bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Discovering shine through feedback seeking”---feedback seeking among new graduate nurses: a qualitative study
Authors: Song Ziling , Shen Yuanyuan , Yao Xin , Wen Siqi , Wang Jing , Chen Yanyan , Zhang Peihua , Huang Xiaoqiong 
Published: January 2024

Abstract
Background
Feedback is critical to improving practitioners’ clinical practice and professional growth. Although they are still considered junior practitioners, their feedback-seeking experiences have yet to be investigated. This study aimed to understand the fundamental thoughts and experiences of new graduate nurses regarding feedback-seeking and to identify the main factors that influence their feedback-seeking behaviors.

Methods
Conducting a descriptive phenomenological study, semi-structured in-depth interviews with newly graduated nurses from four hospitals in Zhejiang Province, China, face-to-face or via video call in the hospital conference room through purposive and snowball sampling. Interview data were evaluated using Colaizzi’s 7-step phenomenological data analysis. The COREQ checklist was followed.

Results
A total of 15 new graduate nurses were interviewed as a sample, and 13 categories emerged from our data. They were categorized into four central elements: (1) perceptions and attitudes, (2) drivers, (3) dilemmas and needs, and (4) transformation and growth.

Conclusions
This study found that new graduate nurses have various needs but face dilemmas in the feedback-seeking process. Nursing managers should be proficient at providing positive leadership, collaborating with clinical mentors to foster an atmosphere where new graduate nurses may obtain honest, transparent, and fair feedback, and exercising caution when providing negative feedback.
Association between game metrics in a simulation game and nursing students’ surgical nursing knowledge – a quasi-experimental study
Authors: Koivisto Jaana-Maija , Buure Tuija , Engblom Janne , Rosqvist Kristiina , Haavisto Elina 
Published: January 2024

Abstract
Background
Simulation games are effective for acquiring surgical nursing knowledge during education by offering possibilities to learn theoretical knowledge through practical patient scenarios, thus preparing students for demanding surgical nursing care. Game metrics stored in the game system enable assessment of students’ behaviour while gameplaying. Combining game metrics with the assessment of a student’s surgical nursing knowledge allows versatile information to be obtained about the student’s learning outcomes. However, studies on game metrics stored in systems and their relationship with learning outcomes are scarce.

Methods
The aim here was to evaluate the association between game metrics in a simulation game and nursing students’ surgical nursing knowledge. Nursing students from three universities of applied sciences in Finland participated in a one-week simulation gameplaying intervention that included five surgical nursing scenarios. Students’ surgical nursing knowledge was investigated with a quasi-experimental, one-group, pre- and post-test design using a surgical nursing knowledge test. In total, 280 students filled in the knowledge tests. In addition, cross-sectional game data were collected at a single time point between pre- and post-tests. The data were analysed with descriptive statistics and multivariate analysis methods.

Results
Students’ surgical nursing knowledge improved with the intervention. The total number of playthroughs was 3562. The mean maximum score was 126.2 (maximum score range 76–195). The mean playing time of all playthroughs by all players was 4.3 minutes (SD = 81.61). A statistically significant association was found between mean score and knowledge test total score (p < 0.0072), but no significant association emerged between mean playing time and knowledge test total score.

Conclusion
The results indicated that the higher the mean score the better the students’ surgical nursing knowledge in the knowledge test. This study did not show that the time spent playing had an impact on students’ post-playing knowledge. Our findings support the idea that game metrics can be used in performance evaluation and the results can be used to improve nursing students’ readiness for challenging preoperative and postoperative clinical situations.
Understanding the relationship of academic motivation and social support in graduate nursing education in Egypt
Authors: El-Sayed Mona Metwally , Taha Samah Mohamed , AbdElhay Eman Sameh , Hawash Manal Mohammed 
Published: January 2024

Abstract
Background
Obtaining a postgraduate nursing education in Egypt requires substantial resources, including a robust academic drive and supportive relationships. These resources help students overcome challenges and navigate their educational journey. This study examines the relationship between academic motivation and social support among nursing graduate students.

Design
A cross-sectional survey was conducted at two nursing colleges in Egypt, involving 410 randomly selected graduate students.

Measures
The Academic Motivation Scale—College Version (AMS-C 28) and the Multidimensional Scale of Perceived Social Support (MSPSS) were used.

Findings
Findings revealed a statistically significant positive relationship between academic motivation and perceived social support (r = 0.515, p < 0.001). Hierarchical regression analysis revealed that 12.9% (Adjusted R² = 0.129) of the variance in academic motivation could be explained by perceived social support and level of education.

Conclusion
This study pinpointed intrinsic motivation as the primary impetus for graduate nursing students. Robust social support and active participation in social and recreational activities were also significant motivators. Nursing education programs can enhance intrinsic motivation by integrating authentic learning experiences, providing empowering mentorship, offering condensed doctoral programs, and ensuring substantial peer support. The exploration of the role of novelty in graduate nursing education, facilitated by innovative teaching methods such as collaborative virtual reality simulations, gamification, and team-based research projects, can be advantageous. Building robust social networks is vital for establishing a supportive and motivating learning environment for nursing graduates in Egypt.
Health support of people with intellectual disability and the crucial role of support workers
Authors: Nijhof Kim , Boot Fleur H. , Naaldenberg Jenneken , Leusink Geraline L. , Bevelander Kirsten E. 
Published: January 2024

Abstract
Background
People with intellectual disability have a poorer health status than the general population. In The Netherlands, support workers play a key role in meeting health support needs of people with intellectual disability. Research on how people with intellectual disability and their support workers experience the support worker’s role in preventing, identifying, and following up health needs of people with intellectual disability is scarce. To enhance health support of people with intellectual disability it is crucial that we understand how health support is delivered in everyday practice. Therefore, this study investigated experiences of people with intellectual disability and support workers with the health support of people with intellectual disability.

Method
Data collection consisted of six focus group (FG) discussions with between four and six participants (N = 27). The FGs consisted of three groups with support workers (n = 15), two groups with participants with mild to moderate intellectual disability (n = 8), and one group with family members as proxy informants who represented their relative with severe to profound intellectual disability (n = 4). The data was analysed thematically on aspects relating to health support.

Results
We identified three main themes relevant to the health support of people with intellectual disability: 1) dependence on health support, 2) communication practices in health support, and 3) organizational context of health support. Dependence on health support adresses the way in which support workers meet a need that people with intellectual disability cannot meet themselves, and communication practices and organizational context are identified as systems in which health support takes place.

Conclusion
This study investigated experiences with the health support of people with intellectual disability from the perspectives of people with intellectual disability and support workers. We discuss the dependence of people with intellectual disability and the complexity of health support in everyday practice. We provide practical implications that can strengthen support workers in the provision of health support for people with intellectual disability in everyday practice. The findings of this study emphasize the need for intellectual disability care-provider organizations to establish policies around consistency in support staff to make it easier to identify and follow up health needs, and an environment where support staff can develop their expertise concerning communication practices, lifestyle choices, and identifying and following up health needs.
Deciphering the roles of subcellular distribution and interactions involving the MEF2 binding region, the ankyrin repeat binding motif and the catalytic site of HDAC4 in Drosophila neuronal morphogenesis
Authors: Tan Wei Jun , Hawley Hannah R. , Wilson Sarah J. , Fitzsimons Helen L. 
Published: January 2024

Abstract
Background
Dysregulation of nucleocytoplasmic shuttling of histone deacetylase 4 (HDAC4) is associated with several neurodevelopmental and neurodegenerative disorders. Consequently, understanding the roles of nuclear and cytoplasmic HDAC4 along with the mechanisms that regulate nuclear entry and exit is an area of concerted effort. Efficient nuclear entry is dependent on binding of the transcription factor MEF2, as mutations in the MEF2 binding region result in cytoplasmic accumulation of HDAC4. It is well established that nuclear exit and cytoplasmic retention are dependent on 14–3-3-binding, and mutations that affect binding are widely used to induce nuclear accumulation of HDAC4. While regulation of HDAC4 shuttling is clearly important, there is a gap in understanding of how the nuclear and cytoplasmic distribution of HDAC4 impacts its function. Furthermore, it is unclear whether other features of the protein including the catalytic site, the MEF2-binding region and/or the ankyrin repeat binding motif influence the distribution and/or activity of HDAC4 in neurons. Since HDAC4 functions are conserved in Drosophila, and increased nuclear accumulation of HDAC4 also results in impaired neurodevelopment, we used Drosophila as a genetic model for investigation of HDAC4 function.

Results
Here we have generated a series of mutants for functional dissection of HDAC4 via in-depth examination of the resulting subcellular distribution and nuclear aggregation, and correlate these with developmental phenotypes resulting from their expression in well-established models of neuronal morphogenesis of the Drosophila mushroom body and eye. We found that in the mushroom body, forced sequestration of HDAC4 in the nucleus or the cytoplasm resulted in defects in axon morphogenesis. The actions of HDAC4 that resulted in impaired development were dependent on the MEF2 binding region, modulated by the ankyrin repeat binding motif, and largely independent of an intact catalytic site. In contrast, disruption to eye development was largely independent of MEF2 binding but mutation of the catalytic site significantly reduced the phenotype, indicating that HDAC4 acts in a neuronal-subtype-specific manner.

Conclusions
We found that the impairments to mushroom body and eye development resulting from nuclear accumulation of HDAC4 were exacerbated by mutation of the ankyrin repeat binding motif, whereas there was a differing requirement for the MEF2 binding site and an intact catalytic site. It will be of importance to determine the binding partners of HDAC4 in nuclear aggregates and in the cytoplasm of these tissues to further understand its mechanisms of action.
Identification of potential biological processes and key genes in diabetes-related stroke through weighted gene co-expression network analysis
Authors: He Yong , Bai Yang , Huang Qin , Xia Jian , Feng Jie 
Published: January 2024

Abstract
Background
Type 2 diabetes mellitus (T2DM) is an established risk factor for acute ischemic stroke (AIS). Although there are reports on the correlation of diabetes and stroke, data on its pathogenesis is limited. This study aimed to explore the underlying biological mechanisms and promising intervention targets of diabetes-related stroke.

Methods
Diabetes-related datasets (GSE38642 and GSE44035) and stroke-related datasets (GSE16561 and GSE22255) were obtained from the Gene Expression omnibus (GEO) database. The key modules for stroke and diabetes were identified by weight gene co-expression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes Genomes (KEGG) analyses were employed in the key module. Genes in stroke- and diabetes-related key modules were intersected to obtain common genes for T2DM-related stroke. In order to discover the key genes in T2DM-related stroke, the Cytoscape and protein–protein interaction (PPI) network were constructed. The key genes were functionally annotated in the Reactome database.

Results
By intersecting the diabetes- and stroke-related crucial modules, 24 common genes for T2DM-related stroke were identified. Metascape showed that neutrophil extracellular trap formation was primarily enriched. The hub gene was granulin precursor (GRN), which had the highest connectivity among the common genes. In addition, functional enrichment analysis indicated that GRN was involved in neutrophil degranulation, thus regulating neutrophil extracellular trap formation.

Conclusions
This study firstly revealed that neutrophil extracellular trap formation may represent the common biological processes of diabetes and stroke, and GRN may be potential intervention targets for T2DM-related stroke.
Novel compound heterozygous MYO15A splicing variants in autosomal recessive non-syndromic hearing loss
Authors: Zheng Kaifeng , Lin Sheng , Gao Jian , Chen Shiguo , Su Jindi , Liu Zhiqiang , Duan Shan 
Published: January 2024

Abstract
Background
Hereditary hearing loss is a highly heterogeneous disorder. This study aimed to identify the genetic cause of a Chinese family with autosomal recessive non-syndromic sensorineural hearing loss (ARNSHL).

Methods
Clinical information and peripheral blood samples were collected from the proband and its parents. Two-step high-throughput next-generation sequencing on the Ion Torrent platform was applied to detect variants as follows. First, long-range PCR was performed to amplify all the regions of the GJB2, GJB3, SLC26A4, and MT-RNR1 genes, followed by next-generation sequencing. If no candidate pathogenetic variants were found, the targeted exon sequencing with AmpliSeq technology was employed to examine another 64 deafness-associated genes. Sanger sequencing was used to identify variants and the lineage co-segregation. The splicing of the MYO15A gene was assessed by in silico bioinformatics prediction and minigene assays.

Results
Two candidate MYO15A gene (OMIM, #602,666) heterozygous splicing variants, NG_011634.2 (NM_016239.3): c.6177 + 1G > T and c.9690 + 1G > A, were identified in the proband, and these two variants were both annotated as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Further bioinformatic analysis predicted that the c.6177 + 1G > T variant might cause exon skipping and that the c.9690 + 1G > A variant might activate a cryptic splicing donor site in the downstream intronic region. An in vitro minigene assay confirmed the above predictions.

Conclusions
We identified a compound heterozygous splicing variant in the MYO15A gene in a Han Chinese family with ARNSHL. Our results broaden the spectrum of MYO15A variants, potentially benefiting the early diagnosis, prevention, and treatment of the disease.
Identification and validation of iron metabolism genes in osteoporosis
Authors: Li Zutao , Xu Jiangbo , Shi Shouyin , Weng Youlin , Guo Bin , Che Lixin , Sun Jungang 
Published: January 2024

Abstract
Background
Osteoporosis is the most common metabolic bone disease in humans. Exploring the expression difference of iron metabolism-related genes in osteoporosis can provide a new target for diagnosis and treatment.

Methods
First, we used online databases to identify differentially expressed genes (DEGs) related to iron metabolism in patients with osteoporosis. The differential genes were comprehensively analyzed by bioinformatics method (GO, KEGG, GSEA, immune infiltration analysis, PPI). The expression levels of hub genes and important signaling pathways were verified by qRT-PCR and Western blotting.

Results
A total of 23 iron metabolism-related genes with significant differences were identified, which were enriched in “regulation of protein dephosphorylation” and “negative regulation of protein dephosphorylation”. The GSEA results, heme metabolism and Myc targets v1 were among the top two pathways, both upregulated. The immune infiltration analysis revealed that the expressions of genes such as ABCA5, D2HGDH, GNAI2, and CTSW were correlated with the infiltration degree of significantly different cells. The PPI network contained 12 differentially expressed iron metabolism-related genes. Additionally, YWHAE, TGFB1, PPP1R15A, TOP2A, and CALR were mined as hub genes using the Cytoscape software. qRT PCR showed that the expression of TGF-β1, YWHAE, TOP2A and CALR increased. We also verified the expression of related proteins and genes in the oxidative stress signaling pathway by qRT PCR and Western blotting. The results showed that Mob1, YAP and TAZ molecules were highly expressed at the gene and protein levels.

Conclusions
These differentially expressed iron metabolism-related genes could provide new potential targets for the diagnosis and treatment of osteoporosis.
Nano-modified viruses prime the tumor microenvironment and promote the photodynamic virotherapy in liver cancer
Authors: Ou Da-Liang , Liao Zi-Xian , Kempson Ivan M. , Li Lin , Yang Pan-Chyr , Tseng S.-Ja 
Published: January 2024

Abstract
Background
As of 2020, hepatocellular carcinoma (HCC), a form of liver cancer, stood as the third most prominent contributor to global cancer-related mortality. Combining immune checkpoint inhibitors (ICI) with other therapies has shown promising results for treating unresectable HCC, offering new opportunities. Recombinant adeno-associated viral type 2 (AAV2) virotherapy has been approved for clinical use but it efficacy is stifled through systemic administration. On the other hand, iron oxide nanoparticles (ION) can be cleared via the liver and enhance macrophage polarization, promoting infiltration of CD8+ T cells and creating a more favorable tumor microenvironment for immunotherapy.

Methods
To enhance the efficacy of virotherapy and promote macrophage polarization towards the M1-type in the liver, ION-AAV2 were prepared through the coupling of ION-carboxyl and AAV2-amine using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC)/N-hydroxysulfosuccinimide (Sulfo-NHS). Efficacy after systemic delivery of ION-AAV2 in an orthotopic HCC model was evaluated.

Results
After 28 days, the tumor weight in mice treated with ION-AAV2 was significantly reduced by 0.56-fold compared to the control group. The ION-AAV2 treatment led to an approximate 1.80-fold increase in the level of tumor associated M1-type macrophages, while the number of M2-type macrophages was reduced by 0.88-fold. Moreover, a proinflammatory response increased the population of tumor-infiltrating CD8+ T cells in the ION-AAV2 group. This transformation converted cold tumors into hot tumors.

Conclusions
Our findings suggest that the conjugation of ION with AAV2 could be utilized in virotherapy while simultaneously exploiting macrophage-modulating cancer immunotherapies to effectively suppress HCC growth.
PDGF-BB accelerates TSCC via fibroblast lactates limiting miR-26a-5p and boosting mitophagy
Authors: Xu Jianguo , Bian Li , You Dingyun , Li Ziliang , Wang Tingting , Li Yiting , Ren Xiaobin , He Yongwen 
Published: January 2024

AbstractThe tumor microenvironment and cancer-associated fibroblasts (CAFs) play crucial roles in tumor development, and their metabolic coupling remains unclear. Clinical data showed a positive correlation between PDGF-BB, CAFs, and glycolysis in the tumor microenvironment of oral tongue squamous cell carcinoma patients. In vitro, CAFs are derived from hOMF cells treated with PDGF-BB, which induces their formation and promotes aerobic glycolysis. Mitophagy increased the PDGF-BB-induced formation of CAF phenotypes and aerobic glycolysis, while autophagy inhibition blocked PDGF-BB-induced effects. Downregulation of miR-26a-5p was observed in CAFs; upregulation of miR-26a-5p inhibited the expression of mitophagy-related proteins ULKI, Parkin, PINK1, and LC3 and aerobic glycolysis in PDGF-BB-induced CAFs. PDGF-BB-induced CAFs promoted tumor cell proliferation, invasion, metastasis, NF-κB signaling pathway activation, and PDGF-BB secretion. Thus, PDGF-BB is associated with lactate-induced CAF formation and glucose metabolism reprogramming. These findings indicate potential therapeutic targets in oral tongue squamous cell carcinoma.
LncRNA FOXD1-AS1 regulates pancreatic cancer stem cell properties and 5-FU resistance by regulating the miR-570-3p/SPP1 axis as a ceRNA
Authors: Ouyang Liu , Sun Min-min , Zhou Ping-sheng , Ren Yi-wei , Liu Xin-yu , Wei Wan-ying , Song Zhen-shun , Lu Kai , Yang Li-xue 
Published: January 2024

AbstractCancer stem cells (CSCs) play a pivotal role in the pathogenesis of human cancers. Previous studies have highlighted the role of long non-coding RNA (lncRNA) in modulating the stemness of CSCs. In our investigation, we identified an upregulation of lncRNA FOXD1-AS1 in CSCs. The enforced expression of lncRNA FOXD1-AS1 promotes tumorigenesis and self-renewal in pancreatic cancer CSCs. Conversely, the knockdown of lncRNA FOXD1-AS1 inhibits tumorigenesis and self-renewal in pancreatic cancer CSCs. Furthermore, our findings reveal that lncRNA FOXD1-AS1 enhances self-renewal and tumorigenesis in pancreatic cancer CSCs by up-regulating osteopontin/secreted phosphoprotein 1(SPP1) and acting as a ceRNA to sponge miR-570-3p in pancreatic cancer (PC) CSCs. Additionally, lncRNA FOXD1-AS1 depleted pancreatic cancer cells exhibit heightened sensitivity to 5-FU-indued cell growth inhibition and apoptosis. Analysis of patient-derived xenografts (PDX) indicates that a low level of lncRNA FOXD1-AS1 may serve as a predictor of 5-FU benefits in PC patients. Moreover, the introduction of SPP1 can reverse the sensitivity of lncRNA FOXD1-AS1-knockdown PC cells to 5-FU-induced cell apoptosis. Importantly, molecular studies have indicated that the elevated levels of lncRNAFOXD1-AS1 in PC are facilitated through METTL3 and YTHDF1-dependent m6A methylation. In summary, our results underscore the critical functions of lncRNA FOXD1-AS1 in the self-renewal and tumorigenesis of pancreatic cancer CSCs, positioning lncRNA FOXD1-AS1 as a promising therapeutic target for PC.