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In-Hospital Mortality Patterns And Readmissions In Patients With Chronic Obstructive Pulmonary Disease: An Analysis Of The Role Of Pulmonary Hypertension, Saad Afzal Khan, Trishna Parikh, Adishwar Rao, Akriti Agrawal, Aarohi Parikh, Farah Kazzaz, Sarah Shin, Harry Karmouty-Quintana, Maulin Patel, Kha Dinh, Bela Patel, Bindu Akkanti Dec 2026

In-Hospital Mortality Patterns And Readmissions In Patients With Chronic Obstructive Pulmonary Disease: An Analysis Of The Role Of Pulmonary Hypertension, Saad Afzal Khan, Trishna Parikh, Adishwar Rao, Akriti Agrawal, Aarohi Parikh, Farah Kazzaz, Sarah Shin, Harry Karmouty-Quintana, Maulin Patel, Kha Dinh, Bela Patel, Bindu Akkanti

Faculty, Staff and Student Publications

Chronic obstructive pulmonary disease (COPD) may be complicated by pulmonary hypertension (PH). We aimed to understand the impact of PH on in-hospital mortality and quantify the 30-day readmission rate among patients with COPD. For this cross-sectional study, we used the Nationwide Readmissions Database from 2017-2020 to identify adults ≥18 years with COPD. Patients were stratified according to PH diagnosis. Baseline characteristics between groups were compared using the Pearson chi-square test and two-sample t-test. Predictors of in-hospital mortality were determined using multivariate logistic regression analysis adjusted for demographics and confounders. The 30-day readmission rate and prevalence of PH subgroups by baseline …


Hydroxyethyl Starch And Perioperative Complications: A Systematic Review And Meta-Analysis, Daniel I Sessler, Lorenzo Pradelli, Massimiliano Povero, Daniel Chappell, E Wang Sep 2026

Hydroxyethyl Starch And Perioperative Complications: A Systematic Review And Meta-Analysis, Daniel I Sessler, Lorenzo Pradelli, Massimiliano Povero, Daniel Chappell, E Wang

Faculty, Staff and Student Publications

Background: Based on renal injury reported in critically ill and septic patients, the U.S. Food and Drug Administration issued a black box warning regarding hydroxyethyl starch (HES 130/0.4) use in 2013 and expanded the warning to surgical and trauma patients in 2021. Similarly, the European Medicines Agency initiated withdrawal of hydroxyethyl starch in 2022. This study was a new meta-analysis focused on renal injury designed to complement a 2021 meta-analysis of perioperative hydroxyethyl starch use, adding 45 trials and 6,895 patients. The focus was acute kidney injury and preoperative-to-postoperative change in creatinine concentration in surgical patients.

Methods: This study searched …


Spcc: Inferring Spatial Cell-Cell Interaction By Integrating Single-Cell And Spatial Transcriptomics, Tiangang Wang, Yu Zhou, Xi Liu, Sijia Wu, Liyu Huang, Kexin Huang, Xiaobo Zhou Aug 2026

Spcc: Inferring Spatial Cell-Cell Interaction By Integrating Single-Cell And Spatial Transcriptomics, Tiangang Wang, Yu Zhou, Xi Liu, Sijia Wu, Liyu Huang, Kexin Huang, Xiaobo Zhou

Faculty, Staff and Student Publications

Study of single-cell spatial biology reveals the importance of integrating single-cell and spatial data for capturing spatial structure at individual cell resolution in various fields. With the lack of cellular-level information in most spatial data, it is necessary to integrate single-cell and spatial data. Here, we developed a deep learning computational framework for alignment and mapping of unpaired single-cell and the spatial data by using adversarial joint-variational autoencoder and Random Forest model (SPCC). SPCC will generate a mapping matrix for single-cell and spatial positions that can transfer spatial location to individual cells. SPCC can be used to perform downstream analysis, …


Computable Phenotypes For Research Using Real-World Data: Experiences From The Nih Pragmatic Trials Collaboratory, Marisa L Conte, Judith M Schlaeger, Guilherme Del Fiol, James R Campbell, Andrea L Cheville, Keith Marsolo, Kari A Stephens, Miriam O Ezenwa, Andrew D Boyd, Juanita E Darby, Nadine S Matthie, P Michael Ho, Alice Pressman, Morgan Justice, Carol Reynolds Geary, Keturah R Faurot, Alex Fist, Karen Staman, Hulin Wu, Rachel L Richesson Aug 2026

Computable Phenotypes For Research Using Real-World Data: Experiences From The Nih Pragmatic Trials Collaboratory, Marisa L Conte, Judith M Schlaeger, Guilherme Del Fiol, James R Campbell, Andrea L Cheville, Keith Marsolo, Kari A Stephens, Miriam O Ezenwa, Andrew D Boyd, Juanita E Darby, Nadine S Matthie, P Michael Ho, Alice Pressman, Morgan Justice, Carol Reynolds Geary, Keturah R Faurot, Alex Fist, Karen Staman, Hulin Wu, Rachel L Richesson

Faculty, Staff and Student Publications

Objectives: Embedded pragmatic clinical trials (ePCTs) are conducted as part of routine clinical care and therefore use data collected from real-world data sources, such as electronic health record systems and administrative claims. A common approach for using these types of data across all phases of trial conduct is to create a computable phenotype (an explicitly defined data query data, including specified data types, data codes, and logical parameters) to capture patients with a clinical condition, exposure, symptom, characteristic, treatment, or outcome of interest.

Materials and methods: The Electronic Health Record (EHR) Core Working Group of the NIH Pragmatic Trials Collaboratory …


Spae: Deciphering Cell Cycle Dynamics And Cell States In Single-Cell Rna-Seq Data, Jiahao Yi, Jiajia Liu, Peng Guo, Yuan-Nong Ye, Xiaobo Zhou Jul 2026

Spae: Deciphering Cell Cycle Dynamics And Cell States In Single-Cell Rna-Seq Data, Jiahao Yi, Jiajia Liu, Peng Guo, Yuan-Nong Ye, Xiaobo Zhou

Faculty, Staff and Student Publications

Rapid advances in single-cell RNA sequencing (scRNA-seq) technology have enabled the investigation of gene expression changes at the single-cell level, particularly for elucidating the heterogeneity among cells and complex biological processes. This technique reveals subtle molecular differences within individual cells, thereby offering a unique viewpoint for the investigation of cell cycle progression, cellular differentiation, and disease pathogenesis. However, accurately identifying and analyzing cell cycle dynamics in scRNA-seq data remains challenging due to the complexity of the data and the subtle differences between cell states. To address this challenge, we developed the integrated Sinusoidal and Piecewise AutoEncoder (SPAE), an autoencoder-based piecewise …


Effects Of Non-Surgical Periodontal Therapy On Dental Plaque Microbiome, Qingguo Wang, Bing-Yan Wang, Derek Wilus, Hua Xie Jul 2026

Effects Of Non-Surgical Periodontal Therapy On Dental Plaque Microbiome, Qingguo Wang, Bing-Yan Wang, Derek Wilus, Hua Xie

Faculty, Staff and Student Publications

Periodontitis, a chronic inflammatory disease affecting approximately 40% of U.S. adults aged 30 years and older, is characterized by dysbiosis of the dental plaque microbiome. However, although scaling and root planing (SRP) is the cornerstone of periodontal treatment, its effects on the taxonomic composition and functional potential of the dental plaque microbiome remain incompletely understood. In this study, we used whole-metagenome shotgun sequencing to characterize taxonomic composition and functional potential in dental plaque microbiomes collected from 39 patients with Stage II or III generalized periodontitis before and 3–4 months after SRP. Consistent with clinical improvement, periodontal therapy significantly reduced probing …


Loss Of Atp-Dependent Citrate Lyase Drives Left Ventricular Dysfunction By Metabolic Remodeling, Shijie Liu, Seth T Gammon, Lin Tan, Yaqi Gao, Kyoungmin Kim, Mahmoud H Elbatreek, Adrian Arrieta, Ian K Williamson, Rebecca L Salazar, Janet Pham, Angela Davidian, Radhika Khanna Neicheril, Benjamin D Gould, Heidi Vitrac, Alia Sadiq, An Q Dinh, Evan C Lien, Francisca N De Luna Vitorino, Joanna M Gongora, Sara A Martinez, Melanie T Odenkirk, Anna K Boatman, Jessie R Chappel, Lawrence S C Czer, Evan P Kransdorf, David J Lefer, Blake M Hanson, Benjamin A Garcia, Erin M Baker, Matthew G Vander Heiden, Philip L Lorenzi, Heinrich Taegtmeyer, David Piwnica-Worms, James F Martin, Anja Karlstaedt Jul 2026

Loss Of Atp-Dependent Citrate Lyase Drives Left Ventricular Dysfunction By Metabolic Remodeling, Shijie Liu, Seth T Gammon, Lin Tan, Yaqi Gao, Kyoungmin Kim, Mahmoud H Elbatreek, Adrian Arrieta, Ian K Williamson, Rebecca L Salazar, Janet Pham, Angela Davidian, Radhika Khanna Neicheril, Benjamin D Gould, Heidi Vitrac, Alia Sadiq, An Q Dinh, Evan C Lien, Francisca N De Luna Vitorino, Joanna M Gongora, Sara A Martinez, Melanie T Odenkirk, Anna K Boatman, Jessie R Chappel, Lawrence S C Czer, Evan P Kransdorf, David J Lefer, Blake M Hanson, Benjamin A Garcia, Erin M Baker, Matthew G Vander Heiden, Philip L Lorenzi, Heinrich Taegtmeyer, David Piwnica-Worms, James F Martin, Anja Karlstaedt

Faculty, Staff and Student Publications

Background: Metabolic adaptation and maladaptation are hallmarks of the failing heart and may be a target for therapeutic interventions. For example, sustained glucose oxidation during cardiac stress is associated with increased activity and abundance of ACL (ATP-dependent citrate lyase, Acly), which produces acetyl-coenzyme A (CoA) from citrate and CoA and supports de novo lipid synthesis. However, our understanding of how ACL supports cardiac metabolic adaptation and its potential to modulate disease pathophysiology has not yet been investigated.

Methods: We used human heart tissue samples from healthy donors and patients with nonischemic cardiomyopathy. Next, we used CRISPR (clustered, regularly interspaced …


Molecular Mechanism Leading To Human Coronary Atherosclerosis Assessed By Proteomic Analysis And Rna Sequences, Sarah J Parker, Chunhong Mao, David L Caudell, Austin Lyle Seals, Yizhi Wang, Thomas D Green, Joseph M Mcclung, Joshua T Maxwell, Jacolby T Roddey, Kiarash Shakeriastani, Chiung-Ting Wu, Yingzhou Lu, Do-Kyun Kim, Justyna Fert-Bober, Dongping Du, Archana Bhat, Niveda Sundararaman, Matthew Ayres, Rakhi Pandey, Saurabh Bhardwaj, Genesio M Karere, Dana Troxclair, Fannie Jackson, Gordon L Love, Richard Vander Heide, James Hixson, Jennifer E Van Eyk, Yue Wang, David Herrington Jul 2026

Molecular Mechanism Leading To Human Coronary Atherosclerosis Assessed By Proteomic Analysis And Rna Sequences, Sarah J Parker, Chunhong Mao, David L Caudell, Austin Lyle Seals, Yizhi Wang, Thomas D Green, Joseph M Mcclung, Joshua T Maxwell, Jacolby T Roddey, Kiarash Shakeriastani, Chiung-Ting Wu, Yingzhou Lu, Do-Kyun Kim, Justyna Fert-Bober, Dongping Du, Archana Bhat, Niveda Sundararaman, Matthew Ayres, Rakhi Pandey, Saurabh Bhardwaj, Genesio M Karere, Dana Troxclair, Fannie Jackson, Gordon L Love, Richard Vander Heide, James Hixson, Jennifer E Van Eyk, Yue Wang, David Herrington

Faculty, Staff and Student Publications

Background and aims: Atherosclerosis results from cellular and extracellular changes in the arterial wall, preceded by molecular shifts that initiate disease and drive tissue conversion, yet these changes are not yet fully described. More data are needed concerning these early changes in the coronary artery molecular landscape that signify the initiation of atherosclerosis and the subsequent tissue pheno-conversion to atherosclerotic plaque. This report summarizes results from a large biorepository of human coronary artery tissue, applying state-of-the-art omics technology, advanced data analytic methods, and an arterial organoid model system to predict molecular dynamics and identify potential regulatory mechanisms that could interrupt …


Metabolic Syndrome Is Associated With Increased Mortality In Patients With Breast Or Prostate Cancer, Jessica P Hwang, Ning Zhang, Mercy W Misoi, Sabhi Gull, Zayd A Razouki, Justin R Gregg, Natalia I Heredia, Sharon H Giordano Jul 2026

Metabolic Syndrome Is Associated With Increased Mortality In Patients With Breast Or Prostate Cancer, Jessica P Hwang, Ning Zhang, Mercy W Misoi, Sabhi Gull, Zayd A Razouki, Justin R Gregg, Natalia I Heredia, Sharon H Giordano

Faculty, Staff and Student Publications

We investigated the association of metabolic syndrome (MetS) with mortality in patients with breast and prostate cancer. Breast and prostate cancer cohorts were created retrospectively using the SEER-Medicare database. Patients with first primary breast or prostate cancer diagnosed in 2008-2019 were identified using ICD-O-3 site and histology codes. Among those, patients with MetS were identified using ICD-9/10-CM codes, CPT/HCPCS codes, and prescription drug use from Medicare claims files. We defined continuous enrollment from 12 months before through 12 months after diagnosis, exposure during the first 12 months after diagnosis, and survival follow-up starting 12 months after diagnosis. We used multivariable …


Longitudinal Genomic Surveillance Of Sars-Cov-2 In A University Microcosm Reflects Global Evolutionary Trends, Sankar Prasad Chaki, Melissa M Kahl-Mcdonagh, Benjamin W Neuman, Loni A Taylor, Rebecca S B Fischer, Blake M Hanson, Marlisa S Hardy, Jo Ann Culpepper, Eric Boerwinkle, Kurt A Zuelke Jul 2026

Longitudinal Genomic Surveillance Of Sars-Cov-2 In A University Microcosm Reflects Global Evolutionary Trends, Sankar Prasad Chaki, Melissa M Kahl-Mcdonagh, Benjamin W Neuman, Loni A Taylor, Rebecca S B Fischer, Blake M Hanson, Marlisa S Hardy, Jo Ann Culpepper, Eric Boerwinkle, Kurt A Zuelke

Faculty, Staff and Student Publications

SARS-CoV-2 transmission has declined, yet ongoing viral evolution continues to pose public health challenges. This study conducted long-term (2020-2024) genomic surveillance within a large and globally diverse university community. Viral genomes obtained from clinical (n = 1,786) and surveillance (n = 888) testing samples were classified under clade, lineage, and variant systems, and compared with global genomic data sets. Local patterns broadly paralleled global evolutionary trends, including the phased emergence of major variants, episodic introductions of new lineages, and shifts in dominant clades. Lineage diversity peaked during fall semesters and was highest among undergraduate-aged individuals, with similar distributions …


Gene Transcriptional Expression Of Cerebral Blood Flow Alterations In Parkinson’S Disease: A Transcription-Neuroimaging Association Study, Jiaqi Cui, Qiane Yu, Haifeng Ran, Kexin Huang, Jie Hu, Tijiang Zhang Jul 2026

Gene Transcriptional Expression Of Cerebral Blood Flow Alterations In Parkinson’S Disease: A Transcription-Neuroimaging Association Study, Jiaqi Cui, Qiane Yu, Haifeng Ran, Kexin Huang, Jie Hu, Tijiang Zhang

Faculty, Staff and Student Publications

Aim: Despite the intimate link between cerebral blood flow (CBF) alterations and Parkinson's disease (PD) pathogenesis and cognitive decline, the precise pathophysiological mechanisms driving this relationship remain elusive. This study seeks to correlate changes in CBF with regional gene expression to advance mechanistic understanding of the disease.

Methods: CBF group differences were first determined from ASL data in 53 PD and 40 healthy controls (HC) and subsequently correlated with cognitive scores (Dataset 1). A coordinate-based meta-analysis of published literature provided a second set of CBF differences (Dataset 2). Transcriptomic data from the Allen Human Brain Atlas were then correlated with …


Aberrant Ciliogenesis Induced By Enhanced Bmp Signaling Causes Heterotopic Ossification, Hiroyuki Yamaguchi, Jianbo Wang, Fangfang Yan, Jiarui Bi, Radbod Darabi, William R. Lagor, Zhongming Zhao, Aris N. Economides, Yuji Mishina, Yoshihiro Komatsu Jul 2026

Aberrant Ciliogenesis Induced By Enhanced Bmp Signaling Causes Heterotopic Ossification, Hiroyuki Yamaguchi, Jianbo Wang, Fangfang Yan, Jiarui Bi, Radbod Darabi, William R. Lagor, Zhongming Zhao, Aris N. Economides, Yuji Mishina, Yoshihiro Komatsu

Faculty, Staff and Student Publications

Bone morphogenetic protein (BMP) signaling is a principal driver of heterotopic ossification (HO), yet how aberrant BMP activity structurally reprograms cellular signaling machinery to develop HO remains unclear. Here, we identify BMP signaling as a direct upstream regulator of ciliogenesis that coordinates a multi-stage, pro-osteochondrogenic signaling relay during HO. Using a conditional gain-of-function BMP mouse model (Acvr1Q207D/+), we demonstrate that enhanced BMP signaling promotes primary cilium biogenesis and axonemal elongation through canonical Smad1/5/9-dependent transcriptional activation of intraflagellar transport (IFT) Ift20, a core component of the IFT machinery. Rather than operating via a singular downstream cascade, these elongated …


Advancing Bioinformatics With Language Models: Components, Applications, And Perspectives, Jiajia Liu, Mengyuan Yang, Yankai Yu, Haixia Xu, Tiangang Wang, Kang Li, Xiaobo Zhou Jul 2026

Advancing Bioinformatics With Language Models: Components, Applications, And Perspectives, Jiajia Liu, Mengyuan Yang, Yankai Yu, Haixia Xu, Tiangang Wang, Kang Li, Xiaobo Zhou

Faculty, Staff and Student Publications

Large language models (LLMs) are deep learning-based artificial intelligence models that have achieved remarkable success in natural language processing. Typically composed of neural networks with billions of parameters, they are trained on massive unlabeled datasets using self-supervised or semi-supervised learning. Beyond language, LLMs hold immense potential for addressing complex bioinformatics challenges. This review provides a comprehensive overview of transformer-based model applications in genomics, transcriptomics, proteomics, drug discovery, and single-cell analysis. We discuss critical components, including tokenization strategies for diverse biological data, transformer architectures, attention mechanisms, and pretraining approaches. We also survey currently available foundation models and their downstream applications across …


Pangenome Analysis Of Proteus Mirabilis Reveals Lineage-Specific Antimicrobial Resistance Profiles And Discordant Genotype-Phenotype Correlations, Namrata Deka, Aimee L Brauer, Katherine Connerton, Blake M Hanson, Jennifer N Walker, Chelsie E Armbruster Jul 2026

Pangenome Analysis Of Proteus Mirabilis Reveals Lineage-Specific Antimicrobial Resistance Profiles And Discordant Genotype-Phenotype Correlations, Namrata Deka, Aimee L Brauer, Katherine Connerton, Blake M Hanson, Jennifer N Walker, Chelsie E Armbruster

Faculty, Staff and Student Publications

Urinary tract infections (UTIs) impose a large healthcare burden, with escalating antimicrobial resistance (AMR), and treatment failure. Proteus mirabilis is an undercharacterized and challenging UTI pathogen due to intrinsic resistance and biofilm formation. To understand P. mirabilis population genomics, we combined pangenome analysis, in silico AMR prediction, and phenotypic antimicrobial susceptibility testing (AST) across 1,027 P. mirabilis genomes derived from human urine specimens. This revealed a mosaic pangenome driven by extensive accessory genome plasticity. Multilocus sequence typing (MLST) identified 213 MLSTs, with only 7% having ≥10 genomes, highlighting strain diversity. AMR gene profiles were largely lineage-specific, with 25% of genomes …


Mosaic Loss Of Y Chromosome Associates With Lung Function, Emphysema, And Epigenetic Aging, Woei-Yuh Saw, Kangjin Kim, Yichen Huang, Jeong H Yun, Xiaolong Ma, Jason Bacon, Yash Pershad, Daniel Levy, George T O'Connor, Eric Boerwinkle, R Graham Barr, Stephen S Rich, Jerome I Rotter, April P Carson, Laura M Raffield, Sina A Gharib, Traci M Bartz, Bruce M Psaty, Tamar Sofer, Kari E North, Robert C Kaplan, Elizabeth C Oelsner, Ani Manichaikul, Alexander G Bick, Paul Scheet, Alexander P Reiner, Nhlbi Trans-Omics For Precision Medicine Consortium, Yasminka A Jakubek, Paul L Auer, Michael H Cho, Dawn L Demeo Jul 2026

Mosaic Loss Of Y Chromosome Associates With Lung Function, Emphysema, And Epigenetic Aging, Woei-Yuh Saw, Kangjin Kim, Yichen Huang, Jeong H Yun, Xiaolong Ma, Jason Bacon, Yash Pershad, Daniel Levy, George T O'Connor, Eric Boerwinkle, R Graham Barr, Stephen S Rich, Jerome I Rotter, April P Carson, Laura M Raffield, Sina A Gharib, Traci M Bartz, Bruce M Psaty, Tamar Sofer, Kari E North, Robert C Kaplan, Elizabeth C Oelsner, Ani Manichaikul, Alexander G Bick, Paul Scheet, Alexander P Reiner, Nhlbi Trans-Omics For Precision Medicine Consortium, Yasminka A Jakubek, Paul L Auer, Michael H Cho, Dawn L Demeo

Faculty, Staff and Student Publications

Rationale: As the global population ages, identifying risk factors for age-related diseases, such as COPD, is crucial for public health. Mosaic loss of Y chromosome (mLOY) in blood cells is an age-related somatic mosaicism event, but its relationship with pulmonary health remains undercharacterized.

Objectives: To examine the association between mLOY and pulmonary outcomes in men.

Methods: Leveraging mLOY assessment (cell fraction ≥ 5%) in over 12 000 men, including 5097 from the COPDGene Study and 7235 from six additional cohorts in the Trans-Omics for Precision Medicine program, we investigated mLOY associations with respiratory outcomes and epigenetic aging using multivariable cross-sectional, …


Kras G12c And Kras G12d Respond To Lipid Metabolism In An Allele-Specific Manner, Neha Arora, Hong Liang, Walaa Kattan, Wantong Yao, Haoqiang Ying, Junchen Liu, Yong Zhou Jul 2026

Kras G12c And Kras G12d Respond To Lipid Metabolism In An Allele-Specific Manner, Neha Arora, Hong Liang, Walaa Kattan, Wantong Yao, Haoqiang Ying, Junchen Liu, Yong Zhou

Faculty, Staff and Student Publications

KRAS mutated at hotspots G12, G13, and Q61 possess profound allele-specific oncogenesis. Signaling of KRAS mutants is mostly compartmentalized to the proteolipid nanoclusters on the plasma membrane (PM), illustrating critical roles of spatiotemporal organization in KRAS cancer signaling. The activated GTP-bound KRAS molecules, including the wild type and mutants, have been traditionally thought to favor similar lipids. We recently reported distinct lipid sensing capabilities of different KRAS mutants, especially with KRASG12D favoring unsaturated lipids and KRASG12C gaining additional enrichment of saturated lipids. As such, KRAS mutants may respond to lipid acyl chain remodeling in an allele-specific manner. Lysophosphatidylcholine acyltransferase 1 …


Quantitative Analysis Of Peri-Implant Collagen Fiber Orientation Around External Hexagon And Morse Taper Implant Connections: A Dog Model Study, Daniel Sartorelli Marques De Castro, Jefferson David Melo De Matos, Jozely Francisca Mello Lima, Maria Angelica Rehder De Araujo, Mário Alexandre Coelho Sinhoreti, Daher Antonio Queiroz, Adriano Piattelli, Carlos Dos Reis Pereira De Araújo Jul 2026

Quantitative Analysis Of Peri-Implant Collagen Fiber Orientation Around External Hexagon And Morse Taper Implant Connections: A Dog Model Study, Daniel Sartorelli Marques De Castro, Jefferson David Melo De Matos, Jozely Francisca Mello Lima, Maria Angelica Rehder De Araujo, Mário Alexandre Coelho Sinhoreti, Daher Antonio Queiroz, Adriano Piattelli, Carlos Dos Reis Pereira De Araújo

Faculty, Staff and Student Publications

Background: Peri-implant soft tissue stability depends on the implant-abutment interface and collagen fiber organization. Unlike natural teeth, peri-implant fibers exhibit a less favorable orientation, potentially weakening the biological seal. Implant connection design may influence this collagen arrangement and tissue integrity.

Materials and methods: Eighteen immediately loaded implants (n = 9 per group) were placed in nine mongrel dogs. Group I received external hexagon implants, while Group II received Morse taper implants. After a 4-month healing period, animals were euthanized and specimens were processed for histological evaluation. Collagen fiber orientation was analyzed using polarized light microscopy and quantified with ImageJ software. …


Erk-Mediated Phosphorylation Of Yap Defines A Noncanonical Fgf Signaling Mechanism In Stem Cells, Xiaolei Zhao, Shannon Erhardt, Li Tang, Xiaotong Chen, Stephen M Farmer, Zixiu Cheng, Wen Chen, Ella Ziyuan Lu, Kihan Sung, Chang-Ru Tsai, Mingjie Zheng, Sheng Zhang, Yang Liu, Jianxin Wang, Min Li, James F Martin, Jun Wang Jul 2026

Erk-Mediated Phosphorylation Of Yap Defines A Noncanonical Fgf Signaling Mechanism In Stem Cells, Xiaolei Zhao, Shannon Erhardt, Li Tang, Xiaotong Chen, Stephen M Farmer, Zixiu Cheng, Wen Chen, Ella Ziyuan Lu, Kihan Sung, Chang-Ru Tsai, Mingjie Zheng, Sheng Zhang, Yang Liu, Jianxin Wang, Min Li, James F Martin, Jun Wang

Faculty, Staff and Student Publications

While Fgf and Hippo-Yap signaling are fundamental for proper development, homeostasis, and disease, their crosstalk remains largely unknown. Here, we identified that Yap and Taz, canonical Hippo effectors, function as noncanonical effectors of Fgf signaling to maintain the proper function of neural crest (NC) lineages. NC cells are a multipotent stem cell population during vertebrate embryogenesis that contribute to numerous structures and diverse cell lineages, including craniofacial and cardiac tissues, neurons, and suture mesenchymal cells (SMCs), a specified cell population required for cranial bone growth and repair. We observed that activation of Fgf signaling in NC cells and NC-derived SMCs …


Sex Differences In The Protective Effect Of Brain Volume: Age Attenuates Protection In Women, Javier Gomez-Farias, Ngoc Mai Le, Joseph N Samaha, Bruna Kfoury, Hussain M Azeem, Ritesh Bajaj, Mahnoor Khalid, Freya Kanakhara, Shikha Tripathi, Shayan Shams, Luca Giancardo, Eunyoung A Lee, Robert W Regenhardt, Louise D Mccullough, Sunil A Sheth Jul 2026

Sex Differences In The Protective Effect Of Brain Volume: Age Attenuates Protection In Women, Javier Gomez-Farias, Ngoc Mai Le, Joseph N Samaha, Bruna Kfoury, Hussain M Azeem, Ritesh Bajaj, Mahnoor Khalid, Freya Kanakhara, Shikha Tripathi, Shayan Shams, Luca Giancardo, Eunyoung A Lee, Robert W Regenhardt, Louise D Mccullough, Sunil A Sheth

Faculty, Staff and Student Publications

Background: Sex differences in outcomes after acute ischemic stroke are well recognized, but mechanisms remain unclear. This study evaluates whether parenchymal brain volume (PBV), age, and final infarct volume explain sex-specific differences in poststroke disability.

Methods: We analyzed a prospectively collected multicenter registry of acute ischemic stroke patients treated between 2015 and 2024. Automated pipelines quantified PBV from noncontrast computed tomography and diffusion-weighted imaging-derived final infarct volume from 24- to 48-hour magnetic resonance imaging. With the primary outcome being 90-day functional independence (modified Rankin Scale score 0-2), sex-stratified logistic regression models evaluated its association with PBV. Stratified logistic and linear …


Medadl: High-Throughput Information Extraction Of Functional Status From Electronic Health Records To Advance Frailty Assessment In Older Adults, Sunyang Fu, Zhiyi Yue, Jennyly T Nguyen, Huipeng Liu, Jaerong Ahn, Vanessa Ramirez, Jude Des Bordes, Hongfang Liu, Min Ji Kwak, Nahid J Rianon Jul 2026

Medadl: High-Throughput Information Extraction Of Functional Status From Electronic Health Records To Advance Frailty Assessment In Older Adults, Sunyang Fu, Zhiyi Yue, Jennyly T Nguyen, Huipeng Liu, Jaerong Ahn, Vanessa Ramirez, Jude Des Bordes, Hongfang Liu, Min Ji Kwak, Nahid J Rianon

Faculty, Staff and Student Publications

Background: Functional status is essential for assessing frailty and planning care in older adults but is often under-documented in the structured fields of electronic health records. Manual chart review can capture functional status information but is labor-intensive and time-consuming. In this study, we developed and validated a scalable natural language processing (NLP) model to extract functional status information from unstructured electronic health record (EHR) notes.

Methods: This retrospective cohort study included 110 older adults seen at a geriatric osteoporosis clinic. A large language model-augmented symbolic NLP pipeline (MedADL) was developed to extract activities of daily living (ADL) and instrumental activities …


Qualitative Evaluation Of The Seated Physical Activity Intervention (Spin) Randomized Controlled Trial For Wheelchair Users With Multiple Sclerosis (Ms): Formative Feedback And Future Directions, Angela J Piasecki, Robert W Motl, Katherine Froehlich-Grobe, Stephanie L Silveira Jun 2026

Qualitative Evaluation Of The Seated Physical Activity Intervention (Spin) Randomized Controlled Trial For Wheelchair Users With Multiple Sclerosis (Ms): Formative Feedback And Future Directions, Angela J Piasecki, Robert W Motl, Katherine Froehlich-Grobe, Stephanie L Silveira

Faculty, Staff and Student Publications

Background/objectives: Wheelchair users with multiple sclerosis (MS) often face barriers that restrict participation in physical activity and exercise training. This manuscript reports on participant feedback to guide evaluating and refining a novel exercise training program, Seated Physical activity INtervention (SPIN). SPIN was adapted from the Guidelines for Exercise in MS (GEMS) approach using a three-step community-engaged research framework based on meeting the needs of wheelchair users with MS.

Methods: Semi-structured interviews were conducted with 9 participants who completed the 16-week SPIN intervention. The key SPIN intervention components were the exercise prescription, exercise equipment, and behavioral coaching grounded in Social Cognitive …


Toolkit For Multistate Disease Progression Simulation And Treatment Decision-Making Aid, Can Xie, Ruosha Li, Wael Saber, Jorge E Cortes, Nicholas J Short, Xuelin Huang Jun 2026

Toolkit For Multistate Disease Progression Simulation And Treatment Decision-Making Aid, Can Xie, Ruosha Li, Wael Saber, Jorge E Cortes, Nicholas J Short, Xuelin Huang

Faculty, Staff and Student Publications

Background: The optimal timing of a treatment within therapy lines can maximize its benefit while minimizing risks and side effects. Because patients differ in clinical and biological characteristics, personalized treatment planning can support physicians' decision-making. However, multistate disease progression complicates the comparison of treatment strategies, motivating the development of a user-friendly web tool for multistate disease progression simulation and treatment decision support. Microsimulation is a natural approach for comparing prespecified treatment-timing strategies, where it generates disease trajectories for a large number of virtual patients matched to an individual patient's observed data. In our framework, microsimulation is performed using a multistate …


Qeith: Quantifies Tumor Ecosystem Heterogeneity To Predict Cancer Progression And Treatment Benefit, Qiqi Liu, Jiangti Luo, Jiawei Wang, Bangqi Zhao, Xiaosheng Wang, Linjun You Jun 2026

Qeith: Quantifies Tumor Ecosystem Heterogeneity To Predict Cancer Progression And Treatment Benefit, Qiqi Liu, Jiangti Luo, Jiawei Wang, Bangqi Zhao, Xiaosheng Wang, Linjun You

Faculty, Staff and Student Publications

Intratumor heterogeneity (ITH) is a fundamental driver of therapeutic failure and disease progression. However, the complexity of the tumor ecosystem is a critical yet underexplored aspect, making its precise quantification essential for fully deciphering ITH and its clinical implications. To address this, we developed Quantifying Ecosystem Intratumor Heterogeneity (QeITH), a computational framework that applies Shannon entropy to quantify ecosystem heterogeneity by measuring the diversity and distributional entropy of cellular compositions and functional states across single-cell, bulk, and spatial transcriptomics. At the single-cell resolution, QeITH identifies elevated ITH as intrinsic markers of malignant transformation, yet enhanced sensitivity to therapy. Pan-cancer bulk …


Oral Cancer Numerical Index (Ocni): Development And Validation Of A Cytology-Based Risk Assessment For Oral Lesions, Michael P Mcrae, Nadarajah Vigneswaran, Alexander Ross Kerr, Spencer W Redding, Martin H Thornhill, Craig Murdoch, Paul M Speight, Rachelle Wolk, Kritika S Rajsri, Pooja Gaikwad, Nancy Ruel, Nicolaos J Christodoulides, John T Mcdevitt Jun 2026

Oral Cancer Numerical Index (Ocni): Development And Validation Of A Cytology-Based Risk Assessment For Oral Lesions, Michael P Mcrae, Nadarajah Vigneswaran, Alexander Ross Kerr, Spencer W Redding, Martin H Thornhill, Craig Murdoch, Paul M Speight, Rachelle Wolk, Kritika S Rajsri, Pooja Gaikwad, Nancy Ruel, Nicolaos J Christodoulides, John T Mcdevitt

Faculty, Staff and Student Publications

Background/Objectives: Oral potentially malignant disorders (OPMDs) require accurate risk stratification to identify patients at the highest risk for severe oral epithelial dysplasia (OED) or oral squamous cell carcinoma (OSCC). We developed and internally validated the oral cancer numerical index (OCNI), a quantitative risk score derived from clinical features and deep learning-based brush cytology measurements.

Methods: This retrospective model development and internal validation study was conducted using data from the multicenter Grand Opportunity study. Prospectively recruited subjects with OPMD with complete data were divided at the subject level into a training set (n = 384) and a holdout test set …


Publisher Correction: Whole Genome Sequence Analysis Of Pulmonary Function And Copd In 44,287 Multi-Ancestry Participants, Wonji Kim, Xiaowei Hu, Kangjin Kim, Sung Chun, Peter Orchard, Dandi Qiao, Ingo Ruczinski, Aabida Saferali, Francois Aguet, Lucinda Antonacci-Fulton, Pallavi P Balte, Traci M Bartz, Wardatul Jannat Anamika, Xiaobo Zhou, Junyi Duan, Jennifer A Brody, Brian E Cade, Martha L Daviglus, Harshavadran Doddapaneni, Shannon Dugan-Perez, Susan K Dutcher, Christian D Frazar, Stacey B Gabriel, Sina A Gharib, Namrata Gupta, Brian D Hobbs, Silva Kasela, Laura R Loehr, Ginger A Metcalf, Donna M Muzny, Elizabeth C Oelsner, Laura J Rasmussen-Torvik, Colleen M Sitlani, Joshua Smith, Tamar Sofer, Hanfei Xu, Bing Yu, David Zhang, John Ziniti, R Graham Barr, April P Carson, Myriam Fornage, Lifang Hou, Ravi Kalhan, Robert Kaplan, Tuuli Lappalainen, Stephanie J London, Alanna C Morrison, George T O'Connor, Bruce M Psaty, Laura M Raffield, Susan Redline, Stephen S Rich, Jerome I Rotter, Edwin K Silverman, Ani Manichaikul, Michael H Cho Jun 2026

Publisher Correction: Whole Genome Sequence Analysis Of Pulmonary Function And Copd In 44,287 Multi-Ancestry Participants, Wonji Kim, Xiaowei Hu, Kangjin Kim, Sung Chun, Peter Orchard, Dandi Qiao, Ingo Ruczinski, Aabida Saferali, Francois Aguet, Lucinda Antonacci-Fulton, Pallavi P Balte, Traci M Bartz, Wardatul Jannat Anamika, Xiaobo Zhou, Junyi Duan, Jennifer A Brody, Brian E Cade, Martha L Daviglus, Harshavadran Doddapaneni, Shannon Dugan-Perez, Susan K Dutcher, Christian D Frazar, Stacey B Gabriel, Sina A Gharib, Namrata Gupta, Brian D Hobbs, Silva Kasela, Laura R Loehr, Ginger A Metcalf, Donna M Muzny, Elizabeth C Oelsner, Laura J Rasmussen-Torvik, Colleen M Sitlani, Joshua Smith, Tamar Sofer, Hanfei Xu, Bing Yu, David Zhang, John Ziniti, R Graham Barr, April P Carson, Myriam Fornage, Lifang Hou, Ravi Kalhan, Robert Kaplan, Tuuli Lappalainen, Stephanie J London, Alanna C Morrison, George T O'Connor, Bruce M Psaty, Laura M Raffield, Susan Redline, Stephen S Rich, Jerome I Rotter, Edwin K Silverman, Ani Manichaikul, Michael H Cho

Faculty, Staff and Student Publications

This corrects the article "Whole genome sequence analysis of pulmonary function and COPD in 44,287 multi-ancestry participants", 28.


Behavioural Activation For The Prevention Of Poststroke Depression In Low-Income Older Stroke Survivors (Live Wel): Protocol For A Randomised Controlled Trial, Jennifer E S Beauchamp, Sean I Savitz, Anjail Sharrief, Belinda M Reininger, Ronald Acierno, Robert Suchting, Jason Burnett, Lauren Rosales, Jenan Ahmed Albaqali, Rinitha Rajan, Namkee G Choi Jun 2026

Behavioural Activation For The Prevention Of Poststroke Depression In Low-Income Older Stroke Survivors (Live Wel): Protocol For A Randomised Controlled Trial, Jennifer E S Beauchamp, Sean I Savitz, Anjail Sharrief, Belinda M Reininger, Ronald Acierno, Robert Suchting, Jason Burnett, Lauren Rosales, Jenan Ahmed Albaqali, Rinitha Rajan, Namkee G Choi

Faculty, Staff and Student Publications

Introduction: Poststroke depression (PSD) affects approximately 33% of stroke survivors and is associated with worse outcomes, poor quality of life (QOL) and mortality. Despite its prevalence and consequences, there is no consensus on the most effective strategy for PSD prevention. Behavioural activation (BA) is an effective intervention for depression across diverse populations and is considered safer, better tolerated and a longer-lasting alternative to antidepressant medications. This study aims to test the effectiveness of a remotely delivered BA intervention to prevent PSD (Tele-BA-S).

Methods and analysis: We will conduct a randomised effectiveness trial of 350 low-income adults (≥ 55 years) within …


Decoding Growth Hormone Actions On Human Growth Plate Stem Cells, Shion Orikasa, Noriaki Ono Jun 2026

Decoding Growth Hormone Actions On Human Growth Plate Stem Cells, Shion Orikasa, Noriaki Ono

Faculty, Staff and Student Publications

The epiphyseal growth plate is the key target of growth hormone (GH) therapy. Although growth plate stem cells are well defined in mice, their presence in humans was unclear. Using rare surgical specimens, the study by Chu et al. reveals conserved, GH-responsive stem cells in the human pubertal growth plate.


Nmda Receptor Subunit Nmr-2 Regulates Pathogen-Induced Immune Responses Via The Nervous System In C. Elegans, Benson Otarigho, Jonathan Lalsiamthara, Alejandro Aballay Jun 2026

Nmda Receptor Subunit Nmr-2 Regulates Pathogen-Induced Immune Responses Via The Nervous System In C. Elegans, Benson Otarigho, Jonathan Lalsiamthara, Alejandro Aballay

Faculty, Staff and Student Publications

Neural control of innate immunity must balance restraint of basal immune activity with rapid activation upon pathogen encounter. Glutamate, the primary excitatory neurotransmitter in the nervous system, has been implicated in several neurological disorders associated with inflammation, suggesting a potential link to immune regulation. However, how glutamatergic signaling contributes to immune balance remains unknown. Here, we demonstrated that the NMDA-type ionotropic glutamate receptor subunit NMR-2, a component of the NMDA receptor complex, acts in the


Association Of Insulin Resistance And Fracture Risk In The Osteoporotic Fractures In Men (Mros) Cohort, Jeonghoon Ha, Li-Yung Lui, Kristine Ensrud, Qian Xiao, Andrew R Hoffman, Joy Y Wu Jun 2026

Association Of Insulin Resistance And Fracture Risk In The Osteoporotic Fractures In Men (Mros) Cohort, Jeonghoon Ha, Li-Yung Lui, Kristine Ensrud, Qian Xiao, Andrew R Hoffman, Joy Y Wu

Faculty, Staff and Student Publications

Context: Insulin resistance (IR) is more prevalent in men than in women, but evidence directly linking IR to fracture risk in older men remains limited.

Objective: To evaluate the association between insulin resistance (IR), estimated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and the triglyceride-glucose (TyG) index, and fracture risk in older men.

Methods: Data from 5994 men (≥65 years) in the MrOS cohort were analyzed. A total of 5416 participants were included in the HOMA-IR analysis and 5384 in the TyG index analysis. Fractures were self-reported and confirmed radiographically. Participants were grouped into quartiles based on IR …


Age And Sex Affect The Prevalence And Severity Of Periodontal Conditions In An Academic Setting, Karo Parsegian, Nikolaos Soldatos, Tonia C Carter, Nikola Angelov, Neel Shimpi, Krishna Kumar Kookal, David K Okano, Effie Ioannidou Jun 2026

Age And Sex Affect The Prevalence And Severity Of Periodontal Conditions In An Academic Setting, Karo Parsegian, Nikolaos Soldatos, Tonia C Carter, Nikola Angelov, Neel Shimpi, Krishna Kumar Kookal, David K Okano, Effie Ioannidou

Faculty, Staff and Student Publications

Background: The aim of the present study was to examine whether age and sex affected the prevalence and severity of periodontal conditions in patients attending an academic dental clinic.

Methods: Electronic health record (EHR) data on the demographic characteristics and periodontal conditions of patients presented for a comprehensive periodontal evaluation were extracted from the institutional dental EHR database. Retrospective analysis of independent associations of age, sex, and other subject characteristics with periodontal conditions was determined using multinomial logistic regression. The null hypothesis stating that age and sex were not associated with the increased prevalence and/or severity of periodontal conditions was …