bluuebunny/crossref_metadata_2025 huggingface dataset:
ANALISE DAS PROPRIEDADES MECÂNICAS E MICROESTRUTURAIS DO AÇO INOX DUPLEX SUBMETIDO A PROCESSOS DE SOLDAGEM
Authors: Gheno Simoni Maria , Gonçalves Felipe Do Nascimento , Oliveira Jeferson De , Bovério Maria Aparecida
Published: March 2021

A ampla utilização do aço inoxidável duplex se deve especialmente a combinação de excelentes propriedades mecânicas e alta resistência à corrosão. Nesse trabalho estudou-se as propriedades mecânicas e as fases microestruturais do aço inoxidável duplex após os processos de soldagem: eletrodo revestido (SMAW), Metal Inert Gás (MIG) e Tungstênio Inert Gás (TIG). Em seguida ao processo de soldagem, o material era submetido ao tratamento térmico a uma temperatura de 475 ⁰C. As microestruturas foram analisadas com ataque Behara, para verificação de precipitação nas temperaturas próximas de 475 ⁰C e posteriormente realizado o ensaio de microdureza Vickers. Observou-se um pequeno aumento de dureza nos corpos de prova especificamente na região de soldagem, porém observou-se também a presença da precipitação da fase α’. Em relação aos processos de soldagem adotados, eles mostraram que ao longo do processo, a estrutura do material apresentou o defeito de falta de fusão que foi mais bem caracterizado após análise de microscopia óptica feita com o objetivo de quantificar e verificar os defeitos apresentados nas amostras. Todas as amostras analisadas apresentaram o defeito de falta de fusão, apesar da falta de penetração obtida em todas as amostras. Em todas elas fica evidente a ausência de trincas, mordeduras e sobreposição, mostrando que todos os processos podem ser eficazes no aço inox duplex.
A LOGÍSTICA REVERSA E OS FATORES SOCIOAMBIENTAIS E ECONÔMICOS
Authors: Nascimento Manuella Cristine , Dos Santos Mariana Angélica , Ferreira Gabriela Souza Assis
Published: March 2021

Este artigo tem como objetivo analisar e identificar os motivos pelos quais as empresas estudadas aplicam a Logística Reversa e como, a partir desse processo, conseguiram buscar benefícios, além de reduzir custos. Com o constante avanço do conhecimento da população em geral e um mundo cada vez mais globalizado, a Logística Reversa chega para agregar valor a esse cenário, trazendo, em sua amplitude, a preocupação com o retorno dos produtos de pós-venda ou pós-consumo. Após análise das empresas O Boticário, Natura, Soya e Liza, por meio de informações disponibilizadas nos sites das empresas, foi possível observar que o primeiro motivo para aplicar esse processo é a preocupação com a legislação ambiental, pois as empresas geram constantemente resíduos que precisam ter uma destinação correta. Nota-se que, após cumprimento das leis ambientais, surgem ideias e inovações, fazendo com que as embalagens descartadas sejam recolhidas e encaminhadas para o processo de reciclagem, gerando renda, empregos para a população e parcerias com pequenas empresas. Há também a utilização do óleo usado para a produção de biodiesel, que pode ser vendido para diversas finalidades, gerando receita para as empresas, além de reduzir a poluição de milhares de litros de água e evitar a emissão de Co². Dessa maneira, o desejável é que os consumidores analisem e adquiram produtos de empresas responsáveis ambientalmente.
PRÁTICAS DE RECOMPENSAS NAS ORGANIZAÇÕES
Authors: Neri José Mário Cardoso , Tamashiro Helenita Rodrigues da Silva , Ferreira Valéria Aparecida Martins , Jabur Mara Regina Mellini
Published: March 2021

O objetivo central desta pesquisa foi analisar as percepções dos funcionários sobre as práticas de recompensas praticadas pelas organizações. Para tanto, realizou-se uma pesquisa quantitativa, composta por uma amostra de 237 respondentes. No tratamento dos dados, adotou-se a análise de frequência para traçar o perfil geral dos respondentes. Nos tratamentos dos demais dados, relacionados ao objeto estudado, utilizou-se a Modelagem de Equações Estruturais PLS para a purificação dos dados, por meio do software Statistic Package for Social Sciences (SPSS), versão 21.0 e, também, o software SmarthPLS 2.0, amplamente utilizados em estudos acadêmicos que trabalham com a Modelagem de Equação Estrutural – (MEE). Os resultados indicam haver forte correlação entre as variáveis independentes e dependentes, dimensões analisadas na pesquisa, com exceção da variável dependente, motivação.
ESTUDO PARA REDUÇÃO DE CUSTOS E OTIMIZAÇÃO DO PROCESSO DE PINTURA DE COMPONENTES INDUSTRIAIS DA EMPRESA “CEI”.
Authors: Bosquetti Péricles , Silva Narieli Soares , Badaró Elaine Almeida , Muniz Antônio Carlos , Bosquetti Diógenes
Published: March 2021

Considerando-se a atual crise do Brasil e o mercado altamente competitivo, torna-se fundamental reduzir os custos de um processo produtivo. Neste trabalho o objetivo foi de apresentar uma solução para redução de altos custos na realização de jateamento e pintura industrial focando as necessidades de uma empresa, denominada "CEI". Para isso, buscou-se analisar vários pontos relacionado aos custos de um processo de pintura, desde o levantamento de orçamento dos equipamentos necessários até a realização da pintura nas peças, a fim de localizar o que ocasiona os elevando os custos. Como resultados, fez-se uma proposta da aquisição de uma cabine de jateamento e pintura dentro da própria empresa. Para esta proposta, foram necessários levantar os custos para implantação da mesma, apresentar simulações de como a implantação da cabine poderia trazer lucros e em quanto tempo seria possível a recuperação dos investimentos, explanando as economias geradas.
Quantifying Breast Cancer-Driven Fiber Alignment and Collagen Deposition in Primary Human Breast Tissue
Authors: Gurrala Rakesh , Byrne C. Ethan , Brown Loren M. , Tiongco Rafael Felix P. , Matossian Margarite D. , Savoie Jonathan J. , Collins-Burow Bridgette M. , Burow Matthew E. , Martin Elizabeth C. , Lau Frank H.
Published: March 2021

Solid tumor progression is significantly influenced by interactions between cancer cells and the surrounding extracellular matrix (ECM). Specifically, the cancer cell-driven changes to ECM fiber alignment and collagen deposition impact tumor growth and metastasis. Current methods of quantifying these processes are incomplete, require simple or artificial matrixes, rely on uncommon imaging techniques, preclude the use of biological and technical replicates, require destruction of the tissue, or are prone to segmentation errors. We present a set of methodological solutions to these shortcomings that were developed to quantify these processes in cultured, ex vivo human breast tissue under the influence of breast cancer cells and allow for the study of ECM in primary breast tumors. Herein, we describe a method of quantifying fiber alignment that can analyze complex native ECM from scanning electron micrographs that does not preclude the use of replicates and a high-throughput mechanism of quantifying collagen content that is non-destructive. The use of these methods accurately recapitulated cancer cell-driven changes in fiber alignment and collagen deposition observed by visual inspection. Additionally, these methods successfully identified increased fiber alignment in primary human breast tumors when compared to human breast tissue and increased collagen deposition in lobular breast cancer when compared to ductal breast cancer. The successful quantification of fiber alignment and collagen deposition using these methods encourages their use for future studies of ECM dysregulation in human solid tumors.
Assessing the Potential Association Between Microbes and Corrosion of Intra-Oral Metallic Alloy-Based Dental Appliances Through a Systematic Review of the Literature
Authors: Gopalakrishnan Umarevathi , Felicita A. Sumathi , Mahendra Lodd , Kanji Masroor Ahmed , Varadarajan Saranya , Raj A. Thirumal , Feroz Shaikh Mohammed Abdul , Mehta Deepak , Baeshen Hosam Ali , Patil Shankargouda
Published: March 2021

Objective: Systematic review assessing the association between oral microorganisms and corrosion of intra-oral metallic alloy-based dental appliances.

Design: PubMed, Scopus, and Web of Science were searched using keyword combinations such as microbes and oral and corrosion; microbes and dental and corrosion; microorganisms and oral and corrosion; microorganisms and dental and corrosion.

Results: Out of 141 articles, only 25 satisfied the selection criteria. Lactobacillus reuteri, Streptococcus mutans, Streptococcus sanguis, Streptococcus mitis, Streptococcus sobrinus, Streptococcus salivarius, sulfate-reducing bacteria, sulfate oxidizing bacteria, Veilonella, Actinomyces, Candida albicans were found to have a potential association with corrosion of intraoral metallic alloys such as stainless steel, titanium, nickel, cobalt-chromium, neodymium-iron-boron magnets, zirconia, amalgam, copper aluminum, and precious metal alloys.

Conclusion: The included studies inferred an association between oral microorganisms and intra-oral metallic alloys-based dental appliances, although, it is vital to acknowledge that most studies in the review employed an in-vitro simulation of the intra-oral condition.
Optimal Seismic Design of Stiffness and Gap of Hysteretic-Viscous Hybrid Damper System in Nonlinear Building Frames for Simultaneous Reduction of Interstory Drift and Acceleration
Authors: Ishida Soichiro , Takewaki Izuru
Published: March 2021

The viscous-hysteretic hybrid (HVH) damper system recently introduced by one of the authors has a clear property that, when the hysteretic dampers with gap mechanism become active (stiffness element starts working), the acceleration of building frames with this damper system as a stopper attains large values in spite of the advantageous feature to prevent excessive deformation. It is therefore desired that both the maximum interstory drift and the maximum acceleration exhibit an acceptable value with appropriate compromise. The double impulse as a simplified version of one-cycle sine wave as a representative of the main part of near-fault ground motions can simulate the maximum interstory drifts properly. However, it cannot simulate the maximum accelerations due to its impulsive nature. In this case, the sine wave corresponding to the double impulse can play an important role in the reliable simulation of the maximum accelerations. Even in such circumstance, the analysis using the double impulse is important because it enables to obtain the critical timing of the input, i.e. the nonlinear resonant frequency of the sine wave without repetition. The investigations on the criticality of the sine wave corresponding to the critical double impulse show that the critical timing of the double impulse leads to the nonlinear resonant frequency of the sine wave in view of the maximum interstory drift, the maximum top acceleration and the maximum relative acceleration for the constant input acceleration and the constant input velocity except for some cases. It is demonstrated finally that the index in terms of the maximum interstory drift and the maximum acceleration can be introduced as an appropriate parameter for deriving the optimally compromised gap quantity of hysteretic dampers with gap mechanism for various input velocity levels and various hysteretic damper stiffness ratios.
How the Discovery of the CD4/CD8-p56lck Complexes Changed Immunology and Immunotherapy
Authors: Rudd Christopher E.
Published: March 2021

The past 25 years have seen enormous progress in uncovering the receptors and signaling mechanisms on T-cells that activate their various effecter functions. Until the late 1980s, most studies on T-cells had focused on the influx of calcium and the levels of cAMP/GMP in T-cells. My laboratory then uncovered the interaction of CD4 and CD8 co-receptors with the protein-tyrosine kinase p56lckwhich are now widely accepted as the initiators of the tyrosine phosphorylation cascade leading to T-cell activation. The finding explained how immune recognition receptors expressed by many immune cells, which lack intrinsic catalytic activity, can transduce activation signals via non-covalent association with non-receptor tyrosine kinases. The discovery also established the concept that a protein tyrosine phosphorylation cascade operated in T-cells. In this vein, we and others then showed that the CD4- and CD8-p56lckcomplexes phosphorylate the TCR complexes which led to the identification of other protein-tyrosine kinases such as ZAP-70 and an array of substrates that are now central to studies in T-cell immunity. Other receptors such as B-cell receptor, Fc receptors and others were also subsequently found to usesrckinases to control cell growth. In T-cells, p56lckdriven phosphorylation targets include co-receptors such as CD28 and CTLA-4 and immune cell-specific adaptor proteins such as LAT and SLP-76 which act to integrate signals proximal to surface receptors. CD4/CD8-p56lckregulated events in T-cells include intracellular calcium mobilization, integrin activation and the induction of transcription factors for gene expression. Lastly, the identification of the targets of p56lckin the TCR and CD28 provided the framework for the development of chimeric antigen receptor (CAR) therapy in the treatment of cancer. In this review, I outline a history of the development of events that led to the development of the “TCR signaling paradigm” and its implications to immunology and immunotherapy.
Inflammatory Markers Predict Survival in Patients With Advanced Gastric and Colorectal Cancers Receiving Anti–PD-1 Therapy
Authors: Fan Xiaona , Wang Dan , Zhang Wenjing , Liu Jinshuang , Liu Chao , Li Qingwei , Ma Zhigang , Li Hengzhen , Guan Xin , Bai Yibing , Yang Jiani , Lou Changjie , Li Xiaobo , Wang Guangyu , Li Zhiwei
Published: March 2021

There is a lack of useful biomarkers for predicting the efficacy of anti–programmed death-1 (PD-1) therapy for advanced gastric and colorectal cancer. To address this issue, in this study we investigated the correlation between inflammatory marker expression and survival in patients with advanced gastric and colorectal cancer. Data for 111 patients with advanced gastric and colorectal cancer treated with anti–PD-1 regimens were retrospectively analyzed. Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and clinical characteristics of each patient were selected as the main variables. Overall response rate, disease control rate, and progression-free survival were primary endpoints, and overall survival and immune-related adverse events (irAEs) were secondary endpoints. The chi-squared test and Fisher’s exact test were used to evaluate relationships between categorical variables. Uni- and multivariate Cox regression analyses were performed, and median progression-free survival and overall survival were estimated with the Kaplan–Meier method. The overall response rate and disease control rate of anti–PD-1therapy in advanced gastric and colorectal tumors were 12.61 and 66.66%, respectively. The patients with MLR < 0.31, NLR < 5, and PLR < 135 had a significantly higher disease control rate than those with MLR > 0.31, NLR > 5, and PLR > 135 (P < 0.05). The multivariate analysis revealed that MLR < 0.31, BMI > 18.5, and anti–PD-1 therapy in first-line were associated with prolonged PFS. MLR < 0.31 and BMI > 18.5 were associated with prolonged overall survival. The irAE rate differed significantly between PLR groups, and PLR < 135 was associated with an increased rate of irAEs (P = 0.028). These results indicate that the inflammatory markers NLR, MLR, and PLR have clinical utility for predicting survival or risk of irAEs in patients with advanced gastric cancer and colorectal cancer.
Exploring the Causality Between Hypothyroidism and Non-alcoholic Fatty Liver: A Mendelian Randomization Study
Authors: Qiu Shizheng , Cao Peigang , Guo Yu , Lu Haoyu , Hu Yang
Published: March 2021

The etiology of non-alcoholic fatty liver disease (NAFLD) involves complex interaction of genetic and environmental factors. A large number of observational studies have shown that hypothyroidism contributes to a high risk of NAFLD. However, the exact causality is still unknown. Due to the progress of genome-wide association study (GWAS) and the discovery of Mendelian randomization (MR), it is possible to explore the causality between the two diseases. In this study, in order to research into the influence of intermediate phenotypes on outcome, nine independent genetic variants of hypothyroidism obtained from the GWAS were used as instrumental variables (IVs) to perform MR analysis on NAFLD. Since there was no heterogeneity between IVs (P= 0.70), a fixed-effects model was used. The correlation between hypothyroidism and NAFLD was evaluated by using inverse-variance weighted (IVW) method and weighted median method. Then the sensitivity test was analyzed. The results showed that there was a high OR (1.7578; 95%CI 1.1897–2.5970;P= 0.0046) and a low intercept (−0.095;P= 0.431). None of the genetic variants drove the overall result (P< 0.01). Simply, we proved for the first time that the risk of NAFLD increases significantly on patients with hypothyroidism. Furthermore, we explained possible causes of NAFLD caused by hypothyroidism.
Long Non-coding RNA SENP3-EIF4A1 Functions as a Sponge of miR-195-5p to Drive Triple-Negative Breast Cancer Progress by Overexpressing CCNE1
Authors: Chen Lie , Miao Xiaofei , Si Chenchen , Qin An , Zhang Ye , Chu Chunqiang , Li Zengyao , Wang Tong , Liu Xiao
Published: March 2021

Triple-negative breast cancer (TNBC) has high malignancy and limited treatment, so novel molecular therapeutic targets are urgently needed. Cyclin E1 (CCNE1) promotes progression in breast cancer, but its role and inherent mechanisms in TNBC are yet to be elucidated. Competing endogenous RNA (ceRNA) may be a potential mechanism. CCNE1 was selected though bioinformatics and clinical samples, and cell lines were utilized to verify CCNE1 expression by qRT-PCR and western blot. Predicting tools provided potential miR-195-5p and SENP3-EIF4A1 and tested from multilevel. Functional experiments were conducted in vitro and in vivo. Luciferase reporter assay and RNA immunoprecipitation experiments were implemented to ensure the interaction between miR-195-5p and SENP3-EIF4A1/CCNE1 in TNBC. Bioinformatics found DNA hypermethylation of miR-195-5p and preliminarily verified. Mechanistically, SENP3-EIF4A1-miR-195-5p-associated ceRNA could drive TNBC progress though regulating CCNE1. DNA hypermethylation of miR-195-5p might be another reason. In summary, SENP3-EIF4A1-miR-195-5p-CCNE1 axis promotes TNBC progress and may contribute to the novel diagnosis and treatment of TNBC.
A Community-Based Model to the COVID-19 Humanitarian Crisis
Authors: Nacoti Mirco , Ciocca Andrea , Brambillasca Pietro , Fazzi Francesco , Pisano Michele , Giupponi Massimo , Pesenti Antonio , Valoti Oliviero , Cereda Maurizio
Published: March 2021

A multidisciplinary group, mainly from Bergamo region - the epicenter of the COVID-19 pandemic crisis in Italy on march 2020– has developed concept of creating intermediate care facilities and proposes a three-tier model of community-based care, with the goal of reducing hospital admissions, contagion and mortality related to hospital overloading and optimizing human resources.
The Relationship Between Circulating Growth Differentiation Factor 15 Levels and Diabetic Retinopathy in Patients With Type 2 Diabetes
Authors: Niu Yixin , Zhang Weiwei , Shi Jie , Liu Yueming , Zhang Hongmei , Lin Ning , Li Xiaoyong , Qin Li , Yang Zhen , Su Qing
Published: March 2021

Objective

Growth differentiation factor 15 (GDF-15) is a member of the TGF-β superfamily that has anti-inflammatory properties. The objective of this study was to evaluate the relationship between circulating GDF-15 levels and diabetic retinopathy (DR) in patients with type 2 diabetes.

Materials/Methods

A case–control study was performed in which 402 patients with type 2 diabetes were enrolled. Of these, 171 patients had DR and the remaining 231 patients without DR acted as controls. The plasma GDF-15 levels were measured using ELISA, while DR was diagnosed using the canon ophthalmic digital imaging system and the Canon EOS 10D digital camera (Canon, Tokyo, Japan) through a non-pharmacologically dilated pupil.

Results

The levels of GDF-15 were significantly higher in patients with DR [168.9 (112.9–228.3) pg/ml vs. 127.8 (96.1–202.8) pg/ml, P < 0.001] compared to controls. Results of the Spearman correlation analysis showed that the GDF-15 levels were positively associated with the duration of diabetes morbidity, fasting plasma glucose, systolic blood pressure, albumin/creatinine ratio, creatinine, and liver enzymes, but negatively associated with eGFR (both P < 0.001). The participants in the highest GDF-15 quartile had a significantly increased risk for DR (OR = 2.15, 95% CI 1.53–3.02) after adjusting for potential cofounders.

Conclusions

The circulating GDF-15 levels are positively associated with DR independent of potential cofounders.
Documentation of Microplastics in Tissues of Wild Coastal Animals
Authors: Haave Marte , Gomiero Alessio , Schönheit Jürgen , Nilsen Hanne , Olsen Anne Berit
Published: March 2021

Microplastic pollution is omnipresent in biota around the globe, and concerns are rising that humans are exposed to microplastics (MP) through food. Investigations of MP in wild animals relevant for human consumption and the effects in exposed birds and mammals is warranted. We investigated the concentrations of MP in organs and tissues of fish, seabirds, terrestrial and marine mammals from a plastic polluted area near Bergen, Norway. A standardized autopsy included evaluation of condition, bacteriological and histopathological analyzes. Tissues were analyzed for MP (>10 µm) by pyrolysis Gas Chromatography Mass Spectrometry (py-GCMS) and inspected by polarized light microscopy. We analyzed samples of stomach and intestinal wall, liver and muscle/fillet from three flounders, three cod, three seabirds, three otters and one seal, kidneys from seabirds, otters and the seal, and gills from the fishes. No large plastic items were observed in the gastrointestinal tracts. Eight of 13 animals had MP in one or several tissues. MP was found in intestine (5), stomach (4), liver (3), muscle (3). No MP was found in the seal, and only in the stomach wall of one otter. In seabirds, MP was found in the intestine, stomach and liver, but not muscle. The highest concentration was 3.4 µg/g wet weight in cod liver. Three of the nine investigated polymers were found above the Limit of Quantification (LOQ): Polyvinylchloride>polystyrene>>polyethylene terephthalate. MP was quantified in one of four replicates of cod muscle and one of two replicates of cod liver. No MP was observed by microscopy. The results show levels under or close to the current LOQ. Replicates indicate uneven MP distribution in tissues and resulted in higher prevalence of MP for cod. No adverse effects could be related to MP. The sample size was small, and conclusions cannot be drawn regarding effects or risks. The animals were by-catch, and mostly in good condition when caught. Procedural blanks and air-controls showed very low MP, and support that the MP come from environmental sources. Further studies are needed to determine levels of microplastic in edible tissues and the current wildlife exposure through the food web.
Brain Magnetic Resonance Imaging Phenome-Wide Association Study With Metal Transporter Gene SLC39A8
Authors: Hermann Evan R. , Chambers Emily , Davis Danielle N. , Montgomery McKale R. , Lin Dingbo , Chowanadisai Winyoo
Published: March 2021

The SLC39A8 gene encodes a divalent metal transporter, ZIP8. SLC39A8 is associated with pleiotropic effects across multiple tissues, including the brain. We determine the different brain magnetic resonance imaging (MRI) phenotypes associated with SLC39A8. We used a phenome-wide association study approach followed by joint and conditional association analysis. Using the summary statistics datasets from a brain MRI genome-wide association study on adult United Kingdom (UK) Biobank participants, we systematically selected all brain MRI phenotypes associated with single-nucleotide polymorphisms (SNPs) within 500 kb of the SLC39A8 genetic locus. For all significant brain MRI phenotypes, we used GCTA-COJO to determine the number of independent association signals and identify index SNPs for each brain MRI phenotype. Linkage equilibrium for brain phenotypes with multiple independent signals was confirmed by LDpair. We identified 24 brain MRI phenotypes that vary due to MRI type and brain region and contain a SNP associated with the SLC39A8 locus. Missense ZIP8 polymorphism rs13107325 was associated with 22 brain MRI phenotypes. Rare ZIP8 variants present in a published UK Biobank dataset are associated with 6 brain MRI phenotypes also linked to rs13107325. Among the 24 datasets, an additional 4 association signals were identified by GCTA-COJO and confirmed to be in linkage equilibrium with rs13107325 using LDpair. These additional association signals represent new probable causative SNPs in addition to rs13107325. This study provides leads into how genetic variation in SLC39A8, a trace mineral transport gene, is linked to brain structure differences and may affect brain development and nervous system function.
A Novel Method to Identify the Differences Between Two Single Cell Groups at Single Gene, Gene Pair, and Gene Module Levels
Authors: Cui Lingyu , Wang Bo , Ren Changjing , Wang Ailan , An Hong , Liang Wei
Published: March 2021

Single-cell sequencing technology can not only view the heterogeneity of cells from a molecular perspective, but also discover new cell types. Although there are many effective methods on dropout imputation, cell clustering, and lineage reconstruction based on single cell RNA sequencing (RNA-seq) data, there is no systemic pipeline on how to compare two single cell clusters at the molecular level. In the study, we present a novel pipeline on comparing two single cell clusters, including calling differential gene expression, coexpression network modules, and so on. The pipeline could reveal mechanisms behind the biological difference between cell clusters and cell types, and identify cell type specific molecular mechanisms. We applied the pipeline to two famous single-cell databases, Usoskin from mouse brain and Xin from human pancreas, which contained 622 and 1,600 cells, respectively, both of which were composed of four types of cells. As a result, we identified many significant differential genes, differential gene coexpression and network modules among the cell clusters, which confirmed that different cell clusters might perform different functions.
Monocyte TREM-1 Levels Associate With Anti-TNF Responsiveness in IBD Through Autophagy and Fcγ-Receptor Signaling Pathways
Authors: Prins Marileen M. , Verstockt Bram , Ferrante Marc , Vermeire Séverine , Wildenberg Manon E. , Koelink Pim J.
Published: March 2021

The expression of Triggering Receptor Expressed on Myeloid cells (TREM)-1 has been described as a predictive marker for anti-Tumor Necrosis Factor (TNF)-α monoclonal antibody (mAb) therapy responsiveness in patients with inflammatory bowel disease (IBD). Here we investigated expression of TREM-1 specifically in CD14+ monocytes in relation to anti-TNF response. The pretreatment TREM-1 expression levels of CD14+ monocytes of Crohn’s disease (CD) patients were predictive of outcome to anti-TNF mAb therapy, with low TREM-1 expression associated with response to anti-TNF. FACSorting of CD14+ monocytes with different TREM-1 levels showed that differentiation towards regulatory CD206+ M2 type macrophages by anti-TNF was suppressed in CD14+ monocytes with high TREM-1 expression. Activity of the Fcγ-Receptor and autophagy pathway, both necessary for M2 type differentiation and the response to anti-TNF, were decreased in CD14+ monocytes with high expression of TREM-1. We confirmed that the activity of the Fcγ-Receptor pathway was decreased in the CD patients that did not respond to anti-TNF therapy and that it was negatively correlated with TREM-1 expression levels in the CD patient cohort. In conclusion, our results indicate that TREM-1 expression levels in CD14+ monocytes associate with decreased autophagy and FcγR activity resulting in decreased differentiation to M2 type regulatory macrophages upon anti-TNF mAb treatment, which may explain anti-TNF non-response in IBD patients with high expression levels of TREM-1.
Integrin-α9β1 as a Novel Therapeutic Target for Refractory Diseases: Recent Progress and Insights
Authors: Xu Shihan , Zhang Tingwei , Cao Zhengguo , Zhong Wenjie , Zhang Chuangwei , Li Han , Song Jinlin
Published: March 2021

Integrins refer to heterodimers consisting of subunits α and β. They serve as receptors on cell membranes and interact with extracellular ligands to mediate intracellular molecular signals. One of the least-studied members of the integrin family is integrin-α9β1, which is widely distributed in various human tissues and organs. Integrin-α9β1 regulates the physiological state of cells through a variety of complex signaling pathways to participate in the specific pathological processes of some intractable diseases. In recent years, an increasing amount of research has focused on the role of α9β1 in the molecular mechanisms of different refractory diseases and its promising potential as a therapeutic target. Accordingly, this review introduces and summarizes recent research related to integrin-α9β1, describes the synergistic functions of α9β1 and its corresponding ligands in cancer, autoimmune diseases, nerve injury and thrombosis and, more importantly, highlights the potential of α9β1 as a distinctive target for the treatment of these intractable diseases.
Coastlines, Coastal Cities, and Climate Change: A Perspective on Urgent Research Needs in the United States
Authors: Sandifer Paul A. , Scott Geoffrey I.
Published: March 2021

This paper builds upon Friedman et al. (2020) and other reviews and statements but provides an explicit focus on research needed to improve the resilience and survivability of coastal communities as they face existential threats from climate change. It does not attempt a prescriptive analysis of potential research emphases, but instead recommends some key research areas that we believe will help provide a solid foundation for community adaptation. Our perspective is based on our experiences over a combined nearly 95 years of work in research, management, and policy, much of it related to coastal environments and their communities, rather than expert deliberation within a large group or a systematic review. We present a list of 25 research priorities binned into 12 categories and targeted to leaders of coastal communities, interested researchers, funders, students, and the public. These priorities are intended to help start more discussion of research needs with and within communities, and help focus attention of researchers on actions that have potential to identify critical decision points and make positive differences for communities. We conclude that priority research should be undertaken with urgency and a much greater level of trans- and interdisciplinarity and community-participatory approaches than yet seen.
Taxonomy and Ecology of Sympatric Ampelisca Species (Crustacea, Amphipoda) From the Strait of Gibraltar to the Strait of Dover, North-Eastern Atlantic
Authors: Dauvin Jean-Claude , Sampaio Leandro , Rodrigues Ana Maria , Quintino Victor
Published: March 2021

The Ampeliscidae Kröyer, 1842 is amongst the most diverse amphipod families; it comprises four genera, Ampelisca being the richest with more than 200 species. The Ampelisca genus presents high morphological homogeneity and the identification of the species by ecologists remains difficult. Ampelisca are also characterized by a high degree of sympatry, a rare situation in amphipods, and in this study we report up to nine species coexisting at the same site. Recent benthic sampling and publications, namely on the Portuguese continental shelf and the English Channel, permit to revisit the available data on the taxonomy and propose an updated species identification key, as well as the distribution and ecology of the 40-recorded Ampelisca species along the North Eastern Atlantic coast, from the Strait of Gibraltar, in the South, to the Strait of Dover, in the North. The data allow discussing on the sympatry and syntopy of such diverse amphipod family with the co-occurrence of several species at various scales of observations, from the wider regional area, to the narrower local habitat. Two Ampelisca species were recorded exclusively on hard bottom, while the other tend to inhabit specific types of soft bottom, ranging from deep mud to shallow coarse sand and gravel, with a preference for continental shelf muddy and sandy habitats. A future sea water temperature increase scenario could modify the species geographical distribution and reproductive cycle, in this temperate North-eastern Atlantic province.
Laboratory Performance Evaluation on the Recovering of Aged Bitumen With Vegetable Oil Rejuvenator
Authors: Suo Zhi , Chen Huan , Yan Qiang , Tan Yitian , Li Xinghai , Zhang Ao
Published: March 2021

Generally, the conventional rejuvenator contains many mineral oils to supply the missing components of aged bitumen. The mineral oils could recover the performance of aged bitumen go through a long-term aging process. However, the mineral oils are easy to volatilize at higher recycling temperature. The higher volatilization will reduce the effect of rejuvenator and limit proportion of reclaimed asphalt pavement (RAP) in recycled asphalt mixture (RAP contents less than 30%). The main components of vegetable oil are straight chain higher fatty acids and glycerides. The esters of straight chain higher fatty acids and glycerol are not volatile at high temperature. Therefore, they can be used to recover the micro chemical composition of bitumen and a change in colloidal stability of asphaltene. In this research, two newly kinds of bitumen rejuvenator were developed by replacing mineral oil with waste cooking corn and soybean oil. The two kinds of vegetable and a mineral bitumen rejuvenators were utilized to recover aged bitumen with 2–10% by weigh. The objectives of the research are evaluating the rheological properties, high temperature and fatigue performance of the recovered bitumen. The Dynamic Shear Rheometer Test and Rotational Viscosity Test were conducted according to the AASHTO and ASTM standards. Additionally, the crack resistance of bitumen was evaluated by using the bending beam rheometer (BBR) test at −12 and −18°C. The result of laboratory test and statistical analysis of ANOVA showed that the vegetable oil rejuvenators effectively reduce the viscosity and stiffness of aged bitumen. It will improve both the fatigue resistance and low temperature crack resistance. In addition, when the content of vegetable oil is higher, the rejuvenating agent can make the recovered bitumen have lower viscosity and stiffness. Considering that the rutting resistance under high temperature, it is suggested that 6 and 8% vegetable oil be used to recover the aged bitumen.
Early Viral Clearance and Antibody Kinetics of COVID-19 Among Asymptomatic Carriers
Authors: Xiao Tongyang , Wang Yanrong , Yuan Jing , Ye Haocheng , Wei Lanlan , Liao Xuejiao , Wang Haiyan , Qian Shen , Wang Zhaoqin , Liu Lei , Zhang Zheng
Published: March 2021

Asymptomatic carriers contribute to the spread of Coronavirus Disease 2019 (COVID-19), but their clinical characteristics, viral kinetics, and antibody responses remain unclear. A total of 56 COVID-19 patients without symptoms at admission and 19 age-matched symptomatic patients were enrolled. RNA of SARS-CoV-2 was tested using transcriptase quantitative PCR, and the total antibodies (Ab), IgG, IgA, and IgM against the SARS-CoV-2 were tested using Chemiluminescence Microparticle Immuno Assay. Among 56 patients without symptoms at admission, 33 cases displayed symptoms and 23 remained asymptomatic throughout the follow-up period. 43.8% of the asymptomatic carriers were children and none of the asymptomatic cases had recognizable changes in C-reactive protein or interleukin-6, except one 64-year-old patient. The initial threshold cycle value of nasopharyngeal SARS-CoV-2 in asymptomatic carriers was similar to that in pre-symptomatic and symptomatic patients, but the positive viral nucleic acid detection period of asymptomatic carriers (9.63 days) was shorter than pre-symptomatic patients (13.6 days). There were no obvious differences in the seropositive conversion rate of total Ab, IgG, and IgA among the three groups, though the rates of IgM varied largely. The average peak IgG and IgM COI of asymptomatic cases was 3.5 and 0.8, respectively, which is also lower than those in symptomatic patients with peaked IgG and IgM COI of 4.5 and 2.4 (p < 0.05). Young COVID-19 patients seem to be asymptomatic cases with early clearance of SARS-CoV-2 and low levels of IgM generation but high total Ab, IgG, and IgA. Our findings provide empirical information for viral clearance and antibody kinetics of asymptomatic COVID-19 patients.
Assessment of Malaria Microscopy Competency at Primary Health Institutions in the Chongqing Municipality
Authors: Fei Luo , Shuang Zhou , Yi Yuan , Shan-Shan Li , Yan Tan , Jing-Ru Xu , Yang Zhou
Published: March 2021

Background: In April 2019, Chongqing passed the national malaria elimination assessment. However, around 30 imported malaria cases are still being reported every year, and Anopheles sinensis was widely distributed in Chongqing, meaning the risk of malaria resurgence still exists. Early diagnosis and treatment for malaria cases are effective measures to prevent malaria resurgence. The primary health institutions are the first station where potential malaria cases may seek treatment. The competency with which primary health institutions diagnose malaria will directly affect the timeliness of malaria diagnosis. Nowadays, most primary health institutions in Chongqing use microscopy to confirm malaria cases. This study assessed the microscopy competence of primary health institutions, studied and analyzed the results, and provided a scientific basis for malaria prevention and control after malaria elimination in Chongqing.

Methods: According to the stratified sampling principle, four plasmodium microscopy technicians (156 in total) were selected from each of the 39 districts/counties of Chongqing to test the plasmodium microscopy competence. Descriptive statistical analysis, correlation analysis, spatial self-correlation analysis, and ROC curve analysis were carried out on the test results.

Result: The average of the technicians' test scores was 4.33 ± 0.47 (min: 3, mid: 4.5, max: 5); The spatial clustering of the scores was significant (MoranI = 0.338, Z = 3.618, P < 0.01). The test scores were positively correlated with the “level of work institutions” (R = 0.21, P < 0.01) but were negatively correlated with “age” (R = −0.31, P < 0.01). The highest Sensitivity of the technicians' microscopy was in qualitative diagnosis (98.92%, CI: 98.00–99.69%). The Delong's test showed that the diagnostic efficiency of the technicians' microscopy to P. falciparum was the best (P < 0.01), however to P. ovale was the worst (P < 0.01).

Conclusion: The microscopy technicians in primary health institutions in Chongqing have good microscopy competency in qualitative diagnosis, but there were deficiencies in the identification of plasmodium species. Township level health institutions in Central China have weaker microscopy than those in other areas.
Positive Impact of Targeted Educational Intervention in Children With Low Adherence to Growth Hormone Treatment Identified by Use of the Easypod™ Electronic Auto-injector Device
Authors: Assefi Aria Reza , Roca Fernanda , Rubstein Adrián , Chareca Cinthia
Published: March 2021

Background: It is important to identify patients with low adherence to recombinant human growth hormone (r-hGH) therapy and initiate actions to improve adherence. The Merck Patient Support Program (PSP) aims to raise the awareness of these patients and their parents of the importance of good adherence in achieving optimal growth outcomes. The easypod™ digitally-enhanced injection device provides accurate, reliable adherence data for the PSP by recording the exact dose, time and date of injections given. In this study, we aimed to measure the effect of an educational intervention on adherence in patients using the easypod™ device to deliver their r-GH therapy.

Methods: This was a 12-month observational, retrospective cohort study. Patients previously identified by data recorded from their easypod™ injection device as having low adherence (<80%) were followed over the 6 months before and after a targeted educational visit by a PSP nurse. Patient adherence and demographic data were extracted from the PSP database. Statistical analyzes were carried out with STATA 15.0 software.

Results: Data from 80 patients (65% male) with low adherence were analyzed. Patients were aged 2–18 (mean: 11.77) years with diagnoses of growth hormone deficiency (71.25%), small for gestational age (20%), Turner syndrome (7.50%) and chronic renal disease (1.25%). Duration of treatment was 0.40–11.13 (median: 3.62) years. At baseline, median adherence to r-hGH therapy was 67%; after the intervention it increased to 76%, a statistically significant median improvement of 9% (p = 0.0000, Wilcoxon signed-rank test). Additionally, 36% (29/80) of patients increased their adherence to r-hGH therapy to ‘good’ (≥80%). Both changes were clinically relevant.

Conclusions: We conclude that a nurse-led educational intervention, supported by digital medication adherence monitoring, is a simple method to improve adherence to r-hGH therapy, and recommend this intervention to reduce the gap between the indication/recommendation of the specialist and patients' behavior.
Emergence of IMP-8-Producing Comamonas thiooxydans Causing Urinary Tract Infection in China
Authors: Guo Xiaobing , Wang Qian , Xu Hao , He Xiaohong , Guo Lihua , Liu Shuxiu , Wen Peipei , Gou Jianjun
Published: March 2021

The emergence of carbapenem resistance (CR) caused by hydrolytic enzymes called carbapenemases has become a major concern worldwide. So far, CR genes have been widely detected in various bacteria. However, there is no report of CR gene harboring Comamonas thiooxydans. We first isolated a strain of an IMP-8-producing C. thiooxydans from a patient with urinary tract infection in China. Species identity was determined using MALDI-TOF MS analysis and carbapenemase-encoding genes were detected using PCR. The complete genomic sequence of C. thiooxydans was identified using Illumina Novaseq and Oxford Nanopore PromethION. Antimicrobial susceptibility analysis indicated that the C. thiooxydans strain ZDHYF418 was susceptible to imipenem, intermediate to meropenem, and was resistant to aztreonam, fluoroquinolones, and aminoglycosides. The blaIMP–8 gene was chromosomally located, and was part of a Tn402-like class 1 integron characterized by the following structure: DDE-type integrase/transposase/recombinase-tniB-tniQ-recombinase family protein-aac(6′)-Ib-cr-blaIMP–8-intI1. Phylogenetic analysis demonstrated that the closest relative of ZDHYF418 is C. thiooxydans QYY (accession number: CP053920.1). We detected 330 SNP differences between ZDHYF418 and C. thiooxydans QYY. Strain QYY was isolated from activated sludge in Jilin province, China in 2015. In summary, we isolated a strain of C. thiooxydans that is able to produce IMP-8 and a novel blaOXA. This is the first time that a CR gene has been identified in C. thiooxydans. The occurrence of the strain needs to be closely monitored.
Treatment Approaches for Atypical CIDP
Authors: Menon Deepak , Katzberg Hans Dieter , Bril Vera
Published: March 2021

The variants of chronic inflammatory demyelinating polyneuropathy (CIDP) differ not just in their clinical, pathological and electrophysiological characteristics, but often in their indifferent response to conventional immunosuppressive agents which are effective in typical CIDP. High quality evidence is lacking as far as the management of these atypical variants is concerned. In this review, we summarize the treatment approaches to each of these CIDP variants based on existing data. Distal acquired demyelinating symmetric polyneuropathy (DADS) has the phenotype of a symmetric, demyelinating sensory, length-dependent polyneuropathy and is frequently associated with paraproteinemia and anti myelin associated glycoprotein (MAG) antibodies. While the management of idiopathic DADS (DADS-I) is the same as CIDP, DADS-M responds suboptimally and has a favorable response to rituximab. Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) manifests as a chronic progressive demyelinating mononeuropathy multiplex which can evolve to a confluent pattern indistinguishable from CIDP. Evidence favors treating MADSAM with conventional immunomodulatory therapy (IMT), but this disorder responds less favorably than CIDP. Some patients present with purely sensory symptoms, known as pure sensory CIDP or chronic inflammatory sensory polyradiculoneuropathy (CISP), the latter localizing to a pre-ganglionic pathology. Both respond well to first line IMT, particularly to intravenous immunoglobulin (IVIG), but patients relapse without maintenance therapy. Pure motor CIDP resembles multifocal motor neuropathy with conduction block (MMNCB), but the previously reported worsening status after steroid treatment was not reproduced in recent studies, and IVIG remains the first-line therapy. Some focal forms of CIDP defy exact classification, but respond well to first-line IMT including IVIG. Overall, atypical CIDP responds to treatment with first-line IMT, but has a suboptimal response compared to CIDP. There is evidence for effectiveness with agents such as rituximab, especially in DADS-M, and this medication can also be used in cases refractory to conventional IMTs. Rituximab is also effective in CIDP with IgG4 antibodies which has distinct clinical features and is mostly refractory to first-line IMT.
Systematic Review of Fatigue in Individuals With Cerebral Palsy
Authors: Puce Luca , Pallecchi Ilaria , Chamari Karim , Marinelli Lucio , Innocenti Tiziano , Pedrini Riccardo , Mori Laura , Trompetto Carlo
Published: March 2021

In this systematic review, we collected and analyzed literature works comparing self-reported fatigue and objectively-measured fatigue in individuals with cerebral palsy (CP) and in age-matched typically developing/typically developed (TD) controls (Healthy). The search was conducted on four electronic databases/platforms (PubMed, Web of Science, Cochrane Library, and Scopus) using the key words “cerebral palsy” combined with “fatig*,” where the asterisk was used as a wildcard. As a critical appraisal tool, the Joanna Briggs Institute Critical Appraisal Checklist for Quasi-Experimental Studies (2017) was used. A total of 22 studies passed the critical appraisal rating and were included in both narrative and quantitative analyses. The overall evidence quality of the findings was considered very good. Data of objectively-measured fatigue in performing maximal fatiguing tasks indicated lower fatigue levels in participants with CP, possibly due to their pathological inability to recruit highly fatigable muscle fibers. Highly trained individuals with CP and TD controls performing maximal fatiguing tasks seem to be an exception to this, as they exhibited similar levels of fatigue. In submaximal fatiguing tasks, including daily physical activities, either objectively-measured or self-reported fatigue was higher in participants with CP than in TD controls, indicating a lower ability for development of neurophysiological compensation for fatigue among participants with CP. Further studies on fatigue are needed to gain an insight into the multifold mechanisms of fatigue in individuals with CP. Understanding fatigue mechanisms could help in setting up strategies for effective intervention programs, with benefits in healthcare and improved quality of life of individuals with CP.

Systematic Review Registration: [PROSPERO 2019], identifier [CRD42019143524].