Medicine and Health Sciences Commons^™

Spinal Cord Injury: Tissue Bridge Influence On Neurophysiology And Functional Recovery, Alyssa I. Canales, Marylu Cabello

Research Colloquium

Introduction: Spinal cord injuries affect about 300,000 individuals in the United States and cause varying degrees of motor and sensory impairment. The standard of care for those with a spinal cord injury typically involves traditional rehabilitation. Unfortunately, over a year of rehabilitation is often required to achieve meaningful improvements in motor or sensory function. In order to improve rehabilitative efforts for those with spinal cord injury, it is critical to identify biomarkers that could serve as indicators for those who would respond to standard rehabilitation efforts.

Objective: Following spinal cord injury, edema forms around the area of injury in the …

Medical School Watercooler Newsletter - October 5, 2023, Lindsey Lyle

Watercooler Newsletter

This is the October 5, 2023 edition of the Frederick P. Whiddon College of Medicine's newsletter - Watercooler.

Contents Include:

• Meet a Med Student: Alexander Polski
• Simpkins selected as AAFP emerging leader institute scholar
• Bauer named assistant dean for admissions at Whiddon college of medicine

Clinical Presentation Of Patients With Lower Limb Spasticity Undergoing Routine Treatment With Botulinum Toxin: Baseline Findings From An International Observational Study, Alberto Esquenazi, Richard D. Zorowitz, Stephen Ashford, Pascal Maisonobe, Simon Page, Jorge Jacinto

Moss-Magee Rehabilitation Papers

OBJECTIVE: Describe how people with lower limb spasticity present for treatment in routine clinical practice.

METHODS: Prospective, observational study (Clinicaltrials.gov: NCT04050527) of ambulatory adult patients (≥ 18 years) with unilateral lower limb spasticity (able to take ≥ 5 steps with or without assistance) presenting for routine spasticity management, including treatment with abobotulinumtoxinA.

RESULTS: The study population included 430 adults with lower limb spasticity. Despite their relatively young age (mean ± standard deviation 53.7 ± 13.9 years), only 20% of patients were employed. Most patients had an acquired brain injury due to cerebrovascular disease; 84.1% reported having concomitant upper limb spasticity. …

Literature-Based Predictions Of Mendelian Disease Therapies, Cole A Deisseroth, Won-Seok Lee, Jiyoen Kim, Hyun-Hwan Jeong, Ryan S Dhindsa, Julia Wang, Huda Y Zoghbi, Zhandong Liu

Faculty, Staff and Students Publications

In the effort to treat Mendelian disorders, correcting the underlying molecular imbalance may be more effective than symptomatic treatment. Identifying treatments that might accomplish this goal requires extensive and up-to-date knowledge of molecular pathways-including drug-gene and gene-gene relationships. To address this challenge, we present "parsing modifiers via article annotations" (PARMESAN), a computational tool that searches PubMed and PubMed Central for information to assemble these relationships into a central knowledge base. PARMESAN then predicts putatively novel drug-gene relationships, assigning an evidence-based score to each prediction. We compare PARMESAN's drug-gene predictions to all of the drug-gene relationships displayed by the Drug-Gene Interaction …

Severe Pediatric Open Skull Fracture With Exposed Brain Matter: A Case Report, Sophia Mirkin, Michael Wu, Jessica Colon, Jose J. Burgos, Fernando Perez

HPD Articles

Head trauma in the pediatric population carries a high rate of morbidity and mortality. The major causes of head trauma are related to falls, recreational activities, motor vehicle accidents, and gunshot wounds. Traumatic brain injury (TBI) can occur after severe head trauma and is defined as an alteration in brain function, or other evidence of brain pathology, caused by an external force. Intracranial edema and herniation are common consequences of a TBI in pediatric patients and are commonly relieved via decompressive craniectomy. This case study describes a 13-year-old male presenting to the trauma center after an unhelmeted all-terrain vehicle (ATV) …

Évaluation De L’Impact De La Coexposition Sur Les Biomarqueurs D’Exposition Aux Pesticides Pyréthrinoïdes Chez Les Travailleurs Agricoles, Michèle Bouchard, Marc Bossou, Jonathan Côté

Rapports de recherche scientifique

Il existe peu de données publiées sur l'impact de la coexposition sur la toxicocinétique des pesticides chez les travailleurs agricoles, nécessaires pour une interprétation adéquate des données de biosurveillance de l’exposition. La présente recherche a visé à évaluer l’impact de la coexposition sur les niveaux de biomarqueurs d’exposition aux pesticides pyréthrinoïdes chez les travailleurs agricoles. Le pyréthrinoïde lambda-cyhalothrine (LCT) et le fongicide captane ont été utilisés comme pesticides sentinelles, puisqu’ils sont largement employés en culture agricole.

Dans le volet 1, les profils temporels individuels des biomarqueurs d'exposition à la lambda-cyhalothrine ont été comparés chez des opérateurs après un épisode …

Greater Number Of Weekly Stairs Climbed Is Associated With Lower Low Back Pain Prevalence Among Female But Not Male Physical Therapists, Amy H. Amabile, Sharon L. Larson, Lisa T. Hoglund, John P. Guarnieri, Maureen Mcdonald, Madeline R. Reich

Department of Physical Therapy Faculty Papers

INTRODUCTION: Certain cardiovascular health benefits of stair climbing are now widely accepted, but no prior studies have as yet been found linking the quantity of stairs climbed to low back pain (LBP) morbidity. Low back pain is a common musculoskeletal impairment, and research has begun to show an association between LBP and gluteus maximus (GM) weakness. With stair climbing being the activity which most activates GM, the aim of the present research was to assess the relationship between stair ambulation and LBP prevalence. The hypothesis of this cross-sectional study was that individuals with LBP would report a significantly lower numbers …

Greater Number Of Weekly Stairs Climbed Is Associated With Lower Low Back Pain Prevalence Among Female But Not Male Physical Therapists, Amy H. Amabile, Sharon L. Larson, Lisa T. Hoglund, John P. Guarnieri, Maureen Mcdonald, Madeline R. Reich

Department of Physical Therapy Faculty Papers

INTRODUCTION: Certain cardiovascular health benefits of stair climbing are now widely accepted, but no prior studies have as yet been found linking the quantity of stairs climbed to low back pain (LBP) morbidity. Low back pain is a common musculoskeletal impairment, and research has begun to show an association between LBP and gluteus maximus (GM) weakness. With stair climbing being the activity which most activates GM, the aim of the present research was to assess the relationship between stair ambulation and LBP prevalence. The hypothesis of this cross-sectional study was that individuals with LBP would report a significantly lower numbers …

Sparx: Elucidate Single-Cell Spatial Heterogeneity Of Drug Responses For Personalized Treatment, Ziyang Tang, Xiang Liu, Zuotian Li, Tonglin Zhang, Baijian Yang, Jing Su, Qianqian Song

Publications

Spatial cellular authors heterogeneity contributes to differential drug responses in a tumor lesion and potential therapeutic resistance. Recent emerging spatial technologies such as CosMx, MERSCOPE and Xenium delineate the spatial gene expression patterns at the single cell resolution. This provides unprecedented opportunities to identify spatially localized cellular resistance and to optimize the treatment for individual patients. In this work, we present a graph-based domain adaptation model, SpaRx, to reveal the heterogeneity of spatial cellular response to drugs. SpaRx transfers the knowledge from pharmacogenomics profiles to single-cell spatial transcriptomics data, through hybrid learning with dynamic adversarial adaption. Comprehensive benchmarking demonstrates the …

Rare Variants In Long Non-Coding Rnas Are Associated With Blood Lipid Levels In The Topmed Whole-Genome Sequencing Study, Yuxuan Wang, Margaret Sunitha Selvaraj, Xihao Li, Zilin Li, Jacob A Holdcraft, Donna K Arnett, Joshua C Bis, John Blangero, Eric Boerwinkle, Donald W Bowden, Brian E Cade, Jenna C Carlson, April P Carson, Yii-Der Ida Chen, Joanne E Curran, Paul S De Vries, Susan K Dutcher, Patrick T Ellinor, James S Floyd, Myriam Fornage, Barry I Freedman, Stacey Gabriel, Soren Germer, Richard A Gibbs, Xiuqing Guo, Jiang He, Nancy Heard-Costa, Bertha Hildalgo, Lifang Hou, Marguerite R Irvin, Roby Joehanes, Robert C Kaplan, Sharon Lr Kardia, Tanika N Kelly, Ryan Kim, Charles Kooperberg, Brian G Kral, Daniel Levy, Changwei Li, Chunyu Liu, Don Lloyd-Jone, Ruth Jf Loos, Michael C Mahaney, Lisa W Martin, Rasika A Mathias, Ryan L Minster, Braxton D Mitchell, May E Montasser, Alanna C Morrison, Joanne M Murabito, Take Naseri, Jeffrey R O'Connell, Nicholette D Palmer, Michael H Preuss, Bruce M Psaty, Laura M Raffield, Dabeeru C Rao, Susan Redline, Alexander P Reiner, Stephen S Rich, Muagututi'a Sefuiva Ruepena, Wayne H-H Sheu, Jennifer A Smith, Albert Smith, Hemant K Tiwari, Michael Y Tsai, Karine A Viaud-Martinez, Zhe Wang, Lisa R Yanek, Wei Zhao, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Jerome I Rotter, Xihong Lin, Pradeep Natarajan, Gina M Peloso

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) are known to perform important regulatory functions in lipid metabolism. Large-scale whole-genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess more associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with measurement of blood lipids and lipoproteins (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants …

Disease-Modifying Therapies And Features Linked To Treatment Response In Type 1 Diabetes Prevention: A Systematic Review, Jamie L Felton, Kurt J Griffin, Richard A Oram, Cate Speake, S Alice Long, Suna Onengut-Gumuscu, Stephen S Rich, Gabriela S F Monaco, Carmella Evans-Molina, Linda A Dimeglio, Heba M Ismail, Andrea K Steck, Dana Dabelea, Randi K Johnson, Marzhan Urazbayeva, Stephen Gitelman, John M Wentworth, Maria J Redondo, Emily K Sims, Ada/Easd Pmdi

Faculty, Staff and Students Publications

BACKGROUND: Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Prevention efforts have focused on immune modulation and supporting beta cell health before or around diagnosis; however, heterogeneity in disease progression and therapy response has limited translation to clinical practice, highlighting the need for precision medicine approaches to T1D disease modification.

METHODS: To understand the state of knowledge in this area, we performed a systematic review of randomized-controlled trials with ≥50 participants cataloged in PubMed or Embase from the past 25 years testing T1D disease-modifying therapies and/or identifying features linked to treatment response, analyzing bias using a …

Genomic Variant Benchmark: If You Cannot Measure It, You Cannot Improve It, Sina Majidian, Daniel Paiva Agustinho, Chen-Shan Chin, Fritz J Sedlazeck, Medhat Mahmoud

Faculty, Staff and Students Publications

Genomic benchmark datasets are essential to driving the field of genomics and bioinformatics. They provide a snapshot of the performances of sequencing technologies and analytical methods and highlight future challenges. However, they depend on sequencing technology, reference genome, and available benchmarking methods. Thus, creating a genomic benchmark dataset is laborious and highly challenging, often involving multiple sequencing technologies, different variant calling tools, and laborious manual curation. In this review, we discuss the available benchmark datasets and their utility. Additionally, we focus on the most recent benchmark of genes with medical relevance and challenging genomic complexity.

Global Effect Of Modifiable Risk Factors On Cardiovascular Disease And Mortality, Global Cardiovascular Risk Consortium, Christina Magnussen, Francisco M Ojeda, Darryl P Leong, Jesus Alegre-Diaz, Philippe Amouyel, Larissa Aviles-Santa, Dirk De Bacquer, Christie M Ballantyne, Antonio Bernabé-Ortiz, Martin Bobak, Hermann Brenner, Rodrigo M Carrillo-Larco, James De Lemos, Annette Dobson, Marcus Dörr, Chiara Donfrancesco, Wojciech Drygas, Robin P Dullaart, Gunnar Engström, Marco M Ferrario, Jean Ferrières, Giovanni De Gaetano, Uri Goldbourt, Clicerio Gonzalez, Guido Grassi, Allison M Hodge, Kristian Hveem, Licia Iacoviello, M Kamran Ikram, Vilma Irazola, Modou Jobe, Pekka Jousilahti, Pontiano Kaleebu, Maryam Kavousi, Frank Kee, Davood Khalili, Wolfgang Koenig, Anna Kontsevaya, Kari Kuulasmaa, Karl J Lackner, David M Leistner, Lars Lind, Allan Linneberg, Thiess Lorenz, Magnus Nakrem Lyngbakken, Reza Malekzadeh, Sofia Malyutina, Ellisiv B Mathiesen, Olle Melander, Andres Metspalu, J Jaime Miranda, Marie Moitry, Joseph Mugisha, Mahdi Nalini, Vijay Nambi, Toshiharu Ninomiya, Karen Oppermann, Eleonora D'Orsi, Andrzej Pająk, Luigi Palmieri, Demosthenes Panagiotakos, Arokiasamy Perianayagam, Annette Peters, Hossein Poustchi, Andrew M Prentice, Eva Prescott, Ulf Risérus, Veikko Salomaa, Susana Sans, Satoko Sakata, Ben Schöttker, Aletta E Schutte, Sadaf G Sepanlou, Sanjib Kumar Sharma, Jonathan E Shaw, Leon A Simons, Stefan Söderberg, Abdonas Tamosiunas, Barbara Thorand, Hugh Tunstall-Pedoe, Raphael Twerenbold, Diego Vanuzzo, Giovanni Veronesi, Julia Waibel, S Goya Wannamethee, Masafumi Watanabe, Philipp S Wild, Yao Yao, Yi Zeng, Andreas Ziegler, Stefan Blankenberg

Faculty, Staff and Students Publications

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease (CVD) and all-cause mortality. The regional and sex-specific prevalence of these modifiable risk factors and their impact on CVD and all-cause mortality have not been evaluated using individual-level data.

METHODS: The Global Cardiovascular Risk Consortium harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions. Associations between body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, smoking, and diabetes with incident CVD and all-cause mortality were examined using Cox regression analyses and stratified by geographic region, age and sex. Population-attributable fractions were estimated for 10-year incident …

In-Utero Exposure To Antibiotics And Risk Of Colorectal Cancer In A Prospective Cohort Of 18 000 Adult Offspring, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Dean P Jones, Timothy Zaki, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among younger adults and in mid-life, implicating exposures in early life as risk factors. We examined the association between in-utero exposure to antibiotics and risk of CRC in adult offspring.

METHODS: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California, with deliveries through June 1967. Diagnosed conditions and all prescribed medications were abstracted from mothers' medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received antibiotics in pregnancy, including penicillins, tetracyclines, short-acting sulfonamides …

Pls3 Missense Variants Affecting The Actin-Binding Domains Cause X-Linked Congenital Diaphragmatic Hernia And Body-Wall Defects, Florence Petit, Mauro Longoni, Julie Wells, Richard S Maser, Eric L Bogenschutz, Matthew J Dysart, Hannah T M Contreras, Frederic Frénois, Barbara R Pober, Robin D Clark, Philip F Giampietro, Hilger H Ropers, Hao Hu, Maria Loscertales, Richard Wagner, Xingbin Ai, Harrison Brand, Anne-Sophie Jourdain, Marie-Ange Delrue, Brigitte Gilbert-Dussardier, Louise Devisme, Boris Keren, David J Mcculley, Lu Qiao, Rebecca Hernan, Julia Wynn, Tiana M Scott, Daniel G Calame, Zeynep Coban-Akdemir, Patricia Hernandez, Andres Hernandez-Garcia, Hagith Yonath, James R Lupski, Yufeng Shen, Wendy K Chung, Daryl A Scott, Carol J Bult, Patricia K Donahoe, Frances A High

Faculty, Staff and Student Publications

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical …

An Intrinsically Disordered Region Controlling Condensation Of A Circadian Clock Component And Rhythmic Transcription In The Liver, Kun Zhu, Isaac J Celwyn, Dongyin Guan, Yang Xiao, Xiang Wang, Wenxiang Hu, Chunjie Jiang, Lan Cheng, Rafael Casellas, Mitchell A Lazar

Faculty, Staff and Students Publications

Circadian gene transcription is fundamental to metabolic physiology. Here we report that the nuclear receptor REV-ERBα, a repressive component of the molecular clock, forms circadian condensates in the nuclei of mouse liver. These condensates are dictated by an intrinsically disordered region (IDR) located in the protein's hinge region which specifically concentrates nuclear receptor corepressor 1 (NCOR1) at the genome. IDR deletion diminishes the recruitment of NCOR1 and disrupts rhythmic gene transcription in vivo. REV-ERBα condensates are located at high-order transcriptional repressive hubs in the liver genome that are highly correlated with circadian gene repression. Deletion of the IDR disrupts transcriptional …

Müllerian-Type Clear Cell Carcinoma Of Donor Origin In A Male Patient With A Kidney Transplant: Ascertained By Molecular Testing, J Bryan Iorgulescu, Leah K Shaw, Asif Rashid, Priya Rao, Sreedhar Mandayam, Keyur P Patel, Kathleen M Schmeler, Richard K Yang, Pavlos Msaouel

Faculty, Staff and Student Publications

Clear cell carcinomas of Müllerian origin have a strong female predominance and only extremely rarely will arise within the kidney, presumably due to ectopic Müllerian embryogenesis. Herein, we report a unique case of metastatic Müllerian type clear cell carcinoma in a 37-year-old patient who had previously received a transplanted kidney from his father at age 11 (due to severe bilateral vesicoureteral reflux) and remained on chronic immunosuppression. The tumor was highly aggressive and demonstrated somatic mutations in NF2 and SETD2. Imaging of the transplanted kidney did not reveal any clear evidence of malignancy. However, targeted multigene sequencing and short tandem …

Utility And Precision Evidence Of Technology In The Treatment Of Type 1 Diabetes: A Systematic Review, Laura M Jacobsen, Jennifer L Sherr, Elizabeth Considine, Angela Chen, Sarah M Peeling, Margo Hulsmans, Sara Charleer, Marzhan Urazbayeva, Mustafa Tosur, Selma Alamarie, Maria J Redondo, Korey K Hood, Peter A Gottlieb, Pieter Gillard, Jessie J Wong, Irl B Hirsch, Richard E Pratley, Lori M Laffel, Chantal Mathieu

Faculty, Staff and Students Publications

BACKGROUND: The greatest change in the treatment of people living with type 1 diabetes in the last decade has been the explosion of technology assisting in all aspects of diabetes therapy, from glucose monitoring to insulin delivery and decision making. As such, the aim of our systematic review was to assess the utility of these technologies as well as identify any precision medicine-directed findings to personalize care.

METHODS: Screening of 835 peer-reviewed articles was followed by systematic review of 70 of them (focusing on randomized trials and extension studies with ≥50 participants from the past 10 years).

RESULTS: We find …

Immune Cell Deconvolution Reveals Possible Association Of Γδ T Cells With Poor Survival In Head And Neck Squamous Cell Carcinoma, Anuraag S Parikh, Yize Li, Angela Mazul, Wade Thorstad, Jason Rich, Randal C Paniello, Ryan S Jackson, Patrik Pipkorn, Paul Zolkind, Zongtai Qi, Douglas Adkins, Li Ding, Sidharth V Puram, Et Al.

2020-Current year OA Pubs

(1) Background: The role of rare immune cell subtypes in many solid tumors, chief among them head and neck squamous cell carcinoma (HNSCC), has not been well defined. The objective of this study was to assess the association between proportions of common and rare immune cell subtypes and survival outcomes in HNSCC. (2) Methods: In this cohort study, we utilized a deconvolution approach based on the CIBERSORT algorithm and the LM22 signature matrix to infer proportions of immune cell subtypes from 517 patients with untreated HPV-negative HNSCC from The Cancer Genome Atlas. We performed univariate and multivariable survival analysis, integrating …

Yeast Rad52 Is A Homodecamer And Possesses Brca2-Like Bipartite Rad51 Binding Modes, Jaigeeth Deveryshetty, Rahul Chadda, Jenna R Mattice, Simrithaa Karunakaran, Michael J Rau, Katherine Basore, Nilisha Pokhrel, Noah Englander, James A J Fitzpatrick, Brian Bothner, Edwin Antony

2020-Current year OA Pubs

Homologous recombination (HR) is an essential double-stranded DNA break repair pathway. In HR, Rad52 facilitates the formation of Rad51 nucleoprotein filaments on RPA-coated ssDNA. Here, we decipher how Rad52 functions using single-particle cryo-electron microscopy and biophysical approaches. We report that Rad52 is a homodecameric ring and each subunit possesses an ordered N-terminal and disordered C-terminal half. An intrinsic structural asymmetry is observed where a few of the C-terminal halves interact with the ordered ring. We describe two conserved charged patches in the C-terminal half that harbor Rad51 and RPA interacting motifs. Interactions between these patches regulate ssDNA binding. Surprisingly, Rad51 …

Sars-Cov-2: Tale Of A Microscopic Murderer, Josiah P. Garner

Quest

Independent Study

Research in progress for BIOL1406: Biology for Science Majors I

Faculty Mentor: Amina Tassa, Ph.D.

I am delighted to introduce Josiah Garner’s “SARS-CoV-2: Tale of a Microscopic Murderer.” This independent study assignment explores the impact of a novel, deadly, and worldwide virus. The assignment also examines the fast development of vaccines to control the spread and reduce the symptoms of the virus.

Josiah’s paper focuses on the early history of the emergence of COVID-19, the world response, and vaccine development. He demonstrates critical thinking skills and effectively utilizes various research methods to obtain and communicate his information. Josiah …

Cognitive Decrements In 1991 Gulf War Veterans: Associations With Gulf War Illness And Neurotoxicant Exposures In The Boston Biorepository, Recruitment, And Integrative Network (Bbrain) Cohorts., D Keating, M Krengel, J Dugas, R Toomey, L Chao, L Steele, Lloyd P Janulewicz, T Heeren, E Quinn, N Klimas, K Sullivan

HPD Articles

BACKGROUND: During deployment, veterans of the 1991 Gulf War (GW) were exposed to multiple war-related toxicants. Roughly a third of these veterans continue to exhibit neurotoxicant induced symptoms of Gulf War Illness (GWI), a multi-faceted condition that includes fatigue, pain and cognitive decrements. When studied empirically, both deployed veterans with exposures and those who meet the criteria for GWI are more likely to show deficits in the area of neuropsychological functioning. Although studies have shown cognitive impairments in small sample sizes, it is necessary to revisit these findings with larger samples and newer cohorts to see if other areas of …

Validation Of Automated Data Abstraction For Sccm Discovery Virus Covid-19 Registry: Practical Ehr Export Pathways (Virus-Peep), Diana J. Valencia Morales, Vikas Bansal, Smith F. Heavner, Janna C. Castro, Mayank Sharma, Aysun Tekin, Marija Bogojevic, Simon Zec, Nikhil Sharma, Rodrigo Cartin-Ceba, Rahul S. Nanchal, Devang K. Sanghavi, Abigail T. La Nou, Syed A. Khan, Katherine A. Belden, Jen-Ting Chen, Roman R. Melamed, Imran A. Sayed, Ronald A. Reilkoff, Vitaly Herasevich, Juan Pablo Domecq Garces, Allan J. Walkey, Karen Boman, Vishakha K. Kumar, Rahul Kashyap

Division of Infectious Diseases and Environmental Medicine Faculty Papers

BACKGROUND: The gold standard for gathering data from electronic health records (EHR) has been manual data extraction; however, this requires vast resources and personnel. Automation of this process reduces resource burdens and expands research opportunities.

OBJECTIVE: This study aimed to determine the feasibility and reliability of automated data extraction in a large registry of adult COVID-19 patients.

MATERIALS AND METHODS: This observational study included data from sites participating in the SCCM Discovery VIRUS COVID-19 registry. Important demographic, comorbidity, and outcome variables were chosen for manual and automated extraction for the feasibility dataset. We quantified the degree of agreement with Cohen's …

Feasibility And Outcomes Of Supplemental Gait Training By Robotic And Conventional Means In Acute Stroke Rehabilitation, Mukul Talaty, Alberto Esquenazi

Moss-Magee Rehabilitation Papers

INTRODUCTION: Practicality of implementation and dosing of supplemental gait training in an acute stroke inpatient rehabilitation setting are not well studied but can have positive impact on outcomes.

OBJECTIVES: To determine the feasibility of early, intense supplemental gait training in inpatient stroke rehabilitation, compare functional outcomes and the specific mode of delivery.

DESIGN AND SETTING: Assessor blinded, randomized controlled trial in a tertiary Inpatient Rehabilitation Facility.

PARTICIPANTS: Thirty acute post-stroke patients with unilateral hemiparesis (≥ 18 years of age with a lower limb MAS ≤ 3).

INTERVENTION: Lokomat® or conventional gait training (CGT) in addition to standard mandated therapy time. …

One-Step Simultaneous Liquid Phase Exfoliation-Induced Chirality In Graphene And Their Chirality-Mediated Microrna Delivery, Pranav, Eswara N. H. K. Ghali, Neeraj Chauhan, Rahul Tiwari, Subhash Chauhan, Murali M. Yallapu

School of Medicine Publications

Graphene (G) has established itself as an exciting prospect for a broad range of applications owing to its remarkable properties. Recent innovations in chiral nanosystems have led to sensors, drug delivery, catalysis, etc. owing to the stereospecific interactions between various nanosystems and enantiomers. As the molecular structure of G itself is achiral introducing chirality in G by simple attachment of a functional group (a chiral ligand) on the G nanosheet may result in more diverse applications. Herein, we demonstrate direct liquid phase exfoliation and chiral induction in G nanosheets abbreviated as L-graphene and D-graphene in the presence of chiral L-tyrosine …

Global Impact Of Proteoglycan Science On Human Diseases, Christopher Xie, Liliana Schaefer, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In this comprehensive review, we will dissect the impact of research on proteoglycans focusing on recent developments involved in their synthesis, degradation, and interactions, while critically assessing their usefulness in various biological processes. The emerging roles of proteoglycans in global infections, specifically the SARS-CoV-2 pandemic, and their rising functions in regenerative medicine and biomaterial science have significantly affected our current view of proteoglycans and related compounds. The roles of proteoglycans in cancer biology and their potential use as a next-generation protein-based adjuvant therapy to combat cancer is also emerging as a constructive and potentially beneficial therapeutic strategy. We will discuss …

Excitatory Neuron-Specific Suppression Of The Integrated Stress Response Contributes To Autism-Related Phenotypes In Fragile X Syndrome, Mehdi Hooshmandi, Vijendra Sharma, Carolina Thörn Perez, Rapita Sood, Konstanze Krimbacher, Calvin Wong, Kevin C Lister, Alba Ureña Guzmán, Trevor D Bartley, Cecilia Rocha, Gilles Maussion, Emma Nadler, Patricia Margarita Roque, Ilse Gantois, Jelena Popic, Maxime Lévesque, Randal J Kaufman, Massimo Avoli, Elisenda Sanz, Karim Nader, Randi Jenssen Hagerman, Thomas M Durcan, Mauro Costa-Mattioli, Masha Prager-Khoutorsky, Jean-Claude Lacaille, Veronica Martinez-Cerdeno, Jay R Gibson, Kimberly M Huber, Nahum Sonenberg, Christos G Gkogkas, Arkady Khoutorsky

Faculty, Staff and Students Publications

Dysregulation of protein synthesis is one of the key mechanisms underlying autism spectrum disorder (ASD). However, the role of a major pathway controlling protein synthesis, the integrated stress response (ISR), in ASD remains poorly understood. Here, we demonstrate that the main arm of the ISR, eIF2α phosphorylation (p-eIF2α), is suppressed in excitatory but not inhibitory neurons in a mouse model of fragile X syndrome (FXS; Fmr1−/y). We further show that the decrease in p-eIF2α is mediated via activation of the mTORC1. Genetic reduction of p-eIF2α only in excitatory neurons is sufficient to increase general protein synthesis and cause autism-like …

Bacillus Calmette-Guérin Vaccination As Defense Against Sars-Cov-2 (Badas): A Randomized Controlled Trial To Protect Healthcare Workers In The Usa By Enhanced Trained Immune Responses, Andrew R Dinardo, Moshe Arditi, Ashish M Kamat, Kent J Koster, Santiago Carrero, Tomoki Nishiguchi, Maxim Lebedev, Aaron B Benjamin, Pablo Avalos, Marisa Lozano, Madeleine G Moule, Brittany Mccune, Baysia Herron, Malik Ladki, Daanish Sheikh, Matthew Spears, Ivan A Herrejon, Courtney Dodge, Sathish Kumar, Robert W Hutchison, Theresa U Ofili, Lynne A Opperman, Jessica A Bernard, Seth P Lerner, George Udeani, Gabriel Neal, Mihai G Netea, Jeffrey D Cirillo

Faculty, Staff and Students Publications

BACKGROUND: A large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19. We hypothesize that BCG vaccination can reduce SARS-CoV-2 infection and disease severity.

METHODS: This will be a placebo-controlled adaptive multi-center randomized controlled trial. A total of 1800 individuals considered to be at …

The Use Of Electronic Health Record Data To Identify Variation In Referral, Consent, And Engagement In A Pediatric Intervention For Overweight And Obesity: A Cross-Sectional Study, Joshua S Yudkin, Marlyn A Allicock, Folefac D Atem, Carol A Galeener, Sarah E Messiah, Sarah E Barlow

Faculty, Staff and Student Publications

Clinical weight management programs face low participation. The authors assessed whether using electronic health record (EHR) data can identify variation in referral, consent, and engagement in a pediatric overweight and obesity (OW/OB) intervention. Using Epic EHR data collected between August 2020 and April 2021, sociodemographic and clinical diagnostic data (ie, International Classification of Disease [ICD] codes from visit and problem list [PL]) were analyzed to determine their association with referral, consent, and engagement in an OW/OB intervention. Bivariate analyses and multivariable logistic regression modeling were performed, with Bayesian inclusion criterion score used for model selection. Compared with the 581 eligible …

Disrupted Stiffness Ratio Alters Nuclear Mechanosensing, Brandon K Walther, Adam P Sears, Anahita Mojiri, Reza Avazmohammadi, Jianhua Gu, Olga V Chumakova, Navaneeth Krishna Rajeeva Pandian, Abishai Dominic, Jean-Louis Martiel, Saami K Yazdani, John P Cooke, Jacques Ohayon, Roderic I Pettigrew

Faculty, Staff and Student Publications

The ability of endothelial cells to sense and respond to dynamic changes in blood flow is critical for vascular homeostasis and cardiovascular health. The mechanical and geometric properties of the nuclear and cytoplasmic compartments affect mechanotransduction. We hypothesized that alterations to these parameters have resulting mechanosensory consequences. Using atomic force microscopy and mathematical modeling, we assessed how the nuclear and cytoplasmic compartment stiffnesses modulate shear stress transfer to the nucleus within aging endothelial cells. Our computational studies revealed that the critical parameter controlling shear transfer is not the individual mechanics of these compartments, but the stiffness ratio between them. Replicatively …