authors: Orehovec Iva , Matković Marija , Pehar Isabela , Majhen Dragomira , Piantanida Ivo
Published: May 2021

Newly designed and synthesized diarylethene (DAE) derivatives with aliphatic amine sidearms and one with two pyrenes, revealed excellent photo-switching property of central DAE core in MeOH and water. The only exception was bis-pyrene analogue, its DAE core very readily photochemically closed, but reversible opening completely hampered by aromatic stacking interaction of pyrene(s) with cyclic DAE. In this process, pyrene fluorescence showed to be a reliable monitoring method, an open form characterized by strong emission at 480 nm (typical for pyrene-aggregate), while closed form emitted weakly at 400 nm (typical for pyrene-DAE quenching). Only open DAE-bis-pyrene form interacted measurably with ds-DNA/RNA by flexible insertion in polynucleotide grooves, while self-stacked closed form did not bind to DNA/RNA. For the same steric reasons, flexible open DAE-bis-pyrene form was bound to at least three different binding sites at bovine serum albumin (BSA), while rigid, self-stacked closed form interacted dominantly with only one BSA site. Preliminary screening of antiproliferative activity against human lung carcinoma cell line A549 revealed that all DAE-derivatives are non-toxic. However, bis-pyrene analogue efficiently entered cells and located in the cytoplasm, whereby irradiation by light (315–400 nm) resulted in a strong, photo-induced cytotoxic effect, typical for pyrene-related singlet oxygen species production.
The Cellular Composition of Bovine Coccygeal Intervertebral Discs: A Comprehensive Single-Cell RNAseq Analysis
Authors: Calió Martina , Gantenbein Benjamin , Egli Marcel , Poveda Lucy , Ille Fabian
Published: May 2021

Intervertebral disc (IVD) degeneration and its medical consequences is still one of the leading causes of morbidity worldwide. To support potential regenerative treatments for degenerated IVDs, we sought to deconvolute the cell composition of the nucleus pulposus (NP) and the annulus fibrosus (AF) of bovine intervertebral discs. Bovine calf tails have been extensively used in intervertebral disc research as a readily available source of NP and AF material from healthy and young IVDs. We used single-cell RNA sequencing (scRNAseq) coupled to bulk RNA sequencing (RNAseq) to unravel the cell populations in these two structures and analyze developmental changes across the rostrocaudal axis. By integrating the scRNAseq data with the bulk RNAseq data to stabilize the clustering results of our study, we identified 27 NP structure/tissue specific genes and 24 AF structure/tissue specific genes. From our scRNAseq results, we could deconvolute the heterogeneous cell populations in both the NP and the AF. In the NP, we detected a notochordal-like cell cluster and a progenitor stem cell cluster. In the AF, we detected a stem cell-like cluster, a cluster with a predominantly fibroblast-like phenotype and a potential endothelial progenitor cluster. Taken together, our results illustrate the cell phenotypic complexity of the AF and NP in the young bovine IVDs.
Molecular Aspects of Plant Salinity Stress and Tolerance
Authors: Chen Jen-Tsung , Aroca Ricardo , Romano Daniela
Published: May 2021

Salinity is one of the major abiotic stresses that inhibit the growth, development, and productivity of crops, particularly in hot and dry areas of the world [...]
Epigenetic-Based Therapy—A Prospective Chance for Medulloblastoma Patients’ Recovery
Authors: Strejczek Agata , Woszczyk Dawid , Urbaniak Helena , Różańska Martyna , Robak Michał , Matuszewska Zofia , Barciszewska Anna-Maria
Published: May 2021

Medulloblastoma (MB) is one of the most frequent and malignant brain tumors in children. The prognosis depends on the advancement of the disease and the patient’s age. Current therapies, which include surgery, chemotherapy, and irradiation, despite being quite effective, cause significant side effects that influence the central nervous system’s function and cause neurocognitive deficits. Therefore, they substantially lower the quality of life, which is especially severe in a developing organism. Thus, there is a need for new therapies that are less toxic and even more effective. Recently, knowledge about the epigenetic mechanisms that are responsible for medulloblastoma development has increased. Epigenetics is a phenomenon that influences gene expression but can be easily modified by external factors. The best known epigenetic mechanisms are histone modifications, DNA methylation, or noncoding RNAs actions. Epigenetic mechanisms comprehensively explain the complex phenomena of carcinogenesis. At the same time, they seem to be a potential key to treating medulloblastoma with fewer complications than past therapies. This review presents the currently known epigenetic mechanisms that are involved in medulloblastoma pathogenesis and the potential therapies that use epigenetic traits to cure medulloblastoma while maintaining a good quality of life and ensuring a higher median overall survival rate.
The Role of Monocytes and Macrophages in Homeostasis and Disease and Novel Avenues for Putative Treatments
Authors: Kloc Malgorzata , Kubiak Jacek Z.
Published: May 2021

Macrophages were discovered in the 19th century by Ukrainian biologist Élie Metchnikoff who worked in Ukraine, Russia, and France [...]
Spontaneous Cell Detachment and Reattachment in Cancer Cell Lines: An In Vitro Model of Metastasis and Malignancy
Authors: Vargas-Accarino Elena , Herrera-Montávez Carlos , Ramón y Cajal Santiago , Aasen Trond
Published: May 2021

There is an unmet need for simplified in vitro models of malignancy and metastasis that facilitate fast, affordable and scalable gene and compound analysis. “Adherent” cancer cell lines frequently release “free-floating” cells into suspension that are viable and can reattach. This, in a simplistic way, mimics the metastatic process. We compared the gene expression profiles of naturally co-existing populations of floating and adherent cells in SW620 (colon), C33a (cervix) and HeLa (cervix) cancer cells. We found that 1227, 1367 and 1333 genes were at least 2-fold differentially expressed in the respective cell lines, of which 122 were shared among the three cell lines. As proof of principle, we focused on the anti-metastatic gene NM23-H1, which was downregulated both at the RNA and protein level in the floating cell populations of all three cell lines. Knockdown of NM23-H1 significantly increased the number of floating (and viable) cells, whereas overexpression of NM23-H1 significantly reduced the proportion of floating cells. Other potential regulators of these cellular states were identified through pathway analysis, including hypoxia, mTOR (mechanistic target of rapamycin), cell adhesion and cell polarity signal transduction pathways. Hypoxia, a condition linked to malignancy and metastasis, reduced NM23-H1 expression and significantly increased the number of free-floating cells. Inhibition of mTOR or Rho-associated protein kinase (ROCK) significantly increased cell death specifically in the floating and not the adherent cell population. In conclusion, our study suggests that dynamic subpopulations of free-floating and adherent cells is a useful model to screen and identify genes, drugs and pathways that regulate the process of cancer metastasis, such as cell detachment and anoikis.
Functional Analysis of Autophagy-Related Gene ATG12 in Potato Dry Rot Fungus Fusarium oxysporum
Authors: Khalid A. Rehman , Zhang Shumin , Luo Xiumei , Shaheen Hamayun , Majeed Afshan , Maqbool Mehdi , Zahid Noosheen , Rahim Junaid , Ren Maozhi , Qiu Dan
Published: May 2021

Autophagy is an intracellular process in all eukaryotes which is responsible for the degradation of cytoplasmic constituents, recycling of organelles, and recycling of proteins. It is an important cellular process responsible for the effective virulence of several pathogenic plant fungal strains, having critical impacts on important crop plants including potatoes. However, the detailed physiological mechanisms of autophagy involved in the infection biology of soil-borne pathogens in the potato crop needs to be investigated further. In this study, the autophagy-related gene, FoATG12, in potato dry rot fungus Fusarium oxysporum was investigated by means of target gene replacement and overexpression. The deletion mutant ∆FoATG12 showed reduction in conidial formation and exhibited impaired aerial hyphae. The FoATG12 affected the expression of genes involved in pathogenicity and vegetative growth, as well as on morphology features of the colony under stressors. It was found that the disease symptoms were delayed upon being inoculated by the deletion mutant of FoATG12 compared to the wild-type (WT) and overexpression (OE), while the deletion mutant showed the disease symptoms on tomato plants. The results confirmed the significant role of the autophagy-related ATG12 gene in the production of aerial hyphae and the effective virulence of F. oxysporum in the potato crop. The current findings provid an enhanced gene-level understanding of the autophagy-related virulence of F. oxysporum, which could be helpful in pathogen control research and could have vital impacts on the potato crop.
Identification of SYS1 as a Host Factor Required for Shiga Toxin-Mediated Cytotoxicity in Vero Cells
Authors: Sakuma Chisato , Sekizuka Tsuyoshi , Kuroda Makoto , Hanada Kentaro , Yamaji Toshiyuki
Published: May 2021

Shiga toxin (STx) or Vero toxin is a virulence factor produced by enterohemorrhagic Escherichia coli. The toxin binds to the glycosphingolipid globotriaosylceramide (Gb3) for its entry, and causes cell death by inhibiting ribosome function. Previously, we performed a loss-of-function screen in HeLa cells using a human CRISPR knockout (KO) library and identified various host genes required for STx-induced cell death. To determine whether this library targeted to the human genome is applicable to non-human primate cells and to identify previously unrecognized factors crucial for STx-induced cell death, we herein performed a similar screen in the African green monkey kidney-derived Vero C1008 subline. Many genes relevant to metabolic enzymes and membrane trafficking were enriched, although the number of enriched genes was less than that obtained in the screening for HeLa cells. Of note, several genes that had not been enriched in the previous screening were enriched: one of these genes was SYS1, which encodes a multi-spanning membrane protein in the Golgi apparatus. In SYS1 KO Vero cells, expression of Gb3 and sphingomyelin was decreased, while that of glucosylceramide and lactosylceramide was increased. In addition, loss of SYS1 inhibited the biosynthesis of protein glycans, deformed the Golgi apparatus, and perturbed the localization of trans-Golgi network protein (TGN) 46. These results indicate that the human CRISPR KO library is applicable to Vero cell lines, and SYS1 has a widespread effect on glycan biosynthesis via regulation of intra-Golgi and endosome–TGN retrograde transports.
Calcite as a Precursor of Hydroxyapatite in the Early Biomineralization of Differentiating Human Bone-Marrow Mesenchymal Stem Cells
Authors: Sorrentino Andrea , Malucelli Emil , Rossi Francesca , Cappadone Concettina , Farruggia Giovanna , Moscheni Claudia , Perez-Berna Ana J. , Conesa Jose Javier , Colletti Chiara , Roveri Norberto , Pereiro Eva , Iotti Stefano
Published: May 2021

Biomineralization is the process by which living organisms generate organized mineral crystals. In human cells, this phenomenon culminates with the formation of hydroxyapatite, which is a naturally occurring mineral form of calcium apatite. The mechanism that explains the genesis within the cell and the propagation of the mineral in the extracellular matrix still remains largely unexplained, and its characterization is highly controversial, especially in humans. In fact, up to now, biomineralization core knowledge has been provided by investigations on the advanced phases of this process. In this study, we characterize the contents of calcium depositions in human bone mesenchymal stem cells exposed to an osteogenic cocktail for 4 and 10 days using synchrotron-based cryo-soft-X-ray tomography and cryo-XANES microscopy. The reported results suggest crystalline calcite as a precursor of hydroxyapatite depositions within the cells in the biomineralization process. In particular, both calcite and hydroxyapatite were detected within the cell during the early phase of osteogenic differentiation. This striking finding may redefine most of the biomineralization models published so far, taking into account that they have been formulated using murine samples while studies in human cell lines are still scarce.
Activated ERK Signaling Is One of the Major Hub Signals Related to the Acquisition of Radiotherapy-Resistant MDA-MB-231 Breast Cancer Cells
Authors: Paramanantham Anjugam , Jung Eun Joo , Go Se-IL , Jeong Bae Kwon , Jung Jin-Myung , Hong Soon Chan , Kim Gon Sup , Lee Won Sup
Published: May 2021

Breast cancer is one of the major causes of deaths due to cancer, especially in women. The crucial barrier for breast cancer treatment is resistance to radiation therapy, one of the important local regional therapies. We previously established and characterized radio-resistant MDA-MB-231 breast cancer cells (RT-R-MDA-MB-231 cells) that harbor a high expression of cancer stem cells (CSCs) and the EMT phenotype. In this study, we performed antibody array analysis to identify the hub signaling mechanism for the radiation resistance of RT-R-MDA-MB-231 cells by comparing parental MDA-MB-231 (p-MDA-MB-231) and RT-R-MDA-MB-231 cells. Antibody array analysis unveiled that the MAPK1 protein was the most upregulated protein in RT-R-MDA-MB-231 cells compared to in p-MDA-MB-231 cells. The pathway enrichment analysis also revealed the presence of MAPK1 in almost all enriched pathways. Thus, we used an MEK/ERK inhibitor, PD98059, to block the MEK/ERK pathway and to identify the role of MAPK1 in the radio-resistance of RT-R-MDA-MB-231 cells. MEK/ERK inhibition induced cell death in both p-MDA-MB-231 and RT-R-MDA-MB-231 cells, but the death mechanism for each cell was different; p-MDA-MB-231 cells underwent apoptosis, showing cell shrinkage and PARP-1 cleavage, while RT-R-MDA-MB-231 cells underwent necroptosis, showing mitochondrial dissipation, nuclear swelling, and an increase in the expressions of CypA and AIF. In addition, MEK/ERK inhibition reversed the radio-resistance of RT-R-MDA-MB-231 cells and suppressed the increased expression of CSC markers (CD44 and OCT3/4) and the EMT phenotype (β-catenin and N-cadherin/E-cadherin). Taken together, this study suggests that activated ERK signaling is one of the major hub signals related to the radio-resistance of MDA-MB-231 breast cancer cells.
G4 Matters—The Influence of G-Quadruplex Structural Elements on the Antiproliferative Properties of G-Rich Oligonucleotides
Authors: Roxo Carolina , Kotkowiak Weronika , Pasternak Anna
Published: May 2021

G-quadruplexes (G4s) are non-canonical structures formed by guanine-rich sequences of DNA or RNA that have attracted increased attention as anticancer agents. This systematic study aimed to investigate the anticancer potential of five G4-forming, sequence-related DNA molecules in terms of their thermodynamic and structural properties, biostability and cellular uptake. The antiproliferative studies revealed that less thermodynamically stable G4s with three G-tetrads in the core and longer loops are more predisposed to effectively inhibit cancer cell growth. By contrast, highly structured G4s with an extended core containing four G-tetrads and longer loops are characterized by more efficient cellular uptake and improved biostability. Various analyses have indicated that the G4 structural elements are intrinsic to the biological activity of these molecules. Importantly, the structural requirements are different for efficient cancer cell line inhibition and favorable G4 cellular uptake. Thus, the ultimate antiproliferative potential of G4s is a net result of the specific balance among the structural features that are favorable for efficient uptake and those that increase the inhibitory activity of the studied molecules. Understanding the G4 structural features and their role in the biological activity of G-rich molecules might facilitate the development of novel, more potent G4-based therapeutics with unprecedented anticancer properties.
Simple Design Methodology for R.C. Slabs by Hybrid Reinforcing of Steel Rebars and Uniaxial or Triaxial Geogrids
Authors: Mohamed Ramy Nasr Abdelmonem , El Sebai Ahmed Mohamed , Gabr Ahmed Shaban Abdel-Hay
Published: May 2021

This paper’s objective is to provide simple design relations for the reinforced concrete slabs by a hybrid reinforcing of uniaxial or triaxial geogrids in addition to steel rebars. We hope this can provide guidance for further researchers to estimate the flexural bending capacity of the concrete slabs, the necessary grade of uniaxial or triaxial geogrids, and the necessary count of uniaxial or triaxial geogrids’ layers by conducting first-principles analytical, quantitative analyses for a previously published concrete slabs’ experimental data of reinforced concrete slabs by hybrid reinforcing of steel rebars and uniaxial or triaxial geogrids. Throughout this paper, simple design relations were added to estimate the concrete slabs’ experimental moment at the post-peak load based on the assumption that the uniaxial or triaxial geogrids’ tensile force (as concrete slab’s reinforcement) is equal to its peak tensile strength (obtained by the experimental axial tensile test). This resulted in a variance that frequently has a range of ±10% when compared with the actual experimental data. For more accuracy, simple design relations were added to estimate the uniaxial or triaxial geogrids’ characteristic tensile force at the post-peak load, which resulted in an estimated concrete slab’s experimental moment at the post-peak load with a variance that frequently has a range of ±5% when compared with the actual experimental data.
Platelet Transfusion—Insights from Current Practice to Future Development
Authors: Capraru Annina , Jalowiec Katarzyna Aleksandra , Medri Cesare , Daskalakis Michael , Zeerleder Sacha Sergio , Mansouri Taleghani Behrouz
Published: May 2021

Since the late sixties, therapeutic or prophylactic platelet transfusion has been used to relieve hemorrhagic complications of patients with, e.g., thrombocytopenia, platelet dysfunction, and injuries, and is an essential part of the supportive care in high dose chemotherapy. Current and upcoming advances will significantly affect present standards. We focus on specific issues, including the comparison of buffy-coat (BPC) and apheresis platelet concentrates (APC); plasma additive solutions (PAS); further measures for improvement of platelet storage quality; pathogen inactivation; and cold storage of platelets. The objective of this article is to give insights from current practice to future development on platelet transfusion, focusing on these selected issues, which have a potentially major impact on forthcoming guidelines.
An Adapted Model for Transition to Adult Care in Young Adults with Prader–Willi Syndrome
Authors: Pedersen Maria , Höybye Charlotte
Published: May 2021

Background: Prader–Willi syndrome (PWS) is a rare, neurodevelopmental, genetic disease caused by the lack of expression of paternal genes in chromosome 15. The typical characteristics, including hyperphagia, muscular hypotonia, abnormal body composition, hormonal deficiencies, cognitive disabilities, and behavioral problems, appear or worsen in young adults, and the development of comorbidities increases. The transition of care of young adults with PWS is a challenge due to the complexity of the disease and the vulnerability of the patients. Multidisciplinary transition clinics are optimal but difficult to implement in clinics with few transitions. Methods: The description of transition care meetings was limited to the pediatric and adult endocrinologists and nurses. The presentation of our checklist was developed to optimize the organization of the transition of young adults with PWS. Results: Two to four patients with PWS are transferred to adult care every year in our hospital. Transition with the adapted program was more comfortable for patients and identification of the individual patient’s comorbidities and special needs could clearly be addressed. Conclusions: In smaller settings, an adapted model including a proper introduction and presentation of the adult team and clinic, careful information about comorbidities and special needs, together with a checklist can optimize the transition of care to adult care.
Autoimmune Rheumatic Diseases: An Update on the Role of Atherogenic Electronegative LDL and Potential Therapeutic Strategies
Authors: Chen Der-Yuan , Sawamura Tatsuya , Dixon Richard A. F. , Sánchez-Quesada José Luis , Chen Chu-Huang
Published: May 2021

Atherosclerosis has been linked with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Autoimmune rheumatic diseases (AIRDs) are associated with accelerated atherosclerosis and ASCVD. However, the mechanisms underlying the high ASCVD burden in patients with AIRDs cannot be explained only by conventional risk factors despite disease-specific factors and chronic inflammation. Nevertheless, the normal levels of plasma low-density lipoprotein (LDL) cholesterol observed in most patients with AIRDs do not exclude the possibility of increased LDL atherogenicity. By using anion-exchange chromatography, human LDL can be divided into five increasingly electronegative subfractions, L1 to L5, or into electropositive and electronegative counterparts, LDL (+) and LDL (−). Electronegative L5 and LDL (−) have similar chemical compositions and can induce adverse inflammatory reactions in vascular cells. Notably, the percentage of L5 or LDL (−) in total LDL is increased in normolipidemic patients with AIRDs. Electronegative L5 and LDL (−) are not recognized by the normal LDL receptor but instead signal through the lectin-like oxidized LDL receptor 1 (LOX-1) to activate inflammasomes involving interleukin 1β (IL-1β). Here, we describe the detailed mechanisms of AIRD-related ASCVD mediated by L5 or LDL (−) and discuss the potential targeting of LOX-1 or IL-1β signaling as new therapeutic modalities for these diseases.
The Neuroimmune Role of Intestinal Microbiota in the Pathogenesis of Cardiovascular Disease
Authors: Suslov Andrey V. , Chairkina Elizaveta , Shepetovskaya Maria D. , Suslova Irina S. , Khotina Victoria A. , Kirichenko Tatiana V. , Postnov Anton Y.
Published: May 2021

Currently, a bidirectional relationship between the gut microbiota and the nervous system, which is considered as microbiota-gut-brain axis, is being actively studied. This axis is believed to be a key mechanism in the formation of somatovisceral functions in the human body. The gut microbiota determines the level of activation of the hypothalamic–pituitary system. In particular, the intestinal microbiota is an important source of neuroimmune mediators in the pathogenesis of cardiovascular disease. This review reflects the current state of publications in PubMed and Scopus databases until December 2020 on the mechanisms of formation and participation of neuroimmune mediators associated with gut microbiota in the development of cardiovascular disease.
Safety and Efficacy of Minimum- or Zero-Contrast IVUS–Guided Percutaneous Coronary Interventions in Chronic Kidney Disease Patients: A Systematic Review
Authors: Burlacu Alexandru , Tinica Grigore , Brinza Crischentian , Crisan-Dabija Radu , Popa Iolanda Valentina , Covic Adrian
Published: May 2021

Conventional percutaneous coronary interventions (PCIs) frequently cause severe complications in chronic kidney disease (CKD) patients. Low-to-zero contrast intravascular ultrasound (IVUS) guided PCIs are promising alternatives in the CKD setting. We aim to systematically review up-to-date literature that have reported data and outcomes of low-to-zero contrast PCIs performed in CKD patients. We searched Embase, PubMed, and Cochrane databases for full-text articles that reported original data regarding efficacy and/or safety outcomes of IVUS-guided PCIs in patients with CKD. The quality of non-randomized trials included was assessed using the Newcastle–Ottawa scale. Six papers were included in the present systematic review: One non-randomized trial, two case series, and three case reports. Given the literature reported so far, contrast-free and IVUS-guided PCI procedures in patients with CKD appear to be safe (both in cardiac and renal outcomes) with a comparable efficacy to the conventional procedure, even in complex atherosclerotic lesions. No patient included in the mentioned studies showed renal function deterioration and did not need renal replacement therapy after the zero-contrast IVUS-guided percutaneous procedures. From a cardiovascular point of view, this technique proved to be safe in terms of cardiovascular outcomes. The undesirable consequences of conventional PCI in the CKD population might soon be effectively hampered by safer low-to-zero contrast IVUS-guided PCI procedures after a mandatory and rigorous evidence-based validation in long-awaited randomized controlled trials.
Functionalization with a Polyphenol-Rich Pomace Extract Empowers a Ceramic Bone Filler with In Vitro Antioxidant, Anti-Inflammatory, and Pro-Osteogenic Properties
Authors: Iviglia Giorgio , Torre Elisa , Cassinelli Clara , Morra Marco
Published: May 2021

Oral diseases and periodontitis in particular are a major health burden worldwide, because of their association with various systemic diseases and with conditions such as peri-implantitis. Attempts have been made over the years to reverse bone loss due to the host disproportionate inflammatory response and to prevent failure of dental implants. To this end, the use of biomaterials functionalized with molecules characterized by anti-inflammatory and antioxidant properties could represent a new frontier for regenerating functional periodontal tissues. In this study, a new ceramic granulated biomaterial, named Synergoss Red (SR), functionalized with a polyphenolic mixture extracted from pomace of the Croatina grape variety, is introduced. Following a preliminary in-depth characterization of the extract by HPLC analysis and of the biomaterial surface and composition, we performed evaluations of cytocompatibility and a biological response through in vitro assays. The anti-inflammatory and antioxidant properties of the identified phenolic molecules contained in SR were shown to downregulate inflammation in macrophages, to stimulate in osteoblast-like cells the expression of genes involved in deposition of the early bone matrix, and to mitigate bone remodeling by decreasing the RANKL/OPG ratio. Thanks to its cytocompatibility and assorted beneficial effects on bone regeneration, SR could be considered an innovative regenerative approach in periodontal therapy.
Adaptive Nonsingular Fast Terminal Sliding Mode Tracking Control for an Underwater Vehicle-Manipulator System with Extended State Observer
Authors: Han Lijun , Tang Guoyuan , Cheng Maolin , Huang Hui , Xie De
Published: May 2021

An adaptive nonsingular fast terminal sliding mode control scheme with extended state observer (ESO) is proposed for the trajectory tracking of an underwater vehicle-manipulator system (UVMS), where the system is subjected to the lumped disturbances associating with both parameter uncertainties and external disturbances. The inverse kinematics for the system is obtained by the quaternion-based closed-loop inverse kinematic algorithm. The proposed controller consists of the modified nonsingular fast terminal sliding mode surface (NFTSMS) and ESO, and the adaptive control law. The utilized NFTSMS can ensure the fast convergence of the tracking errors, together with avoiding the singularity in the derivation. According to the ESO method, the estimation error of the lumped disturbance vector can realize the fixed-time convergence to the origin, along with replacing the sign function with the saturation function to attenuate the chattering. A continuous fractional PI-type robust term with adaptive laws is introduced to handle the unknown bound of the estimation error. The closed-loop system is proved to be asymptotically stable by the Lyapunov theory. Simulations are performed on a ten degree-of-freedom UVMS under four different strategies. Comparative simulation results show that the proposed controller can achieve better tracking performance and stronger robustness of the disturbance rejection.
Production of a β-Glucosidase-Rich Cocktail from Talaromyces amestolkiae Using Raw Glycerol: Its Role for Lignocellulose Waste Valorization
Authors: Méndez-Líter Juan A. , de Eugenio Laura I. , Hakalin Neumara L. S. , Prieto Alicia , Martínez María Jesús
Published: May 2021

As β-glucosidases represent the major bottleneck for the industrial degradation of plant biomass, great efforts are being devoted to discover both novel and robust versions of these enzymes, as well as to develop efficient and inexpensive ways to produce them. In this work, raw glycerol from chemical production of biodiesel was tested as carbon source for the fungus Talaromyces amestolkiae with the aim of producing enzyme β-glucosidase-enriched cocktails. Approximately 11 U/mL β-glucosidase was detected in these cultures, constituting the major cellulolytic activity. Proteomic analysis showed BGL-3 as the most abundant protein and the main β-glucosidase. This crude enzyme was successfully used to supplement a basal commercial cellulolytic cocktail (Celluclast 1.5 L) for saccharification of pretreated wheat straw, corroborating that even hardly exploitable industrial wastes, such as glycerol, can be used as secondary raw materials to produce valuable enzymatic preparations in a framework of the circular economy.
Differential Expression Profiles of Cell-to-Matrix-Related Molecules in Adrenal Cortical Tumors: Diagnostic and Prognostic Implications
Authors: Volante Marco , Rapa Ida , Metovic Jasna , Napoli Francesca , Tampieri Cristian , Duregon Eleonora , Terzolo Massimo , Papotti Mauro
Published: May 2021

The molecular mechanisms of adrenocortical carcinoma development are incompletely defined. De-regulation of cellular-to-extracellular matrix interactions and angiogenesis appear among mechanisms associated to the malignant phenotype. Our aim was to investigate, employing PCR-based array profiling, 157 molecules involved in cell-to-matrix interactions and angiogenesis in a frozen series of 6 benign and 6 malignant adrenocortical neoplasms, to identify novel pathogenetic markers. In 14 genes, a significant dysregulation was detected in adrenocortical carcinomas as compared to adenomas, most of them being downregulated. Three exceptions—hyaluronan synthase 1 (HAS-1), laminin α3 and osteopontin genes—demonstrated an increased expression in adrenocortical carcinomas of 4.46, 4.23 and 20.32-fold, respectively, and were validated by immunohistochemistry on a series of paraffin-embedded tissues, including 20 adenomas and 73 carcinomas. Osteopontin protein, absent in all adenomas, was expressed in a carcinoma subset (25/73) (p = 0.0022). Laminin α3 and HAS-1 were mostly expressed in smooth muscle and endothelial cells of the vascular network of both benign and malignant adrenocortical tumors. HAS-1 was also detected in tumor cells, with a more intense pattern in carcinomas. In this group, strong expression was significantly associated with more favorable clinicopathological features. These data demonstrate that cell-to-matrix interactions are specifically altered in adrenocortical carcinoma and identify osteopontin and HAS-1 as novel potential diagnostic and prognostic biomarkers, respectively, in adrenal cortical tumors.
Breast Cancer Screening during COVID-19 Emergency: Patients and Department Management in a Local Experience
Authors: Maio Francesca , Tari Daniele Ugo , Granata Vincenza , Fusco Roberta , Grassi Roberta , Petrillo Antonella , Pinto Fabio
Published: May 2021

Background: During the COVID-19 public health emergency, our breast cancer screening activities have been interrupted. In June 2020, they resumed, calling for mandatory safe procedures to properly manage patients and staff. Methods: A protocol supporting medical activities in breast cancer screening was created, based on six relevant articles published in the literature and in the following National and International guidelines for COVID-19 prevention. The patient population, consisting of both screening and breast ambulatory patients, was classified into one of four categories: 1. Non-COVID-19 patient; 2. Confirmed COVID-19 in an asymptomatic screening patient; 3. suspected COVID-19 in symptomatic or confirmed breast cancer; 4. Confirmed COVID-19 in symptomatic or confirmed breast cancer. The day before the radiological exam, patients are screened for COVID-19 infection through a telephone questionnaire. At a subsequent in person appointment, the body temperature is checked and depending on the clinical scenario at stake, the scenario-specific procedures for medical and paramedical staff are adopted. Results: In total, 203 mammograms, 76 breast ultrasound exams, 4 core needle biopsies, and 6 vacuum-assisted breast biopsies were performed in one month. Neither medical nor paramedical staff were infected on any of these occasions. Conclusion: Our department organization model can represent a case of implementation of National and International guidelines applied in a breast cancer screening program, assisting hospital personnel into COVID-19 infection prevention.