bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Genome DNA Methylation at Inherited Coat Color Dilutions of Rex Rabbits
Authors: Chen Yang , Hu Shuaishuai , Liu Ming , Zhao Bohao , Yang Naisu , Li Jiali , Chen Qiuran , Zhou Juan , Bao Guolian , Wu Xinsheng 
Published: January 2021

Background:The dilution of color in rabbits is associated with many different genetic mechanisms that form different color groups. A number of previous studies have revealed potential regulatory mechanisms by which epigenetics regulate pigmentation. However, the genome-wide DNA methylation involved in animal coat color dilution remains unknown.Results:We compared genome-wide DNA methylation profiles in Rex rabbit hair follicles in a Chinchilla group (Ch) and a diluted Chinchilla group (DCh) through whole-genome bisulfite sequencing (WGBS). Approximately 3.5% of the cytosine sites were methylated in both groups, of which the CG methylation type was in greatest abundance. In total, we identified 126,405 differentially methylated regions (DMRs) between the two groups, corresponding to 11,459 DMR-associated genes (DMGs). Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that these DMGs were principally involved in developmental pigmentation and Wnt signaling pathways. In addition, two DMRs were randomly selected to verify that the WGBS data were reliable using bisulfite sequencing PCR, and seven DMGs were analyzed to establish the relationship between the level of DNA methylation and mRNA expression using qRT-PCR. Due to the limitation of small sample size, replication of the results with a larger sample size would be important in future studies.Conclusion:These findings provide evidence that there is an association between inherited color dilution and DNA methylation alterations in hair follicles, greatly contributing to our understanding of the epigenetic regulation of rabbit pigmentation.
Development and External Validation of a Novel Immune Checkpoint–Related Gene Signature for Prediction of Overall Survival in Hepatocellular Carcinoma
Authors: Zhao Enfa , Chen Shimin , Dang Ying 
Published: January 2021

Objective: The purpose of this study was to develop and validate a novel immune checkpoint–related gene signature for prediction of overall survival (OS) in hepatocellular carcinoma (HCC).Methods: mRNA expression profiles and clinical follow-up information were obtained in the International Cancer Genome Consortium database. An external dataset from The Cancer Genome Atlas (TCGA) Liver Hepatocellular Carcinoma database was used to validate the results. The univariate and multivariate Cox regression analyses were performed based on the differentially expressed genes. We generated a four-mRNA signature to predict patient survival. Furthermore, the reliability and validity were validated in TCGA cohort. An integrated bioinformatics approach was performed to evaluate its diagnostic and prognostic value.Results: A four-gene (epidermal growth factor, mutated in colorectal cancer, mitogen-activated protein kinase kinase 2, and NRAS proto-oncogene, GTPase) signature was built to classify patients into two risk groups using a risk score with different OS in two cohorts (all P &lt; 0.0001). Multivariate regression analysis demonstrated the signature was an independent predictor of HCC. Furthermore, the signature presented an excellent diagnostic power in differentiating HCC and adjacent tissues. Immune cell infiltration analysis revealed that the signature was associated with a number of immune cell subtypes.Conclusion: We identified a four–immune checkpoint–related gene signature as a robust biomarker with great potential for clinical application in risk stratification and OS prediction in HCC patients and could be a potential indicator of immunotherapy in HCC. The diagnostic signature had been validated to accurately distinguish HCC from adjacent tissues.
Estimating Burden of Disease Among Blind Individuals With Non-24-Hour Sleep-Wake Disorder
Authors: Van Draanen Lauren , Xiao Changfu , Polymeropoulos Mihael H. 
Published: January 2021

Purpose: To quantify the burden of disease in blind patients with Non-24-H Sleep- Wake Disorder (N24HSWD), utilizing longitudinal sleep diary data. N24HSWD is a circadian disorder characterized by a cyclical pattern of aberrant circadian and sleep-wake cycles that are associated with increased frequency of sleep episodes during the school/work day hours. Daytime sleep episodes would be predicted to decrease the opportunity for school/work participation, significantly impacting the quality of life of the patient.Methods: We used the sleep diary data of daytime sleep from a period of ~90 days in blind individuals that presented with a sleep complaint. These subjects were identified from a group of blind individuals with N24HSWD (n = 121) and a control group of blind individuals without N24HSWD (n = 57).Results: N24HSWD patients had more frequent and longer episodes of daytime sleep as compared to a control group. Using duration of daytime sleep as a surrogate for defining a healthy or unhealthy day, N24HSWD patients also had significantly fewer healthy days, defined by daytime sleep free days (DSFD), days without a sleep episode between 9:00 a.m. and 5:00 p.m, as compared to the control group.Conclusion: Daytime sleep free day (DSFD) is a useful and specific measure of disease burden in patients with N24HSWD and it is predicted to be correlated with the standardized HRQOL-4, Healthy Days measurement.
Resting State Functional Connectivity of Brain With Electroconvulsive Therapy in Depression: Meta-Analysis to Understand Its Mechanisms
Authors: Sinha Preeti , Joshi Himanshu , Ithal Dhruva 
Published: January 2021

Introduction: Electroconvulsive therapy (ECT) is a commonly used brain stimulation treatment for treatment-resistant or severe depression. This study was planned to find the effects of ECT on brain connectivity by conducting a systematic review and coordinate-based meta-analysis of the studies performing resting state fMRI (rsfMRI) in patients with depression receiving ECT.Methods: We systematically searched the databases published up to July 31, 2020, for studies in patients having depression that compared resting-state functional connectivity (rsFC) before and after a course of pulse wave ECT. Meta-analysis was performed using the activation likelihood estimation method after extracting details about coordinates, voxel size, and method for correction of multiple comparisons corresponding to the significant clusters and the respective rsFC analysis measure with its method of extraction.Results: Among 41 articles selected for full-text review, 31 articles were included in the systematic review. Among them, 13 articles were included in the meta-analysis, and a total of 73 foci of 21 experiments were examined using activation likelihood estimation in 10 sets. Using the cluster-level interference method, one voxel-wise analysis with the measure of amplitude of low frequency fluctuations and one seed-voxel analysis with the right hippocampus showed a significant reduction (p &lt; 0.0001) in the left cingulate gyrus (dorsal anterior cingulate cortex) and a significant increase (p &lt; 0.0001) in the right hippocampus with the right parahippocampal gyrus, respectively. Another analysis with the studies implementing network-wise (posterior default mode network: dorsomedial prefrontal cortex) resting state functional connectivity showed a significant increase (p &lt; 0.001) in bilateral posterior cingulate cortex. There was considerable variability as well as a few key deficits in the preprocessing and analysis of the neuroimages and the reporting of results in the included studies. Due to lesser studies, we could not do further analysis to address the neuroimaging variability and subject-related differences.Conclusion: The brain regions noted in this meta-analysis are reasonably specific and distinguished, and they had significant changes in resting state functional connectivity after a course of ECT for depression. More studies with better neuroimaging standards should be conducted in the future to confirm these results in different subgroups of depression and with varied aspects of ECT.
Gender-Specific Inverse Associations Between Beans Intake, Serum Urate Levels, and Hyperuricemia: A Cross-Sectional Analysis Based on the Henan Rural Cohort Study
Authors: Cui Ningning , Dong Xiaokang , Xue Yuan , Liao Wei , Liu Xiaotian , Li Yuqian , Hou Jian , Huo Wenqian , Li Linlin , Mao Zhenxing , Zheng Zhaohui , Wang Chongjian 
Published: January 2021

Background and Aims: Beans are rich in purines, which are important substances that lead to elevated serum urate, especially exogenous purines. Few studies were conducted to assess the relationship between beans intake and serum urate or hyperuricemia, especially in rural people. The purpose of this study was to validate the association by gender in the rural Chinese population.Methods: A total of 38,855 participants aged 18–79 years old were enrolled from the Henan Rural Cohort Study (Registration number: ChiCTR-OOC-15006699). Dietary data were collected using a validated food frequency questionnaire (FFQ). Linear regression models and logistic regression models were used to examine the associations between beans intake and serum urate levels or hyperuricemia. Restricted cubic spline regression was performed to display the dose–response relationship.Results: In multivariate-adjusted linear regression, an inverse correlation was found between beans intake and serum urate level (the highest quartile Q4 vs. the bottom quartile Q1) in both men (P = 0.008) and women (P &lt; 0.001). Per 10-g increment in beans intake was associated with 0.30 μmol/L decreased concentration of serum urate in men and 0.71 μmol/L in women. The multivariate-adjusted odds ratios (ORs) of hyperuricemia were 0.83 (0.71, 0.97) in men and 0.73 (0.63, 0.84) in women (Q4 vs. Q1). Per 10-g increment in beans intake created a 1% decreased risk of hyperuricemia in men and 3% in women. The cubic spline suggested a risk reduction for hyperuricemia with increasing intake of beans.Conclusion: A higher beans intake was associated with a lower serum urate level and a reduced risk of hyperuricemia in both sexes, and the association was more pronounced in women.
Radiation-Induced Sarcoma of the Head and Neck Following Radiotherapy for Nasopharyngeal Carcinoma: A Single Institutional Experience and Literature Review
Authors: Lou Jianlin , Jiang Lin , Dai Xinshen , Wang Huanhuan , Yang Jia , Guo Liang , Fang Meiyu , Wang Shengye 
Published: January 2021

Background and ObjectiveRadiotherapy (RT) is the primary treatment option for nasopharyngeal carcinoma (NPC), but it is associated with radiation-induced sarcomas (RISs). This study aims to investigate clinicopathological features and head and neck RIS prognosis after NPC RT.MethodsThe medical and radiological records of the NPC patients (n =14,074) referred to Zhejiang Cancer Hospital, Hang Zhou, China between January 1995 and December 2018 were retrospectively reviewed. Among them, 22 patients were determined to have RIS after RT for NPC. The clinicopathological data, diagnosis, treatment, and follow-up results of 22 patients with RIS were analyzed in this retrospective research. All 22 patients underwent surgery as the main treatment. The levels of Overall Survival (OS) were determined through the Log-rank test and Kaplan–Meier method.ResultsAmong these patients, 13 were males and nine females with the male/female ratio of 1.44:1. The age during the primary RT of NPC ranged from 25 to 61 years old (median age: 37 years old). Patients’ ages ranged from 33 to 73 years old (median age: 52.5 years old) when diagnosed with RIS. The latency period for development of the RIS was between 3 and 36 years (median: 8.5 years) after RT. In this cohort, R0 resection was achieved in 13 cases, R1 resection in five cases, and R2 resection in four cases. During the follow-up period ranged from 2 to 102 months (median 14 months), 15 patients had died of the disease. Kaplan–Meier method showed that the 2-year, 3-year, and the 5-year cumulative OS rate was 50.3, 43.2, and 14.4%, respectively. The median survival time was 34 months. Surgical resection with R0 resection achieves a significantly better prognosis (P = 0.012). Patients under the age of 37 years old at the time of initial RT had a relatively better prognosis (P = 0.035).ConclusionsAlthough the incidence of RIS after RT of NPC is generally low, the treatment of RIS is very difficult. The RISs are associated with poor overall prognosis. R0 resection can improve the prognosis thus it should be considered as the primary and optimal choice for the treatment of RIS.
Preoperative Serum Sodium Level as a Prognostic and Predictive Biomarker for Adjuvant Therapy in Esophageal Cancer
Authors: Wang Qifeng , Peng Lin , Han Yongtao , Li Tao , Dai Wei , Wang Yi , Wu Lei , Wei Yang , Xie Tianpeng , Fang Qiang , Li Qiang , Lang Jinyi , Cao Bangrong 
Published: January 2021

BackgroundLow serum sodium has been associated with unfavorable outcome in several cancers. The prognostic value of serum sodium in esophageal carcinoma (EC) remains unclear. This study aimed to investigate preoperative serum sodium in association with outcome and survival benefit of adjuvant therapy for patients with EC.MethodsPreoperative serum sodium and clinicopathological indexes were retrospectively analyzed in 2155 patients who underwent esophagectomy at Sichuan cancer hospital. Overall survival (OS) and disease-free survival (DFS) were analyzed by using Kaplan-Meier method and Cox regression. Benefit of adjuvant therapy was estimated by using Propensity Score Matching.ResultsThe incidence of hyponatremia and hypernatremia were 2% (43/2155) and 3.5% (76/2155) in treatment-naive patients. Both sodium disorders indicated unfavorable OS (hyponatremia, adjusted HR[95% CI] = 1.78[1.2–2.62]; hypernatremia, adjusted HR = 1.52[1.1–2.11]) and DFS (hyponatremia, adjusted HR[95% CI] = 1.52[1.03–2.23]; hypernatremia, adjusted HR = 1.45[1.06–1.99]). Decreased sodium concentrations within the normal range were associated with poor OS and DFS. Postoperative adjuvant therapy was associated with improved three-year OS (56.6 vs. 40%; adjusted HR = 0.55 [95% CI, 0.41–0.73]) and DFS (51.9 vs. 36.2%; adjusted HR = 0.63 [95% CI, 0.48–0.83]) versus surgery alone in patients with low serum sodium (Na &lt; 139.6 mmol/liter), but not in other sodium subgroups. Meanwhile, serum sodium was inversely correlated with cell counts of leukocytes, neutrophils, monocytes and C-reactive protein levels.ConclusionsThese results suggested that low preoperative serum sodium is associated with poor outcome in EC patients, and may predict survival benefit of adjuvant therapy.
Brain Tumor Microenvironment and Angiogenesis in Melanoma Brain Metastases
Authors: Trembath Dimitri G. , Davis Eric S. , Rao Shanti , Bradler Evan , Saada Angelica F. , Midkiff Bentley R. , Snavely Anna C. , Ewend Matthew G. , Collichio Frances A. , Lee Carrie B. , Karachaliou Georgia-Sofia , Ayvali Fatih , Ollila David W. , Krauze Michal T. , Kirkwood John M. , Vincent Benjamin G. , Nikolaishvilli-Feinberg Nana , Moschos Stergios J. 
Published: January 2021

BackgroundHigh tumor-infiltrating lymphocytes (TILs) and hemorrhage are important prognostic factors in patients who have undergone craniotomy for melanoma brain metastases (MBM) before 2011 at the University of Pittsburgh Medical Center (UPMC). We have investigated the prognostic or predictive role of these histopathologic factors in a more contemporary craniotomy cohort from the University of North Carolina at Chapel Hill (UNC-CH). We have also sought to understand better how various immune cell subsets, angiogenic factors, and blood vessels may be associated with clinical and radiographic features in MBM.MethodsBrain tumors from the UPMC and UNC-CH patient cohorts were (re)analyzed by standard histopathology, tumor tissue imaging, and gene expression profiling. Variables were associated with overall survival (OS) and radiographic features.ResultsThe patient subgroup with high TILs in craniotomy specimens and subsequent treatment with immune checkpoint inhibitors (ICIs, n=7) trended to have longer OS compared to the subgroup with high TILs and no treatment with ICIs (n=11, p=0.059). Bleeding was significantly associated with tumor volume before craniotomy, high melanoma-specific expression of basic fibroblast growth factor (bFGF), and high density of CD31+αSMA- blood vessels. Brain tumors with high versus low peritumoral edema before craniotomy had low (17%) versus high (41%) incidence of brisk TILs. Melanoma-specific expression of the vascular endothelial growth factor (VEGF) was comparable to VEGF expression by TILs and was not associated with any particular prognostic, radiographic, or histopathologic features. A gene signature associated with gamma delta (gd) T cells was significantly higher in intracranial than same-patient extracranial metastases and primary melanoma. However, gdT cell density in MBM was not prognostic.ConclusionsICIs may provide greater clinical benefit in patients with brisk TILs in MBM. Intratumoral hemorrhage in brain metastases, a significant clinical problem, is not merely associated with tumor volume but also with underlying biology. bFGF may be an essential pathway to target. VEGF, a factor principally associated with peritumoral edema, is not only produced by melanoma cells but also by TILs. Therefore, suppressing low-grade peritumoral edema using corticosteroids may harm TIL function in 41% of cases. Ongoing clinical trials targeting VEGF in MBM may predict a lack of unfavorable impacts on TIL density and/or intratumoral hemorrhage.
Narrow-Margin Hepatectomy Resulted in Higher Recurrence and Lower Overall Survival for R0 Resection Hepatocellular Carcinoma
Authors: Liu Lihong , Shui Yongjie , Yu Qianqian , Guo Yinglu , Zhang Lili , Zhou Xiaofeng , Yu Risheng , Lou Jianying , Wei Shumei , Wei Qichun 
Published: January 2021

PurposeTo evaluate the impact of resection margin on recurrence pattern and survival for hepatocellular carcinoma (HCC) with narrow margin resection, with the aim to guide postoperative treatment.Materials and MethodsTwo hundred forty HCC patients after curative hepatectomy between 2014 and 2016 were reviewed retrospectively. The cases were divided into narrow-margin (width of resection margin &lt;1cm, n=106) and wide-margin (width of resection margin ≥1cm, n=134) groups based on the width of resection margin. Recurrence pattern, recurrence-free survival (RFS), and overall survival (OS) were compared between the above two groups. An additional cohort of nine cases with positive margin plus post-operative stereotactic body radiotherapy (SBRT) was also analyzed for the recurrence pattern.ResultsPostoperative recurrence was found in 128 (53.3%) patients. The recurrence rate was significantly higher in narrow-margin group than that in wide-margin group (P=0.001), especially for the pattern of marginal recurrence (20.8 vs. 4.5%, P=0.003). The 1-, 2-, 3-year RFS rates for the narrow-margin and wide-margin groups were 55.8, 43.9, 36.9, and 78.7, 67.9, 60.2%, respectively, with significant difference between the two groups (P&lt;0.001). Patients with narrow margin showed a tendency of decreased OS than those with wide margin (P&lt;0.001). As comparison, the nine cases with positive margin treated with postoperative SBRT showed low recurrence rate and no marginal recurrence was found.ConclusionPatients with narrow resection margin were associated with higher recurrence rate and worse survival than those with wide resection margin. These patients may benefit from adjuvant local treatment, such as radiotherapy.
Abnormalities of Serum Fatty Acids in Children With Henoch–Schönlein Purpura by GC-MS Analysis
Authors: Wen Min , Feng Shipin , Dang Xiqiang , Ding Xuewei , Xu Zhiquan , Huang Xiaoyan , Lin Qiuyu , Xiang Wei , Li Xiaoyan , He Xiaojie 
Published: January 2021

Purpose: The objectives of this work were to test the levels of serum medium- and long- chain fatty acids (MLCFAs) in children and to discover their possible relationship with Henoch-Schönlein Purpura (HSP), also known as Immunoglobulin A vasculitis.Methods: A total of 57 children with HSP (HSP group) and 28 healthy children (CON group) were recruited for this study. Serum specimens were collected to detect the compositions and contents of MLCFAs by gas chromatography with mass spectrometry (GC-MS) analysis.Results: The contents of all detected 37 MLCFAs in the HSP group were higher than the healthy group. Thirty-one species of MLCFAs were discovered to have a significant difference (p &lt; 0.05) in two groups. Comparing to healthy controls, there were 31, 31, 18 fatty acids showed a statistical difference in the untreated group, regular treated group, and withdrawal group of HSP, respectively. The trend of fatty acids in the three HSP groups was similar to the healthy controls, as well as the untreated group and regular treated group changed more obviously than the withdrawal group. Almitate (C16:0) and 18 carbon atoms (C18) of fatty acids were abundant in all three HSP groups, divided according to the treatment of glucocorticoid. Some fatty acids were found having considerable differences (p &lt; 0.05) in three groups. Monounsaturated fatty acids (MUFAs), including elaidate (C18:1T), cis-11,14,17-eicosatrienoic acid ester (C20:1), and cis-15-tetracosenoate (C24:1), were distinctly higher in HSP children with renal damage.Conclusion: Our study revealed that the abnormalities in MLCFA may be associated with the development of HSP. Another interesting finding was that fatty acids contents were changing during the glucocorticoid treatment. Meanwhile, long-chain MUFAs may have an impact on renal damage in HSP patients. Further studies need to be carried out in order to explore the specific mechanism of fatty acids in the course of HSP.