bluuebunny/crossref_metadata_2025 huggingface dataset:
Comorbidity Risk Score in Association with Cancer Incidence: Results from a Cancer Screenee Cohort
Authors: Hoang Tung , Lee Jeonghee , Kim Jeongseon
Published: July 2020

The combined effects of comorbidities can cause cancer incidence, while the effects of individual conditions, alone, might not. This study was conducted to investigate the joint impact of comorbidities on cancer incidence. The dietary score for energy-adjusted intake was calculated by applying a Gaussian graphical model and was then categorized into tertiles representing light, normal, and heavy eating behaviors. The risk point for cancer, according to the statuses of blood pressure, total cholesterol, fasting glucose, and glomerular filtration rate was computed from a Cox proportional hazard model adjusted for demographics and eating behavior. The comorbidity risk score was defined as the sum of the risk points for four comorbidity markers. We finally quantified the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between the strata of the comorbidity risk score and cancer incidence. A total of 13,644 subjects were recruited from the Cancer Screenee Cohort from 2007–2014. The comorbidity risk score was associated with cancer incidence in a dose-dependent manner (HR = 2.15, 95% CI = 1.39, 3.31 for those scoring 16–30 vs. those scoring 0–8, P-trend < 0.001). Subgroup analysis still showed significant dose-dependent relationships (HR = 2.39, 95% CI = 1.18, 4.84 for males and HR = 1.99, 95% CI = 1.11, 3.59 for females, P-trend < 0.05). In summary, there was a dose-dependent impact of comorbidities on cancer incidence; Highlights: Previous studies have generally reported that hypertension, hypercholesterolemia, diabetes, and chronic kidney disease might predispose patients to cancer. Combining these chronic diseases into a single score, this study found a dose-dependent association between the data-driven comorbidity risk score and cancer incidence.
Regulation of DNA Damage Response and Homologous Recombination Repair by microRNA in Human Cells Exposed to Ionizing Radiation
Authors: Szatkowska Magdalena , Krupa Renata
Published: July 2020

Ionizing radiation may be of both artificial and natural origin and causes cellular damage in living organisms. Radioactive isotopes have been used significantly in cancer therapy for many years. The formation of DNA double-strand breaks (DSBs) is the most dangerous effect of ionizing radiation on the cellular level. After irradiation, cells activate a DNA damage response, the molecular path that determines the fate of the cell. As an important element of this, homologous recombination repair is a crucial pathway for the error-free repair of DNA lesions. All components of DNA damage response are regulated by specific microRNAs. MicroRNAs are single-stranded short noncoding RNAs of 20–25 nt in length. They are directly involved in the regulation of gene expression by repressing translation or by cleaving target mRNA. In the present review, we analyze the biological mechanisms by which miRNAs regulate cell response to ionizing radiation-induced double-stranded breaks with an emphasis on DNA repair by homologous recombination, and its main component, the RAD51 recombinase. On the other hand, we discuss the ability of DNA damage response proteins to launch particular miRNA expression and modulate the course of this process. A full understanding of cell response processes to radiation-induced DNA damage will allow us to develop new and more effective methods of ionizing radiation therapy for cancers, and may help to develop methods for preventing the harmful effects of ionizing radiation on healthy organisms.
Coding of Glioblastoma Progression and Therapy Resistance through Long Noncoding RNAs
Authors: Zottel Alja , Šamec Neja , Videtič Paska Alja , Jovčevska Ivana
Published: July 2020

Glioblastoma is the most aggressive and lethal primary brain malignancy, with an average patient survival from diagnosis of 14 months. Glioblastoma also usually progresses as a more invasive phenotype after initial treatment. A major step forward in our understanding of the nature of glioblastoma was achieved with large-scale expression analysis. However, due to genomic complexity and heterogeneity, transcriptomics alone is not enough to define the glioblastoma “fingerprint”, so epigenetic mechanisms are being examined, including the noncoding genome. On the basis of their tissue specificity, long noncoding RNAs (lncRNAs) are being explored as new diagnostic and therapeutic targets. In addition, growing evidence indicates that lncRNAs have various roles in resistance to glioblastoma therapies (e.g., MALAT1, H19) and in glioblastoma progression (e.g., CRNDE, HOTAIRM1, ASLNC22381, ASLNC20819). Investigations have also focused on the prognostic value of lncRNAs, as well as the definition of the molecular signatures of glioma, to provide more precise tumor classification. This review discusses the potential that lncRNAs hold for the development of novel diagnostic and, hopefully, therapeutic targets that can contribute to prolonged survival and improved quality of life for patients with glioblastoma.
TIAM2S Mediates Serotonin Homeostasis and Provokes a Pro-Inflammatory Immune Microenvironment Permissive for Colorectal Tumorigenesis
Authors: Chan Ya-Ling , Lai Wei-Chung , Chen Jia-Shing , Tseng Joseph Ta-Chien , Chuang Pei-Chin , Jou Jonathan , Lee Chung-Ta , Sun H. Sunny
Published: July 2020

The short isoform of human TIAM2 has been shown to promote proliferation and invasion in various cancer cells. However, the roles of TIAM2S in immune cells in relation to tumor development have not been investigated. To characterize the effects of TIAM2S, we generated TIAM2S-overexpressing mouse lines and found that aged TIAM2S-transgenic (TIAM2S-TG) developed significantly higher occurrence of lymphocytic infiltration and tumorigenesis in various organs, including colon. In addition, TIAM2S-TG is more sensitized to AOM-induced colon tumor development, suggesting a priming effect toward tumorigenesis. In the light of our recent findings that TIAM2S functions as a novel regulator of cellular serotonin level, we found that serotonin, in addition to Cox2, is a unique inflammation marker presented in the colonic lesion sites in the aged TG animals. Furthermore, our results demonstrated that ectopic TIAM2S altered immunity via the expansion of T lymphocytes; this was especially pronounced in CD8+ T cells in combination with CXCL13/BCA-1 pro-inflammatory chemokine in the serum of TIAM2S-TG mice. Consequently, T lymphocytes and B cells were recruited to the lesion sites and stimulated IL-23/IL17A expression to form the tertiary lymphoid organs. Collectively, our research suggests that TIAM2S provokes a pro-inflammatory immune microenvironment permissive to colorectal tumorigenesis through the serotonin-induced immunomodulatory effects.
Molecular Basis of Mismatch Repair Protein Deficiency in Tumors from Lynch Suspected Cases with Negative Germline Test Results
Authors: Olkinuora Alisa , Gylling Annette , Almusa Henrikki , Eldfors Samuli , Lepistö Anna , Mecklin Jukka-Pekka , Nieminen Taina Tuulikki , Peltomäki Päivi
Published: July 2020

Some 10–50% of Lynch-suspected cases with abnormal immunohistochemical (IHC) staining remain without any identifiable germline mutation of DNA mismatch repair (MMR) genes. MMR proteins form heterodimeric complexes, giving rise to distinct IHC patterns when mutant. Potential reasons for not finding a germline mutation include involvement of an MMR gene not predicted by the IHC pattern, epigenetic mechanism of predisposition, primary mutation in another DNA repair or replication-associated gene, and double somatic MMR gene mutations. We addressed these possibilities by germline and tumor studies in 60 Lynch-suspected cases ascertained through diagnostics (n = 55) or research (n = 5). All cases had abnormal MMR protein staining in tumors but no point mutation or large rearrangement of the suspected MMR genes in the germline. In diagnostic practice, MSH2/MSH6 (MutS Homolog 2/MutS Homolog 6) deficiency prompts MSH2 mutation screening; in our study, 3/11 index individuals (27%) with this IHC pattern revealed pathogenic germline mutations in MSH6. Individuals with isolated absence of MSH6 are routinely screened for MSH6 mutations alone; we found a predisposing mutation in MSH2 in 1/7 such cases (14%). Somatic deletion of the MSH2-MSH6 region, joint loss of MSH6 and MSH3 (MutS Homolog 3) proteins, and hindered MSH2/MSH6 dimerization offered explanations to misleading IHC patterns. Constitutional epimutation hypothesis was pursued in the MSH2 and/or MSH6-deficient cases plus 38 cases with MLH1 (MutL Homolog 1)-deficient tumors; a primary MLH1 epimutation was identified in one case with an MLH1-deficient tumor. We conclude that both MSH2 and MSH6 should be screened in MSH2/6- and MSH6-deficient cases. In MLH1-deficient cases, constitutional epimutations of MLH1 warrant consideration.
Detecting Progression of Melanocytic Choroidal Tumors by Sequential Imaging: Is Ultrasonography Necessary?
Authors: Roelofs Kelsey A. , O’Day Roderick , Al Harby Lamis , Hay Gordon , Arora Amit K. , Cohen Victoria M. L. , Sagoo Mandeep S. , Damato Bertil E.
Published: July 2020

Purpose: To determine if ultrasonography is necessary to detect progression of choroidal melanocytic tumors undergoing sequential multi-modal imaging with color photography, autofluorescence (AF) and optical coherence tomography (OCT). Methods: All patients with choroidal melanoma undergoing treatment at Moorfields Eye Hospital between January 2016 and March 2020 were reviewed to identify those with treatment deferred by ≥2 months. Tumors that showed progression prior to treatment, defined as an increase in (a) basal dimensions (b) thickness (c) orange pigment and/or (d) sub-retinal fluid, were included. Mushroom shape, Orange pigment, Large size, Enlargement and Sub-retinal fluid (MOLES) scores were assigned to all tumors at earliest date and date of treatment. Results: A total of 99 patients with a mean age of 66 years (range: 26–90) were included. The initial MOLES score was 1 in 2 cases, 2 in 23 cases, and ≥3 in 74 cases. Progression was detected with sequential color photography alone in 100% of MOLES 1/2 and 97% of lesions with a MOLES score of ≥3. When findings on AF and OCT were included, sensitivity for detecting subtle change without ultrasonography improved to 100% for MOLES 3 and 97% for MOLES 4/5. Only one patient included in this study had an isolated increase in thickness that may have been missed had sequential ultrasonography not been performed. Overall, the sensitivity for detecting progression with color photographs alone was 97% (95% CI 93–100%) and increased to 99% (95% CI 97–100%) by including autofluorescence and OCT. Conclusions: Monitoring of choroidal nevi, particularly those classified as MOLES 1 or 2 (i.e., low-risk or high-risk naevi), can be accomplished safely without the need for ultrasonography. The findings of this study may remove barriers to the implementation of tele-oncology clinics for the monitoring of choroidal melanocytic tumors.
Metformin and Probiotics in the Crosstalk between Colitis-Associated Colorectal Cancer and Diabetes in Mice
Authors: Al Kattar Sahar , Jurjus Rosalyn , Pinon Aline , Leger David Yannick , Jurjus Abdo , Boukarim Chawki , Diab-Assaf Mona , Liagre Bertrand
Published: July 2020

The co-occurrence of colorectal cancer (CRC) and diabetes mellitus along with inflammation and dismicrobism has been frequently reported. Several studies shed light on the antioncogenic potential of metformin on colorectal carcinogenesis. This study aimed to demonstrate that metformin in association with probiotics acts in a synergic effect in breaking the crosstalk, thus inhibiting CRC progression, improving diabetes, and reducing inflammation. Ninety-six male Balb/c mice, 6–8 weeks old, were divided into 16 control and experimental groups to assess the effect of the different treatments and combinations at the clinical, histological, and molecular levels. Metformin and probiotics showed beneficial outcomes on CRC and diabetes, alone and most importantly in combination. Their effects were exerted by inhibiting the inflammatory process whereby a downregulation of IL-6 and TNF-α as well as oxidative stress were depicted. The characterization of the effects of probiotics and metformin on CRC and diabetes sheds light on the role of inflammation and microbiota in this crosstalk. Deciphering the downstream signaling pathways elicited by these compounds will help in developing new effective targeted treatment modalities.
Hormones Secretion and Rho GTPases in Neuroendocrine Tumors
Authors: Streit Laura , Brunaud Laurent , Vitale Nicolas , Ory Stéphane , Gasman Stéphane
Published: July 2020

Neuroendocrine tumors (NETs) belong to a heterogeneous group of neoplasms arising from hormone secreting cells. These tumors are often associated with a dysfunction of their secretory activity. Neuroendocrine secretion occurs through calcium-regulated exocytosis, a process that is tightly controlled by Rho GTPases family members. In this review, we compiled the numerous mutations and modification of expression levels of Rho GTPases or their regulators (Rho guanine nucleotide-exchange factors and Rho GTPase-activating proteins) that have been identified in NETs. We discussed how they might regulate neuroendocrine secretion.
A Molecular Stratification of Chilean Gastric Cancer Patients with Potential Clinical Applicability
Authors: Pinto Mauricio P. , Córdova-Delgado Miguel , Retamal Ignacio N. , Muñoz-Medel Matías , Bravo M. Loreto , Durán Doris , Villanueva Francisco , Sanchez César , Acevedo Francisco , Mondaca Sebastián , Koch Erica , Ibañez Carolina , Galindo Héctor , Madrid Jorge , Nervi Bruno , Peña José , Torres Javiera , Owen Gareth I. , Corvalán Alejandro H. , Armisén Ricardo , Garrido Marcelo
Published: July 2020

Gastric cancer (GC) is a complex and heterogeneous disease. In recent decades, The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) defined GC molecular subtypes. Unfortunately, these systems require high-cost and complex techniques and consequently their impact in the clinic has remained limited. Additionally, most of these studies are based on European, Asian, or North American GC cohorts. Herein, we report a molecular classification of Chilean GC patients into five subtypes, based on immunohistochemical (IHC) and in situ hybridization (ISH) methods. These were Epstein–Barr virus positive (EBV+), mismatch repair-deficient (MMR-D), epithelial to mesenchymal transition (EMT)-like, and accumulated (p53+) or undetected p53 (p53−). Given its lower costs this system has the potential for clinical applicability. Our results confirm relevant molecular alterations previously reported by TCGA and ACRG. We confirm EBV+ and MMR-D patients had the best prognosis and could be candidates for immunotherapy. Conversely, EMT-like displayed the poorest prognosis; our data suggest FGFR2 or KRAS could serve as potential actionable targets for these patients. Finally, we propose a low-cost step-by-step stratification system for GC patients. To the best of our knowledge, this is the first Latin American report on a molecular classification for GC. Pending further validation, this stratification system could be implemented into the routine clinic
Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease
Authors: Fougerat Anne , Montagner Alexandra , Loiseau Nicolas , Guillou Hervé , Wahli Walter
Published: July 2020

Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, frequently associated with obesity and type 2 diabetes. Steatosis is the initial stage of the disease, which is characterized by lipid accumulation in hepatocytes, which can progress to non-alcoholic steatohepatitis (NASH) with inflammation and various levels of fibrosis that further increase the risk of developing cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is influenced by interactions between genetic and environmental factors and involves several biological processes in multiple organs. No effective therapy is currently available for the treatment of NAFLD. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate many functions that are disturbed in NAFLD, including glucose and lipid metabolism, as well as inflammation. Thus, they represent relevant clinical targets for NAFLD. In this review, we describe the determinants and mechanisms underlying the pathogenesis of NAFLD, its progression and complications, as well as the current therapeutic strategies that are employed. We also focus on the complementary and distinct roles of PPAR isotypes in many biological processes and on the effects of first-generation PPAR agonists. Finally, we review novel and safe PPAR agonists with improved efficacy and their potential use in the treatment of NAFLD.
Inflammation Differentially Modulates the Biological Features of Adult Derived Human Liver Stem/Progenitor Cells
Authors: El-Kehdy Hoda , Najar Mehdi , De Kock Joery , Agha Douaa Moussa , Rogiers Vera , Merimi Makram , Lagneaux Laurence , Sokal Etienne M. , Najimi Mustapha
Published: July 2020

The progression of mesenchymal stem cell-based therapy from concept to cure closely depends on the optimization of conditions that allow a better survival and favor the cells to achieve efficient liver regeneration. We have previously demonstrated that adult-derived human liver stem/progenitor cells (ADHLSC) display significant features that support their clinical development. The current work aims at studying the impact of a sustained pro-inflammatory environment on the principal biological features of ADHLSC in vitro. METHODS: ADHLSC from passages 4–7 were exposed to a cocktail of inflammatory cytokines for 24 h and 9 days and subsequently analyzed for their viability, expression, and secretion profiles by using flow cytometry, RT-qPCR, and antibody array assay. The impact of inflammation on the hepatocytic differentiation potential of ADHLSC was also evaluated. RESULTS: ADHLSC treated with a pro-inflammatory cocktail displayed significant decrease of cell yield at both times of treatment while cell mortality was observed at 9 days post-priming. After 24 h, no significant changes in the immuno-phenotype of ADHLSC expression profile could be noticed while after 9 days, the expression profile of relevant markers has changed both in the basal conditions and after inflammation treatment. Inflammation cocktail enhanced the release of IL-6, IL-8, CCL5, monocyte-chemo-attractant protein-2 and 3, CXCL1/GRO, and CXCL5/ENA78. Furthermore, while IP-10 secretion was increased after 24 h priming, granulocyte macrophage colony-stimulating factor enhanced secretion was noticed after 9 days treatment. Finally, priming of ADHLSC did not affect their potential to differentiate into hepatocyte-like cells. CONCLUSION: These results indicate that ADHLSCs are highly sensitive to inflammation and respond to such signals by adjusting their gene and protein expression. Accordingly, monitoring the inflammatory status of patients at the time of cell transplantation, will certainly help in enhancing ADHLSC safety and efficiency.
Regulation of Error-Prone DNA Double-Strand Break Repair and Its Impact on Genome Evolution
Authors: Hanscom Terrence , McVey Mitch
Published: July 2020

Double-strand breaks are one of the most deleterious DNA lesions. Their repair via error-prone mechanisms can promote mutagenesis, loss of genetic information, and deregulation of the genome. These detrimental outcomes are significant drivers of human diseases, including many cancers. Mutagenic double-strand break repair also facilitates heritable genetic changes that drive organismal adaptation and evolution. In this review, we discuss the mechanisms of various error-prone DNA double-strand break repair processes and the cellular conditions that regulate them, with a focus on alternative end joining. We provide examples that illustrate how mutagenic double-strand break repair drives genome diversity and evolution. Finally, we discuss how error-prone break repair can be crucial to the induction and progression of diseases such as cancer.
Downregulation of Drp1 and Fis1 Inhibits Mitochondrial Fission and Prevents High Glucose-Induced Apoptosis in Retinal Endothelial Cells
Authors: Kim Dongjoon , Sankaramoorthy Aravind , Roy Sayon
Published: July 2020

Diabetic retinopathy is a prevalent microvascular complication characterized by apoptotic vascular cell loss in the retina. Previous studies have shown that high glucose (HG)-induced mitochondrial fragmentation plays a critical role in promoting retinal vascular cell apoptosis. Here, we investigated whether downregulation of mitochondrial fission genes, Fis1 and Drp1, which are overexpressed in HG condition, prevents mitochondrial fragmentation, preserves mitochondrial function, and protects retinal endothelial cells from apoptosis. Rat retinal endothelial cells (RRECs) were grown in normal (5 mM glucose) or HG (30 mM glucose) medium; in parallel, cells grown in HG medium were transfected with either Fis1 siRNA or Drp1 siRNA, or both siRNAs in combination, or scrambled siRNA as control. Live-cell confocal imaging showed decreased mitochondrial fission in cells transfected with Fis1 siRNA or Drp1 siRNA concomitant with reduced TUNEL-positive cells and a decrease in the expression of pro-apoptotic proteins, Bax and cleaved caspase 3, under HG condition. Importantly, the combined siRNA approach against Fis1 and Drp1 prevented HG-induced changes in the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). The findings from this study indicate that reducing HG-induced overexpression of mitochondrial fission genes preserves mitochondrial morphology and prevents retinal vascular cell apoptosis associated with diabetic retinopathy.
Unravelling the Complex Duplication History of Deuterostome Glycerol Transporters
Authors: Yilmaz Ozlem , Chauvigné François , Ferré Alba , Nilsen Frank , Fjelldal Per Gunnar , Cerdà Joan , Finn Roderick Nigel
Published: July 2020

Transmembrane glycerol transport is an ancient biophysical property that evolved in selected subfamilies of water channel (aquaporin) proteins. Here, we conducted broad level genome (>550) and transcriptome (>300) analyses to unravel the duplication history of the glycerol-transporting channels (glps) in Deuterostomia. We found that tandem duplication (TD) was the major mechanism of gene expansion in echinoderms and hemichordates, which, together with whole genome duplications (WGD) in the chordate lineage, continued to shape the genomic repertoires in craniates. Molecular phylogenies indicated that aqp3-like and aqp13-like channels were the probable stem subfamilies in craniates, with WGD generating aqp9 and aqp10 in gnathostomes but aqp7 arising through TD in Osteichthyes. We uncovered separate examples of gene translocations, gene conversion, and concerted evolution in humans, teleosts, and starfishes, with DNA transposons the likely drivers of gene rearrangements in paleotetraploid salmonids. Currently, gene copy numbers and BLAST are poor predictors of orthologous relationships due to asymmetric glp gene evolution in the different lineages. Such asymmetries can impact estimations of divergence times by millions of years. Experimental investigations of the salmonid channels demonstrated that approximately half of the 20 ancestral paralogs are functional, with neofunctionalization occurring at the transcriptional level rather than the protein transport properties. The combined findings resolve the origins and diversification of glps over >800 million years old and thus form the novel basis for proposing a pandeuterostome glp gene nomenclature.
Soluble St2 Induces Cardiac Fibroblast Activation and Collagen Synthesis via Neuropilin-1
Authors: Matilla Lara , Arrieta Vanessa , Jover Eva , Garcia-Peña Amaia , Martinez-Martinez Ernesto , Sadaba Rafael , Alvarez Virginia , Navarro Adela , Fernandez-Celis Amaya , Gainza Alicia , Santamaria Enrique , Fernandez-Irigoyen Joaquín , Rossignol Patrick , Zannad Faiez , Lopez-Andres Natalia
Published: July 2020

Circulating levels of soluble interleukin 1 receptor-like 1 (sST2) are increased in heart failure and associated with poor outcome, likely because of the activation of inflammation and fibrosis. We investigated the pathogenic role of sST2 as an inductor of cardiac fibroblasts activation and collagen synthesis. The effects of sST2 on human cardiac fibroblasts was assessed using proteomics and immunodetection approaches to evidence the upregulation of neuropilin-1 (NRP-1), a regulator of the profibrotic transforming growth factor (TGF)-β1. In parallel, sST2 increased fibroblast activation, collagen and fibrosis mediators. Pharmacological inhibition of nuclear factor-kappa B (NF-κB) restored NRP-1 levels and blocked profibrotic effects induced by sST2. In NRP-1 knockdown cells, sST2 failed to induce fibroblast activation and collagen synthesis. Exogenous NRP-1 enhanced cardiac fibroblast activation and collagen synthesis via NF-κB. In a pressure overload rat model, sST2 was elevated in association with cardiac fibrosis and was positively correlated with NRP-1 expression. Our study shows that sST2 induces human cardiac fibroblasts activation, as well as the synthesis of collagen and profibrotic molecules. These effects are mediated by NRP-1. The blockade of NF-κB restored NRP-1 expression, improving the profibrotic status induced by sST2. These results show a new pathogenic role for sST2 and its mediator, NRP-1, as cardiac fibroblast activators contributing to cardiac fibrosis.
Evaluation of a Reduced Graphene Oxide-Sb Nanoparticles Electrochemical Sensor for the Detection of Cadmium and Lead in Chamomile Tea
Authors: Nunes Erik W. , Silva Martin K. L. , Cesarino Ivana
Published: July 2020

The development of electroanalytical sensors for heavy metals detection in complex matrices holds great interest. Herein, a sensor based on a reduced graphene oxide (rGO) modified with antimony nanoparticles (Sb) was developed for the electrochemical detection of divalent cadmium ions (Cd2+) and lead ions (Pb2+). The simultaneous determination of both metals covered a range of 0.1 to 3.0 µmol L−1, with limits of detection (LOD) of 70.03 and 45.50 nmol L−1 for Cd2+ and Pb2+, respectively. For the individual detection, LOD of 20.50 nmol L−1 (Cd2+) and 2.01 nmol L−1 (Pb2+) were found. The analytical performance of this new sensor in detecting both metals in chamomile tea samples was satisfactorily evaluated.
Feasibility Study of Selective Laser Melting for Metal Matrix Diamond Tools
Authors: Fang Xiaohong , Yang Zhan , Tan Songcheng , Duan Longchen
Published: July 2020

Metal matrix diamond composite samples were fabricated by selective laser melting (SLM) at different forming parameters to investigate the feasibility and new challenges when SLM is applied to diamond tools manufacturing. The surface topographies, Rockwell hardness, compactness, microstructure, and diamond thermal damage of the samples were investigated in this study. The fabricated samples had high porosity and relatively low Rockwell hardness and compactness, and some ridge-shaped bulges and textures were observed at the edges and surfaces. Microstructure analyses showed that diamond particles were homogeneously distributed and metallurgically bonded within the metal matrix. The thermal damage pits on the diamond crystals along the scanning direction were the dominant damage type for SLM, which was completely different from conventional vacuum brazing and hot-pressing sintering. Although some challenges need to be further studied, our results demonstrate that SLM has great potential to propel the development of metal matrix diamond tools.
Numerical Simulation of Ice Fractures Process of the Yellow River Based on Disk Specimen
Authors: Wang Juan , Zhou Jiao , Deng Yu , Vadim Goncharov , Zhang Peng
Published: July 2020

To study the influence of the changes in crystals on a micro scale as well as their effect on the macro mechanical properties of river ice and to mitigate the limitation of the objective conditions in a physical examination of river ice, it is necessary to analyze the fracture process of river ice using a micro numerical calculation method. Thus, a numerical model was established to simulate the cracking process of river ice based on disk specimen. Upon comparison with the physical experiment, the results of the numerical model show agreement with the fracture toughness and cracking process. Based on the numerical model, the obtained material parameters of Yellow River ice laid a foundation for the study of the cracking process of river ice on a macro-, meso-, and multiscale.
N-Acetyl Indole Linked to a Fused Triazolo/Thiadiazole Scaffold: Synthesis, Single Crystal X-Ray Structure, and Molecular Insight
Authors: Boraei Ahmed T. A. , Soliman Saied M. , Yousuf Sammer , Bibi Memoona , Barakat Assem
Published: July 2020

The designed target compound of N-acetyl indole linked to a fused triazolo/thiadiazole scaffold was synthesized via the reaction of 4-amino-5-(1H-indol-2-yl)-1,2,4-triazol-3(2H)-thione as the starting material with acetic anhydride under reflux conditions for 6 h, resulting in an excellent and pure chemical yield. The structural features of the designed compound were confirmed using spectroscopic tools including single crystal X-ray diffraction analysis along with 1H-NMR, 13C-NMR, 2D-NMR, and high resolution mass spectrometry. Using Hirshfeld analysis, we determined the molecular packing depends on strong interactions (O···H and N···H) along with weak interactions (S···H, C···H and H···H). The shortest contacts corresponding to the N3···H12 (2.490 Å), N2···H5 (2.503 Å), and O1···H2 (2.490 Å) interactions were confirmed based on the Hirshfeld analysis. The calculated dipole moment was 6.6557 Debye. The atomic charge distribution, molecular electrostatic potential map, and reactivity descriptors are also discussed. The computed NMR spectra of the requisite compound correlated well with the results obtained experimentally. The UV-Vis electronic spectra of the requisite compound were simulated using the TD-DFT method and compared with the experimental data. The different σ→σ*, π→π*, n→σ*, and n→π* donor–acceptor interactions and their interaction energies stabilized the studied system to 9.84, 20.65, 29.33, and 45.82 kcal/mol, respectively.
Carbon Nanotubes-Filled Siloxane Composite Foams for Oil Recovery Application: Compression Properties
Authors: Piperopoulos Elpida , Calabrese Luigi , Mastronardo Emanuela , Proverbio Edoardo , Milone Candida
Published: July 2020

This paper studies the correlation between oil recovery usability and mechanical behavior under compression loads of an innovative oil recovery material. The examined composites are silicone foams filled with carbon nanotubes (CNT). Here, the reutilization of oil recovery processes of the newly developed composite foams is evaluated. In this regard, static and cyclic compressive tests are carried out. Samples filled with pristine and functionalized CNT are tested to evaluate the influence of the filler’s characteristics on the composite foam’s mechanical behavior. The results show that the presence of CNT (CNT-0) increases the elastic modulus (0.030 MPa) and collapse stress (0.010 MPa) of the siloxane matrix. On the contrary, as the CNT functionalization degree increases, a worsening of the composite’s mechanical performance is observed. CNT-0 foam evidences, also, the optimal mechanical stability to cyclic compressive loads, maintaining high stress values until 30 cycles. Furthermore, a correlation between the absorption capacity, elastic modulus, and cyclability is reported, highlighting a simplified approach to tailor the high absorption durability performance of filled CNT silicone foams. The promising results confirm the possible reuse of these new composite foams as absorbent materials for oil spill recovery applications.
Quantitative Proteomics of Urinary Bladder Cancer Cell Lines Identify UAP1 as a Potential Therapeutic Target
Authors: Puttamallesh Vinuth N. , Deb Barnali , Gondkar Kirti , Jain Ankit , Nair Bipin , Pandey Akhilesh , Chatterjee Aditi , Gowda Harsha , Kumar Prashant
Published: July 2020

Bladder carcinoma (BC) incidence and mortality rates are increasing worldwide. The development of novel therapeutic strategies is required to improve clinical management of this cancer. Aberrant protein expression may lead to cancer initiation and progression. Therefore, the identification of these potential protein targets and limiting their expression levels would provide alternative treatment options. In this study, we utilized a liquid-chromatography tandem mass spectrometry-based global proteomics approach to identify differentially expressed proteins in bladder cancer cell lines. A total of 3913 proteins were identified in this study, of which 479 proteins were overexpressed and 141 proteins were downregulated in 4 out of 6 BC cell lines when compared with normal human urothelial cell line (TERT-NHUC). We evaluated the role of UDP-N-acetylhexosamine pyrophosphorylase (UAP1) in bladder cancer pathogenesis. The silencing of UAP1 led to reduction in proliferation, invasion, colony formation and migration capability of bladder cancer cell lines. Thus, our study reveals UAP1 as a promising therapeutic target for bladder cancer.
Ectopic Expressions of the GhLETM1 Gene Reveal Sensitive Dose Effects on Precise Stamen Development and Male Fertility in Cotton
Authors: Zhang Li , Zhang Yao , Fan Yijie , Guo Haixia , Guo Huihui , Wu Jianfei , Wang Hongmei , Zhao Yunlei , Lian Xin , Gou Zhongyuan , Sun Yuxiao , Zheng Congcong , Chen Cuixia , Zeng Fanchang
Published: July 2020

The homologous leucine zipper/EF-hand-containing transmembranes (LETMs) are highly conserved across a broad range of eukaryotic organisms. The LETM functional characteristics involved in biological process have been identified primarily in animals, but little is known about the LETM biological function mode in plants. Based on the results of the current investigation, the GhLETM1 gene crucially affects filament elongation and anther dehiscence of the stamen in cotton. Both excessive and lower expression of the GhLETM1 gene lead to defective stamen development, resulting in shortened filaments and indehiscent anthers with pollen abortion. The results also showed that the phenotype of the shortened filaments was negatively correlated with anther defects in the seesaw model under the ectopic expression of GhLETM1. Moreover, our results notably indicated that the gene requires accurate expression and exhibits a sensitive dose effect for its proper function. This report has important fundamental and practical significance in crop science, and has crucial prospects for genetic engineering of new cytoplasmic male sterility lines and breeding of crop hybrid varieties.
Comparing Forward Conditional Analysis and Forward Logistic Regression Methods in a Landslide Susceptibility Assessment: A Case Study in Sicily
Authors: Costanzo Dario , Irigaray Clemente
Published: July 2020

Forward logistic regression and conditional analysis have been compared to assess landslide susceptibility across the whole territory of the Sicilian region (about 25,000 km2) using previously existing data and a nested tiered approach. These approaches were aimed at singling out a statistical correlation between the spatial distribution of landslides that have affected the Sicilian region in the past, and a set of controlling factors: outcropping lithology, rainfall, landform classification, soil use, and steepness. The landslide inventory used the proposal of building the models like the official one obtained in the PAI (hydro geologic asset plan) project, amounting to more than 33,000 events. The 11 types featured in PAI were grouped into 4 macro-typologies, depending on the inherent conditions believed to generate various kinds of failures and their kinematic evolution. The study has confirmed that it is possible to carry out a regional landslide susceptibility assessment based solely on existing data (i.e., factor maps and the landslide archive), saving a considerable amount of time and money. For scarp landslides, where the selected factors (steepness, landform classification, and lithology) are more discriminate, models show excellent performance: areas under receiver operating characteristic (ROC) (AUCs) average > 0.9, while hillslope landslide results are highly satisfactory (average AUCs of about 0.8). The stochastic approach makes it possible to classify the Sicilian territory depending on its propensity to landslides in order to identify those municipalities which are most susceptible at this level of study, and are potentially worthy of more specific studies, as required by European-level protocols.
Risk Prediction for Early Chronic Kidney Disease: Results from an Adult Health Examination Program of 19,270 Individuals
Authors: Shih Chin-Chuan , Lu Chi-Jie , Chen Gin-Den , Chang Chi-Chang
Published: July 2020

Developing effective risk prediction models is a cost-effective approach to predicting complications of chronic kidney disease (CKD) and mortality rates; however, there is inadequate evidence to support screening for CKD. In this study, four data mining algorithms, including a classification and regression tree, a C4.5 decision tree, a linear discriminant analysis, and an extreme learning machine, are used to predict early CKD. The study includes datasets from 19,270 patients, provided by an adult health examination program from 32 chain clinics and three special physical examination centers, between 2015 and 2019. There were 11 independent variables, and the glomerular filtration rate (GFR) was used as the predictive variable. The C4.5 decision tree algorithm outperformed the three comparison models for predicting early CKD based on accuracy, sensitivity, specificity, and area under the curve metrics. It is, therefore, a promising method for early CKD prediction. The experimental results showed that Urine protein and creatinine ratio (UPCR), Proteinuria (PRO), Red blood cells (RBC), Glucose Fasting (GLU), Triglycerides (TG), Total Cholesterol (T-CHO), age, and gender are important risk factors. CKD care is closely related to primary care level and is recognized as a healthcare priority in national strategy. The proposed risk prediction models can support the important influence of personality and health examination representations in predicting early CKD.
Increasing Competitiveness through the Implementation of Lean Management in Healthcare
Authors: Prado-Prado J. Carlos , García-Arca Jesús , Fernández-González Arturo J. , Mosteiro-Añón Mar
Published: July 2020

The main aim of this paper was two-fold: first, to design a participative methodology that facilitates lean management implementation in healthcare by adopting the action research approach; second, to illustrate the usefulness of this methodology by applying it to the sleep unit of a public hospital in Spain. This methodology proposes the implementation of lean management in its broadest sense: adopting both lean principles and some of its practical tools or practices in order to achieve competitive advantage. The complete service value chain was considered when introducing changes through lean management implementation. This implementation involved training and involving staff in the project (personnel pillar), detecting and analysing “waste” in value chain processes (processes pillar) and establishing control and measurement mechanisms in line with objectives (key performance indicators pillar) and putting in place improvement actions to achieve these objectives. The application of this methodology brought about an improvement in the management of patient flow in terms of effectiveness, efficiency and quality but also an internal transformation towards lean culture.
Countering Vaccine Hesitancy among Pregnant Women in England: The Case of Boostrix-IPV
Authors: Ryan Mairead , Marlow Laura A V , Forster Alice
Published: July 2020

This study explored the effects of message framing on vaccine hesitancy for the antenatal whooping cough vaccine. The study also assessed whether the Theory of Planned Behaviour (TPB) constructs had any explanatory utility for vaccine intentions and behaviours in pregnant women. A between-subjects, cross-sectional design was employed. Participants (n = 282) were women who were pregnant (mean = 28 weeks, SD = 7.0), living in England and between 18 and 44 years of age. A self-report web-based survey was used to collect data. Participants were randomly assigned to read either (i) disease risk, (ii) myth busting, or (iii) control information before answering questions based on the TPB. No significant effects of message framing were found. Attitudes (Beta = 0.699; p < 0.001) and subjective norms (Beta = 0.262, p < 0.001) significantly predicted intention to vaccinate but perceived behavioural control did not. The TPB constructs accounted for 86% and 36% of the variance in vaccine intention and vaccine history respectively. Disease risk information did not influence vaccine acceptability in this sample of English pregnant women. The study offered preliminary evidence that interventions targeting constructs from the TPB may promote vaccine acceptability among pregnant women.
Long-Term Influence of the Practice of Physical Activity on the Self-Perceived Quality of Life of Women with Breast Cancer: A Randomized Controlled Trial
Authors: García-Soidán Jose L. , Pérez-Ribao Ignacio , Leirós-Rodríguez Raquel , Soto-Rodríguez Anxela
Published: July 2020

Background: There is still no consensus on the most suitable interventions for exercise practice in breast cancer survivors. Therefore, the aim of this study was to evaluate the effect of a two-year physical activity intervention (strength, aqua fitness and aerobic exercise programs) on the self-perceived quality of life and physical functionality of female breast cancer survivors. Methods: A randomized, controlled, experimental trial with a sample of 316 women (63 ± 7 years), who had been diagnosed with breast cancer. The evaluations were performed using the Rikli & Jones Senior Fitness Test, and the Short Form 12 Health Survey (SF-12). Results: The participants in the strength program showed statistically significant improvements in all the items of the SF-12. The aqua fitness program obtained significant improvements in Physical Functioning and Limitations, Pain and Emotional Limitations, General Health, Vitality, Social Functioning and the physical and mental components of the SF-12. The participants in the aerobic program showed a progressive deterioration of Vitality and Mental Health. Conclusion: When assigning breast cancer survivors to an exercise program, the preferential or predominant activity should include strength exercises. On the other hand, as the second choice, those patients with particularly low levels of Vitality or Physical Limitations will show greater improvement with an aqua fitness program.
Comparative Toxicity of Helicoverpa armigera and Helicoverpa zea (Lepidoptera: Noctuidae) to Selected Insecticides
Authors: da Silva Fernando R. , Trujillo Dario , Bernardi Oderlei , Verle Rodrigues Jose Carlos , Bailey Woodward D. , Gilligan Todd M. , Carrillo Daniel
Published: July 2020

Until recently, the Old World bollworm (OWB) Helicoverpa armigera (Hübner) and the corn earworm Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) were geographically isolated. Both species are major pests of agricultural commodities that are known to develop insecticide resistance, and they now coexist in areas where H. armigera invaded the Americas. This is the first study to compare the susceptibility of the two species to conventional insecticides. The susceptibility of third instar H. armigera and H. zea larvae to indoxacarb, methomyl, spinetoram, and spinosad was determined using a diet-overlay bioassay in a quarantine laboratory in Puerto Rico. Mortality was assessed at 48 h after exposure for up to eight concentrations per insecticide. Spinetoram exhibited the highest acute toxicity against H. armigera, with a median lethal concentration (LC50) of 0.11 µg a.i./cm2, followed by indoxacarb and spinosad (0.17 µg a.i./cm2 for both) and methomyl (0.32 µg a.i./cm2). Spinetoram was also the most toxic to H. zea (LC50 of 0.08 µg a.i./cm2), followed by spinosad (0.17 µg a.i./cm2) and methomyl (0.18 µg a.i./cm2). Indoxacarb was the least toxic to H. zea, with an LC50 of 0.21 µg a.i./cm2. These findings could serve as a comparative reference for monitoring the susceptibility of H. armigera and H. zea to indoxacarb, methomyl, spinetoram, and spinosad in Puerto Rico, and may facilitate the detection of field-selected resistance for these two species and their potential hybrids in areas recently invaded by H. armigera.
Organ Stiffness in the Work-Up of Myelofibrosis and Philadelphia-Negative Chronic Myeloproliferative Neoplasms
Authors: Benedetti Edoardo , Tavarozzi Rita , Morganti Riccardo , Bruno Benedetto , Bramanti Emilia , Baratè Claudia , Balducci Serena , Iovino Lorenzo , Ricci Federica , Ricchiuto Vittorio , Buda Gabriele , Galimberti Sara
Published: July 2020

To define the role of spleen stiffness (SS) and liver stiffness (LS) in myelofibrosis and other Philadelphia (Ph)-negative myeloproliferative neoplasms (MPNs), we studied, by ultrasonography (US) and elastography (ES), 70 consecutive patients with myelofibrosis (MF) (no.43), essential thrombocythemia (ET) (no.10), and polycythemia vera (PV) (no.17). Overall, the median SS was not different between patients with MF and PV (p = 0.9); however, both MF and PV groups had significantly higher SS than the ET group (p = 0.011 and p = 0.035, respectively) and healthy controls (p < 0.0001 and p = 0.002, respectively). In patients with MF, SS values above 40 kPa were significantly associated with worse progression-free survival (PFS) (p = 0.012; HR = 3.2). SS also correlated with the extension of bone marrow fibrosis (BMF) (p < 0.0001). SS was higher in advanced fibrotic stages MF-2, MF-3 (W.H.O. criteria) than in pre-fibrotic/early fibrotic stages (MF-0, MF-1) (p < 0.0001) and PFS was significantly different in the two cohorts, with values of 63% and 85%, respectively (p = 0.038; HR = 2.61). LS significantly differed between the patient cohort with MF and healthy controls (p = 0.001), but not between the patient cohorts with ET and PV and healthy controls (p = 0.999 and p = 0.101, respectively). We can conclude that organ stiffness adds valuable information to the clinical work-up of MPNs and could be employed to define patients at a higher risk of progression.