bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sources of Variation in Cell-Type RNA-Seq Profiles
Authors: Gustafsson Johan , Held Felix , Robinson Jonathan , Björnson Elias , Jörnsten Rebecka , Nielsen Jens 
Published: February 2020

Abstract
Background Cell-type specific gene expression profiles are needed for many computational methods operating on bulk RNA-Seq samples, such as deconvolution of cell-type fractions and digital cytometry. However, the gene expression profile of a cell type can vary substantially due to both technical factors and biological differences in cell state and surroundings, reducing the efficacy of such methods. Here, we investigated which factors contribute most to this variation. Results We evaluated different normalization methods, quantified the magnitude of variation introduced by different sources, and examined the differences between UMI-based single-cell RNA-Seq and bulk RNA-Seq. We applied methods such as random forest regression to a collection of publicly available bulk and single-cell RNA-Seq datasets containing B and T cells, and found that the technical variation across laboratories is of the same magnitude as the biological variation across cell types. Tissue of origin and cell subtype are less important but still substantial factors, while the difference between individuals is relatively small. We also show that much of the differences between UMI-based single-cell and bulk RNA-Seq methods can be explained by the number of read duplicates per mRNA molecule in the single-cell sample.Conclusions Our work shows the importance of either matching or correcting for technical factors when creating cell-type specific gene expression profiles that are to be used together with bulk samples.
Deconvolution of bulk blood eQTL effects into immune cell subpopulations
Authors: Aguirre-Gamboa Raul , de Klein Niek , Tommaso Jennifer di , Claringbould Annique , Wijst Monique van der , de Vries Dylan , Brugge Harm , Oelen Roy , Võsa Urmo , Zorro Maria , Chu Xiaojin , Bakker Olivier B , Borek Zuzanna , Ricaño-Ponce Isis , Deelen Patrick , Xu Cheng-Jian , Swertz Morris , Jonkers Iris , Withoff Sebo , Joosten Irma , Sanna Serena , Kumar Vinod , Koenen Hans , Joosten Leo A.B. , Netea Mihai , Wijmenga Cisca , Franke Lude , Li Yang 
Published: February 2020

Abstract
Background Expression quantitative trait loci (eQTL) studies are used to interpret the function of disease-associated genetic risk factors. To date, most eQTL analyses have been conducted in bulk tissues, such as whole blood and tissue biopsies, which are likely to mask the cell type context of the eQTL regulatory effects. Although this context can be investigated by generating transcriptional profiles from purified cell subpopulations, the current methods are labor-intensive and expensive. Here we introduce a new method, Decon2, a framework for estimating cell proportions using expression profiles from bulk blood samples (Decon-cell) followed by deconvolution of cell type eQTLs (Decon-eQTL).Results The estimated cell proportions from Decon-cell agree with experimental measurements across cohorts (R ≥ 0.77). Using Decon-cell we can predict the proportions of 34 circulating cell types for 3,194 samples from a population-based cohort. Next we identified 16,362 whole blood eQTLs and deconvoluted cell type interaction (CTi) eQTLs using the predicted cell proportions from Decon-cell. CTi eQTLs show excellent allelic directional concordance with those of eQTL(≥ 96%-100%) and chromatin mark QTL (≥87%-92%) studies that used either purified cell subpopulations or single-cell RNA-seq, outperforming the conventional interaction effect.Conclusions Decon2 provides a method to detect cell type interaction effects from bulk blood eQTLs, which is useful in pinpointing the most relevant cell type for a certain complex disease. Decon2 is available as an R package and Java application. (https://github.com/molgenis/systemsgenetics/tree/master/Decon2), and as a web tool (www.molgenis.org/deconvolution).
Anti-Tyro3 IgG associates with disease activity and reduces efferocytosis of macrophages in new-onset systemic lupus erythematosus
Authors: Zhou Zhuochao , Xu Aining , Teng Jialin , Wang Fan , Tan Yun , Liu Honglei , Cheng Xiaobing , Su Yutong , Shi Hui , Hu Qiongyi , Chi Huihui , Li Jian , Hou Jiaqi , Sun Yue , Yang Chengde , Ye Junna 
Published: February 2020

Abstract
Backgroud: To investigate the role of Tyro3 receptor in macrophages’ efferocytosis of apoptotic cells in systemic lupus erythematosus (SLE), we aimed to reveal the clinical relevance and impact of anti-Tyro3 antibody on SLE. Methods : The serum levels of IgG-type autoantibody against Tyro3 receptor were detected in new-onset, treatment-naïve SLE patients (n =70) and healthy controls (HCs) (n =70) using enzyme-linked immunosorbent assay (ELISA). The correlation of the levels of autoantibodies against Tyro3 receptor with clinical and laboratory characteristics were analyzed by Spearman correlation analysis. Receiver operating characteristic (ROC) curve was used to assess the sensitivity and specificity of anti-Tyro3 IgG for the diagnosis of SLE. The effects of purified Tyro3 autoantibody from SLE patients on the efferocytosis of human monocyte-derived macrophages were measured by flow cytometry and immunofluorescence. Results : The serum levels of IgG-type autoantibody against Tyro3 receptor were significantly elevated in patients with SLE compared to HCs ( p < 0.0001). The levels of anti-Tyro3 IgG were negatively associated with haemoglobin (Hb) ( r =-0.294, p = 0.014), and positively correlated with the presence of oral ulcers ( r = 0.254, p = 0.034), SLE disease activity index (SLEDAI) score ( r = 0.254, p = 0.034), erythrocyte sedimentation rate (ESR) ( r = 0.430, p = 0.000), C-reactive protein (CRP) ( r = 0.246, p = 0.049) and immunoglobulin G (IgG) ( r = 0.408, p = 0.001). Higher levels of anti-Tyro3 antibody were observed in patients with oral ulcers than paitents without oral ulcers ( p = 0.035). Further flow cytometry demonstrated that purified anti-Tyro3 IgG inhibited the efferocytosis of macrophages ( p = 0.004). Immunofluorescence assay also showed a decreased engulfment of apoptotic cells in the macrophages incubated with purified anti-Tyro3 IgG ( p = 0.044) compared with control IgG. Conclusions: These observations indicated that autoantibody against Tyro3 was associated with disease activity and impaired efferocytosis of macrophages, which might be involved in the pathogenesis of SLE.
The Combination of an Inflammatory Peripheral Blood Transcriptome and Imaging Biomarkers Enhance Prediction of Radiographic Progression in Knee Osteoarthritis.
Authors: Attur Mukundan , Krasnokutsky Svetlana , Zhou Hua , Samuels Jonathan , Chang Gregory , Bencardino Jenny T. , Rosenthal Pamela , Rybak Leon , Huebner Janet L. , Kraus Virginia B. , Abramson Steven B. 
Published: February 2020

Abstract
Objective Predictive biomarkers of progression in knee osteoarthritis are sought to enable clinical trials of structure modifying drugs. A peripheral blood leukocyte (PBL) inflammatory gene signature, MRI-based bone marrow lesions (BML) and meniscus extrusion scores), meniscal lesions, and osteophytes on x-ray each have been shown separately to predict radiographic joint space narrowing (JSN) in subjects with symptomatic knee osteoarthritis (SKOA). In these studies, we determined whether the combination of the PBL transcriptome and these imaging findings at baseline enhanced the prognostic value of either alone. Methods An inflammatory PBL transcriptome (increased mRNA for IL-1β, TNFα, and COX-2), routine radiographs, and 3T knee MRI were assessed in two independent populations with SKOA: an NYU cohort, and the Osteoarthritis Initiative (OAI). At baseline and 24 months, subjects underwent standardized fixed-flexion knee radiographs and knee MRI. Medial JSN (mJSN) was determined as the change in medial JSW. Progressors were defined by a mJSN cut-point (≥0.5 mm/24 months). Models were evaluated by odds ratios (OR) and area under the receiver operating characteristic curve (AUC). Results We validated our prior finding in these two independent (NYU and OAI) cohorts, individually and combined, that an inflammatory PBL transcriptome predicted radiographic progression of SKOA after adjustment for age, gender, and BMI. Similarly, the presence of baseline BML and meniscal lesions by MRI or semi-quantitative osteophyte score on x-ray each predicted radiographic medial JSN at 24 months. The combination of the PBL transcriptome and medial BML increased the AUC from 0.66 (p=0.004) to 0.75 (p<0.0001) and the odds ratio from 6.31 to 19.10 (p<0.0001) in the combined cohort of 473 subjects. The addition of osteophyte score to BML and PBL transcriptome further increased the predictive value of any single biomarker. A causal analysis demonstrated that the PBL transcriptome and BML independently influenced mJSN. Conclusion The use of the PBL transcriptome together with imaging biomarkers as combinatorial predictive biomarkers, markedly enhances the identification of radiographic progressors. The identification of the SKOA population at risk for progression will help in the future design of disease-modifying OA drug trials and personalized medicine strategies.
Occurrence and multiple-level ecological risk assessment of pharmaceuticals and personal care products (PPCPs) in two lakes of China
Authors: Liu Na , Jin Xiaowei , Yan Zheng , Luo Ying , Feng Chenglian , Fu Zhiyou , Tang Zhi , Wu Fengchang , Giesy John P. 
Published: February 2020

Abstract
Background: Management of pharmaceuticals and personal care products (PPCPs) in the environment has become a social problem. In the present study, concentrations of 140 PPCPs at 20 sites in Baiyangdian Lake and Tai Lake from 2016 to 2017 were analyzed by Ultra Performance Liquid Chromatography Mass Spectrometer (HPLC-MS). Risk quotients (RQ) were calculated for each detected chemical at all sites and a prioritization index (PI) based on maximum RQ was calculated. To assess the risk of chemicals that identified high priority (PI>1), a more accurate method of joint probability curves (JPCs) was applied.

Results: A total of 41 PPCPs were quantitatively detected in the two lakes, with maximum concentrations ranging from 0.04 to 889 ng/L. Among these, seven PPCPs were identified as high or moderate risk pollutants for at least one site, 3 in Tai Lake and 5 in Baiyangdian Lake. Carbamazepine posed ecological risk at all 20 sites, to which more attention should be paid in the future. Based on results of the JPCs, sulfamethoxazole, caffeine, diethyltoluamide, and carbamazepine were categorized as high or intermediate risk.

Conclusion: Occurrences and distributions of PPCPs were different in the two lakes. Multiple-level risk assessment from simple to more complex was appropriate in chemical risk management.
Significance of incident reports by medical doctors for organizational transparency and driving forces for patient safety
Authors: Fukami Tatsuya , Uemura Masakazu , Nagao Yoshimasa 
Published: February 2020

Abstract
Incident reporting is an effective strategy used to enhance patient safety and quality improvement in healthcare. An incident is an event that could eventually result in harm to a patient. The aim of this study is to re-evaluate the importance of reporting by medical doctors to improve quality in healthcare and patient safety. We conducted a retrospective analysis of the reported incidents registered in our institutional database from April 2015 to March 2019, classified according to eight variables proposed by the National University Hospital Council of Japan, to determine the type of incidents and their potential harm to patients. Registered reports totalled 43,775, approximately 8% of which arise annually from medical doctors in clinical departments. Incidents with higher impact on patients have significantly increased the rate of reporting by medical doctors. The most frequent types of report overall concerned medication incidents, followed by infusion lines, drainage-tube devices, cure, examination, and treatment outside the operating room. The most frequent reports by medical doctors involved operation-related incidents, followed by cure, examination, treatment outside the operation room, and medications. Reporting by medical doctors reflects the organizational transparency and the driving forces behind patient safety and quality improvement in healthcare. Efforts toward seamless improvement in patient safety and quality at our hospital continue apace.
miR-543 inhibits tumor malignant progression by regulating TWIST1 in human gastric cancer
Authors: Lian Guoda , Li Xuanna , Chen Shaojie , Li Jiajia , Li Yaqing , Chen Shangxiang , Lin Xiangan , Lin Haoming , Huang Kaihong , Chen Yinting 
Published: February 2020

Abstract
Background: TWIST1, a highly conserved basic helix-loop-helix (bHLH) transcription factor, is essential to epithelial-mesenchymal transition (EMT) and cancer metastasis in gastric cancer (GC). However, little is known about the post-transcriptional regulation of TWIST1, especially the mechanisms involving microRNAs. Methods: TWIST1 expression were observed on 107 cases of gastric cancer through tissue microarray technology to identify their correlations with clinicopathological parameters and patient survival. The regulation of TWIST1 by miR-543 was confirmed by western blot, dual luciferase activity assays and rescue experiments. Moreover, the functions of miR-543 on cell migration, invasion, tumorigenicity and metastatic potential were evaluated by stably expression strategy in vitro and in vivo. Results: TWIST1 is overexpressed in 74 of 107 GC tumor samples. High TWIST1 expression positively correlated with poor prognosis of GC patients. In addition, TWIST1 was found to be a direct target of miR-543. Expression of miR-543 was obviously decreased in GC cell lines and primary tissues. Overexpression of miR-543 in GC cells inhibited proliferation, colony formation, migration and invasion by suppressing expression of TWIST1. Ectopic expression of miR-543 inhibited tumor growth and prevented liver metastasis of gastric cancer cells in mice. Conclusion: TWIST1 is overexpressed in gastric cancer and regulated by miR-543. Downregulated miR-543 promotes tumor growth and metastasis of GC, indicating the possibility of new strategies for GC therapy.
Can virtual reality improve traditional anatomical education?: A randomized controlled trial on use of 3D skull model
Authors: Chen Shi , Zhu Jiawei , Cheng Cheng , Pan Zhouxian , Liu Lingshan , Du Jianhua , Shen Xinhua , Shen Zhen , Zhu Huijuan , Liu Jihai , Yang Hua , Ma Chao , Pan Hui 
Published: February 2020

Abstract
Background Anatomy teaching is trending towards a mixture of lectures, cadaveric models, 2D atlas and computer simulations. This paper presents a study which compare the educational effectiveness of virtual reality (VR) skull model with that of cadaveric skulls and atlas. Methods A randomized controlled study with 73 medical students was carried out with three different groups: VR skull (N = 25), cadaveric skull (N = 25) and atlas (N = 23). Anatomical structures were taught through an introductory lecture and a model-based learning. All students completed the pre- and post-intervention test, which is composed of a theory test and an identification test. Results Participants in all three groups gained significantly higher total scores at post-intervention test than at pre-intervention test; the post-identification test score of VR group was non-statistically higher than the other group (VR 30 [22-33.5], cadaver 26 [20-31.5], atlas 28[20-33]). Participants in VR and cadaver group provided more positive feedbacks on their learning models (VR 26 [19-30] vs. 25 [19.5-29.5] vs. 12 [9-20], p<0.05). Conclusions VR skull model showed equivalent efficiency in teaching anatomy structure as cadaver skull and atlas. In addition, VR can assist participants in understanding complex anatomy structures with higher motivation and tolerable adverse effects.
Multi-tissue transcriptome analysis using hybrid-seq revealed potential genes and biological pathways associated with azadirachtin A biosynthesis in neem (Azadirachtin indica)
Authors: Wang Huiyan , Wang Ning , Huo Yixin 
Published: February 2020

Abstract
Background: Azadirachtin A is a triterpenoid from neem tree exhibiting excellent activities against over 600 insect species in agriculture. The manufacture of azadirachtin A depends on extraction from neem tissues, which is not ecofriendly and sustainable. The low yield and discontinuous supply impeded the further application. The biosynthetic pathway of azadirachtin A is still well-known.Results: We attempted to explore azadirachtin A biosynthetic pathway and identified key involved genes by analyzing transcriptome data of five neem tissues through hybrid-seq (Illumina HiSeq and Pacific Biosciences Single Molecule Real Time (PacBio SMRT)) technology. A total 219 and 397 up-regulated differentially expressed genes (DEGs) in leaf and fruit tissues than other tissues (root, stem and flower) were isolated. After phylogenetic analysis and domain prediction, 22 candidates encoding 2,3-oxidosqualene cyclase (OSC), alcohol dehydrogenase (ADH), cytochrome P450 (CYP450), acyltransferase (ACT) and esterase (EST) proposed to be involved in azadirachtin A biosynthesis were finally selected. De novo assembled sequences were verified by Quantitative Real-Time PCR (qRT-PCR) analysis.Conclusions: By integrating and analysis data from Illumina HiSeq and PacBio SMRT platform, 22 DEGs were finally selected as candidates involved in azadirachtin A biosynthesis. The obtained reliable and accurate sequencing data provided important novel information for understanding neem genome. Our data shed new light on the understanding of other triterpenoids biosynthesis in neem trees and provide reference for exploring other valuable natural product biosynthesis in plants.
Enriched environment and social isolation affect cognition ability via altering excitatory and inhibitory synaptic density in mice hippocampus
Authors: Wang Hui , Xu Xiaxia , Gao Jing , Zhang Tao 
Published: February 2020

Abstract
Background The purpose of the study was to examine whether the underlying mechanism of the alteration of cognitive ability and synaptic plasticity induced by the housing environment is associated with the balance of excitatory/inhibitory synaptic density. Enriched environment (EE) and social isolation (SI) are two different housing environment, and one is to give multiple sensory environments, the other is to give monotonous and lonely environment. Results Male four-week-old C57 mice were divided into three groups: CON, EE and SI. They were housed in the different cage for 3 months. Morris water maze (MWM) and novel object recognition were performed. Long term potentiation (LTP), depotentiation (DEP) and Local field potential (LFPs) were recorded in the hippocampal perforant pathway (PP) and dentate gyrus (DG). The data showed that EE enhanced the ability of spatial learning, reversal learning and memory as well as LTP/DEP in the hippocampal DG region. Meanwhile, SI reduced those abilities and the level of LTP/DEP. Moreover, there were higher couplings of both phase-amplitude and phase-phase in the EE group, and lower couplings of them in the SI group compared to that in the CON group. Western blot analysis showed that EE significantly enhanced the level of PSD-95, NR2B; however, SI reduced them but enhanced level of GABAAR. Conclusion These date suggests that the cognitive functions, synaptic plasticity and neural oscillatory patterns were significantly impacted by housing environment via possibly changing the balance of excitatory and inhibitory synaptic density.
Impacts of Dialysis Adequacy and Intradialytic Hypotension on Changes in Dialysis Recovery Time
Authors: Guedes Murilo , Pecoits-Filho Roberto , Leme Juliana El Ghoz , Jiao Yue , Raimann Jochen G. , Wang Yuedong , Kotanko Peter , de Moraes Thyago Proença , Thadhani Ravi , Maddux Franklin W. , Usvyat Len A. , Larkin John W. 
Published: February 2020

Abstract
Background:
Patient reported long dialysis recovery time (DRT) is common and associated with higher hospitalization and mortality. The goal of our study was to test the hypothesis that hemodialysis (HD) dose and intradialytic hypotension (IDH) rates are associated with dialysis recovery time (DRT).
Methods:
We analyzed data from adult HD patients who responded to DRT survey ≤180 days from first date of dialysis (FDD) during 2014 to 2017. DRT survey was administered with annual KDQOL survey. DRT survey asks: “How long does it take you to be able to return to your normal activities after your dialysis treatment?” Answers are: <0.5, 0.5-to-1, 1-to-2, 2-to-4, or >4 hours. An adjusted logistic regression model computed odds ratio for increased/maintained longer DRT (increase above DRT >2 hours) in reference to decreased/maintained shorter DRT (decrease below DRT <2 hours, or from DRT >4 hours). Changes in DRT were calculated from incident (≤180 days FDD) to first prevalent (>365-to-≤545 days FDD) and second prevalent (>730-to-≤910 days FDD) years.
Results:
Among 98616 incident HD patients (age 62.6±14.4 years, 57.8% male) who responded to DRT survey, a higher spKt/V in the incident period was associated with 13.5% (OR=0.865; 95%CI 0.801-to-0.935) lower risk of longer DRT in the first-prevalent year. A higher number of HD treatments with IDH episodes/month in the incident period was associated with a 0.8% (OR=1.008; 95%CI 1.001-to-1.015) and 1.6% (OR=1.016; 95%CI 1.006-to-1.027) higher probability of a longer DRT in the first- and second-prevalent years, respectively. Consistently, an increased in incidence of IDH episodes/months was associated to longer DRT over time.
Conclusions:
Incident patients who had higher spKt/V and less sessions with IDH episodes had a lower likelihood of longer DRT in first year of HD. Dose optimization strategies with cardiac stability in fluid removal should be tested.
Mir10a aggravates the ischemia-reperfusion kidney injury by inhibiting the PI3K/AKT signaling pathway
Authors: Xu Dongsheng , Li Wenjun , Zhang Tao , Wang Gang 
Published: February 2020

Abstract
Background To investigate the effect of miR-10a on PI3K/AKT signaling pathway. The ischemia-reperfusion injury models of rats were simulated in vivo . Methods RT-PCR was used to test the expression of miR-10a. The serum creatinine and urea nitrogen levels were determined. The pathological changes and the apoptosis of renal cells were observed. The model of HK-2 cells with hypoxia-reoxygenation was established in vitro. The cell proliferation and apoptosis rate were tested by CCK8, clone formation and flow cytometry, respectively. The apoptosis-related proteins and PIK3CA and PI3K/AKT signaling pathway-related proteins were detected by Western blot both in vivo and intro . The dual luciferase assay was used to verify whether PIK3CA is a target gene of miR-10a. PIK3CA gene was over-expression or silenced. The transfection efficiency was verified by RT-PCR and the above experiments were repeated. Results Compared with I/R group, miR-10a RNA was significantly increased in renal tissue of miR-10a group, serum Cr and BUN levels, and renal injury score and apoptosis index were significantly increased, while the expression of PI3K/AKT signaling pathway-related proteins were significantly inhibited. However, the indicators above were contrary in anti-miR group. In comparison with H/R group, miR-10a RNA expression was remarkably increased in miR-10a cells and the cell proliferation was inhibited. The apoptosis rate was increased and the expression of PI3K/AKT signaling pathway-related proteins were down-regulated. However, the indicators above were contrary in anti-miR group. Conclusion miR-10a can aggravate the ischemia-reperfusion-induced renal injury in rats by targeting PIK3CA and inhibitingPI3K/AKT signaling pathway.