Digital Commons Network^™

Development And Preliminary Validation Of Orca-Pd, An Online Rapid Cognitive Assessment For Parkinson Disease: Mixed Methods Study, Avigail Lithwick Algon, Sarah Brisman, Chi-Ying R Lin, William Saban

Faculty, Staff and Students Publications

Background: Traditional in-person neuropsychological tests for Parkinson disease (PD) lack accessibility, scalability, and PD specificity. Mobility impairments hinder access to in-person assessments, and long waiting times for expert evaluation limit scalability. Common tools for cognitive screening, such as the Montreal Cognitive Assessment, are generic and not specific to PD.

Objective: The goal of this study was to address these challenges by leveraging the internet. This study aimed to develop a sensitive tool to detect cognitive impairments in early- to mid-stage PD in an accessible and scalable manner.

Methods: We developed the Online Rapid Cognitive Assessment for Parkinson's Disease (ORCA-PD), a …

Safety And Synergy Of Finerenone And Empagliflozin In Lowering Blood Pressure, Rajiv Agarwal, Ricardo Correa-Rotter, Sankar D Navaneethan, Hiddo J L Heerspink, Matthew R Weir, Janet B Mcgill, Amy K Mottl, Masaomi Nangaku, Julio Rosenstock, Peter Rossing, Muthiah Vaduganathan, Charlie Scott, Li Li, Meike Brinker, Csaba P Kovesdy, Jennifer B Green, Johannes F E Mann

Faculty, Staff and Students Publications

Background: This secondary analysis of the CONFIDENCE (combination effect of fInerenone and empagliflozin in participants with chronic kidney disease and type 2 diabetes using a UACR endpoint) trial (REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05254002) assessed systolic blood pressure (SBP) changes with empagliflozin/finerenone combination therapy versus monotherapy in people with chronic kidney disease and type 2 diabetes across baseline SBP categories. We assessed SBP response predictors and whether early (day 30) SBP changes mediate urinary albumin-to-creatinine ratio reductions.

Methods: Participants (n=800) were stratified by baseline SBP (< 130 mm Hg; ≥130 mm Hg). Outcomes included SBP response (≥10 mm Hg reduction from baseline at day 180) and longitudinal SBP changes, analyzed by linear mixed-effects models and logistic regression. Causal mediation analysis, a secondary exploratory analysis, evaluated the effect of day 30 SBP change on day 180 urinary albumin-to-creatinine ratio reduction.

Results: At baseline, 532 (66%) participants had SBP ≥130 mm Hg; 268 (34%) …

Global Burden Of Drug-Resistant Tuberculosis In Children: A Systematic Analysis For The Global Burden Of Disease Study, Xuhui Liu, Peierdun Mijiti, Lu Xia, Sylvia M Lacourse, Wulan Talafuhan, Alexander W Kay, Yang Yang, Huarui Liu, Dan Ye, Leonardo Martinez, Shuihua Lu, Adong Shen, Anna M Mandalakas, Feng Li, Christoph Lange, Zhen Huang

Faculty, Staff and Students Publications

Background: Paediatric tuberculosis (TB), particularly drug-resistant TB (DR-TB), is associated with significant mortality. However, the global burden of childhood TB remains poorly understood.

Methods: We analysed incident cases, deaths, and age-standardised incidence and mortality rates among children (0-14 years) with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) and extensively drug-resistant tuberculosis (XDR-TB) using the Global Burden of Disease (GBD) 2021 database. Data were stratified by age, sex, region, country, and HIV/AIDS status. Annual and average annual percentage changes were assessed using joinpoint regression analysis. Secondary analyses compared adult and paediatric TB trends in the End TB era and evaluated the potential impact of the …

Transgenic Hookworm Secretes Anti-Tetrodotoxin Human Single Chain Antibody, Kumar Sachin Singh, Suman Bharti, Bruce A Rosa, Mahdiyeh Bigham, Samuel C Uzoechi, Young-Jun Choi, John C Martin, Danielle Kemper, Slavica Pavlovic Djuranovic, Darren A Pickering, Rachael Ryan, Bethany K Bracken, Maria Elena Bottazzi, Eric C Carnes, Wannaporn Ittiprasert, Matthew Moyle, Paul J Brindley, Alex Loukas, Sergej Djuranovic, Makedonka Mitreva

Faculty, Staff and Students Publications

Biologics, protein- and peptide-based drugs derived from living organisms or cell lines have emerged as effective therapies across a broad range of indications. However, parenteral administration and the need for frequent dosing increase costs and limit compliance, creating an urgent need for innovative platforms capable of continuously, safely, and efficiently delivering sustained biologics in situ within the host. Here, we describe a bioengineered hookworm platform to manufacture and deliver biologic therapeutics in vivo. As proof of concept, we engineer the Ancylostoma ceylanicum secretome by inserting a human single-chain variable fragment antibody (s16-HuScFv) into its genome. Transgene expression does not perturb …

Cytosine Base Editing Of Lpa In Transgenic Mice Averts Large Deletions, Marcel A Chuecos, So Hyun Park, Madhvi M Bhakta, Usosa Too-Chiobi, Daniel Betancourth, Mingming Cao, Marco De Giorgi, Christopher J Walkey, Anjana Tiwari, Biana Godin, Julia M Assini, Donna J Palmer, Philip Ng, Michael B Boffa, Marlys L Koschinsky, Gang Bao, William R Lagor

Faculty, Staff and Students Publications

Lipoprotein(a) (Lp(a)) is a genetically determined causal risk factor for cardiovascular disease, with approximately 20% of the population exhibiting elevated levels. While there are promising drugs in development, there are currently no approved therapies specifically designed to lower Lp(a) levels. For high-risk individuals with extreme levels of Lp(a), liver-directed genome editing could be an effective one-time solution. Genome editing approaches such as CRISPR and TALENs can reduce Lp(a) in LPA-transgenic mouse models, but they frequently induce large and potentially harmful genomic deletions. Here, we report the first application of TadA-derived cytosine base editing (CBE), delivered via helper-dependent adenovirus (HDAdV) and …

A Cross-Sectional Analysis Of The Vaginal Microenvironment In Rheumatoid Arthritis, Marlyd E Mejia, Savannah Bowman, Jessica Lee, Ali El-Halwagi, Keshia Ferguson, Maryjo Maliekel, Yixuan Zhou, Camille Serchejian, Clare M Robertson, Mallory B Ballard, Lee B Lu, Sobia Khan, Olubunmi O Oladunjoye, Shixia Huang, Sandeep K Agarwal, Kathryn A Patras

Faculty, Staff and Students Publications

The human microbiota is implicated in the development and progression of rheumatoid arthritis (RA). Given the increased RA burden in women and well-known correlations between the vaginal microbiota and local inflammation, we seek to understand the vaginal microenvironment in the context of RA pathology. Self-collected vaginal swabs and questionnaires on dietary, menstrual, and health information were obtained from 36 RA and 50 demographically-matched control women, 18–63 years of age. Medication regimen, along with disease activity and severity, was captured for the RA cohort. Vaginal swabs were subjected to long-read 16S rRNA gene sequencing, multiplex cytokine analyses, and quantification of rheumatoid …

Systems Genetic Dissection Of Brain Gene Expression Reveals Excitotoxic Mechanisms Of Alzheimer’S Disease, Pinghan Zhao, Omar El Fadel, Anh Le, Carl Grant Mangleburg, Justin Dhindsa, Timothy Wu, Jinghan Zhao, Meichen Huang, Bismark Amoh, Aditi Sai Marella, Yarong Li, Nicholas T Seyfried, Allan I Levey, Zhandong Liu, Ismael Al-Ramahi, Juan Botas, Joshua M Shulman

Faculty, Staff and Students Publications

Gene expression changes likely mediate the impact of Alzheimer's disease (AD) neuropathology on cognition, but there are challenges to resolve the proximal causal pathways from postmortem brain transcriptome profiles which lack temporal resolution and are further confounded by mixed pathologies. Here, we functionally dissect 30 AD-associated human brain gene co-expression modules using fruit fly (Drosophila melanogaster) models. Integrating longitudinal RNA-sequencing and behavioral phenotyping, we interrogated the consequences of amyloid beta (Aβ) plaques, tau neurofibrillary tangles, and aging, highlighting hundreds of conserved, differentially expressed genes. To pinpoint causal modules and drivers, we manipulated 344 prioritized targets in vivo, identifying 141 modifiers …

Steroid Receptor Coactivators In Immunity – From Function To Emerging Translational Opportunities, Yosef Gilad, David M Lonard

Faculty, Staff and Students Publications

Steroid Receptor Coactivators (SRCs) comprise a family of three paralogous proteins. As transcriptional coactivators SRCs are essential for enabling the full transcriptional output of nuclear receptors (NRs). They regulate the transcriptional activity of nearly all NRs as well as a wide range of non-NR transcription factors. The central role of SRCs in gene regulation is reflected in their broad impact on major physiological and pathological processes, such as development, reproduction, metabolism, immunity and cancer. Although the major impact of SRCs on human health and disease established them as attractive therapeutic targets, their effective pharmacological targeting remained a challenge for nearly …

Structural Determinants Of Ligand Response Specificity In The Mast Cell Activating Gpcr, Mrgprx2, Abiodun Adefola R Adeosun, Melina A Agosto, Olivier Lichtarge, Theodore G Wensel

Faculty, Staff and Students Publications

The mast cell-specific G-protein-coupled receptor (GPCR) MRGPRX2 (Mas-Related G Protein-coupled Receptor X2) has roles in itch and pain, and it mediates clinically relevant allergy-like responses to a diverse assortment of drugs. The varied responses of individuals to MRGPRX2 agonists, leading to drug hypersensitivity reactions in some cases, suggests the presence of consequential variants in the population. However, genetic associations with drug responses are poorly understood. We used heterologously-expressed MRGPRX2 to investigate the effect of 18 naturally occurring non-synonymous single nucleotide polymorphisms on activation by representative compounds from several classes, including neuropeptides, opioid agonists, antibiotics, neuromuscular blocking agents, and polycationic aromatic …

Transient Yap Activation Uncovers The Neurogenic Potential Of Proliferative Mammalian Müller Glia, English J Laserna, Irina V Saltykova, Benjamin M Hall, Xuefei Tong, Justin S Dhindsa, Borna Sarker, Ayrea E Hurley, Paul G Swinton, William R Lagor, Nicholas M Tran, James F Martin, Ross A Poché

Faculty, Staff and Students Publications

The Hippo pathway effector YAP promotes spontaneous proliferation of Müller glia (MG), suggesting that bypassing Hippo signaling and activating YAP could enhance retinal regeneration. However, whether proliferative adult MGs retain meaningful neurogenic competence remains unclear. Here, using viral delivery of a Hippo-resistant YAP variant to wild-type adult MGs, we achieved transient YAP activation in adult MGs, inducing proliferation followed by cell-cycle withdrawal and differentiation. Intersectional genetic lineage tracing and EdU labeling, combined with transcriptomic analyses, revealed that YAP-activated MGs predominantly regenerate MGs, whereas only a subset gives rise to bipolar cell-like neurons. These results indicate that proliferative MGs acquire a …

Spatial Transcriptomics Reveals Coordinated Endothelial And Epithelial Activator Protein-1 Activation In Chronic Lung Allograft Dysfunction, Yasufumi Goda, Tatsuhiko Naito, Mudassir M Banday, Andrew S Potter, Igor Odintsov, Kapil Patel, Nicole Davis, Stefi Lee, Amit Gaggar, Ivan Rosas, Gabriel Loor, Don Hayes, Nirmal S Sharma

Faculty, Staff and Students Publications

Chronic lung allograft dysfunction (CLAD) limits long-term lung graft survival, yet its specific gene expression profiles remain unclear. We performed comprehensive spatial transcriptomic analyses of human lungs from CLAD patients, non-CLAD transplant recipients, and non-transplanted controls. In CLAD, AP-1 target genes, including JUNB and FOS, were significantly upregulated in both the epithelium and endothelium, whereas anti-fibrotic genes such as A2M and surfactant proteins (SFTPA1,2) were upregulated in non-CLAD. The lymphocyte population in CLAD was predominantly composed of T cells, with elevated JAK3-IL7R signaling. TNF and IL-17 signaling pathways were commonly activated in both the epithelium and endothelium, with JUNB and …

Corneal Innervation Research At A Crossroads: A Tool-Driven Roadmap For The Future, Anna Matynia, Ian D Meng, Brian M Davis, Stephen C Pflugfelder, Anat Galor, Victor L Perez, Elizabeth R Felix, Pedram Hamrah, Pantelimon Rompolas, Raul E Ruiz-Lozano, Shamsuddin A Bhuiyan, Kaveh Moghbeli, Evangelia Semizoglou, William Renthal, Harinder Singh, Jishnu Das, Marcin Golczak, Mary Ann Stepp, Catherine W Morgans, Cintia S De Paiva, Carl Y Saab, Igor Spigelman, Rony R Sayegh, Tally M Largent-Milnes, Hao Wu, Wenqin Luo, Sreya Mitra, Heesuk Yoo, Sina Farsiu, Sejiro Littleton, Eden Jacob, Matthew T Mcpheeters, Maryse Lapierre-Landry, Jordan J Smith, Xi Wang, Roxana Florea, Made Airanthi K Widjaja-Adhi, Scott Holmes, Zane Zemborain, Kate E T Laise, Nicholas J Pondelis, Ki-Soo Jeong, Rui Chen, Michael W Jenkins, Vivian Lee, Eric A Moulton, Deborah S Jacobs, Sue A Aicher, Anthony J St Leger, Daniel R Saban

Faculty, Staff and Students Publications

Corneal innervation research has faced long-standing clinical challenges that only recent technological breakthroughs now make tractable. Advances in single-cell analysis, viral vectors, clinical imaging, and artificial intelligence provide integrated approaches for uncovering molecular mechanisms underlying functional outcomes and facilitating clinical applications. The National Eye Institute's U01-funded consortium on ocular surface innervation addresses major knowledge gaps in characterizing corneal-projecting neurons, understanding neuroimmune and epithelial interactions in the cornea, and translating animal model findings to human pathology. The unique properties of the cornea (transparent, avascular, and densely innervated) make it ideal for neurobiology research on peripheral and central sensory processing. Through a …

Systematic Identification Of Cell-Cell Interactions Associated With The Severity Of Patients With Alzheimer’S Disease, Zijian Zhang, Naail Chowdhury, Jing Dong, Lang Wu, Chao Cheng

Faculty, Staff and Students Publications

Background

Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disorder involving dysfunction across multiple brain regions. While accumulating evidence has implicated the roles of diverse cell types, including neurons, glia, and vascular cells in AD pathogenesis, it is still poorly understood how cell type interactions drive or respond to the disease progression and severity.

Objective

This study aimed to systematically characterize cell-type–specific alterations and intercellular communication changes associated with AD progression.

Methods

We leveraged the transcriptome profiling and a previously established statistical framework to present a comprehensive mapping of the cellular interaction landscape in the human brain of AD.

Results …

Curriculum Innovation: Neurocritical Care Eeg Rounds: A Model To Improve Neurology Resident Eeg Interpretation., Ellen Sylvie Sanchez Mas, Mitchell Lloyd Powell, Marco Malaga, Corey Elam Goldsmith, Rahul Damani, Lu Lin

Faculty, Staff and Students Publications

Background and purpose: Rural-urban disparities in neurological care have been well documented, but limited data exist regarding Guillain-Barré Syndrome (GBS). This study examines differences in patient demographics, hospital characteristics, and outcomes among GBS admissions to rural versus urban hospitals in the United States.

Methods: Using the 2021 National Inpatient Sample, we conducted a retrospective cohort study of adult hospitalizations with a principal diagnosis of GBS. Hospitals were classified as rural or urban based on U.S. census designations. Multivariate logistic and linear regression models were used to assess associations between hospital location and outcomes, adjusting for demographic, clinical, and hospital-level factors. …

Human Neuronal Firing Varies With The Frequency Of Local Field Potential Oscillations, Zahra Jourahmad, Raissa K Mathura, Layth S Mattar, Melissa C Franch, Danika L Paulo, Mohammed Hasen, Nicole R Provenza, Benjamin Y Hayden, Sameer A Sheth, Eleonora Bartoli, Andrew J Watrous

Faculty, Staff and Students Publications

Neural oscillations play a critical role in shaping neuronal firing patterns. While phase-locked neuronal firing ("phase tuning") has been extensively studied in animal models and human invasive recordings, much less is known about whether neurons show preferential firing at specific oscillatory frequencies, termed frequency tuning. Here, we employ human intracranial recordings across several brain regions including hippocampus, entorhinal cortex, anterior and posterior cingulate cortex, and orbitofrontal cortex to test the hypothesis that neurons exhibit frequency-specific firing. We analyzed 357 single units recorded simultaneously with local field potentials in 19 neurosurgical patients during awake resting. We estimated the instantaneous frequency of …

Barrett’S Esophagus-Associated Genetic Loci In African Americans: A Case-Control Study Using The All Of Us Research Program, Ashwin Rao, Jinyoung Byun, Aaron P Thrift, Hashem B El-Serag

Faculty, Staff and Students Publications

Background and aims: Barrett's esophagus is the only known precursor lesion to esophageal adenocarcinoma (EAC). Barrett's esophagus and EAC are less common in African Americans than in non-Hispanic Whites. Studies in European populations have identified Barrett's esophagus-associated risk loci; however, none have examined loci in African Americans cohorts. We conducted a case-control targeted replication study to investigate previously identified Barrett's esophagus risk loci in an African Americans cohort in the All of Us (AoU) Research Program.

Methods: We abstracted phenomic and genomic data from 108 African Americans with Barrett's esophagus and 778 African Americans controls in the AoU database. We …

Menopause May Partially Explain Age-Related Increased Risk Of Masld Fibrosis: A Causal Mediation Analysis, Itunu O Sokale, Yan Liu, Hashem B El-Serag, Fasiha Kanwal, Aaron P Thrift, Maya Balakrishnan

Faculty, Staff and Students Publications

No abstract provided.

Generation And Characterization Of Twist1 Acetyl-Mimic And Acetyl-Deficient Mouse Models, Mary Elmeniawi, Xiaobin Yu, Samuel Wen, Gunjan A Bhatia, Lan Liao, Jianming Xu, Walid D Fakhouri

Faculty, Staff and Students Publications

TWIST1 encodes a highly conserved basic helix–loop–helix transcription factor essential for embryonic development from Drosophila to humans. TWIST1 activity is regulated by post‐translational modifications, including phosphorylation during development and cancer metastasis. Recent cancer studies identified acetylation of lysines K73 and K76 as a novel regulatory modification that shifts TWIST1 from a repressive to an activating state during epithelial‐to‐mesenchymal transition (EMT). However, the developmental and in vivo functions of TWIST1 acetylation remain unknown. To investigate the physiological role, we generated the first acetyl‐deficient Twist1 K73,76R K73,76R and acetyl‐mimic Twist1 K73,76Q K73,76Q mouse models using CRISPR/Cas9‐mediated genome editing. Targeted sequencing confirmed substitutions, …

Functional Genomics Studies Of Psychiatric Disorders In Individuals Of Latin American Populations: A Scoping Review, Luz M Porras, Isabelle Rodríguez-Lausell, Gabriel Iglesias-Maldonado, Emily Val F Tuliao, Gabriela Martínez, Chelsey Leveque, Julian Tobon, Rachel Eloy, Sintia Belangero, Cynthia M Bulik, Camila M Loureiro, Carolina Muniz Carvalho, Vanessa Ota, Diego Luiz Rovaris, Eric A Storch, Eva Maria Trujillo-Chi Vacuan, Maria M Velasquez, Latin American Genomics Consortium, Marcos L Santoro, Humberto Nicolini, Elizabeth G Atkinson, Janitza L Montalvo-Ortiz, Paola Giusti-Rodríguez

Faculty, Staff and Students Publications

Over the past 15 years, genetic studies of psychiatric disorders have provided important insight into the contribution of both common variants of small effect, as well as rare exonic and copy number variants with large effect sizes. Genome-wide association studies (GWAS) allow us to understand the intricate polygenicity characteristic of many psychiatric disorders. However, a considerable proportion of single nucleotide polymorphisms (SNPs) implicated in these disorders localize to the non-coding regions of the genome. Unraveling the molecular mechanisms that underlie the etiology of psychiatric illnesses requires integration using functional genomics approaches. Functional genomics methods are critical for developing a mechanistic …

Author Correction: Biallelic Variants In The Noncoding Rna Gene Rnu4-2 Cause A Recessive Neurodevelopmental Syndrome With Distinct White Matter Changes, Rocio Rius, Alexander J M Blakes, Yuyang Chen, Joachim De Jonghe, François Lecoquierre, Ruebena Dawes, Benjamin Cogne, Hyung Chul Kim, Javeria R Alvi, Florence Amblard, Morad Ansari, Annabelle Arlt, Christina Austin-Tse, Sarah Baer, Meena Balasubramanian, Elsa V Balton, Giulia Barcia, Ana Beleza-Meireles, Jonathan A Bernstein, Jasmin Beygo, Pierre Blanc, Nuria C Bramswig, Frederik Braun, Daniel Buchzik, Daniel G Calame, Jamie Campbell, Charles Coutton, Chloe A Cunningham, Nitsuh Dargie, Christel Depienne, Katrina M Dipple, Anne Dieux, Abhijit Dixit, Lauren Dreyer, Haowei Du, Salima El Chehadeh, Michael Field, Lisa J Ewans, Vanessa Geiger, Richard A Gibbs, Ian Glass, Olivier Grunewald, Paul Gueguen, Tobias B Haack, Hamza Hadj Abdallah, Radu Harbuz, Ingo Helbig, Judit Horvath, Alexander Hustinx, Bertrand Isidor, Marie-Line Jacquemont, Fraser Jamie, Médéric Jeanne, Riley Kessler, Hannah Klinkhammer, G Christoph Korenke, Urania Kotzaeridou, Peter Krawitz, Steven Laurie, Richard J Leventer, Rebecca J Levy, James R Lupski, Pierre Marijon, Kaitlin E Mcginnis, Rodrigo Mendez, Olfa Messaoud, Caroline Nava, Mevyn Nizard, Anne O'Donnell-Luria, Melanie C O'Leary, Simone Olivieri, Amitav Parida, Davut Pehlivan, Anna Jenne Prentice, Jennifer E Posey, Chloe M Reuter, Véronique Satre, Caroline Schluth-Bolard, Thomas Smol, Tipu Sultan, John Taylor, Christel Thauvin-Robinet, Julien Thevenon, Eloise Uebergang, Sandra Ueberberg, Catherine Vincent-Delorme, Evangeline Wassmer, Emma Westwood, Matthew T Wheeler, Elif Yilmaz Gulec, Adeline Vanderver, Arastoo Vossough, Stephan J Sanders, Siddharth Banka, Gregory M Findlay, Daniel G Macarthur, Cas Simons, Nicola Whiffin

Faculty, Staff and Students Publications

No abstract provided.

Whole Genome Sequencing Analysis Of Over 3500 Individuals Dementia-Free Over 85 Years Old, Gina M Peloso, Dongyu Wang, Sabrina M Abbruzzese, Joshua C Bis, Seung Hoan Choi, Alexa Beiser, Jan Bressler, Josée Dupuis, Alison E Fohner, Mohsen Ghanbari, Richard A Gibbs, Nancy Heard-Costa, M Arfan Ikram, Paul Lacaze, Quentin Le Grand, Oscar L Lopez, Thomas H Mosley, Moeen Riaz, Aïcha Soumaré, Amber Yaqub, Eric Boerwinkle, Bruce M Psaty, Myriam Fornage, Sudha Seshadri, Anita L Destefano

Faculty, Staff and Students Publications

BACKGROUND:

Identifying genetic variants conferring resilience to Alzheimer’s disease and related dementia (ADRD) may hold promise for developing therapeutics.

OBJECTIVE:

To determine genetic associations with being dementia-free at age 85 (DF85).

METHODS:

We examined genetic associations, using whole genome sequencing data, with DF85 in three Trans-Omics for Precision Medicine cohorts and the Alzheimer’s Disease Sequencing Project Phenotype Harmonization Consortium. We tested common variants individually and aggregation of rare (MAF≤1%) coding and non-coding variants in DF85 participants (n=3,657) against individuals who were not DF85 (n=20,010). We verified associations using a stricter control set who developed dementia before age 85 (n=5,552).

RESULTS: …

Disease-Specific Growth Charts Capture Characteristic Growth Patterns In Children With Pmm2 – Cdg, Kyriakie Sarafoglou, Christina Lam, Andrew C Edmondson, Andrea Miller, Rodrigo T Starosta, Aziza Zeighami, Seishu Horikoshi, Hayden Vreugdenhil, Fernando Scaglia, Tamas Kozicz, Queenie K G Tan, Bradley S Miller, Iván Martínez-Duncker, Gerard T Berry, Peter Mcwilliams, Eva Morava, Yaw Addo

Faculty, Staff and Students Publications

Background: Growth faltering is prevalent in 96% of children with Phosphomannomutase-2 congenital disorder of glycosylation (PMM2-CDG). Published long-term growth data is extremely limited. Growth and weight patterns of PMM2-CDG children differ from the general population limiting the utility of existing normative growth charts to track development trajectory in comparison to peers with PMM2-CDG.

Objective: Create PMM2-CDG disease-specific height-, weight-, and BMI-for-age reference growth charts (0-20 years).

Methods: De-identified growth data was provided by Frontiers in Congenital Disorders of Glycosylation Consortium, CDG Care, Minnesota Partnership for Biotechnology and Medical Genomics, and Glycomine, Inc. Semi-parametric modeling techniques were used to develop PMM2-CDG-specific …

Plasticity And Language In The Anaesthetized Human Hippocampus, Kalman A Katlowitz, Eric R Cole, Elizabeth A Mickiewicz, Shraddha Shah, Melissa Franch, Joshua A Adkinson, James L Belanger, Raissa K Mathura, Domokos Meszéna, Matthew Mcginley, William Muñoz, Garrett P Banks, Sydney S Cash, Chih-Wei Hsu, Angelique C Paulk, Nicole R Provenza, Andrew J Watrous, Ziv Williams, Alica M Goldman, Vaishnav Krishnan, Atul Maheshwari, Sarah R Heilbronner, Robert Kim, Nuttida Rungratsameetaweemana, Benjamin Y Hayden, Sameer A Sheth

Faculty, Staff and Students Publications

Consciousness is a fundamental component of cognition1, but the degree to which higher-order pattern recognition relies on it remains disputed2,3. Here we demonstrate the persistence of oddball discrimination, semantic processing and online prediction in individuals under general-anaesthesia-induced loss of consciousness4,5. Using high-density Neuropixels microelectrodes6 to record both single-unit and local-field-potential neural activity in the human hippocampus while playing a series of tones to anaesthetized patients, we found that hippocampal neurons and local oscillations retained some detection of oddball tones. This effect size grew over the course of the experiment …

Ilae-Yes Global Webinar Series: Integrating Clinical And Basic Science In Epilepsy Research, Cecilie G Nome, Parthvi Ravat, Fabrice Bartolomei, Marco De Curtis, Rossella Di Sapia, Marian Galovic, Maria Gogou, Lukas Imbach, Julia Jacobs, Katja Kobow, Alice D Lam, Christos Panagiotis Lisgaras, Elisa Micalizzi, Eleni Nikalexi, Jeffrey L Noebels, Jeanne T Paz, Avtar Singh Roopra, Sally Shaaban, Laurent Sheybani, Shobi Sivathamboo, Ana Suller Marti, Adam Williamson, Naoto Kuroda

Faculty, Staff and Students Publications

Bridging clinical and basic research is increasingly recognized as a priority in the epilepsy field, yet opportunities for integration remain limited by the time, space, and financial constraints of scientific meetings. To address this gap, the Research Task Force of the Young Epilepsy Section of the International League Against Epilepsy (ILAE-YES) organized a free global webinar series designed to promote translational dialogue and provide accessible research education for early-career clinicians, researchers, and physician-scientists. Based on a preliminary ILAE-YES community survey, eight topics of high interest were selected: (1) epigenetics, (2) EEG biomarkers, (3) ictogenesis, (4) thalamo-cortical network, (5) sudden unexpected …

Hematologic Markers And Machine Learning In Predicting Placenta Accreta: A Case-Control Study, Michael D Jochum, Kelly D Albrecht, Yamely Mendez Martinez, Victoria Zhang, Sanmay Sarada, Brian Burnett, Christina C Reed, Karin A Fox, Amir A Shamshirsaz, Michael A Belfort, Jessian L Munoz, Hennie A Lombaard

Faculty, Staff and Students Publications

Objective: This study aims to enhance antenatal detection of placenta accreta spectrum (PAS) and predict severe hemorrhage at delivery using machine learning by evaluating the association between antenatal hematologic index trends across trimesters, imaging markers, and patient history.

Methods: We retrospectively analyzed 2017-2023 data from a PAS referral center, including demographics, laboratory results, ultrasounds, and outcomes. Patients with confirmed PAS (cases) were compared to those with antenatal risk but no histopathologic evidence of PAS (controls). Statistical analyses and machine learning models were developed to predict PAS. We also used machine learning to predict severe hemorrhage (>1500 mL) in the …

Matching-Adjusted Indirect Comparison Of Acoltremon Ophthalmic Solution 0.003% And Cyclosporine 0.05% Ophthalmic Emulsion For Increased Tear Production In Patients With Dry Eye Disease, Stephen Pflugfelder, Tony Okoro, Margaret Ainslie-Garcia, Anja Haltner, Emily K Prentiss, Elizabeth M Salvo-Halloran, Nikethana Srikanth, Michelle Senchyna, Esen K Akpek

Faculty, Staff and Students Publications

No abstract provided.

Plasma Biomarkers Of Brain Injury In Critically Ill Children Receiving Extracorporeal Membrane Oxygenation, Matthew L Friedman, Michael J Bell, Bonnie A Brooks, Adam S Himebauch, Asavari Kamerkar, Kerri Larovere, Laura L Loftis, Jose A Pineda, Ahmed Said, Hitesh S Sandhu, Martin Stengelin, Catherine Demos, Mark S Wainwright, Alina N West, Allan Barnes, Allen D Everett, Ryan J Felling, Sue J Hong, Jennifer L Roem, Cynthia F Salorio, Derek K Ng, Melania M Bembea

Faculty, Staff and Students Publications

Importance: Timely identification of acute brain injury (ABI) in children receiving extracorporeal membrane oxygenation (ECMO) support is critical for early neuroprotective interventions.

Objectives: To determine if elevations in plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and tau levels in children receiving ECMO precede new ABI confirmed by neuroimaging, and if they are associated with mortality and functional outcomes.

Design, setting, and participants: This was a prospective observational cohort study conducted from 2019 to 2023, with 18-month follow-up completed in 2025. Children aged 2 days to younger than 18 years at ECMO cannulation were recruited from 11 US …

Anterior Cutaneous Nerve Entrapment Syndrome From Glucagon-Like Peptide-1 Receptor Agonist Injection, Neha Singh, Elisa Chaparro, Jordan Michael Shapiro, Emanuel Narcis Husu

Faculty, Staff and Students Publications

Anterior cutaneous nerve entrapment syndrome (ACNES) is an underdiagnosed cause of abdominal pain. We report the first documented ACNES case following subcutaneous administration of glucagon-like peptide-1 receptor agonist. A 44-year-old man developed focal, neuropathic abdominal pain coinciding with initiation of tirzepatide injections. Clinical examination confirmed ACNES diagnosis, and pain improved after relocating injections away from the abdomen and initiating multimodal pharmacotherapy. This case emphasizes the need to consider ACNES in patients endorsing focal abdominal pain with concurrent use of glucagon-like peptide-1 therapy and highlights injection site modification as a simple, effective management strategy while exercising self-restraint with respect to workup.

A Trans-Omics Gene-Smoking Interaction Study Of Lung Cancer Based On Consortium Data, Ning Xie, Xiaowen Xu, Yanru Wang, Aoxuan Wang, Xiang Wang, Xuan Wang, Mengsheng Zhao, Jiacheng Zhou, Yongyue Wei, Manel Esteller, Zhibin Hu, Hongbing Shen, Rayjean J Hung, Christopher I Amos, Yi Li, David C Christiani, Feng Chen, Yang Zhao, Ruyang Zhang

Faculty, Staff and Students Publications

Rationale: Genetically predicted molecular traits provide a cost-effective approach for identifying biomarkers and uncovering underlying biological mechanisms. We extended this framework to investigate gene-smoking interactions in lung cancer susceptibility.

Objectives: To identify trans-omics gene-smoking interactions affecting lung cancer risk and to assess how biomarkers modify effect of smoking.

Methods: We conducted the first trans-omics gene-smoking interaction study of lung cancer by integrating consortium-scale individual genotype data (27 737 cases vs 449 910 noncases) from the International Lung Cancer OncoArray Consortium (ILCCO-OncoArray), Transdisciplinary Research Into Cancer of the Lung (TRICL), Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), and the …

Malaria In Children At 9 Us Hospitals: 2016-2023, Sesh Alexander Sundararaman, Brianne Roper, Amy K F Davis, Karen L Hanze Villavicencio, Jonathan A Mayhew, Michelle L Wang, Nina L Tang, Vijaya L Soma, Ziyi Wang, Margaret E Feeney, Indi Trehan, Jill E Weatherhead, Chandy C John, Jeffrey S Gerber, Audrey R Odom John

Faculty, Staff and Students Publications

Objectives: This study set out to describe imported pediatric malaria in the United States over an 8-year period, including patient demographics, clinical outcomes, and risk factors for severe disease.

Methods: A retrospective descriptive study of pediatric patients treated for malaria at 9 hospitals in the United States from 2016 to 2023 was conducted to analyze patient demographics, clinical outcomes, and risk factors for severe malaria.

Results: A total of 171 children were treated across the 9 US hospitals included in this study from 2016 to 2023. Most patients had traveled to West Africa to visit friends and relatives. Fever was …