bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abundance and Expression of Shiga Toxin Genes in Escherichia coli at the Recto-Anal Junction Relates to Host Immune Genes
Authors: Pan Zhe , Chen Yanhong , McAllister Tim A. , Gänzle Michael , Plastow Graham , Guan Le Luo 
Published: March 2021

Shiga toxin (Stx) is the main virulence factor of Shiga toxin-producing Escherichia coli (STEC), and ruminants are the main reservoir of STEC. This study assessed the abundance and expression of Stx genes and the expression of host immune genes, aiming to determine factors affecting these measures and potential gene markers to differentiate Stx gene expression in the recto-anal junction of feedlot beef cattle. Rectal tissue and content samples were collected from 143 feedlot steers of three breeds (Angus, Charolais, and Kinsella Composite) over 2 consecutive years 2014 (n=71) and 2015 (n=72). The abundance and expression of stx1 and stx2 were quantified using qPCR and reverse-transcription-qPCR (RT-qPCR), respectively. Four immune genes (MS4A1, CCL21, CD19, and LTB), previously reported to be down-regulated in super-shedder cattle (i.e., &gt; 104 CFU g-1) were selected, and their expression was evaluated using RT-qPCR. The stx1 gene abundance was only detected in tissue samples collected in year 2 and did not differ among breeds. The stx2 gene was detected in STEC from all samples collected in both years and did not vary among breeds. The abundance of stx1 and stx2 differed (P &lt; 0.001) in content samples collected across breeds (stx1:AN&gt;CH&gt;KC, stx2: AN=CH&gt;KC) in year 1, but not in year 2. Expression of stx2 was detected in 13 RAJ tissue samples (2014: n=6, 2015: n=7), while expression of stx1 was not detected. Correlation analysis showed that the expression of stx2 was negatively correlated with the expression of MS4A1 (R=-0.56, P=0.05) and positively correlated with the expression of LTB (R=0.60, P=0.05). The random forest model and Boruta method revealed that expression of selected immune genes could be predictive indicators of stx2 expression with prediction accuracy of MS4A1 &gt;LTB &gt;CCL21 &gt;CD19. Our results indicate that the abundance of Stx could be affected by cattle breed and sampling year, suggesting that host genetics and environment may influence STEC colonization of the recto-anal junction of feedlot cattle. Additionally, the identified relationship between expressions of host immune genes and stx2 suggests that the host animal may regulate stx2 expression in colonizing STEC through immune functions.
Streptococcus, the Predominant Bacterium to Predict the Severity of Liver Injury in Alcoholic Liver Disease
Authors: Zhong Xiaodan , Cui Ping , Jiang Junjun , Ning Chuanyi , Liang Bingyu , Zhou Jie , Tian Li , Zhang Yu , Lei Ting , Zuo Taiping , Ye Li , Huang Jiegang , Chen Hui 
Published: March 2021

BackgroundNew evidence implies that the imbalance of gut microbiota is associated with the progression of alcoholic liver disease (ALD) and that the composition of gut microbiota is altered in ALD patients. However, the predominant bacterium in patients involved in the progress of ALD has not been identified. The purpose of this study is to investigate the predominant bacterium in the early and end-stages of ALD as well as the relationship between the bacterium and the degree of liver injury.MethodsWe enrolled 21 alcoholic fatty liver (AFL) patients, 17 alcoholic liver cirrhosis (ALC) patients and 27 healthy controls, and sequenced the 16S rRNA gene of their fecal microbiota. The gut microbiota composition and its relationship with the indicators of clinical hepatic function were assessed using canonical correspondence analysis (CCA), spearman correlation heatmap and multivariate association with linear (MaAsLin) Models.ResultsThe composition and structure of gut microbiota changed greatly in different stages of ALD, and the degree of disorder was aggravated with the progression of ALD, even in the early stage. Moreover, the relative abundance of Streptococcus was highly enriched only in patients with ALC (P &lt;0.001), and positively correlated with AST level (P = 0.029). The abundance of Streptococcus distinguished the liver injury of ALC patients from the controls with an area under the receiver-operating characteristic curve (AUC) of 0.877 (P &lt; 0.001).ConclusionsThese findings indicate that the imbalance of gut microbiota exists at the early and end-stages of ALD, and the degree of disorder is aggravated with the progression of ALD. Streptococcus, as the predominant bacterium, may be a microbiological marker to evaluate the severity of liver injury in ALD patients.
The Growth of Earthquake Clusters
Authors: Fischer Tomas , Hainzl Sebastian 
Published: March 2021

Migration of hypocenters is a common attribute of induced injection seismicity and of earthquake swarms, which distinguishes them from aftershock sequences. Spreading of the triggering front is often examined by fitting the time dependence of hypocenter distances from the origin by the pore pressure diffusion model. The earthquake migration patterns however often exhibit not only spreading envelopes but also fast-growing streaks embedded in the overall migration trends. We review the observed migration patterns and show that in the case of earthquake-driven migration, where the new ruptures are triggered at the edge of previous ruptures, it is more suitable to examine the cluster growth as a function of the event index instead of time. We propose a model that relates the speed of seismicity spreading to the average rupture area and the effective magnitude of the hypocenter cluster. Application of the model to selected linearly growing clusters of the 2008 West Bohemia swarm gives an almost linear increase of the measured total rupture area with the event index, which fits the proposed model. This is confirmed by a self-similar scaling of the average rupture area with the effective magnitude for stress drops ranging from 0.1 to 1 MPa. The relatively small stress drop level indicates the presence of voids along the fault plane and a possible role of aseismic deformation.
Protective Effects of Sodium-Glucose Transporter 2 Inhibitors on Atrial Fibrillation and Atrial Flutter: A Systematic Review and Meta- Analysis of Randomized Placebo-Controlled Trials
Authors: Li Daobo , Liu Yingying , Hidru Tesfaldet Habtemariam , Yang Xiaolei , Wang Yunsong , Chen Cheng , Li Ka Hou Christien , Tang Yuqi , Wei Yushan , Tse Gary , Xia Yunlong 
Published: March 2021

BackgroundHyperglycemia is associated with an increased risk of developing atrial fibrillation (AF) and atrial flutter (AFL). Sodium-glucose transporter 2 inhibitors (SGLT2i) have been reported to prevent AF/AFL in some studies, but not others. Therefore, a meta-analysis was performed to investigate whether SGLT2i use is associated with lower risks of AF/AFL.MethodsPubMed, Scopus, Web of Science, Cochrane library databases were searched for randomized placebo-controlled trials comparing SGLT2i and placebo.ResultsA total of 33 trials involving 66,685 patients were included. The serious adverse events (SAEs) of AF/AFL occurrence were significantly lower in the SGLT2i group than the placebo group (0.96% vs. 1.19%; RR 0.83; 95% CI 0.71–0.96; P = 0.01; I2 25.5%). Similarly, the SAEs of AF occurrence was significantly lower in the SGLT2i group (0.82% vs. 1.06%; RR 0.81; 95% CI 0.69–0.95; P = 0.01; I2 10.2%). The subgroup analysis showed that the reduction in AF/AFL was significant only for dapagliflozin (1.02% vs. 1.49%; RR 0.73; 95% CI 0.59–0.89; P = 0.002; I2 0%), but not for canagliflozin (1.00% vs 1.08%; RR 0.83; 95% CI 0.62–1.12; P = 0.23; I2 0%), empagliflozin (0.88% vs 0.70%; RR 1.20; 95% CI 0.76–1.90; P = 0.43; I2 0%), ertugliflozin (1.01% vs 0.96%; RR 1.08; 95% CI 0.66–1.75; P = 0.76; I2 0%), and sotagliflozin (0.16% vs 0.10%; RR 1.09; 95% CI 0.13–8.86; P = 0.93; I2 0%).ConclusionsSGLT2i use is associated with a 19.33% lower SAEs of AF/AFL compared with the placebo. Dapagliflozin users had the lowest SAEs of AF/AFL incidence. Further studies are needed to determine whether canagliflozin, empagliflozin, ertugliflozin, and sotagliflozin similarly exert protective effects against AF/AFL development.
CXCL12-CXCR4-Mediated Chemotaxis Supports Accumulation of Mucosal-Associated Invariant T Cells Into the Liver of Patients With PBC
Authors: Chen Zhilei , Liu Suying , He Chengmei , Sun Jinlei , Wang Li , Chen Hua , Zhang Fengchun 
Published: March 2021

Objectives: To explore the potential role of CD3+CD8+CD161high TCRVα7.2+ mucosal-associated invariant T (MAIT) cells in the pathogenesis of primary biliary cholangitis (PBC).Methods: We enrolled 55 patients with PBC, 69 healthy controls (HCs), and 8 patients with hepatic hemangioma. Circulating MAIT cells and their chemokine receptor profiles and cytokine production were quantified using flow cytometry. Liver-resident MAIT cells were examined by immunofluorescence staining. CXCL12-mediated chemotaxis of MAIT cells was measured using a transwell migration assay. Plasma interleukin (IL)-18 was measured using ELISA, and cytokine production in IL-18-stimulated MAIT cells was detected using flow cytometry.Result: Peripheral MAIT cells were found to be significantly lower in patients with PBC (3.0 ± 3.2% vs. 9.4 ± 8.0%, p &lt; 0.01) and negatively correlated with alkaline phosphatase (ALP) levels (r = −0.3209, p &lt; 0.05). Liver immunofluorescence staining suggested that MAIT cells might accumulate in PBC liver. MAIT cells from patients with PBC expressed higher levels of CXCR4 (84.8 ± 18.0% vs. 58.7 ± 11.4%, p &lt; 0.01), and the expression of CXCL12 was higher in PBC liver. CXCL12 promoted MAIT cell chemotaxis (70.4 ± 6.8% vs. 52.2 ± 3.5%, p &lt; 0.01), which was attenuated by CXCR4 antagonist. MAIT cells from PBC produced significantly more interferon-γ (IFN-γ) (88.3 ± 4.2% vs. 64.2 ± 10.1%, p &lt; 0.01), tumor necrosis factor-α (TNF-α) (93.0 ± 1.1% vs. 80.1 ± 5.3%, p &lt; 0.01), Granzyme B (89.3 ± 3.3% vs. 72.1 ± 7.0%, p &lt; 0.01), and perforin (46.8 ± 6.6% vs. 34.8 ± 7.7%, p &lt; 0.05). MAIT cells from PBC expressed higher levels of IL18-Rα (83.8 ± 10.2% vs. 58.3 ± 8.7%, p &lt; 0.01). Plasma IL-18 was more abundant in patients with PBC (286.8 ± 75.7 pg/ml vs. 132.9 ± 78.1 pg/ml, p &lt; 0.01). IL-18 promoted IFN-γ production in MAIT cells (74.9 ± 6.6% vs. 54.7 ± 6.7%, p &lt; 0.01), which was partially attenuated by blocking IL-18R (68.6 ± 8.3% vs. 43.5 ± 4.2%, p &lt; 0.01).Conclusion: Mucosal-associated invariant T cells from patients with PBC accumulated in the liver via CXCL12-CXCR4-mediated chemotaxis, produced pro-inflammatory cytokines, and contributed to portal inflammation, which was potentially mediated by elevated IL-18. Targeting MAIT cells might be a therapeutic approach for PBC.
Long-Term Exposure to Ambient Air Pollution and Myocardial Infarction: A Systematic Review and Meta-Analysis
Authors: Zou Li , Zong Qiao , Fu Wenning , Zhang Zeyu , Xu Hongbin , Yan Shijiao , Mao Jin , Zhang Yan , Cao Shiyi , Lv Chuanzhu 
Published: March 2021

Background and Objective: An increasing number of epidemiological original studies suggested that long-term exposure to particulate matter (PM2.5 and PM10) could be associated with the risk of myocardial infarction (MI), but the results were inconsistent. We aimed to synthesized available cohort studies to identify the association between ambient air pollution (PM2.5 and PM10) and MI risk by a meta-analysis.Methods: PubMed and Embase were searched through September 2019 to identify studies that met predetermined inclusion criteria. Reference lists from retrieved articles were also reviewed. A random-effects model was used to calculate the pooled relative risk (RR) and 95% confidence intervals (CI).Results: Twenty-seven cohort studies involving 6,764,987 participants and 94,540 patients with MI were included in this systematic review. The pooled results showed that higher levels of ambient air pollution (PM2.5 and PM10) exposure were significantly associated with the risk of MI. The pooled relative risk (RR) for each 10-μg/m3 increment in PM2.5 and PM10 were 1.18 (95% CI: 1.11–1.26), and 1.03 (95% CI: 1.00–1.05), respectively. Exclusion of any single study did not materially alter the combined risk estimate.Conclusions: Integrated evidence from cohort studies supports the hypothesis that long-term exposure to PM2.5 and PM10 is a risk factor for MI.
Treatment Switching and Discontinuation Over 20 Years in the Big Multiple Sclerosis Data Network
Authors: Hillert Jan , Magyari Melinda , Soelberg Sørensen Per , Butzkueven Helmut , Van Der Welt Anneke , Vukusic Sandra , Trojano Maria , Iaffaldano Pietro , Pellegrini Fabio , Hyde Robert , Stawiarz Leszek , Manouchehrinia Ali , Spelman Tim 
Published: March 2021

Background: Although over a dozen disease modifying treatments (DMTs) are available for relapsing forms of multiple sclerosis (MS), treatment interruption, switching and discontinuation are common challenges. The objective of this study was to describe treatment interruption and discontinuation in the Big MS data network.Methods: We merged information on 269,822 treatment episodes in 110,326 patients from 1997 to 2016 from five clinical registries in this cohort study. Treatment stop was defined as a clinician recorded DMT end for any reason and included treatment interruptions, switching to alternate DMTs and long-term or permanent discontinuations.Results: The incidence of DMT stopping cross the full observation period was lowest in FTY (19.7 per 100 person-years (PY) of treatment; 95% CI 19.2–20.1), followed by NAT (22.6/100 PY; 95% CI 22.2–23.0), IFNβ (23.3/100 PY; 95% CI 23.2–23.5). Of the 184,013 observed DMT stops, 159,309 (86.6%) switched to an alternate DMT within 6 months. Reasons for stopping a drug were stable during the observation period with lack of efficacy being the most common reason followed by lack of tolerance and side effects. The proportion of patients continuing on most DMTs were similarly stable until 2014 and 2015 when drop from 83 to 75% was noted.Conclusions: DMT stopping reasons and rates were mostly stable over time with a slight increase in recent years, with the availability of more DMTs. The overall results suggest that discontinuation of MS DMTs is mostly due to DMT properties and to a lesser extent to risk management and a competitive market.
Outcomes and Prognostic Factors of Salvage Radiation for Postoperative Lymph Node Recurrence of Esophageal Squamous Cell Carcinoma
Authors: Zhang Chi , Ge Xiao-Lin , Huang Chen-Jun , Zhang Shu , Sun Xin-Chen 
Published: March 2021

Purpose: Recurrence of esophageal squamous cell carcinoma (ESCC) in regional lymph nodes (LNs) after surgical section can be treated with salvage resection, radiotherapy (RT) or chemoradiotherapy (CRT). RT or CRT is more widely used in clinic. This paper investigates the effects, toxicities and prognostic risk factors of salvage RT or CRT on patients with LN recurrence.Methods: We retrospectively analyzed the clinical outcomes of 103 patients receiving salvage RT or CRT for LN recurrence after ESCC resection. In total, 39 patients received RT alone and 64 received concurrent CRT. All the patients received intensity modulated radiation therapy (IMRT), administered with a median dose of 62 Gy (range, 50–70 Gy).Results: The median follow-up time was 44.5 months, and median survival was 22.5 months (5.5–99.5 months). One-, 3-, and 5-year overall survival (OS) were 80.6, 37.0, and 25.8%, respectively. One- and 2-year progression free survival (PFS) were 57.3 and 34.0%, respectively. Grade 3 or above toxicity was low (16.5%) and no treatment-related deaths occurred. In univariate analysis of OS, pN0 (p = 0.039), smaller LN volume (≤25 cm3, p = 0.019), combined chemotherapy (p = 0.041) and single LN recurrence (p = 0.001) were associated with prolonged OS. And pT1-2 (p = 0.044), pN0 (p = 0.042), irradiation dose (&gt;60 Gy, p = 0.044), combined chemotherapy (p = 0.019) and single LN recurrence (p = 0.002) were associated with prolonged PFS. In multivariate analysis, the patients with only one recurrent node had a significant better OS (HR = 0.556, 95% CI 0.324–0.956, p = 0.034) and PFS (HR = 0.528, 95% CI 0.339–0.847, p = 0.008).Conclusions: Salvage RT or CRT for regional LN recurrence is effective and acceptable. Fewer recurrent nodes may indicate a better long-term survival.
Effectiveness and Safety of Iguratimod in Treating Primary Sjögren’s Syndrome: A Systematic Review and Meta-Analysis
Authors: Pu Jincheng , Wang Xuan , Riaz Farooq , Zhang Tongyangzi , Gao Ronglin , Pan Shengnan , Wu Zhenzhen , Liang Yuanyuan , Zhuang Shuqi , Tang Jianping 
Published: March 2021

Objectives: We aimed to assess the effectiveness and safety of iguratimod (IGU) in treating primary Sjögren’s syndrome (pSS) by meta-analysis.Methods: Eight databases and two clinical trial websites were searched from conception to August 10, 2020, for relevant randomized controlled trials (RCTs) on outcomes of patients with pSS treated with IGU. Revman 5.4 was used for statistical analysis and creating plots.Results: A total of 1,384 patients with pSS from 19 RCTs were included in this meta-analysis. Pooled results demonstrated that patients treated with IGU + hydroxychloroquine (HCQ) + glucocorticoid (GC) showed significant differences in erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) level, platelet (PLT) count, immunoglobulin G (IgG) level, salivary flow rate, Schirmer’s test result, EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), and efficacy rate (p ≤ 0.01) compared to patients treated with HCQ + GC. Compared to treatment with HCQ and GC, co-administration of IGU with GC showed significant differences in ESR and RF level (p ≤ 0.01); however, no significant differences were noted in IgG level. Conversely, the IgG level showed a significant improvement in the IGU + HCQ + GC group compared to the HCQ + GC group. The results of safety analysis revealed that seven trials showed no significant differences in adverse events (AEs) between the IGU + HCQ + GC and HCQ + GC groups (p = 0.15). Although no severe AEs were noted, gastrointestinal discomfort was the most common AE in the IGU group. No significant differences in AEs were observed between the IGU + GC and HCQ + GC groups.Conclusion: IGU improved the clinical symptoms of patients with pSS, including inflammatory indicators (ESR, IgG, and RF levels), PLT count, secretion function of the salivary and lacrimal glands (salivary flow rate and Schirmer’s test result), and disease indexes (ESSDAI and ESSPRI), when co-administered with HCQ + GC therapy without increasing the risks of AEs. Therefore, IGU can be considered as an effective and safe drug for clinical therapy of pSS. Considering the limitations of the present trials, more long-term, multicenter, and high-quality RCTs are required to assess the effectiveness and safety of IGU for treating patients with pSS.
Cohort Studies on Chronic Non-communicable Diseases Treated With Traditional Chinese Medicine: A Bibliometric Analysis
Authors: Li Yiwen , Liu Yanfei , Cui Jing , Zhao Hui , Liu Yue , Huang Luqi 
Published: March 2021

Cohort studies investigating the treatment of chronic non-communicable diseases (NCDs) with traditional Chinese medicine (TCM) have considerably accumulated in recent years. To systematically and for the first time present the achievements and dilemmas of cohort studies, strict inclusion and exclusion criteria were used to search publications from the Web of Science, PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases for cohort studies on NCDs with TCM since the establishment of these databases. Information on the year of publication, exposure factors, diseases, and outcome indicators was obtained, and a literature quality assessment and bibliometric descriptive analysis were conducted. A total of 182 published articles involving 1,615,106 cases were included. There were 110 non-prospective cohort studies and 72 prospective cohort studies. The diseases involved in the cohort studies were, in the order of the number of published articles, malignant tumors (82 articles, 45.05%), cardiovascular diseases (35 articles, 19.23%), neurological diseases (29 articles, 15.93%), chronic kidney diseases (16 articles, 8.79%), liver cirrhosis (8 articles, 4.40%), diabetes mellitus (8 articles, 4.40%), and chronic respiratory diseases (4 articles, 2.20%). The study participants were mainly from China (177 articles, 97.25%). The number of cohort studies increased significantly in the last 5 years (65 articles, 35.71%), and following the Newcastle-Ottawa Scale (NOS) literature quality evaluation, the number of articles that received a score of four to five was high (116 articles, 63.73%), and the overall quality needs to be improved. The application of cohort studies in the field of TCM for the prevention and treatment of NCDs has developed rapidly in the past 5 years, focusing on the prevention and treatment of tumors as well as cardiovascular and cerebrovascular diseases. However, the design and implementation of cohort studies still have considerable limitations. To provide more clinical evidence, researcher should actively cooperate with evidence-based methodologists and standardize the implementation of cohort studies.
Characteristics of Viral Shedding Time in SARS-CoV-2 Infections: A Systematic Review and Meta-Analysis
Authors: Yan Danying , Zhang Xiaobao , Chen Can , Jiang Daixi , Liu Xiaoxiao , Zhou Yuqing , Huang Chenyang , Zhou Yiyi , Guan Zhou , Ding Cheng , Chen Lu , Lan Lei , Fu Xiaofang , Wu Jie , Li Lanjuan , Yang Shigui 
Published: March 2021

Background: The viral shedding time (VST) of SARS-CoV-2 mainly determines its transmission and duration of infectiousness. However, it was heterogeneous in the existing studies. Here, we performed a meta-analysis to comprehensively summarize the VST of SARS-CoV-2.Methods: We searched PubMed, Web of Science, MedRxiv, BioRxiv, CNKI, CSTJ, and Wanfang up to October 25, 2020, for studies that reported VSTs of SARS-CoV-2. Pooled estimates and 95% CIs for the VSTs were calculated using log-transformed data. The VSTs in SARS-CoV-2 infections based on different demographic and clinical characteristics, treatments and specimens were stratified by subgroup analysis.Results: A total of 35 studies involving 3,385 participants met the inclusion criteria. The pooled mean VST was 16.8 days (95% CI: 14.8–19.4, I2 = 99.56%) in SARS-CoV-2 infections. The VST was significantly longer in symptomatic infections (19.7 days, 95% CI: 17.2–22.7, I2 = 99.34%) than in asymptomatic infections (10.9 days, 95% CI: 8.3–14.3, I2 = 98.89%) (P &lt; 0.05). The VST was 23.2 days (95% CI: 19.0–28.4, I2 = 99.24%) in adults, which was significantly longer than that in children (9.9 days, 95% CI: 8.1–12.2, I2 = 85.74%) (P &lt; 0.05). The VST was significantly longer in persons with chronic diseases (24.2 days, 95% CI: 19.2–30.2, I2 = 84.07%) than in those without chronic diseases (11.5 days, 95% CI: 5.3–25.0, I2 = 82.11%) (P &lt; 0.05). Persons receiving corticosteroid treatment (28.3 days, 95% CI: 25.6–31.2, I2 = 0.00%) had a longer VST than those without corticosteroid treatment (16.2 days, 95% CI: 11.5–22.5, I2 = 92.27%) (P = 0.06). The VST was significantly longer in stool specimens (30.3 days, 95% CI: 23.1–39.2, I2 = 92.09%) than in respiratory tract specimens (17.5 days, 95% CI: 14.9–20.6, I2 = 99.67%) (P &lt; 0.05).Conclusions: A longer VST was found in symptomatic infections, infected adults, persons with chronic diseases, and stool specimens.