bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclin A1 (CCNA1) inhibits osteoporosis by suppressing transforming growth factor-beta (TGF-beta) pathway in osteoblasts
Authors: Du Xiao , Zang Chuanyi , Wang Qinglei 
Published: March 2024

Abstract
Background
Osteoporosis is a genetic disease caused by the imbalance between osteoblast-led bone formation and osteoclast-induced bone resorption. However, further gene-related pathogenesis remains to be elucidated.

Methods
The aberrant expressed genes in osteoporosis was identified by analyzing the microarray profile GSE100609. Serum samples of patients with osteoporosis and normal group were collected, and the mRNA expression of candidate genes was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The mouse cranial osteoblast MC3T3-E1 cells were treated with dexamethasone (DEX) to mimic osteoporosis in vitro. Alizarin Red staining and alkaline phosphatase (ALP) staining methods were combined to measure matrix mineralization deposition of MC3T3-E1 cells. Meanwhile, the expression of osteogenesis related genes including alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), Osterix, and bone morphogenetic protein 2 (BMP2) were evaluated by qRT-PCR and western blotting methods. Then the effects of candidate genes on regulating impede bone loss caused by ovariectomy (OVX) in mice were studied.

Results
Cyclin A1 (CCNA1) was found to be significantly upregulated in serum of osteoporosis patients and the osteoporosis model cells, which was in line with the bioinformatic analysis. The osteogenic differentiation ability of MC3T3-E1 cells was inhibited by DEX treatment, which was manifested by decreased Alizarin Red staining intensity, ALP staining intensity, and expression levels of ALP, OCN, OPN, Osterix, and BMP2. The effects of CCNA1 inhibition on regulating osteogenesis were opposite to that of DEX. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that genes negatively associated with CCNA1 were enriched in the TGF-beta signaling pathway. Inhibitor of TGF-beta signaling pathway partly reversed osteogenesis induced by suppressed CCNA1. Furthermore, suppressed CCNA1 relieved bone mass of OVX mice in vivo.

Conclusion
Downregulation of CCNA1 could activate TGF-beta signaling pathway and promote bone formation, thus playing a role in treatment of osteoporosis.
Identification of novel AKT1 inhibitors from Sapria himalayana bioactive compounds using structure-based virtual screening and molecular dynamics simulations
Authors: Ralte Laldinfeli , Sailo Hmingremhlua , Kumar Rakesh , Khiangte Laldinliana , Kumar Nachimuthu Senthil , Singh Yengkhom Tunginba 
Published: March 2024

AbstractThrough the experimental and computational analyses, the present study sought to elucidate the chemical composition and anticancer potential of Sapria himalayana plant extract (SHPE). An in vitro analysis of the plant extract was carried out to determine the anticancer potential. Further, network pharmacology, molecular docking, and molecular dynamic simulation were employed to evaluate the potential phytochemical compounds for cervical cancer (CC) drug formulations. The SHPE exhibited anti-cancerous potential through inhibition properties against cancer cell lines. The LC-MS profiling showed the presence of 14 compounds in SHPE. Using network pharmacology analysis, AKT1 (AKT serine/threonine kinase 1) is identified as the possible potential target, and EGFR (Epidermal Growth Factor Receptor) is identified as the possible key signal pathway. The major targets were determined to be AKT1, EGFR by topological analysis and molecular docking. An in silico interaction of phytoconstituents employing molecular docking demonstrated a high binding inclination of ergoloid mesylate and Ergosta-5,7,9(11),22-tetraen-3-ol, (3.beta.,22E)- with binding affinities of -15.5 kcal/mol, and -11.3 kcal/mol respectively. Further, MD simulation and PCA analyses showed that the phytochemicals possessed significant binding efficacy with CC protein. These results point the way for more investigation into SHPE compound’s potential as CC treatment.
Graphical Abstract
Measuring the continuing care needs of inpatients in rural China
Authors: Liu Haoran , Wang Zhifan , Hu Juan , Xu Qiushuang , Yang Lei , Jian Weiyan 
Published: March 2024

Abstract
Background
International experience shows that the suitability of a high-performance healthcare system for its given purposes is reflected in its ability to provide a continuum of services that match the changing health status of the given population. Although many low- and middle-income countries have sought to bring movement away from hospital-centered and towards patient-centered healthcare, such efforts have often had poor results, and one of the major reasons for this is the inability to accurately identify which inpatients need continuing care and what kind of continuing of care is needed.

Objectives
To measure and assess the continuing care needs of discharged patients and its influencing factors in rural China.

Methods
Data were obtained from the hospital database of Medical Center M in County Z from May to July 2022. County Z is a county of 1 million people in central China. The database includes basic patient information, disease-related information, and information on readiness for hospital discharge. Factors related to the need for continuing care were included in the analysis. The Readiness for Hospital Discharge Scale was used to assess the need for continuing care. The statistical data are expressed in terms of both frequency and composition ratio. Finally, linear regression was used to analyze the factors influencing the need for continuing care.

Results
The analysis included a total of 3,791 patients, 123 of whom (3.25%) had continuing nursing needs. The need of continuing nursing was related to patients’ age group, mode of admission, occupation and major diagnostic categories (P < 0.05).

Conclusions
Developing continuing care is an important initiative for bridging the fragmentation of health services, and an appropriate supply system for continuing care, interconnected with inpatient services, should be established in rural areas in China as soon as possible. And provide more appropriate care for patients in need.
Design and validation of a conceptual model regarding impact of open science on healthcare research processes
Authors: Zarghani Maryam , Nemati-Anaraki Leila , Sedghi Shahram , Chakoli Abdolreza Noroozi , Rowhani-Farid Anisa 
Published: March 2024

Abstract
Introduction
The development and use of digital tools in various stages of research highlight the importance of novel open science methods for an integrated and accessible research system. The objective of this study was to design and validate a conceptual model of open science on healthcare research processes.

Methods
This research was conducted in three phases using a mixed-methods approach. The first phase employed a qualitative method, namely purposive sampling and semi-structured interview guides to collect data from healthcare researchers and managers. Influential factors of open science on research processes were extracted for refining the components and developing the proposed model; the second phase utilized a panel of experts and collective agreement through purposive sampling. The final phase involved purposive sampling and Delphi technique to validate the components of the proposed model according to researchers’ perspectives.

Findings
From the thematic analysis of 20 interview on the study topic, 385 codes, 38 sub-themes, and 14 main themes were extracted for the initial proposed model. These components were reviewed by expert panel members, resulting in 31 sub-themes, 13 main themes, and 4 approved themes. Ultimately, the agreed-upon model was assessed in four layers for validation by the expert panel, and all the components achieved a score of > 75% in two Delphi rounds. The validated model was presented based on the infrastructure and culture layers, as well as supervision, assessment, publication, and sharing.

Conclusion
To effectively implement these methods in the research process, it is essential to create cultural and infrastructural backgrounds and predefined requirements for preventing potential abuses and privacy concerns in the healthcare system. Applying these principles will lead to greater access to outputs, increasing the credibility of research results and the utilization of collective intelligence in solving healthcare system issues.
Exploring the motivation of health professionals to engage with research at various career stages
Authors: D’Arrietta Louisa M. , Vangaveti Venkat N. , Crowe Melissa J. , Malau-Aduli Bunmi S. 
Published: March 2024

AbstractBackgroundResearch is crucial for improved healthcare and better patient outcomes, but there is a current shortage of clinician-researchers who can connect research and practice in the health professions field. This study aimed to investigate the effect of career stage, previous training and involvement in research on health professionals' (HPs) motivations to engage in research while in public hospital clinical roles. HPs' perceived motivation concerning the importance, value, and barriers attributed to research during different career stages were examined.MethodsA mixed methods study design was adopted for this research. An online survey developed based on the Expectancy-Value-Cost (EVC) theory was distributed to HPs (doctors, nurses, midwives, and allied health professionals) in three North Queensland Public Hospitals. Data analysis included descriptive and inferential statistics for the quantitative data and content analysis for the qualitative text responses.ResultsThree hundred and fifty-five responses were received. Prior research training and involvement in research influenced respondents' perceptions about the importance, attitude, motivators, and barriers to research. Attainment value was the overarching motivation for involvement in research and research training for all career stages and all professional HP groups. Positive attitude to research was significantly higher (P = 0.003) for the allied health group (27.45 ± 4.05), followed by the medical (26.30 ± 4.12) and then the nursing and midwifery group (25.62 ± 4.21). Perceived importance and attitude attributed to research were significantly higher (P < 0.05) for those who had research training (26.66 ± 3.26 and 28.21 ± 3.73) compared to those who did not have research training (25.77 ± 3.77 and 23.97 ± 3.53). Significantly higher (P < 0.05) perceptions of organisational and individual barriers were reported among early career (50.52 ± 7.30) respondents compared to their mid-career (48.49 ± 8.14) and late career (47.71 ± 8.36) counterparts.ConclusionThe findings from this study provide valuable insights into the factors that influence HPs' motivation for research. The results underscore the importance of professional group, involvement in research, exposure to research training, career stage, gender, and organisational support in shaping HPs' attitudes, values, and perceived barriers to research. Understanding these factors can inform the development of targeted strategies to enhance research engagement among HPs and promote evidence-based practice in healthcare.
Breastfeeding is associated with enhanced intestinal gluconeogenesis in infants
Authors: Ni Duan , Tan Jian , Macia Laurence , Nanan Ralph 
Published: March 2024

Abstract
Background
Breastfeeding (BF) confers metabolic benefits to infants, including reducing risks of metabolic syndrome such as obesity and diabetes later in life. However, the underlying mechanism is not yet fully understood. Hence, we aim to investigate the impacts of BF on the metabolic organs of infants.

Methods
Previous literatures directly studying the influences of BF on offspring’s metabolic organs in both animal models and humans were comprehensively reviewed. A microarray dataset of intestinal gene expression comparing infants fed on breastmilk versus formula milk was analyzed.

Results
Reanalysis of microarray data showed that BF is associated with enhanced intestinal gluconeogenesis in infants. This resembles observations in other mammalian species showing that BF was also linked to increased gluconeogenesis.

Conclusions
BF is associated with enhanced intestinal gluconeogenesis in infants, which may underpin its metabolic advantages through finetuning metabolic homeostasis. This observation seems to be conserved across species, hinting its biological significance.
MUC5AC concentrations in lung lavage fluids are associated with acute lung injury after cardiac surgery
Authors: van Paassen Judith , Hiemstra Pieter S. , van der Linden Abraham C. , de Jonge Evert , Zwaginga Jaap Jan , Klautz Robert J.M. , Arbous M. Sesmu 
Published: March 2024

AbstractHeart surgery may be complicated by acute lung injury and adult respiratory distress syndrome. Expression and release of mucins MUC5AC and MUC5B in the lungs has been reported to be increased in acute lung injury. The aim of our study was to [1] investigate the perioperative changes of MUC5AC, MUC5B and other biomarkers in mini-bronchoalveolar lavage (minBAL), and [2] relate these to clinical outcomes after cardiac surgery. In this prospective cohort study in 49 adult cardiac surgery patients pre- and post-surgery non-fiberscopic miniBAL fluids were analysed for MUC5AC, MUC5B, IL-8, human neutrophil elastase, and neutrophils. All measured biomarkers increased after surgery. Perioperative MUC5AC-change showed a significant negative association with postoperative P/F ratio (p = 0.018), and a positive association with ICU stay (p = 0.027). In conclusion, development of lung injury after cardiac surgery and prolonged ICU stay are associated with an early increase of MUC5AC as detected in mini-BAL.
Revisiting the impact of public spaces on the mental health of rural migrants in Wuhan: an integrated multi-source data analysis
Authors: Gao Feifan , Cheng Hanbei , Li Zhigang , Yu Le 
Published: March 2024

AbstractCurrent research on public spaces and mental health often focuses on the independent relationship of one or more social mediators, neglecting the nuanced implications and serial mechanisms inherent in the progressive social process. Using Wuhan city, China, as a study case with multi-source data, this research applies Multilevel Generalized Structural Equation Modeling and deep learning techniques to explore the differential effects of public spaces with varying degrees of publicness (i.e., typical, semi-, and privately owned) on rural migrants’ mental health. Crucially, this study scrutinizes both explicit (social interaction) and implicit (perceived integration) social mechanisms to revisit the relationships. The findings reveal that not all public spaces equally influence mental health, with typical and privately owned public spaces conferring profound benefits. Notably, public spaces impact mental health chiefly through perceived integration instead of through direct social interaction. Social interaction improves mental health primarily by enhancing perceived integration, suggesting that meaningful connections beyond superficial encounters are critical. In particular, we observed significant social effects in typical and privately owned public spaces but limited social functionality in semi-public spaces. This evidence contributes to the knowledge required to create supportive social environments within public spaces, integral to nurturing inclusive urban development.
TMEM160 promotes tumor immune evasion and radiotherapy resistance via PD-L1 binding in colorectal cancer
Authors: Dai Xiaofeng , Wu Zhipeng , Ruan Ruiwen , Chen Jingyi , Huang Chunye , Lei Wan , Yao Yangyang , Li Li , Tang Xiaomei , Xiong Jianping , Feng Miao , Deng Jun 
Published: March 2024

Abstract
Background
The effectiveness of anti-programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1) therapy in treating certain types of cancer is associated with the level of PD-L1. However, this relationship has not been observed in colorectal cancer (CRC), and the underlying regulatory mechanism of PD-L1 in CRC remains unclear.

Methods
Binding of TMEM160 to PD-L1 was determined by co-immunoprecipitation (Co-IP) and GST pull-down assay.The ubiquitination levels of PD-L1 were verified using the ubiquitination assay. Phenotypic experiments were conducted to assess the role of TMEM160 in CRC cells. Animal models were employed to investigate how TMEM160 contributes to tumor growth.The expression and clinical significance of TMEM160 and PD-L1 in CRC tissues were evaluated by immunohistochemistry(IHC).

Results
In our study, we made a discovery that TMEM160 interacts with PD-L1 and plays a role in stabilizing its expression within a CRC model. Furthermore, we demonstrated that TMEM160 hinders the ubiquitination-dependent degradation of PD-L1 by competing with SPOP for binding to PD-L1 in CRC cells. Regarding functionality, the absence of TMEM160 significantly inhibited the proliferation, invasion, metastasis, clonogenicity, and radioresistance of CRC cells, while simultaneously enhancing the cytotoxic effect of CD8 + T cells on tumor cells. Conversely, the upregulation of TMEM160 substantially increased these capabilities. In severely immunodeficient mice, tumor growth derived from lentiviral vector shTMEM160 cells was lower compared with that derived from shNC control cells. Furthermore, the downregulation of TMEM160 significantly restricted tumor growth in immune-competent BALB/c mice. In clinical samples from patients with CRC, we observed a strong positive correlation between TMEM160 expression and PD-L1 expression, as well as a negative correlation with CD8A expression. Importantly, patients with high TMEM160 expression exhibited a worse prognosis compared with those with low or no TMEM160 expression.

Conclusions
Our study reveals that TMEM160 inhibits the ubiquitination-dependent degradation of PD-L1 that is mediated by SPOP, thereby stabilizing PD-L1 expression to foster the malignant progress, radioresistance, and immune evasion of CRC cells. These findings suggest that TMEM160 holds potential as a target for the treatment of patients with CRC.
Clinically relevant gene signatures provide independent prognostic information in older breast cancer patients
Authors: Castresana-Aguirre Miguel , Johansson Annelie , Matikas Alexios , Foukakis Theodoros , Lindström Linda S. , Tobin Nicholas P. 
Published: March 2024

Abstract
Background
The clinical utility of gene signatures in older breast cancer patients remains unclear. We aimed to determine signature prognostic capacity in this patient subgroup.

Methods
Research versions of the genomic grade index (GGI), 70-gene, recurrence score (RS), cell cycle score (CCS), PAM50 risk-of-recurrence proliferation (ROR-P), and PAM50 signatures were applied to 39 breast cancer datasets (N = 9583). After filtering on age ≥ 70 years, and the presence of estrogen receptor (ER) and survival data, 871 patients remained. Signature prognostic capacity was tested in all (n = 871), ER-positive/lymph node-positive (ER + /LN + , n = 335) and ER-positive/lymph node-negative (ER + /LN−, n = 374) patients using Kaplan–Meier and multivariable Cox-proportional hazard (PH) modelling.

Results
All signatures were statistically significant in Kaplan–Meier analysis of all patients (Log-rank P < 0.001). This significance remained in multivariable analysis (Cox-PH, P ≤ 0.05). In ER + /LN + patients all signatures except PAM50 were significant in Kaplan–Meier analysis (Log-rank P ≤ 0.05) and remained so in multivariable analysis (Cox-PH, P ≤ 0.05). In ER + /LN− patients all except RS were significant in Kaplan–Meier analysis (Log-rank P ≤ 0.05) but only the 70-gene, CCS, ROR-P, and PAM50 signatures remained so in multivariable analysis (Cox-PH, P ≤ 0.05).

Conclusions
We found that gene signatures provide prognostic information in survival analyses of all, ER + /LN + and ER + /LN- older (≥ 70 years) breast cancer patients, suggesting a potential role in aiding treatment decisions in older patients.
How does weight gain since the age of 18 years affect breast cancer risk in later life? A meta-analysis
Authors: Han Yunan , Otegbeye Ebunoluwa E. , Stoll Carrie , Hardi Angela , Colditz Graham A. , Toriola Adetunji T. 
Published: March 2024

AbstractEarly life factors are important risk factors for breast cancer. The association between weight gain after age 18 and breast cancer risk is inconsistent across previous epidemiologic studies. To evaluate this association, we conducted a meta-analysis according to PRISMA guidelines and the established inclusion criteria. We performed a comprehensive literature search using Medline (Ovid), Embase, Scopus, Cochrane Library, and ClinicalTrials.gov to identify relevant studies published before June 3, 2022. Two reviewers independently reviewed the articles for final inclusion. Seventeen out of 4,725 unique studies met the selection criteria. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS), and all were of moderate to high quality with NOS scores ranging from 5 to 8. We included 17 studies (11 case-control, 6 cohort) in final analysis. In case-control studies, weight gain after age 18 was associated with an increased risk of breast cancer (odds ratio [OR] = 1.25; 95% CI = 1.07–1.48), when comparing the highest versus the lowest categories of weight gain. Menopausal status was a source of heterogeneity, with weight gain after age 18 associated with an increased risk of breast cancer in postmenopausal women (OR = 1.53; 95% CI = 1.40–1.68), but not in premenopausal women (OR = 1.01; 95% CI = 0.92–1.12). Additionally, a 5 kg increase in weight was positively associated with postmenopausal breast cancer risk (OR = 1.12; 95%CI = 1.05–1.21) in case-control studies. Findings from cohort studies were identical, with a positive association between weight gain after age 18 and breast cancer incidence in postmenopausal women (relative risk [RR] = 1.30; 95% CI = 1.09–1.36), but not in premenopausal women (RR = 1.06; 95% CI = 0.92–1.22). Weight gain after age 18 is a risk factor for postmenopausal breast cancer, highlighting the importance of weight control from early adulthood to reduce the incidence of postmenopausal breast cancer.