bluuebunny/crossref_metadata_2025 huggingface dataset:
Production and identification of two antifungal terpenoids from the Posidonia oceanica epiphytic Ascomycota Mariannaea humicola IG100.
Authors: Botta Lorenzo , Saladino Raffaele , Barghini Paolo , Fenice Massimiliano , Pasqualetti Marcella
Published: September 2020

Background: Marine fungi are an important repository of bioactive molecules with great potential in different technological fields, the annual number of new compounds isolated from marine fungi is impressive and the general trend indicates that it is still on the rise. In this context, the antifungal and antimicrobial activity of the marine strain Mariannaea humicola IG100 was evaluated and two active terpenoids were isolated and characterized.Methods: Preliminary screening of activity of marine strain IG100 was carried out by agar plug diffusion methods against fungal (P. griseofulvum TSF04) and bacterial (Bacillus pumilus KB66 and Escherichia coli JM109) strains. Subsequently, inhibition tests were done by using the cultural broth and the organic extract (ethyl acetate, EtOAc) by the agar well diffusion methods. The main active fractions were identified and tested for their antifungal activity against P. griseofulvum TSF04 in a 24 wells microplate at different concentrations (1000, 100, 10 and 1.0 µg/mL). Two active compounds were characterized and their relative MIC measured by the broth micro-dilution methods in a 96-well microplate against A. flavus IG133, P. griseofulvum TSF04, and T. pleuroticola IG137. Results: Marine strain IG100 presented significant antifungal activity associated with two active compounds, the terpenoids terperstacin 1 and 19-acetyl-4-hydroxydictyodiol 2. Their MIC values were measured for Aspergillus flavus (MIC of 7.9 µg/mL and 31.3 µg/mL for 1 and 2, respectively), P. griseofulvum (MIC of 25 µg/mL and 100 µg/mL for 1 and 2, respectively) and T. pleuroticola (MIC >500 µg/mL and 125 µg/mL for 1 and 2, respectively). They showed a rather good fungistatic effect. Conclusions: In this study, the first marine strain of M. humicola (IG100) was investigated for the production of bioactive molecules. Strain IG100 produced significant amounts of two bioactive terpenoids, terperstacin 1 and 19-acetyl-4-hydroxydictyodiol 2. The two compounds showed significant antifungal activities against A. flavus IG133, T. pleuroticola IG137 and P. griseofulvum TSF04. Compound 2 was identified for the first time in fungi.
Preprint withdrawn
Authors: Withdrawn Authors
Published: September 2020

The authors have requested that this preprint be removed from Research Square.
β-lactamase-mediated resistance in MDR-Pseudomonas aeruginosa from Qatar
Authors: Ahmed Mazen A. Sid , Khan Faisal Ahmad , Sultan Ali A. , Soderquist Bo , Ibrahim Emad Bashir , Jass Jana , Omrani Ali S.
Published: September 2020

Background: The distribution of b-lactamase resistance genes in P. aeruginosa is often closely related to the distribution of certain high-risk international clones. We used whole-genome sequencing (WGS) to identify the predominant sequence types (ST) and b-lactamase genes in clinical isolates of multidrug-resistant (MDR)-P. aeruginosa from QatarMethods: Microbiological identification and susceptibility tests were performed by automated BD Phoenix system and manual Liofilchem MIC Test Strips. Results: Among 75 MDR-P. aeruginosa isolates; the largest proportions of susceptibility were to ceftazidime-avibactam (n=36, 48%), followed by ceftolozane-tazobactam (30, 40%), ceftazidime (n=21, 28%) and aztreonam (n=16, 21.3%). Almost all isolates possessed Class C and Class D b-lactamases (n=72, 96% each), while metallo-β-lactamases were detected in 20 (26.7%) isolates. Eight (40%) metallo-β-lactamases producers were susceptible to aztreonam and did not produce any concomitant extended-spectrum b-lactamases. High risk ST235 (n=16, 21.3%), ST357 (n=8, 10.7%), ST389 and ST1284 (6, 8% each) were most frequent. Nearly all ST235 isolates (15/16; 93.8%) were resistant to all tested b-lactams.Conclusion: MDR-P. aeruginosa isolates from Qatar are highly resistant to antipseudomonal b-lactams. High-risk STs are predominant in Qatar and their associated MDR phenotypes are a cause for considerable concern.
The Impact of COVID-19 on Complementary and Alternative Medicine Providers: A Cross-sectional Survey in Norway
Authors: Stub Trine , Jong Miek C. , Kristoffersen Agnete E.
Published: September 2020

BackgroundThe Norwegian authorities decided on a nationwide lockdown to prevent spread of the COVID-19 virus. The lockdown had huge socioeconomic consequences for the society. The aim of this study was to investigate the impact of COVID-19 on Complementary and Alternative Medicine (CAM) providers in Norway.MethodThis cross-sectional survey analyzed data from a self-administrated questionnaire. A total of 581 CAM providers completed the questionnaire, which was designed to describe consequences for CAM providers and their clinical practice after the nationwide lockdown. Between group differences were analyzed using chi-square, ANOVA and Fisher’s exact test. Significance level was defined as p < 0.05 without adjustment for multiple comparisons.ResultDuring the nationwide lockdown of Norway, 38.4% of respondents were able to provide CAM treatment to their patients. Of those, the majority (96.4%) had reorganized their clinical practice in accordance with COVID-19 hygiene regulations, offered video consultations (57.4%) or telephone consultations (46.6%). To manage financially during the lockdown, half of the providers spent their savings (48.7%). More than one third (35.1%) was supported by their partner, and 26.7% received compensation from the Norwegian state. A total of 26.3% of the CAM providers had other paid work that provided them with income. Nearly a quarter (18.6%) borrowed money from friends and family, changed their loan terms, or took out new bank loans. The majority (62.7%) expressed uncertainty about the future of their practice. CAM providers who had reorganized their practice to online consultations were more optimistic. ConclusionThe impact of COVID-19 on CAM providers was considerable. It adversely affected their clinical practice, financial situation, and view on their future practice. To ensure that the health needs of the Norwegian population regarding CAM use are met during pandemic times like COVID-19, it is recommended to support and train CAM providers in the development of online CAM services, as well as efficient implementation of infection prevention and control measures.
Production of biodiesel from mixed castor seed and microalgal oils: characterization and optimization studies
Authors: Lemma Dejene Beyene , Abagisa Mohammedsani Abdulkadir , Kebede Adisu Befekadu
Published: September 2020

In order to lower the high prices of individual feedstock, extend the life of a more limited feedstock and to improve the fuel properties of biodiesel it imperative to optimize process parameters for biodiesel derived from mixed feedstocks. Samples of castor seeds were collected from Jimma zone, southwest Ethiopia while sample of wet microalgal biomass was obtained from wastewater stabilization ponds using a 60µm filter screen. The castor seeds and algal biomass were sun-dried before further dried at 80 0 C in an oven and ground to pastes. Oils were extracted from dried and milled castor seeds and micro-algae pastes with a Soxhlet apparatus using methanol. The extracted oil was purified and characterized before converted to biodiesel. A transesterification process designed using Response Surface Methodology (RSM) based on central composite design (CCD) experimental design was used to optimize the biodiesel production process parameters from mixed oil using alkaline catalyst. The Design Expert® 12 software was used to analysis experimental results. The effects of catalyst concentration, ethanol to mixed oil molar ratio and reaction temperature on the biodiesel yield were investigated using the experimental results. Accordingly, the optimum conditions for biodiesel production from mixed oil were a catalyst concentration of 1.23% w.t of the oil, alcohol to mixed oil molar ratio of 5.94 :1 (v/v) and reaction temperature of 51.30 0 C. The yield of biodiesel under these conditions was 93.88% . Experiment was conducted under the specified optimum conditions to validate the result predicted by the software. The yield of biodiesel from the experiment was 93.36 % which is very close to the value predicted by the software. The fatty acid composition of the biodiesel from mixed oil was analyzed using Gas chromatograph. The various fuel properties of biodiesel were determined using standard methods and results were compared with ASTM D6751 and EN 14214 standards. The physicochemical properties fulfill both standards.
Young Children Who Eat Animal Sourced Foods Grow Less Stunted: Findings of Contemporaneous and Lagged Analyses from Nepal, Uganda and Bangladesh
Authors: Zaharia Sonia , Ghosh Shibani , Shrestha Robin , Manohar Swetha , Thorne-Lyman Andrew , Bashaasha Bernard , Kabunga Nassul , Gurung Sabi , Namirembe Grace , Heneveld Katherine , Liang Lichen , Webb Patrick
Published: September 2020

In resource constrained countries, animal-sourced foods (ASFs) are an important nutrient-dense source of vitamins, minerals and macronutrients. While several studies have suggested the value of ASFs to child growth, most empirical evidence is based on cross-sectional data which can only provide information about the contemporaneous relationship between diet and anthropometric outcomes. This study uses longitudinal panel data for Nepal, Bangladesh, and Uganda to assess the association between contemporaneous as well as past ASF consumption and linear growth of children aged 6-24 months. Fixed effects models found that ASF consumption was significantly correlated with lower stunting, with a decline in stunting prevalence as high as 10% in Nepali children who had consumed any ASF in the previous year. Consuming two or more ASFs showed an even higher magnitude of association, ranging from a 10% decline in prevalence of stunting associated with lagged consumption in Bangladesh to a 16% decline in Nepal.
Domain Randomization for Neural Network Classification
Authors: Valtchev Svetozar Zarko , Wu Jianhong
Published: September 2020

Large data requirements are often the main hurdle in training neural networks. Synthetic data is a cheap and efficient solution to assemble such large datasets. Using domain randomization, we show that a sufficiently well generated synthetic image dataset can be used to train a neural network classifier, achieving accuracy levels as high as 88% on 2 category classification. We show that the most important domain randomization parameter is a large variety of subjects, while secondary parameters such as lighting and textures are not. Based on our results, there is reason to believe that models trained on domain randomized images transfer to new domains better than those trained on real photos. Model performance seems to diminish slightly as the number of categories increases.
Distance to native niche margins explains establishment success of alien
mammals
Authors: Broennimann Olivier , Petitpierre Blaise , Chevalier Mathieu , González-Suárez Manuela , Jeschke Jonathan , Rolland Jonathan , Gray Sarah , BACHER Sven , Guisan Antoine
Published: September 2020

Why do some alien species introductions fail while others are successful? One key hypothesis is that in order for a species to invade a new range, it must initially establish successfully in conditions within its native climatic niche (NCN). Yet, this hypothesis has largely remained untested at the level of individual release events. Using a dataset of 989 introductions of 177 mammal species worldwide, we show that climatic matching to the NCN, measured by a new Niche Margin Index (NMI), is a stronger predictor of establishment success than most previously tested life-history attributes and historical factors. Contrary to traditional climatic suitability metrics derived from species distribution models, the NMI is based on niche margins and provides a measure of how distant a site is inside or, importantly, outside the NCN. Integrating NMI as a measure of NCN-matching in risk assessments could improve efforts to prevent invasions and avoid costly eradications.
Efficacy of Additional Corticosteroids to Multimodal Cocktail Periarticular Injection in Total Knee Arthroplasty: A Meta-Analysis of Randomized Controlled Trials
Authors: Li Qi , Mu Guo , Liu Xiangbo , Chen Milian
Published: September 2020

Background: As the ultimate method for the treatment of osteoarthritis, total knee arthroplasty (TKA) has been widely used in clinic. Local injection of multimodal cocktails, including corticosteroids, is commonly used for pain management after TKA. This meta-analysis aims to systematically evaluate the effect of periarticular injection of corticosteroids on postoperative pain relief and knee functional recovery in patients undergoing TKA.Methods: PubMed, Cochrane Library, EMBASE and Web of Science databases were comprehensively searched for all randomized controlled trials (RCTs) published before July 1st, 2020 that investigated the efficacy of corticosteroids for TKA.Results: Ten RCTs involving a total of 829 patients were assessed in the meta-analysis. Compared with the control group, the Visual Analogue Scale (VAS) score at rest of the corticosteroids group decreased significantly at postoperative day 1(POD1), POD2 and POD3(P<0.05). Besides, the range of flexion motion of the knee joint in corticosteroids group at POD1 and POD2 was significantly increased(P<0.05), at the same time, the range of extension motion at POD2 and POD3 showed the opposite trend between the two groups(P<0.05). The morphine equivalent of postoperative analgesia was significantly reduced(P<0.05), and the time required for straight leg raising(SLR) was significantly shortened(P<0.05). There was no significant difference between the two groups in terms of postoperative drainage, length of hospital stay, and complications such as infection, nausea and vomiting(P>0.05).Conclusion: The additional corticosteroids to multimodal cocktail periarticular injection can relieve the early pain intensity at rest after TKA, increase the early range of motion(ROM) of the knee joint, reduce the dosage of postoperative analgesics, and shorten the duration of time required for SLR.However, it has no effect on reducing postoperative complications and shortening the length of hospital stay.
Urea - Hydrogen Compost Soil Microbial Fuel Cell for Multifunctional Applications
Authors: Magotra Verjesh Kumar , Kang T.W. , Lee S.J. , Walke Pundalik D. , Rana Abu ul Hassan Sarwar , Jeon Hee Chang
Published: September 2020

Background: This paper provides an overview of the present advances in renewable and sustainable energy resources used for new energy demand in the world. Aiming to address, Urea, Urine resources are abundant like urea-containing wastewater, industrial urea, wastewater treatment plants, becoming an attractive option as anodic fuel for the application in urea fuel cells. And as a hydrogen-rich chemical fuel, urea can also be hydrolysis and electrolyzed to produce hydrogen for energy storage in the near future. Results: We report a novel, urea-hydrogen based compost soil microbial fuel cell (UH-CSMFC). As compost soil is a rich source of bacteria, enzymes, and organic matter, soil provided the necessary ingredients for the operation of the device. While bacteria and enzymes that hydrolysed by urea powered by the fuel cell. The compost soil was also found to exhibit partial electrocatalytic activity itself. This novel UH-CSMFC shows power density of 18.26 mW/m2. For continuous operation of the device, and cleaning of the excess of nitrogen compounds from urea fuel (urine, containing different wastewater energy resources).Conclusion: The constant state is the most desirable, where the device behaviour is entirely irreversibly, which helps to feed the device. Thus, the results of electrochemical studies show that the system is suitable for cleaning, hydrogen, power generation by consuming urea as fuel. This multifunctional device is sustainable, cheap, and eco-friendly for the environment.
Research on Difficult Family Environment and Inequality of Opportunities for Children's health: evidence from seven provinces across China
Authors: Du Benfeng , Wang Xuan , Mu Yuexuan
Published: September 2020

BackgroundFamily is an important environment for the adaptive development of children. A lack of family functions can affect the equality of children's access to health opportunities. Based on past survey data, there are many children in difficult families in China, and the life experiences of living in difficult families have had a serious negative impact on children's health. Therefore, the research on health equality in children in difficult families is particularly important. ObjectiveThe study aimed to examine the difference in the extent of family environment's influence on equal health opportunities between children from difficult families and ordinary families. MethodThe study based on data of a survey, "Health Status of Children in Difficult Families," which was conducted in 7 provinces in China in 2018. The D index was used to calculate the extent to which the family environment influenced the health opportunity equality in children from two types of families. Through conducting the Shapley decomposition based on ordered multi-class regression, the relative level of contribution of different family environment factors to the health opportunities equality in children from two types of families was examined. ResultsThe family variables included in this paper examined had a significant impact on the health opportunities of children from both families, and they had a greater impact on children's mental health. Based on the results of Shapley decomposition on different family environment factors, the family relationship had the greatest impact on the self-reported health opportunities of children from difficult families (32.02%). Living condition was the main factor that influenced the self-reported health opportunities of children from ordinary families (25.72%). In terms of mental health, family economic status was the main factor that affected the mental health opportunity equality in children from difficult families (21.22%). Family relationship was the main factor influencing the mental health opportunity equality in children from ordinary families (36.54%). In terms of cognition, family relationship was the main factor affecting health opportunity equality in children from two types of families (55.72% and 28.05%, respectively). ConclusionThere is a significant difference in the extent to which the family environment influences the health opportunity equality between children from two types of families across different health domains. Family relationship is the most important factor affecting the fairness of children's access to health opportunities in difficult families.
Relation Extraction for Coal Mine Safety Information Using Recurrent Neural Networks with Bidirectional Minimal Gated Unit
Authors: Liu Xiulei , Hou Shoulu , Qin Zhihui , Liu Sihan , Zhang Jian
Published: September 2020

The data of coal mine safety field are massive, multi-source and heterogeneous. It is of practical importance to extract information from big data to achieve disaster precaution and emergency response. Existing approaches need to build more features and rely heavily on the linguistic knowledge of researchers, leading to inefficiency, poor portability and slow update speed. This paper proposes a new relation extraction approach using recurrent neural networks with bidirectional minimal gated unit (MGU) model. This is achieved by adding a back-to-front MGU layer on the basis of original MGU model. It does not require to construct complex text features and can capture the global context information by combining the forward and backward features. Evident from extensive experiments, the proposed approach outperforms the existing initiatives in terms of training time, accuracy, recall rate and F value.
TERT drives fibroblasts reprogramming to promote the invasion of head and neck squamous cell carcinoma via transferring of exosomal MET protein
Authors: Yang Ke , Zhang Shizhou , Zhang Dongsheng , Tao Qian , Liu Xingguang , Zhang Tianqi , Liu Guijun , Ma Li , Zhao Tengda
Published: September 2020

Background

Head and neck squamous cell carcinoma (HNSCC) is characterized by the highly infiltrative capacity and invariably aggressive feature, the oncogenic functions of TERT in cell transformation and tumor progression have well been elucidated; however, very little is known about the effect of TERT on the microenvironment during the tumorigenesis of HNSCC.
Methods

An bioinformatics analysis of TERT was firstly performed from TCGA dataset, and the correlation of TERT activity with tumor microenvironment (TME) was assessed on the basis of the analysis of HNSCC patient specimen in vivo and in vitro co-culture experiments. We next conducted an cDNA microarray analysis and identified the TERT-driven key molecule MET in the functionally regulation of tumor-fibroblasts crosstalk. Furthermore, the phenotypic and functional alteration of primary fibroblasts were detected by a series of molecular biology experiments following treatment with TERT overexpressed/silenced HNSCC cell-derived exosomes or MET transfection, respectively, and the underlying intracellular signaling pathway was tested. Finally, the effect of programming fibroblasts on the aggressive behavior of HNSCC cells were evaluated in vivo and in vitro assays.
Results

Here, we found that TERT was significantly elevated in HNSCC tissues in comparison with normal mucosa tissues, and its level was increased along with malignant progression of the tumor. Furthermore, the activated TERT enhanced cancer-fibroblasts interaction and promoted cancer-associated fibroblasts (CAFs) formation in TME. Mechanistically, TERT-driven normal fibroblast reprogramming into CAFs is exosomal MET dependent, activated TERT could physically interact with MET protein and increase exosomal MET protein released from HNSCC cells, which promotes the intercellular trafficking of MET into fibroblasts and consequently activated AKT and ERK signaling pathways, resulting in primary fibroblast reprogramming through increased cell proliferation, migration and elevation of the pro-inflammatory gene signature. More importantly, the programmed fibroblasts in turn promote the migration and invasion of HNSCC cells.
Conclusions

Our results unveil a novel role of TERT-driven modulation of the TME, which may offer new opportunities for potential therapeutic strategies targeting HNSCC development.
Physiological Metabolism and Antioxidant Capacity of Rainbow Trout (Oncorhynchus Mykiss) Fed Diets with Different Lipid Levels
Authors: Ma Jun , Lou Yanan , Zhang Jing , Li Yong
Published: September 2020

Background: In order to obtain the suitable lipid requirements of rainbow trout (Oncorhynchus mykiss) cultured in the recirculating aquaculture systems (RAS), the effects of dietary lipid levels on fat-related physiological metabolism and antioxidant defenses were investigated. Four isonitrogenous diets containing 45% crude protein with increasing dietary lipid levels of 12%, 15%, 18%, and 21% were fed to 360 fish with initial body weight of 333.25 ± 20.71 g for 77 d. Results: The results showed that a high lipid diet increased lipase and amylase activities in trout livers, whereas a low lipid diet improved lipase and alkaline phosphatase activities in trout intestines. Meanwhile, increased dietary lipid levels elevated low density lipoprotein content and decreased high density lipoprotein, triglyceride, total cholesterol concentrations and the high density lipoprotein/low density lipoprotein ratio in serum. Moreover, increases in superoxide dismutase, glutathione, and malondialdehyde activities were observed in serum with increasing dietary lipid levels, while catalase activity and the catalase/superoxide dismutase ratio decreased. Conclusion: These results indicate that rainbow trout fed diets with low and medium fat levels received adequate fat nutrition and that the diets ensured healthy growth by improving digestive absorption, fat synthesis and transport, and antioxidant levels, and the L12 group had the best growth performance. In conclusion, rainbow trout are healthier when fed diets with approximately 12% lipid levels in RAS.
SLC39A1 contribute to malignant progression and have clinical prognostic impact in gliomas
Authors: Wang Peng , Zhang Jingjing , He Shuai , Xiao Boan , Peng Xiaobin
Published: September 2020

BackgroundGliomas are one of the most common primary tumors of the central nervous system, and have an unfavorable prognosis. SLC39A1 is a zinc ion transport protein which inhibits the progression of prostate cancer. By studying the role and mechanism of SLC39A1 in the progression of gliomas, perhaps a new therapeutic target can be provided for their treatment.MethodThe TCGA, CCGA, GSE16011, GSE44971 and GSE11260 data sets were employed to evaluate the expression level of SLC39A1 in paracancerous and glioma tissues. In addition, Kaplan-Meier analysis, Cox analysis, and the ESTIMATE and CIBERSORT algorithms were used to analyze its prognostic value and immune infiltration correlation. A CCK-8 and flow cytometer were used to measure the effects of SLC39A1 on U87 cell proliferation or apoptosis; RT-qPCR and western blot were used to detect its effects on the expression of MMP2\MMP9.ResultsSLC39A1 has up-regulated expression in glioma tissues. It is an independent prognostic factor for patients with glioma, and is significantly correlated with clinical pathological parameters such as Grade, IDH mutation status, and 1p19q codeletion status. In vitro experimental results show that SLC39A1 promotes proliferation of glioma cells, inhibits their apoptosis, and promotes expression of MMP2\MMP9. In addition, it may affect infiltration of immune cells into the glioma microenvironment.ConclusionSLC39A1 is a new biomarker, an independent prognostic factor for gliomas, and can be used as a potential target for their treatment.
Impact of A Maternal and Newborn Health Results Based Financing Intervention (RBF4MNH) On Stillbirth: A Cross-Sectional Comparison in Four Districts in Malawi.
Authors: Makuluni Regina , Stones William
Published: September 2020

Background: A Results Based Financing (RBF) model for Maternal and Newborn Health, “RBF4MNH” was implemented by the Government of Malawi in four Districts, with the aim of improving health outcomes. We used this setting to examine the impact of this model on antepartum and intrapartum stillbirth, taking women’s risk factors into account. Methods: We used maternity unit delivery registers at hospitals in four districts of Malawi to obtain information about stillbirths. The result based finance for maternal and newborn health intervention was ongoing in two districts and two non-intervention districts were used for comparison. Data were extracted from the maternity registers and analyzed using STATA version 14. Logistic regression models were developed to determine crude and adjusted odds ratios for fresh and macerated stillbirth. Results: In the study period there were 67 stillbirths among 2,772 deliveries representing 24.1 per 1,000 live births of which 52% (n=35) were fresh (intrapartum) stillbirths and 48% (n=32) were macerated (antepartum) losses. Adjusted odds ratios (aOR) for fresh and macerated stillbirth at RBF versus non-RBF sites were 2.67 (95%CI 1.24 to 5.57, P=0.01) and 7.27 (95%CI 2.74 to 19.25 P<0.001) respectively.Gestational age at delivery was significantly associated with stillbirths. Conclusion: The study did not identify a positive impact of result based finance for maternal and newborn health on the reduction of both fresh and macerated stillbirths. There is a need for rigorously designed and tested interventions to strengthen service delivery with a focus on the elements needed to ensure quality of intrapartum care.
eIF6 Promotes the Malignant Progression of Human Hepatocellular Carcinoma via the mTOR Signaling Pathway
Authors: Sun Liping , Liu Shuguang , Wang Xiaopai , Zheng Xuefeng , Chen Ya , Shen Hong
Published: September 2020

Background
Eukaryotic translation initiation factor 6 (eIF6) has a crucial function in the maturation of 60S ribosomal subunits, and it controls the initiation of protein translation. Although emerging studies indicate that eIF6 is aberrantly expressed in various types of cancers, the functions and underlying molecular mechanisms of eIF6 in the pathological progression of hepatocellular carcinoma (HCC) remain unclear. This study aimed to evaluate the potential diagnostic and prognostic value of eIF6 in patients with HCC.
Methods
HCC samples enrolled from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and our cohort were used to explore the role and mechanism of eIF6 in HCC. The diagnostic power of eIF6 was verified by receiver operating characteristic curve (ROC) analysis and its prognostic value was assessed by Kaplan-Meier analysis, and then related biological functions of eIF6 were determined in vitro and in vivo cancer models. In addition, potential molecular mechanism of eIF6 in HCC was unveiled by the gene set enrichment analysis and western blot assay.
Results
We demonstrated that eIF6 expression was markedly increased in HCC, and elevated eIF6 expression correlated with pathological progression of HCC. Besides, eIF6 served as not only a new diagnostic biomarker but also an independent risk factor for OS in HCC patients. Functional studies indicated that the deletion of eIF6 displayed tumor-suppressor activity in HCC cells. Furthermore, we found that eIF6 could activate the mTOR-related signaling pathway and regulate the expression level of its target genes, such as CCND1, CDK4, CDK6, MYC, CASP3 and CTNNBL1, and these activities promoted proliferation and invasion of HCC cells.
Conclusions
The findings of this study provided a novel basis for understanding the potential role of eIF6 in promoting tumor growth and invasion, and exploited a promising strategy for improving diagnosis and prognosis of HCC.
Surfactant Therapy for COVID-19 Related ARDS: A Retrospective Case-Control Pilot Study.
Authors: Piva Simone , Robert DiBlasi , Slee April E , Jobe Alan H , Roccaro Aldo M , Filippini Matteo , Latronico Nicola , Bertoni Michele , Marshall John C , Portman Michael A
Published: September 2020

Background. COVID-19 causes acute respiratory distress syndrome (ARDS) and depletes the lungs of surfactant, leading to prolonged mechanical ventilation and death. The feasibility and safety of surfactant delivery in COVID-19 ARDS patients have not been established. Methods. We performed retrospective analyses of data from patients receiving off-label use of natural surfactant during the COVID-19 pandemic. Seven COVID-19 PCR positive ARDS patients received liquid Curosurf (720 mg) in 150 ml normal saline, divided into five 30 ml aliquots) and delivered via a bronchoscope into second-generation bronchi. Patients were matched with 14 comparable subjects receiving supportive care for ARDS during the same time period. Feasibility and safety were examined as well as the duration of mechanical ventilation and mortality. Results. Patients showed no evidence of acute decompensation following surfactant installation into minor bronchi and lung retention for up to 2 hours. Cox regression showed a reduction of 28-days mortality within the surfactant group, though not significant. The surfactant did not increase the duration of ventilation, and health care providers did not convert to COVID-19 positive. Conclusions. Surfactant delivery through bronchoscopy at a dose of 720 mg in 150 ml normal saline is feasible and safe for COVID-19 ARDS patients and health care providers during the pandemic. Surfactant administration does not cause acute decompensation, and it could be related to improved survival and reduction of mechanical ventilation duration. This study supports the future performance of randomized clinical trials evaluating the efficacy of meticulous surfactant delivery.
Non-invasive Prenatal Testing for Assessing Fetal Sex Chromosome Aneuploidy: A Retrospective Study of 45773 Cases
Authors: Xinran LU , Chaohong WANG , Yuxiu SUN , Junxiang TANG , Keting TONG , Jiansheng ZHU
Published: September 2020

Objective: To assess the positive predictive value (PPV) of non-invasive prenatal testing (NIPT) as a screening test for sex chromosome aneuploidy (SCA) with different maternal characteristics and prenatal decision in positive cases. Materials and Methods: We retrospectively analyzed 45773 singleton pregnancies with different characteristics that were subjected to NIPT in Maternity and Child Health Hospital of Anhui Province. The results were validated by karyotyping. Clinical data, diagnostic results, and pregnancy outcomes were collected.Results: A total of 314 cases were SCA positive by NIPT; among those, 143 underwent invasive prenatal diagnostic testing, and 58 resulted as true-positive. Overall, the PPV for 45,X, 47,XXX, 47,XXY and 47,XYY was 12.5%, 51.72%, 66.67% and 83.33%, respectively. Interestingly, when screening only pregnant women in advanced maternal age (AMA), the PPV for 45,X, 47,XXX, 47,XXY and 47,XYY was 23.81%, 53.33%, 78.95%, and 66.67%, respectively. AMA was a high-risk predictor of having a fetus with SCA. The frequencies of 47, XXX, and 47,XXY were significantly correlated with maternal age.Conclusion: NIPT performed better in predicting sex chromosome trisomies than monosomy X, and patients with 45,X positive fetus were more eager to terminate pregnancy compared to those with 47,XXX and 47, XYY. Our findings may assist in genetic counseling of AMA pregnant women. Our Pre- and post-test counseling are essential for familiarizing pregnant women with the benefits and limitations of the NIPT, which may ease their anxiety and provide them with the informed choice for further diagnosis and pregnancy decision.
Fatigue Analysis of Sub-frame Based on Load Spectrum Extrapolation
Authors: Dong Guojiang , Du Fei , Wei Liuwei , Han Jie
Published: September 2020

The extrapolation of the whole life load spectrum from the strengthened road load spectrum in the test site is the key factor for the accuracy of the fatigue durability evaluation of automobile components. In this paper, aiming at the limitation of parameter method extrapolation single distribution estimation, the non parametric extrapolation estimation is introduced to describe the comprehensive characteristics of the load spectrum distribution, and the two extrapolation methods are compared parametrically, and the optimal fitting extrapolation spectrum is selected to carry out the fatigue damage analysis of the sub-frame. Based on the real vehicle test in the proving ground strengthened road, the stress spectrum of the dangerous point of the sub-frame is extracted by co-simulation of multi-body dynamics and finite element method. The parametric method and non-parametric method are used to calculate the goodness of fit of stress spectrum, the optimal mean value and amplitude value probability density of stress spectrum are selected according to the goodness of fit, and the stress spectrum cycle was extrapolated to 106 times, and then the stress spectrum was divided into eight levels. According to Miner criterion, Haibach and NASA S-N curve correction models considering small load damage were respectively used to estimate fatigue damage of front sub-frame. The results show that the fitting effect of non-parametric extrapolation is better than that of parametric extrapolation, and the goodness of fit of equivalent amplitude is 98.6%, which improves the description accuracy of stress spectrum distribution characteristics and provides more accurate extrapolation spectrum for fatigue durability evaluation of components. Based on the extrapolated spectrum and using Haibach model and NASA model to study the fatigue damage of sub-frame, it is shown that NASA model is more suitable for reliability design of components, while Haibach model is suitable for lightweight design of components.
Successful treatment of COVID-19 with remdesivir in the absence of humoral immunity
Authors: Buckland Matthew S , Galloway James , Fhogartaig Caoimhe Nic , Meredith Luke , Provine Nicholas M. , Bloor Stuart , Ogbe Ane , Zelek Wioleta M. , Smielewska Anna , Yakovleva Anna , Mann Tiffeney , Bergamaschi Laura , Turner Lorinda , Mescia Frederica , Toonen Erik J.M. , Hackstein Carl-Philipp , Akther Hossain Delowar , Vieira Vinicius Adriano , Ceron-Gutierrez Lourdes , Periselneris Jimstan , Kiani-Alikhan Sorena , Grigoriadou Sofia , Vaghela Devan , Lear Sara E. , Torok Estee , Hamilton William L. , Quick Josh , Stockton Joanne , Nelson Peter , Hunter Michael , Coulter Tanya I , Devlin Lisa , Bradley John , Smith Ken , Ouwehand Willem , Estcourt Lise , Simmonds Heli Harvala , Roberts Dave , Wilkinson Ian , Screaton Nick , Loman Nick , Lyons Paul , Doffinger Rainer , Morgan Paul , Goodfellow Ian , Klenerman Paul , Lehner Paul , Matheson Nick , Thaventhiran James
Published: September 2020

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the successful use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. His unusual clinical course identifies a key role for SARS-CoV-2 antibodies in both viral clearance and progression to severe disease. In the absence of these confounders, we took an experimental medicine approach to examine the in vivoutility of remdesivir. Over two independent courses of treatment, we observed a dramatic, temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide unambiguous evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.
In vivo Antimalarial Activity of the Hydroalcoholic Extract of Kniphofia foliosa Hochst and Its Constituents
Authors: Alebachew Yonatan , Bisrat Daniel , Tadesse Solomon , Asres Kaleab
Published: September 2020

Background: Kniphofia foliosa Hochst is endemic to Ethiopian highlands, where its rhizomes are traditionally used for the treatment of malaria, abdominal cramps and wound healing. As a continuation of our search for antimalarial compounds from Ethiopian medicinal plants, we have tested the 80% methanol extract of K. foliosa rhizomes and its constituents against Plasmodium berghei in mice. Methods: Isolation was carried out using column and preparative thin layer chromatography (PTLC). The chemical structures of the compounds were elucidated by spectroscopic methods (ESI-MS, 1D and 2D-NMR). Peters’ 4-day suppressive test against P. berghei in mice was utilized for in vivo antimalarial evaluation of the test substances. Results: Three compounds, namely knipholone, dianellin, and 12-hydroxypentadec-9-en-1-yl methyl phthalate (HPMP) were isolated and characterized from the 80% methanolic extract of K. foliosa rhizomes. The hydroalcoholic extract (400 mg/kg) and knipholone (200 mg/kg) showed the highest activity with chemosuppression values of 61.52 and 60.16%, respectively. From the dose-response plot, the median effective (ED50) doses of knipholone and dianellin were determined to be 81.25 and 92.31 mg/kg, respectively. Molecular docking study revealed that knipholone had a strong binding affinity to Plasmodium falciparum l-lactate dehydrogenase (pfLDH) target. Conclusion: Results of the current study support the traditional use of the plant for the treatment of malaria.
Identifying Human Postural Dynamics and Control from Unperturbed Balance
Authors: Lee Jongwoo , Zhang Kuangen , Hogan Neville
Published: September 2020

Backgrounds: Upright standing requires control of an inherently unstable multi-joint human body within a small base of support, despite biological motor and / or sensory noise which challenge balance. Without applying perturbations, system identification methods have been regarded as inadequate, because the relevant internal biological noise processes are not accessible to direct measurement. As a result, unperturbed balance studies have been limited to investigation of subjects' behavioral response patterns rather than possible underlying control strategies. Methods: In this paper, we present a mathemathically rigorous system identification method that is applicable to study the dynamics and control of unperturbed balance. The method is derived from autocorrelation matrices with non-zero time lags and identifies the system matrix of a discrete-time dynamic system in the presence of unknown noise processes, without requiring any information about the strength of the noise. Results: Unlike reasonable `least-squares' approaches, the performance of the new method is consistent across a range of different combinations of internal and measurement noise strengths, even when measurement noise is substantial. We present a numerical example of a model that simulates human upright balancing and show that its dynamics can be identified accurately. With a biomechanically reasonable choice of state and input variables, a state feedback controller can also be identified. Conclusions: Our numerical results indicate that the system identification method proposed in this paper is applicable to real-world experimental data. Using this method, the dynamics and control of human quiet standing can be studied in depth without concern for adaptation or possible reflex responses evoked by external perturbations, or any need for expensive high-precision measurement equipment. This may enable diagnosis and treatment of individual subjects with impaired balance, and the development of safe and effective assistive and / or rehabilitative technologies.
Developmental Exposure to DDT or DDE Alters Sympathetic Innervation of Brown Adipose in Adult Female Mice
Authors: vonderEmbse Annalise N , Elmore Sarah E , Jackson Kyle B , Habecker Beth A , Manz Katherine E , Pennell Kurt D , Lein Pamela J , Merrill Michele La
Published: September 2020

Background: Exposure to the bioaccumulative pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE) has been associated with increased risk of insulin resistance and obesity in humans and experimental animals. These effects appear to be mediated by reduced brown adipose tissue (BAT) thermogenesis, which is regulated by the sympathetic nervous system. Although the neurotoxicity of DDT is well-established, whether DDT alters sympathetic innervation of BAT is unknown. We hypothesized that perinatal exposure to DDT or DDE promotes thermogenic dysfunction by interfering with sympathetic regulation of BAT thermogenesis. Methods: Pregnant C57BL/6J mice were exposed by oral gavage to environmentally relevant concentrations of DDT (1.7 mg/kg) or DDE (1.31 mg/kg) from gestational day 11.5 to postnatal day 5, and longitudinal body temperature was recorded in male and female offspring. At 4 months of age, metabolic parameters were measured in female offspring via indirect calorimetry with or without the β3 adrenergic receptor agonist, CL 316,243. Immunohistochemical and neurochemical analyses of sympathetic neurons innervating BAT were evaluated.Results: We observed persistent thermogenic impairment in adult female, but not male, mice perinatally exposed to DDT or DDE. Perinatal DDT exposure significantly impaired metabolism in adult female mice, an effect rescued by treatment with CL 316,243 immediately prior to calorimetry experiments. Neither DDT nor DDE significantly altered BAT morphology or the concentrations of norepinephrine and its metabolite DHPG in the BAT of DDT-exposed mice. However, quantitative immunohistochemistry revealed a 20% decrease in sympathetic axons innervating BAT in adult female mice perinatally exposed to DDT, but not DDE, and 48% and 43% fewer synapses in stellate ganglia of mice exposed to either DDT or DDE, respectively, compared to control. Conclusions: These data demonstrate that perinatal DDT and DDE exposure impairs thermogenesis by interfering with patterns of connectivity in sympathetic circuits that regulate BAT.
Effect of Integrated Training on Balance and Ankle Position Sense in Ballet Dancers
Authors: Lin Chai-Wei , Chen Yi-An , You Yu-Lin , Wu Tzu-Chan , Lin Cheng-Feng
Published: September 2020

Background: Ballet dancers are at high risk of ankle sprain. As a result, effective training programs are required for ballet dancers to minimize injury occurrence and improve their balance ability. Our purpose was to investigate the effects of a 6-week integrated training program on the ankle joint position sense and postural stability in ballet dancers.Methods: Twenty-nine female ballet dancers were recruited to the study. Sixteen of the dancers underwent a 6-week integrated training program consisting of plyometric, proprioception and core stability exercises. The remaining ballet dancers performed no additional training, but continued regular ballet practice as usual. For both groups, ankle joint position sensing tests were performed before and after training. Furthermore, for the training group, the postural stability was assessed by measuring the average speed of the center of pressure (COP) and the maximum ankle joint displacements while performing grand plie (deep squatting) and releve en demi-pointe (standing on balls of foot) movements.Results: After 6 weeks, both groups showed significantly smaller absolute ankle joint reposition errors in plantarflexion and eversion. Furthermore, the training group showed a significantly smaller ankle joint reposition error in dorsiflexion. The training group also showed a significantly slower average COP speed and smaller maximum COP displacement in the medial-lateral direction.Conclusions: The 6-week integrated training program improved the ankle joint position sense in dorsiflexion and the postural control in the medial-lateral direction while performing grand-plie and releve en demi-pointe movements. Thus, this integrated training program can be suggested for dancers in order to improve ankle position sense and postural stability during ballet movements.