bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal data in peripheral blood confirm that PM20D1 is a quantitative trait locus (QTL) for Alzheimer’s disease and implicate its dynamic role in disease progression
Authors: Wang Qi , Chen Yinghua , Readhead Benjamin , Chen Kewei , Su Yi , Reiman Eric M. , Dudley Joel T.
Published: December 2020

Background

While Alzheimer’s disease (AD) remains one of the most challenging diseases to tackle, genome-wide genetic/epigenetic studies reveal many disease-associated risk loci, which sheds new light onto disease heritability, provides novel insights to understand its underlying mechanism and potentially offers easily measurable biomarkers for early diagnosis and intervention.

Methods

We analyzed whole-genome DNA methylation data collected from peripheral blood in a cohort (n = 649) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and compared the DNA methylation level at baseline among participants diagnosed with AD (n = 87), mild cognitive impairment (MCI, n = 175) and normal controls (n = 162), to identify differentially methylated regions (DMRs). We also leveraged up to 4 years of longitudinal DNA methylation data, sampled at approximately 1 year intervals to model alterations in methylation levels at DMRs to delineate methylation changes associated with aging and disease progression, by linear mixed-effects (LME) modeling for the unchanged diagnosis groups (AD, MCI and control, respectively) and U-shape testing for those with changed diagnosis (converters).

Results

When compared with controls, patients with MCI consistently displayed promoter hypomethylation at methylation QTL (mQTL) gene locus PM20D1. This promoter hypomethylation was even more prominent in patients with mild to moderate AD. This is in stark contrast with previously reported hypermethylation in hippocampal and frontal cortex brain tissues in patients with advanced-stage AD at this locus. From longitudinal data, we show that initial promoter hypomethylation of PM20D1 during MCI and early stage AD is reversed to eventual promoter hypermethylation in late stage AD, which helps to complete a fuller picture of methylation dynamics. We also confirm this observation in an independent cohort from the Religious Orders Study and Memory and Aging Project (ROSMAP) Study using DNA methylation and gene expression data from brain tissues as neuropathological staging (Braak score) advances.

Conclusions

Our results confirm that PM20D1 is an mQTL in AD and demonstrate that it plays a dynamic role at different stages of the disease. Further in-depth study is thus warranted to fully decipher its role in the evolution of AD and potentially explore its utility as a blood-based biomarker for AD.
Lean body weight versus total body weight to calculate the iodinated contrast media volume in abdominal CT: a randomised controlled trial
Authors: Zanardo Moreno , Doniselli Fabio Martino , Esseridou Anastassia , Agrò Massimiliano , Panarisi Nicol Antonina Rita , Monti Caterina Beatrice , Di Leo Giovanni , Sardanelli Francesco
Published: December 2020

Objectives

Iodinated contrast media (ICM) could be more appropriately dosed on patient lean body weight (LBW) than on total body weight (TBW).

Methods

After Ethics Committee approval, trial registration NCT03384979, patients aged ≥ 18 years scheduled for multiphasic abdominal CT were randomised for ICM dose to LBW group (0.63 gI/kg of LBW) or TBW group (0.44 gI/kg of TBW). Abdominal 64-row CT was performed using 120 kVp, 100–200 mAs, rotation time 0.5 s, pitch 1, Iopamidol (370 mgI/mL), and flow rate 3 mL/s. Levene, Mann–Whitney U, and χ2 tests were used. The primary endpoint was liver contrast enhancement (LCE).

Results

Of 335 enrolled patients, 17 were screening failures; 44 dropped out after randomisation; 274 patients were analysed (133 LBW group, 141 TBW group). The median age of LBW group (66 years) was slightly lower than that of TBW group (70 years). Although the median ICM-injected volume was comparable between groups, its variability was larger in the former (interquartile range 27 mL versus 21 mL, p = 0.01). The same was for unenhanced liver density (IQR 10 versus 7 HU) (p = 0.02). Median LCE was 40 (35–46) HU in the LBW group and 40 (35–44) HU in the TBW group, without significant difference for median (p = 0.41) and variability (p = 0.23). Suboptimal LCE (< 40 HU) was found in 64/133 (48%) patients in the LBW group and 69/141 (49%) in the TBW group, but no examination needed repeating.

Conclusions

The calculation of the ICM volume to be administered for abdominal CT based on the LBW does not imply a more consistent LCE.
Catecholaminergic polymorphic ventricular tachycardia in pregnancy: a case report
Authors: Schumer Amy , Contag Stephen
Published: December 2020

Introduction

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic disorder that can cause fatal tachyarrhythmias brought on by physical or emotional stress. There is little reported in the literature regarding management of CPVT in pregnancy much less during labor.

Case presentation

A gravida 2, para 1 presented to our high-risk clinic at 15 weeks gestation with known CPVT. The Caucasian female patient had been diagnosed after experiencing a cardiac arrest following a motor vehicle accident and found to have a pathogenic cardiac ryanodine receptor mutation. An implantable cardioverter defibrillator was placed at that time. Her pregnancy was uncomplicated, and she was medically managed with metoprolol, flecainide, and verapamil. Her labor course and successful vaginal delivery were uncomplicated and involved a multidisciplinary team comprising specialists in electrophysiology, maternal fetal medicine, anesthesiology, general obstetrics, lactation, and neonatology.

Conclusions

CPVT is likely underdiagnosed and, given that cardiovascular disease is a leading cause of death in pregnancy, it is important to bring further awareness to the diagnosis and management of this inherited arrhythmia syndrome in pregnancy.
Paracrine stimulation of perinatal lung functional and structural maturation by mesenchymal stem cells
Authors: Obendorf Janine , Fabian Claire , Thome Ulrich H. , Laube Mandy
Published: December 2020

Background

Mesenchymal stem cells (MSCs) were shown to harbor therapeutic potential in models of respiratory diseases, such as bronchopulmonary dysplasia (BPD), the most common sequel of preterm birth. In these studies, cells or animals were challenged with hyperoxia or other injury-inducing agents. However, little is known about the effect of MSCs on immature fetal lungs and whether MSCs are able to improve lung maturity, which may alleviate lung developmental arrest in BPD.

Methods

We aimed to determine if the conditioned medium (CM) of MSCs stimulates functional and structural lung maturation. As a measure of functional maturation, Na+transport in primary fetal distal lung epithelial cells (FDLE) was studied in Ussing chambers. Na+transporter and surfactant protein mRNA expression was determined by qRT-PCR. Structural maturation was assessed by microscopy in fetal rat lung explants.

Results

MSC-CM strongly increased the activity of the epithelial Na+channel (ENaC) and the Na,K-ATPase as well as their mRNA expression. Branching and growth of fetal lung explants and surfactant protein mRNA expression were enhanced by MSC-CM. Epithelial integrity and metabolic activity of FDLE cells were not influenced by MSC-CM. Since MSC’s actions are mainly attributed to paracrine signaling, prominent lung growth factors were blocked. None of the tested growth factors (VEGF, BMP, PDGF, EGF, TGF-β, FGF, HGF) contributed to the MSC-induced increase of Na+transport. In contrast, inhibition of PI3-K/AKT and Rac1 signaling reduced MSC-CM efficacy, suggesting an involvement of these pathways in the MSC-CM-induced Na+transport.

Conclusion

The results demonstrate that MSC-CM strongly stimulated functional and structural maturation of the fetal lungs. These effects were at least partially mediated by the PI3-K/AKT and Rac1 signaling pathway. Thus, MSCs not only repair a deleterious tissue environment, but also target lung cellular immaturity itself.
Dissecting molecular mechanisms underlying H2O2-induced apoptosis of mouse bone marrow mesenchymal stem cell: role of Mst1 inhibition
Authors: Zhang Qian , Cheng Xianfeng , Zhang Haizhou , Zhang Tao , Wang Zhengjun , Zhang Wenlong , Yu Wancheng
Published: December 2020

Background

Bone marrow mesenchymal stem cell (BM-MSC) has been shown to treat pulmonary arterial hypertension (PAH). However, excessive reactive oxygen species (ROS) increases the apoptosis of BM-MSCs, leading to poor survival and engraft efficiency. Thus, improving the ability of BM-MSCs to scavenge ROS may considerably enhance the effectiveness of transplantation therapy. Mammalian Ste20-like kinase 1 (Mst1) is a pro-apoptotic molecule which increases ROS production. The aim of this study is to uncover the underlying mechanisms the effect of Mst1 inhibition on the tolerance of BM-MSCs under H2O2condition.

Methods

Mst1 expression in BM-MSCs was inhibited via transfection with adenoviruses expressing a short hairpin (sh) RNA directed against Mst1 (Ad-sh-Mst1) and exposure to H2O2. Cell viability was detected by Cell Counting Kit 8 (CCK-8) assay, and cell apoptosis was analyzed by Annexin V-FITC/PI, Caspase 3 Activity Assay kits, and pro caspase 3 expression. ROS level was evaluated by the ROS probe DCFH-DA, mitochondrial membrane potential (ΔΨm) assay, SOD1/2, CAT, and GPx expression. Autophagy was assessed using transmission electron microscopy, stubRFP-sensGFP-LC3 lentivirus, and autophagy-related protein expression. The autophagy/Keap1/Nrf2 signal in H2O2-treated BM-MSC/sh-Mst1 was also measured.

Results

Mst1 inhibition reduced ROS production; increased antioxidant enzyme SOD1/2, CAT, and GPx expression; maintained ΔΨm; and alleviated cell apoptosis in H2O2-treated BM-MSCs. In addition, this phenomenon was closely correlated with the autophagy/Keap1/Nrf2 signal pathway. Moreover, the antioxidant pathway Keap1/Nrf2 was also blocked when autophagy was inhibited by the autophagy inhibitor 3-MA. However, Keap1 or Nrf2 knockout via siRNA had no effect on autophagy activation or suppression.

Conclusion

Mst1 inhibition mediated the cytoprotective action of mBM-MSCs against H2O2-induced oxidative stress injury. The underlying mechanisms involve autophagy activation and the Keap1/Nrf2 signal pathway.

Graphical abstract
Targeted expression profiling reveals distinct stages of early canine fibroblast reprogramming are regulated by 2-oxoglutarate hydroxylases
Authors: Tobias Ian C. , Kao Mian-Mian C. , Parmentier Thomas , Hunter Hailey , LaMarre Jonathan , Betts Dean H.
Published: December 2020

Background

Ectopic expression of a defined set of transcription factors allows the reprogramming of mammalian somatic cells to pluripotency. Despite continuous progress in primate and rodent reprogramming, limited attention has been paid to cell reprogramming in domestic and companion species. Previous studies attempting to reprogram canine cells have mostly assessed a small number of presumptive canine induced pluripotent stem cell (iPSC) lines for generic pluripotency attributes. However, why canine cell reprogramming remains extremely inefficient is poorly understood.

Methods

To better characterize the initial steps of pluripotency induction in canine somatic cells, we optimized an experimental system where canine fetal fibroblasts (cFFs) are transduced with the Yamanaka reprogramming factors by Sendai virus vectors. We use quantitative PCR arrays to measure the expression of 80 target genes at various stages of canine cell reprogramming. We ask how cFF reprogramming is influenced by small molecules affecting the epigenomic modification 5-hydroxymethylcytosine, specifically L-ascorbic acid and retinoic acid (AA/RA).

Results

We found that the expression and catalytic output of a class of 2-oxoglutarate-dependent (2-OG) hydroxylases, known as ten-eleven translocation (TET) enzymes, can be modulated in canine cells treated with AA/RA. We further show that AA/RA treatment induces TET1 expression and facilitates early canine reprogramming, evidenced by upregulation of epithelial and pluripotency markers. Using a chemical inhibitor of 2-OG hydroxylases, we demonstrate that 2-OG hydroxylase activity regulates the expression of a subset of genes involved in mesenchymal-to-epithelial transition (MET) and pluripotency in early canine reprogramming. We identify a set of transcription factors depleted in maturing reprogramming intermediates compared to pluripotent canine embryonic stem cells.

Conclusions

Our findings highlight 2-OG hydroxylases have evolutionarily conserved and divergent functions regulating the early reprogramming of canine somatic cells and show reprogramming conditions can be rationally optimized for the generation of maturing canine iPSC.
circAKT3 positively regulates osteogenic differentiation of human dental pulp stromal cells via miR-206/CX43 axis
Authors: Zhang Bo , Huo Sibei , Cen Xiao , Pan Xuefeng , Huang Xinqi , Zhao Zhihe
Published: December 2020

Background

Human dental pulp stromal cells (hDPSCs) are promising sources of mesenchymal stem cells (MSCs) for bone tissue regeneration. Circular RNAs (circRNAs) have been demonstrated to play critical roles in stem cell osteogenic differentiation. Herein, we aimed to investigate the role of circAKT3 during osteogenesis of hDPSCs and the underlying mechanisms of its function.

Methods

We performed circRNA sequencing to investigate the expression profiles of circular RNAs during osteogenesis of hDPSCs. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect the expression pattern of circAKT3 and miR-206 in hDPSCs during osteogenesis. We knocked down circAKT3 and interfered the expression of miR-206 to verify their regulatory role in hDPSC osteogenesis. We detected hDPSCs mineralization by alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining and used dual-luciferase reporter assay to validate the direct binding between circAKT3 and miR-206. To investigate in vivo mineralization, we performed subcutaneous transplantation in nude mice and used hematoxylin and eosin, Masson’s trichrome, and immunohistochemistry staining.

Results

Totally, 86 circRNAs were differentially expressed during hDPSC osteogenesis, in which 29 were downregulated while 57 were upregulated. circAKT3 was upregulated while miR-206 was downregulated during hDPSC osteogenesis. Knockdown of circAKT3 inhibited ALP/ARS staining and expression levels of osteogenic genes. circAKT3 directly interacted with miR-206, and the latter one suppressed osteogenesis of hDPSCs. Silencing miR-206 partially reversed the inhibitory effect of circAKT3 knockdown on osteogenesis. Connexin 43 (CX43), which positively regulates osteogenesis of stem cells, was predicted as a target of miR-206, and overexpression or knockdown of miR-206 could correspondingly decrease and increase the expression of CX43. In vivo study showed knockdown of circAKT3 suppressed the formation of mineralized nodules and expression of osteogenic proteins.

Conclusion

During osteogenesis of hDPSCs, circAKT3 could function as a positive regulator by directly sponging miR-206 and arresting the inhibitive effect of miR-206 on CX43 expression.
Design, development, and evaluation of the efficacy of a nucleic acid-free version of a bacterial ghost candidate vaccine against avian pathogenic E. coli (APEC) O78:K80 serotype
Authors: Soleymani Safoura , Tavassoli Amin , Hashemi Tabar Gholamreza , Kalidari Gholam Ali , Dehghani Hesam
Published: December 2020

One of the major bacterial infectious diseases in the poultry industry is avian pathogenic Escherichia coli (APEC), which causes colibacillosis in chickens. To develop a novel nucleic acid-free bacterial ghost (BG) vaccine against the O78:K80 serotype of APEC, in this study we constructed a plasmid that harbored E-lysis and S nuclease (SNUC). Following the expression, the O78:K80 bacteria lost all of their cytoplasmic content and nucleic acids by enzymatic digestion. The functionality of these two proteins in the production procedure of bacterial ghosts was confirmed by monitoring the number of colonies, scanning electron microscopy imaging, gel electrophoresis of genomic DNA, and qPCR on the plasmid content of bacterial ghosts. The protective efficacy of the ghost vaccine generated from O78:K80 serotype of APEC was tested in chickens by injection and inhalation routes and compared with that in chickens that received the injection of a killed vaccine. The O78:K80 BG vaccine candidate, used as injection and inhalation, in comparison with the killed vaccine, triggered higher proinflammatory cytokine expression including IL-6, IL-1β, and TNFSF15; a higher level of antibody-dependent humoral (IgY and IgA) and cellular immune responses (IFNγ and lymphocyte proliferation); and lower lesion scores. According to the results of this study, we suggest that the bacterial ghost technology has the potential to be applied for the development of novel vaccines against avian colibacillosis. This technology provides an effective and reliable approach to make multivalent vaccines for more prevalent APEC strains involved in the establishment of this infectious disease in the poultry industry.
Regulatory effects of chicken TRIM25 on the replication of ALV-A and the MDA5-mediated type I interferon response
Authors: Zhou Jin-run , Liu Jun-hong , Li Hong-mei , Zhao Yue , Cheng Ziqiang , Hou Yan-meng , Guo Hui-jun
Published: December 2020

This study focuses on the immunoregulatory effects of chicken TRIM25 on the replication of subgroup A of avian leukosis virus (ALV-A) and the MDA5-mediated type I interferon response. The ALV-A-SDAU09C1 strain was inoculated into DF1 cells and 1-day-old SPF chickens, and the expression of TRIM25 was detected at different time points after inoculation. A recombinant overexpression plasmid containing the chicken TRIM25 gene (TRIM25-GFP) was constructed and transfected into DF1 cells to analyse the effects of the overexpression of chicken TRIM25 on the replication of ALV-A and the expression of MDA5, MAVS and IFN-β. A small interfering RNA targeting chicken TRIM25 (TRIM25-siRNA) was prepared and transfected into DF1 cells to assess the effects of the knockdown of chicken TRIM25 on the replication of ALV-A and the expression of MDA5, MAVS and IFN-β. The results showed that chicken TRIM25 was significantly upregulated at all time points both in ALV-A-infected cells and in ALV-A-infected chickens. Overexpression of chicken TRIM25 in DF1 cells dramatically decreased the antigenic titres of ALV-A in the cell supernatant and upregulated the relative expression of MDA5, MAVS and IFN-β induced by ALV-A or by poly(I:C); in contrast, knockdown of chicken TRIM25 significantly increased the antigenic titres of ALV-A and downregulated the relative expression of MDA5, MAVS and IFN-β. It can be concluded that chicken TRIM25 can inhibit the replication of ALV-A and upregulate the MDA5 receptor-mediated type I interferon response in chickens. This study can help improve the understanding of the antiviral activities of chicken TRIM25 and enrich the knowledge of antiviral responses in chickens.
Relationship between physical and biogeochemical parameters and the scenario dependence of the transient climate response to cumulative carbon emissions
Authors: Tachiiri Kaoru
Published: December 2020

The transient climate response to cumulative carbon emissions (TCRE) is a key metric in estimating the remaining carbon budget for given temperature targets. However, the TCRE has a small scenario dependence that can be non-negligible for stringent temperature targets. To investigate the parametric correlations and scenario dependence of the TCRE, the present study uses a 512-member ensemble of an Earth system model of intermediate complexity (EMIC) perturbing 11 physical and biogeochemical parameters under scenarios with steady increases of 0.25%, 0.5%, 1%, 2%, or 4% per annum (ppa) in the atmospheric CO2 concentration (pCO2), or an initial increase of 1% followed by an annual decrease of 1% thereafter. Although a small difference of 5% (on average) in the TCRE is observed between the 1-ppa and 0.5-ppa scenarios, a significant scenario dependence is found for the other scenarios, with a tendency toward large values in gradual or decline-after-a-peak scenarios and small values in rapidly increasing scenarios. For all scenarios, correlation analysis indicates a remarkably large correlation between the equilibrium climate sensitivity (ECS) and the relative change in the TCRE, which is attributed to the longer response time of the high ECS model. However, the correlations of the ECS with the TCRE and its scenario dependence for scenarios with large pCO2 increase rates are slightly smaller, and those of biogeochemical parameters such as plant respiration and the overall pCO2–carbon cycle feedback are larger, than in scenarios with gradual increases. The ratio of the TCREs under the overshooting (i.e., 1-ppa decrease after a 1-ppa increase) and 1-ppa increase only scenarios had a clear positive relation with zero-emission commitments. Considering the scenario dependence of the TCRE, the remaining carbon budget for the 1.5 °C target could be reduced by 17 or 22% (before and after considering the unrepresented Earth system feedback) for the most extreme case (i.e., the 67th percentile when using the 0.25-ppa scenario as compared to the 1-ppa increase scenario). A single ensemble EMIC is also used to indicate that, at least for high ECS (high percentile) cases, the scenario dependence of the TCRE should be considered when estimating the remaining carbon budget.
A dynamic causal model on self-regulation of aversive emotion
Authors: Yang Yang , Zhang Xiaofei , Peng Yue , Bai Jie , Lei Xiuya
Published: December 2020

Cognitive regulation of emotion has been proven to be effective to take control the emotional responses. Some cognitive models have also been proposed to explain the neural mechanism that underlies this process. However, some characteristics of the models are still unclear, such as whether the cognitive regulation will be spontaneously employed by participants implicitly. The present study recruited the fMRI experiment to focus on the discomfort induced by viewing aversive pictures, and the emotional self-regulation during picture viewing. By using the dynamic causal modeling (DCM), 50 putative models of brain functional networks were constructed, one optimal model that fitted the real data best won the comparison from the candidates. As a result, the optimal model suggests that both the ventral striatum (VS)-centric bottom-up and the dorsolateral prefrontal cortex (DLPFC)-centric top-down regulations are recruited for self-regulation on negative emotions. The DLPFC will exert modulatory influence on the VS only when the VS fails to suppress the induced emotions by self-inhibition.
Complete remission from peritoneal metastasis of late recurrent breast cancer by endocrine therapy: a case report
Authors: Fuke Azusa , Tabei Isao , Okamoto Tomoyoshi , Takeyama Hiroshi
Published: December 2020

Background

Peritoneal dissemination associated with the postoperative recurrence of breast cancer is relatively low (3–6%). Although the prognosis of patients with peritoneal metastasis is generally short (7–26 months), we experienced a unique case in which complete remission was achieved for more than 6 years with endocrine therapy alone.

Case presentation

An 81-year-old woman presented an upper abdominal tumor and loss of appetite. Computer tomography (CT) scan revealed a tumor in the duodenum and the head of pancreas, which malignant lymphoma was suspected. The exploratory laparotomy demonstrated a tumor located in the greater curvature of the pylorus to the transverse colon, and peritoneal dissemination. Because of the previous history of breast cancer 11 years ago and the immunopathological findings, recurrence of breast cancer was diagnosed. Lung metastasis was also detected postoperatively and the endocrine therapy using letrozole was introduced. After a year, CT scan confirmed complete remission from the metastasis. Two years later, tumor markers fell within the normal limit.

Conclusions

A rare case of late-phase metachronous peritoneal metastasis of the breast cancer where complete remission was obtained by a single endocrine agent was presented.
A case of non-occlusive mesenteric ischaemia caused by pelvic fracture due to fall trauma
Authors: Furutani Yuichiro , Ishiguro Kaname , Tokuraku Masato , Moritomo Hitoshi
Published: December 2020

Background

Non-occlusive mesenteric ischaemia (NOMI) is a condition in which intestinal ischaemia arises due to spasms of peripheral blood vessels; however, there is no obstruction of the main arteries. Risk factors include hypertension, diabetes, and increasing age, but the traumatic injury triggering NOMI onset is rarely reported. We report a case of NOMI caused by a pelvic fracture due to a fall injury.

Case presentation

A 77-year-old man was transported to the hospital due to a fall injury. CT revealed a pelvic fracture and a haematoma in the pelvic extraperitoneal space. The next day, the patient developed shock, and CT revealed an increase in haematoma size. Both internal iliac arteries were embolized by transcatheter arterial embolization (TAE). The next day’s CT revealed intestinal necrosis of the ascending colon, and emergency surgery was planned. During surgery, necrosis was identified in the serosa of the ascending, transverse, and sigmoid colon. We performed subtotal excision from the ascending colon to the sigmoid colon. On postoperative day 10, melena was observed, and CT revealed partial thickening of the small intestine and a decrease in the contrast effect. Considering the post-total colectomy and general condition, we proceeded with conservative treatment. Over time, the patient developed liver and renal dysfunction and died 16 days after surgery.

Conclusions

We experienced a case of NOMI caused by bleeding from a pelvic fracture. It is important to keep in mind the risk of developing NOMI in traumatic bleeding to avoid missing this diagnosis.
An analysis of internal and external feedback in self-regulated learning activities mediated by self-regulated learning tools and open learner models
Authors: Chou Chih-Yueh , Zou Nian-Bao
Published: December 2020

In self-regulated learning (SRL), students organize, monitor, direct, and regulate their learning. In SRL, monitoring plays a critical role in generating internal feedback and thus adopting appropriate regulations. However, students may have poor SRL processes and performance due to their poor monitoring. Researchers have suggested providing external feedback to facilitate better student SRL. However, SRL involves many meta-cognitive internal processes that are hidden and difficult to observe and measure. This study proposed a SRL model to illustrate the relationship among external SRL tools, internal SRL processes, internal feedback, and external feedback. Based on the model, this study designed a system with SRL tools and open leaner models (OLMs) to assist students in conducting SRL, including self-assessing their initial learning performance (i.e. perceived initial performance and monitoring of learning performance) after listening to a teacher’s lecture, being assessed by and receiving external feedback from the OLM (i.e. actual performance) in the system, setting target goals (i.e. desired performance) of follow-up learning, conducting follow-up learning (i.e. strategy implementation), and evaluating their follow-up learning performance (i.e. perceived outcome performance and strategy outcome monitoring). These SRL tools also externalize students’ internal SRL processes and feedback, including perceived initial, desired, and perceived outcome performances, for investigation. In addition, this study explores the impact of external feedback from the OLM on students’ internal SRL processes and feedback. An evaluation was conducted to record and analyze students’ SRL processes and performance, and a questionnaire was administered to ask students about their SRL processes. There are three main findings. First, the results showed that students often have poor internal SRL processes and poor internal feedback, including poor self-assessment, inappropriate target goals, a failure to conduct follow-up learning, and a failure to achieve their goals. Second, the results revealed that the SRL tools and external feedback from the OLM assisted most students in SRL, including monitoring their learning performance, goal-setting, strategy implementation and monitoring, and strategy outcome monitoring. Third, some students still required further support for SRL.
Value of vessel wall magnetic resonance imaging in the diagnosis of cerebrovascular diseases
Authors: Farag Sherien , El-Dien Hany Zaki , Abdelazeem Yasser , Elewa Mohammed Khaled , Abdelmaksoud Khaled , ElSadek Ahmed
Published: December 2020

Background

Intracranial vessel wall imaging can detect non-stenotic lesions with further characterization of stenotic lesions that have already been detected with common angiographic methods. Magnetic resonance imaging (MRI) of the intracranial vessel wall can describe the presence of both large and small atherosclerotic lesions and to characterize the lesions based on enhancement, plaque content, and vulnerability

Objectives

To assess suspicious lesions detected by magnetic resonance angiography for further evaluation by vessel wall MRI.

Methods

A total of sixteen ischemic stroke patients within 2 weeks from onset were recruited to this cross-sectional study. Magnetic resonance angiography was done to document intracranial arterial stenosis. Further high-field MR unit (3 Tesla MRI Scanner) was used to obtain vessel wall MR sequences (T1 pre-post contrast and T2 fat sat) to differentiate between intracranial atherosclerotic plaque, vasculitis, and moyamoya disease and to assess atherosclerotic plaque activity (vulnerability)

Results

Vessel wall MR imaging showed arterial wall thickening with irregular inner margin and eccentric enhancement in cases of intracranial atherosclerosis, where as in case of CNS vasculitis, it showed circumferential wall enhancement with regular smooth inner margin. In cases of moyamoya disease, the vessel wall MR showed a narrowing of the luminal artery without post-contrast enhancement of the wall, no hemorrhagic nor fatty content.

Conclusion

Vessel wall MR imaging is recommended for stroke patients with suspected intracranial large vessel atherosclerosis seen in MRA to assess atherosclerotic plaque activity and characterization of stenotic lesions
Depression and anxiety among patients with Parkinson’s disease: frequency, risk factors, and impact on quality of life
Authors: Khedr Eman M. , Abdelrahman Ahmed A. , Elserogy Yasser , Zaki Ahmed Fathi , Gamea Ayman
Published: December 2020

Background

Depression and anxiety are non-motor symptoms of Parkinson’s disease (PD) that are often overlooked and underrated. This study aimed to highlight the frequency and risk factors of depression and anxiety among subjects with PD.

Methods

Sixty-four patients with PD who were diagnosed according to United Kingdom Parkinson’s Disease Society (UKPDS) Brain Bank Criteria and 50 sex- and age-matched healthy control subjects are evaluated for depression and anxiety. PD severity and staging were assessed using Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn and Yahr scale. Depression and anxiety were diagnosed using DSM-IV TR criteria and scored using Hamilton Depression and Hamilton Anxiety Rating Scales (HAM-D and HAM-A). The World Health Organization Quality of Life (WHOQOL)-BREF was used to assess impact of depression and anxiety on quality of life.

Results

31.25% of patients with PD had depression while 40.6% of patients had anxiety disorder. Depression was higher in females and patients with history of depression and low socioeconomic status (SES). Anxiety was common in young patients and those who had history of anxiety. Overlap between depression and anxiety was recorded in 23.4%. Total UPDRS and Hoehn and Yahr scale accounted for 33.4% of variance for depression. Total UPDRS and earlier age of onset accounted for 39% of variance for anxiety. Advanced disease stage and severity were independent predictors for depression while disease severity and younger age of onset were the main predictors for anxiety. Depression and anxiety have a negative impact on the overall quality of life of PD patients especially on physical and psychosocial domains.

Conclusion

Depression and anxiety are relatively common in PD. Female gender, low SES, and history of depression were the main risk factors for developing depression. Young age and history of anxiety were risk factors for anxiety. Both had negative impact on quality of life.
Motor disability in patients with multiple sclerosis: transcranial magnetic stimulation study
Authors: Mohy Anssam Bassem , Hatem Aqeel Kareem , Kadoori Hussein Ghani , Hamdan Farqad Bader
Published: December 2020

Background

Transcranial magnetic stimulation (TMS) is a non-invasive procedure used in a small targeted region of the brain via electromagnetic induction and used diagnostically to measure the connection between the central nervous system (CNS) and skeletal muscle to evaluate the damage that occurs in MS.

Objectives

The study aims to investigate whether single-pulse TMS measures differ between patients with MS and healthy controls and to consider if these measures are associated with clinical disability.

Patients and methods

Single-pulse TMS was performed in 26 patients with MS who hand an Expanded Disability Status Scale (EDSS) score between 0 and 9.5 and in 26 normal subjects. Different TMS parameters from upper and lower limbs were investigated.

Results

TMS disclosed no difference in all MEP parameters between the right and left side of the upper and lower limbs in patients with MS and controls. In all patients, TMS parameters were different from the control group. Upper limb central motor conduction time (CMCT) was prolonged in MS patients with pyramidal signs. Upper and lower limb CMCT and CMCT-f wave (CMCT-f) were prolonged in patients with ataxia. Moreover, CMCT and CMCT-f were prolonged in MS patients with EDSS of 5–9.5 as compared to those with a score of 0–4.5. EDSS correlated with upper and lower limb cortical latency (CL), CMCT, and CMCT-f whereas motor evoked potential (MEP) amplitude not.

Conclusion

TMS yields objective data to evaluate clinical disability and its parameters correlated well with EDSS.
Immunoglobulins to mitigate paraneoplastic Lambert Eaton Myasthenic Syndrome under checkpoint inhibition in Merkel cell carcinoma
Authors: Dohrn Maike F. , Schöne Ulrike , Küppers Charlotte , Christen Deborah , Schulz Jörg B. , Gess Burkhard , Tauber Simone
Published: December 2020

Lambert-Eaton myasthenic syndrome (LEMS) is a rare, autoimmune or paraneoplastic condition characterized by muscle weakness and fatigability. In cancer therapy, immune checkpoint inhibitors (ICI) sensitize the immune system for tumor antigens.

We report a 62-year-old, female patient with paraneoplastic LEMS as first manifestation of Merkel cell carcinoma. Under avelumab, the LEMS exacerbated with worsening of limb weakness and a severely reduced vital capacity (< 1 l). To treat this immunological side effect, we added a regimen with intravenous immunoglobulins. Hereby, the LEMS improved significantly. As we were able to continue the cancer treatment, the Merkel cell carcinoma has been in remission so far.

This is the first description of paraneoplastic LEMS, avelumab, and Merkel cell carcinoma. We conclude that immunoglobulins are an option to control an ICI-associated deterioration of paraneoplastic symptoms.
The changes in biventricular remodelling and function after atrial septal defect device closure and its relation to age of closure
Authors: Alkhateeb Areej , Roushdy Alaa , Hasan-Ali Hosam , Kishk Yehia Taha , Hassan Ayman K. M.
Published: December 2020

Background

The trans-catheter closure of atrial septal defect (ASD) usually has a rapid impact on biventricular remodelling and functions. Whether the transcatheter closure of ASD at early childhood or at adulthood age would affect the improvement in biventricular dimensions and functions remains an area of active research.

Results

This prospective observational study enrolled 70 subjects (50 ASD cases and 20 control subjects). Tissue Doppler imaging (TDI) and strain (S) were performed for the control group and ASD patients at baseline and at 24 h and 1 month after ASD device closure. The total ASD group was subdivided into two subgroups: group-1—children and adolescent with ASD, who underwent transcatheter closure at age ≤ 19 years; group-2—adult who underwent ASD device closure at age > 19 years old. The right and left ventricular global longitudinal systolic strain (RV/LV-GLS) and RV free wall longitudinal strain (RV free wall LS) showed a significant decline after 24 h of device closure (RVGLS-P = 0.001, LVGLS-P = 0.048, RV free wall LS-P < 0.001). However, after a 1-month follow-up, the LVGLS increased in comparison with 24 h changes after device closure (P = 0.038). The baseline mean value of RV free wall LS of G2 was significantly lower than G1 value (P < 0.001). There was no statistically significant difference between the 2 age subgroups regarding biventricular GLS and RV free wall LS changes after device closure. The changes in LV diastolic function immediately and after 1 month of device closure showed a statistically significant change in e′ and its delta change value in group-2 in comparison with its baseline values and to group-1 delta changes (P = 0.002, P = 0.011, P = 0.019, respectively).

Conclusion

The ASD transcatheter closure reduced biventricular global and RV free wall longitudinal systolic strain within 1 day of intervention and was associated with a short-term improvement in the LV-GLSS after a 1-month duration. The progressive increase in LV preload results in its strain growth and reduction in diastolic function after transcatheter ASD closure. The older age at the time of ASD device closure was associated with a significant decrease in the RV free wall LS and septal e′ velocity towards abnormality.
Comparing VBM and ROI analyses for detection of gray matter abnormalities in patients with bipolar disorder using MRI
Authors: Seyedi Somayyeh , Jafari Raheleh , Talaei Ali , Naseri Shahrokh , Momennezhad Mahdi , Moghaddam Maliheh Dadgar , Akbari-Lalimi Hossein
Published: December 2020

Background

With the increasing efforts to a better understanding of psychiatric diseases, detection of brain morphological alterations is necessary. This study compared two methods—voxel-based morphometry (VBM) and region of interest (ROI) analyses—to identify significant gray matter changes of patients with bipolar disorder type I (BP I).

Results

The VBM findings suggested gray matter reductions in the left precentral gyrus and right precuneus of the patients compared to healthy subjects (α = 0.0005, uncorrected). However, no regions reached the level of significance in ROI analysis using the three atlases, i.e., hammers, lpba40, and neuromorphometrics atlases (α = 0.0005).

Conclusion

It can be concluded that VBM analysis seems to be more sensitive to partial changes in this study. If ROI analysis is employed in studies to detect structural brain alterations between groups, it is highly recommended to use VBM analysis besides.
A rapid pre-implementation evaluation to inform a family engagement navigator program during COVID-19
Authors: Taylor Stephanie Parks , Short Robert T. , Asher Anthony M. , Taylor Brice , Beidas Rinad S.
Published: December 2020

Background

Innovative models of family engagement and support are needed in the intensive care unit (ICU) during times of restricted visitation such as the COVID-19 pandemic. Limited understanding of the factors affecting the uptake and outcomes of different family support models hinders the implementation of best practices. We aimed to conduct a rapid pre-implementation evaluation of stakeholder-perceived facilitators and barriers to design implementation strategies to support a novel program using medical students to facilitate family-centered care in the ICU.

Methods

We conducted a 2-step process. In step 1, we gathered contextual data via interview-style open-ended questions sent to clinicians and navigator stakeholders via email. We used electronic data collection due to the physical distancing requirements, the need to prioritize brief data collection for respondent burden, and the need for rapid knowledge gain. A codebook based on the Consolidated Framework for Implementation Research (CFIR), an integrated framework from the field of implementation science, was used to analyze the findings. In step 2, a pilot of the intervention was implemented with 3 navigators over 2 weeks. Implementation strategies were developed to target barriers identified by the pre-implementation evaluation.

Results

Fourteen (70%) of the identified stakeholders responded to the survey. Ten constructs encompassing all five CFIR domains were present in responses as implementation influencers, with the Intervention domain most frequently represented. Through these results and operational feedback from navigators during the pilot period, stakeholders selected multiple implementation strategies: audit and provide feedback, develop educational materials, conduct ongoing training, promote adaptability, assess and redesign workflow, identify and prepare champions, and engage community resources.

Conclusions

We demonstrated how a conceptually based pre-implementation program evaluation can be used to rapidly inform optimal implementation strategies. We report key factors to inform design and implementation strategies for a novel ICU family engagement navigator program that may be useful to others wishing to adopt similar programs.
Axial skeleton anterior-posterior patterning is regulated through feedback regulation between Meis transcription factors and retinoic acid
Authors: López-Delgado Alejandra C. , Delgado Irene , Cadenas Vanessa , Sánchez-Cabo Fátima , Torres Miguel
Published: December 2020

Vertebrate axial skeletal patterning is controlled by collinear expression of Hox genes and axial level-dependent activity of HOX protein combinations. MEIS transcription factors act as cofactors of HOX proteins and profusely bind to Hox complex DNA, however their roles in mammalian axial patterning remain unknown. Retinoic acid (RA) is known to regulate axial skeletal element identity through the transcriptional activity of its receptors, however, whether this role is related to MEIS/HOX activity remains unknown. Here, we study the role of Meis in axial skeleton formation and its relationship to the RA pathway in mice. Meis elimination in the paraxial mesoderm produces anterior homeotic transformations and rib mis-patterning associated to alterations of the hypaxial myotome. While Raldh2 and Meis positively regulate each other, Raldh2 elimination largely recapitulates the defects associated to Meis-deficiency and Meis overexpression rescues the axial skeletal defects in Raldh2 mutants. We propose a Meis-RA positive feedback loop whose output is Meis levels and is essential to establish anterior-posterior identities and pattern of the vertebrate axial skeleton.
Fernando Collantes - The Political Economy of the Common Agricultural Policy: Coordinated Capitalism or Bureaucratic Monster?
Authors: Δούκας Γιάννης Ελ.
Published: December 2020

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THE ROLE AND PLACE OF INTERSUBJECTIVE INTERPRETATION OF TEXT IN THE THEORY AND PRACTICE OF TRANSLATION
Authors:   Northeastern state university, Zhirova Irene
Published: December 2020

The article presents the problem of rethinking the primary and dominant association with the expression "intersubjective interpretation" with a variety of points of view of two or more interpreters on the object of translation. At the same time, intrasubjective interpretation as the interpretation of an object by one subject can show an intersubjective result.
TO THE PROBLEM OF TRANSLATION OF LITERAL TEXTS TO OSSETIAN LANGUAGE
Authors:   Northeastern state university, Kudzoeva Angela , Chekhov Soslan ,   Northeastern state university
Published: December 2020

The article raises a range of issues related to the translation of liturgical texts into the Ossetian language. These are the causes of the translation tradition and the stages of its development, the problem of the language of worship, the issues associated with the difficulties of an adequate translation of the basic terms, as well as the problem of the formation of terms.
EXTRALINGUISTIC FEATURES OF TRANSFERING MOVIESWHILE DUBBING-IN
Authors:   Northeastern state university, Peregoroda Marina , Sycheva Anastasia ,   Northeastern state university
Published: December 2020

The article considers such a type of audiovisual translation as dubbing in the context of extra-linguistic aspects of recreation of the film text in translation. The question of adaptation stages of a feature film with the help of duplication is touched upon.
WAYS TO TRANSLATE FOREIGN BRANDS INTO CHINESE
Authors:   Northeastern state university, Poleschuk Victoria , Pakhomova Sofya ,   Northeastern state university
Published: December 2020

This article is devoted to the analysis of the peculiarities of the translation of the names of some well-known foreign brands, in particular the ways of their translation. Translation of a foreign brand should be understandable, memorable and attractive to the consumer. There are many ways to achieve high-quality translation. The foreign brand names that we reviewed were translated into Chinese by transliteration, adaptation, literal and free translation.
ABOUT TYPOLOGY OF INTERSEMIOTIC TRANSFORMATIONS
Authors:   Moscow Region State University, FILIPPOVA IRINA
Published: December 2020

We present the author's typology of intersemiotic transformations during the intralinguistic film adaptation of literature adaptation of a work of literature empirically based on the play by M. A. Bulgakov "Ivan Vasilievich" and the film "Ivan Vasilievich changes his profession." Comparative analysis reveals the transformation of various components of the content (realities, external and personal characteristics of characters, genre features) and various degrees (transformation and deformation).
CROSS-CULTURAL SPECIFICS OF EASTERN-ASIATIC ENGLISH PRESS
Authors:   Northeastern state university, Fyodorov Vitaliy
Published: December 2020

The article envisages the content and cultural specifics of contemporary Eastern-Asiatic press in the English language to differentiate its place in socio-political life of China, Japan and Korea in the situation of cross-cultural interaction with Anglophone societies.
THE USAGE OF DIDACTIC POTENTIAL OF TRIZ IN TEACHING ENGLISH LANGUAGE AT HIGHER EDUCATION INSTITUTION
Authors:   Northeastern state university, Shumkova Anastasia
Published: December 2020

The author of the given article points out the necessity of applying the methods of problem-oriented teaching and introducing problem tasks into the modern education program at the university. As a tool for realization of the given approach, the author proposes to use the theory of solving inventive problems (TRIZ), which contributes to the development of non-trivial creative thinking of students and the prevention of psychological inertia.The article gives examples of assignments developed on the base of methods of TRIZ-pedagogics and aimed at the formation of communicative competence of junior students of language universities.