bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intratumor heterogeneity: A new perspective on colorectal cancer research
Authors: Zheng Zicheng , Yu Tao , Zhao Xinyu , Gao Xin , Zhao Yao , Liu Gang 
Published: August 2020

AbstractColorectal cancers generally consist of multiple subclones. These subclones have their own unique characteristics, resulting in intratumor heterogeneity (ITH). As the discussion of ITH has advanced, a model describing the relationship of ITH to the tumor has gradually emerged. ITH can be divided into two types of intraprimary tumor heterogeneity and intraindividual tumor heterogeneity, the former for further understanding of tumor composition, and the latter for providing more information about evolutionary patterns. With the rapid development of new methods, such as next‐generation, polyguanine region sequencing, and Image detection, researchers may unravel the secrets underlying ITH. The higher the ITH of the tumor, the richer the interaction between the subclones maybe, or the greater the chance of the tumor getting more powerful subclones may be, thus increasing the malignant potential of the tumor. Existing evidence suggests that ITH may increase the ability of tumors to resist treatment and can be used as an independent influence on the prognosis of colorectal cancer. We reviewed 80 recent studies to give researchers a new perspective on colorectal cancer. There is still a limited amount of research in this area. Further study of the relationship between ITH and clinical endpoints may lead to the development of new treatment strategies.
CircIL4R facilitates the tumorigenesis and inhibits ferroptosis in hepatocellular carcinoma by regulating the miR‐541‐3p/GPX4 axis
Authors: Xu Qinhong , Zhou Lijing , Yang Ganghua , Meng Fandi , Wan Yong , Wang Lin , Zhang Lei 
Published: August 2020

AbstractFerroptosis is a specific iron‐dependent cell death form that can induce the production of lipid peroxide, but the roles of circular RNAs (circRNAs) in ferroptosis are completely unaware. Circ‐interleukin‐4 receptor (circIL4R) was reported to express highly in hepatocellular carcinoma (HCC). This study focused on the function of circIL4R dysregulation in tumor progression and ferroptosis of HCC, as well as its molecular mechanism. The quantitative real‐time polymerase chain reaction was implemented for measuring RNA expression. Cell proliferation and survival were evaluated using 3‐(4,5‐dimethylthiazol‐2‐y1)‐2,5‐diphenyl tetrazolium bromide. Apoptotic cells were detected via flow cytometry. The quantification of protein expression was executed through western blotting analysis. The target binding was assessed via the dual‐luciferase reporter, RNA immunoprecipitation, and RNA pull‐down assays. The experiment in vivo was performed using a xenograft model. CircIL4R was abnormally overexpressed in HCC tissues and cells. CircIL4R knockdown impeded oncogenesis and expedited ferroptosis of HCC cells. CircIL4R could directly sponge microRNA‐541‐3p (miR‐541‐3p) and miR‐541‐3p inhibition mitigated the effects of circIL4R knockdown on HCC cells. CircIL4R acted as a miR‐541‐3p sponge to regulate its target glutathione peroxidase 4 (GPX4). GPX4 upregulation relieved the miR‐541‐3p‐induced tumor inhibition and ferroptosis aggravation. CircIL4R played an oncogenic role in HCC via the miR‐541‐3p/GPX4 axis in vivo. Our data suggested that circIL4R served for a tumor promoter and ferroptosis inhibitor in HCC by the miR‐541‐3p/GPX4 network.
High‐glucose concentration aggravates TNF‐alpha‐induced cell viability reduction in human CD146‐positive periodontal ligament cells via TNFR‐1 gene demethylation
Authors: Luo Haoyuan , Zhu Wenjun , Mo Weiyan , Liang Min 
Published: August 2020

AbstractPeriodontitis is a chronic inflammatory disease that results in the destruction of periodontal soft tissue and the resorption of alveolar bone. Evidence indicates that in diabetic patients, hyperglycemia suppresses periodontal ligament stem cell (PDLSC) functions and leads to difficulties in periodontal repair. The present study aimed to explore the mechanisms by which high‐glucose concentrations aggravate cell viability reduction in human CD146‐positive PDLCs (CD146+PDLCs) under tumor necrosis factor‐alpha (TNF‐alpha) induction. CD146+PDLCs were isolated from periodontal ligament tissues and treated in the absence or presence of 10 ng/ml of TNF‐alpha and 30 mM glucose. Cell viability was detected using Cell Counting Kit‐8 assays and Luminescent Cell Viability Assays. Western blotting and real‐time polymerase chain reaction were performed to determine tumor necrosis factor‐alpha receptor‐1 (TNFR‐1) protein and messenger RNA expression. Bisulfite and MassArray methylation analyses were used to analyze the methylation status of the TNFR‐1 gene. Our results indicated that cell viability was reduced after treatment with a combination of both high‐glucose concentration and TNF‐alpha. Treatment with 30 mM glucose suppressed DNA methyltransferase (DNMT) activities and DNMT1 protein expression, and this was accompanied by the upregulation of TNFR‐1. Additionally, we found that the CpG island located within the TNFR‐1 gene was hypomethylated under 30 mM glucose conditions. S‐adenosylmethionine, an established methyl donor, reversed TNFR‐1 upregulation and restored cell viability against high‐glucose concentration and TNF‐alpha. In conclusion, the present findings suggest that high‐glucose‐induced CpG island hypomethylation within the TNFR‐1 gene plays an essential role in TNFR‐1 upregulation, and this further enhances the cell viability reduction of CD146+PDLCs caused by TNF‐alpha.
Circular RNA PRMT5 confers cisplatin‐resistance via miR‐4458/REV3L axis in non‐small‐cell lung cancer
Authors: Pang Jun , Ye Liwen , Zhao Dan , Zhao Ding , Chen Qingwei 
Published: August 2020

AbstractMultifactor and multistep processes were elucidated to participate in the progression of non‐small‐cell lung cancer (NSCLC). Circular RNA 0031250 (circ‐PRMT5) was a vital factor in NSCLC. However, the role of circ‐PRMT5 in cisplatin (DDP)‐resistance needed to be further highlighted. Expression profiles of circ‐PRMT5, microRNA (miR)‐4458, and EV3‐like DNA‐directed polymerase ζ catalytic subunit (REV3L) were detected using quantitative real‐time polymerase chain reaction. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, flow cytometry, and transwell assays were performed to determine the half‐maximal inhibitory concentration of DDP, cell viability, apoptosis, and invasion in vitro. Besides, the protein levels of REV3L and indicated proteins were examined by adopting western blot. Dual‐luciferase reporter assay was performed to analyze the interaction between miR‐4458 and circ‐PRMT5 or REV3L. The functional role of circ‐PRMT5 was explored using a xenograft tumor model. Levels of circ‐PRMT5 and REV3L were markedly increased, while miR‐4458 was downregulated in resistant tissues and cells. Knockdown of circ‐PRMT5 enhanced cell apoptosis, DDP‐sensitivity, and declined metastasis in NSCLC with DDP resistance. Besides, miR‐4458 inhibition or REV3L upregulation could revert circ‐PRMT5 absence‐mediated effect on DDP‐sensitivity in vitro. Mechanically, circ‐PRMT5 was a sponge of miR‐4458 to regulate REV3L. Importantly, circ‐PRMT5 silencing could interact with DDP treatment expedite the decrease of tumor growth in vivo. Circ‐PRMT5 promoted DDP resistance via REV3L by sponging miR‐4458 in NSCLC, thus providing a novel therapeutic strategy for patients with NSCLC.
Clinical implication of neointimal burden in in‐stent restenosis treated with drug‐coated balloon
Authors: Lee Jung‐Hee , Kim Ung , Kim Jung‐Sun , Hong Sung‐Jin , Ahn Chul‐Min , Kim Byeong‐Keuk , Ko Young‐Guk , Choi Donghoon , Hong Myeong‐Ki , Jang Yangsoo 
Published: August 2020

AbstractBackgroundAlthough drug‐coated balloon (DCB) angioplasty is a well‐established drug‐eluting stent (DES) in‐stent restenosis (ISR) strategy, there are minimal data regarding the association of neointimal burden on optical coherence tomography (OCT) before and after DCB and adverse clinical events. This study aimed to investigate the clinical impact of neointimal burden measured with OCT in patients with DES ISR after DCB angioplasty.MethodsFrom 2010 through 2013, a total of 122 patients with 122 ISR lesions were treated with DCB, which was preceded and followed by OCT examination. Major adverse cardiac events (MACE, a composite occurrence of cardiovascular cardiac death, nonfatal myocardial infarction [MI], or target lesion revascularization [TLR]) were evaluated.ResultsMACE occurred in 27 patients (4 nonfatal MIs and 23 TLRs) during the follow‐up (median: 55.3 months, interquartile range 43.1–66.0). The mean lumen area was significantly smaller (3.21 ± 2.42 mm2 vs. 4.80 ± 2.53 mm2, p = .005) and the mean percentage of neointimal volume derived by OCT was greater (49.3 ± 9.2% vs. 38.3 ± 17.5%, p = .006) in patients with MACE before DCB angioplasty. The pre‐procedural mean percentage of neointimal volume (cut‐off 50%, area under the receiver operating characteristic [ROC] curve = 0.644, 95% confidence interval [CI] = 0.531–0.758, p = .022) and post‐procedural mean percentage of neointimal volume (cut‐off 25%, area under ROC curve = 0.659, 95% CI = 0.546–0.773, p = .012) were identified as significant parameters to predict MACE.ConclusionThe OCT‐derived mean percentages of neointimal volume before and after DCB angioplasty can be important parameters for predicting future MACE in patients with DES ISR.
High‐Energy Proton‐Beam‐Induced Polymerization/Oxygenation of Hydroxynaphthalenes on Meteorites and Nitrogen Transfer from Urea: Modeling Insoluble Organic Matter?
Authors: Bizzarri Bruno Mattia , Manini Paola , Lino Valeria , d'Ischia Marco , Kapralov Michail , Krasavin Eugene , Mráziková Klaudia , Šponer Jiří , Šponer Judit E. , Di Mauro Ernesto , Saladino Raffaele 
Published: August 2020

AbstractFormation and structural modification of oxygenated polycyclic aromatic hydrocarbons (oxyPAHs) by UV irradiation on minerals have recently been proposed as a possible channel of PAH transformation in astrochemical and prebiotic scenarios of possible relevance for the origin of life. Herein, it is demonstrated that high‐energy proton‐beam irradiation in the presence of various meteorites, including stony iron, achondrite, and chondrite types, promotes the conversion of two representative oxyPAH compounds, 1‐naphthol and 1,8‐dihydroxynaphthalene, to complex mixtures of oxygenated and oligomeric derivatives. The main identified products include polyhydroxy derivatives, isomeric dimers encompassing benzofuran and benzopyran scaffolds, and, notably, a range of quinones and perylene derivatives. Addition of urea, a prebiotically relevant chemical precursor, expanded the range of identified species to include, among others, quinone diimines. Proton‐beam irradiation of oxyPAH modulated by nitrogen‐containing compounds such as urea is proposed as a possible contributory mechanism for the formation and processing of insoluble organic matter in meteorites and in prebiotic processes.
Do single‐stock circuit breakers provide a safety net for Canadian investors?
Authors: Switzer Lorne N. , El Meslmani Nabil , Tahaoglu Cagdas 
Published: August 2020

AbstractThis study looks at the market impact of recent regulatory changes in Canada that provide for trading halts on individual stocks that experience large upside or downside movements. The focus is on all stocks traded on the Toronto Stock Exchange since the inception of the single‐stock circuit breaker rule (SSCB) in February 2012, to replace the short‐sale uptick rule. The results support pricing efficiency: material information that caused the circuit breaker is incorporated in stock prices on the day of the halt (neither overreaction nor underreaction), with no decline in market liquidity. Using trade‐by‐trade data constructed on five‐minute trading intervals, we refine the daily results, and show that shocks in realized volatility are focused in the 10‐minute trading interval surrounding the halts. While circuit breakers provide a limited safety net for investors when their stocks are subject to severe volatility, they do not allow for a quick turnaround for stocks experiencing severe price decline events.
Characterization of spray paints used in street art graffiti by a non‐destructive multi‐analytical approach
Authors: Cortea Ioana Maria , Ratoiu Lucian , Rădvan Roxana 
Published: August 2020

AbstractOften associated with acts of vandalism, graffiti can also be identified with the so‐called street art movement. Moreover, in the historical context of visual arts from the 20th and 21st century, graffiti spray paints feature among the materials employed in the work of representative artists such as Lucio Fontana, Richard Hamilton, Yves Klein, or David Alfaro Siqueiros. In this study, a large number of artist spray paints were analyzed by means of X‐Ray Fluorescence (XRF), Fourier Transform Infrared Spectroscopy (FTIR), spectrophotometry, and Hyperspectral Imaging (HSI). The aim of the study was to provide a chemical characterization of the main organic and inorganic components present within the spray paint formulations by means of a complementary non‐destructive approach. Titanium white, zinc white, bismuth vanadate yellow, ultramarine, strontium sulfide, iron, and copper oxides, along a series of pigments of the azo, phthalocyanine, and quinacridone classes could be identified. High amounts of barium sulfate as well as calcium‐based extenders were also detected. FTIR analysis provided important information regarding the binder composition, mainly modified alkyd resins being identified. Additional information related to the existing chromophores as well as specific binder‐pigments interactions could also be highlighted within the HSI data sets. Overall results provide new insights on the complex chemistry of this new range of materials, which could help future investigations carried on street art graffiti, contemporary murals, or mixed‐media artworks.
Haemoglobin A1c is a predictor of COVID‐19 severity in patients with diabetes
Authors: Merzon Eugene , Green Ilan , Shpigelman Miriam , Vinker Shlomo , Raz Itamar , Golan‐Cohen Avivit , Eldor Roy 
Published: August 2020

AbstractAimPoor outcomes of coronavirus disease 2019 (COVID‐19) have been linked to diabetes, but its relation to pre‐infection glycaemic control is still unclear.Materials and MethodsTo address this question, we report here the association between pre‐infection Haemoglobin A1c (HbA1c) levels and COVID‐19 severity as assessed by need for hospitalization in a cohort of 2068 patients with diabetes tested for COVID‐19 in Leumit Health Services (LHSs), Israel, between 1 February and 30 April 2020. Using the LHS‐integrated electronic medical records system, we were able to collect a large amount of clinical information including age, sex, socio‐economic status, weight, height, body mass index, HbA1c, prior diagnosis of ischaemic heart disease, depression/anxiety, schizophrenia, dementia, hypertension, cerebrovascular accident, congestive heart failure, smoking, and chronic lung disease.ResultsOf the patients included in the cohort, 183 (8.85%) were diagnosed with COVID‐19 and 46 were admitted to hospital. More hospitalized patients were female, came from higher socio‐economic background and had a higher baseline HbA1c. A prior diagnosis of cerebrovascular accident and chronic lung disease conferred an increased risk of hospitalization but not obesity or smoking status. In a multivariate analysis, controlling for multiple prior clinical conditions, the only parameter associated with a significantly increased risk for hospitalization was HbA1c ≥ 9%.ConclusionUsing pre‐infection glycaemic control data, we identify HbA1c as a clear predictor of COVID‐19 severity. Pre‐infection risk stratification is crucial to successfully manage this disease, efficiently allocate resources, and minimize the economic and social burden associated with an undiscriminating approach.
Detection and identification of ACP‐105 and its metabolites in equine urine using LC/MS/MS after oral administration
Authors: Subhahar Michael Benedict , Karakka Kal Abdul Khader , Philip Moses , K. Karatt Tajudheen , N. Ibrahimwaseem , Vazhat Ramees Abdulla , M.P. Muhammed Ajeebsanu 
Published: August 2020

AbstractACP‐105 is a novel nonsteroidal selective androgen receptor modulator (SARM) with a tissue‐specific agonist effect and does not have side effects associated with the use of common androgens. This research reports a comprehensive study for the detection of ACP‐105 and its metabolites in racehorses after oral administration (in vivo) and postulating its structures using mass spectrometric techniques. To obtain the metabolic profile of ACP‐105, a selective and reliable LC‐MS/MS method was developed. The chemical structures of the metabolites were determined based on their fragmentation pattern, accurate mass, and retention time. Under the current experimental condition, a total of 19 metabolites were detected in ACP‐105 drug administered equine urine samples. The study results suggest the following: (1) ACP‐105 is prone to oxidation, which gives corresponding monohydroxylated, dihydroxylated, and trihydroxylated metabolites; (2) along with oxidation, there is a possibility of elimination of water molecule (dehydration) from the third position of the tropine moiety, resulting in the dehydrated analogs of corresponding monohydroxylated, dihydroxylated, and trihydroxylated metabolites; (3) from the study on the metabolites using LC‐MS/MS, it is clear that the fragmentation pattern is identical and a great number of fragment ions are common in all the metabolites and the parent drug. (4) The ACP‐105 and its metabolites were detected for up to 72 h; thus, the result is a valuable tool for evaluating its use and/or misuse in sport.
Formation of the rete testis during mouse embryonic development
Authors: Kulibin Andrey Yu. , Malolina Ekaterina A. 
Published: August 2020

AbstractBackgroundThe rete testis connects seminiferous tubules of the testis with efferent ducts having a mesonephric origin. The development of the rete testis is insufficiently studied, but there is evidence suggesting that it originates from gonadal cells. Here, the formation of the rete testis was investigated from E11.5 to E16.5 using immunofluorescent staining and 3D‐modeling.ResultsThe rete testis became visible by SOX9 and PAX8 staining starting from E12.5. It was located in the mesonephros but connected with testis cords formed by Sertoli cells expressing SOX9, AMH, DMRT1. Between E13.5 and E14.5, AMH+ network of testis cords at the mesonephric side began to disintegrate in a gradient‐dependent manner along the anterior‐posterior axis of the gonad and connections between testis cords gradually lost AMH becoming a part of the rete. Cells combining features of Sertoli and rete cells (PAX8+ AMH+ and DMRT1+ AMH− cells) were detected starting from E14.5, suggesting that some rete cells originated from Sertoli cells. The rete ovarii, a female counterpart of the rete testis, developed in a similar way as the rete testis until E13.5.ConclusionsA part of the rete testis originates from connections between testis cords. Evidence that Sertoli cells contribute to rete cells is provided.
Expander design procedures and selection criterion for small rated organic rankine cycle systems
Authors: Capata Roberto , Pantano Fabio 
Published: August 2020

AbstractThe particular aspect of this work is the new approach to expander design procedure for small rated ORC. In fact, once all the calculation procedures have been defined, they have been implemented in Matlab code. This code, once the design process is complete, provides an indication of the optimal expander configuration to adopting to that specific system. For these reasons, this paper aims to analyze all the preliminary expanders' design procedures, both dynamic and volumetric. The reasons lie in the development of low‐enthalpy heat recovery systems (systems that allow simultaneous production of electrical and thermal energy made available in the form of water at a temperature of 60‐90°C), with the aim of optimizing any energy system. Within these energy systems, the expander is the main component, responsible for power generation. It is, therefore, necessary and useful to analyze in detail every expander configuration, highlighting the different features. For each component will be described the theory on which is based the choice and its design and a possible software implementation is supplied. Finally, a criterion for the choice of the optimal expander is proposed, based on some operational considerations and other construction and structural constraints, such as overall dimensions and weight, lubrication, MTBF, feasibility, reliability, and coupling with the electric generator.
Bipolar fully recurrent deep structured neural learning based attack detection for securing industrial sensor networks
Authors: Alzubi Jafar A. 
Published: August 2020

AbstractAttack detection is a significant problem to be resolved to attain security in industrial sensor network. Few research works have been designed for performing attack discovery process with the help of different classification algorithms. However, classification performance was lowered to accurately find attack nodes and thereby getting higher security level (SL). In order to overcome such limitations, bipolar fully recurrent deep structured neural learning based attack detection (BFRDSNL‐AD) technique is proposed in this article. The BFRDSNL‐AD technique comprises of three main layers, namely, input, hidden, and output layer to accurately carry‐out attack detection process. The input layer in BFRDSNL‐AD Technique takes a number of sensor nodes as input. The designed BFRDSNL‐AD technique utilized numbers of hidden layers in order to deeply examine each sensor node in industrial sensor network. The result of the hidden layer is fed‐back into the network along with the inputs in order to discover the temporal dynamic behavior of sensor nodes. In BFRDSNL‐AD technique, output layer applies bipolar activation function to determine the association between identified node features to give attack detection result. If the output layer result is 1, then sensor node is considered as normal. Otherwise, sensor node is considered as malicious attack in industrial sensor network. Thus, the BFRDSNL‐AD technique increases the attack detection performance with higher accuracy and minimal time. From that, BFRDSNL‐AD technique gets enhanced SL in industrial sensor network. The simulation of BFRDSNL‐AD technique is conducted using metrics such as security, data delivery rate, data loss rate, and delay with respect to a different number of sensor nodes and data packets.