Digital Commons Network^™

How Should We Define A Nociceptor In The Gut-Brain Axis?, Nick J Spencer, Tim Hibberd, Zili Xie, Hongzhen Hu

2020-Current year OA Pubs

In the past few years, there has been extraordinary interest in how the gut communicates with the brain. This is because substantial and gathering data has emerged to suggest that sensory nerve pathways between the gut and brain may contribute much more widely in heath and disease, than was originally presumed. In the skin, the different types of sensory nerve endings have been thoroughly characterized, including the morphology of different nerve endings and the sensory modalities they encode. This knowledge is lacking for most types of visceral afferents, particularly spinal afferents that innervate abdominal organs, like the gut. In fact, …

Fluorescence Imaging Of Beta Cell Primary Cilia, Zipeng A Li, Jung Hoon Cho, Louis G Woodhams, Jing W Hughes

2020-Current year OA Pubs

Primary cilia are slender cell-surface organelles that project into the intercellular space. In pancreatic beta cells, primary cilia coordinate a variety of cell responses including GPCR signaling, calcium influx, and insulin secretion, along with likely many underappreciated roles in islet development and differentiation. To study cilia function in islet biology, direct visualization of primary cilia by microscopic methods is often a necessary first step. Ciliary abundance, distribution, and morphology are heterogeneous among islet cells and are best visualized by fluorescence microscopy, the tools for which are readily accessible to most researchers. Here we present a collection of fluorescence imaging methods …

Infantile-Onset Pompe Disease Complicated By Sickle Cell Anemia: Case Report And Management Considerations, Rodrigo Tzovenos Starosta, Ying-Chen Claire Hou, Katelyn Leestma, Prapti Singh, Luke Viehl, Linda Manwaring, Jorge Luis Granadillo, Molly C Schroeder, Jamie N Colombo, Halana Whitehead, Patricia Irene Dickson, Monica L Hulbert, Hoanh Thi Nguyen

2020-Current year OA Pubs

Infantile-onset Pompe disease (IOPD) is a rare, severe disorder of lysosomal storage of glycogen that leads to progressive cardiac and skeletal myopathy. IOPD is a fatal disease in childhood unless treated with enzyme replacement therapy (ERT) from an early age. Sickle cell anemia (SCA) is a relatively common hemoglobinopathy caused by a specific variant in the hemoglobin beta-chain. Here we report a case of a male newborn of African ancestry diagnosed and treated for IOPD and SCA. Molecular testing confirmed two

Abnormal Synergies And Associated Reactions Post-Hemiparetic Stroke Reflect Muscle Activation Patterns Of Brainstem Motor Pathways, Laura M Mcpherson, Julius P A Dewald

2020-Current year OA Pubs

Individuals with moderate-to-severe post-stroke hemiparesis cannot control proximal and distal joints of the arm independently because they are constrained to stereotypical movement patterns called flexion and extension synergies. Accumulating evidence indicates that these synergies emerge because of upregulation of diffusely projecting brainstem motor pathways following stroke-induced damage to corticofugal pathways. During our recent work on differences in synergy expression among proximal and distal joints, we serendipitously observed some notable characteristics of synergy-driven muscle activation. It seemed that: paretic wrist/finger muscles were activated maximally during contractions of muscles at a different joint; differences in the magnitude of synergy expression occurred when …

The Mobile Sleep Medicine Model In Neurologic Practice: Rationale And Application, Mark I Boulos, Luqi Chi, Oleg Y Chernyshev

2020-Current year OA Pubs

BACKGROUND: Undiagnosed obstructive sleep apnea (OSA) is prevalent in neurological practice and significantly contributes to morbidity and mortality. OSA is prevalent in US adults and causes poor quality sleep and significant neurocognitive, cardiovascular, and cerebrovascular impairments. Timely treatment of OSA reduces cardio-cerebrovascular risks and improves quality of life. However, most of the US population has limited systematic access to sleep medicine care despite its clinical significance.

FOCUS: We discuss the importance of systematic screening, testing, and best-practice management of OSA and hypoventilation/hypoxemia syndromes (HHS) in patients with stroke, neurocognitive impairment, and neuromuscular conditions. This review aims to introduce and describe …

Intraocular Human Cytomegaloviruses Of Ocular Diseases Are Distinct From Those Of Viremia And Are Capable Of Escaping From Innate And Adaptive Immunity By Exploiting Hla-E-Mediated Peripheral And Central Tolerance, Mariko Shirane, Michael Paley, Wayne M Yokoyama, Et Al.

2020-Current year OA Pubs

Human cytomegalovirus (HCMV) infections develop into CMV diseases that result in various forms of manifestations in local organs. CMV-retinitis is a form of CMV disease that develops in immunocompromised hosts with CMV-viremia after viruses in the peripheral circulation have entered the eye. In the HCMV genome, extensive diversification of the UL40 gene has produced peptide sequences that modulate NK cell effector functions when loaded onto HLA-E and are subsequently recognized by the NKG2A and NKG2C receptors. Notably, some HCMV strains carry UL40 genes that encode peptide sequences identical to the signal peptide sequences of specific HLA-A and HLA-C allotypes, which …

Environmentally-Triggered Contraction Of The Norovirus Virion Determines Diarrheagenic Potential, Emily W Helm, Elizabeth A Kennedy, Megan T Baldridge, Et Al.

2020-Current year OA Pubs

Noroviruses are the leading cause of severe childhood diarrhea and foodborne disease worldwide. While they are a major cause of disease in all age groups, infections in the very young can be quite severe with annual estimates of 50,000-200,000 fatalities in children under 5 years old. In spite of the remarkable disease burden associated with norovirus infections in people, very little is known about the pathogenic mechanisms underlying norovirus diarrhea, principally because of the lack of tractable small animal models. We recently demonstrated that wild-type neonatal mice are susceptible to murine norovirus (MNV)-induced acute self-resolving diarrhea in a time course …

Automated Lesion Detection Of Breast Cancer In [18f] Fdg Pet/Ct Using A Novel Ai-Based Workflow, Jeffrey P Leal, Steven P Rowe, Vered Stearns, Roisin M Connolly, Christos Vaklavas, Minetta C Liu, Anna Maria Storniolo, Richard L Wahl, Martin G Pomper, Lilja B Solnes

2020-Current year OA Pubs

UNLABELLED: Applications based on artificial intelligence (AI) and deep learning (DL) are rapidly being developed to assist in the detection and characterization of lesions on medical images. In this study, we developed and examined an image-processing workflow that incorporates both traditional image processing with AI technology and utilizes a standards-based approach for disease identification and quantitation to segment and classify tissue within a whole-body [

METHODS: One hundred thirty baseline PET/CT studies from two multi-institutional preoperative clinical trials in early-stage breast cancer were semi-automatically segmented using techniques based on PERCIST v1.0 thresholds and the individual segmentations classified as to tissue …

Personalized Practice Dosages May Improve Motor Learning In Older Adults Compared To "Standard Of Care" Practice Dosages: A Randomized Controlled Trial, Geneviève N Olivier, Leland E Dibble, Serene S Paul, Keith R Lohse, Christopher S Walter, Ryan J Marker, Heather A Hayes, K Bo Foreman, Kevin Duff, Sydney Y Schaefer

2020-Current year OA Pubs

Standard dosages of motor practice in clinical physical rehabilitation are insufficient to optimize motor learning, particularly for older patients who often learn at a slower rate than younger patients. Personalized practice dosing (i.e., practicing a task to or beyond one's plateau in performance) may provide a clinically feasible method for determining a dose of practice that is both standardized and individualized, and may improve motor learning. The purpose of this study was to investigate whether personalized practice dosages [

The First 20 Months Of The Covid-19 Pandemic: Mortality, Intubation And Icu Rates Among 104,590 Patients Hospitalized At 21 United States Health Systems, Michael C. Fiore, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

MAIN OBJECTIVE: There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic.

STUDY DESIGN AND METHODS: University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR …

Neurofibromatosis-1 Gene Mutational Profiles Differ Between Syndromic Disease And Sporadic Cancers, Alice F. Bewley, Titilope M. Akinwe, Tychele N. Turner, David H. Gutmann

2020-Current year OA Pubs

No abstract provided.

All-Cause And In-Hospital Mortality After Aspirin Use In Patients Hospitalized With Covid-19: A Systematic Review And Meta-Analysis, Nischit Baral, Joshua D Mitchell, Pramod K Savarapu, Maxwell Akanbi, Bandana Acharya, Soumya Kambalapalli, Amith Seri, Krishna P Bashyal, Arvind Kunadi, Niranjan Ojha, Annabelle Santos Volgman, Tripti Gupta, Timir K Paul

2020-Current year OA Pubs

BACKGROUND: With the results of the largest randomized controlled trial (RECOVERY) and the most extensive retrospective cohort study on coronavirus disease 2019 (COVID-19) recently published, we performed a meta-analysis on the association of aspirin with mortality of COVID-19. We aimed to investigate the role of aspirin in COVID-19 hospitalizations.

MATERIALS AND METHODS: We searched PubMed, EMBASE and Cochrane databases for studies from 1 January 2020 until 20 July 2022, that compared aspirin versus non-aspirin use in hospitalized COVID-19 patients. We excluded case reports, review articles and studies on non-hospitalized COVID-19 infections. We used the inverse variance method and random effects …

Variation In Ampicillin Dosing For Lower Respiratory Tract Infections And Neonatal Bacterial Infections In Us Children's Hospitals, Elizabeth A Daniels, Christopher C Mcpherson, Jason G Newland, Brian R Lee

2020-Current year OA Pubs

OBJECTIVE: We examined ampicillin dosing in pediatric patients across 3 conditions: (1) bacterial lower respiratory tract infections (LRTIs) in infants and children >3 months, (2) neonates with suspected or proven sepsis, and (3) neonates with suspected central nervous system (CNS) infections. We compared our findings to dosing guidance for these specific indications.

DESIGN: Retrospective cohort study.

SETTING: The study included data from 32 children's hospitals in the United States.

METHODS: We reviewed prescriptions from the SHARPS study of antimicrobials, a survey of antibiotic prescribing from July 2016 to December 2017. Prescriptions were analyzed for indication, total daily dose per kilogram, …

Theta-Gamma Coupling As A Cortical Biomarker Of Brain-Computer Interface-Mediated Motor Recovery In Chronic Stroke, Nabi Rustamov, Joseph Humphries, Alexandre Carter, Eric C Leuthardt

2020-Current year OA Pubs

Chronic stroke patients with upper-limb motor disabilities are now beginning to see treatment options that were not previously available. To date, the two options recently approved by the United States Food and Drug Administration include vagus nerve stimulation and brain-computer interface therapy. While the mechanisms for vagus nerve stimulation have been well defined, the mechanisms underlying brain-computer interface-driven motor rehabilitation are largely unknown. Given that cross-frequency coupling has been associated with a wide variety of higher-order functions involved in learning and memory, we hypothesized this rhythm-specific mechanism would correlate with the functional improvements effected by a brain-computer interface. This study …

Hydroxychloroquine/Chloroquine For The Treatment Of Hospitalized Patients With Covid-19: An Individual Participant Data Meta-Analysis, Leon Di Stefano, Jane A. O'Halloran, Adriana M. Rauseo, Et Al

2020-Current year OA Pubs

BACKGROUND: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients.

METHODS: We searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 …

A Conformational Variant Of P53 (U-P53az) As Blood-Based Biomarker For The Prediction Of The Onset Of Symptomatic Alzheimer's Disease, S Piccirella, L Van Neste, C Fowler, C L Masters, J Fripp, J D Doecke, C Xiong, D Uberti, P Kinnon

2020-Current year OA Pubs

BACKGROUND: Ongoing research seeks to identify blood-based biomarkers able to predict onset and progression of Alzheimer's disease (AD).

OBJECTIVE: The unfolded conformational variant of p53 (U-p53AZ), previously observed in AD individuals, was evaluated in plasma samples from individuals participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) cohort for diagnostic and prognostic assessment, validated on a neuropsychological-based diagnosis, over the course of six years.

DESIGN: Retrospective Longitudinal Prognostic biomarker study.

SETTING: Single-center study based on the AIBL cohort.

PARTICIPANTS: 482 participants of the AIBL cohort, aged 60-85 years, without uncontrolled diabetes, vascular disease, severe depression or psychiatric illnesses.

MEASUREMENTS: The …

A Comparison Of 64cu-Labeled Bi-Terminally Pegylated A20fmdv2 Peptides Targeting Integrin Ανβ6, Truc T Huynh, Sreeja Sreekumar, Cedric Mpoy, Buck E Rogers

2020-Current year OA Pubs

Expression of epithelial-specific integrin α

Bruton's Tyrosine Kinase Supports Gut Mucosal Immunity And Commensal Microbiome Recognition In Autoimmune Arthritis, Rachel H Bonami, Christina E Thurman, Sonam Verma, Camille S Westlake, Lindsay E Nyhoff, Bridgette B Barron, Andrea Reboldi, Peggy L Kendall

2020-Current year OA Pubs

Bruton's tyrosine kinase (

Rhamnose Is Superior To Mannitol As A Monosaccharide In The Dual Sugar Absorption Test: A Prospective Randomized Study In Children With Treatment-Naïve Celiac Disease, Lori R Holtz, Julie Hoffmann, Laura Linneman, Mai He, Thomas C Smyrk, Ta-Chiang Liu, Nurmohammad Shaikh, Cynthia Rodriguez, Roy B Dyer, Ravinder J Singh, William A Faubion

2020-Current year OA Pubs

BACKGROUND AND AIM: We sought to correlate two different measures of gut permeability [lactulose:mannitol (L:M) and lactulose:rhamnose (L:R)] to the severity of duodenal histopathology in children with and without elevated antibodies to tissue transglutaminase (tTG). A secondary objective was to correlate gut permeability with celiac disease (CD) serology and indices of inflammation and bacterial product translocation.

METHODS: We prospectively randomized children undergoing endoscopy with abnormal (

RESULTS: Of the 54 cases with positive celiac serology, 31 and 69% had modified Marsh 0/1 scores or ≥3a, respectively. Circulating tTG IgA correlated with the modified Marsh score (

CONCLUSIONS: L:R, but not …

Relief Of Chronic Pain Associated With Increase In Midline Frontal Theta Power, Nabi Rustamov, Elizabeth A. Wilson, Alexandra E. Fogarty, Lara W. Crock, Eric C. Leuthardt, Simon Haroutounian

2020-Current year OA Pubs

INTRODUCTION: There is a need to identify objective cortical electrophysiological correlates for pain relief that could potentially contribute to a better pain management. However, the field of developing brain biomarkers for pain relief is still largely underexplored.

OBJECTIVES: The objective of this study was to investigate cortical electrophysiological correlates associated with relief from chronic pain. Those features of pain relief could serve as potential targets for novel therapeutic interventions to treat pain.

METHODS: In 12 patients with chronic pain in the upper or lower extremity undergoing a clinically indicated nerve block procedure, brain activity was recorded by means of electroencephalogram …

Investing In Late-Life Brain Capital, Walter D Dawson, Eric J Lenze, Et Al.

2020-Current year OA Pubs

Within many societies and cultures around the world, older adults are too often undervalued and underappreciated. This exacerbates many key challenges that older adults may face. It also undermines the many positive aspects of late life that are of tremendous value at both an individual and societal level. We propose a new approach to elevate health and well-being in late life by optimizing late-life Brain Capital. This form of capital prioritizes brain skills and brain health in a brain economy, which the challenges and opportunities of the 21st-century demands. This approach incorporates investing in late-life Brain Capital, developing initiatives focused …

Covariance And Correlation Analysis Of Resting State Functional Magnetic Resonance Imaging Data Acquired In A Clinical Trial Of Mindfulness-Based Stress Reduction And Exercise In Older Individuals, Abraham Z Snyder, Tomoyuki Nishino, Joshua S Shimony, Eric J Lenze, Julie Loebach Wetherell, Michelle Voegtle, J Philip Miller, Michael D Yingling, Daniel Marcus, Jenny Gurney, Jerrel Rutlin, Drew Scott, Lisa Eyler, Deanna Barch

2020-Current year OA Pubs

We describe and apply novel methodology for whole-brain analysis of resting state fMRI functional connectivity data, combining conventional multi-channel Pearson correlation with covariance analysis. Unlike correlation, covariance analysis preserves signal amplitude information, which feature of fMRI time series may carry physiological significance. Additionally, we demonstrate that dimensionality reduction of the fMRI data offers several computational advantages including projection onto a space of manageable dimension, enabling linear operations on functional connectivity measures and exclusion of variance unrelated to resting state network structure. We show that group-averaged, dimensionality reduced, covariance and correlation matrices are related, to reasonable approximation, by a single scalar …

Semi-Quantitative Assay To Measure Urease Activity By Urinary Catheter-Associated Uropathogens, Jesus M Duran Ramirez, Jana Gomez, Chloe L P Obernuefemann, Nathaniel C Gualberto, Jennifer N Walker

2020-Current year OA Pubs

Catheter-associated urinary tract infections (CAUTIs) are one of the most common healthcare-associated infections in the US, accounting for over 1 million cases annually and totaling 450 million USD. CAUTIs have high morbidity and mortality rates and can be caused by a wide range of pathogens, making empiric treatment difficult. Furthermore, when urease-producing uropathogens cause symptomatic CAUTI or asymptomatic catheter colonization, the risk of catheter failure due to blockage increases. The enzyme urease promotes catheter blockage by hydrolyzing urea in urine into ammonia and carbon dioxide, which results in the formation of crystals that coat the catheter surface. If CAUTI is …

Role Of Tau Deposition In Early Cognitive Decline In Down Syndrome, Sigan L Hartley, Benjamin L Handen, Dana Tudorascu, Laise Lee, Annie Cohen, Brianna Piro-Gambetti, Matthew Zammit, William Klunk, Charles Laymon, Shahid Zaman, Beau M Ances, Marwan Sabbagh, Bradley T Christian

2020-Current year OA Pubs

INTRODUCTION: Drawing on the amyloid/tau/neurodegeneration (AT[N]) model, the study examined whether the tau positron emission tomography (PET) biomarker [

METHODS: Data from 123 non-demented adults with DS (

RESULTS: In models adjusting for controls, tau SUVR was negatively associated with episodic memory performance in the Aβ+ but not Aβ- group. The Aβ+/T

DISCUSSION: Similar to late-onset and autosomal dominant Alzheimer's disease (AD), high tau was an indicator of early prodromal AD in DS.

Protocol For The Perioperative Outcome Risk Assessment With Computer Learning Enhancement (Periop Oracle) Randomized Study, Bradley Fritz, Christopher King, Yixin Chen, Alex Kronzer, Joanna Abraham, Arbi Ben Abdallah, Thomas Kannampallil, Thaddeus Budelier, Arianna Montes De Oca, Sherry Mckinnon, Bethany Tellor Pennington, Troy Wildes, Michael Avidan

2020-Current year OA Pubs

No abstract provided.

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 …

Co-Clinical Fdg-Pet Radiomic Signature In Predicting Response To Neoadjuvant Chemotherapy In Triple-Negative Breast Cancer, Sudipta Roy, Timothy D Whitehead, Shunqiang Li, Foluso O Ademuyiwa, Richard L Wahl, Farrokh Dehdashti, Kooresh I Shoghi

2020-Current year OA Pubs

PURPOSE: We sought to exploit the heterogeneity afforded by patient-derived tumor xenografts (PDX) to first, optimize and identify robust radiomic features to predict response to therapy in subtype-matched triple negative breast cancer (TNBC) PDX, and second, to implement PDX-optimized image features in a TNBC co-clinical study to predict response to therapy using machine learning (ML) algorithms.

METHODS: TNBC patients and subtype-matched PDX were recruited into a co-clinical FDG-PET imaging trial to predict response to therapy. One hundred thirty-one imaging features were extracted from PDX and human-segmented tumors. Robust image features were identified based on reproducibility, cross-correlation, and volume independence. A …

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 …

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 …

Genetic And Transcriptional Contributions To Relapse In Normal Karyotype Acute Myeloid Leukemia, Allegra A Petti, Saad M Khan, Ziheng Xu, Nichole Helton, Catrina C Fronick, Robert Fulton, Sai M Ramakrishnan, Sridhar Nonavinkere Srivatsan, Sharon E Heath, Peter Westervelt, Jacqueline E Payton, Matthew J Walter, Daniel C Link, John Dipersio, Christopher Miller, Timothy J Ley

2020-Current year OA Pubs

To better understand clonal and transcriptional adaptations after relapse in patients with acute myeloid leukemia (AML), we collected presentation and relapse samples from six normal karyotype AML cases. We performed enhanced whole-genome sequencing to characterize clonal evolution, and deep-coverage single-cell RNA sequencing on the same samples, which yielded 142,642 high-quality cells for analysis. Identifying expressed mutations in individual cells enabled us to discriminate between normal and AML cells, to identify coordinated changes in the genome and transcriptome, and to identify subclone-specific cell states. We quantified the coevolution of genetic and transcriptional heterogeneity during AML progression, and found that transcriptional changes …