bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of Lung Tumor Model for Drug Screening Based on 3D Bio-Printing Technology
Authors: Yang Yadong , Yang Geng , Liu Xingzhu , Xu Yimeng , Zhao Siyu , Zhang Wenyuang 
Published: August 2020

Abstract
Background: The sensitivity of two-dimensional (2D) cultured cells to the drugs cannot effectively mimic the effect of the drug in vivo, although 2D cell culture is the most widely used model for drug screening. With the development of tissue engineering, people are committed to developing 3D tissue models that can better reflect the biology in vivo, and tend to be mass and miniaturized. In this study, three-dimensional (3D) bio-printing was used to develop an appropriate 3D model for screening sensitive anti-lung cancer drugs in vitro. Methods: A549 lung cancer cells were mixed with sodium alginate/gelatin as bio-printing ink to fabricate a cell-laden hydrogel grid scaffold structure. The sensitivity of the printed 3D model to drugs was evaluated with eight anti-tumor traditional Chinese medicines (Oldenlandia，Atractylodes，Mylabris，S. Barbata，Zedoary，Nigrum，Cremastra and Prunella). The crude Chinese medicine was treated by water extraction and alcohol precipitation. A fluorescent live/dead staining was carried out at different time to assess the cell survival rate in the 3D scaffolds. MTT assay was used to determine the inhibitory rate of eight antitumor traditional Chinese medicines on A549 cell proliferation in 3D-printed lung tumor models and conventional 2D culture models. The data of each group were analyzed to clarify the difference between 2D and 3D cultures, and to evaluate the feasibility of 3D-printed lung tumor model as a drug screening model. Results: The growth states of A549 cells on the 3D scaffolds were different from 2D culture. The effect of various traditional Chinese medicines on the proliferation inhibition of tumor cells was positively correlated with the drug concentration, The inhibition rate of 2D cell culture was higher than that of 3D cell culture. However, microscopic observation showed that there were more dead cells in 3D culture than in 2D culture. But the fluorescence value detected by EGFP labeled cells was consistent with the results of MTT. Conclusions: We conclude that 3D printed lung tumor model can be used for drug screening. Before drug screening enters animal level, tissue level screening can be carried out by 3D printed tumor model.
Modern Health Service utilization and associated factors among adults in Southern, Ethiopia
Authors: BITEW SHIMELASH , Mekonen Nigussie , W/Michael Mulugeta , Molla Getahun , Abrha Solomon , Zema Zewde , Tadesse Takele 
Published: August 2020

Abstract
Background Ethiopian government is striving to improve the health status of its population through the expansion and strengthening of primary health care services in both rural and urban settings of the country. The study aimed to measure modern health service utilization and associated factors in Wolaita Sodo town, Ethiopia.Method: A cross-sectional study design was implemented from May to June 2019 in Wolaita Sodo town Ethiopia. All 786 study participants were selected by multistage systematic random sampling. Data were collected by face to face interviews using a pretested structured questionnaire. Data were collected by an open data kit. Stata window version 15.0 was also employed for statistical analysis. Multiple logistic regression was conducted, and a 95% confidence interval was considered for interpretation.Result Health service utilization were 77.2% with (95% CI of 74.1%,80.0%). In terms of health facility in which they visit first 50.6% were at the public health center and 25.5% of them were at Teaching and Referral Hospital. Respondents with marital status married and widowed have higher odds of utilizing health service compared to single marital status [AOR:2.96; 95% CI: 1.7–5.2 and 9.0; 95% CI: 1.69-48.0] respectively. Respondents with middle and highest wealth status have higher odds of health service utilization than poor wealth status with AOR (1.75 95%CI 1.03–2.97 and 1.58 95% CI; 1.01,2.77). Similarly, Respondents who had chronic disease and Perceived health status who had poor have higher odds of health service utilization.Conclusion Modern health services utilization was found to be unsatisfactory. Being married, wealth status being middle and high, having chronic health conditions, and having poor perceived health status were found to have a statistically significant association with health service utilization.
Regulation of DNA Methylation on Key Parasitism Genes of Cysticercus Cellulosae Revealed by Integrative Epigenomic-Transcriptomic Analyses
Authors: Wang Xinrui , Song Weiyi , Song Yining , Ji Guanyu , Luo Xuenong , Sun Shumin 
Published: August 2020

Abstract
Background: The life cycle of Taenia solium is characterized by different stages of development, requiring various kinds of hosts that can appropriately harbor the eggs (proglottids), the oncospheres, the larvae and the adults. Similar to other metazoan pathogens, T. solium undergoes transcriptional and developmental regulation via epigenetics during its complex lifecycle and host interactions.Result: In the present study, we integrated whole-genome bisulfite sequencing and RNA-seq technologies to characterize the genome-wide DNA methylation and its effect on transcription of Cysticercus cellulosae of T. solium. We confirm that the T. solium genome in the cysticercus stage is epigenetically modified by DNA methylation in a pattern similar to that of other invertebrate genomes, i.e., sparsely or moderately methylated. We also observed an enrichment of non-CpG methylation in defined genetic elements of the T. solium genome. Furthermore, an integrative analysis of both the transcriptome and the DNA methylome indicated a strong correlation between these two datasets, suggesting that gene expression might be tightly regulated by DNA methylation. Importantly, our data suggested that DNA methylation might play an important role in repressing key parasitism-related genes, including genes encoding excretion-secretion proteins, thereby raising the possibility of targeting DNA methylation processes as a useful strategy in therapeutics of cysticercosis.
A Potential Suite of Climate Markers of Long-Chain n-Alkanes and Alkenones Preserved in the top Sediments from the Pacific Sector of the Southern Ocean
Authors: Chen Xin , Liu Xiaodong , Lin Da-Cheng , Wang Jianjun , Chen Liqi , Yu Pai-Sen , Wang Linmiao , Xiong Zhifang , Chen Min-Te 
Published: August 2020

Abstract
Investigation of organic compounds in marine sediments can potentially unlock a wealth of new information in these overlooked climate archives. Here we present pilot study results of organic geochemical features of long-chain n-alkanes and alkenones and individual carbon isotope ratios of long-chain n-alkanes from a newly collected, approximately 8-meter long, Pleistocene age sediment core, located in the far reaches of the Pacific sector of the Southern Ocean. We initially analyzed a suite of organic compounds in the core, and the results show abundant long-chain n-alkanes (C29-C35) with predominant odd-over-even carbon preference, which suggests an origin of terrestrial higher plant waxes via long range transport of dust, possibly from Australia and New Zealand. The δ13C values of the C31 n-alkane range from -29.4 to -24.8‰, in which the higher δ13C values suggest more contributions from C4 plants waxes. In the analysis, we found that the mid-chain n-alkanes (C23-C25) have small odd-over-even carbon preference, suggesting that they were derived from marine non-diatom pelagic phytoplankton and microalgae, and terrestrial sources. Furthermore, the C26 and C28 with lower δ13C values (~ -34‰) indicate an origin from marine chemoautotrophic bacteria. We found that the abundances of tetra-unsaturated alkenones (C37:4) in this Southern Ocean sediment core ranges from 11-37%, perhaps a marker of low sea surface temperature (SST). The results of this study strongly indicate that the δ13C values of long-chain n-alkanes and index are potentially useful to reconstruct detailed history of C3/C4 plants and SST change in the higher latitudes of the Southern Ocean.
The Utility of the Rapid Emergency Medicine Score (REMS) compared with SIRS, qSOFA and NEWS for predicting in-Hospital Mortality Among Patients with Suspicion of Sepsis in an Emergency Department
Authors: Ruangsomboon Onlak , Boonmee Phetsinee , Limsuwat Chok , Chakorn Tipa , Monsomboon Apichaya 
Published: August 2020

Abstract
Background Many early warning scores (EWSs) have been validated to prognosticate adverse outcomes secondary to sepsis in the Emergency Department (ED). These EWSs include the Systemic Inflammatory Response Syndrome criteria (SIRS), the quick Sequential Organ Failure Assessment (qSOFA) and the National Early Warning Score (NEWS). However, the Rapid Emergency Medicine Score (REMS) has never been validated for this purpose. We aimed to assess and compare the prognostic utility of REMS with that of SIRS, qSOFA and NEWS for predicting mortality in patients with suspicion of sepsis in the ED.Methods We conducted a retrospective study at the ED of Siriraj Hospital Mahidol University, Thailand. Adult patients suspected of having sepsis in the ED between August 2018 and July 2019 were included. Their EWSs were calculated. The primary outcome was all-cause in-hospital mortality. The secondary outcome was 7-day mortality.Results A total of 1622 patients were included in the study; 574 (28.2%) died at hospital discharge. REMS yielded the highest discrimination capacity for in-hospital mortality (the area under the receiver operator characteristics curves (AUROC) 0.62 (95% confidence interval (CI) 0.59, 0.65)), which was significantly higher than qSOFA (AUROC 0.58 (95%CI 0.55, 0.60); p=0.005) and SIRS (AUROC 0.52 (95%CI 0.49, 0.55); p<0.001) but not significantly superior to NEWS (AUROC 0.61 (95%CI 0.58, 0.64); p=0.27). REMS was the best EWS in terms of calibration and association with the outcome. It could also provide the highest net benefit from the decision curve analysis. Comparison of EWSs plus baseline risk model showed similar results. REMS also performed better than other EWSs for 7-day mortality.ConclusionREMS was an early warning score with higher accuracy than sepsis-related scores (qSOFA and SIRS) and had the highest utility in terms of net benefit compared to SIRS, qSOFA and NEWS in predicting in-hospital mortality in patients presenting to the ED with suspected sepsis.
Biological Properties and Pathological Stages of Chondrocyte Colony-like Clusters in Osteoarthritic Cartilage Tissue
Authors: WANG XIAOJIAN , Wei Lei , Wei Xiaochun , Xue Yan , Sun Changqi , Zhang Zhiqiang , Zhang Yang , Chen Taoyu , Lu Xiao , Guo Songjia , Chang Feng , Su Yunxing , Li Rongshan 
Published: August 2020

Abstract
Objective:In these studies,we investigated the timing and location of chondrocyte colony-like clusters in cartilage tissue during the development of human knee osteoarthritis(OA),and explored the biological properties of chondrocytes in colony-like clusters and their significance for degenerative cartilage tissue.Methods:Osteoarthritis Research Society International (OARSI) grade 0～6 cartilage tissue was obtained from the human tibial plateau, and histologicalsections were made to observe whether there were chondrocyte colony-like clusters in the cartilage tissue and where they occurred. Immunohistochemistry, PCR and western blotting were used to detect the biological properties of chondrocytes in the colony-like clusters and to describe the histopathological stages of the colony-like clusters according to the properties of thechondrocytes in the cluster.Results: There were a large number of chondrocyte colony-like clusters in the middle zone of OARSI grade 3 and grade 4 cartilage tissue.The chondrocytes in the colony-like clusters rapidly proliferated from one to a certain number and then rapidly underwent hypertrophic changes,synthesizing and releasing the MMP-13 protein to degrade cartilage tissue and enlarge chondrocyte lacunae.Eventually, the chondrocytes in the colony-like cluster underwent apoptosis and disappeared, leaving large empty chondrocyte lacunae.According to this process, chondrocyte colony-like clusters could be divided into four stages.Conclusions: Chondrocyte colony-like clusters mainly formed during the development of OA of OARSI grades 3 and 4 could cause the cartilage tissue to become looser and more porous, with more severe cartilage degeneration.
Uterotonic Effects of Aqueous and Methanolic Extracts of Lannea Acida in Wistar Rats: An in Vitro Study.
Authors: ngadjui esther simo , Kouam Jibril Yves , Bonsou Georges Romeo Fozin , Momo Aimé Césaire Tetsatsi , Deeh Patrick Brice Defo , Wankeu-Nya Modeste , Nguelefack Telesphore Benoit , Watcho Pierre 
Published: August 2020

Abstract
Background: Lannea acida (Anacardiaceae), commonly called Kikié in the Noun division (West-Cameroon), is a tree whose bark is used locally to solve difficult childbirth. This study aimed to evaluate the in vitro uterotonic effects of aqueous and methanolic extracts of L. acida in female Wistar rats. Uterine strips isolated from female rats pretreated (48h) with oestradiol (5μg) were mounted in a single-organ bath containing a well aerated and thermostated De Jalon solution (37°C). The effects of L. acida extracts were recorded in a non-cumulative manner after application. The effect of the methanolic extract (the most active extract) was monitored in the presence of atosiban (a competitive antagonist of oxytocin receptors), atropine (a specific type 3 muscarinic receptor antagonist), nifedipine (an L-type calcium channel antagonist) and 2-Aminoethoxydiphenyl borate (2-ADB, a specific antagonist of inositol 1,4,5-triphosphate receptors type 1), and in calcium-free medium containing EGTA. Results: L. acidainduced uterine contraction in a concentration-dependent manner with the methanolic extract (1.506 ± 0.032 gf) being the most effective. Administration of atosiban (2 μmol/l), atropine (1 μmol/l), nifedipine (5 μmol), 2-APB (100 μmol), and calcium free medium containing EGTA (2 mmol) reduced the contractile effect of L. acida. Complete inhibition was observed with nifedipine, 2-APB, and calcium free medium containing EGTA.Conclusions: These results suggest that L. acida possesses an uterotonic effect mediated through oxytocin receptors with mobilization of extracellular calcium.
Positive Effect of Vitamin D and Magnesium Supplementation on Mental health Status of Attention-Deficit Hyperactive Children; A Randomized Double blind Controlled Clinical Trial
Authors: Hemamy Mostafa , Pahlavani Naseh , Askari Gholamreza , Malekahmadi Mahsa 
Published: August 2020

Abstract
Background: Attention-Deficit / Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, characterized by varying severity in attention deficit and hyperactivity. Studies have shown deficiencies in the serum level of magnesium and vitamin D in ADHD. The aim of this study is to determine the effect of Vitamin D and magnesium supplementation on mental health in children with ADHD.Method: This double‑blind, randomized controlled trial was performed on 66 ADHD children. participants were randomly allocated to receive both Vitamin D (50,000 IU/week) and magnesium (6 mg/kg/day) supplements (n = 33) or placebos (n = 33) for 8 weeks. Strengths and difficulties questionnaire were used to evaluate children’s mental health at baseline and at the end of the study.Results: After 8 weeks of intervention, the serum levels of 25‑hydroxy‑Vitamin D3 and magnesium increased significantly in the intervention group compared with the control group. Also a significant decrease in changes of emotional problems (p=0.001), conduct problems (p=0.002), peer problems (p=0.001), prosocial score (p=0.007), total difficulties (p=0.001), externalizing score (p=0.001), and internalizing score (p=0.001) was seen in intervention group at the end of study.Conclusion: Vitamin D (50,000 IU/week) and magnesium (6 mg/kg/day) co-supplementation during 8-week could improve the behavioral function and mental health in ADHD. Although further well-designed studies with a larger sample size are needed.the IRCT registration: IRCT2016030326886N1.
Review A meta-analysis of the efficacy and safety of additional anti-HER2-targeting drugs in HER2-positive advanced breast cancers
Authors: Du Nannan , Chen Bangsheng , Shen Zefeng , Zhou Bin , Fu Xiaojun , Mao Danyi , Mao Feiyan , Ng Derry Minyao , Khadaroo Parikshit Asutosh , Yang Lei 
Published: August 2020

Abstract
Background The purpose of this study was to analyze the efficacy and safety of additional anti-HER2 (human epidermal growth factor receptor 2)-targeting drugs in HER2-positive advanced breast cancers.Methods For this study, the following databases were searched for articles published from its inception until December 2019: PubMed, Web of Science, EBSCO, and Cochrane library, of which the main outcomes were the progression-free survival (PFS) and overall survival (OS).Results We conducted a meta-analysis and the results showed that additional anti-HER2-targeting drugs improved the HER2-positive advanced breast cancer patients’ PFS (HR: 0.66, p < 0.001), OS (HR: 0.77, p < 0.001), respectively. In terms of drug types, the efficacy of lapatinib was the most (HR: 0.53, 95% Cl: 0.39–0.67, p < 0.001), followed by pertuzumab (HR: 0.72, 95% Cl: 0.55–0.89, p = 0.001). Trastuzumab benefited the least, with no difference statistical significance (HR: 0.87, 95% Cl: 0.31–1.44, p = 0.594). In terms of treatment regimen, first-line treatment (HR: 0.67, 95% Cl: 0.52–0.82, p < 0.001) had a greater benefit than non-first-line treatment (HR: 0.82, 95% Cl: 0.71–0.94, p = 0.004). The main adverse events (AEs) observed were diarrhea and the main cardiotoxicity observed was decreased ejection fraction.Conclusions Additional anti-HER2-targting drugs may improve long-term prognosis in HER2-positive advanced breast cancers. Moreover, the AEs were safe and tolerable. Besides, lapatinib had the best benefit, and pertuzumab followed by, trastuzumab had the least benefit in terms of drug selection. From the aspect of treatment, it recommended significantly to use anti-HER2-targeting drugs in first-line therapy based on our research in HER2-positive advanced breast cancers.
Development of a Multi-gene-based Immune Prognostic Signature in Ovarian Cancer
Authors: cao tiefeng , shen huimin 
Published: August 2020

Abstract
Background：Chemotherapeutic resistance is responsible for treatment failure. Immunotherapy is important in ovarian cancer (OC). Systematic exploration of immunogenic landscape and reliable immune gene-based prognostic biomarkers or signature is necessary to be identified. This study aims to identify the immune gene-based prognostic biomarkers and regulatory factors, further to develop an individualized prediction signature.Methods: This study systematically explored the gene expression profiles from RNA-seq data set for The Cancer Genome Atlas (TCGA) ovarian cancer. Differentially expressed and survival-associated immune genes and transcription factors (TFs) were identified using immune genes from ImmPort dataset and TFs from Cistoma database. We developed the prognostic signature based on survival associated immune genes with LASSO (Least absolute shrinkage and selection operator) Cox regression analysis. Further, Network analysis was performed to uncover the potential molecular mechanisms of immune-related genes with the help of computational biology. Results: The prognostic signature, a weighted combination of the 21 immune-related genes, performed moderately in survival prediction with AUC was 0.746, 0.735, and 0.749 for 1, 3, and 5 year overall survival, respectively. Network analysis uncovered the regulatory role of TFs in immune genes. Intriguingly, the prognostic signature reflected infiltration of some immune cell subtypes.Conclusions: We first constructed a signature with 21 immune genes of clinical significance, which showed promising predictive value in the surveillance, prognosis, even immunotherapy response of OC patients.
Enhancement of L-amino Acid Oxidase Production by Bacillus Subtilis HLZ-68 With Oxygen-vector and Asymmetric Degradation of DL Arginine to D-arginine
Authors: xu peng , Pan Changpei , Cui Gongcheng , Wei ChunYan , Wang Lijuan , Li Yanting , Li Xiangping , Huang Shihai 
Published: August 2020

Abstract
The Bacillus subtilis HLZ-68 independently screened by our laboratory can produce L-amino acid oxidase (L-AAO), and DL-arginine can be degraded asymmetrically by suspending the wet bacteria in the degradation liquid. By adding oxygen-vectors to the fermentation medium, the collected amount of wet bacteria can be increased. Taking n-dodecane, n-hexadecane, oleic acid, paraffin, and n-hexane as oxygen-vectors, the optimal oxygen-vector oleic acid was 1.2% (v/v). The weight of wet cells increased by 66.83% compared with before, and the activity of L-AAO in fermentation broth increased by 38.88% compared with before. The standard sample DL-arginine was derivatized by phenyl isothiocyanate, and then subjected to high performance liquid chromatography(HPLC), and the obtained peak area and arginine content were used as standard curves to measure the DL-arginine. The content of D-arginine and L-arginine in the initial degradation solution was 50% each, and the bacterial cells are added to the initial degradation solution of DL-arginine. After 21 hours of reaction, L-arginine was completely Degraded, remaining 47% of D-arginine.D-alanine was easily extracted from the reaction solution using cation-exchange resin,after centrifugation, decolorization, concentration and vacuum drying, and the chemical and optical purity of the extracted d-alanine was 92.68 and 97.46%, respectively.
Memory-assisted Reinforcement Learning for Diverse Molecular De Novo Design
Authors: Blaschke Thomas , Engkvist Ola , Bajorath Jürgen , Chen Hongming 
Published: August 2020

Abstract
In de novo molecular design, recurrent neural networks (RNN) have been shown to be effective methods for sampling and generating novel chemical structures. Using a technique called reinforcement learning (RL), an RNN can be tuned to target a particular section of chemical space with optimized desirable properties using a scoring function. However, ligands generated by current RL methods so far tend to have relatively low diversity, and sometimes even result in duplicate structures when optimizing towards particular properties. Here, we propose a new method to address the low diversity issue in RL. Memory-assisted RL is an extension of the known RL, with the introduction of a so-called memory unit. As proof of concept, we applied our method to generate structures with an optimized logP. In a second case study, we applied our method to design ligands for the dopamine 2 receptor and the 5-hydroxytryptamine 1A receptor. For both receptors, a machine learning model was developed to predict whether generated molecules were active or not for the receptor. In both case studies, it was found that memory-assisted RL led to the generation of more active compounds and with higher chemical diversity, thus achieving better coverage of chemical space of known ligands compared to established RL method.