bluuebunny/crossref_metadata_2025_split huggingface dataset:
SCM-198 Prevents Endometriosis by Reversing Low Autophagy of Endometrial Stromal Cell via Balancing ERα and PR Signals
Authors: Lin Yi-Kong , Li Yun-Yun , Li Yue , Li Da-Jin , Wang Xiao-Lin , Wang Li , Yu Min , Zhu Yi-Zhun , Cheng Jia-Jing , Du Mei-Rong 
Published: June 2022

BackgroundEndometriosis (EMS), an endocrine-related inflammatory disease, is characterized by estrogen and progesterone imbalance in ectopic lesions. However, its pathogenic mechanism has not been fully elucidated. While SCM-198 is the synthetic form of leonurine and has multiple pharmacological activities such as antioxidation and anti-inflammation, it remains unknown whether it could inhibit the progress of EMS by regulating estrogen signaling and inflammation.MethodsThe therapeutic effects of SCM-198 on EMS and its potential mechanism were analyzed by establishing EMS mouse models and performing an RNA sequencing (RNA-seq) assay. ELISA was performed to detect estrogen and tumor necrosis factor (TNF) -α concentrations in normal endometrial stromal cells (nESCs) and ectopic endometrial stromal cells (eESCs) with or without SCM-198 treatment. Western blotting, RNA silencing, and plasmid overexpression were used to analyze the relationship between inflammation, endocrine factors, and autophagy and the regulatory activity of SCM-198 on the inflammation-endocrine-autophagy axis.ResultsIncreased estrogen-estrogen receptor (ER) α signaling and decreased progesterone receptor isoform B (PRB) expression synergistically led to a hypo-autophagy state in eESCs, which further inhibited the apoptosis of eESCs. The high expression of TNF-α in eESCs enhanced the antiapoptotic effect mediated by low autophagy through the activation of the aromatase-estrogen-ERα signaling pathway. SCM-198 inhibited the growth of ectopic lesions in EMS mice and promoted the apoptosis of eESCs both in vivo and in vitro. The apoptotic effect of SCM-198 on eESCs was attained by upregulating the autophagy level via the inhibition of the TNF-α-activated aromatase-estrogen-ERα signal and the increase in PRB expression.ConclusionInflammation facilitated the progress of EMS by disrupting the estrogen regulatory axis. SCM-198 inhibited EMS progression by regulating the inflammation-endocrine-autophagy axis.
Early Initiation of Intermittently Scanned Continuous Glucose Monitoring in a Pediatric Population With Type 1 Diabetes: A Real World Study
Authors: Franceschi Roberto , Cauvin Vittoria , Stefani Lorenza , Berchielli Federica , Soffiati Massimo , Maines Evelina 
Published: June 2022

BackgroundUse of Continuous Glucose Monitoring (CGM) systems early in the course of diabetes has the potential to help glycemic management and to improve quality of life (QoL). No previous research has examined these outcomes in children-adolescents with type 1 diabetes (T1D) who use intermittently scanned CGM (isCGM) starting within the first month after diagnosis.AimTo evaluate the impact of isCGM early after T1D diagnosis, on metabolic control and QoL, comparing a group who started the use of the device within one month from the onset with another one who started at least one year later.Subjects and MethodsPatients who used isCGM within 1 month from T1D diagnosis were enrolled in group A; those who didn’t have the device during the first year were considered as control group (group B). HbA1c and total daily insulin were evaluated at 3 (T1), 6 (T2) and 12 (T3) months post-baseline (T0, diabetes onset), QoL after 1 year. In group A, isCGM glucose metrics were also recorded.Results85 patients were enrolled in group A and 67 patients in group B. In group A isCGM was well accepted during follow up: no patient dropped out; percentage of time with active sensor was in mean &gt; 87%; number of scans/day remained stable. QoL was higher in group A than in group B both in children-adolescents (p&lt;0.0001) and in parents (p 0.003). Group A presented lower HbA1c during the first year after diagnosis (p&lt;0.001), and this data correlated with glucose management indicator (GMI), time in range (TIR) and mean glucose. The honeymoon period lasted more in group A than in B (p 0.028). Furthermore, the mean hypoglycemia duration decreased during follow-up (p 0.001) in group A.ConclusionsEarly use of isCGM, starting within the first month after diagnosis, improves metabolic control and QoL in pediatric patients with T1D.
Effects of Bariatric Endoscopy on Non-Alcoholic Fatty Liver Disease: A Comprehensive Systematic Review and Meta-Analysis
Authors: Ren Mengting , Zhou Xinxin , Zhang Yunyun , Mo Feifei , Yang Jinpu , Yu Mosang , Ji Feng 
Published: June 2022

Background and objectiveEndoscopic bariatric and metabolic therapies (EBMTs) are emerging minimally invasive therapeutic options for obesity and its related complications, including non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the effects of EBMTs on NALFD in patients with obesity.MethodsFour databases were searched until Nov 2021. Randomized controlled trials (RCTs) and observational studies reporting liver-related outcomes following Food and Drug Administration (FDA)-approved and non-FDA-approved EBMTs were included. Liver parameters, metabolic parameters, and weight loss were evaluated. Risk of bias was assessed using the “risk of bias” tool in the Cochrane Collaboration for RCTs and the Methodological Index for Non-Randomized Studies criteria for observational studies.ResultsThirty-three studies with 1710 individuals were included. Regarding the effects of EBMTs on liver fibrosis, a significant decline of NAFLD Fibrosis Score, but not transient elastography-detected liver stiffness or Fibrosis-4 Index, was observed. EBMTs significantly improved liver steatosis (control attenuation parameter and Hepatic Steatosis Index), NAFLD Activity Score, and Homeostasis Model Assessment of Insulin Resistance. EBMTs reduced serum levels of alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transpeptidase considerably. Moreover, EBMTs had reducing effects on the serum levels of triglycerides and total cholesterol as well as body weight.ConclusionsOur meta-analysis suggested that EBMTs could ameliorate NAFLD based on the evidence of improved liver steatosis, liver function, and insulin resistance. Large-scale, prospective, long-term studies are warranted to clarify the role of EBMTs in patients with different stages of NAFLD.
Single-Well Dynamic Permeability Splitting Algorithm and Classification Evaluation: A Case Study of a Super-Thick Carbonate Reservoir in the Middle East
Authors: Cao Peng , Wang Yongjun , Qiao Zhanfeng , Zhu Guangya , Su Haiyang , Shao Guanming , Gong Jie , Deng Haiyang 
Published: June 2022

The permeability interpretation accuracy of single wells in the Middle East super-thick carbonate reservoir can hardly meet the actual demand of water injection development. Therefore, this study develops an iterative split algorithm to calculate single-well segmental dynamic permeability and SPI (specific production index) based on the dynamic and static well test, PLT (production log test), production test, and logging interpretation data. Moreover, the dynamic permeability classification evaluation index was optimized. The detailed steps are as follows: 1) The liquid supply of a single well is split according to tp PLT. 2) For some production intervals, the log interpretation data are applied to carry out the second iteration splitting of formation coefficient and fluid supply. 3) The proportion of liquid supply in the stratification section is calculated based on the calculation results of steps 1 and step 2. 4) The total formation coefficient of well test interpretation is divided based on the calculation results of step 3. 5) The dynamic permeability and SPI are calculated. The research results show that the dynamic permeability and SPI of a single well are accurate to the scale of one meter from the several original meters to tens of meters, which can better meet the needs of water injection development. In addition, SPI can be used as an essential index for permeability classification evaluation. Taking the Halfaya Oilfield and the Mishrif format reservoir as examples, the low penetration rate of the MB1-2 high penetration rate is 200md and the lower specific production index limit is 0.35 bbl/(d·m·psi), respectively. The dynamic foundation of the high-permeability layer is identified. This method offers a new idea for the title of high-permeability streaks. Moreover, this method can provide the scientific basis for correcting the permeability attribute model, water injection plan optimization, single-well completion cementing scheme, and water coning control, which can be popularized and applied in the same reservoirs.
Integrated Analysis of miRNAs and Gene Expression Profiles Reveals Potential Biomarkers for Osteoarthritis
Authors: Li Zhen , Chen Zhenyue , Wang Xiaotan , Li Zehui , Sun He , Wei Jinqiang , Zeng Xianzhong , Cao Xuewei , Wan Chao 
Published: June 2022

Purpose: Currently, the early diagnosis and treatment of osteoarthritis (OA) remain a challenge. In the present study, we attempted to explore potential biomarkers for the diagnosis and treatment of OA.Methods: The differentially expressed genes (DEGs) were identified based on three mRNA datasets of synovial tissues for OA patients and normal controls downloaded from the Gene Expression Omnibus (GEO) database. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used for evaluating gene function related categories. Then, miRNA sequencing was performed for differentially expressed miRNAs’ identification. Finally, weighted gene co-expression network analysis (WGCNA) was performed for genes detected by the three mRNA datasets and a competing endogenous RNA (ceRNA) network with DEGs and differentially expressed microRNAs (miRNAs) was constructed for central genes identification. In addition, the relationship between central gene expression and immune infiltration was analyzed, and the candidate agents for OA were predicted based on the Connectivity Map database. Quantitative RT-PCR (qRT-PCR), Western blotting analysis, and immunofluorescent staining were performed to validate the expression levels of differentially expressed miRNAs and differentially expressed target genes in normal and OA tissues and chondrocytes. MiRNA–mRNA network was also validated in chondrocytes in vitro.Results: A total of 259 DEGs and 26 differentially expressed miRNAs were identified, among which 94 miRNA–mRNA interactions were predicted. The brown module in WGCNA was most closely correlated with the clinical traits of OA. After overlapping the brown module genes with miRNA–mRNA pairs, 27 miRNA–mRNA pairs were obtained. A ceRNA network was constructed with 5505 lncRNA–miRNA–mRNA interactions. B-cell translocation gene 2(BTG2), Abelson-related gene (ABL2), and vascular endothelial growth factor A (VEGFA) were identified to be the central genes with good predictive performance, which were significantly correlated with immune cell infiltration in OA, reflected by declined activated dendritic cells (aDCs), and elevated contents of B cells, macrophages, neutrophils, and T helper cells. Anisomycin, MG-132, thapsigargin, and lycorine were predicted to be the potential candidate agents for OA intervention. In vitro, the expression levels of differentially expressed miRNAs and biomarkers identified in the present study were consistent with the results obtained in normal or OA knee cartilage tissues and chondrocytes. Furthermore, BTG2 was identified to be negatively regulated by miR-125a-5p.Conclusion: BTG2, ABL2, and VEGFA can be regarded as potential predictive and treatment biomarkers for OA, which might guide the clinical therapy of OA.
A Novel Extracellular Matrix Gene-Based Prognostic Model to Predict Overall Survive in Patients With Glioblastoma
Authors: Qian Chen , Xiufu Wu , Jianxun Tang , Zihao Chen , Wenjie Shi , Jingfeng Tang , Kahlert Ulf D. , Renfei Du 
Published: June 2022

Background: Glioblastoma (GBM), one of the most prevalent brain tumor types, is correlated with an extremely poor prognosis. The extracellular matrix (ECM) genes could activate many crucial pathways that facilitate tumor development. This study aims to provide online models to predict GBM survival by ECM genes.Methods: The associations of ECM genes with the prognosis of GBM were analyzed, and the significant prognosis-related genes were used to develop the ECM index in the CGGA dataset. Furthermore, the ECM index was then validated on three datasets, namely, GSE16011, TCGA-GBM, and GSE83300. The prognosis difference, differentially expressed genes, and potential drugs were obtained. Multiple machine learning methods were selected to construct the model to predict the survival status of GBM patients at 6, 12, 18, 24, 30, and 36 months after diagnosis.Results: Five ECM gene signatures (AEBP1, F3, FLNC, IGFBP2, and LDHA) were recognized to be associated with the prognosis. GBM patients were divided into high– and low–ECM index groups with significantly different overall survival rates in four datasets. High–ECM index patients exhibited a worse prognosis than low–ECM index patients. Four small molecules (podophyllotoxin, lasalocid, MG-262, and nystatin) that might reduce GBM development were predicted by the Cmap dataset. In the independent dataset (GSE83300), the maximum values of prediction accuracy at 6, 12, 18, 24, 30, and 36 months were 0.878, 0.769, 0.748, 0.720, 0.705, and 0.868, respectively. These machine learning models were provided on a publicly accessible, open-source website (https://ospg.shinyapps.io/OSPG/).Conclusion: In summary, our findings indicated that ECM genes were prognostic indicators for patient survival. This study provided an online server for the prediction of survival curves of GBM patients.
The Great Majority of Homologous Recombination Repair-Deficient Tumors Are Accounted for by Established Causes
Authors: Štancl Paula , Hamel Nancy , Sigel Keith M. , Foulkes William D. , Karlić Rosa , Polak Paz 
Published: June 2022

Background: Gene-agnostic genomic biomarkers were recently developed to identify homologous recombination deficiency (HRD) tumors that are likely to respond to treatment with PARP inhibitors. Two machine-learning algorithms that predict HRD status, CHORD, and HRDetect, utilize various HRD-associated features extracted from whole-genome sequencing (WGS) data and show high sensitivity in detecting patients with BRCA1/2 bi-allelic inactivation in all cancer types. When using only DNA mutation data for the detection of potential causes of HRD, both HRDetect and CHORD find that 30–40% of cases that have been classified as HRD are due to unknown causes. Here, we examined the impact of tumor-specific thresholds and measurement of promoter methylation of BRCA1 and RAD51C on unexplained proportions of HRD cases across various tumor types.Methods: We gathered published CHORD and HRDetect probability scores for 828 samples from breast, ovarian, and pancreatic cancer from previous studies, as well as evidence of their biallelic inactivation (by either DNA alterations or promoter methylation) in HR-related genes. ROC curve analysis evaluated the performance of each classifier in specific cancer. Tenfold nested cross-validation was used to find the optimal threshold values of HRDetect and CHORD for classifying HR-deficient samples within each cancer type.Results: With the universal threshold, HRDetect has higher sensitivity in the detection of biallelic inactivation in BRCA1/2 than CHORD and resulted in a higher proportion of unexplained cases. When promoter methylation was excluded, in ovarian carcinoma, the proportion of unexplained cases increased from 26.8 to 48.8% for HRDetect and from 14.7 to 41.2% for CHORD. A similar increase was observed in breast cancer. Applying cancer-type-specific thresholds led to similar sensitivity and specificity for both methods. The cancer-type-specific thresholds for HRDetect reduced the number of unexplained cases from 21 to 12.3% without reducing the 96% sensitivity to known events. For CHORD, unexplained cases were reduced from 10 to 9% while sensitivity increased from 85.3 to 93.9%.Conclusion: These results suggest that WGS-based HRD classifiers should be adjusted for tumor types. When applied, only ∼10% of breast, ovarian, and pancreas cancer cases are not explained by known events in our dataset.
Selection Signatures in South African Nguni and Bonsmara Cattle Populations Reveal Genes Relating to Environmental Adaptation
Authors: Kooverjee Bhaveni B. , Soma Pranisha , Van Der Nest Magrieta A. , Scholtz Michiel M. , Neser Frederick W. C. 
Published: June 2022

Climate change is a major influencing factor in beef production. The greenhouse gases produced from livestock production systems contribute to the overall greenhouse gas emissions. The aim of this study was to identify selection signatures within and between Nguni and Bonsmara cattle in relation to production and adaptation. For this purpose, genomic 150 K single nucleotide polymorphism data from Nguni (n = 231) and Bonsmara (n = 252) cattle in South Africa were used. Extended haplotype homozygosity (EHH) based analysis was executed within each population using integrated haplotype score (iHS). The R package rehh was used for detecting selection signatures across the two populations with cross population EHH (XP-EHH). Total of 121 regions of selection signatures were detected (p &lt; 0.0001) in the Bonsmara and Nguni populations. Several genes relating to DNA methylation, heat stress, feed efficiency and nitrogen metabolism were detected within and between each population. These regions also included QTLs associated with residual feed intake, residual gain, carcass weight, stature and body weight in the Bonsmara, while QTLs associated with conception rate, shear force, tenderness score, juiciness, temperament, heat tolerance, feed efficiency and age at puberty were identified in Nguni. Based on the results of the study it is recommended that the Nguni and Bonsmara be utilized in crossbreeding programs as they have beneficial traits that may allow them to perform better in the presence of climate change. Results of this study coincide with Nguni and Bonsmara breed characteristics and performance, and furthermore support informative crossbreeding programs to enhance livestock productivity in South Africa.
Identification of an Immune-Related Prognostic Risk Model in Glioblastoma
Authors: Lin Zhiying , Wang Rongsheng , Huang Cuilan , He Huiwei , Ouyang Chenghong , Li Hainan , Zhong Zhiru , Guo Jinghua , Chen Xiaohong , Yang Chunli , Yang Xiaogang 
Published: June 2022

Background: Glioblastoma (GBM) is the most common and malignant type of brain tumor. A large number of studies have shown that the immunotherapy of tumors is effective, but the immunotherapy effect of GBM is not poor. Thus, further research on the immune-related hub genes of GBM is extremely important.Methods: The GBM highly correlated gene clusters were screened out by differential expression, mutation analysis, and weighted gene co-expression network analysis (WGCNA). Least absolute shrinkage and selection operator (LASSO) and proportional hazards model (COX) regressions were implemented to construct prognostic risk models. Survival, receiver operating characteristic (ROC) curve, and compound difference analyses of tumor mutation burden were used to further verify the prognostic risk model. Then, we predicted GBM patient responses to immunotherapy using the ESTIMATE algorithm, GSEA, and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm.Results: A total of 834 immune-related differentially expressed genes (DEGs) were identified. The five hub genes (STAT3, SEMA4F, GREM2, MDK, and SREBF1) were identified as the prognostic risk model (PRM) screened out by WGCNA and LASSO analysis of DEGs. In addition, the PRM has a significant positive correlation with immune cell infiltration of the tumor microenvironment (TME) and expression of critical immune checkpoints, indicating that the poor prognosis of patients is due to TIDE.Conclusion: We constructed the PRM composed of five hub genes, which provided a new strategy for developing tumor immunotherapy.
Identification of Genes Related to 5-Fluorouracil Based Chemotherapy for Colorectal Cancer
Authors: Huang Xingxing , Ke Kun , Jin Weiwei , Zhu Qianru , Zhu Qicong , Mei Ruyi , Zhang Ruonan , Yu Shuxian , Shou Lan , Sun Xueni , Feng Jiao , Duan Ting , Mou Yiping , Xie Tian , Wu Qibiao , Sui Xinbing 
Published: June 2022

BackgroundColorectal cancer (CRC) is one of the most common malignancies and its incidence and mortality are increasing yearly. 5-Fluorouracil (5-FU) has long been used as a standard first-line treatment for CRC patients. Although 5-FU-based chemotherapy is effective for advanced CRC, the consequent resistance remains a key problem and causes the poor prognosis of CRC patients. Thus, there is an urgent need to identify new biomarkers to predict the response to 5-FU-based chemotherapy.MethodsCRC samples were retrieved from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). The immune-related genes were retrieved from the ImmPort database. Single-cell sequencing results from colorectal cancer were obtained by the ArrayExpress database. 5-FU resistance-related genes were filtered and validated by R packages. ESTIMATE algorithms were used to assess the tumor microenvironment (TME). KEGG and GO analysis were performed to explore the biological signaling pathway for resistant-response patients and sensitive-response patients in the tumor microenvironment. pRRophetic algorithms were used to predict 5-FU sensitivity. GSEA and GSVA analysis was performed to excavate the biological signaling pathway of the RBP7 gene.ResultsNine immune-related genes were identified to be associated with 5-FU resistance and poor disease-free survival (DFS) of CRC patients and the signature of these genes was developed in a DFS-prognostic model. Four immune-related genes were determined to be associated with 5-FU resistance and overall survival (OS) of CRC patients. The signature of these genes was developed an OS-prognostic model. ESTIMATE scores showed a significant difference between 5-FU resistant and 5-FU sensitive CRC patients. Resistant-response patients and sensitive-response patients to 5-FU based chemotherapy showed different GO and KEGG enrichment on the tumor microenvironment. RBP7, as a tumor immune microenvironment (TIME) related gene, was found to have the potential of predicting chemotherapy resistance and poor prognosis of CRC patients. GSEA analysis showed multiple signaling differences between the high and low expression of RBP7 in CRC patients. Hypoxia and TNFα signaling via NFκB gene sets were significantly different between chemotherapy resistant (RBP7High) and chemotherapy sensitive (RBP7Low) patients. Single-cell RNA-seq suggested RBP7 was centrally distributed in endothelial stalk cells, endothelial tip cells, and myeloid cells.ConclusionsImmune-related genes will hopefully be potential prognostic biomarkers to predict chemotherapy resistance for CRC. RBP7 may function as a tumor microenvironment regulator to induce 5-FU resistance, thereby affecting the prognosis of CRC patients.