bluuebunny/crossref_metadata_2025 huggingface dataset:
The synthesis of strategies for the efficient performance of sophisticated technological complexes based on the cognitive simulation modelling
Authors: Zaiets N.A , Savchuk O.V , Shtepa V.M , Lutska N.M , Vlasenko L.O
Published: April 2021

Purpose. Improving the productivity and energy efficiency of complex technological complexes through the development and use of scenario-cognitive modeling in control systems. Methodology. Fuzzy cognitive maps, in the form of a weighted oriented graph, were used to develop a scenario-cognitive model. As a result of the conducted research studies, a new strategy of generalization of an expert estimation of mutual influences of concepts on the basis of methods of the cluster analysis is offered. Findings. Based on experimental research and object-oriented analysis of a complex technological complex, a structure of a fuzzy cognitive model is created. A scenario-cognitive model in the form of a weighted oriented graph (fuzzy cognitive map) has been developed, which illustrates a set of connections and the nature of the interaction of expertly determined factors. To solve the problem of impossibility of operative interrogation of experts in case of change in parameters of functioning of difficult technological complexes, expert estimations of values of weight coefficients of mutual influence of concepts are received. Cluster analysis methods were used to group expert assessments and determine a single value as a result of the research. The results of the scenario-cognitive modeling of the enterprise showed that production shutdowns and abnormal situations related to the failure of electrical equipment, deviations of the technological regime and the quality of wastewater treatment have a significant impact on the dynamics of productivity, energy efficiency and efficient use of equipment. Originality. The new scenario-cognitive model developed for forecasting the situation in the absence of accurate quantitative information consists in creating a fuzzy cognitive map, for modeling which many parameters of complex technological complexes are expertly determined. Using the developed methodology, a degree of interaction of these parameters is found, which allows determining dynamics of change in target criteria of functioning under various management strategies. Practical value. On the basis of the created scenario-cognitive model, software has been developed which allowed analyzing dynamics of change in productivity, energy efficiency and efficiency of use of the equipment under possible scenarios of functioning of difficult technological complexes is developed.
Ethical Characteristics of Research Proposals Related of COVID-19 Pandemic in Nepal: A Retrospective Review
Authors: Ghimire Namita , Hamal Pawan Kumar , Panthee Asmita , Vaidya Anju , Khadka Mira , Mahato Namra Kumar , Karn Mukesh Kumar , Verma Shashi , Dhimal Meghnath , Ghimire Prakash , Gyanwali Pradip
Published: April 2021

Background: Public health emergency is vulnerable time where maintaining ethical principles is obligatory while doing research, on the other hand, it is the same time when breach in ethics is much likely whenever a researcher is unaware, unprepared or hastens to do research. The aim of this study was to assess ethical issues of the coronavirus disease 2019 (COVID-19) related research proposals submitted during the early stages of pandemic in Nepal.Methods: Retrospective analysis of COVID-19 related research proposals and their informed consent document submitted to the ethical review board at Nepal Health Research Council was done for the study. The analysis was done as per the National Ethical Guidelines, Standard Operating Procedure for Health Research in Nepal and World Health Organization guidelines for infectious disease outbreak, 2016 under ethically relevant headings. Descriptive data were analyzed in SPSS v24.Results: The major issues were observed in the informed consent documents where 55% were lacking principal investigator’s contact information, 68% not having participant selection criteria, 70% without clear informed consent taking process, 57% without explanation of possible risks. Similarly, 68% of the interventional studies’ consent form didn’t mention possible adverse events and mitigation mechanisms.Conclusions: Most of the research proposals related to COVID-19 were devoid of major ethical elements which took longer time for receiving approval and eventually delayed the opportunity for evidence generation in critical time. More attention is needed to increase awareness and to develop capacity of researchers, reviewers, ethics committees and relevant stakeholders at the time of health emergencies.Keywords: COVID-19; ethics pandemic; research proposals
ANALISIS KARAKTER TOKOH DALAM CERITA PROSA RAKYAT ETNIK BENGKULU UNTUK MATERI PEMBELAJARAN SASTRA
Authors: Youpika Fitra , Hiasa Fina
Published: April 2021

Penelitian ini bertujuan untuk mengumpulkan dan menyebarluaskan folklor lisan cerita prosa rakyat yang terancam punah melalui pembelajaran sastra sebagai upaya pemertahanan local wisdom etnik Bengkulu. Metode penelitian yang digunakan adalah metode analisis isi. Informan yang dipilih adalah baik laki-laki perempuan yang menguasai atau memahami folklor (cerita rakyat) dan juga memahami budaya setempat. Teknik pengumpulan data yang akan dilakukan adalah observasi, wawancara, rekaman, dan atau mencatat dari sejumlah informan secara sengaja maupun tidak dengan mengikuti prinsip-prinsip baku dalam pengumpulan folklor. Lokasi penelitian adalah di wilayah Provinsi Bengkulu. Teknik keabsahan data adalah dengan mengonsultasikan data (validasi data) kepada pihak ahli (masyarakat). Teknik analis data yaitu mengklasifikasi, mentranskripsi dan penyuntingan, mentransliterasi, dan menyimpulkan. Berdasarkan nilai pendidikan karakter yang ditemukan dalam cerita rakyat etnik Bengkulu dapat disimpulkan bahwa dari 9 cerita yang  terdiri dari 6 dongeng dan 3 legenda, semuanya relevan untuk materi pembelajaran sastra di SMP. Adapun nilai pendidikan karakter yang ditemukan yaitu: pemberani, cerdik, ikhlas, kerja sama, sabar, suka berbagi, patuh, dan kerja keras, pantang menyerah, menepati janji, rajin beribadah, tidak usil, dan sederhana.
Total phenolic content and antioxidant and anticholinesterase activities of medicinal plants from the State’s Cocó Park (Fortaleza-CE, Brazil)
Authors: Morais Selene Maia de , Lopes Francisco Flávio da Silva , Fontenele Gilson Araújo , Silva Marcus Vinícius Ferreira da , Fernandes Victor Borges , Alves Daniela Ribeiro
Published: April 2021

The State’s Cocó Park in the city of Fortaleza-CE present mainly a mangrove flora and include landscape and medicinal plants. The aim of this study is determining the total phenol content, antioxidant activity against the free radical DPPH and the inhibition of the enzyme acetylcholinesterase (AChE) in ethanolic extracts of 30 medicinal plants and thus assess which plants have potential against Alzheimer's Disease.  The plants rich in phenolic compounds with amounts ranging from 297.46 ± 26.94 to 599.30 ± 17.08 mg GAE/g plant extract, which showed greater antioxidant activities (with IC50 against DPPH radical from 3.44 ± 0.16 to 3.73 ± 0.12 µg mL-1) and higher acetylcholinesterase inhibiting power (IC50 < 20 μg mL-1) were Anacardium occidentale, Ceiba pentandraLaguncularia racemosa, Mangifera indica, Myracrodrum urundeuva and Terminalia catappa. Then, these species and their constituents are recommended for more specific studies related to Alzheimer´s Disease.
Os jovens brasileiros e a sua preferência pela disciplina Ciências
Authors: Tonin Kauana Gehrke , Tolentino-Neto Luiz Caldeira Brant de , Ocampo Daniel Morin
Published: April 2021

O projeto ROSE (The Relevance of Science Education) busca compreender dados atitudinais e emocionais de jovens acerca da Ciência e Tecnologia a partir de dados coletados em um questionário já aplicado em mais de 40 países. Os resultados do ROSE-Brasil mostraram que os jovens apresentam um alto interesse pela disciplina ciências, mas que gostam mais de outras disciplinas. Este artigo tenta compreender como os jovens brasileiros se comportam frente à essa divergência ao redor do interesse e da preferência pela disciplina de ciências. Para alcançar nosso objetivo utilizamos os dados brutos da amostra ROSE-Brasil 2011, e nos valeremos de métodos de análises estatísticas. Os jovens brasileiros dividem-se em quatro grupos: Prioridade não específica (3,98%), esse grupo não tem interesse pelas aulas de ciências, mas prefere a disciplina a outras; Baixa prioridade (20,26%), não possuem nem interesse, nem preferência pela disciplina ciências; Prioridade específica (30,6%) possuem interesse e preferem a disciplina ciências a outras; Outras prioridades (45,14%) grupo mais expressivo encontram-se os jovens que têm interesse mas não preferem a disciplina ciências. Desses grupos três são mais representativos da realidade dos jovens brasileiros, tornando relevante investigar as diferenças entre os interesses e hábitos ligados à ciência e tecnologia dos jovens de cada grupo para subsidiar a criação de estratégias que tornem o ensino de ciências mais atrativo.
O gênero Weissella na indústria de alimentos: Uma revisão
Authors: Teixeira Camila Gonçalves , Silva Raiane Rodrigues da , Fusieger Andressa , Martins Evandro , Freitas Rosângela de , Carvalho Antônio Fernandes de
Published: April 2021

O gênero Weissella é composto por bactérias classificadas como Gram-positivas, catalase negativas, não formadoras de esporos, morfologia cocóide ou bacilos curtos. Pertencem ao grupo das bactérias lácticas (BAL), principalmente pela produção de ácido láctico a partir da fermentação de carboidratos. As espécies de Weissella estão distribuídas em diferentes habitats, como solos, ordenhadeiras, cana-de-açúcar e algumas cepas com características tecnológicas interessantes podem ser isoladas de alimentos fermentados, como queijos de leite cru, vegetais fermentados e leite fermentado. Do ponto de vista da tecnologia de alimentos, algumas cepas apresentam potencial na produção de exopolissacarídeos, oligossacarídeos não digeríveis, que está além de seu potencial probiótico. Portanto, as bactérias pertencentes ao gênero Weissella podem ter grande importância tecnológica, estando também envolvidas no controle de doenças de origem alimentar pela produção de bacteriocinas e peróxido de hidrogênio. Este gênero possui grande potencial para uso na indústria alimentícia.
Os índices de trincas e fraturas em laminados cerâmicos são por razões oclusais? Uma revisão sistemática
Authors: Moreno Jéssica Monique Lopes , Oliveira Danila de , Sales Paulo Sergio Morais , Marchiolli Caroline Liberato , Tenório Bruno Mendes , Barion Ariane Rodrigues , Toscano Ricardo Alves , Rocha Eduardo Passos , Assunção Wirley Gonçalves
Published: April 2021

Objetivo: avaliar, a partir de uma revisão sistemática, qual o índice de trincas e fraturas em laminados cerâmicos, a fim de estabelecer as principais causas para essas falhas. Metodologia: Foi realizada uma revisão sistemática de estudos clínicos prospectivos e retrospectivos que analisaram o índice de falhas por trincas ou fratura da restauração de dentes submetidos ao tratamento com laminados cerâmicos. Utilizou-se os descritores “ceramic” e “veneer” adaptados de acordo com as bases de dados consultadas: Science Direct, LILACS, MEDLINE (PubMed) e Google Scholar. Inicialmente foram encontrados 755 artigos, após a leitura e aplicação dos critérios de elegibilidade e exclusão, 4 artigos foram selecionados para a análise quantitativa e 5 para a análise qualitativa. Esta revisão seguiu as recomendações do Preferred Reporting Items for Systematic Reviews and Meta-analyzes (PRISMA). Resultados: A descoloração marginal foi a falha mais comumente encontrada (17,2%), seguida por lesão periodontal ou gengival (12,8%), soltura da peça (4,4%), fratura da cerâmica (2,7%) e trincas da cerâmica (1,7%). As falhas por lesão endodôntica, cárie secundária, fratura do dente e alteração de cor da cerâmica foram menores que 1%. Conclusão: A atenção em relação a oclusão, seus estudos e conceitos, devem ser levados em consideração em todo o processo do tratamento com laminados cerâmicos para garantir a longevidade e sucesso clínico.
Effects of early intervention strategies using telehealth on an infant with Down syndrome: A case study
Authors: Tudella Eloisa , Silva Carolina Fioroni Ribeiro da , Vasconcelos Clarissa Cotrim dos Anjos
Published: April 2021

Purpose: To present the strategies used and the effects of early physiotherapy intervention using telehealth on a Down syndrome infant. Materials and methods: An infant diagnosed with Down syndrome performed the early intervention. Telehealth was performed synchronously according to the biopsychosocial model The assessments were carried out using the International Classification of Functioning, Disability and Health checklist. The Alberta Infant Motor Scale and the Brazilian version of the Affordances in the Home Environment for Motor Development - Infant scale were used to assess the activity component and environmental factors, respectively. Evaluations were performed at 5, 50, 79, and 105 days of corrected age. Results: The infant obtained progressive and constant gains during 100 days of early intervention. It is known that environmental and personal factors interfere with the performance of the infant's skills. Conclusion: Early intervention initiated in the first month of life using telehealth in an infant with Down syndrome proved an effective intervention method.
Predicting Anticancer Drug Response With Deep Learning Constrained by Signaling Pathways
Authors: Zhang Heming , Chen Yixin , Li Fuhai
Published: April 2021

Thanks to the availability of multiomics data of individual cancer patients, precision medicine or personalized medicine is becoming a promising treatment for individual cancer patients. However, the association patterns, that is, the mechanism of response (MoR) between large-scale multiomics features and drug response are complex and heterogeneous and remain unclear. Although there are existing computational models for predicting drug response using the high-dimensional multiomics features, it remains challenging to uncover the complex molecular mechanism of drug responses. To reduce the number of predictors/features and make the model more interpretable, in this study, 46 signaling pathways were used to build a deep learning model constrained by signaling pathways, consDeepSignaling, for anti–drug response prediction. Multiomics data, like gene expression and copy number variation, of individual genes can be integrated naturally in this model. The signaling pathway–constrained deep learning model was evaluated using the multiomics data of ∼1000 cancer cell lines in the Broad Institute Cancer Cell Line Encyclopedia (CCLE) database and the corresponding drug–cancer cell line response data set in the Genomics of Drug Sensitivity in Cancer (GDSC) database. The evaluation results showed that the proposed model outperformed the existing deep neural network models. Also, the model interpretation analysis indicated the distinctive patterns of importance of signaling pathways in anticancer drug response prediction.
Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes
Authors: Huang Yuzhao , He Yuchen , Makarcyzk Meagan J. , Lin Hang
Published: April 2021

Autologous chondrocyte implantation (ACI) is a procedure used to treat articular cartilage injuries and prevent the onset of post-traumatic osteoarthritis. In vitro expansion of chondrocytes, a necessary step in ACI, results in the generation of senescent cells that adversely affect the quality and quantity of newly formed cartilage. Recently, a senolytic peptide, fork head box O transcription factor 4-D-Retro-Inverso (FOXO4-DRI), was reported to selectively kill the senescent fibroblasts. In this study, we hypothesized that FOXO4-DRI treatment could remove the senescent cells in the expanded chondrocytes, thus enhancing their potential in generating high-quality cartilage. To simulate the in vitro expansion for ACI, chondrocytes isolated from healthy donors were expanded to population doubling level (PDL) 9, representing chondrocytes ready for implantation. Cells at PDL3 were also used to serve as the minimally expanded control. Results showed that the treatment of FOXO4-DRI removed more than half of the cells in PDL9 but did not significantly affect the cell number of PDL3 chondrocytes. Compared to the untreated control, the senescence level in FOXO4-DRI treated PDL9 chondrocytes was significantly reduced. Based on the result from standard pellet culture, FOXO4-DRI pre-treatment did not enhance the chondrogenic potential of PDL9 chondrocytes. However, the cartilage tissue generated from FOXO4-DRI pretreated PDL9 cells displayed lower expression of senescence-relevant secretory factors than that from the untreated control group. Taken together, FOXO4-DRI is able to remove the senescent cells in PDL9 chondrocytes, but its utility in promoting cartilage formation from the in vitro expanded chondrocytes needs further investigation.
RETRACTED: GATA4 Regulates Inflammation-Driven Pancreatic Ductal Adenocarcinoma Progression
Authors: Jiang Weiliang , Chen Congying , Huang Li , Shen Jie , Yang Lijuan
Published: April 2021

Cancer-associated inflammation is a key molecular feature in the progression of pancreatic ductal adenocarcinoma (PDAC). GATA4 is a transcription factor that participates in the regulation and normal development of several endoderm- and mesoderm-derived tissues such as the pancreas. However, it remains unclear whether GATA4 is involved in the inflammation-driven development of pancreatic cancer. Here, we employed quantitative reverse transcription PCR, immunohistochemistry, and differential expression analysis to investigate the association between GATA4 and inflammation-driven PDAC. We found that overexpression of GATA4 in pancreatic tumor tissue was accompanied by increased levels of inflammatory macrophages. We used macrophage-conditioned medium to validate inflammation models following treatment with varying concentrations of lipopolysaccharide and determined whether GATA4-dependent inflammatory stimuli affected pancreatic cancer cell invasion and growth in vitro. Nude mouse models of dibutyltin dichloride-induced chronic pancreatitis with orthotopic tumor xenografts were used to evaluate the effect of the inflammatory microenvironment on GATA4 expression in vivo. Our findings indicate that overexpression of GATA4 dramatically aggravated inflammatory stimuli-induced pancreatic cancer cell invasion and growth via NF-κB and STAT3 signaling, whereas silencing of GATA4 attenuated invasion and growth. Overall, our findings suggest that inflammation-driven cancer progression is dependent on GATA4 expression and is mediated through the STAT3 and NF-κB signaling pathways.
ZNRF1 Mediates Epidermal Growth Factor Receptor Ubiquitination to Control Receptor Lysosomal Trafficking and Degradation
Authors: Shen Chia-Hsing , Chou Chih-Chang , Lai Ting-Yu , Hsu Jer-En , Lin You-Sheng , Liu Huai-Yu , Chen Yan-Kai , Ho I-Lin , Hsu Pang-Hung , Chuang Tsung-Hsien , Lee Chih-Yuan , Hsu Li-Chung
Published: April 2021

Activation of the epidermal growth factor receptor (EGFR) is crucial for development, tissue homeostasis, and immunity. Dysregulation of EGFR signaling is associated with numerous diseases. EGFR ubiquitination and endosomal trafficking are key events that regulate the termination of EGFR signaling, but their underlying mechanisms remain obscure. Here, we reveal that ZNRF1, an E3 ubiquitin ligase, controls ligand-induced EGFR signaling via mediating receptor ubiquitination. Deletion of ZNRF1 inhibits endosome-to-lysosome sorting of EGFR, resulting in delayed receptor degradation and prolonged downstream signaling. We further demonstrate that ZNRF1 and Casitas B-lineage lymphoma (CBL), another E3 ubiquitin ligase responsible for EGFR ubiquitination, mediate ubiquitination at distinct lysine residues on EGFR. Furthermore, loss of ZNRF1 results in increased susceptibility to herpes simplex virus 1 (HSV-1) infection due to enhanced EGFR-dependent viral entry. Our findings identify ZNRF1 as a novel regulator of EGFR signaling, which together with CBL controls ligand-induced EGFR ubiquitination and lysosomal trafficking.
Tlx3 Exerts Direct Control in Specifying Excitatory Over Inhibitory Neurons in the Dorsal Spinal Cord
Authors: Monteiro Filipe A. , Miranda Rafael M. , Samina Marta C. , Dias Ana F. , Raposo Alexandre A. S. F. , Oliveira Patrícia , Reguenga Carlos , Castro Diogo S. , Lima Deolinda
Published: April 2021

The spinal cord dorsal horn is a major station for integration and relay of somatosensory information and comprises both excitatory and inhibitory neuronal populations. The homeobox gene Tlx3 acts as a selector gene to control the development of late-born excitatory (dILB) neurons by specifying glutamatergic transmitter fate in dorsal spinal cord. However, since Tlx3 direct transcriptional targets remain largely unknown, it remains to be uncovered how Tlx3 functions to promote excitatory cell fate. Here we combined a genomics approach based on chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) and expression profiling, with validation experiments in Tlx3 null embryos, to characterize the transcriptional program of Tlx3 in mouse embryonic dorsal spinal cord. We found most dILB neuron specific genes previously identified to be directly activated by Tlx3. Surprisingly, we found Tlx3 also directly represses many genes associated with the alternative inhibitory dILA neuronal fate. In both cases, direct targets include transcription factors and terminal differentiation genes, showing that Tlx3 directly controls cell identity at distinct levels. Our findings provide a molecular frame for the master regulatory role of Tlx3 in developing glutamatergic dILB neurons. In addition, they suggest a novel function for Tlx3 as direct repressor of GABAergic dILA identity, pointing to how generation of the two alternative cell fates being tightly coupled.
The Extracellular Matrix Glycoprotein Tenascin C and Adult Neurogenesis
Authors: Tucić Milena , Stamenković Vera , Andjus Pavle
Published: April 2021

Tenascin C (TnC) is a glycoprotein highly expressed in the extracellular matrix (ECM) during development and in the adult central nervous system (CNS) in regions of active neurogenesis, where neuron development is a tightly regulated process orchestrated by extracellular matrix components. In addition, newborn cells also communicate with glial cells, astrocytes and microglia, indicating the importance of signal integration in adult neurogenesis. Although TnC has been recognized as an important molecule in the regulation of cell proliferation and migration, complete regulatory pathways still need to be elucidated. In this review we discuss the formation of new neurons in the adult hippocampus and the olfactory system with specific reference to TnC and its regulating functions in this process. Better understanding of the ECM signaling in the niche of the CNS will have significant implications for regenerative therapies.
Association of Increased Circulating Acetic Acid With Poor Survival in Pseudomonas aeruginosa Ventilator-Associated Pneumonia Patients
Authors: Qi Xiaoling , Zhang Li , Xu Jing , Tao Zheying , Wang Xiaoli , Qiu Yuzhen , Pan Tingting , Liu Zhaojun , Qu Hongping , Tan Ruoming , Liu Jialin
Published: April 2021

Background

We previously found that microbial disruption in Pseudomonas aeruginosa ventilator-associated pneumonia (PA-VAP) patients are long-lasting. Long-term microbial dysbiosis may lead to changes in metabolites. Short-chain fatty acids (SCFAs) are microbial fermentation products and show beneficial effects in patients with pneumonia. In this study, we aimed to explore the association between circulating SCFA levels and clinical outcomes in patients with PA-VAP.

Methods

In this study, we analyzed SCFAs in the serum of 49 patients with PA-VAP by gas chromatography-mass spectrometry analysis. Twenty of these patients died, and 29 survived. The correlation between serum SCFAs and patient survival and immune parameters was analyzed.

Results

We developed a partial least squares discriminant analysis (PLS-DA) model to examine differential SCFAs in 49 patients with PA-VAP. Among the seven SCFAs, only acetic acid was increased in non-survivors (P = 0.031, VIP > 1). Furthermore, high levels of acetic acid (>1.96ug/ml) showed increased 90-day mortality compared to low levels of acetic acid (<1.96ug/ml) in Kaplan-Meier survival analyses (P = 0.027). Increased acetic acid also correlated with reduced circulating lymphocyte and monocyte counts.

Conclusion

Our study showed that increased circulating acetic acid is associated with 90-day mortality in PA-VAP patients. The decrease in lymphocytes and monocytes might be affected by acetic acid and involved in the poor prognosis.
Systematic Evaluation of Design Choices for Deep Facial Action Coding Across Pose
Authors: Niinuma Koichiro , Onal Ertugrul Itir , Cohn Jeffrey F. , Jeni László A.
Published: April 2021

The performance of automated facial expression coding is improving steadily. Advances in deep learning techniques have been key to this success. While the advantage of modern deep learning techniques is clear, the contribution of critical design choices remains largely unknown, especially for facial action unit occurrence and intensity across pose. Using the The Facial Expression Recognition and Analysis 2017 (FERA 2017) database, which provides a common protocol to evaluate robustness to pose variation, we systematically evaluated design choices in pre-training, feature alignment, model size selection, and optimizer details. Informed by the findings, we developed an architecture that exceeds state-of-the-art on FERA 2017. The architecture achieved a 3.5% increase in F1 score for occurrence detection and a 5.8% increase in Intraclass Correlation (ICC) for intensity estimation. To evaluate the generalizability of the architecture to unseen poses and new dataset domains, we performed experiments across pose in FERA 2017 and across domains in Denver Intensity of Spontaneous Facial Action (DISFA) and the UNBC Pain Archive.
Analysis and Classification of Word Co-Occurrence Networks From Alzheimer’s Patients and Controls
Authors: Millington Tristan , Luz Saturnino
Published: April 2021

In this paper we construct word co-occurrence networks from transcript data of controls and patients with potential Alzheimer’s disease using the ADReSS challenge dataset of spontaneous speech. We examine measures of the structure of these networks for significant differences, finding that networks from Alzheimer’s patients have a lower heterogeneity and centralization, but a higher edge density. We then use these measures, a network embedding method and some measures from the word frequency distribution to classify the transcripts into control or Alzheimer’s, and to estimate the cognitive test score of a participant based on the transcript. We find it is possible to distinguish between the AD and control networks on structure alone, achieving 66.7% accuracy on the test set, and to predict cognitive scores with a root mean squared error of 5.675. Using the network measures is more successful than using the network embedding method. However, if the networks are shuffled we find relatively few of the measures are different, indicating that word frequency drives many of the network properties. This observation is borne out by the classification experiments, where word frequency measures perform similarly to the network measures.
Wave Properties of Gas-Hydrate Bearing Sediments Based on Poroelasticity
Authors: Wang Wei , Ba Jing , Carcione José M. , Liu Xu , Zhang Lin
Published: April 2021

Natural gas hydrates have the properties of ice with a microporous structure and its concentration in sediments highly affects the wave velocity and attenuation. Previous studies have performed investigations based on the measurements of laboratory data, sonic-log data, and field data, whereas the variation trend of wave dissipation with increasing hydrate concentration at different frequencies is still unclear. We consider two different models to study this problem, both based on the Biot-Rayleigh double-porosity theory. In the first model, hydrate is part of the pore infill, unbonded from the grains, and brine saturates the remaining pore space. In the second model, hydrate forms a second skeleton and cements the grains. We obtain the P-wave velocity dispersion and attenuation as a function of the inclusion radius, porosity, and hydrate content. The analysis shows that the predictions of both models agree with the experimental data. At sonic log frequencies, the second model predicts much more attenuation, due to wave-induced local fluid flow (mesoscopic loss), and the behavior is such that below a given hydrate concentration the dissipation increases and then decreases beyond that concentration.
The Impact of Social Behavior and Peers’ Attitudes Toward Students With Special Educational Needs on Self-Reported Peer Interactions
Authors: Schwab Susanne , Lehofer Mike , Tanzer Norbert
Published: April 2021

According to the literature, social participation (e.g., peer interactions) of students diagnosed with special educational needs (SEN) has to be focused upon as they are at a higher risk of being socially excluded compared to students without SEN. Research has pointed out that social participation of students with SEN is influenced by their own social behavior as well as the attitudes of peers with no SEN toward them. The present study assessed the impact of the social behavior of students diagnosed with SEN (n= 88; 48 boys and 40 girls) as well as that of the attitudes of their peers without SEN (n= 227; 139 boys and 153 girls) toward them on the social participation. Results indicated that students without SEN were less likely to interact with their classmates with SEN. Peer interactions of students with SEN were not significantly influenced by their own social behavior.
Interpreting Diachronic Size Variation in Prehistoric Central Asian Cereal Grains
Authors: Motuzaite Matuzeviciute Giedre , Mir-Makhamad Basira , Spengler Robert N.
Published: April 2021

The morphology of ancient cereal grains in Central Asia has been heavily discussed as an indicator of specific genetic variants, which are often linked to cultural factors or distinct routes of dispersal. In this paper, we present the largest currently existing database of barley (n= 631) and wheat (n= 349) measurements from Central Asia, obtained from two different periods at the Chap site (ca. 3,500 to 1,000 BC), located in the Tien Shan Mountains of Kyrgyzstan at 2,000 masl. The site is situated at the highest elevation ecocline for successful cereal cultivation and is, therefore, highly susceptible to minor climatic fluctuations that could force gradients up or down in the foothills. We contrast the Chap data with measurements from other second and first millennia BC sites in the region. An evident increase in average size over time is likely due to the evolution of larger grains or the introduction of larger variants from elsewhere. Additionally, site- or region-specific variation is noted, and we discuss potential influences for the formation of genetic varieties, including possible pleiotropic linkages and/or developmental responses to external factors, such as environmental fluctuations, climate, irrigation inputs, soil nutrients, pathologies, and seasonality. External factors acting on developmental or acclamatory responses in plants can be either natural or cultural. We argue that the study of long-term changes in grain morphology on the edges of crop-growing ranges can be informative regarding cultural and environmental constraints in the past.
Modeling Potential Dispersal Routes for Giant Pandas in Their Key Distribution Area of the Qinling Mountains, China
Authors: Liu Xuehua , Liu Lanmei , Liu Linna , Jin Xuelin , Songer Melissa
Published: April 2021

The national surveys on giant panda (Ailuropoda melanoleuca) population and habitat quality have shown a high-density population of this species in the Qinling Mountains, China. We investigated five adjacent nature reserves (NR), i.e., the key distribution area of giant pandas in the Qinling Mountains, to model and identify the potential dispersal routes for giant pandas. We hypothesized that giant pandas will spread to neighboring areas when the population of the species keeps increasing. Habitat suitability was firstly evaluated based on environmental and disturbance factors. We then identified source and sink patches for giant pandas’ dispersal. Further, Minimum Cumulative Resistance (MCR) model was applied to calculate cost of movement. Finally, the Current Theory was adopted to model linkages between source and sink patches to explore potential dispersal routes of giant pandas. Our results showed that (1) the three large source patches and eight potential sink patches were identified; (2) the 14 potential corridors were predicted for giant pandas dispersing from source patches to the neighboring areas; (3) through the predicted corridors, the giant pandas in the source patches could disperse to the west, the south and the east sink patches. Our research revealed possible directional patterns for giant pandas’ dispersal in their key distribution area of the Qinling Mountains, and can provide the strong recommendations in policy and conservation strategies for improving giant panda habitat management in those identified sink patches and also potential dispersal corridors.
Immunosuppressive Mechanisms of Regulatory B Cells
Authors: Catalán Diego , Mansilla Miguel Andrés , Ferrier Ashley , Soto Lilian , Oleinika Kristine , Aguillón Juan Carlos , Aravena Octavio
Published: April 2021

Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting ongoing immune responses and reestablishing immune homeostasis. The important role of Bregs in restraining the pathology associated with exacerbated inflammatory responses in autoimmunity and graft rejection has been consistently demonstrated, while more recent studies have suggested a role for this population in other immune-related conditions, such as infections, allergy, cancer, and chronic metabolic diseases. Initial studies identified IL-10 as the hallmark of Breg function; nevertheless, the past decade has seen the discovery of other molecules utilized by human and murine B cells to regulate immune responses. This new arsenal includes other anti-inflammatory cytokines such IL-35 and TGF-β, as well as cell surface proteins like CD1d and PD-L1. In this review, we examine the main suppressive mechanisms employed by these novel Breg populations. We also discuss recent evidence that helps to unravel previously unknown aspects of the phenotype, development, activation, and function of IL-10-producing Bregs, incorporating an overview on those questions that remain obscure.
The Importance of Glycans of Viral and Host Proteins in Enveloped Virus Infection
Authors: Li Yuqing , Liu Dongqi , Wang Yating , Su Wenquan , Liu Gang , Dong Weijie
Published: April 2021

Animal viruses are parasites of animal cells that have characteristics such as heredity and replication. Viruses can be divided into non-enveloped and enveloped viruses if a lipid bilayer membrane surrounds them or not. All the membrane proteins of enveloped viruses that function in attachment to target cells or membrane fusion are modified by glycosylation. Glycosylation is one of the most common post-translational modifications of proteins and plays an important role in many biological behaviors, such as protein folding and stabilization, virus attachment to target cell receptors and inhibition of antibody neutralization. Glycans of the host receptors can also regulate the attachment of the viruses and then influence the virus entry. With the development of glycosylation research technology, the research and development of novel virus vaccines and antiviral drugs based on glycan have received increasing attention. Here, we review the effects of host glycans and viral proteins on biological behaviors of viruses, and the opportunities for prevention and treatment of viral infectious diseases.
NF-κB c-Rel Is Dispensable for the Development but Is Required for the Cytotoxic Function of NK Cells
Authors: Vicioso Yorleny , Wong Derek P. , Roy Nand K. , Das Nayanika , Zhang Keman , Ramakrishnan Parameswaran , Parameswaran Reshmi
Published: April 2021

Natural Killer (NK) cells are cytotoxic lymphocytes critical to the innate immune system. We found that germline deficiency of NF-κB c-Rel results in a marked decrease in cytotoxic function of NK cells, bothin vitroandin vivo, with no significant differences in the stages of NK cell development. We found that c-Rel binds to the promoters of perforin and granzyme B, two key proteins required for NK cytotoxicity, and controls their expression. We generated a NK cell specific c-Rel conditional knockout to study NK cell intrinsic role of c- Rel and found that both global and conditional c-Rel deficiency leads to decreased perforin and granzyme B expression and thereby cytotoxic function. We also confirmed the role of c-Rel in perforin and granzyme B expression in human NK cells. c-Rel reconstitution rescued perforin and granzyme B expressions in c-Rel deficient NK cells and restored their cytotoxic function. Our results show a previously unknown role of c-Rel in transcriptional regulation of perforin and granzyme B expressions and control of NK cell cytotoxic function.
Next Generation Sequencing for Detecting Somatic FAS Mutations in Patients With Autoimmune Lymphoproliferative Syndrome
Authors: López-Nevado Marta , Docampo-Cordeiro Jorge , Ramos José T. , Rodríguez-Pena Rebeca , Gil-López Celia , Sánchez-Ramón Silvia , Gil-Herrera Juana , Díaz-Madroñero María J. , Delgado-Martín María A. , Morales-Pérez Pablo , Paz-Artal Estela , Magerus Aude , Rieux-Laucat Frederic , Allende Luis M.
Published: April 2021

Autoimmune lymphoproliferative syndrome (ALPS) is a primary immune regulatory disorder clinically defined by chronic and benign lymphoproliferation, autoimmunity and an increased risk of lymphoma due to a genetic defect in the FAS-FASL apoptotic pathway. Genetic defects associated with ALPS are germinal and somatic mutations in FAS gene, in addition to germinal mutations in FASLG, FADD, CASP8 and CASP10 genes. The accumulation of CD3+TCRαβ+CD4-CD8- double negative T-cells (DNT) is a hallmark of the disease and 20-25% of ALPS patients show heterozygous somatic mutations restricted to DNT in the FAS gene (ALPS-sFAS patients). Nowadays, somatic mutations in the FAS gene are detected through Sanger sequencing in isolated DNT. In this study, we report an ALPS-sFAS patient fulfilling clinical and laboratory ALPS criteria, who was diagnosed through NGS with a targeted gene panel using DNA from whole blood. Data analysis was carried out with Torrent Suite Software and variant detection was performed by both germinal and somatic variant caller plugin. The somatic variant caller correctly detected other six ALPS-sFAS patients previously diagnosed in the authors’ laboratories. In summary, this approach allows the detection of both germline and somatic mutations related to ALPS by NGS, avoiding the isolation of DNT as the first step. The reads of the somatic variants could be detected even in patients with DNT in the cut off limit. Thus, custom-designed NGS panel testing may be a faster and more reliable method for the diagnosis of new ALPS patients, including those with somatic FAS mutations (ALPS-sFAS).
Single-Cell Transcriptional Heterogeneity of Neutrophils During Acute Pulmonary Cryptococcus neoformans Infection
Authors: Deerhake M. Elizabeth , Reyes Estefany Y. , Xu-Vanpala Shengjie , Shinohara Mari L.
Published: April 2021

Neutrophils are critical as the first-line defense against fungal pathogens. Yet, previous studies indicate that neutrophil function is complex duringCryptococcus neoformans (Cn)infection. To better understand the role of neutrophils in acute pulmonary cryptococcosis, we analyzed neutrophil heterogeneity by single-cell transcriptional analysis of immune cells in the lung ofCn-infected mice from a published dataset. We identified neutrophils by reference-based annotation and identified two distinct neutrophil subsets generated during acuteCninfection: A subset with an oxidative stress signature (Ox-PMN) and another with enhanced cytokine gene expression (Cyt-PMN). Based on gene regulatory network and ligand-receptor analysis, we hypothesize that Ox-PMNs interact with the fungus and generate ROS, while Cyt-PMNs are longer-lived neutrophils that indirectly respond toCn-derived ligands and cytokines to modulate cell-cell communication with dendritic cells and alveolar macrophages. Based on the data, we hypothesized that, duringin vivofungal infection, there is a division of labor in which each activated neutrophil becomes either Ox-PMN or Cyt-PMN.
The Toolbox for Untangling Chromosome Architecture in Immune Cells
Authors: Liu Shuai , Zhao Keji
Published: April 2021

The code of life is not only encrypted in the sequence of DNA but also in the way it is organized into chromosomes. Chromosome architecture is gradually being recognized as an important player in regulating cell activities (e.g., controlling spatiotemporal gene expression). In the past decade, the toolbox for elucidating genome structure has been expanding, providing an opportunity to explore this under charted territory. In this review, we will introduce the recent advancements in approaches for mapping spatial organization of the genome, emphasizing applications of these techniques to immune cells, and trying to bridge chromosome structure with immune cell activities.
Development and Validation of Automated Visual Field Report Extraction Platform Using Computer Vision Tools
Authors: Saifee Murtaza , Wu Jian , Liu Yingna , Ma Ping , Patlidanon Jutima , Yu Yinxi , Ying Gui-Shuang , Han Ying
Published: April 2021

Purpose: To introduce and validate hvf_extraction_script, an open-source software script for the automated extraction and structuring of metadata, value plot data, and percentile plot data from Humphrey visual field (HVF) report images.

Methods: Validation was performed on 90 HVF reports over three different report layouts, including a total of 1,530 metadata fields, 15,536 value plot data points, and 10,210 percentile data points, between the computer script and four human extractors, compared against DICOM reference data. Computer extraction and human extraction were compared on extraction time as well as accuracy of extraction for metadata, value plot data, and percentile plot data.

Results: Computer extraction required 4.9-8.9 s per report, compared to the 6.5-19 min required by human extractors, representing a more than 40-fold difference in extraction speed. Computer metadata extraction error rate varied from an aggregate 1.2-3.5%, compared to 0.2-9.2% for human metadata extraction across all layouts. Computer value data point extraction had an aggregate error rate of 0.9% for version 1, <0.01% in version 2, and 0.15% in version 3, compared to 0.8-9.2% aggregate error rate for human extraction. Computer percentile data point extraction similarly had very low error rates, with no errors occurring in version 1 and 2, and 0.06% error rate in version 3, compared to 0.06-12.2% error rate for human extraction.

Conclusions: This study introduces and validates hvf_extraction_script, an open-source tool for fast, accurate, automated data extraction of HVF reports to facilitate analysis of large-volume HVF datasets, and demonstrates the value of image processing tools in facilitating faster and cheaper large-volume data extraction in research settings.
Predictive Analytic Model for Diagnosis of Ectopic Pregnancy
Authors: Rueangket Ploywarong , Rittiluechai Kristsanamon
Published: April 2021

Objective: Ectopic pregnancy (EP) is a serious condition. Delayed diagnosis could lead to life-threatening outcomes. The study aimed to develop a diagnostic predictive model for EP to approach suspected cases with prompt intervention before the rupture occurred.

Methods: A retrospective cross-sectional study enrolled 347 pregnant women presenting first-trimester complications (abdominal pain or vaginal bleeding) with diagnosis suspected of pregnancy of unknown location, who were eligible and underwent chart review. The data including clinical risk factors, signs and symptoms, serum human chorionic gonadotropin (hCG), and ultrasound findings were analyzed. The statistical predictive score was developed by performing logistic regression analysis. The testing data of 30 patients were performed to test the validation of predictive scoring.

Results: From a total of 22 factors, logistic regression method–derived scoring model was based on five potent factors (history of pelvic inflammatory disease, current use of emergency pills, cervical motion tenderness, serum hCG ≥1,000 mIU/ml, and ultrasound finding of adnexal mass) using a cutoff score ≥3. This predictive index score was able to determine ectopic pregnancy with an accuracy of 77.8% [95% confidence interval (CI) = 73.1–82.1], specificity of 91.0% (95% CI = 62.1–72.0), sensitivity of 67.0% (95% CI = 88.0–94.0), and area under the curve of 0.906 (95% CI = 0.875–0.937). In the validation group, no patient with negative result of this score had an EP.

Conclusion: Statistical predictive score was derived with high accuracy and applicable performance for EP diagnosis. This score could be used to support clinical decision making in routine practice for management of EP.
Frailty and Its Associated Risk Factors: First Phase Analysis of Multicentre Indonesia Longitudinal Aging Study
Authors: Setiati Siti , Soejono Czeresna Heriawan , Harimurti Kuntjoro , Dwimartutie Noto , Aryana I. G. P. Suka , Sunarti Sri , Budiningsih Fatichati , Mulyana Roza , Dwipa Lazuardhi , Sudarso Agus , Rensa Rensa , Istanti Rahmi , Azwar Muhammad Khifzhon , Marsigit Jessica
Published: April 2021

Background: National long-term care development requires updated epidemiological data related to frailty. We aimed to find the prevalence of frailty and its associated factors among Indonesian elderly.

Methods: We conducted first-phase cross-sectional analysis of Indonesia Longitudinal Aging Study (INALAS) data collected from community-dwelling outpatients aged 60 years and older without acute illness in nine geriatric service care centres. Descriptive, bivariate and multivariate analyses were conducted.

Results: Among 908 elderly in this study, 15.10% were robust, 66.20% were pre-frail, and 18.70% were frail. Functional dependence was associated with frailty among Indonesian elderly (OR 5.97, 95% CI 4.04–8.80). Being depressed and at risk for malnutrition were also associated with frailty with OR 2.54, 95% CI 1.56–4.12, and OR 2.56, 95% CI 1.68–3.90, respectively. Prior history of fall (OR 1.77, 95% CI 1.16–2.72) and hospitalization (OR 1.46, 95% CI 0.97–2.20) in the previous 12 months were associated with frailty. There is also significant association between poly pharmacy and frailty (OR 2.42, 95% CI 1.50–3.91).

Conclusion: Approximately one in five Indonesian community-dwelling elderly was frail. Frailty is associated with functional dependence, being at risk for malnutrition or being malnourished, depression, history of fall, history of hospitalization, and poly pharmacy. There may be bidirectional relationships between the risk factors and frailty. The development of long-term care in Indonesia should be considered, without forcing the elderly who need it.