Biostatistics Commons^™

Patients With Obesity And A History Of Metformin Treatment Have Lower Influenza Mortality: A Retrospective Cohort Study, Tammy H. Cummings, Joseph Magagnoli Ph.D., Ms, James W. Hardin, S. Scott Sutton

Faculty Publications

Background: Obesity is a risk factor for the development of influenza by leading to a chronic inflammatory state and T-cell dysfunction. Based upon preclinical research, metformin has influenza activity by restoring T-cell function and improving the immune response. Objective: We aimed to evaluate the potential drug repurposing of metformin for the management of influenza among patients with obesity utilizing national claims data in an electronic health record database. Methods: The VA Informatics and Computing Infrastructure (VINCI) was utilized to obtain individual-level information on demographics, administrative claims, and pharmacy dispensation. A cohort was created among individuals with laboratory confirmed diagnosis of …

Diet Quality And Dietary Inflammatory Index Score Among Women’S Cancer Survivors, Sibylle Kranz, Faten Hasan, Erin Kennedy, Jamie Zoellner, Kristin A. Guertin, Nitin Shivappa Mbbs, Mph, Ph.D., James R. Hébert, Roger Anderson, Wendy Cohn

Faculty Publications

The purpose of this study was to investigate Healthy Eating Index 2015 (HEI-2015) and Energy-Adjusted Dietary Inflammatory Index (E-DIITM) scores in women's cancer survivors and to examine socio-economic (SES) characteristics associated with these two diet indices. In this cross-sectional study, survivors of women's cancers completed a demographic questionnaire and up to three 24-h dietary recalls. HEI-2015 and E-DII scores were calculated from average intakes. One-way ANOVA was used to examine the association of various demographic factors on HEI-2015 and E-DII scores. Pearson Correlation was used to calculate the correlation between the two scores. The average HEI-2015 score was 55.0 +/- …

Angiotensin Blockade Therapy And Survival In Pancreatic Cancer: A Population Study, Scott W Keith, Vittorio Maio, Hwyda A Arafat, Matthew Alcusky, Thomas Karagiannis, Carol Rabinowitz, Harish Lavu, Daniel Z. Louis

College of Population Health Faculty Papers

Background: Pancreatic cancer (PC) is one of the most aggressive and challenging cancer types to effectively treat, ranking as the fourth-leading cause of cancer death in the United States. We investigated if exposures to angiotensin II receptor blockers (ARBs) or angiotensin I converting enzyme (ACE) inhibitors after PC diagnosis are associated with survival.

Methods: PC patients were identified by ICD-9 diagnosis and procedure codes among the 3.7 million adults living in the Emilia-Romagna Region from their administrative health care database containing patient data on demographics, hospital discharges, all-cause mortality, and outpatient pharmacy prescriptions. Cox modeling estimated covariate-adjusted mortality hazard ratios …

Transmodel: An R Package For Linear Transformation Model With Censored Data, Jie Zhou, Jiajia Zhang Ph.D.

Faculty Publications

Linear transformation models, including the proportional hazards model and proportional odds model, under right censoring were discussed by Chen, Jin, and Ying (2002). The asymptotic variance of the estimator they proposed has a closed form and can be obtained easily by plug-in rules, which improves the computational efficiency. We develop an R package TransModel based on Chen's approach. The detailed usage of the package is discussed, and the function is applied to the Veterans' Administration lung cancer data.

Comparison Of Human Urinary Exosomes Isolated Via Ultracentrifugation Alone Versus Ultracentrifugation Followed By Sec Column-Purification, Kun Huang, Sudha Garimella, Alyssa Clay-Gilmour, Lucia Vojtech, Bridget Armstrong, Madison Bessonny, Alexis Stamatikos

Faculty Publications

Chronic kidney disease is a progressive, incurable condition that involves a gradual loss of kidney function. While there are no non-invasive biomarkers available to determine whether individuals are susceptible to developing chronic kidney disease, small RNAs within urinary exosomes have recently emerged as a potential candidate to use for assessing renal function. Ultracentrifugation is the gold standard for urinary exosome isolation. However, extravesicular small RNA contamination can occur when isolating exosomes from biological fluids using ultracentrifugation, which may lead to misidentifying the presence of certain small RNA species in human urinary exosomes. Therefore, we characterized human urinary exosomal preparations isolated …

Marginal Proportional Hazards Models For Clustered Interval-Censored Data With Time-Dependent Covariates, Kaitlyn Cook, Wenbin Lu, Rui Wang

Harvard University Biostatistics Working Paper Series

The Botswana Combination Prevention Project was a cluster-randomized HIV prevention trial whose follow-up period coincided with Botswana’s national adoption of a universal test-and-treat strategy for HIV management. Of interest is whether, and to what extent, this change in policy (i) modified the observed preventative effects of the study intervention and (ii) was associated with a reduction in the population-level incidence of HIV in Botswana. To address these questions, we propose a stratified proportional hazards model for clustered interval-censored data with time-dependent covariates and develop a composite expectation maximization algorithm that facilitates estimation of model parameters without placing parametric assumptions on …

On Assessing Survival Benefit Of Immunotherapy Using Long-Term Restricted Mean Survival Time, Miki Horiguchi, Lu Tian, Hajime Uno

Harvard University Biostatistics Working Paper Series

The pattern of the difference between two survival curves we often observe in randomized clinical trials for evaluating immunotherapy is not proportional hazards; the treatment effect typically appears several months after the initiation of the treatment (i.e., delayed difference pattern). The commonly used logrank test and hazard ratio estimation approach will be suboptimal concerning testing and estimation for those trials. The long-term restricted mean survival time (LT-RMST) approach is a promising alternative for detecting the treatment effect that potentially appears later in the study. A challenge in employing the LT-RMST approach is that it must specify a lower end of …

Scanner: A Web Platform For Annotation, Visualization And Sharing Of Single Cell Rna-Seq Data, Guoshuai Cai, Xuanxuan Yu, Choonhan Youn, Jun Zhou, Feifei Xiao

Faculty Publications

In recent years, efficient scRNA-seq methods have been developed, enabling the transcriptome profiling of single cells massively in parallel. Meanwhile, its high dimensionality and complexity bring challenges to the data analysis and require extensive collaborations between biologists and bioinformaticians and/or biostatisticians. The communication between these two units demands a platform for easy data sharing and exploration. Here we developed Single-Cell Transcriptomics Annotated Viewer (SCANNER), as a public web resource for the scientific community, for sharing and analyzing scRNA-seq data in a collaborative manner. It is easy-to-use without requiring special software or extensive coding skills. Moreover, it equipped a real-time database …

The Isocaloric Substitution Of Plant-Based And Animal-Based Protein In Relation To Aging-Related Health Outcomes: A Systematic Review, Jiali Zheng, Tianren Zhu, Guanghuan Yang, Longgang Zhao, Fangyu Li, Yong-Moon Park, Fred K. Tabung, Susan E. Steck Phd, Mph, Rd, Xiaoguang Li, Hui Wang

Faculty Publications

Plant-based and animal-based protein intake have differential effects on various aging-related health outcomes, but less is known about the health effect of isocaloric substitution of plant-based and animal-based protein. This systematic review summarized current evidence of the isocaloric substitutional effect of plant-based and animal-based protein on aging-related health outcomes. PubMed and Embase databases were searched for epidemiologic observational studies published in English up to 15 March 2021. Studies that included adults ≥18 years old; use of a nutritional substitution model to define isocaloric substitution of plant protein and animal protein; health outcomes covering mortality, aging-related diseases or indices; and reported …

Upregulation Of Cd36, A Fatty Acid Translocase, Promotes Colorectal Cancer Metastasis By Increasing Mmp28 And Decreasing E-Cadherin Expression, James Drury, Piotr G. Rychahou, Courtney O. Kelson, Mariah E. Geisen, Yuanyuan Wu, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers, Yekaterina Y. Zaytseva

Surgery Faculty Publications

Altered fatty acid metabolism continues to be an attractive target for therapeutic intervention in cancer. We previously found that colorectal cancer (CRC) cells with a higher metastatic potential express a higher level of fatty acid translocase (CD36). However, the role of CD36 in CRC metastasis has not been studied. Here, we demonstrate that high expression of CD36 promotes invasion of CRC cells. Consistently, CD36 promoted lung metastasis in the tail vein model and GI metastasis in the cecum injection model. RNA-Seq analysis of CRC cells with altered expression of CD36 revealed an association between high expression of CD36 and upregulation …

Nonlinear Mixed-Effects Models For Hiv Viral Load Trajectories Before And After Antiretroviral Therapy Interruption, Incorporating Left Censoring, Sihaoyu Gao, Lang Wu, Tingting Yu, Roger Kouyos, Huldrych F. Gunthard, Rui Wang

Harvard University Biostatistics Working Paper Series

Characterizing features of the viral rebound trajectories and identifying host, virological, and immunological factors that are predictive of the viral rebound trajectories are central to HIV cure research. In this paper, we investigate if key features of HIV viral decay and CD4 trajectories during antiretroviral therapy (ART) are associated with characteristics of HIV viral rebound following ART interruption. Nonlinear mixed effect (NLME) models are used to model viral load trajectories before and following ART interruption, incorporating left censoring due to lower detection limits of viral load assays. A stochastic approximation EM (SAEM) algorithm is used for parameter estimation and inference. …

Long-Read Sequencing Of The Zebrafish Genome Reorganizes Genomic Architecture, Yelena Chernyavskaya, Xiaofei Zhang, Jinze Liu, Jessica Blackburn

Biostatistics Publications

Background

Nanopore sequencing technology has revolutionized the field of genome biology with its ability to generate extra-long reads that can resolve regions of the genome that were previously inaccessible to short-read sequencing platforms. Over 50% of the zebrafish genome consists of difficult to map, highly repetitive, low complexity elements that pose inherent problems for short-read sequencers and assemblers.

Results

We used long-read nanopore sequencing to generate a de novo assembly of the zebrafish genome and compared our assembly to the current reference genome, GRCz11. The new assembly identified 1697 novel insertions and deletions over one kilobase in length and placed …

Non-Inferiority Testing: Kernel Estimation And Overlap Measure, Larie C. Ward

College of Graduate Studies: Theses & Dissertations

In non-inferiority testing, the decision of whether a proposed treatment is non-inferior to a reference treatment depends on model assumptions and choices of acceptable tolerance limits. Here, we consider a method that employs kernels to estimate the probability density functions of both the experimental and reference populations from two independent samples. Based on these densities, we introduce a quantity called the overlap coefficient or overlap measure. A bootstrap technique is helpful in exploring the distribution and variance empirically. We derive the distribution of this measure and define a hypothesis test that can be applied to the non-inferiority setting under some …

Finding The Best Predictors For Foot Traffic In Us Seafood Restaurants, Isabel Paige Beaulieu

Honors Theses and Capstones

COVID-19 caused state and nation-wide lockdowns, which altered human foot traffic, especially in restaurants. The seafood sector in particular suffered greatly as there was an increase in illegal fishing, it is made up of perishable goods, it is seasonal in some places, and imports and exports were slowed. Foot traffic data is useful for business owners to have to know how much to order, how many employees to schedule, etc. One issue is that the data is very expensive, hard to get, and not available until months after it is recorded. Our goal is to not only find covariates that …

A Simple And Robust Alternative To Bland-Altman Method Of Assessing Clinical Agreement, Abhaya Indrayan Prof

COBRA Preprint Series

Clinical agreement between two quantitative measurements on a group of subjects is generally assessed with the help of the Bland-Altman (B-A) limits. These limits only describe the dispersion of disagreements in 95% cases and do not measure the degree of agreement. The interpretation regarding the presence or absence of agreement by this method is based on whether B-A limits are within the pre-specified externally determined clinical tolerance limits. Thus, clinical tolerance limits are necessary for this method. We argue in this communication that the direct use of clinical tolerance limits for assessing agreement without the B-A limits is more effective …

Multivariate Statistical Modeling For Radio-Genomics Study, Tiantian Zeng

Theses and Dissertations--Statistics

Radiogenomics is a new direction in cancer research that focuses on the associations among radiomics, genomics and clinical outcome. Currently, the major challenge for Radiogenomics lies in the effective integration of genomics and imaging data for promising clinical outcome prediction. Herein, we propose a multivariate joint model that can integrate imaging and genomic data for better predicting the clinical outcome. Specifically, we jointly consider two multivariate group lasso models, one regresses imaging features on genomic features, and the other regresses patient’s clinical outcome on genomic features. An L1 penalty term is introduced for each variable, and weight in the penalty …

Statistical Theory For Specialized Linear Regression Adjustment Methods Compared To Multiple Linear Regression In The Presence And Absence Of Interaction Effects, Leon Su

Theses and Dissertations--Statistics

When building models to investigate outcomes and variables of interest, researchers often want to adjust for other variables. There is a variety of ways that these adjustments are performed. In this work, we will consider four approaches to adjustment utilized by researchers in various fields. We will compare the efficacy of these methods to what we call the ”true model method”, fitting a multiple linear regression model in which adjustment variables are model covariates. Our goal is to show that these adjustment methods have inferior performance to the true model method by comparing model parameter estimates, power, type I error, …

Addressing Ascertainment Bias In The Study Of Cardiovascular Disease Burden In Opioid Use Disorders - Application Of Natural Language Processing Of Electronic Health Records, Jade Huang Singleton

Theses and Dissertations--Epidemiology and Biostatistics

In the United States, the prevalence of long-term exposure to opioid drugs, for both medically and nonmedically indicated purposes, has increased considerably since the mid-1990’s. Concerns have emerged about the potential health effects of opioid use. There is also growing interest in other possible connections with opioid use including cardiovascular disease. Electronic health records (EHR) contain information about patient care in the form of structured codes and unstructured notes. Natural language processing (NLP) provides a tool for processing unstructured textual data in EHR clinical notes and extracts useful information for research with structured formats. The purpose of this dissertation was …

Opioid Use Disorder Treatment With Buprenorphine: Analysis Of Treatment Utilization And Associated Outcomes In Kentucky, Feitong Lei

Theses and Dissertations--Epidemiology and Biostatistics

Opioid use disorder (OUD) is chronic opioid use that results in clinically significant suffering, impairment, or even death. The opioid epidemic in the United States has become a public health and economic crisis, affecting patients' well-being and the nation's overall health and welfare. Eastern Kentucky was among the first regions affected by the opioid crisis, and Kentucky has historically ranked among the top five states for age-adjusted drug overdose mortality rate.

There are three medications (buprenorphine, methadone, naltrexone) approved by the U.S. Food and Drug Administration to treat OUD. As a partial opioid agonist, buprenorphine is a safe medication for …

Framework For The Evaluation Of Perturbations In The Systems Biology Landscape And Inter-Sample Similarity From Transcriptomic Datasets — A Digital Twin Perspective, Mariah Marie Hoffman

Dissertations and Theses

One approach to interrogating the complexities of human systems in their well-regulated and dysregulated states is through the use of digital twins. Digital twins are virtual representations of physical systems that are descriptive of an individual's state of health, an object fundamentally related to precision medicine. A key element for building a functional digital twin type for a disease or predicting the therapeutic efficacy of a potential treatment is harmonized, machine-parsable domain knowledge. Hypothesis-driven investigations are the gold standard for representing subsystems, but their results encompass a limited knowledge of the full biosystem. Multi-omics data is one rich source of …