Digital Commons Network^™

Mri Radiomic Signature Of White Matter Hyperintensities Is Associated With Clinical Phenotypes, Martin Bretzner, Laura Heitsch, Chia-Ling Phuah, Et Al

Open Access Publications

Objective: Neuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes.

Methods: We analyzed a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images with total brain and WMH segmentations. Radiomic features were extracted from normal-appearing brain tissue (brain mask-WMH …

Disentangling The Complexity Of The Rumen Microbial Diversity Through Fractionation Using A Sucrose Density Gradient, Ruth Hernández, Hugo Jimenez, Cesar Vargas-Garcia, Alejandro Caro-Quintero, Alejandro Reyes

Open Access Publications

The ruminal microbial community is an important element in health, nutrition, livestock productivity, and climate impact. Despite the historic and current efforts to characterize this microbial diversity, many of its members remain unidentified, making it challenging to associate microbial groups with functions. Here we present a low-cost methodology for rumen sample treatment that separates the microbial community based on cell size, allowing for the identification of subtle compositional changes. In brief, the sample is centrifuged through a series of sucrose density gradients, and cells migrate to their corresponding density fraction. From each fraction, DNA is extracted and

Functional Disruptions Of The Brain In Low Back Pain: A Potential Imaging Biomarker Of Functional Disability, Bidhan Lamichhane, Dinal Jayasekera, Rachel Jakes, Wilson Z Ray, Eric C Leuthardt, Ammar H Hawasli

Open Access Publications

Chronic low back pain (LBP) is one of the leading causes of disability worldwide. While LBP research has largely focused on the spine, many studies have demonstrated a restructuring of human brain architecture accompanying LBP and other chronic pain states. Brain imaging presents a promising source for discovering noninvasive biomarkers that can improve diagnostic and prognostication outcomes for chronic LBP. This study evaluated graph theory measures derived from brain resting-state functional connectivity (rsFC) as prospective noninvasive biomarkers of LBP. We also proposed and tested a hybrid feature selection method (Enet-subset) that combines Elastic Net and an optimal subset selection method. …

Pattern And Degree Of Individual Brain Atrophy Predicts Dementia Onset In Dominantly Inherited Alzheimer's Disease, Ophir Keret, Randal J Bateman, Tammie L S Benzinger, John C Morris, Beau M Ances, Nelly Joseph-Mathurin, Richard J Perrin, Brian A Gordon, Dominantly Inherited Alzheimer Network, Et Al

Open Access Publications

Introduction: Asymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD-MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD-MC and could help predict risk for dementia during trial enrollment.

Methods: We created a dementia risk score by entering standardized gray-matter volumes from 231 DIAD-MC into a logistic regression to classify participants with and without dementia. The score's predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD-MC followed longitudinally.

Results: Our risk score separated asymptomatic versus demented …

Predicting Self-Intercepted Medication Ordering Errors Using Machine Learning, Christopher Ryan King, Joanna Abraham, Bradley A. Fritz, Zhicheng Cui, William Galanter, Yixin Chen, Thomas Kannampallil

Open Access Publications

Current approaches to understanding medication ordering errors rely on relatively small manually captured error samples. These approaches are resource-intensive, do not scale for computerized provider order entry (CPOE) systems, and are likely to miss important risk factors associated with medication ordering errors. Previously, we described a dataset of CPOE-based medication voiding accompanied by univariable and multivariable regression analyses. However, these traditional techniques require expert guidance and may perform poorly compared to newer approaches. In this paper, we update that analysis using machine learning (ML) models to predict erroneous medication orders and identify its contributing factors. We retrieved patient demographics (race/ethnicity, …

Microglia In Alzheimer's Disease At Single-Cell Level. Are There Common Patterns In Humans And Mice?, Yun Chen, Marco Colonna

Open Access Publications

Alzheimer's disease (AD) is characterized by extracellular aggregates of amyloid β peptides, intraneuronal tau aggregates, and neuronal death. This pathology triggers activation of microglia. Because variants of genes expressed in microglia correlate with AD risk, microglial response to pathology plausibly impacts disease course. In mouse AD models, single-cell RNA sequencing (scRNA-seq) analyses delineated this response as progressive conversion of homeostatic microglia into disease-associated microglia (DAM); additional reactive microglial populations have been reported in other models of neurodegeneration and neuroinflammation. We review all of these microglial signatures, highlighting four fundamental patterns: DAM, IFN-microglia, MHC-II microglia, and proliferating microglia. We propose that …

Structure-Guided Microbial Targeting Of Antistaphylococcal Prodrugs, Justin J. Miller, Ishaan T. Shah, Jayda Hatten, Yasaman Barekatain, Elizabeth A. Mueller, Ahmed M. Moustafa, Rachel L. Edwards, Cynthia S. Dowd, Paul J. Planet, Florian L. Muller, Joseph M. Jez, Audrey R. Odom John

Open Access Publications

Carboxy ester prodrugs are widely employed to increase oral absorption and potency of phosphonate antibiotics. Prodrugging can mask problematic chemical features that prevent cellular uptake and may enable tissue-specific compound delivery. However, many carboxy ester promoieties are rapidly hydrolyzed by serum esterases, limiting their therapeutic potential. While carboxy ester-based prodrug targeting is feasible, it has seen limited use in microbes as microbial esterase-specific promoieties have not been described. Here we identify the bacterial esterases, GloB and FrmB, that activate carboxy ester prodrugs in

Tailoring Of Arteriovenous Graft‑To‑Vein Anastomosis Angle To Attenuate Pathological Flow Fields, Dillon Williams, Eric C. Leuthardt, Guy M. Genin, Mohamed Zayed

Open Access Publications

No abstract provided.

Visceral Obesity And Insulin Resistance Associate With Cd36 Deletion In Lymphatic Endothelial Cells, Vincenza Cifarelli, Sila Appak-Baskoy, Vivek S. Peche, Andrew Kluzak, Trevor Shew, Ramkumar Narendran, Kathryn M. Pietka, Marina Cella, Curtis W. Walls, Rafael Czepielewski, Stoyan Ivanov, Gwendalyn J. Randolph, Hellmut G. Augustin, Nada A. Abumrad

Open Access Publications

No abstract provided.

A Voxel-Wise Assessment Of Growth Differences In Infants Developing Autism Spectrum Disorder, A Cárdenas-De-La-Parra, J D Lewis, V S Fonov, K N Botteron, R C Mckinstry, G Gerig, J R Pruett Jr, S R Dager, J T Elison, M A Styner, A C Evans, J Piven, D L Collins, Ibis Network

Open Access Publications

Autism Spectrum Disorder (ASD) is a phenotypically and etiologically heterogeneous developmental disorder typically diagnosed around 4 years of age. The development of biomarkers to help in earlier, presymptomatic diagnosis could facilitate earlier identification and therefore earlier intervention and may lead to better outcomes, as well as providing information to help better understand the underlying mechanisms of ASD. In this study, magnetic resonance imaging (MRI) scans of infants at high familial risk, from the Infant Brain Imaging Study (IBIS), at 6, 12 and 24 months of age were included in a morphological analysis, fitting a mixed-effects model to Tensor Based Morphometry …

Multi-Modal Biomarkers Of Low Back Pain: A Machine Learning Approach, Bidhan Lamichhane, Dinal Jayasekera, Rachel Jakes, Matthew F Glasser, Justin Zhang, Chunhui Yang, Derayvia Grimes, Tyler L Frank, Wilson Z Ray, Eric C Leuthardt, Ammar H Hawasli

Open Access Publications

Chronic low back pain (LBP) is a very common health problem worldwide and a major cause of disability. Yet, the lack of quantifiable metrics on which to base clinical decisions leads to imprecise treatments, unnecessary surgery and reduced patient outcomes. Although, the focus of LBP has largely focused on the spine, the literature demonstrates a robust reorganization of the human brain in the setting of LBP. Brain neuroimaging holds promise for the discovery of biomarkers that will improve the treatment of chronic LBP. In this study, we report on morphological changes in cerebral cortical thickness (CT) and resting-state functional connectivity …

A Decade In Review After Idiopathic Scoliosis Was First Called A Complex Trait-A Tribute To The Late Dr. Yves Cotrel For His Support In Studies Of Etiology Of Scoliosis, Nelson L S Tang, Matthew B Dobbs, Christina A Gurnett, Yong Qiu, T P Lam, Jack C Y Cheng, Nancy Hadley-Miller

Open Access Publications

Adolescent Idiopathic Scoliosis (AIS) is a prevalent and important spine disorder in the pediatric age group. An increased family tendency was observed for a long time, but the underlying genetic mechanism was uncertain. In 1999, Dr. Yves Cotrel founded the Cotrel Foundation in the Institut de France, which supported collaboration of international researchers to work together to better understand the etiology of AIS. This new concept of AIS as a complex trait evolved in this setting among researchers who joined the annual Cotrel meetings. It is now over a decade since the first proposal of the complex trait genetic model …

The Treatment Gap In Osteoporosis, Nazia Ayub, Malak Faraj, Sam Ghatan, Joannes A A Reijers, Nicola Napoli, Ling Oei

Open Access Publications

Worldwide, there are millions of people who have been diagnosed with osteoporosis, a bone disease that increases the risk of fracture due to low bone mineral density and deterioration of bone architecture. In the US alone, there are approximately ten million men and women diagnosed with osteoporosis and this number is still growing. Diagnosis is made by measuring bone mineral density. Medications used for the treatment of osteoporosis are bisphosphonates, denosumab, raloxifene, and teriparatide. Recently, romosozumab has been added as well. In recent years, a number of advances have been made in the field of diagnostic methods and the diverse …

Molecular Genetics And Complex Inheritance Of Congenital Heart Disease, Nicholas S Diab, Syndi Barish, Weilai Dong, Shujuan Zhao, Garrett Allington, Xiaobing Yu, Kristopher T Kahle, Martina Brueckner, Sheng Chih Jin

Open Access Publications

Congenital heart disease (CHD) is the most common congenital malformation and the leading cause of mortality therein. Genetic etiologies contribute to an estimated 90% of CHD cases, but so far, a molecular diagnosis remains unsolved in up to 55% of patients. Copy number variations and aneuploidy account for ~23% of cases overall, and high-throughput genomic technologies have revealed additional types of genetic variation in CHD. The first CHD risk genotypes identified through high-throughput sequencing were de novo mutations, many of which occur in chromatin modifying genes. Murine models of cardiogenesis further support the damaging nature of chromatin modifying CHD mutations. …

Consequences Of Sur2[A478v] Mutation In Skeletal Muscle Of Murine Model Of Cantu Syndrome, Rosa Scala, Fatima Maqoud, Nicola Zizzo, Giuseppe Passantino, Antonietta Mele, Giulia Maria Camerino, Conor Mcclenaghan, Theresa M Harter, Colin G Nichols, Domenico Tricarico

Open Access Publications

(1) Background: Cantu syndrome (CS) arises from gain-of-function (GOF) mutations in the

The Top 100 Cited Papers In The Field Of Iron Deficiency In Humans: A Bibliometric Study, John L. Frater

Open Access Publications

No abstract provided.

Autosomal Dominant Ano5-Related Disorder Associated With Myopathy And Gnathodiaphyseal Dysplasia, Aziz Shaibani, Shaida Khan, Marwan Shinawi

Open Access Publications

No abstract provided.

Genomic And Clinical Characterization Of Early T-Cell Precursor Lymphoblastic Lymphoma, Xinjie Xu, Christian N. Paxton, Robert J. Hayashi, Kimberly P. Dunsmore, Stuart S. Winter, Stephen P. Hunger, Naomi J. Winick, William L. Carroll, Mignon L. Loh, Meenakshi Devidas, Thomas G. Gross, Catherine M. Bollard, Sherrie L. Perkins, Rodney R. Miles

Open Access Publications

No abstract provided.

Impact Of Breast Reconstruction Patients On Cosmetic Practice, Danielle C. Cooper, Ali A. Qureshi, Ketan Sharma, Marissa M. Tenenbaum, Terence M. Myckatyn

Open Access Publications

No abstract provided.

Mitochondria In Epithelial Ovarian Carcinoma Exhibit Abnormal Phenotypes And Blunted Associations With Biobehavioral Factors, Snehal Bindra, Marlon A. Mcgill, Marina K. Triplett, Anisha Tyagi, Premal H. Thaker, Laila Dahmoush, Michael J. Goodheart, R. Todd Ogden, Edward Owusu-Ansah, Kalpita R. Karan, Steve Cole, Anil K. Sood, Susan K. Lutgendorf, Martin Picard

Open Access Publications

No abstract provided.

Taxonomic Changes In The Gut Microbiota Are Associated With Cartilage Damage Independent Of Adiposity, High Fat Diet, And Joint Injury, Kelsey H. Collins, Drew J. Schwartz, Kristin L. Lenz, Charles A. Harris, Farshid Guilak

Open Access Publications

No abstract provided.

Orthogonal Targeting Of Osteoclasts And Myeloma Cells For Radionuclide Stimulated Dynamic Therapy Induces Multidimensional Cell Death Pathways, Alexander Zheleznyak, Matthew Mixdorf, Lynne Marsala, Julie Prior, Xiaoxia Yang, Grace Cui, Baogang Xu, Steven Fletcher, Francesca Fontana, Gregory Lanza, Samuel Achilefu

Open Access Publications

No abstract provided.

Restoration Of The Molecular Clock Is Tumor Suppressive In Neuroblastoma, Myrthala Moreno-Smith, Thomas P. Burris, Et Al.

Open Access Publications

No abstract provided.

Progress In Diagnosing Primary Ciliary Dyskinesia: The North American Perspective, Michael Glenn O'Connor, Amjad Horani, Adam J Shapiro

Open Access Publications

Primary Ciliary Dyskinesia (PCD) is a rare, under-recognized disease that affects respiratory ciliary function, resulting in chronic oto-sino-pulmonary disease. The PCD clinical phenotype overlaps with other common respiratory conditions and no single diagnostic test detects all forms of PCD. In 2018, PCD experts collaborated with the American Thoracic Society (ATS) to create a clinical diagnostic guideline for patients across North America, specifically considering the local resources and limitations for PCD diagnosis in the United States and Canada. Nasal nitric oxide (nNO) testing is recommended for first-line testing in patients ≥5 years old with a compatible clinical phenotype; however, all low …

Gene Therapy For Aromatic L-Amino Acid Decarboxylase Deficiency By Mr-Guided Direct Delivery Of Aav2-Aadc To Midbrain Dopaminergic Neurons, Toni S. Pearson, Et Al.

Open Access Publications

No abstract provided.

Adipose Tissue Hyaluronan Production Improves Systemic Glucose Homeostasis And Primes Adipocytes For Cl 316,243-Stimulated Lipolysis, Yi Zhu, Gordon I. Smith, Samuel Klein, Et Al

Open Access Publications

No abstract provided.

Substrate Reduction Therapy For Krabbe Disease And Metachromatic Leukodystrophy Using A Novel Ceramide Galactosyltransferase Inhibitor, Michael C. Babcock, Christina R. Mikulka, Hemanth R. Nelvagal, Xuntian Jiang, Mark S. Sands, Et Al

Open Access Publications

No abstract provided.

Comparison Of Complication Risk For Open Carpal Tunnel Release: In-Office Versus Operating Room Settings, Dustin J. Randall, Kate Peacock, Katelin B. Nickel, Margaret Olsen, Andrew R. Tyser, Nikolas H. Kazmers

Open Access Publications

No abstract provided.

Lower Extremity Nerve Transfers In Acute Flaccid Myelitis Patients: A Case Series, Amy M. Moore, Carrie Roth Bettlach, Thomas T. Tung, Julie M. West, Stephanie A. Russo

Open Access Publications

No abstract provided.

A Multi-Step Nucleation Process Determines The Kinetics Of Prion-Like Domain Phase Separation, Erik W. Martin, Tyler S. Harmon, Jesse B. Hopkins, Srinivas Chakravarthy, J. Jeremías Incicco, Peter Schuck, Andrea Soranno, Tanja Mittag

Open Access Publications

No abstract provided.