bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Response of Severe Aplastic Anemia to Rabbit-Antithymocyte Immunoglobulin Based Immunosuppressive Therapy Combined With Eltrombopag
Authors: Li Ruixin , Zhou Jiongtao , Liu Zhengyuan , Chen Xi , Long Qiqiang , Yang Yan , Lin Shengyun , Jia Jinsong , He Guangsheng , Li JianYong 
Published: June 2022

Addition of eltrombopag (E-PAG) to intensive immunosuppressive therapy (IST) contributes to restoring hematopoiesis in patients with severe aplastic anemia (SAA). Used at relatively low doses in the East Asian population, the efficacies of E-PAG and the predictors for efficacy are not clear. We conducted a retrospective, multicenter study to analyze the efficacy and the possible predicting factors at 6 months in 58 adult SAA patients with rabbit ATG-based IST and E-PAG. The response rate and complete response rate at 6 months were 76% and 21%, respectively. The baseline reticulocyte percentage [area under a curve (AUC)=0.798, 95% confidence interval (CI) 0.640-0.956, P=0.006], absolute reticulocyte count (ARC) (AUC =0.808, 95%CI 0.647-0.970, P=0.004), red cell distribution width – coefficient of variation (RDW-CV) (AUC=0.722, 95%CI 0.494-0.950, P=0.040), and absolute lymphocyte count (ALC) (AUC=0.706, 95%CI 0.522-0.890, P=0.057) were highly predictive of response at 6 months. The tipping values of reticulocyte percentage, ARC, RDW-CV, and ALC were 0.45%, 7.36×109/L, 11.75%, and 1.06×109/L, respectively. The sensitivity and specificity of reticulocyte percentages were 81.6% and 66.7%; ARC were 86.8% and 66.7%, RDW-CV were 94.7% and 55.6%; ALC were 55.3% and 88.9%. At a median follow-up of 15.5 months, the 2-year cumulative overall survival was 92%. The baseline reticulocyte percentage, ARC, RDW-CV, and ALC were potential factors in predicting a favorable effect of rabbit-ATG based IST plus E-PAG in SAA patients of East Asia (ChiCTR2100045895).Clinical Trial Registrationhttp://www.chictr.org.cn/edit.aspx?pid=125480&amp;htm=4, identifier ChiCTR2100045895.
Targeting PCSK9 Ameliorates Graft Vascular Disease in Mice by Inhibiting NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells
Authors: Zou Yanqiang , Chen Zhang , Zhang Xi , Yu Jizhang , Xu Heng , Cui Jikai , Li Yuan , Niu Yuqing , Zhou Cheng , Xia Jiahong , Wu Jie 
Published: June 2022

BackgroundGraft vascular disease (GVD), which limits the long-term survival of patients after solid-organ transplantation, is associated with both immune responses and nonimmune factors, including dyslipidemia. Recent studies have shown that inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), a U.S. Federal Drug Administration-approved treatment for hyperlipidemia, reduces cardiovascular events, regulates inflammatory responses, and enhances the efficacy of immune checkpoint therapy in cancer treatment through a cholesterol-independent mechanism. However, whether targeting PCSK9 is a potential therapeutic strategy for GVD remains unknown.MethodsSerum samples and grafts were harvested from male mice undergoing abdominal aortic transplantation. The pathological alterations in the aortic grafts were detected by hematoxylin and eosin staining, Verhoeff’s Van Gieson staining, and Masson staining. Inflammatory cell infiltration and proinflammatory cytokine expression in the aortic grafts were detected by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. The regulatory effects of PCSK9 on vascular smooth muscle cell (VSMC) migration and proliferation were examined by transwell, EdU, and western blot assays. The effect of Evolocumab, a PCSK9 inhibitor, on GVD in humanized PCSK9 mice was also evaluated.ResultsPCSK9 was upregulated in the serum, grafts, and liver of mice in the allograft group subjected to abdominal aortic transplantation. Pcsk9 knockout significantly reduced vascular stenosis, the intimal hyperplasia area and collagen deposition. Pcsk9 depletion also inhibited macrophage recruitment and the mRNA expression of proinflammatory cytokines in aortic grafts. Furthermore, Pcsk9 knockout suppressed the migration and proliferation of VSMCs, which was related to the inhibition of NLRP3 inflammasome activation. Meanwhile, Evolocumab significantly ameliorated GVD in humanized PCSK9 mice.ConclusionPCSK9 is upregulated in a mouse model of GVD, and Pcsk9 knockout reduces vascular occlusion, suggesting that PCSK9 may be a promising target for the treatment of GVD.
A Bibliometric Analysis of the Innate Immune DNA Sensing cGAS-STING Pathway from 2013 to 2021
Authors: Shi Xuan , Wang Sheng , Wu Yutong , Li Quanfu , Zhang Tong , Min Keting , Feng Di , Liu Meiyun , Wei Juan , Zhu Lina , Mo Wei , Xiao Zhuoran , Yang Hao , Chen Yuanli , Lv Xin 
Published: June 2022

Background and aimsCyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) are key components of the innate immune system. This study aims to evaluate the research of cGAS-STING pathway and predict the hotspots and developing trends in this field using bibliometric analysis.MethodsWe retrieved publications from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC) in 1975-2021 on 16 March 2022. We examined the retrieved data by bibliometrix package in R software, VOSviewer and CiteSpace were used for visualizing the trends and hotspots of research on the cGAS-STING pathway.ResultsWe identified 1047 original articles and reviews on the cGAS-STING pathway published between 1975 and 2021. Before 2016, the publication trend was increasing steadily, but there was a significant increase after 2016. The United States of America (USA) produced the highest number of papers (Np) and took the highest number of citations (Nc), followed by China and Germany. The University of Texas System and Frontiers in Immunology were the most prolific affiliation and journal respectively. In addition, collaboration network analysis showed that there were tight collaborations among the USA, China and some European countries, so the top 10 affiliations were all from these countries and regions. The paper published by Sun LJ in 2013 reached the highest local citation score (LCS). Keywords co-occurrence and co-citation cluster analysis revealed that inflammation, senescence, and tumor were popular terms related to the cGAS-STING pathway recently. Keywords burst detection suggested that STING-dependent innate immunity and NF-κB-dependent broad antiviral response were newly-emerged hotspots in this area.ConclusionsThis bibliometric analysis shows that publications related to the cGAS-STING pathway tend to increase continuously. The research focus has shifted from the mechanism how cGAS senses dsDNA and cGAMP binds to STING to the roles of the cGAS-STING pathway in different pathological state.
Changing Trends of Adverse Pregnancy Outcomes With Maternal Pre-pregnancy Body Mass Index: A Join-Point Analysis
Authors: Hu Rong , Yin Huifen , Li Xiaotian 
Published: June 2022

ObjectiveAdverse pregnancy outcomes have been related to obesity and thinness; however, the changing trends of the specific outcome with pre-pregnancy BMI remain unknown. The aim of this study was to investigate the change in risk trends of specific adverse outcomes for different pre-pregnancy BMI and analyze the recommended BMI range for pre-pregnancy counseling.MethodsData were extracted from the medical records of 39 public hospitals across 14 provinces in China from 2011 to 2012. The eligibility criteria were singleton birth with delivery week ≥28 weeks. Join-point analysis was adopted to explore changing trends with pre-pregnancy BMI and calculate slopes and join points of different pregnancy complications.ResultsA total of 65,188 women were eligible for analysis. There were three categories of trend style. Continuously increasing trends were linear for intrahepatic cholestasis of pregnancy, postpartum hemorrhage, and low 1-min Apgar score, and non-linear for cesarean delivery with one join point of BMI 23, hypertension disorder in pregnancy with two join points of BMI 20 and 28, gestational diabetes mellitus with one join point of BMI 22, and macrosomia with one join point of BMI 19. The trend was continuously and linearly decreasing for anemia. The bidirectional trends were downward and upward for premature rupture of the membrane with join BMI 22, preterm premature rupture of the membrane with join BMI 22, placenta abruption with join BMI 23, preterm birth with join BMI 19, and low birth weight with join BMI 19.ConclusionsThe changes in the trends of specific outcomes differed with pre-pregnancy BMI. Our results suggested that a pre-pregnancy BMI ranging between 19 and 23 may help reduce the risk of poor maternal and neonatal outcomes.
Performances of Corneal Topography and Tomography in the Diagnosis of Subclinical and Clinical Keratoconus
Authors: Nicula Cristina Ariadna , Bulboacă Adriana Elena , Nicula Dorin , Nicula Ariadna Patricia , Horvath Karin Ursula , Bolboacă Sorana D. 
Published: June 2022

AimThe purpose of the study was to assess the efficacy of topographical and tomographical indices given by the Pentacam (pachymetric, tomopetric, and aberometric) in clinical and subclinical keratoconus (KCN) diagnosis.Material and MethodsIn this observational analytic retrospective study, patients with abnormal findings in topography and tomography maps but with no signs on clinical examination (subclinical KCN group, sKCN), patients with clinical keratoconus (KCN group), and healthy subjects (Control group) were evaluated.ResultsThe KCN group proved significantly different (p &lt; 0.001) values of the investigated parameters than the Control group. Eleven out of 28 investigated parameters proved significantly different in the sKCN group compared to controls (p &lt; 0.001). Two topographic measurements, namely I-S (cut-off = 1.435, a large value indicates the presence of KCN) and CCT (cut-off = 537, a small value indicates the presence of KCN), showed AUCs equal to 1 [0.999 to 1]. Six other Pentacam measurements, including Back maximum keratometry (Back Kmax) proved to be excellent parameters for case-finding and screening. In distinguishing sKCN from normal eyes, Pentacam index of vertical asymmetry (IVA), inferior-superior difference (I-S) value, thinnest point (TP), Belin Ambrosio Enhanced Ectasia Display (BAD_D) and root mean square total (RMS total) performed best.ConclusionsIn distinguishing sKCN from normal eyes, Back Kmax, IVA, I-S, and RMS total values demonstrated higher accuracy and utility. Six indices, namely ISV, IVA, KISA, PRC, RMS-HOA, and Back Kmax demonstrate excellent utility in case-finding and screening for clinical KCN.
Targeted Temperature Management for Cardiac Arrest Due to Non-shockable Rhythm: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Zhu Yi-Bing , Yao Yan , Ren Yu , Feng Jing-Zhi , Huang Hui-Bin 
Published: June 2022

BackgroundTargeted temperature management (TTM) is recommended in adult patients following cardiac arrest (CA) with any rhythm. However, as to non-shockable (NSR) CA, high-quality evidence of TTM supporting its practices remains uncertain. Thus, we aimed to conduct a systematic review and meta-analysis with randomized controlled trials (RCTs) to explore the efficacy and safety of TTM in this population.MethodsWe searched PubMed, Embase, and Cochrane library databases for potential trials from inception through Aug 25, 2021. RCTs evaluating TTM for CA adults due to NSR were included, regardless of the timing of cooling initiation. Outcome measurements were mortality and good neurological function. We used the Cochrane bias tools to evaluate the quality of the included studies. Heterogeneity, subgroup analyses, and sensitivity analysis were investigated to test the robustness of the primary outcomes.ResultsA total of 14 RCTs with 4,009 adults were eligible for the final analysis. All trials had a low to moderate risk of bias. Of the included trials, six compared NSR patients with or without TTM, while eight compared pre-hospital to in-hospital TTM. Pooled data showed that TTM was not associated with improved mortality (Risk ratio [RR] 1.00; 95% CI, 0.944–1.05; P = 0.89, I2 = 0%) and good neurological outcome (RR 1.18; 95% CI 0.90–1.55; P = 0.22, I2 = 8%). Similarly, use of pre-hospital TTM resulted in neither an improved mortality (RR 0.99, 95% CI 0.97–1.03; I2 = 0%, P = 0.32) nor favorable neurological outcome (RR 1.13, 95% CI 0.93–1.38; I2 = 0%, P = 0.22). These results were further confirmed in the sensitivity analyses and subgroup analyses.ConclusionsOur results showed that using the TTM strategy did not significantly affect the mortality and neurologic outcomes in CA survival presenting initial NSR.
KCNN4 is a Potential Biomarker for Predicting Cancer Prognosis and an Essential Molecule that Remodels Various Components in the Tumor Microenvironment: A Pan-Cancer Study
Authors: Chen Shaohua , Su Xiaotao , Mo Zengnan 
Published: June 2022

Objectives: Potassium Calcium-Activated Channel Subfamily N Member 4 (KCNN4) is a member of the KCNN family. Studies have revealed that KCNN4 is implicated in various physiological processes as well as promotes the malignant phenotypes of cancer cells. However, little is known about its associations with survival outcomes across varying cancer types.Methods: Herein, we systematically explored the prognostic value of KCNN4 in the pan-cancer dataset retrieved from multiple databases. Next, we performed correlation analysis of KCNN4 expression with tumor mutational burden (TMB) and microsatellite instability (MSI), and immune checkpoint genes (ICGs) to assess its potential as a predictor of immunotherapy efficacy. Afterwards, patients were divided into increased-risk group and decreased-risk group based on the contrasting survival outcomes in various cancer types. Furthermore, the underlying mechanisms of the distinctive effects were analyzed using ESTIMATE, CIBERSORT algorithms, and Gene Set Enrichment Analysis (GSEA) analysis.Results: KCNN4 expression levels were aberrant in transcriptomic and proteomic levels between cancer and normal control tissues in pan-cancer datasets, further survival analysis elucidated that KCNN4 expression was correlated to multiple survival data, and clinical annotations. Besides, KCNN4 expression was correlated to TMB and MSI levels in 14 types and 12 types of pan-cancers, respectively. Meanwhile, different types of cancer have specific tumor-infiltrating immune cell (TICs) profiles.Conclusions: Our results revealed that KCNN4 could be an essential biomarker for remodeling components in the tumor microenvironment (TME), and a robust indicator for predicting prognosis as well as immunotherapy response in pan-cancer patients.
Membrane Lipids in the Thyroid Comparing to Those in Non-Endocrine Tissues Are Less Sensitive to Pro-Oxidative Effects of Fenton Reaction Substrates
Authors: Stępniak Jan , Rynkowska Aleksandra , Karbownik-Lewińska Małgorzata 
Published: June 2022

Iron is an essential microelement for the proper functioning of many organs, among others it is required for thyroid hormone synthesis. However, its overload contributes to the increased formation of reactive oxygen species via Fenton chemistry (Fe2++H2O2→Fe3++˙OH + OH−), and it is potentially toxic. Individual organs/tissues are affected differently by excess iron. The excessive absorption of iron with subsequent deposition in various organs is associated with diseases such as hemochromatosis. Such an iron deposition also occurs in the thyroid gland where it can disturb thyroid hormone synthesis. In turn, melatonin is an effective antioxidant, which protects against oxidative damage. This study aims to check if lipid peroxidation resulting from oxidative damage to membrane lipids, is caused by Fenton reaction substrates, and if protective effects of melatonin differ between the thyroid and various non-endocrine porcine tissues (liver, kidney, brain cortex, spleen, and small intestine). To mimic the conditions of iron overload, Fe2+ was used in extremely high concentrations. Homogenates of individual tissues were incubated together with Fenton reaction substrates, i.e., FeSO4 (9.375, 18.75, 37.5, 75, 150, 300, 600, 1,200, 1,800, 2,100, 2,400, 3,000, 3,600, 4,200, and 4,800 µM)+H2O2 (5 mM), either without or with melatonin (5 mM). The concentration of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA), as the LPO index, was evaluated by a spectrophotometrical method. Fenton reaction substrates increased concentrations of LPO products in all chosen tissues. However, in the thyroid, compared to non-endocrine tissues, the damaging effect was generally weaker, it was not observed for the two lowest concentrations of iron, and the LPO peak occurred with higher concentrations of iron. Melatonin reduced experimentally induced LPO in all examined tissues (without differences between them), and these protective effects did not depend on iron concentration. In conclusion, membrane lipids in the thyroid compared to those in non-endocrine tissues are less sensitive to pro-oxidative effects of Fenton reaction substrates, without differences regarding protective effects of melatonin.
RNA Sequencing Unveils Very Small RNAs With Potential Regulatory Functions in Bacteria
Authors: Diallo Idrissa , Ho Jeffrey , Lalaouna David , Massé Eric , Provost Patrick 
Published: June 2022

RNA sequencing (RNA-seq) is the gold standard for the discovery of small non-coding RNAs. Following a long-standing approach, reads shorter than 16 nucleotides (nt) are removed from the small RNA sequencing libraries or datasets. The serendipitous discovery of an eukaryotic 12 nt-long RNA species capable of modulating the microRNA from which they derive prompted us to challenge this dogma and, by expanding the window of RNA sizes down to 8 nt, to confirm the existence of functional very small RNAs (vsRNAs &lt;16 nt). Here we report the detailed profiling of vsRNAs in Escherichia coli, E. coli-derived outer membrane vesicles (OMVs) and five other bacterial strains (Pseudomonas aeruginosa PA7, P. aeruginosa PAO1, Salmonella enterica serovar Typhimurium 14028S, Legionella pneumophila JR32 Philadelphia-1 and Staphylococcus aureus HG001). vsRNAs of 8–15 nt in length [RNAs (8-15 nt)] were found to be more abundant than RNAs of 16–30 nt in length [RNAs (16–30 nt)]. vsRNA biotypes were distinct and varied within and across bacterial species and accounted for one third of reads identified in the 8–30 nt window. The tRNA-derived fragments (tRFs) have appeared as a major biotype among the vsRNAs, notably Ile-tRF and Ala-tRF, and were selectively loaded in OMVs. tRF-derived vsRNAs appear to be thermodynamically stable with at least 2 G-C basepairs and stem-loop structure. The analyzed tRF-derived vsRNAs are predicted to target several human host mRNAs with diverse functions. Bacterial vsRNAs and OMV-derived vsRNAs could be novel players likely modulating the intricate relationship between pathogens and their hosts.
The Effect of Modified Tai Chi Exercises on the Physical Function and Quality of Life in Elderly Women With Knee Osteoarthritis
Authors: Song Jiulong , Wei Lijun , Cheng Kai , Lin Qiang , Xia Peng , Wang Xinwei , Wang Xiaoju , Yang Ting , Chen Baoyi , Ding Aimei , Sun Mingyi , Chen Anliang , Li Xueping 
Published: June 2022

BackgroundKnee osteoarthritis (KOA) is the leading cause of pain and stiffness, affecting older adults’ physical function and quality of life. As a form of mind-body exercise, Tai Chi has been recommended as an exercise prescription for KOA patients. This study examined the effects and continuation of modified Tai Chi exercises on physical function and quality of life in elderly women with KOA.MethodsWe conducted a single-blind, randomized controlled trial (RCT) on 40 older women with KOA. The participants were randomized to a 12 weeks Tai Chi or control group. The Tai Chi group attended a kind of modified Tai Chi training sessions three times per week; the control group attended wellness education sessions once a week. The primary outcome was the Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Secondary outcomes were the Berg Balance Scale (BBS), Timed Up and Go (TUG), Short-Form 36 (SF-36), Pittsburgh Sleep Quality of Index (PSQI), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS).ResultsAfter the 12-weeks the Tai Chi group showed significan improvement in the WOMAC pain (mean difference, −5.09 points, p = 0.001), WOMAC stiffness (mean difference, −3.60 points, p = 0.002), WOMAC physical function (mean difference, −11.21 points, p = 0.001) compared to the control group. In addition, the Tai Chi group had also significant improvement in the BBS (mean difference, 1.70 points, p = 0.008), TUG (mean difference, −0.52s, p = 0.001), SF-36PCS (mean difference, 7.60 points, p = 0.001), MCS (mean difference, 7.30 points, p = 0.001), PSQI (mean difference, −3.71 points, p = 0.001), SDS (mean difference, −5.37 points, p = 0.025) and SAS (mean difference, −5.06 points, p = 0.002).ConclusionThe modified Tai Chi exercises are an effective treatment for improved physical function and quality of life in elderly women with KOA.Clinical Trial RegistrationThe trial was registered in Chinese Clinical Trial Registry (ChiCTR2000040721), http://www.chictr.org.cn/edit.aspx?pid=65419&amp;htm=4.
Evaluation of an Antibiotic Cocktail for Fecal Microbiota Transplantation in Mouse
Authors: Tan Jijun , Gong Jiatai , Liu Fengcheng , Li Baizhen , Li Zhanfeng , You Jiaming , He Jianhua , Wu Shusong 
Published: June 2022

ObjectiveThis study aimed to evaluate the effect of an antibiotic cocktail on gut microbiota and provide a reference for establishing an available mouse model for fecal microbiota transplantation (FMT) of specific microbes.DesignC57BL/6J mice (n = 24) had free access to an antibiotic cocktail containing vancomycin (0.5 g/L), ampicillin (1 g/L), neomycin (1 g/L), and metronidazole (1 g/L) in drinking water for 3 weeks. Fecal microbiota was characterized by 16S rDNA gene sequencing at the beginning, 1st week, and 3rd week, respectively. The mice were then treated with fecal microbiota from normal mice for 1 week to verify the efficiency of FMT.ResultsThe diversity of microbiota including chao1, observed species, phylogenetic diversity (PD) whole tree, and Shannon index were decreased significantly (P &lt; 0.05) after being treated with the antibiotic cocktail for 1 or 3 weeks. The relative abundance of Bacteroidetes, Actinobacteria, and Verrucomicrobia was decreased by 99.94, 92.09, and 100%, respectively, while Firmicutes dominated the microbiota at the phylum level after 3 weeks of treatment. Meanwhile, Lactococcus, a genus belonging to the phylum of Firmicutes dominated the microbiota at the genus level with a relative abundance of 80.63%. Further FMT experiment indicated that the fecal microbiota from the receptor mice had a similar composition to the donor mice after 1 week.ConclusionThe antibiotic cocktail containing vancomycin, ampicillin, neomycin, and metronidazole eliminates microbes belonging to Bacteroidetes, Actinobacteria, and Verrucomicrobia, which can be recovered by FMT in mice.