bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contact correction of postkeratoplastic ametropia in patients after deep anterior lamellar keratoplasty
Authors: Sinitsyn M. V. , Pozdeeva N. A. , Bodrova S. G. 
Published: December 2022

Purpose. To conduct a clinical and functional analysis of contact correction of postkeratoplastic ametropia with rigid gas-permeable scleral lenses (RGPSL) in patients after deep anterior lamellar keratoplasty.Material and methods. Clinical and functional results of correction of postkeratoplastic ametropia with RGPSL were analyzed on the basis of a comprehensive examination of 35 eyes (35 patients) after deep anterior lamellar keratoplasty (DALK) performed for stage III keratoconus. The examination included patients who had low corrected visual acuity with spectacle correction and the corneal suture was removed 1 year or more after deep anterior lamellar keratoplasty. All patients underwent: autorefractokeratometry, visometry, biomicroscopy, computed keratotopography, aberrometry, endothelial cell density calculation, analysis of corneal graft biomechanical properties, optical coherence tomography of the corneal graft. The mean age of the patients was 29 ± 8 years. In all patients, RGPSL was selected on average 1.5 ± 0.85 years after DALK. All RGPSL were from OKVision (OKV-RGP Onefit Med, Canada). The follow-up period was 6 months.Results. The uncorrected visual acuity was 1.0 ± 1.18 LogMAR, the best corrected visual acuity (BCVA) with glasses was 0.5 ± 0.8 LogMAR, the spherical refractive component was 2.44 ± 2.12 D, the cylindrical refractive component was -6,25 ± 1.24 D. The average value of BCVA in RGPSL increased to 0.72 ± 0.14 (p = 0.0054). The obtained result remained stable during 6 months of observation. In the analysis of corneal aberrations measured with the OPD-Scan II device before and after 6 months after wearing of RGPSL was noted a statistically significant decrease in total corneal aberrations, including higher-order ones. After 6 months of observation, according to Confoscan-4 data was noted the decrease in the density of corneal graft endothelial cells from 2526 ± 332 to 2510 ± 302 cells/mm² (p = 0.0326) and it corresponded to physiological losses.Conclusions. Clinical and functional analysis of the correction of postkeratoplastic ametropia with rigid gas-permeable scleral lenses during 6 months of follow-up showed high optical eﬃciency and safety of their use during the entire observation period.
Genome-wide transposon mutagenesis analysis of Burkholderia pseudomallei reveals essential genes for in vitro and in vivo survival
Authors: Wong Yee-Chin , Naeem Raeece , Abd El Ghany Moataz , Hoh Chee-Choong , Pain Arnab , Nathan Sheila 
Published: December 2022

IntroductionBurkholderia pseudomallei, a soil-dwelling microbe that infects humans and animals is the cause of the fatal disease melioidosis. The molecular mechanisms that underlie B. pseudomallei’s versatility to survive within a broad range of environments are still not well defined.MethodsWe used the genome-wide screening tool TraDIS (Transposon Directed Insertion-site Sequencing) to identify B. pseudomallei essential genes. Transposon-flanking regions were sequenced and gene essentiality was assessed based on the frequency of transposon insertions within each gene. Transposon mutants were grown in LB and M9 minimal medium to determine conditionally essential genes required for growth under laboratory conditions. The Caenorhabditis elegans infection model was used to assess genes associated with in vivo B. pseudomallei survival. Transposon mutants were fed to the worms, recovered from worm intestines, and sequenced. Two selected mutants were constructed and evaluated for the bacteria’s ability to survive and proliferate in the nematode intestinal lumen.ResultsApproximately 500,000 transposon-insertion mutants of B. pseudomallei strain R15 were generated. A total of 848,811 unique transposon insertion sites were identified in the B. pseudomallei R15 genome and 492 genes carrying low insertion frequencies were predicted to be essential. A total of 96 genes specifically required to support growth under nutrient-depleted conditions were identified. Genes most likely to be involved in B. pseudomallei survival and adaptation in the C. elegans intestinal lumen, were identified. When compared to wild type B. pseudomallei, a Tn5 mutant of bpsl2988 exhibited reduced survival in the worm intestine, was attenuated in C. elegans killing and showed decreased colonization in the organs of infected mice.DiscussionThe B. pseudomallei conditional essential proteins should provide further insights into the bacteria’s niche adaptation, pathogenesis, and virulence.
Phenotype and function of peripheral blood γδ T cells in HIV infection with tuberculosis
Authors: Zou Shi , Xiang Yanni , Guo Wei , Zhu Qi , Wu Songjie , Tan Yuting , Yan Yajun , Shen Ling , Feng Yong , Liang Ke 
Published: December 2022

BackgroundAlthough γδ T cells play an essential role in immunity againstHuman Immunodeficiency Virus(HIV) orMycobacterium tuberculosis(MTB), they are poorly described in HIV infection with tuberculosis (TB).MethodsThe phenotypic and functional properties of peripheral blood γδ T cells in patients with HIV/TB co-infection were analyzed compared to healthy controls and patients with HIV mono-infection or TB by direct intracellular cytokine staining (ICS).ResultsThe percentage of Vδ1subset in HIV/TB group was significantly higher than that in TB group, while the decreased frequency of the Vδ2and Vγ2Vδ2subsets were observed in HIV/TB group than in TB group. The percentage of CD4+CD8-Vδ2subset in HIV/TB group was markedly lower than in TB group. However, the percentage of CD4+CD8+Vδ2subset in HIV/TB group was markedly higher than HIV group or TB group. A lower percentage TNF-α and a higher percentage of IL-17A of Vδ2subset were observed in HIV/TB group than that in HIV mono-infection. The percentage of perforin-producing Vδ2subset was significantly lower in HIV/TB group than that in HIV group and TB group.ConclusionsOur data suggested that HIV/TB co-infection altered the balance of γδ T cell subsets. The influence of HIV/TB co-infection on the function of γδ T cells to produce cytokines was complicated, which will shed light on further investigations on the mechanisms of the immune response against HIV and/or MTB infection.
5mC modification patterns provide novel direction for early acute myocardial infarction detection and personalized therapy
Authors: Guo Yiqun , Jiang Hua , Wang Jinlong , Li Ping , Zeng Xiaoquan , Zhang Tao , Feng Jianyi , Nie Ruqiong , Liu Yulong , Dong Xiaobian , Hu Qingsong 
Published: December 2022

BackgroundMost deaths from coronary artery disease (CAD) are due to acute myocardial infarction (AMI). There is an urgent need for early AMI detection, particularly in patients with stable CAD. 5-methylcytosine (5mC) regulatory genes have been demonstrated to involve in the progression and prognosis of cardiovascular diseases, while little research examined 5mC regulators in CAD to AMI progression.MethodTwo datasets (GSE59867 and GSE62646) were downloaded from Gene Expression Omnibus (GEO) database, and 21 m5C regulators were extracted from previous literature. Dysregulated 5mC regulators were screened out by “limma.” The least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithm were employed to identify hub 5mC regulators in CAD to AMI progression, and 43 clinical samples (Quantitative real-time PCR) were performed for expression validation. Then a logistic model was built to construct 5mC regulator signatures, and a series of bioinformatics algorithms were performed for model validation. Besides, 5mC-associated molecular clusters were studied via unsupervised clustering analysis, and correlation analysis between immunocyte and 5mC regulators in each cluster was conducted.ResultsNine hub 5mC regulators were identified. A robust model was constructed, and its prominent classification accuracy was verified via ROC curve analysis (area under the curve [AUC] = 0.936 in the training cohort and AUC = 0.888 in the external validation cohort). Besides, the clinical effect of the model was validated by decision curve analysis. Then, 5mC modification clusters in AMI patients were identified, along with the immunocyte infiltration levels of each cluster. The correlation analysis found the strongest correlations were TET3—Mast cell in cluster-1 and TET3-MDSC in cluster-2.ConclusionNine hub 5mC regulators (DNMT3B, MBD3, UHRF1, UHRF2, NTHL1, SMUG1, ZBTB33, TET1, and TET3) formed a diagnostic model, and concomitant results unraveled the critical impact of 5mC regulators, providing interesting epigenetics findings in AMI population vs. stable CAD.
Influence of placental exosomes from early onset preeclampsia women umbilical cord plasma on human umbilical vein endothelial cells
Authors: Gu Mengqi , Zhang Fengyuan , Jiang Xiaotong , Chen Pengzheng , Wan Shuting , Lv Qingfeng , Lu Yuan , Zhou Qian , Wang Yanyun , Li Lei 
Published: December 2022

BackgroundEarly onset preeclampsia (EOSP, PE) is characterized by hypertension, proteinuria, and endothelial dysfunction. Oxidative stress-induced trophoblast dysfunction is a major pathology in PE. Placental exosomes are extracellular vesicles that are involved in “mother-placenta-foetal communication” and can regulate the biological functions of endothelial cells. Our study was designed to evaluate placental exosomes effects on endothelial cells.MethodsUmbilical cord blood from normal pregnant women and patients with PE were collected. A hypoxia/reoxygenation (H/R) model in human first trimester extravillous trophoblast cell (HTR8/SVneo) line to simulate the PE model of oxidative stress in vitro. Then, placental exosomes (i.e., NO-exo, H/R-exo, N-exo, and PE-exo) were extracted and identified. Finally, the effects of placental exosomes on the biological functions of human umbilical vein endothelial cells (HUVECs) were further evaluated by performing a series of experiments.ResultsPlacental exosomes had a double-membrane cup structure with diameters of 30–150 nm, and there was no obvious difference in placental exosomes. Compared with NO-exo and N-exo, H/R-exo and PE-exo inhibited HUVECs proliferation, tube formation and migration, increased permeability and apoptosis in vitro.ConclusionWe hypothesize that H/R-exo and PE-exo impair vessel development by disrupted biological functions in endothelial cells, which may result in vascular disorders in offspring.
An updated meta-analysis of device related thrombus following left atrial appendage closure in patients with atrial fibrillation
Authors: Zhang Song , Xiong Si-huai , Guan Yu-gen , Zhao Xian-xian , Qin Yong-wen , Guo Zhi-fu , Bai Yuan 
Published: December 2022

AimsDevice related thrombus (DRT) is a known complication of left atrial appendage closure (LAAC). However, the relation between DRT and elevated risk of ischemic events remains controversial. This study is sought to reassessed the incidence of DRT following LAAC and the relation between DRT and elevated risk of ischemic stroke and systemic embolism (SE) with latest clinical trials included.MethodsThe PubMed, Embase, and Cochrane Library databases were systematically searched from their inception until April 2022 for studies that reported the incidence of DRT and compared the incidence of both stroke and SE between DRT patients and non-DRT patients.ResultsIn 59 eligible studies, the incidence of DRT was 366/12,845 (2.8%, ranging from 0 to 11%, I2 = 64%). The incidence of DRT was not statistically different between single-seal device (SS) and dual-seal device (DS) in subgroup analysis [171/6,190 (2.8%) vs. 78/3,023 (3.6%); p = 0.93]. The pooled incidence of stroke (26 studies, 7,827 patients) in patients with and without DRT was 11.5% in DRT patients and 2.9% among non-DRT patients (OR: 5.08; 95% CI = 3.47–7.44). In the sensitivity analysis, DRT was associated with higher rate of stroke (12.1 vs. 3.2%; OR: 4.14; 95% CI = 2.69–6.38) and SE (16.0 vs. 3.8%; OR: 4.48; 95% CI = 3.04–6.62).ConclusionThe incidence of DRT was low and similar between SS and DS devices. DRT was associated with increased rates of ischemic events. The occurrence rate of ischemic events associated DRT was comparable between two occlusion mechanism devices.Systematic review registration[https://www.crd.york.ac.uk/], identifier [CRD42022326179].
Elevated serum leptin levels are associated with lower renal function among middle-aged and elderly adults in Taiwan, a community-based, cross-sectional study
Authors: Shih Yu-Lin , Shih Chin-Chuan , Chen Sun-Yi-Fan , Chen Jau-Yuan 
Published: December 2022

BackgroundPlasma leptin is considered a risk factor for obesity and cardio-metabolic disease, but the link between serum leptin and renal function is still under evaluation. In our study, we focused on the relationship between serum leptin and renal function, and we investigated the relationship in more detail.MethodsThe 396 middle-aged and elderly Taiwanese adults recruited for our health survey were the subject of our research. All participants agreed to participate and signed a consent form before they joined and completed our study. We divided the participants into three groups according to eGFR tertiles and analyzed the parameters between each group. Then, we used Pearson’s correlation test to investigate the relationship between eGFR levels and cardio-metabolic risk factors with adjustment for age. The scatter plot indicates the trend between serum leptin levels and eGFR levels. Participants were reclassified into three subgroups according to their leptin levels and the bar chart reveals the prevalence of chronic kidney disease (CKD) in each group. Finally, we used multivariate linear regression to evaluate the relationship between serum leptin and eGFR levels with adjustment for age, sex, smoking status, drinking status, body mass index (BMI), uric acid levels, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia.ResultsIn our study, we analyzed the data from 396 eligible participants. A total of 41.4% of the participants were male, and the average age of all participants was 64.81 years ( ± 8.78). The participants in the high eGFR group were more likely to have lower serum leptin levels. Furthermore, eGFR values were negatively correlated with serum leptin levels even after adjustment for age. The prevalence of CKD in the high serum leptin group was higher than that in the low serum leptin group. Serum leptin levels showed significant negative correlations with eGFR levels (β=-0.14, p&lt;0.01) in the multivariate linear regression after adjusting for age, sex, smoking status, drinking status, BMI, uric acid levels, HTN, DM, and dyslipidemia.ConclusionAccording to our study, serum leptin levels show a negative relationship with eGFR levels in middle-aged and elderly people in Taiwan. In addition, high serum leptin levels could be an novel marker to survey kidney failure in clinical practices.
Potential role of 25(OH)D insufficiency in the dysfunction of glycolipid metabolism and cognitive impairment in patients with T2DM
Authors: Sun Hui-min , Yu Yue , Gao Xin-ran , Wei Ya-dong , Qi Chuan-zong , Ma Meng-die , Xu Dan-dan , Xu Ya-yun , Ge Jin-fang 
Published: December 2022

PurposeTo investigate the changes of plasma 25(OH)D levels in type 2 diabetes mellitus (T2DM) patients and explore its role in the dysfunction of glucose and lipid metabolism and cognition.MethodsOne hundred and thirty-two T2DM patients were enrolled and the demographic and clinical data were collected. The plasma concentration of 25(OH)D was detected and the patients were divided into two groups including a Vitamin D insufficient (VDI) group and a normal VD group according to the clinical diagnostic criterial of VDI with the plasma 25(OH)D level less than 29 ng/mL. The glycolipid metabolic and routine blood biochemical indices were detected, the plasma concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble myeloid soluble trigger receptor 1 (sTREM1) were measured. The cognitive function was assessed using the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). The depressive symptomatology was assessed using the Center for Epidemiological Survey Depression Scale (CES-D). Sleep quality was assessed using the Pittsburgh sleep quality index (PSQI).ResultsThere were 70 T2DM patients with VDI (70/132, 53.03%) in this study. The plasma concentrations of glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial blood glucose (PBG), IL-6, and sTREM1 were remarkably increased in T2DM patients with VDI as compared with that with the normal VD, accompanied with an elevated BRIEF-A scores. There was no significant difference between groups with regard to the indices of blood lipid, liver function, and scores in CES-D and PSQI. Moreover, results of Pearson correlation test showed that the plasma 25(OH)D levels were negatively correlated with HbA1c, FPG, PBG, CRP, IL-6, sTREM1, CES-D sum scores, and PSQI sum scores, but positively correlated with the plasma levels of Serum creatinine (Scr). Furthermore, result of Receiver Operating Characteristic (ROC) curve analysis showed a predictive role of VDI levels in discriminating T2DM patients with higher cognitive impairments, with the sensitivity and specificity being 62.12% and 62.12%, respectively.ConclusionVDI is harmful for T2DM patients with a significant relation with the hyperglycosemia and cognitive dysfunction.
Membrane-bound IL-2 improves the expansion, survival, and phenotype of CAR Tregs and confers resistance to calcineurin inhibitors
Authors: Kremer Jakob , Henschel Pierre , Simon Daniel , Riet Tobias , Falk Christine , Hardtke-Wolenski Matthias , Wedemeyer Heiner , Noyan Fatih , Jaeckel Elmar 
Published: December 2022

BackgroundRegulatory T cells (Tregs) play an important role in the maintenance of immune homeostasis and the establishment of immune tolerance. Since Tregs do not secrete endogenous IL-2, they are especially dependent on external IL-2. IL-2 deficiency leads to lower Treg numbers, instability of the Treg phenotype and loss of immune regulation. After organ transplantation, patients are treated with calcineurin inhibitors (CNIs), which further limits available IL-2. Application of low-dose IL-2 expands Tregs but also activates NK and CD8+ T cells. It was recently shown that graft-specific Tregs recognizing mismatched MHC I molecules via a chimeric antigen receptor were far more potent than polyclonal Tregs in the regulation of immune responses after solid organ transplantation in a humanized mouse model.MethodsTherefore, our aim was to enhance the function and stability of transferred CAR-Tregs via expression of membrane-associated IL-2 (mbIL-2).ResultsmbIL-2 promoted higher survival, phenotypic stability, and function among CAR-Tregs than observed in clinical trials. The cells were also more stable under inflammatory conditions. In a preclinical humanized mouse model, we demonstrated that mbIL-2 CAR Tregs survive better in the Treg niche than control CAR Tregs and are even resistant to CNI therapy without affecting other Tregs, thus acting mainly in cis.DiscussionThe functional and phenotypic improvements observed after membrane-attached IL-2 expression in CAR-Tregs will be important step for enhancing CAR-Treg therapies currently being tested in clinical trials for use after kidney and liver transplantation as well as in autoimmune diseases.
Ferric carboxymaltose and SARS-CoV-2 vaccination-induced immunogenicity in kidney transplant recipients with iron deficiency: The COVAC-EFFECT randomized controlled trial
Authors: Vinke Joanna Sophia J. , Altulea Dania H. A. , Eisenga Michele F. , Jagersma Renate L. , Niekolaas Tessa M. , van Baarle Debbie , Heiden Marieke van Der , Steenhuis Maurice , Rispens Theo , Abdulahad Wayel H. , Sanders Jan-Stephan F. , De Borst Martin H. 
Published: December 2022

BackgroundKidney transplant recipients (KTRs) have an impaired immune response after vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Iron deficiency (ID) may adversely affect immunity and vaccine efficacy. We aimed to investigate whether ferric carboxymaltose (FCM) treatment improves humoral and cellular responses after SARS-CoV-2 vaccination in iron-deficient KTRs.MethodsWe randomly assigned 48 iron-deficient KTRs to intravenous FCM (1-4 doses of 500mg with six-week intervals) or placebo. Co-primary endpoints were SARS-CoV-2-specific anti-Receptor Binding Domain (RBD) Immunoglobulin G (IgG) titers and T-lymphocyte reactivity against SARS-CoV-2 at four weeks after the second vaccination with mRNA-1273 or mRNA-BNT162b2.ResultsAt four weeks after the second vaccination, patients receiving FCM had higher plasma ferritin and transferrin saturation (P&lt;0.001 vs. placebo) and iron (P=0.02). However, SARS-CoV-2-specific anti-RBD IgG titers (FCM: 66.51 [12.02-517.59] BAU/mL; placebo: 115.97 [68.86-974.67] BAU/mL, P=0.07) and SARS-CoV-2-specific T-lymphocyte activation (FCM: 93.3 [0.85-342.5] IFN-ɣ spots per 106 peripheral blood mononuclear cells (PBMCs), placebo: 138.3 [0.0-391.7] IFN-ɣ spots per 106 PBMCs, P=0.83) were not significantly different among both arms. After the third vaccination, SARS-CoV-2-specific anti-RBD IgG titers remained similar between treatment groups (P=0.99).ConclusionsIntravenous iron supplementation efficiently restored iron status but did not improve the humoral or cellular immune response against SARS-CoV-2 after three vaccinations.
Comprehensive analysis of a glycolysis and cholesterol synthesis-related genes signature for predicting prognosis and immune landscape in osteosarcoma
Authors: Xu Fangxing , Yan Jinglong , Peng Zhibin , Liu Jingsong , Li Zecheng 
Published: December 2022

BackgroundGlycolysis and cholesterol synthesis are crucial in cancer metabolic reprogramming. The aim of this study was to identify a glycolysis and cholesterol synthesis-related genes (GCSRGs) signature for effective prognostic assessments of osteosarcoma patients.MethodsGene expression data and clinical information were obtained from GSE21257 and TARGET-OS datasets. Consistent clustering method was used to identify the GCSRGs-related subtypes. Univariate Cox regression and LASSO Cox regression analyses were used to construct the GCSRGs signature. The ssGSEA method was used to analyze the differences in immune cells infiltration. The pRRophetic R package was utilized to assess the drug sensitivity of different groups. Western blotting, cell viability assay, scratch assay and Transwell assay were used to perform cytological validation.ResultsThrough bioinformatics analysis, patients diagnosed with osteosarcoma were classified into one of 4 subtypes (quiescent, glycolysis, cholesterol, and mixed subtypes), which differed significantly in terms of prognosis and tumor microenvironment. Weighted gene co-expression network analysis revealed that the modules strongly correlated with glycolysis and cholesterol synthesis were the midnight blue and the yellow modules, respectively. Both univariate and LASSO Cox regression analyses were conducted on screened module genes to identify 5 GCSRGs (RPS28, MCAM, EN1, TRAM2, and VEGFA) constituting a prognostic signature for osteosarcoma patients. The signature was an effective prognostic predictor, independent of clinical characteristics, as verified further via Kaplan-Meier analysis, ROC curve analysis, univariate and multivariate Cox regression analysis. Additionally, GCSRGs signature had strong correlation with drug sensitivity, immune checkpoints and immune cells infiltration. In cytological experiments, we selected TRAM2 as a representative gene to validate the validity of GCSRGs signature, which found that TRAM2 promoted the progression of osteosarcoma cells. Finally, at the pan-cancer level, TRAM2 had been correlated with overall survival, progression free survival, disease specific survival, tumor mutational burden, microsatellite instability, immune checkpoints and immune cells infiltration.ConclusionTherefore, we constructed a GCSRGs signature that efficiently predicted osteosarcoma patient prognosis and guided therapy.