Medicine and Health Sciences Commons^™

Unique Molecular Identifier-Based High-Resolution Hla Typing And Transcript Quantitation Using Long-Read Sequencing, Caleb Cornaby, Maureen C Montgomery, Chang Liu, Eric T Weimer

2020-Current year OA Pubs

HLA typing provides essential results for stem cell and solid organ transplants, as well as providing diagnostic benefits for various rheumatology, gastroenterology, neurology, and infectious diseases. It is becoming increasingly clear that understanding the expression of patient HLA transcripts can provide additional benefits for many of these same patient groups. Our study cohort was evaluated using a long-read RNA sequencing methodology to provide rapid HLA genotyping results and normalized HLA transcript expression. Our assay used NGSEngine to determine the HLA genotyping result and normalized mRNA transcript expression using Athlon2. The assay demonstrated an excellent concordance rate of 99.7%. Similar to …

The Association Of Prescription Opioid Use With Suicide Attempts: An Analysis Of Statewide Medical Claims Data, Chongliang Luo, Kun Chen, Riddhi Doshi, Nathaniel Rickles, Yong Chen, Harold Schwartz, Robert H. Aseltine

2020-Current year OA Pubs

BACKGROUND: Suicides and opioid overdose deaths are among the most pressing public health concerns in the US. However direct evidence for the association between opioid use and suicidal behavior is limited. The objective of this article is to examine the association between frequency and dose of prescription opioid use and subsequent suicide attempts.

METHODS AND FINDINGS: This retrospective cohort study analyzed 4 years of statewide medical claims data from the Connecticut All-Payer Claims Database. Commercially insured adult patients in Connecticut (n = 842,773) who had any medical claims beginning in January 2012 were followed through December 2015. The primary outcome …

Preeclampsia Is Associated With Reduced Isg15 Levels Impairing Extravillous Trophoblast Invasion, Asli Ozmen, Anthony O Odibo, Et Al

2020-Current year OA Pubs

Among several interleukin (IL)-6 family members, only IL-6 and IL-11 require a gp130 protein homodimer for intracellular signaling due to lack of intracellular signaling domain in the IL-6 receptor (IL-6R) and IL-11R. We previously reported enhanced decidual IL-6 and IL-11 levels at the maternal-fetal interface with significantly higher peri-membranous IL-6 immunostaining in adjacent interstitial trophoblasts in preeclampsia (PE) vs. gestational age (GA)-matched controls. This led us to hypothesize that competitive binding of these cytokines to the gp130 impairs extravillous trophoblast (EVT) differentiation, proliferation and/or invasion. Using global microarray analysis, the current study identified inhibition of interferon-stimulated gene 15 (

Experiences Using A Multidisciplinary Model For Treating Injection Drug Use Associated Infections: A Qualitative Study, Nathanial S Nolan, Emily Gleason, Laura R Marks, Tracey Habrock-Bach, Stephen Y Liang, Michael J Durkin

2020-Current year OA Pubs

Background: Over the past two decades, the United States has experienced a dramatic increase in the rate of injection drug use, injection associated infections, and overdose mortality. A hospital-based program for treating opioid use disorder in people who inject drugs presenting with invasive infections was initiated at an academic tertiary care center in 2020. The goal of this program was to improve care outcomes, enhance patient experiences, and facilitate transition from the hospital to longer term addiction care. The purpose of this study was to interview two cohorts of patients, those admitted before vs. after initiation of this program, to …

Beta-Adrenergic Antagonist Tolerance In Amyloid Cardiomyopathy, Stuart Ramsell, Carlos Arias Bermudez, Cyril Ayuk Mbeng Takem Baiyee, Brandon Rodgers, Samir Parikh, Salem Almaani, Nidhi Sharma, Samantha Lorusso, Miriam Freimer, Elyse Redder, Naresh Bumma, Ajay Vallkati, Yvonne Efebera, Rami Kahwash, Courtney M Campbell

2020-Current year OA Pubs

Background: Beta-adrenergic antagonists or blockers (BB) are a cornerstone of cardiac therapy for multiple indications. However, BB are considered relatively contraindicated in amyloid cardiomyopathy due to poor tolerance. This intolerance is hypothesized to be due to concomitant neuropathy and significant restrictive cardiomyopathy. This study analyzes the incidence and characteristics of BB tolerance in patients with amyloid cardiomyopathy.

Methods: Through a single-center retrospective chart review, patients with amyloid cardiomyopathy, confirmed by endomyocardial biopsy or technetium-99 pyrophosphate scan, were identified and clinical data was collected. Statistical methods included Chi-square test and two sample

Results: Of 135 cardiac amyloidosis patients, 27 patients (20.0%) …

Modulation Of Gut Microbiota By Bioactive Compounds For Prevention And Management Of Type 2 Diabetes, Basista Rabina Sharma, Swarna Jaiswal, P.V. Ravindra

Articles

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia and insulin resistance. Gut microbiota (GM) are specific groups of microbes colonized in the gastrointestinal (GI) tract. They profoundly influence health, disease protection, and associated with metabolic activities, and play a vital role in the production of functional metabolites from dietary substances. Dysbiosis of GM has been linked to the onset of T2DM and can be altered to attain eubiosis by intervention with various nutritional bioactive compounds such as polyphenols, prebiotics, and probiotics. This review presents an overview of the evidence and underlying mechanisms by which bioactive …

Identifying Key Elements To Assess Patient’S Acceptability Of Neurorehabilitation In Stroke Survivors–A Delphi Method, Manonita Ghosh, Kaoru Nosaka, Lisa Whitehead, Kazunori Nosaka

Research outputs 2014 to 2021

Purpose: Assessing patient acceptability of treatment is a clinical concern. No guidance exists to determine the best way to measure acceptability in stroke neurorehabilitation. This study identifies key elements to measure patient’s acceptance of stroke neurorehabilitation by establishing expert consensus.

>Materials and methods: A four-phase Delphi method with a three-round electronic-based survey was conducted. Experts were considered as stroke survivors or their caregivers and professionals in stroke neurorehabilitation. A twenty-five-item list was sourced from a literature review and discussion with a consumer panel (n = 22). In Round-1 (n = 118) and Round-2 (n = 80), experts …

The Relevance Of Rich Club Regions For Functional Outcome Post-Stroke Is Enhanced In Women, Anna K. Bonkhoff, Laura Heitsch, Chia-Ling Phuah, Et Al.

2020-Current year OA Pubs

No abstract provided.

Age Differences In The Association Between Sleep And Alzheimer's Disease Biomarkers In The Epad Cohort, Sharon L Naismith, Yue Leng, Jake R Palmer, Brendan P Lucey

2020-Current year OA Pubs

INTRODUCTION: We aimed to determine the independent association between sleep quality and Alzheimer's disease (AD) biomarkers, and whether the associations differ with age.

METHODS: We included 1240 individuals aged ≥50, without dementia from the

RESULTS: For the youngest age tertile, shorter sleep duration and higher sleep efficiency were associated with greater p-tau/Aβ42 ratio. For the oldest tertile, longer sleep latency was associated with greater p-tau/Aβ42.

DISCUSSION: Differential relationships between sleep and AD pathology depend on age. Short sleep duration and sleep efficiency are relevant in middle age whereas time taken to fall asleep is more closely linked to AD biomarkers …

Clinical And Molecular Characteristics Of A Novel Rare De Novo Variant In Ppp2ca In A Patient With A Developmental Disorder, Autism, And Epilepsy, Iris Verbinnen, Sara S Procknow, Lisa Lenaerts, Sara Reynhout, Aujan Mehregan, Chris Ulens, Veerle Janssens, Katherine A King

2020-Current year OA Pubs

PP2A-related (neuro) developmental disorders are a family of genetic diseases caused by a heterozygous alteration in one of several genes encoding a subunit of type 2A protein phosphatases. Reported affected genes, so far, are

Donor Chimerism And Immune Reconstitution Following Haploidentical Transplantation In Sickle Cell Disease, Yaya Chu, Brenda Grossman, Shalini Shenoy, Et Al

2020-Current year OA Pubs

INTRODUCTION: We previously reported the initial results of a phase II multicenter transplant trial using haploidentical parental donors for children and aolescents with high-risk sickle cell disease achieving excellent survival with exceptionally low rates of graft-versus-host disease and resolution of sickle cell disease symptoms. To investigate human leukocyte antigen (HLA) sensitization, graft characteristics, donor chimerism, and immune reconstitution in these recipients.

METHODS: CD34 cells were enriched using the CliniMACS

RESULTS: HLA antibodies were detected in 7 of 11 (64%) evaluable patients but rarely were against donor antigens. Myeloid engraftment was rapid (100%) at a median of 9 days. At 30 …

White Matter Abnormalities In The Hdc Knockout Mouse, A Model Of Tic And Ocd Pathophysiology, Kantiya Jindachomthong, Chengran Yang, Yuegao Huang, Daniel Coman, Maximiliano Rapanelli, Fahmeed Hyder, Joseph Dougherty, Luciana Frick, Christopher Pittenger

2020-Current year OA Pubs

INTRODUCTION: An inactivating mutation in the

MATERIALS AND METHODS: We performed exploratory RNA-seq to identify pathological alterations in several brain regions in

RESULTS: Exploratory RNA-Seq analysis revealed, unexpectedly, that genes associated with oligodendrocytes and with myelin production are upregulated in the dorsal striatum of these mice. This was confirmed by qPCR, immunostaining, and immunoblotting. These results suggest an abnormality in myelination in the striatum. To test this in an intact mouse brain, we performed whole-brain

DISCUSSION: While the DTI literature in individuals with TS is sparse, these results are consistent with findings of disrupted descending cortical projections in patients with …

Resting State Network Mapping In Individuals Using Deep Learning, Patrick H Luckett, John J Lee, Ki Yun Park, Ryan V Raut, Karin L Meeker, Evan M Gordon, Abraham Z Snyder, Beau M Ances, Eric C Leuthardt, Joshua S Shimony

2020-Current year OA Pubs

INTRODUCTION: Resting state functional MRI (RS-fMRI) is currently used in numerous clinical and research settings. The localization of resting state networks (RSNs) has been utilized in applications ranging from group analysis of neurodegenerative diseases to individual network mapping for pre-surgical planning of tumor resections. Reproducibility of these results has been shown to require a substantial amount of high-quality data, which is not often available in clinical or research settings.

METHODS: In this work, we report voxelwise mapping of a standard set of RSNs using a novel deep 3D convolutional neural network (3DCNN). The 3DCNN was trained on publicly available functional …

Expert Guidance On Prophylaxis And Treatment Of Dermatologic Adverse Events With Tumor Treating Fields (Ttfields) Therapy In The Thoracic Region, Milan J Anadkat, Mario Lacouture, Adam Friedman, Zachary D Horne, Jae Jung, Benjamin Kaffenberger, Sujith Kalmadi, Liza Ovington, Rupesh Kotecha, Huda Ismail Abdullah, Federica Grosso

2020-Current year OA Pubs

Tumor Treating Fields (TTFields) are electric fields, delivered via wearable arrays placed on or near the tumor site, that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. As a first-in-class treatment, TTFields therapy is approved for use in newly diagnosed glioblastoma, recurrent glioblastoma, and pleural mesothelioma. Additionally, TTFields therapy is being investigated in non-small cell lung cancer (NSCLC), brain metastases from NSCLC, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, and gastric adenocarcinoma. Because TTFields therapy is well tolerated and delivery is locoregional, there is low risk of additive systemic adverse events (AEs) when used …

Postnatal Osterix But Not Dmp1 Lineage Cells Significantly Contribute To Intramembranous Ossification In Three Preclinical Models Of Bone Injury, Evan G Buettmann, Susumu Yoneda, Pei Hu, Jennifer A Mckenzie, Matthew J Silva

2020-Current year OA Pubs

Murine models of long-bone fracture, stress fracture, and cortical defect are used to discern the cellular and molecular mediators of intramembranous and endochondral bone healing. Previous work has shown that Osterix (Osx

3d Bi-Directional Transformer U-Net For Medical Image Segmentation, Xiyao Fu, Zhexian Sun, Haoteng Tang, Eric M Zou, Heng Huang, Yong Wang, Liang Zhan

2020-Current year OA Pubs

As one of the popular deep learning methods, deep convolutional neural networks (DCNNs) have been widely adopted in segmentation tasks and have received positive feedback. However, in segmentation tasks, DCNN-based frameworks are known for their incompetence in dealing with global relations within imaging features. Although several techniques have been proposed to enhance the global reasoning of DCNN, these models are either not able to gain satisfying performances compared with traditional fully-convolutional structures or not capable of utilizing the basic advantages of CNN-based networks (namely the ability of local reasoning). In this study, compared with current attempts to combine FCNs and …

Mortality In Pediatric Oncology And Stem Cell Transplant Patients With Bloodstream Infections, Daniel N Willis, Mary Claire Mcglynn, Patrick J Reich, Robert J Hayashi

2020-Current year OA Pubs

BACKGROUND: Bloodstream infections (BSI) continue to represent a significant source of morbidity for pediatric oncology patients, however less is known regarding this population's risk of death. We sought to evaluate the risk of BSI and death at a large pediatric cancer center.

METHODS: We retrospectively collected inpatient data from pediatric oncology and hematopoietic stem cell transplant (HSCT) patients over a 9-year period. We performed univariate and multivariable modeling to assess risk of BSI and mortality examining the following variables: demographics, underlying malignancy, history of HSCT, central line type, and febrile neutropenia (FN).

RESULTS: During the study period, 6763 admissions from …

Top-Down And Bottom-Up Propagation Of Disease In The Neuronal Ceroid Lipofuscinoses, John R Ostergaard, Hemanth R Nelvagal, Jonathan D Cooper

2020-Current year OA Pubs

BACKGROUND: The Neuronal Ceroid Lipofuscinoses (NCLs) may be considered distinct neurodegenerative disorders with separate underlying molecular causes resulting from monogenetic mutations. An alternative hypothesis is to consider the NCLs as related diseases that share lipofuscin pathobiology as the common core feature, but otherwise distinguished by different a) initial anatomic location, and b) disease propagation.

METHODS: We have tested this hypothesis by comparing known differences in symptomatology and pathology of the CLN1 phenotype caused by complete loss of

RESULTS: Despite displaying similar pathological endpoints, the clinical phenotypes and the evidence of imaging and

DISCUSSION: The propagation of disease in these two …

Decision-Making Factors For An Autologous Stem Cell Transplant For Older Adults With Newly Diagnosed Multiple Myeloma: A Qualitative Analysis, Owais Mian, Martine Puts, Arleigh Mccurdy, Tanya M Wildes, Mark A Fiala, Matthew Kang, Mary Salib, Shabbir Alibhai, Hira Mian

2020-Current year OA Pubs

PURPOSE: A utologous stem cell transplant (ASCT) remains a standard of care among older adults (aged ≥65) with multiple myeloma (MM). However, heterogeneity in the eligibility and utilization of ASCT remains. We identified decision-making factors that influence ASCT eligibility and utilization among older adults with MM.

METHODS: A qualitative study across two academic and two community centres in Ontario was conducted between July 2019-July 2020. Older adults with MM (newly diagnosed MM aged 65-75 in whom a decision had been made about ASCT in <12 months) and treating oncologists completed a baseline survey and a subsequent interview, which was analyzed using thematic analysis.

RESULTS: Eighteen patients completed the survey and 9 follow-up interviews were conducted. Patients were happy with …

Stat3 Gain-Of-Function Syndrome, Tiphanie P Vogel, Jennifer W Leiding, Megan A Cooper, Lisa R Forbes Satter

2020-Current year OA Pubs

STAT3 gain-of-function (GOF) syndrome is a multi-organ primary immune regulatory disorder characterized by early onset autoimmunity. Patients present early in life, most commonly with lymphoproliferation, autoimmune cytopenias, and growth delay. However, disease is often progressive and can encompass a wide range of clinical manifestations such as: enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, and rarely neurologic disease, vasculopathy, and malignancy. Treatment of the autoimmune and immune dysregulatory features of STAT3-GOF patients relies heavily on immunosuppression and is often challenging and fraught with complications including severe infections. Defects in the T cell compartment leading to effector T cell accumulation …

Do The Expert Recommendations For Implementing Change (Eric) Strategies Adequately Address Sustainment?, Nicole Nathan, Byron J Powell, Rachel C Shelton, Celia V Laur, Luke Wolfenden, Maji Hailemariam, Sze Lin Yoong, Rachel Sutherland, Melanie Kingsland, Thomas J Waltz, Alix Hall

2020-Current year OA Pubs

BACKGROUND: Sustainability science is an emerging area within implementation science. There is limited evidence regarding strategies to best support the continued delivery and sustained impact of evidence-based interventions (EBIs). To build such evidence, clear definitions, and ways to operationalize strategies specific and/or relevant to sustainment are required. Taxonomies and compilations such as the Expert Recommendations for Implementing Change (ERIC) were developed to describe and organize implementation strategies. This study aimed to adapt, refine, and extend the ERIC compilation to incorporate an explicit focus on sustainment. We also sought to classify the specific phase(s) of implementation when the ERIC strategies could …

"Provider Discretionary Power Practices To Support Implementation Of Patient-Centered Hiv Care In Lusaka, Zambia", Chanda Mwamba, Njekwa Mukamba, Anjali Sharma, Kasapo Lumbo, Marksman Foloko, Herbert Nyirenda, Sandra Simbeza, Kombatende Sikombe, Charles B Holmes, Izukanji Sikazwe, Carolyn Bolton Moore, Aaloke Mody, Elvin Geng, Laura K Beres

2020-Current year OA Pubs

INTRODUCTION: Traditional patient-provider relationships privilege the providers, as they possess the formal authority and clinical knowledge applied to address illness, but providers also have discretion over how they exercise their power to influence patients' services, benefits, and sanctions. In this study, we assessed providers' exercise of discretionary power in implementing patient-centered care (PCC) practices in Lusaka, Zambia.

METHODS: HIV clinical encounters between patients on antiretroviral therapy (ART) and providers across 24 public health facilities in Lusaka Province were audio recorded and transcribed verbatim. Using qualitative content analysis, we identified practices of discretionary power (DP) employed in the implementation of PCC …

Low Risk For Developing Diabetes Among The Offspring Of Individuals With Exceptional Longevity And Their Spouses, Iva Miljkovic, Ryan Cvejkus, Ping An, Bharat Thyagarajan, Kaare Christensen, Mary Wojczynski, Nicole Schupf, Joseph M Zmuda

2020-Current year OA Pubs

Little is known about the risk of type 2 diabetes (T2D) among the offspring of individuals with exceptional longevity. We determined the incidence of and potential risk and protective factors for T2D among the offspring of probands and offspring's spouses (mean age=60 years, range 32-88 years) in the Long Life Family Study (LLFS), a multicenter cohort study of 583 two-generation families with a clustering of healthy aging and exceptional longevity. Incident T2D was defined as fasting serum glucose ≥126 mg/dl, or HbA1c of ≥6.5%, or self-reported with doctor diagnosis of T2D, or the use of anti-diabetic medication during a mean …

Outcomes Following In-Hospital Cardiopulmonary Resuscitation In People Receiving Maintenance Dialysis, Fahad Saeed, Haris F Murad, Richard E Wing, Jianbo Li, Jesse D Schold, Kevin A Fiscella

2020-Current year OA Pubs

RATIONALE & OBJECTIVE: Previous studies showing poor cardiopulmonary resuscitation (CPR) outcomes in the dialysis population have largely been derived from claims data and are somewhat limited by a lack of detailed characterization of CPR events. We aimed to analyze CPR-related outcomes in individuals receiving maintenance dialysis.

STUDY DESIGN: Retrospective chart review.

SETTING & PARTICIPANTS: Using electronic medical records from a single academic health care system, we identified all hospitalized adult patients receiving maintenance dialysis who had undergone in-hospital CPR between 2006 and 2014.

EXPOSURE: Initial in-hospital CPR.

OUTCOMES: Overall survival, predictors of unsuccessful CPR, predictors of death during the same …

Alopecia Areata After Mogamulizumab Treatment, Neel S Raval, Nora A Alexander, Karlee De Monnin, Christine C Yokoyama, Neha Mehta-Shah, Ilana S Rosman, Amy C Musiek

2020-Current year OA Pubs

No abstract provided.

Calorie Restriction Improves Lipid-Related Emerging Cardiometabolic Risk Factors In Healthy Adults Without Obesity: Distinct Influences Of Bmi And Sex From Calerie™ A Multicentre, Phase 2, Randomised Controlled Trial, Kim M Huffman, Susan B Racette, Et Al.

2020-Current year OA Pubs

BACKGROUND: For many cardiovascular risk factors there is no lower limit to which further reduction will result in decreased disease risk; this includes values within ranges considered normal for healthy adults. This seems to be true for new emerging metabolic risk factors identified by innovative technological advances. Further, there seems to be ever evolving evidence of differential responses to lifestyle interventions by sex and body compositions in the normal range. In this secondary analysis, we had the opportunity to test these principles for newly identified molecular biomarkers of cardiometabolic risk in a young (21-50 years), normal weight healthy population undergoing …

Multiple Conserved States Characterize The Twist Landscape Of The Bacterial Actin Homolog Mreb, Benjamin D Knapp, Michael D Ward, Gregory R Bowman, Handuo Shi, Kerwyn Casey Huang

2020-Current year OA Pubs

Filament formation by cytoskeletal proteins is critical to their involvement in myriad cellular processes. The bacterial actin homolog MreB, which is essential for cell-shape determination in many rod-shaped bacteria, has served as a model system for studying the mechanics of cytoskeletal filaments. Previous molecular dynamics (MD) simulations revealed that the twist of MreB double protofilaments is dependent on the bound nucleotide, as well as binding to the membrane or the accessory protein RodZ, and MreB mutations that modulate twist also affect MreB spatial organization and cell shape. Here, we show that MreB double protofilaments can adopt multiple twist states during …

Evaluating The Implementation Of A Multi-Level Mhealth Study To Improve Hydroxyurea Utilization In Sickle Cell Disease, J S Hankins, A A King, A A Baumann, L M. Klesges, Et Al.

2020-Current year OA Pubs

BACKGROUND: Sickle Cell Disease (SCD) is a progressive genetic disease that causes organ damage and reduces longevity. Hydroxyurea is an underutilized evidence-based medication that reduces complications and improves survival in SCD. In a multi-site clinical trial, part of the NIH-funded Sickle Cell Disease Implementation Consortium (SCDIC), we evaluate the implementation of a multi-level and multi-component mobile health (mHealth) patient and provider intervention to target the determinants and context of low hydroxyurea use. Given the complexity of the intervention and contextual variability in its implementation, we combined different behavioral and implementation theories, models, and frameworks to facilitate the evaluation of the …

Automatic Wide Complex Tachycardia Differentiation Using Mathematically Synthesized Vectorcardiogram Signals, Anthony H Kashou, Sarah Lococo, Trevon D Mcgill, Christopher M Evenson, Abhishek J Deshmukh, David O Hodge, Daniel H Cooper, Sandeep S Sodhi, Phillip S Cuculich, Samuel J Asirvatham, Peter A Noseworthy, Christopher V Desimone, Adam M May

2020-Current year OA Pubs

BACKGROUND: Automated wide complex tachycardia (WCT) differentiation into ventricular tachycardia (VT) and supraventricular wide complex tachycardia (SWCT) may be accomplished using novel calculations that quantify the extent of mean electrical vector changes between the WCT and baseline electrocardiogram (ECG). At present, it is unknown whether quantifying mean electrical vector changes within three orthogonal vectorcardiogram (VCG) leads (X, Y, and Z leads) can improve automated VT and SWCT classification.

METHODS: A derivation cohort of paired WCT and baseline ECGs was used to derive five logistic regression models: (i) one novel WCT differentiation model (i.e., VCG Model), (ii) three previously developed WCT …

Characterization Of The Genomic And Immunologic Diversity Of Malignant Brain Tumors Through Multisector Analysis, Maximilian O Schaettler, Megan M Richters, Anthony Z Wang, Zachary L Skidmore, Bryan Fisk, Albert H Kim, Michael R Chicoine, Joshua W Osbun, Eric C Leuthardt, Joshua L Dowling, Gregory J Zipfel, Ralph G Dacey, Hsiang-Chih Lu, Tanner M Johanns, Obi L Griffith, Malachi Griffith, Gavin P Dunn, Et Al.

2020-Current year OA Pubs

Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary brain malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated in treatment resistance, it remains unclear whether this diversity is observed within brain metastases and to what extent cancer cell-intrinsic heterogeneity sculpts the local immune microenvironment. Here, we profiled the immunogenomic state of 93 spatially distinct regions from 30 malignant brain tumors through whole-exome, RNA, and T-cell receptor sequencing. Our analyses identified differences between primary and secondary malignancies, with gliomas displaying more spatial heterogeneity at the genomic and neoantigen …