bluuebunny/crossref_metadata_2025 huggingface dataset:
Motivação docente no contexto da educação física escolar
Authors: Lima Heitor Felipe Cantarinho de , Caccalano Willian de Oliveira , Marques Yara Ferreira , Portella Daniel Leite , Brito Carlos Alexandre Felício
Published: November 2020

Introdução: A motivação, de acordo com a Teoria da Autodeterminação, apresenta-se em três níveis: motivação extrínseca, motivação intrínseca e desmotivação. Objetivo: O estudo teve como objetivo verificar e compreender, a partir da percepção dos professores, quais são os fatores que poderiam influenciar a motivação dos profissionais da Educação Física no contexto escolar. Metodologia: Para a pesquisa utilizou-se a metodologia qualitativa do tipo exploratória e descritiva. Entrevistou-se 12 professores do ensino médio de escolas públicas e privadas de Santo André e São Caetano do Sul.A pesquisa foi conduzida por meio de questionário, porém desenvolvido para este estudo, contendo 10 perguntas abertas. A forma de análise dos resultados foi por meio da técnica denominada por Analise de Conteúdo. Resultado: Dos resultados mais expressivos destacou-se o salário, pois representou cerca de 29,64% dos fatores considerados mais influenciadores (motivação extrínseca). Conclusão: O desenvolvimento do presente estudo possibilitou verificar quais fatores podem influenciar na motivação do professor de Educação Física do ensino médio e, com efeito, pensar em ações para possíveis modificações. Os fatores extrínsecos mostraram-se os mais influenciadores da motivação e entre eles, representados hierarquicamente, o salário, gestão escolar e rotina de trabalho foram considerados o de maior relevância para a motivação profissional, enquanto que os fatores intrínsecos como amor pela profissão e relacionamento do professor com o seu trabalho, também devem ser considerados relevantes.
Rabbit as sustainable meat source: carcass traits and technological quality of meat and of mechanically deboned meat
Authors: Paula Marielle Maria de Oliveira , Bittencourt Márcia Teixeira , Oliveira Thales Leandro Coutinho de , Bueno Lethícia Olímpio , Rodrigues Lorena Mendes , Soares Elizânia Ribeiro , Machado Luiz Carlos , Ramos Alcinéia de Lemos Souza , Ramos Eduardo Mendes
Published: November 2020

This study aimed to characterize rabbit carcass traits, meat quality, and mechanically deboned meat (MDRM) from New Zealand × Botucatu crossbred rabbits to determine the potential use by the meat industry. Average yields of the carcass (52.46%) and retail hind leg (33.88%), foreleg (15.51%), loin (11.63%), and back (39.83%) cuts were assessed, with total meat-to-bone ratio of 1.65. The meat proximate composition and technological characteristics pH, water retention capacity, and total collagen were similar to meat of commonly market species. Rabbit meat color was light (L* = 65.93) and with a low shade of red (C * = 19.24 and h = 52.79 °) due to the low content of heme pigments (19.89 µg acid hematin/g). The obtained MDRM met the levels of protein and fat required by Brazilian legislation, but a high calcium content (1.45% dry basis). It can be concluded that rabbits represent a viable unconventional meat resource with high potential for use in processing. In addition to raw meat, MDRM can also be obtained to be used as a meat ingredient in industrial products.
O contexto histórico e a importância das atividades lúdicas no ensino de química para construção de conhecimento
Authors: Tizzo Danielle Ferreira , Ribeiro Antonio Carlos Chaves , Felício Cinthia Maria
Published: November 2020

Nos últimos anos houve um aumento considerável no número de publicações envolvendo a aplicação de jogos para o ensino de Química. No entanto, tais publicações não vêm necessariamente acompanhadas de referenciais teóricos adequados, ou, quando utilizados, não se relacionam diretamente com questões de ensino e aprendizagem. Dessa forma, esse trabalho tem como objetivo analisar uma série de artigos científicos de diversas revistas, entre os anos 2015-2020. Foram separados em três categorias: a) jogos tradicionais aplicados em qualquer disciplina; b) jogos tradicionais no ensino de química; c) aplicação de jogos virtuais no ensino de Química. Nessa última categoria, foram analisados três artigos para verificar quais as metodologias utilizadas para a validação dos dados obtidos a partir da aplicação dos jogos tradicionais, tradicionais e virtuais, ou virtuais. Os resultados apontam que os alunos aceitam bem todo tipo de jogo (tradicional ou virtual), conseguem fixar e compreender melhor o conteúdo ministrado pelo professor. Assim, através da diversificação da metodologia o professor pode despertar a motivação dos alunos pelas aulas e pelos conteúdos, fazendo com que facilite a absorção do conteúdo, e ao mesmo tempo melhorar o rendimento escolar dos alunos.
Optimisation of ultrasound assisted extraction of antiacetylcholinesterase and antioxidant compounds from manuka (Leptospermum scoparium) for use as a phytomedicine against Alzheimer’s disease
Authors: Majid Hafiz , Silva Filipa V. M.
Published: November 2020

Background: Alzheimer’s disease is a progressive mental deterioration related to ageing and senility. Approved drugs that inhibit acetylcholinesterase (AChE) enzyme activity in the human brain are one of the ways to control the natural progression of this disease. The present study reports on the optimisation of ultrasound-assisted extraction of antiacetylcholinesterase and antioxidant compounds from manuka leaves using response surface methodology.
Methods: A Box-Behnken design was used to investigate the effect of extraction temperature (40–60°C), time (1–20 min), and ethanol concentration (30–70%) on AChE inhibition, antioxidant activity, and extraction yield.
Results: The values of AChE, radical scavenging activity (RSA) and yield predicted by the models generated were similar to the experimental values. Extraction time, ethanol concentration and temperature were significant in all the responses. Optimum extraction conditions for maximum AChE inhibition (74%), RSA (79%) and yield (50%) were successfully validated experimentally and the IC50 of the optimised extracts were reduced to 28.5 (from 66.0) and 2.37 (from 32.4) ?g/ mL for AChE and antioxidant activity, respectively. The optimisation enabled an increase in the extraction yield from 21% to 49%.
Conclusions: In view of the significant bioactive properties determined, with possible beneficial effects on memory deficit, we would encourage the use of the manuka leaf extract for the development of new phytopharmaceuticals to improve brain function and control dementias such as Alzheimer’s disease. One other application could be as a beverage for the preparation of tea infusions.
Comparative study of the hemolymph microbiome between live and recently dead American lobsters Homarus americanus
Authors: Jung J , Gillevet PM , Sikaroodi M , Andrews J , Song B , Shields JD
Published: November 2020

Lobsters and other crustaceans do not have sterile hemolymph. Despite this, little is known about the microbiome in the hemolymph of the lobsterHomarus americanus. The purpose of this study was to characterize the hemolymph microbiome in lobsters. The lobsters were part of a larger study on the effect of temperature on epizootic shell disease, and several died during the course of the study, providing an opportunity to examine differences in the microbiomes between live and recently dead (1-24 h) animals. The hemolymph microbiomes of live lobsters was different from those in dead animals and both were different from the tank microbiome in which the animals had been held. The microbiomes of live lobsters were more diverse and had a different suite of bacteria than those from dead animals. The dominant taxa in live lobsters belonged toFlavobacteriaceaeandRhodobacteraceae, whereasVibrionaceaeandEnterobacteriaceaewere predominant in the dead lobsters. Although aquarium microbiomes overlapped with the hemolymph microbiomes, there was less overlap and lower abundance of taxa in comparison with hemolymph from live lobsters. Previous studies reporting bacteria in the digestive tract of lobsters suggested thatVibrionaceaeandEnterobacteriaceaehad invaded the hemolymph via the gut. Our study suggests that hemolymph bacteria abundant in live lobsters do not originate from the tank milieu and comprise a rich, natural, or native background of bacterial constituents.
Co-occurrence of gray whales and vessel traffic in the North Pacific Ocean
Authors: Silber GK , Weller DW , Reeves RR , Adams JD , Moore TJ
Published: November 2020

All species of large whales are susceptible to vessel strikes, but the true scale and geographical extent of such strikes is not known. This paper provides a qualitative assessment of the range-wide risks posed to gray whalesEschrichtius robustusby vessels, by comparing patterns of whale distribution with the density of vessel traffic seasonally throughout the North Pacific in 2019. Areas of very high vessel density were evident year-round near many coastlines, along inter-continental trade routes, and at hubs of commercial shipping near port entrances. Gray whales were exposed to vessel strikes throughout their range and in their feeding, southbound migration, wintering, and northbound migration periods. Areas of apparently high risk were in the Russian Far East (Kamchatka peninsula and Okhotsk Sea), Bering Sea (including the Aleutian Islands), Gulf of Alaska, and along the entire west coast of North America. Risk appeared greatest during south- and northbound migration when much of the gray whale population is moving through waters near shore. Tanker, container, and bulk-carrier ships represent considerable risk to whales in the North Pacific Ocean, but the large geographical extent of commercial fishing activities suggests that fisheries are also a substantial source of risk. Vessel-strike risk maps indicate the relative extent of exposure of gray (and other) whales to underwater vessel noise. The number of gray whales killed by ship strikes each year may be in the tens, or perhaps the low hundreds. Additional analyses, including quantitative assessments, are warranted to further clarify the risk of vessel strikes to gray whales.
Agent-based modeling and genetics reveal the Limfjorden, Denmark, as a well-connected system for mussel larvae
Authors: Pastor A , Larsen J , Hansen FT , Simon A , Bierne N , Maar M
Published: November 2020

Fishery of blue mussels Mytilus edulis constitutes a very important economic activity in Denmark, whereas mussel farming on long-lines or nets is a new, growing sector. Spawning from natural mussel beds takes place during early summer, and larvae disperse via water currents before settling on the bottom or on spat collectors in the farms. In the present study, we coupled a 3D physical model system (FlexSem) with an agent-based model in order to examine the connectivity of this marine system in terms of mussel larval dispersal and settling potential. To address this question, we (1) estimated the dispersal and connectivity between 17 areas in the Limfjorden, (2) identified the main donor and receiver areas of mussel larvae and (3) identified possible dispersal barriers. The results show that the central narrow strait in the Limfjorden was the main donor area in all the studied years, and that the adjacent eastern areas were the main receiver areas. Towards the inner basins of the Limfjorden, isolation increased and limited connectivity was observed. The results from the cluster analysis grouped the Limfjorden into 3 to 5 clusters, but there was still some exchange of simulated larvae observed among these clusters. Analysis of molecular markers revealed no genetic differentiation between areas and supports the model results, indicating that despite distinguishable hydrographic boundaries, the mussel populations in the Limfjorden are well connected. This study demonstrates how connectivity modeling can be used to support site selection processes in aquaculture.
Üretici Bakış Açısıyla Çorum İlinde Makarnalık Buğdayın Dünü, Bugünü ve Geleceği
Authors: TAŞCI Rahmi , BOLAT Merve , ÖZERCAN Belma , TARHAN Sinem , HAMARAT Tuğçe , KARABAK Sevinç , ARSLAN Selda , BAYRAMOĞLU Zeki
Published: November 2020

Bu çalışmanın amacı; Çorum ilinde bitkisel üretim deseni içinde makarnalık buğdaya yer veren tarım işletmelerinin makarnalık buğday üretimi ve pazarlama yapısının incelenmesidir. Türkiye’nin makarnalık buğday üretiminde uzun yıllardır önemli illerinden birisi olan Çorum ilinde üreticilerin makarnalık buğday ekim alanlarının yıllar itibarıyla azaldığı görülürken, üreticiler tarafından en fazla tanınan ve en geniş alanlarda ekilişi gerçekleştirilen makarnalık buğday çeşidinin Çeşit- 1252 olduğu belirlenmiştir. Makarnalık buğdayları hammadde olarak kullanan makarna ve bulgur fabrikalarının Çorum ilinde faaliyet göstermesi; Çorum ilinde makarnalık buğday üretiminin sürdürülebilmesi açısından önemli bir faktör olarak görülmektedir. Üreticilerin makarnalık buğday çeşit tercihinde; verimi fazla olan, yörenin iklim ve toprak yapısına uygun ve kolay pazarlanabilen çeşitleri tercih ettiği gözlenirken, Çorum ilinde makarnalık buğday satış fiyatlarının, uzun yıllar boyunca ekmeklik buğday satış fiyatlarından fazla olduğu belirlenmiştir. Makarnalık buğday ıslah programlarının planlanmasında ve yürütülmesinde çeşit geliştiren kurum / kuruluşlar ile tarıma dayalı sanayicilerin ve üreticilerin de ihtiyacına yönelik yeni çeşit geliştirme işbirliklerinin arttırılması ile birlikte yeni geliştirilen ve yöreye uygun makarnalık buğday çeşitlerinin ve üretim tekniklerinin üreticiye ulaştırılma çalışmalarının artarak sürdürülmesi gereklidir. Bununla birlikte gelecek yıllardaki makarnalık buğday ekim alanlarında ve üretim miktarında azalmanın olabileceği de göz önünde bulundurularak, özellikle Güneydoğu Anadolu ve Orta Anadolu Bölgelerinde makarnalık buğday üretim alanları belirlenerek, bu alanlarda makarnalık buğdaya ayrı bir tarımsal destekleme modeli önerilebilir.
A Cloud-Enabled Application Framework for Simulating Regional-Scale Impacts of Natural Hazards on the Built Environment
Authors: Deierlein Gregory G. , McKenna Frank , Zsarnóczay Adam , Kijewski-Correa Tracy , Kareem Ahsan , Elhaddad Wael , Lowes Laura , Schoettler Matthew J. , Govindjee Sanjay
Published: November 2020

With the goal to facilitate evaluation and mitigation of the risks from natural hazards, the Natural Hazards Engineering Research Infrastructure’s Computational Modeling, and Simulation Center (NHERI SimCenter) is developing computational workflows for regional hazard simulations. These simulations enable research to combine detailed assessments of individual facilities with comprehensive regional-scale simulations of natural hazard effects. By integration of multi-fidelity and multi-resolution models to assess natural hazard impacts on buildings, infrastructure systems and other constructed facilities, the approach enables the engineering analysis of public policies and socio-economic impacts. Effective development of platforms for high-resolution regional simulations requires modular workflows that can integrate state-of-the-art models with information technologies and high-performance computing resources. In this paper, the modular architecture of the computational workflow models is described and illustrated through testbed applications to evaluate regional building damage under an earthquake and a hurricane scenario. Developed and disseminated as open-source software on the NHERI DesignSafe Cyberinfrastructure, the computational models and workflows are enabling multi-disciplinary collaboration on research to mitigate the effects of natural hazard disasters.
Inherent Adaptive Structures Using Nature-Inspired Compound Elements
Authors: Chenaghlou Mohammad Reza , Kheirollahi Mohammad , Abedi Karim , Akbari Ahmad , Fathpour Aydin
Published: November 2020

Biomimicry studies have attracted significant attention in research and practice, leading to effective engineering solutions to develop new types of structures inspired by natural systems. The objective of this study is to employ natural structures' inherent adaptivity under changing loading conditions. Three new types of compound elements are proposed that are able to improve the structure load-bearing capacity through passive inherent adaptivity. A self-centering system, inspired by the human spine, which comprises a column pre-stressed through cables, is employed as a kinematic isolator. A similar self-centering system is applied to increase the load-bearing capacity of unreinforced masonry columns. An axially loaded element, inspired by the bamboo stem, which comprises a steel core reinforced by a series of cylindrical plates that are encased in a steel tube, is employed to control the onset of instability in long-span truss structures. Application to typical frame, masonry, and truss structures is investigated through finite element analysis. Results show that the proposed compound elements are effective to increase the structure load-bearing capacity and to reduce the response under seismic excitation owning to their inherent adaptive features.
The Bone-Forming Properties of Periosteum-Derived Cells Differ Between Harvest Sites
Authors: Groeneveldt Lisanne C. , Herpelinck Tim , Maréchal Marina , Politis Constantinus , van IJcken Wilfred F. J. , Huylebroeck Danny , Geris Liesbet , Mulugeta Eskeatnaf , Luyten Frank P.
Published: November 2020

The development of alternatives for autologous bone grafts is a major focus of bone tissue engineering. To produce living bone-forming implants, skeletal stem and progenitor cells (SSPCs) are envisioned as key ingredients. SSPCs can be obtained from different tissues including bone marrow, adipose tissue, dental pulp, and periosteum. Human periosteum-derived cells (hPDCs) exhibit progenitor cell characteristics and have well-documentedin vivobone formation potency. Here, we have characterized and compared hPDCs derived from tibia with craniofacial hPDCs, from maxilla and mandible, respectively, each representing a potential source for cell-based tissue engineered implants for craniofacial applications. Maxilla and mandible-derived hPDCs display similar growth curves as tibial hPDCs, with equal trilineage differentiation potential toward chondrogenic, osteogenic, and adipogenic cells. These craniofacial hPDCs are positive for SSPC-markers CD73, CD164, and Podoplanin (PDPN), and negative for CD146, hematopoietic and endothelial lineage markers. Bulk RNA-sequencing identified genes that are differentially expressed between the three sources of hPDC. In particular, differential expression was found for genes of the HOX and DLX family, forSOX9and genes involved in skeletal system development. Thein vivobone formation, 8 weeks after ectopic implantation in nude mice, was observed in constructs seeded with tibial and mandibular hPDCs. Taken together, we provide evidence that hPDCs show different profiles and properties according to their anatomical origin, and that craniofacial hPDCs are potential sources for cell-based bone tissue engineering strategies. The mandible-derived hPDCs display - bothin vitroandin vivo -chondrogenic and osteogenic differentiation potential, which supports their future testing for use in craniofacial bone regeneration applications.
Glycogen Phosphorylase B Is Regulated by miR101-3p and Promotes Hepatocellular Carcinoma Tumorigenesis
Authors: Cui Guangying , Wang Huifen , Liu Wenli , Xing Jiyuan , Song Wengang , Zeng Zhaohai , Liu Liwen , Wang Haiyu , Wang Xuemei , Luo Hong , Leng Xiaoyang , Shen Shen
Published: November 2020

Glycogen metabolism plays a key role in tumorigenesis. High expression levels of glycogen phosphorylase B (PYGB) were reported in several cancers and might be served as a prognostic biomarker for cancer from precancerous lesions. Previous studies indicated the high expression of PYGB in hepatocellular carcinoma (HCC) tissues. However, the detailed roles of PYGB in HCC, as well as the regulatory mechanisms, are still unclear. In this study, we confirmed that PYGB was overexpressed in HCC tissues. PYGB overexpression was significantly associated with an aggressive tumor phenotype and poor prognosis of HCC patients. Functionally, PYGB knockdown suppressed HCC cell proliferation, migration and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Bioinformatics analysis indicated that PYGB overexpression might enhance epithelial to mesenchymal transition (EMT) in HCC. Moreover, miR-101-3p was identified to post-transcriptionally inhibit the expression of PYGB via binding to 3′-UTR of PYGB. Overexpression of PYGB antagonized the regulatory effect of miR-101-3p on cell proliferation, migration and invasion in HCC cells. In summary, our results suggest that miR-101-3p/PYGB axis has an important role in HCC and PYGB could be served as a novel prognostic biomarker and therapeutic target for improving the prognosis of HCC patients.
The Role of Autophagy in Osteoarthritis
Authors: Duan Ran , Xie Hui , Liu Zheng-Zhao
Published: November 2020

Chondrocytes are the only cell type in normal cartilage. The pathological changes of osteoarthritis (OA) mostly revolve around the apoptosis and dysfunction of chondrocytes. Autophagy, as an intracellular degradation system that maintains the steady state of energy metabolism in cells, has been shown to restore the function of damaged chondrocytes, alleviating the occurrence and progression of OA. In this review, we explored the relationship between autophagy and OA and the key molecules of autophagy pathway that regulate the progression of OA, providing new ideas for OA treatment by targeting autophagy.
Single-Nucleotide RNA Maps for the Two Major Nosocomial Pathogens Enterococcus faecalis and Enterococcus faecium
Authors: Michaux Charlotte , Hansen Elisabeth E. , Jenniches Laura , Gerovac Milan , Barquist Lars , Vogel Jörg
Published: November 2020

Enterococcus faecalisandfaeciumare two major representative clinical strains of the Enterococcus genus and are sadly notorious to be part of the top agents responsible for nosocomial infections. Despite their critical implication in worldwide public healthcare, essential and available resources such as deep transcriptome annotations remain poor, which also limits our understanding of post-transcriptional control small regulatory RNA (sRNA) functions in these bacteria. Here, using the dRNA-seq technique in combination with ANNOgesic analysis, we successfully mapped and annotated transcription start sites (TSS) of bothE. faecalis V583andE. faecium AUS0004at single nucleotide resolution. Analyzing bacteria in late exponential phase, we capture ~40% (E. faecalis) and 43% (E. faecium) of the annotated protein-coding genes, determine 5′ and 3′ UTR (untranslated region) length, and detect instances of leaderless mRNAs. The transcriptome maps revealed sRNA candidates in both bacteria, some found in previous studies and new ones. Expression of candidate sRNAs is being confirmed under biologically relevant environmental conditions. This comprehensive global TSS mapping atlas provides a valuable resource for RNA biology and gene expression analysis in the Enterococci. It can be accessed online atwww.helmholtz-hiri.de/en/datasets/enterococcusthrough an instance of the genomic viewer JBrowse.
Queensland Telepaediatric Service: A Review of the First 15 Years of Service
Authors: Smith Anthony C. , Armfield Nigel R. , Coulthard Mark G. , Williams Michael L. , Caffery Liam J.
Published: November 2020

In November 2000, the Queensland Telepaediatric Service (QTS) was established in Brisbane, Australia, to support the delivery of telehealth services to patients and clinicians in regional and remote locations. The QTS was built on a centralized coordination model, where telehealth services could be effectively managed by a dedicated telehealth coordinator. In doing so, telehealth referral and consultation processes were efficient and clinicians felt better supported as they adjusted to new processes for engaging with patients. We have conducted a retrospective review of activity associated with the QTS and summarized key activities which have arisen from this extensive program of work. Telehealth service records and associated publications were used to describe the evolution of the QTS over a 15-year period. From November 2000 to March 2016, 23,054 telehealth consultations were delivered for 37 pediatric clinical specialties. The most common service areas included child and youth mental health, neurology, burns care, surgery, and ear nose and throat services. A range of different telehealth service models were developed to align with different clinical service needs and location of services. Whilst most work involved video consultation between hospitals, some services involved the delivery of telehealth services into the home, schools or community health centres. Despite its longevity, the QTS was not immune to the usual challenges associated with telehealth implementation, service redesign and sustainability. Experience reported from the QTS will be useful for other health services seeking to develop comprehensive telehealth services in a rapidly changing healthcare environment.
Environmental Reliance Traps and Pathways – Theory and Analysis of Empirical Data From Rural Nepal
Authors: Walelign Solomon Zena , Jiao Xi , Smith-Hall Carsten
Published: November 2020

Existing theoretical and empirical work on poverty traps does not in detail investigate interactions between environmental reliance and socioeconomic factors over time. A string of studies has documented that environmental products provide rural households with both subsistence and cash income and that high environmental reliance is often associated with poverty. These studies are snapshots and do not allow an understanding of environmental reliance dynamics – are households trapped at high levels of environmental reliance, what factors enable movement from high to low reliance, and how are such movements associated with total household income? Here we develop and present a theory of environmental reliance traps that allows analysis and explanation of changes in household-level environmental reliance over time. We propose operational parametric and non-parametric models for empirical investigation of the theory and employ these using an environmentally augmented three-wave panel household income and asset dataset (n = 427, pooled n = 1212) from Nepal. We found no evidence of an environmental reliance trap in the study population, meaning that all households converged on a single long-term environmental reliance equilibrium point. Households with high environmental reliance moving down toward the equilibrium (n = 358) have low income and asset endowments; while households with low environmental reliance moving up toward the equilibrium (n = 854) are better off, in terms of both income and assets. The approach identified the poorer households that make a living from harvesting substantial amounts of environmental products The probability of being a high-downward moving household is negatively associated with the size of landholding, market access, and female headship, and positively associated with the household head being born in the village and belonging to the most common caste. We argue that the identification of environmental reliance pathways can simultaneously inform interventions aimed at environmental conservation and poverty reduction.
Identification of a Transcriptomic Prognostic Signature by Machine Learning Using a Combination of Small Cohorts of Prostate Cancer
Authors: Vittrant Benjamin , Leclercq Mickael , Martin-Magniette Marie-Laure , Collins Colin , Bergeron Alain , Fradet Yves , Droit Arnaud
Published: November 2020

Determining which treatment to provide to men with prostate cancer (PCa) is a major challenge for clinicians. Currently, the clinical risk-stratification for PCa is based on clinico-pathological variables such as Gleason grade, stage and prostate specific antigen (PSA) levels. But transcriptomic data have the potential to enable the development of more precise approaches to predict evolution of the disease. However, high quality RNA sequencing (RNA-seq) datasets along with clinical data with long follow-up allowing discovery of biochemical recurrence (BCR) biomarkers are small and rare. In this study, we propose a machine learning approach that is robust to batch effect and enables the discovery of highly predictive signatures despite using small datasets. Gene expression data were extracted from three RNA-Seq datasets cumulating a total of 171 PCa patients. Data were re-analyzed using a unique pipeline to ensure uniformity. Using a machine learning approach, a total of 14 classifiers were tested with various parameters to identify the best model and gene signature to predict BCR. Using a random forest model, we have identified a signature composed of only three genes (JUN, HES4, PPDPF) predicting BCR with better accuracy [74.2%, balanced error rate (BER) = 27%] than the clinico-pathological variables (69.2%, BER = 32%) currently in use to predict PCa evolution. This score is in the range of the studies that predicted BCR in single-cohort with a higher number of patients. We showed that it is possible to merge and analyze different small and heterogeneous datasets altogether to obtain a better signature than if they were analyzed individually, thus reducing the need for very large cohorts. This study demonstrates the feasibility to regroup different small datasets in one larger to identify a predictive genomic signature that would benefit PCa patients.
ROS1 Fusion Mediates Immunogenicity by Upregulation of PD-L1 After the Activation of ROS1–SHP2 Signaling Pathway in Non-Small Cell Lung Cancer
Authors: Cai Liangliang , Duan Jianchun , Qian Li , Wang Zhijie , Wang Shuhang , Li Sini , Wang Chao , Zhao Jie , Zhang Xue , Bai Hua , Wang Jie
Published: November 2020

The drug resistance of first-line crizotinib therapy for ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) fusion non-small cell lung cancer (NSCLC) is inevitable. Whether the administration of immune checkpoint inhibitor (ICI) therapy is suitable for ROS 1 fusion NSCLCs or after the development of crizotinib resistance is still unknown. In this study, five different crizotinib resistant concentration cell lines (HCC78CR1-5) from primary sensitive HCC78 cells were cultured. Ba/F3 cells expressing crizotinib sensitive ROS1 fusion and crizotinib resistant ROS1-G2032R mutation were used to explore the relationship between ROS1 fusion, ROS1-G2032R mutation and programmed death-ligand 1 (PD-L1) expression and the clinical potential of anti-PD-L1 ICI therapy. The signaling pathway net was compared between HCC78 and HCC78CR1-5 cells using RNA sequencing. Anti- PD-L1 ICI therapy was performed on mouse xenograft models with Ba/F3 ROS1 fusion or ROS1-G2032R mutation. HCC78CR1-5 showed more immunogenicity than HCC78 in immune-related pathways. The PD-L1 expression level was remarkably higher in HCC78CR1-5 with ROS1 fusion upregulation than HCC78 primary cell. Furthermore, the expression of PD-L1 was down-regulated by RNA interference with ROS1 siRNAs and up-regulated lower in Ba/F3 ROS1-G2032R resistant mutation than ROS1 fusion. Western blotting analysis showed the ROS1–SHP2 signaling pathway activation in HCC78CR1-5 cells, Ba/F3 ROS1 fusion and ROS1-G2032R resistant mutation. Mouse xenograft models with Ba/F3 ROS1 fusion showed more CD3+PD-1+ T cells both in blood and tissue, and more sensitivity than the cells with Ba/F3 ROS1-G2032R resistant mutation after anti-PD-L1 therapy. Our findings indicate that PD-L1 upregulation depends on ROS1 fusion more than ROS1-G2032R mutation. We share our insights of NSCLCs treatment management into the use of anti-PD-L1 ICI therapy in ROS1 fusion and not in ROS1-G2032R resistant mutation.
Phenotyping of Adaptive Immune Responses in Inflammatory Diseases
Authors: Humrich Jens Y. , Bernardes Joana P. , Ludwig Ralf J. , Klatzmann David , Scheffold Alexander
Published: November 2020

Immunophenotyping on the molecular and cellular level is a central aspect for characterization of patients with inflammatory diseases, both to better understand disease etiopathogenesis and based on this to develop diagnostic and prognostic biomarkers which allow patient stratification and tailor-made treatment strategies. Technology-driven developments have considerably expanded the range of analysis tools. Especially the analysis of adaptive immune responses, often regarded as central though mostly poorly characterized disease drivers, is a major focus of personalized medicine. The identification of the disease-relevant antigens and characterization of corresponding antigen-specific lymphocytes in individual patients benefits significantly from recent developments in cytometry by sequencing and proteomics. The aim of this workshop was to identify the important developments for state-of-the-art immunophenotyping for clinical application and precision medicine. We focused here on recent key developments in analysis of antigen-specific lymphocytes, sequencing, and proteomics approaches, their relevance in precision medicine and the discussion of the major challenges and opportunities for the future.
Improving Situational Awareness in the Arctic Ocean
Authors: Rainville Luc , Wilkinson Jeremy , Durley Mary Ellen J. , Harper Scott , DiLeo Julia , Doble Martin J. , Fleming Andrew , Forcucci David , Graber Hans , Hargrove John T. , Haverlack John , Hughes Nick , Hembrough Brett , Jeffries Martin O. , Lee Craig M. , Mendenhall Brendon , McCormmick David , Montalvo Sofia , Stenseth Adam , Shilling Geoffrey B. , Simmons Harper L. , Toomey James E. , Woods John
Published: November 2020

To successfully operate in a harsh environment like the Arctic Ocean, one must be able to understand and predict how that environment will evolve over different spatial and temporal scales. This is particularly challenging given the on-going and significant environmental changes that are occurring in the region. Access to the most recent environmental information provides timely knowledge that enables ship-based operations to proceed efficiently, effectively and safely in this difficult arena. Knowledge of the evolving environmental conditions during a field campaign is critical for effective planning, optimal execution of sampling strategies, and to provide a broader context to data collected at specific times and places. We describe the collaborations and processes that enabled an operational system to be developed to provide a remote field-team, located on USCGC Healy in the Beaufort Sea, with near real-time situational awareness information regarding the weather, sea ice conditions, and oceanographic processes. The developed system included the punctual throughput of near real-time products such as satellite imagery, meteorological forecasts, ice charts, model outputs, and up to date locations of key sea ice and ocean-based assets. Science and operational users, as well as onshore personnel, used this system for real-time practical considerations such as ship navigation, and to time scientific operations to ensure the appropriate sea ice and weather conditions prevailed. By presenting the outputs of the system within the context of case studies our results clearly demonstrate the benefits that improved situational awareness brings to ship-based operations in the Arctic Ocean, both today and in the future.
Gene Co-expression Networks Identifies Common Hub Genes Between Cutaneous Sarcoidosis and Discoid Lupus Erythematosus
Authors: Nickles Melissa A. , Huang Kai , Chang Yi-Shin , Tsoukas Maria M. , Sweiss Nadera J. , Perkins David L. , Finn Patricia W.
Published: November 2020

In this study we analyzed gene co-expression networks of three immune-related skin diseases: cutaneous sarcoidosis (CS), discoid lupus erythematosus (DLE), and psoriasis. We propose that investigation of gene co-expression networks may provide insights into underlying disease mechanisms. Microarray expression data from two cohorts of patients with CS, DLE, or psoriasis skin lesions were analyzed. We applied weighted gene correlation network analysis (WGCNA) to construct gene-gene similarity networks and cluster genes into modules based on similar expression profiles. A module of interest that was preserved between datasets and corresponded with case/control status was identified. This module was related to immune activation, specifically leukocyte activation, and was significantly increased in both CS lesions and DLE lesions compared to their respective controls. Protein-protein interaction (PPI) networks constructed for this module revealed seven common hub genes between CS lesions and DLE lesions: TLR1, ITGAL, TNFRSF1B, CD86, SPI1, BTK, and IL10RA. Common hub genes were highly upregulated in CS lesions and DLE lesions compared to their respective controls in a differential expression analysis. Our results indicate common gene expression patterns in the immune processes of CS and DLE, which may have indications for future therapeutic targets and serve as Th1-mediated disease biomarkers. Additionally, we identified hub genes unique to CS and DLE, which can help differentiate these diseases from one another and may serve as unique therapeutic targets and biomarkers. Notably, we find common gene expression patterns in the immune processes of CS and DLE through utilization of WGCNA.
Nanoparticle-Based Devices in the Control of Antibiotic Resistant Bacteria
Authors: Gómez-Núñez Mario F. , Castillo-López Mariel , Sevilla-Castillo Fernando , Roque-Reyes Oscar J. , Romero-Lechuga Fernanda , Medina-Santos Diana I. , Martínez-Daniel Ricardo , Peón Alberto N.
Published: November 2020

Antimicrobial resistance (AR) is one of the most important public health challenges worldwide as it represents a serious complication that is able to increase the mortality, morbidity, disability, hospital stay and economic burden related to infectious diseases. As such, the spread of AR–pathogens must be considered as an emergency, and interdisciplinary approaches must be undertaken in order to develop not only drugs, but holistic strategies to undermine the epidemic and pathogenic potentials of multi-drug resistant (MDR) pathogens. One of such approaches has focused on the use of antimicrobial nanoparticles (ANPs), as they have demonstrated to possess strong antimicrobial effects on MDR pathogens. On the other hand, the ability of bacteria to develop resistance to such agents is minimal. In this way, ANPs may seem a good choice for the development of new drugs, but there is no certainty about their safety, which may delay its translation to the clinical setting. As MDR pathogens are quickly becoming more prevalent and drug development is slow and expensive, there is an increasing need for the rapid development of new strategies to control such agents. We hereby explore the possibility of designing ANP-based devices such as surgical masks and fabrics, wound dressings, catheters, prostheses, dentifrices, water filters, and nanoparticle-coated metals to exploit the potential of such materials in the combat of MDR pathogens, with a good potential for translation into the clinical setting.
Antibiotic Resistance and Virulence of Extraintestinal Pathogenic Escherichia coli (ExPEC) Vary According to Molecular Types
Authors: Duan Yitao , Gao Huihui , Zheng Liyang , Liu Shuangqing , Cao Yang , Zhu Siyuan , Wu Zhenzhe , Ren Hongqiang , Mao Daqing , Luo Yi
Published: November 2020

Extraintestinal pathogenic Escherichia coli (ExPEC) can cause many human extraintestinal infections. Resistance and virulence of ExPEC are inextricably linked to its phylogenetic background. However, studies on type-specific distribution of resistance and virulence and the connection between resistance/virulence and molecular typing are lacking. Here, 411 ExPEC strains were collected and characterized using antimicrobial susceptibility testing and molecular typing. Among these, 74 representative strains were selected for whole genome sequencing and the Galleria mellonella killing assay. CH40-30-ST131, CH37-27-ST405, CH40-41-ST131, and CH13-5-ST12 isolates had high resistance rates to all antimicrobials tested. BlaCTX–M played a significant role in the β-lactam resistance of ExPEC isolates. CH14-64-ST1193, CH40-30-ST131, and CH35-27-ST69 isolates were highly virulent in the G. mellonella model. Virulence factors (VFs) involved in adherence (papB, papI, papX, and fimA), autotransporter (sat), invasion (aslA, kpsD), iron uptake (except for entD), or toxin (senB) might be responsible for pathogenicity in vivo. Specific antibiotic resistance genes (ARGs) or VFs were prevalent in specific types of strains, including papB, papI, fimA, sat, kpsD, senB, and aerobactin genes in CH14-64-ST1193 isolates; blaCTX–M–15, aac(6′)-Ib-cr, papB, papI, sat, iucA, iucB, iucC, chuT, chuX, and shuU in CH40-30-ST131 isolates; tetB in CH35-27-ST69 and CH13-5-ST12 isolates. Type distribution also differed by VF score. CH37-27-ST405 and CH26-5-ST38 isolates carried more ARGs and VFs indicating that they had a high resistance and virulence potential. This study demonstrates the type-specific distribution of resistance and virulence thus providing a basis for further research, prevention and treatment of ExPEC infections.
Stroke-Induced Modulation of Myeloid-Derived Suppressor Cells (MDSCs) and IL-10-Producing Regulatory Monocytes
Authors: Achmus Lennart , Ruhnau Johanna , Grothe Sascha , von Sarnowski Bettina , Bröker Barbara M. , Dressel Alexander , Schulze Juliane , Vogelgesang Antje
Published: November 2020

Background: Stroke patients are at risk of acquiring secondary infections due to stroke-induced immune suppression (SIIS). Immunosuppressive cells comprise myeloid-derived suppressor cells (MDSCs) and immunosuppressive interleukin 10 (IL-10)-producing monocytes. MDSCs represent a small but heterogeneous population of monocytic, polymorphonuclear (or granulocytic), and early progenitor cells (“early” MDSC), which can expand extensively in pathophysiological conditions. MDSCs have been shown to exert strong immune-suppressive effects. The role of IL-10-producing immunosuppressive monocytes after stroke has not been investigated, but monocytes are impaired in oxidative burst and downregulate human leukocyte antigen—DR isotype (HLA-DR) on the cell surface.

Objectives: The objective of this work was to investigate the regulation and function of MDSCs as well as the immunosuppressive IL-10-producing monocytes in experimental and human stroke.

Methods: This longitudinal, monocentric, non-interventional prospective explorative study used multicolor flow cytometry to identify MDSC subpopulations and IL-10 expression in monocytes in the peripheral blood of 19 healthy controls and 27 patients on days 1, 3, and 5 post-stroke. Quantification of intracellular STAT3p and Arginase-1 by geometric mean fluorescence intensity was used to assess the functionality of MDSCs. In experimental stroke induced by electrocoagulation in middle-aged mice, monocytic (CD11b+Ly6G−Ly6Chigh) and polymorphonuclear (CD11b+Ly6G+Ly6Clow) MDSCs in the spleen were analyzed by flow cytometry.

Results: Compared to the controls, stroke patients showed a relative increase in monocytic MDSCs (percentage of CD11b+ cells) in whole blood without evidence for an altered function. The other MDSC subgroups did not differ from the control. Also, in experimental stroke, monocytic, and in addition, polymorphonuclear MDSCs were increased. The numbers of IL-10-positive monocytes did not differ between the patients and controls. However, we provide a new insight into monocytic function post-stroke since we can report that a differential regulation of HLA-DR and PD-L1 was found depending on the IL-10 production of monocytes. IL-10-positive monocytes are more activated post-stroke, as indicated by their increased HLA-DR expression.

Conclusions: MDSC and IL-10+ monocytes can induce immunosuppression within days after stroke.
Case Report: Myelin Oligodendrocyte Glycoprotein Antibody-Associated Relapse With COVID-19
Authors: Woodhall Mark , Mitchell James W. , Gibbons Emily , Healy Sarah , Waters Patrick , Huda Saif
Published: November 2020

A 39-year-old lady with relapsing myelin oligodendrocyte glycoprotein antibody (MOG-IgG) associated disease developed coryzal symptoms, malaise, sweating, and postural dizziness. Six days later she presented with painful progressive right visual loss consistent with optic neuritis. COVID-19 was confirmed by nasopharyngeal swab and MOG-IgG serological reversion was noted. Visual function improved following steroids and plasma exchange. This case highlights a possible causal association between inflammation due to COVID-19 and a relapse of MOG-IgG associated disease. It also highlights the clinical relevance of reporting MOG-IgG titers in MOG-IgG associated disease.
Can I Discharge My Stroke Patient Home After Inpatient Neurorehabilitation? LIMOS Cut-Off Scores for Stroke Patients “Living Alone” and “Living With Family”
Authors: Ottiger Beatrice , Lehnick Dirk , Pflugshaupt Tobias , Vanbellingen Tim , Nyffeler Thomas
Published: November 2020

Background: Discharge planning of stroke patients during inpatient neurorehabilitation is often difficult since it depends both on the patient's ability to perform activities of daily living (ADL) and the social context. The aim of this study was to define ADL cut-off scores using the Lucerne ICF-based multidisciplinary observation scale (LIMOS) that allow the clinicians to decide whether stroke patients who “live alone” and “live with a family” can be discharged home or must enter a nursing home. Additionally, we investigated whether age and gender factors influence these cut-off scores.

Methods: A single-center retrospective cohort study was conducted to establish cut-off discharge scores for the LIMOS. Receiver-operating-characteristics curves were calculated for both patient groups “living alone” and “living with family” to illustrate the prognostic potential of the LIMOS total score with respect to their discharge goals (home alone or nursing home; home with family or nursing home). A logistic regression model was used to determine the (age- and gender-adjusted) odds ratios of being released home if the LIMOS total score was above the cut-off. A single-center prospective cohort study was then conducted to verify the adequacy of the cut-off values for the LIMOS total score.

Results: A total of 687 stroke inpatients were included in both studies. For the group “living alone” a LIMOS total score above 158 indicated good diagnostic accuracy in predicting discharge home (sensitivity 93.6%; specificity 95.4%). A LIMOS total cut-off score above 130 points was found for the group “living with family” (sensitivity 92.0%; specificity 88.6%). The LIMOS total score odds ratios, adjusted for age and gender, were 292.5 [95% CI: (52.0–1645.5)] for the group “living alone” and were 89.4 [95% CI: (32.3–247.7)] for the group “living with family.”

Conclusion: Stroke survivors living alone needed a higher ADL level to return home than those living with a family. A LIMOS total score above 158 points allows a clinician to discharge a patient that lives alone, whereas a lower LIMOS score above 130 points can be sufficient in a patient that lives with a family. Neither age nor gender played a significant role.