bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Prevalence, Distribution, and Extent of Subclinical Atherosclerosis and Its Relation With Serum Uric Acid in Hypertension Population
Authors: Liu Fei , Hui Simei , Hidru Tesfaldet H. , Jiang Yinong , Zhang Ying , Lu Yan , Lv Haichen , Lee Sharen , Xia Yunlong , Yang Xiaolei 
Published: April 2021

Background: Data are limited on the prevalence, distribution, and extent of subclinical atherosclerosis (SCA) in populations with primary hypertension and an in-depth evaluation is required to explore the impact of elevated serum uric acid (SUA) levels on the systemic extent of SCA.Methods: A total of 1,534 individuals with blood pressure-controlled primary hypertension registered from January 1, 2015 to May 31, 2018 were included. The systemic extent and risk factors of SCA in the carotid, coronary, thoracic, and renal territories were investigated by Doppler ultrasound and computed tomography.Results: SCA was present in 85.9% of patients. The proportion of focal, intermediate and generalized SCA was 17.9, 21.3, and 46.6%. Plaques were most common in the thoracic aorta (74%), followed by the coronary (55.3%), carotid (51.6%), and renal (45.8%) arteries, respectively. Participants were stratified into quartiles based on gender-specific SUA levels. Compared with patients in the first quartile, the Odds Ratio (OR) [95% confidence interval] for SCA in the second, third and fourth quartile were 1.647 (1.011–2.680), 3.013 (1.770–5.124), and 5.081 (3.203–10.496), respectively. Patients with elevated SUA levels at high 10-year Framingham risk had a higher likelihood of a more severe risk of SCA (95.8%). However, extensive SCA was also present in a substantial number of low 10-year-Framingham risk patients at the higher quartiles of SUA (53.8%).Conclusions: SCA was highly prevalent in the hypertension population and the thoracic aorta was the most frequently affected vascular site. Elevated SUA concentration was significantly associated with the prevalence and severity of SCA regardless of territories.
Predictive Factors of Conception and the Cumulative Pregnancy Rate in Subfertile Couples Undergoing Timed Intercourse With Ultrasound
Authors: Ahn So Hyun , Lee Inha , Cho SiHyun , Kim Hye In , Baek Hye Won , Lee Jae Hoon , Park Yun Jeong , Kim Heeyon , Yun Bo Hyon , Seo Seok Kyo , Park Joo Hyun , Choi Young Sik , Lee Byung Seok 
Published: April 2021

The aim of this study was to determine predictive factors for pregnancy and assess the cumulative pregnancy rate (CPR) and live birth rate (CLBR) in subfertile couples undergoing timed intercourse (TI) using ultrasound. This retrospective cohort study included 285 women (854 cycles) who started TI with ultrasound between January 2017 and October 2019. The overall clinical pregnancy rate was 28.1% (80/285) per couple and 9.4% (80/854) per cycle. Pregnant women had a higher body mass index (BMI), higher percentage of irregular menstrual cycles, a shorter duration of subfertility, lower serum follicle-stimulating hormone levels, and higher anti-Müllerian hormone levels than non-pregnant women. A longer duration of subfertility (≥24 months vs. &lt;12 months; odds ratio: 0.193; 95% confidence interval: 0.043-0.859) and endometriosis (vs. ovulatory factors; odds ratio: 0.282; 95% confidence interval: 0.106-0.746) as causes of subfertility were unfavorable factors that independently affected clinical pregnancy. In subgroup analysis, old age ≥ 35 years [vs. &lt; 35 years; odds ratio: 0.279; 95% confidence interval: 0.083-0.938), a longer duration of infertility ≥24 months (vs. &lt;24 months; odds ratio: 0.182; 95% confidence interval: 0.036-0.913) and a higher BMI ≥ 25 kg/m2(vs. &gt;25 kg/m2; odds ratio: 3.202; 95% confidence interval: 1.020-10.046) in couples with ovulatory factor and a longer duration of infertility ≥24 months (vs. &lt;24 months; odds ratio: 0.185; 95% confidence interval: 0.042-0.819) in couples with non-ovulatory factors were significant independent predictive factors for pregnancy. No significant differences were found in the cycle characteristics between pregnant and non-pregnant women. The CPR substantially increased during the first three cycles and significantly increased until the sixth cycle. No significant increase was observed in the CPR after the sixth cycle. The CLBRs substantially increased during the first three cycles and significantly increased until the fourth cycle. No significant increase was observed in the CLBRs after the fifth cycle. When comparing CPRs and CLBRs according to subfertile causes, CRPs was significantly different and CLBRs was different with borderline significance. Our findings may indicate that women with a longer duration of subfertility or subfertility due to endometriosis have poor outcomes during TI with ultrasound. Women who failed to achieve conception by the fourth or fifth cycle of TI with ultrasound may be encouraged to consider advancing to the next treatment strategy.
Elevated microRNA-21 Is a Brake of Inflammation Involved in the Development of Nasal Polyps
Authors: Liu Ruowu , Du Jintao , Zhou Jiao , Zhong Bing , Ba Luo , Zhang Jie , Liu Yafeng , Liu Shixi 
Published: April 2021

BackgroundCRSwNP is an inflammatory disease but the mechanism is not yet fully understood. MiR-21, a member of miRNAs, has been reported to play roles in mediating inflammation. However, the expression of miR-21 and its role in patients with CRSwNP remain elusive.MethodsTurbinates from control subjects, uncinate processes from CRSsNP, polyp tissues from CRSwNP, and nasal epithelial cells brushed from nasal mucosa were collected. The expression of miR-21 and cytokines in nasal tissues and epithelial cells were detected by qPCR. The localization of miR-21 was detected by ISH, and its target was identified by bioinformation analysis, qPCR, IHC, WB, and luciferase reporter system. The protein and mRNA of PDCD4 and NF-κB P65 were determined by WB and qPCR after miR-21 transfection in HNEpC. The role of miR-21 on cytokines was analyzed in HNEpC and nasal polyp explants.ResultsMiR-21 was upregulated in CRSwNP relative to control subjects by qPCR, which was determined mainly in nasal epithelial cells of CRSwNP by ISH. Both pro-inflammation cytokines (IL-1β, IL-6, IL-8, IL-25, and TSLP) and a suppressive cytokine (IL-10) were overexpressed in the epithelial cells of CRSwNP. The expression of miR-21 was positively correlated with IL-10 and negatively correlated with IL-6, IL-8, IL-33, and TSLP in the epithelial cells of CRSwNP. As a potential target of miR-21, the expression of PDCD4 was negatively correlated with miR-21 in CRSwNP. In HNEpC, miR-21 could reduce the expression of PDCD4 at both mRNA and protein levels, and bioinformation analysis and luciferase reporter system confirmed PDCD4 as one target of miR-21. Furthermore, miR-21 could decrease the activation of NF-κB and increase IL-10 mRNA. Both SEB and LPS could elevate miR-21, with IL-25, IL-33, TSLP induced by SEB and IL-1β, IL-6, IL-8 induced by LPS, while the miR-21 could regulate the expression of IL-33, TSLP, IL-1β, IL- 6 and IL-8 in vitro and ex vivo. Clinically, miR-21 expression was inversely correlated with the Lund-Mackay CT scores and the Lund-Kennedy scores in CRSwNP.ConclusionMiR-21 could be a prominent negative feedback factor in the inflammation process to attenuate the expression of pro-inflammatory cytokines, thereby playing an anti-inflammation role in CRSwNP.
Decreased Serum 25-(OH)-D Level Associated With Muscle Enzyme and Myositis Specific Autoantibodies in Patients With Idiopathic Inflammatory Myopathy
Authors: Yu Zhen , Cheng Hao , Liang Yuying , Ding Tingting , Yan Chenglan , Gao Chong , Wen Hongyan 
Published: April 2021

ObjectivesTo determine whether there is serum vitamin D deficiency and the low levels of serum vitamin D are correlated with serological and immunological indexes in patients with idiopathic inflammatory myopathy (IIM).MethodsA total of 63 newly diagnosed patients with IIM, and 55 age- and sex- matched healthy controls were enrolled. Serum levels of 25-(OH)-D were measured by enzyme-linked immunosorbent assay. The correlations of 25-(OH)-D levels with disease indicators and T cell subsets were analyzed.ResultThe levels of serum 25-(OH)-D in IIM were significantly lower than those in healthy controls (9.36 ± 5.56 vs 26.56 ± 5.37 ng/ml, p&lt;0.001). The levels of serum liver enzyme ALT and AST and muscle enzyme CK, CKMB, LDH and HBDH were elevated as deficiency of vitamin D. In addition, the serum 25-(OH)-D levels were negatively correlated to ALT (r = -0.408, p = 0.001) and AST (r = -0.338, p = 0.007). The 25-(OH)-D levels in IIM patients in presence of anti-Jo-1 were significantly lower than those in patients without anti-Jo-1 (5.24 ± 3.17 vs 9.32 ± 5.60 ng/ml; p = 0.037). Similar results were found in patients with or without anti-Mi-2 antibody. The serum 25-(OH)-D levels were positively associated with total T (r = 0.203, p = 0.012) and Treg cells (r = 0.331, p = 0.013). The patients with deficient levels of vitamin D were more likely to have heliotrope, gastrointestinal and liver involvement.ConclusionsVitamin D deficiency existed in IIM patients, which was significantly correlated with muscle enzyme, presence of anti-Jo-1 and anti-Mi-2 antibody, and the absolute numbers of total T and Treg cells in IIM. It is suggested that vitamin D may play an important role in the immunological pathogenesis of IIM.
Immune Polarization Potential of the S. aureus Virulence Factors SplB and GlpQ and Modulation by Adjuvants
Authors: Mrochen Daniel M. , Trübe Patricia , Jorde Ilka , Domanska Grazyna , Brandt Cindy van den , Bröker Barbara M. 
Published: April 2021

Protection against Staphylococcus aureus is determined by the polarization of the anti-bacterial immune effector mechanisms. Virulence factors of S. aureus can modulate these and induce differently polarized immune responses in a single individual. We proposed that this may be due to intrinsic properties of the bacterial proteins. To test this idea, we selected two virulence factors, the serine protease-like protein B (SplB) and the glycerophosphoryl diester phosphodiesterase (GlpQ). In humans naturally exposed to S. aureus, SplB induces a type 2-biased adaptive immune response, whereas GlpQ elicits type 1/type 3 immunity. We injected the recombinant bacterial antigens into the peritoneum of S. aureus-naïve C57BL/6N mice and analyzed the immune response. This was skewed by SplB toward a Th2 profile including specific IgE, whereas GlpQ was weakly immunogenic. To elucidate the influence of adjuvants on the proteins’ polarization potential, we studied Montanide ISA 71 VG and Imject™Alum, which promote a Th1 and Th2 response, respectively. Alum strongly increased antibody production to the Th2-polarizing protein SplB, but did not affect the response to GlpQ. Montanide enhanced the antibody production to both S. aureus virulence factors. Montanide also augmented the inflammation in general, whereas Alum had little effect on the cellular immune response. The adjuvants did not override the polarization potential of the S. aureus proteins on the adaptive immune response.
IFNγ, and to a Lesser Extent TNFα, Provokes a Sustained Endothelial Costimulatory Phenotype
Authors: Valenzuela Nicole M. 
Published: April 2021

BackgroundVascular endothelial cells (EC) are critical for regulation of local immune responses, through coordination of leukocyte recruitment from the blood and egress into the tissue. Growing evidence supports an additional role for endothelium in activation and costimulation of adaptive immune cells. However, this function remains somewhat controversial, and the full repertoire and durability of an enhanced endothelial costimulatory phenotype has not been wholly defined.MethodsHuman endothelium was stimulated with continuous TNFα or IFNγ for 1-48hr; or primed with TNFα or IFNγ for only 3hr, before withdrawal of stimulus for up to 45hr. Gene expression of cytokines, costimulatory molecules and antigen presentation molecules was measured by Nanostring, and publicly available datasets of EC stimulation with TNFα or IFNγ were leveraged to further corroborate the results. Cell surface protein expression was detected by flow cytometry, and secretion of cytokines was assessed by Luminex and ELISA. Key findings were confirmed in primary human endothelial cells from 4-6 different vascular beds.ResultsTNFα triggered mostly positive immune checkpoint molecule expression on endothelium, including CD40, 4-1BB, and ICOSLG but in the context of only HLA class I and immunoproteasome subunits. IFNγ promoted a more tolerogenic phenotype of high PD-L1 and PD-L2 expression with both HLA class I and class II molecules and antigen processing genes. Both cytokines elicited secretion of IL-15 and BAFF/BLyS, with TNFα stimulated EC additionally producing IL-6, TL1A and IL-1β. Moreover, endothelium primed for a short period (3hr) with TNFα mostly failed to alter the costimulatory phenotype 24-48hr later, with only somewhat augmented expression of HLA class I. In contrast, brief exposure to IFNγ was sufficient to cause late expression of antigen presentation, cytokines and costimulatory molecules. In particular HLA class I, PD-1 ligand and cytokine expression was markedly high on endothelium two days after IFNγ was last present.ConclusionsEndothelia from multiple vascular beds possess a wide range of other immune checkpoint molecules and cytokines that can shape the adaptive immune response. Our results further demonstrate that IFNγ elicits prolonged signaling that persists days after initiation and is sufficient to trigger substantial gene expression changes and immune phenotype in vascular endothelium.
The Effect of Coronary Angiography Timing on Cardiac Surgery Associated Acute Kidney Injury Incidence and Prognosis
Authors: Liu Kang , Li Meiyuan , Li Li , Wu Buyun , Xu Xueqiang , Ge Yifei , Mao Huijuan , Xing Changying 
Published: April 2021

Introduction: Acute kidney injury has been identified as a common complication of cardiac surgery. To date, the effect of the time interval from coronary angiography to cardiac surgery on postoperative acute kidney injury is still controversial. The aim of this study was to investigate the relationship between the timing of coronary angiography and cardiac surgery associated acute kidney injury.Methods: Eight hundred thirteen patients who underwent coronary angiography and cardiac surgery successively from January 2017 to December 2018 were included in this retrospective cohort study. We applied multivariate logistic regression, propensity score analysis, and subgroup analysis to evaluate the association between the time interval and postoperative acute kidney injury incidence and prognosis. Meta-analysis was conducted to verify the results.Results: The overall incidence of the cardiac surgery associated acute kidney injury was 28.8%. Age (OR = 1.046, 95%CI: 1.017–1.075), cardiopulmonary bypass (OR = 3.439, 95%CI: 1.316–8.986) and diabetes (OR = 2.522, 95%CI: 1.439–4.417) were found to be independent risk factors of postoperative acute kidney injury in multivariate logistic regression and propensity score analysis. Undergoing cardiac surgery within 7 days after coronary angiography was not associated with increased incidence of postoperative acute kidney injury or worse prognosis. Meta-analysis obtained consistent results.Conclusions: The time interval shorter than 7 days had no influence on cardiac surgery associated acute kidney injury incidence and prognosis. The decision of delaying the surgery should be made after comprehensive evaluation of the patient.
Presence of Atrial Fibrillation in Stroke Patients With Patent Foramen Ovale: Systematic Review and Meta-Analysis
Authors: Chen Jessie Ze-Jun , Thijs Vincent N. 
Published: April 2021

Purpose: Patent foramen ovale (PFO) is associated with ischemic stroke, especially in patients with embolic stroke of undetermined source. This study aims to evaluate the presence of atrial fibrillation (AF) in ischemic stroke patients with PFO.Methods: We systematically searched EMBASE and MEDLINE databases on May 21, 2020 for studies that analyzed the presence of AF in patients with PFO. The primary outcome was the presence of AF in patients with PFO compared with those without. Outcomes were pooled using a random-effects model using the method of DerSimonian and Laird. We recorded demographic characteristics and the methods used for AF detection in the studies included (unspecified, history/medical records review, ECG, Holter monitor, or loop recorder).Results: A total of 14 studies and 13,245 patients fulfilled the entry criteria. The average age was 61.2 years and 41.3% of the participants were female. There was a lower risk of AF in patients with PFO compared with those without (RR 0.52, 95% confidence interval, 0.41–0.63, p &lt; 0.001). There was no evidence of heterogeneity. The lower risk of AF was found in cross-sectional and longitudinal studies and in studies stratified by average age (&lt;60 or ≥60) and in cryptogenic stroke. Meta-regression by PFO detection technique suggested that studies using transoesophageal echocardiogram for PFO detection reported higher risk of AF (1.39, 95% confidence interval 1.14–1.70, p = 0.004).Conclusion: The presence of a PFO in patients with ischemic stroke/TIA may be associated with a lower risk of AF. Few studies have estimated the risk of future AF in patients with PFO.
Hemodynamic Signal Changes During Motor Imagery Task Performance Are Associated With the Degree of Motor Task Learning
Authors: Iso Naoki , Moriuchi Takefumi , Fujiwara Kengo , Matsuo Moemi , Mitsunaga Wataru , Hasegawa Takashi , Iso Fumiko , Cho Kilchoon , Suzuki Makoto , Higashi Toshio 
Published: April 2021

PurposeThis study aimed to investigate whether oxygenated hemoglobin (oxy-Hb) generated during a motor imagery (MI) task is associated with the motor learning level of the task.MethodsWe included 16 right-handed healthy participants who were trained to perform a ball rotation (BR) task. Hemodynamic brain activity was measured using near-infrared spectroscopy to monitor changes in oxy-Hb concentration during the BR MI task. The experimental protocol used a block design, and measurements were performed three times before and after the initial training of the BR task as well as after the final training. The BR count during training was also measured. Furthermore, subjective vividness of MI was evaluated three times after NIRS measurement using the Visual Analog Scale (VAS).ResultsThe results showed that the number of BRs increased significantly with training (P &lt; 0.001). VAS scores also improved with training (P &lt; 0.001). Furthermore, oxy-Hb concentration and the region of interest (ROI) showed a main effect (P = 0.001). An interaction was confirmed (P &lt; 0.001), and it was ascertained that the change in oxy-Hb concentrations due to training was different for each ROI. The most significant predictor of subjective MI vividness was supplementary motor area (SMA) oxy-Hb concentration (coefficient = 0.365).DiscussionHemodynamic brain activity during MI tasks may be correlated with task motor learning levels, since significant changes in oxy-Hb concentrations were observed following initial and final training in the SMA. In particular, hemodynamic brain activity in the SMA was suggested to reflect the MI vividness of participants.
The Expression of Three Negative Co-Stimulatory B7 Family Molecules in Small Cell Lung Cancer and Their Effect on Prognosis
Authors: Qiu Meng-jun , Xia Qin , Chen Yao-bing , Fang Xie-fan , Li Qiu-ting , Zhu Li-sheng , Jiang Xin , Xiong Zhi-fan , Yang Sheng-li 
Published: April 2021

BackgroundIn recent years, immune checkpoint inhibitors have shown significant effects in a variety of solid tumors. However, due to the low incidence of small cell lung cancer (SCLC) and its unclear mechanism, immune checkpoints in SCLC have not been fully studied.MethodsWe evaluated the expression of PD-L1, B7-H3, and B7-H4 in 115 SCLC tissue specimens using immunohistochemistry. The clinical data of patients with SCLC were retrospectively reviewed to investigate three negative co-stimulatory B7 family molecules’ ability to affect the prognosis of SCLC.ResultsAmong the SCLC patients with complete follow-up data (n = 107), sixty-nine (64.49%) expressed moderate to high B7-H3 levels, which correlated positively with tumor sizes (P &lt; 0.001). Eighty (74.77%) patients expressed moderate to high B7-H4 levels, which correlated positively with metastases (P = 0.049). The positive expression of B7-H3 and B7-H4 correlated significantly with shortened overall survival (OS) (B7-H3, P = 0.006; B7-H4, P = 0.019). PD-L1 was positively expressed only in 13.08% of cancer tissues, and there was no significant correlation with prognosis. The Cox proportional hazards regression showed that B7-H3 was an independent prognostic indicator of OS (P = 0.028; HR = 2.125 [95% CI = 0.985-4.462]).ConclusionsOur results suggest that B7-H3 has a negative predictive effect on SCLC. This outcome provides a theoretical basis for the subsequent research on immune checkpoint inhibitors targeting B7-H3.
Prediction Model of Tumor Regression Grade for Advanced Gastric Cancer After Preoperative Chemotherapy
Authors: Xu Wei , Ma Qianchen , Wang Lingquan , He Changyu , Lu Sheng , Ni Zhentian , Hua Zichen , Zhu Zhenglun , Yang Zhongyin , Zheng Yanan , Feng Runhua , Yan Chao , Li Chen , Yao Xuexin , Chen Mingmin , Liu Wentao , Yan Min , Zhu Zhenggang 
Published: April 2021

BackgroundPreoperative chemotherapy (PCT) has been considered an important treatment for advanced gastric cancer (AGC). The tumor regression grade (TRG) system is an effective tool for the assessment of patient responses to PCT. Pathological complete response (TRG = 0) of the primary tumor is an excellent predictor of better prognosis. However, which patients could achieve pathological complete response (TRG = 0) after chemotherapy is still unknown. The study aimed to find predictors of TRG = 0 in AGC.MethodsA total of 304 patients with advanced gastric cancer from July 2009 to November 2018 were enrolled retrospectively. All patients were randomly assigned (2:1) to training and internal validation groups. In addition, 124 AGC patients receiving PCT from December 2018 to June 2020 were included prospectively in the external validation cohort. A prediction model for TRG = 0 was established based on four predictors in the training group and was validated in the internal and external validation groups.ResultsThrough univariate and multivariate analyses, we found that CA199, CA724, tumor differentiation and short axis of the largest regional lymph node (LNmax) were independent predictors of TRG = 0. Based on the four predictors, we established a prediction model for TRG = 0. The AUC values of the prediction model in the training, internal and external validation groups were 0.84, 0.73 and 0.82, respectively.ConclusionsWe found that CA199, CA724, tumor differentiation and LNmax were associated with pathological response in advanced gastric cancer. The prediction model could provide guidance for clinical work.