Medicine and Health Sciences Commons^™

A Proteogenomic Analysis Of Cervical Cancer Reveals Therapeutic And Biological Insights, Jing Yu, Li Ding, Et Al.

2020-Current year OA Pubs

Although the incidence of cervical cancer (CC) has been reduced in high-income countries due to human papillomavirus (HPV) vaccination and screening strategies, it remains a significant public health issue that poses a threat to women's health in low-income countries. Here, we perform a comprehensive proteogenomic profiling of CC tumors obtained from 139 Chinese women. Integrated proteogenomic analysis links genetic aberrations to downstream pathogenesis-related pathways and reveals the landscape of HPV-associated multi-omic changes. EP300 is found to enhance the acetylation of FOSL2-K222, consequently accelerating the malignant proliferation of CC cells. Proteomic stratification identifies three patient subgroups with distinct features in prognosis, …

Lymphocytic Choriomeningitis Arenavirus Utilises Intercellular Connections For Cell To Cell Spread, Owen Byford, Amelia B Shaw, Hiu Nam Tse, Alex Moon-Walker, Erica Ollmann Saphire, Sean P J Whelan, Martin Stacey, Roger Hewson, Juan Fontana, John N Barr

2020-Current year OA Pubs

The Arenaviridae family of segmented RNA viruses contains nearly 70 species with several associated with fatal haemorrhagic fevers, including Lassa, Lujo and Junin viruses. Lymphocytic choriomeningitis arenavirus (LCMV) is associated with fatal neurologic disease in humans and additionally represents a tractable model for studying arenavirus biology. Within cultured cells, a high proportion of LCMV spread is between directly neighbouring cells, suggesting infectivity may pass through intercellular connections, bypassing the canonical extracellular route involving egress from the plasma membrane. Consistent with this, we visualized abundant actin- and tubulin-rich connections conjoining LCMV-infected and uninfected cells within cultures, resembling tunnelling nanotubes (TNTs). Within …

Modulation Of Monocyte Effector Functions And Gene Expression By Human Cytomegalovirus Infection, Matthew Planchon, Jay Fishman, Joseph El Khoury

SKMC Student Presentations and Publications

Monocytes are crucial players in innate immunity. The human cytomegalovirus (CMV) infection has significant impacts on monocyte effector functions and gene expression. CMV, a β-herpesvirus, disrupts key monocyte roles, including phagocytosis, antigen presentation, cytokine production, and migration, impairing their ability to combat pathogens and activate adaptive immune responses. CMV modulates monocyte gene expression, decreasing their capacity for antigen presentation and phagocytosis while increasing pro-inflammatory cytokine production, which can contribute to tissue damage and chronic inflammation. CMV also alters monocyte migration to sites of infection while promoting trans-endothelial migration, thus aiding viral dissemination. Additionally, the virus affects reactive oxygen species (ROS) …

Whole-Genome Analysis Of Plasma Fibrinogen Reveals Population-Differentiated Genetic Regulators With Putative Liver Roles, Jennifer E Huffman, Jayna Nicholas, Julie Hahn, Adam S Heath, Laura M Raffield, Lisa R Yanek, Jennifer A Brody, Florian Thibord, Laura Almasy, Traci M Bartz, Lawrence F Bielak, Russell P Bowler, Germán D Carrasquilla, Daniel I Chasman, Ming-Huei Chen, David B Emmert, Mohsen Ghanbari, Jeffrey Haessler, Jouke-Jan Hottenga, Marcus E Kleber, Ngoc-Quynh Le, Jiwon Lee, Joshua P Lewis, Ruifang Li-Gao, Jian'an Luan, Anni Malmberg, Massimo Mangino, Riccardo E Marioni, Angel Martinez-Perez, Nathan Pankratz, Ozren Polasek, Anne Richmond, Benjamin A T Rodriguez, Jerome I Rotter, Maristella Steri, Pierre Suchon, Stella Trompet, Stefan Weiss, Marjan Zare, Paul Auer, Michael H Cho, Paraskevi Christofidou, Gail Davies, Eco De Geus, Jean-François Deleuze, Graciela E Delgado, Lynette Ekunwe, Nauder Faraday, Martin Gögele, Andreas Greinacher, He Gao, Tom Howard, Peter K Joshi, Tuomas O Kilpeläinen, Jari Lahti, Allan Linneberg, Silvia Naitza, Raymond Noordam, Ferran Paüls-Vergés, Stephen S Rich, Frits R Rosendaal, Igor Rudan, Kathleen A Ryan, Juan Carlos Souto, Frank J A Van Rooij, Heming Wang, Wei Zhao, Lewis C Becker, Andrew Beswick, Michael R Brown, Brian E Cade, Harry Campbell, Kelly Cho, James D Crapo, Joanne E Curran, Moniek P M De Maat, Margaret Doyle, Paul Elliott, James S Floyd, Christian Fuchsberger, Niels Grarup, Xiuqing Guo, Sarah E Harris, Lifang Hou, Ivana Kolcic, Charles Kooperberg, Cristina Menni, Matthias Nauck, Jeffrey R O'Connell, Valeria Orrù, Bruce M Psaty, Katri Räikkönen, Jennifer A Smith, Jose Manuel Soria, David J Stott, Astrid Van Hylckama Vlieg, Hugh Watkins, Gonneke Willemsen, Peter W F Wilson, Yoav Ben-Shlomo, John Blangero, Dorret Boomsma, Simon R Cox, Abbas Dehghan, Johan G Eriksson, Edoardo Fiorillo, Myriam Fornage, Torben Hansen, Caroline Hayward, M Arfan Ikram, J Wouter Jukema, Sharon L R Kardia, Leslie A Lange, Winfried März, Rasika A Mathias, Braxton D Mitchell, Dennis O Mook-Kanamori, Pierre-Emmanuel Morange, Oluf Pedersen, Peter P Pramstaller, Susan Redline, Alexander Reiner, Paul M Ridker, Edwin K Silverman, Tim D Spector, Uwe Völker, Nicholas J Wareham, James F Wilson, Jie Yao, David-Alexandre Trégouët, Andrew D Johnson, Alisa S Wolberg, Paul S De Vries, Maria Sabater-Lleal, Alanna C Morrison, Nicholas L Smith

Faculty, Staff and Student Publications

Genetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole-genome sequencing (WGS) data provide better coverage of the genome and better representation of non-European variants. To better understand the genetic landscape regulating plasma fibrinogen levels, we meta-analyzed WGS data from the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine (TOPMed) program (n = 32 572), with array-based genotype data from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 131 …

Genetic Risk Classification For Adults With Aml Receiving Less-Intensive Therapies: The 2024 Eln Recommendations, Hartmut Döhner, Courtney D Dinardo, Frederick R Appelbaum, Charles Craddock, Hervé Dombret, Benjamin L Ebert, Pierre Fenaux, Lucy A Godley, Robert P Hasserjian, Richard A Larson, Ross L Levine, Yasushi Miyazaki, Dietger Niederwieser, Gert Ossenkoppele, Christoph Röllig, Jorge Sierra, Eytan M Stein, Martin S Tallman, Hwei-Fang Tien, Jianxiang Wang, Agnieszka Wierzbowska, Andrew H Wei, Bob Löwenberg

Faculty, Staff and Student Publications

The European LeukemiaNet (ELN) genetic risk classifications were developed based on data from younger adults receiving intensive chemotherapy. Emerging analyses from patients receiving less-intensive therapies prompted a proposal for an ELN genetic risk classification specifically for this patient population.

Teen Dating Violence And The Covid-19 Pandemic: Trends From A Longitudinal Study In Texas, Leila Wood, Elizabeth Baumler, Morgan E Pettyjohn, Jeff R Temple

Faculty, Staff and Student Publications

Purpose: Teen dating violence (TDV) is a global public health and safety issue causing health impacts to youth people. This study aimed to examine: (1) the impact of the pandemic on TDV victimisation rates and (2) socioecological factors associated with sustained risk for TDV victimisation during the first year of COVID-19.

Methods: Data are from an ongoing randomised controlled trial of a TDV prevention programme in Texas (n=2768). We conducted annual assessments in 2019-2021. We used regression modelling to assess demographic, individual, peer and family factors associated with TDV risks.

Results: TDV rates declined from 11.9% in 2019 to 5.2% …

Firearm Access, Carriage And Use In An Ethnically Diverse Sample Of Young Adults In Texas, Usa, Yu Lu, Elizabeth Baumler, Annalyn Saludares Demello, Leila Wood, Hillary Mcguire, Jeff R Temple

Faculty, Staff and Student Publications

Background Despite the high rates of firearm ownership and firearm-related injuries and mortalities in Southern US states, understandings on the factors contributing to these are lacking.

Methods Using wave 10 (2021) data from a longitudinal study, we examined firearm-related experiences among 636 ethnically diverse young adults (mean age=26 years; 62% female) in Texas, USA.

Results Just over half of participants had ready access to firearms, with 22.3% having carried a firearm outside of their home, 4.9% having been threatened with a firearm by a romantic partner and 4.4% by a non-romantic partner. More firearm access and carriage were reported in …

Genetic Risk Stratification And Outcomes Among Treatment-Naive Patients With Aml Treated With Venetoclax And Azacitidine, Hartmut Döhner, Keith W Pratz, Courtney D Dinardo, Andrew H Wei, Brian A Jonas, Vinod A Pullarkat, Michael J Thirman, Christian Récher, Andre C Schuh, Sunil Babu, Xiaotong Li, Grace Ku, Zihuan Liu, Yan Sun, Jalaja Potluri, Monique Dail, Brenda Chyla, Daniel A Pollyea

Faculty, Staff and Student Publications

The European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems are based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. This pooled analysis of the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to the 2017 and 2022 ELN risk classifications and derived new molecular signatures differentiating venetoclax-azacitidine-treated patients based on overall survival (OS). Overall, 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. The ELN 2017 or 2022 prognostic criteria classified most …

Comparison Of The Bristol Stool Scale And Modified Version For Children: Use By Providers Vs Children, James Orozco, Mariella M Self, Sara Grisales, Bruno P Chumpitazi, Danita I Czyzewski, Meagan S Mcmullen, Rebecca Berger, Clarissa A Gonzalez, Amber L Cunha, Robert J Shulman

Faculty, Staff and Students Publications

Introduction: Accurate report of stool form is essential to diagnosis and assessment of treatment response. The modified Bristol Stool Form Scale for Children (mBSFS-C) classifies stool form into 5 types and is reliable and valid. However, a direct comparison of provider's and children's ratings using the mBSFS-C vs the traditional BSFS that uses 7 stool form types has not been done.

Methods: Pediatric gastroenterology providers and children rated the same 35 stool photographs, reflecting diverse stool forms, using both scales. The order of photograph presentation and scale use were randomized. For each photograph, the most common rating (modal rating) was …

Insights Into Human Norovirus Cultivation In Human Intestinal Enteroids, Khalil Ettayebi, Gurpreet Kaur, Ketki Patil, Janam Dave, B Vijayalakshmi Ayyar, Victoria R Tenge, Frederick H Neill, Xi-Lei Zeng, Allison L Speer, Sara C Di Rienzi, Robert A Britton, Sarah E Blutt, Sue E Crawford, Sasirekha Ramani, Robert L Atmar, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are a significant cause of epidemic and sporadic acute gastroenteritis worldwide. The lack of a reproducible culture system hindered the study of HuNoV replication and pathogenesis for almost a half-century. This barrier was overcome with our successful cultivation of multiple HuNoV strains in human intestinal enteroids (HIEs), which has significantly advanced HuNoV research. We optimized culture media conditions and generated genetically modified HIE cultures to enhance HuNoV replication in HIEs. Building upon these achievements, we now present new insights into this culture system, which involve testing different media, unique HIE lines, and additional virus strains. HuNoV infectivity …

Genotype-Specific Effects Of Elamipretide In Patients With Primary Mitochondrial Myopathy: A Post Hoc Analysis Of The Mmpower-3 Trial, Amel Karaa, Enrico Bertini, Valerio Carelli, Bruce Cohen, Gregory M Ennes, Marni J Falk, Amy Goldstein, Gráinne Gorman, Richard Haas, Michio Hirano, Thomas Klopstock, Mary Kay Koenig, Cornelia Kornblum, Costanza Lamperti, Anna Lehman, Nicola Longo, Maria Judit Molnar, Sumit Parikh, Han Phan, Robert D S Pitceathly, Russekk Saneto, Fernando Scaglia, Serenella Servidei, Mark Tarnopolsky, Antonio Toscano, Johan L K Van Hove, John Vissing, Jerry Vockley, Jeffrey S Finman, Anthony Abbruscato, David A Brown, Alana Sullivan, James A Shiffer, Michelango Mancuso, Mmpower-3 Trial Investigators

Faculty, Staff and Students Publications

BACKGROUND: As previously published, the MMPOWER-3 clinical trial did not demonstrate a significant benefit of elamipretide treatment in a genotypically diverse population of adults with primary mitochondrial myopathy (PMM). However, the prespecified subgroup of subjects with disease-causing nuclear DNA (nDNA) pathogenic variants receiving elamipretide experienced an improvement in the six-minute walk test (6MWT), while the cohort of subjects with mitochondrial DNA (mtDNA) pathogenic variants showed no difference versus placebo. These published findings prompted additional genotype-specific post hoc analyses of the MMPOWER-3 trial. Here, we present these analyses to further investigate the findings and to seek trends and commonalities among those …

Plasmodium Berghei Liver Stage Parasites Exploit Host Gabarap Proteins For Tfeb Activation, Jacqueline Schmuckli-Maurer, Annina F Bindschedler, Rahel Wacker, Oliver M Würgler, Ruth Rehmann, Timothy Lehmberg, Leon O Murphy, Thanh N Nguyen, Michael Lazarou, Jlenia Monfregola, Andrea Ballabio, Volker T Heussler

Duncan NRI Faculty and Staff Publications

Plasmodium, the causative agent of malaria, infects hepatocytes prior to establishing a symptomatic blood stage infection. During this liver stage development, parasites reside in a parasitophorous vacuole (PV), whose membrane acts as the critical interface between the parasite and the host cell. It is well-established that host cell autophagy-related processes significantly impact the development of Plasmodium liver stages. Expression of genes related to autophagy and lysosomal biogenesis is orchestrated by transcription factor EB (TFEB). In this study, we explored the activation of host cell TFEB in Plasmodium berghei-infected cells during the liver stage of the parasite. Our results …

Mode Of Injury And Level Of Synovitis Alter Inflammatory Chondrocyte Gene Expression And Associated Pathways, Megan L Libke, Daniel J Cunningham, Bridgette D Furman, John S Yi, Jonathan M Brunger, Virginia B Kraus, Farshid Guilak, Amy L Mcnulty, Steven A Olson

2020-Current year OA Pubs

Although various joint injuries result in post-traumatic osteoarthritis (PTOA), differences in chondrocyte response to specific injuries, such as blunt compression or fracture, are unclear. Furthermore, the role of underlying joint inflammation, or synovitis, is often not considered. We investigated how injury mechanisms and underlying synovitis affect chondrocyte gene expression using osteochondral injury models with synovial co-culture. We hypothesized that the state of synovitis as well as the mechanism of biomechanical cartilage injury differentially alter the gene expression of chondrocytes and that these responses are regulated by the pro-inflammatory cytokine interleukin 1 (IL-1). The mechanism of injury and level of synovial …

Does Muscle Pain Induce Alterations In The Pelvic Floor Motor Unit Activity Properties In Interstitial Cystitis/Bladder Pain Syndrome? A High-Density Semg-Based Study, Monica Albaladejo-Belmonte, Michael Houston, Nicholas Dias, Theresa Spitznagle, Henry Lai, Yingchun Zhang, Javier Garcia-Casado

2020-Current year OA Pubs

Several studies have shown interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic condition that poses challenges in both diagnosis and treatment, is associated with painful pelvic floor muscles (PFM) and altered neural drive to these muscles. However, its pathophysiology could also involve other alterations in the electrical activity of PFM motor units (MUs). Studying these alterations could provide novel insights into IC/BPS and help its clinical management. This study aimed to characterize PFM activity at the MU level in women with IC/BPS and pelvic floor myalgia using high-density surface electromyography (HD-sEMG). Signals were recorded from 15 patients and 15 healthy controls …

Immune Responses Drive Chorioretinitis And Retinal Pathology After Neonatal Cmv Infection, Jessica L. Mccord, John Y.S. Han, Ross E. Staudt, Nancy J. Philp Phd, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Human cytomegalovirus (CMV) causes a common congenital infection leading to long-term neurological impairments including brain, cochlear, and ocular pathology. Infection of newborn mice with murine (M)CMV is an established model of neuropathology caused by congenital CMV infection, with recent work suggesting that brain pathology may be driven by immune responses. In the eye, however, CMV retinitis is thought to result from virus-driven necrosis in the absence of T cell responses. We found that MCMV infection of newborn mice recapitulates human eye disease after congenital CMV infection, including focal chorioretinitis, inflamed vasculature, and disrupted blood-retinal barriers. Moreover, infection drove extensive T …

Analyzing Longitudinal Trait Trajectories Using Gwas Identifies Genetic Variants For Kidney Function Decline, Simon Wiegrebe, Mathias Gorski, Janina M Herold, Klaus J Stark, Barbara Thorand, Christian Gieger, Carsten A Böger, Johannes Schödel, Florian Hartig, Han Chen, Thomas W Winkler, Helmut Küchenhoff, Iris M Heid

Faculty, Staff and Student Publications

Understanding the genetics of kidney function decline, or trait change in general, is hampered by scarce longitudinal data for GWAS (longGWAS) and uncertainty about how to analyze such data. We use longitudinal UK Biobank data for creatinine-based estimated glomerular filtration rate from 348,275 individuals to search for genetic variants associated with eGFR-decline. This search was performed both among 595 variants previously associated with eGFR in cross-sectional GWAS and genome-wide. We use seven statistical approaches to analyze the UK Biobank data and simulated data, finding that a linear mixed model is a powerful approach with unbiased effect estimates which is viable …

Phase I Dose Escalation Study Of Io-108, An Anti-Lilrb2 Antibody, In Patients With Advanced Solid Tumors, Matthew H Taylor, Aung Naing, John Powderly, Paul Woodard, Luke Chung, Wen Hong Lin, Hongyu Tian, Nathan Siemers, Hong Xiang, Rong Deng, Kyu Hong, Donna Valencia, Tao Huang, Ying Zhu, X Charlene Liao, Xiao Min Schebye, Manish R Patel

Faculty, Staff and Student Publications

Purpose: In this first-in-human dose escalation study, the safety and efficacy of IO-108, a fully human monoclonal antibody targeting leukocyte immunoglobulin-like receptor B2 (LILRB2), was investigated in patients with advanced solid tumors as monotherapy and in combination with pembrolizumab, an anti-programmed cell death protein 1 (PD-1) antibody.

Methods: The study included patients with histologically or cytologically confirmed advanced and relapsed solid tumors, with measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1. Patients were treated with escalating doses of IO-108 every 3 weeks (Q3W) as monotherapy and in combination with pembrolizumab. Safety and tolerability were the primary objectives. …

Spatiotemporal Mapping Of Auditory Onsets During Speech Production, Garret Lynn Kurteff, Alyssa M Field, Saman Asghar, Elizabeth C Tyler-Kabara, Dave Clarke, Howard L Weiner, Anne E Anderson, Andrew J Watrous, Robert J Buchanan, Pradeep N Modur, Liberty S Hamilton

Faculty, Staff and Students Publications

The human auditory cortex is organized according to the timing and spectral characteristics of speech sounds during speech perception. During listening, the posterior superior temporal gyrus is organized according to onset responses, which segment acoustic boundaries in speech, and sustained responses, which further process phonological content. When we speak, the auditory system is actively processing the sound of our own voice to detect and correct speech errors in real time. This manifests in neural recordings as suppression of auditory responses during speech production compared with perception, but whether this differentially affects the onset and sustained temporal profiles is not known. …

High-Coverage Nanopore Sequencing Of Samples From The 1000 Genomes Project To Build A Comprehensive Catalog Of Human Genetic Variation, Jonas A Gustafson, Sophia B Gibson, Nikhita Damaraju, Miranda P G Zalusky, Kendra Hoekzema, David Twesigomwe, Lei Yang, Anthony A Snead, Phillip A Richmond, Wouter De Coster, Nathan D Olson, Andrea Guarracino, Qiuhui Li, Angela L Miller, Joy Goffena, Zachary B Anderson, Sophie H R Storz, Sydney A Ward, Maisha Sinha, Claudia Gonzaga-Jauregui, Wayne E Clarke, Anna O Basile, André Corvelo, Catherine Reeves, Adrienne Helland, Rajeeva Lochan Musunuri, Mahler Revsine, Karynne E Patterson, Cate R Paschal, Christina Zakarian, Sara Goodwin, Tanner D Jensen, Esther Robb, 1000 Genomes Ont Sequencing Consortium, University Of Washington Center For Rare Disease Research (Uw-Crdr), Genomics Research To Elucidate The Genetics Of Rare Diseases (Gregor) Consortium, William Richard Mccombie, Fritz J Sedlazeck, Justin M Zook, Stephen B Montgomery, Erik Garrison, Mikhail Kolmogorov, Michael C Schatz, Richard N Mclaughlin, Harriet Dashnow, Michael C Zody, Matt Loose, Miten Jain, Evan E Eichler, Danny E Miller

Faculty, Staff and Students Publications

Fewer than half of individuals with a suspected Mendelian or monogenic condition receive a precise molecular diagnosis after comprehensive clinical genetic testing. Improvements in data quality and costs have heightened interest in using long-read sequencing (LRS) to streamline clinical genomic testing, but the absence of control data sets for variant filtering and prioritization has made tertiary analysis of LRS data challenging. To address this, the 1000 Genomes Project (1KGP) Oxford Nanopore Technologies Sequencing Consortium aims to generate LRS data from at least 800 of the 1KGP samples. Our goal is to use LRS to identify a broader spectrum of variation …

Leveraging The T2t Assembly To Resolve Rare And Pathogenic Inversions In Reference Genome Gaps, Kristine Bilgrav Saether, Jesper Eisfeldt, Jesse D Bengtsson, Ming Yin Lun, Christopher M Grochowski, Medhat Mahmoud, Hsiao-Tuan Chao, Jill A Rosenfeld, Pengfei Liu, Marlene Ek, Jakob Schuy, Adam Ameur, Hongzheng Dai, Undiagnosed Diseases Network, James Paul Hwang, Fritz J Sedlazeck, Weimin Bi, Ronit Marom, Josephine Wincent, Ann Nordgren, Claudia M B Carvalho, Anna Lindstrand

Faculty, Staff and Students Publications

Chromosomal inversions (INVs) are particularly challenging to detect due to their copy-number neutral state and association with repetitive regions. Inversions represent about 1/20 of all balanced structural chromosome aberrations and can lead to disease by gene disruption or altering regulatory regions of dosage-sensitive genes in cis. Short-read genome sequencing (srGS) can only resolve ∼70% of cytogenetically visible inversions referred to clinical diagnostic laboratories, likely due to breakpoints in repetitive regions. Here, we study 12 inversions by long-read genome sequencing (lrGS) (n = 9) or srGS (n = 3) and resolve nine of them. In four cases, the …

Jaha At Scientific Sessions 2023: Moving Toward Social Justice In Cardiovascular Health In The United States, Carissa M. Baker-Smith, Salina P. Waddy, Sara Hassani, Mahasin Mujahid, Tochi Okwuosa, Emmanuel Peprah, Bernadette Boden-Albala

Department of Medicine Faculty Papers

Attention to social justice is essential to improving cardiovascular health outcomes. In the absence of social justice, equitable cardiovascular health is impossible. This viewpoint provides a brief synopsis of the 2023 Journal of the American Heart Association (JAHA)–sponsored session titled “Moving Towards Social Justice in Cardiovascular Health.” We define social justice and summarize the burden of cardiovascular disease inequity in the United States. We also highlight strategies for achieving social justice, including addressing workforce diversity, integrating social determinants into cardiovascular research, designing cardiovascular interventions to close the equity gap, and improving inclusivity in cardiovascular disease trials.

Human Studies Of The Efficacy And Safety Of Stem Cells In The Treatment Of Diabetic Peripheral Neuropathy: A Systematic Review And Meta-Analysis, Seyed Danial Alizadeh, Shima Jahani, Mohammad Rezaei Zadeh Rukerd, Reza Tabrizi, Rasoul Masoomi, Seyedeh Zahra Banihashemian, Mahgol Sadat Hassan Zadeh Tabatabaei, Zahra Ghodsi, Ahmad Pour-Rashidi, James Harrop, Vafa Rahimi-Movaghar

Department of Neurosurgery Faculty Papers

OBJECTIVE: To assess the efficacy and safety of stem cell therapy in human studies for diabetic peripheral neuropathy (DPN).

METHODS: A comprehensive literature review was performed across multiple databases, including Ovid MEDLINE ALL, Embase via Ovid SP, Scopus, Web of Science Core Collection, and Cochrane CENTRAL, up to January 31, 2024. Keywords and controlled vocabularies related to diabetic neuropathy and stem cell therapy were used. Inclusion criteria encompassed all controlled trials examining stem cell therapy for DPN, excluding animal or in vitro studies, review papers, conference abstracts, and editor letters. Data extraction and risk of bias assessment were independently performed …

Endovascular Treatment Of Patients With Acute Ischemic Stroke With Tandem Lesions Presenting With Low Alberta Stroke Program Early Computed Tomography Score, Milagros Galecio-Castillo, Mudassir Farooqui, Waldo R Guerrero, Marc Ribo, Ameer E Hassan, Mouhammad A Jumaa, Afshin A Divani, Michael G Abraham, Nils H Petersen, Johanna T Fifi, Amer Malik, James E Siegler, Thanh N Nguyen, Sunil A Sheth, Guillermo Linares, Nazli Janjua, Jazba Soomro, Darko Quispe-Orozco, Marta Olivé-Gadea, Wondewossen G Tekle, Syed F Zaidi, Sara Y Sabbagh, Tiffany Barkley, Ayush Prasad, Reade A De Leacy, Mohamad Abdalkader, Sergio Salazar-Marioni, Weston Gordon, Charoskhon Turabova, Aaron Rodriguez-Calienes, Mahmoud Dibas, Maxim Mokin, Dileep R Yavagal, Albert J Yoo, Amrou Sarraj, Tudor G Jovin, Santiago Ortega-Gutierrez

Faculty, Staff and Student Publications

Background: Recent trials confirmed the efficacy and safety of endovascular thrombectomy in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS); however, evidence in tandem lesions is limited. This study evaluates endovascular thrombectomy safety and efficacy in patients with acute large-vessel occlusion with tandem lesions, stratified by baseline ASPECTS.

Methods and results: We conducted a retrospective analysis of data from 16 centers. Inclusion criteria included the following: age ≥18 years, anterior circulation tandem lesions, endovascular thrombectomy < 24 hours of symptom onset, and ≥70% internal carotid artery stenosis/occlusion. Patients were categorized into low (0-5) and high (6-10) ASPECTS. Inverse probability of treatment weighting matching was used to balance the groups. Primary outcomes included the following: 90-day modified Rankin Scale (mRS) score 0 to 2 and symptomatic intracranial hemorrhage. Secondary outcomes included the following: ordinal mRS, mRS 0 to 3, modified Thrombolysis in Cerebral Infarction ≥2b and 2c-3, petechial hemorrhage, parenchymal hematoma (1/2), early neurologic improvement, and mortality. Of 691 patients, 44 had ASPECTS 0 to 5 and 505 had ASPECTS 6 to 10. Patients with low ASPECTS had lower odds of 90-day mRS 0 to 2 (adjusted odds ratio [OR], 0.48; P=0.036) and higher odds of symptomatic intracranial hemorrhage (adjusted OR, 3.78; P=0.014). Additional significant differences were found in mRS shift, …

Frontline Ph-Negative B-Cell Precursor Acute Lymphoblastic Leukemia Treatment And The Emerging Role Of Blinatumomab, Elias J Jabbour, Hagop M Kantarjian, Nicola Goekbuget, Bijal D Shah, Sabina Chiaretti, Jae H Park, Anita W Rijneveld, Lia Gore, Shaun Fleming, Aaron C Logan, Josep M Ribera, Tobias F Menne, Khalid Mezzi, Faraz Zaman, Kelly Velasco, Nicolas Boissel

Faculty, Staff and Student Publications

This narrative review seeks to summarize chemotherapeutic regimens commonly used for patients with newly diagnosed Philadelphia (Ph) chromosome-negative B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in the frontline setting and to describe the latest clinical research using the bispecific T-cell-engaging immunotherapy blinatumomab in the first-line treatment setting. Current standard-of-care chemotherapeutic backbones for newly diagnosed Ph-negative BCP-ALL are based on the same overarching treatment principle: to reduce disease burden to undetectable levels and maintain lasting remission. The adult treatment landscape has progressively evolved following the adoption of pediatric-inspired regimens. However, these intense regimens are not tolerated by all, and high-risk patients still …

Ethical Issues In Implementation Science: Perspectives From A National Heart, Lung, And Blood Institute Workshop, Neal W Dickert, Donna Spiegelman, Jennifer S Blumenthal-Barby, Garth Graham, Steven Joffe, Jeremy M Kahn, Nancy E Kass, Scott Y H Kim, Meeta P Kerlin, Aisha T Langford, James V Lavery, Daniel D Matlock, Kathleen N Fenton, George A Mensah

Center for Medical Ethics and Health Policy Staff Publications

Ethical issues arise in the context of implementation science that may differ from those encountered in other research settings. This report, developed out of a workshop convened by the Center for Translation Research and Implementation Science within the United States National Heart, Lung, and Blood Institute, identifies six key themes that are important to the assessment of ethical dimensions of implementation science. First, addressing ethical challenges in implementation science does not require new ethical principles, commitments, or regulations. However, it does require understanding of the specific contexts arising in implementation research related to both study design and the intervention being …

Electrical Impedance Tomography Monitoring In Adult Icu Patients: State-Of-The-Art, Recommendations For Standardized Acquisition, Processing, And Clinical Use, And Future Directions, Gaetano Scaramuzzo, Bhushan H Katira, Et Al.

2020-Current year OA Pubs

Electrical impedance tomography (EIT) is an emerging technology for the non-invasive monitoring of regional distribution of ventilation and perfusion, offering real-time and continuous data that can greatly enhance our understanding and management of various respiratory conditions and lung perfusion. Its application may be especially beneficial for critically ill mechanically ventilated patients. Despite its potential, clear evidence of clinical benefits is still lacking, in part due to a lack of standardization and transparent reporting, which is essential for ensuring reproducible research and enhancing the use of EIT for personalized mechanical ventilation. This report is the result of a four-day expert meeting …

Discovery Of Highly Potent And Alk2/Alk1 Selective Kinase Inhibitors Using Dna-Encoded Chemistry Technology, Ravikumar Jimmidi, Diana Monsivais, Hai Minh Ta, Kiran L Sharma, Kurt M Bohren, Srinivas Chamakuri, Zian Liao, Feng Li, John M Hakenjos, Jian-Yuan Li, Yuji Mishina, Haichun Pan, Xuan Qin, Matthew B Robers, Banumathi Sankaran, Zhi Tan, Suni Tang, Yasmin M Vasquez, Jennifer Wilkinson, Damian W Young, Stephen S Palmer, Kevin R Mackenzie, Choel Kim, Martin M Matzuk

Faculty, Staff and Students Publications

Activin receptor type 1 (ACVR1; ALK2) and activin receptor like type 1 (ACVRL1; ALK1) are transforming growth factor beta family receptors that integrate extracellular signals of bone morphogenic proteins (BMPs) and activins into Mothers Against Decapentaplegic homolog 1/5 (SMAD1/SMAD5) signaling complexes. Several activating mutations in ALK2 are implicated in fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine gliomas, and ependymomas. The ALK2 R206H mutation is also present in a subset of endometrial tumors, melanomas, non-small lung cancers, and colorectal cancers, and ALK2 expression is elevated in pancreatic cancer. Using DNA-encoded chemistry technology, we screened 3.94 billion unique compounds from our diverse …

Discovery Of Highly Potent And Alk2/Alk1 Selective Kinase Inhibitors Using Dna-Encoded Chemistry Technology, Ravikumar Jimmidi, Diana Monsivais, Hai Minh Ta, Kiran L Sharma, Kurt M Bohren, Srinivas Chamakuri, Zian Liao, Feng Li, John M Hakenjos, Jian-Yuan Li, Yuji Mishina, Haichun Pan, Xuan Qin, Matthew B Robers, Banumathi Sankaran, Zhi Tan, Suni Tang, Yasmin M Vasquez, Jennifer Wilkinson, Damian W Young, Stephen S Palmer, Kevin R Mackenzie, Choel Kim, Martin M Matzuk

Faculty, Staff and Students Publications

Activin receptor type 1 (ACVR1; ALK2) and activin receptor like type 1 (ACVRL1; ALK1) are transforming growth factor beta family receptors that integrate extracellular signals of bone morphogenic proteins (BMPs) and activins into Mothers Against Decapentaplegic homolog 1/5 (SMAD1/SMAD5) signaling complexes. Several activating mutations in ALK2 are implicated in fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine gliomas, and ependymomas. The ALK2 R206H mutation is also present in a subset of endometrial tumors, melanomas, non–small lung cancers, and colorectal cancers, and ALK2 expression is elevated in pancreatic cancer. Using DNA-encoded chemistry technology, we screened 3.94 billion unique compounds from our diverse …

Association Of Binge Alcohol Use With Functional Outcomes Among Individuals With Covid-19 Infection, Sebastian T. Tong, Michael Gottlieb, Imtiaz Ebna Mannan, Zihan Zheng, Manisha Sinha, Michelle Santangelo, Kristyn Gatling, Efrat Kean, Phillip Watts, Ralph Wang, Juan Carlos Montoy, Ahamed Idris, Samuel Macdonald, Ryan Huebinger, Mandy Hill, Kelli N O'Laughlin, Nicole L. Gentile, Jocelyn Dorney, Caitlin Malicki, Joann G. Elmore, Kate Diaz Roldan, Gary Chan, Zhenqiu Lin, Robert A. Weinstein, Kari A. Stephens

Department of Medicine Faculty Papers

AIMS: Alcohol consumption along with negative sequelae from excess alcohol intake increased during the COVID-19 pandemic. We evaluated the association between binge alcohol use and long-term functional outcomes among COVID-19-positive individuals.

METHODS: Using a prospective, longitudinal, multisite cohort study design, we evaluated the association between binge alcohol use and mental and physical functional outcomes using Patient-Reported Outcomes Measurement Information System (PROMIS)-29 scores three and six months postinfection. Eligible patients were those who presented with COVID-19-like symptoms, tested positive for COVID-19, and completed a three-month survey. Binge drinking was identified at the time of infection using the Tobacco, Alcohol, Prescription medication …

Long-Term Outcomes Following Posterior Fossa Decompression In Pediatric Patients With Chiari Malformation Type 1, A Population-Based Cohort Study, Victor Gabriel El-Hajj, Erik Öhlén, Ulrika Sandvik, Jenny Pettersson-Segerlind, Elias Atallah, Pascal Jabbour, Mohamad Bydon, David J. Daniels, Adrian Elmi-Terander, Erik Edström

Department of Neurosurgery Faculty Papers

OBJECTIVE: Posterior fossa decompression for Chiari malformation type I (Chiari 1) is effective and associated with a low risk of complication. However, up to 20% of patients may experience continued deficits or recurring symptoms after surgical intervention. For pediatric patients, there are no established tools to predict outcomes, and the risk factors for unfavorable postoperative outcomes are poorly understood. Hence, our aim was to investigate baseline data and early postoperative predictors of poor outcomes as determined by the Chicago Chiari outcome scale (CCOS).

METHODS: All pediatric patients (< 18 years) receiving a posterior fossa decompression for Chiari 1 between the years of 2005 and 2020 at the study center were eligible for inclusion. Patients with congenital anomalies were excluded.

RESULTS: Seventy-one pediatric patients with a median age of 9 years were …