bluuebunny/crossref_metadata_2025_split huggingface dataset:
The combination of β-asarone and icariin inhibits amyloid-β and reverses cognitive deficits by promoting mitophagy in models of Alzheimer’s disease
Authors: Wang Nanbu , Wang Haoyu , Pan Qi , Kang Jian , Liang Ziwen , Zhang Ronghua 
Published: April 2021

Abstract
Background: β-Asarone is the main constituent of Acorus tatarinowii Schott and exhibits important effects in diseases such as neurodegenerative and neurovascular diseases. Icariin (ICA) is a major active ingredient of Epimedium that has attracted increasing attention because of its unique pharmacological effects in degenerative disease. In this paper, we primarily explored the effects of the combination of β-asarone and ICA in clearing noxious proteins and reversing cognitive deficits. The accumulation of damaged mitochondria and mitophagy are characteristics of ageing and age-related neurodegeneration, including AD.Methods: APP/PS1 mice and in Aβ1-42-induced PC12 cell models were used. The groups were divided into five: normal group, model group (above animals and cells), icariin combined with β-asarone group, A3 and CSA group. Transmission electron microscopy was used to observe brain tissues (hippocampus and temporal lobe)/cell mitochondria, autophagosomes and other structures. IF and WB were used to detect the expression of Beclin-1, LC3, p62, Pink1, Parkin and p-Parkin. Dal-autophagy combined with LSCM was used to detect the occurrence of Autophagy. Mitophagy Detection Kit combined with LSCM was used to detect the occurrence of mitochondrial autophagy, and the effects of icariin combined with β-asarone on mitochondrial autophagy in AD animal and cell model were investigated.Results: We showed evidence that autophagy/mitophagy is damaged in the hippocampus of APP/PS1 mice and in Aβ1-42-induced PC12 cell models. Then, we found that the combination therapy can reduce the cytotoxicity caused by Aβ1-42, increase cell viability, inhibit the expression of Aβ, APP, PS1 and BACE1, and promote the expression of SYN. The efficacy of the combination is better than that of the single drug. What’s more, it also promoted the expression of Beclin-1, LC3 Ⅰ/ in, Pink1, Parkin and p-parkin while inhibited p62. Conclusion: These conclusions suggest that weakened removal of defective mitochondria is a pivotal event in AD pathogenesis and that combination treatment with mitophagy inducers represents a potential strategy for therapeutic intervention.
Retrospective analysis of video-instructed dispatcher-assisted cardiopulmonary resuscitation in Seoul, a metropolitan city
Authors: Lee Hee Soon , You Kicheol , Jeon Jin Pyeong , Kim Chulho , Kim Sungeun 
Published: April 2021

Abstract
We aimed to investigate whether video-instructed dispatcher-assisted (DA)-cardiopulmonary resuscitation (CPR) improved neurologic recovery and survival to discharge compared to audio-instructed DA-CPR in adult out-of-hospital cardiac arrest (OHCA) patients in a metropolitan city with sufficient experience and facilities. A retrospective cohort study was conducted for adult bystander-witnessed OHCA patients administered DA-CPR due to presumed cardiac etiology between January 2018 and October 2019 in Seoul, Korea. The primary and secondary outcomes were the differences in favorable neurologic outcome and survival to discharge rates in adult OHCA patients in the two instruction groups. Binary logistic regression analysis was performed to identify the outcome predictors after DA-CPR. A total of 2109 adult OHCA patients with DA-CPR were enrolled. The number of video and audio instructed DA-CPR procedures was 387 (18.3%) and 1722 (81.7%), respectively. Elderly patients and those outside the home or medical facility were more likely to receive video instruction. Favorable neurologic outcome was observed more in patients who received video-instructed DA-CPR (n = 75, 19.4%) than in patients who received audio-instructed DA-CPR (n = 117, 6.8%). The survival to discharge rate was also higher in video-instructed DA-CPR (n = 105, 27.1%) than in audio-instructed DA-CPR (n = 211, 12.3%). Video-instructed DA-CPR was significantly associated with neurologic recovery (aOR = 2.11, 95% CI: 1.48–3.01) and survival to discharge (aOR = 1.81, 95% CI: 1.33–2.46) compared to audio-instructed DA-CPR in adult OHCA patients. Video-instructed DA-CPR was associated with favorable outcomes in adult patients with OHCA in a metropolitan city equipped with sufficient experience and facilities.
Ischemic post-conditioning promotes mitochondrial translocation of DJ-1 and stabilizes binding to Bcl- xL to attenuate myocardial ischemic-reperfusion injury in STZ-induced diabetic rats
Authors: Li Wei , Xiong Yong-Hong , Leng Yan , Li Wen-Yuan , Cheng Rong , Xue Rui , Meng Qing-Tao , Xia Zhong-Yuan 
Published: April 2021

Abstract
Background Ischemic post-conditioning (IPO) is a strategy in reducing myocardial ischemic-reperfusion (I/R) injury, but its specific molecular mechanism is incompletely understood. Deletions or mutations in the DJ-1 gene are directly linked to the cardiovascular system. DJ-1 plays a critical role in regulating mitochondrial homeostasis in response to stress through translocation of DJ-1 from the cytoplasm into the nucleus. Meanwhile, how the DJ-1 is removed in myocardial I/R injury and regulating apoptosis is needed to further verified. Given the discovery mentioned above, we hypothesize that DJ-1 translocate to mitochondria recover IPO induced cardioprotection in STZ-induced diabetic rats. To evaluate our hypothesis, we overexpressed the DJ-1 protein under high glucose condition, subjected IPO or not. And then measure the expression of DJ-1 in mitochondria and cytoplasm after myocardial I/R. Results We found that DJ-1 translocated to mitochondria combined with Bcl-xL was reduced cardiomyocyte injury and apoptosis in diabetic myocardial I/R heart. Additionally, the binding of DJ-1 and Bcl-xL is dependent on the oxidative state of DJ-1(oxidation of DJ-1 at Cys-106 is important for its protective effect). Conclusions If our hypothesis is correct, promote DJ-1 mitochondrial transfer may be critical with respect to restoring myocardial responsiveness to IPO in diabetes.
Propagatory dynamics of nucleus-acoustic waves excited in gyrogravitating degenerate quantum plasmas electrostatically confined in curved geometry
Authors: Dasgupta Sayanti , Karmakar Pralay Kumar 
Published: April 2021

Abstract
A theoretic model to investigate the dynamics of the longitudinal nucleus-acoustic waves (NAWs) in gyrogravitating electrostatically confined degenerate quantum plasma (DQP) system in spherically symmetric geometry is constructed. The model setup consists of non-degenerate heavy nuclear species (HNS), lighter nuclear species (LNS), and quantum degenerate electronic species (DES). It specifically considers the influences of the Bohm potential, Coriolis rotation, viscoelasticity, and electrostatic confinement pressure (ECP, scaling quadratically in density). A standard normal spherical mode analysis gives a generalized dispersion relation (septic). It highlights the dependency of various atypical instability response on the equilibrium plasma parameters. A numerical illustrative platform portrays that the relative nuclear charge-to-mass coupling parameter (β) acts as a destabilizing agency and the heavy-to-light nuclear charge density ratio (µ) acts as a stabilizing agency in both the non-relativistic (NR) and ultra-relativistic (UR) limits. Another interesting conjuncture is that the Coriolis rotation introduces a destabilizing influence on the system in both the limits. The progressive analysis presented herein has correlations and consistencies in the dynamic growth backdrop of various compact astroobjects and their circumvent atmospheres, such as white dwarfs, neutron stars, etc.
Association Between Cortisol and Left Ventricular Diastolic Dysfunction in Patients With Diabetes Mellitus: A Case Control Study
Authors: SAGARA RIKAKO , Inoue Tomoaki , Sonoda Noriyuki , Yano Chieko , Motoya Misato , Umakoshi Hironobu , Sakamoto Ryuichi , Ogawa Yoshihiro 
Published: April 2021

Abstract
Introduction:

Diabetes mellitus (DM) is a major risk factor for the development of cardiovascular diseases. Heart failure with preserved ejection fraction is characterized by left ventricular diastolic dysfunction (LVDD). It has been reported that excess cortisol found in patients with Cushing’s syndrome was associated with the development of LVDD. However, the relationship between cortisol concentration and LVDD in patients with DM has not been addressed.
Research Design and Methods:

We enrolled 109 patients with DM and 104 patients without DM who had undergone echocardiographic examination at Kyushu University Hospital, Japan, between November 2016 and March 2019. Left ventricular function was evaluated and the ratio of early diastolic velocity from transmitral inflow to early diastolic velocity (E/eʹ) was used as an index of diastolic function. Plasma cortisol concentrations, glycemic control, lipid profiles, treatment with anti-diabetic drugs, and other clinical characteristics were evaluated, and their associations with E/eʹ were determined using univariate and multivariate analyses.
Results

Multivariate linear regression analysis showed that log E/eʹ was positively correlated with age (p = 0.017), log systolic blood pressure (p = 0.004), and cortisol (p = 0.037) and negatively correlated with eGFR (p = 0.016) and the usage of SGLT2 inhibitors (p = 0.042) in patients with DM. Multivariate analysis showed that cortisol was positively correlated with age (p = 0.016) and HbA1c (p = 0.011). There was no association between E/eʹ and cortisol in patients without DM.
Conclusions

Increased cortisol levels may increase the risk of developing LVDD in DM patients.
Autism Spectrum Disorder: Understanding the Impact of SNPs on Biological Pathways in the Fetal and Adult Cortex
Authors: Golovina Evgeniia , Fadason Tayaza , Lints Thierry Jean , Walker Caroline , Vickers Mark Hedley , O’Sullivan Justin Martin 
Published: April 2021

Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by significant and complex genetic etiology. GWAS studies have identified genetic variants associated with ASD, but the functional impacts of these variants remain unknown. Here, we integrated four distinct levels of biological information (GWAS, eQTL, spatial genome organization and protein-protein interactions) to identify potential regulatory impacts of ASD-associated SNPs (p < 5×10-8) on biological pathways within fetal and adult cortical tissues. We found 80 and 58 SNPs that mark regulatory regions (i.e. expression quantitative trait loci or eQTLs) in the fetal and adult cortex, respectively. These eQTLs were also linked to other psychiatric disorders (e.g. schizophrenia, ADHD, bipolar disorder). Functional annotation of ASD-associated eQTLs revealed that they are involved in diverse regulatory processes. In particular, we found significant enrichment of eQTLs within regions repressed by Polycomb proteins in the fetal cortex compared to the adult cortex. Furthermore, we constructed fetal and adult cortex-specific protein-protein interaction networks and identified that ASD-associated regulatory SNPs impact on immune pathways, fatty acid metabolism, ribosome biogenesis, aminoacyl-tRNA biosynthesis and spliceosome in the fetal cortex. By contrast in the adult cortex, they largely affect immune pathways. Overall, our findings highlight potential regulatory mechanisms and pathways important for the etiology of ASD in early brain development and adulthood. This approach, in combination with clinical studies on ASD, will contribute to individualized mechanistic understanding of ASD development.
Gene Panel Screening Across Canine Eye Disorders Highlights Genetic Heterogeneity and the Need for Molecular Discoveries
Authors: Pettinen Inka-Tuulevi , Donner Jonas , Turunen Joni A. , Kaukonen Maria , Lohi Hannes 
Published: April 2021

Abstract
Blinding inherited eye diseases affect millions of people worldwide. Despite a large number of gene discoveries, many patients lack the molecular description of their condition. The domestic dog has become a widely used model to study inherited eye disease genetics and therapeutics during the past 15 years, and nearly 50 genes have been implicated across breeds. Despite a continuous discovery of new causative variants across canine eye disease groups, the genetic cause in most cases is expected to remain unknown. We tested this hypothesis by screening 49 known variants in 194 dogs from 71 breeds affected with progressive retinal atrophy (PRA), glaucoma, or lens luxation and validated the results in additional 1180 dogs. We found that eleven variants in ten genes explained 28% of the studied cases. We also observed new PRA-affected breeds for the RPGRIP1 c.340_341insA29GGAAGCAACAGGATG variant, and clinical support for the pathogenicity of the PDE6A c.1940delA and ADAMTS10 c.2231G>A variants for PRA and glaucoma in two new breeds, respectively. Our findings indicate extensive genetic heterogeneity and the lack of molecular descriptions in more than two-thirds of the LL, glaucoma, and PRA cases by the current gene tests. There is an urgent need for discoveries that would be critical not only for veterinary molecular diagnostics and breeding programs but also for establishing models to characterize pathophysiology and new therapeutic options for the corresponding human eye disorders.
Barriers and Facilitators to Identify and Discuss Depression and Anxiety in Visually Impaired Adults: A Qualitative Study on the Service User’s Perspective
Authors: Munster Edine P.J. van , Aa Hilde P.A. van der , Verstraten Peter , Nispen Ruth M.A. van 
Published: April 2021

Abstract
Background. Depression and anxiety are highly prevalent, but often unrecognized in adults with visual impairment (VI). The purpose of this study was to explore service users’ views on facilitators and barriers in identifying and discussing mental health problems in adults with VI. Methods. Semi-structured interviews, based on the Integrated Model for Change, were conducted with 16 service users from three Dutch low vision service organizations. Interview data was analyzed using the framework approach. Results. Prominent themes in service users’ cognitions and skills were their focus on VI, lack of health literacy, misattribution of symptoms and difficulties in acknowledging their VI and mental health problems. Informal and formal support were seen as facilitators. However, participants mentioned the need of improving healthcare providers’ knowledge, skills and attitude to increase the likelihood of detection and communication about depression and anxiety. Conclusion. Our findings suggest that, compared to barriers experienced in general population, adults with VI face additional barriers in identifying and discussing mental health problems, partly caused by their impairment and increased vulnerability. Healthcare providers and social support systems seem essential for them in reducing these barriers. However, there might be a mismatch between service users’ needs and healthcare providers’ knowledge, skills and attitude. Training healthcare providers may improve detection of depression and anxiety in adults with VI.
Lipids, Anthropometric Measures, Smoking and Physical Activity Mediate the Causal Pathway from Education to Breast Cancer in Women: A Mendelian Randomization Study
Authors: Li Hongkai , Hou Lei , Yu Yuanyuan , Sun Xiaoru , Liu Xinhui , Yan Ran , Yu Yifan , Wu Sijia , He Yina , Wu Yutong , He Li , Xue Fuzhong 
Published: April 2021

Abstract
Background
Our objective is to investigate whether obtaining a higher level of education was causally associated with lower breast cancer risk and to identify the causal mechanism linking them.
Methods
Firstly, we performed a meta-analysis for educational attainment on breast cancer using 33 MR studies, including 15 case-control studies, 10 cross-sectional studies, and 8 cohort studies. Secondly, the main data analysis used publicly available summary-level data from two large GWAS consortia (Breast Cancer Association Consortium [BCAC] and the Social Science Genetic Association Consortium [SSGAC]). Mendelian randomization (MR) analysis used 65 genetic variants derived from the SSGAC as instrumental variables for years of schooling. The outcomes were the overall breast cancer risk (122,977 cases/105,974 controls in women) and its two subtypes: estrogen receptor (ER)-positive breast cancer (ER+: 69,501 cases) and ER-negative breast cancer (ER-: 21,468 cases). Furthermore, six additional consortia were analyzed to investigate the causal pathways from education to breast cancer. The fixed and random effects inverse variance weighted methods were used to estimate the causal effects, along with other additional MR methods as sensitivity analyses.
Results
The results showed that each additional standard deviation of 4.2 years of education was causally associated with a 27% lower risk of ER- (OR 0.73, 95% CI [0.64, 0.84]; P-value < 0.001). However, very weak causal relationship was found with overall breast cancer and no causal association with ER + risk, consistent with the sensitivity analyses. A genetic predisposition for higher education was causally associated with lower ER- risk and was found to be partially related to hip circumference, body mass index, triglyceride and HDL levels, smoking, and physical activity.
Conclusion
A low level of education is a causal risk factor in the development of ER- as it is associated with a poor lipid profile, anthropometric measurements, smoking, and types of physical activity.
Trigonelline regulates Wnt/β-catenin signaling in glomerular mesangial cells under high glucose conditions
Authors: Chen Chen , Shi Yan , Chen Zhen , Li Xiangjun , Sun Bo , Yu Xiaoyan , Ma Jiulong , Zhang Huayu , Ren Xinran , Zhang Ming , Zhao Yan 
Published: April 2021

Abstract
Background: Trigonelline have hypoglycemic effects. In previous animal experiments, we observed that trigonelline (TRL) treat-ment attenuated metabolic abnormalities associated with hyperglycemic conditions in the experimental DN model. In streptozotocin (STZ)-induced rats, TRL treatment reduced albuminuria, lowered blood sugar, improved renal function and alleviated the pathological alterations within the glomerulus. Methods: We stimulated human mesangial cells (HMC) with high glucose (30 mmol / L) medium. HMCs were transfected with β-catenin plasmid or siRNA to investigate the effect of trigonelline on high glucose-induced excessive proliferation and apoptosis of HMCs, and to understand its mechanism of action. Cell viability was measured by MTT assay. Flow cytometry was used to detect the cell cycle. Cell apoptosis was evaluated by flow cytometry and terminal dUTP transferase nick end labeling (TUNEL) assay. Protein and mRNA expression of β-catenin, Wnt5a, TCF4, Cyclin D1, and CDK4 were detected by western blotting and RT-PCR, respectively. Results: Trigonelline inhibited cell proliferation by blocking cell-cycle progression at the G1 phase and decreased apoptosis via the Wnt/β-catenin pathway. Elevated glucose levels enhanced the expression of β-catenin, an important modulator of diabetic nephropathy, while trigonelline restored up-regulation. Conclusions: High glucose and high expression of β-catenin could lead to cell injury; however, this effect was mitigated by trigonelline via managing the canonical Wnt/β-catenin signaling pathway.
Understanding Therapists’ Perceived Determinants of Trauma Narrative Use
Authors: Frank Hannah E , Last Briana S , AlRabiah Reem , Fishman Jessica , Rudd Brittany N , Kratz Hilary E , Harker Colleen , Fernandez-Marcote Sara , Jackson Kamilah , Comeau Carrie , Shoyinka Sosunmolu , Beidas Rinad 
Published: April 2021

Abstract
Background: Trauma narratives are a critical, exposure-based component of trauma-focused cognitive-behavioral therapy, yet community therapists do not always use them. Given evidence that intentions to deliver elements of cognitive behavioral therapy vary by component, and that intentions to deliver exposure are the weakest, this study focused specifically on trauma narratives. We drew on a social psychology causal theory (Theory of Planned Behavior; TPB) and an implementation science framework (the Consolidated Framework for Implementation Research; CFIR) to glean insight into multilevel influences on trauma narrative use. While the CFIR offers a broad list of factors potentially affecting implementation, the TPB offers causal pathways between constructs that predict behavior, including the uptake of an evidence-based intervention. The integration of these approaches may provide a comprehensive understanding of factors affecting therapists’ use of TNs.Methods: Therapists (n=65) trained in trauma-focused cognitive behavioral therapy completed a survey about their use of and beliefs about trauma narratives. Content analysis was used to identify common beliefs about trauma narratives. A subset of participants (n=17) completed follow-up qualitative interviews, which were analyzed using an integrated approach informed by the CFIR.Results: While most participants reported high intentions to use TNs, nearly half reported that they did not use TNs in the last six months. Survey data indicate a number of TPB-related determinants to using on trauma narratives. Qualitative interviews identified CFIR-relevant contextual factors that may influence constructs central to TPB. ﻿Conclusions: These results highlight the importance of integrating approaches that address multiple theoretical determinants of therapist behavior, including therapist, organizational, and client factors with causal explanations.
Race Disparities in Mortality By Breast Cancer From 2000 to 2017 in São Paulo, Brazil: A Time-Series Study
Authors: Marcelino Ana Cláudia , Gozzi Bruno , Cardoso-Filho Cássio , Machado Helymar , Zeferino Luiz Carlos , Vale Diama Bhadra 
Published: April 2021

Abstract
Background In Brazil, inequalities in access to care are present. This study aimed to evaluate the influence of race on breast cancer mortality in the state of São Paulo, from 2000 to 2017, contextualizing with other causes of death. Methods A retrospective cross-sectional time-series study using age and race as variables. Information on deaths was collected from the Ministry of Health Information System. Only white and black/brown categories were used. Mortality rates were age-adjusted by the standard method. For statistical analysis, trend-tests were carried out. Results: There were 60,940 deaths registered as breast cancer deaths, 46,365 in white and 10,588 in black women. The mortality rates for 100,000 women in 2017 were 16.46 in white and 9.57 in black women, a trend to reduction in white (p=0.002), and to increase in black women (p=0.010). This effect was more significant for white women (p<0.001). The trend to reduction was consistent in all age groups in white women, and the trend to increase was observed only in the 40-49 years group in black women. For 'all-cancer causes', the trend was to a reduction in white (p=0.031) and to increase in black women (p<0.001). For 'ill-defined causes' and 'external causes', the trend was to reduce both races (p<0.001). Conclusion The declared race influenced mortality rates due to breast cancer in São Paulo. The divergences observed between white and black women also were evident in all cancer causes of death, which may indicate inequities in access to highly complex health care in our setting.