bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-Cell Multiomic Approaches Reveal Diverse Labeling of the Nervous System by Common Cre-Drivers
Authors: Keuls Rachel A. , Parchem Ronald J.
Published: April 2021

Neural crest development involves a series of dynamic, carefully coordinated events that result in human disease when not properly orchestrated. Cranial neural crest cells acquire unique multipotent developmental potential upon specification to generate a broad variety of cell types. Studies of early mammalian neural crest and nervous system development often use the Cre-loxP system to lineage trace and mark cells for further investigation. Here, we carefully profile the activity of two common neural crest Cre-drivers at the end of neurulation in mice. RNA sequencing of labeled cells at E9.5 reveals that Wnt1-Cre2 marks cells with neuronal characteristics consistent with neuroepithelial expression, whereas Sox10-Cre predominantly labels the migratory neural crest. We used single-cell mRNA and single-cell ATAC sequencing to profile the expression ofWnt1andSox10and identify transcription factors that may regulate the expression of Wnt1-Cre2 in the neuroepithelium and Sox10-Cre in the migratory neural crest. Our data identify cellular heterogeneity during cranial neural crest development and identify specific populations labeled by two Cre-drivers in the developing nervous system.
Variable Effects of PD-Risk Associated SNPs and Variants in Parkinsonism-Associated Genes on Disease Phenotype in a Community-Based Cohort
Authors: Markopoulou Katerina , Chase Bruce A. , Premkumar Ashvini P. , Schoneburg Bernadette , Kartha Ninith , Wei Jun , Yu Hongjie , Epshteyn Alexander , Garduno Lisette , Pham Anna , Vazquez Rosa , Frigerio Roberta , Maraganore Demetrius
Published: April 2021

Genetic risk factors for Parkinson's disease (PD) risk and progression have been identified from genome-wide association studies (GWAS), as well as studies of familial forms of PD, implicating common variants at more than 90 loci and pathogenic or likely pathogenic variants at 16 loci. With the goal of understanding whether genetic variants at these PD-risk loci/genes differentially contribute to individual clinical phenotypic characteristics of PD, we used structured clinical documentation tools within the electronic medical record in an effort to provide a standardized and detailed clinical phenotypic characterization at the point of care in a cohort of 856 PD patients. We analyzed common SNPs identified in previous GWAS studies, as well as low-frequency and rare variants at parkinsonism-associated genes in the MDSgene database for their association with individual clinical characteristics and test scores at baseline assessment in our community-based PD patient cohort: age at onset, disease duration, Unified Parkinson's Disease Rating Scale I-VI, cognitive status, initial and baseline motor and non-motor symptoms, complications of levodopa therapy, comorbidities and family history of neurological disease with one or more than one affected family members. We find that in most cases an individual common PD-risk SNP identified in GWAS is associated with only a single clinical feature or test score, while gene-level tests assessing low-frequency and rare variants reveal genes associated in either a unique or partially overlapping manner with the different clinical features and test scores. Protein-protein interaction network analysis of the identified genes reveals that while some of these genes are members of already identified protein networks others are not. These findings indicate that genetic risk factors for PD differentially affect the phenotypic presentation and that genes associated with PD risk are also differentially associated with individual disease phenotypic characteristics at baseline. These findings raise the intriguing possibility that different SNPs/gene effects impact discrete phenotypic characteristics. Furthermore, they support the hypothesis that different gene and protein-protein interaction networks that underlie PD risk, the PD phenotype, and the neurodegenerative process leading to the disease phenotype, and point to the significance of the genetic background on disease phenotype.
Large-Volume Intrathecal Administrations: Impact on CSF Pressure and Safety Implications
Authors: Belov Vasily , Appleton Janine , Levin Stepan , Giffenig Pilar , Durcanova Beata , Papisov Mikhail
Published: April 2021

The increasing number of studies demonstrates the high potency of the intrathecal (IT) route for the delivery of biopharmaceuticals to the central nervous system (CNS). Our earlier data exhibited that both the infused volume and the infusion rate can regulate the initial disposition of the administered solute within the cerebrospinal fluid (CSF). This disposition is one of key factors in defining the subsequent transport of the solute to its intended target. On the other hand, fast additions of large volumes of liquid to the CSF inevitably raise the CSF pressure [a.k.a. intracranial pressure (ICP)], which may in turn lead to adverse reactions if the physiologically delimited threshold is exceeded. While long-term biological effects of elevated ICP (hydrocephalus) are known, the safety thresholds pertaining to short-term ICP elevations caused by IT administrations have not yet been characterized. This study aimed to investigate the dynamics of ICP in rats and non-human primates (NHPs) with respect to IT infusion rates and volumes. The safety regimes were estimated and analyzed across species to facilitate the development of translational large-volume IT therapies. The data revealed that the addition of a liquid to the CSF raised the ICP in a rate and volume-dependent manner. At low infusion rates (<0.12 ml/min in rats and <2 ml/min in NHPs), NHPs and rats displayed similar tolerance patterns. Specifically, safe accommodations of such added volumes were mainly facilitated by the accelerated pressure-dependent CSF drainage into the blood, with I stabilizing at different levels below the safety threshold of 28 ± 4 mm Hg in rats and 50 ± 5 mm Hg in NHPs. These ICPs were safely tolerated for extended durations (of at least 2–25 min). High infusion rates (including boluses) caused uncompensated exponential ICP elevations rapidly exceeding the safety thresholds. Their tolerance was species-dependent and was facilitated by the compensatory role of the varied components of craniospinal compliance while not excluding the possibility of other contributing factors. In conclusion, large volumes of liquids can safely be delivered via IT routes provided that ICP is monitored as a safety factor and cross-species physiological differences are accounted for.
Reduced Functional Connectivity in Children With Congenital Cataracts Using Resting-State Electroencephalography Measurement
Authors: Chen Wan , Lan Liping , Xiao Wei , Li Jiahong , Liu Jiahao , Zhao Fei , Wang Chang-Dong , Zheng Yiqing , Chen Weirong , Cai Yuexin
Published: April 2021

Objectives

Numerous task-based functional magnetic resonance imaging studies indicate the presence of compensatory functional improvement in patients with congenital cataracts. However, there is neuroimaging evidence that shows decreased sensory perception or cognition information processing related to visual dysfunction, which favors a general loss hypothesis. This study explored the functional connectivity between visual and other networks in children with congenital cataracts using resting state electroencephalography.

Methods

Twenty-one children with congenital cataracts (age: 8.02 ± 2.03 years) and thirty-five sex- and age-matched normal sighted controls were enrolled to investigate functional connectivity between the visual cortex and the default mode network, the salience network, and the cerebellum network during resting state electroencephalography (eyes closed) recordings.

Result

The congenital cataract group was less active, than the control group, in the occipital, temporal, frontal and limbic lobes in the theta, alpha, beta1 and beta2 frequency bands. Additionally, there was reduced alpha-band connectivity between the visual and somatosensory cortices and between regions of the frontal and parietal cortices associated with cognitive and attentive control.

Conclusion

The results indicate abnormalities in sensory, cognition, motion and execution functional connectivity across the developing brains of children with congenital cataracts when compared with normal controls. Reduced frontal alpha activity and alpha-band connectivity between the visual cortex and salience network might reflect attenuated inhibitory information flow, leading to higher attentional states, which could contribute to adaptation of environmental change in this group of patients.
The Effect of Prenatal Food Restriction on Brain Proteome in Appropriately Grown and Growth Restricted Male Wistar Rats
Authors: Potiris Anastasios , Manousopoulou Antigoni , Zouridis Andreas , Sarli Polyxeni-Maria , Pervanidou Panagiota , Eliades George , Perrea Despina N. , Deligeoroglou Efthymios , Garbis Spiros D. , Eleftheriades Makarios
Published: April 2021

Background

Fetal growth restriction (FGR) has been associated with a higher risk of developing adverse perinatal outcomes and distinct neurodevelopmental and neurobehavioral disorders. The aim of the present study was to investigate the impact of prenatal food restriction on the brain proteome in both FGR and appropriately grown rats and to identify potential pathways connecting maternal malnutrition with altered brain development.

Methods

Ten time-dated pregnant Wistar rats were housed individually at their 12th day of gestation. On the 15th day of gestation, the rats were randomly divided into two groups, namely the food restricted one (n = 6) and the control group (n = 4). From days 15 to 21 the control group had unlimited access to food and the food restricted group was given half the amount of food that was on average consumed by the control group, based on measurements taken place the day before. On the 21st day of gestation, all rats delivered spontaneously and after birth all newborn pups of the food restricted group were weighed and matched as appropriately grown (non-FGR) or growth restricted (FGR) and brain tissues were immediately collected. A multiplex experiment was performed analyzing brain tissues from 4 FGR, 4 non-FGR, and 3 control male offspring. Differentially expressed proteins (DEPs) were subjected to bioinformatics analysis in order to identify over-represented processes.

Results

Proteomic analysis resulted in the profiling of 3,964 proteins. Gene ontology analysis of the common DEPs using DAVID (https://david.ncifcrf.gov/) showed significant enrichment for terms related to cellular morphology, learning, memory and positive regulation of NF-kappaB signaling. Ingenuity Pathway Analysis showed significant induction of inflammation in FGR pups, whereas significant induction of cell migration and cell spreading were observed in non-FGR pups.

Conclusion

This study demonstrated that in both FGR and non-FGR neonates, a range of adaptive neurodevelopmental processes takes place, which may result in altered cellular morphology, chronic stress, poor memory and learning outcomes. Furthermore, this study highlighted that not only FGR, but also appropriately grown pups, which have been exposed to prenatal food deprivation may be at increased risk for impaired cognitive and developmental outcomes.
Abnormal Intrinsic Functional Interactions Within Pain Network in Cervical Discogenic Pain
Authors: Zhang Hong , Xia Dongqin , Wu Xiaoping , Liu Run , Liu Hongsheng , Yang Xiangchun , Yin Xiaohui , Chen Song , Ma Mingyue
Published: April 2021

Cervical discogenic pain (CDP) is mainly induced by cervical disc degeneration. However, how CDP modulates the functional interactions within the pain network remains unclear. In the current study, we studied the changed resting-state functional connectivities of pain network with 40 CDP patients and 40 age-, gender-matched healthy controls. We first defined the pain network with the seeds of the posterior insula (PI). Then, whole brain and seed-to-target functional connectivity analyses were performed to identify the differences in functional connectivity between CDP and healthy controls. Finally, correlation analyses were applied to reveal the associations between functional connectivities and clinical measures. Whole-brain functional connectivity analyses of PI identified increased functional connectivity between PI and thalamus (THA) and decreased functional connectivity between PI and middle cingulate cortex (MCC) in CDP patients. Functional connectivity analyses within the pain network further revealed increased functional connectivities between bilateral PI and bilateral THA, and decreased functional connectivities between left PI and MCC, between left postcentral gyrus (PoCG) and MCC in CDP patients. Moreover, we found that the functional connectivities between right PI and left THA, between left PoCG and MCC were negatively and positively correlated with the visual analog scale, respectively. Our findings provide direct evidence of how CDP modulates the pain network, which may facilitate understanding of the neural basis of CDP.
Variation in Lifestyle-Related Behavior Among Obese Indian Patients With Non-alcoholic Fatty Liver Disease
Authors: Arora Charu , Malhotra Anita , Ranjan Piyush , Vikram Naval K. , Dwivedi S. N. , Singh Namrata , Shalimar  , Singh Vishwajeet
Published: April 2021

Lifestyle modification is the mainstay of treatment in Non-Alcoholic Fatty Liver Disease (NAFLD). Published Indian data on the diet and lifestyle of Indian NAFLD patients is scarce. This study explored variation in lifestyle-related behavior among obese patients with NAFLD. Ultrasonography (USG) diagnosed obese NAFLD patients (n = 140) were assessed for dietary intake [1-day 24 hours recall, food-frequency questionnaire (FFQ)] and physical activity (PA) [Global Physical Activity Questionnaire (GPAQ)]. Diet quality score (0–30) and physical activity (PA) levels were used to study variation in lifestyle and assess the effect of lifestyle on the severity of NAFLD. Compared to the recommendation, calorie consumption was 25.2% higher in nearly half (53.6%) of the subjects and mean macronutrient intake was imbalanced (60.3% carbohydrates, 12.4% protein, 25.5% fats). Variation was seen in terms of diet quality—good (3%), moderate (54.3%), or poor (43.5%) and intensity of PA—high (15%), moderate (47.9%), or low (37.1%). No patient had a combination of high PA and good diet quality within all grades of NAFLD. Our study suggests wide variation in lifestyles of obese patients with NAFLD and need for a more flexible and individualized modification of their diet and PA.
Malignant Transformation in Vestibular Schwannoma: Clinical Study With Survival Analysis
Authors: Li Jiuhong , Wang Qiguang , Zhang Menglan , Zhang Guisheng , Zhang Si , Hui Xuhui
Published: April 2021

Aim

Vestibular schwannomas (VSs) are generally considered benign tumors, and malignant transformation of VSs (MTVSs) are rare findings. The clinical features, treatment strategy, outcomes and prognostic factors remain unclear. We endeavored to analyze the natural history, management, outcomes and prognostic factors of MTVSs.

Materials and Methods

The clinical features, radiologic findings, pathological investigations and surgical outcomes of 4 patients with MTVSs treated at the authors’ institution between 2010 and 2019 were retrospectively collected. Related literature published until December 2019 (63 articles, 67 patients) was evaluated. The authors also made a pooled analysis to evaluate the risk factors for overall survival (OS) time.

Results

Of the 4 cases in our series, 3 cases were malignant transformation following previous treatment (surgery and radiosurgery) and 1 was primary MTVS. Of the 71 MTVSs from the literature, 27 were male and 39 were female, with the mean age of 47.2 ± 17.5 years old. Twelve patients (18.5%) were diagnosed with NF2 (15.4%) or NF1 (3.1%). Forty-three (61.4%) patients underwent previous treatment (surgery and/or radiotherapy) prior to the pathological diagnosis of MTVSs. The mean size of the MTVSs was 35.1 ± 13.2mm. The mean Ki-67 index was 30.6% ± 18.8%. Twenty-four (49.0%) patients underwent gross total resection, 25 (51.0%) patients underwent incomplete resection. Twenty-five (44.6%) underwent adjuvant radiotherapy (RT) postoperatively. During the average follow-up of 9.9 ± 9.5 months (range, 0-40 months), 37 (82.2%) patients developed a local recurrence or metastasis. Forty-seven (73.4%) patients died of tumor progression or postoperative complications. The overall 1-year and 2-year survival rate was 42.3% and 18.6% respectively. Log-rank testing for Kaplan-Meier survival analysis identified that size (P = 0.047) and adjuvant radiotherapy (P=0.001) were significant prognostic factors for OS. Multivariate analysis revealed that adjuvant RT was the only prognostic factor for longer OS (P = 0.005).

Conclusions

MTVSs are rare, fatal disease, prone to recur and metastasize rapidly, resulting in death in most of the cases. We found that GTR did not improve the survival in MTVSs but postoperative adjuvant RT can significantly improve the OS, and we recommend early postoperative RT in MTVSs regardless of extent of resection.
Baicalin Prevents Myocardial Ischemia/Reperfusion Injury Through Inhibiting ACSL4 Mediated Ferroptosis
Authors: Fan Zhenyu , Cai Liangliang , Wang Shengnan , Wang Jing , Chen Bohua
Published: April 2021

Baicalin is a natural flavonoid glycoside that confers protection against myocardial ischemia/reperfusion (I/R) injury. However, its mechanism has not been fully understood. This study focused on elucidating the role of ferroptosis in baicalin-generated protective effects on myocardial ischemia/reperfusion (I/R) injury by using the myocardial I/R rat model and oxygen–glucose deprivation/reoxygenation (OGD/R) H9c2 cells. Our results show that baicalin improved myocardial I/R challenge–induced ST segment elevation, coronary flow (CF), left ventricular systolic pressure , infarct area, and pathological changes and prevented OGD/R-triggered cell viability loss. In addition, enhanced lipid peroxidation and significant iron accumulation along with activated transferrin receptor protein 1 (TfR1) signal and nuclear receptor coactivator 4 (NCOA4)-medicated ferritinophagy were observed in in vivo and in vitro models, which were reversed by baicalin treatment. Furthermore, acyl-CoA synthetase long-chain family member 4 (ACSL4) overexpression compromised baicalin-generated protective effect in H9c2 cells. Taken together, our findings suggest that baicalin prevents against myocardial ischemia/reperfusion injury via suppressing ACSL4-controlled ferroptosis. This study provides a novel target for the prevention of myocardial ischemia/reperfusion injury.
Jianpi Jieyu Decoction, An Empirical Herbal Formula, Exerts Psychotropic Effects in Association With Modulation of Gut Microbial Diversity and GABA Activity
Authors: Liu Lanying , Zou Zhilu , Yang Jiangwei , Li Xiaoqi , Zhu Boran , Zhang Hailou , Sun Yan , Zhang Yuxuan , Zhang Zhang-Jin , Wang Wei
Published: April 2021

Background: Recent studies suggest that gut microbiota was associated with the bidirectional gut-brain axis which could modulate neuropsychological functions of the central nervous system. Gut microbiota could produce gamma aminobutyric acid (GABA) that could modulate the gut–brain axis response. Jianpi Jieyu (JPJY) decoction, a traditional Chinese formula, is mainly composed of Astragalus membranaxeus and Radix Pseudostellariae. Although the JPJY decoction has been used to treat the depression in China, the potential action of its antidepressant has not been well understood. Thus this study was aim to investigate the role of JPJY improve gut microbiota homeostasis in the chronic stress induced depressive mice.

Methods: The antidepressant effect of JPJY on chronic unpredictable mild stress (CUMS) mice was evaluated by using sucrose preference test, tail suspension test and forced swim test. Fatigue-like behaviors were evaluated using degree of redness, grip strength test, and exhaustive swimming test. The new object recognition test was used to evaluate cognition performance. Fecal samples were collected and taxonomical analysis of intestinal microbial distribution was conducted with 16S rDNA. Serum level of GABA was measured using high performance liquid chromatography (HPLC). The expression of GluR1 and p-Tau protein in the hippocampus was determined using Western blotting.

Results: The dose of 9.2 g/kg JPJY produced antidepressant-like effects. JPJY and its major components also modulated gut microbiota diversity in the CUMS mice. Serum level of GABA and the expressions of hippocampal GluR1 and p-Tau were reversed after the administration of JPJY in CUMS mice.

Conclusion: JPJY regulates gut microbiota to produce antidepressant-like effect and improve cognition deficit in depressive mice while its molecular mechanism possibly be enhanced NR1 and Tau expression in hippocampus and increased GABA in serum.
RIPK2 as a New Therapeutic Target in Inflammatory Bowel Diseases
Authors: Honjo Hajime , Watanabe Tomohiro , Kamata Ken , Minaga Kosuke , Kudo Masatoshi
Published: April 2021

Inflammatory bowel diseases (IBDs) are becoming more frequent worldwide. A significant fraction of patients with IBD are refractory to various types of therapeutic biologics and small molecules. Therefore, identification of novel therapeutic targets in IBD is required. Receptor-interacting serine/threonine kinase 2 (RIPK2), also known as receptor-interacting protein 2 (RIP2), is a downstream signaling molecule for nucleotide-binding oligomerization domain 1 (NOD1), NOD2, and Toll-like receptors (TLRs). RIPK2 is expressed in antigen-presenting cells, such as dendritic cells and macrophages. Recognition of microbe-associated molecular patterns by NOD1, NOD2, and TLRs leads to the interaction between RIPK2 and these innate immune receptors, followed by the release of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-12/23p40 through the activation of nuclear factor kappa B and mitogen-activated protein kinases. Thus, activation of RIPK2 plays a critical role in host defense against microbial infections. Recent experimental and clinical studies have provided evidence that activation of RIPK2 is involved in the development of autoimmune diseases, especially IBDs. In addition, the colonic mucosa of patients with IBD exhibits enhanced expression of RIPK2 and associated signaling molecules. Furthermore, the blockage of RIPK2 activation ameliorates the development of experimental murine colitis. Thus, activation of RIPK2 underlies IBD immunopathogenesis. In this review, we attempt to clarify the roles played by RIPK2 in the development of IBD by focusing on its associated signaling pathways. We also discuss the possibility of using RIPK2 as a new therapeutic target in IBD.
Development and Validation of an Interleukin-6 Nomogram to Predict Primary Non-response to Infliximab in Crohn’s Disease Patients
Authors: Chen Yueying , Li Hanyang , Feng Qi , Shen Jun
Published: April 2021

Background: The primary non-response (PNR) rate of infliximab (IFX) varies from 20 to 46% for the treatment of Crohn’s disease (CD). Detected PNR reduces the improper use of specific treatments. To date, there is hardly any knowledge regarding early markers of PNR. The aim of this study was to evaluate the role of Interleukin-6 (IL-6) as an early predictor of PNR of IFX for the treatment of CD.

Methods: We enrolled 322 bio-naïve patients diagnosed with CD from January 2016 to May 2020. Primary response was determined at week 14. Multivariable logistic regression was used to construct prediction models. Area under the curve (AUC), calibration and decision curve analyses (DCA) were assessed in the validation cohort. GEO data were analyzed to identify potential mechanisms of IL-6 in IFX therapy for CD.

Results: PNR occurred in 31.06% (100 of 322) patients who were assessable at week 14. IL-6 levels significantly decreased after IFX therapy (p < 0.001). The validation model containing IL-6 presented enhanced discrimination with an AUC of 0.908 and high calibration. Decision curve analysis (DCA) indicated that the model added extra predictive value. GEO data confirmed the IL-6 levels were increased in the PNR group and IL-6-related differentially expressed genes (DEGs) were enriched in the inflammatory response.

Conclusions: We concluded that IL-6 may be used as a predictive factor to assess the risk of PNR to IFX therapy.
Systematic Review and Network Meta-Analysis: Comparative Efficacy and Safety of Biosimilars, Biologics and JAK1 Inhibitors for Active Crohn Disease
Authors: Wu Guozhi , Yang Yuan , Liu Min , Wang Yuping , Guo Qinghong
Published: April 2021

Background: Crohn disease (CD) is a chronic inflammatory disease that affects quality of life. There are several drugs available for the treatment of CD, but their relative efficacy is unknown due to a lack of high-quality head-to-head randomized controlled trials.

Aim: To perform a mixed comparison of the efficacy and safety of biosimilars, biologics and JAK1 inhibitors for CD.

Methods: We searched PubMed, Web of Science, embase and the Cochrane Library for randomized controlled trials (RCTs) up to Dec. 28, 2020. Only RCTs that compared the efficacy or safety of biosimilars, biologics and JAK1 inhibitors with placebo or another active agent for CD were included in the comparative analysis. Efficacy outcomes were the induction of remission, maintenance of remission and steroid-free remission, and safety outcomes were serious adverse events (AEs) and infections. The Bayesian method was utilized to compare the treatments. The registration number is CRD42020187807.

Results: Twenty-eight studies and 29 RCTs were identified in our systematic review. The network meta-analysis demonstrated that infliximab and adalimumab were superior to certolizumab pegol (OR 2.44, 95% CI 1.35–4.97; OR 2.96, 95% CI 1.57–5.40, respectively) and tofacitinib (OR 2.55, 95% CI 1.27–5.97; OR 3.10, 95% CI 1.47–6.52, respectively) and revealed the superiority of CT-P13 compared with placebo (OR 2.90, 95% CI 1.31–7.59) for the induction of remission. Infliximab (OR 7.49, 95% CI 1.85–34.77), adalimumab (OR 10.76, 95% CI 2.61–52.35), certolizumab pegol (OR 4.41, 95% CI 1.10–21.08), vedolizumab (OR 4.99, 95% CI 1.19–25.54) and CT-P13 (OR 10.93, 95% CI 2.10–64.37) were superior to filgotinib for the maintenance of remission. Moreover, infliximab (OR 3.80, 95% CI 1.49–10.23), adalimumab (OR 4.86, 95% CI 1.43–16.95), vedolizumab (OR 2.48, 95% CI 1.21–6.52) and CT-P13 (OR 5.15, 95% CI 1.05–27.58) were superior to placebo for steroid-free remission. Among all treatments, adalimumab ranked highest for the induction of remission, and CT-P13 ranked highest for the maintenance of remission and steroid-free remission.

Conclusion: CT-P13 was more efficacious than numerous biological agents and JAK1 inhibitors and should be recommended for the treatment of CD. Further head-to-head RCTs are warranted to compare these drugs.
Health-Related Quality of Life Based on EQ-5D Utility Score in Patients With Tuberculosis: A Systematic Review
Authors: Park Hae-Young , Cheon Hyo-Bin , Choi Sun Ha , Kwon Jin-Won
Published: April 2021

Background: Tuberculosis (TB) has significant effects on patients’ health-related quality of life (HRQOL) and this study was conducted to evaluate the HRQOL based on EQ-5D utility score according to various health statuses of TB patients.

Methods: A systematic literature review was conducted to select articles on HRQOLs outcomes of TB patients since 2000. A total of 1,710 articles were searched for primary screening and seven studies that directly assessed all types of TB patients using the EQ-5D were finally selected.

Results: The EQ-5D scores of TB patients were in the ranges of 0.43–0.70. After the completion of TB treatment, the utility weights increased to the ranges of 0.88–0.98 and the EQ VAS values showed similar trend as the results of the EQ-5D. The EQ-5D score for multi-drug-resistant TB was very low at 0.51 during treatment but increased to 0.88 after the treatment was completed. The utility weights of latent TB were not significantly different from those of the general population.

Conclusion: This study showed that the HRQOL based on the EQ-5D utility score of TB patients has significantly decreased, and the TB treatment has a significantly positive effect on the quality of life of patients.
Vitamin D Promotes Skeletal Muscle Regeneration and Mitochondrial Health
Authors: Latham Christine M. , Brightwell Camille R. , Keeble Alexander R. , Munson Brooke D. , Thomas Nicholas T. , Zagzoog Alyaa M. , Fry Christopher S. , Fry Jean L.
Published: April 2021

Vitamin D is an essential nutrient for the maintenance of skeletal muscle and bone health. The vitamin D receptor (VDR) is present in muscle, as is CYP27B1, the enzyme that hydroxylates 25(OH)D to its active form, 1,25(OH)D. Furthermore, mounting evidence suggests that vitamin D may play an important role during muscle damage and regeneration. Muscle damage is characterized by compromised muscle fiber architecture, disruption of contractile protein integrity, and mitochondrial dysfunction. Muscle regeneration is a complex process that involves restoration of mitochondrial function and activation of satellite cells (SC), the resident skeletal muscle stem cells. VDR expression is strongly upregulated following injury, particularly in central nuclei and SCs in animal models of muscle injury. Mechanistic studies provide some insight into the possible role of vitamin D activity in injured muscle. In vitro and in vivo rodent studies show that vitamin D mitigates reactive oxygen species (ROS) production, augments antioxidant capacity, and prevents oxidative stress, a common antagonist in muscle damage. Additionally, VDR knockdown results in decreased mitochondrial oxidative capacity and ATP production, suggesting that vitamin D is crucial for mitochondrial oxidative phosphorylation capacity; an important driver of muscle regeneration. Vitamin D regulation of mitochondrial health may also have implications for SC activity and self-renewal capacity, which could further affect muscle regeneration. However, the optimal timing, form and dose of vitamin D, as well as the mechanism by which vitamin D contributes to maintenance and restoration of muscle strength following injury, have not been determined. More research is needed to determine mechanistic action of 1,25(OH)D on mitochondria and SCs, as well as how this action manifests following muscle injury in vivo. Moreover, standardization in vitamin D sufficiency cut-points, time-course study of the efficacy of vitamin D administration, and comparison of multiple analogs of vitamin D are necessary to elucidate the potential of vitamin D as a significant contributor to muscle regeneration following injury. Here we will review the contribution of vitamin D to skeletal muscle regeneration following injury.
Selection and Validation of Reference Genes For qRT-PCR Analysis of Rhopalosiphum padi (Hemiptera: Aphididae)
Authors: Li Mengyi , Li Xinan , Wang Chao , Li Qiuchi , Zhu Saige , Zhang Yunhui , Li Xiangrui , Yang Fengshan , Zhu Xun
Published: April 2021

Rhopalosiphum padi (L.) (Hemiptera: Aphididae) is an important cosmopolitan pest in cereal crops. Reference genes can significantly affect qRT-PCR results. Therefore, selecting appropriate reference genes is a key prerequisite for qRT-PCR analyses. This study was conducted to identify suitable qRT-PCR reference genes in R. padi. We systematically analyzed the expression profiles of 11 commonly used reference genes. The ΔCt method, the BestKeeper, NormFinder, geNorm algorithms, and the RefFinder online tool were used to evaluate the suitability of these genes under diverse experimental conditions. The data indicated that the most appropriate sets of reference genes were β-actin and GAPDH (for developmental stages), AK and TATA (for populations), RPS18 and RPL13 (for tissues), TATA and GAPDH (for wing dimorphism), EF-1α and RPS6 (for antibiotic treatments), GAPDH and β-actin (for insecticide treatments), GAPDH, TATA, RPS18 (for starvation-induced stress), TATA, RPS6, and AK (for temperatures), and TATA and GAPDH (for all conditions). Our study findings, which revealed the reference genes suitable for various experimental conditions, will facilitate the standardization of qRT-PCR programs, while also improving the accuracy of qRT-PCR analyses, with implications for future research on R. padi gene functions.
Bacillus circulans GN03 Alters the Microbiota, Promotes Cotton Seedling Growth and Disease Resistance, and Increases the Expression of Phytohormone Synthesis and Disease Resistance-Related Genes
Authors: Qin Lijun , Tian Peidong , Cui Qunyao , Hu Shuping , Jian Wei , Xie Chengjian , Yang Xingyong , Shen Hong
Published: April 2021

Plant growth-promoting bacteria (PGPB) are components of the plant rhizosphere that promote plant growth and/or inhibit pathogen activity. To explore the cotton seedlings response to Bacillus circulans GN03 with high efficiency of plant growth promotion and disease resistance, a pot experiment was carried out, in which inoculations levels of GN03 were set at 104 and 108 cfu⋅mL–1. The results showed that GN03 inoculation remarkably enhanced growth promotion as well as disease resistance of cotton seedlings. GN03 inoculation altered the microbiota in and around the plant roots, led to a significant accumulation of growth-related hormones (indole acetic acid, gibberellic acid, and brassinosteroid) and disease resistance-related hormones (salicylic acid and jasmonic acid) in cotton seedlings, as determined with ELISA, up-regulated the expression of phytohormone synthesis-related genes (EDS1, AOC1, BES1, and GA20ox), auxin transporter gene (Aux1), and disease-resistance genes (NPR1 and PR1). Comparative genomic analyses was performed between GN03 and four similar species, with regards to phenotype, biochemical characteristics, and gene function. This study provides valuable information for applying the PGPB alternative, GN03, as a plant growth and disease-resistance promoting fertilizer.
Molecular Interaction and Evolution of Jasmonate Signaling With Transport and Detoxification of Heavy Metals and Metalloids in Plants
Authors: Chen Xuan , Jiang Wei , Tong Tao , Chen Guang , Zeng Fanrong , Jang Sunghoon , Gao Wei , Li Zhen , Mak Michelle , Deng Fenglin , Chen Zhong-Hua
Published: April 2021

An increase in environmental pollution resulting from toxic heavy metals and metalloids [e.g., cadmium (Cd), arsenic (As), and lead (Pb)] causes serious health risks to humans and animals. Mitigation strategies need to be developed to reduce the accumulation of the toxic elements in plant-derived foods. Natural and genetically-engineered plants with hyper-tolerant and hyper-accumulating capacity of toxic minerals are valuable for phytoremediation. However, the molecular mechanisms of detoxification and accumulation in plants have only been demonstrated in very few plant species such as Arabidopsis and rice. Here, we review the physiological and molecular aspects of jasmonic acid and the jasmonate derivatives (JAs) in response to toxic heavy metals and metalloids. Jasmonates have been identified in, limiting the accumulation and enhancing the tolerance to the toxic elements, by coordinating the ion transport system, the activity of antioxidant enzymes, and the chelating capacity in plants. We also propose the potential involvement of Ca2+ signaling in the stress-induced production of jasmonates. Comparative transcriptomics analyses using the public datasets reveal the key gene families involved in the JA-responsive routes. Furthermore, we show that JAs may function as a fundamental phytohormone that protects plants from heavy metals and metalloids as demonstrated by the evolutionary conservation and diversity of these gene families in a large number of species of the major green plant lineages. Using ATP-Binding Cassette G (ABCG) transporter subfamily of six representative green plant species, we propose that JA transporters in Subgroup 4 of ABCGs may also have roles in heavy metal detoxification. Our paper may provide guidance toward the selection and development of suitable plant and crop species that are tolerant to toxic heavy metals and metalloids.
Why Do You Trust News? The Event-Related Potential Evidence of Media Channel and News Type
Authors: Fan Bonai , Liu Sifang , Pei Guanxiong , Wu Yufei , Zhu Lian
Published: April 2021

Media is the principal source of public information, and people's trust in news has been a critical mechanism in social cohesion. In recent years, the vast growth of new media (e.g., internet news portals) has brought huge change to the way information is conveyed, cannibalizing much of the space of traditional media (e.g., traditional newspapers). This has led to renewed attention on media credibility. The study aims to explore the impact of media channel on trust in news and examine the role of news type. Twenty-six participants were asked to make trust–distrust decisions after reading a variety of news headlines from different media channels while undergoing electroencephalography (EEG) monitoring. The electrophysiological results showed that, for hard news (e.g., important news related to public life), the new media condition elicited smaller N100 and larger P200 amplitudes than the traditional media condition. However, for soft news (e.g., entertainment, and non-related to vital interest), there was no significant difference. The study suggests that the fitness of media channel and news type may influence the evaluation of news, impacting participants' affective arousal and attention allocation in the early stage and influencing trust in news. These results provide neurocognitive evidence of individuals' trust toward hard and soft news consumed via different media channels, yielding new insights into trust in media and contributing to media trust theory.
Factor Structure of the Short-Form of Center for Epidemiological Studies Depression Scale for People With Physical Disabilities
Authors: Park Eun-Young
Published: April 2021

This study aimed to examine the factor structure of the short-form of Center for Epidemiological Studies Depression Scale (CES-D-11) using confirmatory factor analysis (CFA). We extracted data from 670 people with physical disabilities (PWPD) from the Korea Welfare Panel. To investigate the model fit regarding factor structure, a one-factor model, four-factor model, and four-factor within bifactor model, as reported in previous studies, were examined using CFA, and goodness-of-fit indices were compared. As a result of the analysis, the four-factor model and the four-factor within bifactor model satisfied the criteria of correspondence with goodness-of-fit indices. Reliability of the four individual factors ranged from 0.722 to 0.834, indicating acceptable reliability. Validity and reliability of the four-factor within bifactor structure was confirmed through CFA and reliability analysis. In future studies using the CES-D-11 to measure depression in PWPD, comparison between four sub-factors and total scores might be possible.
Association Between Adolescent Internet Gaming and Adult Problematic Web-Based Board Gaming
Authors: Ryoo Hanil , Bae Sujin , Kim Sun Mi , Min Kyoung Joon , Han Doug Hyun
Published: April 2021

Introduction: The results of studies comparing the characteristics of Internet gaming with those of Internet gambling have been controversial. We hypothesized that problematic web-based board gaming behaviors are associated with psychological and social interaction factors. We also hypothesized that non-problematic adolescent Internet gaming is a protective factor against problematic web-based board gaming and that problematic Internet gaming is a predictive factor for problematic web-based board gaming.

Methods: We recruited 104 adults who reported engaging in web-based gaming. All participants were asked to complete the Problematic Web Board Gameplay Scale, Center for Epidemiologic Studies Depression Scale (CESD), State-Trait Anxiety Inventory (STAI), Adult Attention Deficit/Hyperactivity Disorder Self-Report Scale (K-AADHD), Family Environmental Scale (FES), Social Avoidance and Distress Scale (SADS), and questionnaires on their web-based board gaming patterns and Internet gaming history.

Results: Problematic web-based board gamers showed a lower history of adolescent Internet gaming but a greater rate of problematic Internet gaming compared with healthy web-based board gamers. Moreover, problematic web-based board gamers showed an increase in CES-D, STAI, K-AADHD, and SADS scores but decreased FES scores compared with healthy web-based board gamers. Joblessness; less experience as an Internet gamer; a history of problematic Internet gaming; higher CES-D, STAI, and K-AADHD scores; and lower FES scores were significant predictors of problematic web-based board gaming.

Discussion: Psychological, social, and environmental factors can positively influence problematic Web-based board gaming. Healthy Internet gaming during adolescence may play a preventive role in adult problematic web-based board gaming. However, because adolescent problematic Internet gaming tends to lead to problematic web-based board gaming, measures should be taken to prevent it.
Case Report: Use of Subcutaneous Midazolam During an Episode of Catatonia
Authors: Raymond Valentin , Véry Etienne , Jullien Adeline , Eyvrard Fréderic , Anguill Loic , Yrondi Antoine
Published: April 2021

Midazolam is a benzodiazepine (BZD) mainly used in anesthetic induction due to its pharmacokinetic features. Its place in the therapeutic management of catatonia remains to be determined. Here we present the case of a 65-year-old man who presented with a first episode of catatonia with opposition to any form of oral treatment, where a single dose of 1 mg of subcutaneous (SC) Midazolam permitted clinical improvement allowing oral treatment to be given. The patient's history notably included a renal transplant linked to Polycystic Kidney Disease (PKD) and no history of psychiatric illness nor of any use of psychotropic drugs. As the patient refused to drink or eat and ceased answering basic questions, a psychiatric assessment was required. A diagnosis of Catatonic disorder due to a general medical condition [DSM 5–293.89/ ICD10 [F06.1]] was made. A Bush-Francis Catatonia Rating Scale (BFCRS) analysis returned a score of 15 out of 62, with stupor, mutism, negativism, staring, withdrawal, rigidity, and stereotypy. As the negativism prevented the patient from taking any form of oral treatment, after a brief discussion with the unit's physician, it was decided to administer 1 mg of SC Midazolam. One hour later, the patient was more responsive and compliant, and agreed to drink, eat, and take medication. Thus, the catatonic signs of mutism, negativism, staring, and withdrawal were resolved, but waxy flexibility and catalepsy appeared, leading to a new BFCRS score of 10 out of 62. Oral treatment with 2.5 mg Lorazepam, 4 times a day, was then initiated. Midazolam could be a safer choice compared with the other options available, such as other SC BZD, considering the complex safety profile of this patient with renal insufficiency. This situation represents the first report of using SC Midazolam as an injectable treatment for catatonia. More studies are needed to assess the clinical pertinence of SC Midazolam in the treatment of catatonia.
The Plasma Universe: A Coherent Science Theme for Voyage 2050
Authors: Verscharen Daniel , Wicks Robert T. , Branduardi-Raymont Graziella , Erdélyi Robertus , Frontera Filippo , Götz Charlotte , Guidorzi Cristiano , Lebouteiller Vianney , Matthews Sarah A. , Nicastro Fabrizio , Rae Iain Jonathan , Retinò Alessandro , Simionescu Aurora , Soffitta Paolo , Uttley Phil , Wimmer-Schweingruber Robert F.
Published: April 2021

In review of the White Papers from the Voyage 2050 process1 and after the public presentation of a number of these papers in October 2019 in Madrid, we as White Paper lead authors have identified a coherent science theme that transcends the divisions around which the Topical Teams are structured. This note aims to highlight this synergistic science theme and to make the Topical Teams and the Voyage 2050 Senior Committee aware of the wide importance of these topics and the broad support that they have across the worldwide science community.
The Importance of a Food Systems Approach to Low and Middle Income Countries and Emerging Economies: A Review of Theories and Its Relevance for Disease Control and Malnutrition
Authors: Alarcon Pablo , Dominguez-Salas Paula , Fèvre Eric M. , Rushton Jonathan
Published: April 2021

Our review explores the changing food production, distribution and consumption environment in low and middle-income countries and emerging economies as a basis for framing how to study food systems in order to address public health issues of food safety and nutrition. It presents the state of knowledge on existing food systems science and its use in terms of sustainable actions for food safety and public health. The review identifies a knowledge gap in food system mapping and governance, with value chain mapping of key commodities often missing. Despite a number of initiatives, the application of food systems methods is highly variable in scope and quality. Most analyses concentrate on specific commodities, rarely taking into account the need for a whole diet approach when looking at nutrition or the assessment of a range of infectious agents and their interactions when looking at food safety. Of the studies included in the review there is a growing observation of “informal” food systems, a term used inconsistently and one that requires revision. “Informal” food systems link to the formal sector to provide food security, yet with trade-offs between economic efficiencies and food safety. Efforts to improve food safety are hampered by inadequate food safety capacities and a lack of policy coherence leading to: inadequate investment; fragmented food quality control systems; weak or non-existent traceability mechanisms; weak foodborne disease surveillance; obsolete food regulation; and weak regulatory enforcement. In-depth food systems assessments can complement risk analysis to identify risky behaviors and understand institutional settings in order to improve codes of practice and enforcement. Methods for looking at food safety from a food systems perspective are emerging, yet existing nutrition and food systems science are not advancing sufficiently in response to nutritional public health problems. There is an urgency for improved understanding of the structure and drivers of the food systems, for better planning of changes that leads to nutrients access and healthy levels of eating. It is proposed that countries and international institutions provide an atlas of food system maps for the key commodities based on an agreed common methodology and developed by multidisciplinary teams.