bluuebunny/crossref_metadata_2025 huggingface dataset:
A Multilevel Road Alignment Model for Spatial-Query-by-Sketch
Authors: Tang Ming , Falomir Zoe , Sheng Yehua
Published: October 2020

A sketch map represents an individual’s perception of a specific location. However, the information in sketch maps is often distorted and incomplete. Nevertheless, the main roads of a given location often exhibit considerable similarities between the sketch maps and metric maps. In this work, a shape-based approach was outlined to align roads in the sketch maps and metric maps. Specifically, the shapes of main roads were compared and analyzed quantitatively and qualitatively in three levels pertaining to an individual road, composite road, and road scene. An experiment was performed in which for eight out of nine maps sketched by our participants, accurate road maps could be obtained automatically taking as input the sketch and the metric map. The experimental results indicate that accurate matches can be obtained when the proposed road alignment approach Shape-based Spatial-Query-by-Sketch (SSQbS) is applied to incomplete or distorted roads present in sketch maps and even to roads with an inconsistent spatial relationship with the roads in the metric maps. Moreover, highly similar matches can be obtained for sketches involving fewer roads.
UAV Deployment Using Two Levels of Stigmergy for Unstructured Environments
Authors: Aznar Fidel , Pujol López Maria del Mar , Rizo Ramón
Published: October 2020

This article will present two swarming behaviors for deployment in unstructured environments using unmanned aerial vehicles (UAVs). These behaviors will use stigmergy for communication. We found that there are currently few realistic deployment approaches that use stigmergy, due mainly to the difficulty of building transmitters and receivers for this type of communication. In this paper, we will provide the microscopic design of two behaviors with different technological and information requirements. We will compare them and also investigate how the number of agents influences the deployment. In this work, these behaviors will be exhaustively analyzed, taking into account different take-off time interval strategies, the number of collisions, and the time and energy required by the swarm. Numerous simulations will be conducted using unstructured maps generated at random, which will enable the establishment of the general functioning of the behaviors independently of the map used. Finally, we will show how both behaviors are capable of achieving the required deployment task in terms of covering time and energy consumed by the swarm. We will discuss how, depending on the type of map used, this task can be performed at a lower cost without using a more informed (but expensive) robotic swarm.
Between Silences: The Coronation of Portuguese Medieval Kings (12th–14th Centuries)
Authors: Varela Fernandes Carla
Published: October 2020

The coronations of Portugal’s first dynasty constitute a complex topic. Approaching the theme requires understanding that an omission of words in written documentation can both affirm and deny possibilities. Likewise, visual documentation, such as illuminations, sculptures and other figurative arts, is scarce, raising a significant number of questions and thus is not trustworthy as a historical source. For this reason, the study of Portuguese coronations is filled with questions and silences. Art does not testify to these ceremonies, but shows that Portuguese kings valued regalia pertaining to both religious and secular ceremonies affirming their power, and that those insignias were different from those used by French or English kings in the same time period. In this study, I will use art, particularly funerary sculpture, but also objects with iconographic value, to demonstrate how these reflect elements of thought and the emotional pulsar of the various European societies that produced them.
A Machine Learning Approach to Investigate the Surface Ozone Behavior
Authors: Gagliardi Roberta Valentina , Andenna Claudio
Published: October 2020

The concentration of surface ozone (O3) strongly depends on environmental and meteorological variables through a series of complex and non-linear functions. This study aims to explore the performances of an advanced machine learning (ML) method, the boosted regression trees (BRT) technique, in exploring the relationships between surface O3 and its driving factors, and in predicting the levels of O3 concentrations. To this end, a BRT model was trained on hourly data of air pollutants and meteorological parameters, acquired, over the 2016–2018 period, in a rural area affected by an anthropic source of air pollutants. The abilities of the BRT model in ranking, visualizing, and predicting the relationship between ground-level O3 concentrations and its driving factors were analyzed and illustrated. A comparison with a multiple linear regression (MLR) model was performed based on several statistical indicators. The results obtained indicated that the BRT model was able to account for 81% of changes in O3 concentrations; it slightly outperforms the MLR model in terms of the predictions accuracy and allows a better identification of the main factors influencing O3 variability on a local scale. This knowledge is expected to be useful in defining effective measures to prevent and/or mitigate the health damages associated with O3 exposure.
Automation: A New Open-Access Journal with a Broad Scope and an Exciting Mission
Authors: Abed Eyad H.
Published: October 2020

It is a sincere pleasure to welcome you to the inaugural issue of Automation [...]
Concentrated Growth Factors (CGF) Induce Osteogenic Differentiation in Human Bone Marrow Stem Cells
Authors: Rochira Alessio , Siculella Luisa , Damiano Fabrizio , Palermo Andrea , Ferrante Franco , Carluccio Maria Annunziata , Calabriso Nadia , Giannotti Laura , Stanca Eleonora
Published: October 2020

Bone regeneration is a complex process regulated by several factors that control overlapping biological processes, coordinating interactions among distinct cell populations. There is a great interest in identifying new strategies for inducing osteogenesis in a safe and efficient manner. Concentrated Growth Factor (CGF) is an autologous blood derived product obtained by centrifugation of venous blood following the procedure set on the Silfradent device. In this study the effects of CGF on osteogenic differentiation of human Bone Marrow Stem Cells (hBMSC) in vitro have been investigated; hBMSC were cultured with CGF or osteogenic medium, for 21 days. The osteogenic differentiation was evaluated measuring alkaline phosphatase (ALP) enzyme activity, matrix mineralization by alizarin red staining and through mRNA and protein quantification of osteogenic differentiation markers by Real-time PCR and Western blotting, respectively. The treatment with CGF stimulated ALP activity and promoted matrix mineralization compared to control and seems to be more effective than osteogenic medium. Also, hBMSC lost mesenchymal markers and showed other osteogenic features. Our study showed for the first time that CGF alone is able to induce osteogenic differentiation in hBMSC. The application of CGF on hBMSC osteoinduction might offer new clinical and biotechnological strategies in the tissue regeneration field.
An Overview of the Ferroptosis Hallmarks in Friedreich’s Ataxia
Authors: Turchi Riccardo , Faraonio Raffaella , Lettieri-Barbato Daniele , Aquilano Katia
Published: October 2020

Background: Friedreich’s ataxia (FRDA) is a neurodegenerative disease characterized by early mortality due to hypertrophic cardiomyopathy. FRDA is caused by reduced levels of frataxin (FXN), a mitochondrial protein involved in the synthesis of iron-sulphur clusters, leading to iron accumulation at the mitochondrial level, uncontrolled production of reactive oxygen species and lipid peroxidation. These features are also common to ferroptosis, an iron-mediated type of cell death triggered by accumulation of lipoperoxides with distinct morphological and molecular characteristics with respect to other known cell deaths. Scope of review: Even though ferroptosis has been associated with various neurodegenerative diseases including FRDA, the mechanisms leading to disease onset/progression have not been demonstrated yet. We describe the molecular alterations occurring in FRDA that overlap with those characterizing ferroptosis. Major conclusions: The study of ferroptotic pathways is necessary for the understanding of FRDA pathogenesis, and anti-ferroptotic drugs could be envisaged as therapeutic strategies to cure FRDA.
Development of Methods Derived from Iodine-Induced Specific Cleavage for Identification and Quantitation of DNA Phosphorothioate Modifications
Authors: Zhu Sucheng , Zheng Tao , Kong Lingxin , Li Jinli , Cao Bo , DeMott Michael , Sun Yihua , Chen Ying , Deng Zixin , Dedon Peter , You Delin
Published: October 2020

DNA phosphorothioate (PT) modification is a novel modification that occurs on the DNA backbone, which refers to a non-bridging phosphate oxygen replaced by sulfur. This exclusive DNA modification widely distributes in bacteria but has not been found in eukaryotes to date. PT modification renders DNA nuclease tolerance and serves as a constitute element of bacterial restriction–modification (R–M) defensive system and more biological functions are awaiting exploration. Identification and quantification of the bacterial PT modifications are thus critical to better understanding their biological functions. This work describes three detailed methods derived from iodine-induced specific cleavage-an iodine-induced cleavage assay (ICA), a deep sequencing of iodine-induced cleavage at PT site (ICDS) and an iodine-induced cleavage PT sequencing (PT-IC-Seq)-for the investigation of PT modifications. Using these approaches, we have identified the presence of PT modifications and quantized the frequency of PT modifications in bacteria. These characterizations contributed to the high-resolution genomic mapping of PT modifications, in which the distribution of PT modification sites on the genome was marked accurately and the frequency of the specific modified sites was reliably obtained. Here, we provide time-saving and less labor-consuming methods for both of qualitative and quantitative analysis of genomic PT modifications. The application of these methodologies will offer great potential for better understanding the biology of the PT modifications and open the door to future further systematical study.
Plasma Levels of a Cleaved Form of Galectin-9 Are the Most Sensitive Biomarkers of Acquired Immune Deficiency Syndrome and Tuberculosis Coinfection
Authors: Padilla Shirley T. , Niki Toshiro , Furushima Daisuke , Bai Gaowa , Chagan-Yasutan Haorile , Telan Elizabeth Freda , Tactacan-Abrenica Rosario Jessica , Maeda Yosuke , Solante Rontgene , Hattori Toshio
Published: October 2020

Acquired immunodeficiency syndrome (AIDS) complicated with tuberculosis (TB) is a global public issue. Due to the paucity of bacteria in AIDS/TB, blood-based biomarkers that reflect disease severity are desired. Plasma levels of matricellular proteins, such as osteopontin (OPN) and galectin-9 (Gal-9), are known to be elevated in AIDS and TB. Therefore, full-length (FL)-Gal9 and FL-OPN, and their truncated forms (Tr-Gal9, Ud-OPN), and 38 cytokines/chemokines were measured in the plasma of 24 AIDS (other than TB), 49 TB, and 33 AIDS/TB patients. Receiver-operating characteristic analysis was used to screen molecules that could distinguish either between disease and normal group, among each disease group, or between deceased patients and survivors. Selected molecules were further analyzed for significant differences. Tr-Gal9 had the highest ability to differentiate TB from AIDS or AIDS/TB, while Ud-OPN distinguished multidrug resistance (MDR)-TB from non-MDR TB, and extra-pulmonary TB from pulmonary TB. Molecules significantly elevated in deceased patients included; FL-Gal9, Tr-Gal9, interleukin (IL)-1 receptor antagonist, IL-17A and transforming growth factor-α in AIDS; IL-6, granulocyte colony-stimulating factor and monocyte chemotactic protein-1 in TB; and macrophage inflammatory protein-1β in AIDS/TB. From the sensitivity, specificity, and significant elevation, Tr-Gal9 is the best biomarker of inflammation and severity in AIDS and AIDS/TB.
Sphingomyelinases and Liver Diseases
Authors: Insausti-Urkia Naroa , Solsona-Vilarrasa Estel , Garcia-Ruiz Carmen , Fernandez-Checa Jose C.
Published: October 2020

Sphingolipids (SLs) are critical components of membrane bilayers that play a crucial role in their physico-chemical properties. Ceramide is the prototype and most studied SL due to its role as a second messenger in the regulation of multiple signaling pathways and cellular processes. Ceramide is a heterogeneous lipid entity determined by the length of the fatty acyl chain linked to its carbon backbone sphingosine, which can be generated either by de novo synthesis from serine and palmitoyl-CoA in the endoplasmic reticulum or via sphingomyelin (SM) hydrolysis by sphingomyelinases (SMases). Unlike de novo synthesis, SMase-induced SM hydrolysis represents a rapid and transient mechanism of ceramide generation in specific intracellular sites that accounts for the diverse biological effects of ceramide. Several SMases have been described at the molecular level, which exhibit different pH requirements for activity: neutral, acid or alkaline. Among the SMases, the neutral (NSMase) and acid (ASMase) are the best characterized for their contribution to signaling pathways and role in diverse pathologies, including liver diseases. As part of a Special Issue (Phospholipases: From Structure to Biological Function), the present invited review summarizes the physiological functions of NSMase and ASMase and their role in chronic and metabolic liver diseases, of which the most relevant is nonalcoholic steatohepatitis and its progression to hepatocellular carcinoma, due to the association with the obesity and type 2 diabetes epidemic. A better understanding of the regulation and role of SMases in liver pathology may offer the opportunity for novel treatments of liver diseases.
Osmotic Adaptation by Na+-Dependent Transporters and ACE2: Correlation with Hemostatic Crisis in COVID-19
Authors: Muhanna Danah , Arnipalli Shanvanth R. , Kumar Shashi B. , Ziouzenkova Ouliana
Published: October 2020

COVID-19 symptoms, including hypokalemia, hypoalbuminemia, ageusia, neurological dysfunctions, D-dimer production, and multi-organ microthrombosis reach beyond effects attributed to impaired angiotensin-converting enzyme 2 (ACE2) signaling and elevated concentrations of angiotensin II (Ang II). Although both SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus) and SARS-CoV-2 utilize ACE2 for host entry, distinct COVID-19 pathogenesis coincides with the acquisition of a new sequence, which is homologous to the furin cleavage site of the human epithelial Na+ channel (ENaC). This review provides a comprehensive summary of the role of ACE2 in the assembly of Na+-dependent transporters of glucose, imino and neutral amino acids, as well as the functions of ENaC. Data support an osmotic adaptation mechanism in which osmotic and hemostatic instability induced by Ang II-activated ENaC is counterbalanced by an influx of organic osmolytes and Na+ through the ACE2 complex. We propose a paradigm for the two-site attack of SARS-CoV-2 leading to ENaC hyperactivation and inactivation of the ACE2 complex, which collapses cell osmolality and leads to rupture and/or necrotic death of swollen pulmonary, endothelial, and cardiac cells, thrombosis in infected and non-infected tissues, and aberrant sensory and neurological perception in COVID-19 patients. This dual mechanism employed by SARS-CoV-2 calls for combinatorial treatment strategies to address and prevent severe complications of COVID-19.
Localised Grey Matter Atrophy in Multiple Sclerosis and Clinically Isolated Syndrome—A Coordinate-Based Meta-Analysis, Meta-Analysis of Networks, and Meta-Regression of Voxel-Based Morphometry Studies
Authors: Singh Sonika , Tench Christopher R. , Tanasescu Radu , Constantinescu Cris S.
Published: October 2020

Background: Atrophy of grey matter (GM) is observed in the earliest stages of multiple sclerosis (MS) and is associated with cognitive decline and physical disability. Localised GM atrophy in MS can be explored and better understood using magnetic resonance imaging and voxel-based morphometry (VBM). However, results are difficult to interpret due to methodological differences between studies. Methods: Coordinate-based analysis is a way to find the reliably observable results across multiple independent VBM studies. This work uses coordinate-based meta-analysis, meta-analysis of networks, and meta-regression to summarise the evidence from voxel-based morphometry of regional GM hanges in patients with MS and clinically isolated syndrome (CIS), and whether these measured changes are relatable to clinical features. Results: Thirty-four published articles reporting forty-four independent experiments using VBM for the assessment of GM atrophy between MS or CIS patients and healthy controls were identified. Analysis identified eight clusters of consistent cross-study reporting of localised GM atrophy involving both cortical and subcortical regions. Meta-network analysis identified a network-like pattern indicating that GM loss occurs with some symmetry between hemispheres. Meta-regression analysis indicates a relationship between disease duration or age and the magnitude of reported statistical effect in some deep GM structures. Conclusions: These results suggest consistency in MRI-detectible regional GM loss across multiple MS studies, and the estimated effect sizes and symmetries can help design prospective studies to test specific hypotheses.
Adjustment of Multiple Variables for Optimal Control of Building Energy Performance via a Genetic Algorithm
Authors: Seong Nam-Chul , Kim Jee-Heon , Choi Wonchang
Published: October 2020

Optimizing the operating conditions and control set points of the heating, ventilation, and air-conditioning (HVAC) system in a building is one of the most effective ways to save energy and improve the building’s energy performance. Here, we optimized different control variables using a genetic algorithm. We constructed and evaluated three optimal control scenarios (cases) to compare the energy savings of each by varying the setting and number and type of the optimized control variables. Case 1 used only air-side control variables and achieved an energy savings rate of about 5.72%; case 2 used only water-side control variables and achieved an energy savings rate of 16.98%; and case 3, which combined all the control variables, achieved 25.14% energy savings. The energy savings percentages differed depending on the setting and type of the control variables. The results show that, when multiple control set points are optimized simultaneously in an HVAC system, the energy savings efficiency becomes more effective. It was also confirmed that the control characteristics and energy saving rate change depending on the location and number of control variables when optimizing using the same algorithm.
Primary Granulocyte Colony-Stimulating Factor Prophylaxis in Metastatic Pancreatic Cancer Patients Treated with FOLFIRINOX as the First-Line Treatment
Authors: Jung Jae Hyup , Shin Dong Woo , Kim Jaihwan , Lee Jong-Chan , Hwang Jin-Hyeok
Published: October 2020

Although FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) has been proven efficacious in metastatic pancreatic cancer (MPC), physicians hesitate to administer it due to its hematologic toxicities. We investigated the usefulness of primary granulocyte colony-stimulating factor (G-CSF) prophylaxis. We reviewed electronic medical records of MPC patients with good performance status who were administered FOLFIRINOX as the first-line treatment from 2011 to 2017. The patients were divided into primary G-CSF prophylaxis users (group A) and non-users or therapeutic/secondary users (group B). Cumulative relative dose (cRDI), adverse effects (AEs), and overall survival (OS) were compared. A total of 165 patients (group A (57) vs. group B (108)) were investigated. Intergroup differences in baseline characteristics were not significant, although the cRDI and the number of treatment cycles were both higher in group A than in group B (cRDI: 80.6% vs. 73.9%, p = 0.007; 9 vs. 6 cycles, p = 0.004). Primary G-CSF prophylaxis reduced the risk of neutropenia (55.6% to 31.6%, p = 0.003) and febrile neutropenia (18.5% to 1.8%, p = 0.002) and improved OS (8.8 to 14.7 months; hazard ratio [HR]: 1.766, 95% CI: 1.257–2.481, p = 0.001). When administering FOLFIRINOX for MPC, primary G-CSF prophylaxis could be rationalized to reduced AEs and improve survival; more prospective studies are needed.
Artesunate Inhibits Growth of Sunitinib-Resistant Renal Cell Carcinoma Cells through Cell Cycle Arrest and Induction of Ferroptosis
Authors: Markowitsch Sascha D. , Schupp Patricia , Lauckner Julia , Vakhrusheva Olesya , Slade Kimberly S. , Mager René , Efferth Thomas , Haferkamp Axel , Juengel Eva
Published: October 2020

Although innovative therapeutic concepts have led to better treatment of advanced renal cell carcinoma (RCC), efficacy is still limited due to the tumor developing resistance to applied drugs. Artesunate (ART) has demonstrated anti-tumor effects in different tumor entities. This study was designed to investigate the impact of ART (1–100 µM) on the sunitinib-resistant RCC cell lines, Caki-1, 786-O, KTCTL26, and A-498. Therapy-sensitive (parental) and untreated cells served as controls. ART’s impact on tumor cell growth, proliferation, clonogenic growth, apoptosis, necrosis, ferroptosis, and metabolic activity was evaluated. Cell cycle distribution, the expression of cell cycle regulating proteins, p53, and the occurrence of reactive oxygen species (ROS) were investigated. ART significantly increased cytotoxicity and inhibited proliferation and clonogenic growth in both parental and sunitinib-resistant RCC cells. In Caki-1, 786-O, and A-498 cell lines growth inhibition was associated with G0/G1 phase arrest and distinct modulation of cell cycle regulating proteins. KTCTL-26 cells were mainly affected by ART through ROS generation, ferroptosis, and decreased metabolism. p53 exclusively appeared in the KTCTL-26 cells, indicating that p53 might be predictive for ART-dependent ferroptosis. Thus, ART may hold promise for treating selected patients with advanced and even therapy-resistant RCC.
Prognostic Role of Non-Identification of Sentinel Lymph Node in Cutaneous Melanoma Patients: An Observational Retrospective Study
Authors: Moro Ruggero , Arjona-Aguilera Cintia , Requena Celia , Pont-Sanjuan Virginia , Traves Victor , Manrique-Silva Esperanza , Nagore Eduardo
Published: October 2020

Background: Sentinel lymph node (SLN) status is recognized as the most important prognostic factor for patients with cutaneous melanoma. However, sometimes it is not possible to identify SLN. The phenomenon of non-identification of SLN and its prognostic role have not been thoroughly evaluated in melanoma literature. The objective of this study was to identify which patient or tumor variables may be associated to non-identification of SLN and to evaluate the prognostic role of non-identification of SLN. Methods: Observational retrospective study of 834 cutaneous melanoma patients who underwent SLN biopsy at Instituto Valenciano de Oncología. Results: Forty-two patients (5%) presented non-identification of SLN. Patients with age at diagnosis of ≥ 64 years, obesity (BMI ≥ 30), and head and neck localization were at higher risk of non-identification of SLN. Non-identified SLN patients had worse nodal disease-free survival with respect to negative SLN patients, but not worse melanoma-specific survival. Conclusions: Our findings suggest a need to follow-up patients with non-identified SLN in the same way as patients with positive SLN.
Challenges and Opportunities for Effective Cancer Immunotherapies
Authors: Slaney Clare Y. , Kershaw Michael H.
Published: October 2020

Using immunotherapy to treat cancers can be traced back to the 1890s, where a New York physician William Coley used heat-killed bacteria to treat cancer patients, which became known as “Coley’s toxin” [...]
Modelling Pancreatic Neuroendocrine Cancer: From Bench Side to Clinic
Authors: Ney Alexander , Canciani Gabriele , Hsuan J. Justin , Pereira Stephen P.
Published: October 2020

Pancreatic neuroendocrine tumours (pNETs) are a heterogeneous group of epithelial tumours with neuroendocrine differentiation. Although rare (incidence of <1 in 100,000), they are the second most common group of pancreatic neoplasms after pancreatic ductal adenocarcinoma (PDAC). pNET incidence is however on the rise and patient outcomes, although variable, have been linked with 5-year survival rates as low as 40%. Improvement of diagnostic and treatment modalities strongly relies on disease models that reconstruct the disease ex vivo. A key constraint in pNET research, however, is the absence of human pNET models that accurately capture the original tumour phenotype. In attempts to more closely mimic the disease in its native environment, three-dimensional culture models as well as in vivo models, such as genetically engineered mouse models (GEMMs), have been developed. Despite adding significant contributions to our understanding of more complex biological processes associated with the development and progression of pNETs, factors such as ethical considerations and low rates of clinical translatability limit their use. Furthermore, a role for the site-specific extracellular matrix (ECM) in disease development and progression has become clear. Advances in tissue engineering have enabled the use of tissue constructs that are designed to establish disease ex vivo within a close to native ECM that can recapitulate tumour-associated tissue remodelling. Yet, such advanced models for studying pNETs remain underdeveloped. This review summarises the most clinically relevant disease models of pNETs currently used, as well as future directions for improved modelling of the disease.
Optimized Combination of HDACI and TKI Efficiently Inhibits Metabolic Activity in Renal Cell Carcinoma and Overcomes Sunitinib Resistance
Authors: Rausch Magdalena , Weiss Andrea , Zoetemelk Marloes , Piersma Sander R. , Jimenez Connie R. , van Beijnum Judy R. , Nowak-Sliwinska Patrycja
Published: October 2020

Clear cell renal cell carcinoma (ccRCC) is characterized by high histone deacetylase (HDAC) activity triggering both cell motility and the development of metastasis. Therefore, there is an unmet need to establish innovative strategies to advance the use of HDAC inhibitors (HDACIs). We selected a set of tyrosine kinase inhibitors (TKIs) and HDACIs to test them in combination, using the validated therapeutically guided multidrug optimization (TGMO) technique based on experimental testing and in silico data modeling. We determined a synergistic low-dose three-drug combination decreasing the cell metabolic activity in metastatic ccRCC cells, Caki-1, by over 80%. This drug combination induced apoptosis and showed anti-angiogenic activity, both in original Caki-1 and in sunitinib-resistant Caki-1 cells. Through phosphoproteomic analysis, we revealed additional targets to improve the translation of this combination in 3-D (co-)culture systems. Cell–cell and cell–environment interactions increased, reverting the invasive and metastatic phenotype of Caki-1 cells. Our data suggest that our optimized low-dose drug combination is highly effective in complex in vitro settings and promotes the activity of HDACIs.
9G TestTM Cancer/Lung: A Desirable Companion to LDCT for Lung Cancer Screening
Authors: Choe Wonho , Chae Jeong Don , Lee Byoung-Hoon , Kim Sang-Hoon , Park So Young , Nimse Satish Balasaheb , Kim Junghoon , Warkad Shrikant Dashrath , Song Keum-Soo , Oh Ae-Chin , Hong Young Jun , Kim Taisun
Published: October 2020

A complimentary biomarker test that can be used in combination with LDCT for lung cancer screening is highly desirable to improve the diagnostic capacity of LDCT and reduce the false-positive rates. Most importantly, the stage I lung cancer detection rate can be dramatically increased by the simultaneous use of a biomarker test with LDCT. The present study was conducted to evaluate 9G testTM Cancer/Lung’s sensitivity and specificity in detecting Stage 0~IV lung cancer. The obtained results indicate that the 9G testTM Cancer/Lung can detect lung cancer with overall sensitivity and specificity of 75.0% (69.1~80.3) and 97.3% (95.0~98.8), respectively. The detection of stage I, stage II, stage III, and stage IV cancers with sensitivities of 77.5%, 78.1%, 67.4%, and 33.3%, respectively, at the specificity of 97.3% have never been reported before. The receiver operating characteristic curve analysis allowed us to determine the population-weighted AUC of 0.93 (95% CI, 0.91–0.95). These results indicate that the 9G testTM Cancer/Lung can be used in conjunction with LDCT to screen lung cancer. Furthermore, obtained results indicate that the use of 9G testTM Cancer/Lung with LDCT for lung cancer screening can increase stage I cancer detection, which is crucial to improve the currently low 5-year survival rates.
Opposite Roles of Tra2β and SRSF9 in the v10 Exon Splicing of CD44
Authors: Oh Jagyeong , Liu Yongchao , Choi Namjeong , Ha Jiyeon , Pradella Davide , Ghigna Claudia , Zheng Xuexiu , Shen Haihong
Published: October 2020

CD44 is a transmembrane glycoprotein involved in cell–cell and cell–matrix interactions. Several CD44 protein isoforms are generated in human through alternative splicing regulation of nine variable exons encoding for the extracellular juxta-membrane region. While the CD44 splicing variants have been described to be involved in cancer progression and development, the regulatory mechanism(s) underlying their production remain unclear. Here, we identify Tra2β and SRSF9 as proteins with opposite roles in regulating CD44 exon v10 splicing. While Tra2β promotes v10 inclusion, SRSF9 inhibits its inclusion. Mechanistically, we found that both proteins are able to target v10 exon, with GAAGAAG sequence being the binding site for Tra2β and AAGAC that for SRSF9. Collectively, our data add a novel layer of complexity to the sequential series of events involved in the regulation of CD44 splicing.
Regulation of Canonical Oncogenic Signaling Pathways in Cancer via DNA Methylation
Authors: Lu Jennifer , Wilfred Premila , Korbie Darren , Trau Matt
Published: October 2020

Disruption of signaling pathways that plays a role in the normal development and cellular homeostasis may lead to the dysregulation of cellular signaling and bring about the onset of different diseases, including cancer. In addition to genetic aberrations, DNA methylation also acts as an epigenetic modifier to drive the onset and progression of cancer by mediating the reversible transcription of related genes. Although the role of DNA methylation as an alternative driver of carcinogenesis has been well-established, the global effects of DNA methylation on oncogenic signaling pathways and the presentation of cancer is only emerging. In this article, we introduced a differential methylation parsing pipeline (MethylMine) which mined for epigenetic biomarkers based on feature selection. This pipeline was used to mine for biomarkers, which presented a substantial difference in methylation between the tumor and the matching normal tissue samples. Combined with the Data Integration Analysis for Biomarker discovery (DIABLO) framework for machine learning and multi-omic analysis, we revisited the TCGA DNA methylation and RNA-Seq datasets for breast, colorectal, lung, and prostate cancer, and identified differentially methylated genes within the NRF2-KEAP1/PI3K oncogenic pathway, which regulates the expression of cytoprotective genes, that serve as potential therapeutic targets to treat different cancers.
Extracellular Vesicle Dissemination of Epidermal Growth Factor Receptor and Ligands and Its Role in Cancer Progression
Authors: Frawley Thomas , Piskareva Olga
Published: October 2020

The epidermal growth factor receptor (EGFR) pathway functions through the autocrine or paracrine activation of cellular EGFR by a number of transmembrane ligands. Amplified or mutant EGFR can lead to tumour formation due to increased cell proliferation, growth, migration and survival signals. These oncogenic effects were thought to be confined to aberrant cells hosting genetic alterations in EGFR. However, in the past decade, numerous studies identified that tumour cells could harness extracellular vesicles (EVs) to disseminate EGFR, mutant EGFR, phosphorylated EGFR and EGFR ligands to local and distant cells. This functions to impart a pro-tumourigenic phenotype in recipient cells. EVs play an essential role in intracellular communication, through receptor signalling or the release of their intra-vesicular content into recipient cells. This review will discuss the role of EVs delivering EGFR or EGFR ligands either to or from tumour cells and how this can promote metastases, pre-metastatic niche formation, osteoclastogenesis, angiogenesis and immune modulation in cancer. We will examine how circulating EVs positive for EGFR may be exploited as diagnostic, prognostic or therapeutic markers in cancers including breast, lung, glioblastoma, ovarian and prostate. Finally, we will explore recent breakthroughs in bio-engineering EVs with EGFR targeting abilities for targeted drug delivery.
Chronic Active Epstein–Barr Virus Infection: Is It Immunodeficiency, Malignancy, or Both?
Authors: Fujiwara Shigeyoshi , Nakamura Hiroyuki
Published: October 2020

Chronic active Epstein–Barr virus (EBV) infection (CAEBV) is a rare syndrome characterized by prolonged infectious mononucleosis-like symptoms and elevated peripheral blood EBV DNA load in apparently immunocompetent persons. CAEBV has been primarily reported in East Asia and Latin America, suggesting a genetic predisposition in its pathogenesis. In most cases of CAEBV, EBV induces proliferation of its unusual host cells, T or natural killer (NK) cells. The clinical course of CAEBV is heterogeneous; some patients show an indolent course, remaining in a stable condition for years, whereas others show an aggressive course with a fatal outcome due to hemophagocytic lymphohistiocytosis, multiple organ failure, or progression to leukemia/lymphoma. The pathogenesis of CAEBV is unclear and clinicopathological investigations suggest that it has aspects of both malignant neoplasm and immunodeficiency. Recent genetic analyses of both viral and host genomes in CAEBV patients have led to discoveries that are improving our understanding of the nature of this syndrome. This article summarizes the latest findings on CAEBV and discusses critical unsolved questions regarding its pathogenesis and disease concept.
Management of γ-Alumina with High-Efficient {111} External Surfaces for HDS Reactions
Authors: Xu Yingrui , Liang Shunqin , Sun Limin , Hu Xiaoli , Zhang Yuqi , Lai Weikun , Yi Xiaodong , Fang Weiping
Published: October 2020

A series of γ-alumina samples with different exposure ratio of {111} facet were synthesized by an efficient hydrothermal method via adjusting the pH value of the gel precursor. The nanorod alumina supported catalyst with the highest exposure of {111} facet exhibited the best hydrodesulfurization (HDS) activities of both thiophene and dibenzothiophene (DBT). Characterization of the sulfided NiMo/Al2O3 catalyst with preferential exposure of {111} facet showed that the MoS2 nano slabs were inclined to distribute in the direction along the edges of alumina nanocrystal in reduced stacking layers. The selective exposure of {111} facet played a decisive role in obtaining alumina-supported HDS catalysts with improved intrinsic activity. This work helps to better understand the relationship between catalytic properties and varied support surfaces, which demonstrate a proper design of the catalyst support morphology on the facet-level.
The Interaction of Hydrogen with Iron Benzene-1,3,5-Tricarboxylate (Fe-BTC)
Authors: Parker Stewart F.
Published: October 2020

Inelastic neutron scattering (INS) spectroscopy is used to explore the 0–12,000 cm−1 range to characterise the interaction of H2 with iron benzene-1,3,5-tricarboxylate (Fe-BTC). Two peaks are observed in the low energy (<350 cm−1) region after exposure to H2. Measurements with hydrogen deuteride (HD) confirm that the peaks originate from H2. The most likely explanation is that there are two populations of H2 (HD) present. For both the H2- and the HD-loaded samples, the higher energy peak is close in energy to that of the pure isotopomer, so it is assigned to bulk-like H2/HD held in pores of the Fe-BTC. The lower energy peak is assigned to H2/HD interacting directly with the Fe ion exposed on dehydration. It was also possible to detect the H–H stretch in the same experiment; however, unfortunately, the instrumental resolution is insufficient to separate the stretch modes of the bound H2 (HD) and that in the pores.
Modeling the Mineralization Kinetics of Visible Led Graphene Oxide/Titania Photocatalytic Ozonation of an Urban Wastewater Containing Pharmaceutical Compounds
Authors: Beltrán Fernando J. , Checa Manuel , Rivas Javier , García-Araya Juan F.
Published: October 2020

In a water ozonation process, dissolved organics undergo two reactions at least: direct ozone attack and oxidation with hydroxyl radicals generated from the ozone decomposition. In the particular case of urban wastewater contaminated with pharmaceuticals, competition between these two reactions can be studied through application of gas–liquid reaction kinetics. However, there is a lack in literature about kinetic modeling of ozone processes in water specially in photocatalytic ozonation. In this work, lumped reactions of ozone and hydroxyl radicals with total organic carbon have been proposed. Urban wastewater containing a mixture of eight pharmaceutical compounds has been used to establish the kinetic model that simulates the mineralization process. The kinetic model is based on a mechanism of free radical and molecular reactions and the knowledge of mass transfer, chemical reaction rate constants, and radiation transfer data. According to the model, both single ozonation and photocatalytic ozonation present two distinct reaction periods characterized by the absence and presence of dissolved ozone. In the first period (less than 10 min), pharmaceuticals mainly disappear by direct ozone reactions and TOC variation due to these compounds has been modeled according to gas–liquid reaction kinetics through a lumped ozone-pharmaceutical TOC fast second order reaction. The corresponding rate constant of this reaction was found to change with time from 3 × 105 to 200 M−1 s−1 with Hatta values higher than 0.3. In the second period (nearly 5 h), competition between direct and hydroxyl radical reactions takes place and a kinetic model based on a direct and free radical reaction mechanism is proposed. Main influencing parameters to be known were: Direct ozone reaction rate constant, catalyst quantum yield, and hydroxyl radical scavengers. The first two take values of 0.5 M−1 s−1 and 5 × 10−4 mol·photon−1, respectively, while a fraction of TOC between 10% and 90% that changes with time was found to possess hydroxyl radical scavenger nature.
Recent Advances in Enzymatic and Chemoenzymatic Cascade Processes
Authors: Losada-Garcia Noelia , Cabrera Zaida , Urrutia Paulina , Garcia-Sanz Carla , Andreu Alicia , Palomo Jose M.
Published: October 2020

Cascade reactions have been described as efficient and universal tools, and are of substantial interest in synthetic organic chemistry. This review article provides an overview of the novel and recent achievements in enzyme cascade processes catalyzed by multi-enzymatic or chemoenzymatic systems. The examples here selected collect the advances related to the application of the sequential use of enzymes in natural or genetically modified combination; second, the important combination of enzymes and metal complex systems, and finally we described the application of biocatalytic biohybrid systems on in situ catalytic solid-phase as a novel strategy. Examples of efficient and interesting enzymatic catalytic cascade processes in organic chemistry, in the production of important industrial products, such as the designing of novel biosensors or bio-chemocatalytic systems for medicinal chemistry application, are discussed
Equine Penile Squamous Cell Carcinomas as a Model for Human Disease: A Preliminary Investigation on Tumor Immune Microenvironment
Authors: Porcellato Ilaria , Mecocci Samanta , Mechelli Luca , Cappelli Katia , Brachelente Chiara , Pepe Marco , Orlandi Margherita , Gialletti Rodolfo , Passeri Benedetta , Ferrari Angelo , Modesto Paola , Ghelardi Alessandro , Razzuoli Elisabetta
Published: October 2020

Penile squamous cell carcinomas (SCCs) are common tumors in older horses, with poor prognosis mostly due to local invasion and recurrence. These tumors are thought to be mainly caused by Equus caballus papillomavirus type 2 (EcPV-2). The aim of this study is to characterize the tumor immune environment (TIME) in equine penile tumors. Equine penile epithelial tumors (17 epSCCs; 2 carcinomas in situ, CIS; 1 papilloma, P) were retrospectively selected; immune infiltrate was assessed by histology and immunohistochemistry; RT-qPCR tested the expression of selected chemokines and EcPV-2 DNA and RNA. The results confirmed EcPV-2-L1 DNA in 18/20 (90%) samples. L1 expression was instead retrieved in 13/20 cases (65%). The samples showed an increased infiltration of CD3+lymphocytes, macrophages (MAC387; IBA1), plasma cells (MUM1), and FoxP3+lymphocytes in the intra/peritumoral stroma when compared to extratumoral tissues (p < 0.05). Only MAC387+neutrophils were increased in EcPV-2high viral load samples (p < 0.05). IL12/p35 was differentially expressed in EcPVhigh and EcPVlow groups (p = 0.007). A significant decrease of IFNG and IL2 expression was highlighted in TGFB1-positive samples (p < 0.05). IBA1 and CD20 were intratumorally increased in cases where IL-10 was expressed (p < 0.005). EpSCCs may represent a good spontaneous model for the human counterpart. Further prospective studies are needed in order to confirm these preliminary results.
The Regulatory Properties of the Ccr4–Not Complex
Authors: Chalabi Hagkarim Nafiseh , Grand Roger J.
Published: October 2020

The mammalian Ccr4–Not complex, carbon catabolite repression 4 (Ccr4)-negative on TATA-less (Not), is a large, highly conserved, multifunctional assembly of proteins that acts at different cellular levels to regulate gene expression. In the nucleus, it is involved in the regulation of the cell cycle, chromatin modification, activation and inhibition of transcription initiation, control of transcription elongation, RNA export, nuclear RNA surveillance, and DNA damage repair. In the cytoplasm, the Ccr4–Not complex plays a central role in mRNA decay and affects protein quality control. Most of our original knowledge of the Ccr4–Not complex is derived, primarily, from studies in yeast. More recent studies have shown that the mammalian complex has a comparable structure and similar properties. In this review, we summarize the evidence for the multiple roles of both the yeast and mammalian Ccr4–Not complexes, highlighting their similarities.
Indigenous Natural and First Law in Planetary Health
Authors: Redvers Nicole , Poelina Anne , Schultz Clinton , Kobei Daniel M. , Githaiga Cicilia , Perdrisat Marlikka , Prince Donald , Blondin Be’sha
Published: October 2020

Indigenous Peoples associate their own laws with the laws of the natural world, which are formally known as or translated as Natural or First Law. These laws come from the Creator and the Land through our ancestral stories and therefore, they are sacred. All aspects of life and existence depend on living and following these natural First Laws. Since colonization, Indigenous Peoples’ Natural Laws have been forcibly replaced by modern-day laws that do not take into account the sacred relationship between the Earth and all of her inhabitants. The force of societies who live outside of Natural Law has ensured the modern-day consequences of not living in balance with nature. Pandemics and global environmental change, including climate change, are all consequences of not following the Natural Laws that are encapsulated by the interconnected nature of the universe. Here we discuss Natural Law from an Indigenous paradigm and worldview which carries implications for planetary health and wider environmental movements around the globe.
Hydrophilic Titania Thin Films from a Molecular Precursor Film Formed via Electrospray Deposition on a Quartz Glass Substrate Precoated with Carbon Nanotubes
Authors: Heita Shafudah Natangue , Nagai Hiroki , Suwazono Yutaka , Ozawa Ryuhei , Kudoh Yukihiro , Takahashi Taiju , Onuma Takeyoshi , Sato Mitsunobu
Published: October 2020

Titania precursor films were electrosprayed on a quartz glass substrate, which was pre-modified with an ultra-thin film obtained by spin-coating a single-walled carbon nanotube (SWCNT) dispersed solution. The X-ray diffraction patterns of the thin films obtained by heat-treating the precursor films at 500 °C in air for 1 h indicated that the formed crystals were anatase. A new route to fabricate transparent thin films on the insulating substrate via electrospray deposition (ESD) was thus attained. The photoluminescence spectrum of the thin film showed a peak at 2.23 eV, assignable to the self-trapped exciton of anatase. The Raman spectrum of the thin film demonstrated that heat treatment is useful for removing SWCNTs. The thin film showed a water contact angle of 14 ± 2° even after being kept under dark conditions for 1 h, indicating a high level of hydrophilicity. Additionally, the thin film had a super-hydrophilic surface with a water contact angle of 1 ± 1° after ultraviolet light irradiation with an intensity of 4.5 mW cm−2 at 365 nm for 1 h. The importance of Ti3+ ions in the co-present amorphous phase, which was dominantly formed via the ESD process, for hydrophilicity was also clarified by means of X-ray photoelectron spectroscopy.
Preparation and Anti-frost Performance of PDMS-SiO2/SS Superhydrophobic Coating
Authors: Jia Li , Sun Jun , Li Xiaoxiao , Zhang Xian , Chen Lin , Tian Xinyou
Published: October 2020

Polydimethylsiloxane modified SiO2/organic silicon sol (PDMS-SiO2/SS) hybrid coating was synthesized via a simple two-step modification route. The nanoparticles (NPs) of PDMS-SiO2 were synthesized through a high temperature dehydration reaction by using silica and excessive PDMS. The NPs lapped with each other and formed a branch and tendril structure. Organic silicon sol (SS) added as basement introduced a hydrophobic group and protected the structure of the NPs. The PDMS-SiO2/SS hybrid coating exhibits a superhydrophobic performance with a maximum water contact angle of 152.82°. The frost test was carried out on a refrigerator evaporator, and the results showed that the coating did not merely delay the frost crystal time about 113 min but also increased the frost layer process time. Meanwhile, the defrosted water droplets rolled off from the coated surface easily which is a benefit for frost suppression performance of the next refrigeration cycle.
Raman Spectroscopy of Crystals
Authors: Krylov Alexander
Published: October 2020

Raman spectroscopy is now finding wide-ranging application in pure and applied science [...]