bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficiency of Foliar Dressing with Micronutrient Fertilizers in Soybean Cultivation Process
Authors:   KubNIITiM, Belik M.A. , Yurina T.A. ,   KubNIITiM, Negreba O.N. ,   KubNIITiM, Chaplygin M.E. ,   VIM
Published: April 2021

The results of testing micronutrientcontained fertilizers developed by Spetsagrokhim LLC and BioEra-Penza LLC in the industrial agrotechnology of soybean cultivation are presented. Based on the results of phenological observations during the entire growing season, the effect of the studied preparations on the growth and development of soybean plants has been assessed. The conditions for the application of micronutrient-contained fertilizers are given according to the recommendations of the developers and taking into account the conducted soil analysis for each option studied. A comparative assessment of the number of formed nodules on soybean roots in the studied options is presented and the influence of the selected options on the formation of yield and quality of soybean seeds is analyzed.
Criteria for the management of a sustainable and safe positioning of the fleet in the conditions of globalization
Authors: Golubkova I , Sienko O , Lysenko N , Frasyniuk T , Parkhomenko I
Published: April 2021

Purpose. To develop a model of minimizing transportation risks for strengthening the criteria for sustainable and safe positioning of the fleet. Methodology. Scientific research, whose results are given in the presented article, is performed using both general and special methods of cognition. Methods of quantitative and qualitative comparison, content analysis, scientific abstraction and systematization and the method of mathematical formalization were used. Findings. An algorithm of a criterion-based approach to sustainable and safe positioning of the fleet in the presence of international transport market constraints is proposed. A mathematical model has been developed for minimizing transportation risks, which will reduce the current costs of the merchant fleet and, accordingly, contribute to its sustainable and safe positioning. Since it is important for industrial enterprises to reduce the time and cost of delivering raw materials, components, reducing transport costs for delivering products to the consumer, the paper presents forecasting of volumes of container transportations through ports of Ukraine and comparative analysis with the forecast trend of container transportations in the world market. This made it possible to form a tool for determining the appropriate positioning of the fleet. Originality. The study developed an algorithm for a criteria-based approach to sustainable and safe fleet positioning under international transport market constraints and a mathematical model to minimize transportation risks. This allows moving over to the formation of an integrated multimodal transport system and coordinated actions of all market participants in transport services. The efficiency and reliability of the system will be enhanced by the ability to predict the reorientation of routes associated with increased risk and dynamic management of traffic flows. Practical value. The results of the study can be used to create integrated automated information systems for dynamic traffic management using alternative routing of traffic flows to minimize risks. The results of the forecast study on container traffic through Ukrainian seaports can be used for practical or scientific purposes.
Investing in road construction infrastructure projects under public-private partnership in the form of concession
Authors: Tsimoshynska O , Koval M , Kryshtal H , Filipishyna L , Arsawan W.E , Koval V
Published: April 2021

Purpose. To substantiate an approach to road development investment management in Ukraine in compliance with the principle of syncretism and the use of Quality Function Deployment methodology, to improve the methodological approach to calculating the concession fee for brown-field and green-field road concession projects. Methodology. The study used a set of general and special methods of cognition: the Quality Function Deployment (QFD) method, the environmental approach, multimodal analysis, Decoupling Index, Decoupling Factor, logical generalization, quantitative and qualitative comparison, scientific abstraction and systematization. Findings. According to the results of research on interrelation of cost of an investment project and volumes of works by their types, an economic-mathematical model of estimation of need for investments in projects for construction, reconstruction, repair and maintenance of public motor roads is offered. The proposed model, unlike the existing ones, is based on lateral understanding of the clarity of delineation of capital needs by type of road construction, which will provide taking management decisions on investment projects with model and information tools that will help obtain the most realistic assessment of need for capital needed to improve the transport operation condition of motor roads in Ukraine. Originality. The organizational-economic mechanism of management of investment activity of road economy and the estimation of efficiency of co-financing investment projects under programs on construction, reconstruction, repair and maintenance of motor roads is advanced. The diagnostics of efficiency of investment of construction of public motor roads under public-private partnership in the form of concession is improved. Practical value. The results of the study can be used in the activities of road industry of Ukraine for the development and implementation of investment projects under motor road development programs.
Motivação ambiente de trabalho - um estudo de casos na Associação de Pais e Amigos dos Excepcionais de Dianópolis (APAE)
Authors: Albuquerque Thaise Torres de , Matias Marcos José de Almeida , Lima Mônica de Souza , Azevedo Denise Barros de
Published: April 2021

A motivação no ambiente de trabalho vem se popularizando entre as empresas em busca de uma boa qualidade de vida de seus colaboradores, visando um bom rendimento e lucratividade para a empresa. O presente estudo tem como objetivo geral é analisar a motivação no ambiente de trabalho dos colaboradores da Associação de Pais e Amigos dos Excepcionais de Dianópolis (APAE), com relação ao ambiente de trabalho. Essa pesquisa se predomina, qualitativa e quantitativa pois, o propósito da pesquisa é analisar o grau de motivação dos colaboradores e envolve uma coleta de dados com acesso a documentos que foi disponibilizado pela empresa para a pesquisadora, o questionário com sete perguntas será aplicado para 31 servidores entre eles, professores de primeiro ao quinto ano, professores do primeiro e segundo seguimento de EJA, coordenadores, secretaria, diretor, auxiliar de serviços gerais, vigias, cozinheira e motoristas da Associação de Pais e Amigos dos Excepcionais (APAE), com o intuito de identificar os fatores que não contribuem para a motivação dos colaboradores, realizado no período de março a outubro de 2020. Diante dessa pesquisa, foi possível visualizar que a hipótese levantada no início deste trabalho foi confirmada parcialmente, pois os demais respondentes estão satisfeitos com ambiente mas não estão 100% satisfeitos com seus colegas de trabalho, tendo ai um conflito a ser resolvido pela instituição.
Residência Multiprofissional em Saúde da Família e Educação Permanente em Saúde: uma construção de vínculo entre a educação e o trabalho
Authors: Rodrigues Daniela de Freitas , Costa Cesar Francisco Silva da , Duarte Priscila Munhoz , Silva Prisciane Cardoso
Published: April 2021

Este artigo objetiva analisar de que forma a Residência Multiprofissional em Saúde da Família contribui para a Educação Permanente em Saúde da equipe da Estratégia Saúde da Família. Para isso, utilizamos como procedimentos metodológicos a pesquisa qualitativa, do tipo exploratória descritiva. O estudo ocorreu com trabalhadores da equipe multiprofissional de uma Unidade Básica Saúde da Família, localizada no município do Rio Grande/RS. A coleta de dados se desenvolveu por entrevista semiestruturada, gravada, com uso da técnica de grupo focal. O método utilizado para a análise qualitativa foi baseado na análise de conteúdo. Os resultados foram apresentados em três categorias temáticas: 1) Contribuições da Residência Multiprofissional em Saúde da Família através da Educação Permanente em Saúde 2) Mudanças no processo de trabalho da equipe 3) A importância e as formas de abordagem da Educação Permanente em Saúde. Evidencia-se que o residente multiprofissional é um catalisador de estímulos, pois agrega mudanças com vistas à formação e ao desenvolvimento pessoal, profissional e das equipes, por meio da ferramenta Educação Permanente em Saúde. Concluiu-se que quando a Residência Multiprofissional em Saúde da Família utiliza a educação como fundamento pedagógico, ela reorganiza o processo de trabalho, por meio da atualização de temas emergentes, estimula a reflexão e a discussão de casos com olhar multiprofissional e ainda institui o espaço de Educação Permanente em Saúde, que adiante qualificará a integralidade da atenção, o acolhimento, a clínica ampliada e a humanização do cuidado.
Accidental nasal fossa perforation during endodontic treatment - Case report
Authors: Ribeiro Kim Henderson Carmo , Sena Neylla Teixeira , Motta Junior Joel , Braga Marcia Raquel Costa Lima , Roseno Ana Carolyna Becher , Barreto Ana Julia Moreno , Matsumoto Mariza Akemi
Published: April 2021

Fracture of an endodontic instrument within the root canal system can occur due to incorrect use of instruments, and clinicians are confronted with a few removal options when considering this situation. The purpose of this article is to present the removal of a fractured endodontic file from the periapical region of the right upper central incisor, that caused a nasal floor perforation and otorhinolaryngological symptoms, with the aid of a dental operating microscope (DOM) and cone bean computed tomography (CBCT). Success was achieved when the fragment was visible and removed from the nasal fossa. The standardized techniques of removal or bypassing fracture file were not effective, and success was obtained with the aid of CBCT that made possible the visualization of the broken file inside the nasal fossa.
Interannual variability in acoustic detection of blue and fin whale calls in the Northeast Atlantic High Arctic between 2008 and 2018
Authors: Ahonen H , Stafford KM , Lydersen C , Berchok CL , Moore SE , Kovacs KM
Published: April 2021

Northern Hemisphere blue and fin whales are regular summer migrants to Arctic waters. Given the profound changes the Arctic is currently undergoing due to global warming, changes in habitat use and distribution of these migratory species are predicted. In this study, 3 passive acoustic recorders, 2 in Fram Strait about 95 km apart and 1 north of the Svalbard Archipelago (Atwain), were used to investigate the spatial and temporal vocal occurrence of these species in the Northeast Atlantic High Arctic. Acoustic data were available for 7 years for western Fram Strait (WFS), 2.5 years for central Fram Strait (CFS) and 3 years for Atwain. At both Fram Strait locations, most blue whale call detections occurred from August through October, though recently (2015-2018) in WFS a clear increase in blue whale call rates was detected in June/July, suggesting an expansion of the seasonal occurrence of blue whales. In WFS, fin whale calls were detected intermittently, at low levels, almost year-round. In CFS, fin whale calls were more frequent but occurred mainly from July through December. At Atwain, blue whale detections commenced in July, both species were recorded in September/October and fin whale calls extended into November. Results from this study provide novel long-term baseline information about the occurrence of blue and fin whales at extreme northerly locations, where traditional ship-based survey methods are seasonally limited. Continued sampling will support investigation of how environmental change influences cetacean distribution and habitat use.
Loyalty and Dissent: Improvement and Clearance in Strathspey after 1853
Authors: Bardgett Frank D.
Published: April 2021

Although Strathspey experienced many of the same trends – agricultural ‘improvement’, enclosure of commons, creation of deer forests, emigration – present elsewhere in Northern Scotland during the nineteenth century, the region was not a flashpoint for unrest. Careful management on behalf of the ruling family, the earls of Seafield, who were the hereditary chiefs of Grant, the local clan; a consistent policy preference to work with existing farming tenants, and a traditional paternalism, all contributed to social stability. The region was not exempt from protest against the impact of the considerable programme of ‘improvement’ pursued from 1853. There were accusations of ‘depopulation’ and ‘clearance’ in Strathspey, but the influence of those who benefitted from the changes, together with the intrinsic and pervasive authority of the Seafield estate, confined discontent to the constitutional channels opening up as the century progressed. Strong expressions of loyalty to the Seafield proprietors were also a feature of the times. Aspects of this narrative of mutual loyalty are examined, and then the spectrum of reaction to improvement and clearance, the growing lobby for land reform, and the experience of depopulation. Although the influence of the Strathspey factor, John Smith, was important in channelling public discourse, a dilution of estate authority as the century progressed is recognised. The article seeks to broaden perceptions of the history of the Highlands by considering a region of the Gaidhealtachd outwith the far North and the North-West.
‘A Very Difficult Troublesome Affair’: Some Unlikely Help for the Pretender
Authors: Cain Robert
Published: April 2021

In April 1746, only weeks after th e decisive defeat of the Jacobite army at Culloden, a British warship, HMS Triton, stopped the Gordon, a suspicious-looking ship off Scotland's northwestern coast, near Skye. The strange craft proved to have been taken over on a voyage to America by its human cargo of Irish indentured servants – men, women and children – some 113 souls, with the intention of joining the Stuart rebel forces in Scotland. After taking the servants as prisoners, Captain Brett of the Triton had to confront the question of how to clear his ship of the unwelcome guests, a dilemma that included such questions as ownership, jurisdiction, claims to compensation, and lines of authority. After weeks of frustration, all was finally resolved by the discharging the bulk of the prisoners to Carrickfergus Castle. Brett was able to resume his naval duties, and most of the servants were soon back on their way to a life in the colonies. This incident, minor as it was in itself, is a possibly unique example of political expression by members of the Irish underclass during the Jacobite insurrection of 1745.
Ortadoğu’da Bir Bölgesel Örgüt Olarak İslam İşbirliği Teşkilatı’nın Etkinliği Üzerine Bir Değerlendirme
Authors: BAKAN Selahaddin , KATILMIŞ Canan
Published: April 2021

Çalışma, bir bölgesel örgüt olarak İslam İşbirliği Teşkilatı’nın Ortadoğu’da etkinliği üzerine bir değerlendirme ortaya koymaya çalışmaktadır. Bu değerlendirme neticesinde, İslam İşbirliği Teşkilatı’nın, gerek bölge içi nedenlerden gerek bölge dışı nedenlerden ötürü, Ortadoğu’da bölgesel bir örgüt olarak etkin olamadığı sonucuna varılmıştır. Ayrıca, bölgesel örgütlerin işlevleri ve özellikleri açısından değerlendirilen İslam İşbirliği Teşkilatı’nın, bölgede etkili bir siyaset yürütemediği görülmüştür. Çalışmada, İslam İşbirliği Teşkilatı’nın etkin olamama nedenleri ortaya konulacaktır. Bu durum, bölgeselleşmenin önem kazanmaya başladığı dünya düzeninde, Ortadoğu devletlerinin kalkınması için bölgesel örgütlerin etkinliğinin ne derece önemli olduğunun anlaşılmasını kolaylaştıracaktır. Bölge devletleri, bölge devletlerinin birbiri ile ve diğer devletler ile olan ilişkisi, bu örgütleri kendi siyasal araçları haline dönüştürmek isteyen uluslararası sistem içindeki büyük güçler ve devlet-dışı aktörler bölge siyasetini şekillendiren temel aktörler olarak sayılabilir. Gerek bölge dışı gerek bölge içi aktörlerin etkisi, Ortadoğu’da bölgesel örgütlerin etkin olmasını engellemiştir. Çalışmada nitel ve tarihsel araştırma yöntemleri kullanılmış olup, değerlendirmeler bu tarihe kadar geçen süreçte gerçekleşen gelişmeler, bu gelişmelere ilişkin açık kaynak verileri, basılı metinler, haber ve internet kaynaklarından faydalanılarak yapılacaktır.
MUHASEBE MESLEĞİNDE KADIN OLMANIN MESLEKİ AÇIDAN DEĞERLENDİRİLMESİ: DİYARBAKIR İLİNDE NİTEL BİR ARAŞTIRMA
Authors: GÜNGÖR KARYAĞDI Nazan
Published: April 2021

Ekonomik sistem içerisinde gerek devlete gerekse işletmelere karşı büyük sorumluluk taşıyan mesleklerden biri de muhasebe mesleğidir. Dünya’da olduğu gibi Türkiye'de de muhasebe meslek mensuplarının profili incelendiğinde erkek sayısının daha fazla olduğu görülmektedir. Ve bu durum kimi zaman bireyler tarafından mesleğin yerine getirilmesinde kadınların rolünün nasıl olduğu yönünde merak uyandırmaktadır. Bu kapsamda ele alınan çalışmanın amacı, kadın meslek mensuplarının muhasebe mesleğini yerine getirirken yaşadıkları sorunların ve deneyimlerin mesleki açıdan değerlendirilmesidir. Bu amaçla Diyarbakır ilinde faaliyet gösteren kadın muhasebecilerle görüşme yapılmış ve veri toplanmıştır. Çalışma sonucunda, kadın muhasebe meslek mensuplarının mesleki olarak birtakım zorluklar yaşadığı ve bu zorlukların aile ve sosyal hayatlarına olumsuz yönde yansıdığına ilişkin sonuçlara ulaşılmıştır.
Agent-Based Learning Model for the Obesity Paradox in RCC
Authors: Belenchia Matteo , Rocchetti Giacomo , Maestri Stefano , Cimadamore Alessia , Montironi Rodolfo , Santoni Matteo , Merelli Emanuela
Published: April 2021

A recent study on the immunotherapy treatment of renal cell carcinoma reveals better outcomes in obese patients compared to lean subjects. This enigmatic contradiction has been explained, in the context of the debated obesity paradox, as the effect produced by the cell-cell interaction network on the tumor microenvironment during the immune response. To better understand this hypothesis, we provide a computational framework for the in silico study of the tumor behavior. The starting model of the tumor, based on the cell-cell interaction network, has been described as a multiagent system, whose simulation generates the hypothesized effects on the tumor microenvironment. The medical needs in the immunotherapy design meet the capabilities of a multiagent simulator to reproduce the dynamics of the cell-cell interaction network, meaning a reaction to environmental changes introduced through the experimental data.
Decentralized, Self-Sovereign, Consortium: The Future of Digital Identity in Canada
Authors: Boysen Andre
Published: April 2021

This article introduces how SecureKey Technologies Inc. (SecureKey) worked with various network participants and innovation partners alongside government, corporate, and consumer-focused collaborators, in a consortium approach to create a mutually beneficial network of self-sovereign identity (SSI) principles with blockchain in Canada. These principles are based on giving users ownership and control over all of their digital identity attributes as an alternative approach to the current status quo of centralized digital identity, which focuses on discrete identities are made within individual online properties. Blockchain is used as the foundation for its strong security protocols to prevent information from being identified, accessed, or misused and uphold SSI principles. This article will consider the current status quo of digital identity known as centralized digital identity and comparisons to the case study’s emphasis on the alternative thinking of SSI with principles with blockchain, which prioritizes a decentralized, self-sovereign, consortium approach as opposed to discrete identities within individual online properties. Each of these principles will be explained in detail before highlighting the practical implications, lessons learned for future applications, and how both the Canadian and global identity landscapes should proceed for wider acceptance of SSI with blockchain. The case study detailed – that of Verified.Me – will demonstrate how blockchain developers can actively work to help partners transition from current identity silos to instead collaborate across varied industries and create a cohesive, secure service and digital identity network that benefits users through SSI principles and the benefits of blockchain. We also offer recommendations for how both the Canadian and global identity landscapes should proceed for wider acceptance of SSI with blockchain, the benefits of doing so, and anticipated barriers affecting the adoption of future decentralized identity initiatives.
What Blockchain Are We Talking About? An Analytical Framework for Understanding Blockchain Applications in Agriculture and Food
Authors: van Wassenaer Lan , Verdouw Cor , Wolfert Sjaak
Published: April 2021

With the many promises it holds in addressing problems concerning information exchange and digital transactions in multi-actor processes, blockchain technology (BCT) has gained considerable traction in the agrifood sector. Governments, international organisations, private companies, consortia of public and private actors are launching various blockchain projects for improving transparency, traceability, and many other key issues in the agrifood sector. This has resulted in a large number of use cases. It is often unclear, however, what and how technical, social and economic aspects were considered in different usecases. Due to the novelty and elusiveness of the technology, there is no ready-to-use analytical framework or guideline yet for assessing its applicability and choosing the right technical and organisational setup. As a result, many stakeholders have to grope in the dark when designing and implementing their “blockchain application.” Based on studies of use cases worldwide and experiences in organizing different blockchain pilots in the Netherlands, this paper seeks to address this problem by providing an overview of the choices to be made at three layers of a blockchain application: the ledger, the governance structure and the ecosystem. This can serve as a reference framework for understanding different blockchain applications and choosing key parameters for new use cases in the agrifood sector. It is expected that such demystification of the blockchain will contribute to more realistic and effective application of the technology to pressing problems in agriculture and food.
Using Real-Time Indoor Resource Positioning to Track the Progress of Tasks in Construction Sites
Authors: Zhao Jianyu , Pikas Ergo , Seppänen Olli , Peltokorpi Antti
Published: April 2021

Lean construction methods have demonstrated potential to improve construction productivity. For example, the location-based management system and the last planner system have increased the reliability of planning and control in construction production. However, these benefits are often reduced because of inaccurate manual data collection. To alleviate these problems, technologies for automated monitoring of workers have been developed to identify site events in chaotic environments. This paper aims to investigate whether a Bluetooth low-energy-based real-time indoor positioning system can monitor task progress from workers’ presence. Our findings suggest that the proposed system is a feasible solution for monitoring task-level progress when there are explicit dependencies between tasks. This method could automatically detect task start and finish times and estimate the hours required to complete a task. This enables the measurement of waste hidden inside tasks, which allows for interventions for improving flows and eliminating waste.
Endocrine Pancreas Development and Dysfunction Through the Lens of Single-Cell RNA-Sequencing
Authors: Szlachcic Wojciech J. , Ziojla Natalia , Kizewska Dorota K. , Kempa Marcelina , Borowiak Malgorzata
Published: April 2021

A chronic inability to maintain blood glucose homeostasis leads to diabetes, which can damage multiple organs. The pancreatic islets regulate blood glucose levels through the coordinated action of islet cell-secreted hormones, with the insulin released by β-cells playing a crucial role in this process. Diabetes is caused by insufficient insulin secretion due to β-cell loss, or a pancreatic dysfunction. The restoration of a functional β-cell mass might, therefore, offer a cure. To this end, major efforts are underway to generate human β-cells de novo, in vitro, or in vivo. The efficient generation of functional β-cells requires a comprehensive knowledge of pancreas development, including the mechanisms driving cell fate decisions or endocrine cell maturation. Rapid progress in single-cell RNA sequencing (scRNA-Seq) technologies has brought a new dimension to pancreas development research. These methods can capture the transcriptomes of thousands of individual cells, including rare cell types, subtypes, and transient states. With such massive datasets, it is possible to infer the developmental trajectories of cell transitions and gene regulatory pathways. Here, we summarize recent advances in our understanding of endocrine pancreas development and function from scRNA-Seq studies on developing and adult pancreas and human endocrine differentiation models. We also discuss recent scRNA-Seq findings for the pathological pancreas in diabetes, and their implications for better treatment.
The Chromatin Regulator Ankrd11 Controls Palate and Cranial Bone Development
Authors: Roth Daniela Marta , Baddam Pranidhi , Lin Haiming , Vidal-García Marta , Aponte Jose David , De Souza Sarah-Thea , Godziuk Devyn , Watson Adrianne Eve Scovil , Footz Tim , Schachter Nathan F. , Egan Sean E. , Hallgrímsson Benedikt , Graf Daniel , Voronova Anastassia
Published: April 2021

Epigenetic and chromatin regulation of craniofacial development remains poorly understood. Ankyrin Repeat Domain 11 (ANKRD11) is a chromatin regulator that has previously been shown to control neural stem cell fates via modulation of histone acetylation. ANKRD11 gene variants, or microdeletions of the 16q24.3 chromosomal region encompassing the ANKRD11 gene, cause KBG syndrome, a rare autosomal dominant congenital disorder with variable neurodevelopmental and craniofacial involvement. Craniofacial abnormalities include a distinct facial gestalt, delayed bone age, tooth abnormalities, delayed fontanelle closure, and frequently cleft or submucosal palate. Despite this, the dramatic phenotype and precise role of ANKRD11 in embryonic craniofacial development remain unexplored. Quantitative analysis of 3D images of KBG syndromic subjects shows an overall reduction in the size of the middle and lower face. Here, we report that mice with heterozygous deletion of Ankrd11 in neural crest cells (Ankrd11nchet) display a mild midfacial hypoplasia including reduced midfacial width and a persistent open fontanelle, both of which mirror KBG syndrome patient facial phenotypes. Mice with a homozygous Ankrd11 deletion in neural crest cells (Ankrd11ncko) die at birth. They show increased severity of several clinical manifestations described for KBG syndrome, such as cleft palate, retrognathia, midfacial hypoplasia, and reduced calvarial growth. At E14.5, Ankrd11 expression in the craniofacial complex is closely associated with developing bony structures, while expression at birth is markedly decreased. Conditional deletion of Ankrd11 leads to a reduction in ossification of midfacial bones, with several ossification centers failing to expand and/or fuse. Intramembranous bones show features of delayed maturation, with bone remodeling severely curtailed at birth. Palatal shelves remain hypoplastic at all developmental stages, with a local reduction in proliferation at E13.5. Our study identifies Ankrd11 as a critical regulator of intramembranous ossification and palate development and suggests that Ankrd11nchet and Ankrd11ncko mice may serve as pre-clinical models for KBG syndrome in humans.
Upregulation of SPP1 Is a Marker for Poor Lung Cancer Prognosis and Contributes to Cancer Progression and Cisplatin Resistance
Authors: Tang Huaping , Chen Jianyou , Han Xiaolei , Feng Yan , Wang Fang
Published: April 2021

The chemoresistance of lung cancer is a significant contributor to its high mortality and morbidity rate. There is an urgent need to identify differentially expressed genes in lung cancer patients with a poor prognosis to develop effective means to overcome drug resistance in subsequent treatment. In this study, we identified the secreted phosphoprotein 1 (SPP1) as a potential gene associated with a poor diagnosis of lung cancer patients using the Cancer Genome Atlas analysis, which suggested that the expression of SPP1 in tumor tissues was significantly higher than normal tissues. The high expression of SPP1 was also correlated with tumor grade and poor clinical prognosis. To understand the roles of SPP1 and the DNA methyltransferase 1 (DNMT1), which regulated SPP1 expression, in affecting cell viability, migration and invasion, SPP1 and DNMT1 were overexpressed in the human lung cancer A549 and NCI-446 cells, followed by analyzing cell viability, migration and invasion. We showed that SPP1 promoted the proliferation, migration and invasion of lung cancer cells, and increased the resistance of lung cancer to the chemotherapeutic drug cisplatin. Knocking down SPP1 in cells restored sensitivity to cisplatin. Further, A549 cells without SPP1 overexpression demonstrated lower tumor growth rate than SPP1 overexpression cells using the xenograft tumor mouse model. High expression of SPP1 in lung cancer tumor tissue was caused by the reduced methylation level of its promoter region mediated by DNMT1. Our data suggested that SPP1 can be used as a marker for highly malignant lung cancer and targeting SPP1 may be a potential lung cancer treatment strategy.
Membrane Processes for Direct Carbon Dioxide Capture From Air: Possibilities and Limitations
Authors: Castel Christophe , Bounaceur Roda , Favre Eric
Published: April 2021

The direct capture of CO2 from air (DAC) has been shown a growing interest for the mitigation of greenhouse gases but remains controversial among the engineering community. The high dilution level of CO2 in air (0.04%) indeed increases the energy requirement and cost of the process compared to carbon capture from flue gases (with CO2 concentrations around 15% for coal power plants). Until now, solid sorbents (functionalized silica, ion exchange resins, metal–organic frameworks, etc.) have been proposed to achieve DAC, with a few large-scale demonstration units. Gas-liquid absorption in alkaline solutions is also explored. Besides adsorption and absorption, membrane processes are another key gas separation technology but have not been investigated for DAC yet. The objective of this study is to explore the separation performances of a membrane unit for CO2 capture from air through a generic engineering approach. The role of membrane material performances and the impact of the operating conditions of the process on energy requirement and module production capacity are investigated. Membranes are shown to require a high selectivity in order to achieve purity in no more than two stages. The specific energy requirement is globally higher than that of the adsorption and absorption processes, together with higher productivity levels. Guidelines on the possibilities and limitations of membranes for DAC are finally proposed.
Peptidyl Activity-Based Probes for Imaging Serine Proteases
Authors: Kasperkiewicz Paulina
Published: April 2021

Proteases catalyze the hydrolysis of peptide bonds. Products of this breakdown mediate signaling in an enormous number of biological processes. Serine proteases constitute the most numerous group of proteases, accounting for 40%, and they are prevalent in many physiological functions, both normal and disease-related functions, making them one of the most important enzymes in humans. The activity of proteases is controlled at the expression level by posttranslational modifications and/or endogenous inhibitors. The study of serine proteases requires specific reagents not only for detecting their activity but also for their imaging. Such tools include inhibitors or substrate-related chemical molecules that allow the detection of proteolysis and visual observation of active enzymes, thus facilitating the characterization of the activity of proteases in the complex proteome. Peptidyl activity-based probes (ABPs) have been extensively studied recently, and this review describes the basic principles in the design of peptide-based imaging agents for serine proteases, provides examples of activity-based probe applications and critically discusses their strengths, weaknesses, challenges and limitations.
Implication of the Type IV Secretion System in the Pathogenicity of Vibrio tapetis, the Etiological Agent of Brown Ring Disease Affecting the Manila Clam Ruditapes philippinarum
Authors: Rahmani Alexandra , Delavat François , Lambert Christophe , Le Goic Nelly , Dabas Eric , Paillard Christine , Pichereau Vianney
Published: April 2021

Vibrio tapetis is a Gram-negative bacterium that causes infections of mollusk bivalves and fish. The Brown Ring Disease (BRD) is an infection caused by V. tapetis that primarily affects the Manila clam Ruditapes philippinarum. Recent studies have shown that a type IV secretion system (T4SS) gene cluster is exclusively found in strains of V. tapetis pathogenic to clams. However, whether the T4SS is implicated or not during the infection process remains unknown. The aim of this study was to create and characterize a V. tapetis T4SS null mutant, obtained by a near-complete deletion of the virB4 gene, in order to determine the role of T4SS in the development of BRD. This study demonstrated that the T4SS is neither responsible for the loss of hemocyte adhesion capacities, nor for the decrease of the lysosomal activity during BRD. Nevertheless, we observed a 50% decrease of the BRD prevalence and a decrease of mortality dynamics with the ΔvirB4 mutant. This work demonstrates that the T4SS of V. tapetis plays an important role in the development of BRD in the Manila clam.
Protein Truncating Variants of colA in Clostridium perfringens Type G Strains
Authors: Van Damme Lore , Cox Natasja , Callens Chana , Dargatz Michelle , Flügel Monika , Hark Sarah , Thiemann Frank , Pelzer Stefan , Haesebrouck Freddy , Ducatelle Richard , Van Immerseel Filip , Goossens Evy
Published: April 2021

Extracellular matrix (ECM) degrading enzymes produced by Clostridium perfringens may play an important role during the initial phases of avian necrotic enteritis by facilitating toxin entry in the intestinal mucosa and destruction of the tissue. C. perfringens is known to produce several ECM-degrading proteases, such as kappa toxin, an extracellular collagenase that is encoded by the colA gene. In this study, the colA gene sequence of a collection of 48 C. perfringens strains, including pathogenic (i.e. toxinotype G) and commensal (i.e. toxinotype A) chicken derived strains and strains originating from other host species, was analyzed. Although the colA gene showed a high level of conservation (>96% nucleotide sequence identity), several gene variants carrying different nonsense mutations in the colA gene were identified, leading to the definition of four truncated collagenase variant types (I-IV). Collagenase variant types I, III and IV have a (nearly) complete collagenase unit but lack parts of the C-terminal recruitment domains, whereas collagenase variant types II misses the N-terminal part of collagenase unit. Gene fragments encoding a truncated collagenase were mainly linked with necrotic enteritis associated C. perfringens type G strains with collagenase variant types I and II being the most prevalent types. Gelatin zymography revealed that both recombinant full-length and variant type I collagenase have active auto-cleavage products. Moreover, both recombinant fragments were capable of degrading type I as well as type IV collagen, although variant type I collagenase showed a higher relative activity against collagen type IV as compared to full-length collagenase. Consequently, these smaller truncated collagenases might be able to break down collagen type IV in the epithelial basement membrane of the intestinal villi and so contribute to the initiation of the pathological process leading to necrotic enteritis.
Sex Modifies the Association of Fibroblast Growth Factor 21 With Subclinical Carotid Atherosclerosis
Authors: Chee Yingjie , Toh Grace Lx , Lim Chien Joo , Goh Liuh Ling , Dalan Rinkoo
Published: April 2021

Background and Aims: Fibroblast growth factor 21 (FGF21), an emerging metabolic hepatokine, is associated with atherosclerosis. An interaction with sex has been described in various populations. We aimed to study whether sex modulates the relationship between FGF21 and subclinical carotid atherosclerosis in a diabetes-enriched multiethnic population of Singapore. We explore differences in intermediary mechanisms, in terms of hypertension, lipids, and inflammation, between FGF21 and atherosclerosis.

Methods: We recruited 425 individuals from a single diabetes center in Singapore, and demographics, anthropometry, metabolic profile, FGF21, and carotid ultrasonography were performed. Multivariable logistic regression models were used to study the association between subclinical atherosclerosis and FGF21 adjusting for age, ethnicity, body mass index (BMI), hemoglobin A1c (HbA1c), systolic and diastolic blood pressures, and low-density lipoprotein (LDL)-cholesterol separately for males and females as two groups after an interaction test.

Results: An interaction test assessing interaction by sex on the relationship between subclinical atherosclerosis and FGF21 showed a significant interaction with sex (Pinteraction = 0.033). In the female subgroup, significant independent associations of standardized lnFGF21 with subclinical atherosclerosis were seen, with 1 SD increment in lnFGF21 being associated with 1.48-fold (95% CI: 1.03, 2.12; p = 0.036) increase in risk. In the male subgroup, the association of subclinical atherosclerosis with standardized lnFGF21 was not significant [odds ratio (OR) (95% CI): 0.90 (0.63, 1.28); p = 0.553]. We found sex interactions with pulse pressure being significantly associated in females only and triglycerides and C-reactive protein being associated with males only.

Conclusion: FGF21 is positively associated with subclinical carotid atherosclerosis in women, but not in men. The sex–racial patterns in the mechanisms by which FGF21 causes subclinical atherosclerosis needs to be explored in larger population-based studies and mechanistically studied in greater detail.
Lactate Dehydrogenase B and Pyruvate Oxidation Pathway Associated With Carfilzomib-Related Cardiotoxicity in Multiple Myeloma Patients: Result of a Multi-Omics Integrative Analysis
Authors: Tantawy Marwa , Chekka Lakshmi Manasa , Huang Yimei , Garrett Timothy J. , Singh Sonal , Shah Chintan P. , Cornell Robert F. , Baz Rachid C. , Fradley Michael G. , Waheed Nida , DeRemer David L. , Yuan Lihui , Langaee Taimour , March Keith , Pepine Carl J. , Moreb Jan S. , Gong Yan
Published: April 2021

Multiple myeloma (MM) is the second most frequent hematologic cancer in the United States. Carfilzomib (CFZ), an irreversible proteasome inhibitor being used to treat relapsed and refractory MM, has been associated with cardiotoxicity, including heart failure. We hypothesized that a multi-omics approach integrating data from different omics would provide insights into the mechanisms of CFZ-related cardiovascular adverse events (CVAEs). Plasma samples were collected from 13 MM patients treated with CFZ (including 7 with CVAEs and 6 with no CVAEs) at the University of Florida Health Cancer Center. These samples were evaluated in global metabolomic profiling, global proteomic profiling, and microRNA (miRNA) profiling. Integrative pathway analysis was performed to identify genes and pathways differentially expressed between patients with and without CVAEs. The proteomics analysis identified the up-regulation of lactate dehydrogenase B (LDHB) [fold change (FC) = 8.2, p = 0.01] in patients who experienced CVAEs. The metabolomics analysis identified lower plasma abundance of pyruvate (FC = 0.16, p = 0.0004) and higher abundance of lactate (FC = 2.4, p = 0.0001) in patients with CVAEs. Differential expression analysis of miRNAs profiling identified mir-146b to be up-regulatein (FC = 14, p = 0.046) in patients with CVAE. Pathway analysis suggested that the pyruvate fermentation to lactate pathway is associated with CFZ-CVAEs. In this pilot multi-omics integrative analysis, we observed the down-regulation of pyruvate and up-regulation of LDHB among patients who experienced CVAEs, suggesting the importance of the pyruvate oxidation pathway associated with mitochondrial dysfunction. Validation and further investigation in a larger independent cohort are warranted to better understand the mechanisms of CFZ-CVAEs.
Case Report: Streptococcus alactolyticus as a Rare Pathogen of Mitral Endocarditis
Authors: Vinciguerra Mattia , Santamaria Valeria , Romiti Silvia , D'Abramo Mizar , Toto Gianmarco , De Bellis Antonio , Taliani Gloria , Sangiorgi Giuseppe , Greco Ernesto
Published: April 2021

Streptococcus bovis/Streptococcus equinus complex (SBSEC) is a group of non-enterococcal group D Streptococci that colonizes both humans and animals. Due to gastrointestinal disease, they can switch in opportunistic pathogens passing through intestinal mucosal barrier and may cause bacteremia and distant organs damage. Despite infective endocarditis (IE), extra-cardiac manifestations of organs damage include osteoarticular infections, meningitis, and biliary infections among others; moreover, the association with colonic pathological lesions has been largely described. Streptococcus alactolyticus as a species included in SBSEC may share pathophysiological similarities, although it represents an extremely rare cause of distant organ infections, being reported in literature as causative agent of IE in only two other cases. We describe a case of 69-year-old male admitted to our institution due to mild–moderate dyspnea and fever, affected by cervico-brachialgia for 3 weeks. Streptococcus alactolyticus was identified as causative agent of IE on the mitral valve, causing severe regurgitation.
Association of Carotid Atherosclerosis With White Matter Hyperintensity in an Asymptomatic Japanese Population: A Cross-Sectional Study
Authors: Zhang Li , Zhou Quan , Shao Li Hua , Wen Jun , Xia Jun
Published: April 2021

Objective: A limited number of scholars concentrated on the relationship between carotid atherosclerosis (CAS) and white matter hyperintensity (WMH) (i.e., CAS-WMH relationship). The current research aimed to clarify the CAS-WMH relationship in Japanese population.

Methods: All participants underwent MRI of head and ultrasonography of the carotid artery. WMH was diagnosed from MRI results. The carotid ultrasound findings, carotid artery plaque score (PS), and plaque number (PN) could be achieved to indicate the severity of CAS. We also employed multivariate logistic regression models to estimate the CAS-WMH relationship. Interaction and stratified analyses were undertaken on the basis of a number of factors (e.g., gender, age, smoking status, drinking habit, and history of chronic diseases).

Results: A total of 1,904 Japanese subjects were included, and the prevalence of WMH was 54.8% (1,044/1,904). It was unveiled that frequency of CAS was greater in cases with WMH. In a fully adjusted model, high PS was associated with the frequency of WMH, followed by high PN. Further analyses revealed a dose-response relationship between PS and incidence of WMH.

Conclusion: PS and PN exhibited the greatest influences on determining the frequency of WMH, highlighting the potentially important pathophysiological role of large artery atherosclerosis in intensifying WMH.
Observations of Shallow Methane Bubble Emissions From Cascadia Margin
Authors: Michel Anna P. M. , Preston Victoria L. , Fauria Kristen E. , Nicholson David P.
Published: April 2021

Open questions exist about whether methane emitted from active seafloor seeps reaches the surface ocean to be subsequently ventilated to the atmosphere. Water depth variability, coupled with the transient nature of methane bubble plumes, adds complexity to examining these questions. Little data exist which trace methane transport from release at a seep into the water column. Here, we demonstrate a coupled technological approach for examining methane transport, combining multibeam sonar, a field-portable laser-based spectrometer, and the ChemYak, a robotic surface kayak, at two shallow (<75 m depth) seep sites on the Cascadia Margin. We demonstrate the presence of elevated methane (above the methane equilibration concentration with the atmosphere) throughout the water column. We observe areas of elevated dissolved methane at the surface, suggesting that at these shallow seep sites, methane is reaching the air-sea interface and is being emitted to the atmosphere.
Diabetes and Prediabetes in Children With Cystic Fibrosis: A Systematic Review of the Literature and Recommendations of the Italian Society for Pediatric Endocrinology and Diabetes (ISPED)
Authors: Mozzillo Enza , Franceschi Roberto , Piona Claudia , Passanisi Stefano , Casertano Alberto , Pjetraj Dorina , Maltoni Giulio , Calcaterra Valeria , Cauvin Vittoria , Cherubini Valentino , D’Annunzio Giuseppe , Franzese Adriana , Frongia Anna Paola , Lombardo Fortunato , Lo Presti Donatella , Matteoli Maria Cristina , Piccinno Elvira , Predieri Barbara , Rabbone Ivana , Scaramuzza Andrea Enzo , Toni Sonia , Zucchini Stefano , Maffeis Claudio , Schiaffini Riccardo
Published: April 2021

Cystic fibrosis related diabetes (CFRD) is a comorbidity of cystic fibrosis (CF) that negatively impacts on its clinical course. Prediabetes is an important predictor of either CFRD development and unfavorable prognosis of CF in both pediatric and adult patients. International guidelines recommend insulin only in case of CFRD diagnosis. Whether early detection and treatment of prediabetes may contribute to improve the clinical course of CF is still debated. A subgroup of pediatric diabetologists of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED) performed a systematic review of the literature based on predefined outcomes: impact of pre-diabetes on clinical outcomes and on the risk of developing CFRD; diagnosis of diabetes and pre-diabetes under 10 years of age; effectiveness of therapy on glycemic control, impact of therapy on pulmonary function and nutritional status. Thirty-one papers were selected for the analysis data presented in these papers were reported in tables sorted by outcomes, including comprehensive evidence grading according to the GRADE approach. Following the grading of the quality of the evidence, the entire ISPED diabetes study group achieved consensus for the Italian recommendations based on both evidence and clinical experience. We concluded that in patients with CF, prediabetes should be carefully considered as it can evolve into CFRD. In patients with CF and prediabetic conditions, after complete evaluation of the OGTT trend, glucometrics, glycemic values measured during pulmonary exacerbations and/or steroid therapy, early initiation of insulin therapy could have beneficial effects on clinical outcomes of patients with CF and prediabetes.