bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of Artesunate and WNT974 Induces KRAS Protein Degradation by Upregulating E3 Ligase ANACP2 and β-TrCP in the Ubiquitin–proteasome Pathway
Authors: Gong Rui-Hong , Chen Minting , Huang Chunhua , Wong Hoi Leong Xavier , Kwan Hiu Yee , Bian Zhaoxiang 
Published: August 2021

Abstract
BackgroundKRAS mutation is one of the dominant gene mutations in colorectal cancer (CRC). Up to present, targeting KRAS for CRC treatment remains a clinical challenge. WNT974 (LGK974) is a porcupine inhibitor that interferes Wnt signaling pathway. Artesunate (ART) is a water-soluble semi-synthetic derivative of artemisinin.MethodsThe synergistic effect of ART and WNT974 combination in reducing CRC cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RT-PCR was utilized for the mRNA levels of KRAS, CUL7, ANAPC2, UBE2M, RNF123, SYVN1, or β-TrCP. Western blot assay was utilized for the protein levels of KRAS, ANAPC2, β-TrCP, or GSK-3β. Xenograft mouse model assay was performed for the anti-CRC effect of combination of ART and WNT974 in vivo. IHC assay was utilized for the levels of KRAS, β-TrCP, or GSK-3β in tumor tissues.Results Our study shows that the combination of WNT974 and ART exhibits synergistic effect in reducing CRC growth. The combination treatment significantly reduces KRAS protein level and activity in CRC cells. Interestingly, the combination treatment increases E3 ligases ANAPC2 expression. Our data show that overexpression of ANAPC2 significantly reduces KRAS protein levels, which is reversed by MG132. Knockdown of ANAPC2 in CRC abolishes the combination treatment-reduce KRAS expression. Besides, the treatment also increases the expressions of GSK-3β and E3 ligase β-TrCP that is known to degrade GSK-3β-phosphorylated KRAS protein. Knockdown of β-TrCP- and inhibition of GSK-3β abolish the combination treatment-induce KRAS ubiquitination and reduction in expression.ConclusionsOur data clearly show that the combination treatment significantly enhances KRAS protein degradation via the ubiquitination ubiquitin–proteasome pathway, which is also demonstrated in xenograft mouse model. The study provides strong scientific evidence for the development of the combination of WNT974 and ART as KRAS-targeting therapeutics for CRC treatment.
Barriers and Facilitators of HIV and Hepatitis C Care Among People Who Inject Drugs in Nairobi, Kenya: A Qualitative Study with Peer Educators
Authors: Ludwig-Barron Natasha , Guthrie Brandon L , Mbogo Loice , Bukusi David , Sinkele William , Gitau Esther , Farquhar Carey , Monroe-Wise Aliza 
Published: August 2021

Abstract
Background: In Kenya, people who inject drugs (PWID) are disproportionately affected by HIV and hepatitis C (HCV) epidemics, including HIV-HCV coinfections; however, few have assessed factors affecting their access to and engagement in care through the lens of harm reduction specialists. This qualitative study leverages the personal and professional experiences of peer educators to help identify HIV and HCV barriers and facilitators to care among PWID in Nairobi, including resource recommendations to improve service uptake. Methods: We recruited peer educators from two harm reduction facilities in Nairobi, Kenya, using random and purposive sampling techniques. Semi-structured interviews explored circumstances surrounding HIV and HCV service access, prevention education and resource recommendations. A thematic analysis was conducted using the Modified Social Ecological Model (MSEM) as an underlying framework, with illustrative quotes highlighting emergent themes. Results: Twenty peer educators participated, including six women, with 2 months to 6 years of harm reduction service. Barriers to HIV and HCV care were organized by (a) individual-level themes including competing needs of addiction and misinterpreted symptoms; (b) network-level themes including social isolation and drug pusher interactions; (c) community-level themes including transportation, mental and rural healthcare services, and limited HCV resources; and (d) policy-level themes including nonintegrated services, clinical administration, and law enforcement. Stigma, an overarching barrier, was highlighted throughout the MSEM. Facilitators to HIV and HCV care were comprised of (a) individual-level themes including concurrent care, personal reflections, and religious beliefs; (b) network-level themes including community recommendations, navigation services, family commitment, and employer support; (c) community-level themes including quality services, peer support, and outreach; and (d) policy-level themes including integrated services and medicalized approaches within law enforcement. Participant resource recommendations include (i) additional medical, social and ancillary support services, (ii) national strategies to address stigma and violence and (iii) HCV prevention education. Conclusions : Peer educators provided intimate knowledge of PWID barriers and facilitators to HIV and HCV care that were described at each level of the MSEM, and should be given careful consideration when developing future initiatives. Recommendations emphasized policy and community-level interventions including educational campaigns and program suggestions to supplement existing HIV and HCV services.
Enhanced ROV Survey of Tropical Fish and Benthic Communities Associated With Shallow Oil and Gas Platforms
Authors: McLean Dianne L. , Birt Matthew 
Published: August 2021

Abstract
Understanding the ecology of oil and gas infrastructure in our oceans is required to inform decommissioning such that environmental impacts are minimised, and benefits maximised. This study equipped an industrial remotely operated vehicle (ROV) with a stereo-video system and collected seven hours of high-definition imagery of two platform jackets, for assessments of benthic (type, density, complexity) and fish assemblages (richness, abundance, length) present. Harriet Alpha (25 m depth) and Gibson/South Plato (8 m depth) are located ca. 120 km offshore of north-west Australia, adjacent to Varanus Island. Twenty-one ‘classes’ of benthic biota were observed in high density, with little bare structure on either platform. Encrusting sponges (average 19% cover per virtual quadrat), barnacles (17%) and sponges (16%) were common on Gibson/South Plato while encrusting sponges (16%) and macroalgae (18%) were ubiquitous on quadrats on Harriet Alpha. The sun coral Tubastraea faulkneri was common on Harriet Alpha (38% of quadrats), though coverage was low (<6%). A total of 102 fish species from 27 families were observed. This included 33 fishery target species with an estimated relative mass of 116 kg on Gibson/South Plato and 299 kg on Harriet Alpha, with these species typically concentrated near the seafloor-structure interface. Differences in benthic biota communities present on each platform likely reflect spatial variations in oceanographic processes, proximity to natural habitats and the age, configuration, cleaning regime and depth of the structures themselves. This study demonstrates the value of adding stereo-video systems to ROVs to undertake rapid scientific surveys of oil and gas infrastructure.
A Realist Review Protocol of Community Group-Based Programs to Promote Physical Activity in Immigrant Older Adults.
Authors: Flynn Rachel , Salma Jordana , Ali Sonam , Chamberlain Stephanie , Kennedy Megan , Tong Hongmei , Meherali Salima , Spence John , Jones Allyson 
Published: August 2021

Abstract
Background: Immigrants constitute 30% of Canada’s older adult population. Immigrant older adults have low levels of physical activity coupled with higher risks for cardiovascular disease and obesity in some sub-populations. Community group-based physical activity programs combine both physical and social benefits and are well received by older adults. These programs often lack sensitivity to the needs of equity-deserving groups, such as immigrants, who continue to experience lower levels of participation. Local, accessible, and culturally informed approaches are required to remedy these well documented inequities in who has access to and benefits from such programs. There is a gap, however, in our understanding of the characteristics and conditions for effective program design and delivery when the target population is immigrant older adults.Methods: The aim of this equity-focused realist review is to develop a programme theory that explains how, why, for whom, and under which circumstances community group-based physical activity programs work when delivered to older immigrants. We will first articulate an initial programme theory that explains tentatively how, why and for whom such programs work and then test and refine the programme theory using a systematic realist review process. The initial programme theory will draw from existing theories that inform group-based physical activity programs for older adults, intersectional theory, and stakeholder insights. PROGRESS-Plus factors will be explored in relation to relevance and impact for physical activity interventions. Stakeholders will include service providers, community volunteers and leaders who have extensive knowledge and interactions with immigrant communities. The initial programme theory will then be tested and refined using a systematic process of searching, retrieving, and reviewing literature on physical activity in immigrant populations. The final programme theory will be validated using stakeholder input and the research team’s expertise in aging, health equity, and physical activity. Discussion: Physical activity improves the wellbeing of older adults, decreases frailty, and supports aging in place. Ensuring that all older adults can participate in such programs entails understanding what works for whom, when and under which circumstances. This review will provide recommendations on best practices to support immigrant older adults’ participation in group-based physical activity programs.Systematic review registration: The protocol has been submitted to PROSPERO for registration (ID#258179, Date submitted May 30th, 2021.
Determinants of Financial Inclusion Gender Gap in Ethiopia: Evidence From Decomposition Analysis
Authors: Hundie Shemelis Kebede , Tulu Daniel Tadesse 
Published: August 2021

Abstract
In Ethiopia, the gender gap in financial inclusion is high, and the effect of socioeconomic variables on the gap is not well investigated. As a result, this study uses the World Bank’s Global Findex database from 2017 to analyze magnitude and determinants of the gender gap in financial inclusion in Ethiopia. Using Fairlie decomposition technique, we find statistically significant gender gap in all indicators of financial inclusion under study in Ethiopia. The result shows that the highest financial inclusion gender gap is observed in formal saving followed by formal account holding. The decomposition results show males are 16.5%, 16.6%, 8.9 %, 8.4 %t, and 5.8% more likely to have a formal account, formal saving, borrowing, emergency fund possibility, and debit card ownership, respectively. We further decompose these gaps using Daymont and Andrisani approach and the result reveals that differences in coefficients between males and females explain 57.7% in formal saving, 43.4% in formal account holding, and 110.9% in borrowing from formal financial institutions. About 54.2% of the total gender gap in possibility of raising emergcency fund is attributed to differences in characteristics/predictors between the two genders while gender gap in debit card holding is explained by the iteraction between differences in characterisctics and coefficients. Being older, more educated, and wealthier favor financial inclusion, with age, employment, and education having a greater effect. Furthermore, gaps in coefficients, productivity, and advantage to males and disadvantage to females aggravate the gender gap in financial inclusion in Ethiopia. Gender mainstreaming in economic activities to increase income, employment opportunities and education for females to bridge the gender gap in financial inclusion is important.
Exercise Rehabilitation and/or Astragaloside Attenuate Amyloid-Beta Pathology by Reversing BDNF/TrkB Signaling Deficits and Mitochondrial Dysfunction
Authors: Wang Yu-Ling , Chio Chung-Ching , Kuo Shu-Chun , Yeh Chao-Hung , Ma Jui-Ti , Liu Wen-Pin , Lin Mao-Tsun , Lin Kao-Chang , Chang Ching-Ping 
Published: August 2021

Abstract
Background: Although there are numerous investigations regarding the beneficial effects of exercise rehabilitation (ER) or astragaloside (AST) after amyloid-beta (Ab) pathology, the mechanisms are still not well understood. We aim to assess whether ER and/or AST counteract Ab pathology via diminishing brain-derived neurotrophic factor (BDNF) signaling deficits and mitochondrial dysfunction. Methods: Ab1-42 were microinjected into the bilateral ventricles to induce Ab neuropathology in rats. The Alzet osmotic pump containing full of AST was implanted subcutaneously during surgery. The ER group of rats started at seven days post-surgery and lasted for four weeks. The ANA12 was administrated once per day to the endpoint of the experiments to antagonize the BDNF action. Neurobehavioral functions were evaluated by Y-maze, radial maze, and rotarod tests one day before surgery and 14 to 35 days post-surgery. Cortical and hippocampal expressions of both BDNF/TrkB and cathepsin D were determined by Western blotting method. The rat primary cultured cortical neurons were incubated with BDNF and/or AST and ANA12 followed by exposure to aggregated Ab for 24 hours. The cell viability (by MTT assay), mitochondrial membrane permeability and electrochemical potential (by JC-1 stain), DNA fragmentation (sub-G1 and DNA ladder assay), synaptic plasticity (by immunofluorescence stain), and pTrkB/pAkt/pGSK3b/b-catenin signaling (by Western blot) were determined.Results: ER and/or AST reversed neurobehavioral disorders, downregulation of cortical and hippocampal expression of both BDNF/TrkB and cathepsin D, neural pathology, Ab accumulation, and altered microglial polarization caused by Ab. In vitro studies also confirmed that topical application of BDNF and/or AST reversed the Ab-induced cytotoxicity, apoptosis, mitochondrial distress, synaptotoxicity, and decreased expression of p-TrkB, AKT, p-GSK3b, and b-catenin in altered rat cortical neurons. In particular, the beneficial effects of combined ER (or BDNF) and AST therapy in vivo and in vitro were superior to ER (or BDNF) or AST alone. Furthermore, we observed that any gains from ER (or BDNF) and/or AST could be significantly eliminated by ANA-12, a potent BDNF/TrkB antagonist. Conclusion: These results indicate that whereas ER (or BDNF) and/or AST attenuate Ab pathology by reversing BDNF/TrkB signaling deficits and mitochondrial dysfunction. In particular, AST can be an alternative therapy to replace ER.
Expression and Subcellular Localization of Discoidin Domain Receptor 1 (DDR1) Define Prostate Cancer Aggressiveness
Authors: Bonfil R. Daniel , Chen Wei , Vranic Semir , Sohail Anjum , Shi Dongping , Jang Hyejeong , Kim Hyeong-Reh , Prunotto Marco , Fridman Rafael 
Published: August 2021

Abstract
Background: The Discoidin Domain Receptor 1 (DDR1) is one of the two members of a unique family of receptor tyrosine kinase receptors that signal in response to collagen, which has been implicated in cancer progression. Here, we examined the expression of DDR1 in prostate cancer (PCa), and assessed its potential value as a prognostic marker, as a function of grade, stage and other clinicopathologic parameters.Methods: We investigated the association between the expression level and subcellular localization of DDR1 protein and PCa aggressiveness by immunohistochemistry, using tissue microarrays (TMAs) encompassing 200 cases of PCa with various Gleason scores (GS) and pathologic stages with matched normal tissue, and a highly specific monoclonal antibody. Results: DDR1 was found to be localized in the membrane, cytoplasm, and nuclear compartments of both normal and cancerous prostate epithelial cells. Analyses of DDR1 expression in low GS (≤7[3+4]) vs high GS (≥7[4+3]) tissues showed no differences in nuclear or cytoplasmic DDR1in either cancerous or adjacent normal tissue cores. However, relative to normal-matched tissue, the percentage of cases with higher membranous DDR1 expression was significantly lower in high vs. low GS cancers. Although nuclear localization of DDR1 was consistently detected in our tissue samples and also in cultured human PCa and normal prostate-derived cell lines, its presence in that site could not be associated with disease aggressiveness. No associations between DDR1 expression and overall survival or biochemical recurrence were found in this cohort of patients. Conclusion: The data obtained through multivariate logistic regression model analysis suggest that the level of membranous DDR1 expression status may represent a potential biomarker of utility for better determination of PCa aggressiveness.
Overexpressions of RHOA, CSNK1A1, DVL2, FZD8, and LRP5 Genes Enhance Gastric Cancer Development in the Presence of Helicobacter Pylori
Authors: Demirci Ufuk , Orenay-Boyacioglu Seda , Kasap Elmas , Gerceker Emre , Bilgic Fahri , Yuceyar Hakan , Yildirim Hatice , Baykan Ahmet Ramiz , Ellidokuz Ender Berat , Korkmaz Mehmet 
Published: August 2021

Abstract

Introduction: Intestinal metaplasia (IM), and Helicobacter pylori (HP) infection can be shown as risk factors in the development of gastric cancer (GC). WNT signaling pathway plays a critical role in carcinogenesis. However, the literature studies are limited on the significance of this pathway for the transition from IM to GC.Methods: We aimed to investigate the importance of the genes of WNT signaling pathways diagnostic and prognostic markers in the presence and absence of HP in conversion from IM to GC. 104 patients, (GC group n=35, IM group n=45, control group n=25) were included in this case-control study. Expression of genes in WNT signalling were searched in study groups with qRT-PCR array and qRT-PCR method. Data were analysed using PCR array data analysis software.Results: Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was detected in the GC and IM groups compared to the control group (p <0.05). Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was observed in patients with metastatic GC compared to patients with GC without metastasis (p <0.05). It was found that the RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes were statistically significantly over-expressed in diffuse GC patients compared to non-diffuse GC patients (p <0.05). Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was detected in HP positive IM patients compared to HP negative IM patients (p <0.05).Conclusion: Overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes in IM may suggest that these genes are important markers in the development of IM and inflammation with HP. In addition, these genes are linked to tumor burden in the GC group. Consequently, we can conclude that these genes are poor prognosis biomarkers for GC and have the potential to be used as markers for future treatment monitoring.
A Study on the Reliability and Validity of the Standing Lateral Radiograph Method to Assess Acetabular Component Version
Authors: Zhang wenhui , Xu Jie , Li Deng , Sun Hao , Cai Zhiqing , Ma Ruofan 
Published: August 2021

Abstract
Objectives: Version of the acetabular component on standing position is an important factor influencing the risk of adverse outcomes during functional activities after total hip arthroplasty (THA). The main objective of this study was to evaluate the reliability and validity of a method for measuring cup version on standing lateral (SL) radiograph.Methods: 87 consecutive patients who underwent primary THA were included. SL radiograph and computed tomography (CT) scan were taken 7 days after THA to measure the cup version. The measurement method was based on the cross-table lateral (CL) radiograph. The tangential line of the cup opening face was determined through two intersecting points of the cup outer edge circle and the opening face elliptical arc. The version was measured between the horizonal line and the tangent line by two independent examiners. Radiographic measurements were compared with CT measurements after the uniformization of pelvic tilt (PT).Results: All measurements had excellent intra- and inter-observer reliabilities with an intraclass correlation coefficient (ICC) >0.90. The mean version was 15.56° (SD 11.22°, -19.82° to 38.74°) for SL radiographs and 16.19° (SD 12.09°, -23.00° to 47.20°) for PT-matched CT. There was a positive correlation (r = 0.901, p < 0.001) between radiographic versions and CT versions. The mean difference was -0.63° (SD 5.25°, -14.92° to 12.72°) and the differences were almost within the 95% limits of agreement. Conclusion: SL radiograph allows accurate and practicable evaluation of post-operative functional acetabular cup version, with an advantage to identify the pelvic tilt simultaneously.
Identification of Prognostic lncRNA Related to the Immune Microenvironment of Soft Tissue Sarcoma
Authors: Dai Wang-Ying , Wang Bin , Li Jian-Yi , Zhu Jun-Cheng , Luo Zong-ping 
Published: August 2021

Abstract
Background: Soft tissue sarcoma is a malignant tumor with high degree of malignancy and poor prognosis, originating from mesenchymal tissue. Long non-coding RNAs (lncRNAs) are involved in various biological and pathological processes in the body. They target mRNA through transcription or post-transcription, resulting in the occurrence, invasion, and metastasis of tumors. Therefore, they are highly relevant with regard to early diagnoses and as prognostic indicators.Objective: The objective of the present study was to identify immune-related lncRNAs associated with the tumor microenvironment that can be used to predict soft tissue sarcomas.Methods: Clinical data and follow-up data were obtained from the cBioPortal database, and RNA sequencing data used for the model structure can be accessed from. The Cancer Genome Atlas (TCGA) database. LncRNAs were screened by differential expression analysis and co-expression analysis. The Cox regression model and Kaplan–Meier analysis were used to study the association between lncRNAs and soft tissue sarcoma prognosis in the immune microenvironment. Unsupervised cluster analysis was then completed to discover the impact of screening lncRNAs on disease. Lastly, we constructed an mRNA-lncRNA network by Cytoscape software.Results: Unsupervised cluster analysis revealed that the 210 lncRNAs screened showed strong correlation with the tumor immune microenvironment. Two signatures containing seven and five lncRNAs related to the tumor microenvironment were constructed and used to predict overall survival (OS) and disease-free survival (DFS). The Kaplan–Meier（K-M） survival curve showed that the prognoses of patients in the high-risk and low-risk groups differed significantly, and the prognosis associated with the low-risk group was better than that associated with the high-risk group. Two nomograms with predictive capabilities were established.Conclusion: The results indicate that seven OS- and five DFS-related lncRNAs are correlated with the prognosis of soft tissue sarcoma.