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Grant Details

Grant Number: 5R01CA249096-06 Interpret this number
Primary Investigator: Li, Yi
Organization: University Of Michigan At Ann Arbor
Project Title: New Statistical Methods for Modelling Cancer Outcomes
Fiscal Year: 2026


Abstract

Project Summary/Abstract The proposal addresses two pressing medical problems. First, opioid use is crucial for managing pain in surgical and cancer patients, but over-prescription has led to a significant public health crisis. Opioid overdose deaths have tripled in the past decade, with over half of these fatalities linked to prescription opioids. The lack of reliable, data-driven guidelines has contributed to opioid diversion and increased addiction risks among patients. Thus, there is an urgent need to forecast opioid prescription quantities for surgical patients and measure the associated uncertainty to establish better guidelines for opioid prescriptions. Second, lung cancer remains a major and deadly threat, claiming approximately 150,000 lives annually in the United States, underscoring the need for more effective intervention strategies. Recently, there has been growing interest in understanding the implications of lung muscle metrics on lung cancer mortality. This effort has the potential to lead to personalized interventions that encompass clinical, nutritional, and physical aspects tailored to individual patient profiles. The proposal is motivated by two large databases in which Principal Investigator Dr. Yi Li is actively involved. First, the Michigan Surgical Quality Collaborative (MSQC) project includes data from 21,033 opioid-naïve adult postoperative patients across 70 hospitals, capturing demographic, perioperative, clinical, and mortality characteristics through postoperative surveys. Patients who underwent surgery in Michigan between January 2017 and October 2019 were prescribed opioids at discharge, with ongoing use or refill determined by their pain levels. Second, the Boston Lung Cancer Survival Cohort (BLCSC) study, one of the largest lung cancer cohorts in the country, has enrolled 12,951 lung cancer cases at Massachusetts General Hospital and Dana-Farber Cancer Institute since 1992. It collects comprehensive demographic, smoking, and dietary information, along with pathology, imaging, treatment details, oncogenic mutation status, serum, white blood cells, germline DNA, and tumor tissues. Leveraging these rich databases, we aim to develop new methods to predict and infer adverse outcomes. We propose various methods to predict prescribed opioid dose levels post-surgery, quantify the associated uncertainty, and analyze refill patterns for individual patients. Additionally, we will develop methods to elucidate the impacts of lung muscle metrics on lung cancer mortality, which could have significant interventional implications. In summary, these rich databases and new methodologies will enable our findings to inform individual-based prescription guidelines, detect new prognostic biomarkers and impact medical practice.



Publications

A trans-omics gene-smoking interaction study of lung cancer based on consortium data.
Authors: Xie N. , Xu X. , Wang Y. , Wang A. , Wang X. , Wang X. , Zhao M. , Zhou J. , Wei Y. , Esteller M. , et al. .
Source: American Journal Of Respiratory And Critical Care Medicine, 2026-06-01 00:00:00.0; 212(6), p. 1115-1128.
PMID: 41738161
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DNA methylation and expression of MAPRE3 affect overall survival of early-stage non-small cell lung cancer patients.
Authors: Chen C. , Cheng J. , Hou R. , Zheng X. , Su L. , Bjaanæs M.M. , Karlsson A. , Planck M. , Staaf J. , Helland Å. , et al. .
Source: Molecular Oncology, 2026-04-25 00:00:00.0; , .
EPub date: 2026-04-25 00:00:00.0.
PMID: 42033322
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Inference for Deep Neural Network Estimators in Generalized Nonparametric Models.
Authors: Meng X. , Li Y. .
Source: Journal Of The American Statistical Association, 2026-03-17 00:00:00.0; , .
EPub date: 2026-03-17 00:00:00.0.
PMID: 41869283
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Prognostic impact of restrictive ventilatory defects in chronic lung allograft dysfunction without restrictive allograft syndrome-like opacities: Stratification of emerging undefined and unclassified phenotypes.
Authors: Fukuda T. , Nakamura Y. , Ko Y. , Tseng S.C. , Gagne S.M. , Johkoh T. , Li Y. , Christiani D.C. , Ojiri H. , Sholl L. , et al. .
Source: Jhlt Open, 2026 Feb; 11, p. 100445.
EPub date: 2025-11-24 00:00:00.0.
PMID: 41487300
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Xuran Meng and Yi Li's contribution to the Discussion of "On optimal linear prediction" by I. Helland.
Authors: Meng X. , Li Y. .
Source: Scandinavian Journal Of Statistics, Theory And Applications, 2025-12-12 00:00:00.0; , .
EPub date: 2025-12-12 00:00:00.0.
PMID: 41497310
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AI-derived body composition analysis reveals muscle volume and metformin-associated adipose effects and the obesity paradox in non-small cell lung cancer.
Authors: Wang X. , Hata A. , Wada N. , Song J. , Fukuda T. , Nakamura Y. , Nishino M. , Li Y. , Schiebler M.L. , Christiani D.C. , et al. .
Source: Ebiomedicine, 2025 Nov; 121, p. 105995.
EPub date: 2025-10-29 00:00:00.0.
PMID: 41166991
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Statistical inference on high-dimensional covariate-dependent Gaussian graphical regressions.
Authors: Meng X. , Zhang J. , Li Y. .
Source: Biometrics, 2025-10-08 00:00:00.0; 81(4), .
PMID: 41428236
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Effects of Sex on Mortality in Patients With Lung Cancer: A Multiple Mediation Analysis of The Boston Lung Cancer Study.
Authors: Alvarez A.A.R. , Sun Y. , Li Y. , Christiani D.C. .
Source: Clinical Lung Cancer, 2025-09-24 00:00:00.0; , .
EPub date: 2025-09-24 00:00:00.0.
PMID: 41130886
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Characterization of Occupational Endotoxin-Related Small Airway Disease With Longitudinal Paired Inspiratory/Expiratory CT Scans.
Authors: Sun Y. , Kang J. , Zhang F.Y. , Wang H. , Lai P.S. , Washko G.R. , San Jose Estepar R. , Christiani D.C. , Li Y. .
Source: Chest, 2025 Jul; 168(1), p. 43-55.
EPub date: 2025-01-18 00:00:00.0.
PMID: 39832623
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Integrative omics and multi-cohort identify IRF1 and biological targets related to sepsis-associated acute respiratory distress syndrome.
Authors: Chen J. , Hou R. , Xu X. , Xie N. , Tang J. , Li Y. , Nie X. , Meyer N.J. , Su L. , Christiani D.C. , et al. .
Source: Journal Of Biomedical Research, 2025-05-27 00:00:00.0; 40(1), p. 11-22.
PMID: 40420582
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Radiological distribution patterns in restrictive chronic lung allograft dysfunction: Impact on survival across all phenotypes.
Authors: Fukuda T. , Nakamura Y. , Tseng S.C. , Ko Y. , Gagne S.M. , Johkoh T. , Li Y. , Christiani D.C. , Ojiri H. , Sholl L. , et al. .
Source: Jhlt Open, 2025 May; 8, p. 100232.
EPub date: 2025-02-18 00:00:00.0.
PMID: 40144724
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Residual Volume and Total Lung Capacity at Diagnosis Predict Overall Survival in Non-Small Cell Lung Cancer Patients.
Authors: Zhai T. , Li Y. , Brown R. , Lanuti M. , Gainor J.F. , Christiani D.C. .
Source: Cancer Medicine, 2025 May; 14(10), p. e70962.
PMID: 40371871
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Comparing Analgesic Regimen Effectiveness and Safety after Surgery (CARES): protocol for a pragmatic, international multicentre randomised trial.
Authors: Bicket M.C. , Ladha K.S. , Haroutounian S. , McFarlin K. , Neff M. , McDuffie R.L. , Waljee J.F. , Wijeysundera D.N. , Brummet C. , Li Y. , et al. .
Source: Bmj Open, 2025-04-05 00:00:00.0; 15(4), p. e099925.
EPub date: 2025-04-05 00:00:00.0.
PMID: 40187774
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Bidirectional Mendelian randomization and mediation analysis of million-scale data reveal causal relationships between thyroid-related phenotypes, smoking, and lung cancer.
Authors: Wang X. , Wang X. , Zhao M. , Lin L. , Li Y. , Xie N. , Wang Y. , Wang A. , Xu X. , Ju C. , et al. .
Source: Journal Of Biomedical Research, 2025-03-10 00:00:00.0; 39(5), p. 441-451.
PMID: 40065519
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A Pseudo-Value Approach to Causal Deep Learning of Semi-Competing Risks.
Authors: Salerno S. , Li Y. .
Source: Arabian Journal Of Mathematics, 2025-03-03 00:00:00.0; , .
EPub date: 2025-03-03 00:00:00.0.
PMID: 41268055
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Assessing the prognostic utility of clinical and radiomic features for COVID-19 patients admitted to ICU: challenges and lessons learned.
Authors: Sun Y. , Salerno S. , Pan Z. , Yang E. , Sujimongkol C. , Song J. , Wang X. , Han P. , Zeng D. , Kang J. , et al. .
Source: Harvard Data Science Review, 2024 Winter; 6(1), .
EPub date: 2024-01-31 00:00:00.0.
PMID: 38974963
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Multi-task Learning for Gaussian Graphical Regressions with High Dimensional Covariates.
Authors: Zhang J. , Li Y. .
Source: Journal Of Computational And Graphical Statistics : A Joint Publication Of American Statistical Association, Institute Of Mathematical Statistics, Interface Foundation Of North America, 2024-12-20 00:00:00.0; , .
EPub date: 2024-12-20 00:00:00.0.
PMID: 40786561
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Bayesian Estimation of Propensity Scores for Integrating Multiple Cohorts with High-Dimensional Covariates.
Authors: Guha S. , Li Y. .
Source: Statistics In Biosciences, 2024-12-09 00:00:00.0; , .
EPub date: 2024-12-09 00:00:00.0.
PMID: 40857526
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A two-phase epigenome-wide four-way gene-smoking interaction study of overall survival for early-stage non-small cell lung cancer.
Authors: Chen L. , Wang X. , Xie N. , Zhang Z. , Xu X. , Xue M. , Yang Y. , Liu L. , Su L. , Bjaanæs M. , et al. .
Source: Molecular Oncology, 2024-12-04 00:00:00.0; , .
EPub date: 2024-12-04 00:00:00.0.
PMID: 39630602
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Automated Interstitial Lung Abnormality Probability Prediction at CT: A Stepwise Machine Learning Approach in the Boston Lung Cancer Study.
Authors: Hata A. , Aoyagi K. , Hino T. , Kawagishi M. , Wada N. , Song J. , Wang X. , Valtchinov V.I. , Nishino M. , Muraguchi Y. , et al. .
Source: Radiology, 2024 Sep; 312(3), p. e233435.
PMID: 39225600
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Causal meta-analysis by integrating multiple observational studies with multivariate outcomes.
Authors: Guha S. , Li Y. .
Source: Biometrics, 2024-07-01 00:00:00.0; 80(3), .
PMID: 39073772
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Bayesian Inference for High Dimensional Cox Models with Gaussian and Diffused-Gamma Priors: A Case Study of Mortality in COVID-19 Patients Admitted to the ICU.
Authors: Song J. , Guha S. , Li Y. .
Source: Statistics In Biosciences, 2024 Apr; 16(1), p. 221-249.
EPub date: 2023-11-04 00:00:00.0.
PMID: 38651050
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Penalized deep partially linear cox models with application to CT scans of lung cancer patients.
Authors: Sun Y. , Kang J. , Haridas C. , Mayne N. , Potter A. , Yang C.F. , Christiani D.C. , Li Y. .
Source: Biometrics, 2024-01-29 00:00:00.0; 80(1), .
PMID: 38412302
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What evidence is needed to inform postoperative opioid consumption guidelines? A cohort study of the Michigan Surgical Quality Collaborative.
Authors: Song J. , Li Y. , Waljee J.F. , Gunaseelan V. , Brummett C.M. , Englesbe M.J. , Bicket M.C. .
Source: Regional Anesthesia And Pain Medicine, 2024-01-11 00:00:00.0; 49(1), p. 23-29.
EPub date: 2024-01-11 00:00:00.0.
PMID: 37247946
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What evidence is needed to inform postoperative opioid consumption guidelines? A cohort study of the Michigan Surgical Quality Collaborative.
Authors: Song J. , Li Y. , Waljee J.F. , Gunaseelan V. , Brummett C.M. , Englesbe M.J. , Bicket M.C. .
Source: Regional Anesthesia And Pain Medicine, 2024-01-11 00:00:00.0; 49(1), p. 23-29.
EPub date: 2024-01-11 00:00:00.0.
PMID: 37247946
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Incidence and severity of pulmonary embolism in COVID-19 infection: Ancestral, Alpha, Delta, and Omicron variants.
Authors: Wada N. , Li Y. , Gagne S. , Hino T. , Valtchinov V.I. , Gay E. , Nishino M. , Hammer M.M. , Madore B. , Guttmann C.R.G. , et al. .
Source: Medicine, 2023-12-01 00:00:00.0; 102(48), p. e36417.
PMID: 38050198
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Debiased lasso for stratified Cox models with application to the national kidney transplant data.
Authors: Xia L. , Nan B. , Li Y. .
Source: The Annals Of Applied Statistics, 2023 Dec; 17(4), p. 3550-3569.
EPub date: 2023-10-30 00:00:00.0.
PMID: 38106966
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WNT9A Affects Late-Onset Acute Respiratory Distress Syndrome and 28-Day Survival: Evidence from a Three-Step Multiomics Study.
Authors: Chen J. , Tang J. , Nie M. , Li Y. , Wurfel M.M. , Meyer N.J. , Wei Y. , Zhao Y. , Frank A.J. , Thompson B.T. , et al. .
Source: American Journal Of Respiratory Cell And Molecular Biology, 2023 Aug; 69(2), p. 220-229.
PMID: 37094100
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Simultaneous selection and inference for varying coefficients with zero regions: a soft-thresholding approach.
Authors: Yang Y. , Pan Z. , Kang J. , Brummett C. , Li Y. .
Source: Biometrics, 2023-07-17 00:00:00.0; , .
EPub date: 2023-07-17 00:00:00.0.
PMID: 37459178
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Statistical Inference for Cox Proportional Hazards Models with a Diverging Number of Covariates.
Authors: Xia L. , Nan B. , Li Y. .
Source: Scandinavian Journal Of Statistics, Theory And Applications, 2023 Jun; 50(2), p. 550-571.
EPub date: 2022-04-25 00:00:00.0.
PMID: 37408772
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Use of machine learning to assess the prognostic utility of radiomic features for in-hospital COVID-19 mortality.
Authors: Sun Y. , Salerno S. , He X. , Pan Z. , Yang E. , Sujimongkol C. , Song J. , Wang X. , Han P. , Kang J. , et al. .
Source: Scientific Reports, 2023-05-05 00:00:00.0; 13(1), p. 7318.
EPub date: 2023-05-05 00:00:00.0.
PMID: 37147440
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Prediagnosis Smoking Cessation and Overall Survival Among Patients With Non-Small Cell Lung Cancer.
Authors: Wang X. , Romero-Gutierrez C.W. , Kothari J. , Shafer A. , Li Y. , Christiani D.C. .
Source: Jama Network Open, 2023-05-01 00:00:00.0; 6(5), p. e2311966.
EPub date: 2023-05-01 00:00:00.0.
PMID: 37145597
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Asynchronous and error-prone longitudinal data analysis via functional calibration.
Authors: Chang X. , Li Y. , Li Y. .
Source: Biometrics, 2023-04-12 00:00:00.0; , .
EPub date: 2023-04-12 00:00:00.0.
PMID: 37042741
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Traction Bronchiectasis/Bronchiolectasis in Interstitial Lung Abnormality: Follow-up in the COPDGene.
Authors: Hata A. , Hino T. , Li Y. , Johkoh T. , Christiani D.C. , Lynch D.A. , Cho M.H. , Silverman E.K. , Hunninghake G.M. , Hatabu H. , et al. .
Source: American Journal Of Respiratory And Critical Care Medicine, 2023-03-10 00:00:00.0; , .
EPub date: 2023-03-10 00:00:00.0.
PMID: 36898128
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High-Dimensional Survival Analysis: Methods and Applications.
Authors: Salerno S. , Li Y. .
Source: Annual Review Of Statistics And Its Application, 2023 Mar; 10(1), p. 25-49.
EPub date: 2022-10-06 00:00:00.0.
PMID: 36968638
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INDIVIDUALIZED RISK ASSESSMENT OF PREOPERATIVE OPIOID USE BY INTERPRETABLE NEURAL NETWORK REGRESSION.
Authors: Sun Y. , Kang J. , Brummett C. , Li Y. .
Source: The Annals Of Applied Statistics, 2023 Mar; 17(1), p. 434-453.
EPub date: 2023-01-24 00:00:00.0.
PMID: 37006707
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OWL: an optimized and independently validated machine learning prediction model for lung cancer screening based on the UK Biobank, PLCO, and NLST populations.
Authors: Pan Z. , Zhang R. , Shen S. , Lin Y. , Zhang L. , Wang X. , Ye Q. , Wang X. , Chen J. , Zhao Y. , et al. .
Source: Ebiomedicine, 2023 Feb; 88, p. 104443.
EPub date: 2023-01-24 00:00:00.0.
PMID: 36701900
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Inference for High-Dimensional Censored Quantile Regression.
Authors: Fei Z. , Zheng Q. , Hong H.G. , Li Y. .
Source: Journal Of The American Statistical Association, 2023; 118(542), p. 898-912.
EPub date: 2021-08-20 00:00:00.0.
PMID: 37309513
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Serial laboratory biomarkers are associated with ICU outcomes in patients hospitalized with COVID-19.
Authors: Wang X. , White E. , Giacona F. , Khurana A. , Li Y. , Christiani D.C. , Alladina J.W. .
Source: Plos One, 2023; 18(11), p. e0293842.
EPub date: 2023-11-07 00:00:00.0.
PMID: 37934759
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A trans-omics assessment of gene-gene interaction in early-stage NSCLC.
Authors: Chen J. , Song Y. , Li Y. , Wei Y. , Shen S. , Zhao Y. , You D. , Su L. , Bjaanaes M.M. , Karlsson A. , et al. .
Source: Molecular Oncology, 2022-11-21 00:00:00.0; , .
EPub date: 2022-11-21 00:00:00.0.
PMID: 36408734
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Prior Knowledge Guided Ultra-high Dimensional Variable Screening with Application to Neuroimaging Data.
Authors: He J. , Kang J. .
Source: Statistica Sinica, 2022 Oct; 32(4), p. 2095-2117.
PMID: 36052338
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Sex disparities in lung cancer survival rates based on screening status.
Authors: Rodriguez Alvarez A.A. , Yuming S. , Kothari J. , Digumarthy S.R. , Byrne N.M. , Li Y. , Christiani D.C. .
Source: Lung Cancer (amsterdam, Netherlands), 2022 09; 171, p. 115-120.
EPub date: 2022-08-01 00:00:00.0.
PMID: 35939954
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Sex disparities in lung cancer survival rates based on screening status.
Authors: Rodriguez Alvarez A.A. , Yuming S. , Kothari J. , Digumarthy S.R. , Byrne N.M. , Li Y. , Christiani D.C. .
Source: Lung Cancer (amsterdam, Netherlands), 2022 09; 171, p. 115-120.
EPub date: 2022-08-01 00:00:00.0.
PMID: 35939954
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A Large-Scale Genome-Wide Gene-Gene Interaction Study of Lung Cancer Susceptibility in Europeans With a Trans-Ethnic Validation in Asians.
Authors: Zhang R. , Shen S. , Wei Y. , Zhu Y. , Li Y. , Chen J. , Guan J. , Pan Z. , Wang Y. , Zhu M. , et al. .
Source: Journal Of Thoracic Oncology : Official Publication Of The International Association For The Study Of Lung Cancer, 2022 08; 17(8), p. 974-990.
EPub date: 2022-04-30 00:00:00.0.
PMID: 35500836
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Spirometry at diagnosis and overall survival in non-small cell lung cancer patients.
Authors: Zhai T. , Li Y. , Brown R. , Lanuti M. , Gainor J.F. , Christiani D.C. .
Source: Cancer Medicine, 2022-05-12 00:00:00.0; , .
EPub date: 2022-05-12 00:00:00.0.
PMID: 35545892
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APOLLO: An accurate and independently validated prediction model of lower-grade gliomas overall survival and a comparative study of model performance.
Authors: Chen J. , Shen S. , Li Y. , Fan J. , Xiong S. , Xu J. , Zhu C. , Lin L. , Dong X. , Duan W. , et al. .
Source: Ebiomedicine, 2022 May; 79, p. 104007.
EPub date: 2022-04-15 00:00:00.0.
PMID: 35436725
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Epigenome-wide three-way interaction study identifies a complex pattern between TRIM27, KIAA0226, and smoking associated with overall survival of early-stage NSCLC.
Authors: Ji X. , Lin L. , Fan J. , Li Y. , Wei Y. , Shen S. , Su L. , Shafer A. , Bjaanaes M.M. , Karlsson A. , et al. .
Source: Molecular Oncology, 2021-12-21 00:00:00.0; , .
EPub date: 2021-12-21 00:00:00.0.
PMID: 34932879
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Rejoinder to discussions of "distributional independent component analysis for diverse neuroimaging modalities".
Authors: Wu B. , Pal S. , Kang J. , Guo Y. .
Source: Biometrics, 2021-11-15 00:00:00.0; , .
EPub date: 2021-11-15 00:00:00.0.
PMID: 34780668
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Debiased lasso for generalized linear models with a diverging number of covariates.
Authors: Xia L. , Nan B. , Li Y. .
Source: Biometrics, 2021-10-25 00:00:00.0; , .
EPub date: 2021-10-25 00:00:00.0.
PMID: 34693983
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Distributional independent component analysis for diverse neuroimaging modalities.
Authors: Wu B. , Pal S. , Kang J. , Guo Y. .
Source: Biometrics, 2021-10-25 00:00:00.0; , .
EPub date: 2021-10-25 00:00:00.0.
PMID: 34694629
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