bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ensemble Adaboost classifier for accurate and fast detection of botnet attacks in connected vehicles
Authors: Rehman Javed Abdul , Jalil Zunera , Atif Moqurrab Syed , Abbas Sidra , Liu Xuan 
Published: August 2020

AbstractThe key characteristic of smart cities (ie, connectivity and intelligence) has enabled connected vehicles to work together to accomplish complex jobs that they are unable to perform individually. Connectivity not only being an inevitable blessing but also poses growing cybersecurity challenges for connected vehicles. The overall risk of connected vehicles is wide as the cybercriminals are nowadays applying versatile approaches (botnets, phishing, zero‐days, rootkits, etc) to disrupt their communication. The botnet, capable of launching distributed denial of service attack, is a potential threat for any connected ecosystem due to its excessive capabilities of using maximum compromised devices. Hence, the detection of botnet attacks has become a pinnacle point for cybersecurity analysts. Existing studies lack in detecting botnet at the earliest and accurately. This article presents an approach to detect the botnet attacks at an early stage and accurately utilizing typical network traffic and temporal features. The proposed approach use machine learning algorithms for the detection of botnet attack(s) and present a detailed comparison of the decision tree, probabilistic neural network, sequential minimal optimization, and Adaboost classifiers, as well as comparison of the proposed approach with existing studies in this domain, is also done. Furthermore, it investigates the role of temporal features for botnet detection. The proposed approach accomplishes the promising true positive rate of 99.7%. Results show that our methodology is efficient compared with the existing studies.
Yes‐Associated Protein Is Crucial for Constitutive Androstane Receptor‐Driven Hepatocyte Proliferation But Not for Induction of Drug Metabolism Genes in Mice
Authors: Bhushan Bharat , Molina Laura , Koral Kelly , Stoops John W. , Mars Wendy M. , Banerjee Swati , Orr Anne , Paranjpe Shirish , Monga Satdarshan P. , Locker Joseph , Michalopoulos George K. 
Published: August 2020

Background and Aims
Constitutive androstane receptor (CAR) agonists, such as 1,4‐bis [2‐(3,5‐dichloropyridyloxy)] benzene (TCPOBOP), are known to cause robust hepatocyte proliferation and hepatomegaly in mice along with induction of drug metabolism genes without any associated liver injury. Yes‐associated protein (Yap) is a key transcription regulator that tightly controls organ size, including that of liver. Our and other previous studies suggested increased nuclear localization and activation of Yap after TCPOBOP treatment in mice and the potential role of Yap in CAR‐driven proliferative response. Here, we investigated a direct role of Yap in CAR‐driven hepatomegaly and hepatocyte proliferation using hepatocyte‐specific Yap‐knockout (KO) mice.

Approach and Results
Adeno‐associated virus 8‐thyroxine binding globulin promoter‐Cre recombinase vector was injected to Yap‐floxed mice for achieving hepatocyte‐specific Yap deletion followed by TCPOBOP treatment. Yap deletion did not decrease protein expression of CAR or CAR‐driven induction of drug metabolism genes (including cytochrome P450 [Cyp] 2b10, Cyp2c55, and UDP‐glucuronosyltransferase 1a1 [Ugt1a1]). However, Yap deletion substantially reduced TCPOBOP‐induced hepatocyte proliferation. TCPOBOP‐driven cell cycle activation was disrupted in Yap‐KO mice because of delayed (and decreased) induction of cyclin D1 and higher expression of p21, resulting in decreased phosphorylation of retinoblastoma protein. Furthermore, the induction of other cyclins, which are sequentially involved in progression through cell cycle (including cyclin E1, A2, and B1), and important mitotic regulators (such as Aurora B kinase and polo‐like kinase 1) was remarkably reduced in Yap‐KO mice. Microarray analysis revealed that 26% of TCPOBOP‐responsive genes that were mainly related to proliferation, but not to drug metabolism, were altered by Yap deletion. Yap regulated these proliferation genes through alerting expression of Myc and forkhead box protein M1, two critical transcriptional regulators of CAR‐mediated hepatocyte proliferation.

Conclusions
Our study revealed an important role of Yap signaling in CAR‐driven hepatocyte proliferation; however, CAR‐driven induction of drug metabolism genes was independent of Yap.
Influence of carbon nanotubes on heat transfer in MHD nanofluid flow over a stretchable rotating disk: A numerical study
Authors: Iqbal Muhammad S. , Mustafa Irfan , Riaz Iram , Ghaffari Abuzar , Khan Waqar A. 
Published: August 2020

AbstractThe transfer of heat is an important phenomenon in the several areas due to its numerous applications in industries. Several fluids like water, ethylene glycol and oil, and so on have very‐low thermal conductivities due to which the transfer of heat in these fluids become very low. To enhance heat transfer rate, carbon nanotubes (CNTs) including single‐walled CNTs and multi‐walled CNTs are suspended into base fluids, this mixture is known as nanofluid. The aim of this study is to examine the heat transfer rate of nanofluid in the presence of CNTs over a stretchable rotating disk. The mathematical model, developed by Tiwari and Das, is used and solved numerically by using the shooting method. The impacts of governing constraints on the dimensionless velocities, temperature, skin friction, and Nusselt number are investigated. It is noted that heat transfer rate increases by enhancing the concentration of CNTs into base fluids. The numerical results show that the solid volume fraction of the CNTs augment heat transfer rate more in ethylene glycol as compared with water.
MHD mixed convective radiative flow of Eyring‐Powell fluid over an oscillatory stretching sheet using bivariate spectral method on overlapping grids
Authors: Mkhatshwa Musawenkhosi P. , Motsa Sandile S. , Sibanda Precious 
Published: August 2020

AbstractThe bivariate spectral quasilinearization method (BSQLM) on overlapping grids is presented and applied in the analysis of unsteady magnetohydrodynamic mixed convection flow of Eyring‐Powell fluid over an oscillatory stretching sheet embedded in a non‐Darcy porous medium with nonlinear radiative heat flux and variable thermophysical properties. The fluid properties, namely the fluid viscosity, thermal conductivity, and mass diffusivity, are assumed to vary with temperature. It is assumed that the first‐order chemical reaction with heat generation/absorption takes place in the flow. The flow domain is subject to uniform transverse magnetic field perpendicular to the stretching surface. The transformed flow equations are solved numerically using BSQLM on overlapping grids. The convergence properties and accuracy of the method are assessed. The proposed method is computationally efficient, and it gives stable and highly accurate results after few iterations and using few grid points in each subinterval. The improved accuracy rests upon the use of the overlapping grid, which produces sparse coefficient matrices that are easy to invert and have small condition numbers. The effects of physical parameters on the flow fields, local skin friction, the Nusselt number, and the Sherwood number are exhibited through graphs and tables. Amongst other findings, we found that the amplitude of the fluid flow along with flow characteristics may efficiently improve through the utilization of variable fluid viscosity. Heat and mass transportation processes enhance with the inclusion of nonlinear radiative heat flux, temperature‐dependent thermal conductivity, and mass diffusion coefficient, whereas they diminish with the increase in the local inertia coefficient. The current flow analysis can be useful in various engineering applications including paper production, polymer solution, glass blowing, extrusion of thermal system manufacturing process, and heat transportation enhancement.
Determining the causality between U.S. presidential prediction markets and global financial markets
Authors: Abolghasemi Yaser , Dimitrov Stanko 
Published: August 2020

AbstractPrediction markets trade securities with final prices contingent on the outcome of future events, for example, who will win the next political election. We show how the outcome of a United States presidential election, information captured by prediction markets, impacts global financial markets. We investigate the existence of a causal relationship between various prediction markets and global financial markets time series for over 27 different countries and regions using Dow Jones Global Indexes. We construct vector auto‐regressive models and use the Toda–Yamamoto causality test to deal with non‐stationary time series. Preliminary results indicate that prediction markets may be used to predict some global financial markets.
Bioethics training in reproductive health in Mexico
Authors: Ortiz‐Millán Gustavo , Kissling Frances 
Published: August 2020

AbstractBioethical approaches to reproductive health have been of utmost importance for the last three decades in Mexico. As Mexican laws regarding abortion, assisted reproduction, and conscientious objection have been modified, a number of social actors with an interest in these areas have realized that they have to educate the different agents who take part in these procedures in a bioethical approach to reproductive health and rights. This strategy was first used in Mexico by the Catholic Church and many Catholic universities. Advocates, scientists, and feminist organizations, as well as some public universities, have also realized that a grounding in bioethics could help health providers to have an ethical frame that supports the provision of abortion services. Bioethics is also a good framework for supporting the legalization of abortion and for more liberal laws regarding assisted reproduction. So, for the last few years, one of the priorities of these two sides, Catholic and secular groups, has been to train healthcare personnel, lawyers, and members of ethics committees and members of Congress in the application of their respective bioethical perspectives.
IL‐18 and infections: Is there a role for targeted therapies?
Authors: Vecchié Alessandra , Bonaventura Aldo , Toldo Stefano , Dagna Lorenzo , Dinarello Charles A. , Abbate Antonio 
Published: August 2020

AbstractInterleukin (IL)‐18 is a pro‐inflammatory cytokine belonging to the IL‐1 family, first identified for its interferon‐γ‐inducing properties. IL‐18 regulates both T helper (Th) 1 and Th2 responses. It acts synergistically with IL‐12 in the Th1 paradigm, whereas with IL‐2 and without IL‐12 it can induce Th2 cytokine production from cluster of differentation (CD)4+ T cells, natural killer (NK cells, NKT cells, as well as from Th1 cells. IL‐18 also plays a role in the hemophagocytic lymphohistiocytosis, a life‐threatening condition characterized by a cytokine storm that can be secondary to infections. IL‐18‐mediated inflammation was largely studied in animal models of bacterial, viral, parasitic, and fungal infections. These studies highlight the contribution of either IL‐18 overproduction by the host or overresponsiveness of the host to IL‐18 causing an exaggerated inflammatory burden and leading to tissue injury. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is responsible for the coronavirus disease 2019 (COVID‐19). The damage in the later phase of the disease appears to be driven by a cytokine storm, including interleukin IL‐1 family members and secondary cytokines like IL‐6. IL‐18 may participate in this hyperinflammation, as it was previously found to be able to cause injury in the lung tissue of infected animals. IL‐18 blockade has become an appealing therapeutic target and has been tested in some IL‐18‐mediated rheumatic diseases and infantile‐onset macrophage activation syndrome. Given its role in regulating the immune response to infections, IL‐18 blockade might represent a therapeutic option for COVID‐19, although further studies are warranted to investigate more in detail the exact role of IL‐18 in SARS‐CoV‐2 infection.
The flavonoids of Sophora flavescens exerts anti-inflammatory activity via promoting autophagy of Bacillus Calmette-Guérin-stimulated macrophages
Authors: Kan Lea Ling-Yu , Liu Dehua , Chan Ben Chung-Lap , Tsang Miranda Sin-Man , Hou Tianheng , Leung Ping Chung , Lam Christopher Wai-Kei , Wong Chun Kwok 
Published: August 2020

Abstract
Tuberculosis (TB), a highly infectious air-borne disease, has remained a global health problem. Conventional treatment and preventions such as antibiotics and Bacilli Calmette-Guerin (BCG) vaccine can be unreliable. In view of the increasing prevalence of anti-TB drug resistance, adjunctive therapy may be necessary to shorten the recovery time. We have previously shown that flavonoids in the medicinal herb Sophora flavescens exhibit anti-inflammatory and bactericidal activities. The aim of this study was to investigate the molecular and cellular characteristics of flavonoids of S. flavescens (FSF) in BCG-stimulated macrophages for assessing their roles in anti-inflammation and autophagy. Mouse alveolar macrophage (MH-S) cell line and primary mouse peritoneal macrophages were stimulated in vitro with heat-inactivated BCG and treated with FSF, with or without autophagy inhibitor Bafilomycin A1 (BafA1). Gene expression was analyzed using quantitative PCR, and cytokine/chemokine release was analyzed by Milliplex assay and ELISA. Autophagy-related proteins were quantified by Western blot and flow cytometry, and autophagolysosomes were detected using fluorescence microscopy. In both MH-S cell line and mouse peritoneal macrophages stimulated by heat-inactivated BCG, FSF was found to up-regulate autophagy-related proteins microtubule-associated protein 1A/1B-light chain 3 (LC3) and protein 62 (p62), and suppress the induced proinflammatory cytokine TNF-α, CCL5, and IL-6. FSF actively modulates immune processes through suppressing BCG-mediated inflammation by promoting autophagy in MH-S cells and mouse peritoneal macrophages. We suggest that FSF may be useful as an adjunctive therapeutic agent for TB infection by modulating cell survival through autophagy and reducing inflammation.
Mismatch between circulating cytokines and spontaneous cytokine production by leukocytes in hyperinflammatory COVID-19
Authors: Kahn Robin , Schmidt Tobias , Golestani Karan , Mossberg Anki , Gullstrand Birgitta , Bengtsson Anders A , Kahn Fredrik 
Published: August 2020

Abstract
The disease COVID-19 has developed into a worldwide pandemic. Hyperinflammation and high levels of several cytokines, for example, IL-6, are observed in severe COVID-19 cases. However, little is known about the cellular origin of these cytokines. Here, we investigated whether circulating leukocytes from patients with COVID-19 had spontaneous cytokine production. Patients with hyperinflammatory COVID-19 (n = 6) and sepsis (n = 3) were included at Skåne University Hospital, Sweden. Healthy controls were also recruited (n = 5). Cytokines were measured in COVID-19 and sepsis patients using an Immulite immunoassay system. PBMCs were cultured with brefeldin A to allow cytokine accumulation. In parallel, LPS was used as an activator. Cells were analyzed for cytokines and surface markers by flow cytometry. High levels of IL-6 and measurable levels of IL-8 and TNF, but not IL-1β, were observed in COVID-19 patients. Monocytes from COVID-19 patients had spontaneous production of IL-1β and IL-8 (P = 0.0043), but not of TNF and IL-6, compared to controls. No spontaneous cytokine production was seen in lymphocytes from either patients or controls. Activation with LPS resulted in massive cytokine production by monocytes from COVID-19 patients and healthy controls, but not from sepsis patients. Finally, monocytes from COVID-19 patients produced more IL-1β than from healthy controls (P = 0.0087) when activated. In conclusion, monocytes contribute partly to the ongoing hyperinflammation by production of IL-1β and IL-8. Additionally, they are responsive to further activation. This data supports the notion of IL-1β blockade in treatment of COVID-19. However, the source of the high levels of IL-6 remains to be determined.
Natural killer cell impairment in ovarian clear cell carcinoma
Authors: Patrizi Ornella , Rampinelli Fabio , Coltrini Daniela , Pesce Silvia , Carlomagno Simona , Sivori Simona , Pascale Andre , Marcenaro Emanuela , Parolini Silvia , Tabellini Giovanna 
Published: August 2020

Abstract
In the present study, we report the analysis of NK cells derived from patients suffering from a rare ovarian cancer histotype of clear cell carcinoma (OCCC) resistant to conventional chemotherapies. We analyzed the phenotype of NK cells derived from peripheral blood (PB) and peritoneal fluid (PF) and evaluated cytotoxic interactions between NK cells and autologous tumor cells (ATC) derived from patients. We provided evidence of impaired degranulation capacity of NK cells derived from patients’ PF in the presence of ATC. Analyzing tumor cell ligands recognized by NK cell receptors, we found that ATC are characterized by an HLA class I+ phenotype (although the level of HLA-I expression varies among all patients) and by a heterogeneous expression of ligands for activating NK receptors (from normal to decreased expression of some markers). Furthermore, we observed a down-regulation of crucial NK cell activating receptors, primarily DNAX Accessory Molecule-1 (DNAM-1), on tumor-associated NK cells. Based on these results, we propose that this severe lysis defect may be due to both negative interactions between HLA-I-specific inhibitory NK cell receptors/HLA-I molecules and to defective interactions between activating NK receptors and cognate ligands. In conclusion, for the first time, the phenotypic and functional properties of tumor-associated NK cells and their ATC derived from PF of patients with advanced stage of OCCC were characterized. Taken together results indicate altered interactions between NK cells and ATC and shed light on the aggressive mechanisms of this cancer histotype. Further studies on this rare tumor will be helpful to improve and define more effective therapies.
What are the predictors of emergency department utilization and readmission following extremity bone sarcoma resection?
Authors: Wellings Elizabeth P. , Wagner Eric R. , Wilke Benjamin K. , Asante Dennis , Sangaralingham Lindsey R. , Rose Peter S. , Moran Steven L. , Houdek Matthew T. 
Published: August 2020

AbstractIntroductionTreatment for bone sarcomas are large undertakings. Emergency department (ED) visits and unplanned hospital readmissions are a potential target for cost containment. The purpose of this study was to evaluate the risk factors for ED visits and unplanned readmissions following extremity bone sarcoma surgery.MethodsData from Optum Labs Data Warehouse, a national administrative claims database, was analyzed to identify patients with extremity bone sarcomas from 2006 to 2017. Multivariable logistic regression was used to identify factors associated with ED visits and readmissions.ResultsOf 1390 (743 males, 647 female) adult patients, 137 (12%) visited the ED and 245 (18%) were readmitted within 30 days of discharge. The most common indication for ED visits (n = 63, 45.9%) and readmission (n = 119, 48.5%) were complications of surgery. Length of stay >10 days was associated with ED utilization (OR, 1.83; P = .01) and readmission (OR, 4.47; P < .001).ConclusionOne in ten patients will use the ED, and one in five patients will be readmitted to the hospital within 30 days of discharge following extremity bone sarcoma surgery. Length of stay was associated with ED visits and readmission. These patients could be targeted with alternative management strategies in the outpatient setting with early clinical follow‐up to minimize readmission.
Isoindigo (IID)‐Based Semiconductor with F⋯S Interaction Locked Conformation for High‐Performance Ambipolar Bottom‐Gate Top‐Contact Field‐Effect Transistors
Authors: Qiao Xiaolan , Wei Qibing , Wu Hongzhuo , Li Hongxiang 
Published: August 2020

AbstractThe development of high‐performance ambipolar polymer semiconductors is critical to organic electronics. Herein, isoindigo (IID)‐based copolymers PIIDDTBT and PIIDDTffBT are synthesized and characterized. Both polymers have suitable highest occupied molecular orbital and lowest unoccupied molecular orbital energy levels for hole and electron injection. Density functional theory calculation reveals F⋯S intramolecular interactions are formed in PIIDDTffBT, which locks the molecular conformation and leads to a more planar backbone. Thin film transistor characterization shows both polymers display ambipolar charge carrier transport behavior. The hole/electron mobilities are 0.29/0.1 cm2 V−1 s−1 for PIIDDTffBT and 0.053/0.013 cm2 V−1 s−1 for PIIDDTBT in the bottom‐gate/top‐contact (BGTC) device structures. The hole/electron mobilities of PIIDDTffBT are one of the highest values for IID‐based ambipolar polymer transistors in BGTC device structure. Atomic force microscopy and X‐ray diffraction results reveal PIIDDTffBT films have higher film quality, crystallinity, and more ordered microstructures, being ascribed to the F⋯S interactions locked backbone. These results demonstrate that the introduction of F⋯S interactions is an effective strategy to design high‐performance ambipolar polymer semiconductors.
SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain‐dependent regulation of Wnt/β‐catenin signaling
Authors: Chen Luyao , Xie Yongpeng , Ma Xin , Zhang Yu , Li Xintao , Zhang Fan , Gao Yu , Fan Yang , Gu Liangyou , Wang Lei , Zhang Xu , Fu Bin 
Published: August 2020

AbstractSex‐determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, SOX6 expression in ccRCC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor‐related function and the underlying molecular mechanism of SOX6 in ccRCC. We confirmed that SOX6 was frequently downregulated in ccRCC tissues and cell lines. Besides, downregulation of SOX6 was significantly associated with larger tumor sizes, advanced tumor stage, higher Fuhrman grades, and its expression could act as an independent prognostic factor for ccRCC (hazards ratio = 0.590, P = .026). Gain/loss‐of‐function experiments demonstrated that SOX6 could remarkably inhibit tumor cell growth and foci formation in vitro and xenograft tumorigenesis in vivo, respectively. Mechanistically, SOX6 could influence cell cycle by regulating the G1/the S phase transition and had an inhibitory effect on Wnt/β‐catenin signaling as well as its target genes, c‐Myc and cyclin D1. Interesting, the tumor‐suppressive function of SOX6 was proved to be dependent on its specific high‐mobility‐group (HMG) domain. In general, our findings indicated that SOX6 was a novel tumor suppressor and prognostic biomarker in ccRCC. SOX6 could inhibit tumor growth by negatively regulating the Wnt/β‐catenin signaling pathway in an HMG domain‐dependent manner in ccRCC, which might provide a novel therapeutic approach for ccRCC.