Medicine and Health Sciences Commons^™

Sugar Functionalized Collagen Material For Local Modulation Of Innate Immunity, John Otto Martinez, Silvia Minardi, Laura Pandolfi, Xing Wang, Ennio Tasciotti, Kavindra V Singh, Cesar A Arias, Bruna Corradetti

Faculty, Staff and Students Publications

Small alterations during the early stages of the innate immune response to an implant can drive large changes in adaptive immunity. Biomaterials for regenerative purposes can be engineered to modulate this immune response in beneficial ways. This study presents an innovative patch designed and functionalized to target the innate immunity at the implant site. Mannose moieties are incorporated into collagen patches, resulting in a technology called Local Immunotuning Patch (LIP), designed to directly interact with antigen presenting cells through their mannose receptor. In vitro, LIP shows anti-inflammatory effects on bone marrow-derived macrophages and inhibitory properties even on methicillin-resistant bacterial strains. …

The Splicing Factor Kinase Srpk1 Is A Therapeutic Target For Peripheral Vascular Disease, Amira Zawia, Federica Riu, Yizhuo Gao, Jyoti Agrawal, Amy P Lynch, Maria J C Machado, Tom Hawtrey, Ryosuke Kikuchi, Kathryn R Green, Lydia Teboul, Claire Allen, Zoe Blackley, Keerthana Rajaji, Jennifer Batson, Steven J Harper, Sebastian Oltean, Winfried Amoaku, Andrew V Benest, Jonathan C Morris, Bruce Braithwaite, David O Bates

Faculty, Staff and Students Publications

In peripheral arterial disease (PAD), antiangiogenic VEGF-A165b isoform overexpression in monocytes contributes to impaired collateralization. Serine-arginine protein-kinase-1 (SRPK1) regulates VEGF splicing. To determine whether SRPK1 controlled monocytic VEGF, impairing collateralization, we investigated SRPK1 inhibition and monocyte-specific knockout in mouse models of and in human monocytes from PAD. VEGF-A165b activity was measured by coculture of monocytes from patients with PAD with endothelial cells with SRPK1 inhibition. Mice with impaired revascularization due to soluble-frizzled-related-protein-5 knockout (Sfrp5-/-), monocyte-specific Wnt5a gain-of-function (LysM-Wnt5aGOF), or obese mice on a high-fat high-sucrose (HF/HS) diet were subjected to femoral artery ligation and treated with …

The Influence Of Ultra-Wide Field Fluorescein Angiography On The Diagnosis And Management Of Diabetic Retinopathy, Joelle A Hallak, Rawan Allozi, Aziz A Khanifar, Thanos D Papakostas, Christina Y Weng, Ronald C Gentile, J Peter Campbell, Jessica G Lee, Gennady Landa, Felix Y Chau, William F Mieler, Meenakashi Gupta, Amani A Fawzi, Judy E Kim, Jennifer I Lim, Robison Vernon Paul Chan

Faculty, Staff and Students Publications

Purpose: To study the influence of ultra-widefield fluorescein angiography (FA) on the diagnosis and management of diabetic retinopathy (DR).

Methods: Ten experts in DR completed an online survey in which they were asked to diagnose and manage DR cases using different imaging modalities. Experts independently reviewed 20 cases of DR and provided a diagnosis and management plan for each case, first based on ultra-widefield color-free and red-free images alone and again with the corresponding ultra-widefield FA images. Experts were polled on their diagnostic confidence, use of FA in clinical practice, and opinions on the value of ultra-widefield FA. Based on …

Minimum Core Data Elements For Evaluation Of Thoracic Aortic Disease, Kathryn W Holmes, Maya Brown-Zimmerman, John Elefteriades, Catherine M Otto, Nicholas S Burris, Carlos Alberto Campello Jorge, Scott C Deroo, Maral Ouzounian, Matthew D Solomon, Jay D Humphrey, Bart Loeys, Shaine A Morris, Guillaume Jondeau, Scott A Lemaire, Sherene Shalhub, Siddharth K Prakash

Faculty, Staff and Students Publications

Thoracic aortic aneurysms predisposing to aortic dissections are rare but potentially deadly conditions that can be inherited in families. Understanding the natural history and genetic causes of thoracic aortic disease (TAD) requires international collaboration. The aim of this project is to provide core data elements that can be assessed directly and summarized efficiently in research records while developing standards to harmonize data across registries and clinical trials. Ten contemporary TAD registries were analyzed to identify significant gaps in the amount and types of data that are needed for accurate, verifiable, and reproducible studies. The set of data elements recommended by …

Incidence, Predictors, And Indications Of Permanent Pacemaker Implantation Following Orthotopic Heart Transplantation: A Single-Center Experience, Edward Graviss, Duc T Nguyen, Paul A Schurmann, Rayan Yousefzai

Faculty, Staff and Students Publications

In the modern era of orthotopic heart transplantation (OHT) with bicaval anastomosis, there is a paucity of data on permanent pacemaker implantation (PPI) in this population. This is a retrospective study describing the incidence, indication, and predictors in patients who underwent PPI after OHT. Using the transplant database from our institution between January 2016 and December 2022, 370 patients who had de-novo OHT were identified. The incidence of PPI post-OHT was 8.1% (n = 30 patients). The average time from OHT to PPI was 30.5 days. The most common indication for PPI was sinus node dysfunction, accounting for 83% …

Outcomes Of Suprapatellar Intramedullary Nail Fixation Of Tibial Shaft Fractures In Skeletally Immature Patients, David D Spence, Jonathan K Rowland, Derek M Kelly, Benjamin W Sheffer

Faculty, Staff and Students Publications

Background: Tibial shaft fractures in children require individualized treatment approaches, including elastic nails, plates and screws, intramedullary rigid nails (IMN), and external fixators, with selection based on fracture characteristics and patient factors. IMN risks damaging the physis, but can provide enhanced stability and immediate weight bearing. While both infrapatellar and suprapatellar approaches exist for IMN placement, studies in adults have demonstrated that the suprapatellar approach offers higher patient satisfaction, less anterior knee pain, and lower radiation exposure. However, there is a lack of data on IMN for pediatric tibial fractures.

Methods: This single-center, retrospective cohort study analyzed patients aged 11-16 …

Mx1-Labeled Pulp Progenitor Cells Are The Main Contributors Of Odontoblast And Dentin Regeneration In Murine Molars, Jea Giezl Solidum, Dongsu Park

Faculty, Staff and Students Publications

Regeneration of dentin and odontoblasts from dental pulp progenitor cells is essential for the maintenance of permanent tooth. However, the in vivo identity of endogenous pulp progenitor cells and how they contribute to reparative dentinogenesis remain elusive. Here we show that comparative single-cell analysis of pulp cells before and after molar eruption reveal that endogenous pulp progenitor cells are enriched in coronal papilla-like cells with Mx1-Cre and Cxcl12–GFP expression. Further, lineage tracing and fluorescence-activated cell sorting analysis indicated that Mx1-labeled (Mx1+) pulp cells include long-term repopulating progenitor cells with higher expression of stem cell markers. Notably, …

Incidence Of And Risk Factors For Hospital-Acquired Bleeding In People With Cancer: A Systematic Review, Laura Haines, Ang Li, Neil A Zakai

Faculty, Staff and Students Publications

Background: Hospital-acquired (HA) bleeding (bleeding occurring during hospitalization) in cancer patients is poorly characterized, potentially increasing morbidity and mortality due to under- or overprescription of low-dose anticoagulation for venous thromboembolism prevention.

Objectives: To perform a systematic review and meta-analysis (as appropriate) to identify the incidence of and risk factors for HA bleeding in people with cancer.

Methods: A systematic English-language search was conducted using Ovid MEDLINE, Ovid EMBASE, Google Scholar, and Cochrane Library. Keywords and controlled vocabulary related to bleeding risk in hospitalized cancer patients were iteratively refined. Studies assessing HA bleeding as a primary or coprimary endpoint were included, …

A Simple, Interpretable Machine Learning Model Based On Clinical Factors Accurately Predicts Incident Dysplasia Or Malignancy In Barrett's Esophagus, Aaron P Thrift, Theresa Nguyen-Wenker, Hashem B El-Serag

Faculty, Staff and Students Publications

Purpose: Identifying patients likely to develop dysplasia or malignancy is critical for effective surveillance in patients with Barrett's Esophagus (BE). However, current predictive models are limited. We evaluated the performance of machine learning (ML) models in predicting incident dysplasia or malignancy in a cohort of veteran patients with BE.

Methods: We analyzed data from 598 patients newly diagnosed with non-dysplastic BE (NDBE), BE indefinite for dysplasia (BE-IND), and BE with non-persistent low-grade dysplasia (LGD) at the Michael DeBakey Veterans Affairs Medical Center from November 1990 to January 2019 with follow-up through January 2024. Progressors were patients who developed persistent LGD, …

Linking Chronic Kidney Disease To Incident Heart Failure And Adverse Cardiac Remodeling Through The Plasma Proteome: The Aric Study, Yue Ren, Kunihiro Matsushita, Ryan T Demmer, Ruth F Dubin, Rajat Deo, Peter Ganz, Christie M Ballantyne, Ron C Hoogeveen, Bing Yu, Amil M Shah

Faculty, Staff and Student Publications

Background: Investigation of circulating plasma proteins may reveal insights into molecular pathways that contribute to the development of heart failure (HF) among people with chronic kidney disease.

Objectives: The authors aimed to identify circulating kidney function-related plasma proteins that are associated with the risk of incident HF.

Methods: The authors studied participants of the ongoing longitudinal ARIC (Atherosclerosis Risk In Communities) study. Relative plasma concentrations of 4,697 unique proteins were measured with the use of an aptamer assay (Somalogic). Each protein was tested for associations with estimated glomerular filtration rate (eGFR), log-transformed urine albumin-to-creatinine ratio (UACR), and incident HF by …

Associations Between Social Support, Social Control, And Stage Of Change With Self-Reported And Objectively Assessed Physical Activity In Adult Latino Dyads, Deanna M Hoelscher, Larkin L Strong

Faculty, Staff and Student Publications

Health behaviors such as physical activity (PA) are socially influenced, such that individuals from shared social networks or living environments may exhibit similar habits. This cross-sectional study examined associations of social support, social control, and family member stage of change with moderate-to-vigorous self-reported and objective PA in dyads of adult Hispanic family members. We used the Godin Leisure-Time Physical Activity Questionnaire to assess self-reported PA and accelerometry for objective PA. Validated scales assessed social support, social control, and stage of change. We performed multivariable multilevel analysis using generalized estimating equations (GEE) to account for within-dyad correlations. We conducted multivariable negative …

Racial Disparities In The Receipt Of Therapies For Cancer, Hypertension, And Diabetes, And In Mortality In A Large Population-Based Cohort Of Older Men With Prostate Cancer

Faculty, Staff and Student Publications

Background: Racial disparities in treatment and mortality were widely studied among prostate cancer patients; however, few studies considered the prevalence of hypertension and diabetes and their treatment status.

Objectives: To determine whether there are racial discrepancies in the use of anti-cancer, antihypertensive, and antidiabetic drugs in a cohort of long-term survivors of prostate cancer diagnosed in 2007-2015; and to examine racial disparities in mortality after adjustments for their differences in those treatments.

Methods: We used the SEER (Surveillance, Epidemiology, and End Results)-Medicare linked database and included records for patients with prostate cancer at age 65 years or older diagnosed from …

Accelerometer-Measured Chronoactivity And Type 2 Diabetes Risk: A Prospective Study In Uk Biobank Participants, Qian Xiao

Faculty, Staff and Student Publications

Objective: We assessed whether timing of physical activity, independent from the total activity amount, - which we refer to as chronoactivity - is associated with type 2 diabetes (T2D) risk.

Methods: We included UK Biobank participants with valid accelerometry data (UK, exposure measurement: 2013-2015, follow-up till November 2023) and without diabetes mellitus at baseline (N = 89,439; mean age: 61.7 [SD:7.9] years). Relative hourly physical activity was calculated by dividing the average hourly clock time physical activity by the average hourly physical activity in a week. Participants were categorized into different chronoactivity clusters using k-means cluster analysis on relative hourly …

The Synaptic Architecture Of Layer 5 Thick Tufted Excitatory Neurons In Mouse Visual Cortex, Leila Elabbady, Alex Mallen, Andi Bergeson, Derrick Brittain, Joann Buchanan, Daniel J Bumbarger, Rachel Dalley, Clare Gamlin, Emily Joyce, Daniel Kapner, Sam Kinn, Gayathri Mahalingam, Sharmishtaa Seshamani, Shelby Suckow, Marc Takeno, Russel Torres, Wenjing Yin, J Alexander Bae, Manuel A Castro, Sven Dorkenwald, Akhilesh Halageri, Zhen Jia, Chris Jordan, Nico Kemnitz, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Eric Mitchell, Shanka Subhra Mondal, Shang Mu, Barak Nehoran, Sergiy Popovych, William Silversmith, Nicholas L Turner, Szi-Chieh Yu, William Wong, Jingpeng Wu, Brendan Celii, Luke Campagnola, Stephanie C Seeman, Tim Jarsky, Naixin Ren, Anton Arkhipov, Jacob Reimer, H Sebastian Seung, R Clay Reid, Forrest Collman, Nuno Maçarico Da Costa

Faculty, Staff and Students Publications

Despite significant progress in characterizing neocortical cell types, a complete understanding of the synaptic connections of individual excitatory cells remains elusive. This study investigates the connectivity of mouse visual cortex thick tufted layer 5 pyramidal cells, also known as extratelencephalic neurons (L5-ETns), using a 1 mm3 publicly available electron microscopy dataset. The analysis reveals that, in their immediate vicinity, L5-ETns primarily establish connections with a group of inhibitory cell types, which, in turn, specifically target the L5-ETns back. The most common excitatory targets of L5-ETns are layer 5 intertelencephalic neurons (L5-ITns) and layer 6 (L6) pyramidal cells, whereas synapses with …

First Assembly Of A Draft Genome Of The Critically Endangered Northern Muriqui ( Brachyteles Hypoxanthus , Primates, Atelidae) Including Non‐Invasive Genotyping Strategies For The Species, Tomas Marques-Bonet, Lukas Kuderna, Kyle Farh, Jeffrey Rogers, Mariane Da Cruz Kaizer, Jean Philippe Boubli, Fabiano Rodrigues De Melo, Rhewter Nunes, Mariana Pires De Campos Telles

Faculty, Staff and Students Publications

Genomic resources, such as draft genomes, are vital for biodiversity monitoring and conservation. For endangered species, they enable the development of tools like organellar genomes and molecular markers, which are crucial for population genetics. Advances in sequencing technologies now allow high‐throughput genotyping with detailed amplicon sequences, enhancing genetic variation studies. The northern muriqui ( Brachyteles hypoxanthus ), a critically endangered primate endemic to Brazil's Atlantic Forest, currently lacks both nuclear and mitochondrial genome data and species‐specific microsatellite markers for population genetic studies. We assembled a 2.52 Gb draft genome for B. hypoxanthus with 202,243 contigs (N50 = 29,134 bp), and …

Outcomes Of Fenestrated-Branched Endovascular Aortic Repair Of Thoracoabdominal Aortic Aneurysms In Patients With Heritable Thoracic Aortic Diseases, Thanila A Macedo, Bernardo C Mendes, Steven Maximus, Ying Huang, Felipe Nasser, Gustavo S Oderich

Faculty, Staff and Students Publications

Objective: Open surgical repair is the first-line treatment for patients with complex aortic aneurysms and heritable thoracic aortic diseases (HTADs). Fenestrated-branched endovascular aortic repair (FB-EVAR) has been used selectively in higher-risk patients. This study assessed early- and midterm outcomes of FB-EVAR for complex aortic aneurysms in patients with HTADs.

Methods: We reviewed clinical data, imaging, and outcomes of consecutive patients treated by FB-EVAR for complex abdominal and thoracoabdominal aneurysms from April 2007 to June 2024. Patients with confirmed Marfan syndrome, Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome, or ACTA2 mutation were included. End points included 30-day mortality and major adverse events, cumulative …

High Risk Of Drug-Resistant Tuberculosis In Igra-Negative Contacts: Should Preventive Treatment Be Considered?, Jürgen Welling, Anna Maria Mandalakas, Vinicius Fava, Erwin Schurr, Christoph Lange

Faculty, Staff and Students Publications

Purpose: Deciding whether to provide preventive treatment to contacts of individuals with multidrug-resistant (MDR) tuberculosis is complex.

Methods: We present the diagnostic pathways, clinical course and outcome of tuberculosis treatment in eight siblings from a single family. Tuberculosis disease was diagnosed by Mycobacterium tuberculosis culture and molecular detection of M. tuberculosis-specific DNA from bronchopulmonary specimens using GeneXpert® MTB/RIF. M. tuberculosis infection was diagnosed by an interferon-gamma release assay (IGRA; QuantiFERON®-TB Gold Plus). Whole exome sequencing for genetic predisposition to mycobacterial infection was performed in one patient.

Results: Six of eight siblings aged 16-20 years from a migrant family of Somali …

Deterioration And Manifestation Of Cerebral Fat Embolism Triggered By Bone Reaming During Femur Fracture Surgery: A Case Report, Yohei Fujimoto, Masahiro Miyashita, Tadashi Matsuura, Takashi Mori

Faculty, Staff and Students Publications

The role of intramedullary reaming in triggering fat embolism syndrome (FES) remains debated. This case, where FES developed during reaming, provides further evidence supporting reaming as a potential risk factor for FES.

Privacy In Perspective: Research Participants’ Priorities And Concerns Related To Sharing Data Generated In Human Neuroscience Studies, Mary A Majumder, Kathryn Maxson Jones, Whitney Bash Brooks, Sameer A Sheth, Amy L Mcguire

Faculty, Staff and Students Publications

The societal benefits from sharing and reusing data collected in human neuroscience studies are widely appreciated. However, there are persistent barriers to data sharing as well as privacy concerns related to unauthorized access, misuse, and reidentification of deidentified data. Thus far, few studies have been conducted with neuroscience research participants to understand their data sharing priorities and concerns. We conducted a survey utilizing an experimental design with N=52 participants in neuroscience studies funded by the U.S. National Institutes of Health representing diverse neurotechnologies and health conditions. Respondents prioritized sharing practices that maximize reuse of data to benefit patients and reduce …

Improving Pediatric Heart Failure Outcomes Through Collaboration And Innovation: The Current Status Of The Advanced Cardiac Therapies Improving Outcomes Network (Action), Jenna M Murray, Matthew J O'Connor, Christina J Vanderpluym, David N Rosenthal, Lauren Smyth, Angela Lorts

Faculty, Staff and Students Publications

The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) was founded in 2017 as a learning health care system to bring together all stakeholders with the aim of improving outcomes for pediatric and congenital heart disease patients with heart failure. From an initial focus on the ventricular assist device (VAD) population, work in the network has expanded to encompass the scope of heart failure in these patients. Through the collection and use of real-world data, the field has gained greater understanding of best practices in care of these patients, as well as improved access to devices with pediatric labeling of devices …

The Psychiatric Genomics Consortium: Discoveries And Directions, Ole A Andreassen, Elizabeth G Atkinson, Karmel W Choi, Aiden Corvin, Helena L Davies, Lea K Davis, Anna R Docherty, Howard J Edenberg, Barbara Franke, Joel Gelernter, Paola Giusti-Rodríguez, John M Hettema, Jens Hjerling-Leffler, Hailiang Huang, Emma C Johnson, Cathryn M Lewis, Yi Lu, Mary-Ellen Lynall, Joanna Martin, Andrew M Mcintosh, Janitza L Montalvo-Ortiz, Niamh Mullins, Caroline M Nievergelt, Kevin S O'Connell, Michael C O'Donovan, Adeniran Okewole, Roseann E Peterson, Danielle Posthuma, Jonathan Sebat, Jordan W Smoller, Reeteka Sud, Biju Viswanath, James T R Walters, Hyejung Won, Naomi R Wray, Patrick F Sullivan, Coordinating Committee Of The Psychiatric Genomics Consortium

Faculty, Staff and Students Publications

The Psychiatric Genomics Consortium (PGC) has fueled discoveries of common and rare genetic variation contributing to liability to many psychiatric and neurodevelopmental conditions. This narrative review reflects on major findings from the past half decade of research by this international group of investigators in five priority areas: discovery of common variants using GWAS; rare variation and its interplay with polygenic risk; leveraging genetics to go beyond diagnostic boundaries; ascribing functional attributes to genomic discoveries; and developing and implementing processes for data sharing, outreach to various communities, and training. The insights gained in these domains frame the agenda for the next …

A Clinic-Based Healthcare Transition Preparation Program For Adolescents And Young Adults With Type 1 Diabetes: Study Protocol For The Shift Randomized Clinical Trial, Edmond P Wickham, Marisa E Hilliard, Laura M Thornton, Melanie K Bean

Faculty, Staff and Students Publications

Background: A striking 83 % of adolescents and young adults (AYA) with type 1 diabetes (T1D) have glycemic outcomes outside the target range, placing them at risk for acute and chronic complications. Identification of evidence-based strategies to enhance T1D management in AYAs, prior to the transition from pediatric to adult healthcare, is needed to optimize AYA health and adequately prepare them for independence. We present the design of Supporting Health Improvement for Transition in T1D (SHIFT), a randomized clinical trial of a clinic-based transition preparation intervention for AYAs with T1D.

Methods: Participants will be 50 AYAs with T1D (age 16-22 …

Differences In Wait-List Mortality: Temporary Vs Durable Circulatory Support Devices, Katelyn Ingram, Sapna Legha, Rayan Yousefzai, Ju Kim, Imad Hussain, Cindy M Martin, Janardhana Gorthi, Adeel Ahsan Syed, Nadia Fida, Arvind Bhimaraj, Edward A Graviss, Ashrith Guha

Faculty, Staff and Students Publications

Background: In 2018, changes in the United Network for Organ Sharing (UNOS) allocation system led to a shift in practices, making durable left ventricular assist devices less desirable as a bridge to transplantation compared to temporary mechanical circulatory support. This study compares the composite outcome of waitlist mortality and delisting incidence at 1 year between these two support types.

Methods: All actively listed adult patients on mechanical circulatory support listed for heart transplantation under the current UNOS system from October 2018 to October 2021 were included, excluding those with right ventricular devices, biventricular devices, total artificial hearts, and extracorporeal membrane …

Implementation Outcomes Of A Patient Decision-Aid In A Diverse Population With Systemic Lupus Erythematosus In 15 Us Rheumatology Clinics, W Winn Chatham, Sonali Narain, Narender Annapureddy, Diane L Kamen, Kimberly Trotter, Vikas Majithia, Cathy Lee Ching, Zineb Aouhab, Swamy Venuturupalli, Daniel J Wallace, Rosalind Ramsey-Goldman, Alfred Kim, Maureen Mcmahon, S Sam Lim, Kalpana Bhairavarasu, Alexa Meara, Kenneth Kalunian, T Mark Beasley

Faculty, Staff and Students Publications

Objective: The objective of this study was to examine the clinical outcomes during the implementation of a self-administered patient decision-aid (PtDA) for lupus.

Methods: We provided an effective computerized lupus PtDA in 15 rheumatology outpatient clinics 2019-2024 (including the COVID pandemic). We undertook Organizational Readiness to Implement Change Surveys (ORICs) and Team Learning and Psychological Safety Surveys (TLPSSs) at baseline. The primary study outcome objective measure, percent penetration/reach, was defined as the number of patients who viewed the lupus PtDA at the end of the study, divided by the total number of eligible patients (times 100). We used validated clinical …

Relapse Patterns Among Children And Adolescents With Kaposi Sarcoma In Malawi, William Kamiyango, Jimmy Villiera, Parth S Mehta, Erin Peckham-Gregory, Mark Zobeck, Michael E Scheurer, Carl E Allen, Rizine Mzikamanda, Nmazuo W Ozuah, Nader Kim El-Mallawany

Faculty, Staff and Students Publications

Kaposi Sarcoma (KS) is a common childhood cancer in Malawi, but few studies have exploredclinical characteristicsofrelapsed disease. We aimed to characterize clinical patterns of relapse to improve treatment and, ultimately, long-term survival in patients with pediatric KS.A retrospective cohort study was conducted among patients ages < 19 years of age at time of KS diagnosis in Lilongwe, Malawi between August 1, 2010 and March 15, 2020. Specifically, emphasis was placed on patients who had relapsed disease and excluded patients with refractory disease or those who died whilst receiving front-line treatment. Salvage therapy typically involved an intensified chemotherapy regimen compared to front-line therapy—namely nonliposomaldoxorubicin plus bleomycin/vincristine or paclitaxel monotherapy.One-hundred and ninety patients with pediatric KS were included in this analysis, 50 of whom experienced relapse (26%).Older median age was associated with occurrence of relapse (10 vs 6.7 years, p-value = 0.004). Median time from diagnosis to first relapse was 10.6 months (range 2.3–49 months). Three-year post-relapse overall survival (OS) for the entire cohort was 60% with a median follow-up time of 4.7 years after relapse.Survival was significantly higher for patients who relapsed with the woody edema clinical phenotype of pediatric KS versus those with visceral/disseminated disease—3-year OS 79% (95% CI 62–100) versus 29% (14–61).These data demonstrate potential for continued survival after KS relapse in the pediatric population and identify subsets of high-risk patients. The higher mortality observed in patients with visceral/disseminated KS highlights the need for improved therapeutic strategies.

Integrative Exome Sequencing And Machine Learning Identify Micb And Interferon Pathway Genes As Contributors To Ssc Risk, David Murdock, Brian Dawson, Marialbert Acosta-Herrera, Martin Kerick, Javier Martin, Kevin Wilhelm, Jennifer Kay Asmussen, Olivier Lichtarge, Regeneron Genetics Center, Shervin Assassi, Maureen D Mayes, Brendan H Lee

Faculty, Staff and Students Publications

Objectives: Systemic sclerosis (SSc) is a complex autoimmune disease with both known and unidentified genetic contributors. While genome-wide association studies (GWAS) have implicated multiple loci, many reside in noncoding regions. We aimed to identify novel protein-coding variants and pathogenic pathways using exome sequencing (ES) integrated with an Evolutionary Action-Machine Learning (EAML) framework, single-cell RNA sequencing (scRNA-seq), and expression quantitative trait locus (eQTL) analysis.

Methods: GWAS was conducted in 2,559 SSc cases and 893 controls of Caucasian ancestry, with replication in 9,846 cases and 18,333 controls of European ancestry. EAML prioritized genes with high-impact missense variants predictive of disease. Public scRNA-seq …

Stool-Based Molecular Tuberculosis Treatment Monitoring: A Faster Means For Detecting Persistent Mycobacteria Compared To Phenotypic Culture, Anca Vasiliu, Lucia Carratala-Castro, Bariki Mtafya, Nontobeko Maphalala, Shilzia Munguambe, Belen Saavedra, Tara Ness, Gugu Maphalala, Sozinho Acacio, Edson Mambuque, Joanna Ehrlich, Rojelio Mejia, Mangaliso Ziyane, H Lester Kirchner, Christoph Lange, Alexander Kay, Alberto L Garcia-Basteiro, Anna Mandalakas, Andrew R Dinardo

Faculty, Staff and Students Publications

Background: Tuberculosis (TB) treatment monitoring is hindered by the lack of a rapidly measured biomarker that accurately predicts clinically relevant outcomes. Symptom screening poorly correlates with bacillary burden. Although culture is a direct measure of viable bacillary burden, the long turnaround time makes it clinically irrelevant.

Methods: The TB treatment monitoring potential of stool-based, quantitative polymerase chain reaction (qPCR) was prospectively assessed among 231 participants of all ages from Eswatini, Tanzania, and Mozambique with microbiologically confirmed TB. Stool qPCR results were compared to sputum culture, persistent symptoms, drug resistance, and World Health Organization TB outcomes.

Results: Quantitative bacillary burden measured …

Data-Driven Approach To Dynamic Resting State Functional Connectivity In Post-Traumatic Stress Disorder: An Enigma-Pgc Ptsd Study, Courtney C Haswell, Chadi G Abdallah, Michael Angstadt, Justin T Baker, Hannah Berg, Jennifer U Blackford, Josh Cisler, Andrew S Cotton, Judith K Daniels, Nicholas D Davenport, Richard J Davidson, Terri A Deroon-Cassini, Seth G Disner, Wissam El Hage, Negar Fani, Jessie L Frijling, Evan M Gordon, Daniel W Grupe, Xiaofu He, Ryan Herringa, David Hofmann, Ashley A Huggins, Ahmed Hussain, Jonathan Ipser, Neda Jahanshad, Tanja Jovanovic, Milissa L Kaufman, Yoojean Kim, Anthony King, Saskia B J Koch, Sheri Koopowitz, Amit Lazarov, Lauren A M Lebois, Isreal Liberzon, Shmuel Lissek, Antje Manthey, Geoffrey May, Katie A Mclaughlin, Laura Nawijn, Steven M Nelson, Yuval Neria, Jack B Nitschke, Bunmi O Olatunji, Miranda Olff, Matthew Peverill, Yann Quidé, Orren Ravid, Kerry Ressler, Marisa Ross, Lauren E Salminen, Kelly Sambrook, Chiahao Shih, Anika Sierk, Scott R Sponheim, Dan J Stein, Jennifer Stevens, Thomas Straube, Benjamin Suarez-Jimenez, Paul M Thompson, Nic J A Van Der Wee, Steven J A Van Der Werff, Sanne J H Van Rooij, Mirjam Van Zuiden, Dick J Veltman, Robert R J M Vermeiren, Henrik Walter, Xin Wang, Hong Xie, Xi Zhu, Sigal Zilcha-Mano, Christine L Larson, Rajendra Morey

Faculty, Staff and Students Publications

Using functional magnetic resonance imaging (fMRI), symptoms of posttraumatic stress disorder (PTSD) have been associated with aberrations in brain networks in the absence of a given cognitive demand or task, called resting-state networks. Prior work has focused on disruption in the static functional connectivity (FC) among specific regions constrained by a priori hypotheses. However, dynamic FC, an approach that examines brain network characteristics over time, may provide a more sensitive measure to understand the network properties underlying dysfunction in PTSD. Further, using a data-driven analytic approach may reveal the contribution of other larger network disturbances beyond those revealed by hypothesis-driven …

Ruptured Arteriovenous Malformation Mortality: Incidence, Risk Factors, And Inpatient Outcome Score, Bridget Nolan, Smit Patel, Nir Lavi-Romer, Zehavya Stadlan, Alis Dicpinigaitis, Jose Dominguez, Haris Kamal, Steven D Shapiro, Arundhati Biswas, Omar Tanweer, Ketan Bulsara, Carrie Muh, Jared Pisapia, Simon Hanft, Stephan Mayer, Chirag D Gandhi, Fawaz Al-Mufti

Faculty, Staff and Students Publications

Background

Limited literature exists on the morbidity and mortality of AVM associated intracerebral hemorrhage (ICH) compared with non-AVM ICH.

Objective

We examine morbidity and mortality in cAVM in a large nationwide inpatient sample to create a prognostic inpatient ruptured AVM mortality score.

Methods

This retrospective cohort study from 2008 to 2014 compares outcomes in cAVM related hemorrhages and ICH utilizing the National Inpatient Sample database. Diagnostic codes for ICH and AVM underlying ICH were identified. We compared case fatality according to medical complications. Multivariate analysis was used to derive hazard ratios and 95% confidence intervals to assess odds of mortality. …

The Glycosyltransferase Poglut1 Regulates Muscle Stem Cell Development And Maintenance In Mice, Beatriz Rodriguez-Gonzalez, Youxi Yuan, Raquel Cano, Arjun A Rambhiya, Radbod Darabi, Robert S Haltiwanger, Carmen Paradas, Hamed Jafar-Nejad

Faculty, Staff and Students Publications

Mutations in protein O-glucosyltransferase 1 (POGLUT1) cause a recessive limb-girdle muscular dystrophy (LGMDR21) with reduced satellite cell number and NOTCH1 signaling in adult patient muscles and impaired myogenic capacity of patient-derived muscle progenitors. However, the in vivo roles of POGLUT1 in the development, function, and maintenance of satellite cells are not well understood. Here, we show that conditional deletion of mouse Poglut1 in myogenic progenitors leads to early lethality, postnatal muscle growth defects, reduced Pax7 expression, abnormality in muscle extracellular matrix, and impaired muscle repair. Poglut1-deficient muscle progenitors exhibit reduced proliferation, enhanced differentiation, and accelerated fusion into myofibers. Inducible loss …