bluuebunny/crossref_metadata_2025 huggingface dataset:
Cortical and Subcortical Network Dysfunction in a Female Patient With NEXMIF Encephalopathy
Authors: Cioclu Maria Cristina , Coppola Antonietta , Tondelli Manuela , Vaudano Anna Elisabetta , Giovannini Giada , Krithika S. , Iacomino Michele , Zara Federico , Sisodiya Sanjay M. , Meletti Stefano
Published: September 2021

The developmental and epileptic encephalopathies (DEE) are the most severe group of epilepsies. Recently, NEXMIF mutations have been shown to cause a DEE in females, characterized by myoclonic–atonic epilepsy and recurrent nonconvulsive status. Here we used advanced neuroimaging techniques in a patient with a novel NEXMIF de novo mutation presenting with recurrent absence status with eyelid myoclonia, to reveal brain structural and functional changes that can bring the clinical phenotype to alteration within specific brain networks. Indeed, the alterations found in the patient involved the visual pericalcarine cortex and the middle frontal gyrus, regions that have been demonstrated to be a core feature in epilepsy phenotypes with visual sensitivity and eyelid myoclonia with absences.
Multimodal Prediction of Alzheimer's Disease Severity Level Based on Resting-State EEG and Structural MRI
Authors: Jesus Belmir , Cassani Raymundo , McGeown William J. , Cecchi Marco , Fadem K. C. , Falk Tiago H.
Published: September 2021

While several biomarkers have been developed for the detection of Alzheimer's disease (AD), not many are available for the prediction of disease severity, particularly for patients in the mild stages of AD. In this paper, we explore the multimodal prediction of Mini-Mental State Examination (MMSE) scores using resting-state electroencephalography (EEG) and structural magnetic resonance imaging (MRI) scans. Analyses were carried out on a dataset comprised of EEG and MRI data collected from 89 patients diagnosed with minimal-mild AD. Three feature selection algorithms were assessed alongside four machine learning algorithms. Results showed that while MRI features alone outperformed EEG features, when both modalities were combined, improved results were achieved. The top-selected EEG features conveyed information about amplitude modulation rate-of-change, whereas top-MRI features comprised information about cortical area and white matter volume. Overall, a root mean square error between predicted MMSE values and true MMSE scores of 1.682 was achieved with a multimodal system and a random forest regression model.
SLC25A21 Suppresses Cell Growth in Bladder Cancer via an Oxidative Stress-Mediated Mechanism
Authors: Wang Yong , Gao Jiawen , Hu Shasha , Zeng Weiting , Yang Hongjun , Chen Hui , Wang Shuang
Published: September 2021

Background

Bladder cancer (BCa) is a commonly diagnosed malignancy worldwide that has poor survival depending on its intrinsic biologic aggressiveness and a peculiar radio- and chemoresistance features. Gaining a better understanding of tumorigenesis and developing new diagnosis and treatment strategies for BCa is important for improving BCa clinical outcome. SLC25 family member 21 (SLC25A21), a carrier transporting C5-C7 oxodicarboxylates, has been reported to contribute to oxoadipate acidemia. However, the potential role of SLC25A21 in cancer remains absolutely unknown.

Methods

The expression levels of SLC25A21 in BCa and normal tissues were examined by real-time PCR and immunohistochemistry. Gain-of- and loss-of-function experiments were performed to detect the biological functions of SLC25A21 in vitro and in vivo by CCK-8 assay, plate colony formation assay, cell migration, invasion assay and experimental animal models. The subcellular distribution of substrate mediated by SLC25A21, mitochondrial membrane potential and ROS production were assessed to explore the potential mechanism of SLC25A21 in BCa.

Results

We found that the expression of SLC25A21 was downregulated in BCa tissues compared to normal tissues. A significant positive correlation between decreased SLC25A21 expression and poor prognosis was observed in BCa patients. Overexpression of SLC25A21 significantly inhibited cell proliferation, migration and invasion and induced apoptosis in vitro. Moreover, the enhanced SLC25A21 expression significantly suppressed tumor growth in a xenograft mouse model. Furthermore, we revealed that SLC25A21 suppressed BCa growth by inducing the efflux of mitochondrial α-KG to the cytosol, decreasing to against oxidative stress, and activating the ROS-mediated mitochondrion-dependent apoptosis pathway.

Conclusions

Our findings provide the first link between SLC25A21 expression and BCa and demonstrate that SLC25A21 acts as a crucial suppressor in BCa progression, which may help to provide new targets for BCa intervention.
FAIM2 Promotes Non-Small Cell Lung Cancer Cell Growth and Bone Metastasis by Activating the Wnt/β-Catenin Pathway
Authors: She Kelin , Yang Wensheng , Li Mengna , Xiong Wei , Zhou Ming
Published: September 2021

Aim

Bone metastasis is the major reason for the poor prognosis and high mortality rate of non-small cell lung cancer (NSCLC) patients. This study explored the function and underlying mechanism of Fas apoptotic inhibitory molecule 2 (FAIM2) in the bone metastasis of NSCLC.

Methods

Samples of normal lung tissue and NSCLC tissue (with or without bone metastasis) were collected and analyzed for FAIM2 expression. HARA cells with FAIM2 overexpression and HARA-B4 cells with FAIM2 knockdown were tested for proliferation, migration, invasion, anoikis, and their ability to adhere to osteoblasts. Next, whether FAIM2 facilitates bone metastasis by regulating the epithelial mesenchymal transformation (EMT) process and Wnt/β-catenin signaling pathway were investigated. Finally, an in vivo model of NSCLC bone metastasis was established and used to further examine the influence of FAIM2 on bone metastasis.

Results

FAIM2 was highly expressed in NSCLC tissues and NSCLC tissues with bone metastasis. FAIM2 expression was positively associated with the tumor stage, lymph node metastasis, bone metastasis, and poor prognosis of NSCLC. FAIM2 upregulation promoted HARA cell proliferation, migration, and invasion, but inhibited cell apoptosis. FAIM2 knockdown in HARA-B4 cells produced the opposite effects. HARA-B4 cells showed a stronger adhesive ability to osteocytes than did HARA cells. FAIM2 was found to be related to the adhesive ability of HARA and HARA-B4 cells to osteocytes. FAIM2 facilitated bone metastasis by regulating the EMT process and Wnt/β-catenin signaling pathway. Finally, FAIM2 was found to participate in regulating NSCLC bone metastasis in vivo.

Conclusions

FAIM2 promoted NSCLC cell growth and bone metastasis by regulating the EMT process and Wnt/β-catenin signaling pathway. FAIM2 might be useful for diagnosing and treating NSCLC bone metastases.
TRIM50 Suppresses Pancreatic Cancer Progression and Reverses the Epithelial-Mesenchymal Transition via Facilitating the Ubiquitous Degradation of Snail1
Authors: Li Rongkun , Zhu Lili , Peng Yangxizi , Zhang Xiaoxin , Dai Chunhua , Liu Dejun
Published: September 2021

Emerging evidence suggests that the tripartite motif (TRIM) family play important roles in tumor development and progression. Tripartite motif-containing 50 (TRIM50) is a member of the TRIM family, but little is known regarding its expression and potential functional roles in cancer. In this study, we first analyzed the expression pattern and clinical significance of TRIM50 in pancreatic cancer and found that TRIM50 expression is significantly reduced in pancreatic cancer tissues and its downregulation is associated with poor survival for pancreatic cancer patients. Functionally, TRIM50 overexpression in pancreatic cancer cells decreases their proliferation and motility capabilities and reverses the epithelial-mesenchymal transition (EMT) process, whereas TRIM50 depletion had the opposite effects. Mechanically, TRIM50 directly interacts with Snail1, a key regulator of EMT, and acts as an E3 ubiquitin ligase to target Snail1 for ubiquitous degradation. The function of TRIM50 in suppressing cell migration and EMT depends on TRIM50-promoted Snail1 degradation. In conclusion, our findings identify TRIM50 as a tumor suppressor that inhibits pancreatic cancer progression and reverses EMT via degrading Snail1 and provide new insights into the progression of pancreatic cancer.
Comprehensive Genomic Landscape in Chinese Clear Cell Renal Cell Carcinoma Patients
Authors: Huang Jiwei , Cai Wen , Cai Biao , Kong Wen , Zhai Wei , Zhang Jin , Chen Yonghui , Chen Shiqing , Bai Yuezong , Huang Yiran , Xue Wei
Published: September 2021

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC). The genomic landscape in Chinese ccRCC needs to be elucidated. Herein, we investigated the molecular features of Chinese ccRCC patients. Genomic profiling of DNA was performed through next-generation sequencing (NGS) in Chinese patients with ccRCC between January 2017 and March 2020. Clinical information including age, gender, and tumor histology was collected. Immunohistochemistry (IHC) staining for PD-L1 expression was performed using PD-L1 IHC 22C3 pharmDx assay or Ventana PD-L1 SP263 assay. Data analyses were performed using R 3.6.1. A total of 880 Chinese ccRCC patients who have undergone NGS were included in this study. The most common somatic alterations were detected in VHL (59.7%), PBRM1 (18.0%), SETD2 (12.2%), BAP1 (10.2%), and TP53 (9.4%). Compared with The Cancer Genome Atlas (TCGA) database, a higher mutation frequency of VHL (59.7% vs. 50.0%, p < 0.001) and TP53 (9.4% vs. 3.5%, p < 0.001) and a lower mutation frequency of PBRM1 (18.0% vs. 31.0%, p < 0.001) were found in the Chinese cohort. Of the 460 patients who were evaluated for PD-L1 expression, 139 (30.2%) had positive PD-L1 expression. The median tumor mutational burden (TMB) value was 4.5 muts/Mb (range, 0–46.0). Five (0.7%) patients were identified as microsatellite instability-high (MSI-H). Furthermore, 52 (5.9%) patients were identified to carry pathogenic or likely pathogenic germline mutations in 22 cancer predisposition genes. This is the first large-scale comprehensive genomic analysis for Chinese ccRCC patients, and these results might provide a better understanding of molecular features in Chinese ccRCC patients, which can lead to an improvement in the personalized treatment for these patients.
Perioperative Outcome of Robotic Approach Versus Manual Videothoracoscopic Major Resection in Patients Affected by Early Lung Cancer: Results of a Randomized Multicentric Study (ROMAN Study)
Authors: Veronesi Giulia , Abbas Abbas El-Sayed , Muriana Piergiorgio , Lembo Rosalba , Bottoni Edoardo , Perroni Gianluca , Testori Alberto , Dieci Elisa , Bakhos Charles T. , Car Shamus , Luzzi Luca , Alloisio Marco , Novellis Pierluigi
Published: September 2021

Introduction

We report the results of the first prospective international randomized control trial to compare the perioperative outcome and surgical radicality of the robotic approach with those of traditional video-assisted surgery in the treatment of early-stage lung cancer.

Methods

Patients with clinical stage T1–T2, N0–N1 non-small cell lung cancer (NSCLC) were randomly assigned to robotic-assisted thoracoscopic surgery (RATS) or video-assisted thoracic surgery (VATS) resection arms. The primary objective was the incidence of adverse events including complications and conversion to thoracotomy. The secondary objectives included extent of lymph node (LN) dissection and other indicators.

Results

This trial was closed at 83 cases as the probability of concluding in favor of the robot arm for the primary outcome was null according to the observed trend. In this study, we report the results of the analysis conducted on the patients enrolled until trial suspension. Thirty-nine cases were randomized in the VATS arm and 38 in the robotic arm. Six patients were excluded from analysis. Despite finding no difference between the two arms in perioperative complications, conversions, duration of surgery, or duration of postoperative stay, a significantly greater degree of LN assessment by the robotic technique was observed in regards to the median number of sampled LN stations [6, interquartile range (IQR) 4–6 vs. 4, IQR 3–5; p = 0.0002], hilar LNs (7, IQR 5–10 vs. 4, IQR 2–7; p = 0.0003), and mediastinal LNs (7, IQR 5–10 vs. 5, IQR 3–7; p = 0.0001).

Conclusions

The results of this trial demonstrated that RATS was not superior to VATS considering the perioperative outcome for early-stage NSCLC, but the robotic approach allowed an improvement of LN dissection. Further studies are suggested to validate the results of this trial.

Clinical Trial Registration

clinicaltrials.gov, identifier NCT02804893.
MRI-Based Radiomics Nomogram for Selecting Ovarian Preservation Treatment in Patients With Early-Stage Endometrial Cancer
Authors: Yan Bi Cong , Ma Xiao Liang , Li Ying , Duan Shao Feng , Zhang Guo Fu , Qiang Jin Wei
Published: September 2021

Background

Ovarian preservation treatment (OPT) was recommended in young women with early-stage endometrial cancer [superficial myometrial invasion (MI) and grades (G) 1/2-endometrioid adenocarcinoma (EEC)]. A radiomics nomogram was developed to assist radiologists in assessing the depth of MI and in selecting eligible patients for OPT.

Methods

From February 2014 to May 2021, 209 G 1/2-EEC patients younger than 45 years (mean 39 ± 4.3 years) were included. Of them, 104 retrospective patients were enrolled in the primary group, and 105 prospective patients were enrolled in the validation group. The radiomics features were extracted based on multi-parametric magnetic resonance imaging, and the least absolute shrinkage and selection operator algorithm was applied to reduce the dimensionality of the data and select the radiomics features that correlated with the depth of MI in G 1/2-EEC patients. A radiomics nomogram for evaluating the depth of MI was developed by combing the selected radiomics features with the cancer antigen 125 and tumor size. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the radiomics nomogram and of radiologists without and with the aid of the radiomics nomogram. The net reclassification index (NRI) and total integrated discrimination index (IDI) based on the total included patients to assess the clinical benefit of radiologists with the radiomics nomogram were calculated.

Results

In the primary group, for evaluating the depth of MI, the AUCs were 0.96 for the radiomics nomogram; 0.80 and 0.86 for radiologists 1 and 2 without the aid of the nomogram, respectively; and 0.98 and 0.98 for radiologists 1 and 2 with the aid of the nomogram, respectively. In the validation group, the AUCs were 0.88 for the radiomics nomogram; 0.82 and 0.83 for radiologists 1 and 2 without the aid of the nomogram, respectively; and 0.94 and 0.94 for radiologists 1 and 2 with the aid of the nomogram, respectively. The yielded NRI and IDI values were 0.29 and 0.43 for radiologist 1 and 0.23 and 0.37 for radiologist 2, respectively.

Conclusions

The radiomics nomogram outperformed radiologists and could help radiologists in assessing the depth of MI and selecting eligible OPTs in G 1/2-EEC patients.
Trends in Colorectal Cancer Incidence Rates in Saudi Arabia (2001–2016) Using Saudi National Registry: Early- Versus Late-Onset Disease
Authors: Alyabsi Mesnad , Algarni Mohammed , Alshammari Kanan
Published: September 2021

Early-onset (<50 years old) colorectal cancer (CRC) has been increasing worldwide and is associated with poor outcomes. Over 85% of the Saudi population are <50 years old, which put them at heightened risk of early-onset CRC. No study assessed the trends in CRC incidence rates among the Saudis. The Joinpoint Regression software by the Surveillance, Epidemiology, and End Results (SEER) program was used to estimate the magnitude and direction of CRC incidence trends by age and gender. The annual percentage change (APC) and the average annual percentage change (AAPC) between 2001 and 2016 were computed. In a sensitivity analysis, we also assessed trends using various age groups. Between 2001 and 2016, the early-onset CRC incidence (per 105) increased from 1.32 (95% CI: 1.11, 1.54) to 2.02 (95% CI: 1.83, 2.22) with AAPC (2.6, 95% CI: -0.4, 5.7). At same period, the late-onset incidence increased from 3.54 (95% CI: 3.10, 3.97) to 9.14 (95% CI: 8.62, 9.66) with AAPC (6.1, 95% CI: 3.5, 8.8). Among early-onset CRC patients, age 40–49 has the highest rates and women in this age group has higher rate than men. Our national data showed a gradual increase in CRC incidence rates, which reflect the global concern of early-onset CRC. Further research is needed to understand the etiology of early-onset CRC. Primary health care providers must be alerted about the increasing rate of early-onset CRC. To reduce the future burden of the disease, initiating CRC screening before age 50 is warranted.
Novel Methods and Approaches for Safety Evaluation of Nanoparticle Formulations: A Focus Towards In Vitro Models and Adverse Outcome Pathways
Authors: Tirumala Mounika Gayathri , Anchi Pratibha , Raja Susmitha , Rachamalla Mahesh , Godugu Chandraiah
Published: September 2021

Nanotoxicology is an emerging field employed in the assessment of unintentional hazardous effects produced by nanoparticles (NPs) impacting human health and the environment. The nanotoxicity affects the range between induction of cellular stress and cytotoxicity. The reasons so far reported for these toxicological effects are due to their variable sizes with high surface areas, shape, charge, and physicochemical properties, which upon interaction with the biological components may influence their functioning and result in adverse outcomes (AO). Thus, understanding the risk produced by these materials now is an important safety concern for the development of nanotechnology and nanomedicine. Since the time nanotoxicology has evolved, the methods employed have been majorly relied onin vitrocell-based evaluations, while these simple methods may not predict the complexity involved in preclinical and clinical conditions concerning pharmacokinetics, organ toxicity, and toxicities evidenced through multiple cellular levels. The safety profiles of nanoscale nanomaterials and nanoformulations in the delivery of drugs and therapeutic applications are of considerable concern. In addition, the safety assessment for new nanomedicine formulas lacks regulatory standards. Though thein vivostudies are greatly needed, the end parameters used for risk assessment are not predicting the possible toxic effects produced by various nanoformulations. On the other side, due to increased restrictions on animal usage and demand for the need for high-throughput assays, there is a need for developing and exploring novel methods to evaluate NPs safety concerns. The progress made in molecular biology and the availability of several modern techniques may offer novel and innovative methods to evaluate the toxicological behavior of different NPs by using single cells, cell population, and whole organisms. This review highlights the recent novel methods developed for the evaluation of the safety impacts of NPs and attempts to solve the problems that come with risk assessment. The relevance of investigating adverse outcome pathways (AOPs) in nanotoxicology has been stressed in particular.
Research Progress on the Functions and Mechanism of circRNA in Cisplatin Resistance in Tumors
Authors: Mu Qingchun , Lv Yue , Luo Chunmei , Liu Xiaojing , Huang Chunming , Xiu Youcheng , Tang Longguang
Published: September 2021

Cisplatin is a common chemotherapeutic drug that has been used to treat of numerous tumors, including testicular, lung, bladder, ovarian, liver and head and neck cancers. Although clinical chemotherapy based on cisplatin has shown a remarkable therapeutic effect, the resistance to cisplatin becomes increasingly obvious as a patient uses it for a prolonged period. It not only affects the prognosis of these tumors, but also causes the recurrence of cancer and decreases the overall survival rate. The development of cisplatin resistance involves several mechanisms, including DNA damage repair, ATP-binding cassette (ABC) transporter, autophagy, cancer stem cells (CSCs), epithelial–mesenchymal transition (EMT), and other related signaling pathways. Interestingly, these mechanisms have been found to be influenced by circular RNAs (circRNAs) to regulate tumor proliferation, invasion, chemosensitivity, and other biological behaviors in the tumor microenvironment (TME). In recent years, circRNAs in cisplatin resistance in tumors, especially lung cancer and gastric cancer, have gradually drawn peoples’ attention. This review summarizes recent studies on the functions and mechanisms of circRNAs in cisplatin resistance. We emphasize that circRNA can be used as a promising target gene to improve drug resistance and therapeutic efficacy.
Plasma Kallikrein as a Modulator of Liver Injury/Remodeling
Authors: Ahmed Ibrahim A , Jaffa Miran A , Moussa Mayssam , Hatem Duaa , El-Achkar Ghewa A , Al Sayegh Rola , Karam Mia , Hamade Eva , Habib Aida , Jaffa Ayad A
Published: September 2021

The occurrence and persistence of hepatic injury which arises from cell death and inflammation result in liver disease. The processes that lead to liver injury progression and resolution are still not fully delineated. The plasma kallikrein-kinin system (PKKS) has been shown to play diverse functions in coagulation, tissue injury, and inflammation, but its role in liver injury has not been defined yet. In this study, we have characterized the role of the PKKS at various stages of liver injury in mice, as well as the direct effects of plasma kallikrein on human hepatocellular carcinoma cell line (HepG2). Histological, immunohistochemical, and gene expression analyses were utilized to assess cell injury on inflammatory and fibrotic factors. Acute liver injury triggered by carbon tetrachloride (CCl4) injection resulted in significant upregulation of the plasma kallikrein gene (Klkb1) and was highly associated with the high mobility group box 1 gene, the marker of cell death (r = 0.75, p < 0.0005, n = 7). In addition, increased protein expression of plasma kallikrein was observed as clusters around necrotic areas. Plasma kallikrein treatment significantly increased the proliferation of CCl4-induced HepG2 cells and induced a significant increase in the gene expression of the thrombin receptor (protease activated receptor-1), interleukin 1 beta, and lectin–galactose binding soluble 3 (galectin-3) (p < 0.05, n = 4). Temporal variations in the stages of liver fibrosis were associated with an increase in the mRNA levels of bradykinin receptors: beta 1 and 2 genes (p < 0.05; n = 3–10). In conclusion, these findings indicate that plasma kallikrein may play diverse roles in liver injury, inflammation, and fibrosis, and suggest that plasma kallikrein may be a target for intervention in the states of liver injury.
Cost-Effectiveness of Frontline Treatment for Advanced Renal Cell Carcinoma in the Era of Immunotherapies
Authors: Li SiNi , Li JianHe , Peng LiuBao , Li YaMin , Wan XiaoMin
Published: September 2021

Background: Recent randomized controlled trials have demonstrated that immune checkpoint inhibitors (ICIs) improve patient outcomes, but whether these novel agents are cost-effective for untreated advanced renal cell carcinoma (aRCC) remains unclear.

Materials and Methods: A microsimulation model was created to project the healthcare costs and outcomes of six strategies (lenvatinib-plus-pembrolizumab, nivolumab-plus-cabozantinib, nivolumab-plus-ipilimumab, pembrolizumab-plus-axitinib, avelumab-plus-axitinib, and sunitinib monotherapy) for patients with aRCC. Transition probability of patients was estimated from CLEAR, CheckMate 9ER, CheckMate 214, KEYNOTE-426, JAVELIN Renal 101, and other data sets by using parametric survival modeling. Lifetime direct medical costs, life years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated from a United States payer perspective. One-way and probabilistic sensitivity analyses were performed, along with multiple scenario analyses, to evaluate model uncertainty.

Results: Of the six competing strategies, nivolumab-plus-cabozantinib yielded the most significant health outcomes, and the sunitinib strategy was the least expensive option. The cost-effective frontier consisted of the nivolumab-plus-cabozantinib, pembrolizumab-plus-axitinib, and sunitinib strategies, which displayed the ordered ICERs of $81282/QALY for pembrolizumab-plus-axitinib vs sunitinib and $453391/QALY for nivolumab-plus-cabozantinib vs pembrolizumab-plus-axitinib. The rest of the strategies, such as lenvatinib-plus-pembrolizumab, nivolumab-plus-ipilimumab, and avelumab-plus-axitinib, were dominated. The cost of sunitinib drove the model most influentially.

Conclusions: For aRCC, the pembrolizumab-plus-axitinib strategy is likely to be the most cost-effective alternative at the willingness-to-pay threshold of $100,000.
The Mechanobiology of Endothelial-to-Mesenchymal Transition in Cardiovascular Disease
Authors: Islam Shahrin , Boström Kristina I. , Di Carlo Dino , Simmons Craig A. , Tintut Yin , Yao Yucheng , Hsu Jeffrey J.
Published: September 2021

Endothelial cells (ECs) lining the cardiovascular system are subjected to a highly dynamic microenvironment resulting from pulsatile pressure and circulating blood flow. Endothelial cells are remarkably sensitive to these forces, which are transduced to activate signaling pathways to maintain endothelial homeostasis and respond to changes in the environment. Aberrations in these biomechanical stresses, however, can trigger changes in endothelial cell phenotype and function. One process involved in this cellular plasticity is endothelial-to-mesenchymal transition (EndMT). As a result of EndMT, ECs lose cell-cell adhesion, alter their cytoskeletal organization, and gain increased migratory and invasive capabilities. EndMT has long been known to occur during cardiovascular development, but there is now a growing body of evidence also implicating it in many cardiovascular diseases (CVD), often associated with alterations in the cellular mechanical environment. In this review, we highlight the emerging role of shear stress, cyclic strain, matrix stiffness, and composition associated with EndMT in CVD. We first provide an overview of EndMT and context for how ECs sense, transduce, and respond to certain mechanical stimuli. We then describe the biomechanical features of EndMT and the role of mechanically driven EndMT in CVD. Finally, we indicate areas of open investigation to further elucidate the complexity of EndMT in the cardiovascular system. Understanding the mechanistic underpinnings of the mechanobiology of EndMT in CVD can provide insight into new opportunities for identification of novel diagnostic markers and therapeutic interventions.
The Impact of Micronutrients-Calcium, Vitamin D, Selenium, Zinc in Cardiovascular Health: A Mini Review
Authors: Narayanam Harini , Chinni Suresh V. , Samuggam Sumitha
Published: September 2021

The role of micronutrients in health and disease has increased the curiosity and interest among researchers. The prime focus of this review is the significance of trace elements- calcium, vitamin D, selenium and zinc with cardiovascular health. WHO identified cardiovascular diseases (CVD) as the leading cause of deaths globally. Identifying the risk factors that could be modified and creating new treatment strategies remains to be the main concern for CVD prevention. The data that showed the relationship between trace elements and various ways in which they may contribute to cardiovascular health and disease from clinical trials and observational studies were collected from databases such as PubMed and Embase. Based on these collected data, it shows that either high or low circulating serum levels can be associated with the development of cardiovascular diseases. Micronutrients through diet contribute to improved cardiac health. However, due to our current lifestyle, there is a huge dependency on dietary supplements. Based on the observational studies, it is evident that supplements cause sudden increase in the circulating levels of the nutrients and result in cardiovascular damage. Thus, it is advisable to restrict the use of supplements, owing to the potent risks it may cause. In order to understand the exact mechanism between micronutrients and cardiac health, more clinical studies are required.
Effect of Alternate Wetting and Drying Irrigation on the Nutritional Qualities of Milled Rice
Authors: Song Tao , Das Debatosh , Zhu Fuyuan , Chen Xiaofeng , Chen Moxian , Yang Feng , Zhang Jianhua
Published: September 2021

Alternate wetting and drying (AWD) irrigation has been widely used to save irrigation water during rice production when compared to the traditionally continuous flooding (CF). Although the influence of AWD on water-saving potential and grain yield has been studied before, its detailed effect on grain nutritional quality in milled rice remains relatively unexplored. In this study, AWD could maintain grain yield as compared with CF. Thus, we undertook efforts to compare the nutritional traits of milled rice irrigated with AWD and CF regimes. A targeted metabolome assay on milled rice identified 74 differentially accumulated metabolites (DAMs) with 22 up- and 52 down-accumulated metabolites under AWD vs. CF. Clustering of the metabolite content obtained in this assay suggested that most of the metabolites showing significant changes belonged to “lipids,” “alkaloids,” and “phenolic acids.” In addition, total protein, starch, lipid, and amino acids content were measured to correlate it with the differential accumulation of specific metabolites detected in the metabolome. Overall, the data suggested that AWD may improve the nutritional performance of milled rice by increasing amino acids and phenolic acids and decreasing lipids and alkaloids. Our study provides research proof for the need for the optimization of irrigation to optimize rice nutritional qualities.
ONAC066, A Stress-Responsive NAC Transcription Activator, Positively Contributes to Rice Immunity Against Magnaprothe oryzae Through Modulating Expression of OsWRKY62 and Three Cytochrome P450 Genes
Authors: Yuan Xi , Wang Hui , Bi Yan , Yan Yuqing , Gao Yizhou , Xiong Xiaohui , Wang Jiajing , Li Dayong , Song Fengming
Published: September 2021

NAC transcriptional factors constitute a large family in rice and some of them have been demonstrated to play crucial roles in rice immunity. The present study investigated the function and mechanism of ONAC066 in rice immunity. ONAC066 shows transcription activator activity that depends on its C-terminal region in rice cells. ONAC066-OE plants exhibited enhanced resistance while ONAC066-Ri and onac066-1 plants showed attenuated resistance to Magnaporthe oryzae. A total of 81 genes were found to be up-regulated in ONAC066-OE plants, and 26 of them were predicted to be induced by M. oryzae. Four OsWRKY genes, including OsWRKY45 and OsWRKY62, were up-regulated in ONAC066-OE plants but down-regulated in ONAC066-Ri plants. ONAC066 bound to NAC core-binding site in OsWRKY62 promoter and activated OsWRKY62 expression, indicating that OsWRKY62 is a ONAC066 target. A set of cytochrome P450 genes were found to be co-expressed with ONAC066 and 5 of them were up-regulated in ONAC066-OE plants but down-regulated in ONAC066-Ri plants. ONAC066 bound to promoters of cytochrome P450 genes LOC_Os02g30110, LOC_Os06g37300, and LOC_Os02g36150 and activated their transcription, indicating that these three cytochrome P450 genes are ONAC066 targets. These results suggest that ONAC066, as a transcription activator, positively contributes to rice immunity through modulating the expression of OsWRKY62 and a set of cytochrome P450 genes to activate defense response.
Examining Approach and Avoidance Valences of the 3 X 2 Achievement Goal Types on an Engineering Student Sample: A Validity Approach
Authors: Hunsu Nathaniel , Oje Adurangba V. , Jackson Andrew , Olaogun Olanrewaju Paul
Published: September 2021

Development of the 3 × 2 achievement goal questionnaire (AGQ) advanced approach and avoidance goals in three goal types within the achievement goal framework: task-, self-, and other-based. The purpose of the present study was to examine empirical support for the construct validity, reliability, and measurement invariance of factors on the questionnaire and compare model fit of the 3 × 2 configuration to other alternatives. In addition to validating some of the findings reported in earlier studies, especially the inclusion of task-based goal orientations, the study highlights a limitation and potential boundary of the 3 × 2 AGQ. While the 3 × 2 model was found to be structurally valid, we found multiple validity supports for a definition-based model of the AGQ scale, which does not differentiate between goal approach or avoidance. The study provides some indications that approach and avoidance goals can be indistinguishable to some respondents. Nonetheless, the scale was invariant across multiple groups making group comparison possible.
The Impact of COVID-19-Induced Changes at Schools on Elementary Students' School Engagement
Authors: Thorsteinsen Kjærsti , Parks-Stamm Elizabeth J. , Olsen Marte , Kvalø Marie , Martiny Sarah E.
Published: September 2021

In spring 2020, the COVID-19 pandemic led to the shutdown of schools in many countries. Emerging research documents the negative effects of the pandemic and particularly of the shutdown of schools on children's well-being. The present research extends this research by investigating how structural changes made in schools upon reopening to align with COVID-19 restrictions were related to children's emotional school engagement and subjective well-being. An online questionnaire with elementary school children and their parents conducted in Norway in June 2020 (N = 93 parent–child dyads; 46 boys, 47 girls; mean age children = 9.70 years, SD = 1.81) assessed structural changes in schools and children's coping with these changes, emotional school engagement, subjective well-being, self-reported performance in school, and demographics. Results showed that neither receiving a new teacher nor being assigned to a new (smaller) group were associated with negative outcomes. However, children who did not like their new group showed reduced emotional school engagement and subjective well-being, indicating that specific students particularly suffered from the pandemic-induced restrictions. The relationship between liking one's group and SWB was mediated by emotional school engagement. Applied and theoretical implications are discussed.
Factors Affecting Green Agricultural Production Financing Behavior in Heilongjiang Family Farms: A Structural Equation Modeling Approach
Authors: Wang Hongli , Zhong Shen , Guo Jinguang , Fu Yu
Published: September 2021

Adhering to large-scale agricultural operations is one of the basic ways to develop green agriculture, and it is also an inevitable choice for the development of modern agriculture in the country. Among them, as a major agricultural production province in China, the development of family farms in Heilongjiang Province has a significant impact on green agriculture. Based on the theory of planned behavior (TPB), this study takes the 222-demonstration bases of family farms evaluated in Heilongjiang Province in 2019 as samples and constructs a structural equation model (SEM) to discuss the influence of participation in the family farms in green agricultural production financing behavior in-depth based on directional design, distribution, recycling, and sorting out questionnaires. The research found that the financing willingness of the farmers is determined by the attitude, subjective norms, and perceived behavior system of the family farm manager, and the financing willingness of the farmers and perceived behavioral control are determined by the financing behavior of the farmers. Among them, attitudes, subjective norms, and perceived behavioral control have a significant positive impact on financing intention and have a further effect on financing behavior. Financing willingness and perceived behavioral control have a direct effect on financial behavior and have a significant positive effect on it. This article aims to improve and enhance the financing environment for family farms to participate in green agriculture, to increase the enthusiasm of the new agricultural operators to participate in green agriculture.
The Impact of Social Support and Pregnancy on Subjective Well-Being: A Systematic Review
Authors: Battulga Buyantungalag , Benjamin Marc Reginald , Chen Hong , Bat-Enkh Enkhmandakh
Published: September 2021

Background: Subjective well-being (SWB) has a protective role in mental health maintenance and is prone to change during short stressful moments, such as pregnancy. Longstanding research suggests that social support (SS) from the partner and family members of pregnant women directly or indirectly acts as a buffer against negative mental outcomes. For happier pregnancies, it is important to understand how SS and pregnancy affect the SWB.

Objective: This review aims to examine the extended association of being pregnant and SS on the SWB of pregnant women.

Methods: A systematic review was conducted in PubMed, ScienceDirect, and Google Scholar. Articles published in peer-reviewed journals were included regardless of the year and if they had assessed the impact of at least one SWB or SS outcome among healthy pregnant women. The tools of the National Heart, Lung, and Blood Institute were used for quality assessment.

Results: Thirty-four studies that assessed the domains of SWB measurements, such as happiness, quality of life (QoL), life satisfaction, positive and negative effects, and well-being, were included and its association with either pregnancy or SS was summarized. Variable results, such as life satisfaction, happiness, and mental component of QoL, were found to be high during pregnancy, but positive emotion and physical components of QoL had decreased. Almost universally, SS during pregnancy was found to have a positive association with all measurements of SWB.

Conclusion: This study had found that, despite some arising trends, pregnancy itself does not necessarily have similar impacts on SWB across healthy pregnant women. However, SS had a significant effect on SWB.
Generalized Anxiety Disorder, Depressive Symptoms, and Sleep Problem During COVID-19 Outbreak in Ethiopia Among Police Officers: A Cross-Sectional Survey
Authors: Tsehay Mekonnen , Necho Moges , Gelaye Habtam , Beyene Abeba , Birkie Mengesha
Published: September 2021

Background: Coronavirus disease 2019 (COVID-19) is an outbreak that caused serious threats to people worldwide. Police officers are one of those frontline fighters during pandemic. Our study is the first to examine psychological health response among police officers in Ethiopia during the COVID-19 outbreak.

Methods: A cross-sectional study design with a self-administered questionnaire was conducted among police officers from Dessie town from June 20 to July 10, 2020. A total of 385 questionnaires were completed correctly accounting for 91% of the total. The data were collected by using demographic information and psychological health assessment tools. The Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder 7-item scale (GAD-7), Insomnia Severity Index (ISI), and Brief Resilient Coping Scale questionnaire were used to assess depression, anxiety, sleep, and coping status of participants.

Results: The rate of depression was found to be 28.9%. Of these, 19.7% had mild, 7.3% had moderate, 1.6 had moderate–severe, and 0.3% had severe depression symptoms. The rate of general anxiety symptoms was found to be 30.2%. Of these, 22.1% of the police officers had mild, 2.6% had moderate, and 5.5% had severe anxiety. Moreover, 13.8% of police officers had subthreshold insomnia and 2.1% had clinical (moderate–severe) insomnia. Participants who are men, married, highly resilient, and have high social support were associated with lower depression, anxiety, and insomnia scores than those of women, being single or widowed/divorced, low resilient coping score, and low social support, respectively.

Conclusion: A psychological health problem was found to be higher among police officers in Dessie town. Younger age, sex, marital status, having chronic diseases, coping, and social support with depression, general anxiety, and insomnia were found to be significantly associated with psychological health problems. There is a need for mental health services, support, and care of police officers during the pandemic.
The Relationships Among Structural Social Support, Functional Social Support, and Loneliness in Older Adults: Analysis of Regional Differences Based on a Multigroup Structural Equation Model
Authors: Li Haifeng , Wang Cong
Published: September 2021

Objective: This study investigated the relationship between structural social support and loneliness and explored whether functional social support had an intermediate role therein. It also employed a multigroup structural equation model to compare mediation models among older adults living in cities, towns, and rural areas.

Methods: Using a self-made demographics questionnaire, the structural-functional social support scale, and the 3-item UCLA loneliness scale, this study collected information from 1,325 older adults identified via convenient sampling.

Results: The results showed that as: (1) compared with older adults living in towns, older urban, and rural adults had higher structural social support and experienced less loneliness, while older adults’ functional social support showed no difference among the three regions (2) An analysis of the models of regional differences indicated that functional social support served as a full mediator in the relationship between structural social support and loneliness in urban older adults, and a partial mediator for older adults living in towns and rural areas.

Conclusion: The relationship between structural social support and loneliness is mediated by functional social support, and this mediation model varies between older adults in cities and towns/rural areas. This study helps us understand possible mechanisms through which structural social support impacts loneliness. It suggests that nursing strategies for older adults should be adjusted according to the region and direct greater focus on the function (or quality) of the social support network and older adults living in towns.
FAAH and CNR1 Polymorphisms in the Endocannabinoid System and Alcohol-Related Sleep Quality
Authors: Soundararajan Soundarya , Kazmi Narjis , Brooks Alyssa T. , Krumlauf Michael , Schwandt Melanie L. , George David T. , Hodgkinson Colin A. , Wallen Gwenyth R. , Ramchandani Vijay A.
Published: September 2021

Sleep disturbances are common among individuals with alcohol use disorder (AUD) and may not resolve completely with short-term abstinence from alcohol, potentially contributing to relapse to drinking. The endocannabinoid system (ECS) is associated with both sleep and alcohol consumption, and genetic variation in the ECS may underlie sleep-related phenotypes among individuals with AUD. In this study, we explored the influence of genetic variants in the ECS (Cannabinoid receptor 1/CNR1: rs806368, rs1049353, rs6454674, rs2180619, and Fatty Acid Amide Hydrolase/FAAH rs324420) on sleep quality in individuals with AUD (N = 497) and controls without AUD (N = 389). We assessed subjective sleep quality (from the Pittsburgh Sleep Quality Index/PSQI) for both groups at baseline and objective sleep efficiency and duration (using actigraphy) in a subset of individuals with AUD at baseline and after 4 weeks of inpatient treatment. We observed a dose-dependent relationship between alcohol consumption and sleep quality in both AUD and control groups. Sleep disturbance, a subscale measure in PSQI, differed significantly among CNR1 rs6454674 genotypes in both AUD (p = 0.015) and controls (p = 0.016). Only among controls, neuroticism personality scores mediated the relationship between genotype and sleep disturbance. Objective sleep measures (sleep efficiency, wake bouts and wake after sleep onset), differed significantly by CNR1 rs806368 genotype, both at baseline (p = 0.023, 0.029, 0.015, respectively) and at follow-up (p = 0.004, p = 0.006, p = 0.007, respectively), and by FAAH genotype for actigraphy recorded sleep duration at follow-up (p = 0.018). These relationships suggest a significant role of the ECS in alcohol-related sleep phenotypes.
Research Trends and Hotspots on Montessori Intervention in Patients With Dementia From 2000 to 2021: A Bibliometric Analysis
Authors: Zhou Ting , Qu Jiling , Sun Huiping , Xue Mengxin , Shen Yijing , Liu Yongbing
Published: September 2021

Background: Patients with dementia experience a variety of neuropsychiatric symptoms and behavioral disturbances. The Montessori method is a type of non-pharmacological intervention to care for people with dementia. However, there are few bibliometric studies on the application of Montessori methods. We aimed to analyze the hotspots and trends of research on the application of Montessori methods to the care of dementia patients.

Methods: Microsoft Office Excel, Co-Occurrence 9.9, and CiteSpace were used to analyze the articles on Montessori intervention in patients with dementia from 2000 to 2021 in China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, Web of Science core collection database, PubMed, and Scopus.

Results: A total of 23 Chinese language publications and 113 English language publications were included. The number of English language publications was on the rise, while the number of Chinese language publications was low. There are many issuing institutions which published articles in this field, mostly concentrated in universities. English language publication sources were more than Chinese language publication sources. The hot research topic in Chinese language publications and English language publications was the care of agitated behavior of dementia patients based on the Montessori method. The psychological problems of dementia patients are likely to become a hot issue of concern for scholars in Chinese. There will be a lot of research focusing on dementia patients and their family caregivers in this field.

Conclusion: The bibliometric and visualization analysis helps us understand the current research status and hotspots of Montessori intervention in dementia patients in Chinese language publications and English language publications.
Covid-19 Incidence and Mortality by Age Strata and Comorbidities in Mexico City: A Focus in the Pediatric Population
Authors: González-García Nadia , Castilla-Peón María F. , Solórzano Santos Fortino , Jiménez-Juárez Rodolfo Norberto , Martínez Bustamante Maria Elena , Minero Hibert Miguel Angel , Garduño-Espinosa Juan
Published: September 2021

Background: SARS-COV2 appears less frequently and less severely in the pediatric population than in the older age groups. There is a need to precisely estimate the specific risks for each age group to design health and education policies suitable for each population.

Objective: This study aimed to describe the risk of death in SARS-COV2 infected subjects by age group and according to the presence of comorbidities.

Methods: We analyzed data of confirmed SARS-COV2 infection cases where symptoms began between February 22th, 2020, and April 18th, 2021, as published by the General Epidemiology Direction (DGE) of the Mexican Ministry of Health. We calculated COVID-19 incidence and mortality by age group using population data from the Statistics and Population National Institute (INEGI), and estimated the association between risk of death and the presence of comorbidities.

Results: Mortality in SARS-COV2 infected people varied considerably, between 7 and 155 deaths per million per year in the under-20 age groups compared to 441 to 15,929 in the older age groups. Mortality in pediatric populations is strongly associated with comorbidities (OR: 4.6-47.9) compared to the milder association for older age groups (OR: 3.16–1.23).

Conclusion: The risk of death from SARS-COV2 infection in children is low and is strongly associated with comorbidities.