bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sociocultural and perceived public image of nurses among nursing students: the mediating role of self-concept
Authors: Sacgaca Lailani , an Eddieson Pasay , Alqarni Aida Sanad , Pangket Petelyne , Alshammari Salman Amish , Ramadan Magda Yousif , Alonezei Ameera Khaled , Alamoudi Fatmah Ahmed , Mohammed Insaf Hassan Ahmed , Cabansag Dolores , Benjamin Lizy Sonia 
Published: April 2024

Abstract
Background
Studying the public perception of nurses among nursing students is vital in establishing strategic solutions to recruit and retain more students in nursing programs and to contain nurses in the health care system.

Aim
This study aimed to determine the mediating role of self-concept in the relationship between sociocultural and perceived public image of nurses.

Methods
This study employed a correlational approach using convenience sampling of 1390 participants. This study was conducted at six large universities in three regions of Saudi Arabia (central, northern, and eastern). Student nurses in their second to fourth years of study were included as participants, with an 89.7% response rate. Data were collected from January to April 2023.

Results
A significant positive relationship was observed between sociocultural factors and self-concept (r = .685, p = .0001). In addition, there was a significant positive relationship between self-concept and public image (PI) (r = .352, p value = 0.0001). Furthermore, there was a significant positive relationship between sociocultural and public image (r = .456, p = .0001); sociocultural had a direct effect on self-concept (β = 0.324, SE = 0.098, t = 9.429, p < .0001) and public image (β = 0.605, SE = 0.038, t = 22.617, p < .0001). Furthermore, sociocultural had an indirect effect on public image through self-concept (H6) (β = 0.389, SE = 0.123, t = 12.766, p < .0001).

Discussion
The study findings suggest that nursing school programs should take measures to foster a supportive environment that promotes self-concept and public image, while also being mindful of the sociocultural background. This would also open the scope for further research on the matter involving multiple centers.

Conclusions
This study suggests the need for programs to boost self-concept and public image that consider sociocultural influences. These ’findings have crucial implications for student nurses’ social and psychological wellbeing as they improve the understanding of how sociocultural affects self-concept and public image.
Arginine and its metabolites stimulate proliferation, differentiation, and physiological function of porcine trophoblast cells through β-catenin and mTOR pathways
Authors: Li Shuai , Ye Xiangyang , Wen Xiaolu , Yang Xuefen , Wang Li , Gao Kaiguo , Xiao Hao , Jiang Zongyong 
Published: April 2024

AbstractArginine, which is metabolized into ornithine, proline, and nitric oxide, plays an important role in embryonic development. The present study was conducted to investigate the molecular mechanism of arginine in proliferation, differentiation, and physiological function of porcine trophoblast cells (pTr2) through metabolic pathways. The results showed that arginine significantly increased cell viability (P < 0.05). The addition of arginine had a quadratic tendency to increase the content of progesterone (P = 0.06) and protein synthesis rate (P = 0.03), in which the maximum protein synthesis rate was observed at 0.4 mM arginine. Arginine quadratically increased (P < 0.05) the intracellular contents of spermine, spermidine and putrescine, as well as linearly increased (P < 0.05) the intracellular content of NO in a dose-dependent manner. Arginine showed a quadratic tendency to increase the content of putrescine (P = 0.07) and a linear tendency to increase NO content (P = 0.09) in cell supernatant. Moreover, increasing arginine activated (P < 0.05) the mRNA expressions for ARG, ODC, iNOS and PCNA. Furthermore, inhibitors of arginine metabolism (L-NMMA and DFMO) both inhibited cell proliferation, while addition of its metabolites (NO and putrescine) promoted the cell proliferation and cell cycle, the mRNA expressions of PCNA, EGF and IGF-1, and increased (P < 0.05) cellular protein synthesis rate, as well as estradiol and hCG secretion (P < 0.05). In conclusion, our results suggested that arginine could promote cell proliferation and physiological function by regulating the metabolic pathway. Further studies showed that arginine and its metabolites modulate cell function mainly through β-catenin and mTOR pathways.
Exploring the role of spending on malaria incidence in Uganda using the auto-regressive distributed lag approach
Authors: Katushabe Jemimah , Nnyanzi John Bosco , Muwanga Gertrude Sebunya 
Published: April 2024

Abstract
Background
Malaria has remained a persistent global health problem. Despite multiple government and donor initiatives to eradicate malaria and its detrimental effects on Uganda's health outcomes, the incidence of malaria is worrying as it appears higher than the average of 219 cases per 1000 for sub-Saharan Africa for the period 2017–2018. This study investigated the effect of public and private healthcare spending on the incidence of malaria in Uganda.

Methods
Employing time series data spanning over 20 years from the first quarter of 2000 to the last quarter of 2019, the study builds a model based on the Grossman framework for analysing demand for health. The estimation technique used was the ARDL approach that takes into account reverse causality and incidental relationships. Prior to the adoption of the technique, a bounds test was performed to determine whether the variables contained in the model have a long-term relationship. Several diagnostic tests for serial correlation, functional normality, and heteroskedastic specification error were carried out to verify the ARDL model's goodness of fit. Additionally, the cumulative sum of recursive (CUSUM) and cumulative sum of squares of recursive residuals (CUSUMSQ) were used to test model stability.

Results
The results indicate that in the long run, an increase in public spending of one percent significantly reduces malaria incidence by 0.196 at the 10 percent level of significance. On the other hand, there is no significant evidence of private health expenditure's effect on malaria incidence. However, in the short run, public spending reduces malaria incidence by a smaller magnitude of 0.158 percent relative to the long-run. Still, private expenditure is found to exhibit no significant effect. Additional findings point to the importance of GDP per capita and urban population growth in reducing malaria incidence, whereas female unemployment, income inequality, as well as female-headed household. In the short run, however, the female-headed households and urban population growth are found to significantly reduce malaria incidence while an improvement in regulatory quality decreases malaria incidence by 0.129 percent.

Conclusions
There is need for further government interventions to reduce malaria incidence in the country via budget allocation, as well as the strengthening of programmes to raise household income to support private health spending, in addition to the development of strategies to promote well-planned and organized urban centres.
Ångstrom-scale gold particles loaded with alendronate via alpha-lipoic acid alleviate bone loss in osteoporotic mice
Authors: Gao Weihang , Li Jiao Jiao , Shi Jingyu , Lan Hongbing , Guo Yuanyuan , Fu Dehao 
Published: April 2024

AbstractOsteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of bone microarchitecture, resulting in reduced bone strength and increased fracture risk. Current treatment options for osteoporosis are limited by factors such as efficacy, cost, availability, side effects, and acceptability to patients. Gold nanoparticles show promise as an emerging osteoporosis therapy due to their osteogenic effects and ability to allow therapeutic delivery but have inherent constraints, such as low specificity and the potential for heavy metal accumulation in the body. This study reports the synthesis of ultrasmall gold particles almost reaching the Ångstrom (Ång) dimension. The antioxidant alpha-lipoic acid (LA) is used as a dispersant and stabilizer to coat Ångstrom-scale gold particles (AuÅPs). Alendronate (AL), an amino-bisphosphonate commonly used in drug therapy for osteoporosis, is conjugated through LA to the surface of AuÅPs, allowing targeted delivery to bone and enhancing antiresorptive therapeutic effects. In this study, alendronate-loaded Ångstrom-scale gold particles (AuÅPs-AL) were used for the first time to promote osteogenesis and alleviate bone loss through regulation of the WNT signaling pathway, as shown through in vitro tests. The in vivo therapeutic effects of AuÅPs-AL were demonstrated in an established osteoporosis mouse model. The results of Micro-computed Tomography, histology, and tartrate-resistant acid phosphatase staining indicated that AuÅPs-AL significantly improved bone density and prevented bone loss, with no evidence of nanoparticle-associated toxicity. These findings suggest the possible future application of AuÅPs-AL in osteoporosis therapy and point to the potential of developing new approaches for treating metabolic bone diseases using Ångstrom-scale gold particles.
Biomimetic nanodrug blocks CD73 to inhibit adenosine and boosts antitumor immune response synergically with photothermal stimulation
Authors: Li Tan , Zhang Xingyu , Shi Chengyu , Liu Qiao , Zhao Yuetao 
Published: April 2024

AbstractCombination of tumor immunotherapy with photothermal therapy (PTT) is a feasible tactic to overcome the drawback of immunotherapy such as poor immune response. Via triggering the immunogenic cells death (ICD), PTT can stimulate the activity of immune cells, but meanwhile, the level of adenosine is elevated via the CD73-induced decomposition of ATP which is overexpressed accompanying with the PTT process, resulting in negative feedback to impair the immune stimulation. Herein, we developed a novel biomimetic photothermal nanodrug to specifically block CD73 for inhibition of adenosine production and more efficient priming of the suppressive immune microenvironments. The nanodrug, named as AptEM@CBA, is constructed by encapsulation of photothermal agent black phosphorus quantum dots (BPQDs) and selective CD73 inhibitor α, β-Methyleneadenosine 5′-diphosphate (AMPCP) in chitosan nanogels, which are further covered with aptamer AS1411 modified erythrocyte membrane (EM) for biomimetic camouflage. With AS1411 induced active targeting and EM induced long blood circulation time, the enrichment of the nanodrug tumor sites is promoted. The photothermal treatment promotes the maturation of dendritic cells. Meanwhile, the release of AMPCP suppress the adenosine generation via CD73 blockade, alleviating the impairment of adenosine to dendritic cells and suppressing regulatory T cells, synergically stimulate the activity of T cells. The combination of CD73 blockade with PTT, not only suppresses the growth of primary implanted tumors, but also boosts strong antitumor immunity to inhibit the growth of distal tumors, providing good potential for tumor photoimmunotherapy.
Loss of tumor-derived SMAD4 enhances primary tumor growth but not metastasis following BMP4 signalling
Authors: Chi Lap Hing , Redfern Andrew D. , Roslan Suraya , Street Ian P. , Burrows Allan D. , Anderson Robin L. 
Published: April 2024

Abstract
Background
Bone morphogenetic protein 4 (BMP4) is a potent inhibitor of breast cancer metastasis. However, a tumor-promoting effect of BMP4 is reported in other tumor types, especially when SMAD4 is inactive.

Methods
To assess the requirement for SMAD4 in BMP4-mediated suppression of metastasis, we knocked down SMAD4 in two different breast tumors and enforced SMAD4 expression in a third line with endogenous SMAD4 deletion. In addition, we assessed the requirement for SMAD4 in tumor cell-specific BMP signalling by expression of a constitutively active BMP receptor. Delineation of genes regulated by BMP4 in the presence or absence of SMAD4 was assessed by RNA sequencing and a BMP4-induced gene, MYO1F was assessed for its role in metastasis. Genes regulated by BMP4 and/or SMAD4 were assessed in a publicly available database of gene expression profiles of breast cancer patients.

Results
In the absence of SMAD4, BMP4 promotes primary tumor growth that is accompanied by increased expression of genes associated with DNA replication, cell cycle, and MYC signalling pathways. Despite increased primary tumor growth, BMP4 suppresses metastasis in the absence of tumor cell expression of SMAD4. Consistent with the anti-metastatic activity of BMP4, enforced signalling through the constitutively active receptor in SMAD4 positive tumors that lacked BMP4 expression still suppressed metastasis, but in the absence of SMAD4, the suppression of metastasis was largely prevented. Thus BMP4 is required for suppression of metastasis regardless of tumor SMAD4 status. The BMP4 upregulated gene, MYO1F, was shown to be a potent suppressor of breast cancer metastasis. Gene signature upregulated by BMP4 in the absence of SMAD4 was associated with poor prognosis in breast cancer patients, whereas gene signature upregulated by BMP4 in the presence of SMAD4 was associated with improved prognosis.

Conclusions
BMP4 expression is required for suppression of metastasis regardless of the SMAD4 status of the tumor cells. Since BMP4 is a secreted protein, we conclude that it can act both in an autocrine manner in SMAD4-expressing tumor cells and in a paracrine manner on stromal cells to suppress metastasis. Deletion of SMAD4 from tumor cells does not prevent BMP4 from suppressing metastasis via a paracrine mechanism.
Developing and validating a clinlabomics-based machine-learning model for early detection of retinal detachment in patients with high myopia
Authors: Li Shengjie , Li Meiyan , Wu Jianing , Li Yingzhu , Han Jianping , Song Yunxiao , Cao Wenjun , Zhou Xingtao 
Published: April 2024

Abstract
Background
Retinal detachment (RD) is a vision-threatening disorder of significant severity. Individuals with high myopia (HM) face a 2 to 6 times higher risk of developing RD compared to non-myopes. The timely identification of high myopia-related retinal detachment (HMRD) is crucial for effective treatment and prevention of additional vision impairment. Consequently, our objective was to streamline and validate a machine-learning model based on clinical laboratory omics (clinlabomics) for the early detection of RD in HM patients.

Methods
We extracted clinlabomics data from the electronic health records for 24,440 HM and 5607 HMRD between 2015 and 2022. Lasso regression analysis assessed fifty-nine variables, excluding collinear variables (variance inflation factor > 10). Four models based on random forest, gradient boosting machine (GBM), generalized linear model, and Deep Learning Model were trained for HMRD diagnosis and employed for internal validation. An external test of the models was done. Three random data sets were further processed to validate the performance of the diagnostic model. The primary outcomes were the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUCPR) to diagnose HMRD.

Results
Nine variables were selected by all models. Given the AUC and AUCPR values across the different sets, the GBM model was chosen as the final diagnostic model. The GBM model had an AUC of 0.8550 (95%CI = 0.8322–0.8967) and an AUCPR of 0.5584 (95%CI = 0.5250–0.5879) in the training set. The AUC and AUCPR in the internal validation were 0.8405 (95%CI = 0.8060–0.8966) and 0.5355 (95%CI = 0.4988–0.5732). During the external test evaluation, it reached an AUC of 0.7579 (95%CI = 0.7340–0.7840) and an AUCPR of 0.5587 (95%CI = 0.5345–0.5880). A similar discriminative capacity was observed in the three random data sets. The GBM model was well-calibrated across all the sets. The GBM-RD model was implemented into a web application that provides risk prediction for HM individuals.

Conclusion
GBM algorithms based on nine features successfully predicted the diagnosis of RD in patients with HM, which will help ophthalmologists to establish a preliminary diagnosis and to improve diagnostic accuracy in the clinic.
Fusobacterium periodonticum BCT protein targeting glucose metabolism to promote the epithelial-mesenchymal transition of esophageal cancer cells by lactic acid
Authors: Guo Xinxin , Wan Ping , Shen Weitao , Sun Mingjun , Peng Zhenyan , Liao Yinghao , Huang Yang , Liu Ran 
Published: April 2024

Abstract
Background
The cancer microbiota was considered the main risk factor for cancer progression. We had proved that Fusobacterium periodonticum (F.p) was higher abundance in Esophageal cancer(EC)tissues. Bioinformation analysis found that BCT was a key virulence protein of F.p. However, little is known about the role and mechanism of BCT in EC. This study aimed to recognize the key virulence protein of F.p and explore the mechanism of BCT in promoting EC.

Methods
We constructed a eukaryotic expression vector and purified the recombinant protein BCT. CCK8 used to analyzed the activity of EC after treated by different concentration of BCT. UPLC-MS/MS and ELISA used to detect the metabonomics and metabolites. The ability of migration and invasion was completed by transwell assay. RT-QPCR, WB used to analyze the expression of relevant genes.

Results
Our data showed that BCT was higher expression in EC tumor tissues (p < 0.05) and BCT in 20 µg/mL promoted the survival, invasion and migration of EC cells (EC109) (p < 0.05). Meanwhile, UPLC-MS/MS results suggested that BCT resulted in an augmentation of hypotaurine metabolism, arachidonic acid metabolism, glycolysis/gluconeogenesis, tryptophan metabolism, citrate cycle activity in EC109. The metabolic changes resulted in decreasing in glucose and pyruvate levels but increase in lactate dehydrogenase (LDH) activity and lactic acid (LA) as well as the expression of glucose transporter 1, Hexokinase 2, LDH which regulated the glycolysis were all changed (p < 0.05). The BCT treatment upregulated the expression of TLR4, Akt, HIF-1α (p < 0.05) which regulated the production of LA. Furthermore, LA stimulation promoted the expression of GPR81, Wnt, and β-catenin (p < 0.05), thereby inducing EMT and metastasis in EC109 cells.

Conclusion
Altogether, these findings identified that impact of BCT in regulation of glycolysis in EC109 and its involves the TLR4/Akt/HIF-1α pathway. Meanwhile, glycolysis increasing the release of LA and promote the EMT of EC109 by GPR81/Wnt/β-catenin signaling pathway. In summary, our findings underscore the potential of targeting BCT as an innovative strategy to mitigate the development of EC.
Targeting interleukin-6 as a treatment approach for peritoneal carcinomatosis
Authors: Dadgar Neda , Sherry Christopher , Zimmerman Jenna , Park Hyun , Lewis Catherine , Donnenberg Albert , Zaidi Ali H. , Fan Yong , Xiao Kunhong , Bartlett David , Donnenberg Vera , Wagner Patrick L. 
Published: April 2024

AbstractPeritoneal carcinomatosis (PC) is a complex manifestation of abdominal cancers, with a poor prognosis and limited treatment options. Recent work identifying high concentrations of the cytokine interleukin-6 (IL-6) and its soluble receptor (sIL-6-Rα) in the peritoneal cavity of patients with PC has highlighted this pathway as an emerging potential therapeutic target. This review article provides a comprehensive overview of the current understanding of the potential role of IL-6 in the development and progression of PC. We discuss mechansims by which the IL-6 pathway may contribute to peritoneal tumor dissemination, mesothelial adhesion and invasion, stromal invasion and proliferation, and immune response modulation. Finally, we review the prospects for targeting the IL-6 pathway in the treatment of PC, focusing on common sites of origin, including ovarian, gastric, pancreatic, colorectal and appendiceal cancer, and mesothelioma.
PGRN is involved in macrophage M2 polarization regulation through TNFR2 in periodontitis
Authors: Zhang Liguo , Nie Fujiao , Zhao Jingjing , Li Shutong , Liu Wenchuan , Guo Hongmei , Yang Pishan 
Published: April 2024

Abstract
Background and objective
Progranulin (PGRN), a multifunctional growth factor, plays indispensable roles in the regulation of cancer, inflammation, metabolic diseases, and neurodegenerative diseases. Nevertheless, its immune regulatory role in periodontitis is insufficiently understood. This study attempts to explore the regulatory effects of PGRN on macrophage polarization in periodontitis microenvironment.

Methods
Immunohistochemical (IHC) and multiplex immunohistochemical (mIHC) stainings were performed to evaluate the expression of macrophage-related markers and PGRN in gingival samples from periodontally healthy subjects and periodontitis subjects. RAW264.7 cells and bone marrow-derived macrophages (BMDMs) were polarized towards M1 or M2 macrophages by the addition of LPS or IL-4, respectively, and were treated with or without PGRN. Real-time fluorescence quantitative PCR (qRT-PCR), immunofluorescence staining (IF), enzyme-linked immunosorbent assay (ELISA), and flow cytometry were used to determine the expressions of M1 and M2 macrophage-related markers. Co-immunoprecipitation was performed to detect the interaction between PGRN and tumor necrosis factor receptor 2 (TNFR2). Neutralizing antibody was used to block TNFR2 to confirm the role of TNFR2 in PGRN-mediated macrophage polarization.

Results
The IHC and mIHC staining of human gingival slices showed a significant accumulation of macrophages in the microenvironment of periodontitis, with increased expressions of both M1 and M2 macrophage markers. Meanwhile, PGRN was widely expressed in the gingival tissue of periodontitis and co-expressed mainly with M2 macrophages. In vitro experiments showed that in RAW264.7 cells and BMDMs, M1 markers (CD86, TNF-α, iNOS, and IL-6) substantially decreased and M2 markers (CD206, IL-10, and Arg-1) significantly increased when PGRN was applied to LPS-stimulated macrophages relatively to LPS stimulation alone. Besides, PGRN synergistically promoted IL-4-induced M2 markers expression, such as CD206, IL-10, and Arg1. In addition, the co-immunoprecipitation result showed the direct interaction of PGRN with TNFR2. mIHC staining further revealed the co-localization of PGRN and TNFR2 on M2 macrophages (CD206+). Blocking TNFR2 inhibited the regulation role of PGRN on macrophage M2 polarization.

Conclusions
In summary, PGRN promotes macrophage M2 polarization through binding to TNFR2 in both pro- and anti-inflammatory periodontal microenvironments.