Miracle-dz/UniFAR-FTUs huggingface dataset:
Abnormality of m6A mRNA Methylation Is Involved in Alzheimer’s Disease

Alzheimer’s disease (AD), the most common form of dementia, is highly prevalent in older adults. The main clinical feature is the progressive decline of memory function, which eventually leads to the decline of cognitive function. At present, the pathogenesis of AD is unclear. In the disease process, synaptic changes are the key. Recent studies have shown that the dysregulation of RNA methylation is related to many biological processes, including neurodevelopment and neurodegenerative diseases. N6-methyladenosine (m6A) is the most abundant modification in eukaryotic RNA. In this study, RNA m6A methylation was quantified in APP/PS1 transgenic mice, which is an AD mouse model, and C57BL/6 control mice, and data showed that m6A methylation was elevated in the cortex and the hippocampus of APP/PS1 transgenic mice. Next, the alterations of m6A RNA methylation in AD and in C57BL/6 mice were investigated using high-throughput sequencing. Genome-wide maps of m6A mRNA showed that the degrees of m6A methylation were higher in many genes and lower in others in AD mice. Interestingly, the expression of the m6A methyltransferase METTL3 was elevated and that of the m6A demethylase FTO was decreased in AD mice. The data were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and pathways that might be related to synaptic or neuron development and growth were constructed. The related pathways and genes predicted the potential roles of the differentially expressed m6A methylation RNA in AD. Collectively, our findings demonstrate that the m6A methylation of RNA promotes the development of AD.
Heterogeneity of Liver Disease in Common Variable Immunodeficiency Disorders

Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency (PID) in adulthood and is characterized by severe reduction of immunoglobulin serum levels and impaired antibody production in response to vaccines and pathogens. Beyond the susceptibility to infections, CVID encompasses a wide spectrum of clinical manifestations related to a complex immune dysregulation that also affects liver. Although about 50% CVID patients present persistently deranged liver function, burden, and nature of liver involvement have not been systematically investigated in most cohort studies published in the last decades. Therefore, the prevalence of liver disease in CVID widely varies depending on the study design and the sampling criteria. This review seeks to summarize the evidence about the most relevant causes of liver involvement in CVID, including nodular regenerative hyperplasia (NRH), infections and malignancies. We also describe the clinical features of liver disease in some monogenic forms of PID included in the clinical spectrum of CVID as ICOS, NFKB1, NFKB2, CTLA-4, PI3Kδ pathway, ADA2, and IL21-R genetic defects. Finally, we discuss the clinical applications of the various diagnostic tools and the possible therapeutic approaches for the management of liver involvement in the context of CVID.
The Relationship Between Care Burden and Coping Strategies in Caregivers of Hemodialysis Patients in Kermanshah, Iran

Objective The purpose of this study was to investigate the relationship between care burden and coping strategies in caregivers of hemodialysis patients. Methods This cross-sectional survey was conducted from September to December 2018 in Kermanshah, Iran. A total of 130 caregivers of patients admitted to the hemodialysis wards of Imam Reza and Imam Khomeini hospitals of Kermanshah, Iran were selected via convenience sampling. Data-collection tools included a demographic information form, caregiver-burden inventory, and coping inventory for stressful situations. Data were analyzed using descriptive and analytical tests. Results The mean age of the caregivers was 35.8±13.7 years, and 71 (54.6%) were patients’ children. The mean caregiver-burden score was 58.5±20.5 out of 96. Mean scores of time-dependent, evolutionary, physical, social, and emotion-dependent care burdens were 17.5±5.3, 12.2±6.3, 9.1±4.7, 8.2±4.0, and 11.4±5.1, respectively. Mean scores of problem-focused, emotion-focused, and avoidance-oriented coping strategies were 46.0±80.8, 43.1±9.0, and 48.9±9.5, respectively. Among the strategies, only the avoidance-oriented one had a significant positive relationship with total care burden and all its subscales. Conclusion Caregivers of hemodialysis patients experienced a relatively high care burden. However, they did not use appropriate coping strategies; therefore, they should be trained to select an effective coping strategy.
Conventional and Novel Treatment Modalities in Rosacea

Abstract Rosacea is a common skin disease that is troublesome for both the patients and the dermatologists. Erythema, telengiectasia, papulopustular changes and phymatous changes are the main problems faced by the patients and dermatologists in everyday practice. Due to the chronic and relapsing nature of the disease, patients are usually unsatisfied with conventional treatment methods. This article aims at redefining rosacea according to the 2017 consensus and reviewing the different treatment modalities for different manifestations of the disease in depth.
Regulations of miR-183-5p and Snail-Mediated Shikonin-Reduced Epithelial-Mesenchymal Transition in Cervical Cancer Cells

Background Shikonin, the main ingredient of Lithospermum erythrorhizon, has been reported to have antitumor effects via multiple targets and signaling pathways. However, the detailed mechanism underlying the effects in cervical cancer still remained unknown. Methods MTT, wound-healing, transwell assays and flow cytometry experiments were used to measure cell growth, migration, invasion, and cell cycle analysis. Western blot was used to examine protein levels of Snail, Vimentin and E-cadherin. The expression level of miR-183-5p was measured via qRT-PCR. The E-cadherin promoter activity was detected via Secrete-PairTM Dual Luminescence Assay Kit. The transient transfection experiments were used for silencing of E-cadherin and overexpression of Snail genes. Tumor xenograft and bioluminescent imaging experiments were carried out to confirm the in vitro findings. Results We showed that shikonin inhibited cell viability, migration and invasion, and induced cell cycle arrest in a dose-dependent manner in cervical cancer Hela and C33a cells. Mechanistically, we found that shikonin increased miR-183-5p expression and inhibited expression of transcription factor Snail protein. The mimics of miR-183-5p reduced, while the inhibitors of miR-183-5p reversed shikonin-inhibited Snail protein expression. In addition, shikonin decreased Vimentin, increased E-cadherin protein expressions and E-cadherin promoter activity, the latter was reversed in cells transfected with exogenous Snail overexpression vectors. Moreover, silencing of E-cadherin significantly abolished shikonin-inhibited cervical cancer cell growth. Similar findings were also observed in vivo using one xenograft mouse model. Conclusion Our results show that shikonin inhibits EMT through inhibition of Snail and stimulation of miR-183-5p expressions, which resulted in induction of E-cadherin expression. Thus, blockade of EMT could be a novel mechanism underlying the anti-cervical cancer effects of shikonin.
Acinetobacter baumannii Efflux Pumps and Antibiotic Resistance

Abstract Acinetobacter baumannii is a nosocomial pathogen and gram-negative coccobacillus that is responsible for opportunistic infections, pneumonia, and infections of the urinary tract, bloodstream, skin, and soft tissue. This bacterium poses a major public health problem due to inducing resistance to several drugs, isolates, multidrug treatment, and occasionally pan drugs. Drug resistance is not only a major concern caused by A. baumannii but also is considered as the main challenge in many other pathogens. Several factors such as the efflux pump are associated with antibiotic resistance, biofilm production, and genetic mutations. In this review, A. baumannii is introduced in then some of the practical works conducted on the existing efflux pump are reviewed. The importance of the efflux pump is considered in this paper in relation to the antibiotic resistance and mechanisms developed for the inhibition of these pumps as well.
Barriers to older adults’ uptake of mobile-based mental health interventions

Background To address increasing demand of mental healthcare treatments for older adults and the need to reduce delivery costs, healthcare providers are turning to mobile applications. The importance of psychological barriers have been highlighted in the uptake of mobile-based mental health interventions and efforts have been made to identify these barriers in order to facilitate initial uptake and acceptance. However, limited research has focused on older adults’ awareness of these applications and factors that might be hindering their use. Objective The purpose of this study was to explore the perceived barriers that older adults experience in the uptake of mobile-based mental health interventions. Methods Semi-structured interviews were conducted with a sample of 10 older adults, 50 years or older (female = 7, mean age = 68 years), who experienced periods of low mood. National Health Service applications were demonstrated to facilitate conversation and explore participants’ understanding of mental health and mobile-based mental health interventions. Thematic analysis was used to analyse the interview transcripts. Results The social ecological model was adopted as an organising framework for the thematic analysis which identified six distinct barriers to older adults’ uptake of mobile-based mental health interventions: mental electronic-health (e-health) awareness, interaction with technology, discontinuation, ‘seeing’ facilitates therapeutic alliance, incongruent role of the general practitioner and privacy and confidentiality. Conclusions Older adults experience a number of barriers to uptake ranging from the individual level to a macro, organisational level. The practical implications of these barriers are discussed such as the need for increased awareness of mobile-based mental health interventions among older adults.
Expression of lncRNA MEG3 in asthma with different phenotypes and its relationship with course of disease

The purpose of this study was to explore the application value of lncRNA MEG3 in lung cancer. From March 2017 to March 2019, 119 asthma patients and 125 healthy people undergoing physical examination in the same period were selected as the research objects. The levels of lncRNA MEG3 in the peripheral blood of the two groups were compared, and the predictive value of MEG3 for asthma as well as the differences in different inflammatory phenotypes were analyzed. The expression of MEG3 was low in asthma patients (P<0.050), the diagnostic sensitivity and specificity for asthma were 79.83 and 66.40%, respectively (P<0.001), it was the lowest in mixed granulocytic asthma (P<0.050) and was negatively correlated with the course of disease (r=−0.666, P<0.001). Logistic regression analysis showed that course of disease, inflammatory phenotype and MEG3 were independent factors affecting recurrence of asthma (P<0.050). MEG3 was low expressed in asthma and had good predictive value for it; in mixed granulocytic asthma, its expression was the lowest and the course of disease was closely related. It might be the key to the diagnosis and treatment of asthma in the future.
Cross-Cultural Adaptation and Face Validity of the Functional Mobility Assessment into Brazilian Portuguese

Introduction. The Functional Mobility Assessment (FMA) measures satisfaction with mobility devices in daily life. However, in Brazil, there is a lack of instruments which measure functional mobility. Objective We aim to report the cross-cultural adaptation process and face validity of the FMA for use in Brazil. Methods Two international guidelines were used in the cross-cultural adaptation process. Two independent translators translated the instrument from English to Brazilian Portuguese, and the two versions were reconciled. Two different translators back translated this reconciled version, and an expert committee analysed the resulting synthesis. For face validity, the FMA was applied with 24 participants, divided into two groups, users with disabilities (n = 12) and occupational therapy students (n = 12) and occupational therapy students ( Results The cross-cultural adaptation of the FMA was concluded, and its face validity presented that both groups understood most or completely all instrument items. Conclusion The Brazilian version of FMA is now available in Brazilian Portuguese and has face validation. Further studies should test its psychometric properties.
Statin Use and the Risk of Subsequent Hospitalized Exacerbations in COPD Patients with Frequent Exacerbations

Rationale The potential benefits of statins for the prevention of exacerbations in patients with COPD remains controversial. No previous studies have investigated the impact of statins on clinical outcomes in COPD patients with frequent exacerbations. Objective This study aimed to evaluate the association between the use of statins and the risk of subsequent hospitalized exacerbations in COPD frequent exacerbators. Materials and Methods We conducted a population-based cohort study using the Taiwan National Health Insurance Research Database. 139,223 COPD patients with a first hospitalized exacerbation between 2004 and 2012 were analyzed. Among them, 35,482 had a second hospitalized exacerbation within a year after the first exacerbation, and were defined as frequent exacerbators. 1:4 propensity score matching was used to create matched samples of statin users and non-users. The competing risk regression analysis model was used to evaluate the association between statin use and exacerbation risk. Results The use of statins was associated with a significantly reduced risk in subsequent hospitalized exacerbations in COPD patients after their first hospitalized exacerbation (adjusted subdistribution hazard ration [SHR], 0.89; 95% CI, 0.85–0.93, P<0.001). In frequent exacerbators, the SHR for subsequent hospitalized exacerbations in statins users was 0.88 (95% CI, 0.81–0.94, P=0.001). Subgroup analysis among frequent exacerbators demonstrated that the use of statins only provided a protective effect against subsequent hospitalized exacerbations in male patients aged 75 years and older, with coexisting diabetes mellitus, hypertension or cardiovascular disease, and no protective effect was observed in those with lung cancer or depression. Current use of statins was associated with a greater protective effect for reducing subsequent hospitalized exacerbation. Conclusion The use of statins was associated with a significant reduction in the risk of hospitalized exacerbations in COPD patients after a first hospitalized exacerbation and in specified COPD frequent exacerbators.
Arabidopsis Mitochondrial Voltage-Dependent Anion Channels Are Involved in Maintaining Reactive Oxygen Species Homeostasis, Oxidative and Salt Stress Tolerance in Yeast

Voltage-dependent anion channels (VDACs) are conserved proteins of the mitochondria. We have functionally compared Arabidopsis VDACs using Saccharomyces cerevisiae Δpor1 and M3 yeast system. VDAC (1, 2, and 4) were able to restore Δpor1 growth in elevated temperature, in oxidative and salt stresses, whereas VDAC3 only partially rescued Δpor1 in these conditions. The ectopic expression of VDAC (1, 2, 3, and 4) in mutant yeast recapitulated the mitochondrial membrane potential thus, enabled it to maintain reactive oxygen species homeostasis. Overexpression of these VDACs (AtVDACs) in M3 strain did not display any synergistic or antagonistic activity with the native yeast VDAC1 (ScVDAC1). Collectively, our data suggest that Arabidopsis VDACs are involved in regulating respiration, reactive oxygen species homeostasis, and stress tolerance in yeast.
Lipids in the Physiopathology of Hereditary Spastic Paraplegias

Hereditary spastic paraplegias (HSP) are a group of neurodegenerative diseases sharing spasticity in lower limbs as common symptom. There is a large clinical variability in the presentation of patients, partly underlined by the large genetic heterogeneity, with more than 60 genes responsible for HSP. Despite this large heterogeneity, the proteins with known function are supposed to be involved in a limited number of cellular compartments such as shaping of the endoplasmic reticulum or endolysosomal function. Yet, it is difficult to understand why alteration of such different cellular compartments can lead to degeneration of the axons of cortical motor neurons. A common feature that has emerged over the last decade is the alteration of lipid metabolism in this group of pathologies. This was first revealed by the identification of mutations in genes encoding proteins that have or are supposed to have enzymatic activities on lipid substrates. However, it also appears that mutations in genes affecting endoplasmic reticulum, mitochondria, or endolysosome function can lead to changes in lipid distribution or metabolism. The aim of this review is to discuss the role of lipid metabolism alterations in the physiopathology of HSP, to evaluate how such alterations contribute to neurodegenerative phenotypes, and to understand how this knowledge can help develop therapeutic strategy for HSP.
The Glucagon-Like Peptide-1 Analogue Liraglutide Reduces Seizures Susceptibility, Cognition Dysfunction and Neuronal Apoptosis in a Mouse Model of Dravet Syndrome

Dravet syndrome (DS) is a refractory epilepsy typically caused by heterozygous mutations of the Scn1a gene, which encodes the voltage-gated sodium channel Nav1.1. Glucagon-like peptide-1 (GLP-1) analogues, effective therapeutic agents for the treatment of diabetes, have recently become attractive treatment modalities for patients with nervous system disease; however, the impact of GLP-1 analogues on DS remains unknown. This study aimed to determine the neuroprotective role of liraglutide in mouse and cell models of Scn1a KO-induced epilepsy. Epileptic susceptibility, behavioral changes, and behavioral seizures were assessed using electroencephalography (EEG), IntelliCage (TSE Systems, Bad Homburg, Germany), and the open field task. Morphological changes in brain tissues were observed using hematoxylin and eosin (HE) and Nissl staining. Expression of apoptosis-related proteins and the mammalian target of rapamycin (mTOR) signaling pathway were determined using immunofluorescence and western blotting in Scn1a KO-induced epileptic mice in vitro. Scn1a KO model cell proliferation was evaluated using the Cell Counting Kit-8 assay, and the effect of liraglutide on cellular apoptosis levels was examined using Annexin V-FITC/PI flow cytometry. Apoptotic signal proteins and mTOR were assessed using reverse transcription - quantitative polymerase chain reaction (RT-qPCR) and western blotting. Our results showed that liraglutide significantly increased mRNA ((0.31 ± 0.04) *10-3 vs. (1.07 ± 0.08) * 10-3, P = 0.0004) and protein (0.10 ± 0.02 vs. 0.27 ± 0.02, P = 0.0006) expression of Scn1a in Scn1a KO-induced epileptic mice. In addition, liraglutide significantly alleviated electroencephalographic seizures, the severity of responses to epileptic seizures (96.53 ± 0.45 % vs. 85.98 ± 1.24 %, P = 0.0003), cognitive dysfunction, and epileptic-related necrotic neurons (9.76 ± 0.91 % vs. 19.65 ± 2.64 %, P = 0.0005) in Scn1a KO-induced epileptic mice. Moreover, liraglutide protected against Scn1a KO-induced apoptosis, which was manifested in the phosphorylation of mTOR (KO+NS: 1.99 ± 0.31 vs. KO+Lira: 0.97 ± 0.18, P = 0.0004), as well as the downregulation of cleaved caspase-3 (KO+NS: 0.49 ± 0.04 vs. KO+Lira: 0.30 ± 0.01, P = 0.0003) and restoration of the imbalance between BAX (KO+NS: 0.90 ± 0.02 vs. KO+Lira: 0.75 ± 0.04, P = 0.0005) and BCL-2 (KO+NS: 0.46 ± 0.02 vs. KO+Lira: 0.61 ± 0.02, P = 0.0006). Collectively, these results show that liraglutide reduces seizure susceptibility and cognitive dysfunction in the mouse model of Dravet syndrome, and exerts anti-apoptotic and neuroprotective effects in Scn1a KO mice and cells.
A 14-Week Intervention Study on Changing Preservice Teachers’ Psychological Perspectives on Inclusion: Explicit and Implicit Attitudes, Self-Efficacy, and Stress Perception Toward Inclusion

Research has indicated the importance of preservice teacher education programs that focus on fostering positive psychological aspects relevant to teaching in inclusive settings, such as attitudes or self-efficacy. Previous research lacks theoretical underpinning and is limited because of methodological characteristics of the studies (e.g., no control group). Thus, in a quasi-experimental design the current study aimed to investigate the effects of theoretically derived interventions (IG1: information-based cognitive intervention group; IG2: information-based and practical field experience intervention group) in comparison to a control group (CG) on changes in preservice teachers’ perspective on teaching inclusively, i.e. explicit and implicit attitudes, self-efficacy, and stress perception, all relevant to teach in inclusive settings. Results of four separated repeated-measure analysis of variances, with time of assessment (before vs. after) as a within-subject factor and group (CG, IG1, and IG2) as a between-subject factor, showed no differences in the development (pre- to post-intervention) between CG and IG1 as well as CG and IG2 in any of the dependent variables. However, significant differences in changes in explicit attitudes and stress perception were found between IG1 and IG2 in favor of IG2. Results will be discussed considering confounding variables that future research should further investigate.