bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impacts of patient and family engagement in hospital planning and improvement: qualitative interviews with patient/family advisors and hospital staff
Authors: Anderson Natalie N , Dong Kelly , Baker G. Ross , Moody Lesley , Scane Kerseri , Urquhart Robin , Wodchis Walter P , Gagliardi Anna R 
Published: March 2022

Abstract
Background
Patient engagement (PE) in hospital planning and improvement is widespread, yet we lack evidence of its impact. We aimed to identify benefits and harms that could be used to assess the impact of hospital PE.

Methods
We interviewed hospital-affiliated persons involved in PE activities using a qualitative descriptive approach and inductive content analysis to derive themes. We interpreted themes by mapping to an existing framework of healthcare performance measures and reported themes with exemplar quotes.

Results
Participants included 38 patient/family advisors, PE managers and clinicians from 9 hospitals (2 < 100 beds, 4 100 + beds, 3 teaching). Benefits of PE activities included 9 impacts on the capacity of hospitals. PE activities involved patient/family advisors and clinicians/staff in developing and spreading new PE processes across hospital units or departments, and those involved became more adept and engaged. PE had beneficial effects on hospital structures/resources, clinician staff functions and processes, patient experience and patient outcomes. A total of 14 beneficial impacts of PE were identified across these domains. Few unintended or harmful impacts were identified: overextended patient/family advisors, patient/family advisor turnover and clinician frustration if PE slowed the pace of planning and improvement.

Conclusions
The 23 self reported impacts were captured in a Framework of Impacts of Patient/Family Engagement on Hospital Planning and Improvement, which can be used by decision-makers to assess and allocate resources to hospital PE, and as the basis for ongoing research on the impacts of hospital PE and how to measure it.
Relationship between human resources strategies and organizational performance based on the balanced scorecard in a public hospital in Iran: a cross-sectional study
Authors: Nafari Ebrahim , Rezaei Behrooz 
Published: March 2022

AbstractBackgroundToday, due to the complex environment and rapidly changing of health industry, hospitals should optimize their organizational performance to achieve a competitive advantage. One of the important factors for achieving a competitive advantage is effective human resource management through the application of appropriate human resources strategies. This study investigated the relationship between human resources strategies and organizational performance based on balanced scorecard.MethodsA cross-sectional study was conducted among clinical and administrative staff in a public hospital in Isfahan province, Iran. All eligible staff entered the study (n=200). Data were collected using two self-reported questionnaires during July 2018. The main questionnaire contained 32 items that investigated human resources strategies (including seven types of strategies) and organizational performance based on the balanced scorecard approach. Data were analyzed via Pearson correlation coefficient and multivariate regression using SPSS/21 software (P<0.05).ResultsIn this study, 154 questionnaires were completed and returned (return rate=77%). Human resources strategies and organizational performance were evaluated at the intermediate level. There was a significant positive correlation between human resources strategies and organizational performance (r=0.73,p=0.001). The organizational performance in learning & growth perspective had the highest correlation (r=0.669,p=0.001) with human resources strategies while the financial perspective had the lowest (r=0.455,p=0.001). Multivariate regression analysis showed that all human resources strategies were effective on organizational performance (R=0.998,R2=0.997, ADJ.R2=0.997). Staff training and development strategy (Beta=0. 265,p=0.000), staff compensation & reward strategy (Beta =0.212,p= 0.000) and recruitment strategy (Beta = 0.208, B,P=0.000) had the greatest impact on organizational performance, respectively.ConclusionsTo improve hospital performance (especially in non financial perspectives), the development of human resources strategies (especially staff training and development strategy, staff compensation & reward strategy, and compensation strategy) can be considered by hospital managers. The findings of this study can be used for developing hospital performance in a similar context.
Analysis of potential genetic biomarkers using machine learning methods and immune infiltration regulatory mechanisms underlying atrial fibrillation
Authors: Wu Li-Da , Li Feng , Chen Jia-Yi , Zhang Jie , Qian Ling-Ling , Wang Ru-Xing 
Published: March 2022

Abstract
Objective
We aimed to screen out biomarkers for atrial fibrillation (AF) based on machine learning methods and evaluate the degree of immune infiltration in AF patients in detail.

Methods
Two datasets (GSE41177 and GSE79768) related to AF were downloaded from Gene expression omnibus (GEO) database and merged for further analysis. Differentially expressed genes (DEGs) were screened out using “limma” package in R software. Candidate biomarkers for AF were identified using machine learning methods of the LASSO regression algorithm and SVM-RFE algorithm. Receiver operating characteristic (ROC) curve was employed to assess the diagnostic effectiveness of biomarkers, which was further validated in another independent validation dataset of GSE14975. Moreover, we used CIBERSORT to study the proportion of infiltrating immune cells in each sample, and the Spearman method was used to explore the correlation between biomarkers and immune cells.

Results
129 DEGs were identified, and CYBB, CXCR2, and S100A4 were identified as key biomarkers of AF using LASSO regression and SVM-RFE algorithm. Both in the training dataset and the validation dataset, CYBB, CXCR2, and S100A4 showed favorable diagnostic effectiveness. Immune infiltration analysis indicated that, compared with sinus rhythm (SR), the atrial samples of patients with AF contained a higher T cells gamma delta, neutrophils and mast cells resting, whereas T cells follicular helper were relatively lower. Correlation analysis demonstrated that CYBB, CXCR2, and S100A4 were significantly correlated with the infiltrating immune cells.

Conclusions
In conclusion, this study suggested that CYBB, CXCR2, and S100A4 are key biomarkers of AF correlated with infiltrating immune cells, and infiltrating immune cells play pivotal roles in AF.
Ferroptosis-related gene SLC1A5 is a novel prognostic biomarker and correlates with immune infiltrates in stomach adenocarcinoma
Authors: Zhu Dandan , Wu Sifan , Li Yafang , Zhang Yu , Chen Jierong , Ma Jianhong , Cao Lixue , Lyu Zejian , Hou Tieying 
Published: March 2022

Abstract
Background
Stomach adenocarcinoma (STAD) is associated with high morbidity and mortality rates. Ferroptosis is an iron-dependent form of cell death, which plays an important role in the development of many cancers. Tumor-associated competing endogenous RNAs (ceRNAs) regulate tumorigenesis and development. Our study aimed to construct ceRNA networks and explore the relationship between ferroptosis-related genes in the ceRNA network and immune infiltration in STAD.

Methods
Based on the interactions among long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs), a ceRNA network was constructed to illustrate the relationships among lncRNAs, miRNAs, and mRNAs. Subsequently, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment analyses were carried out to explore the functions and interactions of the differentially expressed (DE) mRNAs related to the ceRNA network. Differential expression and prognostic analysis of ferroptosis-related genes in the ceRNA network were performed using the R package “limma” and “survminer.” The correlation between ferroptosis-related genes and tumor-infiltrating immune cells was analyzed using Spearman correlation analysis and CIBERSORT. Quantitative real-time PCR (qRT-PCR) was used to validate the expression of ferroptosis-related genes in STAD cells lines.

Results
A ceRNA network consisting of 29 DElncRNAs, 31 DEmiRNAs, and 182 DEmRNAs was constructed. These DEmRNAs were significantly enriched in pathways related to the occurrence and development of STAD. The ferroptosis-related gene SLC1A5 was upregulated in STAD (P < 0.001) and was associated with better prognosis (P = 0.049). The CIBERSORT database and Spearman correlation analysis indicated that SLC1A5 was correlated with eight types of tumor-infiltrating immune cells and immune checkpoints, including PD-L1(CD-274) and PD-1(PDCD1). The SLC1A5 mRNA was found to be highly expressed in STAD cells lines.

Conclusions
Our study provides insights into the function of ceRNAs in STAD and identifies biomarkers for the development of therapies for STAD. The ferroptosis-related gene SLC1A5 in the ceRNA network was associated with both tumor-infiltrating immune cells and immune checkpoints in the tumor microenvironment, suggesting that SLC1A5 may be a novel prognostic marker and a potential target for STAD immunotherapy in the future.
Mechanistic study of silica nanoparticles on the size-dependent retinal toxicity in vitro and in vivo
Authors: Zhang Zhuhong , Zhao Laien , Ma Yuanyuan , Liu Jia , Huang Yanmei , Fu Xiaoxuan , Peng Shengjun , Wang Xiaojie , Yang Yun , Zhang Xiaoyan , Ding Wanru , Yu Jinguo , Zhu Yanping , Yan Hua , Yang Shubin 
Published: March 2022

Abstract
Background
Silica nanoparticles (SiO2 NPs) are extensively applied in the biomedical field. The increasing medical application of SiO2 NPs has raised concerns about their safety. However, studies on SiO2 NP-induced retinal toxicity are lacking.

Methods
We investigated the retinal toxicity of SiO2 NPs with different sizes (15 and 50 nm) in vitro and in vivo along with the underlying mechanisms. The cytotoxicity of SiO2 NPs with different sizes was assessed in R28 human retinal precursor cells by determining the ATP content and LDH release. The cell morphologies and nanoparticle distributions in the cells were analyzed by phase-contrast microscopy and transmission electron microscopy, respectively. The mitochondrial membrane potential was examined by confocal laser scanning microscopy. The retinal toxicity induced by SiO2 NPs in vivo was examined by immunohistochemical analysis. To further investigate the mechanism of retinal toxicity induced by SiO2 NPs, reactive oxygen species (ROS) generation, glial cell activation and inflammation were monitored.

Results
The 15-nm SiO2 NPs were found to have higher cytotoxicity than the larger NPs. Notably, the 15-nm SiO2 NPs induced retinal toxicity in vivo, as demonstrated by increased cell death in the retina, TUNEL-stained retinal cells, retinal ganglion cell degeneration, glial cell activation, and inflammation. In addition, The SiO2 NPs caused oxidative stress, as demonstrated by the increase in the ROS indicator H2DCF-DA. Furthermore, the pretreatment of R28 cells with N-acetylcysteine, an ROS scavenger, attenuated the ROS production and cytotoxicity induced by SiO2 NPs.

Conclusions
These results provide evidence that SiO2 NPs induce size-dependent retinal toxicity and suggest that glial cell activation and ROS generation contribute to this toxicity.

Graphical Abstract
Longitudinal surface measurements of human blastocysts show that the dynamics of blastocoel expansion are associated with fertilization method and ongoing pregnancy
Authors: van Marion Eva S. , Chavli Effrosyni A. , Laven Joop S. E. , Steegers-Theunissen Régine P. M. , Koster Maria P. H. , Baart Esther B. 
Published: March 2022

Abstract
Background
Despite all research efforts during this era of novel time-lapse morphokinetic parameters, a morphological grading system is still routinely being used for embryo selection at the blastocyst stage. The blastocyst expansion grade, as evaluated during morphological assessment, is associated with clinical pregnancy. However, this assessment is performed without taking the dynamics of blastocoel expansion into account. Here, we studied the dynamics of blastocoel expansion by comparing longitudinal blastocoel surface measurements using time-lapse embryo culture. Our aim was to first assess if this is impacted by fertilization method and second, to study if an association exists between these measurement and ongoing pregnancy.

Methods
This was a retrospective cohort study including 225 couples undergoing 225 cycles of in vitro fertilization (IVF) treatment with time-lapse embryo culture. The fertilization method was either conventional IVF, intracytoplasmic sperm injection (ICSI) with ejaculated sperm or ICSI with sperm derived from testicular sperm extraction (TESE-ICSI). This resulted in 289 IVF embryos, 218 ICSI embryos and 259 TESE-ICSI embryos that reached at least the full blastocyst stage. Blastocoel surface measurements were performed on time-lapse images every hour, starting from full blastocyst formation (tB). Linear mixed model analysis was performed to study the association between blastocoel expansion, the calculated expansion rate (µm2/hour) and both fertilization method and ongoing pregnancy.

Results
The blastocoel of both ICSI embryos and TESE-ICSI embryos was significantly smaller than the blastocoel of IVF embryos (beta -1121.6 µm2; 95% CI: -1606.1 to -637.1, beta -646.8 µm2; 95% CI: -1118.7 to 174.8, respectively). Still, the blastocoel of transferred embryos resulting in an ongoing pregnancy was significantly larger (beta 795.4 µm2; 95% CI: 15.4 to 1575.4) and expanded significantly faster (beta 100.9 µm2/hour; 95% CI: 5.7 to 196.2) than the blastocoel of transferred embryos that did not, regardless of the fertilization method.

Conclusion
Longitudinal blastocyst surface measurements and expansion rates are promising non-invasive quantitative markers that can aid embryo selection for transfer and cryopreservation.

Trial registration
Our study is a retrospective observational study, therefore trial registration is not applicable.
Out-of-pocket payments for treatment of COVID-19 in Iran
Authors: Yusefi Ali Reza , Mehralian Gholamhossein , Khodamoradi Abdolvahed , Abbasi Roghaye , Vatankhah Fatemeh , Heaidari Fatemeh , Bastani Peivand 
Published: March 2022

Abstract
Introduction
Out-of-pocket (OOP) is among the payment methods in Iran’s health system. The present study aimed to examine the OOP treatment costs for patients with COVID-19 in Iran.

Methods
A descriptive-analytical, cross-sectional study was conducted in 2021. In this study, the cost records of 550 patients with COVID-19 hospitalized in a referral center of COVID-19 were selected using the stratified random sampling method. The required data were collected using a researcher-made questionnaire. Data were analyzed by t-test, ANOVA, and Pearson’s correlation coefficient in SPSS software version 23 at p = 0.05.

Results
The total direct costs were 1,037,992.15 US $. Moreover, the shares of patients (OOP), basic insurance, government subsidy, supplementary insurance, discounts, and out-of-government subsidy in the total direct costs were US $ 92,231.21, 746,932.99 US $, 155,127.08 US $, 39,690.25 US $ and 4010.61 US $, respectively. In addition, the results confirmed that there was a positive and significant relationship between the patients’ OOP payments and the length of stay. It also found that the patients’ OOP payments are subject to the type of insurance program and discharge method.

Conclusion
According to the results, 8.89% of the total direct costs were directly paid out of the patients’ pockets. The research findings confirm the urgent need to make decisions and implement effective interventions for COVID-19 disease by controlling risk factors and exploiting other countries’ successful experiences and international organizations’ recommendations to decrease the prevalence of the infected and consequently reduce the financial pressure of the disease on patients by approving the expansion of the insurance organizations’ role.
RETRACTED ARTICLE: Down-regulation of kappa opioid receptor promotes ESCC proliferation, invasion and metastasis via the PDK1-AKT signaling pathway
Authors: Huang Han-Ming , He Xin-Hua , Huang Xiao-Yu , Wang Guo-Yun , Xia Qiao-Xi , Du Ze-Peng , Zhang Yong-Fa 
Published: March 2022

Abstract
Background
As a class of the opioid receptors, the kappa opioid receptor (KOR) has been verified to be a potential biomarker and therapeutic target for human malignant tumors. However, a thorough understanding of whether KOR affects progression of esophageal squamous cell carcinoma (ESCC) is still lacking. This study focused on exploring the effect of knocking down KOR in ESCC and its underlying mechanism.

Methods
Bioinformatics analysis was used to compare the different expression level of OPRK1 (KOR gene) in tumor and adjacent normal tissues, and predict the relationship between KOR expression and overall survival. RNA-sequence analysis was performed to detect the altered functions and mechanisms after down regulating KOR. The in vitro and in vivo assays were used to detect the effects of down-regulated KOR on cell proliferation, migration and invasion. Substrate gel zymography and 3D cell culture assays were used to find the effect of KOR knockdown on the degradation of extracellular matrix (ECM), and immunefluorescence was performed to detect the altered cytoskeleton. Western blotting and immunohistochemistry were used to explore the underlying mechanism pathway.

Results
Bioinformatics analysis revealed that the expression of OPRK1 was lower in tumor tissue than that in adjacent normal tissues, and lowered expression of KOR was associated with poorer overall survival. The in vitro assays demonstrated that down-regulation of KOR enhanced ESCC proliferation, metastasis and invasion. Western blotting revealed that down-regulation of KOR could activate PDK1-AKT signaling pathway, which actively regulated the cancer progression. Down-regulation of KOR enhanced the formation of invadopodia, secretion of matrix metalloproteinase-2 (MMP2) and rearrangement of cytoskeleton, which were positively related with the invasion of ESCC. KOR knockdown enhanced the tumor invasion and elevated the AKT phosphorylation in nude mice. The AKT kinase inhibition could reverse the effect of down-regulation of KOR.

Conclusion
KOR might act as a tumor suppressor in ESCC and down-regulation of KOR could enhance the ESCC tumor phenotype.

Graphical abstract
Fair play? Participation equity in organised sport and physical activity among children and adolescents in high income countries: a systematic review and meta-analysis
Authors: Owen Katherine B. , Nau Tracy , Reece Lindsey J. , Bellew William , Rose Catriona , Bauman Adrian , Halim Nicole K. , Smith Ben J. 
Published: March 2022

Abstract
Background
Physical activity and sport have numerous health benefits and participation is thought to be lower in disadvantaged children and adolescents. However, evidence for the disparity in physical activity is inconsistent, has not been reviewed recently, and for sport has never been synthesised. Our aim was to systematically review, and combine via meta-analyses, evidence of the socioeconomic disparities in physical activity and sport participation in children and adolescents in high income countries.

Methods
We conducted searches of five electronic databases using physical activity, sport, and socioeconomic disparity related terms. Two independent reviewers assessed 21,342 articles for peer-reviewed original research, published in English that assessed socioeconomic disparities in physical activity and sport participation in children and adolescents. We combined evidence from eligible studies using a structural equation modelling approach to multilevel meta-analysis.

Results
From the 104 eligible studies, we meta-analysed 163 effect sizes. Overall, children and adolescents living in higher socioeconomic status households were more likely to participate in sport (OR: 1.87, 95% CIs 1.38, 2.36) and participated for a longer duration (d = 0.24, 95% CIs 0.12, 0.35). The socioeconomic disparity in the duration of sport participation was greater in children (d = 0.28, 95% CIs 0.15, 0.41) compared with adolescents (d = 0.13, 95% CIs − 0.03, 0.30).
Overall, children and adolescents living in higher socioeconomic status households were more likely to meet physical activity guidelines (OR: 1.21, 95% CIs 1.09, 1.33) and participated for a longer duration (d = 0.08, 95% CIs 0.02, 0.14). The socioeconomic disparity in the duration of total physical activity between low and high socioeconomic status households was greater in children (d = 0.13, 95% CIs 0.04, 0.21) compared with adolescents (d = 0.05, 95% CIs − 0.05, 0.15).
There was no significant disparity in leisure time physical activity (d = 0.13, 95% CIs − 0.06, 0.32).

Conclusions
There was evidence of socioeconomic disparities in sport participation and total physical activity participation among children and adolescents. Socioeconomic differences were greater in sport compared to total physical activity and greater in children compared with adolescents. These findings highlight the importance of targeting sport programs according to socio-economic gradients, to reduce inequities in access and opportunity to organised sport.
The molecular mechanism of SARS-CoV-2 evading host antiviral innate immunity
Authors: Gu Wenjing , Gan Hui , Ma Yu , Xu Lina , Cheng Zhangkai J. , Li Bizhou , Zhang Xinxing , Jiang Wujun , Sun Jinlv , Sun Baoqing , Hao Chuangli 
Published: March 2022

AbstractThe newly identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a global health emergency (COVID-19) because of its rapid spread and high mortality. Since the virus epidemic, many pathogenic mechanisms have been revealed, and virus-related vaccines have been successfully developed and applied in clinical practice. However, the pandemic is still developing, and new mutations are still emerging. Virus pathogenicity is closely related to the immune status of the host. As innate immunity is the body’s first defense against viruses, understanding the inhibitory effect of SARS-CoV-2 on innate immunity is of great significance for determining the target of antiviral intervention. This review summarizes the molecular mechanism by which SARS-CoV-2 escapes the host immune system, including suppressing innate immune production and blocking adaptive immune priming. Here, on the one hand, we devoted ourselves to summarizing the combined action of innate immune cells, cytokines, and chemokines to fine-tune the outcome of SARS-CoV-2 infection and the related immunopathogenesis. On the other hand, we focused on the effects of the SARS-CoV-2 on innate immunity, including enhancing viral adhesion, increasing the rate of virus invasion, inhibiting the transcription and translation of immune-related mRNA, increasing cellular mRNA degradation, and inhibiting protein transmembrane transport. This review on the underlying mechanism should provide theoretical support for developing future molecular targeted drugs against SARS-CoV-2. Nevertheless, SARS-CoV-2 is a completely new virus, and people’s understanding of it is in the process of rapid growth, and various new studies are also being carried out. Although we strive to make our review as inclusive as possible, there may still be incompleteness.