bluuebunny/crossref_metadata_2025_split huggingface dataset:
TVAR: Assessing Tissue-specific Functional Effects of Non-coding Variants with Deep Learning
Authors: Yang Hai , Chen Rui , Wang Quan , Wei Qiang , Ji Ying , Zhong Xue , Li Bingshan 
Published: December 2020

Abstract
Analysis of whole genome-sequencing (WGS) for genetics of disease is still a challenge due to lack of accurate functional annotation of noncoding variants, especially the rare ones. As eQTLs have been extensively implicated in genetics of human diseases, we hypothesize that noncoding rare variants discovered in WGS play a regulatory role in predisposing disease risk. With thousands of tissue- and cell type-specific epigenomic features, we propose TVAR, a multi-label learning based deep neural network that predicts the functionality of noncoding variants in the genome based on eQTLs across 49 human tissues in GTEx. TVAR learns the relationships between high-dimensional epigenomics and eQTLs across tissues, taking the correlation among tissues into account to learn shared and tissue-specific eQTL effects. As a result, TVAR outputs tissue-specific annotations, with an average of 0.77 across these tissues. We evaluate TVAR’s performance on four complex diseases (coronary artery disease, breast cancer, Type 2 diabetes, and Schizophrenia), using TVAR’s tissue-specific annotations, and observe its superior performance in predicting functional variants for both common and rare variants, compared to five existing state-of-the-art tools. We further evaluate TVAR’s G-score, a scoring scheme across all tissues, on ClinVar, fine-mapped GWAS loci, Massive Parallel Reporter Assay (MPRA) validated variants, and observe consistently better performance of TVAR compared to other competing tools.
The Effect of the mGluR8 Agonist, S-3,4-DCPG on Acquisition and Expression of Morphine-Induced Conditioned Place Preference in Male Rats
Authors: Kahvandi Nazanin , Ebrahimi Zahra , Karimi Seyed Asaad , Shahidi Siamak , Salehi Iraj , Naderishahab Marzieh , Sarihi Abdolrahman 
Published: December 2020

Abstract
BackgroundThe nucleus accumbens (NAc) plays a principal role in drug reward. It has been reported that metabotropic glutamate receptors (mGluRs) play a key role in the rewarding pathway(s). Previous studies have shown the vast allocation of the different types of mGluRs, including mGluR8, in regions that are associated with opioid rewards, such as the NAc. The aim of the present study was to evaluate the role of mGlu8 receptors within the NAc in the acquisition and expression phases of morphine induced conditioned place preference (CPP). Adult male Wistar rats were bilaterally implanted by two cannulas' in the NAc and were evaluated in a CPP paradigm. Selective mGluR8 allosteric agonist (S-3,4-DCPG) was administered at doses of 0.03, 0.3, and 3μg/0.5 μL saline per side into the NAc on both sides during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase, or before place preference test, or post-conditioning (expression) phase of morphine-induced CPP. ResultsThe results revealed that intra-accumbal administration of S-3,4-DCPG (0.3 and 3 μg) markedly decreased the acquisition in a dose-dependent manner but had no effect on expression of morphine-induced CPP. ConclusionsThe findings suggest that activation of mGlu8 receptors in the NAc dose-dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine which may be related to the glutamate activity into the NAc and/or synaptic plasticity of this system in reward pathway(s).
Identification of unique bile acid-metabolizing bacteria from the microbiome of centenarians
Authors: Honda Kenya , Sato Yuko , Atarashi Koji , Plichta Damian , Arai Yasumichi , Sasajima Satoshi , Kearney Sean , Suda Wataru , Takeshita Kozue , Sasaki Takahiro , Okamoto Shoki , Skelly Ashwin , Okamura Yuki , Vlamakis Hera , Li Youxian , Tanoue Takeshi , Takei Hajime , Nittono Hiroshi , Narushima Seiko , Irie Junichiro , Itoh Hiroshi , Moriya Kyoji , Sugiura Yuki , Suematsu Makoto , Moritoki Nobuko , Shibata Shinsuke , Littman Dan , Fischbach Michael , Hattori Masahira , Murai Tsuyoshi , Xavier Ramnik , Hirose Nobuyoshi 
Published: December 2020

Abstract
Centenarians, or individuals who have lived more than a century, represent the ultimate model of successful longevity associated with decreased susceptibility to ageing-associated illness and chronic inflammation. The gut microbiota is considered to be a critical determinant of human health and longevity. Here we show that centenarians (average 107 yo) have a distinct gut microbiome enriched in microbes capable of generating unique secondary bile acids, including iso-, 3-oxo-, and isoallo-lithocholic acid (LCA), as compared to elderly (85-89 yo) and young (21-55 yo) controls. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from a centenarian’s faecal microbiota, we identified Parabacteroides merdae and Odoribacteraceae strains as effective producers of isoalloLCA. Furthermore, we generated and tested mutant strains of P. merdae to show that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3βHSDH) were responsible for isoalloLCA production. This secondary bile acid derivative exerted the most potent antimicrobial effects among the tested bile acid compounds against gram-positive (but not gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and vancomycin-resistant Enterococcus faecium. These findings suggest that specific bile acid metabolism may be involved in reducing the risk of pathobiont infection, thereby potentially contributing to longevity.
Association of Cardiovascular Risk Factors and Metabolic Syndrome with Non-alcoholic and Alcoholic Fatty Liver Disease
Authors: Han A lum 
Published: December 2020

Abstract
Background: This study aimed to evaluate differences between the incidence of cardiovascular risk factors and metabolic syndrome in non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) Methods: We compared the incidence of cardiovascular risk factors and metabolic syndrome between three groups of subjects (n = 913): healthy, NAFLD, and AFLD groups. The healthy group had no liver disease. Drinking quantity for diagnosis was based on a previously accepted standard. Both the NAFLD and AFLD groups comprised patients with fatty liver disease diagnosed using computed tomography (CT). Metabolic syndrome risk was compared between the NAFLD and AFLD groups. Results: No significant differences in several cardiovascular risk factors were observed between the NAFLD and AFLD groups. Upon analyzing the metabolic syndrome status in each group after making appropriate adjustments, the odds ratios (OR) in the NAFLD (OR = 2.397, P = 0.002) and AFLD groups (OR = 4.445, P = 0.001) were found to be significantly higher than that in the healthy group; the incidence rate of metabolic syndrome was similar in the NAFLD and AFLD groups. Conclusion: Both the NAFLD and AFLD groups had more cardiovascular risk factors and higher metabolic syndrome risk than the healthy group. Thus, the prevention of fatty liver disease, regardless of the specific type, should involve the identification of cardiovascular and metabolic syndrome risk factors. If abdominal CT reveals a fatty liver, whether NAFLD or AFLD, the risk of cardiovascular disease and metabolic syndrome should be assessed.
Establishment of a Veno-venous Extracorporeal Membrane Oxygenation in a Rat Model of acute Respiratory Distress Syndrome
Authors: Li Yongnan , Huang Jian , Zhang Rongzhi , Wang Shixiong , Cheng Xingdong , Zhang Pengbin , Zhai Kerong , Wang Wei , Liu Debin , Gao Bingren 
Published: December 2020

Abstract
Background: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is now considered a reasonable option to salvage acute respiratory distress syndrome (ARDS). However, we lack a rodent model for experimental studies. This study was undertaken to establish an animal model of VV-ECMO in ARDS rats.Methods: Fifteen Sprague-Dawley (SD) rats (350 ± 50 g) were used in this study. Using a rat model of oleic acid (OA)-induced ARDS, VV-ECMO was established through bi-caval cannulation of the right jugular vein for venous drainage and venous reinfusion with a specially designed three-cavity catheter. Continuous arterial pressure monitoring was implemented by using a catheter through cannulation of the right femoral artery. The central temperature was monitored with a rectal probe. Arterial blood gas monitoring was implemented by a blood gas analyzer at three-time points: at baseline, 1-hour (after OA modeling), and 3.5-hour (after VV-ECMO support). Lung tissue and bronchoalveolar lavage fluid were harvested respectively for protein concentration and pulmonary histologic evaluation to confirm the alleviation of lung injury during VV-ECMO.Results: Following ARDS induced by OA, ten rats were successfully established on VV-ECMO without failure, and survived from the ECMO procedure. VV-ECMO alleviated lung injury and restored adequate circulation for the return of lung function and oxygen. VV-ECMO was associated with decreased lung injury score, wet/dry weight ratio, and ﬂuid leakage into airspaces. Conclusion: We have established a reliable, economical, and functioning ARDS rat model of VV-ECMO.
Bidirectional Association of Neurodevelopment with Growth: A Prospective Cohort Study
Authors: Wei Xiaotong , Hu Jiajin , Yang Liu , Gao Ming , Li Lin , Ding Ning , Ma Yanan , Wen Deliang 
Published: December 2020

Abstract
Background: The study aims to use the cross-lagged models and utilize data from the Born in Shenyang Cohort Study to characterize the bidirectional associations of the term-born infants’ neurodevelopment in five domains and physical growth in the early life. Method: This study consists of 688 mother-child dyads from the Born in Shenyang Cohort Study. Infants' anthropometric and development in neurological outcomes were measured twice by the Gesell Development Scale and administered by staff at six and twelve months of age. Cross-lagged analyses and multiple linear regression analyses were used to explore the longitudinal relationships in both directions. Results: In terms of longitudinal studies, the negative associations between gross motor and social behavior at six months with BMI Z -score at twelve months were found (gross motor: aβ=-0.20, 95% CI: -0.31 to- 0.09; social behavior: aβ=-0.23, 95% CI: -0.33 to- 0.13). Instead , higher infant Z -scored BMI at 6 months predicted lower gross motor at twelve months (aβ=-0.08, 95% CI: -0.12 to- 0.04). The only bidirectional neurological development, gross motor, had a more significant impact on infants’ BMI Z -score than the reverse (β=-0.21 vs. β=-0.09; P<0.001). The similar associations had been found in weight gain velocity. Conclusion: We found bidirectional relationships between infants’ neurodevelopment of gross motor with physical growth and suggested the term-born infants, who are on the edge of the developmental danger, should not be overlooked.
Akt Inhibition Improves the Efficacy of Cabazitaxel Nanomedicine in Preclinical Taxane-Resistant Cancer Models
Authors: Li Tongyu , Shi Linlin , Wan Jianqin , Hu Xiaoxiao , Chen Wanzhi , Wang Hangxiang 
Published: December 2020

Abstract
Background: Drug resistance continues to be a major clinical challenge in achieving cures in cancer patients. Cabazitaxel has shown the ability to surmount drug resistance through bypassing the transporter-mediated drug expulsion; however, the substantially high toxicity in patients hampered its clinical application. In addition, upregulation of certain self-defense proteins (e.g, Akt) was reportedly involved in drug resistance, which may further compromise the activity of cabazitaxel. We have previously developed several prodrug-based strategies to deliver nanoparticles encapsulating cabazitaxel derivatives in tumors with enhanced efficacy and improved in vivo tolerability. Therefore, we hypothesized that combing cabazitaxel nanotherapeutics with a pan-Akt inhibitor MK-2206 would synergistically eliminate the resistant cancers with reduced systemic toxicity.Methods: Activation of Akt in resistant cancers upon cabazitaxel treatment was determined by western blotting assay. The effect of combing MK-2206 with cabazitaxel on cell viability was evaluated by CCK-8 assay. To improve the in vivo biocompatibility, the delivery of potent cabazitaxel was feasibly achieved via the integration of oligolactide-conjugated cabazitaxel into the PEG-b-PLA matrix. Both the synergism and safety of cabazitaxel nanomedicine-based combination were evaluated through a series of in vitro and in vivo experiments, including Western blotting assay, CCK-8 assay, EdU assay, flow cytometry, migration assay, transwell assay, MTD study, myelosuppression study, nude mouse xenograft, and immunostaining analyses. Results: We found that resistant cells adapted to activate Akt signaling upon cabazitaxel treatment, which potentially discounts the efficacy of cabazitaxel. The addition of MK-2206 reversed this situation and potentiated the activity of cabazitaxel nanomedicine against resistant cells. Mechanistically, suppression of the Akt pathway increased the microtubule-stabilizing effect of cabazitaxel. Their collaboration was demonstrated to maximize the efficacy in a xenograft model bearing paclitaxel-resistant tumors. In particular, the nanoformulation substantially improved drug tolerability in animals, and combined treatment with MK-2206 was proven to be safe for synergistic cancer therapy. Conclusion: The preclinical studies demonstrate the therapeutic efficacy of our binary system consisting of a better-tolerated nanotherapy and a specific pathway modulator against resistant cells, thereby highlighting the potential applications for the clinical treatment of patients with multidrug-resistant malignancies.
What are the Survival Factors in Surgically Resected Synchronous Multiple Primary Lung Cancers: A Retrospective Study
Authors: Li Haichao , Wang Kai , Zhang Xingxing , Chen Rong , Zhao Jian 
Published: December 2020

Abstract
Background: With the popularization of high-resolution computed tomography (HRCT), the detection rate of synchronous multiple primary lung cancer (SMPLC) is increasing. We retrospectively analyzed the surgical results of SMPLC patients in our hospital to determine the best treatment, surgical prognosis and survival analysis.Methods: A total of 78 SMPLC patients met the diagnostic criteria underwent complete resection and lymph node dissection or sampling without any preoperative induction therapy in the Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University. We analyzed the postoperative survival rate, and further studied the relationship between survival rates and sex, age, preoperative symptoms, tumor location, tumor number, tumor size, lymph node metastasis, TNM stage, surgical type, surgical frequency, histopathologic types, vascular infiltration, visceral pleural invasion and postoperative therapy.Results: Among 78 patients, the 1-,2-,3-,4- and 5-year disease free survival (DFS) rates were 93.42%, 86.84%, 77.78%, 62.96%, and 60.00%, respectively, while the 1-,2-,3-,4- and 5-year overall survival (OS) rates were 94.73%, 92.11%, 82.22%, 77.78%, and 65.00%, respectively. TNM stage of the largest tumor (II:HR=7.40,III:9.01,p=0.002) was an independent risk factor for DFS. Smoking history (HR=4.34,p=0.039) and TNM stage of the largest tumor (II:HR=9.38,III:9.42,p=0.003) were independent risk factors for overall survival.Conclusions: First, SMPLC is different from intrapulmonary metastasis and its clinical stage is also different from the 8th (2015) edition TNM classification for lung cancer. Second, when pulmonary function permits, surgery (complete resection and lymph node dissection) is a significantly beneficial treatment for patients with SMPLC. Third, TNM stage of the largest tumor (II:HR=7.40,III:9.01,p=0.002) was an independent risk factor for DFS. Smoking history (HR=4.34,p=0.039) and TNM stage of the largest tumor (II:HR=9.38,III:9.42,p=0.003) were independent risk factors for overall survival.
Prevalence and Subtype Distribution of Blastocystis in Tibetan Sheep in Qinghai Province, Northwestern China
Authors: Yang Fan , Gou Jing-min , Yang Bing-ke , Du Jia-yue , Yao Hui-zhong , Ren Mei , Lin Qing 
Published: December 2020

Abstract

Background: Blastocystis is one of the most common intestinal pathogens in humans and a great number of animals, including sheep and goats. High prevalence and multiple subtypes of Blastocystis have been reported in sheep in several regions of China and abroad. Tibetan sheep is an important economic species for herdsmen in the Qinghai-Tibetan Plateau areas. However, there is a dearth of knowledge about Blastocystis in Tibetan sheep. Here, we detected the prevalence and subtype distribution of Blastocystis in Tibetan sheep.Methods: A total of 761 fecal samples were collected from Tibetan sheep in seven counties of Qinghai Province, northwestern China, and were examined for the prevalence and subtypes of Blastocystis using molecular technology based on the partial small subunit ribosomal RNA gene of Blastocystis.Results: The overall prevalence of Blastocystis in the investigated Tibetan sheep was 10.12% (77/761), and significant differences in prevalence were observed among ruminants from the seven counties (P < 0.01, χ2 = 323.03, df = 6) and across four seasons (P < 0.01, χ2 = 113.91, df = 3). Among them, the highest prevalence was observed among the animals from Haixi County (62.7%) and in summer (28.8%). Sequence analysis revealed three animal-adapted subtypes (ST14, ST10, and ST12) of Blastocystis sp. in these Tibetan sheep, with ST14 as the predominant subtype.Conclusions: To our knowledge, this is the first report on Blastocystis infection in Tibetan sheep, and our findings provide fundamental data for the establishment of effective measures to control this pathogen in Tibetan sheep as well as in other animals.
Hodgkin's Lymphoma: Epidemiological Clinical Characteristics in a Reference Hospital in Oncology in the Eastern Amazon.
Authors: Vieira Bárbara Rafaela Bastos , Oliveira Leonam Oliver Durval , Martins Claúdia Nazaré de Souza Almeida Titan , Homci Váleria Pereira Braz , Quaresma Juarez Antônio Simões , Costa Igor Brasil 
Published: December 2020

Abstract
Background: Lymphomas are a type of cancer that starts in the lymphatic system. This system is made up of organs, tissues and vessels responsible for immune function. Hodgkin's lymphoma is characterized by giant cells, well differentiated and binucleated. It is divided into two groups: classical hodgkin's lymphoma and hodgkin's lymphoma predominant in nodular lymphocytes. The classic in turn is subdivided into four more histological subtypes: nodular sclerosis, rich in lymphocytes, depleted in lymphocytes and mixed cellularity. This study analyzed the spatial distribution and clinical-epidemiological and Hodgkin's lymphoma characteristics and their histological types in patients diagnosed with the disease at a Reference Hospital in Oncology in the Eastern Amazon between the years 2006 to 2015.Methods: A study was carried out cross-sectional, retrospective, analytical and descriptive study through the analysis of the medical records of 336 patients diagnosed with the disease in that given period and location, the G test was performed to demonstrate the association between the variables. Results: The cases of Hodgkin's Lymphoma came from the following Brazilian states: Pará (318 cases), Amapá (15 cases), Maranhão (2 cases), Piauí (1 case). It affected more men (62%) and young adults (mean age 26 years). The most frequent histological type was nodular sclerosis (65%). The primary location of the tumor was predominant in the cervical lymph nodes (65%). Mostly, patients with no metastases (98%), but the presence of metastases was more frequent in Hodgkin's lymphoma, Nodular Lymphocytic Predominance (18%). Conclusion: The data obtained in this study allow to know some regional peculiarities about Hodgkin's Lymphoma, which can contribute to regional preventive policies, as well as can support comparisons about the disease in other regions, contributing to better understand the heterogeneity of LH.
WITHDRAWN: Combined Transcriptomic and Metabolic Analysis Reveals the Potential Mechanism for Fruit Development and Quality Control of Rubus chingii Hu
Authors: Chen Zhen 
Published: December 2020

Abstract
Background: Rubus chingii Hu (Chinese raspberry) is an important dual functional food with nutraceutical and pharmaceutical values. Comprehensive understanding of fruit development and bioactive components synthesis and regulation could accelerate genetic analysis and molecular breeding for the unique species.﻿Results: A combined transcriptomic and metabolic analysis of R. chingii fruits from different developmental stages was conducted in this study. A total of 89,188 unigenes was generated and 57,545 unigenes (64.52%) were got annotated. Differential expression genes (DEGs) and differential ions mainly involved in biosynthesis of secondary metabolites. Phenolic acids and flavonol glycosides syntheses were strongly activated at earlier stages, while amino acids, linolenic acid metabolism and anthocyanins synthesis were dominant at later stages. The core genes participated in biosynthesis of ellagic acid (EA) and kaempferol-3-O-rutinoside (K-3-R) and their corresponding metabolites were elaborately characterized. And some probable MYB and bHLH transcription factors controlling flavonoids synthesis were also identified. Conclusion: Combined transcriptomic and metabolic analysis initially reveals molecular and chemical mechanism of fruit development of R. chingii Hu fruit. The fruit launched the biosynthesis of phenolic acids and flavonols at the very beginning of fruit set and then coordinately accumulated and converted. And it was tightly regulated by expressions of the related genes and transcription factors. The results provide a solid foundation for genetic analysis, functional genes isolation, fruit quality improvement and modifiable breeding.
Synthesis, Structural Characterization, Carbon Dioxide and Hydrogen Adsorption of a New 3D MOF Zn(BTC)4
Authors: Yan Jing , Gong Jiashun , Song Li 
Published: December 2020

Abstract
A novel three-dimensional porous MOF Zn (BTC)4(BTC= benzene-1,3,5-tricarboxylic acid) was synthesized by solvothermal method. This structure was characterized by X-ray single crystal diffraction, SEM and TG. This MOF crystallizes in Monoclinic, P2(1)/n, V=1795.7(2)Å3, Z=4, Dc=1.449mg/cm3, α=90.00°, β=97.2200(10)°, γ=90.00°, a=9.5077(5)Å, b=16.3950(16)Å, c=11.6119(9)Å. The TG analysis shows the material can be stabilized up to 350℃ , then the skeleton collapsed on 350~510℃. The luminescence test shows that the material gives out strong emission at 384nm and 462nm. The hydrogen storage capacity of this MOF is 2.01 wt% at 77K and the pressure of 10bar. The carbon dioxide storage capacity of this MOF is 4.17 mmol/g at 298K and the pressure of 10bar.