bluuebunny/crossref_metadata_2025 huggingface dataset:
MODELLING OF AN INTRUSION DETECTION SYSTEM USING C4.5 MACHINE LEARNING ALGORITHM
Authors: Olanrewaju Oyenike Mary , Echobu Faith Oluwatosin , Mogaji Abubakar
Published: June 2021

The increasing growth of wireless networking and new mobile computing devices has caused boundaries between trusted and malicious users to be blurred. The shift in security priorities from the network perimeter to information protection and user resources security is an open area for research which is concerned with the protection of user information’s confidentiality, integrity and availability. Intrusion detection systems are programs or software applications embedded in sophisticated devices to monitor the activities on networks or systems for security, policy or protocol violation or malicious activities detection. In this work, an intrusion detection model was proposed using C4.5 algorithm which was implemented with WEKA tool and RAPID MINER. The model showed good performance when trained and tested with validation techniques. Implementation of the proposed model was conducted on the Network Security Laboratory Knowledge Discovery in Databases (NSL-KDD) dataset, an improved version of KDD 99 dataset, which showed that the proposed model approach has an average detection rate of 99.62% and reduced false alarm rate of 0.38%.
Analisis Pengaruh Infrastruktur Listrik, Jalan Dan Kesehatan Terhadap Produk Domestik Regional Bruto Di Kabupaten Sidoarjo
Authors: Aldona Yurike , Primandhana Wiwin Priana , Wahed Muhammad
Published: June 2021

Gross Regional Domestic Product (GDP) is one of the economic indicators according to various economic instruments in which clearly visible macro-economic conditions of a region. Infrastructure is the most primary public infrastructure in supporting a country's economic activities, and the availability of infrastructure greatly determines the level of efficiency and effectiveness of economic activities. This study aims to analyze how much electricity, road, and health infrastructure affects gross regional domestic product in Sidoarjo Regency. This research covers the area of Sidoarjo Regency. This study uses secondary data obtained from the Central Statistics Agency with a period of 15 years from 2005-2019. The analysis technique used is Multiple Linear Regression Analysis with Ordinary Least Square (OLS) model using computer tools SPSS program (Statistic Program For Social Science) Version 13.0 that shows the influence between free variables and bound variables. The end result is that electricity infrastructure variables have a positive and significant influence on gross regional domestic product in Sidoarjo Regency. Variable road infrastructure and health infrastructure have a positive but insignificant influence on gross regional domestic product in Sidoarjo Regency.
COMMUNICATION IN STEM EDUCATION: A NON-INTRUSIVE METHOD FOR ASSESSMENT & K20 EDUCATOR FEEDBACK
Authors: Borowczak Mike
Published: June 2021

The current push to educate highly qualified and productive Science, Technology, Engineering and Mathematics (STEM) professionals typically culminates in collegiate capstone projects. These group projects attempt to prepare STEM professionals for entry into the real world as they exemplify early career group dynamics and expose the reality that communication and other soft-skills are often just as important as technical skills. Since attitudes of STEM students and early career professions are established throughout the entire K-20 curriculum, this article also provides some feedback to educators. The research presented utilized, a free cloud based collaboration tool to observe the communication habits of three senior capstone teams (n= 13 participants) and was able to predict communication success and failures through straight-forward analysis of several key parameters, including: discussion frequency, number of responses and the distribution of work over time.
Key words: communication in STEM, communication assessment, senior capstones, non-intrusive soft-skill assessment, engineering education, ABET.
THE IMPLEMENTATION OF CHILDRENADOPTION LICENSING IN THE BENGKULU PROVINCE BASED ON GOVERNMENT REGULATION NUMBER 54 OF 2007 CONCERNING THE IMPLEMENTATION OF CHILDREN ADOPTION
Authors: Hidayanti Willy Purnama , Satmaidi Edra , Amancik Amancik
Published: June 2021

The State and the Government are obliged and responsible for the orderliness of children adoption practices, both in terms of administration and legal certainty. Therefore several policies were issued through legislation and jurisprudence that regulates and handles the issue of children adoption. The implementation of children adoption must be based on Government Regulation of the Republic of Indonesia Number 54 of 2007 concerning Children Adoption. This study aims to get an overview and explanation of the Implementation of Licensing for ChildrenAdoption in Bengkulu Province Based on Government Regulation 54 of 2007 concerning the Implementation of Children Adoption. The children adoption process requires regulations that are in accordance with the Laws and Government Regulations and needs control of how they are implemented in the field. In addition to the Social Department of Bengkulu Province as the technical executor of adoption activities, it is necessary to establish a Regional Consultation Team for Children Adoption (known as PIPA in Indonesian abbreviation), to avoid irregularities in the process of implementation of children adoption, such as the adoption of children carried out without proper procedures, falsification of data and the existence of child trafficking, so the goal of adopting a child for the best interests of the child is not achieved. In analyzing the data in this thesis, the researcher applied a qualitative juridical analysis approach that describes the picture of the data obtained by researcher in the field and connects with each other to get a general conclusion. From the results of the qualitative juridical analysis, it can be seen and obtained inductive conclusions, namely the way of thinking in taking conclusions in general was based on facts that are specific. Data collection methods in this study were done through in-depth interview techniques, observation and documentation.The informants in this study were determined by selecting informants who comprehended and were directly involved in the implementation of child adoption programs. The informants consisted of the Head of Social Rehabilitation Division at the Social Department of Bengkulu Province, Head of Children and Elderly Social Rehabilitation Section at the Social Department of Bengkulu Province, Head of ChildrenProtection Section of the Women Empowerment Department and Children Protection in Bengkulu Province, Children Social Workers and Parents or Prospective Adoptive Parents who follow procedural for children adoption in accordance with applicable regulations. Data processing and analysis were conducted through data reduction, data presentation and conclusion drawing.
KAJIAN PERWATAKAN TOKOH-TOKOH NOVEL” LAUT BERCERITA” KARYA LEILA S. CHUDORI
Authors: Renita Pebrina , Amrizal Amrizal , Chanafiah Yayah
Published: June 2021

Tujuan penelitian ini adalah untuk mengetahui perwatakan tokoh-tokoh dalam Novel Laut Bercerita Karya Leila S. Chudori. Penelitian ini menggunakan metode deskriptif kualitatif. Teknik analisis data (a) Peneliti menganalisis unsur-unsur novel Laut Bercerita yang mendukung perwatakan tokoh-tokoh novel Laut Bercerita (b) Peneliti menganalisis perwatakan tokoh-tokoh novel Laut Bercerita karya Laila S.Chudori. Hasil penelitian menunjukkan bahwa data yang memuat unsur-unsur novel Laut Bercerita. Unsur-Unsur tersebut adalah tema, alur, dan latar. Tema dalam novel Laut Bercerita karya Laila S.Chudori adalah legitimasi dan perjuangan melawan masa Orde Baru.Alur dari Novel Laut Bercerita adalah alur maju yang mendeskripsikan pengenalan tokoh, pokok persoalan dan klimaks cerita. Latar cerita novel Laut Bercerita banyak terjadi di Desa, Kampus dan di Sekretariat. Pokok pembahasan dalam penelitian ini adalah Biru Laut dalam novel Laut Bercerita digambarkan pengarang sebagai tokoh yang memiliki watak bersemangat, tidak mudah terpengaruh/teguh pendirian, pendiam, pemalu, penyayang, pemberani, pantang menyerah, dan tenang. Ditinjau dari segi psikologi sastra Sigmund Freud tokoh Biru Laut memiliki id berupa mudah khawatir atau cemas, pendiam.  Ego pemalu, penyayang. Super Ego pemberani, tenang, bersemangat dan pantang menyerah
Face-to-Face and Remote Learning During the Confinement Due to Covid19: The Experience of Higher Education Students
Authors: Leal Fátima , Chaleta Maria Elisa
Published: June 2021

Due to COVID19 disease contingencies, in several countries, universities were forced to replace the face-to-face classes for a non-face-to-face system, also called as Emergency Remote Teaching - ERT. In this scenario, both teachers and students experienced several challenges and had to adapt to new ways of teaching and learning. The goal of this study was to understand how students experienced this situation. Through a qualitative methodology, we interviewed eight higher education students from social sciences scientific areas. Thematic analysis was used to identify and interpret patterns and themes in students’ responses. Results show that students experimented several difficulties at different levels: cognitive level (e.g., attention, concentration, and information storage), motivational (e.g., demotivation to study), tiredness; organizational (e.g., time and tasks management), and social level (e.g., interpersonal relationship and lack of contact with people). These results bring new knowledge to this problematic area and can be useful for students, teachers, and higher education institutions.
Bactérias multirresistentes e seus impactos na saúde pública: Uma responsabilidade social
Authors: Carvalho Juliana Jeanne Vieira de , Boaventura Felipe Gomes , Silva Anitha de Cássia Ribeiro da , Ximenes Rhuana Lima , Rodrigues Luana Kamila Castilho , Nunes Diego Antônio de Almeida , Souza Viviane Krominski Graça de
Published: June 2021

Introdução: Seres humanos convivem de modo comensal com inúmeras bactérias, porém espécies patogênicas assolaram a humanidade por milênios até o advento dos primeiros antibióticos. Entretanto, o uso indiscriminado de antibióticos, tanto em hospitais quanto na agropecuária, tem gerado altas taxas de resistência bacteriana e se tornado um problema com disrupção eminente. O presente estudo visa analisar a etiologia multifatorial dos mecanismos de multirresistência bacteriana, a prevalência das principais bactérias envolvidas nesse processo e seu impacto na saúde pública. Metodologia: Trata-se uma revisão integrativa de literatura acerca dos processos e consequências da resistência bacteriana. O critério de inclusão foi a compatibilidade com o tema e a relevância. Resultados: Analisados 46 artigos dos quais metade são artigos originais. Dentre estes, 6 artigos realizaram levantamento da prevalência de bactérias farmacorresistentes em ambientes nosocomiais, com amostragem de 646 pacientes nos quais foram isolados Klebsiella pneumoniae em 27,11%, Pseudomonas aeruginosa em 19%, seguida por Escherichia coli com 16%, e Staphylococcus aureus com 4,75%. Discussão: Com 25 a 50% das administrações antibióticas em hospitais consideradas irregulares, seu uso indiscriminado e a lenta formulação de novas opções terapêuticas, entre outros, contribuiu com o desenvolvimento de cepas bacterianas multirresistentes durante a era dos antimicrobianos. Os principais mecanismos de farmacorresistência incluem modificação antibiótica; impedimento da ação do antibiótico em seu alvo; alteração do sítio primário de ligação; e produção de alvo alternativo para burlar o efeito do fármaco. Considerações Finais: A multirresistência bacteriana aumenta a morbimortalidade, tempo de internação e gastos com insumos e equipe especializada. Estabeleceu-se como um problema que tende a agravar com o tempo, portanto, estudos abrangentes focados na prevalência bacteriana são necessários para traçar estratégias de saúde pública visando seu controle.
A infecção pela Covid-19 provoca manifestações bucais? Uma revisão de litertura
Authors: Furtado Guilherme Silva , Menezes Beatriz Leal de Siqueira , Menezes Kaytlhen Kayllen Carvalho de , Feitosa Maria Áurea Lira , Lima Darlon Martins , Casanovas Rosana Costa
Published: June 2021

Diversas pesquisas encontram-se em andamento pelo mundo nos últimos meses em busca de respostas sobre o SARS-CoV-2, causador da pandemia gerada pela Covid-19. Esta é uma doença de rápido e fácil contágio, visto que a principal forma de transmissão é por contato direto com gotículas salivares contendo o vírus. Tem-se demonstrado o aparecimento de vários sinais bucais em pacientes acometidos pela Covid-19, levando-se a teoria de que a infecção viral seja responsável pelo aparecimento de manifestações bucais e outras infecções secundárias por outros microorganismos patogênicos. O objetivo desse estudo é condensar as informações sobre a presença e tipos de manifestações orais relatadas nos pacientes com Covid-19. Realizou-se uma busca nas bases PubMed, SciELO, LILACS, Google acadêmico utilizando descritores, estratégias e critérios pré-estabelecidos por dois avaliadores, de forma independente. As estratégias de pesquisa identificaram 439 artigos. Após triagem dos trabalhos, 426 foram excluídos e 13 selecionados para compor esta revisão. Concluiu-se que é possível associar o surgimento de manifestações orais com a Covid-19. Porém, não se tem comprovação que são alterações secundárias ao tratamento ou se estão diretamente relacionadas ao coronavírus.
Epic of Manas as a Source of Studying Folk Medicine of the Kyrgyz People
Authors: Tentigul kyzy N. , Beksultanova Ch.
Published: June 2021

This article identifies the types of traditional medicine based on the largest monument of Kyrgyz folklore — the Epic of Manas. The epic Manas, the world’s largest epic, the “encyclopedia of the life of the Kyrgyz people”, provides valuable information about traditional medicine. Traditional Kyrgyz knowledge divides diseases into two types: “cold” and “hot” diseases and methods of treatment. The article defines the types of traditional medicine and their representatives according to the Epic of Manas, i. e. the classification of traditional medicine into religious, empirical and rational types is given. Representatives of these species and their characteristic methods and methods of treatment are also described. The names, properties of medicinal herbs and methods of treatment in the form of decoctions and tinctures, mentioned in the Epic of Manas, are disclosed. The role and significance in the life of the people are shown in detail, as well as methods of treatment of various diseases by Kyrgyz healers — tabyp.
Viewing I, Daniel Blake in the English Regions: Towards an Understanding of Realism through Audience Interpretation
Authors: Forrest David , Merrington Peter
Published: June 2021

This article examines focus group responses to Ken Loach's I, Daniel Blake (2016). Situated in four English regions (North East, North West, South West and Yorkshire and Humber), the focus groups were structured around a process of film elicitation that gathered a set of plural and richly textured responses to the film. Focusing on the participants’ understanding of realism within the film, the article complements existing textual analyses of realism in order to understand better the kinds of interpretive resources that audiences bring to their engagement with films such as I, Daniel Blake. We examine in detail how participants drew on different interpretive resources as a set of personal, emotional and intellectual anchoring points that they used to situate and articulate their readings of the film. These resources ranged from related life experiences and personal memories to emotional responses and political views. In particular, we examine how participants interpreted the film through differing degrees of personal familiarity and empathy with the narrative, characters and places depicted, how the participants dealt with the emotional labours of realism and the feelings evoked through representations of place. Using film elicitation to understand the plurality of interpretations of realism has allowed us to develop a located and multifaceted understanding of the affective dimensions of realist film, and to extend the reach of audience studies to a hitherto under-explored genre.
Jack Ellitt as Director: Documentary Films of the 1940s
Authors: Birtwistle Andy
Published: June 2021

This article examines the work of the film-maker and composer Jack Ellitt (1902–2001) who remains something of an enigmatic and marginal figure in historical accounts of British documentary cinema. Research on Ellitt has so far focused on two key aspects of his life and career: firstly, his association with the New Zealand-born film-maker and artist Len Lye, and secondly, his pioneering work as a composer of electro-acoustic music. However, little research been undertaken on the work that he produced during the three decades he spent working as a documentary director in the British film industry, beginning in the early 1940s and ending with his retirement in the 1970s. He was a member of the remarkable generation of film-makers associated with the British documentary movement, and a composer whose radical experiments with recorded sound might well have secured him a more prominent place in the history of experimental music than is currently the case.

Focusing on films made by Ellitt during the 1940s, the primary aim of this article is to offer a chronological appraisal of his early work as documentary director, while also considering what new perspectives this group of films might offer on his earlier creative collaboration with Lye, and the extent to which his radical experiments in electro-acoustic composition may have influenced the use of sound within the films he directed.
nZVI Impacts Substrate Conversion and Microbiome Composition in Chain Elongation From D- and L-Lactate Substrates
Authors: Contreras-Dávila Carlos A. , Esveld Johan , Buisman Cees J. N. , Strik David P. B. T. B.
Published: June 2021

Medium-chain carboxylates (MCC) derived from biomass biorefining are attractive biochemicals to uncouple the production of a wide array of products from the use of non-renewable sources. Biological conversion of biomass-derived lactate during secondary fermentation can be steered to produce a variety of MCC through chain elongation. We explored the effects of zero-valent iron nanoparticles (nZVI) and lactate enantiomers on substrate consumption, product formation and microbiome composition in batch lactate-based chain elongation. In abiotic tests, nZVI supported chemical hydrolysis of lactate oligomers present in concentrated lactic acid. In fermentation experiments, nZVI created favorable conditions for either chain-elongating or propionate-producing microbiomes in a dose-dependent manner. Improved lactate conversion rates and n-caproate production were promoted at 0.5–2 g nZVI⋅L–1 while propionate formation became relevant at ≥ 3.5 g nZVI⋅L–1. Even-chain carboxylates (n-butyrate) were produced when using enantiopure and racemic lactate with lactate conversion rates increased in nZVI presence (1 g⋅L–1). Consumption of hydrogen and carbon dioxide was observed late in the incubations and correlated with acetate formation or substrate conversion to elongated products in the presence of nZVI. Lactate racemization was observed during chain elongation while isomerization to D-lactate was detected during propionate formation. Clostridium luticellarii, Caproiciproducens, and Ruminococcaceae related species were associated with n-valerate and n-caproate production while propionate was likely produced through the acrylate pathway by Clostridium novyi. The enrichment of different potential n-butyrate producers (Clostridium tyrobutyricum, Lachnospiraceae, Oscillibacter, Sedimentibacter) was affected by nZVI presence and concentrations. Possible theories and mechanisms underlying the effects of nZVI on substrate conversion and microbiome composition are discussed. An outlook is provided to integrate (bio)electrochemical systems to recycle (n)ZVI and provide an alternative reducing power agent as durable control method.
Comprehensive Transcriptomic Analysis Reveals Prognostic Value of an EMT-Related Gene Signature in Colorectal Cancer
Authors: Mo Shaobo , Dai Weixing , Zhou Zheng , Gu Ruiqi , Li Yaqi , Xiang Wenqiang , Han Lingyu , Zhang Long , Wang Renjie , Cai Guoxiang , Cai Sanjun , Gan Lu , Li Qingguo
Published: June 2021

Lymph node metastasis (LNM) is closely related to the postoperative recurrence of colorectal cancer (CRC), and greatly affects patient survival. Conducting Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA), we found that the epithelial-mesenchymal transition (EMT) signaling pathway is the signaling pathway most relevant to the process of LNM. An EMT-related gene signature was identified from a discovery dataset obtained 489 patients using LIMMA and LASSO Cox methods. Six external independent dataset analyses including a total of 1,045 CRC patients and stratification analysis showed that EMT-related gene signature could sort out those high- and low-risk CRC patients accurately. Functional analysis and loss-of-function exploration in vitro and in vivo indicated that the EMT-related-signature-associated coding genes might play functional roles in the sophisticated regulation of CRC proliferation and metastasis. Prognostic nomograms integrating the EMT-related gene signature and clinicopathological risk factors were constructed for use as numerical prediction tools to assess clinical prognosis and clinical decision-makings. The comprehensive transcriptomic analysis in this article highlights the prognostic value of an EMT-related gene signature for postoperative disease recurrence in CRC patients and reveals a potential prognostic and therapeutic biomarker for CRC.
X-Inactive-Specific Transcript: Review of Its Functions in the Carcinogenesis
Authors: Ghafouri-Fard Soudeh , Dashti Sepideh , Farsi Molood , Taheri Mohammad , Mousavinejad Seyed Ali
Published: June 2021

X-inactive–specific transcript (XIST) is one of the firstly discovered long non-coding RNAs with prominent roles in the process of X inactivation. Moreover, this transcript contributes in the carcinogenic process in different tissues. In addition to interacting with chromatin modifying molecules, XIST can be served as a molecular sponge for miRNAs to modulate expression of miRNA targets. Most of the studies have indicated an oncogenic role for XIST. However, in prostate cancer, a single study has indicated a tumor suppressor role for this lncRNA. Similar result has been reported for XIST in oral squamous cell carcinoma. In hepatocellular carcinoma, breast cancer, ovarian cancer, osteosarcoma, and renal cell carcinoma, different studies have reported inconsistent results. In the present manuscript, we review function of XIST in the carcinogenesis.
Site-Specific N- and O-Glycosylation Analysis of Human Plasma Fibronectin
Authors: Liu Ding , Wang Shuaishuai , Zhang Junping , Xiao Weidong , Miao Carol H. , Konkle Barbara A. , Wan Xiu-Feng , Li Lei
Published: June 2021

Human plasma fibronectin is an adhesive protein that plays a crucial role in wound healing. Many studies had indicated that glycans might mediate the expression and functions of fibronectin, yet a comprehensive understanding of its glycosylation is still missing. Here, we performed a comprehensive N- and O-glycosylation mapping of human plasma fibronectin and quantified the occurrence of each glycoform in a site-specific manner. Intact N-glycopeptides were enriched by zwitterionic hydrophilic interaction chromatography, and N-glycosite sites were localized by the 18O-labeling method. O-glycopeptide enrichment and O-glycosite identification were achieved by an enzyme-assisted site-specific extraction method. An RP–LC–MS/MS system functionalized with collision-induced dissociation and stepped normalized collision energy (sNCE)-HCD tandem mass was applied to analyze the glycoforms of fibronectin. A total of 6 N-glycosites and 53 O-glycosites were identified, which were occupied by 38 N-glycoforms and 16 O-glycoforms, respectively. Furthermore, 77.31% of N-glycans were sialylated, and O-glycosylation was dominated by the sialyl-T antigen. These site-specific glycosylation patterns on human fibronectin can facilitate functional analyses of fibronectin and therapeutics development.
GH Replacement in the Elderly: Is It Worth It?
Authors: Ricci Bitti Silvia , Franco Marta , Albertelli Manuela , Gatto Federico , Vera Lara , Ferone Diego , Boschetti Mara
Published: June 2021

Growth hormone (GH), once the age of linear growth is completed, continues to play a fundamental role for the human body. In adulthood, GH contributes to regulate muscle, cardiovascular and bone metabolism. The same happens in old age, although there is less data on the effect of GH in the elderly. Regardless the age of onset, a reduced quality of life (QoL), an increased cardiovascular risk and an accelerated age-related decline in physical strength have been demonstrated in the elderly with GH deficiency (EGHD). In adults with GH deficiency (AGHD), recent studies suggest a role of GH replacement therapy (GHrt) in improving lean/fat mass ratio, blood pressure, lipid profile, bone metabolism and QoL. Despite these recent studies, there is still a lack of randomized controlled trials proving these positive effects in EGHD. Moreover, the lack of a long-term positive outcome on mortality, and the cost of GHrt could often impact on treatment decision-making and lead to postpone or avoid the prescription. The aim of this mini-review is to summarize the available data on GHrt in EGHD, in order to highlight its weaknesses and strengths and to provide directions to clinicians that will help in the management of this specific set of patients.
Identification of the Signature Associated With m6A RNA Methylation Regulators and m6A-Related Genes and Construction of the Risk Score for Prognostication in Early-Stage Lung Adenocarcinoma
Authors: Guo Bingzhou , Zhang Hongliang , Wang Jinliang , Wu Rilige , Zhang Junyan , Zhang Qiqin , Xu Lu , Shen Ming , Zhang Zhibo , Gu Fangyan , Zeng Weiliang , Jia Xiaodong , Yin Chengliang
Published: June 2021

Background

N6-methyladenosine (m6A) RNA modification is vital for cancers because methylation can alter gene expression and even affect some functional modification. Our study aimed to analyze m6A RNA methylation regulators and m6A-related genes to understand the prognosis of early lung adenocarcinoma.

Methods

The relevant datasets were utilized to analyze 21 m6A RNA methylation regulators and 5,486 m6A-related genes in m6Avar. Univariate Cox regression analysis, random survival forest analysis, Kaplan–Meier analysis, Chi-square analysis, and multivariate cox analysis were carried out on the datasets, and a risk prognostic model based on three feature genes was constructed.

Results

Respectively, we treated GSE31210 (n = 226) as the training set, GSE50081 (n = 128) and TCGA data (n = 400) as the test set. By performing univariable cox regression analysis and random survival forest algorithm in the training group, 218 genes were significant and three prognosis-related genes (ZCRB1, ADH1C, and YTHDC2) were screened out, which could divide LUAD patients into low and high-risk group (P < 0.0001). The predictive efficacy of the model was confirmed in the test group GSE50081 (P = 0.0018) and the TCGA datasets (P = 0.014). Multivariable cox manifested that the three-gene signature was an independent risk factor in LUAD. Furthermore, genes in the signature were also externally validated using the online database. Moreover, YTHDC2 was the important gene in the risk score model and played a vital role in readers of m6A methylation.

Conclusion

The findings of this study suggested that associated with m6A RNA methylation regulators and m6A-related genes, the three-gene signature was a reliable prognostic indicator for LUAD patients, indicating a clinical application prospect to serve as a potential therapeutic target.
Solubility Controlling Peptide Tags of Opposite Charges Generate a Bivalent Immune Response Against Dengue ED3 Serotypes 3 and 4
Authors: Rahman Nafsoon , Miura Shiho , Okawa Mami , Kibria Md. Golam , Islam Mohammad Monirul , Kuroda Yutaka
Published: June 2021

We previously demonstrated that a protein’s immunogenicity could be substantially increased by attaching a hydrophobic solubility controlling peptide tag (SCP-tag) producing small sub-visible aggregates. Here, we report the oligomerization of Dengue envelop protein domain 3 (ED3), and consequently, its immunogenicity increase by mixing ED3s attached with SCP-tags of opposite charges at equimolar concentration. We used ED3 of serotype 3 (D3ED3) and serotype 4 (D4ED3), which are, respectively, moderately and poorly immunogenic, and their SCP tagged variants constructed by attaching either a C-termini 5-Aspartic acid (C5D) or a 5-Lysine (C5K) tag. Light scattering indicated that the isolated tagged ED3s remained monomeric, but mixing the C5D and C5K tagged ED3s at equimolar concentration generated sub-visible aggregates or oligomers of ~500 nm through electrostatic interaction. In addition, the oligomerized ED3s remained in a native-like state, as assessed by fluorescence spectroscopy and circular dichroism. The in vivo immunogenicity of the D3ED3 and D4ED3 oligomers generated by the charged tags increased by 5 and 16 fold, respectively. Furthermore, injection of heterotypic ED3 oligomers (D3C5D+D4C5K) induced an immune response against both D3ED3 and D4ED3 in 3 of 4 responsive mice, and the IgG titer of the bivalent anti-D3C5D-D4C5K sera was over 100 times higher than that generated by co-injecting the untagged D3ED3 and D4ED3 (D3+D4). Altogether, these observations suggest that SCP-tags could be used as a platform for producing a long-sought tetravalent dengue vaccine.
Humanized Mouse Model as a Novel Approach in the Assessment of Human Allogeneic Responses in Organ Transplantation
Authors: Ajith Ashwin , Mulloy Laura L. , Musa Md. Abu , Bravo-Egana Valia , Horuzsko Daniel David , Gani Imran , Horuzsko Anatolij
Published: June 2021

The outcome of organ transplantation is largely dictated by selection of a well-matched donor, which results in less chance of graft rejection. An allogeneic immune response is the main immunological barrier for successful organ transplantation. Donor and recipient human leukocyte antigen (HLA) mismatching diminishes outcomes after solid organ transplantation. The current evaluation of HLA incompatibility does not provide information on the immunogenicity of individual HLA mismatches and impact of non-HLA-related alloantigens, especiallyin vivo. Here we demonstrate a new method for analysis of alloimmune responsiveness between donor and recipientin vivoby introducing a humanized mouse model. Using molecular, cellular, and genomic analyses, we demonstrated that a recipient’s personalized humanized mouse provided the most sensitive assessment of allogeneic responsiveness to potential donors. In our study, HLA typing provided a better recipient-donor match for one donor among two related donors. In contrast, assessment of an allogeneic response by mixed lymphocyte reaction (MLR) was indistinguishable between these donors. We determined that, in the recipient’s humanized mouse model, the donor selected by HLA typing induced the strongest allogeneic response with markedly increased allograft rejection markers, including activated cytotoxic Granzyme B-expressing CD8+T cells. Moreover, the same donor induced stronger upregulation of genes involved in the allograft rejection pathway as determined by transcriptome analysis of isolated human CD45+cells. Thus, the humanized mouse model determined the lowest degree of recipient-donor alloimmune response, allowing for better selection of donor and minimized immunological risk of allograft rejection in organ transplantation. In addition, this approach could be used to evaluate the level of alloresponse in allogeneic cell-based therapies that include cell products derived from pluripotent embryonic stem cells or adult stem cells, both undifferentiated and differentiated, all of which will produce allogeneic immune responses.
Nonlinearity of Subtidal Estuarine Circulation in the Pearl River Estuary, China
Authors: Xu Hongzhou , Shen Jian , Wang Dongxiao , Luo Lin , Hong Bo
Published: June 2021

The Pearl River Estuary (PRE) is a bell-shaped estuary with a narrow deep channel and wide shoals. This unique topographic feature leads to different dynamics of the subtidal estuarine circulation (SEC) in the PRE compared with a narrow and straight estuary. In this study, the nonlinear dynamics of the SEC in the PRE under mean circumstance are analyzed by using a validated 3D numerical model. Model results show that the nonlinear advections reach leading order in the along-channel momentum balance. Modulated by tide, the nonlinear advections show significant temporal variations as they have much larger values during spring tide than that during neap tide. Unlike straight and narrow estuaries, both tidally and cross-sectionally averaged axial and lateral advections play important roles in driving the SEC in the PRE in which the axial advection dominates the nonlinear effect, but the two nonlinear terms balance each other largely resulting in a reduced nonlinear effect. Despite this, the total nonlinear advection is still comparable with other terms, and it acts as the baroclinic pressure to reinforce the SEC, especially during the ebb tide, suggesting a flood–ebb asymmetry of the nonlinear dynamics in the PRE. In addition, diagnostic analyses of the along-channel vorticity budget show that nonlinear advections also make significant contribution to drive the lateral circulation in the PRE as Coriolis and baroclinic pressure terms, indicating complex dynamics of the circulation in the PRE.
Spatial Variation in Pelagic Wildlife Assemblages in the Ascension Island Marine Protected Area: Implications for Monitoring and Management
Authors: Thompson Christopher D. H. , Meeuwig Jessica J. , Brown Judith , Richardson Andrew J. , Friedlander Alan M. , Miller Peter I. , Weber Sam B.
Published: June 2021

Bathymetric features such as islands and seamounts, as well as dynamic ocean features such as fronts often harbour rich marine communities. We deployed mid-water baited remote underwater video systems on three expeditions in Ascension Island’s Exclusive Economic Zone (EEZ), surveying the waters associated with six different bathymetric and dynamic ocean features: Ascension Island, two shallow seamounts (summits ≤ 101 m), one deeper seamount (summit > 250 m), apparent fronts, and haphazardly sampled open ocean areas. At Ascension Island, the pelagic assemblage consisted of a moderate proportion of predators and a diverse range of other taxa, including turtles, dolphins, and large non-piscivores. At the two shallow seamounts, sharks, tunas, billfish, and other large pelagic predators formed the vast majority of the assemblage, contributing > 99.9% of biomass and > 86% of abundance. At the deeper seamount, the pelagic community was comparatively depauperate, however the functional composition of its assemblage indicated some similarities to the shallow seamounts. Apparent fronts did not significantly differ from random offshore sites for metrics such as total abundance and taxonomic richness. However, they harboured assemblages with more abundant sharks, tunas, and large piscivores than random ocean open locations and these differences may be driven by certain front-associated species. Our results illustrate that pelagic assemblages vary markedly among different physical and oceanographic features and that seamounts appear particularly important for pelagic predators. The diversity and abundance of the assemblage, as well as the threatened status of many of the species observed, serve to highlight the conservation value of the Ascension Island EEZ. Our results also provide important baseline information of pelagic wildlife assemblages against which the performance of the recently implemented Ascension Island Marine Protected Area can be evaluated.
Detection of Macrobenthos Species With Metabarcoding Is Consistent in Bulk DNA but Dependent on Body Size and Sclerotization in eDNA From the Ethanol Preservative
Authors: Derycke Sofie , Maes Sara , Van den Bulcke Laure , Vanhollebeke Joran , Wittoeck Jan , Hillewaert Hans , Ampe Bart , Haegeman Annelies , Hostens Kris , De Backer Annelies
Published: June 2021

DNA metabarcoding is a promising method to increase cost and time efficiency of marine monitoring. While substantial evidence exists that bulk DNA samples adequately reflect diversity patterns of marine macrobenthos, the potential of eDNA in the ethanol preservative of benthic samples for biodiversity monitoring remains largely unexplored. We investigated species detection in bulk DNA and eDNA from the ethanol preservative in samples from four distinct macrobenthic communities in the North Sea. Bulk DNA and eDNA were extracted with different extraction kits and five COI primer sets were tested. Despite the availability of a nearly complete reference database, at most 22% of the amplicon sequence variants (ASVs) were assigned taxonomy at the phylum level. However, the unassigned ASVs represented only a small fraction of the total reads (13%). The Leray primer set outperformed the four other primer sets in the number of non-chimeric reads and species detected, and in the recovery of beta diversity patterns. Community composition differed significantly between bulk DNA and eDNA samples, but both sample types were able to differentiate the four communities. The probability of detecting a species in the eDNA from the ethanol preservative was significantly lower than for bulk DNA for macrobenthos species having small to medium body size and for species having chitine or CaCO3 in their cuticula. Detection in the bulk DNA samples was not affected by the investigated morphological traits, indicating that monitoring of macrobenthos species will be most robust when using bulk DNA as template for metabarcoding.
Thermoelectric Properties of Arsenic Triphosphide (AsP3) Monolayer: A First-Principles Study
Authors: Fan Liangshuang , Yang Hengyu , Xie Guofeng
Published: June 2021

Recently, monolayer of triphosphides (e.g., InP3, SnP3, and GaP3) attracts much attention due to their good thermoelectric performance. Herein, we predict a novel triphosphide monolayer AsP3 and comprehensively investigate its thermoelectric properties by combining first-principles calculations and semiclassical Boltzmann transport theory. The results show that AsP3 monolayer has an ultralow thermal conductivity of 0.36 and 0.55 Wm K−1 at room temperature along the armchair and zigzag direction. Surprisingly, its maximum Seebeck coefficient in the p-type doping reaches 2,860 µVK−1. Because of the ultralow thermal conductivity and ultrahigh Seebeck coefficient, the thermoelectric performance of AsP3 monolayer is excellent, and the maximum ZT of p-type can reach 3.36 at 500 K along the armchair direction, which is much higher than that of corresponding bulk AsP3 at the same temperature. Our work indicates that the AsP3 monolayer is the promising candidate in TE applications and will also stimulate experimental scientists’ interest in the preparation, characterization, and thermoelectric performance tuning.
Clickable Radiocomplexes With Trivalent Radiometals for Cancer Theranostics: In vitro and in vivo Studies
Authors: D'Onofrio Alice , Silva Francisco , Gano Lurdes , Karczmarczyk Urszula , Mikołajczak Renata , Garnuszek Piotr , Paulo António
Published: June 2021

Pre-targeting approaches based on the inverse-electron-demand Diels-Alder (iEDDA) reaction between strained trans-cyclooctenes (TCO) and electron-deficient tetrazines (Tz) have emerged in recent years as valid alternatives to classic targeted strategies to improve the diagnostic and therapeutic properties of radioactive probes. To explore these pre-targeting strategies based on in vivo click chemistry, a small family of clickable chelators was synthesized and radiolabelled with medically relevant trivalent radiometals. The structure of the clickable chelators was diversified to modulate the pharmacokinetics of the resulting [111In]In-radiocomplexes, as assessed upon injection in healthy mice. The derivative DOTA-Tz was chosen to pursue the studies upon radiolabelling with 90Y, yielding a radiocomplex with high specific activity, high radiochemical yields and suitable in vitro stability. The [90Y]Y-DOTA-Tz complex was evaluated in a prostate cancer PC3 xenograft by ex-vivo biodistribution studies and Cerenkov luminescence imaging (CLI). The results highlighted a quick elimination through the renal system and no relevant accumulation in non-target organs or non-specific tumor uptake. Furthermore, a clickable bombesin antagonist was injected in PC3 tumor-bearing mice followed by the radiocomplex [90Y]Y-DOTA-Tz, and the mice imaged by CLI at different post-injection times (p.i.). Analysis of the images 15 min and 1 h p.i. pointed out an encouraging quick tumor uptake with a fast washout, providing a preliminary proof of concept of the usefulness of the designed clickable complexes for pre-targeting strategies. To the best of our knowledge, the use of peptide antagonists for this purpose was not explored before. Further investigations are needed to optimize the pre-targeting approach based on this type of biomolecules and evaluate its eventual advantages.
Comparison of Intra-Arterial Chemotherapy Efficacy Delivered Through the Ophthalmic Artery or External Carotid Artery in a Cohort of Retinoblastoma Patients
Authors: Jia Shichong , Wen Xuyang , Zhou Min , He Xiaoyu , Han Minglei , Fan Jiayan , Jia Renbing , Fan Xianqun
Published: June 2021

Purpose: To evaluate the efficacy of an external carotid artery (ECA) alternative route in intra-arterial chemotherapy (IAC) for treatment of retinoblastoma.

Methods: In this retrospective, single-centre, case-control study, 98 retinoblastoma patients who received successful IAC were included. The drug delivery routes were the primary ophthalmic artery (OA) route and the ECA route when OA catheterization was not feasible.

Results: A total of 337 successful IAC procedures were performed in our study, of which 32 (9.5%) procedures were performed through the ECA route. Eighteen eyes (18.4%) accepted at least one IAC through branches of the ECA. Statistical analysis showed that there was no significant difference in ocular clinical results (enucleation, death, recurrence and event-free) between the ECA and OA routes. No significant association was found between the route of drug delivery and the ocular survival time (p = 0.69). The use of ECA catheterization in at least one IAC cycle was not a predictor of enucleation (HR: 1.58; 95% CI: 0.56–4.46, p = 0.39). The increasing number of procedures through the ECA route did not increase the risk of enucleation (HR: 1.64; 95% CI: 0.42–6.39, p = 0.48).

Conclusion: The ECA alternative route did not affect the efficacy of IAC in retinoblastoma. When the standard OA approach is not feasible, ECA system catheterization should be considered.
Local Functional MR Change Pattern and Its Association With Cognitive Function in Objectively-Defined Subtle Cognitive Decline
Authors: Cui Liang , Zhang Zhen , Zac Lo Chun-Yi , Guo Qihao
Published: June 2021

Introduction: To identify individuals with preclinical cognitive impairment, researchers proposed the concept of objectively-defined subtle cognitive decline (Obj-SCD). However, it is not clear whether Obj-SCD has characteristic brain function changes. In this study, we aimed at exploring the changing pattern of brain function activity in Obj-SCD individuals and the similarities and differences with mild cognitive impairments (MCI).

Method: 37 healthy control individuals, 25 Obj-SCD individuals (with the impairment in memory and language domain), and 28 aMCI individuals were included. Resting-state fMRI and neuropsychological tests were performed. fALFF was used to reflect the local functional activity and compared between groups. Finally, we analyzed the correlation between the fALFF values of significantly changed regions and neuropsychological performance.

Results: We found similar functional activity enhancements in some local brain regions in the Obj-SCD and aMCI groups, including the left orbital part of the inferior frontal gyrus and the left median cingulate and paracingulate gyri. However, some changes in local functional activities of the Obj-SCD group showed different patterns from the aMCI group. Compared with healthy control (HC), the Obj-SCD group showed increased local functional activity in the right middle occipital gyrus, decreased local functional activity in the left precuneus and the left inferior temporal gyrus. In the Obj-SCD group, in normal band, the fALFF value of the right middle occipital gyrus was significantly negatively correlated with Mini-Mental State Examination (MMSE) score (r = −0.450, p = 0.024) and Animal Verbal Fluency Test (AFT) score (r = −0.402, p = 0.046); the left inferior temporal gyrus was significantly positively correlated with MMSE score (r = 0.588, p = 0.002). In slow-4 band, the fALFF value of the left precuneus was significantly positively correlated with MMSE score (r = 0.468, p = 0.018) and AFT score (r = 0.600, p = 0.002). In the aMCI group, the fALFF value of the left orbital part of the inferior frontal gyrus was significantly positively correlated with Auditory Verbal Learning Test (AVLT) long delay cued recall score (r = 0.506, p = 0.006).

Conclusion: The Obj-SCD group showed a unique changing pattern; the functional changes of different brain regions have a close but different correlation with cognitive impairment, indicating that there may be a complex pathological basis inside. This suggests that Obj-SCD may be a separate stage of cognitive decline before aMCI and is helpful to the study of preclinical cognitive decline.
Encapsulating Anti-Parasite Benzimidazole Drugs into Lipid-Coated Calcium Phosphate Nanoparticles to Efficiently Induce Skin Cancer Cell Apoptosis
Authors: Movahedi Fatemeh , Gu Wenyi , Soares Christiane Pienna , Xu Zhi Ping
Published: June 2021

Benzimidazole (BMZ) family of anti-worm drugs has been now repurposed as anti-cancer drugs. However, offering a general reformulation method for these drugs is essential due to their hydrophobicity and low aqueous solubility. In this work, we developed a general approach to load typical BMZ drugs as tiny nanocrystals within lipid-coated calcium phosphate (LCP) nanoparticles. BMZ drug-loaded LCP nanoparticles increased their solubility in PBS by 100–200% and significantly enhanced the anti-cancer efficacy in the treatment of B16F0 melanoma cells. These drug-LCP nanoparticles induced much more cancer cell apoptosis, generated much more reactive oxygen species (ROS) and inhibited Bcl-2 expression of cancer cells. Moreover, BMZ drug-loaded LCP nanoparticles caused morphological change and extension disruption of cancer cells, and significantly reduced migration activity, representing high possibility for inhibition of tumor dissemination and metastasis. Very advantageously, BMZ drug-loaded LCP nanoparticles did not show any obvious toxicity, Bcl-2 inhibition and morphological changes in HEK293T healthy cells. In conclusion, BMZ drug-incorporated LCP nanoformulations may be a valuable nanomedicine that is able to inhibit primary tumors and prevent tumor dissemination with minimum side effects on healthy cells and tissues.