Digital Commons Network^™

Aberrant Cd25 And Increased Cd123 Expression Are Common In Acute Myeloid Leukemia With Kmt2a Partial Tandem Duplication And Are Associated With Flt3 Internal Tandem Duplication, Qing Wei, Guilin Tang, Shaoying Li, Sa A Wang, Pei Lin, Wei Wang, Sanam Loghavi, Wei J Wang, L Jeffrey Medeiros, Jie Xu

Faculty, Staff and Student Publications

Background: KMT2A partial tandem duplication (PTD) occurs in approximately 5-10% of acute myeloid leukemia (AML) cases and is associated with poor prognosis. While its cytogenetic and molecular features are well described, the immunophenotypic characteristics of AML with KMT2A-PTD remain incompletely defined.

Methods: We identified 47 cases of AML with KMT2A-PTD by optical genome mapping. All cases underwent flow cytometric immunophenotypic analysis and next-generation sequencing using an 81-gene panel.

Results: The cohort included 32 men and 15 women with a median age of 67 years (range, 19-87). Thirty-eight cases were de novo AML, and nine were secondary to myelodysplastic …

Integrative Spatial Multi-Omics Reveal Niche-Specific Inflammatory Signaling And Differentiation Hierarchies In Aml, Enes Dasdemir, Ivo Veletic, Christopher P Ly, Andres E Quesada, Christopher D Pacheco, Fatima Z Jelloul, Pamella Borges, Sreyashi Basu, Sonali Jindal, Zhiqiang Wang, Alexander Lazar, Khalida M Wani, Dinler A Antunes, Patrick K Reville, Preethi H Gunaratne, Robert J Tower, Padmanee Sharma, Hussein A Abbas

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is a clonal disorder characterized by immature blasts and arrested differentiation that primarily affects the bone marrow (BM) and occasionally presents as extramedullary (EM) disease. EM manifestations highlight AML's adaptability to distinct microenvironments, which we examined using spatial analyses of medullary and EM tissues. We describe a workflow for Visium-based spatial transcriptomics in medullary and EM AML, revealing insights into cell-cell communication and the spatial organization of AML hierarchies. In BM, monocytes and granulocyte-monocyte progenitors colocalized with leukemic populations, sharing molecular signatures with those in EM sample. CXCL12-CXCR4-mediated communication correlated with PI3K/AKT/mTOR signaling in inflammatory niches.

Teriparatide Use In Osteopenic Patients Undergoing Single-Level Lumbar Fusion Associated With Decreased 2-Year Revision Rates, Mitchell K. Ng, Ariel N. Rodriguez, Abigail Razi, Ahmed K. Emara, Brian T. Ford, Ameer Tabbaa, Divya Gouni, Jacquelyn J. Xu, Paul G. Mastrokostas, Jad Bou Monsef, Afshin E. Razi

Rothman Institute Papers

Context:  Low bone density is common among lumbar fusion patients and increases the risks of pseudarthrosis, hardware failure, and revision. Teriparatide improves bone mass and fusion in osteoporosis, but its benefit in osteopenia or normal bone remains uncertain.

Aims:  To evaluate the association between teriparatide exposure and (1) postoperative complications, (2) 90-day readmission, and (3) 2-year reoperation, stratified by bone health status (osteoporotic, osteopenic, and normal) in patients undergoing single-level lumbar fusion.

Setting and Design:  A retrospective cohort study using the PearlDiver database from 2010 to 2021 identified patients undergoing single-level lumbar fusion.

Subjects and Methods:  Patients on teriparatide were …

Rab5c Increases Endothelial Release Of Vwf By Regulating Vesicle Trafficking, Paula Reventun, Pablo Toledano-Sanz, Maria Delgado-Marin, Maria Viskadourou, D Brian Foster, Paul S De Vries, Maria Sabater-Lleal, Nunzio Alcharani, Claudia Gonzalez-Cucharero, William O Osburn, Alanna C Morrison, Alisa S Wolberg, Nicholas L Smith, Marios Arvanitis, Charles J Lowenstein

Faculty, Staff and Student Publications

Background: Abnormal levels of VWF (von Willebrand Factor) are a risk factor for venous thromboembolism (VTE) and bleeding. Genome-wide association studies for VWF have identified novel candidate genes that may regulate VWF levels in humans, including RAB5C (RAS-associated protein RAB5C). We hypothesized that RAB5C regulates VWF release from endothelial cells.

Methods: We studied the effect of RAB5C on vesicle trafficking in human endothelial cells. We performed CRISPR (clustered regularly interspaced short palindromic repeats) interference targeting 2 genetic variants linked to altered VWF levels and evaluated RAB5C expression by reverse transcription-quantitative polymerase chain reaction. We silenced RAB5C or overexpressed RAB5C wild-type, …

The Impact Of Indigenous American-Like Ancestry On The Risk Of Acute Lymphoblastic Leukemia In Hispanic/Latino Children, Jalen Langie, Tsz Fung Chan, Wenjian Yang, Alice Y Kang, Libby Morimoto, Daniel O Stram, Nicholas Mancuso, Xiaomei Ma, Catherine Metayer, Philip J Lupo, Karen R Rabin, Michael E Scheurer, Joseph L Wiemels, Jun J Yang, Adam J De Smith, Charleston W K Chiang

Faculty, Staff and Students Publications

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with Hispanic/Latino children having a higher incidence of ALL than other racial/ethnic groups. Among the genetic variants previously implicated in ALL risk, a number of them were found to be enriched in Indigenous American (IA)-like ancestries and inherited by many Hispanic/Latino individuals. However, due to potential confounding from environmental factors, the association between IA-like ancestry and risk for ALL has remained unclear. In this study, we characterized the impact of IA-like ancestry on overall ALL risk and on the frequency and effect size of known risk alleles, while accounting for …

C Elegans As A Tractable Infection Model For The Emerging Fungal Pathogen Candida Auris, Melissa Martinez, Melissa R Cruz, Danielle A Garsin, Michael C Lorenz

Faculty, Staff and Student Publications

Candida auris is an emerging multidrug-resistant fungal pathogen. The genetic factors contributing to the virulence, drug resistance, and stress-tolerant nature of C. auris are mostly unknown. Additional animal models of virulence are needed, especially those amenable to high-throughput analysis. The nematode Caenorhabditis elegans has been validated as an effective tool for studying multiple fungal and bacterial pathogens. We describe here a C. elegans infection model in which exposure to C. auris is lethal to worms with kinetics similar to killing by Candida albicans; in contrast to C. albicans, C. auris does not form hyphae, indicating distinct virulence mechanisms. …

Bdcd: A Comprehensive Brain Disease Cell-Cell Communication Database, Xinyi Liu, Citu Citu, Gang Qu, Wendao Liu, Nitesh Enduru, Andi Liu, Chia-Hao Tung, Zhongming Zhao

Faculty, Staff and Student Publications

Dysregulated cell–cell communication (CCC) is increasingly recognized as a driver of brain disease pathology, contributing to neuroinflammation, synaptic dysfunction, and neurodegeneration. Nevertheless, existing resources remain limited in brain specificity, regional coverage, and functional annotation. To address this gap, we develop the Brain Disease Cell-cell communication Database (BDCD), the first comprehensive resource focused on CCC networks across major brain diseases. BDCD integrates 38 manually curated datasets, comprising 8 519 425 single cells from single-cell RNA-seq studies and 140 744 spots from spatial transcriptomic maps, spanning 14 brain regions and 13 canonical cell types covering Alzheimer’s disease, Parkinson’s disease, schizophrenia, bipolar disorder, …

Epigenome-Wide Association Study Meta-Analysis Of Bmi In African Americans, Kendra Ferrier, Mariaelisa Graff, Iain R Konigsberg, Maggie Stanislawski, Heather M Highland, Laura M Raffield, April P Carson, Eric Boerwinkle, Jill M Norris, Chris R Gignoux, Audrey E Hendricks, Sridharan Raghavan, Kari E North, Kristin L Young, Anne E Justice, Matthew A Allison, Mathew J Budoff, Silva Kasela, François Aguet, Joshua J Joseph, Charles Kooperberg, Stephen S Rich, Jerome I Rotter, Ethan M Lange, Leslie A Lange

Faculty, Staff and Student Publications

Despite considerable advances in identifying risk factors for obesity, gaps remain in our understanding about its etiology. Genetic variants explain only a small portion of variation in obesity-related traits such as body mass index (BMI). Epigenetic regulation, which controls gene expression and is influenced by environmental and genetic factors, may account for additional variability in BMI. Epigenetic studies of BMI have largely been conducted in European ancestry populations, despite the disproportionate burden of obesity in African Americans (AAs). We conducted a sex-stratified BMI epigenome-wide association study meta-analysis in AA participants from the Jackson Heart Study (n = 1,604) and …

The Effects Of Bone-Remodeling Therapy On Survival, Pain, And Skeletal Related Events In The Setting Of Renal Cell Carcinoma With Bone Metastases: A Multicenter Investigation From A Large Global Health Research Network (Trinetx), Brian H. Im, Kevin K. Zarrabi, Aaron R. Hochberg, Mihir M. Shah, Md, James R. Mark, Joseph K. Izes, Patrick T. Gomella, Costas D. Lallas, Leonard G. Gomella, Adam R. Metwalli

Department of Urology Faculty Papers

INTRODUCTION: Renal cell carcinoma (RCC) is the most common renal malignancy-bone metastases (BM) are indicative of aggressive disease with a poor prognosis. We aim to evaluate the overall mortality of patients with RCC with and without BM, and to elucidate the effects of bone-remodeling therapy on mortality, incidence of skeletal-related events, and opioid usage patterns in patients with BM.

METHODS: A retrospective cohort study was conducted using TriNetX, a large, collaborative network sourced from electronic medical records of over 110 million patients from over 100 healthcare organizations. All adult patients with RCC and RCC with BM were queried.

RESULTS: There …

Real-World Multicenter Assessment Of Sustained Clinical Outcomes After Digital Deep Brain Stimulation, Alireza Gharabaghi, Sergiu Groppa, Elena Casas, Alfons Schnitzler, Laura Muñoz-Delgado, Vicky L. Marshall, Jessica Karl, Lin Zhang, Ramiro Alvarez, Mary S. Feldman, Michael J. Soileau, Lan Luo, Benjamin L. Walter, Chengyuan Wu, Hong Lei, Damian M. Herz, Devyani Nanduri, Claudia A. Salazar, Corneliu Luca, Daniel Weiss

Department of Neurosurgery Faculty Papers

Remote, internet-based deep brain stimulation programming for Parkinson's disease accelerates clinical benefits postoperatively by improving access to therapy adjustments compared to in-clinic optimization. After completion of the initial digital programming phase, we show that clinical outcomes, quality of life, and safety remain sustained over at least twelve months under routine care conditions. Embedding a randomized trial within a larger cohort study enables long-term, real-world evaluation, offering a scalable and pragmatic model for assessing complex digital interventions in routine clinical care. (NCT05269862 registered on 2022-03-08 and NCT04071847 registered on 2019-08-28).

Ophiobolin A Impacts Mitochondrial Redox Biology In An Epithelial-Mesenchymal Transition (Emt)-Specific Manner, Haleigh N Parker, Yongfeng Tao, Jenna Tobin, Kayla L Haberman, Samantha Davis, Emily York, Alysia Martinez, Nobuyuki Matsumoto, Jaquelin Aroujo, Jun Hyoung Park, Bernd Zechmann, Benny Abraham Kaipparettu, Angela Boari, Christie M Sayes, Antonio Evidente, Alexander Kornienko, Benjamin Cravatt, Daniel Romo, Joseph H Taube

Faculty, Staff and Students Publications

Breast cancer progression is facilitated by the epithelial to mesenchymal transition (EMT), generating cancer cells with enhanced metastatic capacity and resistance to chemotherapeutics. The fungus-derived sesterterpenoid natural produce compound, ophiobolin A (OpA), possesses nanomolar cytotoxic activity and a high therapeutic index, although its molecular targets and mechanism of action are not well characterized. Herein, we utilized a model of mammary epithelial cells and breast cancer cell lines with and without EMT features to characterize the mechanism of selectivity towards EMT(+) cells by OpA. Proteins interacting with OpA in EMT(+) cells, including mitochondrial glutathione transporter SLC25A40, were identified through via mass …

Neuroradiological Features Across Major Psychiatric Disorders And Behavioral Variant Of Alzheimer’S Disease: A Concise Multimodal Synthesis, Sina Dindarian, Joga Chaganti, Nazanin Rafiei, Scott H. Faro

Department of Radiology Faculty Papers

Psychiatric disorders are complex, disabling conditions that continue to rely on subjective diagnostic criteria due to the absence of objective biological markers. Neuroradiology has become a critical discipline for examining the structural, functional, and biochemical underpinnings of these disorders through advanced brain imaging. This review synthesizes findings from five major psychiatric conditions including major depressive disorder, schizophrenia, autism spectrum disorder, obsessive-compulsive disorder, and generalized anxiety disorder, and briefly discusses the behavioral variant of Alzheimer's disease, a variant with neuropsychological overlay, across multiple imaging modalities, including structural magnetic resonance imaging (MRI), diffusion tensor imaging, functional MRI, magnetic resonance spectroscopy, functional near-infrared …

Resolution Of A Human Chromosomal Mystery: Evolutionary Complexity Revealed, Jeffrey Rogers

Faculty, Staff and Students Publications

The human complement of chromosomes differs from our closest primate relatives by virtue of a unique chromosome fusion event. In this issue of Cell Genomics, Yang et al. provide the first detailed analysis of the site of chromosome fusion and reconstruct the complex evolutionary relationships among the genomic elements within the human fusion site and their related sequences in our great ape relatives.

Progress And Challenges In Profiling Protein-Rna And Protein-Associated Rna-Rna Interactions, Zhuoyi Song, Eric L Van Nostrand

Faculty, Staff and Students Publications

RNA binding proteins (RBPs) play essential roles in post-transcriptional gene regulation by interacting with a wide range of RNA targets. In addition to regulating RNA processing via individual RBP-RNA interactions, there is a growing appreciation of the regulatory impact of protein-associated RNA-RNA interactions that include both well-studied examples of small regulatory RNAs (e.g. microRNAs, snRNAs, snoRNAs, piRNAs) guiding ribonucleoprotein complexes to their targets as well as structured RNA elements defining the interaction landscape for an RBP. To elucidate the full scope of RBP-RNA interactions, CLIP ( crosslinking and immunoprecipitation)-based methods have emerged as powerful tools. Even with the wide application …

Prevalence And Outcomes Of Her2-Low Versus Her2-0 Status In Patients With Metastatic Breast Cancer, Akshara Singareeka Raghavendra, Diane D Liu, Senthil Damodaran, Sarah Pasyar, Yu Shen, Jason A Mouabbi, Carlos H Barcenas, Kelly K Hunt, Debu Tripathy

Faculty, Staff and Student Publications

Background: HER2-low breast cancer (HER2 immunohistochemical [IHC] score 1+, or IHC 2+ without HER2 gene amplification) is distinct from HER2-positive and HER2-0 breast cancer (IHC 0), with a differing prognosis and specific therapeutic options. The DESTINY-Breast04 trial demonstrated notable efficacy of the HER2 antibody-drug conjugate trastuzumab deruxtecan over standard chemotherapy in patients with metastatic breast cancer (MBC) defined as HER2-low. More recently, the DESTINY-Breast06 trial confirmed this benefit in hormone receptor-positive and HER2-ultralow (less than 1+, but with ≤10% of infiltrating cancer cells showing incomplete and faint/weak membrane staining) cases, prompting re-evaluation of HER2 diagnostic thresholds and treatment strategies.

Methods …

Autograft Enlargement After The Ross Procedure In Pediatric Patients: Somatic Growth Or Pathologic Dilatation?, Ioannis Zoupas, Alexander C Mills, Scott D Olson, Damien J Lapar

Faculty, Staff and Student Publications

Purpose of ReviewPulmonary autograft autotransplantation represents a popular surgical approach for pediatric patients requiring aortic valve replacement due to the potential for autograft enlargement to accommodate somatic growth. Nevertheless, autograft dilatation and the subsequent need for reintervention are quite common. Published data suggest that autograft enlargement may result from pathological passive remodeling rather than active somatic growth and vice versa. The present review serves to comprehensively evaluate available evidence related to the fate of the pulmonary autograft after the Ross procedure as it relates to the etiology, risk factors and patterns of autograft failure.ResultsStudies present conflicting results supporting both pathological …

Diet-Responsive Genetic Determinants Of Intestinal Colonization In The Yeast Candida Albicans, Musfirat Shubaita, Mazen Oneissi, Elena Lindemann-Pérez, Cecilia Fadhel Alvarez, Anne-Marie Krachler, Diana M Proctor, J Christian Pérez

Faculty, Staff and Student Publications

Dietary components influence microbial composition in the digestive tract. Although often viewed as energy sources, dietary components are likely to shape microbial determinants of intestinal colonization beyond metabolism. Here, we report that a dietary long-chain fatty acid enhances the yeast Candida albicans colonization of the murine gut partly by eliciting modifications to the fungal cell surface. Mice fed an oleic acid-rich diet were readily colonized by C. albicans and exhibited higher fungal load in feces compared with rodents fed an isocaloric control diet. Surprisingly, β-oxidation, a catabolic process to break down fatty acids for energy production, was dispensable for C. …

Safety And Effectiveness Of Bolt-Mounted Versus Tunnelled External Ventricular Drains: A Systematic Review, Meta-Analysis And Trial-Sequential Analysis, Shaan Patel, Shiva A. Nischal, Ayush Sinha, Kush Kale, Pious D. Patel, Jack Jallo, Srinivas K. Prasad

Department of Neurosurgery Faculty Papers

BACKGROUND: External ventricular drains (EVDs) are fundamental to neurocritical care, yet substantial procedural heterogeneity persists, particularly regarding bolt-mounted versus tunnelled catheter fixation. The relative safety and effectiveness of these approaches remain unclear, with conflicting data from observational studies and a lack of trial-level evidence.

OBJECTIVE: To compare bolt-mounted and tunnelled EVDs across accuracy, reoperation, and key safety outcomes using systematic review, meta-analysis, and trial-sequential analysis.

METHODS: Following PRISMA guidelines, PubMed, Embase, and CENTRAL databases were searched (November 2025) for randomised or observational studies comparing bolt-mounted with tunnelled EVDs in adults. Two reviewers independently screened studies, extracted data, and assessed risk …

Disease Burden Of Asthma Patients Utilizing Short-Acting Beta-2 Agonist-Only Inhalers As Rescue In The United States, Njira Lugogo, Rena C. Moon, Yen Chung, Joy David, Omar Motawakel, Ning A. Rosenthal, Neil Skolnik

Department of Family & Community Medicine Faculty Papers

Purpose: We aimed to describe the disease burden of asthma and examine relationships between short-acting beta-2 agonist (SABA) use and asthma exacerbations. Patients and Methods: This retrospective cohort study used geographically diverse Premier Healthcare Database (PHD) and linked insurance claims (10/01/2021-09/30/2022) for US patients aged ≥18 years with a SABA-only prescription and a history of asthma exacerbation within 12 months before index date (the earliest SABA prescription date). Three asthma control groups were defined based on SABA usage: well controlled-low (0–1 prescriptions), not well controlled-medium (2–3 prescriptions), very poorly controlled-high (≥4 prescriptions). Four asthma severity groups were defined using asthma …

Identifying Priority Research Questions For Decentralized Wastewater, Bryan W Brooks, Timothy Callahan, Jacob K Stanley, Jamie Holodak, Kevin M Stroski, Alissa H Cox, Thomas W Groves, Anish Jantrania, Jeff C Moeller, Kris Neset, Christopher Walker, Harry Zhang, Amal Bakchan, Kelly D Alley, Jim Bell, Allison Blodig, Eric Casey, Donna Cosper, Victor D'Amato, Mark A Elliott, Greg Graves, Roxanne Groover, Robert Himschoot, Mary G Lusk, Jillian Maxcy-Brown, David Meints, Rojelio Mejia, Matt Pace, Benjamin J Ryan, Brian Scheffe, Tom Schimelfenig, June E Wolfe, Sara F Heger

Faculty, Staff and Students Publications

Decentralized wastewater treatment and reuse represent critical infrastructure across the rural-periurban-urban continuum around the world. Effective, efficient, resilient, and equitable implementation of on-premise technologies and management systems is part of a One Water approach and necessary to protect public health and the environment, yet inconsistent delivery of essential public health services persists in many regions, including across states, tribes, and territories of the United States. We initiated a groundbreaking effort to understand challenges and to identify research opportunities related to the science and practice of decentralized wastewater. A horizon scanning exercise using a bottom up and transparent key questions approach …

The Biomedical Landscape Of Genomic Structural Variation In The Qatari Population, Elbay Aliyev, Najeeb Syed, Alessia Visconti, Taghi Aliyev, Aziz Belkadi, Mohammadmersad Ghorbani, Niccolò Rossi, Haroon Naeem, Geethanjali Devadoss Gandhi, Gaurav Thareja, Aljazi Al-Maraghi, Waleed Aamer, Amal Abdulsalam Ibrahim, Rulan Shaath, Farooq Omar Al-Ajli, Rozaimi Mohamad Razali, Fritz J Sedlazeck, Sonia Davila, Ammira Akil, Karsten Suhre, Younes Mokrab, Mario Falchi, Khalid A Fakhro

Faculty, Staff and Students Publications

We present a large-scale study of structural variation (SV) in the Qatari population, based on short-read whole-genome sequencing (WGS) of 6,141 individuals, identifying 153,946 variants across 5 classes reflecting the region's diversity and evolutionary history. Leveraging consanguinity and biobank phenotypes, we identify >180 putative gene knockouts, and use proteomics to show functional consequences in homozygotes. Conversely, 52 genes show significant depletion of homozygous deletions, eight of which cause severe pediatric disease or murine embryonic lethality. Examining phenotypic extremes uncovers several non-exonic homozygous deletions with large effect, including in SPIRE2 (creatinine), MAGI2 (leanness) and a chr19 microRNA cluster (extreme obesity). Further, …

Repeated Mild Head Injury Establishes A Senescent Cranial Bone Marrow Niche That Impairs Brain Metabolism, Patrick J Devlin, Romeesa Khan, Trang H Do, Bryce E West, Janelle M Korf, Gary U Guzman, Chunfeng Tan, John Ahn, Rene Flores, Micheal E Maniskas, Sean P Marrelli, Anna Malovannaya, Erica Underwood, Rodney M Ritzel

Faculty, Staff and Students Publications

Traumatic brain injury (TBI) of any severity is associated with long-term systemic inflammation and increased risk of peripheral comorbidities, yet the mechanisms driving immune dysregulation and accelerated aging after repeated mild head impacts remain poorly defined. Here, we investigated the acute and chronic effects of repeated mild TBI (rmTBI) on distal and proximal bone marrow compartments in the femur and calvaria, respectively. Using a modified weight-drop mouse model delivering rotational and acceleration-deceleration forces (3 hits/week for up to 16 weeks), rmTBI produced no mortality, skull fracture, hemorrhage, or brain leukocyte infiltration. One day after three consecutive impacts, rmTBI induced robust …

Therapeutic Responses In Patients With Advanced Nsclc Enrolled In Early-Phase Clinical Trials At Md Anderson, Jeong Uk Lim, Heather Y Lin, Lei Kang, Hung Le, Tin-Yun Tang, Stephane Champiat, Ecaterina Elena Dumbrava, Xiuning Le, Aung Naing, Sarina A Piha-Paul, Jordi Rodon Ahnert, Apostolia Maria Tsimberidou, Timothy A Yap, Siqing Fu, Funda Meric-Bernstam, David S Hong

Faculty, Staff and Student Publications

We evaluated clinical outcomes and safety profiles in patients with non-small cell lung cancer (NSCLC) treated in early-phase trials. A retrospective review of 546 NSCLC cases treated from January 2016 to December 2024 at The University of Texas MD Anderson Cancer Center was performed using the MD Anderson CHIMERA database. Patients were categorized into seven groups based on treatment regimen. The overall objective response rate (ORR) was 19.9%, and the highest ORRs were in the targeted combination (30.8%) and targeted monotherapy (29.7%) groups. Gene alteration–matched therapy, serum albumin level, metastatic burden, treatment group, and liver metastasis were independently associated with …

Mini-Hyper-Cvd Plus Venetoclax And Navitoclax For Relapsed/Refractory Acute Lymphoblastic Leukemia, Nicholas J Short, Hagop Kantarjian, Nitin Jain, Tapan M Kadia, Jayastu Senapati, Fadi G Haddad, Manuel M Maroun, Koji Sasaki, Lianchun Xiao, Xuelin Huang, Omer Karrar, Regina Abramova, Min Zhao, Rebecca Garris, Marina Konopleva, Farhad Ravandi, Elias Jabbour

Faculty, Staff and Student Publications

No abstract provided.

Genome-Wide Gene By Sleepiness Interaction Analysis For Sleep Apnea, Pavithra Nagarajan, Nuzulul Kurniansyah, Jiwon Lee, Sina A Gharib, Yushan Xu, Yiyan Zhang, Brian Spitzer, Tariq Faquih, Hufeng Zhou, Eric Boerwinkle, Han Chen, Daniel J Gottlieb, Xiuqing Guo, Nancy L Heard-Costa, Bertha A Hidalgo, Daniel Levy, Peter Y Liu, Hao Mei, Rebecca Montalvan, Sutapa Mukherjee, Kari E North, George T O'Connor, Lyle J Palmer, Sanjay R Patel, Bruce M Psaty, Shaun M Purcell, Laura M Raffield, Stephen S Rich, Jerome I Rotter, Richa Saxena, Albert V Smith, Katie L Stone, Xiaofeng Zhu, Topmed Sleep Trait Working Group, Brian E Cade, Tamar Sofer, Susan Redline, Heming Wang

Faculty, Staff and Student Publications

Study objectives: Excessive daytime sleepiness (EDS), influenced by environmental and social-behavioral factors, is reported by a subset of patients with sleep apnea-a group that may be at elevated cardiovascular risk. However, it is unclear whether sleep apnea with and without EDS have distinct genetic underpinnings. In this study, we perform gene-by-EDS interaction analyses for apnea hypopnea index, a diagnostic marker of sleep apnea severity, to understand EDS's influence on its underlying genetic risk.

Methods: Discovery interaction analyses for common variants and gene-based rare variants were conducted respectively using multi-ethnic Trans-Omics for Precision Medicine (N = 11 619) data, followed by …

Perioperative Fluid Management In Pancreaticoduodenectomy In The Era Of Goal-Directed Fluid Therapy: A Review Of The Literature, Meghan D Grim, Richard Zheng, Nader Hanna, Harish Lavu, Charles J. Yeo, Avinoam Nevler

Department of Surgery Faculty Papers

BACKGROUND: Pancreaticoduodenectomy (PD) is the only curative option for localized pancreatic head and periampullary malignancies. However, PD is associated with significant perioperative morbidity. Perioperative fluid management has emerged as an important modifiable factor influencing surgical outcomes in PD.

METHODS: In this qualitative review, PubMed/Medline searches were performed between March and August 2025 to review the terms "pancreaticoduodenectomy," "fluid management," "Enhanced Recovery After Surgery," "complications," and related terms.

RESULTS: Historically, liberal fluid administration was favored to compensate for third-space losses, but contemporary evidence has linked excessive fluid volumes to complications, such as postoperative pancreatic fistula, anastomotic edema, and increased inflammatory responses. …

Tumor-Specific Immune Responses And Biomarkers In Pediatric Patients With High-Risk Hodgkin Lymphoma, Keri Toner, Lindsay A Renfro, Hema Dave, Gloria Pezzella, Qinglin Pei, Lisa Giulino-Roth, Terzah Horton, Frank G Keller, Kara M Kelly, Sharon M Castellino, Catherine M Bollard

Faculty, Staff and Students Publications

There is an unmet need to examine antitumor immune responses and predictive biomarkers in the peripheral blood to guide effective combination immunotherapies in classical Hodgkin lymphoma (cHL). We sought to evaluate T-cell specific immune responses as well as cytokine and chemokine profiles including levels of soluble CD30 (sCD30), sCD163, and thymus and activation-regulated chemokine (TARC) in relation to event-free survival in patients with cHL. The Children’s Oncology Group (COG) clinical trial AHOD1331 was a randomized phase 3 trial for patients with newly diagnosed high-risk cHL, aged 2 to 21 years, which compared standard chemotherapy and doxorubicin, bleomycin, vincristine, etoposide, prednisone, …

High-Dose Oral Pyrophosphate Inhibits Connective Tissue Calcification In Abcc6 Null Mice But May Affect Bone Structure, Ibtesam Rajpar, Nicholas Yancy, Jacob Beiriger, Christina Shao, Syed Naqvi, Deana Mancuso, Fatemeh Niaziorimi, Ryan E Tomlinson, Koen Van De Wetering

Department of Orthopaedic Surgery Faculty Papers

Pseudoxanthoma elasticum (PXE) is a rare inherited disorder marked by abnormal calcium phosphate deposition in soft connective tissues, particularly the skin, arteries, and eyes. It is caused by inactivating mutations in the ABCC6 gene, which encodes a hepatic efflux transporter. Loss of ABCC6 function leads to reduced plasma levels of pyrophosphate (PPi), a key inhibitor of calcification, thereby promoting ectopic mineralization. Oral PPi therapy has emerged as a potential treatment, but its effectiveness is uncertain. Most ingested PPi is hydrolyzed in the gut to inorganic phosphate, which may worsen calcification. Moreover, its impact on mineralized tissues remains largely unexplored. Abcc6−/− …

Dynamic Fib-4 Score Changes And Hcc Risk In Patients With Masld And Elevated Liver Enzymes: A Nationwide Cohort Study, Yee Hui Yeo, Hsiu J Ho, Tsai-Wei Huang, Teng-Yu Lee, Ju Dong Yang, George Cholankeril, Chien-Jen Chen, Hawi-I Yang, Chuen-Fei Chen, Hung-Chuen Chang, Chun-Ying Wu

Faculty, Staff and Students Publications

Introduction: Hepatocellular carcinoma (HCC) can develop in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) without cirrhosis, especially in those with elevated liver enzymes. However, there is currently no low-cost, scalable screening tool for this population. To address this need, we investigated the association between serial changes in FIB-4 (fibrosis-4) scores over a 3-year period and the risk of developing HCC in a large, diverse cohort of patients with MASLD without cirrhosis.

Methods: This study utilized a nationwide cohort from the National Health Insurance Research Database (NHIRD), including 810,698 patients with MASLD who had demographic and laboratory data at baseline …

Chek2 Loss Endows Chemotherapy Resistance To Hematopoietic Stem Cells, Jing Zhou, Tianyuan Hu, Dian Li, Sanming Li, Minhua Li, Xiangguo Shi, Daisuke Nakada

Faculty, Staff and Students Publications

Individuals with history of chemo- or radiotherapy frequently exhibit somatic mosaicism in the blood, often involving mutations in genes responsible for DNA damage responses (DDR), such as CHEK2. However, the mechanisms by which CHEK2 mutations promote the expansion of mutant cells following chemo- or radiotherapy remain poorly understood. Here, we demonstrate that loss of CHEK2 confers resistance to chemotherapy in hematopoietic stem and progenitor cells (HSPCs). Through a CRISPR-based screen, we identified CHEK2 as a gene whose loss enhances resistance to cytotoxic chemotherapies. A complementary drug screen revealed that CHEK2-mutant cells are also resistant to DNA hypomethylating agents. Chek2-deficient HSPCs …