bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluación e intervención Neuropsicológica en un caso de trastorno del espectro autista (TEA) severo
Authors: García Escárpita Ferrer Cynthia Raquel , Solovieva Yulia , Quintanar Rojas Luis
Published: May 2021

El presente estudio se dedica a la propuesta de evaluación e intervención neuropsicológica en el caso de un niño con características del Trastorno del Espectro Autista (TEA). El niño fue evaluado por presentar retraso en el lenguaje, conductas estereotipadas, además de dificultades cognoscitivas y motoras. El diagnóstico de la evaluación neuropsicológica permitió precisar los aspectos fuertes y débiles del desarrollo psicológico del niño. La propuesta de programa de intervención fue elaborada de acuerdo con la postura teórico metodológica histórico cultural y la teoría de la actividad, que consideran la localización sistémica y dinámica de los mecanismos cerebrales, así como, las características esenciales de la edad psicológica. El periodo de intervención fue de 24 meses, dividiéndose en 180 sesiones individuales y 160 sesiones grupales de 60 minutos cada una. Después de la intervención se realizó una revaloración neuropsicológica del paciente, encontrando cambios favorables principalmente en el desarrollo de la función reguladora, comprensión del lenguaje oral e integración social.
Burnout, salud y capital psicológico: un acercamiento desde la teoría de la conservación de recursos
Authors: Fernández Valera Maria Magdalena , Sanchez Soler Maria Isabel , Meseguer de Pedro Mariano
Published: May 2021

La investigación realizada sobre Burnout ha mostrado de manera reiterada que es un síndrome presente en el contexto laboral con graves consecuencias para la salud del trabajador. Sin embargo, los estudios que proponen medidas eficaces para reducir los niveles de exposición al Burnout son escasos. Investigaciones previas han relacionado al capital psicológico de manera negativa y significativa con el burnout. El objetivo de este trabajo es analizar el papel mediador del capital psicológico en la relación entre las tres dimensiones del Burnout y la salud autopercibida de los trabajadores. La muestra está compuesta por 195 trabajadores españoles de distintos sectores de actividad. Los resultados muestran que el capital psicológico media la relación entre las tres dimensiones del burnout y la salud autopercibida de los trabajadores. Para finalizar, se pone de manifiesto la importancia de los recursos psicológicos personales para reducir las consecuencias negativas del Burnout en el bienestar de los empleados.
Toward QbD Process Understanding on DNA Vaccine Purification Using Design of Experiment
Authors: Hocharoen Lalintip , Noppiboon Sarawuth , Kitsubun Panit
Published: May 2021

DNA vaccines, the third generation of vaccines, are a promising therapeutic option for many diseases as they offer the customization of their ability on protection and treatment with high stability. The production of DNA vaccines is considered rapid and less complicated compared to others such as mRNA vaccines, viral vaccines, or subunit protein vaccines. However, the main issue for DNA vaccines is how to produce the active DNA, a supercoiled isoform, to comply with the regulations. Our work therefore focuses on gaining a process understanding of the purification step which processes parameters that have impacts on the critical quality attribute (CQA), supercoiled DNA and performance attribute (PA), and step yield. Herein, pVax1/lacZ was used as a model. The process parameters of interest were sample application flow rates and salt concentration at washing step and at elution step in the hydrophobic interaction chromatography (HIC). Using a Design of Experiment (DoE) with central composite face centered (CCF) approach, 14 experiments plus four additional runs at the center points were created. The response data was used to establish regression predictive models and simulation was conducted in 10,000 runs to provide tolerance intervals of these CQA and PA. The approach of this process understanding can be applied for Quality by Design (QbD) on other DNA vaccines and on a larger production scale as well.
A Technical System for the Large-Scale Application of Metabolites From Paecilomyces variotii SJ1 in Agriculture
Authors: Wang Qingbin , Peng Chune , Shi Liran , Liu Zhiguang , Zhou Dafa , Meng Hui , Zhao Hongling , Li Fuchuan , Zhang Min
Published: May 2021

Compared with endophytes, metabolites from endophytes (MEs) have great potential in agriculture. However, a technique for industrializing the production of MEs is still scarce. Moreover, the establishment of effective methods for evaluating the quality of MEs is hampered by the fact that some compounds with beneficial effects on crops have not been clearly identified. Herein, a system was established for the production, quality control and application of MEs by using the extract from Paecilomyces variotii SJ1 (ZNC). First, the extraction conditions of ZNC were optimized through response surface methodology, after which each batch (500 L) met the consumption requirements of crops in 7,467 hectares. Then, chromatographic fingerprinting and enzyme-linked immunosorbent assay were applied to evaluate the similarity and specificity of unknown effective components in ZNC, ensuring a similarity of more than 90% and a quantitative accuracy of greater than 99.9% for the products from different batches. Finally, the bioactivity of industrially produced ZNC was evaluated in the field, and it significantly increased the potato yields by 4.4–10.8%. Overall, we have established a practical technical system for the large-scale application of ZNC in agriculture.
Agarose, Alginate and Chitosan Nanostructured Aerogels for Pharmaceutical Applications: A Short Review
Authors: Guastaferro Mariangela , Reverchon Ernesto , Baldino Lucia
Published: May 2021

In this short review, drug delivery systems, formed by polysaccharide-based (i.e., agarose, alginate, and chitosan) aerogels, are analyzed. In particular, the main papers, published in the period 2011–2020 in this research field, have been investigated and critically discussed, in order to highlight strengths and weaknesses of the traditional production techniques (e.g., freeze-drying and air evaporation) of bio-aerogels with respect to supercritical CO2 assisted drying. Supercritical CO2 assisted drying demonstrated to be a promising technique to produce nanostructured bio-aerogels that maintain the starting gel volume and shape, when the solvent removal occurs at negligible surface tension. This characteristic, coupled with the possibility of removing also cross-linking agent residues from the aerogels, makes these advanced devices safe and suitable as carriers for controlled drug delivery applications.
Serine Metabolism Regulates YAP Activity Through USP7 in Colon Cancer
Authors: Zhao Xiaoya , Fu Jianfei , Hu Bin , Chen Lin , Wang Jing , Fang Jinyong , Ge Chenyang , Lin Haiping , Pan Kailing , Fu Liang , Wang Lude , Du Jinlin , Xu Wenxia
Published: May 2021

Metabolic reprogramming is a vital factor in the development of many types of cancer, including colon cancer. Serine metabolic reprogramming is a major feature of tumor metabolism. Yes-associated protein (YAP) participates in organ size control and tumorigenesis. However, the relationship between YAP and serine metabolism in colon cancer is unclear. In this study, RNA sequencing and metabolomics analyses indicated significant enrichment of the glycine, serine, and threonine metabolism pathways in serine starvation–resistant cells. Short-term serine deficiency inhibited YAP activation, whereas a prolonged response dephosphorylated YAP and promoted its activity. Mechanistically, USP7 increases YAP stability under increased serine conditions by regulating deubiquitination. Verteporfin (VP) effectively inhibited the proliferation of colon cancer cells and organoids and could even modulate serine metabolism by inhibiting USP7 expression. Clinically, YAP was significantly activated in colon tumor tissues and positively correlated with the expression of phosphoglycerate dehydrogenase (PHGDH) and USP7. Generally, our study uncovered the mechanism by which serine metabolism regulates YAP via USP7 and identified the crucial role of YAP in the regulation of cell proliferation and tumor growth; thus, VP may be a new treatment for colon cancer.
The Effects of Fecal Microbiota Transplantation on the Symptoms and the Duodenal Neurogenin 3, Musashi 1, and Enteroendocrine Cells in Patients With Diarrhea-Predominant Irritable Bowel Syndrome
Authors: Mazzawi Tarek , El-Salhy Magdy , Lied Gülen Arslan , Hausken Trygve
Published: May 2021

Introduction

Interactions between the gut microbiota and enteroendocrine cells play important role in irritable bowel syndrome (IBS). Reduced stem cell densities and their differentiation into enteroendocrine cells may cause abnormal densities of the duodenal enteroendocrine cells in IBS patients.

Materials and Methods

We aimed to investigate the effects of fecal microbiota transplantation (FMT) on stem cell differentiation into enteroendocrine cells as detected by neurogenin 3, stem cells as detected by Musashi 1, and the enteroendocrine cells in the duodenum of IBS patients. The study included 16 IBS patients according to Rome III criteria. Four patients were excluded. The remaining patients (n = 12, four females and eight males) were divided according to the cause of IBS into post-infectious (n = 6) and idiopathic (n = 6) IBS. They completed the following questionnaires before and 3 weeks after FMT: IBS-Symptom Severity Scoring system (IBS-SSS) and IBS-Symptom Questionnaire (IBS-SQ). Feces donated by healthy relatives of the patients were transplanted via gastroscope. Biopsies were taken from the descending part of the duodenum at baseline and 3 weeks after FMT. They were immunostained for neurogenin 3, Musashi 1, and all types of duodenal enteroendocrine cells and quantified by computerized image analysis. Microbiota analyses of feces collected just before and 3 weeks after FMT were performed using GA-map™ Dysbiosis test (Genetic Analysis AS, Oslo, Norway).

Results

The total scores for IBS-SSS and IBS-SQ were significantly improved 3 weeks after receiving FMT, P = 0.0009 and <0.0001, respectively. The stem cell densities of neurogenin 3 increased significantly following FMT (P = 0.0006) but not for Musashi 1 (P = 0.42). The cell densities of chromogranin A, cholecystokinin, gastric inhibitory peptide, serotonin, and somatostatin, but not for secretin, have significantly changed in both IBS groups after 3 weeks from receiving FMT.

Conclusion

More than two-thirds of IBS patients experienced improvement in their symptoms parallel to changes in the enteroendocrine cells densities 3 weeks after FMT. The changes in the enteroendocrine cell densities do not appear to be caused by changes in the stem cells or their early progenitors rather by changes in the differentiation progeny as detected by neurogenin 3. The study was retrospectively registered at ClinicalTrials.gov (ID: NCT03333291).

Clinical Trial Registration

ClinicalTrials.gov, identifier NCT03333291.
Long Noncoding RNA: Regulatory Mechanisms and Therapeutic Potential in Sepsis
Authors: Wang Wei , Yang Ni , Wen Ri , Liu Chun-Feng , Zhang Tie-Ning
Published: May 2021

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is characterized by a hyperinflammatory state accompanied by immunosuppression. Long noncoding RNAs (lncRNAs) are noncoding RNAs longer than 200 nucleotides and have important roles in mediating various biological processes. Recently, lncRNAs were found to exert both promotive and inhibitory immune functions in sepsis, thus participating in sepsis regulation. Additionally, several studies have revealed that lncRNAs are involved in sepsis-induced organ dysfunctions, including cardiovascular dysfunction, acute lung injury, and acute kidney injury. Considering the lack of effective biomarkers for early identification and specific treatment for sepsis, lncRNAs may be promising biomarkers and even targets for sepsis therapies. This review systematically highlights the recent advances regarding the roles of lncRNAs in sepsis and sheds light on their use as potential biomarkers and treatment targets for sepsis.
KSHV Reprogramming of Host Energy Metabolism for Pathogenesis
Authors: Liu Xiaoqing , Zhu Caixia , Wang Yuyan , Wei Fang , Cai Qiliang
Published: May 2021

Reprogramming of energy metabolism is a key for cancer development. Kaposi’s sarcoma-associated herpesvirus (KSHV), a human oncogenic herpesvirus, is tightly associated with several human malignancies by infecting B-lymphocyte or endothelial cells. Cancer cell energy metabolism is mainly dominated by three pathways of central carbon metabolism, including aerobic glycolysis, glutaminolysis, and fatty acid synthesis. Increasing evidence has shown that KSHV infection can alter central carbon metabolic pathways to produce biomass for viral replication, as well as the survival and proliferation of infected cells. In this review, we summarize recent studies exploring how KSHV manipulates host cell metabolism to promote viral pathogenesis, which provides the potential therapeutic targets and strategies for KSHV-associated cancers.
Increased Macrolide Resistance Rate of M3562 Mycoplasma pneumoniae Correlated With Macrolide Usage and Genotype Shifting
Authors: Wang Yacui , Xu Baoping , Wu Xirong , Yin Qingqin , Wang Yi , Li Jieqiong , Jiao Weiwei , Quan Shuting , Sun Lin , Wang Yonghong , Shen Adong
Published: May 2021

To characterize Mycoplasma pneumoniae (MP) strains and to clarify the continuous high rates of macrolide resistance, 1,524 oropharyngeal swabs collected from children in Beijing Children’s Hospital infected with MP during 2016-2019 were analyzed. Among the 1,524 samples, 1,386 harbored mutations associated with macrolide resistance; 1,049 samples were successfully classified into 11 genotypes using multiple locus variable-number tandem-repeat analysis (MLVA). The proportion of the predominant type, M4572, decreased from 84.49 to 70.77% over the time period examined, while that of M3562 increased from 11.63 to 24.67%. Notably, we also found that the frequency of macrolide resistance in M3562 drastically increased, from 60% in 2016 to 93.48% in 2019. Clinical data suggested that the frequency of resistant M3562 was higher in the macrolide usage group than in the nondrug usage group (90.73 vs 53.57%, P<0.0001), while the resistance rate of M4572 was not substantially affected by previous macrolide exposure. These findings validated that antimicrobial application and clonal expansion of resistant MP strains play important roles in the high rates of macrolide resistance.
Communicating and Understanding Ecosystem Services Assessment With Coastal Stakeholders: Obstacles and Opportunities
Authors: DeLorme Denise E. , Stephens Sonia H. , Collini Renee C. , Yoskowitz David W. , Hagen Scott C.
Published: May 2021

This paper reports on insights and lessons learned from stakeholder engagement, particularly focus groups, conducted during a multi-year, NOAA-sponsored transdisciplinary project. A major project goal was to demonstrate and communicate benefits of natural and nature-based features (NNBFs) (e.g., barrier islands, dunes, and marshes) in the northern Gulf of Mexico region through the lens of economic impacts and ecosystem services. Overall, the findings indicate economic impacts and ecosystem services can be challenging topics to communicate because of complexity in conceptualization and valuation. From our experiences, we recommend using “ecosystem services assessment” (ESA), a more encompassing, accurate, and understandable term to stakeholders. ESA recognizes the integrated human (or built) and natural ecosystem and holistic benefits provided by and to both. The paper concludes with a discussion of future research opportunities for improving ESA-oriented science and outreach.
Melatonin and Cardioprotection in Humans: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Domínguez-Rodríguez Alberto , Abreu-González Pedro , Báez-Ferrer Néstor , Reiter Russel J. , Avanzas Pablo , Hernández-Vaquero Daniel
Published: May 2021

Myocardial ischemia/reperfusion (IR) injury represents a critical problem associated with interventional approaches for coronary reperfusion. Pharmacological cardioprotective interventions are advocated to ameliorate IR injury. Melatonin is an anti-inflammatory and antioxidant agent with a wide range of therapeutic properties that may contribute to its cardioprotective effects. No systematic review or meta-analysis has compared melatonin vs. placebo as a cardioprotective agent in humans. The present study, based on a systematic review and meta-analysis, was carried out to assess melatonin's efficacy as a cardioprotective treatment. We performed a systematic review of the available literature. Randomized controlled trials (RCTs) were identified and information was extracted using predefined data extraction forms. The primary outcomes were (a) left ventricular ejection fraction (LVEF) and (b) blood troponin levels in patients who underwent myocardial revascularization and were randomized to melatonin or placebo. The inverse-variance random-effects method was used to pool the estimates. Heterogeneity and publication bias were assessed. Weighted mean differences or standardized mean differences were calculated. A total of 283 records were screened and seven RCTs met all the inclusion criteria. After the pooled analysis, the results on LVEF were consistent across all studies, and a significant heterogeneity was found in the results on troponin levels. The melatonin-treated patients had on average higher LVEF than the placebo-treated individuals with a weighted mean difference = 3.1% (95% CI 0.6–5.5, p = 0.01). Five works compared the levels of troponin after melatonin or placebo treatment. The melatonin-treated patients had lower levels of troponin with a standardized mean difference = −1.76 (95% CI −2.85 to −0.67, p = 0.002). The findings of this meta-analysis revealed that melatonin administration in humans as a cardioprotective agent attenuated heart dysfunction with a favorable effect on the LVEF.
Case Report: Dental Findings Can Aid in Early Diagnosis of APECED Syndrome
Authors: Brenchley Laurie , Ferré Elise M. N. , Schmitt Monica M. , Gardner Pamela J. , Lionakis Michail S. , Moutsopoulos Niki M.
Published: May 2021

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome type 1 (APS-1), is a rare genetic disorder caused most often by biallelic mutations in the AIRE gene. Classic clinical findings of the disease are chronic mucocutaneous candidiasis and autoimmunity that primarily targets endocrine tissues, such as hypoparathyroidism and adrenal insufficiency. Recently, however, it has been appreciated that enamel hypoplasia, together with intestinal malabsorption and a characteristic APECED rash, is a prominent early disease manifestation of APECED which can aid in the diagnosis of disease before other potentially life-threatening disease manifestations occur. To demonstrate this point, we present data from a cohort of APECED patients, ~70% of who present with enamel dysplasia at an early age. Importantly, early life presentation with enamel dysplasia was predictive of likelihood for subsequent APECED diagnosis. Furthermore, we present a case of a patient with APECED and severe enamel defects and discuss the utility of medical-dental professional co-operation in the diagnosis and management of this complex disorder.
Improving the Accuracy of Subseasonal Forecasting of China Precipitation With a Machine Learning Approach
Authors: Wang Cen , Jia Zhaoying , Yin Zhaohui , Liu Fei , Lu Gaopeng , Zheng Jianqiu
Published: May 2021

Precipitation change, which is closely related to drought and flood disasters in China, affects billions of people every year, and the demand for subseasonal forecasting of precipitation is even more urgent. Subseasonal forecasting, which is more difficult than weather forecasting, however, has remained as a blank area in meteorological service for a long period of time. To improve the accuracy of subseasonal forecasting of China precipitation, this work introduces the machine learning method proposed by Hwang et al. in 2019 to predict the precipitation in China 2–6 weeks in advance. The authors used a non-linear regression model called local linear regression together with multitask feature election (MultiLLR) model and chosen 21 meteorological elements as candidate predictors to integrate diverse meteorological observation data. This method automatically eliminates irrelevant predictors so as to establish the forecast equations using multitask feature selection process. The experiments demonstrate that the pressure and Madden–Julian Oscillation (MJO) are the most important physical factors. The average prediction skill is 0.11 during 2011–2016, and there are seasonal differences in forecasting skills, evidenced by higher forecast skills of winter and spring seasons than summer and autumn seasons. The proposed method can provide effective and indicative guidance for the subseasonal prediction of precipitation in China. By adding another three factors, Arctic Oscillation (AO) index, Western North Pacific Monsoon (WNPM) index and Western North Pacific Subtropical High (WNPSH) index into the MultiLLR model, the authors find that AO can improve the forecast skill of China precipitation to the maximum extent from 0.11 to 0.13, followed by WNPSH. Moreover, the ensemble skill of our model and CFSv2 is 0.16. This work shows that our subseasonal prediction of China precipitation should be benefited from the MultiLLR model.
Faculty’s and Students’ Perceptions of Online Learning During COVID-19
Authors: Almahasees Zakaryia , Mohsen Khaled , Amin Mohammad Omar
Published: May 2021

COVID-19 pandemic has disrupted teaching in a vriety of institutions. It has tested the readiness of academic institutions to deal with such abrupt crisis. Online learning has become the main method of instruction during the pandemic in Jordan. After 4 months of online education, two online surveys were distributed to investigate faculty’s and Students’ perception of the learning process that took place over that period of time with no face to face education. In this regard, the study aimed to identify both faculty’s and students’ perceptions of online learning, utilizing two surveys one distributed to 50 faculty members and another 280 students were selected randomly to explore the effectiveness, challenges, and advantages of online education in Jordan. The analysis showed that the common online platforms in Jordan were Zoom, Microsoft Teams offering online interactive classes, and WhatsApp in communication with students outside the class. The study found that both faculty and students agreed that online education is useful during the current pandemic. At the same time, its efficacy is less effective than face-to-face learning and teaching. Faculty and students indicated that online learning challenges lie in adapting to online education, especially for deaf and hard of hearing students, lack of interaction and motivation, technical and Internet issues, data privacy, and security. They also agreed on the advantages of online learning. The benefits were mainly self-learning, low costs, convenience, and flexibility. Even though online learning works as a temporary alternative due to COVID-19, it could not substitute face-to-face learning. The study recommends that blended learning would help in providing a rigorous learning environment.
Exploring Limited Capacity in the Grid: Actors, Problems, and Solutions
Authors: Palm Jenny
Published: May 2021

An extensive and reliable electricity grid is essential for all the sectors of society. In parts of Sweden, the electricity grid has been suffering from a lack of capacity. This is something affecting all the sectors and all the people in these regions. The capacity problems have, however, so far, mainly been analyzed from a technical system perspective, focusing on incumbent actors, whereas other actors have been less researched. This article aims to fill this gap and include a variety of perceptions of Swedish actors’ on the lack of electricity grid capacity. It is, however, a challenge to capture the views of others than the professionals working in the area because the electricity grid is not something people, in general, reflect upon. The article takes an explorative approach to the subject by analyzing the problems and the solutions raised in four arenas: the regulative, the media, the technocratic, and the user. It also focuses on the city of Malmö in Sweden and two projects where the lack of grid capacity has been discussed. Sweden’s lack of capacity concerns that, although electricity is available, the energy grid cannot transmit the required amount of electricity to all parts of the country. The article concludes that the electricity grid has been developed within a technocratic frame, with a few professionals dominating the agenda, which has led to convergence of perspectives and narrowing options. In the regulative arena, which often decides what issues are prioritized and in the end implemented, there is a focus on investment in transformers and lines rather than demand-side solutions and user flexibility. Technological and economical values are dominating all arenas, and other values, such as user engagement and ownership, are marginalized.
Impedance Modeling and Analysis of Medium-Frequency Oscillation Caused by VSC-HVDC Connected to Local Weak Grid and DFIG-Based Wind Farms
Authors: Sun Kun , Yao Wei , Yan Cai , Wen Jinyu
Published: May 2021

In the northwest of China, a strategy to transmit the wind-thermal–bundled power from the local grid and doubly fed induction generator (DFIG)–based wind farms through a voltage source converter–based HVDC (VSC-HVDC) can be widely applied. However, since the local grid is usually weak, a new type of electrical oscillation in the medium-frequency region may occur in the sending-end converter (SEC) of VSC-HVDC with PQ-control. The mechanism of this oscillation caused by the interaction between the DFIG, local grid, and SEC is not entirely understood. In this study, the sequence impedance model of the sending-end converter (SEC) of VSC-HVDC with the PQ-control outer loop and PLL is derived with the explicit analytic expression, and then, the oscillation mechanism is explored based on the intuitive analysis of the system impedance frequency characteristics. Compared with the subsynchronous oscillation (SSO) caused by the DFIG or power inverter, the theoretical analysis shows that this medium-frequency oscillation (MFO) mainly originates from the SEC due to its negative damping effect between about 100 and 200 Hz. In addition, the impact of the system controller parameters and operating conditions of the DFIG, local grid, and SEC on the oscillation characteristics is analyzed in detail. Finally, the correctness of the theoretical analysis is validated by time-domain simulation.
Quantifying Uncertainty in Land-Use/Land-Cover Classification Accuracy: A Stochastic Simulation Approach
Authors: Cheng Ke-Sheng , Ling Jia-Yi , Lin Teng-Wei , Liu Yin-Ting , Shen You-Chen , Kono Yasuyuki
Published: May 2021

In numerous applications of land-use/land-cover (LULC) classification, the classification rules are determined using a set of training data; thus, the results are inherently affected by uncertainty in the selection of those data. Few studies have assessed the accuracy of LULC classification with this consideration. In this article, we provide a general expression of various measures of classification accuracy with regard to the sample data set for classifier training and the sample data set for the evaluation of the classification results. We conducted stochastic simulations for LULC classification of a two-feature two-class case and a three-feature four-class case to show the uncertainties in the training sample and reference sample confusion matrices. A bootstrap simulation approach for establishing the 95% confidence interval of the classifier global accuracy was proposed and validated through rigorous stochastic simulation. Moreover, theoretical relationships among the producer accuracy, user accuracy, and overall accuracy were derived. The results demonstrate that the sample size of class-specific training data and the a priori probabilities of individual LULC classes must be jointly considered to ensure the correct determination of LULC classification accuracy.
CRISPR-Editing of Sweet Basil (Ocimum basilicum L.) Homoserine Kinase Gene for Improved Downy Mildew Disease Resistance
Authors: Zhang Xiaoyu , Low Yee Chen , Lawton Michael A. , Simon James E. , Di Rong
Published: May 2021

Sweet basil (Ocimum basilicum L.) downy mildew disease (DM) caused by Peronospora belbahrii is a worldwide threat to the basil industry due to the lack of natural genetic resistance in sweet basil germplasm collections. In this study, we used CRISPR-gene editing to modify the sweet basil DM susceptibility gene homoserine kinase (ObHSK). Gene-edited plants challenged with P. belbahrii displayed a significantly reduced susceptibility to DM, based on phenotypic disease indices and on in planta pathogen load. These results suggest that ObHSK plays a role in conditioning DM susceptibility, similar to that observed for the AtHSK gene in Arabidopsis. These results demonstrate the utility of CRISPR-gene editing in enhancing DM resistance and contributing to sweet basil breeding programs.
Reconstruction of Litopenaeus vannamei Genome-Scale Metabolic Network Model and Nutritional Requirements Analysis of Different Shrimp Commercial Varieties
Authors: Gao Chenchen , Yang Jiarui , Hao Tong , Li Jingjing , Sun Jinsheng
Published: May 2021

As an important tool for systematic analysis, genome-scale metabolic network (GSMN) model has been widely used in various organisms. However, there are few reports on the GSMNs of aquatic crustaceans. Litopenaeus vannamei is the largest and most productive shrimp species. Feed improvement is one of the important methods to improve the yield of L. vannamei and control water pollution caused by the inadequate absorption of feed. In this work, the first L. vannamei GSMN named iGH3005 was reconstructed and applied to the optimization of feed. iGH3005 was reconstructed based on the genomic data. The model includes 2,292 reactions and 3,005 genes. iGH3005 was used to analyze the nutritional requirements of five different L. vannamei commercial varieties and the genes influencing the metabolism of the nutrients. Based on the simulation, we found that tyrosine-protein kinase src64b like may catalyze different reactions in different commercial varieties. The preference of carbohydrate utilization is different in various commercial varieties, which may due to the different expressions of some genes. In addition, this investigation suggests that a rational and targeted modification in the macronutrient content of shrimp feed would lead to an increase in growth and feed conversion rate. The feed for different commercial varieties should be adjusted accordingly, and possible adjustment schemes were provided. The results of this work provided important information for physiological research and optimization of the components in feed of L. vannamei.
Systemic Bioinformatic Analyses of Nuclear-Encoded Mitochondrial Genes in Hypertrophic Cardiomyopathy
Authors: Tan Zhaochong , Wu Limeng , Fang Yan , Chen Pingshan , Wan Rong , Shen Yang , Hu Jianping , Jiang Zhenhong , Hong Kui
Published: May 2021

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease and mitochondria plays a key role in the progression in HCM. Here, we analyzed the expression pattern of nuclear-encoded mitochondrial genes (NMGenes) in HCM and found that the expression of NMGenes was significantly changed. A total of 316 differentially expressed NMGenes (DE-NMGenes) were identified. Pathway enrichment analyses showed that energy metabolism-related pathways such as “pyruvate metabolism” and “fatty acid degradation” were dysregulated, which highlighted the importance of energy metabolism in HCM. Next, we constructed a protein-protein interaction network based on 316 DE-NMGenes and identified thirteen hubs. Then, a total of 17 TFs (transcription factors) were predicted to potentially regulate the expression of 316 DE-NMGenes according to iRegulon, among which 8 TFs were already found involved in pathological hypertrophy. The remaining TFs (like GATA1, GATA5, and NFYA) were good candidates for further experimental verification. Finally, a mouse model of transverse aortic constriction (TAC) was established to validate the genes and results showed that DDIT4, TKT, CLIC1, DDOST, and SNCA were all upregulated in TAC mice. The present study represents the first effort to evaluate the global expression pattern of NMGenes in HCM and provides innovative insight into the molecular mechanism of HCM.
Case Report: Diagnosis and Assessment of Cure Approaches for Acute Schistosomiasis in Pre-School Children
Authors: Cavalcanti Marta G. , Engel Délia Celser , de Araujo Cunha Aline Fernandes , Peralta José Mauro
Published: May 2021

Acute schistosomiasis (AS) manifests with a broad spectrum of clinical features in pediatric populations. Diagnosis may be difficult in the absence of detectable numbers of eggs. As a result, new approaches may be required to achieve an accurate diagnosis. Optimal praziquantel (PZQ) treatment regimen for young children is debatable. Also, the post-treatment response is still poorly evaluated due to the lack of reliable markers. A group of 6 children (a toddler and 5 pre-school children) and one pre-adolescent were investigated for AS clinical manifestations and followed-up for two years after treatment. Ova detection was performed by Kato-Katz (KK) and presence of Schistosoma mansoni DNA was assessed by real-time PCR (rt-PCR) in stool samples. IgG and IgE anti-Schistosoma levels and urinary antigen were detected by ELISA and point-of-care circulating cathodic antigen (POC-CCA) testing in serum and urine, respectively. AS clinical symptoms were present in 5/7 (71.4%) of the infected children, and hypereosinophilia was detected in all of them. Ova detection and serology were positive in only 3/7 (44.9%) and 4/7 (57.1%), respectively. However, real-time PCR (rt-PCR) showed the presence of Schistosoma DNA in 6/7 (85.7%) of the cases, and urinary antigen was detected in all infected children. The long-term follow-up after treatment with three doses of PZQ (80mg/kg/dose), showed high cure rates (CR) as demonstrated by the DNA-based assay as well as reduced levels of side effects. CR based on urinary antigen detection ranged from 28.6 to 100%, being the highest CR due to double testing the 2-year post-treatment samples. The results suggest that high dose and repeated treatment with PZQ might be effective for AS in young children. Also, new laboratory markers should be considered to diagnosis and monitor the drug response.
Comprehensive Analysis of PD-L1 Expression, Immune Infiltrates, and m6A RNA Methylation Regulators in Esophageal Squamous Cell Carcinoma
Authors: Guo Wei , Tan Fengwei , Huai Qilin , Wang Zhen , Shao Fei , Zhang Guochao , Yang Zhenlin , Li Renda , Xue Qi , Gao Shugeng , He Jie
Published: May 2021

Background

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancer types and represents a threat to global public health. N6-Methyladenosine (m6A) methylation plays a key role in the occurrence and development of many tumors, but there are still few studies investigating ESCC. This study attempts to construct a prognostic signature of ESCC based on m6A RNA methylation regulators and to explore the potential association of these regulators with the tumor immune microenvironment (TIME).

Methods

The transcriptome sequencing data and clinical information of 20 m6A RNA methylation regulators in 453 patients with ESCC (The Cancer Genome Atlas [TCGA] cohort, n = 95; Gene Expression Omnibus [GEO] cohort, n = 358) were obtained. The differing expression levels of m6A regulators between ESCC and normal tissue were evaluated. Based on the expression of these regulators, consensus clustering was performed to investigate different ESCC clusters. PD-L1 expression, immune score, immune cell infiltration and potential mechanisms among different clusters were examined. LASSO Cox regression analysis was utilized to obtain a prognostic signature based on m6A RNA methylation modulators. The relationship between the risk score based on the prognostic signature and the TIME of ESCC patients was studied in detail.

Results

Six m6A regulators (METTL3, WTAP, IGF2BP3, YTHDF1, HNRNPA2B1 and HNRNPC) were observed to be significantly highly expressed in ESCC tissues. Two molecular subtypes (clusters 1/2) were determined by consensus clustering of 20 m6A modulators. The expression level of PD-L1 in ESCC tissues increased significantly and was significantly negatively correlated with the expression levels of YTHDF2, METL14 and KIAA1429. The immune score, CD8 T cells, resting mast cells, and regulatory T cells (Tregs) in cluster 2 were significantly increased. Gene set enrichment analysis (GSEA) shows that this cluster involves multiple hallmark pathways. We constructed a five-gene prognostic signature based on m6A RNA methylation, and the risk score based on the prognostic signature was determined to be an independent prognostic indicator of ESCC. More importantly, the prognostic value of the prognostic signature was verified using another independent cohort. m6A regulators are related to TIME, and their copy-number alterations will dynamically affect the number of tumor-infiltrating immune cells.

Conclusion

Our study established a strong prognostic signature based on m6A RNA methylation regulators; this signature was able to accurately predict the prognosis of ESCC patients. The m6A methylation regulator may be a key mediator of PD-L1 expression and immune cell infiltration and may strongly affect the TIME of ESCC.
Tertiary Lymphoid Structures as a Predictive Biomarker of Response to Cancer Immunotherapies
Authors: Trüb Marta , Zippelius Alfred
Published: May 2021

Tertiary lymphoid structures (TLS) are ectopic lymphoid formations which are formed under long-lasting inflammatory conditions, including tumours. TLS are composed predominantly of B cells, T cells and dendritic cells, and display various levels of organisation, from locally concentrated aggregates of immune cells, through clearly defined B cell follicles to mature follicles containing germinal centres. Their presence has been strongly associated with improved survival and clinical outcome upon cancer immunotherapies for patients with solid tumours, indicating potential for TLS to be used as a prognostic and predictive factor. Although signals involved in TLS generation and main cellular components of TLS have been extensively characterised, the exact mechanism by which TLS contribute to the anti-tumour response remain unclear. Here, we summarise the most recent development in our understanding of their role in cancer and in particular in the response to cancer immunotherapy. Deciphering the relationship between B cells and T cells found in TLS is a highly exciting field of investigation, with the potential to lead to novel, B-cell focused immunotherapies.
Cyclic Helix B Peptide Prolongs Skin Allograft Survival via Inhibition of B Cell Immune Responses in a Murine Model
Authors: Zheng Long , Wang Xuanchuan , Hu Linkun , Gao Wenjun , Zhang Weitao , Zhang Xuepeng , Hu Chao , Rong Ruiming , Yang Cheng , Zhu Dong
Published: May 2021

Antibody-mediated rejection (AMR) represents a major cause of allograft dysfunction and results in allograft failure in solid organ transplantation. Cyclic helix B peptide (CHBP) is a novel erythropoietin-derived peptide that ameliorated renal allograft rejection in a renal transplantation model. However, its effect on AMR remains unknown. This study aimed to investigate the effect of CHBP on AMR using a secondary allogeneic skin transplantation model, which was created by transplanting skin from BALB/c mice to C57BL/6 mice with or without CHBP treatment. A secondary syngeneic skin transplantation model, involving transplantation from C57BL/6 mice to C57BL/6 mice, was also created to act as a control. Skin graft rejection, CD19+ B cell infiltration in the skin allograft, the percentages of splenic plasma cells, germinal center (GC) B cells, and Tfh cells, the serum levels of donor specific antibodies (DSAs), and NF-κB signaling in splenocytes were analyzed. Skin allograft survival was significantly prolonged in the CHBP group compared to the allogeneic group. CHBP treatment also significantly reduced the CD19+ B cell infiltration in the skin allograft, decreased the percentages of splenic plasma cells, GC B cells, and Tfh cells, and ameliorated the increase in the serum DSA level. At a molecular level, CHBP downregulated P100, RelB, and P52 in splenocytes. CHBP prolonged skin allograft survival by inhibiting AMR, which may be mediated by inhibition of NF-κB signaling to suppress B cell immune responses, thereby decreasing the DSA level.
Production Cross-Section Measurements for Terbium Radionuclides of Medical Interest Produced in Tantalum Targets Irradiated by 0.3 to 1.7 GeV Protons and Corresponding Thick Target Yield Calculations
Authors: Duchemin Charlotte , Cocolios Thomas E. , Dockx Kristof , Farooq-Smith Gregory J. , Felden Olaf , Formento-Cavaier Roberto , Gebel Ralf , Köster Ulli , Neumaier Bernd , Scholten Bernhard , Spahn Ingo , Spellerberg Stefan , Stamati Maria E. , Stegemann Simon , Verhoeven Hannelore
Published: May 2021

This work presents the production cross-sections of Ce, Tb and Dy radionuclides produced by 300 MeV to 1.7 GeV proton-induced spallation reactions in thin tantalum targets as well as the related Thick Target production Yield (TTY) values and ratios. The motivation is to optimise the production of terbium radionuclides for medical applications and to find out at which energy the purity of the collection by mass separation would be highest. For that purpose, activation experiments were performed using the COSY synchrotron at FZ Jülich utilising the stacked-foils technique and γ spectrometry with high-purity germanium detectors. The Al-27(p,x)Na-24 reaction has been used as monitor reaction. All experimental data have been systematically compared with the existing literature.
Serum-Urine Matched Metabolomics for Predicting Progression of Henoch-Schonlein Purpura Nephritis
Authors: Zhang Qian , Lai Ling-Yun , Cai Yuan-Yuan , Wang Ma-Jie , Ma Gaoxiang , Qi Lian-Wen , Xue Jun , Huang Feng-Qing
Published: May 2021

Henoch-Schonlein purpura nephritis (HSPN) is a common glomerulonephritis secondary to Henoch-Schonlein purpura (HSP) that affects systemic metabolism. Currently, there is a rarity of biomarkers to predict the progression of HSPN. This work sought to screen metabolic markers to predict the progression of HSPN via serum-urine matched metabolomics. A total of 90 HSPN patients were enrolled, including 46 HSPN (+) patients with severe kidney damage (persistent proteinuria >0.3 g/day) and 44 HSPN (–) patients without obvious symptoms (proteinuria < 0.3 g/day). Untargeted metabolomics was determined by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS). A total of 38 and 50 differential metabolites were, respectively, identified in serum and urine from the comparison between HSPN (+) and HSPN (–) patients. Altered metabolic pathways in HSPN (+) mainly included glycerophospholipid metabolism, pyruvate metabolism, and citrate cycle. A panel of choline and cis-vaccenic acid gave areas under the curve of 92.69% in serum and 72.43% in urine for differential diagnosis between HSPN (+) and HSPN (–). In addition, the two metabolites showed a significant association with clinical indices of HSPN. These results suggest that serum-urine matched metabolomics comprehensively characterized the metabolic differences between HSPN (+) and HSPN (–), and choline and cis-vaccenic acid could serve as biomarkers to predict HSPN progression.
Comprehensive Ecological and Geographic Characterization of Eukaryotic and Prokaryotic Microbiomes in African Anopheles
Authors: Cuesta Eugeni Belda , Coulibaly Boubacar , Bukhari Tullu , Eiglmeier Karin , Kone Raymond , Coulibaly Mamadou B. , Zongo Soumanaba , Barry Mamadou , Gneme Awa , Guelbeogo Wamdaogo M. , Beavogui Abdoul H. , Traore Sekou F. , Sagnon N’Fale , Vernick Kenneth D. , Riehle Michelle M.
Published: May 2021

Exposure of mosquitoes to numerous eukaryotic and prokaryotic microbes in their associated microbiomes has probably helped drive the evolution of the innate immune system. To our knowledge, a metagenomic catalog of the eukaryotic microbiome has not been reported from any insect. Here we employ a novel approach to preferentially deplete host 18S ribosomal RNA gene amplicons to reveal the composition of the eukaryotic microbial communities of Anopheles larvae sampled in Kenya, Burkina Faso and Republic of Guinea (Conakry). We identified 453 eukaryotic operational taxonomic units (OTUs) associated with Anopheles larvae in nature, but an average of 45% of the 18S rRNA sequences clustered into OTUs that lacked a taxonomic assignment in the Silva database. Thus, the Anopheles microbiome contains a striking proportion of novel eukaryotic taxa. Using sequence similarity matching and de novo phylogenetic placement, the fraction of unassigned sequences was reduced to an average of 4%, and many unclassified OTUs were assigned as relatives of known taxa. A novel taxon of the genus Ophryocystis in the phylum Apicomplexa (which also includes Plasmodium) is widespread in Anopheles larvae from East and West Africa. Notably, Ophryocystis is present at fluctuating abundance among larval breeding sites, consistent with the expected pattern of an epidemic pathogen. Species richness of the eukaryotic microbiome was not significantly different across sites from East to West Africa, while species richness of the prokaryotic microbiome was significantly lower in West Africa. Laboratory colonies of Anopheles coluzzii harbor 26 eukaryotic OTUs, of which 38% (n = 10) are shared with wild populations, while 16 OTUs are unique to the laboratory colonies. Genetically distinct An. coluzzii colonies co-housed in the same facility maintain different prokaryotic microbiome profiles, suggesting a persistent host genetic influence on microbiome composition. These results provide a foundation to understand the role of the Anopheles eukaryotic microbiome in vector immunity and pathogen transmission. We hypothesize that prevalent apicomplexans such as Ophryocystis associated with Anopheles could induce interference or competition against Plasmodium within the vector. This and other members of the eukaryotic microbiome may offer candidates for new vector control tools.