Digital Commons Network^™

Driveline Infections Among Patients Supported With Left Ventricular Assist Devices: A Single Center Sixteen-Year Longitudinal Profile, Anh Nguyen, Alexis Shafii, Gabriel Loor, Andrew Civitello, O Howard Frazier, Todd Rosengart, Kenneth Liao

Faculty, Staff and Students Publications

Background: Left ventricular assist device (LVAD) driveline infections significantly impact patient outcomes. This study aimed to identify their risk factors.

Methods: We analyzed LVAD data from our institutional Intermacs database (January 1, 2008-December 31, 2023), combining primary implants and pump exchanges. Patient characteristics were summarized as frequencies for categorical variables and median (IQR) for continuous variables. The nature of repeated infection events was handled by the Andersen-Gill method within a multivariable Cox proportional hazards model for cause-specific hazard of driveline infections, accounting for death and heart transplant as competing risks.

Results: Our cohort included 1026 LVAD implants. Median patient age …

Glp1-Ra And Sglt2-I: Implementation And Insulin Deescalation Strategies, Arthi Palani, Sagar Patel, Shriya Patel, Shivani Srivastava, Jay Patel, Salman Salehin, Yochai Birnbaum, Joseph Allencherril

Faculty, Staff and Students Publications

Purpose of review: This review will summarize the most contemporary trials for glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2-i) and present guidance on management and recommendations on adjunctive tapering of insulin in patients with insulin-dependent diabetes mellitus, which we term "de-insulinization."

Recent findings: GLP1-RA and SGLT2-i are the principal classes of diabetes medications evidencing cardiovascular benefit. However, there is limited consensus on how to effectively prescribe and maintain these medications for patients on other glucose-lowering therapy, especially insulin. Patients with type 2 diabetes and cardiovascular disease should be started on either a GLP-1RA, SGLT-i, or …

Long-Term Outcomes Of Left Bundle-Branch Pacing Vs Biventricular Pacing In Heart Failure: The Heartsync-Lbbp Randomized Clinical Trial, Xueying Chen, Xi Liu, Ruogu Li, Zhongkai Wang, Yixiu Liang, Lei Zhang, Wei Wang, Jin Bai, Jingfeng Wang, Shengmei Qin, Weiwei Zhang, Tianbao Yao, Dong Huang, Ting Chen, Xianxian Zhao, Dening Liao, Jingbo Li, Jialiang Mao, Mihail G Chelu, Yangang Su, Kenneth A Ellenbogen, Junbo Ge

Faculty, Staff and Students Publications

Importance: Left bundle-branch pacing (LBBP) has been proposed as an alternative to biventricular pacing (BiVP) for patients with heart failure with left bundle-branch block (LBBB). However, robust clinical evidence from randomized clinical trials is lacking.

Objective: To evaluate the long-term clinical outcomes of LBBP and BiVP.

Design, setting, and participants: This multicenter, prospective, randomized clinical trial enrolled 200 patients at 6 centers in China with a left ventricular ejection fraction (LVEF) of 35% or less and LBBB from October 2020 to March 2022. This study was took place from October 2020 to September 2024. These data were analyzed September 2024 …

Novel Variants Identified In Families With Snx27 -Related Neurodevelopmental Disorder, Aiding In Characterizing Its Genotypic And Phenotypic Spectrum, Tayyaba Shan, Abrar Hussain, Anushree Acharya, Mulazim Hussain, Yumei Li, Hafiz Muhammad Jafar Hussain, Kiran Afshan, Suzanne M Leal, Rui Chen, Asif Mir, Isabelle Schrauwen, Sabika Firasat

Faculty, Staff and Students Publications

Background:

Sorting Nexin 27 (SNX27), a key regulator of synaptic receptor trafficking and endosomal recycling, has been implicated in maintaining synaptic homeostasis and cognitive function. To date, variants in SNX27 have been reported in a small number of patients across three publications with severe neurodevelopmental phenotypes. However, the genetic and functional landscape of SNX27-related disorders remains poorly understood, and further evidence is needed to confirm its association with disease and to better delineate the associated phenotype.

Methods and Results:

Two unrelated Pakistani families with a total of five affected individuals segregating a neurodevelopmental disorder were investigated via exome …

Black Equality In Ocd Neurogenomics (Belong): Study Protocol, Iasha J Williams, Dalia Y Marquez, Kara E Lopez-Lengowski, Malini Bommiasamy, Ogechi Cynthia Onyeka, Slayton J Underwood, Juliana E Avery, Jacob Gluckman, Thariana Pichardo, Rhea Chandler, Yulu Brown, Katie Mangen, Emma Grace Choplin, Black Equality In Ocd Neurogenomics (Belong) Study Team, Sonyia C Richardson, Joseph D Buxbaum, Eric A Storch, James J Crowley, Sidney H Hankerson, Dorothy E Grice

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) is a chronic, serious psychiatric disorder that affects 2%-3% of the population and is associated with high personal and societal costs. Genetic factors are estimated to explain roughly half the risk of developing OCD, and genomic studies are just beginning to identify common and rare genetic variants mediating this risk. A major goal of genomic studies is to yield insights into the etiology of OCD and identify molecular targets for the development of novel therapeutics. However, the overwhelming majority of subjects in existing genetic studies are of European ancestry, limiting the generalizability of these findings. To address …

Widespread Distribution Of Alu/Alu-Mediated Genomic Rearrangement Predisposing To A Broad Range Of Mendelian Disease And Cancer In Human Populations, Ruizhi Vince Duan, Haowei Du, Shruti Pande, Ahmed K Saad, Meryem M Atik, Minal Jamsandekar, Karen J Coveler, Zain Dardas, Shalini N Jhangiani, Jennifer E Posey, Richard A Gibbs, James R Lupski

Faculty, Staff and Students Publications

Background

Genome-wide distributions of Alu elements contribute to a broad range of structural variants (SVs) through Alu/Alu-mediated genomic rearrangement (AAMR). Yet, the prevalence and characteristics of AAMR on the human genome and its scale in generating pathogenic SVs remain poorly understood.

Methods

We established a disease-focused, AAMR-SV dataset and a control dataset to comprehensively delineate the genomic landscape of Alu mutagenesis. The disease-focused dataset included 407 published pathogenic AAMR-SV alleles in 115 known genes for Mendelian disorders or traits through a literature survey. A control dataset was collected from short-read genome sequencing analyses of 100 randomly selected, healthy individuals. …

Efficient In Vivo Pharmacological Inhibition Of Δfosb, An Ap-1 Transcription Factor, In The Brain, Sean Mcneme, Anil Kumar, Yun Young Yim, Brandon W Hughes, Corey St Romain, Yi Li, Ashwani Kumar, Qichao Bao, Molly Estill, Shanghua Fan, Nadeen Takatka, Earnest P Chen, Matthew Rivera, Haiying Chen, Alfred J Robison, Mischa Machius, Stephen J Haggarty, Jeannie Chin, Eric J Nestler, Jia Zhou, Gabby Rudenko

Faculty, Staff and Students Publications

ΔFOSB, an unusually stable member of the AP-1 family of transcription factors, mediates long-term maladaptations that play a key role in the pathogenesis of drug addiction, cognitive decline, dyskinesia, and several other chronic neurological and psychiatric conditions. We have recently identified that 2-phenoxybenzenesulfonic acid-containing compounds disrupt the binding of ΔFOSB to DNA in vitro in cell-based assays, and one such compound, JPC0661, disrupts ΔFOSB binding to genomic DNA in vivo in the mouse brain with partial efficiency. JPC0661 binds to a groove outside of the DNA-binding cleft of the ΔFOSB/JUND bZIP heterodimer in a cocrystal structure. Here, we generated a …

Robotic Single-Incision Laparoscopic Surgery For The Management Of Endometriosis: First Experience Via The Da Vinci Sp Platform, Qiannan Yang, Daniel Y Lovell, Xiaoming Guan

Faculty, Staff and Students Publications

Objective: To demonstrate the feasibility and mid-term outcomes of Robotic single-port single-incision laparoscopic surgery (RSP-SILS) for endometriosis management.

Methods: A retrospective analysis was conducted on 50 adult women with endometriosis who underwent RSP-SILS via the da Vinci SP platform between November 2023 and July 2025.

Results: Median total operative time was 142 min, robot dock time was 3 min, and robot console time was 99 min. Median estimated blood loss was 25 mL. No conversion occurred. Reported mid-term outcomes included 1 case each of pelvic haematoma, Clostridioides difficile colitis, and umbilical surgical site infection, as well as 3 cases of …

Empiric Azithromycin Alters The Upper Respiratory Microbiome And Resistome Without Anti-Inflammatory Benefit In Covid-19, Abigail Glascock, Cole Maguire, Hoang Van Phan, Emily C Lydon, Joanna Schaenman, Carolyn S Calfee, Esther Melamed, John Greenland, David B Corry, Farrah Kheradmand, Lindsey R Baden, Rafick Sekaly, Grace A Mccomsey, Elias K Haddad, Charles B Cairns, Linda N Geng, Bali Pulendran, Ana Fernandez-Sesma, Viviana Simon, Jordan P Metcalf, Nelson I Agudelo Higuita, William B Messer, Mark M Davis, Kari C Nadeau, Monica Kraft, Christian Bime, David J Erle, Mark A Atkinson, Scott C Brakenridge, Lauren I R Ehrlich, Ruth R Montgomery, Albert C Shaw, Catherine L Hough, David A Hafler, Alison D Augustine, Patrice M Becker, Bjoern Peters, Al Ozonoff, Annmarie Hoch, Seunghee Kim-Schulze, Florian Krammer, Steven Bosinger, Walter Eckalbar, Matthew C Altman, Michael Wilson, Leying Guan, Holden Maecker, Hanno Steen, Impacc Network, Joann Diray-Arce, Nadine Rouphael, Steven H Kleinstein, Naresh Doni Jayavelu, Elaine F Reed, Ofer Levy, Victoria T Chu, Charles R Langelier

Faculty, Staff and Students Publications

Azithromycin is a widely used antibiotic and was frequently used to treat hospitalized patients during the COVID-19 pandemic. The impact of empiric azithromycin use on the respiratory microbiome in patients with viral respiratory infections is unclear. Here we used longitudinal metatranscriptomics on nasal swabs from a prospective multicentre cohort of 1,164 patients hospitalized for COVID-19. We compared the upper respiratory microbiome, resistome and systemic immune response in patients treated with azithromycin (n = 366) with those who received no antibiotics (n = 474) or other antibiotics (n = 324). We found that azithromycin altered microbiome composition and increased the expression …

Aht Diagnoses: The Influences Of Clinical Presentation And Evidence Of Impact, Ruairi Smith-Dewey, Angela Bachim, Colleen Bressler, Kristine Campbell, Lori Frasier, Christopher Greeley, Danielle Horton, Nicole Johnson, Jan Leonard, Megan M Letson, Caitlin Mcnamara, Ashley Sherman, Shalon Nienow, Stuart Sommers, Joanne N Wood, James Anderst

Faculty, Staff and Students Publications

Background: The frequency of abusive head trauma (AHT) diagnoses by child abuse pediatricians (CAPs), especially regarding external evidence of head impact, has been questioned.

Objectives: To compare CAP diagnoses in subjects with subdural hemorrhage (SDH) across clinical presentations, including subgroups with and without external evidence of head impact. Additionally, we aimed to describe subjects with SDH and concomitant suspicious injuries (CSI) without evidence of head impact.

Participants and setting: Multicenter retrospective study including subjects < 24 months old with SDH.

Methods: Subjects were divided into groups based on clinical presentations: Ill SDH only, Non-ill SDH only, and SDH + CSI. Groups were subcategorized based on presence/absence …

Phenome-Wide Analysis Of Copy Number Variants In 470,727 Uk Biobank Genomes, Xueqing Zoe Zou, Fengyuan Hu, Haiyi Lou, Oliver S Burren, Xiaoyin Li, Karyn Megy, Eleanor Wheeler, Qiang Wu, Santosh S Atanur, Marcin Karpinski, Douglas Loesch, Zammy Fairhurst-Hunter, Sri V V Deevi, Erin Oerton, Sean Wen, Xiao Jiang, Cecilia Salvoro, Jonathan Mitchell, Abhishek Nag, Ben Hollis, Amanda O'Neill, Jen Harrow, Stewart Macarthur, Sebastian Wasilewski, Sean O'Dell, Lifeng Tian, Katherine R Smith, Guillermo Del Angel, Margarete Fabre, Ryan S Dhindsa, Quanli Wang, Slavé Petrovski, Keren Carss

Duncan NRI Faculty and Staff Publications

Copy number variants (CNVs) are key drivers of human diversity and disease risk1. Here we evaluate the role of CNVs across a broad range of human phenotypes and diseases by analysing CNVs from 470,727 UK Biobank whole-genome sequences and conducting a variant- and gene-level phenome-wide association study (PheWAS) with 2,941 plasma protein abundance measurements, 13,336 binary clinical phenotypes and 1,911 quantitative traits. Proteomic analyses validated functional associations of CNVs with nearby genes (cis-protein quantitative trait loci; cis-pQTLs)—with deletions and duplications typically associated with reduced and increased protein levels, respectively—and uncovered previously unknown protein–protein interactions …

Diagnostic Criteria And Management Of Melas And Stroke-Like Episodes: Consensus-Based Statements, Michelangelo Mancuso, Marcello Bellusci, Valerio Carelli, Irenaeus De Coo, Daria Diodato, Felix Distelmaier, Omar Hikmat, Michio Hirano, Rita Horvath, Amel Karaa, Thomas Klopstock, Mary Kay Koenig, Cornelia Kornblum, Chiara La Morgia, Piervito Lopriore, Mika Henrik Martikainen, Robert Mcfarland, Olimpia Musumeci, Robert D S Pitceathly, Guido Primiano, Shamima Rahman, Fernando Scaglia, Andrew Schaefer, Manuel Schiff, Luisa Semmler, Costanza Lamperti, Serenella Servidei

Faculty, Staff and Student Publications

Background and purpose: Mitochondrial Encephalomyopathy, Lactic acidosis and Stroke-like episodes (MELAS) is a rare multisystem mitochondrial disorder with clinical heterogeneity. Diagnostic criteria and management strategies for MELAS and mitochondrial stroke-like episodes (SLE) remain inconsistent. This work provides international consensus recommendations on the definition, diagnosis, and management of MELAS and SLE in pediatric and adult populations.

Methods: An international Delphi consensus process was conducted within the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD), in collaboration with the US Mitochondrial Medicine Society, the ERN for Hereditary Metabolic Disorders (MetabERN), and patient representatives. Following a systematic literature review, 54 statements addressing diagnostic …

Weaning Drives Microbiome-Mediated Epigenetic Regulation To Shape Immune Memory In Mice, Li Yang, Robert C Peery, Shirui Zhou, Xiaomin Chen, Leah M Farmer, Fabiola Gutierrez, Stephanie Fowler, Lanjing Zhang, Julia M Salamat, Karen Riggins, Jiejun Shi, Lanlan Shen

Children’s Nutrition Research Center Staff Publications

During weaning, the transition to solid food diversifies the gut microbiome, triggering a programmed immune response critical for long-lasting mucosal immunity. Previous work showed that the gut microbiome mediates epigenetic development in intestinal stem cells (ISCs) during suckling, but what happens during weaning is unclear. Here, genome-wide profiling revealed that weaning-driven microbiome changes shape the DNA methylome and transcriptome of murine ISCs in an IFNγ-dependent manner. Specifically, we observe demethylation of enhancer elements essential for MHC class II genes, which results in a transcriptional memory that persists through differentiation into adulthood. IFNγ blockade, or low-dose penicillin to target Gram-positive bacteria, …

Breast Cancer-Derived Extracellular Vesicle Mir-425-5p (Mir-425) Promotes Brain Metastasis Via Activating Astrocytes Through The Novel Mir-425-Znf24-Ccl8 Signaling Axis, Grace L Wong, Munazza S Khan, Sara Manore, Shivani Bindal, Ravi Singh, Hui-Wen Lo

Faculty, Staff and Student Publications

Mechanisms underlying breast cancer brain metastasis (BCBM) are still not well understood. Here, we identified that BCBM patient serum contained extracellular vesicles (EVs) with high levels of microRNAs (miRNAs)-107 and -425. Levels of miR-107 and miR-425 were elevated in brain metastases, and the elevation was associated with poor patient prognoses. Ectopic expression of miR-107 and miR-425 promoted mammospheres; however, the inhibition of miR-425, but not miR-107, suppressed breast cancer mammosphere formation. We further observed that EVs from miR-425-overexpressing breast cancer cells strongly activated astrocytes whereas their inhibitors abrogated the effect. Conditioned media from miR-425-activated astrocytes promoted mammospheres. To elucidate how …

Free Versus In Situ Right Internal Mammary Artery As A Conduit In Coronary Artery Bypass Surgery: A Meta-Analysis, Yuta Kikuchi, Tomoki Sakata, Tomonari Shimoda, Shinichi Fukuhara, Junichi Shimamura, Makoto Hibino, Tsuyoshi Kaneko, Hiroo Takayama, Hisato Takagi, Michel Pompeu Sa, Toshiki Kuno

Department of Medicine Faculty Papers

OBJECTIVES: There is debate regarding the optimal choice for a second conduit in coronary artery bypass grafting. The right internal mammary artery (RIMA) is commonly employed as a second conduit; however, it is unclear whether the free (fRIMA) or in situ (isRIMA) configuration yields superior outcomes. We performed a systematic review and meta-analysis to compare clinical outcomes between fRIMA and isRIMA as the second conduit.

METHODS: A comprehensive search of PubMed (MEDLINE), EMBASE, and CENTRAL was performed through May 2025 to identify studies comparing outcomes in patients undergoing coronary artery bypass grafting with either fRIMA or isRIMA as a second …

Helminth Coinfections Mitigate Clinical, Parasitological, And Immune Outcomes In Mozambican Children With Malaria, Inocência Cuamba, Rebeca Santano, Berta Grau-Pujol, Marta Vidal, Ruth Aguilar, Anélsio Cossa, Chenjerai Jairoce, Rojelio Mejia, Augusto Nhabomba, Jose Muñoz, Gemma Moncunill, Carlota Dobaño

Faculty, Staff and Students Publications

Background: Clearance of Plasmodium falciparum infection requires a TH1 immune response with production of pro-inflammatory cytokines, IgG1, and IgG3 responses. In contrast, infections with helminths are dominated by TH2/Treg immune responses characterized by production of anti-inflammatory cytokines, IgE, and IgG4, which could potentially interfere with malaria outcomes and immune responses.

Methods: We recruited 441 malaria-symptomatic children aged 2-10 years attending two hospitals in the Manhiça District (Mozambique) and assessed infection by rapid antigen diagnostic test, microscopy, and/or quantitative PCR. Using Luminex, we measured concentrations of 30 cytokines and IgA, IgM, IgE, IgG, and IgG1-4 levels against 12 P. falciparum antigens …

Gene-Agnostic Therapeutic Strategies For Inherited Retinal Diseases: Neuroprotection And Immunomodulation, Lucas W. Rowe, S. Patricia Becerra, Robert E. Maclaren, Robert L. Avery, Charles C. Wykoff, Allen C. Ho, Carl D. Regillo, Dean Eliott, Andrew Osborne, Katie M. Binley, Thomas A. Ciulla

Wills Eye Hospital Papers

Background/Objectives: Inherited retinal diseases (IRDs) represent a genetically heterogeneous group of disorders caused by mutations in over 280 genes with more than 3100 identified variants. While gene-specific replacement therapies have achieved landmark success with voretigene neparvovec (Luxturna) for biallelic RPE65-associated retinal dystrophy, developing individual therapies for each genetic subtype remains impractical. This review examines gene-agnostic therapeutic approaches utilizing neuroprotection and immunomodulation that target common pathophysiological mechanisms shared across multiple IRD genotypes. Methods: We reviewed the literature on neuroprotective and immunomodulatory gene therapy strategies for IRDs, focusing on neurotrophic factors and complement system modulation. Results: Neuroprotective approaches delivering neurotrophic factors—including pigment …

Physical Rehabilitation For Older Patients With Acute Hfpef (Rehab-Hfpef) Trial: Design And Rationale, Amy M. Pastva, Gordon R. Reeves, David J. Whellan, Robert J. Mentz, Haiying Chen, Alain G. Bertoni, Pamela W. Duncan, Mark A. Espeland, Shelby D. Reed, M. Benjamin Nelson, Christopher M. O'Connor, Dalane W. Kitzman

Department of Medicine Faculty Papers

RATIONALE: Older patients hospitalized for acute decompensated heart failure with preserved ejection fraction (HFpEF) experience persistently poor outcomes, including physical disability, cognitive impairment, depression, impaired health-related quality of life (HRQOL), rehospitalizations, loss of independence, and mortality. In our previous phase 2 REHAB-HF trial, an innovative physical rehabilitation intervention, delivered across three phases-inpatient, 12-week outpatient, and 3-month home-based maintenance-produced large improvements in physical function and HRQOL, with signals of reduced clinical events among patients with acute HFpEF. These findings provide a compelling rationale for a definitive, event-powered trial to evaluate clinical outcomes.

HYPOTHESIS: Targeting physical frailty and multisystem functional impairments using …

Cilia Dynamics In Primary Ciliary Dyskinesia: A Biophysical Characterization Of The Rsph4a Founder Variant, Gabriel Rosario-Ortiz, José Muñiz-Hernández, Natalia M Ortiz-Pérez, Marcos J Ramos-Benitez, Ricardo A Mosquera, Wilfredo De Jesús-Rojas

Faculty, Staff and Student Publications

Primary ciliary dyskinesia (PCD) is a rare ciliopathy resulting in chronic oto-sino-pulmonary disease. PCD diagnosis can be achieved by a combination of different diagnostic and adjuvant tools, including high-speed video-microscopy analysis (HSVA). A founder variant has been described in Puerto Rico as the most common cause of PCD in the island. Background/Objectives: In HSVA, objective parameters such as ciliary beat frequency (CBF) and subjective parameters such as ciliary beat pattern (CBP) shed light on the biophysical properties of cilia. However, the subjective nature of CBP creates a gap in knowledge; characteristics such as the length, angle, and bending index of …

The Hexosamine Biosynthetic Pathway Alters The Cytoskeleton To Modulate Cell Proliferation And Migration In Aggressive Prostate Cancer, Rajina Shakya, Praveen Suraneni, Amit Rahi, Michael Y Young, Emily Cousino, Christine B Magdongon, Raju Gajjela, Basil B Mattamana, Alexander Zaslavsky, Ganesh S Palapattu, Arun Sreekumar, Dileep Varma

Faculty, Staff and Students Publications

Castration-resistant prostate cancer (CRPC) progresses despite androgen deprivation therapy, as cancer cells adapt to grow without testosterone, becoming more aggressive and prone to metastasis. CRPC biology complicates the development of effective therapies, posing challenges for patient care. Recent gene-expression and metabolomics studies highlight the Hexosamine Biosynthetic Pathway (HBP) as a critical player, with key components like GNPNAT1 (Glucosamine-phosphate N-acetyltransferase 1) being downregulated in CRPC. GNPNAT1 knockdown in pre-clinical models has been shown to increase growth and metastasis in CRPC tumors, though the mechanisms remain unclear.To investigate the cellular basis of these CRPC phenotypes, we generated a CRISPR-Cas9 knockout model of …

Perinatal Obsessive-Compulsive Symptoms And Maternal-Infant Bonding: A Longitudinal Examination Of Depression And Relationship Quality, Journa Njoh, Jonathan S Abramowitz, Rashelle Musci, Mary C Kimmel, Lauren M Osborne, Jack Samuels, Paul Nestadt, Gerald Nestadt, Eric A Storch

Faculty, Staff and Students Publications

Background

Perinatal obsessive–compulsive (OC) symptoms are common and distressing, yet their impact on early parenting outcomes such as maternal-infant bonding remains poorly understood. Although prior research links maternal depression and anxiety to bonding difficulties, less is known about how perinatal OC symptoms relate to maternal-infant bonding over time, or the extent to which maternal-partner relationship quality is associated with these outcomes, and whether depressive symptoms explain observed associations.

Methods

Data were drawn from a longitudinal study of 256 pregnant women recruited from two U.S. sites between 2020 and 2023. Participants completed self-report and clinician-administered assessments at 20 weeks (PGWK20), 34 …

From Fair To Cure: Guidelines For Computational Models Of Biological Systems, Herbert M. Sauro, Eran Agmon, Michael L. Blinov, John H. Gennari, Joseph L. Hellerstein, Adel Heydarabadipour, Bartholomew E. Jardine, Elebeoba May, David P. Nickerson, Lucian P. Smith, Gary D. Bader, Frank T. Bergmann, Patrick M. Boyle, Andreas Dräger, James R. Faeder, Song Feng, Juliana Freire, Fabian Fröhlich, James A. Glazier, Thomas E. Gorochowski, Tomas Helikar, Henning Hermjakob, Stefan Hoops, Peter Hunter, Princess I. Imoukhuede, Sarah M. Keating, Matthias König, Reinhard Laubenbacher, Leslie M. Loew, Carlos F. Lopez, William W. Lytton, Rahuman S. Malik-Sheriff, Andrew Mcculloch, Pedro Mendes, Lealem Mulugeta, Chris J. Myers, Jerry G. Myers, Anna Niarakis, David D. Van Niekerk, Brett G. Olivier, Alexander A. Patrie, Ellen M. Quardokus, Nicole Radde, Johann M. Rohwer, Sven Sahle, James C. Schaff, Falk Schreiber, T. J. Sego, Janis Shin, Jacky L. Snoep, Rajanikanth Vadigepalli, H. Steven Wiley, Dagmar Waltemath, Ion I. Moraru

Computational Medicine Center Faculty Papers

Guidelines for managing scientific data have been established under the FAIR principles, requiring that data be Findable, Accessible, Interoperable, and Reusable. In many scientific disciplines, especially computational biology, both data and models are key to progress. For this reason, and recognizing that such models are a very special type of "data", we argue that computational models, especially mechanistic models prevalent in medicine, physiology and systems biology, deserve a complementary set of guidelines. We propose the CURE principles, emphasizing that models should be Credible, Understandable, Reproducible, and Extensible. We delve into each principle, discussing verification, validation, and uncertainty quantification for model …

Associations Between Caregiver-Provider Communication Quality And Unmet Care Needs Among Older Adults, Jiaming Liang, Rafael Samper-Ternent, Brian Downer, Zhigang Xie

Faculty, Staff and Student Publications

BACKGROUND: Unmet care needs (lack of assistance with daily activities) among older adults are common and linked to adverse health outcomes, greater healthcare utilization, and caregiver burden. While effective patient-provider communication is known to improve care quality, less is understood about the role of caregiver-provider communication, particularly across sociodemographic, health, and caregiving contexts. METHODS: We conducted a cross-sectional secondary analysis of pooled 2021–2023 National Health and Aging Trends Study (NHATS) and National Study of Caregiving (NSOC) data, restricted to community-dwelling older adults (65 + years) who received assistance from caregivers due to difficulty with daily activities, and had at least …

Measurable Residual Disease Testing In Acute Myeloid Leukemia: Current State, Foundational Models, And Tools For Future Development, Joseph Van Galen, Stephen D. Willis, Ashish Bains, Sara H. Small

Department of Medical Oncology Faculty Papers

Acute myeloid leukemia (AML) is a lethal and rapidly progressive hematologic malignancy with high rates of relapse and treatment refractoriness. Management of AML is complicated by biological heterogeneity in a disease that is broadly defined by the clonal expansion of myeloblasts that otherwise play an important role in healthy marrow tissues. While subtypes of AML are increasingly defined by druggable driver mutations including FLT3-ITD, IDH1, IDH2, and NPM1, conventional chemotherapy and reduced intensity induction regimens (e.g., azacitidine-venetoclax) remain therapeutic backbones. One area of active development for personalization of AML treatment is the assessment of measurable residual disease (MRD). MRD testing …

Functional And Structural Basis Of A Hypermorphic Trpc3 Variant, Briar Bell, Angela M Jaramillo-Granada, Luis O Romero, Irene A Gutierrez, Venkata K P S Mallampalli, Guizhen Fan, Sameer Varma, Matthew L Baker, Irina I Serysheva, Valeria Vásquez, Julio F Cordero-Morales

Faculty, Staff and Student Publications

Cerebellar ataxias are characterized by impaired motor coordination resulting from neuronal dysfunction within the cerebellum. The mechanisms underlying this pathology and its cerebellar-specific neurodegeneration remain unknown. We uncover how a gain-of-function canonical transient receptor potential member 3 (TRPC3) mutation, coupled with a cerebellum-specific isoform, stabilizes the channel’s open state, resists the leading inhibitor Pyr3, and drives calcium-dependent cell death. Restoring calcium homeostasis by expressing a Purkinje cell calcium pump improves cell viability. Transgenic expression of the TRPC3 hypermorphic variant in Caenorhabditis elegans induces neurodegeneration, confirming its pathogenicity across species. Cryo–electron microscopy and molecular simulations reveal the structural basis for the …

Social Isolation And Firearm Secure Storage In The Usa: Results From The 2022 Brfss, Alexander Testa, Daniel Semenza, Dylan B Jackson, Karyn Fu, Sandra Mckay, Kyle T Ganson, Jason M Nagata, Jack Tsai

Faculty, Staff and Student Publications

Background: Firearm secure storage (ie, storing firearms unloaded and locked) is recommended to reduce unintentional injuries and suicides. However, the relationship between psychological states, such as social isolation, and firearm secure storage practices is under-researched.

Methods: Data are from 7136 individuals with firearms in their households from the 2022 Behavioral Risk Factor Surveillance System. Multinomial logistic regression was used to explore the relationship between social isolation and firearm storage.

Results: Among respondents, 71.6% reported storing firearms unloaded, 14.2% stored firearms loaded and locked and 14.2% stored firearms loaded and unlocked. Most respondents reported feeling 'never' (40.7%) or 'rarely' (33.3%) socially …

Specialist Consultation Improves Underdiagnosis Of Surgical Adrenal Incidentaloma: A Trinetx Database Investigation, Aaron R. Hochberg, Monika Shirodkar, Brian H. Im, Xiaoying Deng, Fitsum T. Hailemariam, Sohan S. Shah, Rasheed A. M. Thompson, Francisco Aguirre, Patrick T. Gomella, Mihir S. Shah, Md, Costas D. Lallas, Adam R. Metwalli

Department of Urology Faculty Papers

Objectives: Despite practice guidelines recommending hormonal testing for all cases of incidentally discovered adrenal adenomas (incidentalomas), only 30% of patients receive laboratory workup. This study sought to evaluate hormonal testing and adrenal surgery rates in incidentaloma patients seen by a specialist (endocrinologist, nephrologist, urologist, or general surgeon), compared to those not seen by a specialist.

Methods: We identified incidentaloma cases by querying the TriNetX Research Network for all adult patients with an unspecified adrenal mass occurring within 1 month following abdominal imaging. We compared those seen by a specialist against those not following an incidentaloma diagnosis. Primary outcomes were rates …

Increasing Utilization Trends Of Robotic Assistance In Orthopaedic Surgery, Anish K. Ponna, Alec Giakas, Anthony A. Khoudary, Spencer N. Uggla, Sina Ramtin, Yousef A. Soliman, Asif M. Ilyas

Department of Orthopaedic Surgery Faculty Papers

INTRODUCTION: Robotic-assisted surgeries in orthopaedics have increased, particularly in hip and knee arthroplasty and spine surgeries. This study evaluates national utilization trends of robotic-assisted orthopaedic surgeries and demographic and geographic distribution of patients undergoing these surgeries.

METHODS: A retrospective cohort study was conducted on patients who underwent total hip arthroplasty, total and partial knee arthroplasty, or spine arthrodesis from 2017 to 2023 using the TriNetX database. Relevant International Classification of Diseases, 10th Revision, and Current Procedural Terminology codes identified patients who underwent a primary surgery with a corresponding robot-assisted code on the same day. Temporal trends in procedural volume were …

Explainable Drug Side Effect Prediction In Central Neural System Via Biologically Informed Graph Neural Network, Tongtong Huang, Ko-Hong Lin, Rodrigo Machado-Vieira, Jair C Soares, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

The early detection of potential side effects (SEs) is a critical yet formidable challenge within the realms of drug development and patient healthcare management. Conventional in-vitro or in-vivo approaches for SE detection are often not feasible to scale during the preclinical phase for numerous drug candidates. Innovations in explainable artificial intelligence offer the prospect of early detection of potential SEs for novel therapeutics prior to their release in the market, as well as the explication of the underlying biological mechanisms. In this context, we present a novel biologically informed graph-based model, called HHAN-DSI, which capitalizes on multimodal interactions among molecular …

A Hemorheological Perspective On Coronary Microvascular Dysfunction: Association Of Erythrocyte Parameters With Angiography-Derived Coronary Microcirculatory Resistance, Abdulrahman Alqazzaz, Yanfeng Lu, Jasmine Bao, Gary S. Mintz, Jiahao Feng, Yong Zhang, Shanshan Gao, Qiang Song, Feifei Ning, Hytham H. Al-Samawi, Mohsen Al-Manj, Mohammed Al-Asadi, Xin Huang, Ning Guo

Student Papers, Posters & Projects

BACKGROUND: Coronary microvascular dysfunction (CMD) contributes to myocardial ischemia in patients both without obstructive coronary artery disease (e.g., MINOCA/INOCA) and in those with co-existing epicardial stenosis. While its etiology includes structural and functional causes. hematologic parameters have been linked to cardiovascular outcomes. However, the relationship between red blood cell (RBC) markers and microvascular resistance remains poorly characterized. We aim to evaluate whether RBC parameters are correlated with the angiography-derived index of microcirculatory resistance (angio-IMR).

METHODS: This retrospective study evaluated the association between red blood cell (RBC) parameters and angio-IMR in patients with intermediate coronary artery disease (30%-70% stenosis). Data were …