bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network of “drug-target-SARS-CoV-2&nbsp;Related Genes” Through Integrated Analysis of Pharmacology and Geo Database
Authors: Hou Jin ping , Wang Yong heng , Chen Yu meng , Chen Yi hao , Zhu Xiao , Qin Rui si , Chen Tingting 
Published: December 2020

Abstract
BackgroundCoronavirus Disease 2019 (COVID-19) respiratory disease rapidly caused a global pandemic and social and economic disruption. The combination of Traditional Chinese medicine (TCM) and Conventional Western medicine (CWM) is more effective for COVID-19 treatment. Moreover, TCM and CWM are important data source for developing new drug targets and promote strategies treat SARS-CoV-2 infections. However, many studies have analyzed the therapeutic mechanism of CWM or TCM alone for COVID-19, it is still unclear the interaction mechanism between TCM and CWM on COVID-19.MethodsThis paper integrates network pharmacology and GEO database to mine and identify COVID-19 molecular therapeutic targets, providing potential targets and new ideas for COVID-19 gene therapy and new drug development. It includes: 1) using TCMSP, TTD, PubChem and CTD databases to analyze drug interactions and associated phenotypes for SARS-CoV-2, to correlate drug and disease interaction mechanisms to screen key drug targets; 2) using GEO database to correlate differential genes and drug targets to screen potential antiviral gene therapy targets, to construct regulatory network and key points of SARS-CoV-2 therapeutic drugs; 3) using computer simulation of molecular docking to screen virus-related proteins for new drugs. ResultsIntegrated analysis of network pharmacology discovered that baicalein, estrone and quercetin are the pivotal active ingredients in TCM and CWM. Combining drug target genes in pharmacology database and virus induced genes in GEO database, the result showed the core hub genes related to COVID-19: STAT1, IL1B, IL6, IL8, PTGS2 and NFKBIA, and these genes were significantly downregulated in A549 and NHBE cells by SARS-CoV-2 infection. Moreover, chemical interaction and molecular docking analysis of hub genes showed that folic acid might as be potential therapeutic drug for COVID-19 treatment, and SARS-CoV-2 nucleocapsid phosphoprotein was a potential drug target. The network of “drug-target-SARS-CoV-2 related genes” provide noval potential compounds and targets for further studies of SARS-CoV-2.ConclusionsIntegrated analysis of network pharmacology and big data mining provided noval potential compounds and targets for further studies of SARS-CoV-2. Our research implied folic acid and SARS-CoV-2 N as therapeutic target in TCM and CWM. Our research also suggests that targeting SARS-CoV-2 N protein is likely to be a common mechanism of TCM and CWM. On the one hand, the identification of pivotal genes provides a target for COVID-19 molecular therapy, on the other hand, it provides ideas for the analysis of interaction mechanism between virus and host.
Paternal Obesity and Epigenetic Inheritance of Breast Cancer: The Role of Systemic Effects and Transmission to the Second Generation
Authors: Fontelles Camile C. , Cruz Raquel Santana da , Gonsiewski Alexandra K. , Barin Ersilia , Tekmen Volkan , Jin Lu , Cruz M. Idalia , Loudig Olivier , Warri Anni , Assis Sonia de 
Published: December 2020

Abstract
Background: While genetics explains some familial breast cancer cases, we showed that environmentally-induced epigenetic inheritance of breast cancer can also occur in rodent models. We previously reported that paternal consumption of a high-fat diet and ensuing obesity increased breast cancer susceptibility in the offspring (F1). Nevertheless, it is still unclear whether paternal-induced programming of breast cancer in daughters is associated with systemic alterations or mammary epithelium-specific factors. It also remains to be determined whether the ancestrally programmed breast cancer predisposition in F1 progeny can be transmitted to subsequent generations. Methods: Male mice (F0) were fed either a control (CO) diet or an obesity-inducing diet (OID) for seven weeks and then mated with female mice (F0) reared on a CO diet. The resulting offspring (F1), also exclusively fed CO diet, were either used for mammary gland and tumor transplantation surgeries or to generate the F2 generation. To induce the mammary tumors, female mice were treated with 7,12 dimethylbenz[a]anthracene (DMBA). Total RNA extracted from F0 or F1 males sperm was used for small RNA-Seq analysis. Results: Mammary glands from F1 CO female offspring exhibited enhanced development when transplanted into OID females [OID(CO-MG)], as shown by higher mammary gland area, epithelial branching and elongation, compared to CO females that received a CO mammary gland [CO(CO-MG)]. Similarly, mammary tumors from F1 CO female offspring transplanted into OID females [OID(CO.T)] displayed improved growth with a higher proliferation/apoptosis rate. We also found that granddaughters (F2) from the OID grand-paternal germline showed accelerated tumor growth compared to COxCO granddaughters (F2). Transmission of breast cancer predisposition to the F2 generation through OID male germline was associated with alterations in specific sperm tRNA fragments (tRF) in both F0 and F1 males.Conclusions: Our findings indicate that systemic metabolic and mammary stromal alterations are the most significant contributors to paternal programming of mammary gland development and cancer predisposition in female offspring rather than mammary epithelium confined factors. Our data also show breast cancer predisposition in OID daughters can be transmitted to subsequent generations and could explain some familial cancers, if confirmed in humans.
Laughter as a Paradigm of Socio-emotional Signal Processing in Dementia
Authors: Sivasathiaseelan Harri , Marshall Charles R , Benhamou Elia , Leeuwen Janneke EP van , Bond Rebecca L , Russell Lucy L , Greaves Caroline , Moore Katrina M , Ha Chris JD , Frost Chris , Rohrer Jonathan D , Scott Sophie K , Warren Jason D 
Published: December 2020

Abstract
Background: Laughter is a fundamental communicative signal in our relations with other people and is used to convey a diverse repertoire of social and emotional information. It is therefore potentially a useful probe of impaired socio-emotional signal processing in neurodegenerative diseases. Here we investigated the cognitive and affective processing of laughter systematically in patients representing all major syndromes of frontotemporal dementia, a disease spectrum characterised by severe socio-emotional dysfunction, as well as typical amnestic Alzheimer’s disease in relation to healthy age-matched individuals. Methods: We assessed cognitive labelling and valence rating of samples of spontaneous (mirthful and hostile) and volitional (posed) laughter versus two auditory control conditions (a synthetic laughter-like stimulus and spoken numbers) in 47 patients with frontotemporal dementia (22 with behavioural variant frontotemporal dementia, 12 with semantic variant primary progressive aphasia and 13 with nonfluent-agrammatic primary progressive aphasia), 15 patients with typical amnestic Alzheimer’s disease and 20 healthy age-matched individuals. Neuroanatomical associations of laughter processing were assessed using voxel-based morphometry of patients’ brain MR images. Results: While all dementia syndromes were associated with impaired identification of laughter subtypes relative to healthy controls, this was significantly more severe overall in frontotemporal dementia than in Alzheimer’s disease and particularly in the behavioural and semantic variants, which also showed abnormal affective evaluation of laughter. Certain striking syndromic signatures emerged, including enhanced liking for hostile laughter in behavioural variant frontotemporal dementia, impaired processing of synthetic laughter in the nonfluent-agrammatic variant (consistent with a generic complex auditory perceptual deficit) and ‘numerophilia’ in the semantic variant. Across the patient cohort, overall laughter identification accuracy correlated with regional grey matter in a core network encompassing inferior frontal and cingulo-insular cortices; and more specific correlates of laughter identification accuracy were delineated in cortical regions mediating affective disambiguation (identification of hostile and posed laughter in orbitofrontal cortex) and authenticity (social intent) decoding (identification of mirthful and posed laughter in anteromedial prefrontal cortex).Conclusions: These findings reveal a rich diversity of cognitive and affective laughter phenotypes in canonical dementia syndromes and suggest that laughter is an informative probe of neural mechanisms underpinning socio-emotional dysfunction in neurodegenerative disease.
Effect of Visual Feedback on Behavioral Control and Functional Activity During Bilateral Hand Movement
Authors: Guo Jing , Li Long , Zheng Yang , Quratul Ain , Liu Tian , Wang Jue 
Published: December 2020

Abstract
Background: Previous researches state vision as vital source of information for movement control and more precisely for accurate hand movement. Further, fine bimanual motor activity may be associated to various oscillatory activities within distinct brain areas and inter-hemispheric interactions. However, neural coordination among the distinct brain areas responsible to enhance motor accuracy is still not adequate.Methods: In the current study we investigated task-dependent modulation by simultaneously measuring high time resolution electroencephalogram (EEG), electromyogram (EMG) and force along with bi-maual and uni-manual motor tasks. The errors were controlled using visual feedback. In order to complete the uni-manual tasks, subject was asked to grip the strain gauge using index finger and thumb of right hand thereby exerting force on connected visual feedback system. Whereas the bi-manual task involved finger abduction of left index finger in two contractions along with visual feedback system and at the same time the right hand gripped using definite force on two conditions that whether visual feedback existed or not for right hand.Results: Primarily, the existence of visual feedback for right hand significantly decreased brain network global and local efficiency in theta and alpha band when compared with the elimination of visual feedback.Conclusions: Brain network activity in theta and alpha band coordinate to facilitate fine hand movement. The findings may provide a new neurological insight on virtual reality auxiliary equipment and subjects with neurological disorders that cause movement errors requiring accuracy motor training.
A Fatal Case of MSTN Mutation Calf Pancreatitis
Authors: Yang MiaoMiao , Wei Zhuying , Zhou Xinyu , Bai Chunling , Zhang Ying , Li Guangpeng 
Published: December 2020

Abstract
Background:Myostatin (MSTN) is related to growth and development. MSTN gene-mutated animals are prone to dystocia and fetus enlargement, but there is no report of pancreatitis. Pancreatitis is a disease of the pancreas caused by the self-digesting effect of trypsin. In animals, pancreatitis often occurs in dogs or cats and manifests as edema, congestion, bleeding, or necrosis of the pancreas. Clinically, symptoms such as abdominal pain, bloating, nausea, vomiting, and fever appear. Elevated levels of amylase in blood and urine. Pancreatitis is very dangerous to the survival of animals. We must pay attention to it.Case presentation: This is a fatal case report of a myostatin (MSTN) gene-mutated calf diagnosed with pancreatitis. Analyses of the blood biochemistry, blood routine, postmortem anatomy and tissue section of the 2-month old calf showed that the pancreatitis indexes α-amylase and serum lipase were higher than those of normal MSTN gene-mutated and wild-type cattle. The pancreas was found to be swollen, dark red and bloody. The structure of the acinar cells of the pancreas was unidentifiable, and massive coagulation necrosis and lysis necrosis filled in the lobules of the pancreas. The interlobular spaces became enlarged, the vessels among the lobules were dilated and congested with obvious edema and blood stasis.Conclusions: Evidence from anatomy, histology, blood physiology, and biochemistry parameters indicate that the myostatin mutated calf died of pancreatitis. There are few reports on the pathology of gene-mutated animals. This is the first case of MSTN gene-mutated bovine pancreatitis.
Association between changes in salivary microbiota with glucose levels during pregnancy – findings from a pilot study
Authors: Zhang Xin , Wang Pei , Ma Liangkun , Guo Rongjun , Zhang Yongjing , Wang Peng , Liu Juntao , Zhao Jizhi 
Published: December 2020

Abstract
Background : Microbial shifts that correspond to host variations during pregnancy are vital in health maintenance. Significant changes have been reported in the oral microbiota of pregnant women when compared with nonpregnant women, but little is known about the dynamic shifts in oral microbiota during the pregnancy course. Methods : In this study, changes in salivary microbiota in 81 healthy pregnant women throughout the early stage (G1: 9-14 weeks), middle stage (G2: 21-28 weeks), and late stage (G3: 31-38 weeks) were investigated with 16S rRNA sequencing techniques. Correlations between salivary microbiota and maternal characteristics, including fasting blood glucose (FBG) levels, were evaluated. Results : Alpha diversity indexes were stable throughout pregnancy, but significant changes were found in beta diversity measured by weighted and unweighted UniFrac distances. Fourteen dominant trimester-specific taxa were identified using the LEfSe method, including Bacteroidetes in G1, Proteobacteria in G2 and Firmicutes in G3 at the phylum level. Tax4Fun prediction analysis revealed significant changes in Genetic Information Processing, Environmental Information Processing, Unclassified and Human Diseases in G2 and in Metabolism in G3 when compared to G1. Significant correlations were found between FBG levels and microbial composition, and these correlations were independent of gestational diabetes mellitus (GDM) status. Conclusion : Within the limitations of this study, the dynamic changes in salivary microbiota during pregnancy were characterized, and beyond pregnancy, FBG was also involved in shaping the salivary microbiota.
The Effect of Changes in Cerebral Oximeter Values During Cardiac Surgery on the Incidence of Postoperative Cognitive Dysfunction (POCD): a Retrospective Study Based on Propensity Score Matched Analysis
Authors: Ahn Jin hee , Lee Eun kyung , Kim Doyeon , Kang Sehee , Choi Won-Jun , Byun Jae-hun , Shim Jae-Geum , Lee Sung Hyun 
Published: December 2020

Abstract
Background The occurrence of postoperative cognitive dysfunction(POCD) after major cardiac surgery is associated with an increase in perioperative mortality and morbidity. The increased regional cerebral oxygen saturation(rSO2) value is likely related to increased POCD due to oxidative stress. The incidence of POCD in relation to an increase in rSO2 values is not clinically known yet.Methods Among 3482 patients underwent cardiac surgery, 976 patients were allocated for this retrospective study. Of these, 230 patients (32.5%) were observed to have postoperative neurologic symptoms. After propensity score 1:2 ratio matching, a total of 690 patients were included in the analysis. Recorded data on occurrence of POCD from the postoperative period to predischarge were collected from the electronic records. Results The mean baseline rSO2 value was higher in the POCD (–) group than in the POCD (+) group (61.9 ± 9.6 vs 55.3 ± 11.4; P < 0.001). The mean overall minimum rSO2 value was lower in the POCD (+) group (52.2 ± 8.3 vs 48.3 ±10.5, P < 0.001). As compared with baseline, the POCD (+) group had significantly higher values in the CPB preweaning and CPB post-weaning periods (P < 0.001, respectively). There was a greater decrease in the overall minimum rSO2 values compared with baseline in the POCD (–) group (P < 0.001). The maximum mean rSO2 changes compared with baseline were higher in the POCD (+) group (adjusted odds ratio, 1.08; 95% confidence interval [CI], 1.04–1.11; P < 0.001). The AUROC for delta values of minimal compared with baseline values was 0.62 and the AUROC for the delta values of maximal compared with baseline values was 0.72.Conclusions Increased cerebral oximeter levels relative to baseline values has an effect on the development of POCD. Intraoperative oxidative damage was associated with increased POCD, and increased cerebral oximeter levels during cardiac surgery can also be a risk factor for POCD.
p53+/-Rb1-ASCL1low&nbsp;Phenotype Predicts Better Prognosis After Surgical Resection in Large Cell Neuroendocrine Carcinoma: a Molecular Characteristic and Clinical-pathological Investigation of Lung Neuroendocrine Tumors
Authors: Dong Yuting , Zhang Qian , Wang Guoping , Duan Yaqi , Huo Zitian 
Published: December 2020

Abstract
Background: Based on morphology, necrosis degree, and proliferation status, lung neuroendocrine tumors (NETs) are commonly divided into four subtypes: typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC). However, cases difficult to classify still exist in diagnosis. Methods: We immunohistochemically investigated the molecular phenotypes in lung NETs and assessed their prognostic value. Results: After morphological re-analysis of 179 NETs, 19 cases were classified as undefined, which included 3 cases showing carcinoid morphology with high proliferation (Ki67>20% or mitotic count>10/2mm2), and 16 cases showing intermediate differentiated morphology with Ki67 among 20% to 60%. Furthermore, molecular phenotypes were determined by expression of p53, Rb1, ASCL1, STK11, and gene mutation status of KRAS. Interestingly, p53wtRb1+ distinguished an unique subcategory from undefined lung NET cases which differ from SCLC or LCNEC in prognosis, indicating WD-NET G3 existed in lung NETs. Additionally, in LCNEC, high ASCL1 expression was only relevant to lymph node metastasis rather than overall survival. However, in p53+/-Rb1- LCNEC phenotype, low ASCL1 predicted better outcomes, along with less risk of lymph node metastasis. Conclusion: This study provided evidence for existence of WD-NET G3 in NETs and revealed promising prognosis of p53+/-Rb1- ASCL1low subcategory in LCNEC, which could be beneficial to the evaluation of patient status in future clinic practice.
Invasive Pleomorphic Lobular Carcinoma of the Breast With Multiple Metastases: a Case Report
Authors: Chen Xiangrong , Lei Lei , Tian Chunxiang , Ning Ping 
Published: December 2020

Abstract
Background: Invasive pleomorphic lobular carcinoma (IPLC) accounts for less than 1% of breast cancer, and the proportion is lower when systemic metastasis occurred. This paper reports a case of IPLC with multiple metastases and gives review literature. Case presentation: A 42-year-old female with IPLC and multiple metastases. There was nodular enhancement lesion in the liver and liver function showed that transaminase was significantly increased, albumin was low, bilirubin was high, and coagulation function was significantly abnormal. Multiple abnormal signals of the vertebral body, appendages, and sternum of the whole spine; manifestations of compression fractures of C7, T1, and T9 vertebrae.Conclusions: To the best of our knowledge, this is one of the few reported cases in the IPLC with multiple metastases. For patients with IPLC, we should improve the whole body examination to prevent the omission of metastatic lesions.
Low Level of Macrophages M0 in Primary Tumors is a Favorable Factor for Metastasis in Renal Clear Cell Carcinoma
Authors: Wu Yaohai , Yang Tong , Zuo You , Fu Shuai , Zhao Zhongwei , Li Dawei , Xu Zhonghua , Yu Nengwang 
Published: December 2020

Abstract
Background: The relationship between tumor-infiltrating immune cells (TIICs) and different stages or subtypes, especially the M-stage in primary tumors, remains unknown in renal clear cell carcinoma (KIRC). Therefore, the purpose of this study was to determine the relationship between TIICs and distant metastasis and provide new ideas for immunotherapy in KIRC.Methods: Clinical outcomes and transcriptome data were obtained from The Cancer Genome Atlas (TCGA) kidney cohort to characterize the composition of 22 TIICs in KIRC. Propensity score matching (PSM) and CIBERSORT were used to proceed data.Results: A bar plot, heat map, violin plot, bubble plot, box plots, and survival curves were generated. Bar plot and violin plot showed that T cells CD8 (P = 0.032), macrophages M0 (P = 0.033), macrophages M1 (P = 0.035), and mast cells resting (P = 0.001) were correlated to the M-stage. Survival curves showed that only the macrophages M0 group had a P value <0.05 (0.015) that a higher amount of macrophages M0 was associated with a better survival rate, whereas the remaining P values, including those for T cells CD8 (0.915), macrophages M1 (0.88), and mast cells resting (0.347) were >0.05. Conclusions: we got the conclusion that a low level of macrophages M0 in primary tumors was identified as a favorable factor for metastasis in renal clear cell carcinoma, which could provide us new ideas for immunotherapy in KIRC. In order to decrease the distant metastasis, more attention and focus should be paid to increase the level of macrophages M0 in primary tumors.
Epigenetic Silencing of Tumor Suppressor IncRNA&nbsp;NKILA: Implication on NF-κB Signaling in Non-Hodgkin’s Lymphoma
Authors: Zhang Min Yue , Deng Ming Dan , Au-Yeung Rex K.H. , Wang Lu Qian , Chim Chor Sang 
Published: December 2020

Abstract
Background: NKILA, localized to 20q13.31, is a negative regulator of NF-κB signaling implicated in carcinogenesis. As a CpG island is embedded in the promoter region of NKILA, we hypothesized that NKILA is a tumor suppressor lncRNA reversibly silenced by promoter DNA methylation in non-Hodgkin’s lymphoma (NHL). Methods: Methylation-specific PCR (MSP) and quantitative bisulfite pyrosequencing were performed to detect the methylation of NKILA in normal peripheral blood buffy coats, normal tonsils tissue, NHL cell lines and NHL primary samples. SU-DHL-6 cells were treated with 5-Aza-2'-deoxycytidine for reversal of methylation-associated NKILA silencing. Tumor suppressor properties of NKILA were demonstrated by knockdown of NKILA in SU-DHL-1 cells.Results: By pyrosequencing-verified MSP, NKILA was unmethylated in normal healthy controls, including 10 peripheral blood buffy coats and 11 normal tonsils tissue, but completely methylated in one (10%) NHL cell line SU-DHL-6. Among the lymphoma cell lines, by semi-quantitative RT-PCR, methylation of NKILA was inversely correlated with its expression. In the completely methylated SU-DHL-6 cells, hypomethylation treatment with 5-Aza-2'-deoxycytidine resulted in promoter demethylation and re-expression of NKILA transcript. In NHL primary samples (n=102), NKILA methylation was observed none of mantle cell lymphoma (MCL) cases, but in 29 (51.79%) diffuse large-B cell lymphoma (DLBCL) and 4 (20%) peripheral T-cell lymphoma (PTCL) cases, hence preferentially methylated in DLBCL than MCL (P < 0.0001) and PTCL (P = 0.007). Mechanistically, knockdown of NKILA resulted in promoting IkBα phosphorylation, which was associated with nucleus translocation of total p65 and phosphorylated p65 in SU-DHL-1 cells, hence constitutive NF-κB activation. Functionally, knock-down of NKILA in SU-DHL-1 cells led to decreased cell death and increased cellular proliferation, indicating a tumor suppressor role of NKILA in NHL cells. Conclusions: NKILA was a tumour suppressor lncRNA frequently hypermethylated in DLBCL. Promoter DNA methylation-mediated NKILA silencing led to increase of cellular proliferation and decrease of cell death via repression of NF-κB signaling in NHL cells.