bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Ism1 Reduces the Risk of Type 2 Diabetes but not Diabetes-Associated NAFLD
Authors: Wang Jiajia , Du Juan , Ge Xiaoxu , Peng Wenfang , Guo Xirong , Li Wenyi , Huang Shan 
Published: June 2022

PurposeTo examine the association of serum Ism1, a new adipokine that can regulate glucose uptake, with type 2 diabetes (T2D) in a Chinese population. Considering high prevalence of Nonalcoholic Fatty Liver Disease in patients with type 2 diabetes and the regulating role of Ism1 on glucose uptake of peripheral tissues, we further explored the association between Ism1 and diabetes-associated nonalcoholic fatty liver disease.MethodsA total of 120 newly diagnosed T2D patients and 60 control subjects with normal glucose were recruited in the case-control study. Serum Ism1 concentrations were determined by ELISA. Multivariate logistic regression analysis was used to evaluate the independent association of serum Ism1 concentration with the risk of T2D. The 120 newly diagnosed T2D patients were divided into uncomplicated T2D group and diabetes-associated NAFLD group according to the FLI score.ResultsThe Ism1 level of normoglycemic controls was higher than that of T2D patients (3.91 ± 0.24 ng/ml vs 3.01 ± 0.16 ng/ml, P=0.001). Based on quartile analysis of Ism1 level, the proportion of high circulating Ism1 levels in the control group increased while T2D group decreased, and the distribution difference was statistically significant (P=0.015). Logistic regression analysis indicated that the serum Ism1 level was an independent protective factor of type 2 diabetes (OR=0.69, 95%CI: 0.54-0.89). The decrease of Ism1 level did not increase the risk of non-alcoholic fatty liver disease in diabetic patients by Binary logistic regression analysis (OR=1.08, 95% CI: 0.69-1.69).ConclusionsThe increase of serum Ism1 was associated with a decreased risk of diabetes, and it did not reduce the risk of non-alcoholic fatty liver disease in diabetic patients.
Identification of CD8+ T Cell Related Biomarkers in Ovarian Cancer
Authors: Li Ling , Chen Dian , Luo Xiaolin , Wang Zhengkun , Yu Hanjie , Gao Weicheng , Zhong Weiqiang 
Published: June 2022

Background: Immunotherapy is a promising strategy for ovarian cancer (OC), and this study aims to identify biomarkers related to CD8+ T cell infiltration to further discover the potential therapeutic target.Methods: Three datasets with OC transcriptomic data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Two immunotherapy treated cohorts were obtained from the Single Cell Portal and Mariathasan’s study. The infiltration fraction of immune cells was quantified using three different algorithms, Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), and microenvironment cell populations counter (MCPcounter), and single-sample GSEA (ssGSEA). Weighted gene co-expression network analysis (WGCNA) was applied to identify the co-expression modules and related genes. The nonnegative matrix factorization (NMF) method was proposed for sample classification. The mutation analysis was conducted using the “maftools” R package. Key molecular markers with implications for prognosis were screened by univariate COX regression analysis and K-M survival analysis, which were further determined by the receiver operating characteristic (ROC) curve.Results: A total of 313 candidate CD8+ T cell-related genes were identified by taking the intersection from the TCGA-OV and GSE140082 cohorts. The NMF clustering analysis suggested that patients in the TCGA-OV cohort were divided into two clusters and the Cluster 1 group showed a worse prognosis. In contrast, Cluster 2 had higher amounts of immune cell infiltration, elevated ssGSEA scores in immunotherapy, and a higher mutation burden. CSMD3, MACF1, PDE4DIP, and OBSCN were more frequently mutated in Cluster 1, while SYNE2 was more frequently mutated in Cluster 2. CD38 and CXCL13 were identified by univariate COX regression analysis and K-M survival analysis in the TCGA-OV cohort, which were further externally validated in GSE140082 and GSE32062. Of note, patients with lower CXCL13 expression showed a worse prognosis and the CR/PR group had a higher expression of CXCL13 in two immunotherapy treated cohorts.Conclusion: OC patients with different CD8+ T cell infiltration had distinct clinical prognoses. CXCL13 might be a potential therapeutic target for the treatment of OC.
Case Report: A de novo Variant of CRYGC Gene Associated With Congenital Cataract and Microphthalmia
Authors: Peng Yu , Zheng Yu , Deng Zifeng , Zhang Shuju , Tan Yilan , Hu Zhengmao , Tao Lijuan , Luo Yulin 
Published: June 2022

Background: Congenital cataract is one of the most common causes of blindness in children. A rapid and accurate genetic diagnosis benefit the patients in the pediatric department. The current study aims to identify the genetic defects in a congenital cataract patient without a family history.Case presentation: A congenital cataract patient with microphthalmia and nystagmus was recruited for this study. Trio-based whole-exome sequencing revealed a de novo variant (c.394delG, p.V132Sfs*15) in CRYGC gene. According to the American College of Medical Genetics and Genomics (ACMG) criteria, the variant could be annontated as pathogenic.Conclusion: Our findings provide new knowledge of the variant spectrum of CRYGC gene and are essential for understanding the heterogeneity of cataracts in the Chinese population.
Identification of Biomarkers Associated With CD4+ T-Cell Infiltration With Gene Coexpression Network in Dermatomyositis
Authors: Huang Peng , Tang Li , Zhang Lu , Ren Yi , Peng Hong , Xiao Yangyang , Xu Jie , Mao Dingan , Liu Lingjuan , Liu Liqun 
Published: June 2022

BackgroundDermatomyositis is an autoimmune disease characterized by damage to the skin and muscles. CD4+ T cells are of crucial importance in the occurrence and development of dermatomyositis (DM). However, there are few bioinformatics studies on potential pathogenic genes and immune cell infiltration of DM. Therefore, this study intended to explore CD4+ T-cell infiltration–associated key genes in DM and construct a new model to predict the level of CD4+ T-cell infiltration in DM.MethodsGSE46239, GSE142807, GSE1551, and GSE193276 datasets were downloaded. The WGCNA and CIBERSORT algorithms were performed to identify the most correlated gene module with CD4+ T cells. Matascape was used for GO enrichment and KEGG pathway analysis of the key gene module. LASSO regression analysis was used to identify the key genes and construct the prediction model. The correlation between the key genes and CD4+ T-cell infiltration was investigated. GSEA was performed to research the underlying signaling pathways of the key genes. The key gene-correlated transcription factors were identified through the RcisTarget and Gene-motif rankings databases. The miRcode and DIANA-LncBase databases were used to build the lncRNA-miRNA-mRNA network.ResultsIn the brown module, 5 key genes (chromosome 1 open reading frame 106 (C1orf106), component of oligomeric Golgi complex 8 (COG8), envoplakin (EVPL), GTPases of immunity-associated protein family member 6 (GIMAP6), and interferon-alpha inducible protein 6 (IFI6)) highly associated with CD4+ T-cell infiltration were identified. The prediction model was constructed and showed better predictive performance in the training set, and this satisfactory model performance was validated in another skin biopsy dataset and a muscle biopsy dataset. The expression levels of the key genes promoted the CD4+ T-cell infiltration. GSEA results revealed that the key genes were remarkably enriched in many immunity-associated pathways, such as JAK/STAT signaling pathway. The cisbp_M2205, transcription factor-binding site, was enriched in C1orf106, EVPL, and IF16. Finally, 3,835 lncRNAs and 52 miRNAs significantly correlated with key genes were used to build a ceRNA network.ConclusionThe C1orf106, COG8, EVPL, GIMAP6, and IFI6 genes are associated with CD4+ T-cell infiltration. The prediction model constructed based on the 5 key genes may better predict the level of CD4+ T-cell infiltration in damaged muscle and lesional skin of DM. These key genes could be recognized as potential biomarkers and immunotherapeutic targets of DM.
Early Post-Transplant Red Blood Cell Transfusion Is Associated With an Increased Risk of Transplant Failure: A Nationwide French Study
Authors: Gaiffe Emilie , Vernerey Dewi , Bardiaux Laurent , Leroux Franck , Meurisse Aurelia , Bamoulid Jamal , Courivaud Cécile , Saas Philippe , Tiberghien Pierre , Ducloux Didier 
Published: June 2022

BackgroundRed blood cell (RBC) transfusions are frequently required in the early period after kidney transplantation. However, the consequences of RBC transfusions on long-term outcomes are largely unrecognized.MethodsWe conducted a nationwide French cohort study involving all 31 French kidney transplant centers. Patients having received a first kidney transplant between January 1, 2002 and December 31, 2008 were identified through the national registry of the French BioMedecine Agency (Agence de BioMédecine). Number and date of RBC transfusions were collected from the national database of the French transfusion public service. The primary endpoint was transplant failure defined as graft loss or death with a functional graft.ResultsAmong 12,559 patients included during the study period, 3,483 (28%) were transfused during the first 14 days post-transplant. Median follow-up was 7.6 (7.5-7.8) years. Multivariable analysis determined that post-transplant RBC transfusion was associated with an increased risk in transplant failure (HR 1.650, 95%CI [1.538;1.771] p&lt;0.0001). Both sensitivity and propension score analyses confirmed the previous result.ConclusionsEarly red blood cell transfusion after kidney transplantation is associated with increased transplant failure.
Complement Deposition Predicts Worsening Kidney Function and Underlines the Clinical Significance of the 2010 Renal Pathology Society Classification of Diabetic Nephropathy
Authors: Jiang Shimin , Di Dingxin , Jiao Yuanyuan , Zou Guming , Gao Hongmei , Li Wenge 
Published: June 2022

ObjectivesConverging evidence points towards a role of the complement system in the pathogenesis of diabetic nephropathy (DN). The classification system of diabetic kidney lesions devised by the Renal Pathology Society (RPS) in 2010 are based on the pathogenic process of DN. Therefore, we investigated the correlation between glomerular C3 deposits and RPS DN classification and the combined deleterious effects thereof on kidney function.MethodsThe study analyzed data from 217 diabetic patients who underwent renal biopsy between 2010 and 2021 and were found to have DN as the only glomerular disease. C3 deposition was considered positive if the glomerular C3 immunofluorescence intensity was at the trace or ≥1+ level. We divided DN into five glomerular lesion classes and separately evaluated the degree of interstitial and vascular involvement. The primary outcome was the composite of a ≥50% decline from the initial estimated glomerular filtration rate, end-stage renal disease, and death.ResultsNone of the patients were classified into class I, and few were classified into classes IIa (7.8%) and IV (9.2%). Most patients were classified as IIb (30.9%) and III (52.1%). C3 deposition was detected in 53.9% of patients. Multivariate logistic regression analysis showed that DN class was significantly correlated with C3 deposits [odds ratio, 1.59; 95% confidence interval (CI), 1.08–2.36; p = 0.02). During a median follow-up of 22 months, 123 (56.7%) patients reached the composite outcome. The endpoints occurred more frequently in patients with C3 deposition (69.2 vs. 42%) compared with those without C3 deposition. Patients with C3 deposition in either class IIb [hazards ratio (HR), 3.9 (95% CI, 1.14–13.17) vs. 2.46 (95% CI, 0.68–8.89)] or III [HR, 4.98 (95% CI, 1.53–16.23) vs. 2.63 (95% CI, 0.77–9.0)] had a higher risk of adverse kidney outcomes than those without C3 deposition. The prognostic accuracy of the combination of DN class and C3 deposits at 1 and 3 years was higher than that for DN class only.ConclusionsComplement deposition together with DN class predicts more rapid deterioration of kidney function in DN, which underlines the clinical significance of the DN phenotype according to the RPS classification.
Dynamic Immune Landscape and VZV-Specific T Cell Responses in Patients With Herpes Zoster and Postherpetic Neuralgia
Authors: Peng Qiao , Guo Xuejiao , Luo Yang , Wang Guocan , Zhong Lingyu , Zhu Jiamin , Li Yunze , Zeng Xun , Feng Zhiying 
Published: June 2022

ObjectivesVaricella-zoster virus (VZV) can induce herpes zoster (HZ) and postherpetic neuralgia (PHN). Immune cells play an important role in regulating HZ and PHN pathogenesis, but the dynamic immune profiles and molecular mechanisms remain unclear. This study aimed to screen dynamic immune signatures during HZ progression and elucidate the mechanism of VZV-specific T cells in PHN.MethodsWe used cytometry by time-of-flight (CyTOF) to analyze peripheral blood mononuclear cells (PBMC) samples from 45 patients with HZ and eight age-sex-matched healthy controls, eight PHN samples and seven non-PHN samples. Correlations between the immune subsets and clinical pain-related scores were performed. Further, the characteristics of VZV-specific T cells between PHN and non-PHN patients were evaluated by VZV peptide pools stimulation. The expression level of cytokines, including granzyme B, interleukin (IL)-2, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α was performed via cytometric bead array. Finally, we analyzed the alteration of Ca2+ signals in dorsal root ganglion (DRG)-derived cells after TNF-α stimulation.ResultsWe investigated the dynamic characteristics of the immune landscape of peripheral blood samples of patients with HZ and PHN, and depicted two major dynamic signatures in NK, CD4+ and CD8+ T subsets in patients with HZ, which closely correlated with clinical pain-related scores. The frequency of PD-1+CD4+ T cells, VZV-specific PD-1+CD4+ T cells, and the amount of TNF-α produced by VZV-specific T cells were higher in patients with PHN than without PHN. Furthermore, we showed that TNF-α could induce calcium influx in DRG-derived cells in a dose-dependent manner.ConclusionsOur results profiled the dynamic signatures of immune cells in patients with HZ and highlighted the important role of VZV-specific T cells in the pathogenesis of PHN.
CCL5 Release by CCR9+ CD8 T Cells: A Potential Contributor to Immunopathology of Primary Sjögren’s Syndrome
Authors: Hinrichs Anneline C. , Blokland Sofie L. M. , Kruize Aike A. , Lafeber Floris P. J. , Leavis Helen L. , van Roon Joel A. G. 
Published: June 2022

IntroductionIncreased CCL5 expression and CD8 T cells have been shown to be pivotal regulators of immunopathology in primary Sjögren’s syndrome (pSS) and pSS-like disease. Increased CCL5 expression by CCR9+ CD4 T cells has previously been implicated as a contributor to immunopathology in pSS. The role of CD8 T cells and in particular CCR9+ CD8 T cells and their potential to secrete CCL5 has not previously been studied in pSS. In this study we investigated both CCR9 and CCL5 expression by CD8 T cells in pSS patients compared to healthy controls (HC).MethodsCCR9 expression on CD8 T cells from peripheral blood was compared between patients with pSS and HC by flow cytometry. Intracellular CCL5 expression by naive, memory and effector CCR9- and CCR9+ CD8 T cells was assessed. In addition, the capacity and pace of CCL5 release upon T cell activation was determined for all subsets and compared with CD4 T cells.ResultsThe frequency of circulating CCR9+ CD8 T cells in pSS patients is increased compared to HC. Antigen-experienced CD8 T cells, especially CCR9+ effector CD8 T cells, express the highest CCL5 levels, and release the highest levels of CCL5 upon activation. Memory and effector CD8 T cells of pSS patients express significantly less CCL5 and subsequently release less CCL5 upon stimulation compared to HC. CCR9+ CD8 T cells rapidly release CCL5 and significantly more than CCR9+ CD4 T cells.ConclusionCCR9+ CD8 T cells express more CCL5 than CCR9- CD8 T cells. CCL5 is rapidly released upon activation, resulting in reduced intracellular expression. Reduced CCL5 expression by an elevated number of antigen-experienced CCR9-expressing CD8 T cells in pSS patients points towards increased releasein vivo. This suggests that CCL5 release by CCR9+ CD8 T cells contributes to immunopathology in pSS.
Identification and Validation of a Urinary Biomarker Panel to Accurately Diagnose and Predict Response to Therapy in Lupus Nephritis
Authors: Whittall-Garcia Laura , Goliad Kirubel , Kim Michael , Bonilla Dennisse , Gladman Dafna , Urowitz Murray , Fortin Paul R. , Atenafu Eshetu G. , Touma Zahi , Wither Joan 
Published: June 2022

BackgroundWe have previously shown that 15 urinary biomarkers (of 129 tested by Luminex), discriminate between active Lupus Nephritis (ALN) and non-LN patients. The aim of this study was to evaluate the ability of these 15 previously-identified urinary biomarkers to predict treatment responses to conventional therapy, and for the most predictive of these biomarkers to validate their utility to identify ALN patients in an independent prospectively-acquired lupus cohort.MethodsOur study had a 3-stage approach. In stage 1, we used Luminex to examine whether our previously identified urinary biomarkers at the time of the renal flare ( ± 3 months) or 12 ± 3 months after treatment of biopsy-proven ALN could predict treatment responses. In stage 2, a larger prospectively-acquired cross-sectional cohort was used to further validate the utility of the most predictive urinary biomarkers (identified in stage 1) to detect ALN patients. In this 2ndstage, cut-offs with the best operating characteristics to detect ALN patients were produced for each biomarker and different combinations and/or numbers of elevated biomarkers needed to accurately identify ALN patients were analyzed. In stage 3, we aimed to further corroborate the sensitivity of the cut-offs created in stage 2 to detect ALN patients in a biopsy-proven ALN cohort who had a urine sample collection within 3 months of their biopsy.ResultsTwenty-one patients were included in stage 1. Twelve (57.1%), 4 (19.1%), and 5 (23.8%) patients had a complete (CR), partial (PR) and no (NR) remission at 24 ± 3 months, respectively. The percentage decrease following 12 ± 3 months of treatment for Adiponectin, MCP-1, sVCAM-1, PF4, IL-15 and vWF was significantly higher in patients with CR in comparison to those with PR/NR. In stage 2, a total of 247 SLE patients were included, of which 24 (9.7%) had ALN, 79 (31.9%) had LN in remission (RLN) and 144 (58.3%) were non-LN (NLN) patients. Based on the combinations of biomarkers with the best operating characteristics we propose “rule out” and “rule in” ALN criteria. In stage 3, 53 biopsy-proven ALN patients were included, 35 with proliferative LN and 18 with non-proliferative ALN, demonstrating that our “rule in ALN” criteria operate better in detecting active proliferative than non-proliferative classes.ConclusionsOur results provide further evidence to support the role of Adiponectin, MCP-1, sVCAM-1 and PF4 in the detection of proliferative ALN cases. We further show the clinical utility of measuring multiple rather than a single biomarker and we propose novel “rule in” and “rule out” criteria for the detection of proliferative ALN with excellent operating characteristics.
Long-Term Safety of Rituximab in DLBCL Patients With Hepatitis B-Related Cirrhosis: A Retrospective Case Series
Authors: Song Zaiwei , Ma Yi , Jiang Dan , Zhao Rongsheng , Dong Fei 
Published: June 2022

ObjectiveChemotherapy regimens containing rituximab (RTX) have been extensively used to treat diffuse large B cell lymphoma (DLBCL). However, data looking at long-term safety of DLBCL patients with hepatitis B-related cirrhosis are still lacking. This study aims to report the safety and outcomes of RTX administration in DLBCL patients with hepatitis B-related cirrhosis.MethodsA retrospective case series was designed and implemented, using data from January 1, 2011 to December 31, 2020. Consecutive patients who were diagnosed with DLBCL and hepatitis B-related cirrhosis receiving RTX treatment were included. The primary outcomes included HBV reactivation, hepatitis flares or abnormal liver function. Survival status, the secondary outcome measure, was observed until death, loss to follow-up, or the end of follow-up, whichever occurred first.ResultsA total of 8 DLBCL patients combined with hepatitis B-related cirrhosis were included in this study [4 men; median age 62.5 years (range, 44–77 years); median RTX-containing regimen course 5 (range, 2–11)]. Of them, 6 patients had current HBV infection with HBsAg-positive and anti-HBc-positive, whereas 2 patients had previously resolved HBV infection with HBsAg-negative and anti-HBc-positive. The HBV reactivation was observed in only one patient, who received 11 courses of RTX-containing immunochemotherapies within 15 months. No hepatitis flares or abnormal liver function occurred in any patients included. All patients received standardized antiviral therapy for a lifelong time. Of 8 patients included, 3 patients died, and 1 patient was lost to follow-up, and the median overall survival among patients was 39 months (range, 7–82 months).ConclusionThe findings provide support for the concept that, on the premise of standardized and valid management strategy, RTX containing regimens may be a safe option for use as the treatment of DLBCL patients combined with hepatitis B-related cirrhosis.
Differential Urinary Microbiota Composition Between Women With and Without Recurrent Urinary Tract Infection
Authors: Huang Lei , Li Xiangyan , Zheng Bo , Li Pengtao , Wei Dali , Huang Chenwei , Sun Liying , Li Haixia 
Published: June 2022

BackgroundRecurrent urinary tract infection (RUTI) is common and burdensome in women. Due to the low concentration or slow-growing of uropathogens in RUTI, standard urine cultures (SUCs) are often negative. Next-generation sequencing (NGS) of bacterial 16S rRNA gene is more sensitive and could be used to reveal the differential microbiota between patients with RUTI and asymptomatic controls.MethodsWomen (aged ≥ 18 years) with clinically diagnosed RUTI with negative SUC and age-matched women asymptomatic controls with normal urinalysis were enrolled. Their midstream voided urine specimens were collected and processed for NGS (Illumina MiSeq) targeting the bacterial 16S rRNA gene V3-V4 region. The dataset was clustered into operational taxonomic units (OTUs) using QIIME. Taxonomic analysis, alpha diversity, beta diversity, multivariate statistical analysis, and linear discriminant analysis effect size (LEfSe) for differential analysis were performed and compared between patients with RUTI and asymptomatic controls.ResultsA total of 90 patients with RUTI and 62 asymptomatic controls were enrolled in this study. Among them, 74.4% (67/90) and 71.0% (44/62) were successfully amplified and sequenced their bacterial 16S rRNA gene. In the alpha diversity analysis, the chao1 index and observed species index were significantly lower in the RUTI group than in the control group (P = 0.015 and 0.028, respectively). In the beta diversity analysis, there was a significant difference between the 2 groups [Analysis of similarities (ANOSIM), R = 0.209, P = 0.001]. The relative abundance of 36 bacterial taxa was significantly higher, and another 24 kinds of bacteria were significantly lower in the RUTI group compared with the control group [LEfSe analysis, P &lt; 0.05, linear discriminative analysis (LDA) score &gt; 3], suggesting that Ralstonia, Prevotella, Dialister, and Corynebacterium may play an important role in RUTI.ConclusionThe urinary microbiota of women with clinically diagnosed RUTI were significantly different from age-matched asymptomatic controls.