Digital Commons Network^™

Epidemiology Of Healthcare-Associated Ventriculitis And Meningitis (Hcavm) And Community-Acquired Meningitis/Encephalitis And Evaluation Of An Off-Label Pcr Panel For Hcavm Diagnosis, Jaime Nassur, Katarina Schnell, Christine Dolon, Laura Walters, Devin Weber, Matthew Pettengill

Department of Medicine Faculty Papers

Healthcare-associated ventriculitis and meningitis (HCAVM) is associated with high morbidity and mortality, but rapid diagnostic tests intended to cover microorganisms that typically cause HCAVM are not commercially available. We sought to evaluate the etiology of HCAVM compared to community-acquired meningitis/encephalitis (CAME) at our healthcare system, and to study the utility of repurposing a multiplex molecular panel intended for positive blood cultures for HCAVM cases. Our epidemiologic review demonstrated that HCAVM cases were primarily caused by bacteria and fungi also associated with bloodstream infections, in contrast with CAME cases, which were primarily caused by herpesviruses and Cryptococcus. Eighty-two cerebrospinal fluid …

Immunogenicity And Efficacy Of A Rabies-Based Vaccine Against Highly Pathogenic Influenza H5n1 Virus, Nir Paran, Christoph Wirblich, Randy Albrecht, Leila Zabihi Diba, Alessandro Tarquinio, Drishya Kurup, Charalambos C. Solomides, Adolfo García-Sastre, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

The recent spillover of highly pathogenic influenza A/H5N1 (HPAI-H5N1) viruses to cattle, other mammals, and humans poses a major risk to animal and human health. Virus adaptation to new species highlights the need for effective vaccines for animals and humans. We recently developed a rabies virus-based H5 vaccine encoding the HPAI-H5 antigen and presenting it on the surface of the rabies virus particle. To test the immunogenicity and efficacy of the vaccine in eliciting systemic and mucosal immune response, we vaccinated mice intramuscularly or intranasally with either live or inactivated and adjuvanted vaccine. The vaccine elicited neutralizing antibodies against RABV …

Imodmix: Integrative Module Analysis For Multi-Omics Data., Isis Narváez-Bandera, Ashley Lui, Yonatan Ayalew Mekonnen, Vanessa Rubio, Augustine Takyi, Noah Sulman, Christopher Wilson, Hayley D. Ackerman, Oscar E. Ospina, Guillermo Gonzalez-Calderon, Elsa R. Flores, Qian Li, Ann Chen, Brooke L. Fridley, Paul A. Stewart

Manuscripts, Articles, Book Chapters and Other Papers

SUMMARY: Integrative Module Analysis for Multi-omics Data (iModMix) is a biology-agnostic framework that enables the discovery of novel associations across any type of quantitative abundance data, including but not limited to transcriptomics, proteomics, and metabolomics. Instead of relying on pathway annotations or prior biological knowledge, iModMix constructs data-driven modules using graphical lasso to estimate sparse networks from omics features. These modules are summarized into eigenfeatures and correlated across datasets for horizontal integration, while preserving the distinct feature sets and interpretability of each omics type. iModMix operates directly on matrices containing expression or abundances for a wide range of features, including …

Cd8+ T Cells In The Tumor Microenvironment Modulate The Response To Endocrine Therapy In Breast Cancer, Fabiana Napolitano, Yunguan Wang, Dhivya R Sudhan, Paula I Gonzalez-Ericsson, Luigi Formisano, Nisha Unni, Shahbano Shakeel, James Z Zhu, Khushi Ahuja, Lei Guo, María Rosario Chica-Parrado, Yuki Matsunaga, Pamela Luna, Chang-Ching A Lin, Yasuaki Uemoto, Kyung-Min Lee, Hongli Ma, Nathaniel J Evans, Alberto Servetto, Saurabh Mendiratta, Spencer D Barnes, Roberto Bianco, Yisheng V Fang, Lin Xu, Jeon Lee, Tao Wang, Justin M Balko, Gordon B Mills, Marilyne Labrie, Ariella B Hanker, Carlos L Arteaga

Faculty, Staff and Student Publications

The role of the tumor immune microenvironment (TIME) in modulating responses to antiestrogen therapy in hormone receptor-positive (HR+) breast cancers remains unclear. We analyzed pre- and on-treatment biopsies from patients with HR+ breast cancer treated with letrozole to induce estrogen deprivation (ED). Stromal tumor-infiltrating lymphocytes, assessed by H&E staining, and immune-related gene sets, including IFN-γ signaling genes, measured by RNA-Seq, were increased in ED-resistant tumors. Cyclic immunofluorescence and spatial transcriptomics revealed an abundance of CD8+ T cells and enhanced antigen processing and immune gene signatures in ED-resistant tumors. In this group, the expression of CXCL9, CXCL10, and CXCL11 - chemokine …

Osimertinib Activates A Tgf-Β2-Dependent Secretory Program That Drives Lung Adenocarcinoma Progression, Madhurima Ghosh, Chao Wu, Abhishek Kumar, Monique Nilsson, John V Heymach, Weina Zhao, Jiang Yu, Xin Liu, Na Ding, Shike Wang, Guan-Yu Xiao, Angelo Chen, Kate Grimley, William K Russell, Chad J Creighton, Xiaochao Tan, Jonathan M Kurie

Faculty, Staff and Student Publications

EGFR-mutant lung adenocarcinomas (LUADs) that are vulnerable to the EGFR antagonist osimertinib (Osi) eventually relapse, owing in part to the emergence of drug-tolerant persister (DTP) cells that arise through epigenetic mechanisms. Intratumoral DTP cells can herald a worse clinical outcome, but the way in which DTP cells influence LUAD progression remains unclear. Osi-resistant (OR) cells exhibit typical DTP cell features, including a propensity to undergo senescence and epithelial-mesenchymal transition (EMT), which can activate heightened secretory states. Therefore, we postulated that OR cells influence LUAD progression through paracrine mechanisms. To test this hypothesis, we utilized congenic pairs of EGFR-mutant LUAD cell …

Longitudinal Multiomic Signatures Of Ards And Sepsis Inflammatory Phenotypes Identify Pathways Associated With Mortality, Narges Alipanah-Lechner, Pratik Sinha, Et Al.

2020-Current year OA Pubs

BACKGROUNDCritically ill patients with acute respiratory distress syndrome (ARDS) and sepsis exhibit distinct inflammatory phenotypes with divergent clinical outcomes, but the underlying molecular mechanisms remain poorly understood. These phenotypes, derived from clinical data and protein biomarkers, were associated with metabolic differences in a pilot study.METHODSWe performed integrative multiomics analysis of blood samples from 160 patients with ARDS in the ROSE trial, randomly selecting 80 patients from each latent class analysis-defined inflammatory phenotype (hyperinflammatory and hypoinflammatory) with phenotype probability greater than 0.9. Untargeted plasma metabolomics and whole-blood transcriptomics at day 0 and day 2 were analyzed using multimodal factor analysis (MEFISTO). …

Estimated Effectiveness Of 2024-2025 Covid-19 Vaccination Against Severe Covid-19, Kevin C Ma, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: As SARS-CoV-2 JN.1 lineage descendants continue to evolve, evaluating COVID-19 vaccine effectiveness (VE) against severe COVID-19 remains important to guide vaccination strategies.

OBJECTIVE: To estimate the VE of the 2024-2025 COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes overall and by time since dose (7-89, 90-179, and ≥180 days), JN.1 descendant lineage (KP.3.1.1, XEC, LP.8.1), and spike protein mutations associated with immune evasion.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, test-negative, case-control study conducted by the Investigating Respiratory Viruses in the Acutely Ill Network included adult patients (aged ≥18 years) hospitalized between September 1, 2024, and April 30, 2025, …

Costs Of Single Maintenance And Reliever Therapy Vs Traditional Therapy For Asthma, Tri Pham, Abigail R Barker, Sarah A Eisenstein, Eliot Jost, Anna Volerman, Krutika Chauhan, Ross C Brownson, Timothy Mcbride, Mark D Huffman, Kaharu Sumino, Lynn B Gerald, Mario Castro, Anne E Dixon, James G Krings

2020-Current year OA Pubs

IMPORTANCE: Despite strong guideline support, single maintenance and reliever therapy (SMART) for asthma is underused in the US. Limited insurance coverage of SMART-compatible inhalers remains a major barrier to its adoption.

OBJECTIVE: To compare the annual asthma management costs of SMART vs traditional therapy from a US health care payer perspective.

DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation used a probabilistic decision-tree model with Monte Carlo simulations to compare the total asthma management costs for patients prescribed SMART vs traditional therapy, conducting analyses from September 1, 2024, to March 13, 2025. Input data were extracted through a systematic review of …

Demographic And Clinicopathologic Factors Associated With Colorectal Adenoma Recurrence, Usman Ayub Awan, Qingyuan Song, Kristen K Ciombor, Adetunji T Toriola, Jungyoon Choi, Timothy Su, Xiao-Ou Shu, Kamran Idrees, Kay M Washington, Wei Zheng, Wanqing Wen, Zhijun Yin, Xingyi Guo

2020-Current year OA Pubs

IMPORTANCE: Current colorectal surveillance guidelines emphasize adenoma characteristics but overlook temporal, racial, and sex-based heterogeneity in recurrence risk, a gap that limits equitable and personalized care.

OBJECTIVE: To evaluate the associations of demographic factors, obesity, and adenoma features with recurrence risk over time in a large longitudinal surveillance cohort.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included adults who underwent their first colonoscopic polypectomy between January 1990 and July 2024 at a tertiary medical center.

EXPOSURES: Demographic variables included race and ethnicity, sex, obesity (body mass index >30), family history of colorectal cancer (CRC) or polyps, and age at …

Insomnia In Stimulant Use Disorders: Prevalence And Associations With Negative Affect, Isabella G Bourtin, Constanza De Dios, Jessica Vincent, Joy M Schmitz, Scott D Lane, Heather E Webber

Faculty, Staff and Student Publications

Research suggests that sleep disturbances are common among people who use psychostimulants, including cocaine use and methamphetamine use. These sleep disturbances hinder recovery, heighten relapse risk, and worsen physical and mental health outcomes. This study aimed to estimate the prevalence and severity of insomnia among individuals who use cocaine and methamphetamine and to explore potential psychological factors that are associated with more severe insomnia. The sample included participants who completed in-person screening assessments for ongoing studies at an outpatient research clinic. As a part of this screening, participants completed the Insomnia Severity Index (ISI) and validated assessments of psychological domains …

An Itpr1 Variant In The Ip3-Itpr1 Binding Pocket Associated With A Clinical Phenotype Of Athetoid Cerebral Palsy., Thania Ordaz, Jagadish Chandrabose Sundaramurthi, Adam S Arterbery, Anita M Bagley, Michael A Gargano, Jeremy P Bauer, Daniel Danis, Philip Giampietro, Ellen Raney, Lauren Rekerle, Mallory Shingle, Jon R Davids, Peter N Robinson

Faculty Research 2026

A de novo, missense variant in ITPR1-inositol 1,4,5-trisphosphate receptor type 1 (ITPR1), p.(Tyr567Cys), was identified by trio whole-genome sequencing in an individual diagnosed with Spinocerebellar ataxia 29 (SCA29) who was affected by cerebral palsy and global developmental delay. The variant affects a residue involved in Inositol 1,4,5-trisphosphate (IP3)-ITPR1 binding. Genotype-Phenotype correlation analysis of the set of missense variants affecting nine residues involved in IP3-ITPR1 binding in the current case and 170 reports of individuals with ITPR1 variants showed a significantly higher frequency of phenotypic features related to neurodevelopmental delay in these variants than in other ITPR1 variants. Our proband was …

Nrn1 As A Therapeutic Target For Alzheimer's Disease., Derian A Pugh, Gregory Cary, Kelsey M Greathouse, Lauren C Nassour-Caswell, Emma L Hobby, Nicholas T Seyfried, Jeremy H Herskowitz

Faculty Research 2026

INTRODUCTION: Neuritin-1 (NRN1) was identified as a synaptic protein associated with cognitive resilience to Alzheimer's disease (AD).

METHODS: Target risk score and cell type expression profiles were generated for NRN1 using methods developed by the Emory-Sage-SGC-JAX Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) Center and Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD). Antibody characterization was conducted using Western blots and densitometry to assess the relative protein abundances of NRN1 in rodents, humans, and cell models.

RESULTS: NRN1 has a TREAT-AD target risk score of 3.29 out of 5. Based on single-nucleus RNA sequencing from SEA-AD, NRN1 expression …

Beyond The Streetlight: A Treat-Ad Perspective On Where To Find New Alzheimer's Targets., Gregory Cary, Jesse C Wiley, Gregory W. Carter, Allan I Levey

Faculty Research 2026

Despite extensive investments in Alzheimer's disease (AD) therapeutic development, progress toward effective interventions remains modest. The landscape of potential novel therapeutic strategies is rapidly growing, but prioritization, validation, and tools to advance targets to trial are lagging. The Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) consortium has integrated systems-level data from large-scale studies profiling thousands of human brains, yielding target-specific risk scores that partition disease risk into discrete biological domains and enable data-driven target interrogation. Here, we compared clinical trial targets with top-ranked TREAT-AD targets and found a limited overlap as well as differences in the biology …

Nrn1 As A Therapeutic Target For Alzheimer's Disease., Derian A Pugh, Gregory Cary, Kelsey M Greathouse, Lauren C Nassour-Caswell, Emma L Hobby, Nicholas T Seyfried, Jeremy H Herskowitz

Faculty Research 2026

INTRODUCTION: Neuritin-1 (NRN1) was identified as a synaptic protein associated with cognitive resilience to Alzheimer's disease (AD).

METHODS: Target risk score and cell type expression profiles were generated for NRN1 using methods developed by the Emory-Sage-SGC-JAX Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) Center and Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD). Antibody characterization was conducted using Western blots and densitometry to assess the relative protein abundances of NRN1 in rodents, humans, and cell models.

RESULTS: NRN1 has a TREAT-AD target risk score of 3.29 out of 5. Based on single-nucleus RNA sequencing from SEA-AD, NRN1 expression …

Beyond The Streetlight: A Treat-Ad Perspective On Where To Find New Alzheimer's Targets., Gregory Cary, Jesse C Wiley, Gregory W. Carter, Allan I Levey

Faculty Research 2026

Despite extensive investments in Alzheimer's disease (AD) therapeutic development, progress toward effective interventions remains modest. The landscape of potential novel therapeutic strategies is rapidly growing, but prioritization, validation, and tools to advance targets to trial are lagging. The Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) consortium has integrated systems-level data from large-scale studies profiling thousands of human brains, yielding target-specific risk scores that partition disease risk into discrete biological domains and enable data-driven target interrogation. Here, we compared clinical trial targets with top-ranked TREAT-AD targets and found a limited overlap as well as differences in the biology …

Somatic Deficiency Of The Human E3 Ubiquitin Ligase Cbl In Leukocytes Impairs B Cell But Not T Cell Development And Function., Taja Vatovec, Anna-Lena Neehus, Katherine J L Jackson, Danielle T Avery, Ivan Bagarić, Lucia Erazo, Carlos A Arango-Franco, Masato Ogishi, Syed F Ahmed, Axel Cederholm, Amanda J Russell, Erika Della Mina, Dena Al-Rifai, Rowena Bull, Lori Buetow, Steicy Sobrino, Allison Zhang, Lara Wahlster, Marine Michelet, Nima Parvaneh, Jessica Peel, Federica Barzaghi, Davide Leardini, Quentin Philippot, Francesco Saettini, Jacques Dutrieux, Benedicte De Muylder, Francesca Vendemini, Francesco Baccelli, Albert Catala, Eleonora Gambineri, Marinella Veltroni, Vignesh Pandiarajan, Yurena Aguilar, Filomeen Haerynck, Michael Elliott, Stuart Turville, Fabienne Brillot, Taushif Khan, Filippo Consonni, Laureline Berteloot, William A Sewell, Geetha Rao, Laetitia Largeaud, Francesca Conti, Cecile Roullion, Cécile Masson, Francesco Pegoraro, Tianyi Ye, Samantha Joubran, Emily Villalpando, Boris Bessot, Yoann Seeleuthner, Tom Le Voyer, Jérémie Rosain, Hailun Li, Zarah Janda, Edoardo Muratore, Camille Soudée, Eric Delabesse, Claire Goulvestre, Mohammad Shahrooei, Anne Puel, Isabelle André, Christine Bole-Feysot, Laurent Abel, Miriam Erlacher, Vivien Béziat, Chantal Lagresle-Peyrou, Remi Cheynier, Emmanuelle Six, Nico Marr, Marlène Pasquet, Laia Alsina, Christopher C Goodnow, Nils Landegren, Alessandro Aiuti, Peng Zhang, Riccardo Masetti, Danny T Huang, Cindy S Ma, Jean-Laurent Casanova, Vijay G Sankaran, Jacinta Bustamante, Stuart G Tangye, Jonathan Bohlen

Faculty Research 2026

The E3 ubiquitin ligase Casitas B-lineage lymphoma (CBL) promotes positive selection and antigen responses in mouse T lymphocytes by ubiquitinating ZAP70. Conversely, mouse CBL and CBL-B mutually redundantly regulate SYK ubiquitination and B cell receptor signaling. Here we studied individuals with somatically homozygous CBL loss-of-function variants in leukocytes. Human CBL is largely redundant for the development and function of human T cells. Conversely, B cell development is altered at the immature stage, with a tenfold increase in transitional cells, enhanced survival of autoreactive clones and impaired tolerance manifested by autoantibody production. B cell maturation is intrinsically impaired by reduced apoptosis …

Transcriptomics And Metabolomics Analysis Reveal Cell Subpopulations Of Trophoblast Cells Associated With Preeclampsia, Xiaojun Zhu, Ying Jiang, Lilin Wang, Peiyue Jiang, Zixing Zhong, Hetong Li, Caihong Zheng, Lujiao Chen, Juan Wei, Xishi Lin, Peng Ding, Zehua Dong, Xiaosheng Wang, Qiong Luo

Faculty, Staff and Student Publications

Placental abnormalities are central to preeclampsia (PE), yet the cellular and molecular mechanisms underlying this dysfunction remain unclear. We applied a multi-layered, integrative approach to investigate placental tissue from patients with PE and matched controls. Single-cell RNA sequencing (scRNA-seq; GSE173193) and bulk RNA sequencing (bulk RNA-seq; GSE203507) datasets were obtained from the Gene Expression Omnibus. The scRNA-seq dataset included two PE and two control samples, whereas the bulk RNA-seq dataset focused on eight early-onset PE and five uncomplicated term births. Trophoblast subpopulations were identified via scRNA-seq, and pseudotime analysis was used to trace differentiation trajectories. Differential expression and pathway enrichment …

Single-Cell Atlas Of The Transcriptome And Chromatin Accessibility In The Human Retina, Jin Li, Jun Wang, Ignacio L Ibarra, Xuesen Cheng, Malte D Luecken, Jiaxiong Lu, Aboozar Monavarfeshani, Wenjun Yan, Yiqiao Zheng, Zhen Zuo, Samantha Lynn Zayas Colborn, Berenice Sarahi Cortez, Leah A Owen, Brittney Wick, Xuan Bao, Jongsu Choi, Maximilian Haeussler, Nicholas M Tran, Karthik Shekhar, Joshua R Sanes, J Timothy Stout, Shiming Chen, Yumei Li, Margaret M Deangelis, Fabian J Theis, Rui Chen

Faculty, Staff and Students Publications

Single-cell sequencing has revolutionized the scale and resolution of molecular profiling of tissues and organs. Here we present an integrated dual-modal reference atlas of the most accessible portion of the mammalian central nervous system, the retina. We compiled around 3.9 million cells from 125 donors of diverse ancestral backgrounds, including 8 published studies and 2.7 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) with more than 130 cell types identified. We annotated each cluster, identified marker genes and characterized cis-regulatory elements and gene regulatory networks. Our analysis uncovered differences in transcriptome, chromatin and gene regulatory …

Hyperglycemia, Receptor For Advanced Glycation End Products, And Small Airways Dysfunction In Asthma, Paula Sierra Salas, Dennis T Villareal, Vickram Tejwani, Amrit Koirala, Cristian Coarfa, Meredith C Mccormack, Nicola A Hanania, Tianshi David Wu

Faculty, Staff and Students Publications

Background: Diabetes and insulin resistance are associated with higher risk of asthma exacerbation and preserved ratio impaired spirometry (PRISm), but the pathophysiology is unclear. These conditions may cause small airways dysfunction (SAD), which is an under-recognized cause of PRISm.

Objective: To determine whether insulin resistance and poor glucose control associate with SAD and to explore whether proteins prognostic of diabetes end-organ complications predict lung function abnormalities.

Methods: We recruited a prospective cohort of adults with physician-diagnosed asthma. Fasting insulin, glucose, hemoglobin A1c, and concentrations of 13 proteins prognostic of diabetes end-organ complications were measured. Static insulin resistance was calculated by …

Deep Brain Stimulation Response Circuits In Obsessive-Compulsive Disorder, Andreas Horn, Ningfei Li, Garance M Meyer, Ron Gadot, Nicole R Provenza, Sameer A Sheth

Faculty, Staff and Students Publications

In the field of deep brain stimulation (DBS), two major themes are currently making significant progress. First, the framework of connectomic DBS, in which circuits that are associated with improvements of specific symptoms are described and targeted to improve and potentially personalize treatment. Second, the concept of brain sensing and adaptive DBS, which aims at identifying neural biomarkers that may guide stimulation in a closed-loop fashion.

In DBS for Obsessive Compulsive Disorder (OCD), substantial progress has been made on both ends, over the last five years. Together, results begin to draw a picture of exactly which circuit is …

Integrated Transcriptomic Landscape Of Medulloblastoma And Ependymoma Reveals Novel Tumor Subtype-Specific Biology, Sonali Arora, Nicholas Nuechterlein, Matt Jensen, Gregory Glatzer, Philipp Sievers, Srinidhi Varadharajan, Andrey Korshunov, Felix Sahm, Stephen C Mack, Michael D Taylor, Taranjit S Gujral, Eric C Holland

Faculty, Staff and Students Publications

Background: Medulloblastoma and ependymoma are common pediatric central nervous system tumors with significant molecular and clinical heterogeneity. While molecular subgrouping has enabled classification into molecular subtypes, the extent of heterogeneity within these subgroups remains poorly defined.

Methods: We collected bulk RNA sequencing data from 888 medulloblastoma and 370 ependymoma tumors to establish a comprehensive reference landscape. After rigorous batch effect correction, normalization, and dimensionality reduction, we generated a unified landscape to explore gene expression, signaling pathways, RNA fusions, and copy number variations.

Results: Our transcriptional analysis revealed distinct clustering patterns, including two primary ependymoma compartments, EPN-E1 and EPN-E2, each with …

Cyclic Amp-Dependent Regulation Of Ryanodine Receptors In Healthy And Diseased Hearts, Mohit M Hulsurkar, Isabelle Ong, Joshua A Keefe, Issam H Abu-Taha, Dobromir Dobrev, Xander H T Wehrens

Faculty, Staff and Students Publications

Cyclic adenosine monophosphate (cAMP) is a critical second messenger in cardiomyocytes, regulating essential cellular functions. Upon G-protein-coupled receptor stimulation, adenylyl cyclase (AC) synthesizes cAMP, which phosphodiesterase (PDE) enzymes subsequently degrade. Recent studies challenge the traditional view of uniform cAMP signaling, revealing nanodomain-specific regulation within cardiomyocytes. This localized cAMP signaling modulates key Ca2+-handling proteins, including ryanodine receptor type-2 (RyR2), through channel-bound protein kinases and PDEs. Additionally, nucleoside-diphosphate kinases (NDPKs), particularly NDPK-C, contribute to cAMP synthesis and RyR2 regulation. Elevated NDPK-C levels in failing hearts correlate with increased cAMP levels, enhanced sarcoplasmic reticulum Ca2+ release, and cardiac arrhythmias. Furthermore, cAMP influences the …

Catatonia And Elevated Mortality: A Population-Wide Cohort Study With Healthy, Sibling, And Schizophrenia Spectrum Controls, Chih-Wei Hsu, Yang-Chieh Brian Chen, Marco Solmi, Chih-Sung Liang, Mu-Hong Chen, Yao-Hsu Yang, Liang-Jen Wang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Aim: To determine whether catatonia is associated with increased long-term all-cause and cause-specific mortality.

Methods: Using Taiwan's National Health Insurance Database (2000-2022), we assembled a population-based cohort of all adults (≥18 years) with catatonia and matched each to four controls without catatonia on sex and birthdate. Mortality was compared between (1) individuals with catatonia and their unaffected siblings and (2) individuals with schizophrenia spectrum disorders with catatonia and those with schizophrenia spectrum disorders without catatonia. The primary outcome was all-cause mortality; secondary outcomes were natural- and unnatural-cause deaths. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with …

Scper: A Rigorous Computational Approach To Determine Cellular Subtypes In Tumors Aligned With Cancer Phenotypes From Total Rna Sequencing, Bingrui Li, Xiaobo Zhou, Raghu Kalluri

Faculty, Staff and Student Publications

Single-cell RNA sequencing (scRNA-seq) is a powerful technique for understanding cellular diversity, but processing large patient cohorts to identify phenotype-associated cell populations remains challenging. Here, scPER (Estimating cell Proportions using single-cell RNA-seq Reference), a rigorous approach combining adversarial autoencoder and extreme gradient boosting to estimate tumor microenvironment cell compositions and identify phenotype-associated subclusters for bulk RNA-seq samples. Integrating scRNA-seq datasets from diverse studies, scPER constructed comprehensive reference panels and disentangled confounders from true signals. scPER achieved superior accuracy in cellular proportion estimation compared to CIBERSORTx, BayesPrism, Scaden, MuSiC, SCDC, DeSide and ReCIDE. It showed high accuracy in predicting metastatic melanoma …

Genetic Architecture Of N-Terminal Pro-B-Type Natriuretic Peptide In A Multiancestry Study Population, Naman S Shetty, Akhil Pampana, Mokshad Gaonkar, Amrita Nayak, Harshvir S Bal, Nirav Patel, Nehal Vekariya, J Gustav Smith, Alanna C Morrison, Bing Yu, Bruce M Psaty, Eric Boerwinkle, James S Floyd, Jerome I Rotter, Kent D Taylor, Leslie A Lange, Marguerite R Irvin, Mary Cushman, Stephen S Rich, Ramachandran S Vasan, Thomas J Wang, Xiuqing Guo, Peng Li, Garima Arora, Pankaj Arora

Faculty, Staff and Student Publications

Background: NPs (natriuretic peptides) are bioactive hormones crucial for regulating blood pressure, glucose homeostasis, and lipid metabolism. Despite the high heritability of circulating NP levels, the genetic determinants of NP regulation, particularly across ancestries and sexes, remain poorly understood. The objective of the current study was to identify genetic variants associated with NT-proBNP (N-terminal pro-B-type NP) levels in a multiancestry study population.

Methods: Whole genome sequencing and array-based data from 81 213 individuals without heart failure were analyzed from the Trans-Omics for Precision Medicine cohorts, UK Biobank, All of Us Research Program, and REGARDS (Reasons for Geographic and Racial Differences …

Cellstaar: Incorporating Single-Cell-Sequencing-Based Functional Data To Boost Power In Rare Variant Association Testing Of Noncoding Regions, Eric Van Buren, Yi Zhang, Xihao Li, Margaret Sunitha Selvaraj, Zilin Li, Hufeng Zhou, Nicholette D Palmer, Donna K Arnett, John Blangero, Eric Boerwinkle, Brian E Cade, Jenna C Carlson, April P Carson, Yii-Der Ida Chen, Joanne Curran, Ravindranath Duggirala, Myriam Fornage, Nora Franceschini, Misa Graff, Charles Gu, Xiuqing Guo, Jiang He, Nancy Heard-Cosa, Lifang Hou, Yi-Jen Hung, Rita R Kalyani, Sharon L R Kardia, Eimear Kenny, Charles Kooperberg, Brian G Kral, Leslie Lange, Dan Levy, Changwei Li, Simin Liu, Donald Lloyd-Jones, Ruth J F Loos, Ani W Manichaikul, Lisa Warsinger Martin, Rasika Mathias, Ryan L Minster, Braxton D Mitchell, Josyf C Mychaleckyj, Take Naseri, Kari North, Jeff O'Connell, James A Perry, Patricia A Peyser, Bruce M Psaty, Laura M Raffield, Ramachandran S Vasan, Susan Redline, Alex P Reiner, Stephen S Rich, Jennifer A Smith, Brian Spitzer, Hua Tang, Kent D Taylor, Russell Tracy, Satupa'itea Viali, Lisa Yanek, Wei Zhao, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Jerome I Rotter, Gina M Peloso, Pradeep Natarajan, Xihong Lin

Faculty, Staff and Student Publications

Understanding how rare genetic variants influence complex traits remains a major challenge, particularly when these variants lie in noncoding regions of the genome. The effects of variants within candidate cis-regulatory elements (cCREs) often depend on the cell type, making interpretation difficult. Here we introduce cellSTAAR, which integrates whole-genome sequencing data with single-cell assay for transposase-accessible chromatin using sequencing data to capture variability in chromatin accessibility across cell types via the construction of cell-type-specific functional annotations and regulatory elements. To reflect the uncertainty in cCRE-gene linking, cellSTAAR uses a comprehensive strategy to link cCREs to their target genes. We applied cellSTAAR …

Volumetric Buccal Bone Alterations At Immediate Implant Sites With Or Without Soft Tissue Augmentation: A 6-Month Assessment, Mary Jung, Duong Tran, Chi-Ching Chang, Sung K Kim, Yosuke Tsukiboshi, Seiko Min, Srinivas Ayilavarapu, Chun-Teh Lee

Faculty, Staff and Student Publications

Background: This study is part of a randomized controlled trial investigating the impact of soft tissue augmentation (STA) using subepithelial connective tissue graft (SCTG) (immediate implant with subepithelial connective tissue graft [ICT] group) or acellular dermal matrix (ADM) (immediate implant with acellular dermal matrix [IAD] group) versus no STA (control) on the clinical outcomes following immediate implant placement (IIP). This study aimed to investigate volumetric buccal bone dimensional changes at immediate implant sites 6 months after the surgery.

Methods: Forty-five patients requiring extraction of a maxillary anterior tooth or premolar and randomly assigned to one of the three groups were …

Clinical Evaluation Of Nasal Swab Specimens In Vtm/Utm And Respdirect Estm Using The Panther Fusion Sars-Cov-2/Flu A/B/Rsv Assay., Salika M. Shakir, Robert K. Mccall, Rangaraj Selvarangan, Dithi Banerjee, Yitz Goldstein, Christine Lansang, Rachel Bogh, Carmelle V. Remillard, Respdirect Clinical Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Respiratory viral infections by SARS-CoV-2, influenza A and B viruses, and RSV overlap in disease signs and symptomology, but differ in treatment modality. Nasal swab specimens have been shown to be an effective alternative specimen type for SARS-CoV-2 detection.

OBJECTIVES: This study evaluated the performance of the Panther Fusion® SARS-CoV-2/Flu A/B/RSV assay in anterior nasal swab specimens (self- or healthcare professional [HCP]-) collected in either viral/universal (VTM/UTM) transport media or the Hologic® RespDirect® collection kit (RespDirect swab in enhanced specimen transport media [eSTM]).

STUDY DESIGN: A multicenter study was conducted from October 2022 to March 2024. A total of …

Loss Of Ctlh Component Maea Impairs Dna Repair And Replication And Leads To Developmental Delay., Søren H. Hough, Satpal S. Jhujh, Samah W. Awwad, Oliver E. Lewis, Simon Lam, John C. Thomas, Thorsten Mosler, Aldo Bader, Lauren E. Bartik, Shane Mckee, Shivarajan Amudhavalli, Estelle Colin, Nadirah Damseh, Emma Clement, Pilar Cacheiro, Anirban Majumdar, Damian Smedley, Joël Fluss, Rosalinda Giannini, Isabelle Thiffault, Guido Zagnoli Vieira, Rimma Belotserkovskaya, Stephen J Smerdon, Petra Beli, Yaron Galanty, Christopher J. Carnie, Grant S. Stewart, Stephen P. Jackson

Manuscripts, Articles, Book Chapters and Other Papers

Ubiquitin E3 ligases play crucial roles in the DNA damage response (DDR) by modulating the turnover, localization, activation, and interactions of DDR and DNA replication proteins. We performed a CRISPR-Cas9 knockout screen focused on ubiquitin E3 ligases and related proteins with the DNA topoisomerase I inhibitor camptothecin. This led us to establish that MAEA, a core subunit of the CTLH E3 ligase complex, is a critical regulator of homologous recombination and the replication stress response. In tandem, we identified eight patients with variants in MAEA who present with a neurodevelopmental disorder that we term DIADEM (Developmental delay and Intellectual disability …

Maternal Myo-Inositol Intake And Congenital Heart Defects In Offspring: A Population-Based Case-Control Study, Ruiqi Cen, L Joseph Su, Jun Ying, Mohammed S Orloff, Elijah H Bolin, Xiangyang Lou, Lynn M Almli, Lorenzo D Botto, Marilyn L Browne, Richard H Finnell, Mary M Jenkins, Eirini Nestoridi, Andrew F Olshan, Paul A Romitti, Gary M Shaw, Wendy N Nembhard

Faculty, Staff and Students Publications

Objective: To investigate associations between maternal periconceptional (three months prior through the third pregnancy month) myo-inositol intake and the odds of selected congenital heart defects in offspring.

Design: A population-based case-control study using the National Birth Defects Prevention Study (NBDPS) database.

Setting: United States.

Population or sample: Women with singleton live births without major birth defects (controls) and women with singleton live births, stillbirths, or terminations with selected nonsyndromic congenital heart defects (CHD; cases).

Methods: Descriptive analyses, logistic regression models, ascertainment of myo-inositol intake from supplements and food using a shortened food frequency questionnaire and survey.

Main outcome measures: Odds …