bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengaruh Peran Tenaga Kesehatan, Peran Keluarga, Kondisi Kesehatan Fisik, Dan Motivasi Terhadap Kecemasan Pada Ibu Menopause
Authors: Wati Mega , Yani Hida
Published: February 2021

Kecemasan menjelang menopause merupaka suatu bentuk kekhawatiran akibat adanya perubahan-perubahan, baik dari segi fisik maupun psikis, dimana ditandai dengan adanya gejala-gejala yang muncul dari segi kognitif, afektif, somatik, dan motorik. Kecemasan ibu saat menopause akan menimbulkan masalah dalam kehidupan seksual suami istri, gejala-gejala fisik dan psikologi seperti keringat berlebihan dan perasaan tidak berguna karena tidak bisa melahirkan anak lagi. Tujuan penelitian ini untuk mengetahui pengaruh peran tenaga kesehatan, peran keluarga, kondisi lingkungan fisik dan motivasi terhadap kecemasan ibu menopause di Desa Pagarawan Tahun 2018. Desain penelitian menggunakan cross sectional.  Metode analisis menggunakan Smart PLS 2.0 dan dan SPSS 18. Populasi penelitianibu menopause sebanyak 68 orang. Hasil pengujian hipotesis dengan Structural Equation Model (SEM) dengan metode smartPLS menghasilkan temuan penelitian yaitu peran tenaga kesehatan (17,02%), peran keluarga (11,79%), kondisi kesehatan fisik (26,18%) dan motivasi (26,29%). Pengaruh langsung kecemasan ibu menopause sebesar 81,28% dan pengaruh tidak langsung sebesar 1,44%. Total pengaruh langsung dan tidak langsung kecemasan ibu menopause sebesar 82,72%. Motivasi merupakan faktor dominan yang sangat mempengaruhi kecemasan ibu menopause. Peneliti menyarankan agar seluruh sektor bekerja sama untuk memotivasi ibu mulai dari persiapan premenopause hingga ibu bisa beradaptasi dengan masa menopause.
Metformin-Enhanced Cardiac AMP-Activated Protein Kinase/Atrogin-1 Pathways Inhibit Charged Multivesicular Body Protein 2B Accumulation in Ischemia–Reperfusion Injury
Authors: Li Tian , Yin Yue , Mu Nan , Wang Yishi , Liu Manling , Chen Mai , Jiang Wenhua , Yu Lu , Li Yan , Ma Heng
Published: February 2021

Background: Cardiac autophagic flux is impaired during myocardial ischemia/reperfusion (MI/R). Impaired autophagic flux may exacerbate MI/R injury. Charged multivesicular body protein 2B (CHMP2B) is a subunit of the endosomal sorting complex required for transport (ESCRT-III) complex that is required for autophagy. However, the reverse role of CHMP2B accumulation in autophagy and MI/R injury has not been established. The objective of this article is to elucidate the roles of AMP-activated protein kinase (AMPK)/atrogin-1 pathways in inhibiting CHMP2B accumulation in ischemia–reperfusion injury.

Methods: Male C57BL/6 mice (3–4 months) and H9c2 cardiomyocytes were used to evaluate MI/R and hypoxia/reoxygenation (H/R) injury in vivo and in vitro, respectively. MI/R was built by a left lateral thoracotomy and occluded the left anterior descending artery. H9c2 cells were firstly treated in 95% N2 and 5% CO2 for 15 h and reoxygenation for 1 h. Metformin (100 mg/kg/d) and CHMP2B (Ad-CHMP2B) transfected adenoviruses were administered to the mice. The H9c2 cells were treated with metformin (2.5 mM), MG-132 (10 μM), bafilomycin A1 (10 nM), and compound C (20 μM).

Results: Autophagic flux was found to be inhibited in H/R-treated cardiomyocytes and MI/R mice, with elevated cardiac CHMP2B accumulation. Upregulated CHMP2B levels in the in vivo and in vitro experiments were shown to inhibit autophagic flux leading to the deterioration of H/R-cardiomyocytes and MI/R injury. This finding implies that CHMP2B accumulation increases the risk of myocardial ischemia. Metformin suppressed CHMP2B accumulation and ameliorated H/R-induced autophagic dysfunction by activating AMPK. Activated AMPK upregulated the messenger RNA expression and protein levels of atrogin-1, a muscle-specific ubiquitin ligase, in the myocardium. Atrogin-1 significantly enhanced the interaction between atrogin-1 and CHMP2B, therefore, promoting CHMP2B degradation in the MI/R myocardium. Finally, this study revealed that metformin-inhibited CHMP2B accumulation induced autophagic impairment and ischemic susceptibility in vivo through the AMPK-regulated CHMP2B degradation by atrogin-1.

Conclusion: Impaired CHMP2B clearance in vitro and in vivo inhibits autophagic flux and weakens the myocardial ischemic tolerance. Metformin treatment degrades CHMP2B through the AMPK-atrogin-1-dependent pathway to maintain the homeostasis of autophagic flux. This is a novel mechanism that enriches the understanding of cardioprotection.
Graphene and its Derivatives-Based Optical Sensors
Authors: Gao Xiao-Guang , Cheng Ling-Xiao , Jiang Wen-Shuai , Li Xiao-Kuan , Xing Fei
Published: February 2021

Being the first successfully prepared two-dimensional material, graphene has attracted extensive attention from researchers due to its excellent properties and extremely wide range of applications. In particular, graphene and its derivatives have displayed several ideal properties, including broadband light absorption, ability to quench fluorescence, excellent biocompatibility, and strong polarization-dependent effects, thus emerging as one of the most popular platforms for optical sensors. Graphene and its derivatives-based optical sensors have numerous advantages, such as high sensitivity, low-cost, fast response time, and small dimensions. In this review, recent developments in graphene and its derivatives-based optical sensors are summarized, covering aspects related to fluorescence, graphene-based substrates for surface-enhanced Raman scattering (SERS), optical fiber biological sensors, and other kinds of graphene-based optical sensors. Various sensing applications, such as single-cell detection, cancer diagnosis, protein, and DNA sensing, are introduced and discussed systematically. Finally, a summary and roadmap of current and future trends are presented in order to provide a prospect for the development of graphene and its derivatives-based optical sensors.
Comprehensive Analysis of the Immune Infiltrates and Aberrant Pathways Activation in Atherosclerotic Plaque
Authors: Han Hukui , Du Rongsheng , Cheng Panke , Zhang Jiancheng , Chen Yang , Li Gang
Published: February 2021

Atherosclerosis is the pathological basis of many cardiovascular and cerebrovascular diseases. The development of gene chip and high-throughput sequencing technologies revealed that the immune microenvironment of coronary artery disease (CAD) in high-risk populations played an important role in the formation and development of atherosclerotic plaques. Three gene expression datasets related to CAD were assessed using high-throughput profiling. CIBERSORT analysis revealed significant differences in five types of immune cells: activated dendritic cells (DCs), T follicular helper cells (Tfhs), resting CD4+ T cells, regulatory T cells (Tregs), and γδ T cells. Immune transcriptome analysis indicated higher levels of inflammatory markers (cytolytic activity, antigen presentation, chemokines, and cytokines) in the cases than in the controls. The level of activated DCs and the lipid clearance signaling score were negatively correlated. We observed a positive correlation between the fraction of Tfhs and lipid biosynthesis. Resting CD4+ T cells and the activity of pathways related to ossification in bone remodeling and glutathione synthesis showed a negative correlation. Gamma delta T cells negatively correlated with IL-23 signaling activity. GSEA revealed a close association with the inflammatory immune microenvironment. The present study revealed that CAD patients may have an inflammatory immune microenvironment and provides a timely update on anti-inflammatory therapies under current investigation.
Advanced Research of Abdominal Aortic Aneurysms on Metabolism
Authors: Hou Yangfeng , Guo Wenjun , Fan Tianfei , Li Bolun , Ge Weipeng , Gao Ran , Wang Jing
Published: February 2021

Abdominal aortic aneurysm (AAA) is a cardiovascular disease with a high risk of death, seriously threatening the life and health of people. The specific pathogenesis of AAA is still not fully understood. In recent years, researchers have found that amino acid, lipid, and carbohydrate metabolism disorders play important roles in the occurrence and development of AAA. This review is aimed to summarize the latest research progress of the relationship between AAA progression and body metabolism. The body metabolism is closely related to the occurrence and development of AAA. It is necessary to further investigate the pathogenesis of AAA from the perspective of metabolism to provide theoretical basis for AAA diagnosis and drug development.
Carbon Isotope Chemostratigraphy Across the Permian-Triassic Boundary at Chaotian, China: Implications for the Global Methane Cycle in the Aftermath of the Extinction
Authors: Saitoh Masafumi , Isozaki Yukio
Published: February 2021

During the end-Permian extinction, a substantial amount of methane (CH4) was likely released into the ocean-atmosphere system associated with the Siberian Traps volcanism, although fluctuations in the global CH4cycle in the aftermath of the extinction remain poorly understood. The carbon (C) isotopic composition of carbonate (δ13Ccarb) across the Permian-Triassic boundary (P-TB) was analyzed at Chaotian, South China. The δ13Ccarbvalues decrease from ca. +1 to –2‰ across the P-TB, possibly caused by a collapse of primary productivity associated with the shallow-marine extinction. The frequent intercalation of felsic tuff layers around the P-TB suggests that a volcanogenic carbon dioxide (CO2) input to the surface oceans may also have contributed to the δ13Ccarbdecline. The magnitude of the δ13Ccarbdecrease (∼3‰) is substantially smaller than the magnitude of a decrease in C isotopic composition of organic matter (δ13Corg) in the same P-TB interval (∼7‰). This apparent δ13Ccarb-δ13Corgdecoupling could be explained by proliferation of methanogen (“methanogenic burst”) in the sediments. A global δ13C compilation shows a large variation in marine δ13Corgrecords, implying that the “methanogenic burst” according to the Siberian Traps volcanism may have contributed, at least in part, to the δ13Corgvariability and to the elevated CH4levels in the atmosphere. The present and previous observations allow us to infer that the global CH4cycle may have fluctuated substantially in the aftermath of the extinction.
Impact of the Anomalous Latent Heat Flux Over the Kuroshio Extension on Western North American Rainfall in Spring: Interannual Variation and Mechanism
Authors: Long Jingchao , Liu Chunlei , Liu Zifeng , Xu Jianjun
Published: February 2021

The Kuroshio and its extension (KE) significantly influences regional climate through meridional heat transport from the tropical ocean. In this study, the observational and reanalysis datasets are used to investigate the impact of the latent heat flux (LHF) over the KE region on downstream rainfall and the underlying mechanism. The result shows a “seesaw” structure in rainfall anomaly, dominating the Western Canada and the southwestern North America with a correlation coefficient of 0.77 between the two modes. In strong LHF years, strengthened LHF favors to enhance precipitation in the Western Canada and reduce that in the southwestern North America. This is primarily associated with an anomalous cyclonic circulation over the KE region, which enhances southwesterly precipitation and latent heating in the middle troposphere. The heating excites an anomalous cyclonic circulation to its west and an anticyclonic circulation to its east, helping to reinforce the existing anomalous cyclonic circulation in turn and form a positive feedback. The conditions associated with La Niña events favor to above processes. To the upper troposphere, the deepened anomalous cyclonic circulation due to enhanced eddy activities and atmospheric baroclinic instability over the KE strengthens subtropical westerly jet stream and thereby extends eastward on the 200 hPa level. Correspondingly, an elongated zonally lower level cyclonic circulation anomaly across the North Pacific leads to a moisture convergence in the Western Canada, which is mainly resulted from the anomalous positive vorticity advection over the left side of the exit region of the jet stream. The opposite circumstance occurs in weak LHF years, presenting an opposed anomalous circulation and rainfall pattern.
Predictors of Electronic Learning Self-Efficacy: A Cross-Sectional Study in Saudi Arabian Universities
Authors: Aldhahi Monira I. , Baattaiah Baian A. , Alqahtani Abdulfattah S.
Published: February 2021

This study aims at describing academic self-efficacy in online learning and exploring the determinant factors of learners’ academic self-efficacy. In this cross-sectional survey-based study, 892 respondents voluntarily participated in and completed the survey. Online learning self-efficacy was assessed using an online academic self-efficacy questionnaire. The sociodemographic characteristics showed that 85% of the respondents were female, 21% were medical students, and 13% were postgraduate students. Most respondents reported insufficient self-efficacy for learning and time management, whereas 51% showed good self-efficacy for technology. When considering the study’s field, more medical students reported good self-efficacy scores for learning and technology (36% and 68%, respectively) than non-medical students (33% and 47%, respectively). Time management self-efficacy was mostly reported to be good (47%) among those with a high grade point average. The results showed that educational status, field of study, and learning satisfaction were significant predictors of self-efficacy for learning and technology (p < 0.001). Gender, academic performance, and learning satisfaction were significant predictors of self-efficacy for time management (p < 0.001). Self-efficacy can play a major role in online learning, particularly in circumstances like the sudden transformation of the educational system that has occurred during the COVID-19 pandemic. An effective academic self-efficacy of learning, use of technology, and time management skills should also be emphasized. The value of this research lies in exploring the electronic learning self-efficacy and its predictor among university students. The research findings help us improve students’ academic self-efficacy to enhance the learning environment by planning new studies.
CCR8 Signaling via CCL1 Regulates Responses of Intestinal IFN-γ Producing Innate Lymphoid CelIs and Protects From Experimental Colitis
Authors: Kang Le , Schmalzl Angelika , Leupold Tamara , Gonzalez-Acera Miguel , Atreya Raja , Neurath Markus F. , Becker Christoph , Wirtz Stefan
Published: February 2021

A diverse spectrum of immune cells populates the intestinal mucosa reflecting the continuous stimulation by luminal antigens. In lesions of patients with inflammatory bowel disease, an aberrant inflammatory process is characterized by a very prominent infiltrate of activated immune cells producing cytokines and chemokines. These mediators perpetuate intestinal inflammation or may contribute to mucosal protection depending on the cellular context. In order to further characterize this complex immune cell network in intestinal inflammation, we investigated the contribution of the chemokine receptor CCR8 to development of colitis using a mouse model of experimental inflammation. We found that CCR8−/− mice compared to wildtype controls developed strong weight loss accompanied by increased histological and endoscopic signs of mucosal damage. Further experiments revealed that this gut protective function of CCR8 seems to be selectively mediated by the chemotactic ligand CCL1, which was particularly produced by intestinal macrophages during colitis. Moreover, we newly identified CCR8 expression on a subgroup of intestinal innate lymphoid cells producing IFN-γ and linked a functional CCL1/CCR8 axis with their abundance in the gut. Our data therefore suggest that this pathway supports tissue-specific ILC functions important for intestinal homeostasis. Modulation of this regulatory circuit may represent a new strategy to treat inflammatory bowel disease in humans.
Intensive Care Unit-Specific Virtual Reality for Psychological Recovery After ICU Treatment for COVID-19; A Brief Case Report
Authors: Vlake Johan H. , van Bommel Jasper , Hellemons Merel E. , Wils Evert-Jan , Gommers Diederik , van Genderen Michel E.
Published: February 2021

A substantial number of ICU survivors are expected due to the SARS-CoV-2 outbreak, who are at risk for psychological impairments, such as post-traumatic stress disorder (PTSD), anxiety, and depression. We designed a COVID-19 intensive care unit-specific virtual reality (ICU-VR) intervention and tested it on one of our COVID-19 patients. The impact of event scale-revised and the hospital anxiety and depression scale showed that this patient suffered from PTSD, anxiety, and depression on the day of the intervention. One week after receiving ICU-VR, levels of PTSD, anxiety and depression had normalized, and stayed normalized until 6 months after discharge. In conclusion, innovative technologies, such as VR, have the potential to improve psychological rehabilitation, and should therefore be considered by clinicians for the treatment of ICU-related psychological sequelae after COVID-19.
Obesity and Mortality Among Patients Diagnosed With COVID-19: A Systematic Review and Meta-Analysis
Authors: Poly Tahmina Nasrin , Islam Md. Mohaimenul , Yang Hsuan Chia , Lin Ming Chin , Jian Wen-Shan , Hsu Min-Huei , Jack Li Yu-Chuan
Published: February 2021

Coronavirus disease 2019 (COVID-19) has already raised serious concern globally as the number of confirmed or suspected cases have increased rapidly. Epidemiological studies reported that obesity is associated with a higher rate of mortality in patients with COVID-19. Yet, to our knowledge, there is no comprehensive systematic review and meta-analysis to assess the effects of obesity and mortality among patients with COVID-19. We, therefore, aimed to evaluate the effect of obesity, associated comorbidities, and other factors on the risk of death due to COVID-19. We did a systematic search on PubMed, EMBASE, Google Scholar, Web of Science, and Scopus between January 1, 2020, and August 30, 2020. We followed Cochrane Guidelines to find relevant articles, and two reviewers extracted data from retrieved articles. Disagreement during those stages was resolved by discussion with the main investigator. The random-effects model was used to calculate effect sizes. We included 17 articles with a total of 543,399 patients. Obesity was significantly associated with an increased risk of mortality among patients with COVID-19 (RRadjust: 1.42 (95%CI: 1.24–1.63, p < 0.001). The pooled risk ratio for class I, class II, and class III obesity were 1.27 (95%CI: 1.05–1.54, p = 0.01), 1.56 (95%CI: 1.11–2.19, p < 0.01), and 1.92 (95%CI: 1.50–2.47, p < 0.001), respectively). In subgroup analysis, the pooled risk ratio for the patients with stroke, CPOD, CKD, and diabetes were 1.80 (95%CI: 0.89–3.64, p = 0.10), 1.57 (95%CI: 1.57–1.91, p < 0.001), 1.34 (95%CI: 1.18–1.52, p < 0.001), and 1.19 (1.07–1.32, p = 0.001), respectively. However, patients with obesity who were more than 65 years had a higher risk of mortality (RR: 2.54; 95%CI: 1.62–3.67, p < 0.001). Our study showed that obesity was associated with an increased risk of death from COVID-19, particularly in patients aged more than 65 years. Physicians should aware of these risk factors when dealing with patients with COVID-19 and take early treatment intervention to reduce the mortality of COVID-19 patients.
Characterization of the Oral Microbiome of Medicated Type-2 Diabetes Patients
Authors: Almeida-Santos Ana , Martins-Mendes Daniela , Gayà-Vidal Magdalena , Pérez-Pardal Lucía , Beja-Pereira Albano
Published: February 2021

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that is becoming a significant global health care problem. Several studies have shown that people with diabetes are more susceptible to oral problems, such as periodontitis and, although the causes are still inconclusive, oral microbiota is considered to play a major role in oral health. This study aimed to characterize the oral microbiome of a sample representing T2DM patients from Portugal and exploit potential associations between some microorganisms and variables like teeth brushing, smoking habits, average blood sugar levels, medication and nutrient intake. By sequencing the hypervariable regions V3-V4 of the 16S rRNA gene in 50 individuals belonging to a group of diabetes patients and a control group, we found a total of 232 taxa, from which only 65% were shared between both groups. No differences were found in terms of alpha and beta diversity between categories. We did not find significant differences in the oral microbiome profiles of control and diabetes patients. Only the class Synergistia and the genus TG5, which are related to periodontitis, were statistically more frequent in the control group. The similar microbiome profiles of medicated diabetics and the control group indicates that the relationship between the T2DM and the oral microbiome might be more related to either the lifestyle/diet rather than diabetes per se. Moreover, this study provides, for the first time, insights into the oral microbiome of a population with a high prevalence of diabetes.
Burkholderiaceae Are Key Acetate Assimilators During Complete Denitrification in Acidic Cryoturbated Peat Circles of the Arctic Tundra
Authors: Hetz Stefanie A. , Horn Marcus A.
Published: February 2021

Cryoturbated peat circles (pH 4) in the Eastern European Tundra harbor up to 2 mM pore water nitrate and emit the greenhouse gas N2O like heavily fertilized agricultural soils in temperate regions. The main process yielding N2O under oxygen limited conditions is denitrification, which is the sequential reduction of nitrate/nitrite to N2O and/or N2. N2O reduction to N2is impaired by pH < 6 in classical model denitrifiers and many environments. Key microbes of peat circles are important but largely unknown catalysts forC- andN-cycling associated N2O fluxes. Thus, we hypothesized that the peat circle community includes hitherto unknown taxa and is essentially unable to efficiently perform complete denitrification, i.e., reduce N2O, due to a lowin situpH. 16S rRNA analysis indicated a diverse active community primarily composed of the bacterial class-level taxa Alphaproteobacteria, Acidimicrobiia, Acidobacteria, Verrucomicrobiae, and Bacteroidia, as well as archaeal Nitrososphaeria. Euryarchaeota were not detected.13C2- and12C2-acetate supplemented anoxic microcosms with endogenous nitrate and acetylene at anin situnear pH of 4 were used to assess acetate dependent carbon flow, denitrification and N2O production. Initial nitrate and acetate were consumed within 6 and 11 days, respectively, and primarily converted to CO2and N2, suggesting complete acetate fueled denitrification at acidic pH. Stable isotope probing coupled to 16S rRNA analysis via Illumina MiSeq amplicon sequencing identified acetate consuming key players of the familyBurkholderiaceaeduring complete denitrification correlating withRhodanobacterspp. The archaeal community consisted primarily of ammonia-oxidizing Archaea of Nitrososphaeraceae, and was stable during the incubation. The collective data indicate that peat circles (i) host acid-tolerant denitrifiers capable of complete denitrification at pH 4–5.5, (ii) other parameters like carbon availability rather than pH are possible reasons for high N2O emissionsin situ, and (iii)Burkholderiaceaeare responsive key acetate assimilators co-occurring withRhodanobactersp. during denitrification, suggesting both organisms being associated with acid-tolerant denitrification in peat circles.
Sexual Regional Dimorphism of Post-Adolescent and Middle Age Brain Maturation. A Multi-center 3T MRI Study
Authors: Delvecchio Giuseppe , Maggioni Eleonora , Pigoni Alessandro , Crespo-Facorro B. , Nenadić Igor , Benedetti Francesco , Gaser Christian , Sauer Heinrich , Roiz-Santiañez Roberto , Poletti Sara , Rossetti Maria G. , Bellani Marcella , Perlini Cinzia , Ruggeri Mirella , Diwadkar Vaibhav A. , Brambilla Paolo
Published: February 2021

Sex-related differences are tied into neurodevelopmental and lifespan processes, beginning early in the perinatal and developmental phases and continue into adulthood. The present study was designed to investigate sexual dimorphism of changes in gray matter (GM) volume in post-adolescence, with a focus on early and middle-adulthood using a structural magnetic resonance imaging (MRI) dataset of healthy controls from the European Network on Psychosis, Affective disorders and Cognitive Trajectory (ENPACT). Three hundred and seventy three subjects underwent a 3.0 T MRI session across four European Centers. Age by sex effects on GM volumes were investigated using voxel-based morphometry (VBM) and the Automated Anatomical Labeling atlas regions (ROI). Females and males showed overlapping and non-overlapping patterns of GM volume changes during aging. Overlapping age-related changes emerged in bilateral frontal and temporal cortices, insula and thalamus. Both VBM and ROI analyses revealed non-overlapping changes in multiple regions, including cerebellum and vermis, bilateral mid frontal, mid occipital cortices, left inferior temporal and precentral gyri. These findings highlight the importance of accounting for sex differences in cross-sectional analyses, not only in the study of normative changes, but particularly in the context of psychiatric and neurologic disorders, wherein sex effects may be confounded with disease-related changes.
Depression-/Anxiety-Like Behavior Alterations in Adult Slit2 Transgenic Mice
Authors: Huang Guilan , Wang Sheng , Yan Jie , Li Changxi , Feng Jianwen , Chen Qi , Zheng Xiaomeng , Li Huimin , He Yajun , Young Andrew J. , Li Haobin , Li Weidong , Li Jiangchao , Wang Lijing
Published: February 2021

Background: Slit2 is a member of the Slit family of secreted glycoproteins that plays highly conserved roles in neuronal axon guidance and cellular migration. Our previous experimental results showed Alzheimer's disease-like alterations and increased permeability of the blood–brain barrier in Slit2-overexpressing transgenic (Slit2-Tg) mice aged 8–9 months. Nevertheless, relatively little is known about behavioral alterations in adult Slit2-Tg mice (2–6 months of age). To observe the age-related behavioral effects of Slit2 overexpression in adult mice, we performed a battery of behavioral tests with adult Slit2-Tg mice at 2–6 months of age.

Results: The body weight of Slit2-Tg mice was lower than that of the wild-type mice from 15 weeks of age. Compared with the control mice, depression-like behaviors were found in Slit2-Tg mice from 15 to 21 weeks of age in the sucrose preference test, although Slit2-Tg mice were hyperactive in the tail suspension test. The anxiety-like behaviors were found in Slit2-Tg mice in the open field test, as well as increased locomotor activity. The anxiety-like behaviors were also found in adult Slit2-Tg mice in the elevated plus maze. Compared to wild-type mice at 23 weeks old, impairment of the hippocampal neurons were found in Slit2-Tg mice at the same age in hematoxylin–eosin staining (H&E), including some eccentric dispersion and expansion of neuronal bodies. In addition, the messenger RNA (mRNA) expression of TNF-α was elevated in the hippocampus of adult Slit2-Tg mice.

Conclusions: Slit2 overexpression causes depression-/anxiety-like behaviors in adult mice that may be related to an increase in inflammatory factors and damage to hippocampal neurons.
Organoid Models of Glioblastoma and Their Role in Drug Discovery
Authors: Rybin Matthew J. , Ivan Michael E. , Ayad Nagi G. , Zeier Zane
Published: February 2021

Glioblastoma (GBM) is a devastating adult brain cancer with high rates of recurrence and treatment resistance. Cellular heterogeneity and extensive invasion of surrounding brain tissues are characteristic features of GBM that contribute to its intractability. Current GBM model systems do not recapitulate some of the complex features of GBM and have not produced sufficiently-effective treatments. This has cast doubt on the effectiveness of current GBM models and drug discovery paradigms. In search of alternative pre-clinical GBM models, various 3D organoid-based GBM model systems have been developed using human cells. The scalability of these systems and potential to more accurately model characteristic features of GBM, provide promising new avenues for pre-clinical GBM research and drug discovery efforts. Here, we review the current suite of organoid-GBM models, their individual strengths and weaknesses, and discuss their future applications with an emphasis on compound screening.
Thalamic Injury and Cognition in Multiple Sclerosis
Authors: Amin Moein , Ontaneda Daniel
Published: February 2021

Multiple sclerosis (MS) produces demyelination and degeneration in both gray and white matter. Both cortical and deep gray matter injury is observed during the course of MS. Among deep gray matter structures, the thalamus has received special attention, as it undergoes volume loss in different MS subtypes and is involved in the earliest form of the disease, radiologically isolated syndrome. The thalamus plays an important role as an information relay center, and involvement of the thalamus in MS has been associated with a variety of clinical manifestations in MS, including fatigue, movement disorders, pain, and cognitive impairment (CI). Similar to thalamic volume loss, CI is seen from the earliest stages of MS and is potentially one of the most debilitating manifestations of the disease. The thalamus, particularly the dorsomedial nucleus as part of the basolateral limbic circuit and anterior thalamic nuclei through connections with the prefrontal cortex, has been shown to be involved in CI. Specifically, several cognitive performance measures such as processing speed and memory correlate with thalamic volume. Thalamic atrophy is one of the most important predictors of CI in MS, and both thalamic volume, diffusion tensor imaging measures, and functional activation correlate with the degree of CI in MS. Although the exact mechanism of thalamic atrophy is not well-understood, it is hypothesized to be secondary to degeneration following white matter injury resulting in secondary neurodegeneration and neuronal loss. The thalamus may represent an ideal biomarker for studies aiming to test neuroprotective or restorative therapies aimed at cognition.
Imaging Identification and Prognosis of the Distal Internal Carotid Artery With Near and Complete Occlusion After Recanalization
Authors: Sun Tao , Wang Chao , Han Mengtao , Wang Fei , He Yiming , Wang Yunyan , Li Xingang , Wang Donghai
Published: February 2021

Background and Purpose: Previous studies have mainly focused on treatment strategies and clinical outcomes for internal carotid artery near occlusion (ICANO) and internal carotid artery complete occlusion (ICACO). However, reports on the morphological changes of distal internal carotid artery (ICA) after recanalization are scarce. This study aimed at illustrating identifying features, assessing prognosis of the distal ICA after recanalization, and exploring best practices for treatment for ICANO and ICACO.

Materials and Methods: We retrospectively studied the clinical characteristics of 57 patients with ICANO or ICACO who underwent surgical recanalization. The clinical data, angiographic morphology, technical successful rate, perioperative complications, and the lumen changes of distal ICA before and after successful recanalization were analyzed.

Results: Fifty-two patients who achieved successfully recanalization were studied. Based on the postoperative lumen diameter changes in the distal ICA, 19 cases were classified as distal-dilatation and the remaining 33 as distal-narrowness. Patients in the distal-narrowness group mostly had ICACO (21.1 vs. 54.5%) and were men (68.4 vs. 93.9%). In the distal-narrowness group, the lumen of the distal ICA recovered to normal in 32 of the 33 patients during the follow-up period. Of the 32 patients reviewed, the ICA of 28 patients dilated back to normal after 1 week of surgery; the ICA of remaining patients 4 dilated 2 weeks postoperatively.

Conclusions: Narrowness of the distal ICA after hybrid recanalization was more prevalent in male patients with ICACO. Homogeneous stenosis of the whole course of the distal ICA is a low-perfusion narrowness which does not require intervention and will spontaneously recover after successful recanalization with an increase in the forward flow.
Neural Mechanisms of Acceptance and Commitment Therapy for Chronic Pain: A Network-Based fMRI Approach
Authors: Aytur Semra A. , Ray Kimberly L. , Meier Sarah K. , Campbell Jenna , Gendron Barry , Waller Noah , Robin Donald A.
Published: February 2021

Over 100 million Americans suffer from chronic pain (CP), which causes more disability than any other medical condition in the United States at a cost of $560–$635 billion per year (Institute of Medicine, 2011). Opioid analgesics are frequently used to treat CP. However, long term use of opioids can cause brain changes such as opioid-induced hyperalgesia that, over time, increase pain sensation. Also, opioids fail to treat complex psychological factors that worsen pain-related disability, including beliefs about and emotional responses to pain. Cognitive behavioral therapy (CBT) can be efficacious for CP. However, CBT generally does not focus on important factors needed for long-term functional improvement, including attainment of personal goals and the psychological flexibility to choose responses to pain. Acceptance and Commitment Therapy (ACT) has been recognized as an effective, non-pharmacologic treatment for a variety of CP conditions (Gutierrez et al., 2004). However, little is known about the neurologic mechanisms underlying ACT. We conducted an ACT intervention in women (n = 9) with chronic musculoskeletal pain. Functional magnetic resonance imaging (fMRI) data were collected pre- and post-ACT, and changes in functional connectivity (FC) were measured using Network-Based Statistics (NBS). Behavioral outcomes were measured using validated assessments such as the Acceptance and Action Questionnaire (AAQ-II), the Chronic Pain Acceptance Questionnaire (CPAQ), the Center for Epidemiologic Studies Depression Scale (CES-D), and the NIH Toolbox Neuro-QoLTM (Quality of Life in Neurological Disorders) scales. Results suggest that, following the 4-week ACT intervention, participants exhibited reductions in brain activation within and between key networks including self-reflection (default mode, DMN), emotion (salience, SN), and cognitive control (frontal parietal, FPN). These changes in connectivity strength were correlated with changes in behavioral outcomes including decreased depression and pain interference, and increased participation in social roles. This study is one of the first to demonstrate that improved function across the DMN, SN, and FPN may drive the positive outcomes associated with ACT. This study contributes to the emerging evidence supporting the use of neurophysiological indices to characterize treatment effects of alternative and complementary mind-body therapies.
Studying Implicit Attitudes Towards Smoking: Event-Related Potentials in the Go/NoGo Association Task
Authors: Wagner-Altendorf Tobias A. , van der Lugt Arie H. , Banfield Jane F. , Deibel Jacqueline , Cirkel Anna , Heldmann Marcus , Münte Thomas F.
Published: February 2021

Cigarette smoking and other addictive behaviors are among the main preventable risk factors for several severe and potentially fatal diseases. It has been argued that addictive behavior is controlled by an automatic-implicit cognitive system and by a reflective-explicit cognitive system, that operate in parallel to jointly drive human behavior. The present study addresses the formation of implicit attitudes towards smoking in both smokers and non-smokers, using a Go/NoGo association task (GNAT), and behavioral and electroencephalographic (EEG) measures. The GNAT assesses, via quantifying participants’ reaction times, the strength of association between a target category and either pole of an evaluative dimension (positive or negative). EEG analysis is performed to determine the temporal course of the event-related potential (ERP) components underlying Go/NoGo decisions and implicit attitude formation. Both smokers and non-smokers showed prolonged reaction times to smoking-related pictures when the pictures were coupled with positive evaluative words (“incongruent condition”). This indicates negative implicit attitudes towards smoking in both groups alike at the time point of the behavioral response (600–700 ms post-stimulus). However, only the non-smokers, not the smokers, were found to show a delay of the N200 component in the incongruent condition. This is interpreted as reflecting ambivalent or even positive implicit attitudes towards smoking in the smoker group at the time point of the N200 (300–400 ms post-stimulus). Our study thus provides evidence for the hypothesis that implicit attitudes are subject to changes within several hundred milliseconds after stimulus presentation, and can be altered in the course of their formation.
Neural Mechanisms of Hearing Recovery for Cochlear-Implanted Patients: An Electroencephalogram Follow-Up Study
Authors: Wang Songjian , Lin Meng , Sun Liwei , Chen Xueqing , Fu Xinxing , Yan LiLi , Li Chunlin , Zhang Xu
Published: February 2021

Background

Patients with severe profound hearing loss could benefit from cochlear implantation (CI). However, the neural mechanism of such benefit is still unclear. Therefore, we analyzed the electroencephalogram (EEG) and behavioral indicators of auditory function remodeling in patients with CI. Both indicators were sampled at multiple time points after implantation (1, 90, and 180 days).

Methods

First, the speech perception ability was evaluated with the recording of a list of Chinese words and sentences in 15 healthy controls (HC group) and 10 patients with CI (CI group). EEG data were collected using an oddball paradigm. Then, the characteristics of event-related potentials (ERPs) and mismatch negative (MMN) were compared between the CI group and the HC group. In addition, we analyzed the phase lag indices (PLI) in the CI group and the HC group and calculated the difference in functional connectivity between the two groups at different stages after implantation.

Results

The behavioral indicator, speech recognition ability, in CI patients improved as the implantation time increased. The MMN analysis showed that CI patients could recognize the difference between standard and deviation stimuli just like the HCs 90 days after cochlear implantation. Comparing the latencies of N1/P2/MMN between the CI group and the HC group, we found that the latency of N1/P2 in CI patients was longer, while the latency of MMN in CI users was shorter. In addition, PLI-based whole-brain functional connectivity (PLI-FC) showed that the difference between the CI group and the HC group mainly exists in electrode pairs between the bilateral auditory area and the frontal area. Furthermore, all those differences gradually decreased with the increase in implantation time.

Conclusion

The N1 amplitude, N1/P2/MMN latency, and PLI-FC in the alpha band may reflect the process of auditory function remodeling and could be an objective index for the assessment of speech perception ability and the effect of cochlear implantation.
MEG-Based Detection of Voluntary Eye Fixations Used to Control a Computer
Authors: Ovchinnikova Anastasia O. , Vasilyev Anatoly N. , Zubarev Ivan P. , Kozyrskiy Bogdan L. , Shishkin Sergei L.
Published: February 2021

Gaze-based input is an efficient way of hand-free human-computer interaction. However, it suffers from the inability of gaze-based interfaces to discriminate voluntary and spontaneous gaze behaviors, which are overtly similar. Here, we demonstrate that voluntary eye fixations can be discriminated from spontaneous ones using short segments of magnetoencephalography (MEG) data measured immediately after the fixation onset. Recently proposed convolutional neural networks (CNNs), linear finite impulse response filters CNN (LF-CNN) and vector autoregressive CNN (VAR-CNN), were applied for binary classification of the MEG signals related to spontaneous and voluntary eye fixations collected in healthy participants (n = 25) who performed a game-like task by fixating on targets voluntarily for 500 ms or longer. Voluntary fixations were identified as those followed by a fixation in a special confirmatory area. Spontaneous vs. voluntary fixation-related single-trial 700 ms MEG segments were non-randomly classified in the majority of participants, with the group average cross-validated ROC AUC of 0.66 ± 0.07 for LF-CNN and 0.67 ± 0.07 for VAR-CNN (M ± SD). When the time interval, from which the MEG data were taken, was extended beyond the onset of the visual feedback, the group average classification performance increased up to 0.91. Analysis of spatial patterns contributing to classification did not reveal signs of significant eye movement impact on the classification results. We conclude that the classification of MEG signals has a certain potential to support gaze-based interfaces by avoiding false responses to spontaneous eye fixations on a single-trial basis. Current results for intention detection prior to gaze-based interface’s feedback, however, are not sufficient for online single-trial eye fixation classification using MEG data alone, and further work is needed to find out if it could be used in practical applications.
Loss of Choline Agonism in the Inner Ear Hair Cell Nicotinic Acetylcholine Receptor Linked to the α10 Subunit
Authors: Moglie Marcelo J. , Marcovich Irina , Corradi Jeremías , Carpaneto Freixas Agustín E. , Gallino Sofía , Plazas Paola V. , Bouzat Cecilia , Lipovsek Marcela , Elgoyhen Ana Belén
Published: February 2021

The α9α10 nicotinic acetylcholine receptor (nAChR) plays a fundamental role in inner ear physiology. It mediates synaptic transmission between efferent olivocochlear fibers that descend from the brainstem and hair cells of the auditory sensory epithelium. The α9 and α10 subunits have undergone a distinct evolutionary history within the family of nAChRs. Predominantly in mammalian vertebrates, the α9α10 receptor has accumulated changes at the protein level that may ultimately relate to the evolutionary history of the mammalian hearing organ. In the present work, we investigated the responses of α9α10 nAChRs to choline, the metabolite of acetylcholine degradation at the synaptic cleft. Whereas choline is a full agonist of chicken α9α10 receptors it is a partial agonist of the rat receptor. Making use of the expression of α9α10 heterologous receptors, encompassing wild-type, heteromeric, homomeric, mutant, chimeric, and hybrid receptors, and in silico molecular docking, we establish that the mammalian (rat) α10 nAChR subunit underscores the reduced efficacy of choline. Moreover, we show that whereas the complementary face of the α10 subunit does not play an important role in the activation of the receptor by ACh, it is strictly required for choline responses. Thus, we propose that the evolutionary changes acquired in the mammalian α9α10 nAChR resulted in the loss of choline acting as a full agonist at the efferent synapse, without affecting the triggering of ACh responses. This may have accompanied the fine-tuning of hair cell post-synaptic responses to the high-frequency activity of efferent medial olivocochlear fibers that modulate the cochlear amplifier.
Tecticornia sp. (Samphire)—A Promising Underutilized Australian Indigenous Edible Halophyte
Authors: Srivarathan Sukirtha , Phan Anh Dao Thi , Hong Hung Trieu , Chua Elvis T. , Wright Olivia , Sultanbawa Yasmina , Netzel Michael E.
Published: February 2021

Salinization is gradually increasing over cropping soils and is challenging Governments in many countries, including Australia. There has been a high demand for utilizing arid and semi-arid land for sustainable food production. Currently, the main crops and forage plants are salt sensitive, while halophytes can tolerate a wide range of salinities. Samphire is an Australian indigenous edible halophyte and belongs to the genus Tecticornia. It is an underutilized, succulent plant growing on arid or semi-arid land. Most samphire species have a long history of use as food, but also as non-food (fodder and medicine), among indigenous communities in Australia, while scientific information is limited on their nutritional composition and potential bioactivity. The present study reports, for the first time, the nutritional composition, bioactive compounds (phytochemicals) and antioxidant capacity of six Australian grown samphire from different locations. The results showed that celosianin II and isocelosianin II could be identified as the predominant betalains (phytochemicals) in pigmented samphire species. Proximates and fiber varied significantly (p < 0.05) between the samphire species with a highest value of fiber of 46.8 g/100 g dry weight (DW). Furthermore, samphire could be identified as a valuable source of essential minerals and trace elements, such as iron (41.5 mg/100 g DW), magnesium (1.2 g/100 g DW) and sodium (16.7 g/100 g DW). The fatty acid profile, mainly palmitic, stearic, oleic, linoleic and α-linolenic acid, was similar among the studied species. Total phenolic content and DPPH-radical scavenging capacity were different (p < 0.05) between the six samphire samples. These initial results are very promising and indicate that Australian grown samphire may have the potential to be utilized as a functional food ingredient.
A Review of Newly Diagnosed Glioblastoma
Authors: Oronsky Bryan , Reid Tony R. , Oronsky Arnold , Sandhu Navjot , Knox Susan J.
Published: February 2021

Glioblastoma is an aggressive and inevitably recurrent primary intra-axial brain tumor with a dismal prognosis. The current mainstay of treatment involves maximally safe surgical resection followed by radiotherapy over a 6-week period with concomitant temozolomide chemotherapy followed by temozolomide maintenance. This review provides a summary of the epidemiological, clinical, histologic and genetic characteristics of newly diagnosed disease as well as the current standard of care and potential future therapeutic prospects.