bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Chelate Compounds on the Hydration Process of MgO–Al2O3 Phase System under Hydrothermal Conditions
Authors: Prorok Ryszard , Ramult Jakub , Nocun-Wczelik Wieslawa , Madej Dominika
Published: March 2021

In refractory castables during heat treatment, there is a dynamic change from a hydraulic bond to a ceramic bond. During heating, the emission of water takes place; this changes the conditions inside the material to something similar to the hydrothermal ones. This influences the processes that occur during the heating of the castables, and in consequence, the properties of the final material. The aim of the work was to evaluate the influence of the chelate compounds like citric and tartaric acids, often used in castables as dispersing agents, on the properties of the MgO–Al2O3 phase system during hydrothermal treatment. The performed tests included an XRD analysis, a thermal analysis (TG–DSC–EGA), infrared spectroscopy (FTIR), and an SEM–EDS analysis. Based on the obtained results, it was found that even small amounts of chelate compounds have a strong impact on the processes under hydrothermal conditions which results in changes in the phase composition of the materials.
Three-Dimension Resolution Enhanced Microscopy Based on Parallel Detection
Authors: Zhang Zhimin , Liu Shaocong , He Minfei , Huang Yuran , Kuang Cuifang , Han Yubing , Hao Xiang , Liu Xu
Published: March 2021

Pixel reassignment image scanning microscopy (PRISM) is a useful tool to improve the resolution of confocal laser scanning microscopy (CLSM) only equipped with a detector array. However, while it can improve the lateral resolution, it has little effect on the axial resolution. Here, new microscopy has been proposed which combines three-dimension fluorescence emission difference microscopy (3D FED) with PRISM to further improve three-dimension resolution. We call this method three-dimension pixel reassignment fluorescence emission difference microscopy (3D-PRFED). Detailed theoretical analysis and simulation are presented in this paper. Additionally, the performance of lateral and axial resolution improvement of this method has been demonstrated by imaging 100 nm fluorescent beads and nuclear pore complexes samples. Experiment results show that this method in our system can improve lateral resolution by a factor of 1.85 and axial resolution by a factor of 1.48 compared with CLSM.
Nodule Detection with Convolutional Neural Network Using Apache Spark and GPU Frameworks
Authors: Venkatesan Nikitha Johnsirani , Shin Dong Ryeol , Nam Choon Sung
Published: March 2021

In the pharmaceutical field, early detection of lung nodules is indispensable for increasing patient survival. We can enhance the quality of the medical images by intensifying the radiation dose. High radiation dose provokes cancer, which forces experts to use limited radiation. Using abrupt radiation generates noise in CT scans. We propose an optimal Convolutional Neural Network model in which Gaussian noise is removed for better classification and increased training accuracy. Experimental demonstration on the LUNA16 dataset of size 160 GB shows that our proposed method exhibit superior results. Classification accuracy, specificity, sensitivity, Precision, Recall, F1 measurement, and area under the ROC curve (AUC) of the model performance are taken as evaluation metrics. We conducted a performance comparison of our proposed model on numerous platforms, like Apache Spark, GPU, and CPU, to depreciate the training time without compromising the accuracy percentage. Our results show that Apache Spark, integrated with a deep learning framework, is suitable for parallel training computation with high accuracy.
Refined Characteristics of Moisture Cycling over the Inland River Basin Using the WRF Model and the Finer Box Model: A Case Study of the Heihe River Basin
Authors: Pan Xiaoduo , Ma Weiqiang , Zhang Ying , Li Hu
Published: March 2021

The Heihe River Basin (HRB), located on the northeastern edge of the Tibetan Plateau, is the second-largest inland river basin in China, with an area of 140,000 km2. The HRB is a coupling area of the westerlies, the Qinghai–Tibet Plateau monsoon and the Southeast monsoon circulation system, and is a relatively independent land-surface water-circulating system. The refined characteristics of moisture recycling over the HRB was described by using the Weather Research and Forecasting (WRF) model for a long-term simulation, and the “finer box model” for calculating the net water-vapor flux. The following conclusions were drawn from the results of this study: (1) The water vapor of the HRB was dominantly transported by the wind from the west and from the north, and the west one was much larger than the north one. The net vapor transported by the west wind was positive, and by the north wind was negative. (2) The precipitation over the HRB was triggered mainly by the vapor from the west, which arose from the lower vertical layer to higher one during transporting from west to east. The vapor from the north sank from a higher layer to a lower one, and crossed the south edge of the HRB. (3) The moisture-recycling ratio of evapotranspiration to precipitation over the HRB was much higher than the other regions, which may be due to the strong land–atmosphere interaction in the arid inland river basin.
FLT3-ITD Allelic Burden and Acute Promyelocytic Leukemia Risk Stratification
Authors: Li Andrew Y. , Kashanian Sarah M. , Hambley Bryan C. , Zacholski Kyle , Duong Vu H. , El Chaer Firas , Holtzman Noa G. , Gojo Ivana , Webster Jonathan A. , Norsworthy Kelly J. , Smith Bruce Douglas , DeZern Amy E. , Levis Mark J. , Baer Maria R. , Kamangar Farin , Ghiaur Gabriel , Emadi Ashkan
Published: March 2021

The significance of FLT3-ITD in acute promyelocytic leukemia (APL) is not well-established. We performed a bi-center retrospective study of 138 APL patients, 59 (42.8%) of whom had FLT3-ITD. APL patients with FLT3-ITD had higher baseline white blood cell counts (WBCs) (p < 0.001), higher hemoglobin, (p = 0.03), higher aspartate aminotransferase (p = 0.001), lower platelets (p = 0.004), lower fibrinogen (p = 0.003), and higher incidences of disseminated intravascular coagulation (p = 0.005), M3v variant morphology (p < 0.001), and the bcr3 isoform (p < 0.001). FLT3-ITD was associated with inferior post-consolidation complete remission (CR) (p = 0.02) and 5-year overall survival (OS) of 79.7%, compared to 94.4% for FLT3-WT (wild-type) (p = 0.02). FLT3-ITD was strongly associated with baseline WBCs ≥ 25 × 109/L (odds ratio (OR): 54.4; 95% CI: 10.4–286.1; p < 0.001). High FLT3-ITD allelic burdens correlated with high-risk (HR) Sanz scores and high WBCs, with every 1% increase in allelic burden corresponding to a 0.6 × 109/L increase in WBC. HR APL was associated with a 38.5% increase in allelic burden compared with low-risk (LR) APL (95% CI: 19.8–57.2; p < 0.001). Our results provide additional evidence that FLT3-ITD APL is a distinct subtype of APL that warrants further study to delineate potential differences in therapeutic approach.
Association between 30-s Chair Stand-Up Test and Anthropometric Values, Vibration Perception Threshold, FHSQ, and 15-D in Patients with Type 2 Diabetes Mellitus
Authors: Domínguez-Muñoz Francisco Javier , Carlos-Vivas Jorge , Villafaina Santos , García-Gordillo Miguel A. , Hernández-Mocholi Miguel Ángel , Collado-Mateo Daniel , Gusi Narcis , Adsuar José C.
Published: March 2021

Background: Type 2 diabetes mellitus (T2DM) is a chronic, worldwide disease affecting more than 400 million people. This pathology involves several associated problems, such as diabetic neuropathy complications, obesity, and foot problems, both in terms of health and sensitivity. Objective: The objective of this study was to explore the relationships of the 30-s chair stand-up test with the Foot Health Status Questionnaire (FHSQ), the vibration perception threshold (VPT), and the 15-dimensional (15-D) questionnaire in T2DM people. Methodology: Ninety participants with T2DM were assessed in terms of fat mass percentage, VPT, foot health, health-related quality of life (HRQoL), and the 30-s chair stand-up test. Results: The 30-s chair stand-up test was found to exhibit a moderate relationship with “physical activity” (rho = 0.441; p ≤ 0.001) and “vigor” (rho = 0.443; p ≤ 0.001) from FHSQ. The 30-s chair stand-up test was also found to be weakly associated with foot pain (rho = 0.358; p = 0.001), 15-D total score (rho = 0.376; p ≤ 0.001), “sleeping” (rho = 0.371; p < 0.001), and “depression” (rho = 0.352; p = 0.001). Conclusions: The 30-s chair stand-up test is associated with “physical activity”, “vigor”, and “foot pain” from the FHSQ and the 15-D questionnaire total score and its dimensions “sleeping” and “depression” in type 2 diabetes mellitus patients. Therefore, following the results obtained, qualified clinicians can use the 30-s chair stand-up test as a good tool for monitoring and managing type 2 diabetes.
Neuropathology of Animal Prion Diseases
Authors: Orge Leonor , Lima Carla , Machado Carla , Tavares Paula , Mendonça Paula , Carvalho Paulo , Silva João , Pinto Maria de Lurdes , Bastos Estela , Pereira Jorge Cláudio , Gonçalves-Anjo Nuno , Gama Adelina , Esteves Alexandra , Alves Anabela , Matos Ana Cristina , Seixas Fernanda , Silva Filipe , Pires Isabel , Figueira Luis , Vieira-Pinto Madalena , Sargo Roberto , Pires Maria dos Anjos
Published: March 2021

Transmissible Spongiform Encephalopathies (TSEs) or prion diseases are a fatal group of infectious, inherited and spontaneous neurodegenerative diseases affecting human and animals. They are caused by the conversion of cellular prion protein (PrPC) into a misfolded pathological isoform (PrPSc or prion- proteinaceous infectious particle) that self-propagates by conformational conversion of PrPC. Yet by an unknown mechanism, PrPC can fold into different PrPSc conformers that may result in different prion strains that display specific disease phenotype (incubation time, clinical signs and lesion profile). Although the pathways for neurodegeneration as well as the involvement of brain inflammation in these diseases are not well understood, the spongiform changes, neuronal loss, gliosis and accumulation of PrPSc are the characteristic neuropathological lesions. Scrapie affecting small ruminants was the first identified TSE and has been considered the archetype of prion diseases, though atypical and new animal prion diseases continue to emerge highlighting the importance to investigate the lesion profile in naturally affected animals. In this report, we review the neuropathology and the neuroinflammation of animal prion diseases in natural hosts from scrapie, going through the zoonotic bovine spongiform encephalopathy (BSE), the chronic wasting disease (CWD) to the newly identified camel prion disease (CPD).
The Cys Sense: Thiol Redox Switches Mediate Life Cycles of Cellular Proteins
Authors: Radzinski Meytal , Oppenheim Tal , Metanis Norman , Reichmann Dana
Published: March 2021

Protein homeostasis is an essential component of proper cellular function; however, sustaining protein health is a challenging task, especially during the aerobic lifestyle. Natural cellular oxidants may be involved in cell signaling and antibacterial defense; however, imbalanced levels can lead to protein misfolding, cell damage, and death. This merges together the processes of protein homeostasis and redox regulation. At the heart of this process are redox-regulated proteins or thiol-based switches, which carefully mediate various steps of protein homeostasis across folding, localization, quality control, and degradation pathways. In this review, we discuss the “redox code” of the proteostasis network, which shapes protein health during cell growth and aging. We describe the sources and types of thiol modifications and elaborate on diverse strategies of evolving antioxidant proteins in proteostasis networks during oxidative stress conditions. We also highlight the involvement of cysteines in protein degradation across varying levels, showcasing the importance of cysteine thiols in proteostasis at large. The individual examples and mechanisms raised open the door for extensive future research exploring the interplay between the redox and protein homeostasis systems. Understanding this interplay will enable us to re-write the redox code of cells and use it for biotechnological and therapeutic purposes.
Coupling Machine Learning and Lipidomics as a Tool to Investigate Metabolic Dysfunction-Associated Fatty Liver Disease. A General Overview
Authors: Castañé Helena , Baiges-Gaya Gerard , Hernández-Aguilera Anna , Rodríguez-Tomàs Elisabet , Fernández-Arroyo Salvador , Herrero Pol , Delpino-Rius Antoni , Canela Nuria , Menendez Javier A. , Camps Jordi , Joven Jorge
Published: March 2021

Hepatic biopsy is the gold standard for staging nonalcoholic fatty liver disease (NAFLD). Unfortunately, accessing the liver is invasive, requires a multidisciplinary team and is too expensive to be conducted on large segments of the population. NAFLD starts quietly and can progress until liver damage is irreversible. Given this complex situation, the search for noninvasive alternatives is clinically important. A hallmark of NAFLD progression is the dysregulation in lipid metabolism. In this context, recent advances in the area of machine learning have increased the interest in evaluating whether multi-omics data analysis performed on peripheral blood can enhance human interpretation. In the present review, we show how the use of machine learning can identify sets of lipids as predictive biomarkers of NAFLD progression. This approach could potentially help clinicians to improve the diagnosis accuracy and predict the future risk of the disease. While NAFLD has no effective treatment yet, the key to slowing the progression of the disease may lie in predictive robust biomarkers. Hence, to detect this disease as soon as possible, the use of computational science can help us to make a more accurate and reliable diagnosis. We aimed to provide a general overview for all readers interested in implementing these methods.
An Overview of Bio-Inspired Intelligent Imprinted Polymers for Virus Determination
Authors: Zaidi Shabi Abbas
Published: March 2021

The molecular imprinting polymers (MIPs) have shown their potential in various applications including pharmaceuticals, chemical sensing and biosensing, medical diagnosis, and environmental related issues, owing to their artificial selective biomimetic recognition ability. Despite the challenges posed in the imprinting and recognition of biomacromolecules, the use of MIP for the imprinting of large biomolecular oragnism such as viruses is of huge interest because of the necessity of early diagnosis of virus-induced diseases for clinical and point-of-care (POC) purposes. Thus, many fascinating works have been documented in which such synthetic systems undoubtedly explore a variety of potential implementations, from virus elimination, purification, and diagnosis to virus and bacteria-borne disease therapy. This study is focused comprehensively on the fabrication strategies and their usage in many virus-imprinted works that have appeared in the literature. The drawbacks, challenges, and perspectives are also highlighted.
A Simple Distance Paper-Based Analytical Device for the Screening of Lead in Food Matrices
Authors: Katelakha Kasinee , Nopponpunth Vanida , Boonlue Watcharee , Laiwattanapaisal Wanida
Published: March 2021

A simple and rapid distance paper-based analytical device (dPAD) for the detection of lead (Pb) in foods is proposed herein. The assay principle is based on competitive binding between carminic acid (CA) and polyethyleneimine (PEI) to Pb in a food sample. The paper channels were pre-immobilized with PEI, before reacting with a mixture of the sample and CA. Pb can strongly bind to the CA; hence, the length of the red color deposition on the flow channel decreased as a lower amount of free CA bound to PEI. The dPAD exhibited good linear correlation, with ranges of 5–100 µg·mL−1 (R2 = 0.974) of Pb. Although, the limit of detection (LOD) of this platform was rather high, at 12.3 µg·mL−1, a series of standard additions (8.0, 9.0, and 10.0 µg·mL−1) can be used to interpret the cutoff of Pb concentrations at higher or lower than 2 µg·mL−1. The presence of common metal ions such as calcium, magnesium, nickel, and zinc did not interfere with the color distance readout. The validity of the developed dPAD was demonstrated by its applicability to screen the contamination of Pb in century egg samples. The results obtained from the dPAD are in accordance with the concentration measured by atomic absorption spectroscopy (AAS) (n = 9). In conclusion, this proposed dPAD, combined with the standard addition method, could be applied for screening Pb contamination in food matrices. This platform is, therefore, potentially applicable for field measurements of Pb in developing countries, because it is cheap and rapid, and it requires no significant laborious instruments.
An ALE Meta-Analysis on Investment Decision-Making
Authors: Ortiz-Teran Elena , Diez Ibai , Lopez-Pascual Joaquin
Published: March 2021

It is claimed that investment decision-making should rely on rational analyses based on facts and not emotions. However, trying to make money out of market forecasts can trigger all types of emotional responses. As the question on how investors decide remains controversial, we carried out an activation likelihood estimation (ALE) meta-analysis using functional magnetic resonance imaging (fMRI) studies that have reported whole-brain analyses on subjects performing an investment task. We identified the ventral striatum, anterior insula, amygdala and anterior cingulate cortex as being involved in this decision-making process. These regions are limbic-related structures which respond to reward, risk and emotional conflict. Our findings support the notion that investment choices are emotional decisions that take into account market information, individual preferences and beliefs.
Promoting Generalized Learning in Balance Recovery Interventions
Authors: Harper Sara A. , Beethe Anne Z. , Dakin Christopher J. , Bolton David A. E.
Published: March 2021

Recent studies have shown balance recovery can be enhanced via task-specific training, referred to as perturbation-based balance training (PBT). These interventions rely on principles of motor learning where repeated exposure to task-relevant postural perturbations results in more effective compensatory balance responses. Evidence indicates that compensatory responses trained using PBT can be retained for many months and can lead to a reduction in falls in community-dwelling older adults. A notable shortcoming with PBT is that it does not transfer well to similar but contextually different scenarios (e.g., falling sideways versus a forward trip). Given that it is not feasible to train all conditions in which someone could fall, this limited transfer presents a conundrum; namely, how do we best use PBT to appropriately equip people to deal with the enormous variety of fall-inducing scenarios encountered in daily life? In this perspective article, we draw from fields of research that explore how general learning can be promoted. From this, we propose a series of methods, gleaned from parallel streams of research, to inform and hopefully optimize this emerging field where people receive training to specifically improve their balance reactions.
Carbide-Derived Carbons: WAXS and Raman Spectra for Detailed Structural Analysis
Authors: Härmas Riinu , Palm Rasmus , Kurig Heisi , Puusepp Laura , Pfaff Torben , Romann Tavo , Aruväli Jaan , Tallo Indrek , Thomberg Thomas , Jänes Alar , Lust Enn
Published: March 2021

Quick characterization methods to determine the structure of carbon materials are sought after for a wide array of technical applications. In this study we present the combined analysis of the structure of carbide-derived carbons (CDCs) with Raman spectroscopy and wide-angle X-ray scattering (WAXS) methods. We present the optimal deconvolution method to be used for the detailed analysis of Raman spectroscopy data of CDCs and comparison to corresponding WAXS results is made. For a broad set of CDCs both WAXS and Raman spectroscopy data showed that the average graphene layer extent increases with synthesis temperature of CDC, while the coherent domain lengths obtained from Raman spectroscopy higher by an average of 4.4 nm. In addition, the presence of correlations between the parameters (D-band width and the parameter A∑D/A∑G) from Raman spectroscopy and the synthesis temperature are established. Based on the WAXS and Raman spectra data analysis the strong influence of the precursor carbide structure on the graphitization pathway is shown.
Electrochemotherapy in the Treatment of Head and Neck Cancer: Current Conditions and Future Directions
Authors: Enokida Tomohiro , Tahara Makoto
Published: March 2021

Despite recent advances in the development of chemotherapeutic drug, treatment for advanced cancer of the head and neck cancer (HNC) is still challenging. Options are limited by multiple factors, such as a prior history of irradiation to the tumor site as well as functional limitations. Against this background, electrochemotherapy (ECT) is a new modality which combines administration of an antineoplastic agent with locally applied electric pulses. These pulses allow the chemotherapeutic drug to penetrate the intracellular space of the tumor cells and thereby increase its cytotoxicity. ECT has shown encouraging efficacy and a tolerable safety profile in many clinical studies, including in heavily pre-treated HNC patients, and is considered a promising strategy. Efforts to improve its efficacy and broaden its application are now ongoing. Moreover, the combination of ECT with recently developed novel therapies, including immunotherapy, represented by immune checkpoint inhibitor (ICI)s, has attracted attention for its potent theoretical rationale. More extensive, well-organized clinical studies and timely updating of consensus guidelines will bring this hopeful treatment to HNC patients under challenging situations.
High-Dose Vitamin C: Preclinical Evidence for Tailoring Treatment in Cancer Patients
Authors: Giansanti Manuela , Karimi Terry , Faraoni Isabella , Graziani Grazia
Published: March 2021

High-dose vitamin C has been proposed as a potential therapeutic approach for patients with advanced tumors who failed previous treatment with chemotherapy. Due to vitamin C complex pharmacokinetics, only intravenous administration allows reaching sufficiently high plasma concentrations required for most of the antitumor effects observed in preclinical studies (>0.250 mM). Moreover, vitamin C entry into cells is tightly regulated by SVCT and GLUT transporters, and is cell type-dependent. Importantly, besides its well-recognized pro-oxidant effects, vitamin C modulates TET enzymes promoting DNA demethylation and acts as cofactor of HIF hydroxylases, whose activity is required for HIF-1α proteasomal degradation. Furthermore, at pharmacological concentrations lower than those required for its pro-oxidant activity (<1 mM), vitamin C in specific genetic contexts may alter the DNA damage response by increasing 5-hydroxymethylcytosine levels. These more recently described vitamin C mechanisms offer new treatment opportunities for tumors with specific molecular defects (e.g., HIF-1α over-expression or TET2, IDH1/2, and WT1 alterations). Moreover, vitamin C action at DNA levels may provide the rationale basis for combination therapies with PARP inhibitors and hypomethylating agents. This review outlines the pharmacokinetic and pharmacodynamic properties of vitamin C to be taken into account in designing clinical studies that evaluate its potential use as anticancer agent.
Identifying Molecular Signatures of Distinct Modes of Collective Migration in Response to the Microenvironment Using Three-Dimensional Breast Cancer Models
Authors: Ardila Diana Catalina , Aggarwal Vaishali , Singh Manjulata , Chattopadhyay Ansuman , Chaparala Srilakshmi , Sant Shilpa
Published: March 2021

Collective cell migration is a key feature of transition of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) among many other cancers, yet the microenvironmental factors and underlying mechanisms that trigger collective migration remain poorly understood. Here, we investigated two microenvironmental factors, tumor-intrinsic hypoxia and tumor-secreted factors (secretome), as triggers of collective migration using three-dimensional (3D) discrete-sized microtumor models that recapitulate hallmarks of DCIS-IDC transition. Interestingly, the two factors induced two distinct modes of collective migration: directional and radial migration in the 3D microtumors generated from the same breast cancer cell line model, T47D. Without external stimulus, large (600 µm) T47D microtumors exhibited tumor-intrinsic hypoxia and directional migration, while small (150 µm), non-hypoxic microtumors exhibited radial migration only when exposed to the secretome of large microtumors. To investigate the mechanisms underlying hypoxia- and secretome-induced directional vs. radial migration modes, we performed differential gene expression analysis of hypoxia- and secretome-induced migratory microtumors compared with non-hypoxic, non-migratory small microtumors as controls. We propose unique gene signature sets related to tumor-intrinsic hypoxia, hypoxia-induced epithelial-mesenchymal transition (EMT), as well as hypoxia-induced directional migration and secretome-induced radial migration. Gene Set Enrichment Analysis (GSEA) and protein-protein interaction (PPI) network analysis revealed enrichment and potential interaction between hypoxia, EMT, and migration gene signatures for the hypoxia-induced directional migration. In contrast, hypoxia and EMT were not enriched in the secretome-induced radial migration, suggesting that complete EMT may not be required for radial migration. Survival analysis identified unique genes associated with low survival rate and poor prognosis in TCGA-breast invasive carcinoma dataset from our tumor-intrinsic hypoxia gene signature (CXCR4, FOXO3, LDH, NDRG1), hypoxia-induced EMT gene signature (EFEMP2, MGP), and directional migration gene signature (MAP3K3, PI3K3R3). NOS3 was common between hypoxia and migration gene signature. Survival analysis from secretome-induced radial migration identified ATM, KCNMA1 (hypoxia gene signature), and KLF4, IFITM1, EFNA1, TGFBR1 (migration gene signature) to be associated with poor survival rate. In conclusion, our unique 3D cultures with controlled microenvironments respond to different microenvironmental factors, tumor-intrinsic hypoxia, and secretome by adopting distinct collective migration modes and their gene expression analysis highlights the phenotypic heterogeneity and plasticity of epithelial cancer cells.
Key Matrix Remodeling Enzymes: Functions and Targeting in Cancer
Authors: Piperigkou Zoi , Kyriakopoulou Konstantina , Koutsakis Christos , Mastronikolis Stylianos , Karamanos Nikos K.
Published: March 2021

Tissue functionality and integrity demand continuous changes in distribution of major components in the extracellular matrices (ECMs) under normal conditions aiming tissue homeostasis. Major matrix degrading proteolytic enzymes are matrix metalloproteinases (MMPs), plasminogen activators, atypical proteases such as intracellular cathepsins and glycolytic enzymes including heparanase and hyaluronidases. Matrix proteases evoke epithelial-to-mesenchymal transition (EMT) and regulate ECM turnover under normal procedures as well as cancer cell phenotype, motility, invasion, autophagy, angiogenesis and exosome formation through vital signaling cascades. ECM remodeling is also achieved by glycolytic enzymes that are essential for cancer cell survival, proliferation and tumor progression. In this article, the types of major matrix remodeling enzymes, their effects in cancer initiation, propagation and progression as well as their pharmacological targeting and ongoing clinical trials are presented and critically discussed.
Targeting CX3CR1 Suppresses the Fanconi Anemia DNA Repair Pathway and Synergizes with Platinum
Authors: Lehto Jemina , Huguet Ninou Anna , Chioureas Dimitrios , Jonkers Jos , Gustafsson Nina M. S.
Published: March 2021

The C-X3-C motif chemokine receptor 1 (CX3CR1, fractalkine receptor) is associated with neoplastic transformation, inflammation, neurodegenerative diseases and aging, and the small molecule inhibitor KAND567 targeting CX3CR1 (CX3CR1i) is evaluated in clinical trials for acute systemic inflammation upon SARS-CoV-2 infections. Here we identify a hitherto unknown role of CX3CR1 in Fanconi anemia (FA) pathway mediated repair of DNA interstrand crosslinks (ICLs) in replicating cells. FA pathway activation triggers CX3CR1 nuclear localization which facilitates assembly of the key FA protein FANCD2 into foci. Interfering with CX3CR1 function upon ICL-induction results in inability of replicating cells to progress from S phase, replication fork stalling and impaired chromatin recruitment of key FA pathway factors. Consistent with defective FA repair, CX3CR1i results in increased levels of residual cisplatin-DNA adducts and decreased cell survival. Importantly, CX3CR1i synergizes with platinum agents in a nonreversible manner in proliferation assays including platinum resistant models. Taken together, our results reveal an unanticipated interplay between CX3CR1 and the FA pathway and show for the first time that a clinical-phase small molecule inhibitor targeting CX3CR1 might show benefit in improving responses to DNA crosslinking chemotherapeutics.
Low MicroRNA-19b Expression Shows a Promising Clinical Impact in Locally Advanced Rectal Cancer
Authors: Rubio Jaime , Cristóbal Ion , Santos Andrea , Caramés Cristina , Luque Melani , Sanz-Alvarez Marta , Zazo Sandra , Madoz-Gúrpide Juan , Rojo Federico , García-Foncillas Jesús
Published: March 2021

The standard treatment for patients with locally advanced colorectal cancer (LARC) is neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy (CRT) followed by surgical mesorectal excision. However, the lack of response to this preoperative treatment strongly compromises patient outcomes and leads to surgical delays and undesired toxicities in those non-responder cases. Thus, the identification of effective and robust biomarkers to predict response to preoperative CRT represents an urgent need in the current clinical management of LARC. The oncomiR microRNA-19b (miR-19b) has been reported to functionally play oncogenic roles in colorectal cancer (CRC) cells as well as regulate 5-FU sensitivity and determine outcome in CRC patients. However, its clinical impact in LARC has not been previously investigated. Here, we show that miR-19b deregulation is a common event in this disease, and its decreased expression significantly associates with lower tumor size after CRT (p = 0.003), early pathological stage (p = 0.003), and absence of recurrence (p = 0.001) in LARC patients. Interestingly, low miR-19b expression shows a predictive value of better response to neoajuvant CRT (p < 0.001), and the subgroup of LARC patients with low miR-19b levels have a markedly longer overall (p = 0.003) and event-free survival (p = 0.023). Finally, multivariate analyses determined that miR-19b independently predicts both patient outcome and response to preoperative CRT, highlighting its potential clinical usefulness in the management of LARC patients.
Synthesis of Novel Heteroleptic Oxothiolate Ni(II) Complexes and Evaluation of Their Catalytic Activity for Hydrogen Evolution
Authors: Kamatsos Fotios , Bethanis Kostas , Mitsopoulou Christiana A.
Published: March 2021

Two heteroleptic nickel oxothiolate complexes, namely [Ni(bpy)(mp)] (1) and [Ni(dmbpy)(mp)] (2), where mp = 2-hydroxythiophenol, bpy = 2,2′-bipyridine and dmbpy = 4,4′-dimethyl-2,2′-bipyridine were synthesized and characterized with various physical and spectroscopic methods. Complex 2 was further characterized by single crystal X-ray diffraction data. The complex crystallizes in the monoclinic P 21/c system and in its neutral form. The catalytic properties of both complexes for proton reduction were evaluated with photochemical and electrochemical studies. Two different in their nature photosensitizers, namely fluorescein and CdTe-TGA-coated quantum dots, were tested under various conditions. The role of the electron donating character of the methyl substituents was revealed in the light of the studies. Thus, catalyst 2 performs better than 1, reaching 39.1 TONs vs. 4.63 TONs in 3 h, respectively, in electrochemical experiments. In contrast, complex 1 is more photocatalytically active than 2, achieving a TON of over 6700 in 120 h of irradiation. This observed reverse catalytic activity suggests that HER mechanism follows different pathways in electrocatalysis and photocatalysis.
P-Glycoprotein Inhibitor Tariquidar Plays an Important Regulatory Role in Pigmentation in Larval Zebrafish
Authors: Kasica Natalia , Jakubowski Piotr , Kaleczyc Jerzy
Published: March 2021

Zebrafish has emerged as a powerful model in studies dealing with pigment development and pathobiology of pigment diseases. Due to its conserved pigment pattern with established genetic background, the zebrafish is used for screening of active compounds influencing melanophore, iridophore, and xanthophore development and differentiation. In our study, zebrafish embryos and larvae were used to investigate the influence of third-generation noncompetitive P-glycoprotein inhibitor, tariquidar (TQR), on pigmentation, including phenotype effects and changes in gene expression of chosen chromatophore differentiation markers. Five-day exposure to increasing TQR concentrations (1 µM, 10 µM, and 50 µM) resulted in a dose-dependent augmentation of the area covered with melanophores but a reduction in the area covered by iridophores. The observations were performed in three distinct regions—the eye, dorsal head, and tail. Moreover, TQR enhanced melanophore renewal after depigmentation caused by 0.2 mM 1-phenyl-2-thiourea (PTU) treatment. qPCR analysis performed in 56-h post-fertilization (hpf) embryos demonstrated differential expression patterns of genes related to pigment development and differentiation. The most substantial findings include those indicating that TQR had no significant influence on leukocyte tyrosine kinase, GTP cyclohydrolase 2, tyrosinase-related protein 1, and forkhead box D3, however, markedly upregulated tyrosinase, dopachrome tautomerase and melanocyte inducing transcription factor, and downregulated purine nucleoside phosphorylase 4a. The present study suggests that TQR is an agent with multidirectional properties toward pigment cell formation and distribution in the zebrafish larvae and therefore points to the involvement of P-glycoprotein in this process.
A Molecular Networking Strategy: High-Throughput Screening and Chemical Analysis of Brazilian Cerrado Plant Extracts against Cancer Cells
Authors: Cortelo Patrícia C. , Demarque Daniel P. , Dusi Renata G. , Albernaz Lorena C. , Braz-Filho Raimundo , Goncharova Ekaterina I. , Bokesch Heidi R. , Gustafson Kirk R. , Beutler John A. , Espindola Laila S.
Published: March 2021

Plants have historically been a rich source of successful anticancer drugs and chemotherapeutic agents, with research indicating that this trend will continue. In this contribution, we performed high-throughput cytotoxicity screening of 702 extracts from 95 plant species, representing 40 families of the Brazilian Cerrado biome. Activity was investigated against the following cancer cell lines: colon (Colo205 and Km12), renal (A498 and U031), liver (HEP3B and SKHEP), and osteosarcoma (MG63 and MG63.3). Dose-response tests were conducted with 44 of the most active extracts, with 22 demonstrating IC50 values ranging from <1.3 to 20 µg/mL. A molecular networking strategy was formulated using the Global Natural Product Social Molecular Networking (GNPS) platform to visualize, analyze, and annotate the compounds present in 17 extracts active against NCI-60 cell lines. Significant cytotoxic activity was found for Salacia crassifolia, Salacia elliptica, Simarouba versicolor, Diospyros hispida, Schinus terebinthifolia, Casearia sylvestris var. lingua, Magonia pubescens, and Rapanea guianensis. Molecular networking resulted in the annotation of 27 compounds. This strategy provided an initial overview of a complex and diverse natural product data set, yielded a large amount of chemical information, identified patterns and known compounds, and assisted in defining priorities for further studies.
Molecular Genetic Features of Cerebral Cavernous Malformations (CCM) Patients: An Overall View from Genes to Endothelial Cells
Authors: Riolo Giulia , Ricci Claudia , Battistini Stefania
Published: March 2021

Cerebral cavernous malformations (CCMs) are vascular lesions that affect predominantly microvasculature in the brain and spinal cord. CCM can occur either in sporadic or familial form, characterized by autosomal dominant inheritance and development of multiple lesions throughout the patient’s life. Three genes associated with CCM are known: CCM1/KRIT1 (krev interaction trapped 1), CCM2/MGC4607 (encoding a protein named malcavernin), and CCM3/PDCD10 (programmed cell death 10). All the mutations identified in these genes cause a loss of function and compromise the protein functions needed for maintaining the vascular barrier integrity. Loss of function of CCM proteins causes molecular disorganization and dysfunction of endothelial adherens junctions. In this review, we provide an overall vision of the CCM pathology, starting with the genetic bases of the disease, describing the role of the proteins, until we reach the cellular level. Thus, we summarize the genetics of CCM, providing a description of CCM genes and mutation features, provided an updated knowledge of the CCM protein structure and function, and discuss the molecular mechanisms through which CCM proteins may act within endothelial cells, particularly in endothelial barrier maintenance/regulation and in cellular signaling.
Eating Disorders in Top Elite Beach Handball Players: Cross Sectional Study
Authors: Martínez-Rodríguez Alejandro , Vicente-Martínez Manuel , Sánchez-Sánchez Javier , Miralles-Amorós Laura , Martínez-Olcina María , Sánchez-Sáez Juan Antonio
Published: March 2021

(1) Background: The preoccupation with the increasing appearance of eating disorders (ED) in athletes continues to grow, especially in athletes who practice team sports. ED severely affects the eating habits of the athletes, who tend to use unhealthy approaches to control their body weight. The development of nutritional education and early interventions by training staff is essential, and these factors are widely perceived as beneficial in sports medicine. This study evaluates the frequency at which beach handball (BH) players develop ED, also comparing the differences by sex and age (junior: adolescents vs. senior: young adults). In addition, the relation between body composition variables and ED was studied. (2) Methods: A descriptive and cross-sectional study was carried out in 69 top elite handball players (36 males and 33 females) from the Spanish National BH Team; who were separated by age (junior: adolescents and senior: young adults). The athletes completed the Eating Attitudes Test in its 26 item version (EAT-26). (3) Results: The prevalence of ED indicated that 11% of females had a high possibility of developing an ED, and 3% of males. Regarding the EAT-26 total score and subscales, no significant differences were found between female and male participants, or between the junior and senior categories. The correlations showed an association between body composition, in terms of body mass index, and the EAT-26 total score in both males and females. In the case of males, the correlation was negative. (4) Conclusions: Although there are no significant differences between sex or categories, it has been found that elite athletes are a population that is at high risk of developing ED.
Control of the Pore Structure of Plasma-Sprayed Thermal Barrier Coatings through the Addition of Unmelted Porous YSZ Particles
Authors: Li Yuanjun , Huang Jibo , Wang Weize , Ye Dongdong , Fang Huanjie , Gao Dong , Tu Shantung , Guo Xueping , Yu Zexin
Published: March 2021

In this study, a new pore structure control method for plasma-sprayed thermal barrier coatings (TBCs) through the addition of unmelted, porous yttria-stabilized zirconia (YSZ) particles was investigated. Through a unique way of feeding powder, two powder feeders were used simultaneously at different positions of the plasma flame to deposit a composite structure coating in which a conventional plasma-sprayed coating was used as a matrix and unmelted micro-agglomerated YSZ particles were dispersed in the dense conventional coating matrix as second-phase particles. The effects of the distribution and content of second-phase particles on the microstructure, mechanical properties, and lifetime were explored in a furnace cyclic test (24 h) of the composite coating. The mechanical properties and lifetime of the composite coating depend on the content and morphology of the particles embedded in the coating. The lifetime of the composite structure coatings is significantly higher than that of the conventional coatings. By adjusting the spraying parameters, the lifetime of the composite coating prepared under the optimum process is up to 145 days, which is about three times that of the conventional coating. The results of this study provide guidance for the preparation of high-performance composite structure TBCs.
The Effect of Threads Geometry on Insertion Torque (IT) and Periotest Implant Primary Stability: A High-Density Polyurethane Simulation for the Anterior Mandible
Authors: Fanali Stefano , Tumedei Margherita , Pignatelli Pamela , Petrini Morena , Piattelli Adriano , Iezzi Giovanna
Published: March 2021

The implant geometry provides a key role in the osseointegration process and is able to improve the mechanical interaction and primary stability into the bone tissue. The aim of the present investigation was to compare different implant profiles to evaluate their influence on the primary stability on high-density polyurethane block. Methods: A total of 100 implants were used on 20 pcf polyurethane density in the present investigation, i.e., 20 implants for each of 5 groups (A, B, C, D, and E), characterized by different thread pitch and geometry. The insertion torque (IT), and Periotest mean values were recorded during the implant positioning. Results: Mean values for insertion torque values were higher for the group C and group E implant profiles when compared to all other groups (p < 0.01). No significant differences were detected between these two groups (p < 0.05). Lower IT (<20 Ncm2) were presented by groups A, B, and D (p < 0.05). All groups showed negative Periotest values. Group C implants showed the lowest level of Periotest values (p < 0.05). No significant Periotest differences were found between group B and group D and between group A and group E (p > 0.05). Conclusions: Implants with a wider and V-thread profile and a round apex showed a higher stability in a standardized polyurethane foam. Their use could be suggested in high-density bone in clinical practice.
PTEN R130Q Papillary Tumor of the Pineal Region (PTPR) with Chromosome 10 Loss Successfully Treated with Everolimus: A Case Report
Authors: Assi Hazem I. , Kakati Rasha T. , Berro Juliett , Saikali Ibrahim , Youssef Bassem , Hourany Roula , Alameh Ibrahim , Tabbarah Abeer , Khoury Jessica , Darwish Houssein , Alame Saada
Published: March 2021

Papillary tumors of the pineal region (PTPR) can be observed among adults with poor prognosis and high recurrence rates. Standards of therapy involve total surgical excision along with radiation therapy, with no promising prospects for primary adjuvant chemotherapy, as long-term treatment options have not been explored. Chromosome 10 loss is characteristic of PTPR, and PTEN gene alterations are frequently encountered in a wide range of human cancers and may be treated with mTORC1 inhibitors such as everolimus. In parallel, there are no reports of treating PTPR with everolimus alone as a monopharmacotherapy. We report the case of a patient diagnosed with PTPR (grade III) characterized by a PTEN R130Q alteration with chromosome 10 loss that was treated with everolimus pharmacotherapy alone, resulting in an asymptomatic course and tumor regression, a rare yet notable phenomenon not described in the literature so far with potential to alter the management approach to patients with PTPR.
Sexual Dimorphisms and Asymmetries of the Thalamo-Cortical Pathways and Subcortical Grey Matter of Term Born Healthy Neonates: An Investigation with Diffusion Tensor MRI
Authors: Saadani-Makki Fadoua , Aarabi Ardalan , Fouladivanda Mahshid , Kazemi Karman , Makki Malek
Published: March 2021

Diffusion-tensor-MRI was performed on 28 term born neonates. For each hemisphere, we quantified separately the axial and the radial diffusion (AD, RD), the apparent diffusion coefficient (ADC) and the fractional anisotropy (FA) of the thalamo-cortical pathway (THC) and four structures: thalamus (TH), putamen (PT), caudate nucleus (CN) and globus-pallidus (GP). There was no significant difference between boys and girls in either the left or in the right hemispheric THC, TH, GP, CN and PT. In the combined group (boys + girls) significant left greater than right symmetry was observed in the THC (AD, RD and ADC), and TH (AD, ADC). Within the same group, we reported left greater than right asymmetry in the PT (FA), CN (RD and ADC). Different findings were recorded when we split the group of neonates by gender. Girls exhibited right > left AD, RD and ADC in the THC and left > right FA in the PT. In the group of boys, we observed right > left RD and ADC. We also reported left > right FA in the PT and left > right RD in the CN. These results provide insights into normal asymmetric development of sensory-motor networks within boys and girls.
Pancreatic Ductal Adenocarcinoma: Epidemiology and Risk Factors
Authors: Ushio Jun , Kanno Atsushi , Ikeda Eriko , Ando Kozue , Nagai Hiroki , Miwata Tetsurou , Kawasaki Yuki , Tada Yamato , Yokoyama Kensuke , Numao Norikatsu , Tamada Kiichi , Lefor Alan Kawarai , Yamamoto Hironori
Published: March 2021

The number of new cases of pancreatic ductal adenocarcinoma is increasing with a cumulative total of 495,773 cases worldwide, making it the fourteenth most common malignancy. However, it accounts for 466,003 deaths per year and is the seventh leading cause of cancer deaths. Regional differences in the number of patients with pancreatic ductal adenocarcinoma appear to reflect differences in medical care, as well as racial differences. Compared to the prevalence of other organ cancers in Japan, pancreatic ductal adenocarcinoma ranks seventh based on the number of patients, eighth based on morbidity, and fourth based on the number of deaths, with a continuing increase in the mortality rate. Risk factors for developing pancreatic ductal adenocarcinoma include family history, genetic disorders, diabetes, chronic pancreatitis, and intraductal papillary mucinous neoplasms. An issue that hinders improvement in the prognosis of patients with pancreatic ductal adenocarcinoma is the development of a strategy to identify patients with these risk factors to facilitate detection of the disease at a stage when intervention will improve survival.