Digital Commons Network^™

Capn2 Correlates With Insulin Resistance States In Pcos As Evidenced By Multi-Dataset Analysis, Xi Luo, Yunhua Dong, Haishan Zheng, Xiaoting Zhou, Lujuan Rong, Xiaoping Liu, Yun Bai, Yunxiu Li, Ze Wu

Journal Articles

OBJECTIVE: IR emerges as a feature in the pathophysiology of PCOS, precipitating ovulatory anomalies and endometrial dysfunctions that contribute to the infertility challenges characteristic of this condition. Despite its clinical significance, a consensus on the precise mechanisms by which IR exacerbates PCOS is still lacking. This study aims to harness bioinformatics tools to unearth key IR-associated genes in PCOS patients, providing a platform for future therapeutic research and potential intervention strategies.

METHODS: We retrieved 4 datasets detailing PCOS from the GEO, and sourced IRGs from the MSigDB. We applied WGCNA to identify gene modules linked to insulin resistance, utilizing IR …

What Quantifies Good Primary Care In The United States? A Review Of Algorithms And Metrics Using Real-World Data, Yun Wang, Jianwei Zheng, Todd Schneberk, Yu Ke, Alexandre Chan, Tao Hu, Jerika Lam, Mary Gutierrez, Ivan Portillo, Dan Wu, Chi-Hung Chang, Yang Qu, Lawrence Brown, Michael B. Nichol

Pharmacy Faculty Articles and Research

Primary care physicians (PCPs) play an indispensable role in providing comprehensive care and referring patients for specialty care and other medical services. As the COVID-19 outbreak disrupts patient access to care, understanding the quality of primary care is critical at this unprecedented moment to support patients with complex medical needs in the primary care setting and inform policymakers to redesign our primary care system. The traditional way of collecting information from patient surveys is time-consuming and costly, and novel data collection and analysis methods are needed. In this review paper, we describe the existing algorithms and metrics that use the …

A Novel Imputation Approach For Sharing Protected Public Health Data, Elizabeth A Erdman, Leonard D Young, Dana L Bernson, Cici Bauer, Kenneth Chui, Thomas J Stopka

Journal Articles

No abstract provided.

Variant-Specific Inflation Factors For Assessing Population Stratification At The Phenotypic Variance Level, Tamar Sofer, Xiuwen Zheng, Cecelia A Laurie, Stephanie M Gogarten, Jennifer A Brody, Matthew P Conomos, Joshua C Bis, Timothy A Thornton, Adam Szpiro, Jeffrey R O'Connell, Ethan M Lange, Yan Gao, L Adrienne Cupples, Bruce M Psaty, Kenneth M Rice

Journal Articles

In modern Whole Genome Sequencing (WGS) epidemiological studies, participant-level data from multiple studies are often pooled and results are obtained from a single analysis. We consider the impact of differential phenotype variances by study, which we term 'variance stratification'. Unaccounted for, variance stratification can lead to both decreased statistical power, and increased false positives rates, depending on how allele frequencies, sample sizes, and phenotypic variances vary across the studies that are pooled. We develop a procedure to compute variant-specific inflation factors, and show how it can be used for diagnosis of genetic association analyses on pooled individual level data from …

Structural Insights Into The Disruption Of Tnf-Tnfr1 Signalling By Small Molecules Stabilising A Distorted Tnf, David Mcmillan, Carlos Martinez-Fleites, John Porter, David Fox, Rachel E. Davis, Prashant Mori, Tom Ceska, Bruce Carrington, Alastair Lawson, Tim Bourne, James O'Connell

Faculty Publications

Tumour necrosis factor (TNF) is a trimeric protein which signals through two membrane receptors, TNFR1 and TNFR2. Previously, we identified small molecules that inhibit human TNF by stabilising a distorted trimer and reduce the number of receptors bound to TNF from three to two. Here we present a biochemical and structural characterisation of the small molecule-stabilised TNF-TNFR1 complex, providing insights into how a distorted TNF trimer can alter signalling function. We demonstrate that the inhibitors reduce the binding affinity of TNF to the third TNFR1 molecule. In support of this, we show by X-ray crystallography that the inhibitor-bound, distorted, TNF …

Mapping Of Lymphatic Filariasis In Loiasis Areas: A New Strategy Shows No Evidence For Wuchereria Bancrofti Endemicity In Cameroon, Samuel Wanji, Mathias Eyong Esum, Abdel Jelil Njouendou, Amuam Andrew Mbeng, Patrick W Chounna Ndongmo, Raphael Awah Abong, Jerome Fru, Fanny F. Fombad, Gordon Takop Nchanji, Glory Ngongeh, Narcisse V. Ngandjui, Peter Ivo Enyong, Helen Storey, Kurt C. Curtis, Kerstin Fischer, Joseph R. Fauver, Daphne Lew, Charles W. Goss, Peter U. Fischer

Journal Articles: Epidemiology

BACKGROUND: Mapping of lymphatic filariasis (LF) caused by Wuchereria bancrofti largely relies on the detection of circulating antigen using ICT cards. Several studies have recently shown that this test can be cross-reactive with sera of subjects heavily infected with Loa loa and thus mapping results in loiasis endemic areas may be inaccurate.

METHODOLOGY/PRINCIPAL FINDINGS: In order to develop an LF mapping strategy for areas with high loiasis prevalence, we collected day blood samples from 5,001 subjects residing in 50 villages that make up 6 health districts throughout Cameroon. Antigen testing using Filarial Test Strip (FTS, a novel platform that uses …

Evaluation Of Plan Quality And Treatment Efficiency For Single-Isocenter/Two-Lesion Lung Stereotactic Body Radiation Therapy, Lana Sanford, Janelle A. Molloy, Sameera S. Kumar, Marcus Randall, Ronald C. Mcgarry, Damodar Pokhrel

Radiation Medicine Faculty Publications

Purpose/objectives: To evaluate the plan quality and treatment delivery efficiency of single‐isocenter/two‐lesions volumetric modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT).

Materials/methods: Eight consecutive patients with two peripherally located early stage nonsmall‐cell‐lung cancer (NSCLC) lung lesions underwent single‐isocenter highly conformal noncoplanar VMAT SBRT treatment in our institution. A single‐isocenter was placed between the two lesions. Doses were 54 or 50 Gy in 3 and 5 fractions respectively. Patients were treated every other day. Plans were calculated in Eclipse with AcurosXB algorithm and normalized to at least 95% of the planning target volume (PTV) receiving 100% of the prescribed …

Automated Ecological Assessment Of Physical Activity: Advancing Direct Observation., Jordan A. Carlson, Bo Liu, James F. Sallis, Jacqueline Kerr, J Aaron Hipp, Vincent S. Staggs, Amy Papa, Kelsey Dean, Nuno M. Vasconcelos

Manuscripts, Articles, Book Chapters and Other Papers

Technological advances provide opportunities for automating direct observations of physical activity, which allow for continuous monitoring and feedback. This pilot study evaluated the initial validity of computer vision algorithms for ecological assessment of physical activity. The sample comprised 6630 seconds per camera (three cameras in total) of video capturing up to nine participants engaged in sitting, standing, walking, and jogging in an open outdoor space while wearing accelerometers. Computer vision algorithms were developed to assess the number and proportion of people in sedentary, light, moderate, and vigorous activity, and group-based metabolic equivalents of tasks (MET)-minutes. Means and standard deviations (SD) …

A Statistical Method For The Conservative Adjustment Of False Discovery Rate (Q-Value)., Yinglei Lai

Epidemiology Faculty Publications

BACKGROUND: q-value is a widely used statistical method for estimating false discovery rate (FDR), which is a conventional significance measure in the analysis of genome-wide expression data. q-value is a random variable and it may underestimate FDR in practice. An underestimated FDR can lead to unexpected false discoveries in the follow-up validation experiments. This issue has not been well addressed in literature, especially in the situation when the permutation procedure is necessary for p-value calculation.

RESULTS: We proposed a statistical method for the conservative adjustment of q-value. In practice, it is usually necessary to calculate p-value by a permutation procedure. …

Applications Of The Wei-Lachin Multivariate One-Sided Test For Multiple Outcomes On Possibly Different Scales, John M. Lachin

GW Biostatistics Center

Many studies aim to assess whether a therapy has a beneficial effect on multiple outcomes simultaneously relative to a control. Often the joint null hypothesis of no difference for the set of outcomes is tested using separate tests with a correction for multiple tests, or using a multivariate T2-like MANOVA or global test. However, a more powerful test in this case is a multivariate one-sided or one-directional test directed at detecting a simultaneous beneficial treatment effect on each outcome, though not necessarily of the same magnitude. The Wei-Lachin test is a simple 1 df test obtained from a simple …

Why 'Down Under' Is A Cut Above: A Comparison Of Rates Of And Reasons For Caesarean Section In England And Australia, Samantha J. Prosser, Yvette D. Miller, Rachel Thompson, Maggie Redshaw

Dartmouth Scholarship

Background: Most studies examining determinants of rising rates of caesarean section have examined patterns in documented reasons for caesarean over time in a single location. Further insights could be gleaned from cross-cultural research that examines practice patterns in locations with disparate rates of caesarean section at a single time point.

Methods: We compared both rates of and main reason for pre-labour and intrapartum caesarean between England and Queensland, Australia, using data from retrospective cross-sectional surveys of women who had recently given birth in England (n = 5,250) and Queensland (n = 3,467).

Highly Variable Recessive Lthal Or Nearly Lethal Mutation Rates During Germ-Line Development Of Male Drosophila Melanogaster, Jian-Jun Gao, Xue-Rong Pan, Jing Hu, Li Ma, Jian-Min Wu, Ye-Lin Shao, Sara A Barton, Ronny C Woodruff, Ya-Ping Zhang, Yun-Xin Fu

Journal Articles

Each cell of higher organism adults is derived from a fertilized egg through a series of divisions, during which mutations can occur. Both the rate and timing of mutations can have profound impacts on both the individual and the population, because mutations that occur at early cell divisions will affect more tissues and are more likely to be transferred to the next generation. Using large-scale multigeneration screening experiments for recessive lethal or nearly lethal mutations of Drosophila melanogaster and recently developed statistical analysis, we show for male D. melanogaster that (i) mutation rates (for recessive lethal or nearly lethal) are …

Extended Kalman Filter For Estimation Of Parameters In Nonlinear State-Space Models Of Biochemical Networks, Xiaodian Sun, Li Jin, Momiao Xiong

Journal Articles

It is system dynamics that determines the function of cells, tissues and organisms. to develop mathematical models and estimate their parameters are an essential issue for studying dynamic behaviors of biological systems which include metabolic networks, genetic regulatory networks and signal transduction pathways, under perturbation of external stimuli. In general, biological dynamic systems are partially observed. Therefore, a natural way to model dynamic biological systems is to employ nonlinear state-space equations. Although statistical methods for parameter estimation of linear models in biological dynamic systems have been developed intensively in the recent years, the estimation of both states and parameters of …

Differential Dynamic Properties Of Scleroderma Fibroblasts In Response To Perturbation Of Environmental Stimuli, Momiao Xiong, Frank C. Arnett, Xinjian Guo, Hao Xiong, Xiaodong Zhou

Journal Articles

Diseases are believed to arise from dysregulation of biological systems (pathways) perturbed by environmental triggers. Biological systems as a whole are not just the sum of their components, rather ever-changing, complex and dynamic systems over time in response to internal and external perturbation. In the past, biologists have mainly focused on studying either functions of isolated genes or steady-states of small biological pathways. However, it is systems dynamics that play an essential role in giving rise to cellular function/dysfunction which cause diseases, such as growth, differentiation, division and apoptosis. Biological phenomena of the entire organism are not only determined by …

Gpnn: Power Studies And Applications Of A Neural Network Method For Detecting Gene-Gene Interactions In Studies Of Human Disease, Alison A. Motsinger, Stephen L. Lee, George Mellick, Marylyn D. Ritchie

Dartmouth Scholarship

The identification and characterization of genes that influence the risk of common, complex multifactorial disease primarily through interactions with other genes and environmental factors remains a statistical and computational challenge in genetic epidemiology. We have previously introduced a genetic programming optimized neural network (GPNN) as a method for optimizing the architecture of a neural network to improve the identification of gene combinations associated with disease risk. The goal of this study was to evaluate the power of GPNN for identifying high-order gene-gene interactions. We were also interested in applying GPNN to a real data analysis in Parkinson's disease.

Laboratory Diagnosis Of Tuberculosis In Primary Care, David Brett-Major, Thomas E. Walsh

Journal Articles: Epidemiology

No abstract provided.

Diagnosing Crohn's Disease: An Economic Analysis Comparing Wireless Capsule Endoscopy With Traditional Diagnostic Procedures, Neil I. Goldfarb, Laura T. Pizzi, Joseph P. Fuhr Jr., Christopher Salvador, Vanja Sikirica, Asher Kornbluth, Blair Lewis

College of Population Health Faculty Papers

The purpose of this study was to review economic considerations related to establishing a diagnosis of Crohn's disease, and to compare the costs of a diagnostic algorithm incorporating wireless capsule endoscopy (WCE) with the current algorithm for diagnosing Crohn's disease suspected in the small bowel. Published literature, clinical trial data on WCE in comparison to other diagnostic tools, and input from clinical experts were used as data sources for (1) identifying contributors to the costs of diagnosing Crohn's disease; (2) exploring where WCE should be placed within the diagnostic algorithm for Crohn's; and (3) constructing decision tree models with sensitivity …