Medicine and Health Sciences Commons^™

Genome-Wide Epistatic Network Analyses Of Semantic Fluency In Older Adults, Qihua Tan, Weilong Li, Marianne Nygaard, Ping An, Mary Feitosa, Mary K Wojczynski, Joseph Zmuda, Konstantin Arbeev, Svetlana Ukraintseva, Anatoliy Yashin, Kaare Christensen, Jonas Mengel-From

2020-Current year OA Pubs

Semantic fluency impairment has been attributed to a wide range of neurocognitive and psychiatric conditions, especially in the older population. Moderate heritability estimates on semantic fluency were obtained from both twin and family-based studies suggesting genetic contributions to the observed variation across individuals. Currently, effort in identifying the genetic variants underlying the heritability estimates for this complex trait remains scarce. Using the semantic fluency scale and genome-wide SNP genotype data from the Long Life Family Study (LLFS), we performed a genome-wide association study (GWAS) and epistasis network analysis on semantic fluency in 2289 individuals aged over 60 years from the …

Hyper-Physiologic Mechanical Cues, As An Osteoarthritis Disease-Relevant Environmental Perturbation, Cause A Critical Shift In Set Points Of Methylation At Transcriptionally Active Cpg Sites In Neo-Cartilage Organoids, Niek G C Bloks, Amanda Dicks, Zainab Harissa, Rob G H H Nelissen, Ghazaleh Hajmousa, Yolande F M Ramos, Rodrigo Coutinho De Almeida, Farshid Guilak, Ingrid Meulenbelt

2020-Current year OA Pubs

BACKGROUND: Osteoarthritis (OA) is a complex, age-related multifactorial degenerative disease of diarthrodial joints marked by impaired mobility, joint stiffness, pain, and a significant decrease in quality of life. Among other risk factors, such as genetics and age, hyper-physiological mechanical cues are known to play a critical role in the onset and progression of the disease (Guilak in Best Pract Res Clin Rheumatol 25:815-823, 2011). It has been shown that post-mitotic cells, such as articular chondrocytes, heavily rely on methylation at CpG sites to adapt to environmental cues and maintain phenotypic plasticity. However, these long-lasting adaptations may eventually have a negative …

Substrate Mechanics Unveil Early Structural And Functional Pathology In Ipsc Micro-Tissue Models Of Hypertrophic Cardiomyopathy, Jingxuan Guo, Huanzhu Jiang, David Schuftan, Jonathan D Moreno, Ghiska Ramahdita, Lavanya Aryan, Druv Bhagavan, Jonathan Silva, Nathaniel Huebsch

2020-Current year OA Pubs

Hypertension is a major cause of morbidity and mortality in patients with hypertrophic cardiomyopathy (HCM), suggesting a potential role for mechanics in HCM pathogenesis. Here, we developed an

Cerebral Near‐Infrared Spectroscopy Use In Neonates: Current Perspectives, Zachary A. Vesoulis, Danielle P. Sharp, Natasha Lalos, Devon P. Swofford, Valerie Y. Chock

2020-Current year OA Pubs

No abstract provided.

The Ire1Α/Xbp1 Pathway Sustains Cytokine Responses Of Group 3 Innate Lymphoid Cells In Inflammatory Bowel Disease, Siyan Cao, Jose L. Fachi, Kaiming Ma, Alina Ulezko Antonova, Qianli Wang, Zhangying Cai, Randal J. Kaufman, Matthew A. Ciorba, Parakkal Deepak, Marco Colonna

2020-Current year OA Pubs

Group 3 innate lymphoid cells (ILC3s) are key players in intestinal homeostasis. ER stress is linked to inflammatory bowel disease (IBD). Here, we used cell culture, mouse models, and human specimens to determine whether ER stress in ILC3s affects IBD pathophysiology. We show that mouse intestinal ILC3s exhibited a 24-hour rhythmic expression pattern of the master ER stress response regulator inositol-requiring kinase 1α/X-box-binding protein 1 (IRE1α/XBP1). Proinflammatory cytokine IL-23 selectively stimulated IRE1α/XBP1 in mouse ILC3s through mitochondrial ROS (mtROS). IRE1α/XBP1 was activated in ILC3s from mice exposed to experimental colitis and in inflamed human IBD specimens. Mice with Ire1α deletion …

A Systematic Review To Determine The Effect Of Strategies To Sustain Chronic Disease Prevention Interventions In Clinical And Community Settings: Study Protocol, Edward Riley-Gibson, Byron J Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: The primary purpose of this review is to synthesise the effect of strategies aiming to sustain the implementation of evidenced-based interventions (EBIs) targeting key health behaviours associated with chronic disease (i.e. physical inactivity, poor diet, harmful alcohol use, and tobacco smoking) in clinical and community settings. The field of implementation science is bereft of an evidence base of effective sustainment strategies, and as such, this review will provide important evidence to advance the field of sustainability research.

METHODS: This systematic review protocol is reported in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) checklist. Methods …

Distinct Autoantibody Profiles Across Checkpoint Inhibitor Types And Toxicities, Hong Mu-Mosley, Mitchell S Von Itzstein, Farjana Fattah, Jialiang Liu, Chengsong Zhu, Yang Xie, Edward K Wakeland, Jason Y Park, Brad S Kahl, Catherine S Diefenbach, David E Gerber

2020-Current year OA Pubs

Immune checkpoint inhibitors (ICI) are increasingly used in combination. To understand the effects of different ICI categories, we characterized changes in circulating autoantibodies in patients enrolled in the E4412 trial (NCT01896999) of brentuximab vedotin (BV) plus ipilimumab, BV plus nivolumab, or BV plus ipilimumab-nivolumab for Hodgkin Lymphoma. Cycle 2 Day 1 (C2D1) autoantibody levels were compared to pre-treatment baseline. Across 112 autoantibodies tested, we generally observed increases in ipilimumab-containing regimens, with decreases noted in the nivolumab arm. Among 15 autoantibodies with significant changes at C2D1, all nivolumab cases exhibited decreases, with more than 90% of ipilimumab-exposed cases showing increases. Autoantibody …

A Common Polymorphism In The Intelectin-1 Gene Influences Mucus Plugging In Severe Asthma, Jamie L Everman, Kaharu Sumino, David S. Gierada, Et Al.

2020-Current year OA Pubs

By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC

Hiv-1 Capsid Stability And Reverse Transcription Are Finely Balanced To Minimize Sensing Of Reverse Transcription Products Via The Cgas-Sting Pathway, Jenna E Eschbach, Maritza Puray-Chavez, Shawn Mohammed, Qiankun Wang, Ming Xia, Lin-Chen Huang, Liang Shan, Sebla B Kutluay

2020-Current year OA Pubs

UNLABELLED: A critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms the conical core when it rearranges around the dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune sensing of HIV-1, a direct link between core stability and sensing of HIV-1 nucleic acids has not been established. Herein, we assessed how manipulating the stability of the CA lattice through chemical and genetic approaches affects innate immune recognition of HIV-1. We found that destabilization of the CA lattice resulted in potent sensing of reverse transcription products when destabilization

IMPORTANCE: …

Visual Deprivation During Mouse Critical Period Reorganizes Network-Level Functional Connectivity, Siyu Chen, Rachel M Rahn, Annie R Bice, Seana H Gaines, Jonah A Padawer-Curry, Keith B Hengen, Joseph D Dougherty, Joseph P Culver

2020-Current year OA Pubs

A classic example of experience-dependent plasticity is ocular dominance (OD) shift, in which the responsiveness of neurons in the visual cortex is profoundly altered following monocular deprivation (MD). It has been postulated that OD shifts also modify global neural networks, but such effects have never been demonstrated. Here, we use wide-field fluorescence optical imaging (WFOI) to characterize calcium-based resting-state functional connectivity during acute (3 d) MD in female and male mice with genetically encoded calcium indicators (

Assessment Of The Characteristics Of Covid-19 Infection Among Healthcare Personnel Working In Long-Term Care Facilities, Armaghan-E-Rehman Mansoor, Caroline A O'Neil, David Mcdonald, Victoria J Fraser, Hilary M Babcock, Jennie H Kwon

2020-Current year OA Pubs

Between May and June 2021, healthcare personnel at two long-term care facilities underwent SARS-CoV-2 anti-nucleocapsid immunoglobulin G testing and completed a survey on COVID-19 exposures and symptoms. Antibody positivity rate was 8.9%. Similar rates of COVID-19 exposure occurred in non-occupational and occupational settings, with high self-reported adherence to workplace infection prevention practices.

Urinary Proteomics And Outcomes In Heart Failure With Preserved Ejection Fraction, Corinne Carland, Ali Javaheri, Douglas L Mann, Et Al.

2020-Current year OA Pubs

BACKGROUND: Although several studies have addressed plasma proteomics in heart failure with preserved ejection fraction, limited data are available on the prognostic value of urinary proteomics. The objective of our study was to identify urinary proteins/peptides associated with death and heart failure admission in patients with heart failure with preserved ejection fraction.

METHODS AND RESULTS: The study population included participants enrolled in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). The relationship between urine protein levels and the risk of death or heart failure admission was assessed using Cox regression, in both nonadjusted analyses and …

Persistent Inequities In Intravenous Thrombolysis For Acute Ischemic Stroke In The United States: Results From The Nationwide Inpatient Sample, Philip Sun, Ling Zheng, Michelle Lin, Steven Cen, Gmerice Hammond, Karen E Joynt Maddox, May Kim-Tenser, Nerses Sanossian, William Mack, Amytis Towfighi

2020-Current year OA Pubs

BACKGROUND: Despite its approval for acute ischemic stroke >25 years ago, intravenous thrombolysis (IVT) remains underused, with inequities by age, sex, race, ethnicity, and geography. Little is known about IVT rates by insurance status.

METHODS AND RESULTS: We assessed temporal trends from 2002 to 2015 in IVT for acute ischemic stroke in the Nationwide Inpatient Sample using adjusted, survey

CONCLUSIONS: IVT for acute ischemic stroke increased among adults. Despite some encouraging trends, the remaining disparities highlight the need for intensified efforts at addressing inequities.

Deficiency Of Il-22-Binding Protein Enhances The Ability Of The Gut Microbiota To Protect Against Enteric Pathogens, José L Fachi, Blanda Di Luccia, Susan Gilfillan, Hao-Wei Chang, Christina Song, Jiye Cheng, Marina Cella, Marco Aurelio Vinolo, Jeffrey I Gordon, Marco Colonna

2020-Current year OA Pubs

Interleukin 22 (IL-22) promotes intestinal barrier integrity, stimulating epithelial cells to enact defense mechanisms against enteric infections, including the production of antimicrobial peptides. IL-22 binding protein (IL-22BP) is a soluble decoy encoded by the

Racial Disparities In Blood Pressure At Time Of Acute Ischemic Stroke Presentation: A Population Study, Yasmin N Aziz, Opeolu Adeoye, Et Al.

2020-Current year OA Pubs

BACKGROUND: Hypertension is a stroke risk factor with known disparities in prevalence and management between Black and White patients. We sought to identify if racial differences in presenting blood pressure (BP) during acute ischemic stroke exist.

METHODS AND RESULTS: Adults with acute ischemic stroke presenting to an emergency department within 24 hours of last known normal during study epochs 2005, 2010, and 2015 within the Greater Cincinnati/Northern Kentucky Stroke Study were included. Demographics, histories, arrival BP, National Institutes of Health Stroke Scale score, and time from last known normal were collected. Multivariable linear regression was used to determine differences in …

Memory-Like Differentiation Enhances Nk Cell Responses Against Colorectal Cancer, Nancy D Marin, Michelle Becker-Hapak, Wilbur M Song, Quazim A Alayo, Lynne Marsala, Naomi Sonnek, Melissa M Berrien-Elliott, Mark Foster, Jennifer A Foltz, Jennifer Tran, Pamela Wong, Celia C Cubitt, Patrick Pence, Kimberly Hwang, Alice Y Zhou, Miriam T Jacobs, Timothy Schappe, David A Russler-Germain, Ryan C Fields, Matthew A Ciorba, Todd A Fehniger

2020-Current year OA Pubs

Metastatic (m) colorectal cancer (CRC) is an incurable disease with a poor prognosis and thus remains an unmet clinical need. Immune checkpoint blockade (ICB)-based immunotherapy is effective for mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) mCRC patients, but it does not benefit the majority of mCRC patients. NK cells are innate lymphoid cells with potent effector responses against a variety of tumor cells but are frequently dysfunctional in cancer patients. Memory-like (ML) NK cells differentiated after IL-12/IL-15/IL-18 activation overcome many challenges to effective NK cell anti-tumor responses, exhibiting enhanced recognition, function, and in vivo persistence. We hypothesized that ML differentiation enhances the …

Crizanlizumab For Retinal Vasculopathy With Cerebral Leukoencephalopathy In A Phase Ii Clinical Study, Wilson X. Wang, Dan Spiegelman, P. Kumar Rao, Andria L. Ford, Rajendra S. Apte

2020-Current year OA Pubs

BackgroundRetinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare, autosomal dominant, universally fatal disease without effective treatment options. This study explores the safety and preliminary efficacy of crizanlizumab, a humanized monoclonal antibody against P-selectin approved for the prevention of sickle cell crises, in slowing retinal nonperfusion and preserving vision in patients with RVCL-S.METHODSEleven patients with RVCL-S with confirmed exonuclease 3 prime repair exonuclease 1 (TREX1) mutations received monthly crizanlizumab infusions over 2 years. The study measured the nonperfusion index within 3 retinal zones and the total retina with fluorescein angiography, visual acuity, intraocular pressure (IOP), and optical …

Wormbase 2024: Status And Transitioning To Alliance Infrastructure, Paul W Sternberg, Tim Schedl, Et Al.

2020-Current year OA Pubs

WormBase has been the major repository and knowledgebase of information about the genome and genetics of Caenorhabditis elegans and other nematodes of experimental interest for over 2 decades. We have 3 goals: to keep current with the fast-paced C. elegans research, to provide better integration with other resources, and to be sustainable. Here, we discuss the current state of WormBase as well as progress and plans for moving core WormBase infrastructure to the Alliance of Genome Resources (the Alliance). As an Alliance member, WormBase will continue to interact with the C. elegans community, develop new features as needed, and curate …

Stay On Track: A Pilot Randomized Control Trial On The Feasibility Of A Diet And Exercise Intervention In Patients With Breast Cancer Receiving Radiotherapy, Gopika Senthilkumar, Aronne M Schottstaedt, Lindsay L Peterson, Lauren N Pedersen, Christopher R Chitambar, Alexis Vistocky, Anjishnu Banerjee, John M Longo, Tracy Kelly, Adam Currey, Melinda R Stolley, Carmen Bergom

2020-Current year OA Pubs

PURPOSE: Among patients with breast cancer undergoing radiotherapy, posttreatment cardiovascular disease and worsened quality of life (QoL) are leading causes of morbidity and mortality. To overcome these negative radiotherapy effects, this prospective, randomized clinical trial pilots a 12-week Stay on Track exercise and diet intervention for overweight patients with nonmetastatic breast cancer undergoing whole-breast radiotherapy.

EXPERIMENTAL DESIGN: The intervention group (n = 22) participated in three personal exercise and dietary counseling sessions, and received three text reminders/week to adhere to recommendations. The control group (n = 22) was administered a diet/exercise information binder. All patients received a Fitbit, and at …

Examining The Gateway Hypothesis And Mapping Substance Use Pathways On Social Media: Machine Learning Approach, Yunhao Yuan, Erin Kasson, Jordan Taylor, Patricia Cavazos-Rehg, Munmun De Choudhury, Talayeh Aledavood

2020-Current year OA Pubs

BACKGROUND: Substance misuse presents significant global public health challenges. Understanding transitions between substance types and the timing of shifts to polysubstance use is vital to developing effective prevention and recovery strategies. The gateway hypothesis suggests that high-risk substance use is preceded by lower-risk substance use. However, the source of this correlation is hotly contested. While some claim that low-risk substance use causes subsequent, riskier substance use, most people using low-risk substances also do not escalate to higher-risk substances. Social media data hold the potential to shed light on the factors contributing to substance use transitions.

OBJECTIVE: By leveraging social media …

Attention Lstm U-Net Model For Drosophila Melanogaster Heart Tube Segmentation In Optical Coherence Microscopy Images, Xiangping Ouyang, Abigail Matt, Fei Wang, Elena Gracheva, Ekaterina Migunova, Saathvika Rajamani, Edward B Dubrovsky, Chao Zhou

2020-Current year OA Pubs

Optical coherence microscopy (OCM) imaging of the

Does Point-Of-Care Ultrasound Affect Fluid Resuscitation Volume In Patients With Septic Shock: A Retrospective Review, Enyo A Ablordeppey, Amy Zhao, Jeffery Ruggeri, Ahmad Hassan, Laura Wallace, Mansi Agarwal, Sean P Stickles, Christopher Holthaus, Daniel Theodoro

2020-Current year OA Pubs

BACKGROUND: Fixed, large volume resuscitation with intravenous fluids (IVFs) in septic shock can cause inadvertent hypervolemia, increased medical interventions, and death when unguided by point-of-care ultrasound (POCUS). The primary study objective was to evaluate whether total IVF volume differs for emergency department (ED) septic shock patients receiving POCUS versus no POCUS.

METHODS: We conducted a retrospective observational cohort study from 7/1/2018 to 8/31/2021 of atraumatic adult ED patients with septic shock. We agreed upon

RESULTS: 304 patients met criteria and 26% (78/304) underwent POCUS. Cardiac POCUS demonstrated reduced ejection fraction in 15.4% of patients. Lung ultrasound showed normal findings in …

Association Between Retinal Microvascular Abnormalities And Late-Life Brain Amyloid-Β Deposition: The Aric-Pet Study, Marco Egle, Jennifer A Deal, Keenan A Walker, Dean F Wong, A Richey Sharrett, Rebecca F Gottesman

2020-Current year OA Pubs

BACKGROUND: Retinal microvascular signs are accessible measures of early alterations in microvascular dysregulation and have been associated with dementia; it is unclear if they are associated with AD (Alzheimer's disease) pathogenesis as a potential mechanistic link. This study aimed to test the association of retinal microvascular abnormalities in mid and late life and late life cerebral amyloid.

METHODS: Participants from the ARIC-PET (Atherosclerosis Risk in Communities-Positron Emission Tomography) study with a valid retinal measure (N = 285) were included. The associations of mid- and late-life retinal signs with late-life amyloid-β (Aβ) by florbetapir PET were tested. Two different measures of …

Diet-Omics In The Study Of Urban And Rural Crohn Disease Evolution (Source) Cohort, Tzipi Braun, Ta-Chiang Liu, Et Al.

2020-Current year OA Pubs

Crohn disease (CD) burden has increased with globalization/urbanization, and the rapid rise is attributed to environmental changes rather than genetic drift. The Study Of Urban and Rural CD Evolution (SOURCE, n = 380) has considered diet-omics domains simultaneously to detect complex interactions and identify potential beneficial and pathogenic factors linked with rural-urban transition and CD. We characterize exposures, diet, ileal transcriptomics, metabolomics, and microbiome in newly diagnosed CD patients and controls in rural and urban China and Israel. We show that time spent by rural residents in urban environments is linked with changes in gut microbial composition and metabolomics, which …

Effects Of Amyloid Beta (Aβ) Oligomers On Blood–Brain Barrier Using A 3d Microfluidic Vasculature-On-A-Chip Model, Samuel C. Uzoechi, Boyce E. Collins, Cody J. Badeaux, Yan Li, Sang S. Kwak, Doo Y. Kim, Daniel T. Laskowitz, Jin-Moo Lee, Yeoheung Yun

2020-Current year OA Pubs

No abstract provided.

Sdpr Expression In Human Trabecular Meshwork And Its Potential Role In Racial Disparities Of Glaucoma, Ying-Bo Shui, Ying Liu, Andrew J W Huang, Carla J Siegfried

2020-Current year OA Pubs

In order to identify how differential gene expression in the trabecular meshwork (TM) contributes to racial disparities of caveolar protein expression, TM dysfunction and development of primary open angle glaucoma (POAG), RNA sequencing was performed to compare TM tissue obtained from White and Black POAG surgical (trabeculectomy) specimens. Healthy donor TM tissue from White and Black donors was analyzed by PCR, qPCR, immunohistochemistry staining, and Western blot to evaluate SDPR (serum deprivation protein response; Cavin 2) and CAV1/CAV2 (Caveolin 1/Caveolin 2). Standard transmission electron microscopy (TEM) and immunogold labeled studies were performed. RNA sequencing demonstrated reduced SDPR expression in TM …

Kenya Psychosis-Risk Outcomes Study (Kepros): Development Of An Accelerated Medicine Partnership Schizophrenia-Aligned Project In Africa, Daniel Mamah, Michael P. Harms, Andrey P. Anokhin, Shingshiun Chen, Jerome Nashed, Yazen Al-Hosni, Alaina Yarber, Semyon Golosheykin, Masoomeh Faghankhani, Megan Sneed, Et Al.

2020-Current year OA Pubs

No abstract provided.

Novel Loss-Of-Function Variants Expand Abcc9-Related Intellectual Disability And Myopathy Syndrome, Stephanie Efthymiou, Robert C Tryon, Colin G Nichols, Et Al.

2020-Current year OA Pubs

Loss-of-function mutation of ABCC9, the gene encoding the SUR2 subunit of ATP sensitive-potassium (KATP) channels, was recently associated with autosomal recessive ABCC9-related intellectual disability and myopathy syndrome (AIMS). Here we identify nine additional subjects, from seven unrelated families, harbouring different homozygous loss-of-function variants in ABCC9 and presenting with a conserved range of clinical features. All variants are predicted to result in severe truncations or in-frame deletions within SUR2, leading to the generation of non-functional SUR2-dependent KATP channels. Affected individuals show psychomotor delay and intellectual disability of variable severity, microcephaly, corpus callosum and white matter abnormalities, seizures, spasticity, short stature, muscle …

Global Prevalence Of Aspirin Use For Primary Prevention Of Cardiovascular Disease: A Cross-Sectional Study Of Nationally Representative, Individual-Level Data, Sang Gune K Yoo, Mark D Huffman, Et Al.

2020-Current year OA Pubs

No abstract provided.

Identifying Long-Term Survivors And Those At Higher Or Lower Risk Of Relapse Among Patients With Cytogenetically Normal Acute Myeloid Leukemia Using A High-Dimensional Mixture Cure Model, Kellie J Archer, Han Fu, Krzysztof Mrózek, Deedra Nicolet, Alice S Mims, Geoffrey L Uy, Wendy Stock, John C Byrd, Wolfgang Hiddemann, Jan Braess, Karsten Spiekermann, Klaus H Metzeler, Tobias Herold, Ann-Kathrin Eisfeld

2020-Current year OA Pubs

Patients with cytogenetically normal acute myeloid leukemia (CN-AML) may harbor prognostically relevant gene mutations and thus be categorized into one of the three 2022 European LeukemiaNet (ELN) genetic-risk groups. Nevertheless, there remains heterogeneity with respect to relapse-free survival (RFS) within these genetic-risk groups. Our training set included 306 adults on Alliance for Clinical Trials in Oncology studies with de novo CN-AML aged <  60 years who achieved a complete remission and for whom centrally reviewed cytogenetics, RNA-sequencing, and gene mutation data from diagnostic samples were available (Alliance trial A152010). To overcome deficiencies of the Cox proportional hazards model when long-term survivors are present, we developed a penalized semi-parametric mixture cure model (MCM) to predict RFS where RNA-sequencing data comprised the predictor space. To validate model performance, we employed an independent test set from the German Acute Myeloid Leukemia Cooperative Group (AMLCG) consisting of 40 de novo CN-AML patients aged <  60 years who achieved a complete remission and had RNA-sequencing of their pre-treatment sample. For the training set, there was a significant non-zero cure fraction (p = 0.019) with 28.5% of patients estimated to be cured. Our MCM included 112 genes associated with cure, or long-term RFS, and 87 genes associated with latency, or shorter-term time-to-relapse. The area under the curve and C-statistic were respectively, 0.947 and 0.783 for our training set and 0.837 and 0.718 for our test set. We identified a novel, prognostically relevant molecular signature in CN-AML, which allows identification of patient subgroups independent of 2022 ELN genetic-risk groups.Trial registration Data from companion studies CALGB 8461, 9665 and 20202 (trials registered at www.clinicaltrials.gov as, respectively, NCT00048958, NCT00899223, and NCT00900224) were obtained from Alliance for Clinical Trials in Oncology under data sharing study A152010. Data from the AMLCG 2008 trial was registered at www.clinicaltrials.gov as NCT01382147.