Medicine and Health Sciences Commons^™

Enhancement Of The Endocannabinoid System Through Monoacylglycerol Lipase Inhibition Relieves Migraine-Associated Pain In Mice, Elizaveta Mangutov, Yaseen Awad-Igbaria, Kendra Siegersma, Francois Gastambide, Ayodeji A Asuni, Amynah A A Pradhan

2020-Current year OA Pubs

BACKGROUND: Migraine affects over 1 billion people worldwide and is a leading cause of disability. Targeting the cannabinoid system offers a promising approach for pain and migraine relief. This study evaluated a novel monoacylglycerol lipase (MAGL) inhibitor to prolong endocannabinoid action in acute and chronic mouse models of migraine. It also examined MAGL and cannabinoid receptor 1 (CB

METHODS: C57BL6/J male and female mice received the human migraine trigger nitroglycerin (NTG) acutely or every other day for 9 days. Allodynia was assessed by von Frey hair stimulation of the periorbital area. A single dose of MAGL inhibitor (ABD-1970) was tested …

Injured Tubular Epithelia-Derived Ccn1 Promotes The Mobilization Of Fibroblasts Toward Injury Sites After Kidney Injury, Tomohiro Nakata, Benjamin D Humphreys, Et Al.

2020-Current year OA Pubs

Humoral factors that prompt fibroblasts to migrate to an injury site at an appropriate time point are deemed indispensable for repair after kidney injury. We herein demonstrated the pivotal roles of injured tubule-derived cellular communication network factor 1 (CCN1) in the mobilization of fibroblasts to the injury site after kidney injury. Based on analyses of ligand-receptor interactions

Molecular Mechanism Establishing The Off Pathway In Vision, Florentina Soto, Chin-I Lin, Andrew Jo, Ssu-Yu Chou, Ellen G Harding, Philip A Ruzycki, Gail K Seabold, Ronald S Petralia, Daniel Kerschensteiner

2020-Current year OA Pubs

Parallel ON and OFF (positive- and negative-contrast) pathways fundamental to vision arise at the complex synapse of cone photoreceptors. Cone pedicles form spatially segregated functionally opposite connections with ON and OFF bipolar cells. Here, we discover that mammalian cones express LRFN2, a cell-adhesion molecule, which localizes to the pedicle base. LRFN2 stabilizes basal contacts between cone pedicles and OFF bipolar cell dendrites to guide pathway-specific partner choices, encompassing multiple cell types. In addition, LRFN2 trans-synaptically organizes glutamate receptor clusters, determining the contrast preferences of the OFF pathway. ON and OFF pathways converge in the inner retina to regulate bipolar cell …

Mechanism Of Dna Replication Fork Breakage And Parp1 Hyperactivation During Replication Catastrophe, Pedro Ortega, Elodie Bournique, Junyi Li, Ambrocio Sanchez, Gisselle Santiago, Brooke R Harris, Josefine Striepen, John Maciejowski, Abby M Green, Rémi Buisson

2020-Current year OA Pubs

Ataxia telangiectasia and Rad3-related (ATR) inhibition triggers a surge in origin firing, resulting in increased levels of single-stranded DNA (ssDNA) that rapidly deplete all available RPA. This leaves ssDNA unprotected and susceptible to breakage, a phenomenon known as replication catastrophe. However, the mechanism by which unprotected ssDNA breaks remains unclear. Here, we reveal that APOBEC3B is the key enzyme targeting unprotected ssDNA at replication forks, initiating a reaction cascade that induces fork collapse and poly(ADP-ribose) polymerase 1 (PARP1) hyperactivation. Mechanistically, we demonstrate that uracils generated by APOBEC3B at replication forks are removed by UNG2, resulting in abasic sites that are …

Mendelian Randomization Study Of Sleep Traits And Risk Of Colorectal Cancer, Olympia Dimopoulou, Yin Cao, Et Al.

2020-Current year OA Pubs

A potential association of endogenous circadian rhythm disruption with risk of cancer development has been suggested, however, epidemiological evidence for the association of sleep traits with colorectal cancer (CRC) is limited and often contradictory. Here we investigated whether genetically predicted chronotype, insomnia and sleep duration are associated with CRC risk in males, females and overall and according to CRC anatomical subsites using Mendelian randomization (MR). The two-sample inverse variance weighted (IVW) method was applied using summary-level data in up to 58,221 CRC cases and 67,694 controls and genome-wide association data of genetic variants for self-reported sleep traits. Secondary analyses using …

Brain-Like Border Ownership Signals Support Prediction Of Natural Videos, Zeyuan Ye, Ralf Wessel, Tom P Franken

2020-Current year OA Pubs

To make sense of visual scenes, the brain must segment foreground from background. This is thought to be facilitated by neurons that signal border ownership (BOS), which indicate which side of a border in their receptive field is owned by an object. How these signals emerge without a teaching signal of what is foreground remains unclear. Here we find that many units in PredNet, a self-supervised deep neural network trained to predict future frames in natural videos, are selective for BOS. They share key properties with BOS neurons in the brain, including robustness to object transformations and hysteresis. Ablation revealed …

Determining Potential Immunomodulatory Drug Efficacy In Sepsis Using Elispot, Andrew H Walton, Dale F Osborne, Ethan B Davitt, Anne M Drewry, Richard S Hotchkiss, Et Al.

2020-Current year OA Pubs

This study evaluated the ability of ELISpot to identify potential immuno-modulatory drug therapies in sepsis. ELISpot was performed ex vivo on whole blood from septic patients and healthy controls. Innate and adaptive immunity were evaluated by production of TNF-α and IFN-γ, respectively. Drug efficacy was determined by their effects to modulate the both the number of cytokine-producing cells and amount of cytokine produced per cell. The corticosteroid dexamethasone was evaluated for its ability to down modulate TNF-α and IFN-γ production. The TLR7/8 agonist resiquimod (R848) and T cell stimulants IL-7 and anti-PD-1 mAb were tested for their ability to enhance …

Age-Related Meningeal Extracellular Matrix Remodeling Compromises Cns Lymphatic Function, Kate Hitpass Romero, Taylor J Stevenson, Leon C D Smyth, Ben Watkin, Samuel J C Mccullough, Luca Vinnell, Amy M Smith, Patrick Schweder, Jason A Correia, Jonathan Kipnis, Mike Dragunow, Justin Rustenhoven

2020-Current year OA Pubs

Efficient clearance of central nervous system (CNS) waste proteins and appropriate immune surveillance is essential for brain health. These processes are facilitated by lymphatic networks present in the meninges that drain cerebrospinal fluid (CSF). Age-related impairments to meningeal lymphatic drainage contribute to CNS waste accumulation and immune dysfunction, yet the underlying mechanisms remain poorly understood. Here, we identify extracellular matrix (ECM) remodeling in the aged dura as a key driver of CSF clearance deficits, demonstrating that peri-lymphatic collagen accumulation disrupts lymphatic function. Exploring immune-derived factors contributing to this ECM remodeling, we identify transforming growth factor beta 1 (TGFβ1) as a …

Prevalence Of Medical Writing In Hematological Malignancy Review Articles, Héctor A Vaquera-Alfaro, Elham Nasrollahi, Yashvin Onkarappa Mangala, David Russler-Germain, Aaron Goodman, Ghulam Rehman Mohyuddin

2020-Current year OA Pubs

BACKGROUND: Medical writing services, initially developed to streamline manuscript preparation, have raised ethical concerns due to their association with industry influence and spin. While prevalent in oncology and malignant hematology clinical trials, medical writing involvement in review articles remains underexplored, particularly in the hematology literature. Furthermore, conflict of interests of the writers may also affect the content of review articles. This study investigates the prevalence, characteristics, and funding sources of medical writing in malignant hematology review articles and their relationship with the financial conflicts of interest (CoI) among authors.

METHODS: We conducted a cross-sectional analysis of review articles published in …

Asynchronous Development Of The Mouse Auditory Cortex Is Driven By Hemispheric Identity And Sex, Ashlan P Reid, Demetrios Neophytou, Robert Levy, Cody Pham, Hysell V Oviedo

2020-Current year OA Pubs

Lateralized auditory processing is essential for specialized functions such as speech processing, typically dominated by the Left Auditory Cortex (ACx) in humans. Hemispheric specializations also occur in the adult mouse ACx, but their developmental origins are unclear. Our study finds that the Left and Right ACx in mice reach developmental milestones at different ages. Thalamocortical responses and maturation of synaptic dynamics develop earlier in the Right ACx than the Left. We show that this timing offset predicts hemisphere-dependent differences in sensory-driven plasticity. Juvenile tone exposure at specific times results in imbalanced adult tone frequency representations in the Right and Left …

The Essential Calcium Channel Of Sperm Catsper Is Temperature-Gated, Dilip K Swain, Citlalli Vergara, Júlia Castro-Arnau, Polina V Lishko

2020-Current year OA Pubs

The flagellar calcium channel CatSper is essential for male fertility, as it regulates calcium influx to trigger the hyperactive motility required for sperm to fertilize the egg. Precise activation of CatSper is critical, as premature activation can impair sperm function. While optimal temperature is known to influence fertilization, its effect on CatSper remains unknown. By directly recording from mouse spermatozoa, we reveal that CatSper functions as a temperature-gated ion channel, with a thermal threshold of 33.5 °C and a temperature coefficient Q

Imaging Peripheral Nerves In Vivo With Ct Neurogram Using Novel 2,4,6-Tri-Iodinated Lidocaine Contrast Agent, Rui Tang, Ron Perez, David M Brogan, Mikhail Y Berezin, James E Mccarthy

2020-Current year OA Pubs

Peripheral nerve injuries are a significant concern in surgical procedures, often leading to chronic pain and functional impairment. Despite advancements in imaging, preoperative and intraoperative visualization of peripheral nerves remains a challenge. This study introduces and evaluates a novel tri-iodinated lidocaine-based contrast agent for computed tomography neurography, aiming to enhance the intraoperative visibility of peripheral nerves in vivo. A tri-iodinated lidocaine analogue was synthesized and characterized for its radiodensity, sodium channel binding and nerve affinity. Sodium channel affinity was performed using molecular docking. In vitro contrast enhancement was assessed by comparing the agent's Hounsfield unit (HU) values with those of …

Elevated Mitochondrial Membrane Potential Is A Therapeutic Vulnerability In Dnmt3a-Mutant Clonal Hematopoiesis, Kira A Young, Grant A Challen, Et Al.

2020-Current year OA Pubs

The competitive advantage of mutant hematopoietic stem and progenitor cells (HSPCs) underlies clonal hematopoiesis (CH). Drivers of CH include aging and inflammation; however, how CH-mutant cells gain a selective advantage in these contexts is an unresolved question. Using a murine model of CH (Dnmt3a

Mri Distance Measures As A Predictor Of Subsequent Clinical Status During The Preclinical Phase Of Alzheimer's Disease And Related Disorders, Xinyi Zhang, John C Morris, Tammie L S Benzinger, Et Al.

2020-Current year OA Pubs

Brain atrophy over time, as measured by magnetic resonance imaging (MRI), has been shown to predict subsequent cognitive impairment among individuals who were cognitively normal when first evaluated, indicating that subtle brain atrophy associated with Alzheimer's disease (AD) may begin years before clinical symptoms appear. Traditionally, atrophy has been quantified by differences in brain volume or thickness over a specified timeframe. Research indicates that the rate of atrophy varies across different brain regions, which themselves exhibit complex spatial and hierarchical organizations. These characteristics collectively emphasize the need for diverse summary measures that can effectively capture the multidimensional nature of degeneration. …

Label-Free Evaluation Of Mouse Embryo Quality Using Time-Lapse Bright Field And Optical Coherence Microscopy, Fei Wang, Senyue Hao, Kibeom Park, Ali Ahmady, Chao Zhou

2020-Current year OA Pubs

The selection of high-quality embryos is essential to enhance the implantation rate for in vitro fertilization (IVF). Optical coherence microscopy (OCM) can noninvasively provide three-dimensional (3D) high-resolution imaging of developing embryos. The revealed microstructures can be used for accurate embryo evaluation. Here, we acquire time-lapse 3D OCM images with co-registered bright-field imaging on mouse embryo development from the one-cell stage to the fully hatched blastocyst inside an incubator. Our results demonstrate the capability of OCM to detect structural features of the developing embryos. The second and third embryonic cell cycles are indicated to be associated with blastocyst formation and the …

Attitudes Of Female Carriers Of X-Linked Hypohidrotic Ectodermal Dysplasia Towards Prenatal Treatment And Their Decisions During A Pregnancy With A Male Fetus, Holm Schneider, Michael Schneider, Massimiliano Lia, Dorothy K Grange, Smail Hadj-Rabia, Angus Clarke, Mary Fete, Agnes Jaulent, Marlene Guiraud, Anthony Odibo, Florian Faschingbauer

2020-Current year OA Pubs

BACKGROUND: X-linked hypohidrotic ectodermal dysplasia (XLHED) is a severe genetic disorder that may be treatable with short-term protein replacement therapy during fetal development. This is currently being investigated in a multicenter clinical trial. Affected fetuses can be identified by the number of tooth germs during a routine ultrasound scan in mid-gestation. To understand the attitudes of female XLHED carriers towards prenatal treatment and ultrasonographic screening of the fetus, we analyzed an earlier and a very recent survey among those women and the actual decisions of potential trial participants.

METHODS: Initial analyses were based on a self-administered survey of 167 female …

Cerebrospinal Fluid Proteomics Identification Of Biomarkers For Amyloid And Tau Pet Stages, Zhibo Wang, Yuhan Chen, Katherine Gong, Bote Zhao, Yuye Ning, Meilin Chen, Yan Li, Muhammad Ali, Jigyasha Timsina, Menghan Liu, Carlos Cruchaga, Jianping Jia

2020-Current year OA Pubs

Accurate staging of Alzheimer's disease (AD) pathology is crucial for therapeutic trials and prognosis, but existing fluid biomarkers lack specificity, especially for assessing tau deposition severity, in amyloid-beta (Aβ)-positive patients. We analyze cerebrospinal fluid (CSF) samples from 136 participants in the Alzheimer's Disease Neuroimaging Initiative using more than 6,000 proteins. We apply machine learning to predict AD pathological stages defined by amyloid and tau positron emission tomography (PET). We identify two distinct protein panels: 16 proteins, including neurofilament heavy chain (NEFH) and SPARC-related modular calcium-binding protein 1 (SMOC1), that distinguished Aβ-negative/tau-negative (A-T-) from A+ individuals and nine proteins, such as …

Outcomes Evidence Must Keep Up With The Implementation Of The 4ms Framework To Ensure Age-Friendly Health System Transformation, James D Harrison, Stephanie E Rogers, Benjamin Rosner, Estelle Martin, Sunny C Lin, Jarmin Yeh, Julia Adler-Milstein

2020-Current year OA Pubs

The Age-Friendly Health System (AFHS) movement was conceptualized as a transformative solution to reliably deliver evidence-based care to older adults. Guided by the 4Ms framework: What Matters, Mobility, Mentation, and Medication, AFHS healthcare systems have been given the flexibility to tailor 4Ms interventions and care processes to their context, preferences and populations. This flexibility has facilitated the widespread adoption of 4Ms care. However, as our understanding of 4Ms implementation grows, evidence of the impact of 4Ms care on outcomes must keep up with implementation to ensure AFHS transformation. It is only through assessing the 4Ms as a whole and understanding …

Synapsin Condensation Is Governed By Sequence-Encoded Molecular Grammars, Christian Hoffmann, Kiersten M Ruff, Irina A Edu, Min Kyung Shinn, Johannes V Tromm, Matthew R King, Avnika Pant, Hannes Ausserwöger, Jennifer R Morgan, Tuomas P J Knowles, Rohit V Pappu, Dragomir Milovanovic

2020-Current year OA Pubs

Multiple biomolecular condensates coexist at the pre- and post- synapse to enable vesicle dynamics and controlled neurotransmitter release in the brain. In pre-synapses, intrinsically disordered regions (IDRs) of synaptic proteins are drivers of condensation that enable clustering of synaptic vesicles (SVs). Using computational analysis, we show that the IDRs of SV proteins feature evolutionarily conserved non-random compositional biases and sequence patterns. Synapsin-1 is essential for condensation of SVs, and its C-terminal IDR has been shown to be a key driver of condensation. Focusing on this IDR, we dissected the contributions of two conserved features namely the segregation of polar and …

Immunotherapeutic Strategies In Head And Neck Cancer: Challenges And Opportunities, Xia Liu, R. Alex Harbison, Mark A. Varvares, Sidharth V. Puram, Guangyong Peng

2020-Current year OA Pubs

HNSCC remains a substantial health issue, with treatment options including surgery, radiation, and platinum-based chemotherapy. Unfortunately, despite progress in research, only modest gains have been made in disease control, with existing treatments resulting in significant functional and quality-of-life issues. The introduction of immunotherapy in the treatment of HNSCC has resulted in some improvements in outlook for patients and is now standard of care for populations with both recurrent and metastatic disease. However, despite the early successes, responses to immune checkpoint inhibition (ICI) remain modest to low, approaching 14%-22% objective response rates. Challenges to the effectiveness of ICI and other immunotherapies …

Understanding Implementation Determinants Of Universal School Meals Through An Equity-Driven Mixed Methods Approach, Gabriella M Mcloughlin, Molly Kerstetter, Yerusalem Yohannes, Omar Martinez, Resa M Jones, Ross C Brownson, Jennifer O Fisher

2020-Current year OA Pubs

BACKGROUND: Policies, such as Universal School Meals (USM), are essential for preventing inequities in chronic disease risk among socially and economically marginalized populations. Implementing USM reduces food insecurity and obesity risk, among other academic/health outcomes; unfortunately, across the nation student participation (i.e., reach) is lower than expected, limiting its public health impact. Grounded in implementation science and health equity frameworks, this study aimed to: 1) investigate the determinants of implementing USM in a large, urban school district and 2) assess key challenges and supports across schools with varying levels of participation in USM.

METHODS: A needs and assets assessment was …

Atm-Dependent Dna Damage Response Constrains Cell Growth And Drives Clonal Hematopoiesis In Telomere Biology Disorders, Christopher M. Sande, Karolyn A. Oetjen, Daniel C. Link, Andrew E. Gelman, Laneshia K. Tague, Et Al.

2020-Current year OA Pubs

Telomere biology disorders (TBDs) are genetic diseases caused by defective telomere maintenance. TBD patients often develop bone marrow failure and have an increased risk of myeloid neoplasms. To better understand the factors underlying hematopoietic outcomes in TBD, we comprehensively evaluated acquired genetic alterations in hematopoietic cells from 166 pediatric and adult TBD patients. Of these patients, 47.6% (28.8% of children, 56.1% of adults) had clonal hematopoiesis. Recurrent somatic alterations involved telomere maintenance genes (7.6%), spliceosome genes (10.4%, mainly U2AF1 p.S34), and chromosomal alterations (20.2%), including 1q gain (5.9%). Somatic variants affecting the DNA damage response (DDR) were identified in 21.5% …

H3.1k27m-Induced Misregulation Of The Tonsoku-H3.1 Pathway Causes Genomic Instability, Wenxin Yuan, Yi-Chun Huang, Chantal Leblanc, Axel Poulet, Francisca N De Luna Vitorino, Devisree Valsakumar, Renee Dean, Benjamin A Garcia, Josien C Van Wolfswinkel, Philipp Voigt, Yannick Jacob

2020-Current year OA Pubs

The oncomutation lysine 27-to-methionine in histone H3 (H3K27M) is frequently identified in tumors of patients with diffuse midline glioma-H3K27 altered (DMG-H3K27a). H3K27M inhibits the deposition of the histone mark H3K27me3, which affects the maintenance of transcriptional programs and cell identity. Cells expressing H3K27M are also characterized by defects in genome integrity, but the mechanisms linking expression of the oncohistone to DNA damage remain mostly unknown. In this study, we demonstrate that expression of H3.1K27M in the model plant Arabidopsis thaliana interferes with post-replicative chromatin maturation mediated by the H3.1K27 methyltransferases ATXR5 and ATXR6. As a result, H3.1 variants on nascent …

Left Ventricular Hypertrophy Among Adults In A Population-Based Cohort In Haiti, Anju Ogyu, Lisa De Las Fuentes, Victor G Dávila-Román, Et Al.

2020-Current year OA Pubs

Left ventricular hypertrophy (LVH) is one of the strongest predictors of cardiovascular disease (CVD) and mortality; yet the means to diagnose LVH in resource-constrained settings remain limited. The objectives of this study were to determine LVH prevalence by transthoracic echocardiography (TTE) in a high-risk group, and compare TTE vs. electrocardiography (ECG-LVH) for LVH detection. We analyzed enrollment data from the Haiti cardiovascular disease cohort study on adults (≥ 18 years, n = 3,005) in Port-au-Prince between 2019 and 2021. All participants underwent questionnaires, vital signs, physical exams, and 12-lead ECGs. TTEs were acquired on those with hypertension or exhibiting CVD …

Pilot First-In-Human Ccr2 Pet/Ct To Detect Abdominal Aortic Aneurysm Wall Instability, Santiago Elizondo-Benedetto, Deborah Sultan, Ryan Wahidi, Mahdjoub Hamdi, Mohamed S Zaghloul, Shahab Hafezi, Batool Arif, Laura K Mcdonald, Kitty Harrison, Dakkota Thies, Gyu Seong Heo, Hannah Luehmann, Lisa Detering, J Westley Ohman, Zachary J Wanken, Luis A Sanchez, Joseph E Ippolito, Jie Zheng, Robert J Gropler, Richard Laforest, Yongjian Liu, Mohamed A Zayed

2020-Current year OA Pubs

No abstract provided.

The Antimicrobial Resistance-Water-Corporate Interface: Exploring The Connections Between Antimicrobials, Water, And Pollution, Jason P Burnham

2020-Current year OA Pubs

Antibiotic resistance is a public health emergency, with ten million deaths estimated annually by the year 2050. Water systems are an important medium for the development and dissemination of antibiotic resistance from a variety of sources, explored in this perspective review. Hospital wastewater and wastewater systems more broadly are breeding grounds for antibiotic resistance because of the nature of their waste and how it is processed. Corporations from various sectors contribute to antibiotic resistance in many direct and indirect ways. Pharmaceutical factory runoff, agricultural antibiotic use, agricultural use of nitrogen fertilizers, heavy metal pollution, air pollution (atmospheric deposition, burning of …

Behavioral And Psychological Symptoms Of Dementia And Alzheimer's Disease Progression In Down Syndrome, Melissa R Jenkins, Beau M Ances, Et Al.

2020-Current year OA Pubs

BACKGROUND: Adults with Down syndrome (DS) have a 90% lifetime risk for Alzheimer's disease (AD), with neurobiological pathology present decades prior to dementia onset. The profile and timing of cognitive decline in DS is well-documented. However, there is a small body of research on whether Behavioral and Psychological Symptoms of Dementia (BPSD) occur early on in the progression of AD in DS and are associated with early AD pathology (i.e., amyloid-beta [Aβ] and neurofibrillary tau tangles [NFT]).

METHODS: Data were analyzed from 337 adults with DS (M = 45.13 years, SD = 9.53 years) enrolled in a large cohort study. …

Whole Genome Sequencing Analysis Of Body Mass Index Identifies Novel African Ancestry-Specific Risk Allele, Xinruo Zhang, D C Rao, Et Al.

2020-Current year OA Pubs

Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals (P <  5 × 10

Time Required To Implement A Computerized Patient Decision Aid For Lupus In Outpatient Visits, Nathan W Carroll, Aizhan Karabukayeva, Larry R Hearld, Diane Kamen, Alfred H J Kim, Sonali Narain, Narender Annapureddy, Zineb Aouhab, Maureen Mcmahon, Vikas Majithia, Cathy Lee Ching, Winn Chatham, Jasvinder A Singh

2020-Current year OA Pubs

BACKGROUND: Patient decision aids have the potential to lower decision conflict for patients and to improve patient-physician communication. However, uptake of decision aids has been poor, in part because the time required to incorporate these into clinical practice is not well understood.

OBJECTIVE: To estimate the time required for a rheumatology clinic to implement a validated decision aid for patients with lupus.

METHODS: Using a cohort of eight implementation sites, study investigators identified the activities required to administer a decision aid. Site coordinators embedded within the clinics timed the duration of each activity. To estimate the effect of viewing the …

Novel Recurrent Cytogenetic Abnormalities Predict Overall Survival In Tetraploid/Near-Tetraploid Myelodysplastic Syndrome And Acute Myeloid Leukemia, Matthew R Avenarius, Zachary B Abrams, Ling Guo, James S Blachly, Cecelia R Miller, Nyla A Heerema, Guilin Tang, Kevin R Coombes, Lynne V Abruzzo

2020-Current year OA Pubs

BACKGROUND/OBJECTIVES: Tetraploidy (4n = 92 chromosomes) and near-tetraploidy (81-103 chromosomes) (T/NT) are uncommon cytogenetic events in MDS/AML (~1%). Abnormalities reported to be associated with T/NT MDS/AML include -5/del(5q), -7/del(7q), +8, and +21. However, other clinically relevant abnormalities likely remain "hidden" in long strings of ISCN cytogenetic nomenclature when evaluated visually. To date, no studies have had the statistical power and a computational method to identify novel recurrent abnormalities associated with the T/NT karyotype or overall survival (OS).

METHODS: Using CytoGPS, a bioinformatic tool we developed, we converted karyotypes from a combined cohort of 75 T/NT MDS/AML cases from two institutions …