bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome Analysis Reveals the Mechanism of Natural Ovarian Ageing
Authors: Chen Lili , Ding Bo , Wu Liju , Qiu Jialing , Li Qiong , Ye Zheng , Yang Jinmei 
Published: July 2022

BackgroundThe decline in the quantity and quality of oocytes due to ovarian ageing in women is now a significant threat to reproductive health today as the concept of delayed fertility becomes widespread. However, the molecular mechanisms of natural ovarian ageing have not been fully elucidated.MethodHere, we used transcriptomic data from 180 normal ovarian tissues from GTEx V8 to analyze the expression profile of ovarian tissues from women with age segments of 20-29 (22 individuals), 30-39 (14 individuals), 40-49 (37 individuals), 50-59 (61 individuals), 60-69 (42 individuals), and 70-79 (4 individuals), respectively. XCELL was used to assess the infiltration score of 64 cell types of the ovary. WGCNA was used to characterize the co-expression network during the natural aging of the ovary. ClusterprofileR was used for functional enrichment analysis of co-expression modules. MsViper was used for master regulator analysis.ResultsThe infiltration score of endothelial cells and activated antigen-presenting cells during natural ovarian ageing increased significantly at ages 30-39, 40-49, and then decreased, whereas CD4+ Tcm increased with age. WGCNA identified six co-expression modules from ovarian tissue transcriptomic data species. The red module was significantly and positively correlated with senescence and CD4+ Tcm, and the turquoise module was significantly and positively correlated with Endothelial Cells. We further explored ovarian tissue for women aged 20-29 and 30-39 years. The GSEA results showed that the Chemokine signaling pathway was significantly activated in the 30-39-year-old group, while Oocyte meiosis was significantly inhibited. Finally, the results of msviper found that transcription factors such as KDM1A, PRDM5, ZNF726, PPARG, FOXJ2, and GLI2 were mainly activated in the 20-29 years group, while VAV1, RUNX3, ZC3H12D, MYCL, and IRF5 were mainly activated in the 30-39 years group and that these transcription factor activities were diagnostic of natural ovarian ageing (AUC: 0.65-0.71).ConclusionNatural ageing of the ovary is significantly correlated with immune cell infiltration and activation of inflammation-related signaling pathways, with inflammation levels reaching a maximum during early ovarian ageing (30-39, 40-49) and then gradually decreasing after that. These studies provide a research basis for exploring the mechanisms of natural ovarian ageing.
Comparing Clinical and Genetic Characteristics of De Novo and Inherited COL1A1/COL1A2 Variants in a Large Chinese Cohort of Osteogenesis Imperfecta
Authors: Mei Yazhao , Zhang Hao , Zhang Zhenlin 
Published: July 2022

PurposeNearly 85%-90% of osteogenesis imperfecta (OI) cases are caused by autosome dominant mutations of COL1A1 and COL1A2 genes, of which de novo mutations cover a large proportion, whereas their characteristics remain to be elucidated. This study aims to compare the differences in clinical and genetic characteristics of de novo and inherited COL1A1/COL1A2 mutations of OI, assess the average paternal and maternal age at conception in de novo mutations, and research the rate of nonpenetrance in inherited mutations.Materials and MethodsA retrospective comparison between de novo and inherited mutations was performed among 135 OI probands with COL1A1/COL1A2 mutations. Mutational analyses of all probands and their family members were completed by Sanger sequencing. A new clinical scoring system was developed to assess the clinical severity of OI quantitatively.ResultsA total of 51 probands (37.78%) with de novo mutations and 84 probands (62.22%) with inherited mutations were grouped by the results of the parental gene verification. The proportion of clinical type III (P&lt;0.001) and clinical scores (P&lt;0.001) were significantly higher in de novo mutations. Missense mutations covered a slightly higher proportion of de novo COL1A1 mutations (46.34%) compared with inherited COL1A1 mutations (33.33%), however, lacking a significant difference (P=0.1923). The mean BMD Z/T-score at the lumbar spine in de novo mutations was -2.3 ± 1.5, lower than inherited mutations (-1.7 ± 1.8), but lacking statistical significance (P=0.0742). There was no significant difference between the two groups in OI-related phenotypes (like fracture frequency, blue sclera, and hearing loss) and biochemical indexes. In de novo mutations, the average paternal and maternal age at conception was 29.2 (P&lt;0.05) and 26.8 (P&lt;0.0001), respectively, which were significantly younger than the average gestational age of the population. Additionally, 98.04% of pedigrees (50/51) with de novo mutations were spontaneous conception. The rate of nonpenetrance of parents with pathogenic variants in the inherited mutation group was 25.64% (20/78).ConclusionsOur data revealed that the proportion of clinical type III and clinical scores were significantly higher in de novo mutations than in inherited mutations, demonstrating that de novo mutations are more damaging because they have not undergone purifying selection.
Experimental Investigation on Two-Phase Rotating Detonation Fueled by Kerosene in a Hollow Directed Combustor
Authors: Xue Sainan , Ying Zhuojun , Ma Hu , Zhou Changsheng 
Published: July 2022

The operating characteristic of two-phase rotating detonation fueled by kerosene in a hollow combustor with the isolation section is experimentally studied. When the air mass flow rate is 1.5 kg/s, the equivalence ratio is 0.98, and the total temperature of the mixture is 650 K, the stable rotating detonation wave (RDW) is obtained, which verifies the feasibility of the designed two-phase rotating detonation combustor (RDC). It is found that there is a high-frequency oblique shock induced by the upstream rotating detonation wave in the isolation section. A series of experimental tests have been carried out by changing the total temperature of incoming air , which is an important factor affecting the initiation. When the equivalent ratio of reactants is between 0.950–1.152, a stable single-wave detonation is formed. With the increase of equivalent ratio, the time of detonation wave establishment decreases, the intensity and frequency of detonation wave increases, and the temperature of engine tail flame rises. The equivalent chamber pressure Δpφ was defined, and the curve of the performance of the RDC with the equivalent ratio was obtained. The velocity of the RDW increases with the increase of equivalent ratio, and the chamber pressure has an optimal value, a higher or lower equivalent ratio will lead to the decrease of equivalent chamber pressure and the combustion chamber performance.
Characterization of Fatty Acid Metabolism in Lung Adenocarcinoma
Authors: Wang Suyu , Chen Aona , Zhu Wanli , Feng Di , Wei Juan , Li Quanfu , Shi Xuan , Lv Xin , Liu Meiyun 
Published: July 2022

Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer. Fatty acid metabolism takes part in malignancy progression. However, the roles fatty acid metabolism plays in LUAD are still unclear.Methods: The transcriptomic and clinical data of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were extracted. ssGSEA, WGCNA, univariable Cox regression, and LASSO Cox regression analyses were performed to identify the fatty acid metabolism-related genes which influenced the overall survival (OS) and build a fatty acid-related risk score (FARS) model. A nomogram was established based on the FARS and other clinicopathological features, and ROC and calibration plots were used to validate the prediction accuracy. The tumor microenvironment (TME) of patients with high and low FARS was compared.Results: A total of 38 genes were identified to be independently related to the survival outcome and put into a FARS model. High FARS patients exhibited significantly worse OS. The nomogram included the FARS and pathological stage, and the AUC of the nomogram predicting 1-, 2-, 3-, 4-, and 5-year OS was 0.789, 0.807, 0.798, 0.809, and 0.753, respectively. Calibration plots also indicated good accuracy. Moreover, the samples of the high FARS had higher expression of PDL1.Conclusion: We constructed a FARS model which could accurately predict the survival outcome of the LUAD patients. The genes of the FARS are related to the tumor microenvironment and patients with high FARS can potentially benefit more from anti-PD1/PDL1 immunotherapy. In addition, the mechanisms of the genes in the FARS affecting prognosis are worthy of further research to develop new gene-targeted drugs.
Integrated Bioinformatics Analysis Identifies Robust Biomarkers and Its Correlation With Immune Microenvironment in Nonalcoholic Fatty Liver Disease
Authors: Zhang Feng , Zhang Zhengwei , Li Yapeng , Sun Yi , Zhou Xinliang , Chen Xiaoning , Sun Shibo 
Published: July 2022

Objective: Nonalcoholic fatty liver disease (NAFLD) is a serious threat to human health worldwide. In this study, the aim is to analyze diagnosis biomarkers in NAFLD and its relationship with the immune microenvironment based on bioinformatics analysis.Methods: We downloaded microarray datasets (GSE48452 and GSE63067) from the Gene Expression Omnibus (GEO) database for screening differentially expressed genes (DEGs). The hub genes were screened by a series of machine learning analyses, such as support vector machine (SVM), least absolute shrinkage and selection operator (LASSO), and weighted gene co-expression network analysis (WGCNA). It is worth mentioning that we used the gene enrichment analysis to explore the driver pathways of NAFLD occurrence. Subsequently, the aforementioned genes were validated by external datasets (GSE66676). Moreover, the CIBERSORT algorithm was used to estimate the proportion of different types of immune cells. Finally, the Spearman analysis was used to verify the relationship between hub genes and immune cells.Results: Hub genes (CAMK1D, CENPV, and TRHDE) were identified. In addition, we found that the pathogenesis of NAFLD is mainly related to nutrient metabolism and the immune system. In correlation analysis, CENPV expression had a strong negative correlation with resting memory CD4 T cells, and TRHDE expression had a strong positive correlation with naive B cells.Conclusion: CAMK1D, CENPV, and TRHDE play regulatory roles in NAFLD. In particular, CENPV and TRHDE may regulate the immune microenvironment by mediating resting memory CD4 T cells and naive B cells, respectively, and thus influence disease progression.
The Protective Effect of the Soluble Egg Antigen of Schistosoma japonicum in A Mouse Skin Transplantation Model
Authors: Jiang Jie , Li Junhui , Zhang Yu , Zhou Chen , Guo Chen , Zhou Zhaoqin , Ming Yingzi 
Published: July 2022

BackgroundOrgan transplantation is currently an effective method for treating organ failure. Long-term use of immunosuppressive drugs has huge side effects, which severely restricts the long-term survival of patients.Schistosomacan affect the host’s immune system by synthesizing, secreting, or excreting a variety of immunomodulatory molecules, but its role in transplantation was not well defined. In order to explore whetherSchistosoma-related products can suppress rejection and induce long-term survival of the transplant, we used soluble egg antigen (SEA) ofSchistosoma japonicumin mouse skin transplantation models.Materials and methodsEach mouse was intraperitoneally injected with 100 μg of SEA three times a week for four consecutive weeks before allogenic skin transplant. Skin transplants were performed on day 0 to observe graft survival. Pathological examination of skin grafts was conducted 7 days post transplantation. The skin grafts were subjected to mRNA sequencing. Bioinformatics analysis was conducted and the expression of hub genes was verified by qPCR. Flow cytometry analysis was performed to evaluate the immune status and validate the results from bioinformatic analysis.ResultsThe mean survival time (MST) of mouse skin grafts in the SEA-treated group was 11.67 ± 0.69 days, while that of the control group was 8.00 ± 0.36 days. Pathological analysis showed thatSjSEA treatment led to reduced inflammatory infiltration within skin grafts 7 days after allogenic skin transplantation. Bioinformatics analysis identified 86 DEGs between theSjSEA treatment group and the control group, including 39 upregulated genes and 47 downregulated genes. Further analysis revealed thatSjSEA mediated regulation on cellular response to interferon-γ, activation of IL-17 signaling and chemokine signaling pathways, as well as cytokine–cytokine receptor interaction. Flow cytometry analysis showed that SEA treatment led to higher percentages of CD4+IL-4+T cells and CD4+Foxp3+T cells and decreased CD4+IFN-γ+T cells in skin transplantation.ConclusionSjSEA treatment suppressed rejection and prolonged skin graft survival by regulating immune responses.SjSEA treatment might be a potential new therapeutic strategy to facilitate anti-rejection therapy and even to induce tolerance.
Urine Soluble CD163 Is a Promising Biomarker for the Diagnosis and Evaluation of Lupus Nephritis
Authors: Huang Yun-Ju , Lin Chiung-Hung , Yang Huang-Yu , Luo Shue-Fen , Kuo Chang-Fu 
Published: July 2022

IntroductionUrine-soluble CD163 (usCD163) is released from alternatively activated macrophages involved in the resolution of inflammation in glomeruli and plays an important role in glomerulonephritis. This study explored the role of usCD163 in patients with systemic lupus erythematosus (SLE).Materials and MethodsusCD163 concentrations were measured cross-sectionally in 261 SLE patients in Taiwan. Clinical and laboratory data were collected, and SLE disease activity scores were calculated to assess the correlation with usCD163.ResultsSLE patients with high usCD163 levels tended to be younger, with a higher hospital admission rate, higher prednisolone dose, lower estimated glomerular filtration rate, higher urine protein creatinine ratio (UPCR), more pyuria and hematuria, higher levels of inflammatory markers, higher rates of anemia, neutropenia, and lymphopenia, lower complement 3 (C3) levels, higher anti-double-stranded DNA antibody (anti-dsDNA Ab) levels, and higher disease activity scores (p &lt; 0.05). usCD163 levels were significantly higher in patients with active lupus nephritis (LN) than in those with extrarenal or inactive SLE and correlated with UPCR, disease activity, and anti-dsDNA Ab levels. SLE patients with high usCD163 levels tended to have a higher chronic kidney disease stage.Discussion and conclusionThe usCD163 level correlates with the severity of LN and disease activity in renal SLE.
Efficacy and safety of camrelizumab in combination with neoadjuvant chemotherapy for ESCC and its impact on esophagectomy
Authors: Qiao Yujin , Zhao Cong , Li Xiangnan , Zhao Jia , Huang Qi , Ding Zheng , Zhang Yan , Jiao Jia , Zhang Guoqing , Zhao Song 
Published: July 2022

BackgroundEsophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China. The use of neoadjuvant immunotherapy for the treatment of ESCC is gradually increasing. Camrelizumab is one such immune checkpoint inhibitor (ICI) used for treatment. In this retrospective study, we explored the efficacy, safety, and short-term perioperative prognosis of camrelizumab in combination with neoadjuvant chemotherapy for ESCC.Materials and MethodsA total of 254 Chinese patients with ESCC were enrolled in the study; 48 received camrelizumab in combination with neoadjuvant chemotherapy (C-NC group), and 206 received neoadjuvant chemotherapy (NC group). All patients underwent surgery after the completion of 2 cycles of neoadjuvant therapy.ResultsTwenty patients (20/48, 41.7%) in the C-NC group and 22 patients (22/206, 10.7%) in the NC group achieved a pathologic complete response (pCR) (p&lt;0.001). Twenty-nine patients (29/48, 60.4%) in the C-NC group and 56 patients (56/206, 27.2%) in the NC group achieved major pathologic remission (MPR) (p&lt;0.001). There was a lower incidence of myelosuppression during neoadjuvant therapy in patients in the C-NC group (33/48, 68.8%) than in the NC group (174/206, 84.5%, p=0.012). The total incidence of adverse reactions during neoadjuvant therapy was also lower in the C-NC group (37/48, 77.1%) than in the NC group (189/206, 91.7%, p=0.003). Patients in the C-NC group had more lymph nodes cleared during surgery than those in the NC group (34 vs.30, p&lt;0.001). The logistic model showed that the treatment regimen, age, and presence of lymph node metastasis were influential factors for achieving a pCR in these patients (p&lt;0.001). Regarding other adverse events and surgery-related data, there were no significant differences observed between the two groups.ConclusionCamrelizumab in combination with neoadjuvant chemotherapy is an efficacious neoadjuvant regimen with an acceptable safety profile and does not increase the difficulty of surgery or the incidence of complications. A pCR is more likely to be achieved in patients treated with camrelizumab in combination with neoadjuvant chemotherapy, in younger patients, or in those without lymph node metastases.
Fresh Frozen Plasma in Cases of Acute Upper Gastrointestinal Bleeding Does Not Improve Outcomes
Authors: Liu Shuang , Zhang Xiaoming , Walline Joseph Harold , Yu Xuezhong , Zhu Huadong 
Published: July 2022

BackgroundBlood products are commonly transfused in patients with acute upper gastrointestinal bleeding (UGIB). There exists considerable practice variation and less evidence to guide fresh frozen plasma transfusion in patients with UGIB. The aim of this study was to explore any association between fresh frozen plasma transfusion following acute UGIB and clinical outcomes.MethodsThis was a prospective, observational, multicenter study conducted at 20 tertiary hospitals in China. Patients with acute UGIB with an international normalized ratio ≤ 2.0 at emergency department admission were included. Multivariate logistic regression models were used to examine and quantify any clinical associations.ResultsA total of 976 patients (61.57 ± 15.79 years old, 73.05% male) were included, of whom 17.42% received fresh frozen plasma transfusion. The overall 90-day mortality and rebleeding rates were 10.20 and 12.19%, respectively. After adjusting for confounding factors, transfusion of fresh frozen plasma during hospitalization was associated with higher 90-day mortality [odd ratio (OR), 2.36; 95% confidence interval (CI), 1.36–4.09; p = 0.002] but not rebleeding (OR, 1.5; 95% CI; 0.94-2.54; p = 0.085). In a subgroup analysis, patients with an international normalized ratio &lt;1.5 who were treated with fresh frozen plasma were associated with both significantly higher 90-day mortality (OR, 2.78; 95% CI, 1.49–5.21; p = 0.001) and rebleeding (OR, 2.02; 95% CI, 1.16–3.52; p = 0.013), whereas in patients with an international normalized ratio between 1.5 and 2, we did not find any significant correlation.ConclusionThis study found an association between fresh frozen plasma transfusion following acute UGIB and elevated 90-day mortality. Both 90-day mortality and rebleeding risk were significantly higher in patients with an international normalized ratio &lt; 1.5. Fresh frozen plasma transfusion in acute UGIB does not improve the poor outcomes (Chinese Clinical Trial registry, Number ChiCTR1900028676).
Monitoring the Progression of Cell-Free Expression of Microbial Rhodopsins by Surface Enhanced IR Spectroscopy: Resolving a Branch Point for Successful/Unsuccessful Folding
Authors: Ataka Kenichi , Baumann Axel , Chen Jheng-Liang , Redlich Aoife , Heberle Joachim , Schlesinger Ramona 
Published: July 2022

The translocon-unassisted folding process of transmembrane domains of the microbial rhodopsins sensory rhodopsin I (HsSRI) and II (HsSRII), channelrhodopsin II (CrChR2), and bacteriorhodopsin (HsBR) during cell-free expression has been investigated by Surface-Enhanced Infrared Absorption Spectroscopy (SEIRAS). Up to now, only a limited number of rhodopsins have been expressed and folded into the functional holoprotein in cell free expression systems, while other microbial rhodopsins fail to properly bind the chromophore all-trans retinal as indicated by the missing visible absorption. SEIRAS experiments suggest that all investigated rhodopsins lead to the production of polypeptides, which are co-translationally inserted into a solid-supported lipid bilayer during the first hour after the in-vitro expression is initiated. Secondary structure analysis of the IR spectra revealed that the polypeptides form a comparable amount of α-helical structure during the initial phase of insertion into the lipid bilayer. As the process progressed (&gt;1 h), only HsBR exhibited a further increase and association of α-helices to form a compact tertiary structure, while the helical contents of the other rhodopsins stagnated. This result suggests that the molecular reason for the unsuccessful cell-free expression of the two sensory rhodopsins and of CrChR2 is not due to the translation process, but rather to the folding process during the post-translational period. Taking our previous observation into account that HsBR fails to form a tertiary structure in the absence of its retinal, we infer that the chromophore retinal is an integral component of the compaction of the polypeptide into its tertiary structure and the formation of a fully functional protein.
Age-Related Eye Diseases in Individuals With Mild Cognitive Impairment and Alzheimer's Disease
Authors: Chua Jacqueline , Zhang Zheting , Wong Damon , Tan Bingyao , Kulantayan Bhavani , Sng Chelvin C. A. , Hilal Saima , Venketasubramanian Narayanaswamy , Tan Boon Yeow , Cheung Carol Y. , Garhöfer Gerhard , Popa-Cherecheanu Alina , Wong Tien Yin , Chen Christopher Li-Hsian , Schmetterer Leopold 
Published: July 2022

IntroductionAlzheimer's disease (AD) and age-related eye diseases pose an increasing burden as the world's population ages. However, there is limited understanding on the association of AD/cognitive impairment, no dementia (CIND) with age-related eye diseases.MethodsIn this cross-sectional, memory clinic-based study of multiethnic Asians aged 50 and above, participants were diagnosed as AD (n = 216), cognitive impairment, no dementia (CIND) (n = 252), and no cognitive impairment (NCI) (n = 124) according to internationally accepted criteria. Retinal photographs were graded for the presence of age-related macular degeneration (AMD) and diabetic retinopathy (DR) using standard grading systems. Multivariable-adjusted logistic regression models were used to determine the associations between neurological diagnosis and odds of having eye diseases.ResultsOver half of the adults had at least one eye disease, with AMD being the most common (60.1%; n = 356), followed by DR (8.4%; n = 50). After controlling for age, sex, race, educational level, and marital status, persons with AD were more likely to have moderate DR or worse (OR = 2.95, 95% CI = 1.15–7.60) compared with NCI. In the fully adjusted model, the neurological diagnosis was not associated with AMD (OR = 0.75, 95% CI = 0.45–1.24).ConclusionPatients with AD have an increased odds of having moderate DR or worse, which suggests that these vulnerable individuals may benefit from specific social support and screening for eye diseases.