Margrethe Bang Henriksen, Florian Van Daalen, Leonard Wee, Torben Frøstrup Hansen, Lars Henrik Jensen, Claus Lohman Brasen, Ole Hilberg, Inigo Bermejo
Background
Lung cancer (LC) is the top cause of cancer deaths globally, prompting many countries to adopt LC screening programs. While screening typically relies on age and smoking intensity, more efficient risk models exist. We devised a Bayesian network (BN) for LC detection, testing its resilience with varying degrees of missing data and comparing it to a prior machine learning (ML) model.
Methods
We analyzed data from 9940 patients referred for LC assessment in Southern Denmark from 2009 to 2018. Variables included age, sex, smoking, and lab results. Our experiments varied missing data (0%–30%), BN structure (expert-based vs. data-driven), and discretization method (standard vs. data-driven).
Results
Across all missing data levels, area under the curve (AUC) remained steady, ranging from 0.737 to 0.757, compared to the ML model's AUC of 0.77. BN structure and discretization method had minimal impact on performance. BNs were well calibrated overall, with a net benefit in decision curve analysis when predicted risk exceeded 5%.
Conclusion
BN models showed resilience with up to 30% missing values. Moreover, these BNs exhibited similar performance, calibration, and clinical utility compared to the machine learning model developed using the same dataset. Considering their effectiveness in handling missing data, BNs emerge as a relevant method for the development of future lung cancer detection models.
{"title":"Lung Cancer Detection Using Bayesian Networks: A Retrospective Development and Validation Study on a Danish Population of High-Risk Individuals","authors":"Margrethe Bang Henriksen, Florian Van Daalen, Leonard Wee, Torben Frøstrup Hansen, Lars Henrik Jensen, Claus Lohman Brasen, Ole Hilberg, Inigo Bermejo","doi":"10.1002/cam4.70458","DOIUrl":"10.1002/cam4.70458","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lung cancer (LC) is the top cause of cancer deaths globally, prompting many countries to adopt LC screening programs. While screening typically relies on age and smoking intensity, more efficient risk models exist. We devised a Bayesian network (BN) for LC detection, testing its resilience with varying degrees of missing data and comparing it to a prior machine learning (ML) model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed data from 9940 patients referred for LC assessment in Southern Denmark from 2009 to 2018. Variables included age, sex, smoking, and lab results. Our experiments varied missing data (0%–30%), BN structure (expert-based vs. data-driven), and discretization method (standard vs. data-driven).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Across all missing data levels, area under the curve (AUC) remained steady, ranging from 0.737 to 0.757, compared to the ML model's AUC of 0.77. BN structure and discretization method had minimal impact on performance. BNs were well calibrated overall, with a net benefit in decision curve analysis when predicted risk exceeded 5%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>BN models showed resilience with up to 30% missing values. Moreover, these BNs exhibited similar performance, calibration, and clinical utility compared to the machine learning model developed using the same dataset. Considering their effectiveness in handling missing data, BNs emerge as a relevant method for the development of future lung cancer detection models.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062430","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}
Cancer-associated fibroblasts (CAFs) play a significant role in human breast cancer as a major stromal component. While their role in promoting cancer proliferation and malignancy through interaction with cancer cells in the tumor microenvironment is known, the exact mechanisms behind this interaction are not fully understood.
Results
Our study reveals that lymphoid enhancer-binding factor 1 (LEF1), a central transcription factor for Wnt/β-catenin signaling, is expressed in experimentally generated tumor-promoting CAFs (exp-CAFs) as well as in CAFs from breast cancer patients, particularly those with a poor prognosis. Notably, LEF1-expressing CAFs are prevalent in the stroma of squamous cell carcinoma (SCC), an aggressive metaplastic breast cancer subtype with a limited understanding of its development. To investigate the functional importance of LEF1 expression in CAFs, we depleted LEF1 in the exp-CAFs and subcutaneously implanted them along with breast ductal carcinoma MCF10DCIS.com cells into immunodeficient mice. Depleting LEF1 resulted in reduced xenograft tumor growth, accompanied by decreased cancer-cell proliferation and angiogenesis in the tumors. Additionally, we observed a significant reduction in the expression of SCC markers p40 (ΔNp63) and cytokeratin 5/6 in the xenograft tumors when LEF1 was depleted in the exp-CAFs. Furthermore, we identified 13 genes, none of which are established downstream genes of the Wnt/β-catenin pathway, that exhibit expression patterns similar to LFE1 in our cultured fibroblasts.
Conclusion
In summary, our findings suggest that LEF1 expression contributes to the tumor-promoting abilities of breast CAFs and that LEF1-expressing CAFs may drive transdifferentiation toward SCC, possibly through a pathway independent of the canonical Wnt/β-catenin signaling.
{"title":"Expression of Lymphoid Enhancer-Binding Factor 1 in Cancer-Associated Fibroblasts Mediates Tumor Growth and Transdifferentiation Toward Squamous Cell Carcinoma in Human Breast Cancer","authors":"Hiroya Okazaki, Yoshihiro Mezawa, Yang Shi, Mizuki Sakimoto, Zixu Wang, Akane Ishizuka, Kazunari Yamashita, Asahi Satoh, Yu Koyama, Yuki Fukumura, Kazunori Kajino, Atsushi Takano, Tomoyuki Yokose, Toshinari Yamashita, Yohei Miyagi, Yataro Daigo, Akira Katakura, Takehiro Yasukawa, Akira Orimo","doi":"10.1002/cam4.70627","DOIUrl":"10.1002/cam4.70627","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cancer-associated fibroblasts (CAFs) play a significant role in human breast cancer as a major stromal component. While their role in promoting cancer proliferation and malignancy through interaction with cancer cells in the tumor microenvironment is known, the exact mechanisms behind this interaction are not fully understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study reveals that lymphoid enhancer-binding factor 1 (LEF1), a central transcription factor for Wnt/β-catenin signaling, is expressed in experimentally generated tumor-promoting CAFs (exp-CAFs) as well as in CAFs from breast cancer patients, particularly those with a poor prognosis. Notably, LEF1-expressing CAFs are prevalent in the stroma of squamous cell carcinoma (SCC), an aggressive metaplastic breast cancer subtype with a limited understanding of its development. To investigate the functional importance of LEF1 expression in CAFs, we depleted LEF1 in the exp-CAFs and subcutaneously implanted them along with breast ductal carcinoma MCF10DCIS.com cells into immunodeficient mice. Depleting LEF1 resulted in reduced xenograft tumor growth, accompanied by decreased cancer-cell proliferation and angiogenesis in the tumors. Additionally, we observed a significant reduction in the expression of SCC markers p40 (ΔNp63) and cytokeratin 5/6 in the xenograft tumors when LEF1 was depleted in the exp-CAFs. Furthermore, we identified 13 genes, none of which are established downstream genes of the Wnt/β-catenin pathway, that exhibit expression patterns similar to LFE1 in our cultured fibroblasts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In summary, our findings suggest that LEF1 expression contributes to the tumor-promoting abilities of breast CAFs and that LEF1-expressing CAFs may drive transdifferentiation toward SCC, possibly through a pathway independent of the canonical Wnt/β-catenin signaling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062486","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}
Ana Marcela Rojas Fonseca-Hial, Katya Parisio, Jose Salvador Rodrigues de Oliveira
Background
Dual sources of cells (DSC) with peripheral blood stem cell apheresis (PBSC) and surgical bone marrow (BM) for haploidentical hematopoietic cell transplantation (Hid-HCT) are used in China and some Asian countries. The experience of the Baltimore group for haploidentical transplant with post-transplant cyclophosphamide (PT-Cy) and reduced-intensity-conditioning (RIC) regimen used BM as a source of hematopoietic stem cells.
Methods
We retrospectively analyzed 64 Hid-HCT with DSC and PT-Cy, RIC (n = 57), or myeloablative-conditioning (MAC) (n = 7), from two public health Brazilian centers, with a median follow-up of 23.3 months (6.7–45.4).
Results
The 49 malignant patients were 27/46 (58.7%) beyond the first remission or with no complete response, and three patients did not complete disease status evaluation before transplant. Eight of 62 patients (12.9%) had grade 2 or more Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI), and two patients had no HCT-CI classified. Cytomegalovirus (CMV) viremia occurred in 26 of 57 (45.6%). The cumulative incidence of 100-day grade III-IV acute GVHD was 12.3% (7/57), with a 95% confidence interval (CI) of 3.8% and 20.8%, and 2-year moderate or severe chronic GVHD was 21.1% (11/52; 95% CI, 10.1%–32.3%). The 2-year relapses were 24.5% for malignant disease (12/49; 95% CI, 12.4%–36.5%). The 2-year overall survival (OS) probability was 54.7% (35/64; 95% CI, 42.5%–66.9%). Benign diseases achieve 2-year OS in 73.3% (11/15; 95% CI, 51%–95.7%) of the patients. The HCT-CI were significant in multivariate analyses for DFS (p = 0.002) and OS in uni- and multivariate analyses (both p < 0.001). The number of CD34+ cells by apheresis collection was significant in multivariate analysis for DFS (p = 0.039).
Conclusion
Hid-HCT using PT-Cy, DSC, and RIC is a safe option for benign and malignant diseases.
{"title":"Haploidentical Stem Cell Transplantation With Dual Source of Cells and Post-Transplant Cyclophosphamide","authors":"Ana Marcela Rojas Fonseca-Hial, Katya Parisio, Jose Salvador Rodrigues de Oliveira","doi":"10.1002/cam4.70541","DOIUrl":"10.1002/cam4.70541","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dual sources of cells (DSC) with peripheral blood stem cell apheresis (PBSC) and surgical bone marrow (BM) for haploidentical hematopoietic cell transplantation (Hid-HCT) are used in China and some Asian countries. The experience of the Baltimore group for haploidentical transplant with post-transplant cyclophosphamide (PT-Cy) and reduced-intensity-conditioning (RIC) regimen used BM as a source of hematopoietic stem cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed 64 Hid-HCT with DSC and PT-Cy, RIC (<i>n</i> = 57), or myeloablative-conditioning (MAC) (<i>n</i> = 7), from two public health Brazilian centers, with a median follow-up of 23.3 months (6.7–45.4).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The 49 malignant patients were 27/46 (58.7%) beyond the first remission or with no complete response, and three patients did not complete disease status evaluation before transplant. Eight of 62 patients (12.9%) had grade 2 or more Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI), and two patients had no HCT-CI classified. Cytomegalovirus (CMV) viremia occurred in 26 of 57 (45.6%). The cumulative incidence of 100-day grade III-IV acute GVHD was 12.3% (7/57), with a 95% confidence interval (CI) of 3.8% and 20.8%, and 2-year moderate or severe chronic GVHD was 21.1% (11/52; 95% CI, 10.1%–32.3%). The 2-year relapses were 24.5% for malignant disease (12/49; 95% CI, 12.4%–36.5%). The 2-year overall survival (OS) probability was 54.7% (35/64; 95% CI, 42.5%–66.9%). Benign diseases achieve 2-year OS in 73.3% (11/15; 95% CI, 51%–95.7%) of the patients. The HCT-CI were significant in multivariate analyses for DFS (<i>p</i> = 0.002) and OS in uni- and multivariate analyses (both <i>p</i> < 0.001). The number of CD34<sup>+</sup> cells by apheresis collection was significant in multivariate analysis for DFS (<i>p</i> = 0.039).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Hid-HCT using PT-Cy, DSC, and RIC is a safe option for benign and malignant diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072946","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}
Mackenzie Naert, Kimia Sorouri, Andrea Lanes, Abigail M. Kempf, Lucy Chen, Randi Goldman, Ann H. Partridge, Elizabeth Ginsburg, Serene S. Srouji, Zachary Walker
Introduction
Given the known detrimental impact of cancer treatment on fertility, fertility preservation (FP) is recommended for reproductive age patients who are newly diagnosed with cancer. However, the rate of referral to fertility specialists remains suboptimal. The objective of this study was to determine the impact of a dedicated Nurse Navigator Program (NNP) on the rate of referrals and utilization of FP services.
Methods
A retrospective cohort study of all women ≥ 18 years old referred for FP consultation with a known cancer diagnosis from 2007 to 2021 at a single, large academic center was conducted. FP referrals for non-cancer indications were excluded. Descriptive statistics were performed including comparing referrals received per 30 days and FP utilization rates pre-NNP (October 2007–September 2013) to post-NNP (October 2013–December 2021).
Results
A total of 176 patients were included pre-NNP and 990 patients post-NNP. Overall, the mean age at the time of referral was 31.5 ± 6.9 years. The referral rates post-NNP were higher among those without prior exposure to chemotherapy/radiation (0.33 pre-NNP vs. 2.75 post-NNP per 30 days, p < 0.01) and lower among those with prior exposure to chemotherapy/radiation (1.26 pre-NNP vs. 0.70 post-NNP per 30 days, p < 0.01).
Conclusions
After the launch of a dedicated fertility preservation nurse navigation program at our institution, we observed a higher number of referrals for FP as well as greater use of FP overall. While not the only variable that changed during this period, this program has optimized patient care and clinical workflow at our institution and serves as a model for such improvement.
{"title":"Impact of a Nurse Navigator Program on Referral Rates and Use of Fertility Preservation Among Female Cancer Patients: A 14-Year Retrospective Cohort Study","authors":"Mackenzie Naert, Kimia Sorouri, Andrea Lanes, Abigail M. Kempf, Lucy Chen, Randi Goldman, Ann H. Partridge, Elizabeth Ginsburg, Serene S. Srouji, Zachary Walker","doi":"10.1002/cam4.70529","DOIUrl":"10.1002/cam4.70529","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Given the known detrimental impact of cancer treatment on fertility, fertility preservation (FP) is recommended for reproductive age patients who are newly diagnosed with cancer. However, the rate of referral to fertility specialists remains suboptimal. The objective of this study was to determine the impact of a dedicated Nurse Navigator Program (NNP) on the rate of referrals and utilization of FP services.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective cohort study of all women ≥ 18 years old referred for FP consultation with a known cancer diagnosis from 2007 to 2021 at a single, large academic center was conducted. FP referrals for non-cancer indications were excluded. Descriptive statistics were performed including comparing referrals received per 30 days and FP utilization rates pre-NNP (October 2007–September 2013) to post-NNP (October 2013–December 2021).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 176 patients were included pre-NNP and 990 patients post-NNP. Overall, the mean age at the time of referral was 31.5 ± 6.9 years. The referral rates post-NNP were higher among those without prior exposure to chemotherapy/radiation (0.33 pre-NNP vs. 2.75 post-NNP per 30 days, <i>p <</i> 0.01) and lower among those with prior exposure to chemotherapy/radiation (1.26 pre-NNP vs. 0.70 post-NNP per 30 days, <i>p</i> < 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>After the launch of a dedicated fertility preservation nurse navigation program at our institution, we observed a higher number of referrals for FP as well as greater use of FP overall. While not the only variable that changed during this period, this program has optimized patient care and clinical workflow at our institution and serves as a model for such improvement.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062394","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}
Aythami de Armas-Castellano, Diego Infante-Ventura, Tasmania del Pino-Sedeño, Yadira González Hernández, Raul Quiros, Beatriz León-Salas, Vincent Ribrag, María M. Trujillo-Martín, ERN EuroBlood Working Group
Introduction
Burkitt lymphoma (BL) is a rare and aggressive subtype of non-Hodgkin's lymphoma. Several studies have identified prognostic factors (PFs) for disease progression and mortality among adults with BL. However, there is no consensus on risk stratification based on PFs. This study aims to identify, critically assess, and synthesize the available evidence on PFs for survival in adults with BL.
Methods
A systematic review was conducted. Medline, EMBASE, and CENTRAL were searched from inception to February 22, 2022. Randomized or non-randomized clinical trials and longitudinal observational studies were eligible for inclusion. Reference screening, data extraction, and risk-of-bias assessment were conducted independently and in duplicate. Publication bias was examined by visual inspection of funnel plots. Meta-analyses were conducted when appropriate using Review Manager 5. The certainty of evidence was assessed using GRADE.
Results
The search identified 1119 references. Of these, 76 papers were selected for full-text assessment and 36 studies (N = 10,882) reported in 39 articles were eligible for inclusion. Older age, higher performance status, and central nervous system involvement were associated with poorer overall survival (OS) and progression-free survival (PFS). Black patients exhibited significantly lower OS and relative survival. Bone marrow involvement and higher albumin levels were associated with poorer OS. Treatment with rituximab, and with methotrexate were associated with better OS and PFS.
Conclusion
This study provides a comprehensive and methodologically rigorous evidence review on PFs in adults with BL. Several significant associations of PFs and survival estimates were observed, therefore, providing data to inform treatment decisions and to improve patient care.
{"title":"Prognostic Factors for Survival in Adults With Burkitt Lymphoma: A Systematic Review","authors":"Aythami de Armas-Castellano, Diego Infante-Ventura, Tasmania del Pino-Sedeño, Yadira González Hernández, Raul Quiros, Beatriz León-Salas, Vincent Ribrag, María M. Trujillo-Martín, ERN EuroBlood Working Group","doi":"10.1002/cam4.70513","DOIUrl":"10.1002/cam4.70513","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Burkitt lymphoma (BL) is a rare and aggressive subtype of non-Hodgkin's lymphoma. Several studies have identified prognostic factors (PFs) for disease progression and mortality among adults with BL. However, there is no consensus on risk stratification based on PFs. This study aims to identify, critically assess, and synthesize the available evidence on PFs for survival in adults with BL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic review was conducted. Medline, EMBASE, and CENTRAL were searched from inception to February 22, 2022. Randomized or non-randomized clinical trials and longitudinal observational studies were eligible for inclusion. Reference screening, data extraction, and risk-of-bias assessment were conducted independently and in duplicate. Publication bias was examined by visual inspection of funnel plots. Meta-analyses were conducted when appropriate using Review Manager 5. The certainty of evidence was assessed using GRADE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The search identified 1119 references. Of these, 76 papers were selected for full-text assessment and 36 studies (<i>N</i> = 10,882) reported in 39 articles were eligible for inclusion. Older age, higher performance status, and central nervous system involvement were associated with poorer overall survival (OS) and progression-free survival (PFS). Black patients exhibited significantly lower OS and relative survival. Bone marrow involvement and higher albumin levels were associated with poorer OS. Treatment with rituximab, and with methotrexate were associated with better OS and PFS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides a comprehensive and methodologically rigorous evidence review on PFs in adults with BL. Several significant associations of PFs and survival estimates were observed, therefore, providing data to inform treatment decisions and to improve patient care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057591","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}
Male breast cancer (MBC) is rare and often treated using evidence from female breast cancer (BC) trials due to limited male participation. Previous estimates lacked global coverage and completeness. We aimed to quantify the global MBC burden from 1990 to 2021 and evaluate its current status and trends.
Methods
Based on the global burden of disease (GBD) database, we gathered and analyzed data on the incidence, death, and disability-adjusted life years (DALYs) of MBC while utilizing age-standardized rates (ASRs) as indicators for these measurements. Our study calculated the estimated annual percentage change (EAPC), aiming at measuring the average change in ASRs. Additionally, we evaluated the attributable risk factors (RFs) and trends of MBC across different regions and age groups worldwide.
Results
In 2021, the global MBC age-standardized incidence rates (ASIR), age-standardized death rates (ASDR), and age-standardized DALY rates (ASDALY) per 100,000 persons were 0.941 (95% UI, 0.605–1.155), 0.335 (95% UI, 0.232–0.409), and 9.157 (95% UI, 6.116–11.423), respectively. In comparison to 1990, these rates have increased by 2.212 (95% UI, 2.047–2.378), 0.664 (95% UI, 0.562–0.767), and 0.853 (95% UI, 0.750–0.956) respectively. In Uganda 2021, the ASIR and ASDR of MBC were the highest at 4.541 (95% UI, 3.028–6.808) and 3.510 (95% UI, 2.301–5.195) per 100,000 persons, respectively. Moreover, the burden of MBC exhibited an increase with age. Globally, dietary risk was the most important attributable RF for MBC deaths, with a death percentage of 11.690% (95% UI, −0.003%–24.838%), followed by alcohol use and tobacco.
Conclusion
From 1990 to 2021, the ASIR, ASDR, and ASDALY of MBC have shown significant disparities and an increasing trend. Committing to healthy lifestyle choices, such as decreasing tobacco and alcohol consumption and making positive changes to dietary habits, can assist in reducing MBC risk. The development and execution of robust and effective public health policies are crucial for alleviating the global disease burden.
{"title":"Global, Regional, and National Burden of Male Breast Cancer, 1990–2021: A Systematic Analysis for the Global Burden of Disease Study 2021","authors":"Long Wang, Ping Wen, Qing Shao, Dongping Jiang, Yulan Zhao, Xiaohua Zeng","doi":"10.1002/cam4.70632","DOIUrl":"10.1002/cam4.70632","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Male breast cancer (MBC) is rare and often treated using evidence from female breast cancer (BC) trials due to limited male participation. Previous estimates lacked global coverage and completeness. We aimed to quantify the global MBC burden from 1990 to 2021 and evaluate its current status and trends.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Based on the global burden of disease (GBD) database, we gathered and analyzed data on the incidence, death, and disability-adjusted life years (DALYs) of MBC while utilizing age-standardized rates (ASRs) as indicators for these measurements. Our study calculated the estimated annual percentage change (EAPC), aiming at measuring the average change in ASRs. Additionally, we evaluated the attributable risk factors (RFs) and trends of MBC across different regions and age groups worldwide.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 2021, the global MBC age-standardized incidence rates (ASIR), age-standardized death rates (ASDR), and age-standardized DALY rates (ASDALY) per 100,000 persons were 0.941 (95% UI, 0.605–1.155), 0.335 (95% UI, 0.232–0.409), and 9.157 (95% UI, 6.116–11.423), respectively. In comparison to 1990, these rates have increased by 2.212 (95% UI, 2.047–2.378), 0.664 (95% UI, 0.562–0.767), and 0.853 (95% UI, 0.750–0.956) respectively. In Uganda 2021, the ASIR and ASDR of MBC were the highest at 4.541 (95% UI, 3.028–6.808) and 3.510 (95% UI, 2.301–5.195) per 100,000 persons, respectively. Moreover, the burden of MBC exhibited an increase with age. Globally, dietary risk was the most important attributable RF for MBC deaths, with a death percentage of 11.690% (95% UI, −0.003%–24.838%), followed by alcohol use and tobacco.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>From 1990 to 2021, the ASIR, ASDR, and ASDALY of MBC have shown significant disparities and an increasing trend. Committing to healthy lifestyle choices, such as decreasing tobacco and alcohol consumption and making positive changes to dietary habits, can assist in reducing MBC risk. The development and execution of robust and effective public health policies are crucial for alleviating the global disease burden.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057583","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}
Due to its rarity, there are very limited data available on the cause of death (COD) and its association with comorbidities in Japanese chronic lymphocytic leukemia (CLL) patients.
Methods
To investigate the prevalence of comorbidities and their impact on cause-specific mortality, we retrospectively reviewed 121 Japanese patients with CLL.
Results
The median age was 69 years, with 47.9% having at least one comorbidity listed in the Charlson Comorbidity Index (CCI), and 12.4% were multimorbid. With a median follow-up of 74 months, the 5- and 10-year overall survival rates were 80.6% and 60.1%, respectively. Among the 44 deaths observed, CLL progression was the leading COD (38.6%), which together with infections and other malignancies accounted for nearly 80%. Patients with higher CCI risk categories had significantly higher 5-year all-cause mortality (CCI 1–2: 22.9% and ≥ 3: 31.4%) and non-CLL-specific mortality (CCI 1–2: 18.8% and ≥ 3: 31.4%) compared to those without (CCI 0: 12.6%, p = 0.005; 3.5%, p < 0.001, respectively), whereas CLL-specific mortality was not influenced. On multivariate analysis, age and CCI retained a significant prognostic impact on all-cause mortality (hazard ratio [HR] 1.08, p < 0.001 and HR 1.88, p = 0.004, respectively) and non-CLL-specific mortality (HR 1.12, p < 0.001 and HR 3.81, p < 0.001, respectively).
Conclusions
Our study showed that CLL itself was the leading COD, and comorbidity burden was associated with non-CLL-specific deaths. This highlights the importance of better disease control and effective management of comorbidities.
{"title":"Cause-Specific Mortality and Prognostic Impact of Comorbidity in Japanese Patients With Chronic Lymphocytic Leukemia","authors":"Daisuke Ikeda, Takuya Nunomura, Tsuyoshi Muta, Kosei Matsue","doi":"10.1002/cam4.70613","DOIUrl":"10.1002/cam4.70613","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Due to its rarity, there are very limited data available on the cause of death (COD) and its association with comorbidities in Japanese chronic lymphocytic leukemia (CLL) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To investigate the prevalence of comorbidities and their impact on cause-specific mortality, we retrospectively reviewed 121 Japanese patients with CLL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The median age was 69 years, with 47.9% having at least one comorbidity listed in the Charlson Comorbidity Index (CCI), and 12.4% were multimorbid. With a median follow-up of 74 months, the 5- and 10-year overall survival rates were 80.6% and 60.1%, respectively. Among the 44 deaths observed, CLL progression was the leading COD (38.6%), which together with infections and other malignancies accounted for nearly 80%. Patients with higher CCI risk categories had significantly higher 5-year all-cause mortality (CCI 1–2: 22.9% and ≥ 3: 31.4%) and non-CLL-specific mortality (CCI 1–2: 18.8% and ≥ 3: 31.4%) compared to those without (CCI 0: 12.6%, <i>p</i> = 0.005; 3.5%, <i>p</i> < 0.001, respectively), whereas CLL-specific mortality was not influenced. On multivariate analysis, age and CCI retained a significant prognostic impact on all-cause mortality (hazard ratio [HR] 1.08, <i>p</i> < 0.001 and HR 1.88, <i>p</i> = 0.004, respectively) and non-CLL-specific mortality (HR 1.12, <i>p</i> < 0.001 and HR 3.81, <i>p</i> < 0.001, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study showed that CLL itself was the leading COD, and comorbidity burden was associated with non-CLL-specific deaths. This highlights the importance of better disease control and effective management of comorbidities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051121","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}
Chunfang Kong, Linhui Hu, Ling Zhang, Hongbo Cheng, Qilin Lu, Anna Li, Bo Ke, Wenting Cui, Huixia Zhang, Mei Wu, Qingqing Zhu, Chenghao Jin, Li Yu
Background
Bilirubin has anti-inflammatory, antioxidant, and anti-cancer properties, with an inverse relationship between its levels and cancer risk and prognosis. However, the prognostic value of serum bilirubin in acute myeloid leukemia (AML) remains uncertain.
Methods
This retrospective study analyzed pretreatment serum total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) in 284 AML patients and 316 healthy controls. The prognostic significance of serum bilirubin levels was determined using the Kaplan–Meier method and Cox proportional hazards model.
Results
Pretreatment TBIL and IBIL levels were significantly lower in AML patients compared to controls. TBIL and IBIL levels were significantly higher in the CR/CRh/CRi group than in the non-CR/CRh/CRi group and increased significantly after chemotherapy. Elevated pretreatment TBIL and IBIL were associated with longer overall survival (OS) (p < 0.05) and progression-free survival (PFS) (p < 0.05). Pretreatment IBIL was an independent prognostic factor for OS (hazard ratio [HR], 0.47; 95% confidence interval [CI] 0.28–0.79; p < 0.05) and PFS (HR, 0.53; 95% CI 0.33–0.85; p < 0.05).
Conclusion
Elevated pretreatment IBIL levels are correlated with improved OS and PFS, acting as an independent favorable prognostic indicator for AML.
{"title":"Association of Pretreatment Serum Indirect Bilirubin Levels With Prognostic and Therapeutic Value in Patients With Newly Diagnosed Acute Myeloid Leukemia","authors":"Chunfang Kong, Linhui Hu, Ling Zhang, Hongbo Cheng, Qilin Lu, Anna Li, Bo Ke, Wenting Cui, Huixia Zhang, Mei Wu, Qingqing Zhu, Chenghao Jin, Li Yu","doi":"10.1002/cam4.70572","DOIUrl":"10.1002/cam4.70572","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bilirubin has anti-inflammatory, antioxidant, and anti-cancer properties, with an inverse relationship between its levels and cancer risk and prognosis. However, the prognostic value of serum bilirubin in acute myeloid leukemia (AML) remains uncertain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study analyzed pretreatment serum total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) in 284 AML patients and 316 healthy controls. The prognostic significance of serum bilirubin levels was determined using the Kaplan–Meier method and Cox proportional hazards model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Pretreatment TBIL and IBIL levels were significantly lower in AML patients compared to controls. TBIL and IBIL levels were significantly higher in the CR/CRh/CRi group than in the non-CR/CRh/CRi group and increased significantly after chemotherapy. Elevated pretreatment TBIL and IBIL were associated with longer overall survival (OS) (<i>p</i> < 0.05) and progression-free survival (PFS) (<i>p</i> < 0.05). Pretreatment IBIL was an independent prognostic factor for OS (hazard ratio [HR], 0.47; 95% confidence interval [CI] 0.28–0.79; <i>p</i> < 0.05) and PFS (HR, 0.53; 95% CI 0.33–0.85; <i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Elevated pretreatment IBIL levels are correlated with improved OS and PFS, acting as an independent favorable prognostic indicator for AML.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045123","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}
Valentina Salvestrini, Gabriele Conti, Federica D'Amico, Gianluca Cristiano, Marco Candela, Michele Cavo, Silvia Turroni, Antonio Curti
Background
The management of acute myeloid leukemia (AML) is hindered by treatment-related toxicities and complications, particularly cytopenia, which remains a leading cause of mortality. Given the pivotal role of the gut microbiota (GM) in hemopoiesis and immune regulation, we investigated its impact on hematologic recovery during AML induction therapy.
Methods
We profiled the GM of 27 newly diagnosed adult AML patients using 16S rRNA amplicon sequencing and correlated it with key clinical parameters before and after induction therapy.
Results
Our investigation revealed intriguing associations between the GM composition and crucial recovery indicators, including platelet, lymphocyte, and neutrophil counts, and identified early GM signatures predictive of improved hematologic recovery. Remarkably, patients demonstrating superior recovery had higher alpha diversity and enrichment in health-associated taxa belonging to the genera Faecalibacterium, Ruminococcus, Blautia, and Butyricimonas at diagnosis.
Conclusions
Despite certain study limitations, our findings suggest that evaluating GM features could serve as a potential marker for hematologic recovery. This preliminary work opens avenues for personalized risk assessment and interventions, possibly involving GM modulation tools, to optimize recovery in AML patients undergoing induction therapy and potentially enhancing overall outcomes in individuals with hematologic diseases.
{"title":"Gut Microbiome as a Potential Marker of Hematologic Recovery Following Induction Therapy in Acute Myeloid Leukemia Patients","authors":"Valentina Salvestrini, Gabriele Conti, Federica D'Amico, Gianluca Cristiano, Marco Candela, Michele Cavo, Silvia Turroni, Antonio Curti","doi":"10.1002/cam4.70501","DOIUrl":"10.1002/cam4.70501","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The management of acute myeloid leukemia (AML) is hindered by treatment-related toxicities and complications, particularly cytopenia, which remains a leading cause of mortality. Given the pivotal role of the gut microbiota (GM) in hemopoiesis and immune regulation, we investigated its impact on hematologic recovery during AML induction therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We profiled the GM of 27 newly diagnosed adult AML patients using 16S rRNA amplicon sequencing and correlated it with key clinical parameters before and after induction therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our investigation revealed intriguing associations between the GM composition and crucial recovery indicators, including platelet, lymphocyte, and neutrophil counts, and identified early GM signatures predictive of improved hematologic recovery. Remarkably, patients demonstrating superior recovery had higher alpha diversity and enrichment in health-associated taxa belonging to the genera <i>Faecalibacterium</i>, <i>Ruminococcus</i>, <i>Blautia</i>, and <i>Butyricimonas</i> at diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Despite certain study limitations, our findings suggest that evaluating GM features could serve as a potential marker for hematologic recovery. This preliminary work opens avenues for personalized risk assessment and interventions, possibly involving GM modulation tools, to optimize recovery in AML patients undergoing induction therapy and potentially enhancing overall outcomes in individuals with hematologic diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044980","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}
Junrui Zhang, Anren Zhang, Yibing Guo, Guoliang Miao, Shengchang Liang, Jie Wang, Junhong Wang
Background
Photodynamic therapy (PDT) is a noninvasive cancer treatment that works by using light to stimulate the production of excessive cytotoxic reactive oxygen species (ROS), which effectively eliminates tumor cells. However, the therapeutic effects of PDT are often limited by tumor hypoxia, which prevents effective tumor cell elimination. The oxygen (O2) consumption during PDT can further exacerbate hypoxia, leading to post-treatment adverse events.
Objectives
This review aims to explore the potential of cuproptosis, a recently discovered copper-dependent form of programmed cell death, to enhance the anticancer effects of PDT. Cuproptosis is highly dependent on mitochondrial respiration, specifically the tricarboxylic acid (TCA) cycle, and can increase O2 and ROS levels or decrease glutathione (GSH) levels, thereby improving PDT outcomes.
Methods
The review discusses the latest research advancements in the field, detailing the mechanisms that regulate cuproptosis and PDT. It also explores how nanoparticle (NP)-based strategies can be used to exploit the synergistic potential between cuproptosis and PDT. The article examines the prospects of synergistic anticancer activity guided by nanodelivery systems, which could overcome the challenges associated with hypoxia in cancer treatment.
Conclusions
The combination of cuproptosis and PDT, facilitated by NP-based delivery systems, presents a promising approach to enhance the effectiveness of cancer therapy. The review concludes by discussing the challenges and future research directions for this combination therapy, highlighting the need for further investigation into the mechanisms and optimization of treatment strategies to improve outcomes in cancer treatment.
{"title":"Nanoparticle-Mediated Cuproptosis and Photodynamic Synergistic Strategy: A Novel Horizon for Cancer Therapy","authors":"Junrui Zhang, Anren Zhang, Yibing Guo, Guoliang Miao, Shengchang Liang, Jie Wang, Junhong Wang","doi":"10.1002/cam4.70599","DOIUrl":"10.1002/cam4.70599","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Photodynamic therapy (PDT) is a noninvasive cancer treatment that works by using light to stimulate the production of excessive cytotoxic reactive oxygen species (ROS), which effectively eliminates tumor cells. However, the therapeutic effects of PDT are often limited by tumor hypoxia, which prevents effective tumor cell elimination. The oxygen (O<sub>2</sub>) consumption during PDT can further exacerbate hypoxia, leading to post-treatment adverse events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This review aims to explore the potential of cuproptosis, a recently discovered copper-dependent form of programmed cell death, to enhance the anticancer effects of PDT. Cuproptosis is highly dependent on mitochondrial respiration, specifically the tricarboxylic acid (TCA) cycle, and can increase O<sub>2</sub> and ROS levels or decrease glutathione (GSH) levels, thereby improving PDT outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The review discusses the latest research advancements in the field, detailing the mechanisms that regulate cuproptosis and PDT. It also explores how nanoparticle (NP)-based strategies can be used to exploit the synergistic potential between cuproptosis and PDT. The article examines the prospects of synergistic anticancer activity guided by nanodelivery systems, which could overcome the challenges associated with hypoxia in cancer treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The combination of cuproptosis and PDT, facilitated by NP-based delivery systems, presents a promising approach to enhance the effectiveness of cancer therapy. The review concludes by discussing the challenges and future research directions for this combination therapy, highlighting the need for further investigation into the mechanisms and optimization of treatment strategies to improve outcomes in cancer treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044941","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}
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