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Original Article Open Access
The Development of a Risk Prediction Model to Predict Patients’ Likelihood of Completing Human Papillomavirus Vaccination
Amanda F. Petrik, Eric S. Johnson, Raj Mummadi, Matthew Slaughter, Matthew Najarian, Gloria D. Coronado
Published online December 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00026
Abstract
Human papillomavirus (HPV) infection is the primary cause of cervical, anogenital, and oropharyngeal cancers in the United States. These cancers are preventable through HPV vaccination. [...] Read more.

Human papillomavirus (HPV) infection is the primary cause of cervical, anogenital, and oropharyngeal cancers in the United States. These cancers are preventable through HPV vaccination. Research is critically needed to identify effective strategies for promoting HPV vaccination among high-risk groups. This study develops a risk prediction model to identify patients who are unlikely to complete HPV vaccination, with the goal of using the model to direct resources and increase vaccination rates.

We assessed vaccination status along with patient, provider, and clinic characteristics that predict vaccination completion. We then developed a predictive model to assess the likelihood of completing HPV vaccination, which can be used to target interventions based on patient needs. We used a retrospective cohort from a large integrated delivery system in Oregon. Using logistic regression with data available in the electronic health record, we created a risk model to determine the likelihood of vaccination completion among patients aged 11–17 years.

In a cohort of 61,788 patients, 40,570 (65.7%) had received at least one dose of the HPV vaccine. The full model included 17 demographic, clinical, provider, and community characteristics, achieving a bootstrap-corrected C-statistic of 0.67 with adequate calibration. The reduced model, which retained five demographic and clinical characteristics (age, language, race, ethnicity, and prior vaccinations), had a bootstrap-corrected C-statistic of 0.65 and adequate calibration.

Our findings suggest that a risk prediction model can guide the implementation of targeted interventions and the intensity of those interventions based on the likelihood of vaccination completion.

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Original Article Open Access
The Potential Oncogenic Role of Serum-derived hsa_circ_101555 as a Non-invasive Diagnostic/Prognostic Marker in Patients with Hepatocellular Carcinoma
Mohammed Soliman Gado, Amal Tohamy Abdel Moez, Nashwa El-Khazragy, Hossam El-Deen M. Salem, Nourhan Badwei
Published online March 17, 2025
Gene Expression. doi:10.14218/GE.2025.00012
Abstract
Hepatocellular carcinoma (HCC) represents the most prevalent malignancy in Egypt and globally. However, non-invasive diagnostic/prognostic biomarkers for early detection of HCC [...] Read more.

Hepatocellular carcinoma (HCC) represents the most prevalent malignancy in Egypt and globally. However, non-invasive diagnostic/prognostic biomarkers for early detection of HCC are still lacking. Circular RNAs (circRNAs) are one of the promising biomarkers. They are considered stable, long-stranded non-coding RNAs in a sealed circular form held together by covalent bonds. circRNAs have been observed in several genetic studies to play a vital role in the initiation and progression of malignancy. Our current cross-sectional study aimed to evaluate the potential role of serum-derived hsa_circ_101555 as a diagnostic biomarker for HCC, in addition to comparing its prognostic significance and predicting the response to therapy.

The serum expression level of hsa_circ_101555 was measured using real-time polymerase chain reaction in 62 clinically/radiologically diagnosed Egyptian HCC patients at baseline and three months after HCC treatment. These results were compared to those of 30 healthy subjects.

Our data showed that the mean circRNA value was highest in HCC cases (7.66 ± 3.74) compared to healthy controls (1.21 ± 0.96). Furthermore, the circRNA value showed excellent diagnostic accuracy in differentiating HCC patients from healthy controls at a cutoff point of 1.966, as indicated by an area under the curve of 0.984. In addition, it showed a prognostic role in differentiating between HCC progression and regression in these patients based on response evaluation criteria in solid tumors (RECIST)/ modified- RECIST (mRECIST) response categories at the cutoff point 5.1150, with an area under the curve of 0.891 and a standard error of 0.058. Interestingly, positive correlations between post-intervention circRNA levels and laboratory measurements were observed in our HCC patients, including the albumin-bilirubin score (r = 0.424, P = 0.001**), the neutrophil-to-lymphocyte ratio (r = 0.410, P = 0.001**), alpha-fetoprotein (r = 0.273, P = 0.032*), the aspartate aminotransferase/alanine aminotransferase ratio (r = 0.284, P = 0.025*), fibrosis-4 (r = 0.501, P = 0.000**), and the aspartate aminotransferase to platelet ratio score (r = 0.436, P = 0.000**), indicating an association with worsening liver inflammation, fibrosis, and disease progression. Lastly, post-intervention circRNA values were significantly correlated with clinical/pathological tumor key features, including larger tumors (>5 cm) (P = 0.019), multiplicity (tumor numbers > 3) (P = 0.031), vascular invasion (P = 0.030), Barcelona Clinic Liver Cancer stage C (P = 0.007), and advanced Tomur, Node, Metastasis stage (P = 0.012).

To our knowledge, this is the first study to highlight the expression levels of serum-derived hsa_circ_101555 in Egyptian HCC patients. Our data showed its upregulation in HCC cases compared to healthy subjects. Additionally, its increased levels were associated with tumor progression according to the RECIST/mRECIST categories. Furthermore, its significant correlation with markers/scores of liver inflammation, dysfunction, and tumor pathological features underscores its potential as a promising diagnostic/prognostic biomarker, aiding in better clinical decision-making for the management of hepatocellular carcinoma.

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Original Article Open Access
Effects of Shenfu Decoction on Neutrophil Chemotactic Function in Septic Mice
Jun Zhang, Yi Jiang, Rui Zhu, Kangli Wang, Wei Li, Chenxi Wang, Xucheng Li, Xiaolong Xu, Qingquan Liu
Published online January 22, 2025
Future Integrative Medicine. doi:10.14218/FIM.2024.00040
Abstract
Sepsis involves a complex cascade of inflammatory reactions and immune system dysregulation. Neutrophils play a crucial role in modulating the anti-inflammatory response, which [...] Read more.

Sepsis involves a complex cascade of inflammatory reactions and immune system dysregulation. Neutrophils play a crucial role in modulating the anti-inflammatory response, which is vital for managing sepsis. Impaired chemotaxis of granulocytes can significantly impact the outcome of sepsis. Shenfu Decoction, by tonifying Qi and warming Yang, enhances the propelling function of Qi for promoting the chemotactic function of neutrophils. This study aimed to investigate the effects of Shenfu Decoction on the chemotactic function of neutrophils in septic mice and the underlying mechanisms.

Thirty 10-week-old specific-pathogen-free male C57BL/6J mice were randomly divided into five groups: sham operation, model, and low-, medium-, and high-dose Shenfu Decoction treatment groups (n = 6 in each group). Sepsis was induced using cecum ligation and puncture procedures. The sham-operated group served as the control. The drug was administered 6 h after surgery; the sham-operated and model groups received saline, while the treatment groups were gavaged every 12 h with the respective concentrations of Shenfu Decoction. Four hours after the last gavage, the mice were euthanized, and samples were collected to determine neutrophil counts and related indices. Primary neutrophils were extracted from the peripheral blood of septic mice and divided into blank control, sham-operated, low-dose, and high-dose groups. These cells were cultured with serum containing the respective treatments to measure neutrophil chemotactic distance, intracellular calcium ion concentration, and the expression levels of chemokine receptors and P2X1 receptors.

Compared with the sham-operated group, the total number of colonies and the number of neutrophils in the peritoneal lavage fluid were increased in the model group (P < 0.05). In the treatment groups, the number of neutrophils in the peritoneal lavage fluid was significantly increased (P < 0.05), while the number of neutrophils in the blood was decreased. Compared with the blank control group, the neutrophil chemotaxis distance was significantly prolonged in the sham-operated group. Additionally, the expression levels of P2X1 and FPR1 receptors were decreased, the expression levels of CXCR1 and CXCR2 receptors were increased (P < 0.05), and the calcium ion concentration was decreased (P > 0.05). Compared with the sham-operated group, the treatment groups exhibited a prolonged neutrophil chemotaxis distance, significantly decreased expression levels of P2X1 and FPR1 receptors, significantly increased expression levels of CXCR1 and CXCR2 receptors (P < 0.05), and significantly decreased calcium ion concentrations (P < 0.05). These effects were positively correlated with the Shenfu Decoction dosage.

Shenfu Decoction can improve the chemotactic function of neutrophils, possibly through the downregulation of P2X1 receptor expression. Its effects are positively correlated with the dosage.

Full article
Review Article Open Access
Foundation and Practice of Digital Traditional Chinese Medicine Platforms in Enhanced Recovery After Surgery
Xiaochun Zhang, Guanwen Gong, Zhiwei Jiang, Heiying Jin
Published online March 25, 2025
Future Integrative Medicine. doi:10.14218/FIM.2025.00011
Abstract
This review explores the integration of complexity science—specifically, the biological holographic phenomenon and chaos-fractal theory—with the fundamental principles of traditional [...] Read more.

This review explores the integration of complexity science—specifically, the biological holographic phenomenon and chaos-fractal theory—with the fundamental principles of traditional Chinese medicine (TCM) to optimize perioperative recovery. It examines how these theories provide a scientific foundation for developing a digital TCM diagnosis and treatment platform. Key topics discussed include the application of digital four-diagnosis technology, visualization of perioperative Yin-Yang states, and artificial intelligence-driven biomarker discovery. By quantifying and digitizing core TCM concepts, this approach enables their incorporation into Enhanced Recovery After Surgery protocols. Ultimately, the review highlights the potential of integrating TCM with Western medicine to advance personalized postoperative management, offering both theoretical insights and practical strategies for improving perioperative care.

Full article
Systematic Review Open Access
Receptor Discordance between Primary and Recurrent Breast Cancer: A Systematic Literature Review
Archana Haria, Jonathon Hill, Kylie J. Mansfield
Published online December 25, 2024
Oncology Advances. doi:10.14218/OnA.2024.00027
Abstract
Breast cancer is the most common cancer among women, with hormone receptors playing a crucial role, not only in cancer cell growth but also as primary targets in breast cancer treatment. [...] Read more.

Breast cancer is the most common cancer among women, with hormone receptors playing a crucial role, not only in cancer cell growth but also as primary targets in breast cancer treatment. This systematic literature review aimed to summarize the current evidence on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) discordance rates between primary and recurrent breast cancer. Additionally, it seeks to identify how discordance affects prognosis, metastasis, and the potential evidence of primary tumor heterogeneity.

The databases Web of Science, Scopus, MEDLINE, and PubMed were searched for publications of original research in English from 2013 to 2023. Studies with paired histopathology from primary and recurrent breast cancer that employed immunohistochemistry and fluorescence in situ hybridization were included. Ten studies were deemed eligible for inclusion.

Concordance between primary and recurrent breast cancer was high for ER (80%), PR (65%), and HER2 (85%). Average discordance rates were: ER 19%, PR 34%, and HER2 15%, with PR discordance consistently being the highest. Loss of ER and PR receptors was observed more frequently than gain, while the opposite trend was noted for HER2. Loss of ER and PR was associated with a worse prognosis. Discordance was also observed in cases of tumor metastasis.

Discordance in receptor expression between primary and recurrent breast cancer was common, highlighting the importance of re-biopsy in recurrent or metastatic breast cancer, if possible. Patients who lost hormone receptors experienced worse outcomes, suggesting the development of treatment-resistant tumor clones.

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Review Article Open Access
Advances in Screening and Early Diagnosis of Pancreatic Cancer
Wenhao Luo, Jun Wang, Hao Chen, Zhe Cao, Jiangdong Qiu, Yueze Liu, Yifan Fu, Gang Yang, Jinxin Tao, Guihu Weng, Tao Liu, Yueyang Wang, Liyuan Ye, Cheng Ding, Xiaoyue Lu, Menggang Zhang, Hua Huang, Jianchun Xiao, Lei You, Taiping Zhang
Published online September 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00006S
Abstract
Pancreatic cancer (PC) remains a formidable challenge in oncology due to its notoriously poor prognosis, often resulting from late-stage diagnosis. Early detection through effective [...] Read more.

Pancreatic cancer (PC) remains a formidable challenge in oncology due to its notoriously poor prognosis, often resulting from late-stage diagnosis. Early detection through effective screening methods is crucial not only to improving patient outcomes but also to enhancing their quality of life. This review focuses on the latest advancements in PC screening and early diagnostic strategies. Key areas include the integration of artificial intelligence in radiology, the search for novel biomarkers, and the development of predictive models. This review aimed to provide a comprehensive overview, serving as a stepping stone toward transforming early detection strategies for PC in the digital age.

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Commentary Open Access
Letter to the Editor Open Access
Original Article Open Access
Nutritional Status and Support in Hospitalized Patients with Neurological Diseases: A Cross-sectional Survey
Yali Wan, Yuxin Zhan, Yuanjue Wu, Ping Yao, Yi Chen, Zhaoyu Xiong, Jiaohua Yu, Rong Yan, Suyun Li
Published online December 31, 2024
Neurosurgical Subspecialties. doi:10.14218/NSSS.2024.00005
Abstract
Proper nutritional management has been shown to reduce complications and lead to better clinical outcomes. However, inaccurate nutritional screening and assessment, inappropriate [...] Read more.

Proper nutritional management has been shown to reduce complications and lead to better clinical outcomes. However, inaccurate nutritional screening and assessment, inappropriate nutrition support, and deviations from suggested guidelines were observed in clinical practice. We aimed to investigate the nutritional status and support of hospitalized patients with neurological diseases to identify deficiencies in nutritional assessment and treatment.

A self-designed questionnaire, developed through a literature review, group discussions, and expert consultation, was converted into an electronic form to conduct a cross-sectional survey in a tertiary-level general hospital. The patients’ basic information and the first nutrition assessment were filled out upon admission. The final nutrition assessment were logged at discharge, transfer out, or death. Two-person cross-entry was used to ensure the accuracy of data input.

A total of 620 patients were enrolled in this study. Of these, 24.4% were at nutritional risk upon admission, and 22.7% were identified as at nutritional risk in the final assessment. There were no statistically significant differences in nutritional status between the first and final assessments, except for serum albumin concentration. A total of 118 patients (19.0%) received nutrition therapy. Complications occurred in 35 (45.5%) patients treated with enteral nutrition and 29 (30.5%) patients treated with parenteral nutrition.

The incidence of nutritional risk in inpatients with neurological diseases enrolled in this study was relatively low. However, nutritional treatment in this study was not sufficiently standardized. Nurses are needed to receive relevant professional training to improve quality of nutritional interventions.

Full article
Original Article Open Access
GTF3C2 Promotes the Proliferation of Hepatocellular Carcinoma Cells through the USP21/MEK2/ERK1/2 Pathway
Yani Wu, Yingnan Yang, Youju Zhang, Qiuran Xu, Dongsheng Huang, Kangsheng Tu
Published online February 11, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00386
Abstract
General transcription factor IIIC subunit 2 (GTF3C2) is one of the polymerase III transcription-related factors. Previous studies have revealed that GTF3C2 is involved in regulating [...] Read more.

General transcription factor IIIC subunit 2 (GTF3C2) is one of the polymerase III transcription-related factors. Previous studies have revealed that GTF3C2 is involved in regulating cell proliferation. However, the role of GTF3C2 in hepatocellular carcinoma (HCC) remains unclear. This study aimed to determine its expression, biological function, and mechanism in HCC.

The expression of GTF3C2 in HCC and non-tumor tissues, along with its clinical significance, was investigated using public databases and clinical samples. Reverse transcription-quantitative polymerase chain reaction and Western blot assays were performed to detect the expression of GTF3C2, ubiquitin specific peptidase 21 (USP21), mitogen-activated protein kinase 2 (MEK2), extracellular signal-regulated kinase 1/2 (ERK1/2), and p-ERK1/2 in cells. A luciferase reporter assay was conducted to explore the regulatory effect of GTF3C2 on USP21 transcription. Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine, and colony formation assays were performed to assess HCC cell proliferation. Subcutaneous injection of HCC cells into nude mice was used to evaluate tumor growth in vivo.

GTF3C2 expression was upregulated in HCC tissues and was positively correlated with advanced tumor stages and high tumor grades. HCC patients with high GTF3C2 expression had significantly worse survival outcomes. Knockdown of GTF3C2 suppressed the proliferation of Hep3B and HCCLM3 cells, while overexpression of GTF3C2 facilitated the proliferation of SNU449 and Huh7 cells. GTF3C2 promoted USP21 expression by activating its transcription, which subsequently increased the levels of MEK2 and p-ERK1/2 in HCC cells. Overexpression of both USP21 and MEK2 counteracted the GTF3C2 knockdown-induced inactivation of the ERK1/2 pathway. Moreover, GTF3C2 promoted HCC cell proliferation in vitro and tumor growth in vivo by regulating the USP21/MEK2/ERK1/2 pathway.

Upregulation of GTF3C2 is frequently observed in HCC tissues and predicts poor prognosis. GTF3C2 promotes HCC cell proliferation via the USP21/MEK2/ERK1/2 pathway.

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