bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Somatic Genetic Alterations Using Whole-Exome Sequencing of Uterine Leiomyosarcoma Tumors
Authors: Chen Lihua , Li Jiajia , Wu Xiaohua , Zheng Zhong
Published: June 2021

Background

The genomic abnormalities associated with uterine leiomyosarcoma (uLMS) have not been fully elucidated to date.

Objective

To understand the pathogenesis of uLMS and to identify driver mutations and potential therapeutic targets in uLMS.

Methods

Three matched tumor-constitutional DNA pairs from patients with recurrent uLMS were subjected to whole-exome capture and next-generation sequencing. The role of the selected gene SHARPIN in uLMS was analyzed by the CCK-8 assay and colony formation assay after specific siRNA knockdown.

Results

We identified four genes with somatic SNVs, namely, SLC39A7, GPR19, ZNF717, and TP53, that could be driver mutations. We observed that 30.7% (4/13) of patients with uLMS had TP53 mutations as analyzed by direct sequencing. Analysis of somatic copy number variants (CNVs) showed regions of chromosomal gain at 1q21-23, 19p13, 17q21, and 17q25, whereas regions of chromosomal loss were observed at 2q35, 2q37, 1p36, 10q26, 6p22, 8q24, 11p15, 11q12, and 9p21. The SHARPIN gene was amplified in two patients and mutated in another (SHARPIN: NM_030974: exon2: c.G264C, p.E88D). Amplification of the SHARPIN gene was associated with shorter PFS and OS in soft tissue sarcoma, as shown by TCGA database analysis. Knockdown of SHARPIN expression was observed to decrease cell growth and colony formation in uterine sarcoma cell lines.

Conclusions

Exome sequencing revealed mutational heterogeneity of uLMS. The SHARPIN gene was amplified in uLMS and could be a candidate oncogene.
Roles of Long Noncoding RNAs in Conferring Glioma Progression and Treatment
Authors: Qin Jie , Jiang Chuanlu , Cai Jinquan , Meng Xiangqi
Published: June 2021

Accompanying the development of biomedicine, our knowledge of glioma, one of the most common primary intracranial carcinomas, is becoming more comprehensive. Unfortunately, patients with glioblastoma (GBM) still have a dismal prognosis and a high relapse rate, even with standard combination therapy, namely, surgical resection, postoperative radiotherapy and chemotherapy. The absence of validated biomarkers is responsible for the majority of these poor outcomes, and reliable therapeutic targets are indispensable for improving the prognosis of patients suffering from gliomas. Identification of both precise diagnostic and accurate prognostic markers and promising therapeutic targets has therefore attracted considerable attention from researchers. Encouragingly, accumulating evidence has demonstrated that long noncoding RNAs (lncRNAs) play important roles in the pathogenesis and oncogenesis of various categories of human tumors, including gliomas. Nevertheless, the underlying mechanisms by which lncRNAs regulate diverse biological behaviors of glioma cells, such as proliferation, invasion and migration, remain poorly understood. Consequently, this review builds on previous studies to further summarize the progress in the field of lncRNA regulation of gliomas over recent years and addresses the potential of lncRNAs as diagnostic and prognostic markers and therapeutic targets.
The Identification of Stemness-Related Genes in the Risk of Head and Neck Squamous Cell Carcinoma
Authors: Feng Guanying , Xue Feifei , He Yingzheng , Wang Tianxiao , Yuan Hua
Published: June 2021

Objectives

This study aimed to identify genes regulating cancer stemness of head and neck squamous cell carcinoma (HNSCC) and evaluate the ability of these genes to predict clinical outcomes.

Materials and Methods

The stemness index (mRNAsi) was obtained using a one-class logistic regression machine learning algorithm based on sequencing data of HNSCC patients. Stemness-related genes were identified by weighted gene co-expression network analysis and least absolute shrinkage and selection operator analysis (LASSO). The coefficient of LASSO was applied to construct a diagnostic risk score model. The Cancer Genome Atlas database, the Gene Expression Omnibus database, Oncomine database and the Human Protein Atlas database were used to validate the expression of key genes. Interaction network analysis was performed using String database and DisNor database. The Connectivity Map database was used to screen potential compounds. The expressions of stemness-related genes were validated using quantitative real‐time polymerase chain reaction (qRT‐PCR).

Results

TTK, KIF14, KIF18A and DLGAP5 were identified. Stemness-related genes were upregulated in HNSCC samples. The risk score model had a significant predictive ability. CDK inhibitor was the top hit of potential compounds.

Conclusion

Stemness-related gene expression profiles may be a potential biomarker for HNSCC.
Cystic Duct Carcinoma: A New Classification System and the Clinicopathological Features of 62 Patients
Authors: Nan Lingxi , Wang Changcheng , Dai Yajie , Wang Jie , Bo Xiaobo , Zhang Shulong , Zhang Dexiang , Liu Houbao , Wang Yueqi
Published: June 2021

Background

Cystic duct carcinoma (CDC) is a rare biliary malignancy with a low incidence and poor prognosis. However, the clinical landscape of the disease has not been clarified and no widely applicable classification system has been developed.

Methods

Sixty-two patients with CDC were included in this retrospective study, and a new classification system was established using imaging data. Blood indices, radiological characteristics, pathological features, surgical procedures, and overall survival data were collected. The efficacy of the new classification in predicting resectability was evaluated using receiver operating characteristic (ROC) curves, and K-means clustering and t-distributed stochastic neighbor embedding were applied to verify the conclusion.

Results

The pT stage of patients with type II CDC was significantly worse than that of type I. Patients with type II CDC were more likely to experience distant metastasis and invasion of the nervous system, vascular system, and liver. The resectability of patients with type II CDC was significantly worse than that of patients with type I CDC. Patients with type II CDC had worse prognoses. ROC curve analysis and K-means clustering revealed that the new classification could better categorize patients with CDC than currently available systems.

Conclusion

Patients with type II CDC have significantly worse clinicopathological outcomes. The new classification system has better accuracy in grouping patients with CDC.
A Lung Adenocarcinoma Patient With a Rare EGFR E709_T710delinsD Mutation Showed a Good Response to Afatinib Treatment: A Case Report and Literature Review
Authors: Wei Yu , Cui Yueli , Guo Yao , Li Lei , Zeng Liang
Published: June 2021

For advanced lung adenocarcinoma patients with common epidermal growth factor receptor (EGFR) mutations (exon 19 deletions or the exon 21 L858R mutation), tyrosine kinase inhibitors (TKIs) are the standard therapies, and achieve favorable responses. However, for the rare EGFR deletion-insertion mutation of exon 18, there is no evidence of the efficacy of EGFR TKIs. Herein, we report a lung adenocarcinoma patient harboring a rare EGFR E709_T710delinsD mutation who was treated with afatinib as the first-line therapy and achieved a progression-free survival of 23 months. After the disease progressed, the patient received almonertinib treatment and exhibited a stable disease. This case indicated that non-small cell lung cancer patients harboring the EGFR E709_T710delinsD mutation could benefit from afatinib treatment, followed with almonertinib treatment, as a potential therapeutic strategy.
Sitosterolemia With Atherosclerosis in a Child: A Case Report
Authors: Ba Hongjun , Peng Huimin , He Xiufang , Cheng Liangping , Lin Yuese , Li Xuandi , Wang Huishen , Qin Youzhen
Published: June 2021

Introduction: Sitosterolemia is a rare condition in children and is often misdiagnosed as familial hypercholesterolemia. Serious complications can result if not treated promptly and effectively. When pediatric patients are diagnosed with sitosterolemia, vascular, and cardiac studies are important to evaluate for the presence of atherosclerosis. Few cases of severe atherosclerotic heart disease in children with sitosterolemia have been reported, making this case worthy of presentation.

Case Presentation: Here, we report a case of sitosterolemia in an 8-year-old child. The patient presented with severe hypercholesterolemia and xanthoma. He was diagnosed two and a half years prior with familial hypercholesterolemia because his father had elevated cholesterol levels. After conventional treatment, the patient was dissatisfied with lipid level control and visited our hospital for further management. Genetic tests of the patient and parents found mutations in intron 7 (NM 022436.2, c.904+1G>A) and intron 9 (NM 022436.2, C. 1324+1de1G) of ABCG5. The 7 intron mutation was from his mother, and the 9 intron mutation was from his father. The patient was diagnosed with sitosterolemia.

Results: The child was treated with ezetimibe, a low plant sterol diet, and clopidogrel anticoagulant therapy. After 3 months of treatment, the blood lipid level was significantly lower.

Conclusion: Genetic testing should be completed as soon as possible to avoid misdiagnosis in children with abnormally elevated hypercholesterolemia who have a family history of elevated cholesterol. In addition, clinicians should rule out great arterial lesions and be vigilant in evaluating patients for systemic arterial disease and atherosclerosis.
Case Series: Efficacy and Safety of Hemoadsorption With HA-330 Adsorber in Septic Pediatric Patients With Cancer
Authors: Sazonov Vitaliy , Abylkassov Ramazan , Tobylbayeva Zaure , Saparov Askhat , Mironova Olga , Poddighe Dimitri
Published: June 2021

Background: Sepsis is a frequent cause of death in hospitalized patients and, in detail, in neonatal, pediatric, and adult intensive care units (ICUs). Severe sepsis has a very poor prognosis. Indeed, the mortality rate varies between 30 and 70% during the first 7–14 days. Despite a timely and appropriate therapy, the prognosis of severe sepsis is too often negative. Therefore, new therapeutic resources are under investigation in order to further improve prognosis.

Case series: Here, we reported three septic children in whom we used extracorporeal blood purification therapy with hemoadsorption device HA330 (Jafron Biomedical Co., Ltd., China), aiming to scavenge and eliminate bacterial toxins and inflammatory mediators from the blood.

Discussion and Conclusion: This small case series first showed that hemoperfusion with HA330 cartridge may be an effective and relatively safe adjunctive treatment to counterbalance the cytokine storm in septic children with hematological disorders. Further studies are needed to confirm and further support its safety and efficacy in a large number of pediatric patients.
Nanotechnology-Based Celastrol Formulations and Their Therapeutic Applications
Authors: Wagh Pushkaraj Rajendra , Desai Preshita , Prabhu Sunil , Wang Jeffrey
Published: June 2021

Celastrol (also called tripterine) is a quinone methide triterpene isolated from the root extract of Tripterygium wilfordii (thunder god vine in traditional Chinese medicine). Over the past two decades, celastrol has gained wide attention as a potent anti-inflammatory, anti-autoimmune, anti-cancer, anti-oxidant, and neuroprotective agent. However, its clinical translation is very challenging due to its lower aqueous solubility, poor oral bioavailability, and high organ toxicity. To deal with these issues, various formulation strategies have been investigated to augment the overall celastrol efficacy in vivo by attempting to increase the bioavailability and/or reduce the toxicity. Among these, nanotechnology-based celastrol formulations are most widely explored by pharmaceutical scientists worldwide. Based on the survey of literature over the past 15 years, this mini-review is aimed at summarizing a multitude of celastrol nanoformulations that have been developed and tested for various therapeutic applications. In addition, the review highlights the unmet need in the clinical translation of celastrol nanoformulations and the path forward.
Divergences in Macrophage Activation Markers Soluble CD163 and Mannose Receptor in Patients With Non-cirrhotic and Cirrhotic Portal Hypertension
Authors: Ørntoft Nikolaj Worm , Blé Michel , Baiges Anna , Ferrusquia Jose , Hernández-Gea Virginia , Turon Fanny , Magaz Marta , Møller Søren , Møller Holger Jon , Garcia-Pagan Juan Carlos , Gronbaek Henning
Published: June 2021

Introduction

Macrophages are involved in development and progression of chronic liver disease and portal hypertension. The macrophage activation markers soluble (s)CD163 and soluble mannose receptor (sMR), are associated with portal hypertension in patient with liver cirrhosis but never investigated in patients with non-cirrhotic portal hypertension. We hypothesized higher levels in cirrhotic patients with portal hypertension than patients with non-cirrhotic portal hypertension. We investigated sCD163 and sMR levels in patients with portal hypertension due to idiopathic portal hypertension (IPH) and portal vein thrombosis (PVT) in patients with and without cirrhosis.

Methods

We studied plasma sCD163 and sMR levels in patients with IPH (n = 26), non-cirrhotic PVT (n = 20), patients with cirrhosis without PVT (n = 31) and with PVT (n = 17), and healthy controls (n = 15).

Results

Median sCD163 concentration was 1.51 (95% CI: 1.24–1.83) mg/L in healthy controls, 1.96 (95% CI: 1.49–2.56) in patients with non-cirrhotic PVT and 2.16 (95% CI: 1.75–2.66) in patients with IPH. There was no difference between non-cirrhotic PVT patients and healthy controls, whereas IPH patients had significantly higher levels than controls (P < 0.05). The median sCD163 was significantly higher in the cirrhotic groups compared to the other groups, with a median sCD163 of 6.31 (95% CI: 5.16–7.73) in cirrhotics without PVT and 5.19 (95% CI: 4.18–6.46) with PVT (P < 0.01, all). Similar differences were observed for sMR.

Conclusion

Soluble CD163 and sMR levels are elevated in patients with IPH and patients with cirrhosis, but normal in patients with non-cirrhotic PVT. This suggests that hepatic macrophage activation is more driven by the underlying liver disease with cirrhosis than portal hypertension.
Regenerated Microvascular Networks in Ischemic Skeletal Muscle
Authors: Yin Hao , Arpino John-Michael , Lee Jason J. , Pickering J. Geoffrey
Published: June 2021

Skeletal muscle is the largest organ in humans. The viability and performance of this metabolically demanding organ are exquisitely dependent on the integrity of its microcirculation. The architectural and functional attributes of the skeletal muscle microvasculature are acquired during embryonic and early postnatal development. However, peripheral vascular disease in the adult can damage the distal microvasculature, together with damaging the skeletal myofibers. Importantly, adult skeletal muscle has the capacity to regenerate. Understanding the extent to which the microvascular network also reforms, and acquires structural and functional competence, will thus be critical to regenerative medicine efforts for those with peripheral artery disease (PAD). Herein, we discuss recent advances in studying the regenerating microvasculature in the mouse hindlimb following severe ischemic injury. We highlight new insights arising from real-time imaging of the microcirculation. This includes identifying otherwise hidden flaws in both network microarchitecture and function, deficiencies that could underlie the progressive nature of PAD and its refractoriness to therapy. Recognizing and overcoming these vulnerabilities in regenerative angiogenesis will be important for advancing treatment options for PAD.
Transcriptome Analysis and RNA Interference Reveal GhGDH2 Regulating Cotton Resistance to Verticillium Wilt by JA and SA Signaling Pathways
Authors: Xiong Xian-Peng , Sun Shi-Chao , Zhu Qian-Hao , Zhang Xin-Yu , Liu Feng , Li Yan-Jun , Xue Fei , Sun Jie
Published: June 2021

Verticillium wilt, caused by Verticillium dahliae, is one of the most damaging and widespread soil-borne cotton diseases. The molecular mechanisms underlying the cotton defense against V. dahliae remain largely elusive. Here, we compared the transcriptional differences between Upland cotton cultivars: one highly resistant (HR; Shidalukang 1) and one highly susceptible (HS; Junmian 1). This was done at multiple time points after V. dahliae inoculation, which identified 2010 and 1275 differentially expressed genes (DEGs) in HR and HS, respectively. Plant hormone signal transduction-related genes were enriched in HR, whereas genes related to lignin biosynthesis were enriched in both HR and HS. Weighted gene co-expression network analysis (WGCNA) using the 2868 non-redundant genes differentially expressed between the V. dahliae infected and uninfected samples in HR or HS identified 10 different gene network modules and 22 hub genes with a potential role in regulating cotton defense against V. dahliae infection. GhGDH2, encoding glutamate dehydrogenase (GDH), was selected for functional characterization. Suppressing the expression level of GhGDH2 by virus-induced gene silencing (VIGS) in HS led to inhibition of the salicylic acid (SA) biosynthesis/signaling pathways and activation of the jasmonic acid (JA) biosynthesis/signaling pathways, which resulted in an increase of 42.1% JA content and a reduction of 78.9% SA content in cotton roots, and consequently enhanced V. dahliae resistance. Our finding provides new insights on the molecular mechanisms of cotton resistance to V. dahliae infection and candidate genes for breeding V. dahliae resistance cotton cultivars by genetic modification.
Rhizospheric Bacillus spp. Rescues Plant Growth Under Salinity Stress via Regulating Gene Expression, Endogenous Hormones, and Antioxidant System of Oryza sativa L
Authors: Khan Muhammad Aaqil , Hamayun Muhammad , Asaf Sajjad , Khan Murtaza , Yun Byung-Wook , Kang Sang-Mo , Lee In-Jung
Published: June 2021

Salinity has drastically reduced crop yields and harmed the global agricultural industry. We isolated 55 bacterial strains from plants inhabiting the coastal sand dunes of Pohang, Korea. A screening bioassay showed that 14 of the bacterial isolates secreted indole-3-acetic acid (IAA), 12 isolates were capable of exopolysaccharide (EPS) production and phosphate solubilization, and 10 isolates secreted siderophores. Based on our preliminary screening, 11 bacterial isolates were tested for salinity tolerance on Luria–Bertani (LB) media supplemented with 0, 50, 100, and 150 mM of NaCl. Three bacterial isolates, ALT11, ALT12, and ALT30, had the best tolerance against elevated NaCl levels and were selected for further study. Inoculation of the selected bacterial isolates significantly enhanced rice growth attributes, viz., shoot length (22.8–42.2%), root length (28.18–59%), fresh biomass (44.7–66.41%), dry biomass (85–90%), chlorophyll content (18.30–36.15%), Chl a (29.02–60.87%), Chl b (30.86–64.51%), and carotenoid content (26.86–70%), under elevated salt stress of 70 and 140 mM. Furthermore, a decrease in the endogenous abscisic acid (ABA) content (27.9–23%) and endogenous salicylic acid (SA) levels (11.70–69.19%) was observed in inoculated plants. Antioxidant analysis revealed an increase in total protein (TP) levels (42.57–68.26%), whereas it revealed a decrease in polyphenol peroxidase (PPO) (24.63–34.57%), glutathione (GSH) (25.53–24.91%), SOA (13.88–18.67%), and LPO levels (15.96–26.06%) of bacterial-inoculated plants. Moreover, an increase in catalase (CAT) (26–33.04%), peroxidase (POD) (59.55–78%), superoxide dismutase (SOD) (13.58–27.77%), and ascorbic peroxidase (APX) (5.76–22.74%) activity was observed. Additionally, inductively coupled plasma mass spectrometry (ICP-MS) analysis showed a decline in Na+content (24.11 and 30.60%) and an increase in K+(23.14 and 15.45%) and Mg+(2.82 and 18.74%) under elevated salt stress.OsNHX1gene expression was downregulated (0.3 and 4.1-folds), whereas the gene expression ofOsPIN1A, OsCATA, andOsAPX1was upregulated by a 7–17-fold in bacterial-inoculated rice plants. It was concluded that the selected bacterial isolates, ALT11, ALT12, and ALT30, mitigated the adverse effects of salt stress on rice growth and can be used as climate smart agricultural tools in ecofriendly agricultural practices.
Unraveling the Regulatory Mechanism of Color Diversity in Camellia japonica Petals by Integrative Transcriptome and Metabolome Analysis
Authors: Fu Mingyue , Yang Xu , Zheng Jiarui , Wang Ling , Yang Xiaoyan , Tu Yi , Ye Jiabao , Zhang Weiwei , Liao Yongling , Cheng Shuiyuan , Xu Feng
Published: June 2021

Camellia japonica petals are colorful, rich in anthocyanins, and possess important ornamental, edible, and medicinal value. However, the regulatory mechanism of anthocyanin accumulation in C. japonica is still unclear. In this study, an integrative analysis of the metabolome and transcriptome was conducted in five C. japonica cultivars with different petal colors. Overall, a total of 187 flavonoids were identified (including 25 anthocyanins), and 11 anthocyanins were markedly differentially accumulated among these petals, contributing to the different petal colors in C. japonica. Moreover, cyanidin-3-O-(6″-O-malonyl) glucoside was confirmed as the main contributor to the red petal phenotype, while cyanidin-3-O-rutinoside, peonidin-3-O-glucoside, cyanidin-3-O-glucoside, and pelargonidin-3-O-glucoside were responsible for the deep coloration of the C. japonica petals. Furthermore, a total of 12,531 differentially expressed genes (DEGs) and overlapping DEGs (634 DEGs) were identified by RNA sequencing, and the correlation between the expression level of the DEGs and the anthocyanin content was explored. The candidate genes regulating anthocyanin accumulation in the C. japonica petals were identified and included 37 structural genes (especially CjANS and Cj4CL), 18 keys differentially expressed transcription factors (such as GATA, MYB, bHLH, WRKY, and NAC), and 16 other regulators (mainly including transporter proteins, zinc-finger proteins, and others). Our results provide new insights for elucidating the function of anthocyanins in C. japonica petal color expression.
A Study on Improving Customer Value Based on the Effect of Word of Mouth
Authors: Fan Juan , Dong Lingxin
Published: June 2021

The overlapping effect originates from an extension of Mendel’s law in genetics, where one of the interactions between non-alleles is called additive effect. It is more applied in studies on overlapping brand niches in marketing today, with relatively few researches on continuous customer value creation characterised by user adhesion and need matching. Based on the need matching and user adhesion that are features of the mobile Internet era, this article proposes a model for continuous customer value creation based on overlapping marketing. According to grounded theory, this article extracts three types of factors—demand effect, user effect, and overlapping marketing—that affect continuous customer value creation in the smart terminal business. From the perspective of service perception, this research explores how overlapping marketing affects product requirement matching and user adhesion based on a survey of 491 participants, and validates the theoretical model and hypotheses. It is found that overlapping marketing can effectively enhance need matching, improve user adhesion and increase customer value. This research not only addresses the confusion regarding need matching and user adhesion in the communications market, but also reveals how the smart terminal business affects continuous customer value creation in the era of the mobile Internet through overlapping marketing, combined with need matching and user adhesion.
Development of the SWB-HL: A Scale of the Subjective Well-Being of Older Adults With Hearing Loss
Authors: Humes Larry E.
Published: June 2021

The objective of this research was to develop and evaluate a self-report measure of subjective well-being (SWB) for use with older adults with hearing loss (HL). A convenience sample of 173 local volunteers between the ages of 60 and 88 years (M= 74.4; SD = 7.2 years) participated in this study. The initial 18-item version of the scale was constructed, response characteristics examined, and then subjected to factor analysis, as well as evaluation of the scales' reliability and validity. The analysis of response characteristics and subsequent factor analysis resulted in the elimination of eight of the 18 test items. The SWB-HL Total score was derived from the 10 remaining items. It was shown that the SWB-HL tapped three underlying domains interpreted as: Life Satisfaction (three items); Acceptance of Hearing Loss (Accept HL; four items); and Social Support (three items). Psychometric analysis showed very good reliability and good criterion validity was established for the 10-item SWB-HL Total score. In addition, significant differences were observed between aided and unaided SWB-HL Total scores following 4–6 weeks of hearing aid use. The SWB-HL is a 10-item self-report measure of SWB that shows good reliability and validity when used by older adults with hearing loss and reveals improved SWB following the use of hearing aids.
Bidirectional Interactions With Humpback Whale Singer Using Concrete Sound Elements
Authors: Pénitot Aline , Schwarz Diemo , Nguyen Hong Duc Paul , Cazau Dorian , Adam Olivier
Published: June 2021

We describe an art–science project called “Feral Interactions—The Answer of the Humpback Whale” inspired by humpback whale songs and interactions between individuals based on mutual influences, learning process, or ranking in the dominance hierarchy. The aim was to build new sounds that can be used to initiate acoustic interactions with these whales, not in a one-way direction, as playbacks do, but in real interspecies exchanges. Thus, we investigated how the humpback whales generate sounds in order to better understand their abilities and limits. By carefully listening to their emitted vocalizations, we also describe their acoustic features and temporal structure, in a scientific way and also with a musical approach as it is done withmusique concrète, in order to specify the types and the morphologies of whale sounds. The idea is to highlight the most precise information to generate our own sounds that will be suggested to the whales. Based on the approach developed inmusique concrète, similarities with the sounds produced by bassoon were identified and then were processed to become “concrete sound elements.” This analysis also brought us to design a new music interface that allows us to create adapted musical phrases in real-time. With this approach, interactions will be possible in both directions, from and to whales.
Systematic Review and Meta-Analysis of Fear of COVID-19
Authors: Luo Faxiang , Ghanei Gheshlagh Reza , Dalvand Sahar , Saedmoucheshi Sholeh , Li Qingyun
Published: June 2021

Background:Due to lack of preparedness of health systems, fast spread of the new virus, high mortality rates, and lack of a definite treatment, the outbreak of Coronavirus disease (COVID-19) led to high levels of fear and anxiety in different populations. In addition, isolation, mental disorders, and limitations in social interactions as a result of lockdown and travel ban increased the fear of the new coronavirus.

Methods:International databases, including Scopus, PubMed, Web of Science, and Google scholar, were searched without any time limitation, and all observational studies published in English reporting the mean of fear of COVID-19 based on the Fear of COVID-19 scale (FCV-19S) were included in the analysis. Methodological quality was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Random effects model, subgroup analysis, and meta-regression analysis were used to analyze the data. Heterogeneity across studies was examined using Cochran'sQtest andI2statistic. All the statistical analyses were conducted using R software v4.0.3.

Results:A total of 44 articles with a sample size of 52,462 were reviewed. A pooled mean of 18.57 was found for fear of COVID-19. The mean of fear of COVID-19 was higher in women than in men (20.67 vs. 18.21). The highest and lowest means of fear of COVID-19 had been found in Asia (18.36) and Australia (17.43) based on continent, and in hospital staff (19.51) and college students (17.95) based on target population, respectively. In addition, the highest and lowest means of fear of COVID-19 were related to items #1 and #3 of the scale, respectively. According to the results of meta-regression analysis, there was no significant association between the mean of fear of COVID-19 and sample size and participants' age. In addition, publication error was not significant (P= 0.721).

Conclusion:The mean of fear of COVID-19 was high around the world; therefore, it seems necessary to pay more attention to the negative effects of the COVID-19 pandemic on mental health.
A Comparative Study on the Predictive Value of Different Resting-State Functional Magnetic Resonance Imaging Parameters in Preclinical Alzheimer's Disease
Authors: Wang Sheng-Min , Kim Nak-Young , Kang Dong Woo , Um Yoo Hyun , Na Hae-Ran , Woo Young Sup , Lee Chang Uk , Bahk Won-Myong , Lim Hyun Kook
Published: June 2021

Objective: Diverse resting-state functional magnetic resonance imaging (rs-fMRI) studies showed that rs-fMRI might be able to reflect the earliest detrimental effect of cerebral beta-amyloid (Aβ) pathology. However, no previous studies specifically compared the predictive value of different rs-fMRI parameters in preclinical AD.

Methods: A total of 106 cognitively normal adults (Aβ+ group = 66 and Aβ− group = 40) were included. Three different rs-fMRI parameter maps including functional connectivity (FC), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were calculated. Receiver operating characteristic (ROC) curve analyses were utilized to compare classification performance of the three rs-fMRI parameters.

Results: FC maps showed the best classifying performance in ROC curve analysis (AUC, 0.915, p < 0.001). Good but weaker performance was achieved by using ReHo maps (AUC, 0.836, p < 0.001) and fALFF maps (AUC, 0.804, p < 0.001). The brain regions showing the greatest discriminative power included the left angular gyrus for FC, left anterior cingulate for ReHo, and left middle frontal gyrus for fALFF. However, among the three measurements, ROI-based FC was the only measure showing group difference in voxel-wise analysis.

Conclusion: Our results strengthen the idea that rs-fMRI might be sensitive to earlier changes in spontaneous brain activity and FC in response to cerebral Aβ retention. However, further longitudinal studies with larger sample sizes are needed to confirm their utility in predicting the risk of AD.
Theory of Motivated Cue-Integration and COVID-19: Between Interoception, Somatization, and Radicalization
Authors: Shalev Idit
Published: June 2021

The global dissemination of COVID-19 creates confusion and ambiguity in nearly every aspect of life, including fear of contagion, heightened awareness of the mortality of self and family members, lack of power, and distrust of experts and decision-makers. In this stressful situation, the question arises as to what mechanisms distinguish between adaptive and maladaptive self-regulation. The theory of Motivated Cue-Integration (MCI) is a novel theory of self-regulation that provides a new perspective on the effect of COVID-19 on self-regulation deficiency as an example of psychological distress. Inspired by predictive coding, social cognition, embodied cognition, and experiential approach, MCI suggests that self-regulation is based on interaction between (1) high-level values and goals, (2) low-level interoceptive and exteroceptive signals, and (3) trust in epistemic authority or a significant other. Motivated Cue-Integration posits that individuals create meaning by making moment-to-moment predictions that affect their interpretation of the experience of ambiguity influenced by their relationship with epistemic authority. According to MCI, deficiency in self-regulation during COVID-19 could result either from over-sensitivity or under-sensitivity to low-level interoceptive and exteroceptive cues; rigidity or ambiguity of high-level goals, poor integration between the two levels of processing as well as distrust in epistemic authority. According to MCI, variations of these deficiencies may occur in various clinical phenomena such as alexithymia and somatization, as well as in social phenomena such as goal radicalization. Based on this reasoning, MCI claims that the mentalization of the relationship between interoceptive cues, exteroceptive cues, goals, and psychological needs of the person, as well as the improvement of confidence in epistemic authority, can promote adaptive self-regulation. Psychological intervention can foster trust in epistemic authority, increase the mentalization of interoceptive and exteroceptive cues, and their association with adaptive goals. As such, the integration of these elements in a way that facilitates incentives pathways and insight fosters a more integrated subjective experience, higher clarity of emotion, and positive internal dialogue which promotes action tendency.
Toxoplasma gondii, Suicidal Behavior, and Intermediate Phenotypes for Suicidal Behavior
Authors: Postolache Teodor T. , Wadhawan Abhishek , Rujescu Dan , Hoisington Andrew J. , Dagdag Aline , Baca-Garcia Enrique , Lowry Christopher A. , Okusaga Olaoluwa O. , Brenner Lisa A.
Published: June 2021

Within the general literature on infections and suicidal behavior, studies onToxoplasma gondii(T. gondii) occupy a central position. This is related to the parasite's neurotropism, high prevalence of chronic infection, as well as specific and non-specific behavioral alterations in rodents that lead to increased risk taking, which are recapitulated in humans byT. gondii'sassociations with suicidal behavior, as well as trait impulsivity and aggression, mental illness and traffic accidents. This paper is a detailed review of the associations betweenT. gondiiserology and suicidal behavior, a field of study that started 15 years ago with our publication of associations betweenT. gondiiIgG serology and suicidal behavior in persons with mood disorders. This “legacy” article presents, chronologically, our primary studies in individuals with mood disorders and schizophrenia in Germany, recent attempters in Sweden, and in a large cohort of mothers in Denmark. Then, it reviews findings from all three meta-analyses published to date, confirming our reported associations and overall consistent in effect size [ranging between 39 and 57% elevation of odds of suicide attempt inT. gondiiimmunoglobulin (IgG) positives]. Finally, the article introduces certain links betweenT. gondiiand biomarkers previously associated with suicidal behavior (kynurenines, phenylalanine/tyrosine), intermediate phenotypes of suicidal behavior (impulsivity, aggression) and state-dependent suicide risk factors (hopelessness/dysphoria, sleep impairment). In sum, an abundance of evidence supports a positive link between suicide attempts (but not suicidal ideation) andT. gondiiIgG (but not IgM) seropositivity and serointensity. Trait impulsivity and aggression, endophenotypes of suicidal behavior have also been positively associated withT. gondiiseropositivity in both the psychiatrically healthy as well as in patients with Intermittent Explosive Disorder. Yet, causality has not been demonstrated. Thus, randomized interventional studies are necessary to advance causal inferences and, if causality is confirmed, to provide hope that an etiological treatment for a distinct subgroup of individuals at an increased risk for suicide could emerge.
Community-Based Interventions as Opportunities to Increase HIV Self-Testing and Linkage to Care Among Men Who Have Sex With Men – Lessons From Ghana, West Africa
Authors: Abubakari Gamji M'Rabiu , Turner DeAnne , Ni Zhao , Conserve Donaldson F. , Dada Debbie , Otchere Amma , Amanfoh Yaw , Boakye Francis , Torpey Kwasi , Nelson LaRon E.
Published: June 2021

MSM in Ghana encounter challenges in accessing HIV services and may experience barriers to HIV self-testing due to multiple forms of stigma present in health care settings. We worked with community-based organization partners to implement three interventions that successfully engaged and retained MSM which provides an opportunity for linkage to self-testing and medical care. These interventions were (1) Many Men Many Voices (3MV) a locally-led culturally grounded group-level HIV prevention program, (2) Auntie's Corner: a mobile-app based connecting MSM to health monitoring by a registered nurse and (3) HIV Education, Empathy, & Empowerment (HIVE3): a mobile-app based peer support intervention for MSM living with HIV. The 3MV intervention may be effective in improving HIV self-testing due to its effectiveness in engaging MSM, increasing HIV testing, and improving MSM understanding of the need for HIV testing. The utilization of apps like Auntie's Corner could positively impact HIV self-testing among MSM because it increases contact with nurses and reporting of symptoms. In HIVE3, participants expressed appreciation of the security and privacy that protects their identities as MSM and the peer mentors' abilities to make referrals to the nurses in Auntie's Corners. The confidentiality component has proven key among MSM and connecting MSM to self-testing through apps to report their process and receive care could increase utilization. Together, we show the efficacy of using the community-engaged process in reaching and engaging highly stigmatized populations like Ghana and sub-Saharan Africa, and its potential in increasing HIV self-testing and linkage to HIV care.
The Impact of Armed Conflict on the Epidemiological Situation of COVID-19 in Libya, Syria and Yemen
Authors: Daw Mohamed A.
Published: June 2021

Background: Since the Arab uprising in 2011, Libya, Syria and Yemen have gone through major internal armed conflicts. This resulted in large numbers of deaths, injuries, and population displacements, with collapse of the healthcare systems. Furthermore, the situation was complicated by the emergence of COVID-19 as a global pandemic, which made the populations of these countries struggle under unusual conditions to deal with both the pandemic and the ongoing wars. This study aimed to determine the impact of the armed conflicts on the epidemiology of the novel coronavirus (SARS-CoV-2) within these war-torn countries and highlight the strategies needed to combat the spread of the pandemic and its consequences.

Methods: Official and public data concerning the dynamics of the armed conflicts and the spread of SARS-COV-2 in Libya, Syria and Yemen were collected from all available sources, starting from the emergence of COVID-19 in each country until the end of December 2020. Datasets were analyzed by a set of statistical techniques and the weekly resolved data were used to probe the link between the intensity levels of the conflict and the prevalence of COVID-19.

Results: The data indicated that there was an increase in the intensity of the violence at an early stage from March to August 2020, when it approximately doubled in the three countries, particularly in Libya. During that period, few cases of COVID-19 were reported, ranging from 5 to 53 cases/day. From September to December 2020, a significant decline in the intensity of the armed conflicts was accompanied by steep upsurges in the rate of COVID-19 cases, which reached up to 500 cases/day. The accumulative cases vary from one country to another during the armed conflict. The highest cumulative number of cases were reported in Libya, Syria and Yemen.

Conclusions: Our analysis demonstrates that the armed conflict provided an opportunity for SARS-CoV-2 to spread. The early weeks of the pandemic coincided with the most intense period of the armed conflicts, and few cases were officially reported. This indicates undercounting and hidden spread during the early stage of the pandemic. The pandemic then spread dramatically as the armed conflict declined, reaching its greatest spread by December 2020. Full-blown transmission of the COVID-19 pandemic in these countries is expected. Therefore, urgent national and international strategies should be implemented to combat the pandemic and its consequences.
Talent Identification in an English Premiership Rugby Union Academy: Multidisciplinary Characteristics of Selected and Non-selected Male Under-15 Players
Authors: Dimundo Francesco , Cole Matthew , Blagrove Richard C. , McAuley Alexander B. T. , Till Kevin , Kelly Adam L.
Published: June 2021

Entry into an academy can be a defining moment for a promising young player. The aim of this study was to explore the multidimensional characteristics that differentiated selected and non-selected male under-15 rugby union players at an English Premiership academy. Seventy-four players (mean age 14.6 ± 0.3 years: selected n = 29; non-selected n = 45) were measured across nine characteristics from four overarching factors: (a) anthropometric (n = 2), (b) physiological (n = 5), (c) cognitive (n = 1), and (d) birth quartile. An ANOVA compared differences between groups (selected vs. non-selected), whilst a Welch's t-test and Cohen's d were used for further comparisons. A multivariate logistic regression was also used to predict selection. Results showed significant differences between selected and non-selected players for anthropometric (P = 0.021) and physiological factors (P < 0.001). Moreover, relatively older players were overrepresented with 65% born in the first half of the year, whereas no significant differences were apparent for the cognitive test. More specifically, selected players possessed greater body mass (P = 0.022, d = 0.5) and handgrip strength (P = 0.020, d = 0.5) compared to non-selected players, whilst multivariate analysis showed the 20 m sprint explained 25.4% of the variance (P = 0.001). Overall, it appears selection into an English Premiership rugby union academy may be due to enhanced physical attributes rather than cognitive abilities.
Anticonjugation and Antibiofilm Evaluation of Probiotic Strains Lactobacillus plantarum 22F, 25F, and Pediococcus acidilactici 72N Against Escherichia coli Harboring mcr-1 Gene
Authors: Apiwatsiri Prasert , Pupa Pawiya , Yindee Jitrapa , Niyomtham Waree , Sirichokchatchawan Wandee , Lugsomya Kittitat , Shah Asad Ali , Prapasarakul Nuvee
Published: June 2021

Several species of lactic acid bacteria (LAB) are commonly used as probiotics and as an alternative to antibiotics in various industries, especially in the livestock industry. This study aimed to investigate the anticonjugation and antibiofilm activity of cell-free supernatant (CFS) of Thai LAB strains (Lactobacillus plantarum 22F, 25F, and Pediococcus acidilactici 72N) against colistin-resistant Escherichia coli isolates. A total of six colistin-resistant E. coli strains were isolated from different sources, including pigs, farmers, and farmhouse environments. The E. coli were characterized by plasmid profiling, PCR detection of mcr-1 gene, and antibiotic susceptibility patterns. The CFS at dilutions ≥1:16 was chosen as the proper dilution for anticonjugation assay. Besides, it could significantly reduce the transfer frequencies of resistance gene mcr-1 up to 100 times compared to the neutralizing CFS (pH 6.5). The biofilm production in the planktonic stage was reduced by non-neutralizing and neutralizing CFS determining with crystal violet staining assay up to 82 and 60%, respectively. Moreover, the non-neutralizing CFS also inhibited the biofilm formation in the sessile stage up to 52%. The biofilm illustration was confirmed by scanning electron microscopy (SEM). These results agreed with the findings of the crystal violet technique, which showed a significant reduction in cell density, aggregation, and extracellular polysaccharide (EPS) matrix. The application of Thai LAB may serve as an attractive alternative to antibiotics for reducing biofilm formation and limiting the proliferation of antibiotic-resistant genes.
Preventive Hoof Trimming and Animal-Based Welfare Measures Influence the Time to First Lameness Event and Hoof Lesion Prevalence in Dairy Cows
Authors: Sadiq Mohammed B. , Ramanoon Siti Z. , Shaik Mossadeq Wan Mastura M. , Mansor Rozaihan , Syed-Hussain Sharifah S.
Published: June 2021

Background: The objectives of this study were to, (1) investigate the impact of the Dutch five-step hoof trimming (HT) technique on time to lameness and hoof lesion prevalence in grazing (GR) and non-grazing (NGR) dairy cows, and (2) determine the association between potential benefits of HT and animal-based welfare measures during lactation. A total of 520 non-lame cows without hoof lesions from 5 dairy farms (GR = 2, NGR = 3) were enrolled at early (within 30 days in milk; DIM) and late lactation (above 200 DIM), and randomly allocated to either trimmed (HGR or HNGR) or control groups (CON-GR and CON-NGR). Locomotion scores, body condition, hock condition, leg hygiene, and hoof health were assessed at monthly intervals until the following 270 days in milk. The data were analyzed using Kaplan-Meier survival analysis, multivariable Cox, and logistic regression models. The overall incidence rate of lameness was 36.2 cases/100 cows/month, with corresponding rates of 27.4, 31.9, 48.4, and 45.8 cases/100 cows/month in HGR, HNGR, CON-GR, and CON-NGR, respectively. Time to first lameness event was significantly higher in HGR (mean ± S.E; 8.12 ± 0.15) compared to CON-GR (7.36 ± 0.26), and in HNGR (8.05 ± 0.16) compared to CON-NGR (7.39 ± 0.23). The prevalence of hoof lesions in the enrolled cows was 36.9%, with a higher occurrence in CON-GR (48.8%) than HGR (23.2%), and in CON-NGR (52.6%) compared to HNGR (32.2%). The majority of hoof lesions were non-infectious in grazing (HGR vs. CON-GR; 21.3 vs. 33.3%) and non-grazing herds (HNGR vs. CON-NGR; 25.0 vs. 40.4%). The risk of lameness was higher in underconditioned cows (Hazard ratio; HR = 3.1, 95% CI 1.2–7.4), presence of hoof lesion (HR = 33.1, 95% CI 17.6–62.5), and there was variation between farms. Aside HT, lower parity (OR = 0.4, 95% CI 0.2–0.8), normal hock condition (OR = 0.06; 95% 0.01–0.29), and absence of overgrown hoof (OR = 0.4; 95% 0.2–0.7) were protective against non-infectious hoof lesions. Functional HT is beneficial as a lameness preventive strategy during lactation; however, ensuring older cows are in good body condition and free from hock injuries are equally important.