bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-6/STAT3 Induced Neuron Apoptosis in Hypoxia by Downregulating ATF6 Expression
Authors: Zhou Simin , Zhong Zhifeng , Huang Pei , Xiang Bin , Li Xiaoxu , Dong Huaping , Zhang Gang , Wu Yu , Li Peng 
Published: October 2021

Background: Neuron apoptosis, regulated by endoplasmic reticulum (ER) stress in the hippocampus, is an essential factor influencing the cognitive impairment induced by hypobaric hypoxia. Hypoxia mainly changes the activating transcription factor (ATF6) pathway of ER stress. However, the role of ATF6 in neuron survival, apoptosis, and upstream regulation is still controversial.Methods: We established a hypobaric hypoxia-induced C57BL/6 murine model and cell lines exposed to 1% hypoxia, including PC12 and HT22. First, we tested the expressions of interleukin 6 (IL-6), IL-1β, and IL-10 in C57BL/6 mice’s hippocampus under hypoxia using enzyme-linked immunosorbent assay (ELISA). We determined the signal transducer and activator of transcription 3 (STAT3) phosphorylation at tyrosine (Tyr)705 by western blot and the expression of ATF6, 78-kDa glucose-regulated protein (GRP78), and C/-EBP homologous protein (CHOP) related to ER stress by immunofluorescence (IF), western blot, and qRT-PCR; they were then verified on the cell model. Additionally, IL-6 (40 ng/mL) and STAT3 siRNA were used to treat the PC12 cells for 48 and 4 h to activate or silence STAT3, respectively. Subsequently, the cells of siRNA group were exposed to 1% hypoxia for 48 h. Furthermore, the ATF6 and CHOP expressions were detected with western blot and qRT-PCR. Finally, we examined the binding of STAT3 to the ATF6 promoter by chromatin immunoprecipitation (ChIP)-seq.Results: The results showed that IL-6 increased, IL-10 decreased in the hypoxia group, and IL-1β showed no difference between the hypoxia and the normoxia groups. Neuron apoptosis was significantly elevated by exposure to hypoxia for 48h in PC12 cells. The hypobaric hypoxia-induced ER stress proteins, ATF6, GRP78, and CHOP, and the p-STAT3 (Tyr705) expressions increased both in in vivo and in vitro. Besides, STAT3 silencing significantly promoted the ATF6 expression and inhibited CHOP, while STAT3 activation downregulated the expression of ATF6 and upregulated CHOP in PC12 cells. The ChIP-seq assay demonstrated that p-STAT3 (Tyr705) protein could bind to the ATF6 promoter region in HT22 cells.Conclusion: Phosphorylation of STAT3 at the Tyr705 site contributes to hypoxia-induced neuron apoptosis by downregulating ATF6, which might explain the inflammatory reaction and apoptosis of the hippocampal neurons induced by ER stress.
A Novel Mindful-Compassion Art-Based Therapy for Reducing Burnout and Promoting Resilience Among Healthcare Workers: Findings From a Waitlist Randomized Control Trial
Authors: Ho Andy Hau Yan , Tan-Ho Geraldine , Ngo Thuy Anh , Ong Grace , Chong Poh Heng , Dignadice Dennis , Potash Jordan 
Published: October 2021

Protecting the mental health of healthcare workers is an urgent global public health priority. Healthcare workers, especially those immersed in palliative care, are prone to burnout due to the intense emotions associated with end-of-life caregiving. This study examines the efficacy of a novel, multimodal, and group-based Mindful-Compassion Art-based Therapy (MCAT) that integrates reflective self-awareness with creative emotional expression for protecting healthcare workers’ mental health. A dual-arm open-label waitlist randomized controlled trial was conducted. A total of 56 healthcare workers were recruited from the largest homecare hospice in Singapore and randomized to the immediate-treatment condition of a standardized 6-week, 18-hours MCAT intervention (n=29), or the waitlist-control condition (n=27). Self-administered outcome measures on burnout, resilience, emotional regulation, self-compassion, death attitudes, and quality of life were collected at baseline, post-intervention/second-baseline at 6weeks, and follow-up/post-intervention at 12weeks. Results from mixed model ANOVAs reveal that treatment group participants experienced significant reduction in mental exhaustion, as well as significant improvements in overall emotional regulation, nonreactivity to intrusive thoughts, approach acceptance of death, and afterlife belief as compared to waitlist-control immediately after MCAT completion. Effect sizes of these impacts ranged from medium to large (η2=0.65 to 0.170). Results from one-way ANOVAs further reveal that the treatment gains of reduced mental exhaustion and increased emotional regulation were maintained among treatment group participants at 12-weeks follow-up compared to baseline, with new benefits identified. These include increased ability to observe and describe one’s experiences, elevated overall self-compassion, greater mindful awareness, enhanced common humanity, and better quality of life. Effect sizes of these impacts were large (η2=0.128 to 0.298). These findings reflect the robust effectiveness and positive residual effects of MCAT for reducing burnout, building resilience, nurturing compassion, fostering collegial support, and promoting mental wellness among healthcare workers. The clinical model and applicability of MCAT in larger and more diverse caregiving contexts, such as family dementia care, are discussed.Clinical Trial Registration:ClinicalTrials.gov# NCT03440606, #NCT04548089.
Systematic Review and Bioinformatic Analysis of microRNA Expression in Autism Spectrum Disorder Identifies Pathways Associated With Cancer, Metabolism, Cell Signaling, and Cell Adhesion
Authors: Huang Zhi-Xiong , Chen Yanhui , Guo Hong-Ru , Chen Guo-Feng 
Published: October 2021

Background: Previous studies have identified differentially expressed microRNAs in autism spectrum disorder (ASD), however, results are discrepant. We aimed to systematically review this topic and perform bioinformatic analysis to identify genes and pathways associated with ASD miRNAs.Methods: Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses, we searched the Web of Science, PubMed, Embase, Scopus, and OVID databases to identify all studies comparing microRNA expressions between ASD persons and non-ASD controls on May 11, 2020. We obtained ASD miRNA targets validated by experimental assays from miRTarBase and performed pathway enrichment analysis using Metascape and DIANA-miRPath v3. 0.Results: Thirty-four studies were included in the systematic review. Among 285 altered miRNAs reported in these studies, 15 were consistently upregulated, 14 were consistently downregulated, and 39 were inconsistently dysregulated. The most frequently altered miRNAs including miR-23a-3p, miR-106b-5p, miR-146a-5p, miR-7-5p, miR-27a-3p, miR-181b-5p, miR-486-3p, and miR-451a. Subgroup analysis of tissues showed that miR-146a-5p, miR-155-5p, miR-1277-3p, miR-21-3p, miR-106b-5p, and miR-451a were consistently upregulated in brain tissues, while miR-4742-3p was consistently downregulated; miR-23b-3p, miR-483-5p, and miR-23a-3p were consistently upregulated in blood samples, while miR-15a-5p, miR-193a-5p, miR-20a-5p, miR-574-3p, miR-92a-3p, miR-3135a, and miR-103a-3p were consistently downregulated; miR-7-5p was consistently upregulated in saliva, miR-23a-3p and miR-32-5p were consistently downregulated. The altered ASD miRNAs identified in at least two independent studies were validated to target many autism risk genes. TNRC6B, PTEN, AGO1, SKI, and SMAD4 were the most frequent targets, and miR-92a-3p had the most target autism risk genes. Pathway enrichment analysis showed that ASD miRNAs are significantly involved in pathways associated with cancer, metabolism (notably Steroid biosynthesis, Fatty acid metabolism, Fatty acid biosynthesis, Lysine degradation, Biotin metabolism), cell cycle, cell signaling (especially Hippo, FoxO, TGF-beta, p53, Thyroid hormone, and Estrogen signaling pathway), adherens junction, extracellular matrix-receptor interaction, and Prion diseases.Conclusions: Altered miRNAs in ASD target autism risk genes and are involved in various ASD-related pathways, some of which are understudied and require further investigation.
Prevalence and Factors Associated With Suicidal Ideation in Medical Students With Migraine
Authors: Luo Jia-Ming , Liu En-Zhuo , Yang Hao-Di , Du Cheng-Zhao , Xia Li-Jie , Zhang Zhi-Chao , Li Tong , Ren Jia-Jun , Tang Jia-Qi , Tang Pei-Qi , Tang Yuan-Ru , Zhu Shuang , Bhattarai Nisha , Bhetuwal Anup , Pu Sheng-Xiong 
Published: October 2021

Background: The association between migraine and suicide ideation has been identified. However, the predictive factors of suicidal ideation are still controversial and whether migraine with aura can serve as an independent associated factor is uncertain. This manuscript studied the association between migraine with aura and suicidal ideation and explored the predictive factors for suicidal ideation.Methods: We surveyed 9,057 medical students and included 579 medical students with migraine into our study population. All students completed the General Situation Questionnaire, the Verified Headache Questionnaire, Hamilton Anxiety Scale (24 items), Hamilton Depression Scale (24 items), 36-item Health Survey Brief (SF-36), Headache Impact Text-6 (HIT-6), Test Anxiety Scale (TAS), and Pittsburgh Sleep Quality Index (PSQI). Suicidal ideation was measured by the Self-rating Idea of Suicide Scale (SIOSS).Results: Out of the 579 migraine medical college students, 562 (age 19.6 ± 1.6; 448 women and 114 men) were included in the final study. The positive rate of suicidal ideation was 13.7%. Compared with students suffering from migraine without aura, those having migraine with aura had higher suicidal ideation (p &lt; 0.015). After adjusting for demographic factors and headache characteristics, migraine with aura was found to be independently associated with suicidal ideation. Other independent associated factors include anxiety, depression, test anxiety, sleep, headache, and quality of life. Among these various factors, high quality of life was found to play a protective role against suicidal ideation.Conclusions: Migraine with aura is independently associated with suicidal ideation. Furthermore, anxiety, depression, text anxiety, poor sleep quality, and headache frequency are associated with suicidal ideation among medical college students with migraine.
Impact of School Closure Due to COVID-19 on the Social-Emotional Skills of Japanese Pre-school Children
Authors: Doi Satomi , Miyamura Keitaro , Isumi Aya , Fujiwara Takeo 
Published: October 2021

Objective: This study examines the impact on the social-emotional skills of Japanese pre-school children from downsizing of school activities in conjunction with voluntary school closures due to the first wave of COVID-19, in 2020.Methods: Participants included 32 children aged 4–5 years old from three pre-schools in Tokyo, Japan, where strict lockdown was not implemented and voluntary school closure was recommended. Child social-emotional skills was assessed by classroom teachers using Devereux Student Strengths Assessment mini (DESSA-mini) three times: November 2019, January 2020 (before the COVID-19), and March 2020 (during the first COVID-19 wave). All pre-schools implemented voluntary school closures from March 2nd, and two schools (school A and B) canceled school recitals, while one school (school C) allowed for it to be held on March 4th, with precautions in place to prevent the spread of infection. Repeated measures ANOVA were performed to examine the difference between the T scores of the DESSA-mini three pre-schools before and during the COVID-19 pandemic.Results: In school C, children showed stable T scores of the DESSA-mini, whereas children in school A and B showed lower T scores of the DESSA-mini during COVID-19 than before it started. The interaction effects between time and pre-schools were found (F = 7.05, p &lt; 0.001).Conclusion: Our findings suggest that school recitals in pre-schools were important to maintaining children's social-emotional skills during the COVID-19 pandemic.
The Moderating Role of Resilience in the Personality-Mental Health Relationship During the COVID-19 Pandemic
Authors: Pauly Claire , Ribeiro Fabiana , Schröder Valerie E. , Pauly Laure , Krüger Rejko , Leist Anja K. ,   the CON-VINCE Consortium
Published: October 2021

Background:Associations between personality traits and mental health outcomes (depression, anxiety, loneliness, and stress) have rarely been assessed in a population-representative sample of a high-income country during the COVID-19 pandemic. Additionally, as far as we know, the role of health and social behaviors as well as resilience in the personality-mental health relationship has yet to be explored.Methods:A representative sample of 1,828 residents of Luxembourg filled in validated scales to assess personality traits and resilience, depressive symptoms, generalized anxiety, loneliness, and stress, indicating mental health, in mid-April 2020.Results:Approximately 21% of the participants scored above the cut-off for moderate depression and moderate loneliness. Moderate anxiety and moderate stress were present in 6.2 and 0.3% of the participants, respectively. Higher-educated respondents and those living in higher-value housing reported better mental health. Agreeableness and conscientiousness were most consistently associated with better mental health; neuroticism was most consistently associated with worse mental health. Spending more time on social media was also associated with elevated levels of all four mental health outcomes. Social and health behaviors did not change the personality-mental health relationships. Resilience moderated some of the personality-mental health associations, most consistently in neuroticism.Conclusions:Findings suggest educational and socioeconomic inequalities in mental health in a nationally representative sample during the COVID-19 confinement measures. Personality traits, particularly agreeableness, conscientiousness, and low neuroticism were associated with mental health. The moderating role of resilience in the personality-mental health relationship suggests intervention potential to improve mental health during periods of confinement.
A Systematic Policy Review of Black Maternal Health-Related Policies Proposed Federally and in Massachusetts: 2010–2020
Authors: Carvalho Keri , Kheyfets Anna , Maleki Pegah , Miller Brenna , Abouhala Siwaar , Anwar Eimaan , Amutah-Onukagha Ndidiamaka 
Published: October 2021

Background: Black women in the United States experience maternal mortality three to four times more often than white women (1, 2). States vary in degree of disparity, partially due to programs and policies available to pregnant people. In Massachusetts, Black women were approximately twice as likely as white women to experience pregnancy-associated mortality, with a large percentage of these deaths reported to be preventable (3).Methods: Using Massachusetts as a state-level comparison to national policies, we searched the US Congress and Massachusetts legislative databases for maternal health policies from 2010 to 2020. We screened 1,421 national and 360 Massachusetts bills, following set inclusion/exclusion criteria. Data analysis included (1) assessment of bill characteristics, (2) thematic analysis, and a (3) quality appraisal following an adapted model of the analytical framework for evaluating public health policy proposed by the National Collaborating Centre for Healthy Public Policy. Additionally, our data analysis identified the level of racism (internalized, interpersonal or institutional) that each policy addressed.Results: From 2010 to 2020, 31 national and 16 state-level policies were proposed that address maternal health and racial disparities. The majority of policies addressed racism at the institutional level alone (National: N = 19, 61.3%, Massachusetts: N = 14, 87.5%). Two national and two Massachusetts-level policies became law, while two national policies passed only the House of Representatives. Our critical appraisal revealed that the majority of unintended effects would be neutral or positive, however, some potential negative unintended effects were identified. The appraisal also identified 54.8% (n = 17) of national policies and 68.8% (n = 11) of Massachusetts with positive impact on health equity.Conclusions: There has been an increase in policies proposed addressing racial disparities and health equity in maternal health over the last 10 years. Although half of national policies proposed showed positive impact on health equity, shedding light on the work the U.S. is doing on a federal level to confront the Black maternal health crisis, only two policies made it to law, only one of which addressed racial disparities directly and had a positive impact on health equity.
The Association Between Sarcopenia and Functional Improvement in Older and Younger Patients Who Completed Inpatient Rehabilitation: A Prospective Cohort Study
Authors: Churilov Irina , Churilov Leonid , Brock Kim , Murphy David , MacIsaac Richard J. , Ekinci Elif I. 
Published: October 2021

Objective: To investigate the association between sarcopenia and functional improvement in patients older and younger than 65 years upon completion of an inpatient rehabilitation program.Design: Prospective cohort study.Participants: Adult consecutive patients who completed the inpatient rehabilitation program at a metropolitan tertiary referral hospital general inpatient rehabilitation unit.Methods: Sarcopenia status was determined using the European Working Group on Sarcopenia in Older People 2 algorithm, using muscle mass measured by BioImpedance Analysis and grip strength. Progress in rehabilitation was measured using change in the Functional Independence Measure and Goal Attainment Scaling score. To investigate the age group by sarcopenia status interaction we used quantile regression models with bootstrapped standard error estimation for functional improvement and linear regression model with robust standard error estimation for GAS score.Results: 257 participants [128 (50%) male, median age 63 years (IQR: 52–72)], 33(13%) with sarcopenia, completed inpatient rehabilitation [median length of stay 16 days (IQR: 11–27.5)]. Participants' median Functional Independence Measure change was 24 (IQR 15–33.5) and mean total Goal Attainment Scaling score was 57.6 (SD 10.2). Adjusting for admission Functional Independence Measure score, the median difference in Functional Independence Measure change between participants with and without sarcopenia was: −4.3 (95% CI: −10.6, 1.9); p = 0.17 in participants 65 years and younger, and 4.6 (95% CI: 1.0, 8.2); p = 0.01 in participants older than 65; age-by-sarcopenia interaction p = 0.02.Conclusions: Unlike younger people, older people with sarcopenia have greater functional improvement in inpatient rehabilitation than those without sarcopenia.
Direct Connection Between Auroral Oval Streamers/Flow Channels and Equatorward Traveling Ionospheric Disturbances
Authors: Lyons Larry R. , Nishimura Yukitoshi , Zhang Shunrong , Coster Anthea , Liu Jiang , Bristow William A. , Reimer Ashton S. , Varney Roger H. , Hampton Don L. 
Published: October 2021

We use simultaneous auroral imaging, radar flows, and total electron content (TEC) measurements over Alaska to examine whether there is a direct connection of large-scale traveling ionospheric disturbances (LSTIDs) to auroral streamers and associated flow channels having significant ground magnetic decreases. Observations from seven nights with clearly observable flow channels and/or auroral streamers were selected for analysis. Auroral observations allow identification of streamers, and TEC observations detect ionization enhancements associated with streamer electron precipitation. Radar observations allow direct detection of flow channels. The TEC observations show direct connection of streamers to TIDs propagating equatorward from the equatorward boundary of the auroral oval. The TIDs are also distinguished from the streamers to which they connect by their wave-like TEC fluctuations moving more slowly equatorward than the TEC enhancements from streamer electron precipitation. TIDs previously observed propagating equatorward from the auroral oval have been identified as LSTIDs. Thus, the TIDs here are likely LSTIDs, but we lack sufficient TEC coverage necessary to demonstrate that they are indeed large scale. Furthermore, each of our events shows TID’s connection to groups of a few streamers and flow channels over a period in the order of 15 min and a longitude range of ∼15–20°, and not to single streamers. (Groups of streamers are common during substorms. However, it is not currently known if streamers and associated flow channels typically occur in such groups.) We also find evidence that a flow channel must lead to a sufficiently large ionospheric current for it to lead to a detectable LSTID, with a few tens of nT ground magnetic field decreases not being sufficient.
Novel Approach to Assess Cardiac Function Using Systolic Performance and Myocardial Performance Indices From Simultaneous Electrocardiography and Phonocardiography Recordings in Dogs With Various Stages of Myxomatous Mitral Valve Disease
Authors: Gicana Karlo Romano B. , Lertwanakarn Tuchakorn , Tachampa Kittipong 
Published: October 2021

Background and Objective:Myxomatous mitral valve disease (MMVD) progression entails changes in the structural and functional properties of the heart affecting cardiac timings and intervals within the cardiac cycle. Conventionally, echocardiography is used to determine the cardiac time intervals (CTIs) including systolic and myocardial performance indices (SPI and MPI) in evaluating cardiac function. Alternatively, these CTIs can also be measured using simultaneous recordings of electrocardiography (ECG) and phonocardiography (PCG), but their values in different MMVD stages remain to be established. This study aimed to establish and prove the use of derived SPI and MPI from a dedicated device as a novel approach to assess cardiac function in different stages of MMVD dogs.Materials and Methods:A prospective study in 52 dogs with different MMVD stages measured the CTIs using a novel device. These were compared and correlated with standard echocardiographic parameters. The predictive value of SPI and three new proposed formulas to estimate MPI (i.e., F1, F2, and F3) in association with asymptomatic from symptomatic MMVD dogs were investigated.Results:Our findings revealed that CTI parameters measured from a novel device including QS1, QS2, S1S2, MPI-F1, and MPI-F2 were altered at different stages of MMVD. The SPI and all proposed MPI formulas were comparable with the systolic time interval and Tei index from echocardiography. In addition, the SPI, MPI-F1, and MPI-F2 were significantly correlated with the Tei index. However, the SPI was not able to differentiate the various stages of MMVD. Conversely, only the MPI-F1 (i.e., (QS1 + S2)/S1S2) demonstrated good predictive accuracy when compared between asymptomatic and symptomatic MMVD dogs similar to the Tei index. Moreover, this formula was able to differentiate stages B1 and C with remarkable predictive accuracy, higher sensitivity, and high specificity when compared with the Tei index.Conclusion:We have successfully described the CTI parameters in different MMVD stages using simultaneous ECG and PCG recordings in dogs. Furthermore, we have proven that the concept of using the newly proposed parameters from a novel device is equivalent to the Tei index. Thus, we established a novel approach to evaluate cardiac function and its supportive use in the diagnosis of MMVD patients.