bluuebunny/crossref_metadata_2025_split huggingface dataset:
N6-Methylandenosine-Related lncRNA Signature Is a Novel Biomarkers of Prognosis and Immune Response in Colon Adenocarcinoma Patients
Authors: Zhang Peiling , Liu Guolong , Lu Lin 
Published: July 2021

BackgroundColon adenocarcinoma (COAD) is the most common type of colon cancer. To date, however, the prognostic values of m6A RNA methylation-related long non-coding RNAs (lncRNAs) in COAD are largely unknown.Materials and MethodsThe m6A-related lncRNAs were identified from The Cancer Genome Atlas (TCGA) data set. Univariate and multivariate Cox regression analyses were performed to explore the prognostic m6A-related lncRNAs. Consistent clustering analysis was performed to classify the COAD patients into different subgroups based on the expression of m6A-related lncRNAs. The potential biological functions as well as differences in the stemness index and tumor immune microenvironment between different subgroups were analyzed. The prognostic m6A-related lncRNAs were used to establish an m6A-related lncRNA risk model to predict prognosis and survival status.ResultsWe identified 31 m6A-associated lncRNAs with prognostic values from the TCGA data set. Based on the expression of prognostic m6A-associated lncRNAs, TCGA-COAD patients were classified into three clusters using consistent clustering analysis. There was a low correlation of tumor stemness between the three clusters but a significant correlation with the tumor immune microenvironment as well as the tumor mutational load. Thirty-one prognostic-related m6A-associated lncRNAs were used to construct a risk model, which was further determined by survival analysis, receiver operating characteristic (ROC) curve, and univariate and multifactor Cox analysis. The m6A-related risk model demonstrates good performance in predicting prognosis and survival status. The model-based high-risk group exhibited poorer overall survival (OS) compared with the low-risk group.ConclusionIn this study, we construct a risk model that consists of 31 m6A-related lncRNAs with independent prognostic values in COAD. Our study shows the critical roles of these 31 m6A-related lncRNAs in the tumor immune microenvironment, indicating the prospect of informing prognostic stratification and the development of immunotherapeutic strategies for COAD patients.
The Level of D-Dimer Is Positively Correlated With the Severity of Mycoplasma pneumoniae Pneumonia in Children
Authors: Zheng Yan , Hua Lingling , Zhao Qiannan , Li Mengyao , Huang Meixia , Zhou Yunlian , Wang Yingshuo , Chen Zhimin , Zhang Yuanyuan 
Published: July 2021

ObjectiveMycoplasma pneumoniae pneumonia (MPP) is an important disease in children. Studies have demonstrated that the levels of D-dimer are elevated in some children with MPP, especially those with thrombotic complications. However, the potential association between MPP and D-dimer remains unclear. In our study, we sought to explore the relationship between the levels of plasma D-dimer and clinical characteristics of MPP patients.MethodsRetrospective analysis was conducted on 356 patients who were hospitalized in our hospital for MPP between January 1, 2017, and December 31, 2019. According to the peak value of D-dimer, patients were divided into three groups: the normal group (D-dimer&lt;0.55 mg/L), the mild-moderately elevated group (D-dimer 0.55–5.5 mg/L) and the severely elevated group (D-dimer &gt;5.5 mg/L). The demographic and clinical information, radiological findings, laboratory data, and treatments of patients were compared among different groups.Results106 patients were in the normal group, 204 patients were in the mild-moderately elevated group, and 46 patients were in the severely elevated group. More severe clinical and radiographic manifestations, longer length of fever, hospital stay and antibiotic therapy duration, higher incidences of extra-pulmonary complications, refractory MPP (RMPP), severe MPP (SMPP) were found in the elevated group, when compared with the normal group (P&lt;0.01). Meanwhile, we found that the percentage of neutrophil (N%) and CD8+ lymphocyte (CD8+%), C-reactive protein (CRP), lactate dehydrogenase (LDH), interleukin (IL)-6, IL-10, and interferon-gamma (IFN-γ) trended higher with increasing D-dimer, whereas the percentage of lymphocyte (L%) and prealbumin (PAB) trended lower (P&lt;0.01). In addition, the proportions of patients requiring oxygen therapy, glucocorticoid, bronchoscopy, immunoglobulin use, thoracentesis, or ICU admission were significantly higher in the severely elevated group than those in the other two groups (P&lt;0.01). Correlation analysis showed that N%, L%, CRP, LDH, IL-10, length of fever, length of stay, and length of antibiotic therapy had strong correlations with the level of D-dimer.ConclusionsMPP patients with higher levels of D-dimer had more severe clinical manifestations and needed longer duration of treatment, which might be closely related to the severity of lung inflammation after MP infection.
Peri-procedural Trans-esophageal Echocardiographic Sizing of the Native Left Ventricular Outflow Tract During Edwards INTUITY Valve Implantation
Authors: Lim Kevin , Ho Yan Kit , Chow Simon Chi Ying , Fujikawa Takuya , Lee Alex Pui-Wai , Wong Randolph Hung Leung 
Published: July 2021

Background: The Edwards INTUITY rapid deployment valve was anchored on the left ventricular outflow tract (LVOT) by radial force akin to transcatheter balloon-expandable valves. This design feature facilitates minimally invasive and complex procedures but comes at the price of compressing the atrioventricular conduction bundle and potential requirement for pacemaker implantation.Methods: A retrospective observational study was conducted on 30 consecutive patients who received the INTUITY valve at our institution from August 2018 to January 2021. Demographical, clinical, and echocardiographic parameters were collected for 90 days post-operatively. The diameter of the native LVOT at the landing site of the sub-annular stent was retrospectively measured using archived trans-esophageal echocardiographic images. A line was drawn from the inner edge of the septal endocardium to the inner edge of the anterior mitral leaflet in mid-systole, parallel to the aortic annulus, 6–8 mm apical to the aortic annulus depending on the valve size and the corresponding stent length. Risk factors associated with new onset conduction disturbances, defined as the occurrence of bundle branch block or complete heart block, were analyzed.Results: Operative mortality was 3.3%. Pre-operatively, permanent pacemakers were required for two patients who were excluded from the subsequent analysis. New onset conduction disturbances occurred in four of the remaining 28 patients (14.3%). This included two incidences of persistent left bundle branch block and two incidences of permanent pacemaker implantation due to complete heart block. Univariate analysis identified over-sizing of the native LVOT by 5 mm or more as a significant risk factor associated with conduction disturbance.Conclusion: During INTUITY vale implantation, in addition to the aortic annulus, the landing site of the sub-annular stent within the native LVOT should also be sized pre-bypass. Over-sizing the native LVOT by 5 mm or more was associated with an increased risk of new onset conduction disturbances and should be avoided.
Softening of Temperate Ice by Interstitial Water
Authors: Adams Conner J. C. , Iverson Neal R. , Helanow Christian , Zoet Lucas K. , Bate Charlotte E. 
Published: July 2021

Ice at depth in ice-stream shear margins is thought to commonly be temperate, with interstitial meltwater that softens ice. Models that include this softening extrapolate results of a single experimental study in which ice effective viscosity decreased by a factor of ∼3 over water contents of ∼0.01–0.8%. Modeling indicates this softening by water localizes strain in shear margins and through shear heating increases meltwater at the bed, enhancing basal slip. To extend data to higher water contents, we shear lab-made ice in confined compression with a large ring-shear device. Ice rings with initial mean grain sizes of 2–4 mm are kept at the pressure-melting temperature and sheared at controlled rates with peak stresses of ∼0.06–0.20 MPa, spanning most of the estimated shear-stress range in West Antarctic shear margins. Final mean grain sizes are 8–13 mm. Water content is measured by inducing a freezing front at the ice-ring edges, tracking its movement inward with thermistors, and fitting the data with solutions of the relevant Stefan problem. Results indicate two creep regimes, below and above a water content of ∼0.6%. Comparison of effective viscosity values in secondary creep with those of tertiary creep from the earlier experimental study indicate that for water contents of 0.2–0.6%, viscosity in secondary creep is about twice as sensitive to water content than for ice sheared to tertiary creep. Above water contents of 0.6%, viscosity values in secondary creep are within 25% of those of tertiary creep, suggesting a stress-limiting mechanism at water contents greater than 0.6% that is insensitive to ice fabric development in tertiary creep. At water contents of ∼0.6–1.7%, effective viscosity is independent of water content, and ice is nearly linear-viscous. Minimization of intercrystalline stress heterogeneity by grain-scale melting and refreezing at rates that approach an upper bound as grain-boundary water films thicken might account for the two regimes.
Lateral Lymph Node Metastases in T1a Papillary Thyroid Carcinoma: Stratification by Tumor Location and Size
Authors: Zhang Xiaojun , Chen Wenkuan , Fang Qigen , Fan Jie , Feng Lu , Guo Lanwei , Liu Shanting , Ge Hong , Du Wei 
Published: July 2021

ObjectiveTo analyze the incidence and risk factors for lateral lymph node metastases (LNMs) in T1a papillary thyroid carcinoma (PTC) with a focus on tumor location and size.Materials and MethodsThe incidence of lateral LNM in 345 cases of T1a PTC was retrospectively analyzed. Univariate and multivariate analyses were performed to assess the relationships between lateral LNM and clinicopathological characteristics.ResultsThe incidence of skip metastasis to lateral LNM in T1a PTC located in the upper lobe was 12.1% (8/66). Logistic regression analysis indicated tumor size &gt;5 mm (OR = 5.04, 95% CI = 1.79 to 14.18, P = 0.002), upper lobe location (OR = 7.68, 95% CI = 3.05–19.34, P &lt; 0.001) and the number of central neck LNM (&lt;2: OR = 24.79, 95% CI = 8.23–74.60, P &lt; 0.001; ≥2: OR = 4.99, 95% CI = 1.95–12.73, P &lt; 0.001) were independently associated with lateral LNM. Comparing the lateral and central LNM stratification based on tumor location revealed that both the incidences of lateral (33.3%) and central (30.3%) LNM of T1a PTC located in the upper lobe were higher than those of T1a PTC located in the middle and lower lobes. Of T1a PTC located in the upper lobe, the incidence of lateral LNM was 33.3% (22/66), which was higher than that [30.3% (20/66)] of central LNM. This finding is reversed in all T1a PTC cases and T1a PTC cases with tumor located in the middle and lower lobes.ConclusionA particularly high likelihood of lateral LNM was observed in T1a PTC patients with tumor located in the upper lobe of the thyroid gland, especially the tumor &gt;5 mm in size, which could be considered a risk factor for lateral LNM in the clinical management of T1a PTC.
Gout Augments the Risk of Cardiovascular Disease in Patients With Psoriasis: A Population-Based Cohort Study
Authors: Chen Zhiyong , Xu Yiwen , Chen Miao , Cui Ran , Wang Yu-Hsun , Dai Sheng-Ming , Wei James Cheng-Chung 
Published: July 2021

ObjectivePatients with psoriasis (PsO) have a high frequency of concomitant gout and increased risk of cardiovascular diseases (CVD). We aimed to estimate the synergistic impact of gout on the risk of CVD in patients with PsO.MethodsA population-based cohort of patients registered in the National Health Insurance Research Database of Taiwan between 2000 and 2013 was stratified according to the presence of PsO and gout. Propensity score analysis was used to match age and gender at a ratio of 1:4. Cox proportional hazard models and subgroup analyses were used to estimate the hazard ratios (HRs) for CVD adjusted for traditional risk factors. The Kaplan–Meier method was used to plot the cumulative incidence curves.ResultsPatients with combined PsO and gout (n = 97), PsO alone (n = 388), gout alone (matched, n = 388) and matched controls (n = 388) were identified. Compared with the patients with PsO alone, the patients with combined PsO and gout had a significantly higher risk of CVD (relative risk 2.39, 95% CI 1.56 to 3.65). After adjustment for traditional risk factors, the risk of CVD was higher in patients with gout alone (HR 2.16, 95% CI 1.54 to 3.04) and in patients with combined PsO and gout (HR 2.72, 95% CI 1.73 to 4.28).ConclusionsGout augments the risk of CVD independently of traditional risk factors in patients with PsO.
CD4+CD25+CD127-Foxp3+ and CD8+CD28- Tregs in Renal Transplant Recipients: Phenotypic Patterns, Association With Immunosuppressive Drugs, and Interaction With Effector CD8+ T Cells and CD19+IL-10+ Bregs
Authors: Aly Mostafa G. , Ibrahim Eman H. , Karakizlis Hristos , Weimer Rolf , Opelz Gerhard , Morath Christian , Zeier Martin , Ekpoom Naruemol , Daniel Volker 
Published: July 2021

IntroductionGaps still exist regarding knowledge on regulatory cells in transplant recipients. We studied the phenotypic patterns of CD4+, CD8+CD28- Tregs, and CD19+IL-10+ Bregs in the blood of healthy controls (HC), end-stage kidney disease patients (ESKD), early and late stable renal transplant recipients (Tx), and transplant recipients with steroid-treated acute cellular rejection 1 week–3 months after successful treatment. We also investigated the relationship between immunosuppressive drugs and the aforementioned regulatory cells in transplant recipients.MethodsWe recruited 32 HC, 83 ESKD, 51 early Tx, 95 late Tx, and 9 transplant patients with a recent steroid-treated acute cellular rejection. Besides CD19+IL-10+ Bregs, we analyzed absolute and relative frequencies of CD4+CD25+CD127-Foxp3+ Tregs and CD8+CD28- Tregs and their expression of IL-10, TGF-ß, IFN-g, and Helios.ResultsWe found a negative correlation between absolute CD4+CD25+CD127-Foxp3+ Treg and relative CD19+IL-10+ Breg frequencies in early Tx recipients (r=-0.433, p=0.015, n=31). In that group, absolute CD4+CD25+CD127-Foxp3+ Tregs were negatively associated with steroid dose and tacrolimus trough levels (r=-0.377, p = 0.021, n=37; r=-0.43, p=0.033, n=25, respectively), opposite to IL-10+ Bregs, whose frequency apparently was not negatively affected by potent immunosuppression early posttransplant. We found also lower CD4+CD25+CD127-Foxp3+ Tregs in patients treated with basiliximab or rATG as compared with ESKD patients (p=0.001 and p &lt;0.001, respectively). No difference in absolute IL-10+ Bregs could be detected among these 3 patient groups. Early Tx recipients showed lower CD4+CD25+CD127-Foxp3+ Tregs within 3 months of antibody induction than after 3 months (p = 0.034), whereas IL-10+ Bregs showed higher relative counts during the first 3 months post antibody induction than after 3 months (p = 0.022). Our findings suggest that IL-10+ Bregs decrease with time posttransplantation independent of the effect of antibody induction and dose of other immunosuppressive drugs.ConclusionThese findings suggest that CD19+IL-10+ Bregs and CD4+CD25+CD127-Foxp3+ Tregs behave in opposite ways during the early posttransplant period, possibly due to a predominant negative impact of high doses of immunosuppressants on Tregs. CD19+IL-10+Bregs do not seem to be suppressed by antibody induction and early potent immunosuppression with chemical drugs.
Geographic and Age Variations in Low Body Mass Index Among Community-Dwelling Older People in Xinjiang: A Cross-Sectional Study
Authors: Liu Jinling , Qu Qun , Xuekelati Saiyare , Bai Xue , Wang Li , Xiang Hong , Wang Hongmei 
Published: July 2021

Background: Studies have shown an association between undernutrition and increased adverse outcome, as well as substantial geographic and age variations in undernutrition. Body mass index (BMI), a core indicator of undernutrition, is easy to measure and reflects the nutritional and health status of the human body. It is a simple and suitable tool for epidemiological investigations in large sample populations. Herein, we provide the first description of geographic and age variations in the prevalence of low BMI among community-dwelling older people in Xinjiang.Methods: From January 2019 to December 2019, using a multi-stage random sampling method, we conducted a cross-sectional epidemiological survey of the community-dwelling older people in Xinjiang at different latitudes. Of the 87,000 participants, the statistical analyses included 86,514 participants with complete data.Results: In Xinjiang, the prevalence of low BMI was 7.7% in the community-dwelling older people. The BMI gradually decreased with increasing age and gradually increased with latitude. The prevalence of low BMI in northern Xinjiang was 5.3%, which was significantly lower than that in eastern (7.7%) and southern (9.3%) Xinjiang. In the 60–69-, 70–79-, 80–89-, and ≥90-year age groups, the prevalence rates of low BMI were 5.8, 7.9, 10.0, and 13.9%, respectively. After adjusting for confounding factors (sex, ethnic group, hypertension, diabetes, hyperlipemia, smoking, and drinking), multivariate logistic regression analysis showed that the odds ratios (95% CI) for low BMI in eastern and southern Xinjiang were 1.165 (1.056–1.285) and 1.400 (1.274–1.538), respectively, compared to northern Xinjiang. The adjusted odds ratios (95% CI) for low BMI in the 70–79-, 80–89-, and ≥90-year age groups were 1.511 (1.39–1.635), 2.233 (2.030–2.456), and 3.003 (2.439–3.696), respectively, compared to the 60–69-year age group.Conclusion: The results of this study revealed geographic and age variations in the prevalence of low BMI in the community-dwelling older people in Xinjiang. The prevalence of low BMI gradually increased as the latitude decreased and as age increased.
Soluble CD163 Is a Predictor of Mortality in Patients With Decompensated Cirrhosis
Authors: Zhang Yue , Huang Chenkai , Nie Yuan , Liu Qi , Xiao Nanxi , Liu Linxiang , Zhu Xuan 
Published: July 2021

Background: Soluble CD163 (sCD163) is a scavenger receptor membrane protein expressed almost exclusively on Kupffer cells and other macrophages. It was found to be associated with the severity of liver cirrhosis. The aim of the present study was to determine whether the novel biomarker sCD163 predicts outcomes in patients with decompensated cirrhosis.Materials and Methods: A single-center, observational, prospective study with 345 decompensated cirrhosis patients was conducted in the Gastroenterology Department between January 2017 and December 2020. Their plasma samples were tested by enzyme-linked immunosorbent assay (ELISA) for sCD163 within 24 hours of admission. These patients were followed up at 28 days, 3 months and 6 months. The independent risk factors were identified with uni- and multivariate logistic regression analyses. We evaluated the predictive performance of the new scoring system (including sCD163) and the original scoring system.Results: The sCD163 level was significantly higher in non-surviving patients than in surviving patients. Positive associations were found between sCD163 levels and the Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD) and albumin-bilirubin (ALBI) scores. Logistic regression confirmed that sCD163 was an independent risk factor for 28-day, 3-month, and 6-month mortality. The areas under the receiver operating characteristic curves (AUROCs) of the use of sCD163 for the prediction of 28-day, 3-month, and 6-month mortality were relatively higher (AUROCs: 0.856; 0.823 and 0.811, respectively). The AUROCs of the new scores obtained by adding sCD163 to the original scoring systems (CTP + sCD163, MELD + sCD163 and ALBI + sCD163) showed that the new scoring systems had better predictive performance than the original scoring systems at all time points (P &lt; 0.001).Conclusion: sCD163 is a prognostic predictor of short-term and long-term outcomes in decompensated cirrhosis patients. Accordingly, the addition of sCD163 to the original clinical scoring systems improved their prognostic performance.
Meta-Analysis and Structural Dynamics of the Emergence of Genetic Variants of SARS-CoV-2
Authors: Castonguay Nicolas , Zhang Wandong , Langlois Marc-André 
Published: July 2021

Graphical AbstractErrors are regularly made when SARS-CoV-2 replicates its RNA genome. The viral polymerase complex is error-prone with imperfect proofreading abilities. These errors or mutations often lead to deleterious or neutral effects on the virus. However, sometimes these mutations have a positive effect and create genetic variants of the virus with different features including increased transmissibility, pathogenicity, and immune escape capabilities. When mutations work collaboratively to create a new virus feature, this is called epistasis.
RNF213 p.R4810K (c.14429G > A) Variant Determines Anatomical Variations of the Circle of Willis in Cerebrovascular Disease
Authors: Eto Futoshi , Yoshimoto Takeshi , Okazaki Shuhei , Nishimura Kunihiro , Ogura Shiori , Yamaguchi Eriko , Fukuma Kazuki , Saito Satoshi , Washida Kazuo , Koga Masatoshi , Toyoda Kazunori , Morimoto Takaaki , Maruyama Hirofumi , Koizumi Akio , Ihara Masafumi 
Published: July 2021

IntroductionDysregulation of the RING finger protein 213 (RNF213) gene impairs vascular formation in experimental animal models. In addition, vascular abnormalities in the circle of Willis are associated with cerebrovascular disease. Here, we evaluated the relationship between the East Asian founder variant RNF213 p.R4810K and consequent anatomical variations in the circle of Willis in cerebrovascular disease.Patients and MethodsThe present study is an observational cross-sectional study. It included patients with acute anterior circulation non-cardioembolic stroke admitted to our institution within 7 days of symptom onset or last-known-well from 2011 to 2019, and those who participated in the National Cerebral and Cardiovascular Center Biobank. We compared anatomical variations of the vessels constituting the circle of Willis between RNF213 p.R4810K (c.14429G &gt; A) variant carriers and non-carriers using magnetic resonance angiography and assessed the association between the variants and the presence of the vessels constituting the circle of Willis. Patients with moyamoya disease were excluded.ResultsFour hundred eighty-one patients [146 women (30%); median age 70 years; median baseline National Institutes of Health Stroke Scale score 5] were analyzed. The RNF213 p.R4810K variant carriers (n = 25) were more likely to have both posterior communicating arteries (PComAs) than the variant non-carriers (n = 456) (56% vs. 13%, P &lt; 0.01). Furthermore, variant carriers were less likely to have an anterior communicating artery (AComA) than non-carriers (68% vs. 84%, P = 0.04). In a multivariate logistic regression analysis, the association of RNF213 p.R4810K variant carriers with the presence of both PComAs and the absence of AComA remained significant.ConclusionOur findings suggest that the RNF213 p.R4810K variant is an important factor in determining anatomical variations in the circle of Willis.