bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Global Regulatory Network for Dysregulated Gene Expression and Abnormal Metabolic Signaling in Immune Cells in the Microenvironment of Graves’ Disease and Hashimoto’s Thyroiditis
Authors: Zheng Haitao , Xu Jie , Chu Yongli , Jiang Wenzhou , Yao Wenjie , Mo Shaowen , Song Xicheng , Zhou Jin 
Published: June 2022

BackgroundAlthough the pathogenetic mechanisms of Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) have been elucidated, the molecular mechanisms by which the abnormal immune function of cellular subpopulations trigger an autoimmune attack on thyroid tissue largely remains unexplained.MethodsThe study included 2 HT patients, 2 GD patients, and 1 control donor. The thyroid samples were extracted for single-cell RNA sequencing, whole transcriptome, full-length transcriptome (Oxford Nanopore Technologies), and metabolome sequencing. Identification of immune cells with dysregulated gene expression and abnormal metabolic signaling was performed in the microenvironment, both at the bulk and single-cell levels. Based on functional enrichment analysis, the biological processes and pathways involved in abnormal immune cells were further explored. Finally, according to cell communication analysis, the global regulatory network of immune cells was constructed.ResultsCD4+ T cells, CD8+ T cells, and macrophages were abnormally increased in patients with HT and GD. The differentially expressed genes of these cells were significantly involved in signaling pathways, including Th1 and Th2 cell differentiation, Th17 cell differentiation, cytokine–cytokine receptor interaction, and NF-kappa B signaling pathway. Moreover, in HT, CD4+ T cells interact with macrophages via the IL16-CCR5/FGF10-FGFR1/CXCL13-CXCR3 axis, and macrophages interact with CD8+ T cells via the CD70-CD27 axis, thereby activating the T-cell receptor signaling pathway and NF-kappa B signaling pathway. In GD, CD4+ T cells interact with macrophages via the CXCR3-CXCL10/PKM-CD44/MHCII-NFKBIE axis, and macrophages interact with CD8+ T cells via the IFNG-IFNGR1/CCR7-CCL21 axis, thereby activating T-cell receptor signaling pathway, Th1 and Th2 cell differentiation, and chemokine signaling pathway.ConclusionIn HT and GD, immune dysregulated cells interact and activate relevant immune pathways and further aggravate the immune response. This may trigger the immune cells to target the thyroid tissue and influence the development of the disease.
Relationship Between a Vitamin D Genetic Risk Score and Autoantibodies Among First-Degree Relatives of Probands With Rheumatoid Arthritis and Systemic Lupus Erythematosus
Authors: Vanderlinden Lauren A. , Bemis Elizabeth A. , Seifert Jennifer , Guthridge Joel M. , Young Kendra A. , Demoruelle Mary Kristen , Feser Marie , DeJager Wade , Macwana Susan , Mikuls Ted R. , O’Dell James R. , Weisman Michael H. , Buckner Jane , Keating Richard M. , Gaffney Patrick M. , Kelly Jennifer A. , Langefeld Carl D. , Deane Kevin D. , James Judith A. , Holers Vernon Michael , Norris Jill M. 
Published: June 2022

ObjectiveHigher 25-hydroxyvitamin D (25(OH)D) levels have been associated with reduced risk for autoimmune diseases and are influenced by vitamin D metabolism genes. We estimated genetically-determined vitamin D levels by calculating a genetic risk score (GRS) and investigated whether the vitamin D GRS was associated with the presence of autoantibodies related to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in those at increased risk for developing RA and SLE, respectively.MethodsIn this cross-sectional study, we selected autoantibody positive (aAb+) and autoantibody negative (aAb-) individuals from the Studies of the Etiologies of Rheumatoid Arthritis (SERA), a cohort study of first-degree relatives (FDRs) of individuals with RA (189 RA aAb+, 181 RA aAb-), and the Lupus Family Registry and Repository (LFRR), a cohort study of FDRs of individuals with SLE (157 SLE aAb+, 185 SLE aAb-). Five SNPs known to be associated with serum 25(OH)D levels were analyzed individually as well as in a GRS: rs4588 (GC), rs12785878 (NADSYN1), rs10741657 (CYP2R1), rs6538691 (AMDHD1), and rs8018720 (SEC23A).ResultsBoth cohorts had similar demographic characteristics, with significantly older and a higher proportion of males in the aAb+ FDRs. The vitamin D GRS was inversely associated with RA aAb+ (OR = 0.85, 95% CI = 0.74-0.99), suggesting a possible protective factor for RA aAb positivity in FDRs of RA probands. The vitamin D GRS was not associated with SLE aAb+ in the LFRR (OR = 1.09, 95% CI = 0.94-1.27). The SEC23A SNP was associated with RA aAb+ in SERA (OR = 0.65, 95% CI = 0.43-0.99); this SNP was not associated with SLE aAb+ in LFRR (OR = 1.41, 95% CI = 0.90 – 2.19).ConclusionGenes associated with vitamin D levels may play a protective role in the development of RA aAbs in FDRs of RA probands, perhaps through affecting lifelong vitamin D status. The GRS and the SEC23A SNP may be of interest for future investigation in pre-clinical RA. In contrast, these results do not support a similar association in SLE FDRs, suggesting other mechanisms involved in the relationship between vitamin D and SLE aAbs not assessed in this study.
Clinical Features, Treatment, and Prognostic Factors in Neuronal Surface Antibody-Mediated Severe Autoimmune Encephalitis
Authors: Wang Baojie , Wang Chunjuan , Feng Jianli , Hao Maolin , Guo Shougang 
Published: June 2022

ObjectiveThis study aimed to determine the clinical characteristics and evaluate the efficacy of immunotherapy and the long-term prognosis of severe autoimmune encephalitis (AE) in China.MethodsClinical features, laboratory or radiological findings, and treatment outcomes of 60 severe patients with AE from January 1, 2014, to December 31, 2020, were collected. Continuous variables were compared using the t-test and the nonparametric Mann–Whitney U test, as appropriate. Univariate and multivariable logistic regression analyses were performed to assess the correlations between factors, treatment responses, and prognosis of severe AE.ResultsThe median age of symptom onset was 35 years. Tumors were identified in 23.3% of patients, and 36/60 (60%) patients responded to first-line immunotherapy. Second-line immunotherapy was implemented in 26/60 (43.3%) patients. A significant clinical benefit was observed in 19/26 (73.1%) patients treated with lower dosage rituximab; seven patients were still refractory and received bortezomib as an add-on therapy. During the last follow-up, 48/60 (80%) patients achieved good outcomes (mRS, 0–2), and 10 died. Seventeen patients experienced relapses. A high CD19+ B-cell count (OR, 1.197; 95% CI [1.043–1.496]; p = 0.041) and a lower neutrophil-to-lymphocyte ratio (NLR; OR, 0.686; 95% CI [0.472–0.884]; p = 0.015) predict the response to first-line treatment and good prognosis, respectively.ConclusionsPatients with severe AE were in critical condition at baseline but could be salvaged after effective rescue immunotherapy. A lower dosage of rituximab could be an optimal option for severe AE. CD19+ B-cell count and NLR may provide prognostic information for predicting treatment response and outcome of severe AE.
Zooplankton Dominance Shift in Response to Climate-Driven Salinity Change: A Mesocosm Study
Authors: Hall Clio A. M. , Lewandowska Aleksandra M. 
Published: June 2022

Climate change predictions indicate global changes in salinity with negative implications for plankton food webs; an important baseline for functioning of marine ecosystems. Current understanding of how salinity change will impact plankton communities is mostly limited to the salinization of freshwater environments, with little known about the effects of changing salinity in marine systems. In this study, we investigate the effect of salinity change on zooplankton communities under different salinity change scenarios of the Baltic Sea. Projections for future salinity change derived from regional physical-biogeochemical models were used to set-up an outdoor mesocosm experiment in the coastal area of the Gulf of Finland. Each mesocosm was inoculated with natural plankton using a mixture of both marine and freshwater communities, mimicking the natural influx of freshwater species from rivers into the Baltic Sea. Zooplankton diversity and composition changed possibly due to different salinity tolerances among the species. Among zooplankton, rotifers dominated in low salinities (74%) and cladocerans and copepods (69%) in high salinities. Our results suggest that the zooplankton community will shift to a rotifer dominated community in areas with declining salinity due to the intolerance of other zooplankton groups to freshening.
Otolith Marking With Strontium for Stock Assessment in Coilia nasus
Authors: Liu Ming-Zhi , Jiang Ri-jin , Zhang Hui , Yang Fan , Li Xia-Fang , Feng Guang-Peng , Yin Rui , Chen Feng 
Published: June 2022

Mass stock enhancement and release are excellent ways to recover Coilia nasus resources. However, it is challenging to evaluate stock enhancement effectively, and it is important to establish a method suitable for estimating C. nasus populations. We explored the effectiveness of marking otoliths in these fish with strontium by immersing C. nasus in hexahydrate strontium chloride solutions. We used laser ablation inductively coupled plasma mass spectrometry to measure the strontium content of otoliths and fish bodies. The larvae (40 d post hatch) were reared in five different concentrations of strontium (0, 12, 24, 48, and 60 mg/L) for 7 d, followed by treatment in non-additive water for 3 wk. The results showed that the cumulative mortality rate was not significantly different between treatment and control groups (P&gt;0.05), except in the group treated with 24 mg/L strontium. The swimming and feeding behaviors did not change significantly, indicating that strontium did not negatively affect survival in this species. The strontium/calcium ratios of otoliths in the control group were stable (1.78–2.32 mmol/mol), whereas those of the experimental (marked) groups ranged widely (4.47–61.02 mmol/mol). The strontium/calcium ratios increased with increasing strontium concentration, but gradually returned to baseline values, resulting in a 100% success rate of marking with strontium. Following immersion in 12 mg/L strontium, strontium levels in the body returned to normal after 24 d. In summary, a treatment of 12 mg/L strontium for 4 d was identified as viable for marking. We confirmed the feasibility of strontium marking for the mass marking and release of C. nasus. This marking method does not affect the physiology of the fish and may provide a new approach for reasonable and scientific stock assessment of C. nasus post hatch.
Sacubitril-Valsartan Increases Ultrafiltration in Patients Undergoing Peritoneal Dialysis: A Short-Term Retrospective Self-Controlled Study
Authors: Zhang Fen , Zhang Tingting , Yang Sisi , Wang Di , Zhuo Qianqian , Qin Xianhui , Gong Nirong , Ai Jun 
Published: June 2022

AimThere are few data about the effectiveness and safety of angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan in end-stage renal disease (ESRD) patients undergoing peritoneal dialysis (PD). The present study was conducted to evaluate the association between sacubitril-valsartan treatment and peritoneal ultrafiltration (PUF) in PD patients.Methods and ResultsForty-seven ESRD patients undergoing PD for at least 3 months without severe congestive heart failure (CHF) were included in this study. Sacubitril-valsartan (generally 100 mg b.i.d) was administered after consultation with the nephrologist. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) were required to be discontinued 36 h before prescribing sacubitril-valsartan. Other treatments and dialysis modality did not change. Baseline demographic and clinical parameters were collected before ARNI administration, and daily PUF, urine volume, total output, blood pressure (BP), and body weight were collected within 7 days before and after ARNI treatment. After treated with sacubitril-valsartan, 30 patients (63.8%) had a significant increase of PUF [up to 150.4 (110.7, 232.1) ml per day], while the remaining 17 (36.2%) had a slight decrease. The overall increase of PUF was 66.4 (21.4, 123.2) ml/24 h within the 7 days after sacubitril-valsartan administration, which was significantly higher than those before (P = 0.004). Total output, BP, and body weight also significantly improved. No adverse drug reactions were observed.ConclusionsOur study indicated that sacubitril-valsartan was associated with the increase of short-term PUF and total output in PD patients.
The Influence of HbA1c and Gestational Weight Gain on Pregnancy Outcomes in Pregnant Women With Gestational Diabetes Mellitus
Authors: Zhang Qiuhong , Lee Chee Shin , Zhang Lixia , Wu Qi , Chen Yunyan , Chen Danqing , Qi Lu , Liang Zhaoxia 
Published: June 2022

BackgroundTo investigate the influence of HbA1c level and GWG on pregnancy outcomes in pregnant women with GDM.MethodsA total of 2,171 pregnant women with GDM were retrospectively included and categorized as follows: (1) normal (HbA1c &lt;6%) and elevated (HbA1c ≥6%) HbA1c groups according to the HbA1c level in the second trimester, and (2) inadequate, appropriate, and excessive GWG groups according to the IOM guidelines.ResultsIn pregnant women with GDM, advanced age and high pre-pregnancy BMI were high-risk factors for elevated HbA1c. Pregnant women with elevated HbA1c had higher OGTT levels than those with normal HbA1c, and the risks of adverse pregnancy outcomes were higher (P &lt; 0.05). The risks of primary cesarean section, hypertensive disorders during pregnancy, and macrosomia in pregnant women with excessive GWG were significantly higher than those with inadequate and appropriate GWG (P &lt; 0.05). When GWG was appropriate, the risk of hypertensive disorders during pregnancy in the elevated HbA1c group was higher than that in the normal HbA1c group. When GWG was excessive, the risks of postpartum hemorrhage, macrosomia, and neonatal asphyxia in the elevated HbA1c group were significantly higher than in the normal HbA1c group (P &lt; 0.05).ConclusionMonitoring and controlling blood glucose levels have shown effectiveness in reducing the adverse pregnancy outcomes in women with GDM, particularly for those who had excessive GWG.
A Dynamic Nomogram Predicting Portal Vein Thrombosis in Cirrhotic Patients During Primary Prophylaxis for Variceal Hemorrhage
Authors: Zhang Shuo , Ji Bing , Zhong Xuan , Zhong Lan , Yang Li , Yang Changqing 
Published: June 2022

BackgroundPortal vein thrombosis (PVT) would exert a further increase in resistance to portal blood flow, resulting in worsening portal hypertension and poor outcome. This study aimed to identify risk factors and develop an clinically applicable dynamic nomogram predicting the occurrence of PVT in cirrhotic patients during primary prophylaxis for variveal hemorrhage (VH).MethodsThe multi-center retrospective study enrolled cirrhotic patients with high-risk varices, which were further divided into training and validation cohorts for 3 years follow-up. A dynamic nomogram based on the Cox proportional hazard regression model was developed with the cutoff value calculated by X-title analysis. The performance of the nomogram was evaluated with Harrell’s concordance index (C-index), calibration curve and decision curve analysis.Results91 (34.0%) of the whole cohort were diagnosed with PVT during 3-year follow-up. Variables including carvedilol (P &lt; 0.001), low portal vein velocity (P &lt; 0.001), increased size of esophageal varices (P = 0.005), and high HbA1c (P &lt; 0.001) and procalcitonin (P = 0.015) were identified to be independently associated with PVT, which were further incorporated into the dynamic nomogram with optimal cutoff (8.8 and 14.6) for risk-stratification. The C-indexes (0.894 of internal validation and 0.892 of external validation) and calibration curves demonstrated ideal discrimination and calibration. The thresholds for more reasonable application of the nomogram were 0–0.27, 0–0.66, and 0.04–1.00 at 1, 2, and 3-year, respectively.ConclusionThe dynamic nomogram could be accurately and reliably used for clinical risk-stratification of PVT in cirrhotic patients during primary prophylaxis for VH.
RAB42 is a Potential Biomarker that Correlates With Immune Infiltration in Hepatocellular Carcinoma
Authors: Peng Hao , Du Xuanlong , Zhang Yewei 
Published: June 2022

Backgrounds: Hepatocellular carcinoma (HCC) is a malignant cancer with high mortality. Previous studies have reported that RAB42 is associated with prognosis and progression in glioma. However, the role of RAB42 in HCC is still unknown. Therefore, we aimed to elucidate the value of RAB42 in the predicting prognosis of HCC, and its relationship with immune cells infiltration.Methods: UALCAN, HCCDB, and MethSurv databases were used to examine the expression and methylation levels of RAB42 in HCC and normal samples. cBioPortal and MethSurv were used to identify genetic alterations and DNA methylation of RAB42, and their effect on prognosis. The correlations between RAB42 and the immune cells and cancer-associated fibroblasts infiltration were analyzed by TIMER, TISIDB, and GEPIA database. The LinkedOmics database was used to analyze the enriched pathways associated with genes co-expressed with RAB42. EdU assay was used to evaluate the proliferation ability of liver cancer cells, and transwell assay was used to detect the invasion and migration ability of liver cancer cells.Results: The expression levels of RAB42 were increased in HCC tissues than that in normal tissues. Highly expressed RAB42 was significantly correlated with several clinical parameters of HCC patients. Moreover, increased RAB42 expression clearly predicted poor prognosis in HCC. Furthermore, multivariate Cox regression analysis showed that RAB42 was an independent prognostic factor in HCC. The RAB42 genetic alteration rate was 5%. RAB42 DNA methylation in HCC tissues was lower than that in normal tissues. Among the 7 DNA methylation CpG sites, two were related to the prognosis of HCC. The results of gene set enrichment analysis (GSEA) showed that RAB42 was associated with various immune cells and cancer-associated fibroblasts infiltration in HCC. Meanwhile, we found RAB42 methylation was strongly correlated with immune infiltration levels, immunomodulators, and chemokines. Experiments in vitro indicated that knockdown of RAB42 inhibited the proliferation, invasion, and migration of liver cancer cells.Conclusions: Our study highlights the clinical importance of RAB42 in HCC and explores the effect of RAB42 on immune infiltration in the tumor microenvironment, and RAB42 may act as a pro-oncogene that promotes HCC progression.
Comprehensive Analyses of Ferroptosis-Related Alterations and Their Prognostic Significance in Glioblastoma
Authors: Tian Yuan , Liu Hongtao , Zhang Caiqing , Liu Wei , Wu Tong , Yang Xiaowei , Zhao Junyan , Sun Yuping 
Published: June 2022

Background: This study was designed to explore the implications of ferroptosis-related alterations in glioblastoma patients.Method: After obtaining the data sets CGGA325, CGGA623, TCGA-GBM, and GSE83300 online, extensive analysis and mutual verification were performed using R language-based analytic technology, followed by further immunohistochemistry staining verification utilizing clinical pathological tissues.Results: The analysis revealed a substantial difference in the expression of ferroptosis-related genes between malignant and paracancerous samples, which was compatible with immunohistochemistry staining results from clinicopathological samples. Three distinct clustering studies were run sequentially on these data. All of the findings were consistent and had a high prediction value for glioblastoma. Then, the risk score predicting model containing 23 genes (CP, EMP1, AKR1C1, FMOD, MYBPH, IFI30, SRPX2, PDLIM1, MMP19, SPOCD1, FCGBP, NAMPT, SLC11A1, S100A10, TNC, CSMD3, ATP1A2, CUX2, GALNT9, TNFAIP6, C15orf48, WSCD2, and CBLN1) on the basis of “Ferroptosis.gene.cluster” was constructed. In the subsequent correlation analysis of clinical characteristics, tumor mutation burden, HRD, neoantigen burden and chromosomal instability, mRNAsi, TIDE, and GDSC, all the results indicated that the risk score model might have a better predictive efficiency.Conclusion: In glioblastoma, there were a large number of abnormal ferroptosis-related alterations, which were significant for the prognosis of patients. The risk score-predicting model integrating 23 genes would have a higher predictive value.
Exploring the Association of Leukocyte Telomere Length and Hearing Threshold Shifts of Adults in the United States
Authors: Long Lili , Meng Zhaoli , Jia Zhenchao , Tang Xinghua 
Published: June 2022

BackgroundAlthough telomere length has a significant relationship with various age-related diseases, studies on its relationship with hearing status in adults are limited and equivocal. This study investigated the associations between mean telomere length (MTL) and low-, speech-, and high-frequency hearing threshold shifts of adults in the United States.MethodsA total of 2,027 adults, aged 20-69 years, from the National Health and Nutrition Examination Surveys (NHANES, 1999–2002) were included in the analytic sample. The quantitative polymerase chain reaction method was used for the MTL assay, and MTL was expressed using the telomere-to-single copy gene (T/S) ratio. Hearing loss was defined as a pure-tone average (PTA) for the better ear at ≥ 20 dB HL at frequencies 500, 1,000, 2,000, and 4,000 Hz. Univariate and multivariate linear regression analyses and smooth curve fittings were conducted to evaluate the correlation between MTL and low-, speech-, and high-frequency hearing levels.ResultsThe mean age of the participants was 40.60 ± 12.76 years, including 952 men (weighted, 48.67%) and 303 (weighted, 12.88%) participants with hearing loss. After adjusting for potential confounders in the multivariate linear regression model, the relationship between MTL and hearing thresholds was not statistically significant. Smooth curve fittings indicated a non-linear relationship between MTL and high-frequency PTA hearing threshold shifts. MTL was inversely related to high-frequency PTA to the turning point (T/S ratio = 0.82) (adjusted β−21.45, 95% CI −37.28, −5.62; P = 0.008). When the T/S ratio exceeded0.82, MTL was not associated with high-frequency PTA (adjusted β0.18, 95% CI −2.21, 2.57; P = 0.8809).ConclusionOur findings revealed that MTL was associated with high-frequency PTA hearing threshold shifts of adults in the United States in a non-linear manner.