bluuebunny/crossref_metadata_2025 huggingface dataset:
The Autism Phenome Project: Toward Identifying Clinically Meaningful Subgroups of Autism
Authors: Nordahl Christine Wu , Andrews Derek Sayre , Dwyer Patrick , Waizbard-Bartov Einat , Restrepo Bibiana , Lee Joshua K. , Heath Brianna , Saron Clifford , Rivera Susan M. , Solomon Marjorie , Ashwood Paul , Amaral David G.
Published: January 2022

One of the most universally accepted facts about autism is that it is heterogenous. Individuals diagnosed with autism spectrum disorder have a wide range of behavioral presentations and a variety of co-occurring medical and mental health conditions. The identification of more homogenous subgroups is likely to lead to a better understanding of etiologies as well as more targeted interventions and treatments. In 2006, we initiated the UC Davis MIND Institute Autism Phenome Project (APP) with the overarching goal of identifying clinically meaningful subtypes of autism. This ongoing longitudinal multidisciplinary study now includes over 400 children and involves comprehensive medical, behavioral, and neuroimaging assessments from early childhood through adolescence (2–19 years of age). We have employed several strategies to identify sub-populations within autistic individuals: subgrouping by neural, biological, behavioral or clinical characteristics as well as by developmental trajectories. In this Mini Review, we summarize findings to date from the APP cohort and describe progress made toward identifying meaningful subgroups of autism.
Measuring Arterial Pulsatility With Dynamic Inflow Magnitude Contrast
Authors: Whittaker Joseph R. , Fasano Fabrizio , Venzi Marcello , Liebig Patrick , Gallichan Daniel , Möller Harald E. , Murphy Kevin
Published: January 2022

The pulsatility of blood flow through cerebral arteries is clinically important, as it is intrinsically associated with cerebrovascular health. In this study we outline a new MRI approach to measuring the real-time pulsatile flow in cerebral arteries, which is based on the inflow phenomenon associated with fast gradient-recalled-echo acquisitions. Unlike traditional phase-contrast techniques, this new method, which we dub dynamic inflow magnitude contrast (DIMAC), does not require velocity-encoding gradients as sensitivity to flow velocity is derived purely from the inflow effect. We achieved this using a highly accelerated single slice EPI acquisition with a very short TR (15 ms) and a 90° flip angle, thus maximizing inflow contrast. We simulate the spoiled GRE signal in the presence of large arteries and perform a sensitivity analysis. The sensitivity analysis demonstrates that in the regime of high inflow contrast, DIMAC shows much greater sensitivity to flow velocity over blood volume changes. We support this theoretical prediction with in-vivo data collected in two separate experiments designed to demonstrate the utility of the DIMAC signal contrast. We perform a hypercapnia challenge experiment in order to experimentally modulate arterial tone within subjects, and thus modulate the arterial pulsatile flow waveform. We also perform a thigh-cuff release challenge, designed to induce a transient drop in blood pressure, and demonstrate that the continuous DIMAC signal captures the complex transient change in the pulsatile and non-pulsatile components of flow. In summary, this study proposes a new role for a well-established source of MR image contrast and demonstrates its potential for measuring both steady-state and dynamic changes in arterial tone.
Polyphenols and ω-3 PUFAs: Beneficial Outcomes to Obesity and Its Related Metabolic Diseases
Authors: Siroma Thais Keiko , Machate David Johane , Zorgetto-Pinheiro Verônica Assalin , Figueiredo Priscila Silva , Marcelino Gabriela , Hiane Priscila Aiko , Bogo Danielle , Pott Arnildo , Cury Elenir Rose Jardim , Guimarães Rita de Cássia Avellaneda , Vilela Marcelo Luiz Brandão , Ferreira Rosângela dos Santos , Nascimento Valter Aragão do
Published: January 2022

Obesity is associated with the leading causes of death in the worldwide. On the other hand, the intake of vegetables, fruits and fish is related to the reduction of obesity and other metabolic syndromes. This review aims to highlight the role of ingestion of polyphenols and omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in reducing obesity and related metabolic diseases (RMDs). The consumption of vegetables, fish and by-products rich in polyphenols and α-linolenic acid (ALA), as well as oils rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with a decrease in obesity and its RMDs in consumers. Furthermore, we discussed the adequate amount of extracts, powder, polyphenols, ω-3 PUFAs administrated in animal models and human subjects, and the relevant outcomes obtained. Thus, we appeal to the research institutions and departments of the Ministries of Health in each country to develop a food education joint project to help schools, businesses and families with the aim of reducing obesity and other metabolic diseases.
Efficacy and Safety of Ketone Supplementation or Ketogenic Diets for Alzheimer's Disease: A Mini Review
Authors: Lilamand Matthieu , Mouton-Liger François , Di Valentin Emmanuelle , Sànchez Ortiz Marta , Paquet Claire
Published: January 2022

Alzheimer's disease (AD) is the most frequent age-related neurodegenerative disorder, with no curative treatment available so far. Alongside the brain deposition of β-amyloid peptide and hyperphosphorylated tau, neuroinflammation triggered by the innate immune response in the central nervous system, plays a central role in the pathogenesis of AD. Glucose usually represents the main fuel for the brain. Glucose metabolism has been related to neuroinflammation, but also with AD lesions. Hyperglycemia promotes oxidative stress and neurodegeneration. Insulinoresistance (e.g., in type 2 diabetes) or low IGF-1 levels are associated with increased β-amyloid production. However, in the absence of glucose, the brain may use another fuel: ketone bodies (KB) produced by oxidation of fatty acids. Over the last decade, ketogenic interventions i.e., ketogenic diets (KD) with very low carbohydrate intake or ketogenic supplementation (KS) based on medium-chain triglycerides (MCT) consumption, have been studied in AD animal models, as well as in AD patients. These interventional studies reported interesting clinical improvements in animals and decrease in neuroinflammation, β-amyloid and tau accumulation. In clinical studies, KS and KD were associated with better cognition, but also improved brain metabolism and AD biomarkers. This review summarizes the available evidence regarding KS/KD as therapeutic options for individuals with AD. We also discuss the current issues and potential adverse effects associated with these nutritional interventions. Finally, we propose an overview of ongoing and future registered trials in this promising field.
Hydroxytyrosol Benefits Boar Semen Quality via Improving Gut Microbiota and Blood Metabolome
Authors: Han Hui , Zhong Ruqing , Zhou Yexun , Xiong Bohui , Chen Liang , Jiang Yue , Liu Lei , Sun Haiqing , Tan Jiajian , Tao Fuping , Zhao Yong , Zhang Hongfu
Published: January 2022

Semen quality is one of the most important factors for the success of artificial insemination which has been widely applied in swine industry to take the advantages of the superior genetic background and higher fertility capability of boars. Hydroxytyrosol (HT), a polyphenol, has attracted broad interest due to its strong antioxidant, anti-inflammatory, and antibacterial activities. Sperm plasma membrane contains a large proportion of polyunsaturated fatty acids which is easily impaired by oxidative stress and thus to diminish semen quality. In current investigation, we aimed to explore the effects of dietary supplementation of HT on boar semen quality and the underlying mechanisms. Dietary supplementation of HT tended to increase sperm motility and semen volume/ejaculation. And the follow-up 2 months (without HT, just basal diet), the semen volume was significantly more while the abnormal sperm was less in HT group than that in control group. HT increased the “beneficial microbes” Bifidobacterium, Lactobacillus, Eubacterium, Intestinimonas, Coprococcus, and Butyricicoccus, however, decreased the relative abundance of “harmful microbes” Streptococcus, Oscillibacter, Clostridium_sensu_stricto, Escherichia, Phascolarctobacterium, and Barnesiella. Furthermore, HT increased plamsa steroid hormones such as testosterone and its derivatives, and antioxidant molecules while decreased bile acids and the derivatives. All the data suggest that HT improves gut microbiota to benefit plasma metabolites then to enhance spermatogenesis and semen quality. HT may be used as dietary additive to enhance boar semen quality in swine industry.
DNA Methylation-Driven Genes for Developing Survival Nomogram for Low-Grade Glioma
Authors: Guo Yingyun , Li Yuan , Li Jiao , Tao Weiping , Dong Weiguo
Published: January 2022

Low-grade gliomas (LGG) are heterogeneous, and the current predictive models for LGG are either unsatisfactory or not user-friendly. The objective of this study was to establish a nomogram based on methylation-driven genes, combined with clinicopathological parameters for predicting prognosis in LGG. Differential expression, methylation correlation, and survival analysis were performed in 516 LGG patients using RNA and methylation sequencing data, with accompanying clinicopathological parameters from The Cancer Genome Atlas. LASSO regression was further applied to select optimal prognosis-related genes. The final prognostic nomogram was implemented together with prognostic clinicopathological parameters. The predictive efficiency of the nomogram was internally validated in training and testing groups, and externally validated in the Chinese Glioma Genome Atlas database. Three DNA methylation-driven genes, ARL9, CMYA5, and STEAP3, were identified as independent prognostic factors. Together with IDH1 mutation status, age, and sex, the final prognostic nomogram achieved the highest AUC value of 0.930, and demonstrated stable consistency in both internal and external validations. The prognostic nomogram could predict personal survival probabilities for patients with LGG, and serve as a user-friendly tool for prognostic evaluation, optimizing therapeutic regimes, and managing LGG patients.
Preoperative Contrast-Enhanced MRI in Differentiating Glioblastoma From Low-Grade Gliomas in The Cancer Imaging Archive Database: A Proof-of-Concept Study
Authors: Zhang Huangqi , Zhang Binhao , Pan Wenting , Dong Xue , Li Xin , Chen Jinyao , Wang Dongnv , Ji Wenbin
Published: January 2022

Purpose

This study aimed to develop a repeatable MRI-based machine learning model to differentiate between low-grade gliomas (LGGs) and glioblastoma (GBM) and provide more clinical information to improve treatment decision-making.

Methods

Preoperative MRIs of gliomas from The Cancer Imaging Archive (TCIA)–GBM/LGG database were selected. The tumor on contrast-enhanced MRI was segmented. Quantitative image features were extracted from the segmentations. A random forest classification algorithm was used to establish a model in the training set. In the test phase, a random forest model was tested using an external test set. Three radiologists reviewed the images for the external test set. The area under the receiver operating characteristic curve (AUC) was calculated. The AUCs of the radiomics model and radiologists were compared.

Results

The random forest model was fitted using a training set consisting of 142 patients [mean age, 52 years ± 16 (standard deviation); 78 men] comprising 88 cases of GBM. The external test set included 25 patients (14 with GBM). Random forest analysis yielded an AUC of 1.00 [95% confidence interval (CI): 0.86–1.00]. The AUCs for the three readers were 0.92 (95% CI 0.74–0.99), 0.70 (95% CI 0.49–0.87), and 0.59 (95% CI 0.38–0.78). Statistical differences were only found between AUC and Reader 1 (1.00 vs. 0.92, respectively; p = 0.16).

Conclusion

An MRI radiomics-based random forest model was proven useful in differentiating GBM from LGG and showed better diagnostic performance than that of two inexperienced radiologists.
Identification and Validation of a Novel Six-lncRNA-Based Prognostic Model for Lung Adenocarcinoma
Authors: Yang Lingge , Wu Yuan , Xu Huan , Zhang Jingnan , Zheng Xinjie , Zhang Long , Wang Yongfang , Chen Weiyu , Wang Kai
Published: January 2022

Objective

This study was conducted in order to establish a long non-coding RNA (lncRNA)-based model for predicting overall survival (OS) in patients with lung adenocarcinoma (LUAD).

Methods

Original RNA-seq data of LUAD samples were extracted from The Cancer Genome Atlas (TCGA) database. Univariate Cox survival analysis was performed to select lncRNAs associated with OS. The least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox analysis were performed for building an OS-associated lncRNA prognostic model. Moreover, receiver operating characteristic (ROC) curves were generated to assess predictive values of the hub lncRNAs. Consequently, qRT-PCR was conducted to validate its prognostic value. The potential roles of these lncRNAs in immunotherapy and anti-angiogenic therapy were also investigated.

Results

The lncRNA-associated risk score of OS (LARSO) was established based on the LASSO coefficient of six individual lncRNAs, including CTD-2124B20.2, CTD-2168K21.1, DEPDC1-AS1, RP1-290I10.3, RP11-454K7.3, and RP11-95M5.1. Kaplan–Meier analysis revealed that LUAD patients with higher LARSO values had a shorter OS. Furthermore, a new risk score (NRS), including LARSO, stage, and N stage, could better predict the prognosis of LUAD patients compared with LARSO alone. Evaluation of the prognostic model in our cohort demonstrated that patients with higher scores had a worse prognosis. In addition, correlation analysis between these six lncRNAs and immune checkpoints or anti-angiogenic targets suggested that LUAD patients with high LARSO might not be sensitive to immunotherapy or anti-angiogenic therapy.

Conclusions

This robust six-lncRNA prognostic signature may be used as a novel and powerful prognostic biomarker for lung adenocarcinoma.
Mutations in JAK/STAT and NOTCH1 Genes Are Enriched in Post-Transplant Lymphoproliferative Disorders
Authors: Butzmann Alexandra , Sridhar Kaushik , Jangam Diwash , Song Hanbing , Singh Amol , Kumar Jyoti , Chisholm Karen M. , Pinsky Benjamin , Huang Franklin , Ohgami Robert S.
Published: January 2022

Post-transplant lymphoproliferative disorders (PTLD) are diseases occurring in immunocompromised patients after hematopoietic stem cell transplantation (HCT) or solid organ transplantation (SOT). Although PTLD occurs rarely, it may be associated with poor outcomes. In most cases, PTLD is driven by Epstein-Barr virus (EBV) infection. Few studies have investigated the mutational landscape and gene expression profile of PTLD. In our study, we performed targeted deep sequencing and RNA-sequencing (RNA-Seq) on 16 cases of florid follicular hyperplasia (FFH) type PTLD and 15 cases of other PTLD types that include: ten monomorphic (M-PTLD), three polymorphic (P-PTLD), and two classic Hodgkin lymphoma type PTLDs (CHL-PTLD). Our study identified recurrent mutations in JAK3 in five of 15 PTLD cases and one of 16 FFH-PTLD cases, as well as 16 other genes that were mutated in M-PTLD, P-PTLD, CHL-PTLD and FFH-PTLD. Digital image analysis demonstrated significant differences in single cell area, major axis, and diameter when comparing cases of M-PTLD and P-PTLD to FFH-PTLD. No morphometric relationship was identified with regards to a specific genetic mutation. Our findings suggest that immune regulatory pathways play an essential role in PTLD, with the JAK/STAT pathway affected in many PTLDs.
Impact of Anticipated Awake Surgery on Psychooncological Distress in Brain Tumor Patients
Authors: Staub-Bartelt Franziska , Radtke Oliver , Hänggi Daniel , Sabel Michael , Rapp Marion
Published: January 2022

Background

Brain tumor patients present high rates of distress, anxiety, and depression, in particular perioperatively. For resection of eloquent located cerebral lesions, awake surgery is the gold standard surgical method for the preservation of speech and motor function, which might be accompanied by increased psychological distress. The aim of the present study was to analyze if patients who are undergoing awake craniotomy suffer from increased prevalence or higher scores in distress, anxiety, or depression.

Methods

Patients, who were electively admitted for brain tumor surgery at our neurooncological department, were perioperatively screened regarding distress, anxiety, and quality of life using three established self-assessment instruments (Hospital Anxiety and Depression Scale, distress thermometer, and European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30-BN20). Screening results were correlated regarding operation technique (awake vs. general anesthesia). Retrospective statistical analyses for nominal variables were conducted using chi-square test. Metric variables were analyzed using the Kruskal–Wallis test, the Mann–Whitney U-test, and independent-samples t-tests.

Results

Data from 54 patients (26 male and 28 female) aged 29 to 82 years were available for statistical analyses. A total of 37 patients received primary resection and 17 recurrent tumor resection. Awake surgery was performed in 35 patients. There was no significant difference in awake versus non-awake surgery patients regarding prevalence (of distress (p = 0.465), anxiety (p = 0.223), or depression (p = 0.882). Furthermore, awake surgery had no significant influence on distress thermometer score (p = 0.668), anxiety score (p = 0.682), or depression score (p = 0.630) as well as future uncertainty (p = 0.436) or global health status (p = 0.943). Additionally, analyses revealed that primary or recurrent surgery also did not have any significant influence on the prevalence or scoring of the evaluated items.

Conclusion

Analyses of our cohort’s data suggest that planned awake surgery might not have a negative impact on patients concerning the prevalence and severity of manifestation of distress, anxiety, or depression in psychooncological screening. Patients undergoing recurrent surgery tend to demonstrate increased distress, although results were not significant.
Cold Atmospheric Plasma Attenuates Breast Cancer Cell Growth Through Regulation of Cell Microenvironment Effectors
Authors: Aggelopoulos Christos A. , Christodoulou Anna-Maria , Tachliabouri Myrsini , Meropoulis Stauros , Christopoulou Maria-Elpida , Karalis Theodoros T. , Chatzopoulos Athanasios , Skandalis Spyros S.
Published: January 2022

Breast cancer exists in multiple subtypes some of which still lack a targeted and effective therapy. Cold atmospheric plasma (CAP) has been proposed as an emerging anti-cancer treatment modality. In this study, we investigated the effects of direct and indirect CAP treatment driven by the advantageous nanosecond pulsed discharge on breast cancer cells of different malignant phenotypes and estrogen receptor (ER) status, a major factor in the prognosis and therapeutic management of breast cancer. The main CAP reactive species in liquid (i.e. H2O2, NO2−/NO3−) and gas phase were determined as a function of plasma operational parameters (i.e. treatment time, pulse voltage and frequency), while pre-treatment with the ROS scavenger NAC revealed the impact of ROS in the treatment. CAP treatment induced intense phenotypic changes and apoptosis in both ER+ and ER- cells, which is associated with the mitochondrial pathway as evidenced by the increased Bax/Bcl-2 ratio and cleavage of PARP-1. Interestingly, CAP significantly reduced CD44 protein expression (a major cancer stem cell marker and matrix receptor), while differentially affected the expression of proteases and inflammatory mediators. Collectively, the findings of the present study suggest that CAP suppresses breast cancer cell growth and regulates several effectors of the tumor microenvironment and thus it could represent an efficient therapeutic approach for distinct breast cancer subtypes.
Comparison of Renal Stones and Nephrocalcinosis in Children: Findings From Two Tertiary Centers in Saudi Arabia
Authors: Alhasan Khalid A. , Shalaby Mohamed A. , Albanna Amr S. , Temsah Mohamad-Hani , Alhayek Zainab , Abdalla Mohammed S. , Alotaibi Najlaa G. , Kalakattawi Nada M. , Zaher Zaher Faisal , Kari Jameela A.
Published: January 2022

Background: Renal stones (nephrolithiasis and urolithiasis) and nephrocalcinosis are uncommon in children; however, their incidences in pediatric populations have been increasing.

Patients and Methods: This multicenter retrospective study compared the clinical presentation, etiology, and outcomes of childhood nephrolithiasis or urolithiasis with those of nephrocalcinosis.

Results: The study included 144 children: 93 with renal stones and 51 with nephrocalcinosis. The mean age at presentation was 72 months and 54 months for children with renal stones and nephrocalcinosis, respectively. A history of consanguinity was found in 65% and 76% of the cases of renal stones and nephrocalcinosis, respectively. Congenital anomalies of the kidneys and urinary tract (CAKUT) were present in 28 and 9.8% of the patients with renal stones and nephrocalcinosis, respectively. The most common symptoms of renal stones were flank pain (29%), hematuria (15%), and dysuria (11%). Urinary tract infection was the primary presentation in the nephrocalcinosis group (18%), followed by failure to thrive (16%), polyuria (12%), and dehydration (12%). The majority of renal stone cases were caused by metabolic disorders, including hyperoxaluria (18%), cystinuria (18%), hypercalciuria (12%), and hyperuricosuria (2%). In contrast, the most common underlying disorders in cases of nephrocalcinosis were familial hypomagnesemia, hypercalciuria, nephrocalcinosis (35%), distal renal tubular acidosis (23%), and Bartter syndrome (6%). Clinical outcomes were significantly better in children with nephrolithiasis/urolithiasis than in those with nephrocalcinosis, who showed radiological evidence of worsening/persistent calcinosis and progressed more frequently to chronic kidney disease (stage II-IV) and end-stage kidney disease.

Conclusion: The average age at presentation for children with renal stones was greater than that for those presenting with nephrocalcinosis. More than 25% of the children with renal stones were found to have CAKUT. Nephrocalcinosis was associated with worse clinical outcomes related to kidney function and disease resolution than nephrolithiasis.
GM-CSF: Orchestrating the Pulmonary Response to Infection
Authors: McCormick Thomas S. , Hejal Rana B. , Leal Luis O. , Ghannoum Mahmoud A.
Published: January 2022

This review summarizes the structure and function of the alveolar unit, comprised of alveolar macrophage and epithelial cell types that work in tandem to respond to infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) helps to maintain the alveolar epithelium and pulmonary immune system under physiological conditions and plays a critical role in restoring homeostasis under pathologic conditions, including infection. Given the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and global spread of coronavirus disease 2019 (COVID-19), with subsequent acute respiratory distress syndrome, understanding basic lung physiology in infectious diseases is especially warranted. This review summarizes clinical and preclinical data for GM-CSF in respiratory infections, and the rationale for sargramostim (yeast-derived recombinant human [rhu] GM-CSF) as adjunctive treatment for COVID-19 and other pulmonary infectious diseases.
Differential Activity of Antioxidants in Testicular Tissues Following Administration of Chlorophytum borivilianum in Gamma-Irradiated Swiss Albino Mice
Authors: Vyas Ruchi , Kesari Kavindra Kumar , Slama Petr , Roychoudhury Shubhadeep , Sisodia Rashmi
Published: January 2022

Background: Oxidative stress induced by radiation causes variable expression of antioxidant enzymes in a tissue-specific manner. Testicular tissues carry out the complex process of spermatogenesis, and studies indicate that testicular damages due to irradiation require long-term recovery before complete resumption. Ionizing radiation also causes oxidative stress in tissues, leading to testicular damage. Aims and Objectives: This study measured differential expression of antioxidant enzymes following administration of C. borivilianum root extract (CRB) in response to irradiation-induced oxidative stress. The activity of various important endogenous enzymatic defense systems was evaluated and correlated for strength of association.

Materials and method: Two forms of C. borivilianum (CB) extracts [CB alone and CB-silver nanoparticles (AgNPs)] were administered at a dose of 50 mg/kg body weight to Swiss albino male mice for 7 consecutive days. After that, they were irradiated with 6 Gy irradiation and further used to study various parameters of antioxidant enzymes.

Results: Results indicate a significant increase in the level of glutathione (GSH) and the activity of GSH-related antioxidant enzymes in irradiated mice treated with CRE and CRE-AgNPs (silver nanoparticles biosynthesized using C. borivilianum root extract) in comparison to non-pretreated ones (groups I and II). Reciprocal elevation was observed in related enzymes, that is, glutathione S-transferase activity (GST), glutathione reductase (GR), and glutathione peroxidase activity (GPx). Elevation in the activity of catalase (CAT) and superoxide dismutase (SOD) was also evident in both the irradiated groups pretreated with CRE-AgNPs. However, expression of CAT in the CRE-treated irradiated group was similar to that of the non-treated irradiated group. Higher association among CAT-SOD, CAT-GPx, and GR-GST was observed.

Conclusion: Overall, it was observed that testicular cells post-irradiation in all groups go through intense oxidative stress; however, groups pretreated with CRE or CRE-AgNPs indicated better toleration and resumption of antioxidant capacity. CRE or CRE-AgNPs pretreated non-irradiated groups mostly remained within the control range indicating stimulated expression of antioxidants.
Role of miRNA-671-5p in Mediating Wnt/β-Catenin-Triggered Podocyte Injury
Authors: Wang Chunhong , Liu Jiafeng , Zhang Xiaoyao , Chen Qiyan , Bai Xiaoyan , Hong Xue , Zhou Lili , Liu Youhua
Published: January 2022

Podocyte injury and proteinuria are the most common features of glomerular disease, which is the leading cause of end-stage renal failure. Hyperactivated Wnt/β-catenin signaling is closely associated with podocyte injury, but the underlying mechanisms are incompletely understood. Here we show that miRNA-671-5p (miR-671-5p) plays a crucial role in mediating β-catenin-triggered podocyte injury by targeting Wilms tumor 1 (WT1). Microarray-based expression profiling revealed that miR-671-5p was the most upregulated miRNA in podocytes after β-catenin activation. MiR-671-5p was colocalized with β-catenin in the glomeruli of proteinuric CKD in vivo. Bioinformatics analyses and luciferase reporter assays confirmed that miR-671-5p targeted WT1 mRNA. Overexpression of miR-671-5p mimics inhibited WT1 and impaired podocyte integrity, whereas miR-671-5p antagomir preserved the expression of WT1 and other podocyte-specific proteins under basal conditions or after β-catenin activation. In mouse remnant kidney model, overexpression of miR-671-5p aggravated podocyte injury, worsened kidney dysfunction and exacerbated renal fibrosis after 5/6 nephrectomy. In contrast, miR-671-5p antagomir alleviated podocyte injury and attenuated proteinuria and renal fibrotic lesions after glomerular injury in vivo. These studies underscore a pivotal role of miR-671-5p in mediating WT1 depletion and podocyte injury induced by β-catenin. Targeting miR-671-5p may serve as a new approach to prevent podocyte injury and proteinuria in proteinuric CKD.
Efficacy and Safety of Different Immunosuppressive Therapies in Patients With Membranous Nephropathy and High PLA2R Antibody Titer
Authors: Deng Le , Huang Qipeng , Wang Jiang , Luo Kaiping , Liu Jiarong , Yan Wenjun , Jiang Fang , Xu Gaosi
Published: January 2022

Background: This study aimed to evaluate clinical features and prognosis and therapy option of patients with different risk ranks based on antibody against the M-type phospholipase-A2-receptor (PLA2Rab) level in seropositive M-type phospholipase-A2-receptor (PLA2R)-associated membranous nephropathy (MN) in a large sample size, multi-center study.

Method: Based on the unvalidated cut-off value of PLA2Rab above 150 RU/ml as one of the clinical criteria for high risk of progressive kidney function loss in MN according to 2020 Kidney Disease: Improving Global Outcomes (KDIGO) draft guidelines recommendation, a total of 447 patients who received cyclophosphamide (CTX) or tacrolimus (TAC) combined with corticosteroids treatment for 12 months were divided into high titer (>150 RU/ml) group and non-high titer (20–150 RU/ml) group, which were subdivided into CTX subgroup and TAC subgroup. The overall cohort was classified into CTX group and TAC group as well. Clinical parameters levels and remission rates were recorded at 3, 6, and 12 months follow-up. PLA2Rab was tested by enzyme-linked immunosorbent assay.

Results: Patients with high titer PLA2Rab were associated with more severe proteinuria and hypoalbuminemia compared to those with non-high titer antibody, accompanied by lower complete remission (CR) and total remission (TR) rates at 3, 6, and 12 months, which even took longer to remission. Similar remission rates differences between the two titer groups were observed in the CTX and TAC groups, respectively. PLA2Rab level at baseline was an independent predictive factor for CR and TR. In the high titer group, CR and TR rates in the CTX subgroup were significantly higher than those in the TAC subgroup at 12 months, although serious adverse events were more frequent in the former.

Conclusion: High-risk rank patients with PLA2Rab level above 150 RU/ml have higher disease activity and worse prognosis among patients with seropositive PLA2R-associated MN, even under different immunosuppressive therapeutic models; moreover, CTX combined with corticosteroids was preferred compared to TAC plus corticosteroids, although serious adverse events were more frequent in the former. Additionally, baseline PLA2Rab level was an independent predictive factor for clinical remission.
Synthesis and Antitumor Activity of Erlotinib Derivatives Linked With 1,2,3-Triazole
Authors: Deng Peng , Sun Ge , Zhao Jie , Yao Kaitai , Yuan Miaomiao , Peng Lizeng , Mao Longfei
Published: January 2022

Cervical cancer is one of the most important cause of cancer-related death and presents a major public health problem in many countries. To search for more novel antitumor agents against cervical cancer, 14 erlotinib-linked 1,2,3-triazole compounds were designed, synthesized, and evaluated for their anti-tumor activity. The compounds were confirmed by 1H NMR, 13C NMR, and high-resolution mass spectra (HR MS). Antitumor activity assay results indicated that six of those compounds have remarkable inhibitory activity against human cervical cancer HeLa cells in vitro, among which compound 4m was the most potent with IC50 of 3.79 μM, and compounds 4k, 4i, 4l, 4d, and 4n also demonstrated remarkable antitumor activity with IC50 of 3.79, 4.16, 4.36, 7.02, and 8.21 μM. We found three of the most potent compounds 4d, 4k, and 4l induced potent apoptosis and cell cycle arrest in HeLa cells, and compounds 4d and 4l significantly restrained the cell colony formation and showed moderate epidermal growth factor receptor (EGFR) inhibitory activity with IC50 of 13.01 and 1.76 μM. Therefore, these experiments indicate that these erlotinib-linked 1,2,3-triazole compounds are potential to act as effective anticancer agents against cervical cancer.
Gene Therapy for Acute Respiratory Distress Syndrome
Authors: Liu Jing , Dean David A.
Published: January 2022

Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome that leads to acute respiratory failure and accounts for over 70,000 deaths per year in the United States alone, even prior to the COVID-19 pandemic. While its molecular details have been teased apart and its pathophysiology largely established over the past 30 years, relatively few pharmacological advances in treatment have been made based on this knowledge. Indeed, mortality remains very close to what it was 30 years ago. As an alternative to traditional pharmacological approaches, gene therapy offers a highly controlled and targeted strategy to treat the disease at the molecular level. Although there is no single gene or combination of genes responsible for ARDS, there are a number of genes that can be targeted for upregulation or downregulation that could alleviate many of the symptoms and address the underlying mechanisms of this syndrome. This review will focus on the pathophysiology of ARDS and how gene therapy has been used for prevention and treatment. Strategies for gene delivery to the lung, such as barriers encountered during gene transfer, specific classes of genes that have been targeted, and the outcomes of these approaches on ARDS pathogenesis and resolution will be discussed.
Somatosensory-Evoked Potentials as a Marker of Functional Neuroplasticity in Athletes: A Systematic Review
Authors: Maudrich Tom , Hähner Susanne , Kenville Rouven , Ragert Patrick
Published: January 2022

Background

Somatosensory-evoked potentials (SEP) represent a non-invasive tool to assess neural responses elicited by somatosensory stimuli acquired via electrophysiological recordings. To date, there is no comprehensive evaluation of SEPs for the diagnostic investigation of exercise-induced functional neuroplasticity. This systematic review aims at highlighting the potential of SEP measurements as a diagnostic tool to investigate exercise-induced functional neuroplasticity of the sensorimotor system by reviewing studies comparing SEP parameters between athletes and healthy controls who are not involved in organized sports as well as between athlete cohorts of different sport disciplines.

Methods

A systematic literature search was conducted across three electronic databases (PubMed, Web of Science, and SPORTDiscus) by two independent researchers. Three hundred and ninety-seven records were identified, of which 10 cross-sectional studies were considered eligible.

Results

Differences in SEP amplitudes and latencies between athletes and healthy controls or between athletes of different cohorts as well as associations between SEP parameters and demographic/behavioral variables (years of training, hours of training per week & reaction time) were observed in seven out of 10 included studies. In particular, several studies highlight differences in short- and long-latency SEP parameters, as well as high-frequency oscillations (HFO) when comparing athletes and healthy controls. Neuroplastic differences in athletes appear to be modality-specific as well as dependent on training regimens and sport-specific requirements. This is exemplified by differences in SEP parameters of various athlete populations after stimulation of their primarily trained limb.

Conclusion

Taken together, the existing literature suggests that athletes show specific functional neuroplasticity in the somatosensory system. Therefore, this systematic review highlights the potential of SEP measurements as an easy-to-use and inexpensive diagnostic tool to investigate functional neuroplasticity in the sensorimotor system of athletes. However, there are limitations regarding the small sample sizes and inconsistent methodology of SEP measurements in the studies reviewed. Therefore, future intervention studies are needed to verify and extend the conclusions drawn here.
Preharvest UV-C Hormesis Induces Key Genes Associated With Homeostasis, Growth and Defense in Lettuce Inoculated With Xanthomonas campestris pv. vitians
Authors: Sidibé Amadou , Charles Marie Thérèse , Lucier Jean-François , Xu Yanqun , Beaulieu Carole
Published: January 2022

Preharvest application of hormetic doses of ultraviolet-C (UV-C) generates beneficial effects in plants. In this study, within 1 week, four UV-C treatments of 0.4 kJ/m2 were applied to 3-week-old lettuce seedlings. The leaves were inoculated with a virulent strain ofXanthomonas campestrispv.vitians(Xcv) 48 h after the last UV-C application. The extent of the disease was tracked over time and a transcriptomic analysis was performed on lettuce leaf samples. Samples of lettuce leaves, from both control and treated groups, were taken at two different times corresponding to T2, 48 h after the last UV-C treatment and T3, 24 h after inoculation (i.e., 72 h after the last UV-C treatment). A significant decrease in disease severity between the UV-C treated lettuce and the control was observed on days 4, 8, and 14 after pathogen inoculation. Data from the transcriptomic study revealed, that in response to the effect of UV-C alone and/or UV-C + Xcv, a total of 3828 genes were differentially regulated with fold change (|log2-FC|) > 1.5 and false discovery rate (FDR) < 0.05. Among these, of the 2270 genes of known function 1556 were upregulated and 714 were downregulated. A total of 10 candidate genes were verified by qPCR and were generally consistent with the transcriptomic results. The differentially expressed genes observed in lettuce under the conditions of the present study were associated with 14 different biological processes in the plant. These genes are involved in a series of metabolic pathways associated with the ability of lettuce treated with hormetic doses of UV-C to resume normal growth and to defend themselves against potential stressors. The results indicate that the hormetic dose of UV-C applied preharvest on lettuce in this study, can be considered as an eustress that does not interfere with the ability of the treated plants to carry on a set of key physiological processes namely: homeostasis, growth and defense.
HY5: A Pivotal Regulator of Light-Dependent Development in Higher Plants
Authors: Xiao Yuntao , Chu Li , Zhang Yumeng , Bian Yeting , Xiao Jiahui , Xu Dongqing
Published: January 2022

ELONGATED HYPOCOTYL5 (HY5), a bZIP-type transcription factor, acts as a master regulator that regulates various physiological and biological processes in plants such as photomorphogenesis, root growth, flavonoid biosynthesis and accumulation, nutrient acquisition, and response to abiotic stresses. HY5 is evolutionally conserved in function among various plant species. HY5 acts as a master regulator of light-mediated transcriptional regulatory hub that directly or indirectly controls the transcription of approximately one-third of genes at the whole genome level. The transcription, protein abundance, and activity of HY5 are tightly modulated by a variety of factors through distinct regulatory mechanisms. This review primarily summarizes recent advances on HY5-mediated molecular and physiological processes and regulatory mechanisms on HY5 in the model plant Arabidopsis as well as in crops.
Integrated Analysis of Basic Helix Loop Helix Transcription Factor Family and Targeted Terpenoids Reveals Candidate AarbHLH Genes Involved in Terpenoid Biosynthesis in Artemisia argyi
Authors: Yi Xiaozhe , Wang Xingwen , Wu Lan , Wang Mengyue , Yang Liu , Liu Xia , Chen Shilin , Shi Yuhua
Published: January 2022

Artemisia argyi is a valuable traditional medicinal plant in Asia. The essential oil from its leaves is rich in terpenoids and has been used to enhance health and well-being. In China, the market scale of industries related to A. argyi has attained tens of billions of Chinese Yuan. The basic helix-loop-helix (bHLH) family is one of the largest transcription factors families in plants that plays crucial roles in diverse biological processes and is an essential regulatory component of terpenoid biosynthesis. However, the bHLH TFs and their regulatory roles in A. argyi remain unknown. Here, 53 AarbHLH genes were identified from the transcriptome of A. argyi and were classified into 15 subfamilies based on the classification of bHLH proteins in Arabidopsis thaliana. The MEME analysis showed that the conserved motif 1 and motif 2 constituted the most conserved bHLH domain and distributed in most AarbHLH proteins. Additionally, integrated analysis of the expression profiles of AarbHLH genes and the contents of targeted terpenoids in different tissues group and JA-treated group were performed. Eleven up-regulated AarbHLHs and one down-regulated AarbHLH were screened as candidate genes that may participate in the regulation of terpenoid biosynthesis (TPS-AarbHLHs). Correlation analysis between gene expression and terpenoid contents indicated that the gene expression of these 12 TPS-AarbHLHs was significantly correlated with the content changes of 1,8-cineole or β-caryophyllene. Protein–protein interaction networks further illustrated that these TPS-AarbHLHs might be involved in terpenoid biosynthesis in A. argyi. This finding provides a basis to further investigate the regulation mechanism of AarbHLH genes in terpenoid biosynthesis, and will be helpful to improve the quality of A. argyi.
Weak Effect of Gypsy Retrotransposon Bursts on Sonneratia alba Salt Stress Gene Expression
Authors: Wang Yushuai , Dai Aimei , Tang Tian
Published: January 2022

Transposable elements (TEs) are an important source of genetic diversity and can be co-opted for the regulation of host genes. However, to what extent the pervasive TE colonization of plant genomes has contributed to stress adaptation remains controversial. Plants inhabiting harsh environments in nature provide a unique opportunity to answer this question. We compared TE compositions and their evolutionary dynamics in the genomes of two mangrove species: the pioneer Sonneratia alba and its less salt-tolerant relative S. caseolaris. Age distribution, strength of purifying selection and the removal rate of LTR (long terminal repeat) retrotransposons were estimated. Phylogenetic analysis of LTR retrotransposons and their distribution in the genome of S. alba were surveyed. Small RNA sequencing and whole-genome bisulfite sequencing was conducted using leaves of S. alba. Expression pattern of LTR retrotransposons and their nearby genes were examined using RNA-seq data of S. alba under different salt treatments. S. alba possesses more TEs than S. caseolaris. Particularly, many more young Gypsy LTR retrotransposons have accumulated in S. alba than in S. caseolaris despite an increase in purifying selection against TE insertions. The top two most abundant Gypsy families in S. alba preferentially insert in gene-poor regions. They are under relaxed epigenetic repression, probably due to the presence of CHROMO domains in their 3′-ends. Although a considerable number of TEs in S. alba showed differential expression under salt stress, only four copies were significantly correlated with their nearby genes in expression levels. One such TE-gene pair involves Abscisic acid 8'-hydroxylase 3 functioning in abscisic acid catabolism. This study sheds light on the evolutionary dynamics and potential function of TEs in an extremophile. Our results suggest that the conclusion on co-option of TEs should be cautious even though activation of TEs by stress might be prevalent.
Psychic Income Associated With Shanghai Tennis Masters and Residents’ Attitude
Authors: Zhang Fengyun , Liu Dongfeng , Plumley Daniel , Chai Mengyan
Published: January 2022

Using Shanghai Tennis Masters as an example, this study seeks to explore the psychic income associated with major sports events hosting and whether the psychic income would predict the attitudes of local residents toward events hosting. In addition, the moderating effect of sport involvement on the relationship between psychic income and attitude is also tested. In this study, a questionnaire survey is adopted. The structured questionnaire was developed based on 4 parts, including the demographics of the residents, involvement in the sport event, psychic income from the sport event, and their attitudes toward the sports event, there were 47 items in total. Data were collected from the local residents of Shanghai (including 16 districts or counties), as a result, 1,302 valid questionnaires were collected. A series of statistical analyses were conducted by using SPSS25.0 and AMOS 24.0 to examine the reliability and validity of the scales and to test the hypotheses. The results showed that the event has brought a significant level of psychic income to the local community, and the perceived psychic income would predict the attitudes of the residents toward the event hosting. The moderating effect of sports involvement on the relationship between psychic income and attitude is also confirmed.
To Be Expressive or Not: The Role of Teachers’ Emotions in Students’ Learning
Authors: Wang Yang
Published: January 2022

Understanding the role of teachers’ facial expressions in students’ learning is helpful to improve online teaching. Therefore, this study explored the effects of teacher’s facial expressions on students’ learning through analyzing three groups of video lectures. Participants were 78 students enrolled in three groups: one with an enhanced-expression teacher, one with a conventional-expression teacher, and one with the teacher’s audio only. ANOVA was used to explore whether video lectures instructed by the enhanced-expression teacher were better than those instructed by the conventional-expression teacher and the audio-only teacher for facilitating students’ learning, and what is the role of the teacher’s emotions in students’ perceived social presence, arousal level, cognitive load, and learning. The results showed that the video lecture by the enhanced-expression teacher was better than those with the conventional-expression teacher and with the audio-only for facilitating students’ social presence, arousal level, and long-term learning. Interestingly, it was found that the teacher’s emotions could relieve students’ cognitive load. These results explained the inconsistency of existing studies by exploring the mechanism of teachers’ emotions in students’ learning. It also provides teachers with practical guidance for video lecture design.
Exploring the Structure of Sibling Relationships Among Preschool Children in China and Developing a Questionnaire
Authors: Jiang Meiru , Cao Xiaojun , Huang Qinqin , Wu Siqi , Chen Xu
Published: January 2022

Objective

The objective of this study was to examine the structure of sibling relationships among preschool children in China and develop a questionnaire.

Methods

The concept of sibling relationships among preschool children in China was established through literature review, open interviews, and expert review, and the initial project was designed. Using the questionnaire survey method, with 651 mothers of preschool children as the research objects, we performed item analysis, exploratory factor analysis, confirmatory factor analysis, and reliability and validity tests on the initial questionnaire.

Results

The questionnaire for the sibling relationships among preschool children in China had 18 questions covering dimensions of sibling interaction, sibling acceptance, sibling warmth, and sibling rivalry. The questionnaire fitting indexes were better (χ2/df= 1.829, CFI = 0.930, TLI = 0.917, RMSEA = 0.055, SRMR = 0.053). The internal consistency coefficient between the total questionnaire and each dimension was 0.759–0.8548, and the total questionnaire significantly correlated with each dimension (r= 0.229–0.792) and the total score of parental self-efficacy (r= –0.106 to 0.338).

Conclusion

The Sibling Relationship Questionnaire for Chinese Preschool Children (Parental Version) exhibited good reliability and validity, making it an effective tool for the evaluation of sibling relationships among preschool children.