Digital Commons Network^™

Using Monozygotic Twins To Dissect Common Genes In Posttraumatic Stress Disorder And Migraine, Charlotte K Bainomugisa, Heidi G Sutherland, Richard Parker, Allan F Mcrae, Larisa M Haupt, Lyn R Griffiths, Andrew Heath, Elliot C Nelson, Margaret J Wright, Ian B Hickie, Nicholas G Martin, Dale R Nyholt, Divya Mehta

Open Access Publications

Epigenetic mechanisms have been associated with genes involved in Posttraumatic stress disorder (PTSD). PTSD often co-occurs with other health conditions such as depression, cardiovascular disorder and respiratory illnesses. PTSD and migraine have previously been reported to be symptomatically positively correlated with each other, but little is known about the genes involved. The aim of this study was to understand the comorbidity between PTSD and migraine using a monozygotic twin disease discordant study design in six pairs of monozygotic twins discordant for PTSD and 15 pairs of monozygotic twins discordant for migraine. DNA from peripheral blood was run on Illumina EPIC …

Neuropilin-2 Is Associated With Increased Hepatoblastoma Cell Viability And Motility, Katja Eloranta, Ruth Nousiainen, Stefano Cairo, Mikko P Pakarinen, David B Wilson, Marjut Pihlajoki, Markku Heikinheimo

Open Access Publications

The neuropilins NRP1 and NRP2 are multifunctional glycoproteins that have been implicated in several cancer-related processes including cell survival, migration, and invasion in various tumor types. Here, we examine the role of neuropilins in hepatoblastoma (HB), the most common pediatric liver malignancy. Using a combination of immunohistochemistry, RNA analysis and western blotting, we observed high level expression of

The Stroke Neuro-Imaging Phenotype Repository: An Open Data Science Platform For Stroke Research, Hossein Mohammadian Foroushani, Rajat Dhar, Yasheng Chen, Jenny Gurney, Ali Hamzehloo, Jin-Moo Lee, Daniel S Marcus

Open Access Publications

Stroke is one of the leading causes of death and disability worldwide. Reducing this disease burden through drug discovery and evaluation of stroke patient outcomes requires broader characterization of stroke pathophysiology, yet the underlying biologic and genetic factors contributing to outcomes are largely unknown. Remedying this critical knowledge gap requires deeper phenotyping, including large-scale integration of demographic, clinical, genomic, and imaging features. Such big data approaches will be facilitated by developing and running processing pipelines to extract stroke-related phenotypes at large scale. Millions of stroke patients undergo routine brain imaging each year, capturing a rich set of data on stroke-related …

Loureirin B Exerts Its Immunosuppressive Effects By Inhibiting Stim1/Orai1 And K V 1.3 Channels, Shujuan Shi, Qianru Zhao, Caihua Ke, Siru Long, Feng Zhang, Xu Zhang, Yi Li, Xinqiao Liu, Hongzhen Hu, Shijin Yin

Open Access Publications

Loureirin B (LrB) is a constituent extracted from traditional Chinese medicine Resina Draconis. It has broad biological functions and an impressive immunosuppressive effect that has been supported by numerous studies. However, the molecular mechanisms underlying Loureirin B-induced immune suppression are not fully understood. We previously reported that Loureirin B inhibited K

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 …

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. …

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 …

A Phase 2 Study Of Isatuximab Monotherapy In Patients With Multiple Myeloma Who Are Refractory To Daratumumab, Joseph Mikhael, Ravi Vij, Et Al.

Open Access Publications

No abstract provided.

Constitutive Activation Of Nf-Κb Inducing Kinase (Nik) In The Mesenchymal Lineage Using Osterix (Sp7)- Or Fibroblast-Specific Protein 1 (S100a4)-Cre Drives Spontaneous Soft Tissue Sarcoma, Jennifer L. Davis, Roman Thaler, Linda Cox, Biancamaria Ricci, Heather M. Zannit, Fei Wan, Roberta Faccio, Amel Dudakovic, Andre J. Van Wijnen, Deborah J. Veis

Open Access Publications

Aberrant NF-κB signaling fuels tumor growth in multiple human cancer types including both hematologic and solid malignancies. Chronic elevated alternative NF-κB signaling can be modeled in transgenic mice upon activation of a conditional NF-κB-inducing kinase (NIK) allele lacking the regulatory TRAF3 binding domain (NT3). Here, we report that expression of NT3 in the mesenchymal lineage with Osterix (Osx/Sp7)-Cre or Fibroblast-Specific Protein 1 (FSP1)-Cre caused subcutaneous, soft tissue tumors. These tumors displayed significantly shorter latency and a greater multiple incidence rate in Fsp1-Cre;NT3 compared to Osx-Cre;NT3 mice, regardless of sex. Histological assessment revealed poorly differentiated solid tumors with some spindled patterns, …

Quantitative Imaging Of Membrane Contact Sites For Sterol Transfer Between Endo‑Lysosomes And Mitochondria In Living Cells, Alice Dupont Juhl, Christian W. Heegaard, Stephan Werner, Gerd Schneider, Kathiresan Krishnan, Douglas F. Covey, Daniel Wüstner

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.

Deep Learning The Structural Determinants Of Protein Biochemical Properties By Comparing Structural Ensembles With Diffnets, Michael D. Ward, Maxwell I. Zimmerman, Artur Meller, Moses Chung, S.J. Swamidass, Gregory R. Bowman

Open Access Publications

No abstract provided.

A Metabolomic Endotype Of Bioenergetic Dysfunction Predicts Mortality In Critically Ill Patients With Acute Respiratory Failure, Raymond J. Langley, Patrick Luckett, Et Al.

Open Access Publications

No abstract provided.

Cryo-Em Structure Of Cortical Microtubules From Human Parasite Toxoplasma Gondii Identifies Their Microtubule Inner Proteins, Xiangli Wang, Yong Fu, Wandy L. Beatty, Meisheng Ma, Alan Brown, L. David Sibley, Rui Zhang

Open Access Publications

No abstract provided.

Mapping The Molecular And Structural Specialization Of The Skin Basement Membrane For Inter-Tissue Interactions, Ko Tsutsui, Hiroki Machida, Asako Nakagawa, Kyungmin Ahn, Ritsuko Morita, Kiyotoshi Sekiguchi, Jeffrey H. Miner, Hironobu Fujiwara

Open Access Publications

No abstract provided.

Dopamine D1 + D3 Receptor Density May Correlate With Parkinson Disease Clinical Features, Pengfei Yang, William C Knight, Huifangjie Li, Yingqiu Guo, Joel S Perlmutter, Tammie L S Benzinger, John C Morris, Jinbin Xu

Open Access Publications

OBJECTIVE: Dopamine D2-like receptors - mainly dopamine D2 receptors (D2R) and dopamine D3 receptors (D3R) - are believed to be greatly involved in the pathology of Parkinson disease (PD) progression. However, these receptors have not been precisely examined in PD patients. Our aim was to quantitatively calculate the exact densities of dopamine D1 receptors (D1R), D2R, and D3R in control, Alzheimer disease (AD), and Lewy body disease (LBD) patients (including PD, Dementia with Lewy bodies, and Parkinson disease dementia); and analyze the relationship between dopamine receptors and clinical PD manifestations.

METHODS: We analyzed the densities of D1R, D2R, and D3R …

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 …

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.

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.

Effect Of Clinical Isolate Or Cleavage Site Mutations In The Sars-Cov-2 Spike Protein On Protein Stability, Cleavage, And Cell–Cell Fusion, Chelsea T. Barrett, Hadley E. Neal, Kearstin Edmonds, Carole L. Moncman, Rachel Thompson, Jean M. Branttie, Kerri Beth Boggs, Cheng-Yu Wu, Daisy W. Leung, Rebecca E. Dutch

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 …

Stk39 Promotes Breast Cancer Invasion And Metastasis By Increasing Snai1 Activity Upon Phosphorylation, Zhaoping Qiu, Bo Dong, Weijie Guo, Rychahou Piotr, Greg Longmore, Xiuwei Yang, Zhiyong Yu, Jiong Deng, B. Mark Evers, Yadi Wu

Open Access Publications

No abstract provided.

Psychedelics For Brain Injury: A Mini-Review, Shariq Mansoor Khan, Gregory T Carter, Sunil K Aggarwal, Julie Holland

Open Access Publications

No abstract provided.

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.