Digital Commons Network^™

Development And Validation Of A Dynamic Real-Time Risk Prediction Model For Intensive Care Units Patients Based On Longitudinal Irregular Data: Multicenter Retrospective Study, Zhuo Zheng, Jiawei Luo, Yingchao Zhu, Lei Du, Lan Lan, Xiaobo Zhou, Xiaoyan Yang, Shixin Huang

Faculty, Staff and Student Publications

Background: Timely and accurate prediction of short-term mortality is critical in intensive care units (ICUs), where patients' conditions change rapidly. Traditional scoring systems, such as the Simplified Acute Physiology Score and Acute Physiology and Chronic Health Evaluation, rely on static variables collected within the first 24 hours of admission and do not account for continuously evolving clinical states. These systems lack real-time adaptability, interpretability, and generalizability. With the increasing availability of high-frequency electronic medical record (EMR) data, machine learning (ML) approaches have emerged as powerful tools to model complex temporal patterns and support dynamic clinical decision-making. However, existing models are …

Inhibition Of Soluble Epoxide Hydrolase Confers Neuroprotection And Restores Microglial Homeostasis In A Tauopathy Mouse Model, Shuo Wang, Chuangye Qi, Chetan Rajpurohit, Baijayanti Ghosh, Wen Xiong, Baiping Wang, Yanyan Qi, Sung Hee Hwang, Bruce D Hammock, Hongjie Li, Li Gan, Hui Zheng

Center on Aging Staff Publications

Background: The epoxyeicosatrienoic acids (EETs) are derivatives of the arachidonic acid metabolism with anti-inflammatory activities. However, their efficacy is limited due to the rapid hydrolysis by soluble epoxide hydrolase (sEH). Inhibition of sEH has been shown to stabilize the EETs and reduce neuroinflammation in Aβ mouse models of Alzheimer's disease (AD). However, the role of the sEH-EET signaling pathway in other CNS cell types and neurodegenerative conditions are less understood.

Methods: Here we investigated the mechanisms and functional role of the sEH-EET axis in tauopathy by treating PS19 mice with a small molecule sEH inhibitor TPPU and by crossing the …

Ensemble Learning With Explainable Ai For Improved Heart Disease Prediction Based On Multiple Datasets, Shahid Mohammad Ganie, Pijush Kanti Dutta Pramanik, Zhongming Zhao

Faculty, Staff and Student Publications

Heart disease is one of the leading causes of death worldwide. Predicting and detecting heart disease early is crucial, as it allows medical professionals to take appropriate and necessary actions at earlier stages. Healthcare professionals can diagnose cardiac conditions more accurately by applying machine learning technology. This study aimed to enhance heart disease prediction using stacking and voting ensemble methods. Fifteen base models were trained on two different heart disease datasets. After evaluating various combinations, six base models were pipelined to develop ensemble models employing a meta-model (stacking) and a majority vote (voting). The performance of the stacking and voting …

Dna Methylation Signature Of A Lifestyle-Based Resilience Index For Cognitive Health, Wei Zhang, David Lukacsovich, Juan I Young, Lissette Gomez, Michael A Schmidt, Eden R Martin, Brian W Kunkle, X Steven Chen, Deirdre M O'Shea, James E Galvin, Lily Wang

Faculty, Staff and Students Publications

Cognitive resilience (CR) contributes to the variability in risk for developing and progressing in Alzheimer's disease (AD) among individuals. Beyond genetics, recent studies highlight the critical role of lifestyle factors in enhancing CR and delaying cognitive decline. DNA methylation (DNAm), an epigenetic mechanism influenced by both genetic and environmental factors, including CR-related lifestyle factors, offers a promising pathway for understanding the biology of CR. We studied DNAm changes associated with the Resilience Index (RI), a composite measure of lifestyle factors, using blood samples from the Healthy Brain Initiative (HBI) cohort. After corrections for multiple comparisons, our analysis identified 19 CpGs …

Functional Protein Biomarkers Based On Distributions Of Expression Levels In Single-Cell Imaging Data, Misung Yi, Tingting Zhan, Hallgeir Rui, Inna Chervoneva

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

MOTIVATION: The intra-tumor heterogeneity of protein expression is well recognized and may provide important information for cancer prognosis and predicting treatment responses. Analytic methods that account for spatial heterogeneity remain methodologically complex and computationally demanding for single-cell protein expression. For many functional proteins, single-cell expressions vary independently of spatial localization in a substantial proportion of the tumor tissues, and incorporation of spatial information may not affect the prognostic value of such protein biomarkers.

RESULTS: We developed a new framework for using the distributions of functional single-cell protein expression levels as cancer biomarkers. The quantile functions of single-cell expressions are used …

Tips For Quality Publishing; Lessons From The Neuroscience Editorial Team, Francesca Cirulli, Rachael Dangarembezi, Victor De Lafuente, Anthony J Hannan, Amanda C Kentner, Tatsuya Mima, Laurel Morris, Sarah J Spencer, Long-Jun Wu, Chen Zhang

The Brown Foundation: Institute of Molecular Medicine

In pursuit of excellence in scholarly publishing, the Neuroscience editorial team shares valuable insights that are essential for authors, reviewers, and the broader scientific community. Firstly, we emphasize that impactful research is built on rigorous study design and execution. Beyond fundamental methodological safeguards such as randomization and blinded analysis, we highlight the importance of thoughtfully selecting study models, with deliberate attention to biological variables like sex and gender, as well as appropriate nomenclature. Secondly, as technological innovations reshape research landscapes, we advocate for combining methodological rigor with suitable analytical tools to ensure robust data collection and transparent reporting. Thirdly, for …

Structural Basis For Polθ-Helicase Dna Binding And Microhomology-Mediated End-Joining, Fumiaki Ito, Ziyuan Li, Leonid Minakhin, Htet A. Khant, Richard T. Pomerantz, Xiaojiang S. Chen

Department of Biochemistry and Molecular Biology Faculty Papers

DNA double-strand breaks (DSBs) present a critical threat to genomic integrity, often precipitating genomic instability and oncogenesis. Repair of DSBs predominantly occurs through homologous recombination (HR) and non-homologous end joining (NHEJ). In HR-deficient cells, DNA polymerase theta (Polθ) becomes critical for DSB repair via microhomology-mediated end joining (MMEJ), also termed theta-mediated end joining (TMEJ). Thus, Polθ is synthetically lethal with BRCA1/2 and other HR factors, underscoring its potential as a therapeutic target in HR-deficient cancers. However, the molecular mechanisms governing Polθ-mediated MMEJ remain poorly understood. Here we present a series of cryo-electron microscopy structures of the Polθ helicase domain (Polθ-hel) …

A Nuclear Rna Degradation Code Is Recognized By Paxt For Eukaryotic Transcriptome Surveillance, Lindsey V Soles, Liang Liu, Xudong Zou, Yoseop Yoon, Shuangyu Li, Lusong Tian, Marielle Valdez, Angela M Yu, Hong Yin, Wei Li, Fangyuan Ding, Georg Seelig, Lei Li, Yongsheng Shi

Faculty, Staff and Students Publications

The RNA exosome plays critical roles in eukaryotic RNA degradation, but how it specifically recognizes its targets remains unclear. The poly(A) tail exosome targeting (PAXT) connection is a nuclear adaptor that recruits the exosome to polyadenylated RNAs, especially transcripts polyadenylated at intronic poly(A) sites. Here, we show that PAXT-mediated RNA degradation is induced by the combination of a 5' splice site (ss) and a poly(A) junction (PAJ) but not by either sequence alone. These sequences are bound by U1 small nuclear ribonucleoprotein particle (snRNP) and cleavage/polyadenylation factors, which, in turn, cooperatively recruit PAXT. As the 5' ss-PAJ combination is typically …

Deep Learning-Based Automatic Segmentation Of Cerebral Infarcts On Diffusion Mri, Wi-Sun Ryu, Dawid Schellingerhout, Jonghyeok Park, Jinyong Chung, Sang-Wuk Jeong, Dong-Seok Gwak, Beom Joon Kim, Joon-Tae Kim, Keun-Sik Hong, Kyung Bok Lee, Tai Hwan Park, Sang-Soon Park, Jong-Moo Park, Kyusik Kang, Yong-Jin Cho, Hong-Kyun Park, Byung-Chul Lee, Kyung-Ho Yu, Mi Sun Oh, Soo Joo Lee, Jae Guk Kim, Jae-Kwan Cha, Dae-Hyun Kim, Jun Lee, Man Seok Park, Dongmin Kim, Oh Young Bang, Eung Yeop Kim, Chul-Ho Sohn, Hosung Kim, Hee-Joon Bae, Dong-Eog Kim

Faculty, Staff and Student Publications

We explored effects of (1) training with various sample sizes of multi-site vs. single-site training data, (2) cross-site domain adaptation, and (3) data sources and features on the performance of algorithms segmenting cerebral infarcts on Magnetic Resonance Imaging (MRI). We used 10,820 annotated diffusion-weighted images (DWIs) from 10 university hospitals. Algorithms based on 3D U-net were trained using progressively larger subsamples (ranging from 217 to 8661), while internal testing employed a distinct set of 2159 DWIs. External validation was conducted using three unrelated datasets (n = 2777, 50, and 250). For domain adaptation, we utilized 50 to 1000 subsamples from …

Volumetric Changes In Cerebellar Transverse Zones: Age And Sex Effects In Health And Neurological Disorders, Farshid Ghiyamihoor, Payam Paymani, Jarrad Perron, Azam Asemi-Rad, Mehdi Marzban, Aashka Mohite, Karen Ardila, Bara Aljada, Asghar Marzban, Mehnosh Toback, Sherif Eltonsy, Ji Hyun Ko, Tabrez J Siddiqui, Christopher J Steele, Jiming Kong, Mario Manto, M Ethan Macdonald, Jason S Gill, Roy V Sillitoe, Fuat Balcı, Iman Beheshti, Hassan Marzban

Duncan NRI Faculty and Staff Publications

Cerebellar volumetric changes are intricately linked to aging, with distinct patterns across its transverse zones, the functional subdivisions characterized by unique cytoarchitectural and connectivity profiles. Despite research efforts, the cerebellar aging process in health and neurological disorders remains poorly understood. In this study, we investigated the effects of age and sex on total cerebellum, transverse zone, and lobule volumes using MRI data from over 45,000 participants compiled from six neuroimaging datasets. We also propose a framework for estimating cerebellum age as an indicator of cerebellar health. Significant age‐dependent volume reductions were observed across transverse zones, with the …

Mri Distance Measures As A Predictor Of Subsequent Clinical Status During The Preclinical Phase Of Alzheimer's Disease And Related Disorders, Xinyi Zhang, John C Morris, Tammie L S Benzinger, Et Al.

2020-Current year OA Pubs

Brain atrophy over time, as measured by magnetic resonance imaging (MRI), has been shown to predict subsequent cognitive impairment among individuals who were cognitively normal when first evaluated, indicating that subtle brain atrophy associated with Alzheimer's disease (AD) may begin years before clinical symptoms appear. Traditionally, atrophy has been quantified by differences in brain volume or thickness over a specified timeframe. Research indicates that the rate of atrophy varies across different brain regions, which themselves exhibit complex spatial and hierarchical organizations. These characteristics collectively emphasize the need for diverse summary measures that can effectively capture the multidimensional nature of degeneration. …

Distinguishing Multisystem Inflammatory Syndrome In Children From Typhus Using Artificial Intelligence: Mis-C Versus Endemic Typhus (Ai-Met), Angela Chun, Abraham Bautista-Castillo, Isabella Osuna, Kristiana Nasto, Flor M Munoz, Gordon E Schutze, Sridevi Devaraj, Eyal Muscal, Marietta M De Guzman, Kristen Sexson Tejtel, Tiphanie P Vogel, Ioannis A Kakadiaris

Faculty, Staff and Students Publications

Background: The pandemic emergent disease multisystem inflammatory syndrome in children (MIS-C) following coronavirus disease-19 infection can mimic endemic typhus. We aimed to use artificial intelligence (AI) to develop a clinical decision support system that accurately distinguishes MIS-C versus endemic typhus (MET).

Methods: Demographic, clinical, and laboratory features rapidly available following presentation were extracted for 133 patients with MIS-C and 87 patients hospitalized due to typhus. An attention module assigned importance to inputs used to create the 2-phase AI-MET. Phase 1 uses 17 features to arrive at a classification manually (MET-17). If the confidence level is not surpassed, 13 additional features …

Atm-Dependent Dna Damage Response Constrains Cell Growth And Drives Clonal Hematopoiesis In Telomere Biology Disorders, Christopher M Sande, Stone Chen, Dana V Mitchell, Ping Lin, Diana M Abraham, Jessie Minxuan Cheng, Talia Gebhard, Rujul J Deolikar, Colby Freeman, Mary Zhou, Sushant Kumar, Michael Bowman, Robert L Bowman, Shannon Zheng, Bolormaa Munkhbileg, Qijun Chen, Natasha L Stanley, Kathy Guo, Ajibike Lapite, Ryan Hausler, Deanne M Taylor, James Corines, Jennifer Jd Morrissette, David B Lieberman, Guang Yang, Olga Shestova, Saar Gill, Jiayin Zheng, Kelcy Smith-Simmer, Lauren G Banaszak, Kyle N Shoger, Erica F Reinig, Madilynn Peterson, Peter Nicholas, Amanda J Walne, Inderjeet Dokal, Justin P Rosenheck, Karolyn A Oetjen, Daniel C Link, Andrew E Gelman, Christopher R Reilly, Ritika Dutta, R Coleman Lindsley, Karyn J Brundige, Suneet Agarwal, Alison A Bertuch, Jane E Churpek, Laneshia K Tague, F Brad Johnson, Timothy S Olson, Daria V Babushok

Faculty, Staff and Students Publications

Telomere biology disorders (TBDs) are genetic diseases caused by defective telomere maintenance. TBD patients often develop bone marrow failure and have an increased risk of myeloid neoplasms. To better understand the factors underlying hematopoietic outcomes in TBD, we comprehensively evaluated acquired genetic alterations in hematopoietic cells from 166 pediatric and adult TBD patients. Of these patients, 47.6% (28.8% of children, 56.1% of adults) had clonal hematopoiesis. Recurrent somatic alterations involved telomere maintenance genes (7.6%), spliceosome genes (10.4%, mainly U2AF1 p.S34), and chromosomal alterations (20.2%), including 1q gain (5.9%). Somatic variants affecting the DNA damage response (DDR) were identified in 21.5% …

Atm-Dependent Dna Damage Response Constrains Cell Growth And Drives Clonal Hematopoiesis In Telomere Biology Disorders, Christopher M. Sande, Karolyn A. Oetjen, Daniel C. Link, Andrew E. Gelman, Laneshia K. Tague, Et Al.

2020-Current year OA Pubs

Telomere biology disorders (TBDs) are genetic diseases caused by defective telomere maintenance. TBD patients often develop bone marrow failure and have an increased risk of myeloid neoplasms. To better understand the factors underlying hematopoietic outcomes in TBD, we comprehensively evaluated acquired genetic alterations in hematopoietic cells from 166 pediatric and adult TBD patients. Of these patients, 47.6% (28.8% of children, 56.1% of adults) had clonal hematopoiesis. Recurrent somatic alterations involved telomere maintenance genes (7.6%), spliceosome genes (10.4%, mainly U2AF1 p.S34), and chromosomal alterations (20.2%), including 1q gain (5.9%). Somatic variants affecting the DNA damage response (DDR) were identified in 21.5% …

Outcomes Evidence Must Keep Up With The Implementation Of The 4ms Framework To Ensure Age-Friendly Health System Transformation, James D Harrison, Stephanie E Rogers, Benjamin Rosner, Estelle Martin, Sunny C Lin, Jarmin Yeh, Julia Adler-Milstein

2020-Current year OA Pubs

The Age-Friendly Health System (AFHS) movement was conceptualized as a transformative solution to reliably deliver evidence-based care to older adults. Guided by the 4Ms framework: What Matters, Mobility, Mentation, and Medication, AFHS healthcare systems have been given the flexibility to tailor 4Ms interventions and care processes to their context, preferences and populations. This flexibility has facilitated the widespread adoption of 4Ms care. However, as our understanding of 4Ms implementation grows, evidence of the impact of 4Ms care on outcomes must keep up with implementation to ensure AFHS transformation. It is only through assessing the 4Ms as a whole and understanding …

Bi-Allelic Variants In Brf2 Are Associated With Perinatal Death And Craniofacial Anomalies., Francesca Mattioli, Rún Friðriksdóttir, Anne Hebert, Sissy Bassani, Nazia Ibrahim, Shagufta Naz, Jacqueline Chrast, Clara Pailler-Pradeau, Ásmundur Oddsson, Patrick Sulem, Gisli H. Halldorsson, Páll Melsted, Daníel F. Guðbjartsson, Flavia Palombo, Tommaso Pippucci, Nayereh Nouri, Marco Seri, Emily G. Farrow, Carol J. Saunders, Nicolas Guex, Muhammad Ansar, Kari Stefansson, Alexandre Reymond

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Variants in genes encoding multiple subunits of the RNA Polymerase III complex which synthesizes rRNAs, tRNAs, and other small RNAs were previously associated with neurological disorders, such as syndromic hypomyelination leukodystrophies, pontocerebellar hypoplasia, and cerebellofaciodental syndrome. One new such candidate is BRF2, which encodes a TFIIB-like factor that recruits the RNA polymerase III complex to type 3 promoters to initiate transcription of U6, RnaseP, and 7SK RNAs.

METHODS: We combined sequencing with functional analyses to investigate the effects of BRF2 variants.

RESULTS: We observe that a previously reported significant underrepresentation of double transmission of a splice variant results in …

Vacuum Erectile Devices For Erectile Dysfunction: Recommendations From The 5th International Consultation On Sexual Medicine, Run Wang, Francisco E Martins, David Ralph, Georgios Hatzichristodoulou, Daniar Osmonov, Justin Parker, Sung Hun Sean Park, Ignacio Moncada, Carlo Bettocchi, Ricardo Munarriz, Tobias Köhler

Faculty, Staff and Student Publications

Introduction: Vacuum erectile device (VED) is 1 of the main approved therapies for erectile dysfunction (ED). The introduction of phosphodiesterase type 5 inhibitor (PDE5i) for ED significantly changed the roles of VED in contemporary sexual medicine.

Objective: To provide updated clinical evidence to inform health care providers on best practices with VED.

Methods: A consensus panel was held with leading sexual medicine experts during the 5th International Consultation on Sexual Medicine (ICSM). Relevant peer-reviewed literature was reviewed with focus on research from the last 10 years, but not limited to the last 10 years. The expert panel generated consensus statements …

Long-Read Single-Cell Rna Sequencing Enables The Study Of Cancer Subclone-Specific Genotypes And Phenotypes In Chronic Lymphocytic Leukemia, Gage S Black, Xiaomeng Huang, Yi Qiao, Philip Moos, Deepa Sampath, Deborah M Stephens, Jennifer A Woyach, Gabor T Marth

Faculty, Staff and Student Publications

Bruton tyrosine kinase (BTK) inhibitors are effective for the treatment of chronic lymphocytic leukemia (CLL) due to BTK's role in B cell survival and proliferation. Treatment resistance is most commonly caused by the emergence of the hallmark BTKC481S mutation that inhibits drug binding. In this study, we aimed to investigate cancer subclones harboring a BTKC481S mutation and identify cells with co-occurring CLL driver mutations. In addition, we sought to determine whether BTK-mutated subclones exhibit distinct transcriptomic behavior when compared to other cancer subclones. To achieve these goals, we use scBayes, which integrates bulk DNA sequencing and single-cell …

Results Of The Phase I/Ii Study And Preliminary B-Cell Gene Signature Of Combined Inhibition Of Glutamine Metabolism And Egfr In Colorectal Cancer, Kristen K Ciombor, Seong-Woo Bae, Jennifer G Whisenant, Gregory D Ayers, Quanhu Sheng, Todd E Peterson, Gary T Smith, Kangyu Lin, Saikat Chowdhury, Preeti Kanikarla Marie, Alexey Sorokin, Allison S Cohen, Laura W Goff, Dana B Cardin, John Paul Shen, Scott Kopetz, Cathy Eng, Yu Shyr, Jordan Berlin, H Charles Manning

Faculty, Staff and Student Publications

Purpose: EGFR-targeting mAbs are essential for managing rat sarcoma virus wild-type metastatic colorectal cancer (mCRC), but their limited efficacy necessitates exploring immunologic and metabolic factors influencing response. This study evaluated glutamine metabolism targeting with EGFR inhibition to identify response biomarkers in patients with prior anti-EGFR treatment progression.

Patients and methods: We conducted a phase I/II trial in patients with KRAS wild-type mCRC, combining panitumumab (6 mg/kg) and CB-839 (600 mg/kg or 800 mg/kg), hypothesizing that the dual inhibition of glutamine metabolism and MAPK signaling would enhance outcomes. As study correlatives, we investigated the B-cell activation signature "B-score" and glutamine PET …

Closing The Gaps, And Improving Somatic Structural Variant Analysis And Benchmarking Using Chm13-T2t, Luis F Paulin, Jeremy Fan, Kieran O'Neill, Erin Pleasance, Vanessa L Porter, Steven J M Jones, Fritz J Sedlazeck

Faculty, Staff and Students Publications

The complexities of cancer genomes are becoming more easily interpreted due to advancements in sequencing technologies and improved bioinformatic analysis. Structural variants (SVs) represent an important subset of somatic events in tumors. While the detection of SVs has been markedly improved by the development of long-read sequencing, somatic variant identification and annotation remain challenging. We hypothesized that the use of a completed human reference genome (CHM13-T2T) would improve somatic SV calling. Our findings in a tumor-normal matched benchmark sample and three patient samples show that the CHM13-T2T improves SV detection accuracy compared to GRCh38 with a notable reduction in false-positive …

Unraveling The Hidden Complexity Of Cancer Through Long-Read Sequencing, Qiuhui Li, Ayse G Keskus, Justin Wagner, Michal B Izydorczyk, Winston Timp, Fritz J Sedlazeck, Alison P Klein, Justin M Zook, Mikhail Kolmogorov, Michael C Schatz

Faculty, Staff and Students Publications

Cancer is fundamentally a disease of the genome, characterized by extensive genomic, transcriptomic, and epigenomic alterations. Most current studies predominantly use short-read sequencing, gene panels, or microarrays to explore these alterations; however, these technologies can systematically miss or misrepresent certain types of alterations, especially structural variants, complex rearrangements, and alterations within repetitive regions. Long-read sequencing is rapidly emerging as a transformative technology for cancer research by providing a comprehensive view across the genome, transcriptome, and epigenome, including the ability to detect alterations that previous technologies have overlooked. In this Perspective, we explore the current applications of long-read sequencing for both …

Germline Pathogenic Drosha Variants Are Linked To Pineoblastoma And Wilms Tumor Predisposition, Peter N Fiorica, Lisa Golmard, Jung Kim, Riyue Bao, Frank Y Lin, Angshumoy Roy, Allison Pribnow, Melissa R Perrino, Julien Masliah-Planchon, Sophie Michalak-Provost, Jennifer Wong, Mathilde Filser, Dominique Stoppa-Lyonnet, Franck Bourdeaut, Afane Brahimi, Olivier Ingster, Giselle Saulnier Sholler, Sarah A Jackson, Mark M Sasaki, Trent Fowler, Anita Ng, Ryan J Corbett, Rebecca S Kaufman, Jeremy S Haley, David J Carey, Kuan-Lin Huang, Sharon J Diskin, Jo Lynne Rokita, Hussam Al-Kateb, Rose B Mcgee, Joshua D Schiffman, Kenneth S Chen, Douglas R Stewart, D Williams Parsons, Sharon E Plon, Kris Ann P Schultz, Kenan Onel

Center for Medical Ethics and Health Policy Staff Publications

Purpose: DROSHA, DGCR8, and DICER1 regulate miRNA biogenesis and are commonly mutated in cancer. Although DGCR8 and DICER1 germline pathogenic variants (GPV) cause autosomal dominant tumor predisposition, no association between DROSHA GPVs and clinical phenotypes has been reported.

Experimental design: After obtaining informed consent, sequencing was performed on germline and tumor samples from all patients. The occurrence of germline DROSHA GPVs was investigated in large pediatric and adult cancer datasets. The population prevalence of DROSHA GPVs was investigated in the UK Biobank and Geisinger DiscovEHR cohorts.

Results: We describe nine children from eight families with heterozygous DROSHA GPVs and a …

Pilot First-In-Human Ccr2 Pet/Ct To Detect Abdominal Aortic Aneurysm Wall Instability, Santiago Elizondo-Benedetto, Deborah Sultan, Ryan Wahidi, Mahdjoub Hamdi, Mohamed S Zaghloul, Shahab Hafezi, Batool Arif, Laura K Mcdonald, Kitty Harrison, Dakkota Thies, Gyu Seong Heo, Hannah Luehmann, Lisa Detering, J Westley Ohman, Zachary J Wanken, Luis A Sanchez, Joseph E Ippolito, Jie Zheng, Robert J Gropler, Richard Laforest, Yongjian Liu, Mohamed A Zayed

2020-Current year OA Pubs

No abstract provided.

Machine Learning To Optimize Use Of Natriuretic Peptides In The Diagnosis Of Acute Heart Failure, Dimitrios Doudesis, Kuan Ken Lee, Mohamed Anwar, Adam J. Singer, Judd E. Hollander, Camille Chenevier-Gobeaux, Yann-Erick Claessens, Desiree Wussler, Dominic Weil, Nikola Kozhuharov, Ivo Strebel, Zaid Sabti, Christopher Defilippi, Stephen Seliger, Evandro Tinoco Mesquita, Jan C. Wiemer, Martin Möckel, Joel Coste, Patrick Jourdain, Komukai Kimiaki, Michihiro Yoshimura, Irwani Ibrahim, Shirley Beng Suat Ooi, Win Sen Kuan, Alfons Gegenhuber, Thomas Mueller, Olivier Hanon, Jean-Sébastien Vidal, Peter Cameron, Louisa Lam, Ben Freedman, Tommy Chung, Sean P. Collins, Christopher J. Lindsell, David E. Newby, Alan G. Japp, Anoop S. V. Shah, Humberto Villacorta, A. Mark Richards, John J V Mcmurray, Christian Mueller, James L. Januzzi, Nicholas L. Mills, Gordon Moe, Carlos Fernando, Hanna K. Gaggin, Antoni Bayes-Genis, Roland Rj Van Kimmenade, Yigal Pinto, Joost H. W. Rutten, Anton H. Van Den Meiracker, Luna Gargani, Nicola R. Pugliese, Pemberton Christopher, Michael Neumaier, Michael Behnes, Ibrahim Akin, Michele Bombelli, Guido Grassi, Peiman Nazerian, Giovanni Albano, Philipp Bahrmann

Department of Emergency Medicine Faculty Papers

AIMS: B-type natriuretic peptide (BNP) and mid-regional pro-atrial natriuretic peptide (MR-proANP) testing are guideline-recommended to aid in the diagnosis of acute heart failure. Nevertheless, the diagnostic performance of these biomarkers is uncertain.

METHODS AND RESULTS: We performed a systematic review and individual patient-level data meta-analysis to evaluate the diagnostic performance of BNP and MR-proANP. We subsequently developed and externally validated a decision-support tool called CoDE-HF that combines natriuretic peptide concentrations with clinical variables using machine learning to report the probability of acute heart failure. Fourteen studies from 12 countries provided individual patient-level data in 8493 patients for BNP and 3899 …

Machine Learning To Optimize Use Of Natriuretic Peptides In The Diagnosis Of Acute Heart Failure, Dimitrios Doudesis, Kuan Ken Lee, Mohamed Anwar, Adam J. Singer, Judd Hollander, Md, Camille Chenevier-Gobeaux, Yann-Erick Claessens, Desiree Wussler, Dominic Weil, Nikola Kozhuharov, Ivo Strebel, Zaid Sabti, Christopher Defilippi, Stephen Seliger, Evandro Tinoco Mesquita, Jan C. Wiemer, Martin Möckel, Joel Coste, Patrick Jourdain, Komukai Kimiaki, Michihiro Yoshimura, Irwani Ibrahim, Shirley Beng Suat Ooi, Win Sen Kuan, Alfons Gegenhuber, Thomas Mueller, Olivier Hanon, Jean-Sébastien Vidal, Peter Cameron, Louisa Lam, Ben Freedman, Tommy Chung, Sean P. Collins, Christopher J Lindsell, David E. Newby, Alan G. Japp, Anoop S V Shah, Humberto Villacorta, A Mark Richards, John J V Mcmurray, Christian Mueller, James L. Januzzi, Nicholas L. Mills

Department of Emergency Medicine Faculty Papers

AIMS: B-type natriuretic peptide (BNP) and mid-regional pro-atrial natriuretic peptide (MR-proANP) testing are guideline-recommended to aid in the diagnosis of acute heart failure. Nevertheless, the diagnostic performance of these biomarkers is uncertain.

METHODS AND RESULTS: We performed a systematic review and individual patient-level data meta-analysis to evaluate the diagnostic performance of BNP and MR-proANP. We subsequently developed and externally validated a decision-support tool called CoDE-HF that combines natriuretic peptide concentrations with clinical variables using machine learning to report the probability of acute heart failure. Fourteen studies from 12 countries provided individual patient-level data in 8493 patients for BNP and 3899 …

Disc Edema Secondary To Sleep Apnea: A Case Report, Jeannette A. Wong-Powell Od

Optometric Clinical Practice

Background: Bilateral optic disc edema is associated with multiple systemic conditions of potentially dire consequences. Idiopathic intracranial hypertension (IIH) is a common culprit and diagnosis of exclusion, which has been observed in multiple patients with obstructive sleep apnea (OSA) and raised questions of a pathophysiological link between the two.

Case Report: A 28-year-old Caucasian male with history of transient ischemic attack-like symptoms presented with bilateral disc edema prompting a multi-disciplinary work up that included imaging, lumbar puncture, laboratory analysis, neuroophthalmological, cardiological, and pulmonary evaluations that ultimately led to a diagnosis of OSA. The case is unique in that it followed …

A Case Report Of Vitreopapillary Traction Mistaken For Optic Disc Edema, Breyne Middleton Od, Drew Anderson Od

Optometric Clinical Practice

Background: Traction of the optic disc occurs during incomplete detachment of the posterior vitreous from the peripapillary glial tissue. It can sometimes cause the appearance of disc edema and bilateral cases can be confused with papilledema or cause patients to be worked up for pseudotumor cerebri.

Case Report: A patient presented with an outside diagnosis of unilateral optic disc edema and was found in fact to have vitreopapillary traction.

Conclusion: Costly, ultimately unnecessary testing such as magnetic resonance imaging can be sometimes avoided if vitreopapillary traction is considered as a differential for disc edema. It can be easily identified with …

Large-Scale Multi-Omics Analyses In Hispanic/Latino Populations Identify Genes For Cardiometabolic Traits, Lauren E Petty, Hung-Hsin Chen, Elizabeth G Frankel, Wanying Zhu, Carolina G Downie, Mariaelisa Graff, Phillip Lin, Priya Sharma, Xinruo Zhang, Alyssa C Scartozzi, Rashedeh Roshani, Joshua M Landman, Michael Boehnke, Donald W Bowden, John C Chambers, Anubha Mahajan, Mark I Mccarthy, Maggie C Y Ng, Xueling Sim, Cassandra N Spracklen, Weihua Zhang, Michael Preuss, Erwin P Bottinger, Girish N Nadkarni, Ruth J F Loos, Yii-Der Ida Chen, Jingyi Tan, Eli Ipp, Pauline Genter, Leslie S Emery, Tin Louie, Tamar Sofer, Adrienne M Stilp, Kent D Taylor, Anny H Xiang, Thomas A Buchanan, Kathryn Roll, Chuan Gao, Nicholette D Palmer, Jill M Norris, Lynne E Wagenknecht, Darryl Nousome, Rohit Varma, Roberta Mckean-Cowdin, Xiuqing Guo, Yang Hai, Willa Hsueh, Kevin Sandow, Esteban J Parra, Miguel Cruz, Adan Valladares-Salgado, Niels Wacher-Rodarte, Jerome I Rotter, Mark O Goodarzi, Stephen S Rich, Alain Bertoni, Leslie J Raffel, Jerry L Nadler, Fouad R Kandeel, Ravindranath Duggirala, John Blangero, Donna M Lehman, Ralph A Defronzo, Farook Thameem, Yujie Wang, Sheila Gahagan, Estela Blanco, Raquel Burrows, Alicia Huerta-Chagoya, Jose C Florez, Teresa Tusie-Luna, Clicerio González-Villalpando, Lorena Orozco, Christopher A Haiman, Craig L Hanis, Rebecca Rohde, Eric A Whitsel, Alexander P Reiner, Charles Kooperberg, Yun Li, Qing Duan, Miryoung Lee, Paulina Correa-Burrows, Susan K Fried, Kari E North, Joseph B Mccormick, Susan P Fisher-Hoch, Eric R Gamazon, Andrew P Morris, Josep M Mercader, Heather M Highland, Jennifer E Below

Faculty, Staff and Student Publications

Here, we present a multi-omics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits conducted to date in Hispanic/Latino populations (nmax = 63,184). We conduct a meta-analysis of 16 type 2 diabetes and 19 lipid trait GWAS, identifying 20 genome-wide significant loci for type 2 diabetes, including one novel locus and novel signals at two known loci, based on fine-mapping. We also identify sixty-one genome-wide significant loci across the lipid/lipoprotein traits, including nine novel loci, and novel signals at 19 known loci through fine-mapping. Next, we analyze genetically regulated expression, perform Mendelian randomization, and analyze association with …

Whole Genome Sequencing Analysis Of Body Mass Index Identifies Novel African Ancestry-Specific Risk Allele, Xinruo Zhang, Jennifer A Brody, Mariaelisa Graff, Heather M Highland, Nathalie Chami, Hanfei Xu, Zhe Wang, Kendra R Ferrier, Geetha Chittoor, Navya Shilpa Josyula, Mariah Meyer, Shreyash Gupta, Xihao Li, Zilin Li, Matthew A Allison, Diane M Becker, Lawrence F Bielak, Joshua C Bis, Meher Preethi Boorgula, Donald W Bowden, Jai G Broome, Erin J Buth, Christopher S Carlson, Kyong-Mi Chang, Sameer Chavan, Yen-Feng Chiu, Lee-Ming Chuang, Matthew P Conomos, Dawn L Demeo, Mengmeng Du, Ravindranath Duggirala, Celeste Eng, Alison E Fohner, Barry I Freedman, Melanie E Garrett, Xiuqing Guo, Chris Haiman, Benjamin D Heavner, Bertha Hidalgo, James E Hixson, Yuk-Lam Ho, Brian D Hobbs, Donglei Hu, Qin Hui, Chii-Min Hwu, Rebecca D Jackson, Deepti Jain, Rita R Kalyani, Sharon L R Kardia, Tanika N Kelly, Ethan M Lange, Michael Lenoir, Changwei Li, Loic Le Marchand, Merry-Lynn N Mcdonald, Caitlin P Mchugh, Alanna C Morrison, Take Naseri, Jeffrey O'Connell, Christopher J O'Donnell, Nicholette D Palmer, James S Pankow, James A Perry, Ulrike Peters, Michael H Preuss, D C Rao, Elizabeth A Regan, Sefuiva M Reupena, Dan M Roden, Jose Rodriguez-Santana, Colleen M Sitlani, Jennifer A Smith, Hemant K Tiwari, Ramachandran S Vasan, Zeyuan Wang, Daniel E Weeks, Jennifer Wessel, Kerri L Wiggins, Lynne R Wilkens, Peter W F Wilson, Lisa R Yanek, Zachary T Yoneda, Wei Zhao, Sebastian Zöllner, Donna K Arnett, Allison E Ashley-Koch, Kathleen C Barnes, John Blangero, Eric Boerwinkle, Esteban G Burchard, April P Carson, Daniel I Chasman, Yii-Der Ida Chen, Joanne E Curran, Myriam Fornage, Victor R Gordeuk, Jiang He, Susan R Heckbert, Lifang Hou, Marguerite R Irvin, Charles Kooperberg, Ryan L Minster, Braxton D Mitchell, Mehdi Nouraie, Bruce M Psaty, Laura M Raffield, Alexander P Reiner, Stephen S Rich, Jerome I Rotter, M Benjamin Shoemaker, Nicholas L Smith, Kent D Taylor, Marilyn J Telen, Scott T Weiss, Yingze Zhang, Nancy Heard-Costa, Yan V Sun, Xihong Lin, L Adrienne Cupples, Leslie A Lange, Ching-Ti Liu, Ruth J F Loos, Kari E North, Anne E Justice

Faculty, Staff and Student Publications

Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals (P <  5 × 10

Natural Killer Cells’ Functional Impairment Drives The Immune Escape Of Pre-Malignant Clones In Early-Stage Myelodysplastic Syndromes, Juan Jose Rodriguez-Sevilla, Irene Ganan-Gomez, Bijender Kumar, Natthakan Thongon, Feiyang Ma, Kelly S Chien, Yi J Kim, Hui Yang, Sanam Loghavi, Roselyn Tan, Vera Adema, Zongrui Li, Tomoyuki Tanaka, Hidetaka Uryu, Rashmi Kanagal-Shamanna, Gheath Al-Atrash, Rafael Bejar, Pinaki Prosad Banerjee, Sophia Lynn Cha, Guillermo Montalban-Bravo, Max Dougherty, Maria Claudina Fernandez Laurita, Noelle Wheeler, Baosen Jia, Eirini P Papapetrou, Franco Izzo, Daniela E Dueñas, Salome Mcallen, Yiqian Gu, Gabriele Todisco, Francesca Ficara, Matteo Giovanni Della Porta, Abhinav Jain, Koichi Takahashi, Karen Clise-Dwyer, Stephanie Halene, Maria Teresa Sabrina Bertilaccio, Guillermo Garcia-Manero, May Daher, Simona Colla

Faculty, Staff and Student Publications

Dissecting the preneoplastic disease states' biological mechanisms that precede tumorigenesis can lead to interventions that can slow down disease progression and/or mitigate disease-related comorbidities. Myelodysplastic syndromes (MDS) cannot be cured by currently available pharmacological therapies, which fail to eradicate aberrant hematopoietic stem cells (HSCs), most of which are mutated by the time of diagnosis. Here, we sought to elucidate how MDS HSCs evade immune surveillance and expand in patients with clonal cytopenias of undetermined significance (CCUS), the pre-malignant stage of MDS. We used multi-omic single-cell approaches and functional in vitro studies to show that immune escape at disease initiation is …