bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coronin 1A Expression in Human Astroglia, its Function in Physiology and Astrogliosis in HIV-1 Neuropathogenesis
Authors: Pandey Hriday Shanker , Kapoor Rishabh , Bindu  , Seth Pankaj 
Published: November 2020

Abstract
BackgroundIn most neurodegenerative disorders, including neuroAIDS, reactive astroglia are detrimental to the neuronal population. Calcium and its downstream regulators play a central role in mediating glial activation. Coronin 1A, an acting binding protein, majorly reported in cells of hematopoietic origin, regulates cell activity in a calcium-dependent manner, but its role in astroglial physiology and astrogliosis is largely unknown. We explored the roles of Coronin 1A in astroglia physiology and the mechanisms by which it facilitates reactive astrogliosis. MethodsCoronin 1A expression was assessed in different cell types including astroglia using western blotting and immunocytochemistry. Loss of function assays were performed after siRNA-mediated knockdown of coronin 1A. Live-cell calcium imaging was performed on ATP-stimulated astroglia using confocal microscopy. To induce astrogliosis, HIV-1 Tat B expression vector was used after which gene and protein expressions were assessed using qPCR and western blotting, cytokine release was measured using flow cytometry, glutamate release was assessed using enzyme-kinetics based kit. TUNEL assay was performed to assess the glia-mediated neuronal death on neurons treated with the astrocyte-conditioned media. Small RNA-sequencing and qPCR assays were performed to get miRNAs differentially regulated a result of HIV-1 Tat transfection. Transfection with mimic and inhibitor against selected miRNA, and luciferase assay were performed to confirm the miRNA regulation.ResultsIn this study, we report for the first time, that human primary astroglia express Coronin 1A, and it plays activity-dependent roles in events such as PLCγ1 phosphorylation followed by Calcium mobilization from the intracellular stores. HIV-1 Tat, a potent neurotoxicant that induces astrogliosis, enhances the expression of Coronin 1A, apart from affecting GFAP and pro-inflammatory molecules. Downregulation of Coronin 1A ameliorated the HIV-1 Tat-induced deleterious effects of reactive astroglia, measured as enhanced GFAP expression and release of IL-6, and Glutamate and thus reduced glia-mediated neurodegeneration. Our findings also suggest that out of a pool of dysregulated miRNAs studied by us, hsa-miR-92b-5p regulates Coronin 1A expression which further facilitates reactive astrogliosis under the effect of HIV-1 Tat. ConclusionThese findings highlight the novel roles of Coronin 1A in regulating the astroglial physiology and astrogliosis observed in HIV-1 neuropathogenesis.
The&nbsp;Let's Talk&nbsp;toolkit:&nbsp;developing a theory-informed complex intervention to improve nurse-patient therapeutic engagement on an acute mental health ward by employing Experience-based Co-design and the Behaviour Change Wheel
Authors: McAllister Sarah , Simpson Alan , Tsianakas Vicki , Canham Nick , Meo Vittoria De , Stone Cady , Robert Glenn 
Published: November 2020

Abstract
Background

Lack of high-quality nurse-patient therapeutic engagement is a longstanding problem on acute mental health wards, with a dearth of interventions to address this. A collaborative, theory-driven approach to developing and implementing complex interventions is more likely to be effective and sustainable. This paper describes an integrated co-design-behaviour change approach which developed the Let’s Talk intervention toolkit for improving the quality of therapeutic engagement on acute mental health wards.
Methods

We describe a theory-driven approach to co-designing an intervention by adapting and integrating Experience-based Co-design (EBCD) with the Behaviour Change Wheel (BCW). Fieldwork was informed by the results of a systematic integrative review and was guided by our co-design-behaviour change approach. It was conducted over 12-months at an acute mental health organisation in England. We undertook semi-structured interviews with 14 service users (seven of which were filmed), two carers and 12 clinicians, 80 hours of non-participant observations and a facilitated intervention co-design process that involved two feedback workshops, one joint co-design workshop and seven small co-design team meetings. Data analysis comprised the identification of touchpoints and use of the BCW and behaviour change technique taxonomy to inform intervention development.
Results

The co-designed Let’s Talk toolkit addressed four joint priorities for change: 1) improve communication with withdrawn people; 2) nurses to help service users help themselves; 3) nurses to feel confident when engaging with service users; 4) improving team relations and ward culture. Intervention functions included training, education, enablement, coercion and persuasion; 14 behaviour change techniques supported these functions. We detail how we implemented our integrated co-design-behaviour change approach with service users, carers and clinicians to co-design the toolkit to improve nurse-patient therapeutic engagement.
Conclusions

Our theory-driven approach enhances both EBCD and the BCW. It introduces a robust theoretical approach to guide intervention development within the co-design process and sets out how to meaningfully involve service users and other stakeholders when designing and implementing complex interventions.
The Role of Participatory Action Research on Clinicians’ Attitudes toward Medication Management
Authors: Bakhshi Fatemeh , Mitchell Rebecca , Nasrabadi Alireza Nikbakht , Javadi Mostafa , Varaei Shokoh 
Published: November 2020

Abstract
Background: Medication management is a cyclic and multidisciplinary approach to enhance safe medication therapy. This paper explores clinician attitude toward medication management which is both open to influence and strongly linked to successful changes in mediation behavior.Purpose: To investigate effects of engaging in participatory action research to improve emergency medicine clinicians’ attitudes toward implementing effective medication management.Methodology: Data are drawn from two-cycle participatory action research. Within the study, a total of 85 clinicians including nurses and physicians from emergency department of one university affiliated hospital participated as participants. Eight managers and clinicians participated as representatives. Initially, a situation analysis on the current medication management and clinician views regarding medication management was conducted using three focus groups. Evaluation and reflection data were obtained through qualitative interviews. All qualitative data were analyzed using content analysis. Results: Clinicians initially expressed negative attitudes toward existing and new plans for medication management, in that they were critical of current medication-related policy and procedures, as well as wary of the potential relevance and utility of potential changes to medication management. Through the action research, improvement actions were implemented including interprofessional courses, pharmacist-led interventions, and the development of new guidelines regarding medication management. Participants and their representatives were engaged in all participatory action research stages. Extracted results from evaluation and reflection stages revealed that by engaging in the action research and practice new interventions, clinicians’ attitude toward medication management was improved. Conclusion: The results support the impact of participatory action research on enhanced clinicians’ positive attitudes through involvement in planning and implementing medication management actions.
The Prognostic Influence of Venous Thromboembolism in Non-Small Cell Lung Cancer: A Meta-Analysis and Systematic Review
Authors: Bai Yu , Ma Xu , Han Sen , Fang Jian 
Published: November 2020

Abstract
Background: Patients with non-small cell lung cancer (NSCLC) have a significantly higher risk of developing venous thromboembolism (VTE), a condition that significantly influences the prognosis of these patients. However, the impact of VTE on the survival of NSCLC patients remains unclear. We aim to evaluate the impact of VTE on the mortality of patients with NSCLC. Methods: We systematically reviewed all indexed studies examining the prognosis of NSCLC patients with VTE. Web of Science, EMBASE, PubMed, and the Cochrane Library were searched through December 31, 2019 to identify relevant studies. Fixed- or random-effects models were chosen based on heterogeneity. Results: Twelve articles with 6480 patients were included in this analysis. The heterogeneity of these studies was significant (I2=81%, P<0.01). The overall survival (OS) of NSCLC patients with VTE was shorter compared to patients without VTE (HR=1.71, 95% CI [1.39–2.10], P<0.01). Two small groups of SCLC patients were excluded and the remaining patients were divided into the Asian and non-Asian groups. The Asian group showed low heterogeneity (I2=35%, P=0.20), in which NSCLC patients with VTE also had shorter OS (HR=1.49, 95% CI [1.19–1.88], P<0.01). Conclusions: VTE is significantly associated with a shorter OS of NSCLC patients, especially in Asian patients. Proper prevention and management of VTE is the key to improving the survival of patients with NSCLC.
Validation of the pediatric refractory septic shock definition: Posthoc analysis of a controlled trial
Authors: MORIN Luc , RAMASWAMY Karthik Natayanan , JAYASHREE Muralidharan , Bansal Arun , NALLASAMY Karthi , Tissieres Pierre , SINGHI Sunit 
Published: November 2020

Abstract
BackgroundThe European Society of Pediatric and Neonatal Intensive Care (ESPNIC) developed and validated a definition of pediatric refractory septic shock (RSS), based on two septic shock scores (SSS). Both bSSS and cSSS were found to be strongly associated with mortality. We aimed at assessing the accuracy of the RSS definition on a prospective cohort from India. Methods Post-hoc analysis of a cohort issued from a double-blind randomized trial that compared first-line vasoactive drugs in children with septic shock. Sequential bSSS and cSSS from 60 children (single center study, 53% mortality) were analyzed. The prognostic value of the ESPNIC RSS definition was tested for 28-day all-cause mortality. ResultsIn this septic shock cohort, RSS was diagnosed in 35 patients (58.3%) during the first 24 hours. Death occurred in 30 RSS patients (85.7% mortality) and in 2 non-RSS patients (8% mortality), OR=60.9 [95% CI: 10.5-676.2], p<0.001 with a median delay from sepsis onset of 3 days [1.0-6.7]. Among patients diagnosed with RSS, the mortality was not significantly different according to vasopressors randomization. Diagnosis of RSS with bSSS and cSSS had a high discrimination for death with an area under the receiver operating curve of 0.916 [95% CI: 0.843-0.990] and 0.925 [95% CI: 0.845-1.000], respectively. During the first day of septic shock, the best interval for prognostication was after the 12th hour following septic shock as compared to 0-6 hours or 6-12 hours (AUC 0.973 [95% CI: 0.925-1.000] versus 0.876 [95% CI: 0.780-0.972] and 0.955 [95% CI: 0.899-1.000] respectively), p=0.011. ConclusionsThe ESPNIC SSS accurately identifies children in refractory septic shock with a best interval between 12 and 24 hour of septic shock. Both bSSS and cSSS had high discrimination for 28-day mortality.
Type of Tea Consumption and Depressive Symptoms in Older Adults
Authors: Yao Yao , Chen Huashuai , Chen Lele , Ju Sang-Yhun , Yang Huazhen , Zeng Yi , Gu Danan , NG Tze Pin 
Published: November 2020

Abstract
BackgroundExisting research indicates that tea drinking may exert beneficiary effects on mental health. However, associations between different types of tea intake and mental health such as depression are not fully examined. The purpose of this study was to examine the associations of green tea, fermented tea, and flowering tea consumption with depressive symptoms.MethodsWe used data from the 2018 wave of Chinese Longitudinal Healthy Longevity Survey. The type (green, fermented [black, Oolong, white, yellow, dark, and compressed teas], and flower) and frequency of tea consumption and depressive symptoms for 13,115 participants were assessed. We examined the associations between type and frequency of tea intake and depression, controlling for a set of demographic, socioeconomic, psychosocial, behavioral, and health-related variables. ResultsOverall, intake of green tea, fermented tea, and flower tea were all significantly associated with a lower prevalence of depression, independent of other risk factors. Compared with the group for no tea intake, the adjusted ORs for daily green tea, fermented tea, and flower tea intake were 0.85 (0.76-0.95), 0.87 (0.76-0.99), and 0.70 (0.59-0.82), respectively. Linear associations were observed between frequency of all types of tea intake with depressive symptoms (Ps for trend<0.05). The associations of type and frequency of tea intake and depressive symptoms were robust in several sensitivity analyses.ConclusionsAmong Chinese old adults, regularly consumed any type of tea (green, fermented or flower) were less likely to show depressive symptoms, the associations seemed more pronounced among flower tea and green tea drinkers.
Exome Sequencing Revealed PDE11A as a Novel Candidate Gene for Early-Onset Alzheimer's disease
Authors: Qin Wei , Zhou Aihong , Zuo Xiumei , Jia Longfei , Wei Cuibai , Tang Yi , Wang Fen , Li Fangyu , Wang Qi , Li Ying , Wei Yiping , Jin Hongmei , Cruchaga Carlos , Benitez Bruno A. , Jia Jianping 
Published: November 2020

Abstract
Background: Alzheimer’s disease (AD) is a leading cause of dementia in the elderly and has become a major health issue. However, a large number of genetic risk factors remain undiscovered. Methods: To identify novel risk genes and better understand the molecular pathway underlying AD, whole-exome sequencing (WES) was performed in 215 early-onset AD (EOAD) patients and 55 unrelated healthy controls of Han Chinese ethnicity. Subsequent direct sequencing was performed in 4962 individuals to validate the selected rare mutations. Computational annotation and in vitro functional studies were performed to evaluate the role of candidate mutations in EOAD and the underlying mechanisms.Results: We identified two rare missense mutations in the phosphodiesterase 11A (PDE11A) gene, resulting in p.Arg202His, and p.Leu756Gln, in individuals with EOAD. Both mutations are located in evolutionarily highly conserved amino acids, are predicted to alter the protein conformation, and classified as pathogenic. Furthermore, we found significantly decreased protein levels of PDE11A in brain samples of AD patients. Expression of PDE11A variants and knockdown experiments with specific short hairpin RNA (shRNA) for PDE11A both resulted in an increase of AD-associated Tau hyperphosphorylation at T181, S404, S202, S416, S214, S396 and AT8 epitopes in vitro. PDE11A variants or PDE11A shRNA also caused increased cAMP levels, protein kinase A (PKA) activation, and cAMP response element-binding protein (CREB) phosphorylation. Additionally, pretreatment with a PKA inhibitor (H89) suppressed PDE11A mutation-induced p-Tau formation.Conclusions: Our results demonstrate that both PDE11A mutations and PDE11A knockdown increase Tau phosphorylation through the cAMP/PKA pathway, suggesting that PDE11A is a novel risk gene for AD. This study provides insight into the involvement of Tau phosphorylation via the cAMP/PKA pathway in EOAD pathogenesis and provides a potential new target for intervention.
Gut Flora-Targeted Photobiomodulation Therapy Improves Senile Dementia in an Aß-Induced Alzheimer’s Disease Animal Model
Authors: Chen Qianqian , Wu Jinpeng , Yin Huijuan , Dong Xiaoxi , Shi Xiafei , Su Siying , Che Boshen , Li Yingxin 
Published: November 2020

Abstract
Background: Emerging evidence suggests that the gut microbiota plays an important role in the pathological progression of Alzheimer’s disease (AD). Photobiomodulation (PBM) therapy is believed to have a positive regulatory effect on the imbalance of certain body functions, including inflammation, immunity, wound healing, nerve repair, and pain. Previous studies have found that the intestinal flora of patients with AD is in an unbalanced state. Therefore, we have proposed the use of gut flora-targeted PBM (gf-targeted PBM) as a method to improve AD in an Aß-induced AD mouse model. Methods: PBM was performed on the abdomen of the mice at the wavelengths of 630 nm, 730 nm, and 850 nm at 100 J/cm2 for 8 weeks. Morris water maze test, immunofluorescence and proteomic of hippocampus, and intestinal flora detection of fecal were used to evaluate the treatment effects of gf-targeted PBM on AD rats.Results: PBM at all three wavelengths (especially 630 nm and 730 nm) significantly improved learning retention as measured by the Morris water maze. In addition, we found reduced amyloidosis and tau phosphorylation in the hippocampus by immunofluorescence in AD mice. By using a quantitative proteomic analysis of the hippocampus, we found that gf-targeted PBM significantly altered the expression levels of 509 proteins (the same differentially expressed proteins in all three wavelengths of PBM), which involved the pathways of hormone synthesis, phagocytosis, and metabolism. The 16s rRNA gene sequencing of fecal contents showed that PBM significantly altered the diversity and abundance of intestinal flora. Specifically, PBM treatment reversed the typical increase of Helicobacter and uncultured Bacteroidales and the decrease of Rikenella seen in AD mice. Conclusions: Our data indicate that gf-targeted PBM regulates the diversity of intestinal flora, which may improve damage caused by AD. Gf-targeted PBM has the potential to be a noninvasive microflora regulation method for AD patients.
Family With Sequence Similarity 83, Member A (FAM83A) As a Promising Prognostic Biomarker in Lung Squamous Cell Cancer
Authors: Wang Cong , Lu Longfei , Feng Zitong , Li Yongmeng , Lu Ming , Tian Hui 
Published: November 2020

Abstract
Background: Increasing studies have found the dysregulated FAM83A as a potential biomarker in various cancers. Its function in cancer cells is largely unknown, and especially their role in LUSC remains unclear. We detected the expression level and prognosis role of FAM83A in LUSC.Methods: The bioinformatics methods were performed initially to predict the expression level and prognostic value of FAM83A mRNA in LUSC. We used IHC to examine its protein expression level and identify its prognostic value using 132 pairs of tissues.Results: Results from TCGA and Oncomine databases revealed that FAM83A mRNA expression level was significantly higher in LUSC than that in normal lung tissue. TCGA and GEO databases revealed FAM83A mRNA overexpression was significantly associated with poorer OS of LUSC patients (all P<0.05). Furtherly, our IHC results revealed that FAM83A was overexpressed in 78 (59.1%) patients and 19(14.4%) pancancerous tissues (P<0.001). Kaplan-Meier analyses revealed that high FAM83A protein expression was significantly associated with decreased 5-years’ OS (P = 0.007) and PFS (P = 0.007). Via multivariate analysis, FAM83A expression level was independent prognostic factor for both OS (P = 0.006) and PFS (P = 0.002).Conclusion: FAM83A was overexpressed in LUSC and it could serve as a prognosis prediction biomarker for LUSC. FAM83A could act as one new potential therapeutic target for LUSC treatment.
Cancer-Associated Fibroblasts Promote the Survival of Irradiated Nasopharyngeal Carcinoma Cells via the NF-κB Pathway
Authors: Weiqiang Huang , Longshan Zhang , Mi Yang , Xixix Wu , Xiaoqing Wang , Wenqi Huang , Lu Yuan , Hua Pan , Yin Wang , Zici Wang , Yuting Wu , Jihong Huang , Huazhen Liang , Shaoqun Li , Liwei Liao , Laiyu Liu , Jian Guan 
Published: November 2020

Abstract
Background: Irradiation has emerged as a valid tool for nasopharyngeal carcinoma (NPC) in situ treatment; however, NPC derived from tissues treated with irradiation is a main cause cancer-related death. The purpose of this study is to uncover the underlying mechanism regarding tumor growth after irradiation and provided potential therapeutic strategy. Methods: Fibroblasts were extracted from fresh NPC tissue and normal nasopharyngeal mucosa. Immunohistochemistry was conducted to measure the expression of α-SMA. Cytokines were detected by protein array chip and identified by real-time PCR. CCK-8 assay was used to detect cell proliferation. Radiation-resistant (IRR) 5-8F cell line was established and colony assay was performed to evaluate tumor cell growth after irradiation. Signaling pathways were acquired via gene set enrichment analysis (GSEA). Comet assay was used to measure DNA damage level. Protein expression was detected by western blot assay. Results: We found that radiation-resistant NPC tissues were constantly infiltrated with a greater number of cancer-associated fibroblasts (CAFs) compared to radiosensitive NPC tissues. Further research revealed that CAFs induced the formation of radioresistance and promoted NPC cell survival following irradiation via the IL-8/NF-κB pathway to reduce irradiation-induced DNA damage. Treatment with Tranilast, a CAF inhibitor, restricted the survival of CAF-induced NPC cells and attenuated the of radioresistance properties. Conclusions: Together, these data demonstrate that CAFs can promote the survival of irradiated NPC cells via the NF-κB pathway and induce radioresistance that can be interrupted by Tranilast, suggesting the potential value of Tranilast in sensitizing NPC cells to irradiation.
Dietary Supplementation With Creatine Pyruvate Alter Rumen Microbiota Protein Function in Heat-Stressed Beef Cattle
Authors: Li Yanjiao , Zhao Xianghui , Liu Lin , Mao Kang , Qu Mingren , Lu Guwei , Zang Yitian 
Published: November 2020

Abstract
Background: Creatine pyruvate (CrPyr) is a new multifunctional nutrient that can provide both pyruvate and creatine. It has been shown to relieve the heat stress of beef cattle by improving antioxidant activity and rumen microbial protein synthesis, but the mechanism of CrPyr influencing rumen fermentation remains unclear. This study aimed to combine 16S rDNA sequencing and metaproteomics technologies to investigate the microbial composition and function in rumen fluid samples taken from heat-stressed beef cattle treated with or without 60 g/d CrPyr. Results: 16S rDNA sequencing revealed that there was no significant differences in the α-diversity indices between the two groups. By analyzing the expression profiles of 700 distinct proteins, we found that CrPyr administration increased the fatty acid β-oxidation, promoted the interconversion from pyruvate to phosphoenolpyruvate, acetyl-CoA and malate, up-regulated gluconeogenesis and citrate cycle metabolism, and promoted the biosynthesis of amino acids. Conclusions: The increased generation of ATP during fatty acid β-oxidation or citrate cycle and the up-regulation synthesis of microbial protein in rumen of beef cattle treated with CrPyr, may help decreased oxidative stress, regulate energy metabolism, and further improve the rumen fermentation characteristic under heat stress.