bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network pharmacology combined with metabolomics to explore the mechanism for Lonicerae Japonicae flos against respiratory syncytial virus
Authors: Ding Jie , Li Jing , Zhang Zhe , Du Yaxuan , Liu Yuhong , Wang Ping , Du Haitao 
Published: December 2023

Abstract
Background
Respiratory Syncytial Virus (RSV) stands out as a primary contributor to lower respiratory tract infections and hospitalizations, particularly in infants. Lonicerae japonicae flos (LJF), a traditional Chinese medicine renowned for its efficacy against various viral infections, including RSV, has been widely employed. Despite its common use, the precise therapeutic mechanism of LJF against RSV remains elusive. This study aimed to investigate the underlying mechanism of LJF against RSV through network pharmacology and metabolomics.

Methods
In this study, based on network pharmacology, potential targets related to LJF and RSV were obtained from PubChem and Swiss Target Prediction. The core targets and pathways were established and verified by enrichment analysis and molecular docking. The anti-RSV efficacy of LJF was determined by in vitro experiments. Additionally, metabolomics analysis was integrated, allowing for the identification of differential metabolites and their correlation with targets following LJF treatment in the context of RSV infection.

Results
A total of 23 active ingredients and 780 targets were obtained, of which 102 targets were associated with LJF anti-RSV. The construction of the corresponding Protein–Protein Interaction (PPI) network unveiled potential core targets, including STAT3, TNF, and AKT1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that LJF's anti-RSV effects primarily involve key pathways such as the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, and FoxO signaling pathway. Molecular docking showed that ZINC03978781, 4,5'-Retro-.beta.,.beta.-Carotene -3,3'-dione, 4',5'-didehydro and 7-epi-Vogeloside had better binding ability. The cellular assay showed that the therapeutic index of LJF against RSV was 4.79. Furthermore, 18 metabolites were screened as potential biomarkers of LJF against RSV, and these metabolites were mainly involved in the pathways of purine metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, and other related pathways.

Conclusions
The intergration of network pharmacology and metabolomics can clarify the active targets and related pathways of LJF against RSV, which could provide a valuable reference for further research and clinical application of LJF.
Undergraduate oncology education in Sudanese public medical schools; a national cross-sectional study
Authors: Alrawa Salma S. , Elgadi Ammar , Alfadul Esraa S. A. , Alshikh Shahd , Hammad Nazik , Abdelhafeez Abdelhafeez 
Published: December 2023

Abstract
Background
Cancer was the fifth leading cause of death in Sudan general hospitals in 2020, and its incidence is increasing. Medical students’ cancer education is key in cancer control. Evaluating the current education is the first step in optimizing it. The aim of this study was to assess undergraduate oncology education in Sudan public medical schools as reflected by the graduates of the year 2021–2022.

Method
This was a cross-sectional institution-based study. A validated online questionnaire was sent between 8 September and 11 November 2022 to graduates who were selected using a stratified random sampling technique from 17 Sudan public medical schools. The data were collected using Google Forms and analyzed using R software version 4.2.2 and Microsoft Excel 2022.

Results
A total of 707 graduates completed the questionnaire. They reported generally poor exposure to oncology. Palliative and radiation oncology in addition to chemotherapy daycare units were never attended by 76.0%, 72.0%, and 72.0% of graduates, respectively. The massed oncology curriculum was associated with increased hours of lectures dictated to medical (p = 0.005), radiation (p < 0.001), and palliative oncology (0.035). It was associated with an increased likelihood of assessment in breaking bad news (p < 0.001), counseling cancer patients (p = 0.015), and oncology-related knowledge (p < 0.001). The massed curriculum was associated with a decrease in interest in pursuing an oncology career (p = 0.037). Students were generally confident in their oncology competencies, and no difference was observed in relation to the curriculum approach (p > 0.05).

Conclusion
This study reflected poor exposure to oncology at the undergraduate level in Sudanese public medical schools. The massed oncology curriculum was associated with formal assessment of oncology-related competencies and better exposure to some disciplines, such as radiation and palliative oncology. Nonetheless, it was associated with decreased interest in an oncology career. In spite of the poor exposure, graduates were confident in their skills in oncology-related competencies. Further objective analysis of competence is needed.
Biomechanical stimulation promotes blood vessel growth despite VEGFR-2 inhibition
Authors: Johnson Bronte Miller , Johnson Allison McKenzie , Heim Michael , Buckley Molly , Mortimer Bryan , Berry Joel L. , Sewell-Loftin Mary Kathryn 
Published: December 2023

Abstract
Background
Angiogenesis, or the growth of new vasculature from existing blood vessels, is widely considered a primary hallmark of cancer progression. When a tumor is small, diffusion is sufficient to receive essential nutrients; however, as the tumor grows, a vascular supply is needed to deliver oxygen and nutrients into the increasing mass. Several anti-angiogenic cancer therapies target VEGF and the receptor VEGFR-2, which are major promoters of blood vessel development. Unfortunately, many of these cancer treatments fail to completely stop angiogenesis in the tumor microenvironment (TME). Since these therapies focus on the biochemical activation of VEGFR-2 via VEGF ligand binding, we propose that mechanical cues, particularly those found in the TME, may be a source of VEGFR-2 activation that promotes growth of blood vessel networks even in the presence of VEGF and VEGFR-2 inhibitors.

Results
In this paper, we analyzed phosphorylation patterns of VEGFR-2, particularly at Y1054/Y1059 and Y1214, stimulated via either VEGF or biomechanical stimulation in the form of tensile strains. Our results show prolonged and enhanced activation at both Y1054/Y1059 and Y1214 residues when endothelial cells were stimulated with strain, VEGF, or a combination of both. We also analyzed Src expression, which is downstream of VEGFR-2 and can be activated through strain or the presence of VEGF. Finally, we used fibrin gels and microfluidic devices as 3D microtissue models to simulate the TME. We determined that regions of mechanical strain promoted increased vessel growth, even with VEGFR-2 inhibition through SU5416.

Conclusions
Overall, understanding both the effects that biomechanical and biochemical stimuli have on VEGFR-2 activation and angiogenesis is an important factor in developing effective anti-angiogenic therapies. This paper shows that VEGFR-2 can be mechanically activated through strain, which likely contributes to increased angiogenesis in the TME. These proof-of-concept studies show that small molecular inhibitors of VEGFR-2 do not fully prevent angiogenesis in 3D TME models when mechanical strains are introduced.
Pandemic disruptions in vaccine uptake in a low-income setting: a qualitative inquiry
Authors: Malik Fauzia Aman , Ahsan Nazia , Jabeen Rawshan , Afzal Osama , Siddiqi Alysha , Khan Ayub , Hopkins Kathryn L. , Kazi Abdul Momin 
Published: December 2023

Abstract
Background
While the COVID-19 pandemic has exposed the vulnerabilities of immunization delivery systems globally, the devastating impact of the pandemic on immunization delivery is most pronounced in low and middle-income countries like Pakistan. We conducted a qualitative study to capture the views and experiences of parents and healthcare workers (HWs) and assess the impact of the COVID-19 pandemic on childhood routine immunization (CRI) and COVID-19 vaccination in Pakistan.

Methods
We used a qualitative research design with a purposive sampling approach. Semi-structured interviews (via telephone) and focus group discussions (via Zoom) were conducted with parents/child caregivers and HWs, respectively. All qualitative interviews were conducted between February and July 2021 from three sites (two urban and one rural) in Sindh, Pakistan. Interviews were audio-recorded, transcribed, and coded for a team-based thematic analysis.

Results
Overall, most parents and HWs indicated a strong trust in the benefits of CRI; nonetheless, a substantial disruption in the delivery and uptake of these services was also reported. The barriers towards CRI included closed vaccination centers, drastic reduction in outreach programs, lack of information for parents/child caregivers on vaccine availability, fear in the community regarding vaccine safety, limited vaccine supply, and a lack of healthcare staff. For COVID-19 vaccines, challenges cited included skepticism about the reality of the pandemic and confusion over COVID-19 vaccines due to conflicting (or mis-or-dis) information. Both participant groups showed a willingness to integrate COVID-19 vaccination into Pakistan’s Expanded Program for Immunization if required in the future.

Conclusion
During the COVID-19 pandemic, disruptions of regular immunization delivery in Pakistan were not due to parental unwillingness to vaccinate, but rather to social and logistical challenges caused by a rapidly changing context and difficulties in providing vaccination services safely. Barriers to vaccine access and concerns about COVID-19 exposure during clinic visits also contributed to uncertainty regarding immunization services early in the pandemic. For catchup campaigns and future pandemics, more than focusing interventions on persuading people, strategic approaches to building resilience through system-based interventions, such as investing in surge capacity in the immunization workforce to bounce back quickly after the first shock are required.
Unveiling the role of miR-137-3p/miR-296-5p/SERPINA3 signaling in colorectal cancer progression: integrative analysis of gene expression profiles and in vitro studies
Authors: Liu Huimin , Wu Xingxing , Wang Dandan , Li Quanxi , Zhang Xin , Xu Liang 
Published: December 2023

Abstract
Background
Colorectal cancer (CRC) is a prevalent malignancy worldwide, with increasing incidence and mortality rates. Although treatment options have improved, CRC remains a leading cause of death due to metastasis. Early intervention can significantly improve patient outcomes, making it crucial to understand the molecular mechanisms underlying CRC metastasis. In this study, we performed bioinformatics analysis to identify potential genes associated with CRC metastasis.

Methods
We downloaded and integrated gene expression datasets (GSE89393, GSE100243, and GSE144259) from GEO database. Differential expression analysis was conducted, followed by Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub gene SERPINA3 was selected for further in vitro functional studies. Additionally, the role of miR-137-3p/miR-296-5p/ Serpin family A member 3 (SERPINA3) in CRC cell function was investigated using in vitro assays.

Results
Analysis of the gene expression datasets revealed differentially expressed genes (DEGs) associated with CRC metastasis. GO analysis showed enrichment in biological processes such as blood coagulation regulation and wound healing. Cellular component analysis highlighted extracellular matrix components and secretory granules. Molecular function analysis identified activities such as serine-type endopeptidase inhibition and lipoprotein receptor binding. KEGG analysis revealed involvement in pathways related to complement and coagulation cascades, cholesterol metabolism, and immune responses. The common DEGs among the datasets were further investigated. We identified SERPINA3 as a hub gene associated with CRC metastasis. SERPINA3 exerted enhanced effects on migration, proliferation and epithelial-mesenchymal transition (EMT) and inhibitory effects on caspase-3/-9 activities in HT29 and SW620 cells. MiR-137-3p overexpression increased activities of caspase-3/-9, decreased migration and proliferation, and also repressed EMT in HT29 cells, which were obviously attenuated by SERPINA3 enforced overexpression. Consistently, SERPINA3 enforced overexpression also largely reversed miR-296-5p mimics-induced increased in activities of caspase-3/-9, decrease in migration, proliferation and EMT in HT29 cells.

Conclusion
Through bioinformatics analysis, we identified potential genes associated with CRC metastasis. The functional studies focusing on SERPINA3/miR-137-3p/miR-296-5p further consolidated its role in regulating CRC progression. Our findings provide insights into novel mechanisms underlying CRC metastasis and might contribute to the development of effective treatment strategies. However, the role of SERPINA3/miR-137-3p/miR-296-5p signaling in CRC still requires further investigation.
Understanding the spread of infectious diseases in edge areas of hotspots: dengue epidemics in tropical metropolitan regions
Authors: Lee Ya-Peng , Wen Tzai-Hung 
Published: December 2023

AbstractIdentifying clusters or hotspots from disease maps is critical in research and practice. Hotspots have been shown to have a higher potential for transmission risk and may be the source of infections, making them a priority for controlling epidemics. However, the role of edge areas of hotspots in disease transmission remains unclear. This study aims to investigate the role of edge areas in disease transmission by examining whether disease incidence rate growth is higher in the edges of disease hotspots during outbreaks. Our data is based on the three most severe dengue epidemic years in Kaohsiung city, Taiwan, from 1998 to 2020. We employed conditional autoregressive (CAR) models and Bayesian areal Wombling methods to identify significant edge areas of hotspots based on the extent of risk difference between adjacent areas. The difference-in-difference (DID) estimator in spatial panel models measures the growth rate of risk by comparing the incidence rate between two groups (hotspots and edge areas) over two time periods. Our results show that in years characterized by exceptionally large-scale outbreaks, the edge areas of hotspots have a more significant increase in disease risk than hotspots, leading to a higher risk of disease transmission and potential disease foci. This finding explains the geographic diffusion mechanism of epidemics, a pattern mixed with expansion and relocation, indicating that the edge areas play an essential role. The study highlights the importance of considering edge areas of hotspots in disease transmission. Furthermore, it provides valuable insights for policymakers and health authorities in designing effective interventions to control large-scale disease outbreaks.
Perioperative, function, and positive surgical margin in extraperitoneal versus transperitoneal single port robot-assisted radical prostatectomy: a systematic review and meta-analysis
Authors: Jiang Yu , Liu Yang , Qin Shize , Zhong Shuting , Huang Xiaohua 
Published: December 2023

Abstract
Background
Extraperitoneal and transperitoneal approaches are two common modalities in single-port (SP) robot-assisted radical prostatectomy (RARP), but differences in safety and efficacy between the two remain controversial. This study aimed to compare the perioperative, function, and positive surgical margin of extraperitoneal with transperitoneal approaches SP-RARP.

Methods
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, this study is registered with PROSPERO (CRD 42023409667). We systematically searched databases including PubMed, Embase, Web of Science, and Cochrane Library to identify relevant studies published up to February 2023. Stata 15.1 software was used to analyze and calculate the risk ratio (RR) and weighted mean difference (WMD).

Results
A total of five studies, including 833 participants, were included in this study. The SP-TPRP group is superior to the SP-EPRP group in intraoperative blood loss (WMD: − 43.92, 95% CI − 69.81, − 18.04; p = 0.001), the incidence of postoperative Clavien-Dindo grade II and above complications (RR: 0.55, 95% CI − 0.31, 0.99; p = 0.04), and postoperative continence recovery (RR: 1.23, 95% CI 1.05, 1.45; p = 0.04). Conversely, the hospitalization stays (WMD: 7.88, 95% confidence interval: 0.65, 15.1; p = 0.03) for the SP-EPRP group was shorter than that of the SP-TPRP group. However, there was no significant difference in operation time, postoperative pain score, total incidence of postoperative complications, and positive surgical margin (PSM) rates between the two groups (p > 0.05).

Conclusions
This study demonstrates that both extraperitoneal and extraperitoneal SP-RARP approaches are safe and effective. SP-TPRP is superior to SP-EPRP in postoperative blood loss, the incidence of postoperative Clavien-Dindo grade II and above complications, and postoperative continence recovery, but it is accompanied by longer hospital stays.
Down-regulated TAB1 suppresses the replication of Coxsackievirus B5 via activating the NF-κB pathways through interaction with viral 3D polymerase
Authors: Zhang Jiayu , Teng Peiying , Sun Bo , Zhang Jihong , Zhou Xiaoshuang , Chen Wei 
Published: December 2023

AbstractCoxsackievirus Group B type 5 (CVB5), an important pathogen of hand-foot-mouth disease, is also associated with neurological complications and poses a public health threat to young infants. Among the CVB5 proteins, the nonstructural protein 3D, known as the Enteroviral RNA-dependent RNA polymerase, is mainly involved in viral genome replication and transcription. In this study, we performed immunoprecipitation coupled with liquid chromatography-tandem mass spectrometry (LC–MS/MS) to identify host proteins that interacted with CVB5 3D polymerase. A total of 116 differentially expressed proteins were obtained. Gene Ontology analysis identified that the proteins were involved in cell development and cell adhesion, distributed in the desmosome and envelope, and participated in GTPase binding. Kyoto Encyclopedia of Genes and Genomes analysis further revealed they participated in nerve diseases, such as Parkinson disease. Among them, 35 proteins were significantly differentially expressed and the cellular protein TGF-BATA-activated kinase1 binding protein 1 (TAB1) was found to be specifically interacting with the 3D polymerase. 3D polymerase facilitated the entry of TAB1 into the nucleus and down-regulated TAB1 expression via the lysosomal pathway. In addition, TAB1 inhibited CVB5 replication via inducing inflammatory factors and activated the NF-κB pathway through IκBα phosphorylation. Moreover, the 90-96aa domain of TAB1 was an important structure for the function. Collectively, our findings demonstrate the mechanism by which cellular TAB1 inhibits the CVB5 replication via activation of the host innate immune response, providing a novel insight into the virus-host innate immunity.
Real-world predictors of divorce among outpatients with bipolar disorder: sex differences and clinical implications
Authors: Tokumitsu Keita , Sugawara Norio , Adachi Naoto , Kubota Yukihisa , Watanabe Yoichiro , Miki Kazuhira , Azekawa Takaharu , Edagawa Koji , Katsumoto Eiichi , Hongo Seiji , Goto Eiichiro , Ueda Hitoshi , Kato Masaki , Yoshimura Reiji , Nakagawa Atsuo , Kikuchi Toshiaki , Tsuboi Takashi , Watanabe Koichiro , Yasui-Furukori Norio 
Published: December 2023

Abstract
Background
Bipolar disorder is a mental illness characterized by recurring episodes of mania and depression and is known to cause social impairment. Additionally, it has been revealed that bipolar disorder increases the risk of divorce and loss of family member support, which can worsen the prognosis. However, there is limited evidence regarding the predictive factors of divorce among patients with bipolar disorder in real-world settings.

Methods
This study utilized an observational approach and involved psychiatrists from 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics. They were requested to conduct a retrospective review of medical records and complete a questionnaire focused on patients diagnosed with bipolar disorder. The data collection period for baseline patient characteristics spanned from September to October 2017. Next, we investigated the incidence of divorce over a 2-year period, ranging from baseline to September to October 2019.

Results
A total of 1071 outpatients with bipolar disorder were included in the analysis, and 2.8% (30/1071) experienced divorce during the first 2 years of observation. The incidence of divorce in this population was considerably higher than that in the general Japanese population. Binomial logistic regression analysis confirmed that a younger baseline age and lower BMI values were statistically significant predictors of divorce occurrence for all study participants. The predictors of divorce were then examined separately by sex. The results revealed that for men, a younger age at baseline and having bipolar I disorder compared to bipolar II disorder were statistically significant predictors of divorce. In contrast, for women, having a lower BMI and using anxiolytics emerged as statistically significant predictors of divorce.

Conclusions
In this study, a younger baseline age and lower BMI values were statistically significant predictors of divorce in patients with bipolar disorder. Notably, the predictors of divorce varied significantly between men and women. These findings provide important insights from a family perspective regarding social support for individuals with bipolar disorder in real-world clinical settings.
Biomechanical insights into ankle instability: a finite element analysis of posterior malleolus fractures
Authors: Ying Jichong , Liu Jianlei , Wang Hua , Zhuang Yunqiang , Yu Tianming , Wang Shuaiyi , Huang Dichao 
Published: December 2023

Abstract
Background
Posterior malleolus fractures are known to be associated with ankle instability. The complexities involved in obtaining precise laboratory-based spatial pressure measurements of the ankle highlight the significance of exploring the biomechanical implications of these fractures.

Methods
Finite element analysis was utilized to examine the stress distribution across the contact surface of the ankle joint, both in its natural state and under varied sagittal fracture line angles. The study aimed to identify stress concentration zones and understand the influence of sagittal angles on stress distribution.

Results
Three distinct stress concentration zones were identified on the ankle's contact surface: the anterolateral tibia, the anteromedial tibia, and the fracture line. The most significant stress was observed at the fracture line when a fracture occurs. Stress at the fracture line notably spikes as the sagittal angle decreases, which can potentially compromise ankle stability. Larger sagittal angles exhibited only minor stress variations at the contact surface's three vertices. It was inferred that sagittal angles below 60° might pose risks to ankle stability.

Conclusions
The research underscores the potential implications of fractures on the stress profile of the ankle joint, emphasizing the role of the contact surface in ensuring stability. The identification of three zones of stress concentration and the influence of sagittal angles on stress distribution offers a valuable reference for therapeutic decision-making. Further, the study reinforces the importance of evaluating sagittal fracture angles, suggesting that angles below 60° may compromise ankle stability.