bluuebunny/crossref_metadata_2025 huggingface dataset:
Conceptualizing and Measuring Appetite Self-Regulation Phenotypes and Trajectories in Childhood: A Review of Person-Centered Strategies
Authors: Russell Alan , Leech Rebecca M. , Russell Catherine G.
Published: December 2021

This review uses person-centered research and data analysis strategies to discuss the conceptualization and measurement of appetite self-regulation (ASR) phenotypes and trajectories in childhood (from infancy to about ages 6 or 7 years). Research that is person-centered provides strategies that increase the possibilities for investigating ASR phenotypes. We first examine the utility of examining underlying phenotypes using latent profile/class analysis drawing on cross-sectional data. The use of trajectory analysis to investigate developmental change is then discussed, with attention to phenotypes using trajectories of individual behaviors as well as phenotypes based on multi-trajectory modeling. Data analysis strategies and measurement approaches from recent examples of these person-centered approaches to the conceptualization and investigation of appetite self-regulation and its development in childhood are examined. Where relevant, examples from older children as well as developmental, clinical and educational psychology are drawn on to discuss when and how person-centered approaches can be used. We argue that there is scope to incorporate recent advances in biological and psychoneurological knowledge about appetite self-regulation as well as fundamental processes in the development of general self-regulation to enhance the examination of phenotypes and their trajectories across childhood (and beyond). The discussion and conclusion suggest directions for future research and highlight the potential of person-centered approaches to progress knowledge about the development of appetite self-regulation in childhood.
Meta-Analysis of Postoperative Adjuvant Hepatic Artery Infusion Chemotherapy Versus Surgical Resection Alone for Hepatocellular Carcinoma
Authors: Ke Qiao , Wang Lei , Wu Weimin , Huang Xinhui , Li Ling , Liu Jingfeng , Guo Wuhua
Published: December 2021

Background

To systematically identify the long-term efficacy of postoperative adjuvant hepatic artery infusion chemotherapy (HAIC) for patients with hepatocellular carcinoma (HCC).

Methods

PubMed, MedLine, Embase, the Cochrane Library, and Web of Science were searched to collect the eligible studies up to March 31, 2021, that compared the surgical resection (SR) versus SR+HAIC for HCC patients. The endpoints were overall survival (OS) rates and disease-free survival (DFS) rates, and the effect size was determined by hazard ratio (HR) with 95% CI.

Results

A total of 12 studies (two randomized controlled trials (RCTs) and 10 non-RCTs) including 1,333 patients were eligible for this meta-analysis. The pooled results showed that OS and DFS rates in the SR+HAIC group were both better than those in the SR alone group (HR = 0.56, 95% CI = 0.41–0.77, p < 0.001; HR = 0.66, 95% CI = 0.55–0.78, p < 0.001, respectively). Furthermore, the subgroup analysis showed that patients would benefit from SR+HAIC regardless of chemotherapy regimens and courses (all p < 0.05), and patients with microvascular or macrovascular invasion would also benefit more from SR+HAIC in terms of OS and DFS (all p < 0.05).

Conclusion

Postoperative adjuvant HAIC could improve the long-term prognosis of HCC patients, especially for those with microvascular or macrovascular invasion, regardless of chemotherapy regimens and courses, but it deserves further validation.
m6A Regulator Expression Segregates Meningiomas Into Biologically Distinct Subtypes
Authors: Chen Jiawei , Sun Shuchen , Ren Leihao , Hua Lingyang , Wang Daijun , Xie Qing , Wirsching Hans-Georg , Deng Jiaojiao , Weller Michael , Gong Ye
Published: December 2021

Background

Meningiomas are the most common primary intracranial tumors in adults. According to the 2021 World Health Organization (WHO) classification of central nervous system tumors, approximately 80% of meningiomas are WHO grade 1, that is, histopathologically benign, whereas about 20% are WHO grade 2 or grade 3, showing signs of atypia or malignancy. The dysregulation of N6-methylation (m6A) regulators is associated with disorders of diverse critical biological processes in human cancer. This study aimed to explore whether m6A regulator expression was associated with meningioma molecular subtypes and immune infiltration.

Methods

We evaluated the m6A modification patterns of 160 meningioma samples based on 19 m6A regulators and correlated them with immune infiltration characteristics. Novel molecular subtypes were defined based on prognostic hub gene expression.

Results

Two meningioma clusters were identified based on the expression of 19 m6A regulators. In cluster 1, 607 differentially expressed genes (DEGs) were upregulated and 519 were downregulated. A total of 1,126 DEGs comprised three gene expression modules characterized by turquoise, blue, and gray. Functional annotation suggested that the turquoise module was involved in Wnt-related and other important cancer-related pathways. We identified 32 hub genes in this module by constructing a protein–protein interaction network. The meningioma samples were divided into two molecular subtypes. EPN1, EXOSC4, H2AX, and MZT2B not only showed significant differences between meningioma molecular subtypes but also had the potential to be the marker genes of specific meningioma subtypes.

Conclusion

m6A regulator gene expression may be a novel prognostic marker in meningioma.
A Retrospective Study on Spinal Dissemination of Supratentorial Glioma
Authors: Chen Jianxin , Yang Fan , Shi Qi , Zhao Yuze , Huang Hongyan
Published: December 2021

Objective

Metastatic spinal dissemination (MSD) of supratentorial glioma is very rare and there is no established standard of care. The current study investigates the clinical characteristics and course of spinal dissemination of supratentorial glioma.

Methods

A retrospective analysis of adult patients with MSD of supratentorial glioma treated in the Department of Oncology in Beijing Shijitan Hospital, Capital Medical University from June 2012 until August 2021 was performed. The time to event was estimated using Kaplan–Meier analysis. Univariate analyses were performed using log-rank test and multivariate analysis was performed using the Cox proportional hazards model.

Results

Thirty-four adult patients with MSD of supratentorial glioma were enrolled in this retrospective study. The median time to MSD (TTMSD) and overall survival (OS) were 5 months (range: 0–78 months) and 15 months (range: 0.7–85 months), respectively, in the entire cohort. Univariate analysis demonstrated that the patients who had received TMZ therapy had a longer TTMSD than those who did not (mTTMSD: 15 vs. 3 months, log-rank P = 0.0004). Furthermore, a protracted duration of salvage chemotherapy of >6 months after MSD was associated with longer OS of the patients with MSD of supratentorial glioma (mOS: 13 vs. 5 months, log-rank P = 0.0163) and reduced the death risk by 64.3% (hazard ratio: 0.357, 95% CI: 0.141–0.901, P = 0.029) compared with a duration ≤6 months.

Conclusion

Patients with MSD of supratentorial glioma experienced poor prognosis and adjuvant chemotherapy may delay the occurrence of MSD. The protracted duration of systemic salvage chemotherapy may favor survival after spinal dissemination.
A Study of the Lipidomic Profiles of the CAL-27 and HOK Cell Lines Using EMS Spectra
Authors: Wang Xue-ying , Zhang Ting , Guan Wei-qun , Li Hua-zhu , Lin Ling
Published: December 2021

Objective

The aim of this study was to explore the lipidomic profiles of the CAL-27 human tongue cancer cell line and the human oral keratinocyte (HOK) cell line.

Methods

The lipidomic differences between the CAL-27 and the HOK cell lines were investigated using non-targeted high-performance liquid chromatography–mass spectrometry lipidomic analysis. The resulting data were then further mined via bioinformatics analysis technology and metabolic pathway analysis was conducted in order to map the most affected metabolites and pathways in the two cell lines.

Results

A total of 711 lipids were identified, including 403 glycerophospholipids (GPs), 147 glycerolipids, and 161 sphingolipids. Comparison of the enhanced MS (EMS) spectra of the two cell lines in positive and negative ionization modes showed the lipid compositions of HOK and CAL-27 cells to be similar. The expressions of most GP species in CAL-27 cells showed an increasing trend as compared with HOK, whereas a significant increase in phosphatidylcholine was observed (p < 0.05). Significant differences in the lipid composition between CAL-27 and HOK cells were shown as a heatmap. Through principal component analysis and orthogonal partial least squares discriminant analysis, noticeably clear separation trends and satisfactory clustering trends between groups of HOK and CAL-27 cells were identified. The numbers of specific lipid metabolites that could distinguish CAL-27 from HOK in positive and negative modes were 100 and 248, respectively. GP metabolism was the most significantly altered lipid metabolic pathway, with 4 metabolites differentially expressed in 39 hit products.

Conclusion

This study demonstrated the potential of using untargeted mass spectra and bioinformatics analysis to describe the lipid profiles of HOK and CAL-27 cells.
Geometrical Comparison and Quantitative Evaluation of 18F-FDG PET/CT- and DW-MRI-Based Target Delineation Before and During Radiotherapy for Esophageal Squamous Carcinoma
Authors: Li Huimin , Li Jianbin , Li Fengxiang , Zhang Yingjie , Li Yankang , Guo Yanluan , Xu Liang
Published: December 2021

Background and Purpose

This study aimed to evaluate the geometrical differences in and metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG PET-CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) performed before and during radiotherapy (RT) for patients with esophageal cancer based on the three-dimensional CT (3DCT) medium and explore whether the high signal area derived from DW-MRI can be used as a tool for an individualized definition of the volume in need of dose escalation for esophageal squamous cancer.

Materials and Methods

Thirty-two patients with esophageal squamous cancer sequentially underwent repeated 3DCT, 18F-FDG PET-CT, and enhanced MRI before the initiation of RT and after the 15th fraction. All images were fused with 3DCT images through deformable registration. The gross tumor volume (GTV) was delineated based on PET Edge on the first and second PET-CT images and defined as GTVPETpre and GTVPETdur, respectively. GTVDWIpre and GTVDWIdur were delineated on the first and second DWI and corresponding T2-weighted MRI (T2W-MRI)-fused images. The maximum, mean, and peak standardized uptake values (SUVs; SUVmax, SUVmean, and SUVpeak, respectively); metabolic tumor volume (MTV); and total lesion glycolysis(TLG) and its relative changes were calculated automatically on PET. Similarly, the minimum and mean apparent diffusion coefficient (ADC; ADCmin and ADCmean) and its relative changes were measured manually using ADC maps.

Results

The volume of GTVCT exhibited a significant positive correlation with that of GTVPET and GTVDWI (both p < 0.001). Significant differences were observed in both ADCs and 18F-FDG PET metabolic parameters before and during RT (both p < 0.001). No significant correlation was observed between SUVs and ADCs before and during RT (p = 0.072–0.944) and between ∆ADCs and ∆SUVs (p = 0.238–0.854). The conformity index and degree of inclusion of GTVPETpre to GTVDWIpre were significantly higher than those of GTVPETdur to GTVDWIdur (both p < 0.001). The maximum diameter shrinkage rate (∆LDDWI) (24%) and the tumor volume shrinkage rate (VRRDWI) (60%) based on DW-MRI during RT were significantly greater than the corresponding PET-based ∆LDPET (14%) and VRRPET (41%) rates (p = 0.017 and 0.000, respectively).

Conclusion

Based on the medium of CT images, there are significant differences in spatial position, biometabolic characteristics, and the tumor shrinkage rate for GTVs derived from 18F-FDG PET-CT and DW-MRI before and during RT for esophageal squamous cancer. Further studies are needed to determine if DW-MRI will be used as tool for an individualized definition of the volume in need of dose escalation.
A Prediction Model Using Alternative Splicing Events and the Immune Microenvironment Signature in Lung Adenocarcinoma
Authors: Zhu Liping , Wang Zhiqiang , Sun Yilan , Giamas Georgios , Stebbing Justin , Yu Zhentao , Peng Ling
Published: December 2021

Background

Alternative splicing (AS) is a gene regulatory mechanism that drives protein diversity. Dysregulation of AS is thought to play an essential role in cancer initiation and development. This study aimed to construct a prognostic signature based on AS and explore the role in the tumor immune microenvironment (TIME) in lung adenocarcinoma.

Methods

We analyzed transcriptome profiling and clinical lung adenocarcinoma data from The Cancer Genome Atlas (TCGA) database and lists of AS-related and immune-related signatures from the SpliceSeq. Prognosis-related AS events were analyzed by univariate Cox regression analysis. Gene set enrichment analyses (GSEA) were performed for functional annotation. Prognostic signatures were identified and validated using univariate and multivariate Cox regression, LASSO regression, Kaplan–Meier survival analyses, and proportional hazards model. The context of TIME in lung adenocarcinoma was also analyzed. Gene and protein expression data of Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A) were obtained from ONCOMINE and Human Protein Atlas. Splicing factor (SF) regulatory networks were visualized.

Results

A total of 19,054 survival-related AS events in lung adenocarcinoma were screened in 1,323 genes. Exon skip (ES) and mutually exclusive exons (ME) exhibited the most and fewest AS events, respectively. Based on AS subtypes, eight AS prognostic signatures were constructed. Patients with high-risk scores were associated with poor overall survival. A nomogram with good validity in prognostic prediction was generated. AUCs of risk scores at 1, 2, and 3 years were 0.775, 0.736, and 0.759, respectively. Furthermore, the prognostic signatures were significantly correlated with TIME diversity and immune checkpoint inhibitor (ICI)-related genes. Low-risk patients had a higher StromalScore, ImmuneScore, and ESTIMATEScore. AS-based risk score signature was positively associated with CD8+ T cells. CDKN2A was also found to be a prognostic factor in lung adenocarcinoma. Finally, potential functions of SFs were determined by regulatory networks.

Conclusion

Taken together, our findings show a clear association between AS and immune cell infiltration events and patient outcome, which could provide a basis for the identification of novel markers and therapeutic targets for lung adenocarcinoma. SF networks provide information of regulatory mechanisms.
Bridging the Gap for Children With Compound Health Challenges: An Intervention Protocol
Authors: Elgen Irene , Heggestad Torhild , Tronstad Rune , Greve Gottfried
Published: December 2021

Background: During the last decades, there is a major shift in the panorama of diseases in children and adolescents. More children are referred to the specialized health care services due to less specific symptoms and more complex health challenges. These children are particularly difficult to care for in a “single-disease” oriented system. Our objective was to develop an alternative and more holistic approach better tailored to the complex needs of these children.

Method: The target patient population is children between 6 and 13 years with three or more referrals including both the pediatric department and the mental health services. Furthermore, to be included in the project, the child's actual complaints needed to be clinically considered as an unclear or compound condition in need of an alternative approach. This paper describes the process of developing an intervention where a complementary professional team meets the patient and his/her family altogether for 2.5 h. The consultation focus on clarifying the complex symptomatology and on problem solving. The bio-psycho-social model is applied, emphasizing the patient's story as told on the whiteboard. In the dynamic processes of development, piloting, evaluating, and adjusting the components, feed-back from the patients, their families, professional team members, and external team coaches is important.

The professional teams include pediatricians, psychologists and physiotherapists. Achieving the transformation from a logistic oriented team where members act separately toward a real complementary team, seems to be a success factor.

Discussion: Composing multi-disciplinary and complementary teams was an essential part of the re-designed intervention. Team interaction transforming the professionals from working as a logistic team to act as a complementary team, was one of the important requirements in the process. When re-designing the specialist health service, it is mandatory to anchor all changes among employees as well as the hospital leadership. In addition, it is important to include patient experiences in the process of improvement. Evaluation of long-term outcomes is needed to investigate possible benefits from the new intervention.

Trial Registration: Transitioning Young Patients' Health Care Trajectories, NCT04652154. Registered December 3rd, 2020–Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04652154?term=NCT04652154&draw=2&rank=1.
Inhibition of Brain GTP Cyclohydrolase I Attenuates 3-Nitropropionic Acid-Induced Striatal Toxicity: Involvement of Mas Receptor/PI3k/Akt/CREB/ BDNF Axis
Authors: Mustafa Aya M. , Rabie Mostafa A. , Zaki Hala F. , Shaheen Aya M.
Published: December 2021

GTP cyclohydrolase I (GTPCH I) is the rate-limiting enzyme for tetrahydrobiopterin (BH4) biosynthesis; the latter is an essential factor for iNOS activation that contributes neuronal loss in Huntington’s disease (HD). The aim of the study was to investigate the neuroprotective effect of 2,4-diamino-6-hydroxypyrimidine (DAHP), GTPCH I enzyme inhibitor, against neuronal loss in 3-nitropropinic acid (3-NP)-induced HD in rats and to reveal the possible involved mechanisms mediated through PI3K/Akt axis and its correlation to Mas receptor (MasR). Rats received 3-NP (10 mg/kg/day; i.p.) with or without administration of DAHP (0.5 g/kg/day; i.p.) or wortmannin (WM), a PI3K inhibitor, (15 μg/kg/day; i.v.) for 14 days. DAHP improved cognitive, memory, and motor abnormalities induced by 3-NP, as confirmed by striatal histopathological specimens and immunohistochemical examination of GFAP. Moreover, DAHP treatment inhibited GTPCH I activity, resulting in decreased BH4 levels and iNOS activation. Also, DAHP upregulated the protein expression of survival protein; p85/p55 (pY458/199)-PI3K and pS473-Akt that, in turn, boosted the activation of striatal neurotrophic factors and receptor, pS133-CREB, BDNF and pY515-TrKB, which positively affect MasR protein expression and improve mitochondrial dysfunction, as indicated by enhancing both SDH and PGC-1α levels. Indeed, DAHP attenuates oxidative stress by increasing SOD activity and Nrf2 expression in addition to reducing neuro-inflammatory status by inhibiting NF-κB p65 and TNF-α expression. Interestingly, all the previous effects were blocked by co-administration of WM with DAHP. In conclusion, DAHP exerts neuroprotective effect against neuronal loss induced by 3-NP administration via inhibition of GTPCH I and iNOS activity and activation of MasR/PI3K/Akt/CREB/BDNF/TrKB axis besides its antioxidant and anti-inflammatory effect.
Dysfunctional Vascular Endothelium as a Driver of Atherosclerosis: Emerging Insights Into Pathogenesis and Treatment
Authors: Botts Steven R. , Fish Jason E. , Howe Kathryn L.
Published: December 2021

Atherosclerosis, the chronic accumulation of cholesterol-rich plaque within arteries, is associated with a broad spectrum of cardiovascular diseases including myocardial infarction, aortic aneurysm, peripheral vascular disease, and stroke. Atherosclerotic cardiovascular disease remains a leading cause of mortality in high-income countries and recent years have witnessed a notable increase in prevalence within low- and middle-income regions of the world. Considering this prominent and evolving global burden, there is a need to identify the cellular mechanisms that underlie the pathogenesis of atherosclerosis to discover novel therapeutic targets for preventing or mitigating its clinical sequelae. Despite decades of research, we still do not fully understand the complex cell-cell interactions that drive atherosclerosis, but new investigative approaches are rapidly shedding light on these essential mechanisms. The vascular endothelium resides at the interface of systemic circulation and the underlying vessel wall and plays an essential role in governing pathophysiological processes during atherogenesis. In this review, we present emerging evidence that implicates the activated endothelium as a driver of atherosclerosis by directing site-specificity of plaque formation and by promoting plaque development through intracellular processes, which regulate endothelial cell proliferation and turnover, metabolism, permeability, and plasticity. Moreover, we highlight novel mechanisms of intercellular communication by which endothelial cells modulate the activity of key vascular cell populations involved in atherogenesis, and discuss how endothelial cells contribute to resolution biology – a process that is dysregulated in advanced plaques. Finally, we describe important future directions for preclinical atherosclerosis research, including epigenetic and targeted therapies, to limit the progression of atherosclerosis in at-risk or affected patients.
Strategies for Remodeling the Tumor Microenvironment Using Active Ingredients of Ginseng—A Promising Approach for Cancer Therapy
Authors: Li Mo , Wang Xin , Wang Ying , Bao Shunchao , Chang Qing , Liu Linlin , Zhang Shuai , Sun Liwei
Published: December 2021

The tumor microenvironment (TME) plays a key role in promoting the initiation and progression of tumors, leading to chemoradiotherapy resistance and immunotherapy failure. Targeting of the TME is a novel anti-tumor therapeutic approach and is currently a focus of anti-tumor research. Panax ginseng C. A. Meyer (ginseng), an ingredient of well-known traditional Asia medicines, exerts beneficial anti-tumor effects and can regulate the TME. Here, we present a systematic review that describes the current status of research efforts to elucidate the functions and mechanisms of ginseng active components (including ginsenosides and ginseng polysaccharides) for achieving TME regulation. Ginsenosides have variety effects on TME, such as Rg3, Rd and Rk3 can inhibit tumor angiogenesis; Rg3, Rh2 and M4 can regulate the function of immune cells; Rg3, Rd and Rg5 can restrain the stemness of cancer stem cells. Ginseng polysaccharides (such as red ginseng acidic polysaccharides and polysaccharides extracted from ginseng berry and ginseng leaves) can regulate TME mainly by stimulating immune cells. In addition, we propose a potential mechanistic link between ginseng-associated restoration of gut microbiota and the tumor immune microenvironment. Finally, we describe recent advances for improving ginseng efficacy, including the development of a nano-drug delivery system. Taken together, this review provides novel perspectives on potential applications for ginseng active ingredients as anti-cancer adjuvants that achieve anti-cancer effects by reshaping the tumor microenvironment.
Shenkang Injection and Its Three Anthraquinones Ameliorates Renal Fibrosis by Simultaneous Targeting IƙB/NF-ƙB and Keap1/Nrf2 Signaling Pathways
Authors: Luo Liang-Pu , Suo Ping , Ren Li-Li , Liu Hong-Jiao , Zhang Yamei , Zhao Ying-Yong
Published: December 2021

Oxidative stress and inflammation are important and critical mediators in the development and progression of chronic kidney disease (CKD) and its complications. Shenkang injection (SKI) has been widely used to treat patients with CKD. Although the anti-oxidative and anti-inflammatory activity was involved in SKI against CKD, its bioactive components and underlying mechanism remain enigmatic. A rat model of adenine-induced chronic renal failure (CRF) is associated with, and largely driven by, oxidative stress and inflammation. Hence, we identified the anti-oxidative and anti-inflammatory components of SKI and further revealed their underlying mechanism in the adenine-induced CRF rats. Compared with control rats, the levels of creatinine, urea, uric acid, total cholesterol, triglyceride, and low-density lipoprotein cholesterol in serum were significantly increased in the adenine-induced CRF rats. However, treatment with SKI and its three anthraquinones including chrysophanol, emodin, and rhein could reverse these aberrant changes. They could significantly inhibit pro-fibrotic protein expressions including collagen I, α-SMA, fibronectin, and vimentin in the kidney tissues of the adenine-induced CRF rats. Of note, SKI and rhein showed the stronger inhibitory effect on these pro-fibrotic protein expressions than chrysophanol and emodin. Furthermore, they could improve dysregulation of IƙB/NF-ƙB and Keap1/Nrf2 signaling pathways. Chrysophanol and emodin showed the stronger inhibitory effect on the NF-κB p65 protein expression than SKI and rhein. Rhein showed the strongest inhibitory effect on p65 downstream target gene products including NAD(P)H oxidase subunits (p47phox, p67phox, and gp91phox) and COX-2, MCP-1, iNOS, and 12-LO in the kidney tissues. However, SKI and rhein showed the stronger inhibitory effect on the significantly downregulated anti-inflammatory and anti-oxidative protein expression nuclear Nrf2 and its target gene products including HO-1, catalase, GCLC, and NQO1 in the Keap1/Nrf2 signaling pathway than chrysophanol and emodin. This study first demonstrated that SKI and its major components protected against renal fibrosis by inhibiting oxidative stress and inflammation via simultaneous targeting IƙB/NF-ƙB and Keap1/Nrf2 signaling pathways, which illuminated the potential molecular mechanism of anti-oxidative and anti-inflammatory effects of SKI.
Central Density and Low-Mode Perturbation Control of Inertial Confinement Fusion Dynamic-Shell Targets
Authors: Trickey W. , Goncharov V. N. , Igumenshchev I. V. , Shvydky A. , Collins T. J. B , Campbell E. M.
Published: December 2021

The dynamic-shell target is a new class of design for inertial confinement fusion (ICF). These targets address some of the target fabrication challenges prevalent in current ICF targets and take advantage of advances in manufacturing technologies. This study first examines how the dynamic-shell design can be used to control the density of the central region and therefore convergence ratio, thus expanding the design space for ICF. Additionally, the concern of low-mode perturbation growth is considered. A new class of high-performing beam configurations, based on icosahedral polyhedra and charged-particle simulations is proposed. These configurations achieve low levels of irradiation nonuniformity through selection of beam shapes that suppress the dominant symmetrical mode.
Consensus Indices of Two-Layered Multi-Star Networks: An Application of Laplacian Spectrum
Authors: Huang Da , Bian Jicheng , Jiang Haijun , Yu Zhiyong
Published: December 2021

In this article, the convergence speed and robustness of the consensus for several dual-layered star-composed multi-agent networks are studied through the method of graph spectra. The consensus-related indices, which can measure the performance of the coordination systems, refer to the algebraic connectivity of the graph and the network coherence. In particular, graph operations are introduced to construct several novel two-layered networks, the methods of graph spectra are applied to derive the network coherence for the multi-agent networks, and we find that the adherence of star topologies will make the first-order coherence of the dual-layered systems increase some constants in the sense of limit computations. In the second-order case, asymptotic properties also exist when the index is divided by the number of leaf nodes. Finally, the consensus-related indices of the duplex networks with the same number of nodes but non-isomorphic structures have been compared and simulated, and it is found that both the first-order coherence and second-order coherence of the network D are between A and B, and C has the best first-order robustness, but it has the worst robustness in the second-order case.
Hypoxic Regulation of the Large-Conductance, Calcium and Voltage-Activated Potassium Channel, BK
Authors: Ochoa Sara V. , Otero Liliana , Aristizabal-Pachon Andres Felipe , Hinostroza Fernando , Carvacho Ingrid , Torres Yolima P.
Published: December 2021

Hypoxia is a condition characterized by a reduction of cellular oxygen levels derived from alterations in oxygen balance. Hypoxic events trigger changes in cell-signaling cascades, oxidative stress, activation of pro-inflammatory molecules, and growth factors, influencing the activity of various ion channel families and leading to diverse cardiovascular diseases such as myocardial infarction, ischemic stroke, and hypertension. The large-conductance, calcium and voltage-activated potassium channel (BK) has a central role in the mechanism of oxygen (O2) sensing and its activity has been related to the hypoxic response. BK channels are ubiquitously expressed, and they are composed by the pore-forming α subunit and the regulatory subunits β (β1–β4), γ (γ1–γ4), and LINGO1. The modification of biophysical properties of BK channels by β subunits underly a myriad of physiological function of these proteins. Hypoxia induces tissue-specific modifications of BK channel α and β subunits expression. Moreover, hypoxia modifies channel activation kinetics and voltage and/or calcium dependence. The reported effects on the BK channel properties are associated with events such as the increase of reactive oxygen species (ROS) production, increases of intracellular Calcium ([Ca2+]i), the regulation by Hypoxia-inducible factor 1α (HIF-1α), and the interaction with hemeproteins. Bronchial asthma, chronic obstructive pulmonary diseases (COPD), and obstructive sleep apnea (OSA), among others, can provoke hypoxia. Untreated OSA patients showed a decrease in BK-β1 subunit mRNA levels and high arterial tension. Treatment with continuous positive airway pressure (CPAP) upregulated β1 subunit mRNA level, decreased arterial pressures, and improved endothelial function coupled with a reduction in morbidity and mortality associated with OSA. These reports suggest that the BK channel has a role in the response involved in hypoxia-associated hypertension derived from OSA. Thus, this review aims to describe the mechanisms involved in the BK channel activation after a hypoxic stimulus and their relationship with disorders like OSA. A deep understanding of the molecular mechanism involved in hypoxic response may help in the therapeutic approaches to treat the pathological processes associated with diseases involving cellular hypoxia.
Using Imaging Mass Cytometry to Define Cell Identities and Interactions in Human Tissues
Authors: Kakade Vijayakumar R. , Weiss Marlene , Cantley Lloyd G.
Published: December 2021

In the evolving landscape of highly multiplexed imaging techniques that can be applied to study complex cellular microenvironments, this review characterizes the use of imaging mass cytometry (IMC) to study the human kidney. We provide technical details for antibody validation, cell segmentation, and data analysis specifically tailored to human kidney samples, and elaborate on phenotyping of kidney cell types and novel insights that IMC can provide regarding pathophysiological processes in the injured or diseased kidney. This review will provide the reader with the necessary background to understand both the power and the limitations of IMC and thus support better perception of how IMC analysis can improve our understanding of human disease pathogenesis and can be integrated with other technologies such as single cell sequencing and proteomics to provide spatial context to cellular data.
Mitigation of Environmental Stress-Impacts in Plants: Role of Sole and Combinatory Exogenous Application of Glutathione
Authors: Koh Yi Sze , Wong See Kiat , Ismail Nor Hadiani , Zengin Gokhan , Duangjai Acharaporn , Saokaew Surasak , Phisalprapa Pochamana , Tan Khang Wei , Goh Bey Hing , Tang Siah Ying
Published: December 2021

Glutathione (GSH; γ-glutamyl-cysteinyl-glycine), a low-molecular-weight thiol, is the most pivotal metabolite involved in the antioxidative defense system of plants. The modulation of GSH on the plant in response to environmental stresses could be illustrated through key pathways such as reactive oxygen species (ROS) scavenging and signaling, methylglyoxal (MG) detoxification and signaling, upregulation of gene expression for antioxidant enzymes, and metal chelation and xenobiotic detoxification. However, under extreme stresses, the biosynthesis of GSH may get inhibited, causing an excess accumulation of ROS that induces oxidative damage on plants. Hence, this gives rise to the idea of exploring the use of exogenous GSH in mitigating various abiotic stresses. Extensive studies conducted borne positive results in plant growth with the integration of exogenous GSH. The same is being observed in terms of crop yield index and correlated intrinsic properties. Though, the improvement in plant growth and yield contributed by exogenous GSH is limited and subjected to the glutathione pool [GSH/GSSG; the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG)] homeostasis. Therefore, recent studies focused on the sequenced application of GSH was performed in order to complement the existing limitation. Along with various innovative approaches in combinatory use with different bioactive compounds (proline, citric acid, ascorbic acid, melatonin), biostimulants (putrescine, Moringa leaf extract, selenium, humic acid), and microorganisms (cyanobacteria) have resulted in significant improvements when compared to the individual application of GSH. In this review, we reinforced our understanding of biosynthesis, metabolism and consolidated different roles of exogenous GSH in response to environmental stresses. Strategy was also taken by focusing on the recent progress of research in this niche area by covering on its individualized and combinatory applications of GSH prominently in response to the abiotic stresses. In short, the review provides a holistic overview of GSH and may shed light on future studies and its uses.
Effectors of Root-Knot Nematodes: An Arsenal for Successful Parasitism
Authors: Jagdale Shounak , Rao Uma , Giri Ashok P.
Published: December 2021

Root-knot nematodes (RKNs) are notorious plant-parasitic nematodes first recorded in 1855 in cucumber plants. They are microscopic, obligate endoparasites that cause severe losses in agriculture and horticulture. They evade plant immunity, hijack the plant cell cycle, and metabolism to modify healthy cells into giant cells (GCs) – RKN feeding sites. RKNs secrete various effector molecules which suppress the plant defence and tamper with plant cellular and molecular biology. These effectors originate mainly from sub-ventral and dorsal oesophageal glands. Recently, a few non-oesophageal gland secreted effectors have been discovered. Effectors are essential for the entry of RKNs in plants, subsequently formation and maintenance of the GCs during the parasitism. In the past two decades, advanced genomic and post-genomic techniques identified many effectors, out of which only a few are well characterized. In this review, we provide molecular and functional details of RKN effectors secreted during parasitism. We list the known effectors and pinpoint their molecular functions. Moreover, we attempt to provide a comprehensive insight into RKN effectors concerning their implications on overall plant and nematode biology. Since effectors are the primary and prime molecular weapons of RKNs to invade the plant, it is imperative to understand their intriguing and complex functions to design counter-strategies against RKN infection.
Positive Effects of Prosocial Cartoon Viewing on Aggression Among Children: The Potential Mediating Role of Aggressive Motivation
Authors: Zhang Qian
Published: December 2021

Prosocial cartoon is characterized by helping others solve difficulties, including helping, donating, sharing, comforting, and cooperating. The current study examined whether viewing a prosocial cartoon decreases aggression immediately upon exposure and the potential mediating role of aggressive motivation. Participants involve 168 children (Mage = 5.87 years, SD = 0.41) nominated by teachers as aggressive from three Chinese kindergartens. Children in the treatment group watched a prosocial cartoon (American cartoon “Handy Manny”), while children in the control group watched a nonprosocial cartoon (Chinese cartoon “Fruity Robo”). Afterward, the Hot Sauce Task (HST) was employed to assess aggressive behavior, and Aggressive Motivation Questionnaire (AMQ) was employed to assess aggressive motivation. Results revealed that viewing a prosocial cartoon (vs. a nonprosocial cartoon) did reduce children’s aggression immediately upon exposure. Specifically, males showed less aggressive behavior than females upon prosocial cartoon exposure, while males showed more aggressive behavior than females upon nonprosocial cartoon exposure. Mediational analysis suggested that the prosocial cartoon effect on aggression was partially mediated by aggressive motivation, especially for males. Consistent with general aggression model (GAM), findings of the study indicated that short-term exposure to a prosocial cartoon decreased children’s aggression by reducing aggressive motivation.
The Role of Students’ Self-Regulated Learning, Grit, and Resilience in Second Language Learning
Authors: Wang Liang
Published: December 2021

It has been established that grit has a fundamental role in the learning and teaching process since gritty learners are more likely to take part in classroom activities and they are also motivated to deal with challenges in difficult circumstances. In addition, to guard against these hardships as well as self-control in responding to unpredicted circumstances, a similar construct arouses in positive psychology called resilience that describes perseverance and emphasizes people’s abilities. Besides, language learners’ engagement and performance in the foreign or second language classroom can be improved through self-regulated learning (SRL) which is viewed as one of the most inspected issues in learning and psychology. A present review has been conducted to scrutinize the relationship between language learners’ SRL and learners’ resilience and grit based on their positive theoretical relationship with educational success. Consequently, the issue of educator training and administrative training is illuminated through several aspects.
Moving Toward and Through Trauma: Participant Experiences of Multi-Modal Motion-Assisted Memory Desensitization and Reconsolidation (3MDR)
Authors: Hamilton Tristin , Burback Lisa , Smith-MacDonald Lorraine , Jones Chelsea , Brown Matthew R. G. , Mikolas Cynthia , Tang Emily , O'Toole Kaitlin , Vergis Priyanka , Merino Anna , Weiman Kyle , Vermetten Eric H. G. J. M. , Brémault-Phillips Suzette
Published: December 2021

Introduction:Military members and Veterans are at risk of developing combat-related, treatment-resistant posttraumatic stress disorder (TR-PTSD) and moral injury (MI). Conventional trauma-focused therapies (TFTs) have shown limited success. Novel interventions including Multi-modal Motion-assisted Memory Desensitization and Reconsolidation therapy (3MDR) may prove successful in treating TR-PTSD.

Objective:To qualitatively study the experiences of Canadian military members and Veterans with TR-PTSD who received the 3MDR intervention.

Methods:This study explored qualitative data from a larger mixed-method waitlist control trial testing the efficacy of 3MDR in military members and veterans. Qualitative data were recorded and collected from 3MDR sessions, session debriefings and follow-up interviews up to 6 months post-intervention; the data were then thematically analyzed.

Results:Three themes emerged from the data: (1) the participants' experiences with 3MDR; (2) perceived outcomes of 3MDR; and (3) keys to successful 3MDR treatment. Participants expressed that 3MDR provided an immersive environment, active engagement and empowerment. The role of the therapist as a coach and “fireteam partner” supports the participants' control over their therapy. The multi-modal nature of 3MDR, combining treadmill-walking toward self-selected trauma imagery with components of multiple conventional TFTs, was key to helping participants engage with and attribute new meaning to the memory of the traumatic experience.

Discussion:Preliminary thematic analysis of participant experiences of 3MDR indicate that 3MDR has potential as an effective intervention for combat-related TR-PTSD, with significant functional, well-being and relational improvements reported post-intervention.

Conclusion:Military members and Veterans are at risk of developing TR-PTSD, with worse outcomes than in civilians. Further research is needed into 3MDR and its use with other trauma-affected populations.
The Clinical Consistency and Utility of ICD-11 Diagnostic Guidelines for Gaming Disorder: A Field Study Among the Chinese Population
Authors: Ma Chenyi , Wang Zhe , Li Chuanwei , Lu Jing , Long Jiang , Li Ruihua , Wu Qianying , Jiang Haifeng , Du Jiang , Li Runji , Wang Peiyan , Ma Limin , Li Hongwei , Hui Shuqin , Zhao Wenli , Zhong Na , Zhao Min
Published: December 2021

Purpose: As a new category proposed in the International Classification of Diseases (11th Revision) (ICD-11), the reliability and clinical utility of ICD diagnostic guidelines for gaming disorder (GD) in the Chinese population have not been studied. The purpose of this field study is to clarify the reliability, clinical utility, and cultural applicability of ICD diagnostic guidelines for GD in China and its comparability with Internet GD (IGD) in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5).

Methods: Participants included 21 paired clinical raters consisting of seven psychiatrists and 200 gaming players aged from 15 to 18 years with different risk levels of Internet addiction based on the scores of Young's Internet Addiction Test. Each participant received a semi-structured face-to-face interview by paired clinical raters at the same time. Then clinical raters made the diagnosis and filled the clinical utility questionnaire independently according to the diagnostic guidelines for GD in both ICD-11 and DSM-5.

Results: The diagnostic consistency coefficient (kappa value) between the paired clinical raters was 0.545 (0.490–0.600, p < 0.001) and 0.622 (0.553–0.691, p < 0.001) for ICD-11 and DSM-5 diagnostic guidelines, respectively, for GD. The diagnostic consistency was 0.847 (0.814–0.880, p < 0.001) between GD in ICD-11 and IGD in DSM-5. Meanwhile, 86.7% of responses that agreed with the ICD-11 diagnostic guidelines for GD provided enough detailed implementation characteristics and showed good overall clinical applicability (86.0%), specificity (94.4%), usefulness (84.1%), and acceptable cultural adaptation (74.8%). GD in ICD-11 was slightly more accepted than IGD in DSM-5 (p < 0.001), while the clinical efficiency of ICD-11 was inferior to that of DSM-5 (p < 0.001).

Conclusion: This study indicates that the ICD-11 diagnostic guidelines for GD have acceptable clinical reliability and high consistency with IGD in DSM-5. Their clinical applicability and cultural adaption are comparable with those of DSM-5. Although the guidelines still need to be adjusted for better implementation in China, this is already a great step committed to reducing the serious consequences caused by excessive gaming behaviors through effective identification and normative diagnosis, especially for adolescents.
An Internet Based Intervention for Adults With Autism Spectrum Disorder—A Qualitative Study of Participants Experiences
Authors: Westerberg Britta , Bäärnhielm Sofie , Giles Clover , Hylén Ulrika , Holländare Fredrik , Bejerot Susanne
Published: December 2021

Background: Adults with autism spectrum disorder face several barriers to accessing evidence-based care, including difficulties in communicating needs, social anxiety or in traveling to a health care unit. In recent years, several forms of internet-based treatments have shown to be effective for a variety of psychiatric conditions. Internet-based treatment alternatives allow convenient and flexible formats, and therefore have the potential to increase access to health care for individuals with autism spectrum disorder. However, knowledge about how internet-based treatment features may suit the needs of individuals with autism is limited. The aim of this study was to explore the participant experiences of an internet-based intervention for adults with autism spectrum disorder. The primary focus of the investigation was on autism-specific needs in relation to the features unique to the online format.

Methods: In this qualitative study, semi-structured telephone interviews were conducted with 14 participants who had completed a text-based internet-based intervention for adults with autism spectrum disorder. We used an inductive approach and analyzed the data using qualitative content analysis.

Results: Five main categories were identified: (1) implications of the online format, (2) the fixed non-individualized model, (3) therapist interaction, (4) interacting with other participants, and (5) making use of the treatment content. Overall, participants appreciated the availability and that they could work on their treatment independent of time or location. Among those participating in group-based chat-sessions with the other participants, it was considered a generally positive experience. Furthermore, most participants felt safe and relaxed in relation to the therapist and appreciated the text-based format. However, several participants felt that the format and content of the treatment was not sufficiently adapted to their individual life situation.

Conclusion: In conclusion, this internet-based treatment constitutes an accessible and energy-saving treatment alternative for adults with autism. Further, integrating group-based components seems feasible in an otherwise individual internet-based treatment for individuals with autism. However, group-based components do require a clear purpose and rationale. Future studies should develop and evaluate treatment adaptations tailored to individual needs.
A Method for Estimating the Number of Infections From the Reported Number of Deaths
Authors: Brännström Åke , Sjödin Henrik , Rocklöv Joacim
Published: December 2021

At the outset of an epidemic, available case data typically underestimate the total number of infections due to insufficient testing, potentially hampering public responses. Here, we present a method for statistically estimating the true number of cases with confidence intervals from the reported number of deaths and estimates of the infection fatality ratio; assuming that the time from infection to death follows a known distribution. While the method is applicable to any epidemic with a significant mortality rate, we exemplify the method by applying it to COVID-19. Our findings indicate that the number of unreported COVID-19 infections in March 2020 was likely to be at least one order of magnitude higher than the reported cases, with the degree of underestimation among the countries considered being particularly high in the United Kingdom.