Precision Clinical Medicine最新文献

{"title":"Multidisciplinary treatment and immunotherapy improved the prognosis of advanced small intestine sarcomatoid carcinoma","authors":"Bo Wang, Meng Qiu","doi":"10.1093/pcmedi/pbae014","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae014","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141688106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning-based multi-modal data integration enhancing breast cancer disease-free survival prediction.","authors":"Zehua Wang, Ruichong Lin, Yanchun Li, Jin Zeng, Yongjian Chen, Wenhao Ouyang, Han Li, Xueyan Jia, Zijia Lai, Yunfang Yu, Herui Yao, Weifeng Su","doi":"10.1093/pcmedi/pbae012","DOIUrl":"10.1093/pcmedi/pbae012","url":null,"abstract":"<p><strong>Background: </strong>The prognosis of breast cancer is often unfavorable, emphasizing the need for early metastasis risk detection and accurate treatment predictions. This study aimed to develop a novel multi-modal deep learning model using preoperative data to predict disease-free survival (DFS).</p><p><strong>Methods: </strong>We retrospectively collected pathology imaging, molecular and clinical data from The Cancer Genome Atlas and one independent institution in China. We developed a novel Deep Learning Clinical Medicine Based Pathological Gene Multi-modal (DeepClinMed-PGM) model for DFS prediction, integrating clinicopathological data with molecular insights. The patients included the training cohort (<i>n</i> = 741), internal validation cohort (<i>n</i> = 184), and external testing cohort (<i>n</i> = 95).</p><p><strong>Result: </strong>Integrating multi-modal data into the DeepClinMed-PGM model significantly improved area under the receiver operating characteristic curve (AUC) values. In the training cohort, AUC values for 1-, 3-, and 5-year DFS predictions increased to 0.979, 0.957, and 0.871, while in the external testing cohort, the values reached 0.851, 0.878, and 0.938 for 1-, 2-, and 3-year DFS predictions, respectively. The DeepClinMed-PGM's robust discriminative capabilities were consistently evident across various cohorts, including the training cohort [hazard ratio (HR) 0.027, 95% confidence interval (CI) 0.0016-0.046, <i>P</i> < 0.0001], the internal validation cohort (HR 0.117, 95% CI 0.041-0.334, <i>P</i> < 0.0001), and the external cohort (HR 0.061, 95% CI 0.017-0.218, <i>P</i> < 0.0001). Additionally, the DeepClinMed-PGM model demonstrated C-index values of 0.925, 0.823, and 0.864 within the three cohorts, respectively.</p><p><strong>Conclusion: </strong>This study introduces an approach to breast cancer prognosis, integrating imaging and molecular and clinical data for enhanced predictive accuracy, offering promise for personalized treatment strategies.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11190375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depletion of squalene epoxidase in synergy with glutathione peroxidase 4 inhibitor RSL3 overcomes oxidative stress resistance in lung squamous cell carcinoma","authors":"Guo Li, Lu Chen, Hua Bai, Li Zhang, Jie Wang, Weimin Li","doi":"10.1093/pcmedi/pbae011","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae011","url":null,"abstract":"\u0000 Lung squamous cell carcinoma (LUSC) lacks effective targeted therapies and has a poor prognosis. Disruption of squalene epoxidase (SQLE) has been implicated in metabolic disorders and cancer. However, the role of SQLE as a monooxygenase involved in oxidative stress remains unclear. Here, we investigated the unique role of SQLE expression in the diagnosis and prognosis prediction of LUSC. Knockdown of SQLE or treatment with the SQLE inhibitor terbinafine (TBF) can suppress the proliferation of LUSC cells by inducing apoptosis and reactive oxygen species (ROS) accumulation. However, depletion of SQLE also results in the impairment of lipid peroxidation and ferroptosis resistance such as upregulation of glutathione peroxidase 4 (GPX4). Therefore, prevention of SQLE in synergy with GPX4 inhibitor RSL3 effectively mitigates the proliferation and growth of LUSC. Our study indicates that the low expression of SQLE employs the adaptive survival through regulating the balance of apoptosis and resistance of ferroptosis. In future, the combinational therapy of targeting SQLE and ferroptosis could be a promising approach in treating LUSC.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140999373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TP53-specific mutations serve as a potential biomarker for homologous recombination deficiency in breast cancer: a clinical next-generation sequencing study","authors":"Yongsheng Huang, Shuwei Ren, Li Ding, Yuanling Jiang, Jiahuan Luo, Jinghua Huang, Xinke Yin, Jianli Zhao, Sha Fu, Jianwei Liao","doi":"10.1093/pcmedi/pbae009","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae009","url":null,"abstract":"\u0000 \u0000 \u0000 TP53 mutations and homologous recombination deficiency (HRD) occur frequently in breast cancer. However, the characteristics of TP53 pathogenic mutations in breast cancer patients with/without HRD are not clear.\u0000 \u0000 \u0000 \u0000 Both tumor and paired blood DNA from 119 breast cancer patients were performed clinical next-generation sequencing (NGS) by a 520-gene panel. Mutations, tumor mutation burden (TMB), and genomic HRD scores were assessed from NGS data.\u0000 \u0000 \u0000 \u0000 All TP53 pathogenic mutations in patients were the somatic origin, which was associated with the protein expression of estrogen receptor and progestogen receptor. Compared to patients without TP53 pathologic mutations, patients with TP53 pathologic mutations had higher levels of HRD scores and different genomic alterations. The frequency of TP53 pathologic mutation was higher in the HRD-High group (HRD score≥42) relative to that in the HRD-Low group (HRD score<42). TP53 has different mutational characteristics between the HRD-Low and HRD-High groups. TP53-specific mutation subgroups had diverse genomic features and TMB. Notably, TP53 pathogenic mutations predicted the HRD status of breast cancer patients with an AUC of 0.61. TP53-specific mutations, namely HRD-Low mutation, HRD-High mutation, and HRD common mutation, predicted the HRD status of breast cancer patients with AUC values of 0.32, 0.72, and 0.58, respectively. Interestingly, TP53 HRD-High mutation and HRD common mutation combinations showed the highest AUC values (0.80) in predicting HRD status.\u0000 \u0000 \u0000 \u0000 TP53-specific mutation combinations predict the HRD status of patients, indicating that TP53 pathogenic mutations could serve as a potential biomarker for PARP inhibitors in breast cancer patients.\u0000","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140720823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome and clonal hematopoiesis stability contrasts with immune, cfDNA, mitochondrial, and telomere length changes during short duration spaceflight.","authors":"J Sebastian Garcia-Medina, Karolina Sienkiewicz, S Anand Narayanan, Eliah G Overbey, Kirill Grigorev, Krista A Ryon, Marissa Burke, Jacqueline Proszynski, Braden Tierney, Caleb M Schmidt, Nuria Mencia-Trinchant, Remi Klotz, Veronica Ortiz, Jonathan Foox, Christopher Chin, Deena Najjar, Irina Matei, Irenaeus Chan, Carlos Cruchaga, Ashley Kleinman, JangKeun Kim, Alexander Lucaci, Conor Loy, Omary Mzava, Iwijn De Vlaminck, Anvita Singaraju, Lynn E Taylor, Julian C Schmidt, Michael A Schmidt, Kelly Blease, Juan Moreno, Andrew Boddicker, Junhua Zhao, Bryan Lajoie, Andrew Altomare, Semyon Kruglyak, Shawn Levy, Min Yu, Duane C Hassane, Susan M Bailey, Kelly Bolton, Jaime Mateus, Christopher E Mason","doi":"10.1093/pcmedi/pbae007","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae007","url":null,"abstract":"<p><strong>Background: </strong>The Inspiration4 (I4) mission, the first all-civilian orbital flight mission, investigated the physiological effects of short-duration spaceflight through a multi-omic approach. Despite advances, there remains much to learn about human adaptation to spaceflight's unique challenges, including microgravity, immune system perturbations, and radiation exposure.</p><p><strong>Methods: </strong>To provide a detailed genetics analysis of the mission, we collected dried blood spots pre-, during, and post-flight for DNA extraction. Telomere length was measured by quantitative PCR, while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations. A robust bioinformatic pipeline was used for data analysis, including variant calling to assess mutational burden.</p><p><strong>Result: </strong>Telomere elongation occurred during spaceflight and shortened after return to Earth. Cell-free DNA analysis revealed increased immune cell signatures post-flight. No significant clonal hematopoiesis of indeterminate potential (CHIP) or whole-genome instability was observed. The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight.</p><p><strong>Conclusion: </strong>Our findings provide valuable insights into the physiological consequences of short-duration spaceflight, with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth. CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts, an understudied phenomenon as previous studies have focused on career astronauts. This study will serve as a reference point for future commercial and non-commercial spaceflight, low Earth orbit (LEO) missions, and deep-space exploration.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11022651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of the immediate perioperative dynamics of circulating DNA levels and neutrophil extracellular traps formationin cancer patients","authors":"Andrei Kudriavtsev, B. Pastor, Alexia Mirandola, E. Pisareva, Y. Gricourt, Xavier Capdevila, Alain R. Thierry, Philippe Cuvillon","doi":"10.1093/pcmedi/pbae008","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae008","url":null,"abstract":"\u0000 \u0000 \u0000 Elevated circulating DNA (cirDNA) concentrations were found to be associated with trauma or tissue damage which suggests involvement of inflammation or cell death in post-operative cirDNA release. We carried out the first prospective, multicenter study of the dynamics of cirDNA and neutrophil extracellular traps (NETs) markers during the perioperative period from 24 hours before surgery up to 72 hours after curative surgery in cancer patients.\u0000 \u0000 \u0000 \u0000 We examined the plasma levels of two NETs protein markers (myeloperoxidase (MPO) and neutrophil elastase (NE)), as well as levels of cirDNA of nuclear (cir-nDNA) and mitochondrial (cir-mtDNA) origins in 29 patients colon, prostate and breast cancer and in 114 healthy individuals (HI).\u0000 \u0000 \u0000 \u0000 The synergistic analytical information provided by these markers revealed that: (i) NETs formation contributes to post-surgery conditions; (ii) post-surgery cir-nDNA levels were highly associated with NE and MPO in colon cancer (r=0.60 (p<0.001) and r=0.53 (p<0.01), respectively), but not in prostate and breast cancer; (iii) each tumor type shows a specific pattern of cir-nDNA and NETs marker dynamics, but overall the pre- and post-surgery median values of cir-nDNA, NE, and MPO were significantly higher in cancer patients than in HI.\u0000 \u0000 \u0000 \u0000 Taken as a whole, our work reveals the association of NETs formation with the elevated cir-nDNA release during a cancer patient's perioperative period, depending on surgical procedure or cancer type. By contrast, cir-mtDNA is poorly associated with NETs formation in the studied perioperative period, which would appear to indicate a different mechanism of release or suggest mitochondria dysfunction.\u0000","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140373382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circle-map profiling of extrachromosomal circular DNA as diagnostic biomarkers for lung cancer","authors":"Yongfeng Yang, Tingting Song, Sha Liu, Zhiqiang Liu, Xuehui Wang, Yi Li, Dan Liu","doi":"10.1093/pcmedi/pbae006","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae006","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140211852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accurate prediction of myopic progression and high myopia by machine learning","authors":"Jiahui Li, Simiao Zeng, Zhihuan Li, Jie Xu, Zhuo Sun, Jing Zhao, Meiyan Li, Zixing Zou, Taihua Guan, Jin Zeng, Zhuang Liu, Wenchao Xiao, Ran Wei, Hanpei Miao, Ian Ziyar, Junxiong Huang, Yuanxu Gao, Yangfa Zeng, Xing-Tao Zhou, Kang Zhang","doi":"10.1093/pcmedi/pbae005","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae005","url":null,"abstract":"\u0000 \u0000 \u0000 Myopia is a leading cause of visual impairment in Asia and worldwide. However, accurately predicting the progression of myopia and the high risk of myopia remains a challenge. This study aims to develop a predictive model for the development of myopia.\u0000 \u0000 \u0000 \u0000 We first retrospectively gathered 612 530 medical records from five independent cohorts, encompassing 227 543 patients ranging from infants to young adults. Subsequently, we developed a multivariate linear regression algorithm model to predict the progression of myopia and the risk of high myopia.\u0000 \u0000 \u0000 \u0000 The model to predict the progression of myopia achieved an R-squared (R2) value of 0.964 vs a mean absolute error (MAE) of 0.119D (95% CI: 0.119, 1.146) in the internal validation set. It demonstrated strong generalizability, maintaining consistent performance across external validation sets: R2 of 0.950 vs MAE of 0.119D (95% CI: 0.119, 1.136) in validation Study 1, R2 of 0.950 vs MAE of 0.121D (95% CI: 0.121, 1.144) in validation Study 2, and R2 of 0.806 vs MAE of −0.066D (95% CI: −0.066, 0.569) in Shanghai Children Myopia Study. Beijing Children Eye Study, the model sustained R2 of 0.749 vs MAE of 0.178D (95% CI: 0.178, 1.557). The model to predict the risk of high myopia achieved and an area under the curve (AUC) of 0.99 in the internal validation set and consistently high AUC values of 0.99, 0.99,0.96 and 0.99 in the respective external validation sets.\u0000 \u0000 \u0000 \u0000 Our study demonstrates accurate prediction of myopia progression and risk of high myopia providing valuable insights for tailoring strategies to personalize and optimize the clinical management of myopia in children.\u0000","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140080308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles derived from mesenchymal stem cells: the wine in Hebe's hands to treat skin aging.","authors":"Qixiang Gui, Neng Ding, Zuochao Yao, Minjuan Wu, Ruifeng Fu, Yue Wang, Yunpeng Zhao, Lie Zhu","doi":"10.1093/pcmedi/pbae004","DOIUrl":"10.1093/pcmedi/pbae004","url":null,"abstract":"<p><p>Owing to its constant exposure to the external environment and various stimuli, skin ranks among the organs most vulnerable to manifestations of aging. Preventing and delaying skin aging has become one of the prominent research subjects in recent years. Mesenchymal stem cells (MSCs) are multipotent stem cells derived from mesoderm with high self-renewal ability and multilineage differentiation potential. MSC-derived extracellular vesicles (MSC-EVs) are nanoscale biological vesicles that facilitate intercellular communication and regulate biological behavior. Recent studies have shown that MSC-EVs have potential applications in anti-aging therapy due to their anti-inflammatory, anti-oxidative stress, and wound healing promoting abilities. This review presents the latest progress of MSC-EVs in delaying skin aging. It mainly includes the MSC-EVs promoting the proliferation and migration of keratinocytes and fibroblasts, reducing the expression of matrix metalloproteinases, resisting oxidative stress, and regulating inflammation. We then briefly discuss the recently discovered treatment methods of MSC-EVs in the field of skin anti-aging. Moreover, the advantages and limitations of EV-based treatments are also presented.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10955876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140185854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiomics-based quantitative contrast-enhanced CT analysis of abdominal lymphadenopathy to differentiate tuberculosis from lymphoma","authors":"Meng-ting Shen, Xi Liu, Yue Gao, Rui Shi, Li Jiang, Jin Yao","doi":"10.1093/pcmedi/pbae002","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae002","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139686748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}