bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Artesunate on cardiovascular complications in rats with type 1 diabetes mellitus
Authors: Chen Yi , Li Wei , Nong Xiaolin , Liang Chen , Li Jiaquan , Lu Wei , Wang Bingge , Yuan Zhong , Yang Shiying 
Published: January 2021

AbstractBackgroundThe present study aimed to evaluate the effect of artesunate (ART) on the reduction of cardiovascular complications in a type 1 diabetes model and to investigate the associated mechanism based on the receptor for advanced glycation end-product (RAGE)/NF-κB signaling pathway.MethodsA total of 40 male Sprague-Dawley rats were randomly divided into five groups: The healthy, diabetic, 50 mg/kg ART (ig) treatment diabetic, 100 mg/kg ART (ig) treatment diabetic, and 6 U/kg insulin (iH) treatment diabetic groups. The treatment lasted 4 weeks after the diabetic model was established via intraperitoneal injection of streptozotocin. Blood samples were collected, and cardiovascular tissues were harvested and processed to measure various parameters after the animals were sacrificed. The myocardium and aortic arch tissues were evaluated using hematoxylin-eosin and Masson staining. Expression levels of RAGE, NF-κB, matrix metalloproteinase MMP9, MMP1 and CD68 in the myocardium and aortic arch tissues were detected using immunohistochemistry, and mRNA expression was determined using reverse transcription-quantitative PCR.ResultsThe results of the present study demonstrated that ART treatment may restrain diabetes-induced cardiovascular complications by maintaining heart and body weight while reducing blood glucose, as well as regulating blood lipid indicators to normal level (P < 0.05). The expression levels of NF-κB, CD68, MMP1, MMP9 and RAGE were decreased in the ART-treated diabetic rats (P < 0.05).ConclusionsART treatment may have a protective role against diabetes-associated cardiovascular complications in diabetic rats by inhibiting the expression of proteins in the RAGE/NF-κB signaling pathway and downstream inflammatory factors. High concentrations of ART had a hypoglycemic effect, while a low concentration of ART prevented cardiovascular complications.
Predictors of HIV/AIDS comprehensive knowledge and acceptance attitude towards people living with HIV/AIDS among unmarried young females in Uganda: a cross-sectional study
Authors: Estifanos Tesfaldet Mekonnen , Hui Chen , Tesfai Afewerki Weldezgi , Teklu Mekonnen Estifanos , Ghebrehiwet Matiwos Araya , Embaye Kidane Siele , Andegiorgish Amanuel Kidane 
Published: January 2021

AbstractBackgroundYouth in general and young females, in particular, remain at the center of HIV/AIDS epidemic. To avoid and prevent HIV infection, comprehensive knowledge as well as correct understanding of transmission and prevention strategies are crucial. Thus, the aim of this study is to explore the predictors of comprehensive knowledge on HIV/AIDS and accepting attitude towards PLWHIV.MethodsA cross-sectional study was conducted using data from the 2016 Uganda Demographic Health Survey. A two-stage probability sampling method was applied and data were collected using a standard questionnaire. Of the total 8674 women aged 15–49 years, 1971 eligible women aged 15–24 years were included in this analysis. Data analysis was done using SPSS version 23. A Chi-square test followed by logistic regression analysis was used to explore the relationship between specific explanatory variables and outcome variables. The results were reported using odds ratios with 95% confidence interval.Pvalue less than 0.05 was considered as statistically significant.ResultsOverall, 99.3% of the unmarried women aged 15–24 years were aware of HIV/AIDS, but only 51.9% had comprehensive knowledge on HIV/AIDS. Around 70% of the respondents were aware that "using condoms every time when having sex" and "having only one faithful uninfected partner" can prevent HIV transmission. About 68% of the unmarried women rejected at least two common local misconceptions about HIV/AIDS. An alarmingly small (20.6%) proportion of the respondents had a positive acceptance attitude towards PLWHIV. All variables were significantly associated with having comprehensive knowledge on HIV/AIDS in the unadjusted logistic regression analysis. After adjustment, older age (20–24 years), being educated, wealthier, and ever been tested for HIV/AIDS became predictors of adequate comprehensive HIV/AIDS knowledge. Moreover, respondents with adequate comprehensive knowledge of HIV/AIDS were more likely (OR 1.64, 95% CI 1.30–2.08) to have a positive acceptance attitude towards PLWHIV than their counterparts.ConclusionOur study demonstrated a remarkably high level of awareness about HIV/AIDS among study participants, but the knowledge and positive acceptance attitude towards PLWHIV were not encouraging. Thus, endeavors to expand and strengthen educational campaigns on HIV/AIDS in communities, health facilities, and schools are highly recommended. Attention should particularly focus on young-aged and disadvantaged women with low educational level, poor socioeconomic status and those who have never been tested for HIV/AIDS.
Development of real world learning opportunities in community exercise prescription for healthcare professional programmes - ‘Physio Hub’
Authors: Cunningham Caitriona , Blake Catherine , O Donoghue Grainne , Purcell Ciaran , Mc Carthy Persson Ulrik , Cradock Karen , Mc Mahon Sinead 
Published: January 2021

Abstract
Background
Given the challenge of chronic lifestyle diseases, the shift in healthcare focus to primary care and recognised importance of a preventive approach to health, including exercise prescription, the embedding of related learning in healthcare professional programmes is critical.

Methods
In response to these contemporary demands, a complex curriculum development project was undertaken at University College Dublin, employing a four dimensional curriculum framework for the development of health professional curricula, that focused on (1) future orientation of healthcare practices (the why?), (2) defining capabilities of graduates (the what?), (3) teaching, learning and assessment (the how?) and (4) organisation/institution delivery (the where)? The process was informed by latest exercise, health promotion, educational and health policy literature, alongside engagement with multiple internal university and external community stakeholders.

Results
Having sufficient clinical education opportunity for translating exercise theory into practice was identified as a key need (the Why?). Development of strategies for health promotion and design and delivery of evidence based exercise programmes with inter-professional and inter-sectoral network building were some of the graduate capabilities identified as being critically important. (the what?) The resultant UCD Physio Hub model of clinical education combines ‘on campus’ and ‘community outreach’ activity to facilitate inter-sectoral ‘real world’ experiential student learning in health promotion and exercise prescription for both healthy and clinical populations. Underpinned by social constructivist educational theory, students are encouraged to be creative and to collaborate in responding to identified health needs of specific community groups by designing and delivering community services. (the how?) In developing new student learning opportunities to enhance curriculum, a supportive organisational culture and context was critical with UCD having excellent exercise infrastructure and the Physio Hub project aligning with a community engagement ethos articulated in the university’s strategy. (the where?)

Conclusion
This paper provides an overview of Physio Hub, its services, educational practices and translational research ethos, all of which are combined to deliver a rich exercise and health promotion learning experience. Although developed for physiotherapy in this instance, the curriculum process and resultant education model could be applied across medical and other health professional programmes and to facilitate interdisciplinary learning.
Putative ligand binding sites of two functionally characterized bark beetle odorant receptors
Authors: Yuvaraj Jothi K. , Roberts Rebecca E. , Sonntag Yonathan , Hou Xiao-Qing , Grosse-Wilde Ewald , Machara Aleš , Zhang Dan-Dan , Hansson Bill S. , Johanson Urban , Löfstedt Christer , Andersson Martin N. 
Published: January 2021

AbstractBackgroundBark beetles are major pests of conifer forests, and their behavior is primarily mediated via olfaction. Targeting the odorant receptors (ORs) may thus provide avenues towards improved pest control. Such an approach requires information on the function of ORs and their interactions with ligands, which is also essential for understanding the functional evolution of these receptors. Hence, we aimed to identify a high-quality complement of ORs from the destructive spruce bark beetleIps typographus(Coleoptera, Curculionidae, Scolytinae) and analyze their antennal expression and phylogenetic relationships with ORs from other beetles. Using 68 biologically relevant test compounds, we next aimed to functionally characterize ecologically important ORs, using two systems for heterologous expression. Our final aim was to gain insight into the ligand-OR interaction of the functionally characterized ORs, using a combination of computational and experimental methods.ResultsWe annotated 73 ORs from an antennal transcriptome ofI. typographusand report the functional characterization of two ORs (ItypOR46 and ItypOR49), which are responsive to single enantiomers of the common bark beetle pheromone compounds ipsenol and ipsdienol, respectively. Their responses and antennal expression correlate with the specificities, localizations, and/or abundances of olfactory sensory neurons detecting these enantiomers. We use homology modeling and molecular docking to predict their binding sites. Our models reveal a likely binding cleft lined with residues that previously have been shown to affect the responses of insect ORs. Within this cleft, the active ligands are predicted to specifically interact with residues Tyr84 and Thr205 in ItypOR46. The suggested importance of these residues in the activation by ipsenol is experimentally supported through site-directed mutagenesis and functional testing, and hydrogen bonding appears key in pheromone binding.ConclusionsThe emerging insight into ligand binding in the two characterized ItypORs has a general importance for our understanding of the molecular and functional evolution of the insect OR gene family. Due to the ecological importance of the characterized receptors and widespread use of ipsenol and ipsdienol in bark beetle chemical communication, these ORs should be evaluated for their potential use in pest control and biosensors to detect bark beetle infestations.
Regulator of cullins-1 (ROC1) negatively regulates the Gli2 regulator SUFU to activate the hedgehog pathway in bladder cancer
Authors: Wang W. , Qiu J. , Qu P. , Chen H. , Lan J. , Chen H. , Li L. , Gu M. 
Published: January 2021

Abstract
Background
The regulator of cullins-1 (ROC1) is an essential subunit in the cullin-RING ligase (CRL) protein complex and has been shown to be critical in bladder cancer cell survival and progression. This study aimed to explore the molecular mechanism of ROC1 action in the malignant progression of bladder cancer.

Methods
This study utilized ex vivo, in vitro, and in vivo nude mouse experiments to assess the underlying mechanisms of ROC1 in bladder cancer cells. The expression of the components of the sonic hedgehog (SHH) pathway was determined by western blot analysis. ROC1 expression in human tumors was evaluated by immunohistochemistry.

Results
ROC1 overexpression promoted the growth of bladder cancer cells, whereas knockdown of ROC1 expression had the opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target suppressor of fused homolog (SUFU) for ubiquitin-dependent degradation, allowing Gli2 release from the SUFU complex to activate the SHH pathway. Furthermore, knockdown of SUFU expression partially rescued the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. In ex vivo experiments, tissue microarray analysis of human bladder cancer specimens revealed a positive association of ROC1 expression with the SHH pathway activity.

Conclusion
This study demonstrated that dysregulation of the ROC1–SUFU–GLI2 axis plays an important role in bladder cancer progression and that targeting ROC1 expression is warranted in further investigations as a novel strategy for the future control of bladder cancer.
Targeting androgen receptor signaling with MicroRNAs and Curcumin: a promising therapeutic approach for Prostate Cancer Prevention and intervention
Authors: Javed Zeeshan , Khan Khushbukhat , Rasheed Amna , Sadia Haleema , Shahwani Muhammad Naeem , Irshad Asma , Raza Shahid , Salehi Bahare , Sharifi-Rad Javad , Suleria Hafiz A. R. , Cruz-Martins Natália , Quispe Cristina 
Published: January 2021

AbstractProstate cancer (PC) is a multifactorial disease characterized by the abrogation of androgen receptor signaling. Advancement in microbiology techniques has highlighted the significant role of microRNAs (miRNAs) in the progression of PC cells from an androgen-dependent to an androgen-independent state. At that stage, prostate tumors also fail to respond to currently practiced hormone therapies. So, studies in recent decades are focused on investigating the anti-tumor effects of natural compounds in PC. Curcumin is widely recognized and now of huge prestige for its anti-proliferative abilities in different types of cancer. However, its limited solubility, compatibility, and instability in the aqueous phase are major hurdles when administering. Nanoformulations have proven to be an excellent drug delivery system for various drugs and can be used as potential delivery platforms for curcumin in PC. In this review, a shed light is given on the miRNAs-mediated regulation of androgen receptor (AR) signaling and miRNA-curcumin interplay in PC, as well as on curcumin-based nanoformulations that can be used as possible therapeutic solutions for PC.
The effect of an mLearning application on nurses’ and midwives’ knowledge and skills for the management of postpartum hemorrhage and neonatal resuscitation: pre–post intervention study
Authors: Nishimwe Aurore , Ibisomi Latifat , Nyssen Marc , Conco Daphney Nozizwe 
Published: January 2021

Abstract
Background
Globally, mobile learning (mLearning) tools have attracted considerable attention as a means of continuous training for healthcare workers. Rwanda like other low-resource settings with scarce in-service training opportunities requires innovative approaches that adapt technology to context to improve healthcare workers’ knowledge and skills. One such innovation is the safe delivery application (SDA), a smartphone mLearning application for Basic Emergency Obstetric and Neonatal Care (BEmONC) content. This study assessed the effect of the SDA intervention on nurses’ and midwives’ knowledge and skills for the management of postpartum hemorrhage (PPH) and neonatal resuscitation (NR).

Methods
The study used a pre–post test design to compare knowledge and skills of nurses and midwives in the management of PPH and NR at two measurement points: immediately prior to SDA intervention and after 6 months of SDA intervention. The intervention took place in two district hospitals in Rwanda and included 54 participants. A paired-sample t-test was used to measure the pre–post intervention, mean knowledge and skills scores differences. Confidence intervals (CIs) and effect size were calculated. A t-test and a one-way Anova were used to test for potential confounders.

Results
The analysis included 54 participants. Knowledge scores and skills scores on PPH management and NR increased significantly from baseline to endline measurements. The mean difference for PPH knowledge is 17.1 out of 100; 95% CI 14.69 to 19.49 and 2.6% for PPH skills; 95% CI 1.01 to 4.25. The mean difference for NR knowledge is 19.1 out of 100; 95% CI 16.31 to 21.76 and 5.5% for NR skills; 95% CI 3.66 to 7.41. Increases were unaffected by participants’ attendance to in-service training 6 months prior and during SDA intervention and previous smartphone use. However, pre- and post-intervention skills scores were significantly different by years of experience in obstetric care.

Conclusion
The SDA intervention improved the knowledge and skills of nurses and midwives on the management of PPH and NR as long as 6 months after SDA introduction. The results are highly relevant in low-income countries like Rwanda, where quality of delivery care is challenged by a lack of in-service continuous training for healthcare providers.
LINC00680 enhances hepatocellular carcinoma stemness behavior and chemoresistance by sponging miR-568 to upregulate AKT3
Authors: Shu Gege , Su Huizhao , Wang Zhiqian , Lai Shihui , Wang Yan , Liu Xiaomeng , Dai Luo , Bi Yin , Chen Wei , Huang Weiyu , Zhou Ziyan , He Songqing , Dai Hongliang , Tang Bo 
Published: January 2021

Abstract
Background
Hepatocellular carcinoma (HCC) has an extremely poor prognosis due to the development of chemoresistance, coupled with inherently increased stemness properties. Long non-coding RNAs (LncRNAs) are key regulators for tumor cell stemness and chemosensitivity. Currently the relevance between LINC00680 and tumor progression was still largely unknown, with only one study showing its significance in glioblastoma. The study herein was aimed at identifying the role of LINC00680 in the regulation HCC stemness and chemosensitivity.

Methods
QRT-PCR was used to detect the expression of LINC00680, miR-568 and AKT3 in tissue specimen and cell lines. Gain- or loss-of function assays were applied to access the function of LINC00680 in HCC cells, including cell proliferation and stemness properties. HCC stemness and chemosensitivity were determined by sphere formation, cell viability and colony formation. Luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were performed to examine the interaction between LINC00680 and miR-568 as well as that between miR-568 and AKT3. A nude mouse xenograft model was established for the in vivo study.

Results
We found that LINC00680 was remarkably upregulated in HCC tissues. Patients with high level of LINC00680 had poorer prognosis. LINC00680 overexpression significantly enhanced HCC cell stemness and decreased in vitro and in vivo chemosensitivity to 5-fluorouracil (5-Fu), whereas LINC00680 knockdown led to opposite results. Mechanism study revealed that LINC00680 regulated HCC stemness and chemosensitivity through sponging miR-568, thereby expediting the expression of AKT3, which further activated its downstream signaling molecules, including mTOR, elF4EBP1, and p70S6K.

Conclusion
LINC00680 promotes HCC stemness properties and decreases chemosensitivity through sponging miR-568 to activate AKT3, suggesting that LINC00680 might be a potentially important HCC diagnosis marker and therapeutic target.
Exploiting the GTEx resources to decipher the mechanisms at GWAS loci
Authors: Barbeira Alvaro N. , Bonazzola Rodrigo , Gamazon Eric R. , Liang Yanyu , Park YoSon , Kim-Hellmuth Sarah , Wang Gao , Jiang Zhuoxun , Zhou Dan , Hormozdiari Farhad , Liu Boxiang , Rao Abhiram , Hamel Andrew R. , Pividori Milton D. , Aguet François ,   GTEx GWAS Working Group, Bastarache Lisa , Jordan Daniel M. , Verbanck Marie , Do Ron ,   GTEx Consortium, Stephens Matthew , Ardlie Kristin , McCarthy Mark , Montgomery Stephen B. , Segrè Ayellet V. , Brown Christopher D. , Lappalainen Tuuli , Wen Xiaoquan , Im Hae Kyung 
Published: January 2021

AbstractThe resources generated by the GTEx consortium offer unprecedented opportunities to advance our understanding of the biology of human diseases. Here, we present an in-depth examination of the phenotypic consequences of transcriptome regulation and a blueprint for the functional interpretation of genome-wide association study-discovered loci. Across a broad set of complex traits and diseases, we demonstrate widespread dose-dependent effects of RNA expression and splicing. We develop a data-driven framework to benchmark methods that prioritize causal genes and find no single approach outperforms the combination of multiple approaches. Using colocalization and association approaches that take into account the observed allelic heterogeneity of gene expression, we propose potential target genes for 47% (2519 out of 5385) of the GWAS loci examined.
Community-based intervention for cervical cancer screening uptake in a semi-urban area of Pokhara Metropolitan, Nepal (COBIN-C): study protocol for a cluster-randomized controlled trial
Authors: Shrestha Aamod Dhoj , Neupane Dinesh , Ghimire Sarita , Campbell Christine , Kallestrup Per 
Published: January 2021

Abstract
Background
Previous studies suggest that health intervention designed to increase cervical cancer screening has been effective to reduce cervical cancer incidence and mortality. The aim of this study is to determine the effect of a home-based health education intervention for increasing cervical cancer screening uptake delivered by trained female community health volunteers (FCHVs), a category of community health worker in Nepal.

Methods
A community-based, open-label, two-armed, cluster-randomized trial [seven clusters (geographical wards) randomized for the intervention, and seven for the control arm]. The participants are recruited from a population-based survey with a sample size of 884. Based on population proportion size, 277 women will be recruited for the intervention group and 413 women recruited for the control group. A 12-month community-based health education intervention will be administered mobilizing the FCHVs, based on the Health Belief Model. The primary outcome measure of the study will be the difference in percentage of cervical cancer screening uptake between the two study arms. The primary outcomes will be modeled by using mixed-effect logistic regression analysis.

Discussion
COBIN-C is the first study investigating the effect of a community-based health education intervention by FCHVs on increasing cervical cancer screening uptake among women in Nepal. The purpose of this study is to develop and implement a home-based, culturally sensitive program to increase cervical cancer screening coverage at the community level.

Trial registration
ClinicalTrials.gov NCT03808064. Registered on January 14, 2019.