Cancer Medicine最新文献

Leveraging Artificial Intelligence and Radiomics for Improved Nasopharyngeal Carcinoma Prognostication

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-19 DOI: 10.1002/cam4.70706

Nicholas Brian Shannon, Narayanan Gopalakrishna lyer, Melvin Lee Kiang Chua

Introduction

Nasopharyngeal carcinoma (NPC) typically presents as advanced disease due to the lack of significant symptoms in the early stages. Accurate prognostication is therefore challenging as current methods based on anatomical staging often lack the granularity to differentiate between patients with differing prognoses. This study investigates the potential of radiomics to improve the prediction of locoregional recurrence (LRR) and overall survival in patients with NPC.

Methods

Radiomic features were extracted from radiotherapy planning CT scans for 294 NPC patients divided into training (n = 147) and validation (n = 147) sets. A feature selection step utilising feature clustering and mutual information classifier to select six key radiomic features was employed to reduce redundancy and improve interpretability. Models were trained using clinical data, radiomic features, and these in combination to predict 2-year LRR, with performance assessed on the left-out independent validation set.

Results

Combining radiomic features with clinical data resulted in the best performance for predicting 2-year LRR (Area Under the Curve, AUC 0.76) compared to prediction using clinical or radiomic features alone (mean AUC 0.56 and 0.57, respectively). Risk stratification based on the combined model was significant for LRR-free survival and overall survival (p < 0.01). Key radiomic features included tumour size, intensity distribution, overall textural patterns, and distribution of fine and coarse textured regions.

Discussion

Radiomics holds promise for improving NPC risk stratification, potentially allowing for personalised treatment strategies. The most important radiomics feature, maximum 2D diameter, suggests a need to reconsider tumour size as a prognostic criterion despite its current exclusion from TNM staging. Larger prospective studies are needed to validate these findings.

{"title":"Leveraging Artificial Intelligence and Radiomics for Improved Nasopharyngeal Carcinoma Prognostication","authors":"Nicholas Brian Shannon, Narayanan Gopalakrishna lyer, Melvin Lee Kiang Chua","doi":"10.1002/cam4.70706","DOIUrl":"https://doi.org/10.1002/cam4.70706","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Nasopharyngeal carcinoma (NPC) typically presents as advanced disease due to the lack of significant symptoms in the early stages. Accurate prognostication is therefore challenging as current methods based on anatomical staging often lack the granularity to differentiate between patients with differing prognoses. This study investigates the potential of radiomics to improve the prediction of locoregional recurrence (LRR) and overall survival in patients with NPC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Radiomic features were extracted from radiotherapy planning CT scans for 294 NPC patients divided into training (<i>n</i> = 147) and validation (<i>n</i> = 147) sets. A feature selection step utilising feature clustering and mutual information classifier to select six key radiomic features was employed to reduce redundancy and improve interpretability. Models were trained using clinical data, radiomic features, and these in combination to predict 2-year LRR, with performance assessed on the left-out independent validation set.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Combining radiomic features with clinical data resulted in the best performance for predicting 2-year LRR (Area Under the Curve, AUC 0.76) compared to prediction using clinical or radiomic features alone (mean AUC 0.56 and 0.57, respectively). Risk stratification based on the combined model was significant for LRR-free survival and overall survival (<i>p</i> < 0.01). Key radiomic features included tumour size, intensity distribution, overall textural patterns, and distribution of fine and coarse textured regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Radiomics holds promise for improving NPC risk stratification, potentially allowing for personalised treatment strategies. The most important radiomics feature, maximum 2D diameter, suggests a need to reconsider tumour size as a prognostic criterion despite its current exclusion from TNM staging. Larger prospective studies are needed to validate these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70706","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical Characteristics, Prognostic Factors and Therapeutic Strategies in Gastric Cancer Patients With Bone Metastasis: A Retrospective Analysis

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-19 DOI: 10.1002/cam4.70781

Shiji Ren, Yutao Wei, Wenqi Liu, Yipeng Zhang, Yue Wang, Ju Yang, Baorui Liu, Tao Shi, Jia Wei

Background

Bone metastases are highly refractory and are associated with extremely poor survival. Despite the increasing incidence of bone metastasis in gastric cancer (GC), comprehensive analyses regarding the clinicopathological features, prognosis, and treatment of bone-metastatic GC remain limited.

Methods

We obtained data from 120 bone-metastatic GC patients from Nanjing Drum Tower Hospital and 36,139 GC patients from the SEER database. Chi-square and Mann–Whitney U-tests evaluated clinicopathological features, while Cox models identified prognostic factors. Kaplan–Meier curves and forest plots assessed the effects of different treatment strategies on overall survival after bone metastasis (OS-BM).

Results

Among 120 bone-metastatic GC patients, 55 (45.83%) were diagnosed with poorly cohesive gastric carcinoma (PCC). The higher incidence of bone metastasis was also observed in SRCC patients from the SEER database (p < 0.0001). PCC patients exhibited distinct pathological features compared to non-PCC patients, including lower PD-L1 (p = 0.042) and E-cadherin expression (p = 0.049). Multivariate analysis identified various negative prognostic factors such as metachronous bone metastasis (p < 0.001, HR = 2.35, 95% CI:1.47–3.74) and CA125 expression (p = 0.036, HR = 1.60, 95% CI:1.03–2.48), whereas immunotherapy was a positive prognostic factor (p < 0.001, HR = 0.44, 95% CI:0.29–0.66). Subgroup analysis also showed improved survival among different populations of bone-metastatic GC patients receiving immunotherapy. Moreover, combinational therapies including immunotherapy and other treatments (anti-angiogenic therapy and/or local radiotherapy) further improved patient OS-BM.

Conclusion

Our results suggest bone-metastatic GC patients exhibit distinct clinicopathological features, with a high incidence of bone metastasis in PCC. Immunotherapy-based combination therapies offer improved survival benefits, thus supporting the application of immunotherapy in GC patients at high risk of bone metastasis.

{"title":"Clinical Characteristics, Prognostic Factors and Therapeutic Strategies in Gastric Cancer Patients With Bone Metastasis: A Retrospective Analysis","authors":"Shiji Ren, Yutao Wei, Wenqi Liu, Yipeng Zhang, Yue Wang, Ju Yang, Baorui Liu, Tao Shi, Jia Wei","doi":"10.1002/cam4.70781","DOIUrl":"https://doi.org/10.1002/cam4.70781","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bone metastases are highly refractory and are associated with extremely poor survival. Despite the increasing incidence of bone metastasis in gastric cancer (GC), comprehensive analyses regarding the clinicopathological features, prognosis, and treatment of bone-metastatic GC remain limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We obtained data from 120 bone-metastatic GC patients from Nanjing Drum Tower Hospital and 36,139 GC patients from the SEER database. Chi-square and Mann–Whitney <i>U</i>-tests evaluated clinicopathological features, while Cox models identified prognostic factors. Kaplan–Meier curves and forest plots assessed the effects of different treatment strategies on overall survival after bone metastasis (OS-BM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 120 bone-metastatic GC patients, 55 (45.83%) were diagnosed with poorly cohesive gastric carcinoma (PCC). The higher incidence of bone metastasis was also observed in SRCC patients from the SEER database (<i>p</i> < 0.0001). PCC patients exhibited distinct pathological features compared to non-PCC patients, including lower PD-L1 (<i>p</i> = 0.042) and E-cadherin expression (<i>p</i> = 0.049). Multivariate analysis identified various negative prognostic factors such as metachronous bone metastasis (<i>p</i> < 0.001, HR = 2.35, 95% CI:1.47–3.74) and CA125 expression (<i>p</i> = 0.036, HR = 1.60, 95% CI:1.03–2.48), whereas immunotherapy was a positive prognostic factor (<i>p</i> < 0.001, HR = 0.44, 95% CI:0.29–0.66). Subgroup analysis also showed improved survival among different populations of bone-metastatic GC patients receiving immunotherapy. Moreover, combinational therapies including immunotherapy and other treatments (anti-angiogenic therapy and/or local radiotherapy) further improved patient OS-BM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results suggest bone-metastatic GC patients exhibit distinct clinicopathological features, with a high incidence of bone metastasis in PCC. Immunotherapy-based combination therapies offer improved survival benefits, thus supporting the application of immunotherapy in GC patients at high risk of bone metastasis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70781","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Kynurenine Pathway and Indole Pathway in Tryptophan Metabolism Influence Tumor Progression

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-18 DOI: 10.1002/cam4.70703

Zhanhui Lu, Chengcheng Zhang, Jia Zhang, Wan Su, Guoying Wang, Zhongqi Wang

Tryptophan (Trp), an essential amino acid, is solely acquired through dietary intake. It is vital for protein biosynthesis and acts as a precursor for numerous key bioactive compounds. The Kynurenine Pathway and the Indole Pathway are the main metabolic routes and are extensively involved in the occurrence and progression of diseases in the digestive, nervous, and urinary systems. In the Kynurenine Pathway, enzymes crucial to tryptophan metabolism, indoleamine-2,3-dioxygenase 1 (IDO1), IDO2, and Trp-2,3-dioxygenase (TDO), trigger tumor immune resistance within the tumor microenvironment and nearby lymph nodes by depleting Trp or by activating the Aromatic Hydrocarbon Receptor (AhR) through its metabolites. Furthermore, IDO1 can influence immune responses via non-enzymatic pathways. The Kynurenine Pathway exerts its effects on tumor growth through various mechanisms, including NAD+ regulation, angiogenesis promotion, tumor metastasis enhancement, and the inhibition of tumor ferroptosis. In the Indole Pathway, indole and its related metabolites are involved in gastrointestinal homeostasis, tumor immunity, and drug resistance. The gut microbiota related to indole metabolism plays a critical role in determining the effectiveness of tumor treatment strategies and can influence the efficacy of immunochemotherapy. It is worth noting that there are conflicting effects of the Kynurenine Pathway and the Indole Pathway on the same tumor phenotype. For example, different tryptophan metabolites affect the cell cycle differently, and indole metabolism has inconsistent protective effects on tumors in different regions. These differences may hold potential for enhancing therapeutic efficacy.

{"title":"The Kynurenine Pathway and Indole Pathway in Tryptophan Metabolism Influence Tumor Progression","authors":"Zhanhui Lu, Chengcheng Zhang, Jia Zhang, Wan Su, Guoying Wang, Zhongqi Wang","doi":"10.1002/cam4.70703","DOIUrl":"https://doi.org/10.1002/cam4.70703","url":null,"abstract":"<p>Tryptophan (Trp), an essential amino acid, is solely acquired through dietary intake. It is vital for protein biosynthesis and acts as a precursor for numerous key bioactive compounds. The Kynurenine Pathway and the Indole Pathway are the main metabolic routes and are extensively involved in the occurrence and progression of diseases in the digestive, nervous, and urinary systems. In the Kynurenine Pathway, enzymes crucial to tryptophan metabolism, indoleamine-2,3-dioxygenase 1 (IDO1), IDO2, and Trp-2,3-dioxygenase (TDO), trigger tumor immune resistance within the tumor microenvironment and nearby lymph nodes by depleting Trp or by activating the Aromatic Hydrocarbon Receptor (AhR) through its metabolites. Furthermore, IDO1 can influence immune responses via non-enzymatic pathways. The Kynurenine Pathway exerts its effects on tumor growth through various mechanisms, including NAD+ regulation, angiogenesis promotion, tumor metastasis enhancement, and the inhibition of tumor ferroptosis. In the Indole Pathway, indole and its related metabolites are involved in gastrointestinal homeostasis, tumor immunity, and drug resistance. The gut microbiota related to indole metabolism plays a critical role in determining the effectiveness of tumor treatment strategies and can influence the efficacy of immunochemotherapy. It is worth noting that there are conflicting effects of the Kynurenine Pathway and the Indole Pathway on the same tumor phenotype. For example, different tryptophan metabolites affect the cell cycle differently, and indole metabolism has inconsistent protective effects on tumors in different regions. These differences may hold potential for enhancing therapeutic efficacy.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70703","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cancer Fatalism Among Asian American Adults by Origin Group, 2012–2022

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-18 DOI: 10.1002/cam4.70738

Justine Liu, Yenan Zhu, Ryan Suk, Milkie Vu

Backgrounds

Cancer fatalism, the belief that cancer is predetermined and unpreventable, is associated with lower uptake of cancer prevention. Little is known about cancer fatalism prevalence within various Asian origin groups.

Methods

We conducted a disaggregated analysis of cancer fatalism among Chinese, Filipino, Indian, Vietnamese, and other Asian respondents using the 2012–2022 Health Information National Trends Survey. Pairwise comparisons were conducted to assess differences between each racial and ethnic group.

Results

Significantly lower proportions of Indian respondents (40.36%) endorsed the statement “It seems like everything causes cancer,” when compared with Vietnamese (74.59%, p = 0.0002) and Filipino (75.18%, p = 0.0009) respondents. Lower proportions of Indian and Chinese respondents endorsed the statement “There's not much you can do to lower your chances of getting cancer” when compared with Vietnamese and Filipino respondents, though these differences were not significant.

Conclusions

Findings highlight the heterogeneity among Asian origin groups and emphasize the importance of disaggregated data collection by origin group, which can inform culturally tailored interventions.

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引用次数: 0

Application of GPRC5D Targeting Therapy in Relapsed Refractory Multiple Myeloma

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-17 DOI: 10.1002/cam4.70764

Sijia Yan, Xi Ming, Rubing Zheng, Xiaojian Zhu, Yi Xiao

Background

As a rapidly developing therapeutic method, targeted therapy plays an important role in the treatment of multiple myeloma. In recent years, mature B cell antigen-targeting therapy has brought new hope for patients with refractory/relapsed disease. While an increasing number of patients with relapse are exposed to this type of drug, changing the therapeutic target may be an effective strategy for patients with relapse/refractory multiple myeloma.

Objectives

The expression of G protein-coupled receptor, class C Group 5 member D (GPRC5D), on the surface of myeloma tumor cells makes it a possible target for relapse/refractory multiple myeloma therapy, and relevant studies are in progress.

Results & Conclusions

The review aims to systematically summarize the current advancements in GPRC5D-targeted therapies for multiple myeloma, thereby providing valuable insights and a foundation for future studies.

{"title":"Application of GPRC5D Targeting Therapy in Relapsed Refractory Multiple Myeloma","authors":"Sijia Yan, Xi Ming, Rubing Zheng, Xiaojian Zhu, Yi Xiao","doi":"10.1002/cam4.70764","DOIUrl":"https://doi.org/10.1002/cam4.70764","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>As a rapidly developing therapeutic method, targeted therapy plays an important role in the treatment of multiple myeloma. In recent years, mature B cell antigen-targeting therapy has brought new hope for patients with refractory/relapsed disease. While an increasing number of patients with relapse are exposed to this type of drug, changing the therapeutic target may be an effective strategy for patients with relapse/refractory multiple myeloma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The expression of G protein-coupled receptor, class C Group 5 member D (GPRC5D), on the surface of myeloma tumor cells makes it a possible target for relapse/refractory multiple myeloma therapy, and relevant studies are in progress.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results & Conclusions</h3>\u0000 \u0000 <p>The review aims to systematically summarize the current advancements in GPRC5D-targeted therapies for multiple myeloma, thereby providing valuable insights and a foundation for future studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70764","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring Mechanisms and Biomarkers of Breast Cancer Invasion and Migration: An Explainable Gene–Pathway–Compounds Neural Network

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-17 DOI: 10.1002/cam4.70769

Xia Qian, Dandan Sun, Yichen Ma, Ling Qiu, Jie Wu

Backgrounds

Exploring the molecular features that drive breast cancer invasion and migration remains an important biological and clinical challenge. In recent years, the use of interpretable machine learning models has enhanced our understanding of the underlying mechanisms of disease progression.

Methods

In this study, we present a novel gene–pathway–compound-related sparse deep neural network (GPC-Net) for investigating breast cancer invasion and migration. The GPC-Net is an interpretable neural network model that utilizes molecular data to predict cancer status. It visually represents genes, pathways, and associated compounds involved in these pathways.

Results

Compared with other modeling methods, GPC-Net demonstrates superior performance. Our research identifies key genes, such as ADCY8, associated with invasive breast cancer and verifies their expression in breast cancer cells. In addition, we conducted a preliminary exploration of several pathways.

Conclusion

GPC-Net is among the pioneering deep neural networks that incorporate pathways and compounds, aiming to balance interpretability and performance. It is expected to offer a more convenient approach for future biomedical research.

{"title":"Exploring Mechanisms and Biomarkers of Breast Cancer Invasion and Migration: An Explainable Gene–Pathway–Compounds Neural Network","authors":"Xia Qian, Dandan Sun, Yichen Ma, Ling Qiu, Jie Wu","doi":"10.1002/cam4.70769","DOIUrl":"https://doi.org/10.1002/cam4.70769","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backgrounds</h3>\u0000 \u0000 <p>Exploring the molecular features that drive breast cancer invasion and migration remains an important biological and clinical challenge. In recent years, the use of interpretable machine learning models has enhanced our understanding of the underlying mechanisms of disease progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we present a novel gene–pathway–compound-related sparse deep neural network (GPC-Net) for investigating breast cancer invasion and migration. The GPC-Net is an interpretable neural network model that utilizes molecular data to predict cancer status. It visually represents genes, pathways, and associated compounds involved in these pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with other modeling methods, GPC-Net demonstrates superior performance. Our research identifies key genes, such as ADCY8, associated with invasive breast cancer and verifies their expression in breast cancer cells. In addition, we conducted a preliminary exploration of several pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GPC-Net is among the pioneering deep neural networks that incorporate pathways and compounds, aiming to balance interpretability and performance. It is expected to offer a more convenient approach for future biomedical research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70769","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association Between Systemic Immunity-Inflammation Index (SII) and Fatigue, Cancer, and Cancer-Related Fatigue: Insights From NHANES (2005–2018)

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-17 DOI: 10.1002/cam4.70777

Li Sun, Yanling Wu, Lydia Idowu Akinyemi, Zhiqiu Cao, Zhanhong Fan, Huahua Liu, Ziyi Yang, Leilei Zhang, Feng Zhang

Objective

To investigate the association between the systemic immunity-inflammation index (SII) and fatigue, cancer, and cancer-related fatigue (CRF) populations.

Methods

The National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 provided data for this retrospective cross-sectional study. By dividing the platelet count by the neutrophil count and the lymphocyte count, SII was calculated. Participants were categorized into four groups: normal, fatigue, cancer, and cancer-related fatigue (CRF), with the normal group serving as the reference. Binary logistic regression was applied to assess the correlations. The dose–response relationship between SII and outcomes in the four groups was evaluated using restricted cubic splines. Use threshold effect analysis to determine the optimal SII value for each of the three groups. Stratified and subgroup analyses were performed based on sociodemographic factors and confounders, with specific attention to fatigue severity levels (mild, moderate, severe) in the fatigue and CRF groups.

Results

Data analysis included a total of 32,491 participants, including 14,846 in the normal group, 14,581 in the fatigue group, 1520 in the cancer group, and 1544 in the CRF group. The results of binary logistic regression showed that SII was positively correlated with the fatigue group (1.43[1.33, 1.55]), cancer group (1.67 [1.43, 1.95]) and CRF group (1.93 [1.66, 2.25]). Restricted cubic spline analysis revealed a linear relationship between SII and outcomes. The threshold values (k) for each of these groups were identified as 464.78 × 10³ cells/μL, 448.97 × 10³ cells/μL, and 454.65 × 10³ cells/μL, respectively. Stratified analysis indicates that most groups exhibit significant differences. The subgroup analysis indicated that fatigue severity increased with higher SII levels, with the CRF group exhibiting the highest rate of severe fatigue (171% increase).

Conclusion

SII is positively correlated with fatigue, cancer, and CRF in a linear way. Higher SII values are associated with greater fatigue, particularly in the CRF population.

{"title":"Association Between Systemic Immunity-Inflammation Index (SII) and Fatigue, Cancer, and Cancer-Related Fatigue: Insights From NHANES (2005–2018)","authors":"Li Sun, Yanling Wu, Lydia Idowu Akinyemi, Zhiqiu Cao, Zhanhong Fan, Huahua Liu, Ziyi Yang, Leilei Zhang, Feng Zhang","doi":"10.1002/cam4.70777","DOIUrl":"https://doi.org/10.1002/cam4.70777","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the association between the systemic immunity-inflammation index (SII) and fatigue, cancer, and cancer-related fatigue (CRF) populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 provided data for this retrospective cross-sectional study. By dividing the platelet count by the neutrophil count and the lymphocyte count, SII was calculated. Participants were categorized into four groups: normal, fatigue, cancer, and cancer-related fatigue (CRF), with the normal group serving as the reference. Binary logistic regression was applied to assess the correlations. The dose–response relationship between SII and outcomes in the four groups was evaluated using restricted cubic splines. Use threshold effect analysis to determine the optimal SII value for each of the three groups. Stratified and subgroup analyses were performed based on sociodemographic factors and confounders, with specific attention to fatigue severity levels (mild, moderate, severe) in the fatigue and CRF groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data analysis included a total of 32,491 participants, including 14,846 in the normal group, 14,581 in the fatigue group, 1520 in the cancer group, and 1544 in the CRF group. The results of binary logistic regression showed that SII was positively correlated with the fatigue group (1.43[1.33, 1.55]), cancer group (1.67 [1.43, 1.95]) and CRF group (1.93 [1.66, 2.25]). Restricted cubic spline analysis revealed a linear relationship between SII and outcomes. The threshold values (k) for each of these groups were identified as 464.78 × 10<sup>3</sup> cells/μL, 448.97 × 10<sup>3</sup> cells/μL, and 454.65 × 10<sup>3</sup> cells/μL, respectively. Stratified analysis indicates that most groups exhibit significant differences. The subgroup analysis indicated that fatigue severity increased with higher SII levels, with the CRF group exhibiting the highest rate of severe fatigue (171% increase).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SII is positively correlated with fatigue, cancer, and CRF in a linear way. Higher SII values are associated with greater fatigue, particularly in the CRF population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70777","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Oncogenic Role of UBXN1 in Gastric Cancer Is Attributed to the METTL16-Mediated m6A Methylation and Histone Modifications UBXN1 在胃癌中的致癌作用归因于 METTL16 介导的 m6A 甲基化和组蛋白修饰

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-17 DOI: 10.1002/cam4.70772

Kesong Shi, Yani Chen, Tian Gao, Hua Guo, Xinyao Fu, Yuan Wu, Haiquan Yu

Background

Multiple epigenetic regulatory mechanisms are crucial in tumorigenesis and development. However, the synergistic relationship between N6-methyladenosine (m6A) and histone modifications in regulating gene expression of gastric cancer (GC) requires further investigation.

Results

Here, based on the microarray, RNA-seq, and survival analysis data, the m6A methyltransferase METTL16 was identified as a potential tumorigenic factor of GC. The silence of METTL16 suppresses the malignant phenotype of GC cells, and the NF-κB pathway was activated. By using the weighted correlation network analysis (WGCNA) and integrating RNA-seq and MeRIP-seq data, it was found that METTL16 is significantly positively correlated with UBX domain protein 1 (UBXN1). Furthermore, through the MeRIP-qPCR and dual-luciferase reporter assays, we found that knocking down METTL16 reduced the m6A modification level of the UBXN1 coding sequence in GC. Interestingly, the silencing of METTL16 also downregulated UBXN1 expression by promoting H3K36me3 modification at the UBXN1 promoter. Subsequent investigations found that the silencing of METTL16 upregulated the expression of the major H3K36me3 methyltransferase SETD2 in GC cells by methylating the m6A site in the mRNA coding sequence of SETD2.

Conclusions

Our findings demonstrate the spatio-temporal regulation of UBXN1 expression in GC cells by METTL16 through a combination of transcriptional and post-transcriptional mechanisms. The synergistic interplay of these various epigenetic mechanisms provides new prospects for tumor diagnosis and precision treatment.

{"title":"The Oncogenic Role of UBXN1 in Gastric Cancer Is Attributed to the METTL16-Mediated m6A Methylation and Histone Modifications","authors":"Kesong Shi, Yani Chen, Tian Gao, Hua Guo, Xinyao Fu, Yuan Wu, Haiquan Yu","doi":"10.1002/cam4.70772","DOIUrl":"https://doi.org/10.1002/cam4.70772","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Multiple epigenetic regulatory mechanisms are crucial in tumorigenesis and development. However, the synergistic relationship between N6-methyladenosine (m6A) and histone modifications in regulating gene expression of gastric cancer (GC) requires further investigation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, based on the microarray, RNA-seq, and survival analysis data, the m6A methyltransferase METTL16 was identified as a potential tumorigenic factor of GC. The silence of METTL16 suppresses the malignant phenotype of GC cells, and the NF-κB pathway was activated. By using the weighted correlation network analysis (WGCNA) and integrating RNA-seq and MeRIP-seq data, it was found that METTL16 is significantly positively correlated with UBX domain protein 1 (UBXN1). Furthermore, through the MeRIP-qPCR and dual-luciferase reporter assays, we found that knocking down METTL16 reduced the m6A modification level of the UBXN1 coding sequence in GC. Interestingly, the silencing of METTL16 also downregulated UBXN1 expression by promoting H3K36me3 modification at the UBXN1 promoter. Subsequent investigations found that the silencing of METTL16 upregulated the expression of the major H3K36me3 methyltransferase SETD2 in GC cells by methylating the m6A site in the mRNA coding sequence of SETD2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings demonstrate the spatio-temporal regulation of UBXN1 expression in GC cells by METTL16 through a combination of transcriptional and post-transcriptional mechanisms. The synergistic interplay of these various epigenetic mechanisms provides new prospects for tumor diagnosis and precision treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70772","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Estimating the Burden of False Positives and Implementation Costs From Adding Multiple Single Cancer Tests or a Single Multi-Cancer Test to Standard-Of-Care Screening

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-17 DOI: 10.1002/cam4.70776

Sarina Madhavan, Allan Hackshaw, Earl Hubbell, Ellen T. Chang, Anuraag Kansal, Christina A. Clarke

Background

Blood-based tests present a promising strategy to enhance cancer screening through two distinct approaches. In the traditional paradigm of “one test for one cancer”, single-cancer early detection (SCED) tests a feature high true positive rate (TPR) for individual cancers, but high false-positive rate (FPR). Whereas multi-cancer early detection (MCED) tests simultaneously target multiple cancers with one low FPR, offering a new “one test for multiple cancers” approach. However, comparing these two approaches is inherently non-intuitive. We developed a framework for evaluating and comparing the efficiency and downstream costs of these two blood-based screening approaches at the general population level.

Methods

We developed two hypothetical screening systems to evaluate the performance efficiency of each blood-based screening approach. The “SCED-10” system featured 10 hypothetical SCED tests, each targeting one cancer type; the “MCED-10” system included a single hypothetical MCED test targeting the same 10 cancer types. We estimated the number of cancers detected, cumulative false positives, and associated costs of obligated testing for positive results for each system over 1 year when added to existing USPSTF-recommended cancer screening for 100,000 US adults aged 50–79.

Results

Compared with MCED-10, SCED-10 detected 1.4× more cancers (412 vs. 298), but had 188× more diagnostic investigations in cancer-free people (93,289 vs. 497), lower efficiency (positive predictive value: 0.44% vs. 38%; number needed to screen: 2062 vs. 334), 3.4× the cost ($329 M vs. $98 M), and 150× higher cumulative burden of false positives per annual round of screening (18 vs. 0.12).

Conclusions

A screening system for average-risk individuals using multiple SCED tests has a higher rate of false positives and associated costs compared with a single MCED test. A set of SCED tests with the same sensitivity as standard-of-care screening detects only modestly more cancers than an MCED test limited to the same set of cancers.

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引用次数: 0

Correction to “Chemotherapy for Post-Menopausal Women With Early Breast Cancer Seems Not to Result in Clinically Significant Changes in Thyroid Function”

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-15 DOI: 10.1002/cam4.70766

Marina D, Buch-Larsen K, Gillberg L, et al. Chemotherapy for post-menopausal women with early breast cancer seems not to result in clinically significant changes in thyroid function. Cancer Med. 2024; 13:e70015. doi:10.1002/cam4.70015

The authors have unfortunately identified an error in the Methods section (page 3 of 12), where we incorrectly described the assay as “immunohistochemistry” instead of the correct term “immunoassay.” The accurate sentence should read “Thyroid parameters (s-TSH, s-TT4, s-FT4, s-TT3) were analyzed by immunoassay; s-TgAb and s-TPOAb were analyzed by immunofluorometry, whereas s-TRAb was analyzed by electrochemiluminescence immunoassay.”

Additionally, this error appears two times in the Discussion section (page 9 of 12), where “immunohistochemistry” should also be replaced with “immunoassay.” The accurate sentences should read:

“Our study group conducted an analysis of thyroid hormones using immunoassay, which was the most affordable assay and readily available at a low cost in our department.”

“It has been documented that free thyroid hormones measured by LC–MS/MS correlate better with log-transformed TSH than those measured by immunoassay, particularly in certain patient groups.”

Furthermore, in Supplementary Table S1 (page 3 out of 12), the assay type for the measurements of TSH, TT4, FT4, and TT3 should be corrected again from “immunohistochemistry” to “immunoassay.” The corrected table can be found in the online Supporting Information.

We sincerely apologize for this error.

Marina D, Buch-Larsen K, Gillberg L, et al.对绝经后患早期乳腺癌的妇女进行化疗似乎不会导致甲状腺功能发生临床显著变化。Cancer Med.doi:10.1002/cam4.70015作者不幸在方法部分（第3页，共12页）发现了一个错误，我们错误地将检测方法描述为 "免疫组化"，而不是正确的术语 "免疫测定"。准确的句子应为："甲状腺参数（s-TSH、s-TT4、s-FT4、s-TT3）通过免疫测定法进行分析；s-TgAb和s-TPOAb通过免疫荧光法进行分析，而s-TRAb则通过电化学发光免疫测定法进行分析。"此外，这一错误在讨论部分（12页中的第9页）出现了两次，"免疫组化 "也应改为 "免疫测定"。准确的句子应为："我们的研究小组使用免疫测定法对甲状腺激素进行了分析，这是最经济实惠的检测方法，而且在我们科室很容易以低成本获得。""有文献表明，与免疫测定法相比，LC-MS/MS法测定的游离甲状腺激素与对数转换TSH的相关性更好，尤其是在某些患者群体中。"此外，在补充表S1（共12页，第3页）中，TSH、TT4、FT4和TT3的测定类型应再次从 "免疫组化法 "更正为 "免疫测定法"。更正后的表格可在在线辅助信息中找到。我们对这一错误表示诚挚的歉意。

{"title":"Correction to “Chemotherapy for Post-Menopausal Women With Early Breast Cancer Seems Not to Result in Clinically Significant Changes in Thyroid Function”","authors":"","doi":"10.1002/cam4.70766","DOIUrl":"https://doi.org/10.1002/cam4.70766","url":null,"abstract":"<p>Marina D, Buch-Larsen K, Gillberg L, et al. Chemotherapy for post-menopausal women with early breast cancer seems not to result in clinically significant changes in thyroid function. <i>Cancer Med</i>. 2024; 13:e70015. doi:10.1002/cam4.70015</p><p>The authors have unfortunately identified an error in the <b>Methods section (page 3 of 12)</b>, where we incorrectly described the assay as <b>“immunohistochemistry” instead of the correct term “immunoassay.”</b> The accurate sentence should read “Thyroid parameters (s-TSH, s-TT4, s-FT4, s-TT3) were analyzed by <b>immunoassay</b>; s-TgAb and s-TPOAb were analyzed by immunofluorometry, whereas s-TRAb was analyzed by electrochemiluminescence immunoassay.”</p><p>Additionally, this error appears two times in the <b>Discussion section (page 9 of 12)</b>, where <b>“immunohistochemistry” should also be replaced with “immunoassay.”</b> The accurate sentences should read:</p><p>“Our study group conducted an analysis of thyroid hormones using <b>immunoassay</b>, which was the most affordable assay and readily available at a low cost in our department.”</p><p>“It has been documented that free thyroid hormones measured by LC–MS/MS correlate better with log-transformed TSH than those measured by <b>immunoassay</b>, particularly in certain patient groups.”</p><p>Furthermore, in <b>Supplementary Table S1 (page 3 out of 12)</b>, the assay type for the measurements of TSH, TT4, FT4, and TT3 should be <b>corrected again from “immunohistochemistry” to “immunoassay.”</b> The corrected table can be found in the online Supporting Information.</p><p>We sincerely apologize for this error.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70766","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0