bluuebunny/crossref_metadata_2025_split huggingface dataset:
Level and predictors of nurse caring behaviors among nurses serving in inpatient departments in public hospitals in Harari region, eastern Ethiopia
Authors: Kibret Haregeweyn , Tadesse Barkot , Debella Adera , Degefa Meron , Regassa Lemma Demissie 
Published: April 2022

Abstract
Background
Nursing practice is centered on caring and nurses’ behaviour has an impact on the quality of patient care and it is predictive of patient satisfaction,however, many nurses, in reality, do not exhibit caring behavior when providing nursing care to clients. This study was aimed to assess the level and predictors of nurse caring behaviors among nurses serving in inpatient departments in public hospitals in Harari Region of Ethiopia from March 10 to April 10, 2021.

Method
A cross-sectional study was conducted among 300 nurses providing inpatient service in public hospitals in the Harari region of eastern Ethiopia. All permanent nurses working in major inpatient services of two public hospitals, namely Jugal General Hospital (JGH) and Hiwot Fana Specialized University Hospital (HFSUH) were included. The English version of the CNPI-Nurse scale was used to determine the level of caring behavior. The association was reported using the crude and adjusted odds ratios along with the 95% confidence interval. The statistical significance of the association was declared at p-value < 0.05.

Result
The caring behavior was classified as high and low based on the median score. According to this study only 51.67% (95% CI:45.97, 57.35%) of nurses had good caring behavior. The odds of having good caring behavior were 2.22 (AOR = 2.22, 95%CI: 1.20, 4.10) times higher among nurses working in good working environment compared to those who work in bad working environment. Nurses who were satisfied with their job had 2.79 (AOR: 2.79, 95%CI: 1.54, 5.08) times higher odds of good caring behavior than those who were not satisfied with their job. Similarly, nurses who had a lower workload had a 3.01 (AOR: 3.01, 95%CI: 1.70, 5.33) times higher probability of having good caring behavior from nurses compared to nurses who reported having a high workload.

Conclusion
The level of nurses caring behavior is not satisfactory and it is influenced by working environment characteristics, job satisfaction and workload. Therefore it necessary to creat conducive working environment, provide adequate time and resources inorder to improve the level of nurses caring behaviour.
Consumption and cost trends of EGFR TKIs: influences of reimbursement and national price negotiation
Authors: Wu Di , Xie Jianxiang , Dai Huizhen , Fang Wentong 
Published: April 2022

Abstract
Background
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been widely used in the treatment of EGFR mutation non-small-cell lung cancer. The Chinese government has made great efforts to improve the availability and affordability of these drugs. The aim of this study was to investigate the trends in the consumption and cost of EGFR TKIs in Nanjing, a developed city in China, and evaluate the influence of health insurance coverage and national price negotiation on drug consumption.

Methods
Data about EGFR TKIs applications in 2010–2019 were extracted from Jiangsu Medicine Information Institute. Five types of EGFR TKIs were included. Consumption was expressed in defined daily doses (DDDs) and expenditure. The correlation between defined daily cost (DDC) and DDDs was analyzed by Pearson's correlation test.

Results
The DDC, number of DDDs and expenditure of EGFR TKIs changed little from 2010 to 2015. National price negotiation was initiated as a policy and low-price generic gefitinib came into the market in 2016. Three types of EGFR TKIs moved into the coverage of the national health insurance since 2017. Hence, the DDC decreased, and the number of DDDs increased significantly year by year since 2016. The first generation TKIs always made up of comprised the majority of the total consumption. The predominantly prescribed TKIs were gefitinib and icotinib. DDC was negatively correlated with the number of DDDs. The number of DDDs increased significantly after health insurance enrollment, price negotiation and generic drug replacement.

Conclusion
The consumption of EGFT TKIs has increased and the DDC of EGFR TKIs has decreased since 2016. These trends may be attributed to drug reimbursement, price negotiation and generic drug replacement. Further efforts are needed to translate the high consumption of EGFR TKIs into clinical benefits.
A novel HIF1α-STIL-FOXM1 axis regulates tumor metastasis
Authors: Wang Yi-Wei , Chen Shu-Chuan , Gu De-Leung , Yeh Yi-Chen , Tsai Jhih-Jie , Yang Kuo-Tai , Jou Yuh-Shan , Chou Teh-Ying , Tang Tang K. 
Published: April 2022

AbstractBackgroundMetastasis is the major cause of morbidity and mortality in cancer that involves in multiple steps including epithelial–mesenchymal transition (EMT) process. Centrosome is an organelle that functions as the major microtubule organizing center (MTOC), and centrosome abnormalities are commonly correlated with tumor aggressiveness. However, the conclusive mechanisms indicating specific centrosomal proteins participated in tumor progression and metastasis remain largely unknown.MethodsThe expression levels of centriolar/centrosomal genes in various types of cancers were first examined by in silico analysis of the data derived from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and European Bioinformatics Institute (EBI) datasets. The expression of STIL (SCL/TAL1-interrupting locus) protein in clinical specimens was further assessed by Immunohistochemistry (IHC) analysis and the oncogenic roles of STIL in tumorigenesis were analyzed using in vitro and in vivo assays, including cell migration, invasion, xenograft tumor formation, and metastasis assays. The transcriptome differences between low- and high-STIL expression cells were analyzed by RNA-seq to uncover candidate genes involved in oncogenic pathways. The quantitative polymerase chain reaction (qPCR) and reporter assays were performed to confirm the results. The chromatin immunoprecipitation (ChIP)-qPCR assay was applied to demonstrate the binding of transcriptional factors to the promoter.ResultsThe expression ofSTILshows the most significant increase in lung and various other types of cancers, and is highly associated with patients’ survival rate. Depletion of STIL inhibits tumor growth and metastasis. Interestingly, excess STIL activates the EMT pathway, and subsequently enhances cancer cell migration and invasion. Importantly, we reveal an unexpected role of STIL in tumor metastasis. A subset of STIL translocate into nucleus and associate with FOXM1 (Forkhead box protein M1) to promote tumor metastasis and stemness via FOXM1-mediated downstream target genes. Furthermore, we demonstrate that hypoxia-inducible factor 1α (HIF1α) directly binds to theSTILpromoter and upregulates STIL expression under hypoxic condition.ConclusionsOur findings indicate that STIL promotes tumor metastasis through the HIF1α-STIL-FOXM1 axis, and highlight the importance of STIL as a promising therapeutic target for lung cancer treatment.
CircZDBF2 up-regulates RNF145 by ceRNA model and recruits CEBPB to accelerate oral squamous cell carcinoma progression via NFκB signaling pathway
Authors: Rong Liang , Chen Bo , Liu Ke , Liu Bingyao , He Xinyao , Liu Juan , Li Junxia , He Maodian , Zhu Lei , Liu Ke , Shi Xiaolei , Shuai Yi , Jin Lei 
Published: April 2022

Abstract
Background
Oral squamous cell carcinoma (OSCC), as one of the commonest malignancies showing poor prognosis, has been increasingly suggested to be modulated by circular RNAs (circRNAs). Through GEO (Gene Expression Omnibus) database, a circRNA derived from ZDBF2 (circZDBF2) was uncovered to be with high expression in OSCC tissues, while how it may function in OSCC remains unclear.

Methods
CircZDBF2 expression was firstly verified in OSCC cells via qRT-PCR. CCK-8, along with colony formation, wound healing, transwell and western blot assays was performed to assess the malignant cell behaviors in OSCC cells. Further, RNA pull down assay, RIP assay, as well as luciferase reporter assay was performed to testify the interaction between circZDBF2 and RNAs.

Results
CircZDBF2 expressed at a high level in OSCC cells and it accelerated OSCC cell proliferation, migration, invasion as well as EMT (epithelial-mesenchymal transition) process. Further, circZDBF2 sponged miR-362-5p and miR-500b-5p in OSCC cells to release their target ring finger protein 145 (RNF145). RNF145 expressed at a high level in OSCC cells and circZDBF2 facilitated RNF145 transcription by recruiting the transcription factor CCAAT enhancer binding protein beta (CEBPB). Moreover, RNF145 activated NFκB (nuclear factor kappa B) signaling pathway and regulated IL-8 (C-X-C motif chemokine ligand 8) transcription.

Conclusion
CircZDBF2 up-regulated RNF145 expression by sponging miR-362-5p and miR-500b-5p and recruiting CEBPB, thereby promoting OSCC progression via NFκB signaling pathway. The findings recommend circZDBF2 as a probable therapeutic target for OSCC.

Graphical Abstract
DEPTH2: an mRNA-based algorithm to evaluate intratumor heterogeneity without reference to normal controls
Authors: Song Dandan , Wang Xiaosheng 
Published: April 2022

AbstractBackgroundIntratumor heterogeneity (ITH) is associated with tumor progression, unfavorable prognosis, immunosuppression, genomic instability, and therapeutic resistance. Thus, evaluation of ITH levels is valuable in cancer diagnosis and treatment.MethodsWe proposed a new mRNA-based ITH evaluation algorithm (DEPTH2) without reference to normal controls. DEPTH2 evaluates ITH levels based on the standard deviations of absolute z-scored transcriptome levels in tumors, reflecting the asynchronous level of transcriptome alterations relative to the central tendency in a tumor.ResultsBy analyzing 33 TCGA cancer types, we demonstrated that DEPTH2 ITH was effective in measuring ITH for its significant associations with tumor progression, unfavorable prognosis, genomic instability, reduced antitumor immunity and immunotherapy response, and altered drug response in diverse cancers. Compared to other five ITH evaluation algorithms (MATH, PhyloWGS, ABSOLUTE, DEPTH, and tITH), DEPTH2 ITH showed a stronger association with unfavorable clinical outcomes, and in characterizing other properties of ITH, such as its associations with genomic instability and antitumor immunosuppression, DEPTH2 also displayed competitive performance.ConclusionsDEPTH2 is expected to have a wider spectrum of applications in evaluating ITH in comparison to other algorithms.
The effect of diabetes on surgical versus percutaneous left main revascularization outcomes: a systematic review and meta-analysis
Authors: d’Entremont Marc-André , Yagi Ryuichiro , Salia Soziema J. S. , Zhang Shuqi , Shaban Lamyaa , Bene-Alhasan Yakubu , Papatheodorou Stefania , Couture Étienne L. , Huynh Thao , Nguyen Michel , Hamaya Rikuta 
Published: April 2022

Abstract
Background
The optimal method of coronary revascularization for diabetes mellitus (DM) patients with left main coronary artery disease (LMCAD) is controversial in the drug-eluting stent (DES) era.

Methods
We performed a systematic review and meta-analysis comparing DES-based percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG) for LMCAD in DM patients and tested for effect measure modification (EMM) by diabetes for adverse events. We included all randomized controlled trials (RCTs) and observational studies comparing CABG to DES-based PCI including DM patients with LMCAD published up to March 1, 2021. We completed separate random-effects meta-analyses for four RCTs (4356 patients, mean follow-up of 4.9 years) and six observational studies (9360 patients, mean follow-up of 5.2 years).

Results
In RCTs among DM patients, DES-based PCI, compared to CABG, was associated with a 30% increased relative risk (RR) (RR 1.30, 95% CI 1.09–1.56, I2 = 0%), while among non-DM patients, there was a 25% increased relative risk (RR 1.25, 95% CI 1.07–1.44, I2 = 0%) for the composite endpoint of all-cause mortality, myocardial infarction, stroke, and unplanned revascularization (MACCE). There was no evidence of EMM (p-value for interaction = 0.70). The mean weighted SYNTAX score was 25.7. In observational studies, there was no difference between DES-based PCI and CABG for all-cause mortality in patients with DM (RR 1.13, 95% CI 0.91–1.40, I2 = 0%).

Conclusions
CABG was superior to PCI for LMCAD in RCTs in DM patients for MACCE. Heart teams may consider DM as one of the many components in the clinical decision-making process, but may not want to consider DM as a primary deciding factor between DES-based PCI and CABG for LMCAD with low to intermediate anatomical complexity in the other coronary arteries.

Study registration

CRD42021246931 (PROSPERO).
Liushen Capsules, a promising clinical candidate for COVID-19, alleviates SARS-CoV-2-induced pulmonary in vivo and inhibits the proliferation of the variant virus strains in vitro
Authors: Ma Qinhai , Lei Biao , Chen Ruihan , Liu Bin , Lu Wencong , Jiang Haiming , Chen Zexing , Guo Xiaowen , Wang Yutao , Zhang Lu , Chen Qiaoyan , Li Xiaobo , Yang Zifeng 
Published: April 2022

AbstractBackgroundCoronavirus disease 2019 (COVID-19) causes a global pandemic and has devastating effects around the world, however, there are no specific antiviral drugs and vaccines for the constant mutation of SARS-CoV-2.PurposeIn this study, we evaluted the antiviral and anti-inflammatory activities of Liushen Capsules (LS) on different novel coronavirus in vitro, studied its therapeutic effects on novel SARS-CoV-2 infected mice and observed the LS’s clinical efficacy and safety in COVID-19.MethodsThe antiviral and aiti-inflammatory effects of LS on the 501Y.V2/B.1.35 and G/478K.V1/ B.1.617.2 strains were determined in vitro. A hACE2 mouse model of novel SARS-CoV-2 pneumonia was established. Survival rates, histological changes, inflammatory markers, lung virus titers and the expression of the key proteins in the NF-κB/MAPK signaling pathway was detected by western blotting and immumohistochemical staining in the lungs were measured. Subsequently, the disease duration, prognosis of disease, time of negative nucleic acid and the cytokines levels in serum were used to assess the efficacy of treatment with LS in patients.ResultsThe results showed that LS (2, 1, 0.5 μg/mL) could significantly inhibit the replication of the two SARS-CoV-2 variants and the expression of pro-inflammatory cytokines (IL-6, IL-8, IP-10, CCL-5, MIP-1α, IL-1α) induced by the virus in vitro. As for the survival experiment in mice, the survival rate of virus group was 20%, while LS-treatment groups (40, 80, 160 mg/kg) could increase the survival rate to 60, 100 and 100%, respectively. LS (40, 80, 160 mg/kg) could significantly decrease the lung titers in mice and it could improve the pathological changes, inhibit the excessive inflammatory mediators (IFN-α, IFN-γ, IP-10, MCP-1) and the protein expression of p-NF-κB p65 in mice. Moreover, LS could significantly decrease SARS-CoV-2-induced activation of p-NF-κB p65, p-IκBα, and p-p38 MAPK and increase the protein expression of the IκBα. In addition, the patient got complete relief of symptoms after being treated with LS for 6 days and was proven with negative PCR test after being treated for 23 days. Finally, treatment with LS could reduce the release of inflammatory cytokines (IL-6, PDGF-AA/BB, Eotaxin, MCP-1, MIP-1α, MIP-1β, GRO, CCL-5, MCP-3, IP-10, IL-1α).ConclusionLS effectively alleviated novel SARS-CoV-2 or variants induced pneumonia in vitro and in vivo, and improved the prognosis of COVID-19. In light of the efficacy and safety profiles, LS could be considered for the treatment of COVID-19 with a broad-spectrum antiviral and anti-inflammatory agent.
Chimeric antigen receptors containing the OX40 signalling domain enhance the persistence of T cells even under repeated stimulation with multiple myeloma target cells
Authors: Tan Jingwen , Jia Yujie , Zhou Meixia , Fu Chengcheng , Tuhin Israth Jahan , Ye Jing , Monty Masuma Akter , Xu Nan , Kang Liqing , Li Minghao , Shao Jiaqi , Fang Xiaoyan , Zhu Hongjia , Yan Lingzhi , Qu Changju , Xue Shengli , Jin Zhengming , Chen Suning , Huang Haiwen , Xu Yang , Chen Jia , Miao Miao , Tang Xiaowen , Li Caixia , Yan Zhiqiang , Wu Depei , Yu Lei 
Published: April 2022

AbstractPersistence of CAR-T cell function is associated with relapse rate after CAR-T therapy, while co-stimulatory agents are highly concerned with the persistence of CAR-T cells. In this study, we designed and constructed a series of BCMA-targeting second-generation CAR constructs containing CD28, 41BB, and OX40 molecules, respectively, to identify the costimulatory domains most favorable for persistence. The results of routine in vitro studies showed that OX40-CAR-T and 41BB-CAR-T had similar antitumor effects and were superior to CD28-CAR-T in terms of proliferation and cytotoxicity. Although difficult to distinguish by conventional functional assays, OX40-CAR-T cells exhibited greater proliferation and enhanced immune memory than 41BB-CAR-T cells with the repeated stimulation assay by BCMA-expressing target cells. In vivo studies further demonstrated that OX40-CAR-T cells had stronger proliferative activity than 41BB-CAR-T cells, which was highly consistent with the in vitro antitumor activity and proliferation results. Our study provides for the first time a scientific basis for designing OX40-CAR-T cell therapy to improve relapse in patients with MM after CAR-T treatment.
Association of waist circumference with blood pressure and familial dietary habits in preschool children: a cross-sectional study in northeastern China
Authors: Tang Xiao , Liu Yang , Hu Jiajin , Zhai Lingling , Jia Lihong , Ding Ning , Ma Yanan , Wen Deliang 
Published: April 2022

Abstract
Background
Childhood obesity increases the risk of elevated blood pressure (BP) in children. Body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR) are traditional obesity indices, but the extent to which these indices are associated with elevated BP in childhood remains debatable. Moreover, the familial dietary environment plays an important role in obesity, so it is necessary to determine the most relevant dietary factors for childhood obesity to prevent elevated BP. Our study aimed to identify the obesity indices that are most closely associated with elevated BP and then to determine the independent familial dietary factors for those obesity indices.

Method
A total of 605 children aged 2 to 6 years, as well as their parents, were involved in this study. The weight, height, WC and BP of the children were measured. Information on familial environments was obtained by questionnaires completed by the parents. BMI, WC and WHtR were standardized into z scores, and categorical variables of these three obesity indices were defined as BMI Category, WC Category and WHtR Category. Logistic regression was used to analyse the associations between all obesity indices and elevated BP. Multivariate linear regression and logistic regression were used to determine the independent factors for obesity indices.

Results
The obesity indices that were most closely associated with elevated BP were WC and WC Category. Parental BMI, birth weight, eating wheat as a staple food, appetite, eating speed, snacking while watching TV, parental encouragement to eat a diverse assortment of foods and drinking milk were independently associated with WC in both males and females. The risk of abdominal obesity increased 1.375 times in males and 1.631 times in females if appetite increased one level. If eating speed increased one level, the risk of abdominal obesity increased 1.165 times in males and 0.905 times in females. Females who drank milk more than 6 times per week had a 0.546 times lower risk of abdominal obesity.

Conclusion
WC was an anthropometric parameter more closely associated with elevated BP. In addition to genetics, some familial dietary factors involving eating preference, eating habits and parental feeding practice were independently associated with WC and abdominal obesity in preschool children.
Population-based estimates of age-specific cumulative risk of breast cancer for pathogenic variants in ATM
Authors: Renault Anne-Laure , Dowty James G. , Steen Jason A. , Li Shuai , Winship Ingrid M. , Giles Graham G. , Hopper John L. , Southey Melissa C. , Nguyen-Dumont Tú 
Published: April 2022

AbstractBackgroundMultigene panel tests for breast cancer predisposition routinely includeATMas it is now a well-established breast cancer predisposition gene.MethodsWe includedATMin a multigene panel test applied to the Australian Breast Cancer Family Registry (ABCFR), a population-based case–control–family study of breast cancer, with the purpose of estimating the prevalence and penetrance of heterozygousATMpathogenic variants from the family data, using segregation analysis.ResultsThe estimated breast cancer hazard ratio for carriers of pathogenicATMvariants in the ABCFR was 1.32 (95% confidence interval 0.45–3.87;P = 0.6). The estimated cumulative risk of breast cancer to age 80 years for heterozygous ATMpathogenic variant carriers was estimated to be 13% (95% CI 4.6–30).ConclusionsAlthoughATMhas been definitively identified as a breast cancer predisposition gene, further evidence, such as variant-specific penetrance estimates, are needed to inform risk management strategies for carriers of pathogenic variants to increase the clinical utility of population testing of this gene.
The One Nutrition in Complex Environments (ONCE) study protocol: a cluster-randomized multi-level multi-sectoral intervention to improve nutrition in Uganda
Authors: Griswold Stacy P. , Marshak Anastasia , Fitzpatrick Merry , Lantagne Daniele , Shoenmakers Kate , Hebie Marlene , Radday Anne , De Groote Hugo , Mehta Saurabh , Gottlieb Greg , Webb Patrick , Ghosh Shibani 
Published: April 2022

Abstract
Objective
To implement and measure the effects of a multi-level multi-sectoral social behavior change (SBC) intervention in Agago District of Northern Uganda and to determine the potential for scale-up.

Intervention
Compare the Nutrition Impact and Positive Practice (NIPP) approach to a NIPP+ approach. The NIPP approach involves nutrition education and SBC, whereas the NIPP+ adds agricultural inputs, training, and tools to support improved farm and water quality practices. The intervention effect will be measured through lower levels of aflatoxin in grain, lower water contamination, and improved knowledge on nutrition and health.

Design
This is a three-arm cluster-randomized controlled superiority trial (cRCT). The study arms include the following: group 1: NIPP; group 2: NIPP+, and group 3: control. Groups 1 and 2 will receive a 12-week intervention (NIPP or NIPP+) with active monitoring and longitudinal follow-up at 2, 6, and 12 months post-intervention. Additionally, an in-depth process and performance evaluation of each intervention arm will be undertaken using quantitative and qualitative methods. A total of 60 clusters from 5 subcounties of the Agago district will be randomly selected, and 15 households per cluster will be recruited using specific inclusion/exclusion criteria for a total of 900 households (300/arm). Respondents for the qualitative portion will be purposely selected.

Analysis
We will collect data from all participants at 3 time points: baseline, endline, and 12 months post-intervention. The analysis will utilize intent-to-treat (ITT) using the initial randomization of the treatment arms to determine the overall impact of having the NIPP vs. NIPP+ vs. control. Mixed effects models will be used to determine the role of time-variant and invariant individual household, and community characteristics, as well as measures of exposure and integration on key outcome indicators. A difference-in-difference analysis (baseline/endline, baseline/12 months post-intervention, endline/12 months post-intervention) will also be used to triangulate findings.

Trial registration
NCT04209569. One Nutrition in Complex Environments (ONCE) Registered 24 December 2019