bluuebunny/crossref_metadata_2025 huggingface dataset:
miR-504 Promoted Gastric Cancer Cell Proliferation and Inhibited Cell Apoptosis by Targeting RBM4
Authors: Zhang Yi , Yong Hongmei , Fu Jing , Gao Guangyi , Shi Huichang , Zhou Xueyi , Fu Mingsheng
Published: June 2021

Background. The purpose of this study was to explore the role and underlying mechanism of miR-504 and RBM4 in gastric cancer. Methods. The qRT-PCR or Western blot was performed to determine the expressions of miR-504 and RBM4 in the gastric cancer tissues and normal tissues. Human SGC-7901 cells were transfected with miR-504 mimic/inhibitor or pcDNA-RBM4. Cell proliferation and cell apoptosis were assessed by colony formation assay and flow cytometry, respectively. Luciferase reporter gene assays were used to investigate interactions between miR-504 and RBM4 in SGC-7901 cells. Results. The relative expression of miR-504 was significantly upregulated in the gastric cancer group (

n
=
25

) than in the paired normal group (

n
=
25

), but the relative RBM4 expression was remarkably downregulated in the gastric tumor group, compared with the normal group. Additionally, miR-504 overexpression increased the viability of gastric cancer cells. Moreover, RBM4 is a functional target of miR-504 in gastric cancer cells. miR-504 was further confirmed to promote SGC-7901 cell proliferation and inhibit cell apoptosis by downregulation RBM4 in vitro. Conclusions. miR-504 promotes gastric cancer cell proliferation and inhibits cell apoptosis by targeting RBM4, and this provides a potential diagnostic biomarker and treatment for patients with gastric cancer.
Energy and Fatigue Damage Evolution of Sandstone under Different Cyclic Loading Frequencies
Authors: Sun Yidan , Yang Yu
Published: June 2021

To study the energy dissipation characteristics and damage evolution law of sandstone under cyclic loading, uniaxial cyclic loading tests are conducted on sandstone specimens under different frequencies with an MTS‐815 rock testing machine. Furthermore, the characteristics of elastic modulus and energy evolution law during cyclic loading and unloading are explored. The results show that the loading and unloading moduli increase with the loading frequency. Under higher frequencies, the deformation resistance of the specimen is stronger, the elastic energy stored in a single cycle of loading is larger, the released energy is less, and it is less likely for the specimen to be damaged. At the beginning of loading, the energy dissipation ratio K decreases slowly with increasing loading cycles, and it then remains stable. When the specimen is close to failure, an inflection point of K appears, and K increases rapidly. Furthermore, the evolution equation of the damage variable is derived according to the strength characteristics and energy evolution law in the process of cyclic loading, and the reasons for the failure of sandstone specimens are explained from the perspectives of energy and fatigue damage.
Decision Method of Bridge Deck Pavement Maintenance Based on the Decision Maker’s Objective
Authors: Liang Xiaofei , Shi Jun , Li Zhongmei
Published: June 2021

The performance of reinforced concrete bridge deck pavement will be gradually reduced with the increase of operation time, so the reasonable maintenance measures should be taken to ensure the performance and safety of the bridge structures. The objectives and their hierarchical structures from both state position and enterprise position of the decision makers in bridge engineering decision‐making problems were discussed. By the existing deterioration model, this paper studies the bridge operation safety maintenance strategy, establishes the mathematical model of the influence of different degrees of maintenance measures on the structural performance, combines with the cost‐benefit theory, establishes the maintenance risk decision criteria for the decision makers with different objectives, and makes the decision on the selection of the bridge deck pavement scheme based on the enterprise position through an example.
Eigenvalue Spectrum and Synchronizability of Two Types of Double-Layer Star-Ring Networks with Hybrid Directional Coupling
Authors: Yang Feimei , Jia Zhen , Deng Yang
Published: June 2021

In this study, we studied the eigenvalue spectrum and synchronizability of two types of double-layer hybrid directionally coupled star-ring networks, namely, the double-layer star-ring networks with the leaf node pointing to the hub node (Network I) and the double-layer star-ring networks with the hub node pointing to the leaf node (Network II). We strictly derived the eigenvalue spectrum of the supra-Laplacian matrix of these two types of networks and analyzed the relationship between the synchronizability and the structural parameters of networks based on the master stability function theory. Furthermore, the correctness of the theoretical results was verified through numerical simulations, and the optimum structural parameters were obtained to achieve the optimal synchronizability.
Can Heparin-Coated ECMO Cannulas Induce Thrombocytopenia in COVID-19 Patients?
Authors: Steinlechner Barbara , Kargl Gabriele , Schlömmer Christine , Holaubek Caroline , Scheriau Georg , Eichinger Sabine , Gratz Johannes , Rössler Bernhard
Published: June 2021

Extracorporeal membrane oxygenation (ECMO) is often used in the management of COVID-19-related severe respiratory failure. We report the first case of a patient with COVID-19-related ARDS on ECMO support who developed symptoms of heparin-induced thrombocytopenia (HIT) in the absence of heparin therapy. A low platelet count of 61 G/L was accompanied by the presence of circulating HIT antibodies 12 days after ECMO initiation. Replacement of the ECMO system including cannulas resulted in the normalization of the platelet count. However, the clinical situation did not improve, and the patient died 9 days later. Careful consideration of anticoagulant therapy and ECMO circuit, as well as routine HIT antibody testing, may prevent a fatal course in ECMO-supported COVID-19 patients.
Mechanical Performance Analysis and Parametric Study of a Self‐Anchored Suspension Bridge with Ultra‐Wide Double‐Sided Steel Box Girder
Authors: Wu Fangwen , Tang Wenlong , Liu Shuo , Feng Yanpeng , Wang Guangqian , Du Maohua
Published: June 2021

A sufficient understanding of mechanical performance of self‐anchored suspension bridge with double‐sided steel box girder is essential for design and normal use as such bridges are widely built in urban bridge. Using the Yunlongwan Bridge which is a suspension bridge with ultra‐wide double‐sided steel box girder as an example, this paper investigates its deformation and mechanical performance under vehicle load. Firstly, based on the field test results, the deformation performance of the bridge and the stress distribution of the main girder are analysed, with emphasis on the shear lag effect of double‐sided steel box girder. Then, a multiscale model of the bridge was built, and the accuracy of the model was verified by comparison with the test data. Finally, the influence of design parameters on the mechanical behaviour of double‐sided steel box girder is studied by numerical simulation. The results show that the deformation of the bridge has good symmetry, there is obvious shear lag effect on the main girder, and the U‐rib thickness, diaphragm spacing, and vehicle load could significantly affect the stress of the main girder top plate. The obtained analytical results lead to a better understanding of the mechanical performance and provide reference for the design of self‐anchored suspension bridge with double‐sided steel box girder.
Chemometric Analyses for the Characterization of Raw and Stir-Frying Processed Drynariae Rhizoma Based on HPLC Fingerprints
Authors: Hu Jing , Wang Jiali , Qin Beibei , Wang Lizhi , Li Xia
Published: June 2021

The processing of traditional Chinese medicine (TCM) is a necessary practice and usually occurs before most herbs are prescribed. According to Chinese medicine theory, raw (RDR) and stir-frying processed (PDR) Drynariae Rhizoma have different clinical applications. The purpose of this study was to establish HPLC fingerprints coupled with chemometric methods to evaluate the differences between RDR and PDR. Multivariate chemometric methods were applied to analyze the obtained HPLC fingerprints, including hierarchical cluster analysis (HCA), principle components analysis (PCA), and partial least squares discriminant analysis (PLS-DA). The results indicated that RDR and PDR samples showed a clear classification of the two groups, and seven chemical markers having great contributions to the differentiation were screened out. The findings suggested that 5-hydroxymethyl-2-furaldehyde (5-HMF) with a variable importance in the project (VIP > 1) can be used to differentiate between RDR and PDR. Moreover, 5-HMF, naringin, and neoeriocitrin were determined to evaluate their contents in RDR and PDR. The chemometrics combined with the quantitative analysis based on HPLC fingerprint results indicated that stir-frying processing may change the contents and types of components in Drynariae Rhizoma. These changes are probably responsible for the various pharmacological effects of RDR and PDR.
Comparison of Clinical Features between Primary Aldosteronism and Essential Hypertension in Chinese Patients: A Case-Control Study
Authors: Huang Xiaoyu , Yu Shuang , Xiao Huangmeng , Pei Ling , Chen Yan , Chen Wenzhan , Li Yanbing , Xiao Haipeng , Cao Xiaopei
Published: June 2021

Primary aldosteronism (PA) is one of the most common forms of secondary hypertension. Recent studies suggest that, compared with essential hypertension (EH), PA presents more severe disorders of glycolipid metabolism and organ damages. This case-control retrospective study aimed to ascertain clinical features and metabolic parameters between Chinese patients of PA and EH. 174 PA patients and 174 matched EH patients were recruited. Their clinical features, biochemistry parameters, the ventricular septal thickness, and left ventricular mass index (LVMI) were compared. HOMA-β% and HOMA-IR were calculated to evaluate glucose metabolism. The results showed that there was no significant difference regarding BMI, waist-to-hip ratio, and blood pressure between the two groups. The blood potassium level was significantly lower in PA patients than those in EH patients. The abnormal glucose tolerance and the incidence of diabetes in the PA group were not significantly different from those in EH group, but the insulin secretion levels at 0 min and 30 min were significantly weaker than those in the EH group, and the HOMA-β% was also lower in the PA group than those in the EH group. Left ventricular structural abnormalities in PA patients were more severe than those in EH patients. Subtype analysis indicated that patient with aldosterone-producing adenoma (APA) has more serious hypokalemia and lower levels of HOMA-β% and HOMA-IR comparing to those in the idiopathic adrenal hyperplasia (IHA) patient. These findings demonstrated that PA patients showed more impaired insulin secretion function and more severe left ventricular structural damage compared with EH patients.
Metabonomic Study on the Plasma of High-Fat Diet-Induced Dyslipidemia Rats Treated with Ge Gen Qin Lian Decoction by Ultrahigh-Performance Liquid Chromatography-Mass Spectrometry
Authors: Xu Ziwei , Sheng Yixuan , Zeng Guowei , Zeng Zhijun , Li Bingtao , Jiang Li , Xu Guoliang , Zhang Qiyun
Published: June 2021

Gegen Qinlian decoction (GGQLD) has a definite effect on T2DM in clinic, and it has the effect of lowering blood sugar, improving insulin resistance, and improving the blood lipid level of rats with dyslipidemia, but the intervention mechanism of GGQLD on dyslipidemia has not been clarified. The changes in endogenous metabolites in the plasma of high-fat diet-induced dyslipidemia rats treated with Ge Gen Qin Lian Decoction (GGQLD) were studied to elucidate the therapeutic effects and mechanism of action of GGQLD in dyslipidemia. Based on ultrahigh-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS), the metabolic profiles of rat serum samples were collected. The rat model of dyslipidemia was induced by a 60% fat-fed high-fat diet. After feeding the rats with a high-fat diet for 4 weeks, dyslipidemia appeared. After 5 weeks of GGQLD (14.85 g kg−1) administration, the metabonomics of rats’ plasma samples in the normal group, model group, and administration group were analyzed. Mass profiler professional (MPP), SIMCA-P 14.1, and Graphpad prism 6.0 software were used combined with METLIN biological database and human metabolite database HMDB to screen and identify endogenous biomarkers. Metaboanalyst 4.0 software was used by combining with HMDB and KEGG databases; the enrichment and metabolic pathway of biomarkers were analyzed to explore the metabolic mechanism of dyslipidemia rats induced by high-fat diet and the intervention mechanism of Gegen Qinlian decoction. After 5 weeks of administration of GGQLD, the levels of serum TC and TG were significantly decreased (

P
<
0.05

,

P
<
0.01

), while HDL-C and LDL-C were not significantly affected. After administration, the food intake of rats in the administration group decreased gradually, and the change trend of body weight gradually slowed down. The metabonomics of rat plasma samples results showed that 23 potential biomarkers including α-linolenic acid, arachidonic acid, and lysophosphatidylcholine were significantly changed in positive ion mode. Studies have shown that GGQLD has a significant lipid-lowering effect on dyslipidemia rats induced by a high-fat diet, and its preventive mechanism is related to tryptophan metabolism, fatty acid biosynthesis, α-linolenic acid metabolism, arachidonic acid, and glycerophosphatidyl metabolism pathway.
Upregulation Mitochondrial Carrier 1 (MTCH1) Is Associated with Cell Proliferation, Invasion, and Migration of Liver Hepatocellular Carcinoma
Authors: Chen Guolin , Mo Shanshan , Yuan Di
Published: June 2021

Among the primary causes of cancer‐associated death in the world, liver hepatocellular carcinoma (LIHC) ranks the third. LIHC is defined as the sixth most frequently diagnosed carcinoma. The gene mitochondrial carrier 1 (MTCH1) is a protein‐coding gene. Recent research suggests that MTCH1 may be associated with some diseases. Here, our study attempts to explore the role and implication of MTCH1 in LIHC. Kaplan Meier Plotter and GEPIA (Gene Expression Profiling Interactive Analysis) databases were employed to determine the expression of MTCH1 and its correlation with prognostic status in LIHC patients. For the first time, our results suggested that MTCH1 was aberrantly expressed in human pan‐cancer and highly expressed in LIHC. Its high expression was closely associated with metastasis of tumor, stage of cancer, and poor survival of patients. Then, through enrichment analysis, MTCH1 was found to be closely related to RNA splicing in LIHC. Subsequently, we conducted a series of functional experiments. PCR data showed that LIHC cell lines and samples are highly expressed MTCH1. CCK‐8 (Cell Counting Kit‐8) assays and Transwell assays indicated that silencing MTCH1 certainly suppressed cell proliferation, migration, and invasion. These findings shed the clue that MTCH1 could be regarded as the potential prognosis biomarker of LIHC and a promising therapeutic target for LIHC.
Cellular Contractility Profiles of Human Diabetic Corneal Stromal Cells
Authors: Lam Thi N. , Nicholas Sarah E. , Choi Alexander , Ma Jian-Xing , Karamichos Dimitrios
Published: June 2021

Diabetic keratopathy is a corneal complication of diabetes mellitus (DM). Patients with diabetic keratopathy are prone to developing corneal haze, scarring, recurrent erosions, and significant wound healing defects/delays. The purpose of this study was to determine the contractility profiles in the diabetic human corneal stromal cells and characterize their molecular signatures. Primary human corneal fibroblasts from healthy, Type 1 DM (T1DM), and Type 2 DM (T2DM) donors were cultured using an established 3D collagen gel model. We tracked, measured, and quantified the contractile footprint over 9 days and quantified the modulation of specific corneal/diabetes markers in the conditional media and cell lysates using western blot analysis. Human corneal fibroblasts (HCFs) exhibited delayed and decreased contractility compared to that from T1DMs and T2DMs. Compared to HCFs, T2DMs demonstrated an initial downregulation of collagen I (day 3), followed by a significant upregulation by day 9. Collagen V was significantly upregulated in both T1DMs and T2DMs based on basal secretion, when compared to HCFs. Cell lysates were upregulated in the myofibroblast-associated marker, α-smooth muscle actin, in T2DMs on day 9, corresponding to the significant increase in contractility rate observed at the same time point. Furthermore, our data demonstrated a significant upregulation in IGF-1 expression in T2DMs, when compared to HCFs and T1DMs, at day 9. T1DMs demonstrated significant downregulation of IGF-1 expression, when compared to HCFs. Overall, both T1DMs and T2DMs exhibited increased contractility associated with fibrotic phenotypes. These findings, and future studies, may contribute to better understanding of the pathobiology of diabetic keratopathy and ultimately the development of new therapeutic approaches.
Study on the Lagging Support Mechanism of Anchor Cable in Coal Roadway Based on FLAC3D Modified Model
Authors: Wang Xiangyu , Wang Guanghui , Wu Bowen , Liu Shuaigang
Published: June 2021

Aiming at the broken failure of anchor cable in the mining roadway roof during the mining process, the lagging support scheme of anchor cable is proposed. Based on the results of indoor anchor cable pull‐out test, the Cable element in FLAC3D is modified to realize the extension breaking of anchor cable in the calculation process. Furthermore, the minimum principal stress and volume strain rate mutation point are used as the failure criteria of the anchor cable. Through the comparative analysis of five anchor cable lagging support schemes of 6208 transport tunnel in Wangzhuang Mine Coal, the results demonstrate that the lagging support reduces the initial support resistance of the supporting structure. With the increase of lagging time, the ability of anchor cable to adapt to deformation increases gradually. When the lagging time reaches the gentle area of roadway deformation, its ability to adapt to deformation remains stable. Finally, it was determined that the support should start at 10–15 m of the anchor cable lagging head of the 6208 transport tunnel. Industrial tests show that the lagging support scheme ensures that the anchor cable can withstand a certain deformation, and the support body has no broken failure, which effectively controls the large mining‐induced deformation of surrounding rock.
Analysis on the Influence Degree of Deformation Control Factors of Deep‐Buried Roadway’s Fractured Surrounding Rock Using Orthogonal Design
Authors: Li Ke , Yu Weijian , Xu Youlin , Zhou Ze , Xu Mengtang , Liang Wei
Published: June 2021

It is a complex issue to select the support structure parameters for a deep‐buried roadway with fractured surrounding rock; especially when the support structure parameters need to be adjusted, the influence degree of support structure parameters on roadway deformation needs to be determined. The deformation of deep‐buried roadway’s fractured surrounding rock development was investigated using multi‐index orthoplan in this paper. According to the coal mine field investigation, support structure’s failure often occurs, and some need to be repaired many times. Through the roadway surrounding rock drilling, it was found that the stress of the surrounding rock was relieved, resulting in the cavity and separation of the stratum layer. The two sidewalls’ development and roof fractures are mainly tangential, and the original rock state appears only beyond 6.3∼8.2 m. The length of bolts, the row distance between bolts, the length of cables, and the row distance of U‐shaped steel were selected as control factors in the multi‐index orthogonal design, and roadway’s deformation values were taken as the test indexes. According to the orthoplan, nine numerical simulation schemes were designed, and FLAC3D was used for establishment. The range analysis method was used to analyze the test results. The results show that the control factors’ influence order on the total deformation of the roadway is as follows: row spacing between U‐shaped steel > bolt length > cable length > row spacing between bolts, the influence order on the deformation of the roadway floor is as follows: row spacing between U‐shaped steel > row spacing between bolts > bolt length > cable length, same as the left sidewall and right sidewall, and the influence order on the roadway roof’s deformation is as follows: row spacing between U‐shaped steel > bolt length = cable length > row spacing between bolts, which provide a reference for the support design of deep‐buried roadways with fractured surrounding rock, especially the adjustment of the supporting structure.
Contribution of Growth Arrest-Specific 5/miR-674 to the Hypothalamus Pituitary Adrenal Axis Regulation Effect by Electroacupuncture following Trauma
Authors: Zhu Jing , Guo Chunxia , Lu Pingping , Shao Shuijin , Tu Bing
Published: June 2021

Background: Electroacupuncture (EA) can improve trauma-induced hypothalamus pituitary adrenal axis (HPA) hyperactivity. However, the mechanism underlying the EA effect has not been fully understood. Methods and Study Design: This study was undertaken to explore the role of hypothalamic growth arrest-specific 5 (Gas5) in the regulation of EA on HPA axis function post-surgery. Paraventricular nuclear Gas5 levels were upregulated in rats using an intracerebroventricular injection of pAAV-Gas5. Primary hypothalamic neurons and 293T cells were cultured for miRNA and siRNAs detection. Radioimmunoassay, PCR, Western blot, and immunohistochemistry were used for HPA axis function evaluation. Results: The overexpression of Gas5 abolished the effect of EA on the regulation of trauma-induced HPA axis hyperactivity. Using a bioinformatics analysis and dual luciferase assay, we determined that miRNA-674 was a target of Gas5. Additionally, miRNA-674 levels were found to have decreased in trauma rats, and this effect was reversed after EA intervention. TargetScan analysis showed that serum and glucocorticoid inducible kinase 1 (SGK1) were targets of miR-674. Moreover, we found that SGK1 protein levels increased in trauma rats and SGK1 expression inhibition alleviated HPA axis abnormality post-surgery. EA could improve the number of hypothalamus iba-1 positive cells and hypothalamic interleukin 1 beta protein expression. Conclusions: Our study demonstrated the involvement of the hypothalamic Gas5/miRNA-674/SGK1 signaling pathway in EA regulation of HPA axis function after trauma.
Therapeutic Effects of Add-On Tenapanor for Hemodialysis Patients with Refractory Hyperphosphatemia
Authors: Shigematsu Takashi , Une Yotaro , Ikejiri Kazuaki , Kanda Hironori , Fukagawa Masafumi , Akizawa Tadao
Published: June 2021

Introduction: Phosphate binders are used to treat hyperphosphatemia. Some patients have inappropriately controlled serum phosphorus levels, which may occur for many reasons, including a high pill burden and adverse events (AEs). Tenapanor selectively inhibits the passive paracellular transfer of phosphate in the gastrointestinal tract, thereby reducing serum phosphorus levels. This novel mechanism of action may contribute to improved phosphate management. The efficacy and safety of tenapanor have not been evaluated in Japanese patients with high serum phosphorus levels despite treatment with phosphate binders. This study aimed to assess the efficacy and safety of add-on tenapanor therapy for reducing serum phosphorus levels in this population. Methods: This multicenter, double-blind, randomized, placebo-controlled trial enrolled patients with refractory hyperphosphatemia undergoing hemodialysis. Patients were randomly assigned in a 1:1 ratio to receive tenapanor or placebo as an add-on to their phosphate binder regimen for 6 weeks. Change in serum phosphorus levels at week 6 (day 43) compared with the baseline value (day 1, week 0) (primary endpoint), achievement of target serum phosphorus levels (serum phosphorus level ≤6.0 or ≤5.5 mg/dL), and safety, based on all AEs and drug-related AEs, were among the outcomes evaluated. Results: In total, 24 patients were randomly assigned to the placebo group and 23 to the tenapanor group. The mean serum phosphorus level decreased from 7.01 mg/dL on day 1 to 6.69 mg/dL on day 43 in the placebo group and from 6.77 mg/dL on day 1 to 4.67 mg/dL on day 43 in the tenapanor group. In the placebo and tenapanor groups (modified intent-to-treat population), the mean (standard deviation) change in the serum phosphorus level at day 43 (last observation carried forward [LOCF]) was 0.08 (1.52) mg/dL and −1.99 (1.24) mg/dL, respectively, with a between-group difference of −2.07 (95% confidence interval: −2.89, −1.26; p < 0.001). The target achievement rate (serum phosphorus level ≤6.0 mg/dL at week 6 [LOCF]) was 37.5 and 87.0% in the placebo and tenapanor groups, respectively. Diarrhea was the most common drug-related AE, and it occurred in 8.3 and 65.2% of patients in the placebo and tenapanor groups, respectively. No specific AEs were observed with add-on tenapanor or with phosphate binders. Discussion/Conclusion: Therapy with existing phosphate binders and add-on tenapanor resulted in a significant decrease in serum phosphorus level compared with the placebo group in patients with refractory hyperphosphatemia despite treatment with phosphate binders. No new safety signals were raised, and add-on tenapanor was generally well tolerated.
Streptococcus salivarius Isolates of Varying Acid Tolerance Exhibit F1F0-ATPase Conservation
Authors: Allen Lauren L. , Heng Nicholas C.K. , Tompkins Geoffrey R.
Published: June 2021

Genes encoding the subunits of the membrane-bound F1F0-ATPase (responsible for exporting protons from the cytoplasm and contributing to acid tolerance) were sequenced for 24 non-mutans streptococci isolated from carious lesions. Isolates, mostly Streptococcus salivarius, displayed a continuum of acid tolerance thresholds ranging from pH 4.55 to 3.39, but amino acid alignments of F1F0-ATPase subunits revealed few non-synonymous substitutions and these were unrelated to acid tolerance. Thus, the F1F0-ATPase is highly-conserved among S. salivarius isolates despite varying acid tolerance thresholds, supporting the contention that acid tolerance is determined by the level of gene/protein expression rather than variation in molecular structure.
Endocytoscopy Is Useful for the Diagnosis of Superficial Nonampullary Duodenal Epithelial Tumors
Authors: Hirose Takashi , Kakushima Naomi , Furukawa Kazuhiro , Furune Satoshi , Ishikawa Eri , Sawada Tsunaki , Maeda Keiko , Yamamura Takeshi , Ishikawa Takuya , Ohno Eizaburo , Nakamura Masanao , Nishida Kazuki , Yokoi Takio , Kawashima Hiroki , Fujishiro Mitsuhiro
Published: June 2021

Introduction: Endoscopic criteria for the diagnosis of superficial nonampullary duodenal epithelial tumors (SNADETs) are lacking. The aim of this study was to explore the usefulness of endocytoscopy (ECS) in the duodenum. Methods: A total of 77 ECS images stained by methylene blue and 58 images with double staining of methylene blue and crystal violet were obtained from 20 patients. Images were classified into 3 grades based on nuclear and villi atypia: EC A, B, and C. Diagnostic performance of ECS classification to predict histology and interobserver agreement was evaluated. The performance was compared between staining methods and ×520 or ×936 zoom. Results: With methylene blue staining, high rates of accuracy, sensitivity, specificity, and positive predictive value (PPV) over 90% were achieved for tumor and nontumor diagnosis as assessed by EC A versus EC B. High rates of accuracy, sensitivity, PPV, and negative predictive value over 90% were achieved for the differentiation between the diagnosis of the Vienna category 3 and 4/5 as assessed by EC B versus C. The accuracy rate of interpreting ECS images with ×936 zoom among 10 endoscopists was 82%, and the interobserver agreement rate was 0.803 (Kendall’s coefficient of concordance). In the ×936 zoom group, methylene blue staining was significantly associated with higher accuracy rate (odds ratio 1.76 [1.06–2.92], p value 0.0297). No benefit was observed by double staining. Conclusions: ECS diagnosis with methylene blue provides a high accuracy rate and good interobserver agreement to predict histology of SNADETs.
Pediatric Airway Endoscopy: Recommendations of the Society for Pediatric Pneumology
Authors: Schramm Dirk , Freitag Nadine , Nicolai Thomas , Wiemers Anna , Hinrichs Bernd , Amrhein Peter , DiDio Diana , Eich Christoph , Landsleitner Bernd , Eber Ernst , Hammer Jürg ,   on behalf of the Special Interest Group on Pediatric Bronchoscopy of the Society for Pediatric Pneumology (GPP) and invited Societies involved in pediatric airway endoscopy
Published: June 2021

For many decades, pediatric bronchoscopy has been an integral part of the diagnosis and treatment of acute and chronic pulmonary diseases in children. Rapid technical advances have continuously influenced the performance of the procedure. Over the years, the application of pediatric bronchoscopy has considerably expanded to a broad range of indications. In this comprehensive and up-to-date guideline, the Special Interest Group of the Society for Pediatric Pneumology reviewed the most recent literature on pediatric bronchoscopy and reached a consensus on a safe technical performance of the procedure.
Aortic Valve Surgery After Neonatal Balloon Aortic Valvuloplasty in Congenital Aortic Stenosis
Authors: Kido Takashi , Guariento Alvise , Doulamis Ilias P. , Porras Diego , Baird Christopher W. , del Nido Pedro J. , Nathan Meena
Published: June 2021

Background:

We sought to identify predictive factors for aortic valve (AoV) surgery after neonatal balloon aortic valvuloplasty (BAV) and characterize clinical outcomes of AoV surgery after neonatal BAV.

Methods:

Time-to-event analysis identified predictors for AoV surgery after neonatal BAV. Clinical outcomes of AoV surgery following neonatal BAV were examined.

Results:

This study included 96 consecutive patients who underwent neonatal BAV for congenital aortic stenosis between 1998 and 2018, in 26 of whom a fetal BAV had been performed. Fifty-six patients underwent AoV surgery at a median age of 2.0 years. Significant risk factors for AoV surgery in univariate Cox regression (result presented as hazard ratio [HR], [95% CI];
P
value) were a history of fetal BAV (HR, 4.05 [95% CI, 2.19–7.40];
P
<0.001), AoV annulus diameter
Z
score (HR, 0.56 [95% CI, 0.43–0.75];
P
=0.001), the presence of endocardial fibroelastosis (HR, 2.61 [95% CI, 1.48–4.51];
P
=0.001), severe left ventricular dysfunction before neonatal BAV (HR, 1.75 [95% CI, 1.03–2.97];
P
=0.04), and recent era (HR, 3.08 [95% CI, 1.68–5.91];
P
=0.0002) in the entire cohort. Area under the receiver operating characteristic curve and Youden J index analysis identified a cutoff value for AoV annulus diameter
Z
score of −2.6 in patients without fetal BAV. In 24 patients with midterm cardiac catheterization data, univariate linear regression analysis (result presented as B coefficient [95% CI];
P
) showed that the presence of greater-than-moderate aortic regurgitation immediately after BAV (B coefficient, 4.8 [95% CI, 1.0–8.6];
P
=0.018) and before AoV surgery (B coefficient, 6.1 [95% CI, 2.2–10.0];
P
=0.004) were significant risk factors for elevated left ventricular end-diastolic pressure after AoV surgery, while concomitant endocardial fibroelastosis resection at AoV surgery had a protective effect (B coefficient, −3.8 [95% CI, −7.6 to −0.06];
P
=0.05).

Conclusions:

A small AoV annulus diameter
Z
score with a cutoff value of −2.6 and a history of fetal BAV were significantly associated with AoV surgery after neonatal BAV. Concomitant endocardial fibroelastosis resection is recommended at AoV surgery following neonatal BAV to improve left ventricular diastolic function.
Coronary Artery Disease Evaluation and Management Considerations for High Risk Occupations: Commercial Vehicle Drivers and Pilots
Authors: Sutton Nadia R. , Banerjee Shrilla , Cooper Matthew M. , Arbab-Zadeh Armin , Kim Judy , Arain Mansoor A. , Rao Sunil V. , Blumenthal Roger S.
Published: June 2021

Optimal treatment of stable ischemic heart disease for those in the transportation industry is considered in the context of the individual’s health, as well as with the perspective that sudden impairment could have catastrophic consequences for others. This article focuses on two high risk occupations that one may encounter in practice: commercial motor vehicle drivers and commercial pilots. This article discusses coronary heart disease in patients in high risk occupations and covers current guideline recommendations for screening, treatment, and secondary prevention. The importance of the complimentary perspectives of the regulatory agency, medical examiners, physicians, and pilot or driver are considered in this narrative review, as are considerations for future guideline updates.
Transcatheter Aortic Valve Replacement for Degenerated Transcatheter Aortic Valves: The TRANSIT International Project
Authors: Testa Luca , Agnifili Mauro , Van Mieghem Nicolas M. , Tchétché Didier , Asgar Anita W. , De Backer Ole , Latib Azeem , Reimers Bernhard , Stefanini Giulio , Trani Carlo , Colombo Antonio , Giannini Francesco , Bartorelli Antonio , Wojakowski Wojtek , Dabrowski Maciej , Jagielak Dariusz , Banning Adrian P. , Kharbanda Rajesh , Moreno Raul , Schofer Joachim , van Royen Niels , Pinto Duane , Serra Antoni , Segev Amit , Giordano Arturo , Brambilla Nedy , Popolo Rubbio Antonio , Casenghi Matteo , Oreglia Jacopo , De Marco Federico , Tanja Rudolph , McCabe James M. , Abizaid Alexander , Voskuil Michiel , Teles Rui , Biondi Zoccai Giuseppe , Bianchi Giovanni , Sondergaard Lars , Bedogni Francesco
Published: June 2021

Background:

Transcatheter aortic valve replacement (TAVR) has determined a paradigm shift in the treatment of patients with severe aortic stenosis. However, the durability of bioprostheses is still a matter of concern, and little is known about the management of degenerated TAV. We sought to evaluate the outcomes of patients with a degenerated TAV treated by means of a second TAVR.

Methods:

The TRANSIT is an international registry that included cases of degenerated TAVR from 28 centers. Among around 40 000 patients treated with TAVR in the participating centers, 172 underwent a second TAVR: 57 (33%) for a mainly stenotic degenerated TAV, 97 (56%) for a mainly regurgitant TAV, and 18 (11%) for a combined degeneration. Overall, the rate of New York Heart Association class III/IV at presentation was 73.5%.

Results:

Valve Academic Research Consortium 2 device success rate was 79%, as a consequence of residual gradient (14%) or regurgitation (7%). At 1 month, the overall mortality rate was 2.9%, while rates of new hospitalization and New York Heart Association class III/IV were 3.6% and 7%, respectively, without significant difference across the groups. At 1 year, the overall mortality rate was 10%, while rates of new hospitalization and New York Heart Association class III/IV were 7.6% and 5.8%, respectively, without significant difference across the groups. No cases of valve thrombosis were recorded.

Conclusions:

Selected patients with a degenerated TAV may be safely and successfully treated by means of a second TAVR. This finding is of crucial importance for the adoption of the TAVR technology in a lower risk and younger population.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04500964.
A Variant Noncoding Region Regulates
Prrx1
and Predisposes to Atrial Arrhythmias
Authors: Bosada Fernanda M. , Rivaud Mathilde R. , Uhm Jae-Sun , Verheule Sander , van Duijvenboden Karel , Verkerk Arie O. , Christoffels Vincent M. , Boukens Bastiaan J.
Published: June 2021

Rationale:

Atrial fibrillation (AF) is the most common cardiac arrhythmia diagnosed in clinical practice. Genome-wide association studies have identified AF-associated common variants across 100+ genomic loci, but the mechanism underlying the impact of these variant loci on AF susceptibility in vivo has remained largely undefined. One such variant region, highly associated with AF, is found at 1q24, close to
PRRX1
, encoding the paired-related homeobox 1 transcription factor.

Objective:

To identify the mechanistic link between the variant region at 1q24 and AF predisposition.

Methods and Results:

The mouse orthologue of the noncoding variant genomic region (
R1A
) at 1q24 was deleted using CRISPR genome editing. Among the genes sharing the topologically associated domain with the deleted
R1A
region (
Kifap3
,
Prrx1
,
Fmo2
, and
Prrc2c
), only the broadly expressed gene
Prrx1
was downregulated in mutants, and only in cardiomyocytes. Expression and epigenetic profiling revealed that a cardiomyocyte lineage-specific gene program (
Mhrt
,
Myh6
,
Rbm20
,
Tnnt2
,
Ttn
, and
Ckm
) was upregulated in
R1A
−/−
atrial cardiomyocytes and that Mef2 (myocyte enhancer factor)-binding motifs were significantly enriched at differentially accessible chromatin sites. Consistently,
Prrx1
suppressed Mef2-activated enhancer activity in HL-1 cells. Mice heterozygous or homozygous for the
R1A
deletion were susceptible to atrial arrhythmia induction, had atrial conduction slowing and more irregular RR intervals. Isolated
R1A
−/−
mouse left atrial cardiomyocytes showed lower action potential upstroke velocities and sodium current, as well as increased systolic and diastolic calcium concentrations compared with controls.

Conclusions:

The noncoding AF variant region at 1q24 modulates
Prrx1
expression in cardiomyocytes. Cardiomyocyte-specific reduction of
Prrx1
expression upon deletion of the noncoding region leads to a profound induction of a cardiac lineage-specific gene program and to propensity for AF. These data indicate that AF-associated variants in humans may exert AF predisposition through reduced
PRRX1
expression in cardiomyocytes.
Detection of Atrial Fibrillation After Central Retinal Artery Occlusion
Authors: Mac Grory Brian , Landman Sean R. , Ziegler Paul D. , Boisvert Chantal J. , Flood Shane P. , Stretz Christoph , Madsen Tracy E. , Reznik Michael E. , Cutting Shawna , Moore Elizabeth E. , Hewitt Hunter , Closser James B. , Torres Jose , Lavin Patrick J. , Furie Karen L. , Xian Ying , Feng Wayne , Biousse Valérie , Schrag Matthew , Yaghi Shadi
Published: June 2021

Background:

Central retinal artery occlusion (CRAO) causes sudden, irreversible blindness and is a form of acute ischemic stroke. In this study, we sought to determine the proportion of patients in whom atrial fibrillation (AF) is detected by extended cardiac monitoring after CRAO.

Methods:

We performed a retrospective, observational cohort study using data from the Optum deidentified electronic health record of 30.8 million people cross-referenced with the Medtronic CareLink database of 2.7 million people with cardiac monitoring devices in situ. We enrolled patients in 3 groups: (1) CRAO, (2) cerebral ischemic stroke, and (3) age-, sex-, and comorbidity-matched controls. The primary end point was the detection of new AF (defined as ≥2 minutes of AF detected on a cardiac monitoring device).

Results:

We reviewed 884 431 patient records in common between the two databases to identify 100 patients with CRAO, 6559 with ischemic stroke, and 1000 matched controls. After CRAO, the cumulative incidence of new AF at 2 years was 49.6% (95% CI, 37.4%–61.7%). Patients with CRAO had a higher rate of AF than controls (hazard ratio, 1.64 [95% CI, 1.17–2.31]) and a comparable rate to patients with stroke (hazard ratio, 1.01 [95% CI, 0.75–1.36]). CRAO was associated with a higher incidence of new stroke compared with matched controls (hazard ratio, 2.85 [95% CI, 1.29–6.29]).

Conclusions:

The rate of AF detection after CRAO is higher than that seen in age-, sex-, and comorbidity-matched controls and comparable to that seen after ischemic cerebral stroke. Paroxysmal AF should be considered as part of the differential etiology of CRAO, and those patients may benefit from long-term cardiac monitoring.
Filled-Duration Illusions
Authors: Wearden John H. , Ogden Ruth S.
Published: June 2021

Data relevant to the ‘filled-duration illusion’, the claim that filled intervals appear to last longer than unfilled ones of the same real duration, are reviewed. A distinction is made between divided-time studies (where an empty interval has one or more than one brief dividing stimulus inside it) and filled-duration studies (where the filled intervals are filled with some continuous event). Divided durations appear to last longer than empty ones, and the effect grows with the number of dividers, although it may be restricted to short durations. The best current explanation appears to involve the weighted summation of the different subintervals of which the total duration is composed. When intervals with simple fillers are contrasted with empty ones, they are usually judged as longer, and the effect may grow as the intervals lengthen, at least over short duration ranges. When complex fillers are used, fillers usually have no effect on perceived duration or shorten it. A pacemaker-counter approach can account for some simple filler effects, and division of attention for complex filler effects. Although there are some exceptions, ‘filled-interval illusions’ of all these types are normally found, but some problems, such as questions about the relative perceived variability of filled and unfilled intervals, or stimulus order effects, merit further research.
New concepts and methods for phylogenetic taxonomy and nomenclature in zoology, exemplified by a new ranked cladonomy of recent amphibians (Lissamphibia): corrigenda and addenda
Authors: DUBOIS ALAIN , OHLER ANNEMARIE , PYRON R. ALEXANDER
Published: June 2021

Just after the publication of our paper (Dubois et al. 2021), we discovered that, in Table 1, pages 443 and 444 are identical, and the actual page 443 is missing. We here provide this page, and we took this opportunity to correct a few other errors in this paper. We provide below corrections only in the case of misspellings or other errors that may induce misunderstandings of our text, not for pure format problems (concerning punctuation, parentheses, italics, bold and capital letters), which do not impede understanding of our text.
Correcting precipitation measurements made with Geonor T-200B weighing gauges near the August-one ice cap in the Qilian Mountains, Northwest China
Authors: Zhao Yanni , Chen Rensheng , Han Chuntan , Wang Lei , Guo Shuhai , Liu Junfeng
Published: June 2021

A precipitation observation network was constructed in a high-altitude area of the Qilian Mountains in Northwest China, which contained 23 sets of instruments. Because 21 sets of instruments were surrounded by protective fences, a precipitation intercomparison experiment was carried out at the highest station (4651 m) of the observation network with the same configuration to study the impact of wind on precipitation measurements under this configuration and to develop a correction method suitable for the entire network. The 30-min measured precipitation from June 2018 to October 2019 was corrected by transfer functions provided by Kochendorfer et al. (2017b), and their parameters were recalibrated with a local dataset. The results showed that the transfer functions fitted to the local dataset had a better performance than those using original parameters. Because of the influence of the experimental configuration on wind speed and direction, the root mean square error (RMSE) corrected with the original parameters increased by an average of 86%, but the RMSE adjusted by the new transfer functions decreased by 9%. Moreover, the resultant biases using new transfer functions were close to 0. The new coefficients of snowfall were derived by local measurements and applied to datasets from other sites within the Qilian Mountains observation network to evaluate their performances. The corrected snowfall at 21 stations increased by an average of 32.6 mm, and the relative precipitation increment ranged from 6% to 26%. This method can be used to correct snowfall in the observation network under the non-standard site configuration.
Innovative Methods in the Study of Protest: Editor’s Introduction
Authors: Jenkins J. Craig
Published: June 2021

This special issue examines innovative methods in three areas of protest studies: (1) survey methodology and scaling, (2) the development and assessment of political event data, and (3) methods of contextual analysis. The articles provide new techniques and general methodologies for improving the quality of data that we have about protest, especially in the comparative study of protest.
Assessing bone formation in patients with chronic kidney disease using procollagen type I N-terminal propeptide (PINP): The choice of assay makes a difference
Authors: Tridimas Andreas , Milan Anna , Marks Eileen
Published: June 2021

Background

Measurement of procollagen type I N-terminal propeptide (PINP) concentration in serum reflects the rate of type I collagen synthesis and can therefore be used as a bone formation marker. There are two methods of PINP quantification; the first measures the trimeric propeptide (intact PINP) and the second measures both the trimeric and monomeric propeptides (total PINP). Trimeric PINP is excreted via hepatic endothelial cells, whereas monomeric PINP is cleared renally. Therefore, in renal failure, the total assay has a positive bias with respect to the intact assay, due to monomeric PINP accumulation. The aim of this study was to compare the performance of both assays across all stages of chronic kidney disease.

Methods

Serum was taken from male ( n = 111) and female ( n = 105) patients attending a metabolic bone clinic, and these were partitioned into stages of chronic kidney disease 1–5. Each serum sample was analysed using the Roche electrochemiluminescence immunoassay for total PINP and the Immunodiagnostic Systems chemiluminescence immunoassay for intact PINP.

Results

Passing-Bablok regression analysis comparing both methods showed that with advancing chronic kidney disease there was a proportional positive bias affecting the total assay when compared with the intact assay. This proportional positive bias was statistically significant for chronic kidney disease stages 3b, 4 and 5.

Conclusions

Based on this method comparison study, usage of the total PINP assay should be avoided in chronic kidney disease stages 3b, 4 and 5 (eGFR ≤44 mL/min/1.73 m2) and instead an intact assay used as the total assay overestimates PINP concentrations due to monomeric PINP accumulation.
‘Laity as Teachers in the Ecclesia Docens’
Authors: O’Collins Gerald
Published: June 2021

Vatican II partly dismantled the separation between the hierarchy as teachers ( ecclesia docens) and the laity as believers ( ecclesia discens). The Council recognized the prophetic function of baptized lay persons, noting in particular the function of parents and catechists and reiterating the guidance of the Holy Spirit received by the whole church ( sensus fidei). Special personal charisms invite recognizing the place in the ecclesia docens of many writers, artists, composers, and film directors. Their imaginative gifts have encouraged and renewed the life of faith for innumerable believers.