bluuebunny/crossref_metadata_2025 huggingface dataset:
The Histone Acetyltransferase CfGcn5 Regulates Growth, Development, and Pathogenicity in the Anthracnose Fungus Colletotrichum fructicola on the Tea-Oil Tree
Authors: Zhang Shengpei , Guo Yuan , Chen Siqi , Li He
Published: June 2021

The tea-oil tree (Camellia oleifera Abel.) is a commercial edible-oil tree in China, and anthracnose commonly occurs in its plantations, causing great losses annually. We have previously revealed that CfSnf1 is essential for pathogenicity in Colletotrichum fructicola, the major pathogen of anthracnose on the tea-oil tree. Here, we identified CfGcn5 as the homolog of yeast histone acetyltransferase ScGcn5, which cooperates with ScSnf1 to modify histone H3 in Saccharomyces cerevisiae. Targeted gene deletion revealed that CfGcn5 is important in fungi growth, conidiation, and responses to environmental stresses. Pathogenicity assays indicated that CfGcn5 is essential for C. fructicola virulence both in unwounded and wounded tea-oil tree leaves. Further, we found that CfGcn5 is localized to the nucleus and this specific localization is dependent on both NLS region and HAT domain. Moreover, we provided evidence showing that the nuclear localization is essential but not sufficient for the full function of CfGcn5, and the NLS, HAT, and Bromo domains were proven to be important for normal CfGcn5 functions. Taken together, our studies not only illustrate the key functions of CfGcn5 in growth, development, and pathogenicity but also highlight the relationship between its locations with functions in C. fructicola.
Elucidating Axonal Injuries Through Molecular Modelling of Myelin Sheaths and Nodes of Ranvier
Authors: Saeedimasine Marzieh , Montanino Annaclaudia , Kleiven Svein , Villa Alessandra
Published: June 2021

Around half of the traumatic brain injuries are thought to be axonal damage. Disruption of the cellular membranes, or alternatively cytoskeletal damage has been suggested as possible injury trigger. Here, we have used molecular models to have a better insight on the structural and mechanical properties of axon sub-cellular components. We modelled myelin sheath and node of Ranvier as lipid bilayers at a coarse grained level. We built ex-novo a model for the myelin. Lipid composition and lipid saturation were based on the available experimental data. The model contains 17 different types of lipids, distributed asymmetrically between two leaflets. Molecular dynamics simulations were performed to characterize the myelin and node-of-Ranvier bilayers at equilibrium and under deformation and compared to previous axolemma simulations. We found that the myelin bilayer has a slightly higher area compressibility modulus and higher rupture strain than node of Ranvier. Compared to the axolemma in unmyelinated axon, mechanoporation occurs at 50% higher strain in the myelin and at 23% lower strain in the node of Ranvier in myelinated axon. Combining the results with finite element simulations of the axon, we hypothesizes that myelin does not rupture at the thresholds proposed in the literature for axonal injury while rupture may occur at the node of Ranvier. The findings contribute to increases our knowledge of axonal sub-cellular components and help to understand better the mechanism behind axonal brain injury.
Stress Granules and Neurodegenerative Disorders: A Scoping Review
Authors: Asadi Mohammad Reza , Sadat Moslehian Marziyeh , Sabaie Hani , Jalaiei Abbas , Ghafouri-Fard Soudeh , Taheri Mohammad , Rezazadeh Maryam
Published: June 2021

Cytoplasmic ribonucleoproteins called stress granules (SGs) are considered as one of the main cellular solutions against stress. Their temporary presence ends with stress relief. Any factor such as chronic stress or mutations in the structure of the components of SGs that lead to their permanent presence can affect their interactions with pathological aggregations and increase the degenerative effects. SGs involved in RNA mechanisms are important factors in the pathophysiology of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), frontotemporal degeneration (FTD), and Alzheimer's diseases (AD). Although many studies have been performed in the field of SGs and neurodegenerative disorders, so far, no systematic studies have been executed in this field. The purpose of this study is to provide a comprehensive perspective of all studies about the role of SGs in the pathogenesis of neurodegenerative disorders with a focus on the protein ingredients of these granules. This scoping review is based on a six-stage methodology structure and the PRISMA guideline. A systematic search of seven databases for qualified articles was conducted until December 2020. Publications were screened independently by two reviewers and quantitative and qualitative analysis was performed on the extracted data. Bioinformatics analysis was used to plot the network and predict interprotein interactions. In addition, GO analysis was performed. A total of 48 articles were identified that comply the inclusion criteria. Most studies on neurodegenerative diseases have been conducted on ALS, AD, and FTD using human post mortem tissues. Human derived cell line studies have been used only in ALS. A total 29 genes of protein components of SGs have been studied, the most important of which are TDP-43, TIA-1, PABP-1. Bioinformatics studies have predicted 15 proteins to interact with the protein components of SGs, which may be the constituents of SGs. Understanding the interactions between SGs and pathological aggregations in neurodegenerative diseases can provide new targets for treatment of these disorders.
Ultrastructural Characterization of Human Oligodendrocytes and Their Progenitor Cells by Pre-embedding Immunogold
Authors: Ulloa-Navas María J. , Pérez-Borredá Pedro , Morales-Gallel Raquel , Saurí-Tamarit Ana , García-Tárraga Patricia , Gutiérrez-Martín Antonio J. , Herranz-Pérez Vicente , García-Verdugo Josée M.
Published: June 2021

Oligodendrocytes are the myelinating cells of the central nervous system. They provide trophic, metabolic, and structural support to neurons. In several pathologies such as multiple sclerosis (MS), these cells are severely affected and fail to remyelinate, thereby leading to neuronal death. The gold standard for studying remyelination is the g-ratio, which is measured by means of transmission electron microscopy (TEM). Therefore, studying the fine structure of the oligodendrocyte population in the human brain at different stages through TEM is a key feature in this field of study. Here we study the ultrastructure of oligodendrocytes, its progenitors, and myelin in 10 samples of human white matter using nine different markers of the oligodendrocyte lineage (NG2, PDGFRα, A2B5, Sox10, Olig2, BCAS1, APC-(CC1), MAG, and MBP). Our findings show that human oligodendrocytes constitute a very heterogeneous population within the human white matter and that its stages of differentiation present characteristic features that can be used to identify them by TEM. This study sheds light on how these cells interact with other cells within the human brain and clarify their fine characteristics from other glial cell types.
Incubation of Oxycodone Craving Following Adult-Onset and Adolescent-Onset Oxycodone Self-Administration in Male Rats
Authors: Altshuler Rachel D. , Garcia Kristine T. , Li Xuan
Published: June 2021

Relapse is a major obstacle to curb the ongoing epidemic of prescription opioid abuse. We and others previously demonstrated that oxycodone seeking in adult rats progressively increases after abstinence from oxycodone self-administration (incubation of oxycodone craving). In humans, the onset of oxycodone use in adolescents may increase individuals’ vulnerability to later opioid addiction. However, little is known about incubation of oxycodone craving after adolescent-onset oxycodone self-administration in rats. In the first study, we trained single-housed adolescent (postnatal day 35 at start) and adult (postnatal day 77 at start) male Sprague–Dawley rats to self-administer oxycodone (0.1 mg/kg/infusion, 6 h/day for 10 days) and then tested oxycodone relapse on both abstinence day 1 and day 15. Given that social experience is critical for neurobehavioral development in adolescents, we performed the second study using group-housed adolescent and adult rats. In both studies, we observed no age differences in oxycodone self-administration and incubated oxycodone seeking on abstinence day 15. However, on abstinence day 1, we observed decreased oxycodone seeking in adolescents compared with adults. This pattern of data led to elevated incubation slopes in adolescent rats compared with adult rats. Finally, group-housed rats exhibited attenuated oxycodone seeking compared with single-housed rats on abstinence day 15, but not on day 1. Taken together, these data suggest that adolescents may be resistant to oxycodone relapse during early abstinence, but this resistance dissipates quickly during the transition between adolescent and young adulthood. In addition, group-housing plays a protective role against incubated oxycodone craving.
Neuroinflammation-Driven Lymphangiogenesis in CNS Diseases
Authors: Hsu Martin , Laaker Collin , Sandor Matyas , Fabry Zsuzsanna
Published: June 2021

The central nervous system (CNS) undergoes immunosurveillance despite the lack of conventional antigen presenting cells and lymphatic vessels in the CNS parenchyma. Additionally, the CNS is bathed in a cerebrospinal fluid (CSF). CSF is continuously produced, and consequently must continuously clear to maintain fluid homeostasis despite the lack of conventional lymphatics. During neuroinflammation, there is often an accumulation of fluid, antigens, and immune cells to affected areas of the brain parenchyma. Failure to effectively drain these factors may result in edema, prolonged immune response, and adverse clinical outcome as observed in conditions including traumatic brain injury, ischemic and hypoxic brain injury, CNS infection, multiple sclerosis (MS), and brain cancer. Consequently, there has been renewed interest surrounding the expansion of lymphatic vessels adjacent to the CNS which are now thought to be central in regulating the drainage of fluid, cells, and waste out of the CNS. These lymphatic vessels, found at the cribriform plate, dorsal dural meninges, base of the brain, and around the spinal cord have each been implicated to have important roles in various CNS diseases. In this review, we discuss the contribution of meningeal lymphatics to these processes during both steady-state conditions and neuroinflammation, as well as discuss some of the many still unknown aspects regarding the role of meningeal lymphatics in neuroinflammation. Specifically, we focus on the observed phenomenon of lymphangiogenesis by a subset of meningeal lymphatics near the cribriform plate during neuroinflammation, and discuss their potential roles in immunosurveillance, fluid clearance, and access to the CSF and CNS compartments. We propose that manipulating CNS lymphatics may be a new therapeutic way to treat CNS infections, stroke, and autoimmunity.
Raman Molecular Fingerprints of Rice Nutritional Quality and the Concept of Raman Barcode
Authors: Pezzotti Giuseppe , Zhu Wenliang , Chikaguchi Haruna , Marin Elia , Boschetto Francesco , Masumura Takehiro , Sato Yo-Ichiro , Nakazaki Tetsuya
Published: June 2021

The nutritional quality of rice is contingent on a wide spectrum of biochemical characteristics, which essentially depend on rice genome, but are also greatly affected by growing/environmental conditions and aging during storage. The genetic basis and related identification of genes have widely been studied and rationally linked to accumulation of micronutrients in grains. However, genetic classifications cannot catch quality fluctuations arising from interannual, environmental, and storage conditions. Here, we propose a quantitative spectroscopic approach to analyze rice nutritional quality based on Raman spectroscopy, and disclose analytical algorithms for the determination of: (i) amylopectin and amylose concentrations, (ii) aromatic amino acids, (iii) protein content and structure, and (iv) chemical residues. The proposed Raman algorithms directly link to the molecular composition of grains and allow fast/non-destructive determination of key nutritional parameters with minimal sample preparation. Building upon spectroscopic information at the molecular level, we newly propose to represent the nutritional quality of labeled rice products with a barcode specially tailored on the Raman spectrum. The Raman barcode, which can be stored in databases promptly consultable with barcode scanners, could be linked to diet applications (apps) to enable a rapid, factual, and unequivocal product identification based on direct molecular screening.
Systematic Analysis of Survival-Associated Alternative Splicing Signatures in Thyroid Carcinoma
Authors: Han Baoai , Yang Minlan , Yang Xiuping , Liu Mengzhi , Xie Qiang , Fan Guorun , Hosseini Davood K. , Yu Jintao , Song Peng , Chen Xiong , Sun Haiying
Published: June 2021

Alternative splicing (AS) is a key mechanism involved in regulating gene expression and is closely related to tumorigenesis. The incidence of thyroid cancer (THCA) has increased during the past decade, and the role of AS in THCA is still unclear. Here, we used TCGA and to generate AS maps in patients with THCA. Univariate analysis revealed 825 AS events related to the survival of THCA. Five prognostic models of AA, AD, AT, ES, and ME events were obtained through lasso and multivariate analyses, and the final prediction model was established by integrating all the AS events in the five prediction models. Kaplan–Meier survival analysis revealed that the overall survival rate of patients in the high-risk group was significantly shorter than that of patients in the low-risk group. The ROC results revealed that the prognostic capabilities of each model at 3, 5, and 8 years were all greater than 0.7, and the final prognostic capabilities of the models were all greater than 0.9. By reviewing other databases and utilizing qPCR, we verified the established THCA gene model. In addition, gene set enrichment analysis showed that abnormal AS events might play key roles in tumor development and progression of THCA by participating in changes in molecular structure, homeostasis of the cell environment and in cell energy. Finally, a splicing correlation network was established to reveal the potential regulatory patterns between the predicted splicing factors and AS event candidates. In summary, AS should be considered an important prognostic indicator of THCA. Our results will help to elucidate the underlying mechanism of AS in the process of THCA tumorigenesis and broaden the prognostic and clinical application of molecular targeted therapy for THCA.
Low Expression Levels of SLC22A12 Indicates a Poor Prognosis and Progresses Clear Cell Renal Cell Carcinoma
Authors: Xu Jiaju , Liu Yuenan , Liu Jingchong , Shou Yi , Xiong Zhiyong , Xiong Hairong , Xu Tianbo , Wang Qi , Liu Di , Liang Huageng , Yang Hongmei , Yang Xiong , Zhang Xiaoping
Published: June 2021

Clear cell renal cell carcinoma (ccRCC) accounts for approximately 4/5 of all kidney cancers. Accumulation of minor changes in the cellular homeostasis may be one cause of ccRCC. Therefore, we downloaded the RNA sequencing and survival data of the kidney renal cell carcinoma (KIRC) cohort from the Cancer Genome Atlas (TCGA) database. After the univariate and multivariate Cox regression analyses, 19 kidney-specific differentially expressed genes (DEGs) were found. Solute Carrier Family 22 Member 12 (SLC22A12) resulted in an independent prognostic predictor for both overall survival (OS) and disease-free survival (DFS). SLC22A12 expression was lower in tumoral tissue compared to normal tissue. Moreover, patients in the SLC22A12 low expression group had a higher pathological stage and worse survival than the high expression group. Additionally, qRT-PCR assay, immunoblotting test (IBT), and immunohistochemical (IHC) analyses of cancer tissues/cells and the corresponding normal controls verified that SLC22A12 is downregulated in ccRCC. Receiver operator characteristic (ROC) curves showed that the low expression level of SLC22A12 could be a good diagnostic marker for ccRCC (AUC=0.7258; p <0.0001). Gene set enrichment analysis (GSEA) showed that SLC22A12 expression levels are related to metabolism, cell cycle, and tumor-related signaling pathways. GO and KEGG analyses revealed that SLC22A12 transports multiple organic compounds, ions, and hormones and participates in the extracellular structure organization. Furthermore, SLC22A12 over-expression in vitro inhibited the proliferation, migration, and invasion of renal cancer cells by regulating PI3K/Akt pathways. Such effects were reversed when knocking out SLC22A12. In summary, as a transporter for many vital metabolites, SLC22A12 may affect tumor cell survival through its impacts on the mentioned metabolites. In conclusion, this study uncovered that SLC22A12 is a promising prognostic and diagnostic biomarker for ccRCC.
Evaluating the Histopathology of Pancreatic Ductal Adenocarcinoma by Intravoxel Incoherent Motion-Diffusion Weighted Imaging Comparing With Diffusion-Weighted Imaging
Authors: Liu Qi , Zhang Jinggang , Jiang Man , Zhang Yue , Chen Tongbing , Zhang Jilei , Li Bei , Chen Jie , Xing Wei
Published: June 2021

Objectives

To explore the differences between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and diffusion-weighted imaging (DWI) in evaluating the histopathological characters of pancreatic ductal adenocarcinoma (PDAC).

Methods

This retrospective study enrolled 50 patients with PDAC confirmed by pathology from December 2018 to May 2020. All patients underwent DWI and IVIM-DWI before surgeries. Patients were classified into low- and high-fibrosis groups. Apparent diffusion coefficient (ADC), diffusion coefficient (D), false diffusion coefficient (D*), and perfusion fraction (f) were measured by two radiologists, respectively in GE AW 4.7 post-processing station, wherein ADC values were derived by mono-exponential fits and f, D, D* values were derived by biexponential fits. The tumor tissue was stained with Sirius red, CD34, and CK19 to evaluate fibrosis, microvascular density (MVD), and tumor cell density. Furthermore, the correlation between ADC, D, D*, and f values and histopathological results was analyzed.

Results

The D values were lower in the high-fibrosis group than in the low-fibrosis group, while the f values were opposite. Further, no statistically significant differences were detected in ADC and D* values between the high- and low-fibrosis groups. The AUC of D and f values had higher evaluation efficacy in the high- and low-fibrosis groups than ADC values. A significant negative correlation was established between D values, and fibrosis and a significant positive correlation were observed between f values and fibrosis. No statistical difference was detected between DWI/IVIM parameters values and MVD or tumor cell density except for the positive correlation between D* values and tumor cell density.

Conclusions

D and f values derived from the IVIM model had higher sensitivity and diagnostic performance for grading fibrosis in PDAC compared to the conventional DWI model. IVIM-DWI may have the potential as an imaging biomarker for predicting the fibrosis grade of PDAC.
Clinical Implementation of a 6D Treatment Chair for Fixed Ion Beam Lines
Authors: Sun Jiayao , Kong Lin , Chen Zhi , You Dan , Mao Jingfang , Guan Xiyin , Wu Xiaodong , Sheng Yinxiangzi
Published: June 2021

Purpose

To verify the practicality and safety of a treatment chair with six degrees of freedom (6DTC) through demonstrating the efficacy of the workflow in clinical settings and analyzing the obtained technical data, including intra-fraction patient movement during the use of the 6DTC.

Materials and Methods

A clinical study was designed and conducted to test the clinical treatment workflow and the safety of the 6DTC. Based on the demonstrated dosimetric advantages, fifteen patients with head and neck tumors were selected and treated with the 6DTC. The positional error at the first beam position (PE-B1) and the second beam position (PE-B2) were analyzed and compared with the results from daily quality assurance (QA) procedures of the 6DTC and imaging system performed each day before clinical treatment. The intra-fraction patient movement was derived from the total patient alignment positional error and the QA data based on a Gaussian distribution formulism.

Results

The QA results showed sub-millimeter mechanical accuracy of the 6DTC over the course of the clinical study. For 150 patient treatment fractions, the mean deviations between PE-B1 and PE-B2 were 0.13mm (SD 0.88mm), 0.25mm (SD 1.17mm), -0.57mm (SD 0.85mm), 0.02° (SD 0.35°), 0.00° (SD 0.37°), and -0.02° (SD 0.37°) in the x, y, z (translational), and u, v, w (rotational) directions, respectively. The calculated intra-fraction patient movement was -0.08mm (SD 0.56mm), 0.71mm (SD 1.12mm), -0.52mm (SD 0.84mm), 0.10° (SD 0.32°), 0.09° (SD 0.36°), and -0.04° (SD 0.36°) in the x, y, z, u, v, w directions, respectively.

Conclusions

The performance stability of the 6DTC was satisfactory. The position accuracy and intra-fraction patient movement in an upright posture with the 6DTC were verified and found adequate for clinical implementation.
The Association Between High Birth Weight and Long-Term Outcomes—Implications for Assisted Reproductive Technologies: A Systematic Review and Meta-Analysis
Authors: Magnusson Åsa , Laivuori Hannele , Loft Anne , Oldereid Nan B. , Pinborg Anja , Petzold Max , Romundstad Liv Bente , Söderström-Anttila Viveca , Bergh Christina
Published: June 2021

Background: Studies have shown that the prevalence of children born with high birth weight or large for gestational age (LGA) is increasing. This is true for spontaneous pregnancies; however, children born after frozen embryo transfer (FET) as part of assisted reproductive technology (ART) also have an elevated risk. In recent years, the practice of FET has increased rapidly and while the perinatal and obstetric risks are well-studied, less is known about the long-term health consequences.

Objective: The aim of this systematic review was to describe the association between high birth weight and LGA on long-term child outcomes.

Data Sources: PubMed, Scopus, and Web of Science were searched up to January 2021. Exposure included high birth weight and LGA. Long-term outcome variables included malignancies, psychiatric disorders, cardiovascular disease, and diabetes.

Study Selection: Original studies published in English or Scandinavian languages were included. Studies with a control group were included while studies published as abstracts and case reports were excluded.

Data Extraction: The methodological quality, in terms of risk of bias, was assessed by pairs of reviewers. Robins-I (www.methods.cochrane.org) was used for risk of bias assessment in original articles. For systematic reviews, AMSTAR (www.amstar.ca) was used. For certainty of evidence, we used the GRADE system. The systematic review followed PRISMA guidelines. When possible, meta-analyses were performed.

Results: The search included 11,767 articles out of which 173 met the inclusion criteria and were included in the qualitative analysis, while 63 were included in quantitative synthesis (meta-analyses). High birth weight and/or LGA was associated with low to moderately elevated risks for certain malignancies in childhood, breast cancer, several psychiatric disorders, hypertension in childhood, and type 1 and 2 diabetes.

Conclusions: Although the increased risks for adverse outcome in offspring associated with high birth weight and LGA represent serious health effects in childhood and in adulthood, the size of these effects seems moderate. The identified risk association should, however, be taken into account in decisions concerning fresh and frozen ART cycles and is of general importance in view of the increasing prevalence in high birthweight babies.
Endoscopic and Histologic Predictors of Outcomes in Pediatric Ulcerative Colitis—Caveat Emptor
Authors: Stallard Lorraine , Hussey Séamus
Published: June 2021

The impact of endoscopic and histological mucosal healing on outcomes in adult settings is impressive. Despite many clinical parallels, pediatric ulcerative colitis (UC) is set apart from adult disease in several respects. Many frequently used indices are not fully validated, especially in pediatric settings, and consensus on precise definitions in clinical settings are lacking. Endoscopic mucosal healing is an acceptable long-term treatment goal in pediatrics, but not histologic normalization. Early prediction of disease course in UC may allow treatment stratification of patients according to risks of relapse, acute severe colitis, and colectomy. Putative endoscopic and histologic predictors of poor clinical outcomes in adults have not held true in pediatric settings, including baseline endoscopic extent, endoscopic severity, and specific histologic characteristics which are less prevalent in pediatrics at diagnosis. In this mini-review we appraise predictive endoscopic and histologic factors in pediatric UC with reference to relapse, severe colitis, and colectomy risks. We recommend that clinicians routinely use endoscopic and histologic sores to improve the quality of clinical and research practice. The review summarizes differences between adult and pediatric prediction data, advises special consideration of those with primary sclerosing cholangitis, and suggests areas for future study in this field.
Prevention and Recovery of COVID-19 Patients With Kampo Medicine: Review of Case Reports and Ongoing Clinical Trials
Authors: Takayama Shin , Namiki Takao , Odaguchi Hiroshi , Arita Ryutaro , Hisanaga Akito , Mitani Kazuo , Ito Takashi
Published: June 2021

Coronavirus disease 2019 (COVID-19) spread to Japan in 2020, where the number of infected patients exceeded 250,000 and COVID-related deaths exceeded 3,500 in one year. Basic guidelines for infection control were implemented in Japan, and research and development of effective drugs and vaccines were promoted. This included considering Kampo medicine, which has a long history of treating recurring emerging viral infections. Considering the characteristics of the disease (inflammation of the upper and lower respiratory tract as well as potential neural damage and vasculitis), Kampo medicine could be considered as a treatment strategy due to its antiviral and anti-inflammatory effects induced by multiple active substances that could aid in disease prevention and recovery. In this study, case reports on the management of COVID-19 with Kampo medicine, which were published until March 31, 2021, were reviewed. The search strategy involved the use of Medline and hand-searching. Twenty two patients were treated using Kampo medicines with or without Western medicine, based on individual conditions. On the other hand, the effects of Kampo medicines as a potential preventive treatment (pre-infection), active treatment (especially in the acute and subacute stage), or treatment of sequelae to aid recovery (after infection) in the different stages of COVID-19 are being studied as research projects in the Japan Society for Oriental Medicine (JSOM). JSOM has also organized a pioneering project of clinical trials for COVID-19, some of which are now in progress.
Integrated Omics Reveals the Orchestrating Role of Calycosin in Danggui Buxue Tang, a Herbal Formula Containing Angelicae Sinensis Radix and Astragali Radix, in Inducing Osteoblastic Differentiation and Proliferation
Authors: Kwan Kenneth K L , Wong Tin Yan , Yu Anna X D , Dong Tina T X , Lam Henry H N , Tsim Karl W K
Published: June 2021

Systems biology unravels the black box of signaling pathway of cells; but which has not been extensively applied to reveal the mechanistic synergy of a herbal formula. The therapeutic efficacies of a herbal formula having multi-target, multi-function and multi-pathway are the niches of traditional Chinese medicine (TCM). Here, we reported an integrated omics approach, coupled with the knockout of an active compound, to measure the regulation of cellular signaling, as to reveal the landscape in cultured rat osteoblasts having synergistic pharmacological efficacy of Danggui Buxue Tang (DBT), a Chinese herbal formula containing Angelicae Sinensis Radix and Astragali Radix. The changes in signaling pathways responsible for energy metabolism, RNA metabolism and protein metabolism showed distinct features between DBT and calycosin-depleted DBT. Here, our results show that calycosin within DBT can orchestrate the osteoblastic functions and signaling pathways of the entire herbal formula. This finding reveals the harmony of herbal medicine in pharmacological functions, as well as the design of drug/herbal medicine formulation. The integration of systems biology can provide novel and essential insights into the synergistic property of a herbal formula, which is a key in modernizing TCM.
Allergic Asthma-Induced Cognitive Impairment is Alleviated by Dexamethasone
Authors: Ren Mengli , Feng Min , Long Zhimin , Ma Jing , Peng Xuehua , He Guiqiong
Published: June 2021

Allergic asthma is a typical chronic inflammatory disease of respiratory tract. Clinical data shows that patients with allergic asthma have different degrees of cognitive dysfunction. The molecular mechanism underlying the pathogenesis of asthma-induced cognitive disorder is not yet well defined. Dexamethasone (DEX), one of the first-line drugs being widely used in the treatment of asthma, has not been reported to have an effect on cognitive dysfunction in mice model. To investigate the effect of asthma on cognitive impairment as well as the effect of DEX on asthma-caused morphological and behavioral changes, C57BL/6J mice received treatment with house dust mites (HDM) for 60 days to become allergic asthma model mice, and a group of HDM-treated asthma model mice were treated with DEX. HDM-treated asthma model mice exhibited increased airway hyperresponsiveness (AHR) and inflammatory infiltration in lung tissue. An elevated level of IL-4, IL-5, and TNF-α was detected in bronchoalveolar lavage fluid (BALF) by Luminex liquid suspension chip. Asthma model mice also presented memory deficits accompanied with morphological changes at the synaptic levels in the cortex and hippocampus. Meanwhile, vascular edema and increased expression of HIF-1α and HIF-2α were found in the brain of asthma model mice. Interestingly, DEX treatment could reverse the inflammatory changes in asthma model mice airway, rescue the cognitive impairment and improve the synaptic plasticity. Besides, DEX significantly decreased the expression of HIF-1α and HIF-2α in mice brain and lung. These processes may be used to decipher the complex interplay and pathological changes between asthma and cognition. This study provides laboratory evidence for the prevention and treatment of cognitive malfunction induced by asthma.
Intensity of Glycemic Exposure in Early Adulthood and Target Organ Damage in Middle Age: The CARDIA Study
Authors: Lin Yifen , Zhong Xiangbin , Xiong Zhenyu , Zhang Shaozhao , Liu Menghui , Fan Yongqiang , Huang Yiquan , Sun Xiuting , Zhou Huimin , Xu Xingfeng , Guo Yue , Li Yuqi , Yang Daya , Ye Xiaomin , Zhuang Xiaodong , Liao Xinxue
Published: June 2021

Aim

To determine whether long-term intensity of glycemic exposure (IGE) during young adulthood is associated with multiple target organs function at midlife independent of single fasting glucose (FG) measurement.

Methods

We included 2,859 participants, aged 18–30 years at Y0, in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. IGE was calculated as the sum of (average FG of two consecutive examinations × years between the examinations) over 25 years. Target organs function was indicated by cardiac structure, left ventricular (LV) systolic function, LV diastolic function, coronary artery calcium (CAC), and urine albumin-to-creatinine ratio (UACR) at Y25. We evaluated the associations between IGE with target organs function using linear regression models and estimated the associations between IGE with numbers of organs involved (0, 1, or ≥ 2 organs) using multinomial logistic regression models.

Results

A 1-SD increment of IGE was significantly associated with worse target organs function after multivariable adjustment: left ventricular mass (β [SE], 5.468 [1.175]); global longitudinal strain (β [SE], 0.161 [0.071]); E/e’ ratio (β[SE], 0.192 [0.071]); CAC score (β [SE], 27.948 [6.116]); and log UACR (β [SE], 0.076 [0.010]). Besides, IGE was independently associated with having ≥ 2 organs involved in both overall population (OR [95% CI], 1.48 [1.23, 1.41], P < 0.001) and subgroups stratified by diabetes at Y25.

Conclusion

Higher intensity of glycemic exposure during young adulthood was independently associated with subclinical alterations of target organs function at midlife. Our findings highlight the importance of early screening and management of IGE in youth.
Gravity-Induced Lower-Leg Swelling Can Be Ameliorated by Ingestion of α-Glucosyl Hesperidin Beverage
Authors: Nishimura Naoki , Iwase Satoshi , Takumi Hiroko , Yamamoto Keiko
Published: June 2021

The most likely cause of lower-leg swelling is prolonged sitting, which sometimes induces deep vein thrombosis, also known as, economy class syndrome. We aimed to clarify the influence of intake of 4G-α-glucopyranosyl hesperidin (G-Hsp) beverage on the lower-leg swelling caused by 6 h of sitting in six healthy women. All subjects ingested 100 mL of G-Hsp or Placebo beverages with 100 mL of mineral water after 10 min of rest in a chair. Subsequently, subjects were requested to sit in the chair in a relaxed position for 6 h with two breaks to walk for urination. Calf water content measured by impedance plethysmography, calf circumference, and calf skin temperature by infrared thermography were measured, along with assessment of calf swelling sensation on a visual analog scale. Increase in ankle % circumference was significantly less after the G-Hsp ingestion (101.8 ± 1.5%) than after placebo (103.3 ± 0.8%; P = 0.004). A significant difference was found between percent circumference after the G-Hsp and the placebo, that is, the calf swelling after the placebo was significantly larger (P = 0.043). A gradual increase in skin temperature at the lower limb was observed after G-Hsp ingestion, while there was no change after placebo. Gravity-induced calf and ankle swelling resulted by prolonged sitting can be ameliorated by oral ingestion of hesperidin-derived G-Hsp through production of nitric oxide. It might be helpful in preventing economy-class syndrome caused by enforced sitting for a long duration.
Trajectories of Homoeolog-Specific Expression in Allotetraploid Tragopogon castellanus Populations of Independent Origins
Authors: Boatwright J. Lucas , Yeh Cheng-Ting , Hu Heng-Cheng , Susanna Alfonso , Soltis Douglas E. , Soltis Pamela S. , Schnable Patrick S. , Barbazuk William B.
Published: June 2021

Polyploidization can have a significant ecological and evolutionary impact by providing substantially more genetic material that may result in novel phenotypes upon which selection may act. While the effects of polyploidization are broadly reviewed across the plant tree of life, the reproducibility of these effects within naturally occurring, independently formed polyploids is poorly characterized. The flowering plant genus Tragopogon (Asteraceae) offers a rare glimpse into the intricacies of repeated allopolyploid formation with both nascent (< 90 years old) and more ancient (mesopolyploids) formations. Neo- and mesopolyploids in Tragopogon have formed repeatedly and have extant diploid progenitors that facilitate the comparison of genome evolution after polyploidization across a broad span of evolutionary time. Here, we examine four independently formed lineages of the mesopolyploid Tragopogon castellanus for homoeolog expression changes and fractionation after polyploidization. We show that expression changes are remarkably similar among these independently formed polyploid populations with large convergence among expressed loci, moderate convergence among loci lost, and stochastic silencing. We further compare and contrast these results for T. castellanus with two nascent Tragopogon allopolyploids. While homoeolog expression bias was balanced in both nascent polyploids and T. castellanus, the degree of additive expression was significantly different, with the mesopolyploid populations demonstrating more non-additive expression. We suggest that gene dosage and expression noise minimization may play a prominent role in regulating gene expression patterns immediately after allopolyploidization as well as deeper into time, and these patterns are conserved across independent polyploid lineages.
Expression and Functional Evaluation of Recombinant Anti-receptor Activator of Nuclear Factor Kappa-B Ligand Monoclonal Antibody Produced in Nicotiana benthamiana
Authors: Boonyayothin Wanuttha , Sinnung Sirorut , Shanmugaraj Balamurugan , Abe Yoshito , Strasser Richard , Pavasant Prasit , Phoolcharoen Waranyoo
Published: June 2021

Denosumab, an anti-receptor activator of nuclear factor-kappa B ligand antibody (anti-RANKL), is a fully human monoclonal antibody (mAb) available for the treatment of osteoporosis. In the present study, an anti-RANKL mAb was transiently expressed using the geminiviral expression system in Nicotiana benthamiana, and the functional activity of the plant-produced mAb was determined. The highest expression level of the plant-produced mAb was found at 8 days post-infiltration, and it was estimated to be 0.5 mg/g leaf fresh weight. The recombinant mAb from the plant crude extracts was purified by using Protein A affinity column chromatography. The plant-produced mAb demonstrated good in vitro affinity binding with human RANKL, as determined by RANKL-ELISA binding. The function of the plant-produced mAb was evaluated in vitro. CD14-positive cells isolated from human peripheral blood mononuclear cells (PBMCs) were cultured in vitro in the presence of human RANKL and macrophage-colony-stimulating factor (M-CSF) to stimulate osteoclastogenesis. The results demonstrated that plant-produced mAb could significantly decrease the number of osteoclasts compared to commercial denosumab. These results demonstrated that the plant-produced mAb has the potential to inhibit osteoclast differentiation and that it could be considered for osteoporosis treatment.
Functionality of the Crosswise Model for Assessing Sensitive or Transgressive Behavior: A Systematic Review and Meta-Analysis
Authors: Sagoe Dominic , Cruyff Maarten , Spendiff Owen , Chegeni Razieh , de Hon Olivier , Saugy Martial , van der Heijden Peter G. M. , Petróczi Andrea
Published: June 2021

Tools for reliable assessment of socially sensitive or transgressive behavior warrant constant development. Among them, the Crosswise Model (CM) has gained considerable attention. We systematically reviewed and meta-analyzed empirical applications of CM and addressed a gap for quality assessment of indirect estimation models. Guided by the PRISMA protocol, we identified 45 empirical studies from electronic database and reference searches. Thirty of these were comparative validation studies (CVS) comparing CM and direct question (DQ) estimates. Six prevalence studies exclusively used CM. One was a qualitative study. Behavior investigated were substance use and misuse (k= 13), academic misconduct (k= 8), and corruption, tax evasion, and theft (k= 7) among others. Majority of studies (k= 39) applied the “more is better” hypothesis. Thirty-five studies relied on birthday distribution and 22 of these usedP= 0.25 for the non-sensitive item. Overall, 11 studies were assessed as high-, 31 as moderate-, and two as low quality (excluding the qualitative study). The effect of non-compliance was assessed in eight studies. From mixed CVS results, the meta-analysis indicates that CM outperforms DQ on the “more is better” validation criterion, and increasingly so with higher behavior sensitivity. However, little difference was observed between DQ and CM estimates for items with DQ prevalence estimate around 50%. Based on empirical evidence available to date, our study provides support for the superiority of CM to DQ in assessing sensitive/transgressive behavior. Despite some limitations, CM is a valuable and promising tool for population level investigation.
What Happens When Individuals Answer Questionnaires in Two Different Languages
Authors: Paz Clara , Hermosa-Bosano Carlos , Evans Chris
Published: June 2021

The aim of the present study was to compare scores from the English and the Spanish versions of two well-known measures of psychological distress using a within-subject approach. This method involved bilingual participants completing both measures in four conditions. For two groups of people, measures were offered in the same language both times and for the other two groups, each language version was offered, the order differing between the groups. The measures were the Clinical Outcomes in Routine Evaluation-Outcome Measure and the Schwartz Outcome Scale-10, both originally created in English and then translated to Spanish. In total, 109 bilingual participants (69.7% women) completed the measures in two occasions and were randomly allocated to the four conditions (English-English, English-Spanish, Spanish-English and Spanish-Spanish). Linear mixed effects models were performed to provide a formal null hypothesis test of the effect of language, order of completion and their interaction for each measure. The results indicate that for the total score of the Clinical Outcomes in Routine Evaluation-Outcome Measure just language had a significant effect, but no significant effects were found for completion order or the language by order interaction. For the Schwartz Outcome Scale-10 scores, none of these effects were statistically significant. This method offers some clear advantages over the more prevalent psychometric methods of testing score comparability across measure translations.
Psychological Distress Among Health Care Workers in Health Facilities of Mettu Town During COVID-19 Outbreak, South West Ethiopia, 2020
Authors: Hajure Mohammedamin , Dibaba Bekem , Shemsu Shuayib , Desalegn Defaru , Reshad Mohammed , Mohammedhussein Mustefa
Published: June 2021

Background: During any of the infectious disease outbreak, health care workers were at increased risk of being infected, and psychological distress was a common phenomenon. Therefore, the study aimed to assess the psychological distress related to COVID-19 among healthcare workers in Mettu town.

Methods: A cross sectional study was conducted from May 1–15, 2020 using convenient sampling techniques among 127 health care providers during COVID-19 pandemic in the Mettu town. Self-administered questionnaire was used to collect information. Depression and anxiety were evaluated as subscales from the Depression Anxiety Stress Scale (DASS-21). Psychological distress related to COVID-19 was measured using the Impact of Event Scale Revised (IES-R). Data analysis were done using SPSS version 24. Chi-square test was used to find the association between the outcome and demographic variables. Multivariable logistic regression analyses were used to evaluate the significance of the association at P-value < 0.05.

Result: Using IES-R scale, 40.2% of the participants reported to have the symptoms of psychological distress. The majority of the participants reported mild psychological distress (37%) followed by moderate psychological distress (29%). The multivariate logistic regression analysis revealed that the odds of psychological distress were found to be higher among health care providers who reported to have depressive symptoms, and those who used alcohol, khat and tobacco in the past 3 months shows a significant association with psychological distress.

Conclusion: Our findings revealed that the COVID-19 pandemic had exerted major psychological distress on health care providers. So the findings, seek attention for early psychological intervention needed to manage psychological distress in health care providers regarding identified factors.
INteractive Virtual Expert-Led Skills Training: A Multi-Modal Curriculum for Medical Trainees
Authors: Curtin Michelle , Downs Jennifer , Hunt Amber , Coleman Emily R. , Enneking Brett A. , McNally Keehn Rebecca
Published: June 2021

Background: Internationally, pediatric depression and suicide are significant issues. Additionally, in the context of the COVID-19 pandemic, pediatric mental health needs are rising astronomically. In light of Child & Adolescent Psychiatrist (CAP) subspecialist shortages in the United States (US), there is an increasing call for primary care physicians in Family Medicine and Pediatrics to address an increasingly broad variety of patient needs. Here we report on the development and preliminary evaluation of medical student and resident perceptions on the “INteractive Virtual Expert-led Skills Training” (INVEST) medical education curriculum, a virtual synchronous CAP curriculum employing active learning strategies, including expert-led discussion and video modeling, and discussion designed to meet those priorities.

Methods: In a standardized 60-min training format, our curriculum leverages audience response system polling, video modeling of key clinical skills, and interactive discussion with an expert subspecialist, over a virtual video conferencing platform. The primary educational strategy relies on use of video modeling to demonstrate best practice with CAP led group discussion to solidify and explain important concepts. Five waves of medical students and residents (N = 149) participated in the INVEST curriculum and completed pre- and post-training surveys regarding knowledge and comfort in the management of pediatric patients with depression and suicidality.

Results: Trainee participants reported significant positive gains in perceived likelihood of encountering pediatric suicidality as well as knowledge/comfort with depression screening and suicidality assessment in a primary care setting. Across some competency areas, there was an effect of medical learner level. Learners at lower levels generally reported the highest benefit. Medical students reported significant increases in their comfort interpreting and discussing positive depression screens and evidenced the greatest relative benefit in comfort with discussing suicidality.

Conclusion: To our knowledge, INVEST is the first fully virtual, multimodal curriculum led by expert CAP subspecialists. Our findings suggest that INVEST shows promise for equipping medical learners with baseline knowledge for caring for patients with pediatric depression and suicidality. This synchronous, virtually delivered curriculum allows for critical training delivered to diverse medical learners regardless of geographic location, a particular benefit during the current COVID-19 pandemic.
A Case of Concurrent Molybdenosis, Secondary Copper, Cobalt and Selenium Deficiency in a Small Sheep Herd in Northern Germany
Authors: Helmer Carina , Hannemann Regina , Humann-Ziehank Esther , Kleinschmidt Sven , Koelln Mareike , Kamphues Josef , Ganter Martin
Published: June 2021

To the author’s knowledge this paper describes the first proven report of a combined primary molybdenosis, secondary copper (Cu) deficiency, Ovine White Liver Disease—Cobalt (Co) deficiency, and selenium (Se) deficiency in a small pedigree herd of White Horned Heath sheep in Germany (8 ewes, 2 rams, 3 yearling ewes, 17 lambs) for decades. Clinical signs associated with these mineral deficiencies in a group of pastured ram lambs included emaciation, conjunctivitis, anaemia, growth retardation, discolouration of the wool and photodermatitis. Morbidities and mortalities arose in 4–6-month-old lambs despite intensive veterinary treatment in the summer of 2014 and 2015 (n = 13, 23% died). Se (3/5), Cu (4/7), and Co (3/3) deficiencies in combination with elevated values for Molybdenum (Mo, 2/2) were found. Hamburg is a large industrial city and an input of heavy metals from surrounding industries and coal-fired power stations in combination with a sandy, non-fertilised soil and monoculture grass species might offer a potential explanation for the severity of mineral deficiencies observed in this herd.