Digital Commons Network^™

Intracranial Aneurysms In Sickle Cell Disease Are Associated With Hemodynamic Stress And Anemia, Yan Wang, Jared S Garland, Slim Fellah, Martin N Reis, Matthew S Parsons, Kristin P Guilliams, Melanie E Fields, Amy E Mirro, Josiah B Lewis, Chunwei Ying, Rachel A Cohen, Monica L Hulbert, Allison A King, Yasheng Chen, Jin-Moo Lee, Hongyu An, Andria L Ford

2020-Current year OA Pubs

Although hemodynamic stress plays a key role in aneurysm formation outside of sickle cell disease (SCD), its role is understudied in patients with SCD. We hypothesized that tissue-based markers of hemodynamic stress are associated with aneurysm presence in a prospective SCD cohort. Children and adults with SCD, with and without aneurysms, underwent longitudinal brain magnetic resonance imaging/magnetic resonance angiography (MRA) to assess cerebral blood flow (CBF) and oxygen extraction fraction (OEF). Baseline characteristics were recorded. In the subgroup of adults, stepwise mixed-effect logistic regression examined clinical variables, CBF, and OEF as predictors of aneurysm presence. Cumulative rates of new aneurysm …

Evaluating The Impact Of A Year-Long External Mentorship Pilot Program In Classical Hematology, Zoya Qureshy, Pooja Nair, Sara K Vesely, Allison A King, Alfred I Lee, Nathan T Connell, Annette Von Drygalski, Ida Wong-Sefidan, Martina C Murphy, Ronak H Mistry, Rebecca L Zon, Erin G Reid, Josel Fritz, Soo J Park

2020-Current year OA Pubs

Effective mentorship is a pivotal factor in shaping the career trajectory of trainees interested in classical hematology (CH), which is of critical importance due to the anticipated decline in the CH workforce. However, there is a lack of mentorship opportunities within CH compared with medical oncology. To address this need, a year-long external mentorship program was implemented through the American Society of Hematology Medical Educators Institute. Thirty-five hematology/oncology fellows interested in CH and 34 academically productive faculty mentors from different institutions across North America were paired in a meticulous process that considered individual interests, experiences, and background. Pairs were expected …

Pembrolizumab Plus Carboplatin And Paclitaxel As First-Line Therapy For Recurrent/Metastatic Head And Neck Squamous Cell Carcinoma (Keynote-B10): A Single-Arm Phase Iv Trial, Marcin Dzienis, Peter Oppelt, Et Al.

2020-Current year OA Pubs

PURPOSE: Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is pembrolizumab plus platinum and fluorouracil (FU). However, FU is associated with potential challenges (continuous 4-day infusion, high administration costs, and cardiovascular and gastrointestinal toxicities), creating a clinical need for alternative chemotherapy combinations. We evaluated the efficacy and safety of first-line pembrolizumab plus carboplatin and paclitaxel for R/M HNSCC in the open-label, single-arm, phase IV KEYNOTE-B10 study (ClinicalTrials.gov identifier: NCT04489888).

METHODS: Eligible adults had previously untreated, histologically or cytologically confirmed R/M HNSCC regardless of PD-L1 status, measurable disease per RECIST v1.1 by blinded independent central review …

Cyclic Testing Of Six-Strand Suture Techniques For Zone 2 Flexor Tendon Lacerations, Nozomu Kusano, Melissa A Zaegel, Matthew J Silva

2020-Current year OA Pubs

BACKGROUND: Biomechanical analysis using cyclic testing for repaired flexor tendons is a clinically relevant method. The aim of this study was to evaluate the tensile properties of two six-strand suture techniques, the triple looped suture and Yoshizu #1 suture techniques using cyclic testing under simulating early active mobilization conditions.

METHODS: Twenty-five flexor digitorum profundus tendons harvested from fresh frozen human cadaver hands were repaired in zone 2 utilizing one of three repair techniques: the 2-strand modified Kessler (MK) technique as a control, the triple looped suture (TLS) and Yoshizu #1 suture (Y1) techniques. In each suture technique, 4-0 monofilament nylon …

Beta-Hydroxybutyrate Levels And Risk Of Diabetic Ketoacidosis In Adults With Type 1 Diabetes Treated With Sotagliflozin, Schafer Boeder, Michael J Davies, Janet B Mcgill, Richard Pratley, Manon Girard, Phillip Banks, Jeremy Pettus, Satish Garg

2020-Current year OA Pubs

No abstract provided.

Comprehensive Molecular Profiling Of Multiple Myeloma Identifies Refined Copy Number And Expression Subtypes, Sheri Skerget, Ravi Vij, Et Al.

2020-Current year OA Pubs

Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation's Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study ( NCT01454297 ) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are …

Evaluating The Impact Of Laboratory-Based Eligibility Criteria By Race/Ethnicity In First-Line Clinical Trials Of Dlbcl, Arushi Khurana, Brad S Kahl, Et Al.

2020-Current year OA Pubs

Underrepresentation of racial and ethnic subgroups in cancer clinical trials remains a persistent challenge. Restrictive clinical trial eligibility criteria have been shown to exacerbate this problem. We previously identified that up to 24% of patients treated with standard immunochemotherapy would have been excluded from recent first-line trials in diffuse large B-cell lymphoma (DLBCL) based on 5 laboratory-based criteria. These ineligible patients had worse clinical outcomes and increased deaths related to lymphoma progression, suggesting the potential exclusion of patients who could have benefited most from the novel therapies being evaluated. Using data from the prospectively enrolled Lymphoma Epidemiology Outcomes cohort study, …

Single-Cell Analysis Of Chromatin And Expression Reveals Age- And Sex-Associated Alterations In The Human Heart, David F Read, Yiing Lin, Et Al.

2020-Current year OA Pubs

Sex differences and age-related changes in the human heart at the tissue, cell, and molecular level have been well-documented and many may be relevant for cardiovascular disease. However, how molecular programs within individual cell types vary across individuals by age and sex remains poorly characterized. To better understand this variation, we performed single-nucleus combinatorial indexing (sci) ATAC- and RNA-Seq in human heart samples from nine donors. We identify hundreds of differentially expressed genes by age and sex and find epigenetic signatures of variation in ATAC-Seq data in this discovery cohort. We then scale up our single-cell RNA-Seq analysis by combining …

Heart Failure With Reduced Ejection Fraction Polypill Implementation Strategy In India: A Convergent Parallel Mixed Methods Study, Anubha Agarwal, Raji Devarajan, Salva Balbale, Aashima Chopra, Dorairaj Prabhakaran, Mark D Huffman, Lisa R Hirschhorn, Padinhare P Mohanan

2020-Current year OA Pubs

INTRODUCTION: A polypill-based implementation strategy has been proposed to increase rates of guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction. This has the potential to improve mortality and morbidity in India and undertreated populations globally.

METHODS: We conducted a convergent parallel mixed methods study integrating quantitative data from stakeholder surveys using modified implementation science outcome measures and qualitative data from key informant in-depth interviews. Our objective was to explore physician, nurse, pharmacist, and patient perspectives on a HFrEF polypill implementation strategy in India from January 2021 to April 2021. Quantitative and qualitative data were integrated …

Clinical Features And Disease Progression In Older Individuals With Rett Syndrome, Jeffrey L Neul, Timothy A Benke, Eric D Marsh, Bernhard Suter, Cary Fu, Robin C Ryther, Steven A Skinner, David N Lieberman, Timothy Feyma, Arthur Beisang, Peter Heydemann, Sarika U Peters, Amitha Ananth, Alan K Percy

2020-Current year OA Pubs

Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity in RTT would be associated with genetic variants in

Mice Lacking Astn2 Have Asd-Like Behaviors And Altered Cerebellar Circuit Properties, Michalina Hanzel, Kayla Fernando, Susan E Maloney, Zachi Horn, Shiaoching Gong, Kärt Mätlik, Jiajia Zhao, H Amalia Pasolli, Søren Heissel, Joseph D Dougherty, Court Hull, Mary E Hatten

2020-Current year OA Pubs

Astrotactin 2 (ASTN2) is a transmembrane neuronal protein highly expressed in the cerebellum that functions in receptor trafficking and modulates cerebellar Purkinje cell (PC) synaptic activity. Individuals with

Neuronal Activity In The Gustatory Cortex During Economic Choice, Ahmad Jezzini, Camillo Padoa-Schioppa

2020-Current year OA Pubs

An economic choice entails computing and comparing the values of individual offers. Offer values are represented in the orbitofrontal cortex (OFC)-an area that participates in value comparison-but it is unknown where offer values are computed in the first place. One possibility is that this computation takes place in OFC. Alternatively, offer values might be computed upstream of OFC. For choices between edible goods, a primary candidate is the gustatory region of the anterior insula (gustatory cortex, GC). Here we recorded from the GC of male rhesus monkeys choosing between different juice types. As a population, neurons in GC represented the …

Neoantigen Landscape Supports Feasibility Of Personalized Cancer Vaccine For Follicular Lymphoma, Cody A Ramirez, Michelle Becker-Hapak, Kartik Singhal, David A Russler-Germain, Erica K Barnell, Ethan D Mcclain, Sweta Desai, Timothy Schappe, Onyinyechi C Onyeador, Susanna Kiwala, Jasreet Hundal, Zachary L Skidmore, Marcus P Watkins, Thomas B Mooney, Jason R Walker, Kilannin Krysiak, Felicia Gomez, Catrina C Fronick, Robert S Fulton, Robert D Schreiber, Neha Mehta-Shah, Amanda F Cashen, Brad S Kahl, Nancy L Bartlett, Malachi Griffith, Obi L Griffith, Todd A Fehniger, Et Al.

2020-Current year OA Pubs

Personalized cancer vaccines designed to target neoantigens represent a promising new treatment paradigm in oncology. In contrast to classical idiotype vaccines, we hypothesized that "polyvalent" vaccines could be engineered for the personalized treatment of follicular lymphoma (FL) using neoantigen discovery by combined whole-exome sequencing (WES) and RNA sequencing (RNA-seq). Fifty-eight tumor samples from 57 patients with FL underwent WES and RNA-seq. Somatic and B-cell clonotype neoantigens were predicted and filtered to identify high-quality neoantigens. B-cell clonality was determined by the alignment of B-cell receptor (BCR) CDR3 regions from RNA-seq data, grouping at the protein level, and comparison with the BCR …

Multi-Omic Analysis Of Huntington's Disease Reveals A Compensatory Astrocyte State, Fahad Paryani, Ji-Sun Kwon, Andrew S Yoo, Et Al.

2020-Current year OA Pubs

The mechanisms underlying the selective regional vulnerability to neurodegeneration in Huntington's disease (HD) have not been fully defined. To explore the role of astrocytes in this phenomenon, we used single-nucleus and bulk RNAseq, lipidomics, HTT gene CAG repeat-length measurements, and multiplexed immunofluorescence on HD and control post-mortem brains. We identified genes that correlated with CAG repeat length, which were enriched in astrocyte genes, and lipidomic signatures that implicated poly-unsaturated fatty acids in sensitizing neurons to cell death. Because astrocytes play essential roles in lipid metabolism, we explored the heterogeneity of astrocytic states in both protoplasmic and fibrous-like (CD44+) astrocytes. Significantly, …

Identification Of Genetic Subtypes In Follicular Lymphoma, Victoria Shelton, Brad Kahl, Et Al.

2020-Current year OA Pubs

Follicular lymphoma (FL) exhibits considerable variability in biological features and clinical trajectories across patients. To dissect the diversity of FL, we utilized a Bernoulli mixture model to identify genetic subtypes in 713 pre-treatment tumor tissue samples. Our analysis revealed the existence of five subtypes with unique genetic profiles that correlated with clinicopathological characteristics. The clusters were enriched in specific mutations as follows: CS (CREBBP and STAT6), TT (TNFAIP3 and TP53), GM (GNA13 and MEF2B), Q (quiescent, for low mutation burden), and AR (mutations of mTOR pathway-related genes). The subtype Q was enriched for patients with stage I disease and associated …

Maturation Of Germinal Center B Cells After Influenza Virus Vaccination In Humans, Katherine M Mcintire, Wooseob Kim, Sameer Kumar Malladi, Bassem M Mohammed, Julian Q Zhou, Aaron J Schmitz, Teresa Suessen, William D Middleton, Sharlene A Teefey, Rachel M Presti, Jackson S Turner, Ali H. Ellebedy, Et Al.

2020-Current year OA Pubs

Germinal centers (GC) are microanatomical lymphoid structures where affinity-matured memory B cells and long-lived bone marrow plasma cells are primarily generated. It is unclear how the maturation of B cells within the GC impacts the breadth and durability of B cell responses to influenza vaccination in humans. We used fine needle aspiration of draining lymph nodes to longitudinally track antigen-specific GC B cell responses to seasonal influenza vaccination. Antigen-specific GC B cells persisted for at least 13 wk after vaccination in two out of seven individuals. Monoclonal antibodies (mAbs) derived from persisting GC B cell clones exhibit enhanced binding affinity …

Nf1 Mutation Disrupts Activity-Dependent Oligodendroglial Plasticity And Motor Learning In Mice, Yuan Pan, Corina Anastasaki, Jit Chatterjee, Suzanne Scheaffer, David H Gutmann, Et Al.

2020-Current year OA Pubs

Neurogenetic disorders, such as neurofibromatosis type 1 (NF1), can cause cognitive and motor impairments, traditionally attributed to intrinsic neuronal defects such as disruption of synaptic function. Activity-regulated oligodendroglial plasticity also contributes to cognitive and motor functions by tuning neural circuit dynamics. However, the relevance of oligodendroglial plasticity to neurological dysfunction in NF1 is unclear. Here we explore the contribution of oligodendrocyte progenitor cells (OPCs) to pathological features of the NF1 syndrome in mice. Both male and female littermates (4-24 weeks of age) were used equally in this study. We demonstrate that mice with global or OPC-specific Nf1 heterozygosity exhibit defects …

Neoantigen-Specific Cytotoxic Tr1 Cd4 T Cells Suppress Cancer Immunotherapy, Hussein Sultan, Yoshiko Takeuchi, Jeffrey P Ward, Tian-Tian Liu, Vladimir Sukhov, Yuang Song, Samuel Ameh, Simone Brioschi, Darya Khantakova, Cora D Arthur, J Michael White, Heather Kohlmiller, Kathleen C F Sheehan, Marco Colonna, Kenneth M Murphy, Maxim N Artyomov, Robert D Schreiber, Et Al.

2020-Current year OA Pubs

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Potential Us Health Care Savings Based On Clinician Views Of Feasible Site-Of-Care Shifts, Nikhil R Sahni, Crosbie Marine, David M Cutler, Laura N Medford-Davis, Melvin Mezue, Omar Kattan, Ed Levine, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: Shifting care to alternative sites when clinically appropriate may be associated with reduced US health care spending, improved access, and, in some cases, improved care outcomes.

OBJECTIVE: To fill 2 main gaps in the current literature on site-of-care shifts: (1) understanding the clinician perspective on appropriateness of alternative care sites, given the central role they play in referrals and patient trust and (2) considering all potential sites where care could shift and calculating net savings potential.

DESIGN, SETTING, AND PARTICIPANTS: In this survey study, physicians (MDs and DOs), nurse practitioners, physician assistants, nurse anesthetists, radiology and imaging technicians, and …

A Protocol For The Inclusion Of Minoritized Persons In Alzheimer Disease Research From The Adni3 Diversity Taskforce, Ozioma C Okonkwo, Beau M Ances, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults.

OBJECTIVE: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from a longitudinal, multisite, …

The Space Omics And Medical Atlas (Soma) And International Astronaut Biobank, Eliah G Overbey, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space

A Maternal Brain Hormone That Builds Bone, Muriel E Babey, Xiao Zhang, Erica L Scheller, Et Al.

2020-Current year OA Pubs

In lactating mothers, the high calcium (Ca

Psilocybin Desynchronizes The Human Brain, Joshua S Siegel, Demetrius Perry, Benjamin P Kay, Evan M Gordon, Timothy O Laumann, T Rick Reneau, Nicholas V Metcalf, Samuel R Krimmel, Joshua S Shimony, Julie A Schweiger, Dean F Wong, David A Bender, Kristen M Scheidter, Forrest I Whiting, Jonah A Padawer-Curry, Eric J Lenze, Marcus E Raichle, Abraham Z Snyder, Ginger E Nicol, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials

Lisocabtagene Maraleucel In Follicular Lymphoma: The Phase 2 Transcend Fl Study, Franck Morschhauser, Brad Kahl, Et Al.

2020-Current year OA Pubs

An unmet need exists for patients with relapsed/refractory (R/R) follicular lymphoma (FL) and high-risk disease features, such as progression of disease within 24 months (POD24) from first-line immunochemotherapy or disease refractory to both CD20-targeting agent and alkylator (double refractory), due to no established standard of care and poor outcomes. Chimeric antigen receptor (CAR) T cell therapy is an option in R/R FL after two or more lines of prior systemic therapy, but there is no consensus on its optimal timing in the disease course of FL, and there are no data in second-line (2L) treatment of patients with high-risk features. …

Community-Based Participatory Research And System Dynamics Modeling For Improving Retention In Hypertension Care, Jiancheng Ye, Ikechukwu A Orji, Michelle A Birkett, Lisa R Hirschhorn, Theresa L Walunas, Justin D Smith, Namratha R Kandula, Gabriel L Shedul, Mark D Huffman, Dike B Ojji

2020-Current year OA Pubs

IMPORTANCE: The high prevalence of hypertension calls for broad, multisector responses that foster prevention and care services, with the goal of leveraging high-quality treatment as a means of reducing hypertension incidence. Health care system improvements require stakeholder input from across the care continuum to identify gaps and inform interventions that improve hypertension care service, delivery, and retention; system dynamics modeling offers a participatory research approach through which stakeholders learn about system complexity and ways to model sustainable system-level improvements.

OBJECTIVE: To assess the association of simulated interventions with hypertension care retention rates in the Nigerian primary health care system using …

Posttraumatic Stress Disorder And Type 2 Diabetes Outcomes In Veterans, Jeffrey F Scherrer, Joanne Salas, Wenjin Wang, Kenneth E Freedland, Patrick J Lustman, Paula P Schnurr, Beth E Cohen, Allan S Jaffe, Matthew J Friedman

2020-Current year OA Pubs

IMPORTANCE: Posttraumatic stress disorder (PTSD) symptom reduction is linked with lower risk of incident type 2 diabetes (T2D), but little is known about the association between PTSD and comorbid T2D outcomes. Whether PTSD is a modifiable risk factor for adverse T2D outcomes is unknown.

OBJECTIVE: To determine whether patients with PTSD who improved and no longer met diagnostic criteria for PTSD had a lower risk of adverse T2D outcomes compared with patients with persistent PTSD.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used deidentified data from US Veterans Health Administration (VHA) historical medical records (from October 1, 2011, to …

Traumatic Brain Injury, Seizures, And Cognitive Impairment Among Older Adults, Yiqi Zhu, Jonathan Williams, Kebede Beyene, Jean-Francois Trani, Ganesh M Babulal

2020-Current year OA Pubs

IMPORTANCE: Traumatic brain injury (TBI), seizures, and dementia increase with age. There is a gap in understanding the associations of TBI, seizures, and medications such as antiseizure and antipsychotics with the progression of cognitive impairment across racial and ethnic groups.

OBJECTIVE: To investigate the association of TBI and seizures with the risk of cognitive impairment among cognitively normal older adults and the role of medications in moderating the association.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study was a secondary analysis of the Uniform Data Set collected between June 1, 2005, and June 30, 2020, from the National Alzheimer's Coordination …

Cell-Free Dna For The Detection Of Kidney Allograft Rejection, Olivier Aubert, Tarek Alhamad, Raja Dandamudi, Vikas R Dharnidharka, Et Al.

2020-Current year OA Pubs

Donor-derived cell-free DNA (dd-cfDNA) is an emerging noninvasive biomarker that has the potential to detect allograft injury. The capacity of dd-cfDNA to detect kidney allograft rejection and its added clinical value beyond standard of care patient monitoring is unclear. We enrolled 2,882 kidney allograft recipients from 14 transplantation centers in Europe and the United States in an observational population-based study. The primary analysis included 1,134 patients. Donor-derived cell-free DNA levels strongly correlated with allograft rejection, including antibody-mediated rejection (P < 0.0001), T cell-mediated rejection (P < 0.0001) and mixed rejection (P < 0.0001). In multivariable analysis, circulating dd-cfDNA was significantly associated with allograft rejection (odds ratio 2.275; 95% confidence interval (CI) 1.902-2.739; P < 0.0001) independently of standard of care patient monitoring parameters. The inclusion of dd-cfDNA to a standard of care prediction model showed improved discrimination (area under the curve 0.777 (95% CI 0.741-0.811) to 0.821 (95% CI 0.784-0.852); P = 0.0011) and calibration. These results were confirmed in the external validation cohorts (n = 1,748) including a cohort of African American patients (n = 439). Finally, dd-cfDNA showed high predictive value to detect subclinical rejection in stable patients. Our study provides insights on the potential value of assessing dd-cfDNA, in addition to standard of care monitoring, to improve the detection of allograft rejection. ClinicalTrials.gov registration: NCT05995379 .

Mitochondrial Ca2+-Coupled Generation Of Reactive Oxygen Species, Peroxynitrite Formation, And Endothelial Dysfunction In Cantú Syndrome, Elsayed Metwally, Alfredo Sanchez Solano, Boris Lavanderos, Evan Yamasaki, Pratish Thakore, Conor Mcclenaghan, Natalia Rios, Rafael Radi, Yumei Feng Earley, Colin G. Nichols, Scott Earley

2020-Current year OA Pubs

Cantú syndrome is a multisystem disorder caused by gain-of-function (GOF) mutations in KCNJ8 and ABCC9, the genes encoding the pore-forming inward rectifier Kir6.1 and regulatory sulfonylurea receptor SUR2B subunits, respectively, of vascular ATP-sensitive K+ (KATP) channels. In this study, we investigated changes in the vascular endothelium in mice in which Cantú syndrome-associated Kcnj8 or Abcc9 mutations were knocked in to the endogenous loci. We found that endothelium-dependent dilation was impaired in small mesenteric arteries from Cantú mice. Loss of endothelium-dependent vasodilation led to increased vasoconstriction in response to intraluminal pressure or treatment with the adrenergic receptor agonist phenylephrine. We also …

Plasma Proteomic Signature Predicts Myeloid Neoplasm Risk, Duc Tran, J Scott Beeler, Jie Liu, Brian Wiley, Irenaeus C C Chan, Zilan Xin, Michael H Kramer, Armel L Batchi-Bouyou, Xiaoyu Zong, Matthew J Walter, Giulia E M Petrone, Sarantis Chlamydas, Francesca Ferraro, Stephen T Oh, Daniel C Link, Ben Busby, Yin Cao, Kelly L Bolton

2020-Current year OA Pubs

PURPOSE: Clonal hematopoiesis (CH) is thought to be the origin of myeloid neoplasms (MN). Yet, our understanding of the mechanisms driving CH progression to MN and clinical risk prediction of MN remains limited. The human proteome reflects complex interactions between genetic and epigenetic regulation of biological systems. We hypothesized that the plasma proteome might predict MN risk and inform our understanding of the mechanisms promoting MN development.

EXPERIMENTAL DESIGN: We jointly characterized CH and plasma proteomic profiles of 46,237 individuals in the UK Biobank at baseline study entry. During 500,036 person-years of follow-up, 115 individuals developed MN. Cox proportional hazard …