bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between rest-activity rhythm and cognitive function in the elderly: The U.S. National Health and Nutrition Examination Survey, 2011-2014
Authors: Sun Xinyi , Yu Weiwei , Wang Mingsi , Hu Jun , Li Yunong 
Published: March 2023

BackgroundCircadian rhythm plays an essential role in various physiological and pathological processes related to cognitive function. The rest-activity rhythm (RAR) is one of the most prominent outputs of the circadian system. However, little is known about the relationships between RAR and different domains of cognitive function in older adults. The purpose of this study was to examine the relationships between RAR and various fields of cognitive function in older Americans.MethodsThis study included a total of 2090 older adults ≥ 60 years old from the National Health and Nutrition Examination Survey (NHANES) in 2011-2014. RAR parameters were derived from accelerometer recordings. Cognitive function was assessed using the word learning subtest developed by the Consortium to Establish a Registry for Alzheimer’s disease (CERAD W-L), the Animal Fluency Test (AFT) and the Digital Symbol Substitution Test (DSST). Linear regression was used to determine the relationships between RAR parameters (IS, IV, RA, L5, M10) and cognitive function scores (CERAD W-L, AFT, DSST).ResultsAfter adjusting for potential confounders, lower IS and M10 were associated with lower CERAD W-L scores (P=0.033 and P=0.002, respectively). Weaker RA and higher L5 were associated with lower AFT scores (P&lt;0.001 and P=0.001, respectively). And lower IS, RA, and higher L5 were associated with lower DSST scores (P=0.019, P&lt;0.001 and P&lt;0.001, respectively). In addition, the results of sensitivity analysis were similar to those of our main analyses. The main correlation results between the RAR indicators and cognitive function were robust.ConclusionsThis study suggested that the weakened and/or disrupted RAR was associated with cognitive decline in different domains in Americans over the age of 60.
Exploration of the core gene signatures and mechanisms between NAFLD and sarcopenia through transcriptomic level
Authors: Xu Ziying , Yu Zihui , Li Shang , Tian Ziyan , Yuan Jing , You Fuping 
Published: March 2023

IntroductionThe increased prevalence of non-alcoholic fatty liver disease (NAFLD) and sarcopenia among the elderly are facing a significant challenge to the world’s health systems. Our study aims to identify the coexpressed genes in NAFLD and sarcopenia patients.MethodsWe downloaded the transcriptome data of NAFLD tissue from patients, as well as muscle tissues from sarcopenia patients, from the GEO database in order to investigate the shared transcriptional regulation mechanisms between these two diseases. Then, focusing on the genes that were frequently expressed in these diseases, together with GSVA and WGCNA, we utilized a range of analysis methods to identify the main co-expressed genes in both diseases by taking intersections. We investigated these changes after learning that they mostly affected lipid metabolism and oxidative stress injury pathways.ResultsBy analyzing these genes and their interactions with transcription factors and proteins, we were able to identify 8 genes that share common patterns. From these 8 genes, we were possible to forecast potential future medicines. Our research raises the possibility of NAFLD and sarcopenia transcriptome regulatory pathways in aging populations.DiscussionIn conclusion, a complete transcription pattern mapping was carried out in order to identify the core genes, underlying biological mechanisms, and possible therapeutic targets that regulate aging in NAFLD and sarcopenia patients. It provides novel insights and proof in favor of decreasing the increased prevalence of sarcopenia in the elderly caused by NAFLD.
Pericytes modulate islet immune cells and insulin secretion through Interleukin-33 production in mice
Authors: Burganova Guzel , Schonblum Anat , Sakhneny Lina , Epshtein Alona , Wald Tomer , Tzaig Mika , Landsman Limor 
Published: March 2023

IntroductionImmune cells were recently shown to support β-cells and insulin secretion. However, little is known about how islet immune cells are regulated to maintain glucose homeostasis. Administration of various cytokines, including Interleukin-33 (IL-33), was shown to influence β-cell function. However, the role of endogenous, locally produced IL-33 in pancreatic function remains unknown. Here, we show that IL-33, produced by pancreatic pericytes, is required for glucose homeostasis.MethodsTo characterize pancreatic IL-33 production, we employed gene expression, flow cytometry, and immunofluorescence analyses. To define the role of this cytokine, we employed transgenic mouse systems to delete the Il33 gene selectively in pancreatic pericytes, in combination with the administration of recombinant IL-33. Glucose response was measured in vivo and in vitro, and morphometric and molecular analyses were used to measure β-cell mass and gene expression. Immune cells were analyzed by flow cytometry.ResutsOur results show that pericytes are the primary source of IL-33 in the pancreas. Mice lacking pericytic IL-33 were glucose intolerant due to impaired insulin secretion. Selective loss of pericytic IL-33 was further associated with reduced T and dendritic cell numbers in the islets and lower retinoic acid production by islet macrophages.DiscussionOur study demonstrates the importance of local, pericytic IL-33 production for glucose regulation. Additionally, it proposes that pericytes regulate islet immune cells to support β-cell function in an IL-33-dependent manner. Our study reveals an intricate cellular network within the islet niche.
A united model for diagnosing pulmonary tuberculosis with random forest and artificial neural network
Authors: Zhu Qingqing , Liu Jie 
Published: March 2023

Background: Pulmonary tuberculosis (PTB) is a chronic infectious disease and is the most common type of TB. Although the sputum smear test is a gold standard for diagnosing PTB, the method has numerous limitations, including low sensitivity, low specificity, and insufficient samples.Methods: The present study aimed to identify specific biomarkers of PTB and construct a model for diagnosing PTB by combining random forest (RF) and artificial neural network (ANN) algorithms. Two publicly available cohorts of TB, namely, the GSE83456 (training) and GSE42834 (validation) cohorts, were retrieved from the Gene Expression Omnibus (GEO) database. A total of 45 and 61 differentially expressed genes (DEGs) were identified between the PTB and control samples, respectively, by screening the GSE83456 cohort. An RF classifier was used for identifying specific biomarkers, following which an ANN-based classification model was constructed for identifying PTB samples. The accuracy of the ANN model was validated using the receiver operating characteristic (ROC) curve. The proportion of 22 types of immunocytes in the PTB samples was measured using the CIBERSORT algorithm, and the correlations between the immunocytes were determined.Results: Differential analysis revealed that 11 and 22 DEGs were upregulated and downregulated, respectively, and 11 biomarkers specific to PTB were identified by the RF classifier. The weights of these biomarkers were determined and an ANN-based classification model was subsequently constructed. The model exhibited outstanding performance, as revealed by the area under the curve (AUC), which was 1.000 for the training cohort. The AUC of the validation cohort was 0.946, which further confirmed the accuracy of the model.Conclusion: Altogether, the present study successfully identified specific genetic biomarkers of PTB and constructed a highly accurate model for the diagnosis of PTB based on blood samples. The model developed herein can serve as a reliable reference for the early detection of PTB and provide novel perspectives into the pathogenesis of PTB.
Pan-cancer analysis reveals signal transducer and activator of transcription (STAT) gene family as biomarkers for prognostic prediction and therapeutic guidance
Authors: Cheng Mei , Liu Yifan , Guo Yangkun , Li Man , Xian Shuyuan , Qin Hengwei , Yang Yiting , Qian Weijin , Tang Jieling , Lu Yuwei , Yao Yuntao , Zhang Mengyi , Jin Minghao , Xu Long , Huang Runzhi , Xu Dayuan 
Published: March 2023

Background: The signal transducer and activator of transcription (STAT) gene family have been widely found to regulate cell proliferation, differentiation, apoptosis, and angiogenesis through complex signaling pathways, and thus impacting tumor formation and development in different types of tumor. However, the roles of STATs on prognostic prediction and therapeutic guidance in pan-cancer remain unexplored.Materials and Methods: The dataset of 33 types of TCGA tumor, para-carcinoma and normal tissues, was obtained from the UCSC Xena database, including the gene expression profiles in the formats of FPKM value, demographic characteristics, clinical information, and survival data of STATs. Differential expression and co-expression analyses, WGCNA, clinical relevance analysis, immune subtype analysis, tumor stemness analysis, tumor purity analysis, immune infiltration analysis, immunotherapy related analysis, tumor mutation related analysis, and drug sensitivity analysis were performed by R software.Results: Differential expression of STAT1 was found between normal and BRCA tissues (p &lt; 0.001, log2FC = 0.895). Additionally, the strongest correlation among STATs lied between STAT1 and STAT2 (correlation coefficient = 0.6). Moreover, high expression levels of STAT1 (p = 0.031) were revealed to be notably correlated with poor prognosis in KIRP. In addition, STAT1 expressed the highest value in immune subtypes C1, C2, C3, and C6 in LUAD. What’s more, strong negative correlations were demonstrated between expression of STAT6 and mDNAss and mRNAss of TGCT. Additionally, STAT4 expression was characterized to be significantly negatively correlated with tumor purity of the majority of cancer types. Moreover, STAT1 and STAT3 were shown to be generally high-expressed in pan-cancer myeloid cells, and STATs all had positive correlation with the infiltration of the majority of immune cells. In addition, STATs were revealed to be closely linked with immunotherapy response. What’s more, STAT4 expression was identified to have a strong negative correlation with TMB value in DLBC. Last but not least, positive correlations were accessed between STAT5 and sensitivity of Nelarabine (cor = 0.600, p &lt; 0.001).Conclusion: In the present study, we identified STATs as biomarkers for prognostic prediction and therapeutic guidance in pan-cancer. Hopefully our findings could provide a valuable reference for future STATs research and clinical applications.
Knowledge mapping of autophagy in osteoarthritis from 2004 to 2022: A bibliometric analysis
Authors: Liao Jiahe , Yu Xinbo , Chen Jiaqi , Wu Zihua , He Qian , Zhang Yan , Song Weijiang , Luo Jing , Tao Qingwen 
Published: March 2023

BackgroundAutophagy in osteoarthritis (OA) has become an active area of research with substantial value and potential. Nevertheless, few bibliometric studies have systematically analyzed the available research in the field. The main goal of this study was to map the available literature on the role of autophagy in OA and identify global research hotspots and trends.MethodsThe Web of Science Core Collection and Scopus databases were interrogated for studies of autophagy in OA published between 2004 and 2022. Microsoft Excel, VOSviewer and CiteSpace software were used to analyze and visualize the number of publications and associated citations, and reveal global research hotspots and trends in the autophagy in OA field.Results732 outputs published by 329 institutions from 55 countries/regions were included in this study. From 2004 to 2022, the number of publications increased. China produced the most publications (n=456), prior to the USA (n=115), South Korea (n=33), and Japan (n=27). Scripps Research Institute (n=26) was the most productive institution. Martin Lotz (n=30) was the highest output author, while Caramés B (n=302) was the highest output author. Osteoarthritis and Cartilage was the most prolific and most co-cited journal. Currently, the autophagy in OA research hotspots include chondrocyte, transforming growth factor beta 1 (TGF-β1), inflammatory response, stress, and mitophagy. The emerging research trends in this field are AMPK, macrophage, senescence, apoptosis, tougu xiaotong capsule (TXC), green tea extract, rapamycin, and dexamethasone. Novel drugs targeting specific molecule such as TGF-β and AMPK have shown therapeutic potential but are still in the preclinical stage of development.ConclusionsResearch on the role of autophagy in OA is flourishing. Martin Lotz, Beatriz Caramés, and Osteoarthritis and Cartilage have made outstanding contributions to the field. Prior studies of OA autophagy mainly focused on mechanisms underlying OA and autophagy, including AMPK, macrophages, TGF-β1, inflammatory response, stress, and mitophagy. Emerging research trends, however, are centered around the relationship between autophagy, apoptosis, and senescence, as well as drug candidates such as TXC and green tea extract. The development of new targeted drugs that enhance or restore autophagic activity is a promising strategy for the treatment of OA.
A cis-element at the Rorc locus regulates the development of type 3 innate lymphoid cells
Authors: Chang Dehui , Zhang Hao , Ge Jing , Xing Qi , Guo Xinyi , Wang Xiaohu , Dong Chen 
Published: March 2023

BackgroundAs an important early source of IL-17A and IL-22 in immune responses, type 3 innate lymphoid cells (ILC3s) are critically regulated by the transcription factor retinoic-acid-receptor-related orphan receptor gamma t (RORγt). Previously, we have identified a crucial role of the conserved non-coding sequence 9 (CNS9), located at +5,802 to +7,963 bp of the Rorc gene, in directing T helper 17 differentiation and related autoimmune disease. However, whether cis-acting elements regulate RORγt expression in ILC3s is unknown.ResultsHere we show that CNS9 deficiency in mice not only decreases ILC3 signature gene expression and increases ILC1-gene expression features in total ILC3s, but also leads to generation of a distinct CD4+NKp46+ ILC3 population, though the overall numbers and frequencies of RORγt+ ILC3s are not affected. Mechanistically, CNS9 deficiency selectively decreases RORγt expression in ILC3s, which thus alters ILC3 gene expression features and promotes cell-intrinsic generation of CD4+NKp46+ ILC3 subset.ConclusionOur study thus identifies CNS9 as an essential cis-regulatory element controlling the lineage stability and plasticity of ILC3s through modulating expression levels of RORγt protein.
Microbiota-ear-brain interaction is associated with generalized anxiety disorder through activation of inflammatory cytokine responses
Authors: Feng Renyi , Zhu Qingyong , Li Qingchen , Zhai Yanping , Wang Jiuqi , Qin Chi , Liang Dongxiao , Zhang Rui , Tian Haiyan , Liu Han , Chen Yongkang , Fu Yu , Wang Xuejing , Ding Xuebing 
Published: March 2023

IntroductionGeneralized anxiety disorder (GAD) is one of the most enduring anxiety disorders, being associated with increased systemic inflammation. However, the trigger and mechanisms underlying the activation of inflammatory cytokine responses in GAD remain poorly understood.Materials and methodsWe characterized the ear canal microbiome in GAD patients through 16S rRNA gene sequencing and metagenomic sequencing and identified the serum inflammatory markers in GAD patients. Spearman correlations were applied to test the relationship between the microbiota changes and systemic inflammation.ResultsOur findings showed the higher microbial diversity, accompanied with the significantly increased abundance of Proteobacteria, and decreased abundance of Firmicutes in the ear canal of GAD participants compared to that of the age- and sex-matched healthy controls (HC). Metagenomic sequencing showed that Pseudomonas aeruginosa were significantly increased at species-level in GAD patients. Furthermore, we observed the relative abundance of Pseudomonas aeruginosa was positively associated with elevated systemic inflammatory markers and the severity of disease, suggesting that these ear canal microbiota alterations might be correlated with GAD by activating the inflammatory response.ConclusionsThese findings indicate that microbiota-ear-brain interaction via upregulating inflammatory reaction involve in the development of GAD, as well as suggest that ear canal bacterial communities may be a target for therapeutic intervention.
Differentiation-related genes in tumor-associated macrophages as potential prognostic biomarkers in non-small cell lung cancer
Authors: Li Zhaoxun , Zhou Bin , Zhu Xinsheng , Yang Fujun , Jin Kaiqi , Dai Jie , Zhu Yuming , Song Xiao , Jiang Gening 
Published: March 2023

BackgroundThe purpose of this study was to evaluate the role of differentiation-related genes (DRGs) in tumor-associated macrophages (TAMs) in non-small cell lung cancer (NSCLC).MethodsSingle cell RNA-seq (scRNA-seq) data from GEO and bulk RNA-seq data from TCGA were analyzed to identify DRGs using trajectory method. Functional gene analysis was carried out by GO/KEGG enrichment analysis. The mRNA and protein expression in human tissue were analyzed by HPA and GEPIA databases. To investigate the prognostic value of these genes, three risk score (RS) models in different pathological types of NSCLC were generated and predicted NSCLC prognosis in datasets from TCGA, UCSC and GEO databases.Results1,738 DRGs were identified through trajectory analysis. GO/KEGG analysis showed that these genes were predominantly related to myeloid leukocyte activation and leukocyte migration. 13 DRGs (C1QB, CCL4, CD14, CD84, FGL2, MS4A6A, NLRP3, PLEK, RNASE6, SAMSN1, SPN, TMEM176B, ZEB2) related to prognosis were obtained through univariate Cox analysis and Lasso regression. C1QB, CD84, FGL2, MS4A6A, NLRP3, PLEK, SAMSN1, SPN, and ZEB2 were downregulated in NSCLC compared to non-cancer tissue. The mRNA of 13 genes were significantly expressed in pulmonary macrophages with strong cell specificity. Meanwhile, immunohistochemical staining showed that C1QB, CCL4, SPN, CD14, NLRP3, SAMSN1, MS4A6A, TMEM176B were expressed in different degrees in lung cancer tissues. ZEB2 (HR=1.4, P&lt;0.05) and CD14 (HR=1.6, P&lt;0.05) expression were associated with a worse prognosis in lung squamous cell carcinoma; ZEB2 (HR=0.64, P&lt;0.05), CD84 (HR=0.65, P&lt;0.05), PLEK (HR=0.71, P&lt;0.05) and FGL2 (HR=0.61, P&lt;0.05) expression were associated with a better prognosis in lung adenocarcinoma. Three RS models based on 13 DRGs both showed that the high RS was significantly associated with poor prognosis in different pathological types of NSCLC.ConclusionsThis study highlights the prognostic value of DRGs in TAMs in NSCLC patients, providing novel insights for the development of therapeutic and prognostic targets based on TAM functional differences.
Porcine anti-human lymphocyte immunoglobulin depletes the lymphocyte population to promote successful kidney transplantation
Authors: Zhang Limin , Zou Haoyong , Lu Xia , Shi Huibo , Xu Tao , Gu Shiqi , Yu Qinyu , Yin Wenqu , Chen Shi , Zhang Zhi , Gong Nianqiao 
Published: March 2023

IntroductionPorcine anti-human lymphocyte immunoglobulin (pALG) has been used in kidney transplantation, but its impacts on the lymphocyte cell pool remain unclear.MethodsWe retrospectively analyzed 12 kidney transplant recipients receiving pALG, and additional recipients receiving rabbit anti-human thymocyte immunoglobulin (rATG), basiliximab, or no induction therapy as a comparison group.ResultspALG showed high binding affinity to peripheral blood mononuclear cells (PBMCs) after administration, immediately depleting blood lymphocytes; an effect that was weaker than rATG but stronger than basiliximab. Single-cell sequencing analysis showed that pALG mainly influenced T cells and innate immune cells (mononuclear phagocytes and neutrophils). By analyzing immune cell subsets, we found that pALG moderately depleted CD4+T cells, CD8+T cells, regulatory T cells, and NKT cells and mildly inhibited dendritic cells. Serum inflammatory cytokines (IL-2, IL-6) were only moderately increased compared with rATG, which might be beneficial in terms of reducing the risk of untoward immune activation. During 3 months of follow-up, we found that all recipients and transplanted kidneys survived and showed good organ function recovery; there were no cases of rejection and a low rate of complications.DiscussionIn conclusion, pALG acts mainly by moderately depleting T cells and is thus a good candidate for induction therapy for kidney transplant recipients. The immunological features of pALG should be exploited for the development of individually-optimized induction therapies based on the needs of the transplant and the immune status of the patient, which is appropriate for non-high-risk recipients.
Peripheral blood mononuclear cells reactivity in recent-onset type I diabetes patients is directed against the leader peptide of preproinsulin, GAD65271-285 and GAD65431-450
Authors: Jores Rita D. , Baldera Davide , Schirru Enrico , Muntoni Sandro , Rossino Rossano , Manchinu Maria F. , Marongiu Maria F. , Caria Cristian A. , Ripoli Carlo , Ricciardi Maria R. , Cucca Francesco , Congia Mauro 
Published: March 2023

IntroductionT cell reactivity against pancreatic autoantigens is considered one of the main contributors to the destruction of insulin-producing cells in type 1 diabetes (T1D). Over the years, peptide epitopes derived from these autoantigens have been described in NOD mice and in both HLA class II transgenic mice and humans. However, which ones are involved in the early onset or in the progressive phases of the disease is still unclear.MethodsIn this work we have investigated, in early-onset T1D pediatric patients and HLA-matched controls from Sardinia, the potential of preproinsulin (PPI) and glutamate decarboxylase 65 (GAD65)-derived peptides to induce spontaneous T cell proliferation responses of peripheral blood mononuclear cells (PBMCs).ResultsSignificant T cell responses against PPI1-18, PPI7-19 and PPI31-49, the first two belonging to the leader sequence of PPI, and GAD65271-285 and GAD65431-450, were found in HLA-DR4, -DQ8 and -DR3, -DQ2 T1D children.ConclusionsThese data show that cryptic epitopes from the leader sequence of the PPI and GAD65271-285 and GAD65431-450 peptides might be among the critical antigenic epitopes eliciting the primary autoreactive responses in the early phases of the disease. These results may have implications in the design of immunogenic PPI and GAD65 peptides for peptide-based immunotherapy.