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In clinical and epidemiological studies, there is a growing interest in studying the heterogeneity among patients based on longitudinal characteristics to identify subtypes of the study population. Compared to clustering a single longitudinal marker, simultaneously clustering multiple longitudinal markers allow additional information to be incorporated into the clustering process, which reveals co-existing longitudinal patterns and generates deeper biological insight. In the current study, we propose a Bayesian consensus clustering (BCC) model for multivariate longitudinal data. Instead of arriving at a single overall clustering, the proposed model allows each marker to follow marker-specific local clustering and these local clusterings are aggregated to find a global (consensus) clustering. To estimate the posterior distribution of model parameters, a Gibbs sampling algorithm is proposed. We apply our proposed model to the primary biliary cirrhosis study to identify patient subtypes that may be associated with their prognosis. We also perform simulation studies to compare the clustering performance between the proposed model and existing models under several scenarios. The results demonstrate that the proposed BCC model serves as a useful tool for clustering multivariate longitudinal data. 相似文献
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Stephanie H. Ameis John D. Haltigan Rachael E. Lyon Amanda Sawyer Pat Mirenda Connor M. Kerns Isabel M. Smith Tracy Vaillancourt Joanne Volden Charlotte Waddell Lonnie Zwaigenbaum Teresa Bennett Eric Duku Mayada Elsabbagh Stelios Georgiades Wendy J. Ungar Anat Zaidman-Zait Meng-Chuan Lai Peter Szatmari for the Pathways in ASD Study Team 《Journal of child psychology and psychiatry, and allied disciplines》2022,63(5):553-562
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Laurien J. Zeverijn Eleonora J. Looze Subotheni Thavaneswaran J. Maxime van Berge Henegouwen Robert J. Simes Louisa R. Hoes Katrin M. Sjoquist Hanneke van der Wijngaart Lucille Sebastian Birgit S. Geurts Chee K. Lee Gijsbrecht F. de Wit David Espinoza Paul Roepman Frank P. Lin Anne M. L. Jansen Wendy W. J. de Leng Vincent van der Noort Lindsay V. M. Leek Filip Y. F. L. de Vos Carla M. L. van Herpen Hans Gelderblom Henk M. W. Verheul David M. Thomas Emile E. Voest 《International journal of cancer. Journal international du cancer》2023,153(7):1413-1422
The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible. 相似文献
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目的 通过网络药理学的方法进行预测,再深一步进行动物实验验证来研究柴胡疏肝散治疗CAG的作用机制。方法 首先在TCMSP数据库中检索柴胡疏肝散的所有活性成分与药物靶点;通过收集PharmGkb、OMIM、GeneCards和DrugBank数据库中收录的慢性萎缩性胃炎的相关靶点。将药物靶点与疾病靶点进行映射筛选出交集靶点,将得到的交集靶点构建PPI网络与活性成分-共同靶点网络,并对其进行GO和KEGG富集分析。最后利用Vina软件进行分子对接实验验证,并通过免疫印迹法验证柴胡疏肝散对两种受体蛋白EGFR和STAT1的影响。结果 最终筛选得到柴胡疏肝散活性成分104个,潜在靶点238个,与慢性萎缩性胃炎的交集靶点52个;GO与KEGG富集分析分别得到2166条目和148条目,主要涉及到JAK-STAT信号通路、TNF信号通路、HIF-1信号通路等;分子对接结果显示EGFR、STAT1两个靶点能够与核心活性成分能够自发结合成较为稳定的构像;免疫印迹法实验证明柴胡疏肝散能够降低大鼠胃黏膜组织EGFR和STAT1蛋白表达。结论 通过网络药理学和实验验证,发现柴胡疏肝散可能通过调节EGFR和STAT1蛋白表达来共同调控胃黏膜细胞增殖与凋亡,进而发挥着治疗慢性萎缩性胃炎的效果,为深入进行柴胡疏肝散治疗慢性萎缩性胃炎的作用机制研究提供新思路和新方法。 相似文献
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Proteomic Profiling of Small Extracellular Vesicles Isolated from the Plasma of Vietnamese Patients with Non-Small Cell Lung Cancer Reveals Some Potential Biomarkers 下载免费PDF全文
Thao Phuong Bui Phuong Lan LeLinh Thi Tu Nguyen Le Trung ThoThai Hong Trinh 《Asian Pacific journal of cancer prevention》2022,23(6):1893-1900
Background: Considering the poor prognosis of non-small cell lung cancer (NSCLC), the objective of this study was to examine the potential of plasma-derived vesicles as a source of lung cancer-specific proteins. Extracellular vesicle (EV) cargos are specific to the source cells, hence they have the potential of being a source of cancer-specific proteins. Methods: The proteins differently expressed in cancer were determined and derived from EVs isolated from the plasma of NSCLC patients at the National Lung Hospital. To this end, purification was done using gel filtration chromatography and ultracentrifugation. In addition, nano liquid chromatography mass spectrometry (LC–MS/MS) was used for analyzing. Results: Fifty-seven EV-derived proteins related to NSCLC were highlighted in this research. Some of them have not been addressed before, such as EEF1A1 (elongation factor 1-α1), KPNB1 (Importin subunit beta 1), SRC (proto-oncogene tyrosine-protein kinase) and ACTC1 (actin, alpha cardiac muscle 1). This list was further confirmed through a comparison with ExoCarta and Vesiclepedia. Conclusion: This study is the first work to show the involvement of several novel proteins of small EV (EEF1A1, KPNB1, SRC, and ACTC1) in the progression of NSCLC. The results suggested that they could serve as novel biomarkers for non-small cell lung cancer in the future. 相似文献
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Kerryn W. Reding Aaron K. Aragaki Richard K. Cheng Ana Barac Sylvia Wassertheil-Smoller Jessica Chubak Marian C. Limacher W. Gregory Hundley Ralph D'Agostino Jr. Mara Z. Vitolins Theodore M. Brasky Laurel A. Habel Eric J. Chow Rebecca D. Jackson Chu Chen April Morgenroth Wendy E. Barrington Matthew Banegas Matthew Barnhart Rowan T. Chlebowski 《The oncologist》2020,25(8):712-721
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Malinda Itchins Brandon Lau Amanda L. Hudson Helen Westman Cathy Yi Xia Sarah A. Hayes Viive M. Howell Michael Rodriguez Wendy A. Cooper Heng Wei Michael Buckland Bob T. Li Mark Li Vivek Rathi Stephen B. Fox Anthony J. Gill Stephen J. Clarke Michael J. Boyer Nick Pavlakis 《The oncologist》2020,25(8):641-649