bluuebunny/crossref_metadata_2025 huggingface dataset:
ISLAMIC EDUCATION IN INDUSTRIAL REVOLUTION 4.0 ERA: Considering Fazlur Rahman’s Thought about Islamic Education Modernization
Authors: Maulana Imron
Published: June 2020

Islamic education always intersects with the movement of dynamic times. Islamic education is currently in the industrial revolution 4.0 era. which involves industrial competition. With cyber-based, this competition makes Islamic education at a crossroads. This article efforts to express the thought of Islamic education by considering Fazlur Rahman’s thought and its relevance to education in the industrial revolution 4.0 era. With the descriptive-analysis method, this article shows that Fazlur Rahman is concerned about strengthening the education system and strengthening the quality of Islamic education output through the renewal of Islamic education. Islamic education must be able to answer the needs in modernity, because surviving the old tradition is an intellectual suicide process, so that it is relevant to the industrial revolution 4.0 era.[Pendidikan Islam selalu bersinggungan dengan gerak zaman yang dinamis. Pendidikan Islam saat ini berada pada era revolusi industri 4.0. yang melibatkan persaingan industri. Dengan berbasis cyber, persaingan ini membuat pendidikan Islam berada pada persimpangan jalan. Artikel ini berupaya mengungkapkan pemikiran pendidikan Islam Fazlur Rahman dan relevansinya dengan pendidikan di era revolusi industri 4.0. Dengan metode analisis-deskriptif, artikel ini menunjukkan bahwa Fazlur Rahman memerhatikan penguatan sistem pendidikan serta penguatan kualitas output pendidikan Islam melalui pembaharuan pendidikan Islam. Pendidikan Islam harus mampu menjawab kebutuhan zaman, karena bertahan pada tradisi lama merupakan proses bunuh diri intelektual, sehingga ia relevan dengan era revolusi industri 4.0]
Pero ¿Hubo guerra en Toniná? O de cómo las apariencias engañan
Authors: Ayala Falcón Maricela
Published: June 2020

El propósito de este artículo es presentar la información epigráfica y arqueológica que tenemos sobre Tonina, una ciudad del Clásico maya. Los avances logrados en el desciframiento de la escritura maya han abierto un nuevo campo de información para esta cultura. Desde la publicación de A Form of Kings (Schele y Freidel), muchos investigadores han dedicado sus esfuerzos a la recuperación de la historia prehispánica de los mayas bajo tales enfoques, algunas veces con éxito. En este artículo se presenta un caso en el cual las evidencias no parecen corresponder, en ocasiones, con la tradición maya clásica. En él también se contribuye con nueva información a la recuperación del pasado histórico de la región.
EM BUSCA DE UM TEATRO SAGRADO: ENCONTROS E TRAVESSIAS NO OPEN PROGRAM OF WORKCENTER OF J. GROTOWSKI AND T. RICHARDS
Authors: Piva Bruno Leal
Published: June 2020

Resumo: O presente artigo tem como finalidade analisar a importância da interculturalidade, tratada aqui como hibridez cultural, no percurso artístico de Jerzy Grotowski, sobretudo no Open Program of Workcenter of Jerzy Grotowski and Thomas Richards, que está inserido em sua última fase de pesquisa denominada Arte como Veículo, observando o uso de técnicas e tradições não ocidentais e cantigas ancestrais afro-caribenhas, no encontro da sensibilidade e sinceridade interiores de si através do outro, num processo de resgate do corpo-memória ou espaço “sagrado” produzido por ações vocais e corporais experimentados pelos atuantes em oficina do referido Programa.
Understanding ASEAN Peace Preservation Role in the Korean Peninsula
Authors: Akhli Rangga Amalul
Published: June 2020

Since its inception in 1967, ASEAN has an important role to establish regional security and peace building in Southeast Asia. That effort certainly continues up until now. Realizing that the peace preservation needs to be extended to its northern neighbor, ASEAN initiated mechanisms that would enable it to play greater role in the Korean peninsula. However, the association effort to preserve peace in the region is inseparable from criticism which stated that this association was not effective in reconciling the two Koreas. Amidst the pessimism of ASEAN's role in the Korean Peninsula, this paper is presented to respond that argument. Furthermore, by using the constructivism paradigm, this paper argues that the ASEAN approach that believes in norms building to address security challenges in the Korean peninsula uncovers space for peace preservation in other ways amid such options and mechanisms that other powers offer which in fact last briefly and exacerbate hostility. To conclude, the approach has been useful for several reasons, such as maintaining the continuity of the multilateralism ties with North Korea and being an important actor that can be trusted by the two Koreas in the midst of a vortex of influences involving the big powers competition.
Diferensiasi Kebijakan Polandia dalam Menghadapi Migran Ekonomi dan Pengungsi
Authors: Anandita Rizky , Zein Fadia Ayunabila , Safitri Dasa Feby , Nur Rahmatul Amalia
Published: June 2020

Migrasi merupakan sebuah isu yang tengah menjadi pusat perhatian bagi negara-negara Eropa, khususnya negara-negara yang menjadi anggota dari Uni Eropa. Signifikansi isu migrasi bagi negara-negara Uni Eropa mengalami peningkatan dengan adanya kebijakan dari organisasi supranasional tersebut yang berupaya mendistribusikan tanggung jawab penerimaan imigran dan pengungsi secara merata antara negara-negara anggota. Dengan demikian, Polandia sebagai salah satu negara anggota Uni Eropa dihadapkan pada dua permasalahan, yakni penolakan masyarakat terhadap masuknya imigran dari luar Uni Eropa dan tekanan dari Uni Eropa untuk mematuhi kuota pengungsi, yang diperparah dengan krisis tenaga kerja di Polandia. Kajian ini membahas mengenai respons kebijakan Polandia dalam menghadapi permasalahan-permasalahan yang telah disebutkan, khususnya dalam merespon kelompok imigran dari Timur Tengah dan Afrika. Sebagai hasil dari kajian ini, dapat diketahui bahwa terdapat beragam faktor yang memengaruhi kalkulasi kebijakan imigrasi Polandia, yaitu: 1) faktor lingkungan; 2) budaya dan identitas; 3) pendidikan; 4) adanya asumsi “Trojan Horse”; serta 5) ketidakpuasan penduduk lokal. Kelima faktor tersebut menentukan persepsi masyarakat dan pemerintah Polandia terhadap isu migrasi.
Containment Amerika Serikat terhadap Fenomena Rise of China dalam Perspektif Hegemoni Realisme
Authors: Arseno Ary
Published: June 2020

This paper explains about the United States’ containment strategy towardChina, the argue that the United States’ strategy of containment aimsto contain the China’s rise phenomenon. After the Cold War, China hasdeveloped as a powerful country which has capability to threaten theUnited States’ ‘sole hegemon’ status. Containment is the chosen strategy tokeep Washington at the top of the hierarchy of international system. Theauthor divide this paper into three sections, the first show the relationsthe United States builds to make containment works. Then in the sectiontwo, the author explain the United States’ containment strategy withJohn Mearsheimer’s offensive realism theory. The last section, I end thispaper with conclusion that consists of important points of the paper.
Hambatan yang Dihadapi ASEAN Defense Industry Collaboration (ADIC) dalam Menentukan Platform Persenjataannya
Authors: Ningsih Novri Surya
Published: June 2020

This article is a study of the impediments to the ASEAN Defense IndustryCollaboration (ADIC) in determining its weapons platforms. In analyzingthe impediments, this article refers to the concept of Revolution in MilitaryAffairs (RMA) which formulates that the technology, doctrine, andmilitary organization are influenced by each member of the ADIC. TheRMA is a useful concept for portraying the military characteristics ofeach member. The causality constructed in this research is between thedoctrinaire, technological, and organizational features in the determinationof military and weapons platform in the ADIC. This article findsthat there is discrepancy in existing technologies, doctrines, and militaryorganizations among members of ADIC and it creates a strong impedimentin determining weapons platforms. Without initiating strongercollaboration and setting tangible policy aims to solve common groundabsence, ADIC will not go effectively.
The Effect of Helicobacter Pylori Eradication on Paraoxonase Enzyme Activity
Authors: SACIKARA Muhammed , BULUR Oktay , POLAT Mehmet , NAZLIGUL Yaşar
Published: June 2020

Purpose: Helicobacter pylori (H. pylori) infection is associated with gastrointestinal and extraintestinal diseases either directly via its special virulence factors or indirectly by increasing inflammation and oxidation. Paraoxonase-1 (PON–1) enzyme that is related to HDL cholesterol is responsible for the antioxidant and antiatherogenic effects of HDL cholesterol. PON–1 level is related to the risk of cardiovascular disease. We aimed to investigate the relation between H. pylori infection and PON-1 activity.

Material -Method: We prospectively evaluated 126 adult patients in a tertiary reference hospital in Ankara, Turkey. After H. pylori eradication therapy and checking for treatment success, 38 H. pylori-positive (17 male, 21 female) and 88 H. pylori-negative (43 male, 45 female ) patients were included in this study.

Results: PON–1 enzyme levels after H. pylori eradication therapy were 165,69U/L in H. pylori-negative and 131,68 U/L in H. pylori-positive groups. The difference in PON–1 enzyme levels after treatment in two groups was statistically significant (p=0,02).

Conclusion: Increased PON–1 enzyme levels after H. pylori eradication therapy might play a role in the antiatherosclerotic effect by reducing LDL oxidation.
COVID-19’UN SİNDİRİM SİSTEMİ ÜZERİNE ETKİLERİ
Authors: HAMUTOĞLU Rasim , ÜNVER SARAYDIN Serpil
Published: June 2020

Yeni koronavirüs hastalığı şu anda büyük bir pandemiye neden olmaktadır. Aralık 2019'da Yeni koronavirüs-19’un patlak vermesinden bu yana, virüs bulaşmış hastalarda sıklıkla çeşitli sindirim semptomları bildirilmiştir. Hastalar tipik olarak ateş ve solunum yolu hastalığı ile başvururken, bazı hastalar ishal, kusma ve karın ağrısı gibi sindirim semptomlarını da bildirmektedir. Hastalığın şiddeti arttıkça, sindirim semptomları da belirgin hale gelmektedir. Sindirim semptomları olan hastaların ortalama karaciğer enzim düzeyleri, düşük monosit sayısı ile daha uzun protrombin zamanının olduğu ve sindirim semptomları olmayanlara göre daha fazla antimikrobiyal tedavi gördükleri çeşitli çalışmalarda gösterilmiştir. Klinisyenler, ishal gibi sindirim semptomlarının yaygın olarak Yeni koronavirüs-19 'un özellikleri arasında olduğunu ve sindirim semptomları ile başvuran risk altındaki hastalarda şüphe endeksinin daha erken yükseltilmesi gerektiğini fark etmelidir.
Using Poisson Disk Sampling to Render Oil Particles at Sea
Authors: Do Vancuong , Ren Hongxiang
Published: June 2020

Fluid simulation is one of the most complex tasks in three-dimensional simulation. Specifically, in the case of oil spills at sea, the oil film constantly interacts and is influenced by the environment, thus making its composition and properties change over time. In this paper, we tackle this problem by using both Lehr's spreading model and Hoult's drifting model to build the oil spill physical model. Unlike previous studies that only applied the Poisson disk algorithm to static and solid objects, we applied it in a three-dimensional space to divide the oil film into fluid particles. The track of oil particles under the influence of waves, wind, and currents is rendered by the Unity3D tool with C# programming language, which vividly and realistically simulates the collision of oil particles on the ocean scene with obstacles such as buoys and small islands. The result of this research can be used to predict oil spill direction, thus providing the solution to respond and minimize the damage caused by oil spills at sea. We also discuss some improvements to our model by using the Marching cube algorithm to render the Metaball model.
Avaliações antioxidante e antifúngica dos óleos essenciais de Hymenaea stigonocarpa Mart. ex Hayne e Hymenaea courbaril L.
Authors: Menezes Filho Antonio Carlos Pereira de , Oliveira Filho Josemar Gonçalves de , Castro Carlos Frederico de Souza
Published: June 2020

Hymenaea stigonocarpa e Hymenaea courbaril var. courbaril são espécies vegetais pertencentes a família Leguminosae, sendo encontrados no domínio Cerrado. Apresentam frutificação anual com frutos com casca densa e aromática. O trabalho teve por objetivo avaliar o rendimento, e as atividades antioxidante e antifúngica do óleo puro e mix (mistura de ambos os óleos em igual concentração). Para extração, foi utilizado equipamento tipo Clevenger, o rendimento foi determinado em porcentagem. A atividade antioxidante foi determinada em microplacas utilizando como modelo o radical DPPH nas seguintes concentrações, partindo do óleo puro, 50, 40, 30, 20, 10, 5, 2,5 e 1,25 µL mL-1. A atividade antifúngica foi avaliada por difusão em ágar utilizando sucessivas diluições de óleo essencial puro e nas concentrações  50, 25, 12,5, 6,25, 3,13 e 1,56 µL mL-1 e mix mistura de ambos os óleos em partes iguais em DMSO, sobre Sclerotinia sclerotiorum, Colletotrichum acutatum e gloeosporioides, e para Aspergillus flavus e niger. O rendimento foi de 0,04 e 0,06% para H. stigonocarpa e H. courbaril, respectivamente. A atividade antioxidante apresentou bons resultados, para ambos os óleos essenciais de H. stigonocarpa e H. courbaril com alta redução do radical DPPH para puro e nas concentrações 50 e 40 µL mL-1. Já para o mix a concentração 50 µL mL-1 taxa de 72% de redução. No experimento antifúngico foi observada alta eficiência no controle de crescimento das hifas para o óleo essencial de H. stigonocarpa com 83% sobre Sclerotinia sclerotiorum, 75% sobre C. acutatum, e para A. flavus com 55%, respectivamente. Para o óleo essencial de H. courbaril foi observada taxa de inibição de 100% para S. sclerotiorum, 100% para C. gloeosporioides e de 70% para A. flavus. Já para o mix de óleos essenciais foi observada redução no crecimento de 88% para S. sclerotiorum, 56% C. gloesporioides e de 42% para A. niger. Os óleos essenciais puros e mix apresentaram resultados promissores como agentes antioxidantes e antifúngicos naturais in vitro.
Nominata de Avaliadores 2019
Authors: Filho José Adriano
Published: June 2020

Nominata de Avaliadores 2019
IMAGO DEI: Deus como arquétipo do inconsciente coletivo em C. G. Jung.
Authors: Cazelli Felipe Ribeiro
Published: June 2020

A Psicologia Analítica foi desenvolvida pelo psiquiatra suíço C. G. Jung, parte como uma crítica e busca de superação dos limites da Psicanálise freudiana, parte como crítica ao materialismo moderno. Para Jung, a psique é uma realidade autônoma, cujos fenômenos têm origem na energia psíquica, que pode estar orientada para objetos externos, bem como a realidades internas à psique do indivíduo. A transformação da energia psíquica, fazendo-a transitar entre objetos interiores e exteriores, é operada pelo símbolo, que produz no indivíduo o que Jung chama de experiência religiosa: trata-se da atuação do arquétipo do Self dirigindo a energia psíquica em direção à totalidade da psique, através do poder do símbolo. Para Jung, Self é a imagem de Deus que existe no indivíduo.
Jackson de Figueiredo e a Guerra Cristera
Authors: Ramalho José Rodorval
Published: June 2020

Este artigo analisa textos jornalísticos de Jackson de Figueiredo acerca do conflito armado entre católicos e liberais, que ocorria no México, conhecido como Guerra Cristera. Os textos foram veiculados no jornal carioca Gazeta de Notícias no ano de 1926. Abordaremos os escritos do intelectual católico, sobre o referido conflito, buscando compreender o seu entendimento dos conceitos de Direitos Naturais, Revolução e Civilização.
Evaluation of Protection Level, Respiratory Safety and Practical Aspects of Commercially Available Snorkel Masks as Personal Protection Devices against Aerosolized Contaminants and SARS-CoV2
Authors: Germonpre Peter , Van Rompaey Dirk , Balestra Costantino
Published: June 2020

Introduction: The SARS-CoV2 pandemic has led to an worldwide shortage of Personal Protection Devices (PPD) for medical and paramedical personnel. Adaptation of commercially available snorkel masks to serve as full face masks has been proposed. Even not formally approved as PPD, they are publicized on social media as suitable for this use. Concerns about actual protection levels and risk of carbon dioxide (CO2) accumulation while wearing them for extended periods made us perform a systematic testing of various brands, in order to verify whether they are as safe and effective as claimed. Methods: A ‘fit’ test was performed, analogous to gas mask testing. Respiratory safety was evaluated by measuring end-tidal CO2 and oxygen saturation while wearing the masks in rest and during physical exercise. Masks were tested with 3D adaptors to mount regular bacterial-viral ventilator filters when available, or with snorkel openings covered with N95/FFP2 cloth. Results: Modified masks performed reasonably well on the fit test, comparable to regular N95/FFP2 masks. Not all ventilator filters are equally protective. For all masks, a small initial increase in end-tidal CO2 was noted, remaining within physiological limits. Masks with specific adaptors (3D printed or provided by the manufacturer) are safer, have more flexibility and reliability than makeshift adaptations. Conclusions: These masks can offer benefit as a substitute for complete protective gear as they are easier to don and remove and offer full-face protection. They may be more comfortable to wear for extended periods. Proper selection of mask size, fit testing, quality of 3D printed parts and choice of filter are important.
The Corona Virus (COVID-19) Pandemic and the Challenge of Healthcare Infrastructure in Nigeria: What Role for Public-Private Partnerships
Authors: Arimoro Augustine
Published: June 2020

While it is not new that Nigeria is challenged by a huge infrastructure deficit, the COVID-19 pandemic has exposed the country’s comatose healthcare system. Given the country’s dwindling revenue, massive debt profile and the inability of the public-sector to efficiently manage public facilities in the country, this paper examines how the public-private partnership model of infrastructure procurement can be deployed as a solution for Nigeria’s healthcare crisis. In addition to the above, this paper takes a look at how a partnership with the private sector can aid Nigeria’s quest towards achieving healthcare-related Sustainable Development Goals. The paper also considers two healthcare-based projects as case studies to serve as lessons for future projects in the country. Among others, the paper recommends a holistic long-term solution for the country’s healthcare needs.
Assessment of Epidemiological Determinants of COVID-19 Pandemic Related to Social and Economic Factors Globally
Authors: Hassan Mohammad Mahmudul , Kalam Abul , Shano Shahanaj , Nayem Md. Raihan Khan , Rahman Md. Kaisar , Khan Shahneaz Ali , Islam Ariful
Published: June 2020

The COVID-19 outbreak has severely affected the social and economic conditions across this globe. Little is known about the relationship of COVID-19 with countries’ economic and socio-demographic status. Publicly available data on COVID-19 test rate, attack rate, case fatality rate, and recovery rate were analyzed in relation to country’s economic status, population density, median age, and urban population ratio. We also conducted multinomial logistic regression analysis to predict the influence of countries’ social and economic factors on COVID-19. The results revealed that the median age had significant positive correlation with attack rate (r=0.2389, p=0.003), case fatality rate (r=0.3207, p=0.000) and recovery rate (r=0.4847, p=0.000). The urbanization has positive significant correlation with recovery rate (r=0.1957, p= 0.016). The multinomial logistic regression analysis revealed low-income countries are less likely to have an increased recovery rate (p=0.000) and attack rate (p=0.016) compare to high-income countries. The lower-middle-income and upper-middle-income countries are less likely to have an increased recovery rate (p=0.000 and p=0.001, respectively) compared to high-income countries. Based on the result of this study, these economic and socio-demographic factors should consider in designing appropriate preventive measures as a next step. The low and lower-middle-income countries should invest more in health care services to lower the case fatality rate and increase test and recovery rates as part of pandemic preparation like COVID-19. As the number of COVID-19 attacks, death and recovery rates are constantly changing; however, the intensive study is required to obtain a clear picture.
Automatic measurement of the hand dimensions using consumer 3D cameras
Authors: Marchisotti Daniele , Marzaroli Pietro , Sala Remo , Sculati Michele , Giberti Hermes , Tarabini Marco
Published: June 2020

This article describes the metrological characterisation of two prototypes that use the point clouds acquired by consumer 3D cameras for the measurement of the human hand geometrical parameters. The initial part of the work is focused on the general description of algorithms that allow for the derivation of dimensional parameters of the hand. Algorithms were tested on data acquired using Microsoft Kinect v2 and Intel RealSense D400 series sensors. The accuracy of the proposed measurement methods has been evaluated in different tests aiming to identify bias errors deriving from point-cloud inaccuracy and at the identification of the effect of the hand pressure and the wrist flexion/extension. Results evidenced an accuracy better than 1 mm in the identification of the hand’s linear dimension and better than 20 cm3 for hand volume measurements. The relative uncertainty of linear dimensions, areas, and volumes was in the range of 1-10 %. Measurements performed with the Intel RealSense D400 were, on average, more repeatable than those performed with Microsoft Kinect. The uncertainty values limit the use of these devices to applications where the requested accuracy is larger than 5 % (volume measurements), 3 % (area measurements), and 1 mm (hands’ linear dimensions and thickness).
Neural network models for soil moisture forecasting from remote sensed measurements
Authors: Marini Andrea , Termite Loris Francesco , Garinei Alberto , Marconi Marcello , Biondi Lorenzo
Published: June 2020

Machine learning techniques are employed to describe the temporal behavior of soil moisture using meteorological data as inputs. Three different Artificial Neural Network models, a feedforward Multi-Layer Perceptron, a Long-Short Term Memory and the Adaptive Network-based Fuzzy Inference System, are trained and their results are compared. The soil moisture is expressed in terms of Soil Water Index, derived from satellite retrievals, with the last known value also being used as input. The results are promising as the proposed methodology relies on free-access data with a worldwide coverage, allowing to easily estimate the forthcoming soil moisture. The knowledge of the expected value of this variable could be extremely useful for irrigation scheduling and it is the basis of Decision Support Systems to efficiently manage water resources in agriculture.
Application of machine learning techniques and empirical mode decomposition for the classification of analog modulated signals
Authors: Carnì Domenico Luca , Balestrieri Eulalia , Tudosa Ioan , Lamonaca Francesco
Published: June 2020

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In this article, an automatic Analog Modulation Classifier based on Empirical mode decomposition and Machine learning approaches (AMC-EM) is proposed. The AMC-EM operates without a priori information and can recognise typical analog modulation schemes: amplitude modulation, phase modulation, frequency modulation, and single sideband modulation. The AMC-EM uses Empirical Mode Decomposition (EMD) to evaluate the features of the signal for the successive classification by using Machine Learning (ML). In the design of the AMC-EM, the selection of the specific ML technique is performed by comparing, with numerical tests, the performance of the (i) Support Vector Machine (SVM), (ii) k-nearest neighbor classifier, and (iii) adaptive boosting, since they are commonly used in the field of signal classification. The tests have highlighted that the SVM, specifically the quadratic SVM, permits the best possible performance concerning classification accuracy, by considering different noise intensities superimposed on the signal. To assess the advantages of the proposal, a comparison with other classifiers available in the literature has been undertaken through numerical tests. Finally, the AMC-EM is experimentally evaluated, and the experimental results agree with those of the simulation.
Incorporating Dynamic Production-Logging Data to the Permeability-Estimation Workflow Using Machine Learning
Authors: Guimaraes Ciro S. , Schirmer Luiz , Schardong Guilherme , Barreto Abelardo B. , Lopes Helio
Published: June 2020

The objective of this work is to develop and train feedforward artificial neural networks (ANNs) on the forecasting of layer permeability in heterogeneous reservoirs. The results are validated by comparing the model outputs with permeability curves computed from production logging data.

Production logs are used as targets to train the model. A flow-profile interpretation method is used to compute continuous permeability curves free of wellbore skin effects. In addition, segmentation techniques are applied to high-resolution ultrasonic image logs. These logs provide not only the image of the mega- and giga-pore system but can also identify the permeable facies along the reservoir. The image segmentation jointly with other borehole logs provides the necessary features for the network training process.

The proposed neural network focuses on delivering reliable and validated permeability curves. Its development accounts for formation skin factor, as well as nongeological noise usually found in ultrasonic image logs. The procedure is tested on both synthetic and field data sets. The estimations presented herein demonstrate the model's ability to learn nonlinear relationships between geological input variables and reservoir dynamic data even if the actual physical relationship is complex and not known a priori. Although the preprocessing stages of the procedure involve some expertise in data interpretation, the neural-network structure can be easily coded in any programming language, requiring no assumptions on physics in advance.

For the case studies presented in this work, the proposed procedure provides more accurate permeability curves than the ones obtained from conventional methods, which usually fail to predict the permeability measured on drill-stem tests conducted in dual-porosity reservoirs. The novelty of this work is to incorporate dynamic production-logging (PL) data into the permeability-estimation workflow.

Correction Notice: The preprint paper was updated from its originally published version to correct Fig. 17 on page 11. An erratum detailing the change is included in the Supporting Information section below.
A Protocol for Revealing Oral Neutrophil Heterogeneity by Single-Cell Immune Profiling in Human Saliva
Authors: Choudhury Saibyasachi N. , Novotny Mark , Aevermann Brian D , Lee Steven , Mandava Aishwarya , Qian Yu , Scheuermann Richard , Freire Marcelo
Published: June 2020

Neutrophils are the most abundant white blood cells in the human body responsible for fighting viral, bacterial and fungi infections. Out of the 100 billion neutrophils produced daily, it is estimated that 10 % of these cells end up in oral biofluids. Because saliva is a fluid accessible through non-invasive techniques, it is an optimal source of cells and molecule surveillance in health and disease. While neutrophils are abundant in saliva, scientific advancements in neutrophil biology have been hampered likely due to their short life span, inability to divide once terminally differentiated, sensitivity to physical stress, and low RNA content. Here, we devise a protocol aiming to understand neutrophil heterogeneity by improving isolation methods, single-cell RNA extraction, sequencing and bioinformatic pipelines. Advanced flow cytometry 3D analysis, and machine learning validated our gating system model, by including positive neutrophil markers and excluding other immune cells and uncovered neutrophil heterogeneity. Considering specific cell markers, unique mitochondrial content, stringent and less stringent filtering strategies, our transcriptome single cell findings unraveled novel neutrophil subpopulations. Collectively, this methodology accelerates the discovery of salivary immune landscapes, with the promise of improving the understanding of diversification mechanisms, clinical diagnostics in health and disease, and guide targeted therapies.
Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Location in Patients With EGFR Mutant Metastatic Non-Small Cell Lung Cancer Treated with TKIs
Authors: Xie Xueqi , Li Xiaolin , Tang Wenjie , Chen Jinlong , Yu Jinming , Li Minghuan , Xie Peng
Published: June 2020

Background: Targeted therapy with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has improved the field of metastatic non-small cell lung cancer treatment. Higher neutrophil-to-lymphocyte ratio (NLR) and lower relative lymphocyte counts as inflammatory indicators and associated with worse overall survival and progression free survival (PFS) in several tumor types. Few studies focused on these inflammation markers in field of TKIs eras. Methods: Patients with advanced EGFR mutation NSCLC treated with TKIs were included. Pre-treatment NLR means neutrophil to lymphocyte ratio measured in peripheral blood within one week before treating with TKIs. The baseline clinical characteristics of each group were compared by chi-square and t tests. Cox regression analyses were used to evaluate prognostic value of peripheral blood parameters on progression free survival (PFS). All prognostic factors were explored with multivariable regression. Results: We retrospectively analyzed 221 patients with metastatic NSCLC harboring exon 19 deletion, 21 L858R or rare mutation and receiving TKIs. Finally, a total of 190 patients were analyzed. The optimal cutoff values for pretreatment absolute lymphocyte count (Lym), lymphocyte percentage (Lym%), absolute neutrophil count (Neu), the percentage of neutrophil granulocytes (Neu%) and NLR were 1.625 B, 18.8%, 3.675a, 51.8% and 4.965, respectively. Patients with high neutrophil percent (18.8 months vs 13.0 months, P=0.003), absolute neutrophil counts (12.0 months vs 14.5 months, P=0.014) and NLR (7.0 months vs 15.2 months, P<0.001, one year PFS Rate, 38.4%, respectively) had worse PFS. In contrast, patients with high absolute lymphocyte counts (16.5 months vs 13.0 months, P=0.012) and lymphocyte percent (15.3 months vs 8.8 months, P<0.001) had a better progression-free-survival. Besides, tumor location is also an important factor for prognosis (14.3 months vs 11.6 months, P=0.003). On multivariate analysis, NLR and primary tumor location were both identified as independent and significantly risk indicators for worse PFS. Conclusion: NLR and primary location are both independent prognostic factors for PFS in patients with metastatic EGFR mutated lung tumor. Whether or not NLR and primary location could be useful markers in efficacy prediction of TKIs in advanced NSCLC calls for further investigation.
Spatiotemporal spread pattern of the COVID-19 cases in China
Authors: Feng Yongjiu , Li Qingmei , Tong Xiaohua , Wang Rong , Zhai Shuting , Gao Chen , Lei Zhenkun , Chen Shurui , Zhou Yilun , Wang Jiafeng , Yan Xiongfeng , Xie Huan , Chen Peng , Liu Shijie , Xv Xiong , Liu Sicong , Jin Yanmin , Wang C. , Hong Zhonghua , Luan Kuifeng , Wei Chao , Xu J. , Jiang Hua , Xiao Changjiang , Guo Yiyou
Published: June 2020

COVID-19 is currently spreading widely around the world, causing huge threats on public safety and global society. This study analyzes the spatiotemporal spread pattern of the COVID-19 in China, reveals China’s epicenters of the epidemic through spatial clustering, and delineates the substantial effect of distance to Wuhan on the COVID-19 spread. The results show that the daily new COVID-19 cases mostly occurred in and around Wuhan before March 6, and then moved to the Grand Bay Area (Shenzhen, Hong Kong and Macau). The total COVID-19 cases in China were mainly distributed in the east of the Huhuanyong Line, where the epicenters account for more than 60% of the country’s total on 24 January and 7 February, half on 31 January, and more than 70% from 14 February. The total cases finally stabilized around 84,000, and the inflection point for Wuhan was on 14 February, one week later than those of Hubei (outside Wuhan) and China (outside Hubei). The generalized additive model-based analysis shows that population density and distance to provincial cities significantly associated with the total number of the cases, while distances to prefecture cities and inter-city traffic stations, and population inflow from Wuhan after 24 January, had no strong relationships with the total number of cases. The results and findings should provide valuable insights for understanding the changes in the COVID-19 transmission and controlling the global COVID-19 spread.
Establishment of Multifactor Predictive Models for the Occurrence and Progression of Cervical Intraepithelial Neoplasia
Authors: Chen Mengjie , Wang He , Liang Yuejuan , Hu Mingmiao , Li Li
Published: June 2020

Background
To study the risk factors involved in the occurrence and progression of cervical intraepithelial neoplasia (CIN) and to establish predictive models.
Methods
Genemania was used to build a gene network. Then, the core gene-related pathways associated with the occurrence and progression of CIN were screened in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) experiments were performed to verify the differential expression of the identified genes in different tissues. R language was used for predictive model establishment.
Results
A total of 10 genes were investigated in this study. A total of 30 cases of cervical squamous cell cancer (SCC), 52 cases of CIN and 38 cases of normal cervix were enrolled in. Compared to CIN cases, the age of patients in the SCC group was older, the number of parities was greater, and the percentage of patients diagnosed with CINII + by TCT was higher. The expression of TGFBR2, CSKN1A1, PRKCI and CTBP2 was significantly higher in the SCC groups. Compared to patients with normal cervix tissue, the percentage of patients who were HPV positive and were diagnosed with CINII + by TCT was significantly higher. FOXO1 expression was significantly higher in CIN tissue, but TGFBR2 and CTBP2 expression was significantly lower in CIN tissue. The significantly different genes and clinical factors were included in the models.
Conclusions
Combination of clinical and significant genes to establish the random forest models can provide references to predict the occurrence and prediction of CIN.
A Comprehensive RNA Handling and Transcriptomics Guide for High-Throughput Processing of Plasmodium Blood-Stage Samples.
Authors: Kucharski Michal , Tripathi Jaishree , Nayak Sourav , Zhu Lei , Wirjanata Grennady , Pluijm Rob W. van der , Dhorda Mehul , Dondorp Arjen , Bozdech Zbynek
Published: June 2020

BackgroundSequencing technology advancements opened new opportunities to use transcriptomics for studying malaria pathology and epidemiology. Even though in recent years the study of whole parasite transcriptome proved to be essential in understanding parasite biology there is no compiled up-to-date reference protocol for the efficient generation of transcriptome data from growing number of samples. Here, we present a comprehensive methodology on how to preserve, extract, amplify, and sequence full-length mRNA transcripts from Plasmodium-infected blood samples that can be fully streamlined for high-throughput studies.Results We evaluated the utility of various commercially available RNA-preserving reagents in a range of storage conditions. Similarly, we compared several RNA extraction protocols and established the one most suitable for the extraction of high-quality total RNA from low-parasitemia and low-volume blood samples. Furthermore, we updated the criteria needed to evaluate the quality and integrity of Plasmodium RNA in the presence of human RNA. Optimization of SMART-seq2 amplification method to better suit AT-rich P. falciparum RNA samples allowed us to generate high-quality transcriptomes from as little as 10ng of total RNA and a lower parasitemia limit of 0.05%. Finally, we designed a modified method for depletion of unwanted human hemoglobin transcripts using in vitro CRISPR-Cas9 treatment, thus improving parasite transcriptome coverage in low parasitemia samples. To prove the functionality of the pipeline for both laboratory and field strains, we generated the highest 2-hour resolution RNA-seq transcriptome for Plasmodium falciparum 3D7 intraerythrocytic lifecycle available up-to-date and also applied the entire protocol to create the largest transcriptome data from Southeast Asian field isolates.ConclusionsOverall, our methodology presents an inclusive pipeline for generation of good quality transcriptomic data from a diverse range of Plasmodium-infected blood samples with varying parasitemia and RNA inputs. The flexibility of this pipeline to be adapted to robotic handling will facilitate both small and large scale future transcriptomic studies in the field of malaria.
Geography Matters for Sanitation! Spatial Heterogeneity of the District-level Correlates of Open Defecation in India
Authors: Chakraborty Saurav , Novotný Josef , Das Jadab , Bardahn Aditi , Roy Srijanee , Mondal Swikriti , Patel Priyank Pravin , Santra Sneha , Maity Indranil , Biswas Rimi , Maji Aparajita , Pramanik Suvamoy
Published: June 2020

Background: Sanitation interventions often fail in meeting the desired expectations. A prominent reason is the ecological nature of sanitation phenomena that inherently associates with its high dependence on contextual specifics. This also constrains the generalization of research findings in this domain and substantiates the need to supplement most prevalent micro-level evidence with wider population-level (ecological) studies. This paper thus provides the first quantitative analysis of the spatial heterogeneity of the district-level correlates of open defecation in India. It focuses on a contiguous region of 266 districts (their rural parts) comprising of seven northern and eastern Indian states, all of which had comparatively high open defecation rates in 2011.Methods: We employ standard non-spatial regression, spatially explicit regressions and multi-scale geographically weighted regression to compare the stability of the measurable correlates of open defecation across these different methods as well as across the analyzed spatial units. Results: Attributes like the ownership of household assets, drinking water inaccessibility and prevalent literacy rates were identified as the most stable district-level correlates of open defecation in this region. A higher share of Muslims in the population positively correlated with lower open defecation rates, while this relationship was amplified by the population density. This finding support hypotheses about the positive sanitation externalities stemming from the spatial co-concentrations of Muslim and non-Muslim populations. Conclusions: Our analyses demonstrate notable spatial clustering and significant spatial non-stationarity of the examined variables. Therefore, research findings that ignore the spatial heterogeneity of sanitation drivers possibly provide incomplete information for practice.
Climate Signals in River Flood Damages Emerge under Sound Regional Disaggregation
Authors: Sauer Inga , Reese Ronja , Otto Christian , Geiger Tobias , Willner Sven N. , Guillod Benoit , Bresch David , Frieler Katja
Published: June 2020

Climate change highly affects precipitation patterns. Here, we address the question whether the signal of climate change is already detectable in time series of reported damages caused by fluvial floods. Building on hazard indicators from process-based hydrological simulations, we develop an empirical model to reconstruct reported damages and quantify individual contributions of climate-induced changes in hazard, exposure, and vulnerability to observed trends. Across nine world regions, trends in damages are generally dominated by increasing exposure and decreasing vulnerability, with the latter being most pronounced in less developed regions. However, accounting for heterogeneity in changes of hazard frequency and magnitude within a region, a climate signal is detectable, especially in South and Sub-Saharan Africa as well as in Latin America. Damages in most regions are subject to a monotonous trend even after accounting for natural variability where an effect of long-term global warming can not yet be distinguished from a potential influence from multidecadal oscillations.
Melatonin Maintains Macrophage M1 Phenotype to Reverse LPS-stimulated Tumor Immune Tolerance
Authors: Lin Yukun , Zhang Mengdi , Zhou Lin , Wang Yuehua , Wang Mengqi , Du Jincheng , Kui Fuguang , Gu Wenwen , Lin Haihong , Li Hong , Cen Shihong , Du Gangjun
Published: June 2020

Background: Lipopolysaccharide (LPS) is a potent trigger of macrophage-mediated inflammation and its repeated stimulation results in immune tolerance. This study is to explore the cellular mechanisms of LPS-mediated tumor immune tolerance and to investigate whether melatonin can reverse this tolerance. Methods: The effect of melatonin and LPS on macrophages was assessed by cell proliferation, morphological changes, phagocytosis and autophagy in vitro. The tumor-preventing effect of melatonin and LPS were evaluated in the urethane-induced lung carcinoma model and in the H22 liver cancer allograft model. Immunofluorescence, immunohistochemistry and ELISA were used to examine protein expression. The related targets and pathways of melatonin were predicted by comprehensive bioinformatics, and the clinical association of bacterial infections and survival was evaluated in cancer patients by meta-analysis.Results: In vitro，Raw264.7 macrophages were polarized toward the M1 phenotype by single LPS administration but toward the M2 phenotype by repeated LPS administration. Interestingly, combination treatment with repeated LPS and 10 µM melatonin prevented macrophage polarization toward the M2-like phenotype and exerted lasting antitumor efficacy. In the urethane-induced lung carcinoma model, repeated LPS administration stimulated macrophage polarization toward the M2 phenotype and promoted lung carcinogenesis, which was abrogated by macrophage depletion, while melatonin alone or in combination with repeated LPS challenge restored M1-like macrophages and prevented carcinogenesis. In the H22 liver cancer allograft model, melatonin maintained the macrophage phenotype and promoted the tumor-suppressing effect of repeated LPS challenge. Furthermore, we found that macrophages repeatedly stimulated with LPS had a high level of surface lipid rafts that mediated PI3K/AKT and JAK2/STAT3 signaling and prevented both LPS sensitivity and immune response by self-expression of PD-L1 and surface expression of PD-1 receptor on NK cells, whereas melatonin decreased surface lipid rafts and PI3K/AKT and JAK2/STAT3 signaling. Finally, we conducted a comprehensive bioinformatics analysis of melatonin-relevant targets and pathways involved in M2 macrophage polarization and evaluated the clinical associations of bacterial infections and survival in cancer patients. Conclusions: This study suggests a function of melatonin in regulating macrophage polarization to maintain LPS-stimulated tumor immune surveillance.
Clinical Efficacy of Ribavirin in Adults Hospitalized With Severe Covid-19: A Retrospective Analysis of 208 Patients
Authors: Gong Wei-Jing , Zhou Tao , Wu San-Lan , Ye Jia-Long , Xu Jia-Qiang , Zeng Fang , Su Yu-Yong , Han Yong , Lv Yong-Ning , Zhang Yu , Cai Xue-Feng
Published: June 2020

Background: Coronavirus disease-2019 (COVID-19) spreads rapidly throughout the world. So far, no therapeutics have yet been proven to be effective. Ribavirin was recommended for the treatment of COVID-19 because of its in vitro activity. However, evidence supporting its clinical use with good efficacy is still lacking.Methods: A total of 208 confirmed severe or critical COVID-19 patients who were hospitalized in Wuhan Union West Campus between 1 February 2020 and 10 March 2020 were enrolled in the retrospective study. Patients were divided into two groups based on the use of ribavirin. The primary endpoint was the time to clinical improvement. The secondary endpoints included mortality, survival time, time to throat swab SARS-CoV-2 nucleic acid negative conversion, and hospital duration.Results: 68 patients were treated with ribavirin while 140 not. There were no significant between-group differences in demographic characteristics, baseline laboratory test results, treatment, and distribution of ordinal scale scores at enrollment, except coexisting diseases especially cancer (ribavirin group vs no ribavirin group, P = 0.014). Treatment with ribavirin was not associated with a difference in the time to clinical improvement (P = 0.483, HR = 0.884, 95% CI = 0.627-1.247). There were also no significant differences between-group in the number of patients with SARS-CoV-2 nucleic acid negative conversion, mortality, survival time, and hospital duration. Conclusion: In hospitalized adult patients with severe or critical COVID-19, no significant benefit was observed with ribavirin treatment.
Clinical Characteristics of COVID-19 Patients with Recurrent PCR Positivity After Hospital Discharge
Authors: Wang Kaige , Zhang Qifan , Lan Dong , Li Yalun , Luo Wenxin , Zhao Shengmin , Liu Dan , Panwen Tian , Huang Zhixin , Li Weimin
Published: June 2020

Objective: This study aimed to investigate the clinical characteristics of COVID-19 patients with recurrent SARS-CoV-2 positivity after hospital discharge. Methods: This retrospective study included COVID-19 patients who were readmitted for recurrence of positive SARS-CoV-2 RNA. Univariate and multivariate analyses were performed to assess the risk factors associated to the duration of recurrent RNA positivity.Results: Among the 287 discharged COVID-19 patients, 33 (11.5%) patients with recurrent PCR positivity were included. Among these patients, 21 (63.7%) patients were female, their mean age was 48.7 (±19.7) years old. 22 (66.7%) patients were asymptomatic. The following clinical features were presented in other patients: cough, fatigue, sore throat, fever and expectoration. The chest CT findings revealed that 8 (24.2%) patients were characterized by deterioration compared to the previous results. The median duration of recurrent RNA positivity was 9.0 days (IQR, 6.0, 15.0). We found that increased serum SARS-CoV-2-specific IgG antibody titer, elevated serum creatinine level, and female gender were the risk factors for the prolonged duration of recurrent RNA positivity.Conclusion: SARS-CoV-2 turned positive in a minority of discharged patients with COVID-19. Most patients experienced mild clinical course. Increased IgG antibody titer, creatinine and female gender were correlated to the prolonged RNA clearance time.