bluuebunny/crossref_metadata_2025_split huggingface dataset:
NLRP3 inflammasome priming: A riddle wrapped in a mystery inside an enigma
Authors: McKee Chloe M , Coll Rebecca C 
Published: August 2020

Abstract
The NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome is an immunological sensor that detects a wide range of microbial- and host-derived signals. Inflammasome activation results in the release of the potent pro-inflammatory cytokines IL-1β and IL-18 and triggers a form of inflammatory cell death known as pyroptosis. Excessive NLRP3 activity is associated with the pathogenesis of a wide range of inflammatory diseases, thus NLRP3 activation mechanisms are an area of intensive research. NLRP3 inflammasome activation is a tightly regulated process that requires both priming and activation signals. In particular, recent research has highlighted the highly complex nature of the priming step, which involves transcriptional and posttranslational mechanisms, and numerous protein binding partners. This review will describe the current understanding of NLRP3 priming and will discuss the potential opportunities for targeting this process therapeutically to treat NLRP3-associated diseases.
Baicalin attenuated Mycoplasma gallisepticum‐induced immune impairment in chicken bursa of fabricius through modulation of autophagy and inhibited inflammation and apoptosis
Authors: Ishfaq Muhammad , Zhang Wei , Liu Yuhao , Wang Jian , Wu Zhiyong , Shah Syed WA , Li Rui , Miao Yusong , Chen Chunli , Li Jichang 
Published: July 2020

AbstractBACKGROUNDMycoplasma gallisepticum (MG) is the primary etiologic agent of chronic respiratory disease in poultry. However, the mechanism underlying MG‐induced immune dysregulation in chicken is still elusive. Baicalin shows excellent anti‐bacterial, anti‐inflammatory, anti‐carcinogenic and anti‐viral properties. In the present study, the preventive effects of baicalin against immune impairment in chicken bursa of fabricius (BF) were studied in an MG infection model.RESULTSHistopathological examination showed increased inflammatory cell infiltrations and fragmented nuclei in the model group. Ultrastructural analysis revealed the phenomenon of apoptosis in bursal cells, along with the deformation of mitochondrial membrane and swollen mitochondria in the model group. However, these abnormal morphological changes were partially alleviated by baicalin. Meanwhile, baicalin treatment attenuated the level of proinflammatory cytokines, and suppressed nuclear factor‐kappa B expression at both protein and mRNA level. Terminal deoxynucleotidyl transferase‐mediated dUTP nick endlabeling assay showed extensive apoptosis in BF in the model group. The mRNA and protein expression levels of apoptosis‐related genes were upregulated in BF, while baicalin treatment significantly alleviated apoptosis in BF. In addition, alterations in mRNA and protein expression levels of autophagy‐related genes and mitochondrial dynamics proteins were significantly alleviated by baicalin. Moreover, baicalin treatment significantly attenuated MG‐induced decrease in CD8+ cells and reduced bacterial load in chicken BF compared to the model group.CONCLUSIONSThese results suggested that baicalin could effectively inhibit MG‐induced immune impairment and alleviate inflammatory responses and apoptosis in chicken BF. © 2020 Society of Chemical Industry
A novel dextran‐grafted tetrapeptide resin for antibody purification
Authors: Fang Yu‐Ming , Zhu Hong‐Yun , Lin Dong‐Qiang , Yao Shan‐Jing 
Published: July 2020

AbstractShort peptide biomimetic affinity chromatography as a novel antibody separation chromatography is a potential alternative to protein A chromatography. However, if directly attaching ligand to matrix, the adsorption capacity and mass transfer rate would be affected by pore blockage and steric effect. Grafting resin is an effective method to solve this problem by using polymer as a bridge between matrix and ligand. In this work, a novel resin was prepared by grafting a tetrapeptide to the dextran‐grafted matrix. Then, the adsorption properties for human immunoglobin G and BSA were determined. The results showed the saturation adsorption capacity could reach to 133 mg/g resin at pH 8.9 with a significantly low dissociation constant (0.03 mg/mL). The influence of flow rates to dynamic binding capacity of this resin was less than that of the non‐grafted resin. The separation performance of the resin showed monoclonal antibody could be well isolated from the Chinese hamster ovary culture supernatant at pH 9.0 with the purity of 93.0% and yield of 84.7% by one step. Overall, this resin could achieve higher binding capacity by the possible of gaining higher ligand density, indicating its potential significance for separation in larger scale systems.
Biologically active isoquinoline alkaloids covering 2014–2018
Authors: Shang Xiao‐Fei , Yang Cheng‐Jie , Morris‐Natschke Susan L. , Li Jun‐Cai , Yin Xiao‐Dan , Liu Ying‐Qian , Guo Xiao , Peng Jing‐Wen , Goto Masuo , Zhang Ji‐Yu , Lee Kuo‐Hsiung 
Published: July 2020

AbstractIsoquinoline alkaloids, an important class of N‐based heterocyclic compounds, have attracted considerable attention from researchers worldwide since the early 19th century. Over the past 200 years, many compounds from this class were isolated, and most of them and their analogs possess various bioactivities. In this review, we survey the updated literature on bioactive alkaloids and highlight research achievements of this alkaloid class during the period of 2014–2018. We reviewed over 400 molecules with a broad range of bioactivities, including antitumor, antidiabetic and its complications, antibacterial, antifungal, antiviral, antiparasitic, insecticidal, anti‐inflammatory, antioxidant, neuroprotective, and other activities. This review should provide new indications or directions for the discovery of new and better drugs from the original naturally occurring isoquinoline alkaloids.
Network anomaly detection using a cross‐correlation‐based long‐range dependence analysis
Authors: AsSadhan Basil , Alzoghaiby Abraham , Binsalleeh Hamad , Kyriakopoulos Konstantinos G. , Lambotharan Sangarapillai 
Published: July 2020

SummaryThe detection of anomalies in network traffic is an important task in today's Internet. Among various anomaly detection methods, the techniques based on examination of the long‐range dependence (LRD) behavior of network traffic stands out to be powerful. In this paper, we reveal anomalies in aggregated network traffic by examining the LRD behavior based on the cross‐correlation function of the bidirectional control and data planes traffic. Specifically, observing that the conventional cross‐correlation function has a low measure of dissimilarity between the two planes, which leads to a reduced anomaly detection performance, we propose a modification of the cross‐correlation function to mitigate this issue. The performance of the proposed method is analyzed using a relatively recent Internet traffic captured at King Saud University. The results demonstrate that using the modified cross‐correlation function has the ability to detect low volume and short duration attacks. It also compensates for some misdetections exhibited by using the autocorrelation structures of the bidirectional traffic of the control, data, and WHOLE (combined control and data) planes traffic.
Delay‐dependentrobust control of stochastic systems with convex polynomial uncertainty
Authors: Chang Wen‐Jer , Ku Cheung‐Chieh , Hsu Chih‐Yuan , Chen Guan‐Wei 
Published: August 2020

SummaryThis article addresses a robust control problem of time‐varying stochastic systems with time‐delays. Through Linear Parameter Varying (LPV) modeling approach, the time‐varying parameters can be described via the convex combination. Therefore, the LPV stochastic system is interpreted by a weighting function and multiplicative noised linear systems. Furthermore, stabilization problem for the systems is investigated via Gain‐Scheduled (GS) technique to increase robustness. For the problem, some sufficient conditions are derived by Integral Lyapunov‐Krasovskii Function (ILKF) such that the conservatism caused by derivative of weighting function is ignored. Besides, an Iterative Linear Matrix Inequality algorithm is used to determine the auxiliary variable such that the problem can be solved via the convex calculation. Finally, some simulations are provided to demonstrate effectiveness and applicability of this article.
Global pediatric radiation therapy in resource‐limited settings
Authors: Hess Clayton B. , Parkes Jeannette , Janssens Geert O. , Lin Chi , Wong Kenneth , Zaghloul Mohamed S. , Marconi Daniel G. , Boterberg Tom , Esiashvili Natia 
Published: August 2020

AbstractThis report provides a summary of the global burden of childhood cancer morbidity and mortality, which disproportionately affects low‐ and middle‐income countries as well as low‐ and middle‐income communities within high‐income countries. We review past successes and current challenges to improving clinical pediatric radiotherapy, education, and research in these regions. The Pediatric Radiation Oncology Society Taskforce in Low‐ and Middle‐Income Countries recently outlined specific aims: (a) to increase access and quality of radiotherapy for children and adolescents afflicted with cancer; (b) to enumerate, engage, and educate a global community of providers of childhood and adolescent radiotherapy; and (c) to create evidence establishing the outcomes of setting‐specific treatment standards of care when first‐world standards are not achievable. This report will improve awareness of these disparities and promote attempts to correct them.
Circulating tumor DNA in neuroblastoma
Authors: Wei Meng , Ye Mujie , Dong Kuiran , Dong Rui 
Published: July 2020

AbstractAs a sympathetic nervous system–derived tumor, aggressive neuroblastoma (NB) is currently attracting interest from researchers seeking diagnostic and prognostic markers via less invasive procedures. The analysis of circulating tumor DNA (ctDNA) in peripheral blood can provide genetic information from multiple tumor lesions and is not dependent on a surgical procedure. The identification of genetic alterations, chromosomal variations, and hypermethylation contained within plasma DNA yields clinical value in the diagnosis, risk stratification, monitoring of treatment effects, and survival prediction for patients. With the widespread application of genome sequencing, droplet digital polymerase chain reaction, and other advanced technologies, the detection of ctDNA may guide therapeutic schedules, enhance the quality of life, and improve the prognosis for patients with NB.
No benefit of Interfant protocols compared to BFM‐based protocols for infants with acute lymphoblastic leukemia. Results from an institution in Argentina
Authors: Pennella Carla L. , Deu María A. , Rossi Jorge G. , Baialardo Edgardo M. , Alonso Cristina N. , Rubio Patricia , Guitter Myriam R. , La Rosa Cristian G. Sánchez , Alfaro Elizabeth M. , Zubizarreta Pedro A. , Felice María S. 
Published: July 2020

AbstractBackgroundInfant acute lymphoblastic leukemia (ALL) is an infrequent disease characterized by clinical and biological features related to poor prognosis. Adapted therapies were designed without a clear consensus regarding the best treatment options. We aimed to compare the outcome between infant ALL cases receiving Interfant versus BFM‐based protocols.ProcedureThis is a retrospective observational study. From April 1990 to June 2018, infant ALL cases were enrolled in one of the five consecutive treatment protocols. Clinical, demographic, and biological features and outcome were evaluated. A comparative analysis was performed between Interfant protocols and BFM‐based protocols.ResultsDuring the studied period, 1913 ALL patients were admitted and 116 (6%) were infants. Treatment administered was: ALL‐BFM’90 (n = 16), 1‐ALL96‐BFM/HPG (n = 7), Interfant‐99 (n = 39), Interfant‐06 (n = 35), and ALLIC‐BFM’2009 (n = 19). The 5‐year event‐free survival probability (EFSp) was 31.9(standard error [SE] 4.6)% for the entire population, with a significant difference among risk groups according to Interfant‐06 criteria (P = .0029). KMT2A‐rearrangement status was the strongest prognostic factor (P = .048), independently of the protocol strategy. The median time for relapse was 24.1 months for patients with minimal residual disease (MRD)‐negative versus 11.5 months for those with MRD‐positive (P = .0386). EFSp and cumulative relapse risk probability (CRRp) were similar. Interfant protocols showed comparable induction (8.1% vs 7.1%, P = .852) and complete remission mortality (21.6% vs 28.6%, P = .438), failing to reduce the relapse rate (48.5% vs 30.7%, P = .149).ConclusionsInterfant protocols and BFM‐based protocols presented comparable results. The risk group stratification proposed by Interfant‐06 was validated by our results, and MRD seems useful to identify patients with an increased risk of early relapse.
ADAS Sensors and Computing: A 22 Billion Dollar Market in 2025
Authors: Boulay Pierrick , Malaquin Cédric 
Published: August 2020

AbstractAdvanced driving assistance systems (ADAS) based on a combination of sensors and electronic control units (ECUs) have been developed to support the driver. These systems have helped to reduce road fatalities, alert the driver to potential problems and to avoid collisions.
Remdesivir: A beacon of hope from Ebola virus disease to COVID‐19
Authors: Nili Ali , Farbod Abolfazl , Neishabouri Afarin , Mozafarihashjin Mohammad , Tavakolpour Soheil , Mahmoudi Hamidreza 
Published: July 2020

SummarySince the emergence of coronavirus disease 2019 (Covid‐19), many studies have been performed to characterize severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and find the optimum way to combat this virus. After suggestions and assessments of several therapeutic options, remdesivir (GS‐5734), a direct‐acting antiviral drug previously tested against Ebola virus disease, was found to be moderately effective and probably safe for inhibiting SARS‐CoV‐2 replication. Finally, on 1 May 2020, remdesivir (GS‐5734) was granted emergency use authorization as an investigational drug for the treatment of Covid‐19 by the Food and Drug Administration. However, without a doubt, there are challenging days ahead. Here, we provide a review of the latest findings (based on preprints, post‐prints, and news releases in scientific websites) related to remdesivir efficacy and safety for the treatment of Covid‐19, along with covering remdesivir history from bench‐to‐bedside, as well as an overview of its mechanism of action. In addition, active clinical trials, as well as challenging issues related to the future of remdesivir in Covid‐19, are covered. Up to the date of writing this review (19 May 2020), there is one finished randomized clinical trial and two completed non‐randomized studies, in addition to some ongoing studies, including three observational studies, two expanded access studies, and seven active clinical trials registered on the clinicaltrials.gov and isrctn.com websites. Based on these studies, it seems that remdesivir could be an effective and probably safe treatment option for Covid‐19. However, more randomized controlled studies are required.
The sociocultural dimension of the Software Process Improvement Manifesto: Pilot validation by experts
Authors: Georgiadou Elli , Siakas Kerstin , Berki Eleni , Estdale John , Rahanu Harjinder , Ross Margaret 
Published: July 2020

AbstractThe Software Process Improvement (SPI) Manifesto is based on three basic values: people, business focus and organisational change underpinning the philosophy of SPI. In turn, these values bring up to date certain SPI principles serving as a foundation for action in software development. The authors of this paper carried out a pilot expert validation of the sociocultural dimension of the sociocultural, technical, economic, environmental, political, legal, ethical and demographic analysis of the SPI Manifesto. Further, the authors report on the rationale and results of the pilot validation of both the survey instrument and the qualitative responses generated by the field experts, targeting to enlighten and reinforce the importance of the sociocultural dimension of the SPI Manifesto in research and development. The related literature review findings and the pilot research study strengthen this target. The pilot study with experts in particular provided stronger indications that the sociocultural dimension is considered of high importance by between 62% and 88% of the respondents, who were IT and computing professionals and software practitioners from academia and industry.
Bioassay studies of Risperidone and its active metabolite in rat dried blood spots and dried plasma spots using LC‐ESI‐MS/MS: Comparison of their pharmacokinetic profiles
Authors: Challa Gangu Naidu , Nimmu Narendra Varma , Bondigalla Ramachandra , Arnipalli Manikanta Swamy 
Published: August 2020

AbstractA highly sensitive and specific liquid chromatography‐elctrospray ionization tandem mass spectrometry method was developed and validated for rapid determination of risperidone and its active metabolite in rat dried blood spots and dried plasma spots. Chromatographic separation was achieved through ZIC®‐HILIC (250 × 4.6 mm, 5 µm) at 25°C using 10 mM ammonium acetate (pH: 3.0, adjusted with acetic acid) and acetonitrile (12:88, v/v) as a mobile phase. Tandem mass spectrometry detection was performed in positive ion electrospray ionization using multiple reaction monitoring mode to monitor precursor → product ion transitions m/z 411.2→191.1 for Risperidone, m/z 427.2→207.1 for its metabolite (Risperidone‐9‐OH), respectively. The lower limit of quantification of Risperidone and Risperidone‐9‐OH were 0.95 and 0.90 ng/mL in rat dried blood spots, respectively. The developed bioassay method was successfully applied to study the pharmacokinetic profile of Risperidone and Risperidone‐9‐OH using Iloperidone as an internal standard. As per pharmacokinetic studies, Cmax of Risperidone and Risperidone‐9‐OH in dried blood spots was 36.2 and 28.9 ng/mL; and in dried plasma spots was 38.2 and 30.2 ng/mL, respectively. Similarly, tmax of Risperidone and Risperidone‐9‐OH in dried blood spots was 1.4 and 14.7 h; and in dried plasma spots was 1.54 and 15.4 h, respectively.
Effect of gaseous hydrogen sulphide on growth performance and cecal microbial diversity of weaning pigs
Authors: Cui Jia , Wu Fengyang , Yang Xinyu , Liu Tingting , Xia Xueru , Chang Xingfa , Wang Haonan , Sun Lei , Wei Yuchao , Jia Zenghao , Liu Shudong , Han Shuaijuan , Chen Baojiang 
Published: July 2020

AbstractThe purpose of this study was to examine the effect of gaseous hydrogen sulphide on growth performance and cecal microbial diversity in weaning pigs. A total of 24 weaning pigs (Landrace × Yorkshire × Duroc; average body weight = 8.55 ± 0.68 kg；weaning at 28 days) were selected and randomly divided into four groups (six replicates in each group). The piglets were exposed to hydrogen sulphide (0, 5, 10 and 15 mg/m3) during the experiment period, which lasted 28 days in four controlled environmental chambers. The results showed that exposure to hydrogen sulphide reduced the average daily gain (ADG), average daily feed intake (ADFI), and increased the diarrhoea rate of piglets. Hydrogen sulphide could increase the abundance and diversity of intestinal microbiota. The abundance of Firmicutes and Proteobacteria increased and Bacteroides decreased in the treatment groups. Five biomarkers, such as Eubacterium_1coprostanoligenes, Clostridiales, Phascolarctobacterium, Acidaminococcaceae and Ruminococcaceae_UCG_002 were selected by Lefse analysis. Our results reveal that hydrogen sulphide damaged the growth performance and destroyed the microbial bacteria balance of weaning pigs. The concentrations of hydrogen sulphide should fall below 5 mg/m3.
Conclusion
Authors: Ogbebor Binakuromo 
Published: July 2020

AbstractThis chapter presents highlights on how the media covered the press reform debate that followed the News of the World phone hacking scandal. It argues that rather than serve as a democratic public sphere where diverse voices can have proportionate access to the press reform debate, the media used their gatekeeping powers to advance their views while limiting or preventing arguments that were against their self-interest from gaining entrance into the public sphere. This reduced the quality of the debate on press reform by inhibiting the kind of robust deliberations that produce plurality of views. The author recognises the challenge in asking the press to serve as a democratic public sphere during debates about their policy because bias is inevitable, and every organisation or industry may exhibit some level of bias in its own favour. She, therefore, argues that steps to make the press accountable should also come from outside the press. The author advocates non-governmental public reformism as a means of ensuring press accountability.
Hämoadsorption zur Blutreinigung – Unvergleichbarkeit der klinisch angebotenen Verfahren
Authors: Krenn C. G. , Steltzer H. 
Published: July 2020

Zusammenfassung
Hintergrund
Im Bereich der Intensivmedizin, aber auch verstärkt in der Herzchirurgie, gewinnt der Einsatz von adsorptiven Blutreinigungstechnologien zur Behandlung von hyperinflammatorischen Zuständen an Bedeutung. Neben dem CytoSorb-Verfahren, das zunehmend klinisch akzeptiert und auch aktuell am häufigsten eingesetzt wird, drängen seit Kurzem weitere Firmen – vor allem aus China – mit ähnlichen Konzepten auf den Markt.

Ziel der Arbeit
Vor diesem Hintergrund soll es Ziel dieses Artikels sein, exemplarisch auf unterschiedliche Aspekte zwischen den am Markt angebotenen Hämoadsorptionsprodukten einzugehen und einen kritischen Blick auf die vorhandene Evidenz zu werfen.

Methoden
Analysiert wurden technische Merkmale, applikationsspezifische Besonderheiten und vorhandene Evidenz der Adsorptionstechnologien CytoSorb® (CytoSorbentsTM Inc., Monmouth Junction, NJ, USA), Jafron® HA-Serie (Jafron Biomedical Co., Guangdong, China) sowie der Biosky® MG-Serie (Biosun® Medical Technology Co., Foshan City, Guangdong Province, China). Nicht einbezogen wurden rein substanzspezifische Verfahren zur Endotoxinelimination (Toraymyxin®, Alteco®).

Ergebnisse
Bei umfassender Analyse dieser Kriterien zeigt sich, dass zwischen den verfügbaren Technologien erhebliche Unterschiede hinsichtlich verwendeter Materialien, Adsorptionscharakteristika, Anwendung und verfügbarer Daten zu Sicherheit und klinischer Erfahrungen bestehen. Darüber hinaus wird deutlich, dass bei Blutreinigungstechnologien nicht nur deren Wirksamkeit unter Berücksichtigung eines Effekt-Preis-Leistungs-Verhältnisses betrachtet werden sollte, sondern insbesondere auch die klinische Sicherheit der einzelnen Verfahren von entscheidender Bedeutung ist.

Diskussion
Unter den analysierten Technologien stellt unserer Ansicht nach derzeit CytoSorb das am besten untersuchte und klinisch am weitesten etablierte Verfahren dar. Darüber hinaus ist darauf hinzuweisen, dass klinische Ergebnisse, insbesondere jedoch auch sicherheitsrelevante Aspekte, aufgrund der technisch unterschiedlichen Verfahren nicht zwischen den Produkten übertragbar sind.
The epistemic opacity of autonomous systems and the ethical consequences
Authors: Héder Mihály 
Published: July 2020

AbstractThis paper takes stock of all the various factors that cause the design-time opacity of autonomous systems behaviour. The factors include embodiment effects, design-time knowledge gap, human factors, emergent behaviour and tacit knowledge. This situation is contrasted with the usual representation of moral dilemmas that assume perfect information. Since perfect information is not achievable, the traditional moral dilemma representations are not valid and the whole problem of ethical autonomous systems design proves to be way more empirical than previously understood.