bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of seven in silico tools for evaluating of daphnia and fish acute toxicity: case study on Chinese Priority Controlled Chemicals and new chemicals
Authors: Zhou Linjun , Fan Deling , Yin Wei , Gu Wen , Wang Zhen , Liu Jining , Xu Yanhua , Shi Lili , Liu Mingqing , Ji Guixiang 
Published: March 2021

Abstract
Background
A number of predictive models for aquatic toxicity are available, however, the accuracy and extent of easy to use of these in silico tools in risk assessment still need further studied. This study evaluated the performance of seven in silico tools to daphnia and fish: ECOSAR, T.E.S.T., Danish QSAR Database, VEGA, KATE, Read Across and Trent Analysis. 37 Priority Controlled Chemicals in China (PCCs) and 92 New Chemicals (NCs) were used as validation dataset.

Results
In the quantitative evaluation to PCCs with the criteria of 10-fold difference between experimental value and estimated value, the accuracies of VEGA is the highest among all of the models, both in prediction of daphnia and fish acute toxicity, with accuracies of 100% and 90% after considering AD, respectively. The performance of KATE, ECOSAR and T.E.S.T. is similar, with accuracies are slightly lower than VEGA. The accuracy of Danish Q.D. is the lowest among the above tools with which QSAR is the main mechanism. The performance of Read Across and Trent Analysis is lowest among all of the tested in silico tools. The predictive ability of models to NCs was lower than that of PCCs possibly because never appeared in training set of the models, and ECOSAR perform best than other in silico tools.

Conclusion
QSAR based in silico tools had the greater prediction accuracy than category approach (Read Across and Trent Analysis) in predicting the acute toxicity of daphnia and fish. Category approach (Read Across and Trent Analysis) requires expert knowledge to be utilized effectively. ECOSAR performs well in both PCCs and NCs, and the application shoud be promoted in both risk assessment and priority activities. We suggest that distribution of multiple data and water solubility should be considered when developing in silico models. Both more intelligent in silico tools and testing are necessary to identify hazards of Chemicals.
m7GDisAI: N7-methylguanosine (m7G) sites and diseases associations inference based on heterogeneous network
Authors: Ma Jiani , Zhang Lin , Chen Jin , Song Bowen , Zang Chenxuan , Liu Hui 
Published: March 2021

Abstract
Background
Recent studies have confirmed that N7-methylguanosine (m7G) modification plays an important role in regulating various biological processes and has associations with multiple diseases. Wet-lab experiments are cost and time ineffective for the identification of disease-associated m7G sites. To date, tens of thousands of m7G sites have been identified by high-throughput sequencing approaches and the information is publicly available in bioinformatics databases, which can be leveraged to predict potential disease-associated m7G sites using a computational perspective. Thus, computational methods for m7G-disease association prediction are urgently needed, but none are currently available at present.

Results
To fill this gap, we collected association information between m7G sites and diseases, genomic information of m7G sites, and phenotypic information of diseases from different databases to build an m7G-disease association dataset. To infer potential disease-associated m7G sites, we then proposed a heterogeneous network-based model, m7G Sites and Diseases Associations Inference (m7GDisAI) model. m7GDisAI predicts the potential disease-associated m7G sites by applying a matrix decomposition method on heterogeneous networks which integrate comprehensive similarity information of m7G sites and diseases. To evaluate the prediction performance, 10 runs of tenfold cross validation were first conducted, and m7GDisAI got the highest AUC of 0.740(± 0.0024). Then global and local leave-one-out cross validation (LOOCV) experiments were implemented to evaluate the model’s accuracy in global and local situations respectively. AUC of 0.769 was achieved in global LOOCV, while 0.635 in local LOOCV. A case study was finally conducted to identify the most promising ovarian cancer-related m7G sites for further functional analysis. Gene Ontology (GO) enrichment analysis was performed to explore the complex associations between host gene of m7G sites and GO terms. The results showed that m7GDisAI identified disease-associated m7G sites and their host genes are consistently related to the pathogenesis of ovarian cancer, which may provide some clues for pathogenesis of diseases.

Conclusion
The m7GDisAI web server can be accessed at http://180.208.58.66/m7GDisAI/, which provides a user-friendly interface to query disease associated m7G. The list of top 20 m7G sites predicted to be associted with 177 diseases can be achieved. Furthermore, detailed information about specific m7G sites and diseases are also shown.
Transcriptome analyses of 7-day-old zebrafish larvae possessing a familial Alzheimer’s disease-like mutation in psen1 indicate effects on oxidative phosphorylation, ECM and MCM functions, and iron homeostasis
Authors: Dong Yang , Newman Morgan , Pederson Stephen M. , Barthelson Karissa , Hin Nhi , Lardelli Michael 
Published: March 2021

Abstract
Background
Early-onset familial Alzheimer’s disease (EOfAD) is promoted by dominant mutations, enabling the study of Alzheimer’s disease (AD) pathogenic mechanisms through generation of EOfAD-like mutations in animal models. In a previous study, we generated an EOfAD-like mutation, psen1Q96_K97del, in zebrafish and performed transcriptome analysis comparing entire brains from 6-month-old wild type and heterozygous mutant fish. We identified predicted effects on mitochondrial function and endolysosomal acidification. Here we aimed to determine whether similar effects occur in 7 day post fertilization (dpf) zebrafish larvae that might be exploited in screening of chemical libraries to find ameliorative drugs.

Results
We generated clutches of wild type and heterozygous psen1Q96_K97del 7 dpf larvae using a paired-mating strategy to reduce extraneous genetic variation before performing a comparative transcriptome analysis. We identified 228 differentially expressed genes and performed various bioinformatics analyses to predict cellular functions.

Conclusions
Our analyses predicted a significant effect on oxidative phosphorylation, consistent with our earlier observations of predicted effects on ATP synthesis in adult heterozygous psen1Q96_K97del brains. The dysregulation of minichromosome maintenance protein complex (MCM) genes strongly contributed to predicted effects on DNA replication and the cell cycle and may explain earlier observations of genome instability due to PSEN1 mutation. The upregulation of crystallin gene expression may be a response to defective activity of mutant Psen1 protein in endolysosomal acidification. Genes related to extracellular matrix (ECM) were downregulated, consistent with previous studies of EOfAD mutant iPSC neurons and postmortem late onset AD brains. Also, changes in expression of genes controlling iron ion transport were observed without identifiable changes in the prevalence of transcripts containing iron responsive elements (IREs) in their 3′ untranslated regions (UTRs). These changes may, therefore, predispose to the apparent iron dyshomeostasis previously observed in 6-month-old heterozygous psen1Q96_K97del EOfAD-like mutant brains.
Differential polarization and the expression of efferocytosis receptor MerTK on M1 and M2 macrophages isolated from coronary artery disease patients
Authors: Mohd Idrus Fatin Najiah , Ahmad Nurul Shuhadah , Hoe Chee Hock , Azlan Maryam , Norfuad Farisha Alia , Yusof Zurkurnai , Wan Isa Wan Yus Haniff , Mohamed Ali Akbar Ali , Yvonne-Tee Get Bee 
Published: March 2021

Abstract
Background
Differential polarization of macrophage into M1 and M2 mediates atherosclerotic plaque clearance through efferocytosis. Higher expression of Mer proto-oncogene tyrosine kinase (MerTK) on M2 macrophage helps in maintaining macrophage efferocytic efficiency. In healthy individuals, macrophage polarization into M1 and M2 occurs in tissues in concomitance with the acquisition of functional phenotypes depending on specific microenvironment stimuli. However, whether the macrophage differential polarization and MerTK expression vary in coronary artery disease (CAD) patients remain unknown.

Objective
This study aimed to elucidate the polarization of M1 and M2 macrophage from CAD patients as well as to investigate the expression of MerTK in these macrophage phenotypes.

Methods
A total of 14 (n) CAD patients were recruited and subsequently grouped into “no apparent CAD”, “non-obstructive CAD” and “obstructive CAD” according to the degree of stenosis. Thirty ml of venous blood was withdrawn to obtain monocyte from the patients. The M1 macrophage was generated by treating the monocyte with GMCSF, LPS and IFN-γ while MCSF, IL-4 and IL-13 were employed to differentiate monocyte into M2 macrophage. After 7 days of polarization, analysis of cell surface differentiation markers (CD86+/CD80+ for M1 and CD206+/CD200R+ for M2) and measurement of MerTK expression were performed using flow cytometry.

Results
Both M1 and M2 macrophage expressed similar level of CD86, CD80 and CD206 in all groups of CAD patients. MerTK expression in no apparent CAD patients was significantly higher in M2 macrophage compared to M1 macrophage [12.58 ± 4.40 vs. 6.58 ± 1.37, p = 0.040].

Conclusion
Differential polarization of macrophage into M1 and M2 was highly dynamic and can be varied due to the microenvironment stimuli in atherosclerotic plaque. Besides, higher expression of MerTK in patients with the least coronary obstructive suggest its vital involvement in efferocytosis.
Zinc oxide nanoparticles alleviate the arsenic toxicity and decrease the accumulation of arsenic in rice (Oryza sativa L.)
Authors: Yan Shiwei , Wu Fan , Zhou Song , Yang Jianhao , Tang Xianjin , Ye Wenling 
Published: March 2021

AbstractBackgroundRice is particularly effective, compared to other cereals, at accumulating arsenic (As), a nonthreshold, class 1 human carcinogen in shoot and grain. Nano-zinc oxide is gradually used in agricultural production due to its adsorption capacity and as a nutrient element. An experiment was performed to explore the effects of zinc oxide nanoparticles (nZnO) on arsenic (As) toxicity and bioaccumulation in rice. Rice seedlings were treated with different levels of nZnO (0, 10, 20, 50, 100 mg/L) and As (0, and 2 mg/L) for 7 days.ResultsThe research showed that 2 mg/L of As treatment represented a stress condition, which was evidenced by phenotypic images, seedling dry weight, chlorophyll, and antioxidant enzyme activity of rice shoot. The addition of nZnO (10–100 mg/L) enhanced the growth and photosynthesis of rice seedlings. As concentrations in the shoots and roots were decreased by a maximum of 40.7 and 31.6% compared to the control, respectively. Arsenite [As (III)] was the main species in both roots (98.5–99.5%) and shoots (95.0–99.6%) when exposed to different treatments. Phytochelatins (PCs) content up-regulated in the roots induced more As (III)-PC to be complexed and reduced As (III) mobility for transport to shoots by nZnO addition.ConclusionThe results confirmed that nZnO could improve rice growth and decrease As accumulation in shoots, and it performs best at a concentration of 100 mg/L.
Smart@home – supporting safety and mobility of elderly and care dependent people in their own homes through the use of technical assistance systems and conventional mobility supporting tools: a cross-sectional survey
Authors: Jachan Deborah Elisabeth , Müller-Werdan Ursula , Lahmann Nils Axel , Strube-Lahmann Sandra 
Published: March 2021

Abstract
Background
The use of technical solutions and conventional mobility supporting aids can support the independence of people into old age in their own homes. However, we found relatively few empirical investigations on the effects and costs of these systems.

Methods
The aim of the study was to investigate usability, user satisfaction and the correlation between costs and benefits of different built-in smart home solutions and conventional mobility supporting tools in the home of elderly, partially care-dependent tenants (> 65 years). A cross-sectional survey was conducted from February to March 2018 with tenants of a housing association in apartments equipped with smart home technology and conventional mobility supporting tools. The response rate in the intervention group was n = 37 persons (out of 46 tenants with installed smart home and conventional solutions) and in the control group n = 64 persons (out of 100 tenants without built-in smart home and conventional solutions). Data were collected by a written questionnaire regarding usability and satisfaction of the tenants with the built-in smart home solutions and conventional mobility supporting tools. In addition, both the intervention and the control group were asked general questions about communication, safety and how to deal with the need for long-term care in their own living environment.

Results
Results showed that with regard to usability, satisfaction and price performance ratio of the installed smart home solutions, the installation of the corresponding solutions with an overall score of 1.41 (on a scale of 1 (very good) to 6 (unsatisfactory)) was mostly positively evaluated by the tenants. Overall, users rated the installed smart home solutions better than the conventional mobility supporting tools (such as handholds and increased balcony floor level).

Conclusions
Analysis of the price performance ratio showed that smart home solutions are generally more expensive than conventional tools, but also contribute significantly to an increased security of the tenants, and thus may enable longer living in a familiar environment. We recommend modularized offers consisting of various components of smart home solutions, since this significantly reduces installation costs and allows for an individual composition according to requirements. Moreover, smart home solutions should be considered to be listed as medical aids.
Health lifestyles and Chinese oldest-old’s subjective well-being—evidence from a latent class analysis
Authors: Zhang Li , Bi Xiangyang , Ding Zhihong 
Published: March 2021

Abstract
Background
Previous research on the associations between lifestyle behaviors and health has largely focused on morbidity, mortality and disease prevention. More attention should be paid to examining relationships between lifestyle behaviors and positive health outcomes such as well-being. The aim of the study was to classify Chinese oldest-old’s health lifestyles and evaluate the manner in which health lifestyles have impacted Chinese oldest-old’s subjective well-being.

Methods
Analyzing the 2014 Chinese Longitudinal Healthy Longevity Survey (CLHLS), latent class analysis was applied to identify predominant health lifestyles among Chinese oldest-old aged 85 to 105. Ordinary Least Square (OLS) regression models were used to assess the effects of health lifestyles on Chinese oldest-old’s subjective well-being, adjusting for socio-demographic characteristics.

Results
Four distinct classes representing health lifestyles emerged. Health lifestyles were found to be strongly associated with Chinese oldest-old’s subjective well-being, even after controlling for demographic features as well as individual and parental socioeconomic disadvantage. Findings showed that healthy lifestyle behaviors stimulated Chinese oldest-old’s positive feelings and led to better evaluative subjective well-being. In contrast, less healthy lifestyle behaviors can be a predictor of negative feelings.

Conclusions
The regression results highlighted the importance of integrating health lifestyle choices in promoting oldest-old’s psychological well-being. Elders can tackle healthier lifestyle behaviors in their daily lives to reduce the risk of mental health problems. Practicing healthy lifestyles should be integrated in programs for mental health promotion.
Follow-up study on serum cholesterol profiles and potential sequelae in recovered COVID-19 patients
Authors: Li Guiling , Du Li , Cao Xiaoling , Wei Xiuqi , Jiang Yao , Lin Yuqi , Nguyen Vi , Tan Wenbin , Wang Hui 
Published: March 2021

Abstract
Background
COVID-19 patients develop hypolipidemia. However, it is unknown whether lipid levels have improved and there are potential sequlae in recovered patients.

Objective
In this follow-up study, we evaluated serum lipidemia and various physiopathological laboratory values in recovered patients.

Methods
A 3–6 month follow-up study was performed between June 15 and September 3, 2020, to examine serum levels of laboratory values in 107 discharged COVID-19 patients (mild = 59; severe/critical = 48; diagnoses on admission). Sixty-one patients had a revisit chest CT scan. A Wilcoxon signed-rank test was used to analyze changes in laboratory values at admission and follow-up.

Results
LDL-c and HDL-c levels were significantly higher at follow-up than at admission in severe/critical cases (p <  0.05). LDL-c levels were significantly higher at follow-up than at admission in mild cases (p <  0.05). Coagulation and liver functional values were significantly improved at follow-up than at admission for patients (p <  0.05). Increases in HDL-c significantly correlated with increases in numbers of white blood cells (p <  0.001) during patients’ recovery. With exclusion of the subjects taking traditional Chinese medicines or cholesterol-lowering drugs, LDL-c and HDL-c levels were significantly increased at follow-up than at admission in severe/critical cases (p <  0.05). Residue lesions were observed in CT images in 72% (44 of 61) of follow-up patients.

Conclusions
Improvements of LDL-c, HDL-c, liver functions, and incomplete resolution of lung lesions were observed at 3–6 month follow-up for recovered patients, indicating that a long-term recovery process could be required and the development of sequelae such as pulmonary fibrosis could be expected in some patients.
Current trends and geographical differences in therapeutic profile and outcomes of COVID-19 among pregnant women - a systematic review and meta-analysis
Authors: Dubey Pallavi , Thakur Bhaskar , Reddy Sireesha , Martinez Carla A. , Nurunnabi Md , Manuel Sharron L. , Chheda Sadhana , Bracamontes Christina , Dwivedi Alok K. 
Published: March 2021

AbstractBackgroundCoronavirus disease (COVID-19) has been associated with adverse pregnancy outcomes. Due to the lack of effective treatments for COVID-19, it becomes imperative to assess the geographical differences and trends in the current clinical care and outcomes of COVID-19 in pregnant women.MethodsA PubMed search was performed to screen articles reporting therapeutics and outcomes of confirmed COVID-19 in pregnant women prior to August 27, 2020. We performed searches, quality assessments of eligible studies, extracted and reported data according to PRISMA guidelines. Meta-analyses and cumulative meta-analyses of proportions were performed for estimating each outcome and their pattern over time respectively.ResultsOne thousand two hundred thirty nine pregnant women with COVID-19 from 66 studies were analyzed. In case series analysis reflecting average-risk patients, the proportion of oxygen support, antibiotics, antivirals, and plasma therapy administration except for hydroxychloroquine was substantially higher in Asian studies (55, 78, 80, 6, and 0%) compared to the US (7, 1, 12, 0, and 7%) or European (33, 12, 14, 1, and 26%) studies, respectively. The highest preterm birth and the average length of hospital stay (35%, 11.9 days) were estimated in Asian studies compared to the US studies (13%, 9.4 days) and European studies (29%, 7.3 days), respectively. Even in case reports reflecting severe cases, the use of antivirals and antibiotics was higher in Asian studies compared to the US, Latin American, and European studies. A significant decline in the use of most therapeutics along with adverse outcomes of COVID-19 in pregnant women was observed.ConclusionsGeographical differences in therapeutic practice of COVID-19 were observed with differential rates of maternal and clinical outcomes. Minimizing the use of some therapeutics particularly antibiotics, antivirals, oxygen therapy, immunosuppressants, and hydroxychloroquine by risk stratification and careful consideration may further improve maternal and clinical outcomes.
EML4-ALK induces cellular senescence in mortal normal human cells and promotes anchorage-independent growth in hTERT-transduced normal human cells
Authors: Miyanaga Akihiko , Matsumoto Masaru , Beck Jessica A. , Horikawa Izumi , Oike Takahiro , Okayama Hirokazu , Tanaka Hiromi , Burkett Sandra S. , Robles Ana I. , Khan Mohammed , Lissa Delphine , Seike Masahiro , Gemma Akihiko , Mano Hiroyuki , Harris Curtis C. 
Published: March 2021

Abstract
Background
Chromosomal inversions involving anaplastic lymphoma kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4) generate a fusion protein EML4-ALK in non-small cell lung cancer (NSCLC). The understanding of EML4-ALK function can be improved by a functional study using normal human cells.

Methods
Here we for the first time conduct such study to examine the effects of EML4-ALK on cell proliferation, cellular senescence, DNA damage, gene expression profiles and transformed phenotypes.

Results
The lentiviral expression of EML4-ALK in mortal, normal human fibroblasts caused, through its constitutive ALK kinase activity, an early induction of cellular senescence with accumulated DNA damage, upregulation of p16INK4A and p21WAF1, and senescence-associated β-galactosidase (SA-β-gal) activity. In contrast, when EML4-ALK was expressed in normal human fibroblasts transduced with telomerase reverse transcriptase (hTERT), which is activated in the vast majority of NSCLC, the cells showed accelerated proliferation and acquired anchorage-independent growth ability in soft-agar medium, without accumulated DNA damage, chromosome aberration, nor p53 mutation. EML4-ALK induced the phosphorylation of STAT3 in both mortal and hTERT-transduced cells, but RNA sequencing analysis suggested that the different signaling pathways contributed to the different phenotypic outcomes in these cells. While EML4-ALK also induced anchorage-independent growth in hTERT-immortalized human bronchial epithelial cells in vitro, the expression of EML4-ALK alone did not cause detectable in vivo tumorigenicity in immunodeficient mice.

Conclusions
Our data indicate that the expression of hTERT is critical for EML4-ALK to manifest its in vitro transforming activity in human cells. This study provides the isogenic pairs of human cells with and without EML4-ALK expression.