bluuebunny/crossref_metadata_2025 huggingface dataset:
A Search for Novel Legionella pneumophila Effector Proteins Reveals a Strain Specific Nucleotropic Effector
Authors: Monteiro Inês P. , Sousa Sofia , Borges Vítor , Gonçalves Paulo , Gomes João Paulo , Mota Luís Jaime , Franco Irina S.
Published: June 2022

Legionella pneumophila is an accidental human pathogen that causes the potentially fatal Legionnaires’ disease, a severe type of pneumonia. The main virulence mechanism of L. pneumophila is a Type 4B Secretion System (T4SS) named Icm/Dot that transports effector proteins into the host cell cytosol. The concerted action of effectors on several host cell processes leads to the formation of an intracellular Legionella-containing vacuole that is replication competent and avoids phagolysosomal degradation. To date over 300 Icm/Dot substrates have been identified. In this study, we searched the genome of a L. pneumophila strain (Pt/VFX2014) responsible for the second largest L. pneumophila outbreak worldwide (in Vila Franca de Xira, Portugal, in 2014) for genes encoding potential novel Icm/Dot substrates. This strain Pt/VFX2014 belongs to serogroup 1 but phylogenetically segregates from all other serogroup 1 strains previously sequenced, displaying a unique mosaic genetic backbone. The ability of the selected putative effectors to be delivered into host cells by the T4SS was confirmed using the TEM-1 β-lactamase reporter assay. Two previously unknown Icm/Dot effectors were identified, VFX05045 and VFX10045, whose homologs Lpp1450 and Lpp3070 in clinical strain L. pneumophila Paris were also confirmed as T4SS substrates. After delivery into the host cell cytosol, homologs VFX05045/Lpp1450 remained diffused in the cell, similarly to Lpp3070. In contrast, VFX10045 localized to the host cell nucleus. To understand how VFX10045 and Lpp3070 (94% of identity at amino acid level) are directed to distinct sites, we carried out a comprehensive site-directed mutagenesis followed by analyses of the subcellular localization of the mutant proteins. This led to the delineation of region in the C-terminal part (residues 380 to 534) of the 583 amino acid-long VFX10045 as necessary and sufficient for nuclear targeting and highlighted the fundamental function of the VFX10045-specific R440 and I441 residues in this process. These studies revealed a strain-specific nucleotropism for new effector VFX10045/Lpp3070, which anticipates distinct functions between these homologs.
Peste des Petits Ruminants Virus Exhibits Cell-Dependent Interferon Active Response
Authors: Tang Jingyu , Tang Aoxing , Du Hanyu , Jia Nannan , Zhu Jie , Li Chuanfeng , Meng Chunchun , Liu Guangqing
Published: June 2022

Peste des petits ruminants (PPR) is an acute and highly pathogenic infectious disease caused by peste des petits ruminants virus (PPRV), which can infect goats and sheep and poses a major threat to the small ruminants industry. The innate immune response plays an important role as a line of defense against the virus. The effect of PPRV on the active innate immune response has been described in several studies, with different conclusions. We infected three goat-derived cell lines with PPRV and tested their innate immune response. PPRV proliferated in caprine endometrial epithelial cells (EECs), caprine skin fibroblasts cells (GSFs), and goat fibroblast cells (GFs), and all cells expressed interferon (IFN) by poly (I: C) stimulation. PPRV infection stimulated expression of type I and type III IFN on EECs, and expression of the latter was significantly stronger, but IFN was not stimulated in fibroblasts (GSFs and GFs). Our results suggested that the effect of PPRV on IFN was cell-type specific. Nine IFN-stimulated genes (ISGs) were detected in EECs, but only ISG15 and RSAD2 were significantly upregulated. The effects of PPRV on IFN and IFN-induced ISGs were cell-type specific, which advances our understanding of the innate immune response induced by PPRV and creates new possibilities for the control of PPRV infection.
Chlamydia trachomatis Requires Functional Host-Cell Mitochondria and NADPH Oxidase 4/p38MAPK Signaling for Growth in Normoxia
Authors: Thapa Jeewan , Yoshiiri Gen , Ito Koki , Okubo Torahiko , Nakamura Shinji , Furuta Yoshikazu , Higashi Hideaki , Yamaguchi Hiroyuki
Published: June 2022

Chlamydia trachomatis (Ct) is an intracellular energy-parasitic bacterium that requires ATP derived from infected cells for its growth. Meanwhile, depending on the O2 concentration, the host cells change their mode of ATP production between oxidative phosphorylation in mitochondria (Mt) and glycolysis; this change depends on signaling via reactive oxygen species (ROS) produced by NADPH oxidases (NOXs) as well as Mt. It has been proposed that Ct correspondingly switches its source of acquisition of ATP between host-cell Mt and glycolysis, but this has not been verified experimentally. In the present study, we assessed the roles of host-cell NOXs and Mt in the intracellular growth of CtL2 (L2 434/Bu) under normoxia (21% O2) and hypoxia (2% O2) by using several inhibitors of NOXs (or the downstream molecule) and Mt-dysfunctional (Mtd) HEp-2 cells. Under normoxia, diphenyleneiodonium, an inhibitor of ROS diffusion, abolished the growth of CtL2 and other Chlamydiae (CtD and C. pneumoniae). Both ML171 (a pan-NOX inhibitor) and GLX351322 (a NOX4-specific inhibitor) impaired the growth of CtL2 under normoxia, but not hypoxia. NOX4-knockdown cells diminished the bacterial growth. SB203580, an inhibitor of the NOX4-downstream molecule p38MAPK, also inhibited the growth of CtL2 under normoxia but not hypoxia. Furthermore, CtL2 failed to grow in Mtd cells under normoxia, but no effect was observed under hypoxia. We conclude that under normoxia, Ct requires functional Mt in its host cells as an ATP source, and that this process requires NOX4/p38MAPK signaling in the host cells. In contrast to hypoxia, crosstalk between NOX4 and Mt via p38MAPK may be crucial for the growth of Ct under normoxia.
Clue Cells and Pseudo Clue Cells in Different Morphotypes of Bacterial Vaginosis
Authors: Swidsinski Alexander , Loening-Baucke Vera , Swidsinski Sonja , Sobel Jack D. , Dörffel Yvonne , Guschin Alexander
Published: June 2022

Introduction

Clue cells (epithelial cells heavily covered with adherent bacteria) are an accepted clue to the diagnosis of bacterial vaginosis. However, the exact morphologic criteria of clue cells and bacterial adherence were never elaborated.

Materials and Methods

We investigated adhesive and cohesive patterns of main microbiota groups in vaginal discharge using fluorescence in situ hybridization (FISH). Samples from 500 women diagnosed with bacterial vaginosis and positive for clue cells with classic microscopy were collected from 42 gynecologic practices in Berlin and reexamined in our FISH laboratory for the spatial distribution of Bifidobacteriaceae, Gardnerella, Fannyhessea vaginae (Atopobium); low G+C (guanine+cytosine) bacteria, lactobacilli, Lactobacillus iners; Lactobacillus crispatus, Gamma-Proteobacteria; and Enterobacteriaceae, Prevotella–Bacteroides, Veillonella, and Coriobacterium groups.

Results

Bacterial taxa present in vaginal smears were not accidentally assembled according to their relative abundance but were built in group-specific distribution patterns, which can be well described by two features: cohesiveness to each other and adherence to epithelial cells. Accordingly, four patterns can be distinguished: dispersed (non-adherent bacteria), dispersed adherent bacteria, cohesive (non-adherent) bacteria, and cohesive adherent bacteria. Direct cohesive adherence to the epithelial cells representing true clue cells was unique for Gardnerella species and observed only in 56% of the investigated samples. In the remaining vaginal samples, the epithelial cells were mechanically entrapped in bacterial masses, and the composition was unrelated to the epithelial cell surface, building non-adherent pseudo clue cells. The proportion of women with true clue cells in their samples from different gynecologic practices varied from 19% to 80%.

Discussion

Taxon indifferent imaging is inadequate for the exact analysis of the microbial layer adjacent to the vaginal epithelial cells. Morphologically seen bacterial vaginosis is a mix of at least two different conditions: biofilm vaginosis and bacterial excess vaginosis.
Unveiling the Role of DNA Methylation in Vascular CACNA1C Tissue–Specific Expression
Authors: Zhao Meng , Xu Ting , Lei Jiahui , Ji Bingyu , Gao Qinqin
Published: June 2022

Objective

Calcium voltage-gated channel subunit alpha1 C (CACNA1C) plays a critical role in many vascular physiological and pathological processes. Determining its tissue-specific expression pattern and clarifying the underlying molecular mechanisms are necessary and meaningful.

Methods

We selected several representative vessels from normal male Sprague-Dawley rats. Vessel tissue or primary vascular smooth muscle cells were isolated for vascular function, electrophysiology, gene expression and promoter methylation studies.

Results

We found CACNA1C had tissue-specific expressions in vessels. The specific manifestations were as follows: CACNA1C expression was highest in thoracic aorta, second lowest in middle cerebral and pulmonary artery, and lowest in mesenteric artery. Excitingly, an opposing trend was observed between CACNA1C expression and its promoter methylation.

Conclusions

This study was the first report to indicate that DNA methylation could be involved in regulating CACNA1C tissue-specific expressions and vasoconstriction function in vascular system. This study not only provided more information for further understanding the physiological characteristics of vascular CACNA1C expressions, also strengthened the idea that DNA methylation plays important roles in regulating vascular smooth muscle cells function and the consequent occurrence of vascular diseases.
Brief Research Report: Quantitative Analysis of Potential Coronary Microvascular Disease in Suspected Long-COVID Syndrome
Authors: Doeblin Patrick , Steinbeis Fridolin , Scannell Cian M. , Goetze Collin , Al-Tabatabaee Sarah , Erley Jennifer , Faragli Alessandro , Pröpper Felix , Witzenrath Martin , Zoller Thomas , Stehning Christian , Gerhardt Holger , Sánchez-González Javier , Alskaf Ebraham , Kühne Titus , Pieske Burkert , Tschöpe Carsten , Chiribiri Amedeo , Kelle Sebastian
Published: June 2022

Background

Case series have reported persistent cardiopulmonary symptoms, often termed long-COVID or post-COVID syndrome, in more than half of patients recovering from Coronavirus Disease 19 (COVID-19). Recently, alterations in microvascular perfusion have been proposed as a possible pathomechanism in long-COVID syndrome. We examined whether microvascular perfusion, measured by quantitative stress perfusion cardiac magnetic resonance (CMR), is impaired in patients with persistent cardiac symptoms post-COVID-19.

Methods

Our population consisted of 33 patients post-COVID-19 examined in Berlin and London, 11 (33%) of which complained of persistent chest pain and 13 (39%) of dyspnea. The scan protocol included standard cardiac imaging and dual-sequence quantitative stress perfusion. Standard parameters were compared to 17 healthy controls from our institution. Quantitative perfusion was compared to published values of healthy controls.

Results

The stress myocardial blood flow (MBF) was significantly lower [31.8 ± 5.1 vs. 37.8 ± 6.0 (μl/g/beat), P < 0.001] and the T2 relaxation time was significantly higher (46.2 ± 3.6 vs. 42.7 ± 2.8 ms, P = 0.002) post-COVID-19 compared to healthy controls. Stress MBF and T1 and T2 relaxation times were not correlated to the COVID-19 severity (Spearman r = −0.302, −0.070, and −0.297, respectively) or the presence of symptoms. The stress MBF showed a U-shaped relation to time from PCR to CMR, no correlation to T1 relaxation time, and a negative correlation to T2 relaxation time (Pearson r = −0.446, P = 0.029).

Conclusion

While we found a significantly reduced microvascular perfusion post-COVID-19 compared to healthy controls, this reduction was not related to symptoms or COVID-19 severity.
Association Between Lipids and Arterial Stiffness for Primary Cardiovascular Prevention in a General Middle-Aged European Population
Authors: Vallée Alexandre
Published: June 2022

Background

Dyslipidemia contributes to the progression of arterial stiffness (AS). The purpose of this study was to investigate the association of the different lipid parameters with arterial stiffness index (ASI) in a middle-aged population free of cardiovascular (CV) disease.

Methods

Among 71,326 volunteers from the UK Biobank population, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), lipoprotein (a) [Lp(a)], apolipoproteins A and B (Apo A and Apo B), and ASI were measured. Values for non-HDL, TC/HDL, TG/HDL, and LDL/HDL were calculated. AS was defined as an ASI > 10 m/s. Associations between lipid parameters and ASI were performed using multiple linear logistic regressions. The results reported from univariate models were the squared partial correlation coefficient, r2, and from multivariate models, the adjusted coefficient of determination, R2, to describe the contribution of ASI variability for each lipid parameter.

Results

We found that TG/HDL was mainly associated with ASI [β = 0.53 (0.01), r2 = 3.66%, p < 0.001 and adjusted β = 0.21 (0.01), R2 = 13.58%, p < 0.001] and AS [odds ratio (OR) = 1.86 (1.80–1.92), r2 = 1.65%, p < 0.001 and adjusted OR = 1.15 (1.13–1.17), R2 = 8.54%, p < 0.001] rather than the others. TG/HDL remained the only lipid parameter that showed added value in linear multivariate models. TG/HDL remained less associated with AS than age (r2 = 5.55%, p < 0.001), mean blood pressure (BP; r2 = 5.31%, p < 0.001), and gender (r2 = 4.44%, p < 0.001), but more highly associated than body mass index (BMI; r2 = 1.95%, p < 0.001), heart rate (HR; r2 = 0.81%, p < 0.001), fasting glucose (r2 = 0.18%, p < 0.001), tobacco (r2 = 0.05%, p < 0.001), and glomerular filtration rate (GFR; r2 = 0.01%, p < 0.001).

Conclusions

In primary CV prevention, lipids, especially through the TG/HDL ratio, could be more instructive in preventing the increase in AS than other modifiable factors.
Burden of Aortic Aneurysm and Its Attributable Risk Factors from 1990 to 2019: An Analysis of the Global Burden of Disease Study 2019
Authors: Wang Zhuo , You Yayu , Yin Zhehui , Bao Qinyi , Lei Shuxin , Yu Jiaye , Xie Cuiping , Ye Feiming , Xie Xiaojie
Published: June 2022

Background

Global and national estimates on the epidemiology of aortic aneurysms are prerequisites for disease management and policymaking. Based on the Global Burden of Disease (GBD) 2019, this study aimed to discern the global aortic aneurysm burden by systematically analyzing demographic data on mortality and exploring the attributable risks and relevant factors.

Methods

The data analyzed in this study were available in the Global Health Data Exchange (GHDx) online query tool. The population in our study comprised individuals from 204 countries and territories from 1990 to 2019. The estimated annual percentage changes (EAPCs) were performed to assess the temporal trends of aortic aneurysms and their attributable risks. Spearman correlation analysis was performed to explore the relationship between the burden of aortic aneurysm and covariates.

Results

Although aortic aneurysm-related deaths (82.1%) and disability-adjusted life years (DALYs) (67%) increased from 1990 to 2019, the global trend of age-standardized rate of death (ASRD) (EAPC: −1.34, 95% CI = −1.46 to −1.22, P < 0.001) and age-standardized rate of DALY (ASDALYR) (EAPC: −1.06, 95% CI = −1.17 to −0.95, P < 0.001) decreased, both of which presented age dependence and gender differences. Smoking and high systolic blood pressure (SBP) were the main attributable risks of disease burden and tend to decease globally (EAPC: −1.89, 95% CI = −2.03 to −1.89, P < 0.001; −1.31 95% CI = −1.43 to −1.19, P < 0.001, respectively). Alcohol abstinence (male: R = −0.71, P < 0.001; female: R = −0.73, P < 0.001), smoking age of initiation (male: R = −0.32, P < 0.001; female: R = −0.50, P < 0.001), physical activity (male: R = −0.50, P < 0.001; female: R = −0.55, P < 0.001), and mean temperature (R = −0.62, P < 0.001) had negative correlation with ASRD. However, cholesterol level (male: R = 0.62, P < 0.001; female: R = 0.39, P < 0.001), body mass index (BMI) (male: R = 0.30, P < 0.001; female R = −0.01, P > 0.05), and alcohol consumption (male: R = 0.46, P < 0.001; female: R = 0.42, P < 0.001) had a positive correlation with ASRM. Besides, standard of living and medical resources positively related to burden of aortic aneurysm.

Conclusion

In this study, a decreasing trend of aortic aneurysm burden was found globally, especially in advanced regions. Aged men who smoke and women who have hypertension should pay close attention to, particularly in deprived economic groups, and many approaches can be performed to reduce the burden of aortic aneurysms.
C677T Gene Polymorphism of MTHFR Is a Risk Factor for Impaired Renal Function in Pregnant Women With Preeclampsia in the Chinese Han Population
Authors: Yun Lin , Ge Meiqi , Xu Rui , Zheng Fei , Zhao Xueqiang , Li Xinran
Published: June 2022

Impaired renal function in pregnant women with preeclampsia is particularly common, yet there is no consensus about implementation. This lack of consensus is due in part to uncertainty about risks for disease progression. Limited evidence suggests that C677T gene polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR C677T) may affect impaired renal function in pregnant women with preeclampsia in Chinese Han population. To investigate the association between MTHFR C677T and impaired renal function in pregnant women with preeclampsia, a total of 327 pregnant women diagnosed with gestational hypertension (GH) or preeclampsia-eclampsia (PE) from January 2016 to December 2021 were selected as the study subjects. The personal information, gestational information, clinical indicators, and the C677T gene polymorphism of MTHFR were tested. Compared with the GH group, the PE renal function impairment group had increased in blood pressure, homocysteine level, liver and kidney function indicators (creatinine, uric acid, urea nitrogen, cystatin C, alanine aminotransferase, aspartate aminotransferase, cholyglycine), and blood lipids (total cholesterol, triglycerides and low density lipoprotein) but had reductions in plasma protein (total protein, albumin, globulin, prealbumin), trace elements (calcium and zinc), prothrombin time and fibrinogen. The homocysteine level in the TT genotype was higher than that in the CC and CT genotypes. Binary logistic regression analysis showed that the MTHFR C677T gene polymorphism was associated with PE renal function impairment in the recessive model (OR: 1.620, 95% CI: 1.033–2.541, P < 0.05). These findings show that the C677T gene polymorphism of MTHFR is an independent risk factor for impaired renal function in pregnant Chinese Han women with PE.
Repostioning of Telemedicine in Cardiovascular World Post-COVID-19 Pandemic
Authors: Sharma Kamal , Patel Zeel , Patel Smeet , Patel Kalpen , Dabhi Shweta , Doshi Jinish , Amdani MohmadSabir , Shah Darshini , Patel Dhyanee , Konat Ashwati
Published: June 2022

Background

During the COVID-19 pandemic, telemedicine is a quickest expanding service solution to provide improved access to sophisticated healthcare that is efficient, cost-effective, and time-consuming.

Methods

This analysis is evaluated on the basis of several studies that look at the history, benefits, various techniques, challenges, uses, and impact of telemedicine in the treatment of heart failure and cardiac rehabilitation as during COVID-19 outbreak.

Results

Patients avoided or refused medical treatment during COVID-19 pandemic despite the risk of illness and the threat of infections spreading. Telemedicine has become a non-traditional form of care delivery due to better access and high-end technologies such as virtual consultations, face-to-face video, smartphone visits, two-way text communication, distant patient history, and distal characteristic assessment. Remote monitoring can help manage cardiovascular disease risk factors and increase patient participation in blood pressure, heart failure data, and workout or other activity progress.

Conclusion

Based on the findings of past studies, we can infer that telemedicine is still an emerging subject in the treatment and management of cardiovascular disease. Telemedicine and similar technologies will also revolutionize healthcare services by expanding their reach and providing a big pool of database for better research and analysis.
Impact of a NDUFC2 Variant on the Occurrence of Acute Coronary Syndromes
Authors: Gallo Giovanna , Migliarino Serena , Cotugno Maria , Stanzione Rosita , Burocchi Simone , Bianchi Franca , Marchitti Simona , Autore Camillo , Volpe Massimo , Rubattu Speranza
Published: June 2022

Background

Among several potential mechanisms, mitochondrial dysfunction has been proposed to be involved in the pathogenesis of coronary artery disease (CAD). A mitochondrial complex I deficiency severely impairs cardiovascular health and contributes to CAD development. Previous evidence highlighted a key role of NDUFC2, a subunit of complex I, deficiency in the increased occurrence of renal and cerebrovascular damage in an animal model of hypertension, and of juvenile ischemic stroke occurrence in humans. Furthermore, a significant decrease of NDUFC2 mRNA was detected in peripheral blood mononuclear cells from patients experiencing acute coronary syndrome (ACS). The T allele at NDUFC2/rs23117379 variant is known to associate with reduced gene expression and mitochondrial dysfunction.

Objective

In the present study we tested the impact of the T/C NDUFC2/rs23117379 variant on occurrence of ACS in a prospective cohort of CAD patients (n = 260).

Results

Hypertension, smoking habit, diabetes and hypercholesterolemia were present in a large proportion of patients. Non-ST-elevation myocardial infarction (NSTEMI) represented the most frequent type of ACS (44%, n = 115), followed by ST-elevation myocardial infarction (STEMI) (34%, n = 88) and unstable angina (22%, n = 57). The alleles/genotypes distribution for T/C at NDUFC2/rs23117379 revealed that the TT genotype was associated with a trend toward the development of ACS at an earlier age (TT 61 ± 12, CT 65 ± 12 and CC 66 ± 11 years; p = 0.051 after adjustment for gender, hypertension, smoking habit, diabetes and hypercholesterolemia) and with a significant predictive role for ACS recurrence (hazard ratio [HR]1.671; 95% confidence interval [CI], 1.138–2.472; p = 0.009).

Conclusions

Our findings are consistent with a deleterious effect of NDUFC2 deficiency on acute coronary events predisposition and further support a role of the NDUFC2/rs23117379 variant as a genetic cardiovascular risk factor.
Mineralogical Composition and Origin of Airborne Dust in an Alpine Environment of Hochtor (Hohe Tauern, Austria): Effects on Pedogenesis, Biological Soil Crusts, and Vascular Plant Growth
Authors: Peer Thomas , Zheng Ling-Juan , Neubauer Franz , Friedl Gertrude , Hauzenberger Christoph , Kasper-Giebl Anne
Published: June 2022

There is considerable evidence that mineral dust has an important impact on alpine ecosystems, but the relationship remains unclear in some instances. In an attempt to fill this knowledge gap, we investigated 1) the mineralogical composition of dust components at Hochtor (Hohe Tauern, Austria), 2) its effects on soil formation and biological soil crusts (BSCs), and 3) the effect of mineral dust on plant growth in this interdisciplinary study. Mineral particles such as silicates, carbonates, oxides, volcanic quartz phenocrysts, opaque ore minerals, and spheres, such as microtektites, micrometeorites and fly ash aggregates, were detected using a scanning electron microscope (SEM) equipped with an energy dispersive X-ray spectrometer (SEM-EDX). Rare micrometeorites are of extra-terrestrial origin (cosmic dust) and the decorated spheres are aggregates of fly ashes from anthropogenic origin. In terms of size, fine particles (<100 µm) and coarse particles (>100 µm) characterize the dust composition, originating mainly from adjacent rock outcrops, while the transport from the North African desert appears to be less important and diluted by local sources. The research was carried out as part of the pan-European biodiversity project “Soil Crust International” (SCIN). The results suggest that mineral dust aids in the rapid formation of BSCs in highly disturbed treated plots, and thus, both fine sand and available phosphorus are statistically proven to be determinants of the rapid growth of biocrusts. The number of plant individuals also increases between 2016 and 2020, however at a relatively moderate rate due to permanent mechanical erosion and debris flow within the treatment plots. Silica dust is believed to be a contributing factor to the widespread distribution of silicate plants in limestone habitats, such asPrimula minimaandCerastium uniflorum, two “acidophilic” species that have been tested more closely. Finally, it is deduced that 1) aeolian dust plays a role in the continuous process of soil and crust formation, and 2) it works as a growth regulator in complex biological communities such as BSCs and vascular plant communities by creating new habitats and increasing biodiversity.
Study on the Size and Occurrence Effects of Equivalent Elasticity Modulus of Orthogonal Random Jointed Rock Masses
Authors: Naizhong Xu , Changqing Liu , Chang Su , Tian Zhou
Published: June 2022

Under the engineering background of a + 144-m mining platform on an open pit slope of Xinqiao Mining Corporation, the eigenvalue distribution function of joints was acquired based on the massive statistics of field joints. Next, an orthogonal random joint model was constructed using the Monte Carlo method based on the UDEC software platform. Subsequently, the representative elementary volume (REV) size and occurrence effects of the equivalent elasticity modulus of the orthogonal random jointed rock mass were explored through numerical experiments with lots of discrete elements. The results showed that the equivalent elasticity modulus of the orthogonal random jointed rock mass was of evident size effect, and the relationship between the mean equivalent elasticity modulus Eeq and the REV size of the rock mass followed the negative power function distribution. Before the model size reached the REV size, its Eeq was greatly discrete. Under different joint angles, both the standard deviation σf and coefficient of variation δ of the equivalent elasticity modulus of this model presented discrete distribution. As the model size reached the REV size, the mean equivalent elasticity modulus Eeq showed “two-high and one-low” morphological distribution. Eeq was small when the main joint angle was α∈[30°, 40°], but it was large when α = 0° or 90°. δ was taken as 10%, so the REV size of the corresponding Eeq was 10 m × 20 m. When the model size reaches the REV size, the occurrence effect of its equivalent elasticity modulus was no longer significant.
Risk Evolution Study of Tailings Dam Failures Disaster Based on DEMATEL-MISM
Authors: Zheng Binbin , Wang Jiahe , Feng Tingting , Wang Wensong , Zhou Yuxi , Cao Guansen , Wang Yufei
Published: June 2022

Tailings pond engineering is a complex and extensive system with many risk factors that can trigger a dam failure. It is important to clarify the evolutionary relationships among the factors and to enhance effective management to reduce the risk of dam failure. In this paper, an effective and reliable method for analyzing the evolution of tailings pond dam failure risk by combining DEMATEL and MISM is proposed. Firstly, 35 risk factors affecting tailings pond failure were summarized. An index system for evaluating the imfluence factors of dam failure was constructed from four aspects: personnel, management, environment, and system. Secondly, the Decision-making Trial and Evaluation Laboratory (DEMATEL) was used to study the influence relationships among the factors, for analyzing and identifying the key causal factors. Subsequently, the Modified Interpretative Structural Model Method (MISM) was used to classify the cause factors into five levels of influence as well as to determine the degree of integrated influence between the risk factors. Finally, an evolutionary model of tailings pond dam failure risk was constructed based on the results of the analysis. The results of the study indicated the followings: 1) System risk accounted for 58.58% of the total weight, while personnel risk accounts for 15.51%. To maintain the stability of the tailings pond system, personnel risk should not be neglected in addition to focusing on systemic factors. 2) Rainfall intensity was an essential causal factor. Focusing on rainfall intensity and taking appropriate measures effectively reduced the risk of dam failure. The height of the dam and the depth of the seepage line accounted for a large proportion of the causal factors, making it possible to control the height of the dam and accurately monitor the depth of the seepage line to improve the stability of the dam. 3) In the tailings pond dam risk evolution model, there were 30 factors with higher mutability and correlation, which played a transitional role in risk transfer. A risk factor transfer network diagram was established for this purpose as a diagnostic map. The research results can provide new methods and ideas for tailings dam failure risk analysis research and practice.
Teachers’ Degree of Practicing Social Responsibility at Imam Abdulrahman Bin Faisal University, Saudi Arabia
Authors: Baniawwad Abdelmonim H.
Published: June 2022

This study aims to identify the social responsibility practiced by the faculty members toward the students, university, and society at Imam Abdulrahman Bin Faisal University (IAU), Saudi Arabia. Data were collected through a random sampling of 951 students. The findings reveal that the faculty members are practicing social responsibility and that the most important thing for the faculty members is to inculcate social responsibility among the students by encouraging them, involving them in social and cultural activities, and exercising democratic values. The participants agree that faculty members should maintain university equipment, contribute to seminars and conferences inside and outside of the university, and maintain a safe environment. The participants also agreed that faculty members should participate in the activities of cultural associations and institutions, respect cultural diversity, and get involved in community development. The theoretical and practical implications of the study have been identified to improve social responsibility at the higher institutions in Saudi Arabia as well as in the Gulf region.
In Research of School Resiliency or What Does a Good School Represent in a Digital Society?
Authors: Vinogradov Vladislav , Shatunova Olga , Merzon Elena , Sheymardanov Shamil
Published: June 2022

The role of education as a vertical mobility channel in the digital society engenders the need to assess schools on a “better or worse” scale, both from the perspective of parents (which school should we take our child to?) and education authorities (what measures should be taken?). It is proposed to take the resiliency indicator as a basis for assessing the status of a school, which characterises its ability to ensure the pupils’ results exceeding those expected, with regard for the challenging social context of educational activities and the troubled social structure of the learners’ body. At the same time, the school’s high resiliency ratio does not necessarily secure its high rating positions. Conversely, high rating positions do not condition high extent of the resiliency of the educational organisation. It is proposed to use, as the main indicators pointing at school resiliency, the stability of educational results of schoolchildren for at least 3 years and the ratio of the school’s absolute rating, which does not take into account the conditions of its functioning, vs. its rating with regard for deprivation. The above markers in their totality point to the quality of the school’s educational activities which allow it to achieve better results than in other schools in similar conditions. The research results show that school resiliency in the context of the digitalisation of education is determined not by specifics of its strategy, but by qualitative characteristics of its educational activity.
Developing Preschool Teachers’ Computational Thinking Knowledge, Attitudes, Beliefs, and Teaching Self-Efficacies: A Curriculum-Based Professional Development Program
Authors: Saxena Anika , Chiu Ming Ming
Published: June 2022

Grounded in transformative teacher development through the curriculum-based professional learning (CBPL) approach to teaching-learning, this exploratory study surveyed the computational thinking (CT) views of 25 in-service teachers before and after their CT professional development programme workshops. Multivariate outcome multilevel cross-classification analysis showed that after their workshops, these teachers changed their CT knowledge, CT attitudes, CT beliefs, and CT teaching self-efficacy. Teachers reporting greater CT knowledge than others felt greater overall CT teaching self-efficacy, including for both plugged and unplugged CT activities. Moreover, teachers who reported a school culture of sharing and teamwork or sufficient school resources for CT activities were more likely than other teachers to have greater teaching self-efficacy for plugged CT activities or CT activities overall. These results highlight the importance of school culture, school technology resources, and teachers’ reported CT knowledge to their CT teaching self-efficacy.
Correlation Between Retinal Microstructure Detected by Optical Coherence Tomography and Best Corrected Visual Acuity in Diabetic Retinopathy Macular Edema
Authors: Li Siying , Hua Rui , Jing Zuoqian , Huang Lele , Chen Lei
Published: June 2022

Objective

This study aimed to investigate the correlation between best corrected visual acuity (BCVA) and retinal microstructural parameters detected by optical coherence tomography (OCT) in diabetic retinopathy macular edema (DRME).

Methods

Thirty-nine patients (64 eyes) with DRME were enrolled in this study. These patients underwent OCT to measure the fracture distance of the external limiting membrane (ELM), junction between the inner and outer segments (IS/OS), central foveal thickness (CFT), and edema layer. The correlation between the above parameters and BCVA was discussed.

Results

CFT and the fracture distances of the ELM and IS/OS layers were negatively correlated with BCVA (p<0.05 for all). There was significant difference in Logarithm of the minimum angle of resolution (LogMAR) BCVA among patients with inner retinal edema, outer retinal edema, and mixed retinal edema (F = 5.57, p = 0.01). The LogMAR BCVA of inner retinal edema was the lowest (p < 0.05), and the LogMAR BCVA of outer retinal edema and mixed retinal edema were comparable (p > 0.05).

Conclusion

In eyes with DRME, thin CFT, intact ELM and IS/OS layers, and edema in inner retina is closely correlated with good BCVA.
Extrathyroidal Extension Prediction of Papillary Thyroid Cancer With Computed Tomography Based Radiomics Nomogram: A Multicenter Study
Authors: Yu Pengyi , Wu Xinxin , Li Jingjing , Mao Ning , Zhang Haicheng , Zheng Guibin , Han Xiao , Dong Luchao , Che Kaili , Wang Qinglin , Li Guan , Mou Yakui , Song Xicheng
Published: June 2022

Objectives

To develop and validate a Computed Tomography (CT) based radiomics nomogram for preoperative predicting of extrathyroidal extension (ETE) in papillary thyroid cancer (PTC) patients

Methods

A total of 153 patients were randomly assigned to training and internal test sets (7:3). 46 patients were recruited to serve as an external test set. A radiologist with 8 years of experience segmented the images. Radiomics features were extracted from each image and Delta-radiomics features were calculated. Features were selected by using one way analysis of variance and the least absolute shrinkage and selection operator in the training set. K-nearest neighbor, logistic regression, decision tree, linear-support vector machine (linear -SVM), gaussian-SVM, and polynomial-SVM were used to build 6 radiomics models. Next, a radiomics signature score (Rad-score) was constructed by using the linear combination of selected features weighted by their corresponding coefficients. Finally, a nomogram was constructed combining the clinical risk factors with Rad-scores. Receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and calibration curve were performed on the three sets to evaluate the nomogram’s performance.

Results

4 radiomics features were selected. The six models showed the certain value of radiomics, with area under the curves (AUCs) from 0.642 to 0.701. The nomogram combining the Rad-score and clinical risk factors (radiologists’ interpretation) showed good performance (internal test set: AUC 0.750; external test set: AUC 0.797). Calibration curve and DCA demonstrated good performance of the nomogram.

Conclusion

Our radiomics nomogram incorporating the radiomics and radiologists’ interpretation has utility in the identification of ETE in PTC patients.
Comparison of Bone Mineral Density in US Adults With Diabetes, Prediabetes and Normoglycemia From 2005 to 2018
Authors: Yuan Jing , Jia Pu , Zhou Jian-Bo
Published: June 2022

Background

Accumulating evidence has shown that diabetes has an impact on bone metabolism with conflicting results. Furthermore, little is known about the relationship of prediabetes with bone mineral density (BMD). Therefore, we explored the association between BMD and glucometabolic status in adults in the US.

Methods

In this cross-sectional study, we extracted and analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. A total of 14610 subjects aged 40 ≥ years diagnosed with diabetes, prediabetes, or normal glucose regulation (NGR) and had available data on BMD were eligible.

Results

The prevalence of prediabetes and diabetes in US adults aged 40 ≥ years were 39.2% and 26.4%, respectively. After multivariable adjustment, we found an increasing trend of BMD at the total hip, femoral neck, and lumbar spine with glucometabolic conditions from NGR and prediabetes to diabetes in adults aged ≥ 40 years in the US. This trend was more prominent in women than that in men. Fasting plasma glucose (FPG) and HbA1c levels were also positively correlated with BMD.

Conclusions

Glucometabolic conditions were significantly associated with BMD values in US adults.
Single-Cell Sequencing Analysis of the db/db Mouse Hippocampus Reveals Cell-Type-Specific Insights Into the Pathobiology of Diabetes-Associated Cognitive Dysfunction
Authors: Ma Shizhan , Bi Wenkai , Liu Xueying , Li Shangbin , Qiu Yaxin , Huang Chengcheng , Lv Renjun , Yin Qingqing
Published: June 2022

Diabetes-associated cognitive decline (DCD), is one of the complications of diabetes, which is characterized by a series of neurophysiological and pathological abnormalities. However, the exact pathogenesis of DCD is still unknown. Single-cell RNA sequencing (scRNA-seq) could discover unusual subpopulations, explore functional heterogeneity and identify signaling pathways and potential markers. The aim of this research was to provide deeper opinion into molecular and cellular changes underlying DCD, identify different cellular types of the diabetic mice hippocampus at single-cell level, and elucidate the factors mediating the pathogenesis of DCD. To elucidate cell specific gene expression changes in the hippocampus of diabetic encephalopathy. Single-cell RNA sequencing of hippocampus from db/m and db/db mice was carried out. Subclustering analysis was performed to further describe microglial cell subpopulations. Interestingly using immunohistochemistry, these findings were confirmed at the protein level. Single cell analysis yielded transcriptome data for 14621 hippocampal cells and defined 11 different cell types. Analysis of differentially expressed genes in the microglia compartments indicated that infection- and immune system process- associated terms, oxidative stress and inflammation play vital roles in the progression of DCD. Compared with db/m mouse, experiments at the protein level supported the activation of microglia, increased expression of inflammatory factors and oxidative stress damage in the hippocampus of db/db mouse. In addition, a major finding of our research was the subpopulation of microglia that express genes related to pro-inflammatory disease-associated microglia (DAM). Our research reveals pathological alterations of inflammation and oxidative stress mediated hippocampal damage in the db/db mice, and may provide potential diagnostic biomarkers and therapeutic interventions for DCD.
Fish and the Thyroid: A Janus Bifrons Relationship Caused by Pollutants and the Omega-3 Polyunsaturated Fatty Acids
Authors: Benvenga Salvatore , Famà Fausto , Perdichizzi Laura Giovanna , Antonelli Alessandro , Brenta Gabriela , Vermiglio Francesco , Moleti Mariacarla
Published: June 2022

Benefits of the omega-3 polyunsaturated fatty acids (PUFA) on a number of clinical disorders, including autoimmune diseases, are widely reported in the literature. One major dietary source of PUFA are fish, particularly the small oily fish, like anchovy, sardine, mackerel and others. Unfortunately, fish (particularly the large, top-predator fish like swordfish) are also a source of pollutants, including the heavy metals. One relevant heavy metal is mercury, a known environmental trigger of autoimmunity that is measurable inside the thyroid. There are a number of interactions between the omega-3 PUFA and thyroid hormones, even at the level of the thyroid hormone transport proteins. Concerning the mechanisms behind the protection from/amelioration of autoimmune diseases, including thyroiditis, that are caused by the omega-3 PUFA, one can be the decreased production of chemokines, a decrease that was reported in the literature for other nutraceuticals. Recent studies point also to the involvement of resolvins. The intracellular increase in resolvins is associated with the tissue protection from inflammation that was observed in experimental animals after coadministration of omega-3 PUFA and thyroid hormone. After having presented data on fish consumption at the beginning, we conclude our review by presenting data on the market of the dietary supplements/nutraceuticals. The global omega-3 products market was valued at USD 2.10 billion in 2020, and was projected to go up at a compound annual growth rate of 7.8% from 2020 to 2028. Among supplements, fish oils, which are derived mainly from anchovies, are considered the best and generally safest source of omega-3. Taking into account (i) the anti-autoimmunity and anti-cancer properties of the omega-3 PUFA, (ii) the increasing incidence of both autoimmune thyroiditis and thyroid cancer worldwide, (iii) the predisposing role for thyroid cancer exerted by autoimmune thyroiditis, and (iv) the risk for developing metabolic and cardiovascular disorders conferred by both elevated/trendwise elevated serum TSH levels and thyroid autoimmunity, then there is enough rationale for the omega-3 PUFA as measures to contrast the appearance and/or duration of Hashimoto’s thyroiditis as well as to correct the slightly elevated serum TSH levels of subclinical hypothyroidism.
ASK1-Interacting Protein 1 Acts as a Novel Predictor of Type 2 Diabetes
Authors: Song Zhigao , Chen Cong , He Jipei , Liu Bixia , Ji Weidong , Wu Liangping , He Li
Published: June 2022

Type 2 diabetes (T2D) mellitus is a chronic inflammatory disease characterized with high secretion of tumor necrosis factor (TNF)-α, but the regulatory pathway of TNF-α production in T2D has not been fully elucidated. ASK1-interacting protein 1 (AIP1) is a signaling scaffold protein that modulates several pathways associated with inflammation. In this study, we aimed to investigate the role of AIP1 in T2D development. Our results revealed that AIP1 was downregulated in omental adipose tissue (OAT) of obese patients with T2D compared with that in obese patients. In addition, Pearson’s correlation test showed that AIP1 was negatively correlated with the homeostatic model assessment for insulin resistance (HOMA-IR, r = -0.4829) and waist-to-hip ratio (r = -0.2614), which are major clinical indexes of T2D. As revealed by the proteomic analysis, immunohistochemistry, and ELISA, the OAT and the serum of obese patients with T2D presented high inflammatory status. And the increased inflammatory factors TNF-α and C-reactive protein C (CRP) in the serum of obese patients with T2D showed a positive correlation with HOMA-IR (TNF-α, r = 0.4728; CRP, r = 0.5522). Interestingly, AIP1 deficiency in adipocytes facilitated TNF-α secretion and retarded glucose uptake. Mechanistically, AIP1 deletion in human adipocytes activated JNK, p38 MAPK, and ERK1/2 signaling. Furthermore, inhibition of these signaling pathways using specific inhibitors could suppress these signal activation and insulin resistance caused by AIP1 deficiency. In addition, AIP1 and TNF-α expression in the OAT of patients with T2D recovered to normal levels after laparoscopic Roux-en-Y gastric bypass (RYGB) surgery. These findings indicate that AIP1 is negatively correlated with the clinical indexes of T2D. It modulates TNF-α expression in OAT via JNK, p38 MAPK, and ERK1/2 signaling.
Association Between Plasma Vitamin D2 and Type 2 Diabetes Mellitus
Authors: Qi Jing-Wan , Huang Bing , Wang Shuang , Song Dan , Xu Jing , Cui Ying , Guo Bin
Published: June 2022

Objective

To investigate the relationship between plasma vitamin D2(VD2) and type 2 diabetes(T2DM).

Method

Data from electronic medical records of 797 inpatients treated at Sun Yat Sen Memorial Hospital, Sun Yat-sen University between June 24, 2019 and December 24, 2020 were collected, and a total of 596 patients were enrolled after screening based on inclusion and exclusion criteria. Patients were divided into diabetic and non-diabetic groups according to whether they had T2DM. The Wilcoxon rank sum test was finally selected for the analysis of differences between groups according to the distribution of patients’ plasma VD2, and logistic regression models were used to find the corresponding influencing factors.

Result

Of the 596 hospitalized patients, 138 (23.15%) were diagnosed with T2DM. The Wilcoxon test showed no statistically significant difference in plasma VD2 concentrations between the T2DM and non-T2DM groups (p=0.833). After adjustment for confounders by multivariate logistic regression, there was still no significant difference in plasma VD2 concentrations between the two groups (P=0.316, OR: 1.15 (0.88,1.49)). The uncorrelated relationship between VD2 and T2DM was not found to change after incorporating 12 indicators, including demographic characteristics, laboratory indicators and complications, into the logistic regression model by 3 steps, even the OR (1.08 (0.92,1.26)) did not change in the 3 models. Similarly, the adjusted ORs agreed that there was no statistical association between VD2 and T2DM.

Conclusion

VD2 levels are similar in patients with T2DM compared to those without T2DM. Clinical caution should be exercised in giving VD2 supplementation to patients with T2DM unless other diseases requiring VD2 supplementation (e.g., rickets, osteoporosis) are present.