Digital Commons Network^™

Perspectives On The Future Of The Profession Of Microbiology, Todd L Kelson, Heidi B Kaplan, Michelle Dziejman, Shilpa Gadwal, Irene Hulede, Jennifer Bennett, Roger Greenwell, Shelley Payne, Kyle Maclea, Eric Miller, Diana L Vullo, Rebecca Sparks-Thissen, Astral Bertolio, Jorge Cervantes

Faculty, Staff and Student Publications

The Profession of Microbiology (POM) embodies the bulk of the American Society for Microbiology (ASM) members and represents the career preparation arm of the ASM for academia, industry, and clinical lab professions. The ASM Council on Microbial Sciences hosted a virtual retreat in 2025 to identify the future of the POM. The retreat presentations centered on workforce development, professional development, innovations in technology, and interdisciplinary collaborations. Various aspects were identified, such as the need to prepare for careers in industry, as an important goal of future training. It was also clear that scientists, in all walks of life, need professional …

Eif3d And Eif3e Mediate Selective Translational Control Of Hypoxia That Can Be Inhibited By Small Molecules, Stephen C Purdy, Kate Matlin, Christopher Alderman, Amber Baldwin, Natasha Shrivastava, Goksu Sarioglu, Somnath Dutta, Kristofor J Webb, Arthur Wolin, Dillon P Boulton, Annika Gustafson, Jyoti Kapali, John D Landua, Michael T Lewis, M Cecilia Caino, James C Costello, William Old, Xiang Wang, Rui Zhao, Heide L Ford, Neelanjan Mukherjee

Faculty, Staff and Students Publications

Exposure to hypoxia is linked to increased cellular plasticity and enhanced metastasis, effects that are primarily attributed to the transcriptional activation of large gene programs downstream of hypoxia-inducible factors (HIFs). However, translational effects in hypoxia, which likely precede transcriptional effects, have remained largely unexplored. Using ribosome profiling, we uncovered a selective translational response in acute hypoxia that is eukaryotic initiation factor (eIF)3d/eIF3e dependent and controls downstream hypoxic responses, including HIF1α accumulation and cellular invasion. We further demonstrated that eIF3e copy number and eIF3e and eIF3d expression signatures are associated with worsened outcomes for patients with breast cancer. Finally, we identified …

Current Controversies On Adequate Circulating Vitamin D Levels In Ckd, Adriana S Dusso, Daniela J Porta, Carlos Bernal-Mizrachi

2020-Current year OA Pubs

Management of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) has evolved dramatically over the past five decades, driven by discoveries that have fundamentally reshaped our understanding of the vitamin D endocrine system and its role in disease progression. This review synthesizes the key pathophysiological insights and clinical evidence underlying three critical paradigm shifts. The first shift moved beyond simple calcitriol replacement with the development of selective vitamin D receptor activators (VDRAs) designed to minimize hypercalcemia while maximizing PTH suppression. Crucially, these analogs revealed unexpected survival benefits, suggesting protective VDR actions extending beyond mineral metabolism. The second shift recognized the …

Emotion Regulation Differences Between Gender And Sexuality Groups: A Systematic Review And Meta-Analysis, Jake Camp, Emma Blundell, Patrick Smith, Katharine Rimes

School of Psychology

Gender and sexual minority (GSM) people are at increased risk of mental health difficulties compared to their cisgender-heterosexual peers. This is likely because of exposure to minority stressors. Emotion regulation difficulties have been proposed as an important mechanism for mental health disparities in GSM populations. This systematic review and meta-analysis examined whether GSM groups differ from cisgender and heterosexual groups in global and specific aspects of emotion regulation (e.g., emotion awareness, strategies, impulse control, cognitive appraisal, and emotion suppression), and whether emotion dysregulation mediated the relationship between GSM identity and mental health outcomes. We identified 40 eligible studies, of which …

Transdiagnostic Links Of Reward Processing In Obsessive-Compulsive Disorder And Depression, Kevin M Wagner, Matti Cervin, Jessica S C Cheng, Jasmine Arriaga, Vanessa Zavala Cruz, Dayan Berrones, Josselyn S Muñoz, Renee M Frederick, Jacey L Anderberg, Belinda E Núñez Bracho, Victor R Adorno, Leonardo F Fontenelle, Andrew D Wiese, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Brazilian Obsessive-Compulsive Spectrum Disorder Working Group (Gttoc), James J Crowley, Eric A Storch

Faculty, Staff and Students Publications

Objectives: Transdiagnostic models aim to uncover shared mechanisms across mental disorders. Reward responsiveness (the ability to experience pleasure from rewarding stimuli) is a plausible, yet underexplored, transdiagnostic mechanism linking obsessive-compulsive disorder (OCD) and depression. This study used network analysis to (1) examine how key reward responsiveness domains are interlinked in individuals with OCD and (2) explore how each domain is uniquely associated with OCD and depression.

Methods: A total of 1345 individuals with a history of OCD symptoms (ages 18-88, 71 % women) from Latino communities in the United States (including Puerto Rico) and nine Latin American countries completed validated …

Conservation Of Cis-Regulatory Codes Over Half A Billion Years Of Evolution, Yohey Ogawa, Yu Liu, Connie A Myers, Ala Morshedian, Gordon L Fain, Alapakkam P Sampath, Joseph C Corbo

2020-Current year OA Pubs

Identifying homologous cell types across species is essential for understanding cell type evolution. The retina is ideal for comparative analysis because its six major cell classes have persisted since the origin of vertebrates more than half a billion years ago. Here, we show that the retina's conserved cellular architecture is mirrored by deep conservation of the cis-regulatory codes that govern gene expression. Through single-cell chromatin accessibility analysis of lamprey, fish, bird, and mammalian retinas, we demonstrate cross-species conservation of cis-regulatory codes in all retinal cell classes despite extensive turnover of cis-regulatory regions. Conservation manifests as clustering of high-affinity transcription factor …

Stakeholder Criteria For Trust In Artificial Intelligence-Based Computer Perception Tools In Health Care: Qualitative Interview Study, Ansh Rai, Meghan E Hurley, John Herrington, Eric A Storch, Casey J Zampella, Julia Parrish-Morris, Anika Sonig, Gabriel Lázaro-Muñoz, Kristin Kostick-Quenet

Faculty, Staff and Students Publications

Background: Computer perception (CP) technologies hold significant promise for advancing precision mental health care systems, given their ability to leverage algorithmic analysis of continuous, passive sensing data from wearables and smartphones (eg, behavioral activity, geolocation, vocal features, and ambient environmental data) to infer clinically meaningful behavioral and physiological states. However, successful implementation critically depends on cultivating well-founded stakeholder trust.

Objective: This study aims to investigate, across adolescents, caregivers, clinicians, and developers, the contingencies under which CP technologies are deemed trustworthy in health care.

Methods: We conducted 80 semistructured interviews with a purposive sample of adolescents (n=20) diagnosed with autism, Tourette …

Genetic Modifiers And Ascertainment Drive Variable Expressivity Of Complex Disorders, Matthew Jensen, Corrine Smolen, Anastasia Tyryshkina, Lucilla Pizzo, Jiawan Sun, Serena Noss, Deepro Banerjee, Matthew Oetjens, Hermela Shimelis, Cora M Taylor, Vijay Kumar Pounraja, Hyebin Song, Laura Rohan, Emily Huber, Laila El Khattabi, Ingrid Van De Laar, Rafik Tadros, Connie R Bezzina, Marjon Van Slegtenhorst, Janneke Kammeraad, Paolo Prontera, Jean-Hubert Caberg, Harry Fraser, Siddharth Banka, Anke Van Dijck, Charles Schwartz, Els Voorhoeve, Patrick Callier, Anne-Laure Mosca-Boidron, Nathalie Marle, Mathilde Lefebvre, Kate Pope, Penny Snell, Amber Boys, Paul J Lockhart, Myla Ashfaq, Elizabeth Mccready, Margaret Nowacyzk, Lucia Castiglia, Ornella Galesi, Emanuela Avola, Teresa Mattina, Marco Fichera, Maria Grazia Bruccheri, Giuseppa Maria Luana Mandarà, Francesca Mari, Flavia Privitera, Ilaria Longo, Aurora Curró, Alessandra Renieri, Boris Keren, Perrine Charles, Silvestre Cuinat, Mathilde Nizon, Olivier Pichon, Claire Bénéteau, Radka Stoeva, Dominique Martin-Coignard, Sophia Blesson, Cedric Le Caignec, Sandra Mercier, Marie Vincent, Christa L Martin, Katrin Mannik, Alexandre Reymond, Laurence Faivre, Erik Sistermans, R Frank Kooy, David J Amor, Corrado Romano, Joris Andrieux, Santhosh Girirajan

Faculty, Staff and Student Publications

Variable expressivity of disease-associated variants implies a role for secondary variants that modify clinical features. We assessed the effects of modifier variants on the clinical outcomes of 2,455 individuals with primary variants. Among 124 families with the 16p12.1 deletion, distinct rare and common variant classes conferred risks for specific developmental features, including short tandem repeats for neurological defects. Network analysis suggested distinct mechanisms involving 16p12.1 genes and secondary variants specific to each proband. Within disease and population cohorts of 976 individuals with the 16p12.1 deletion, we found opposing effects of secondary variants on clinical features across ascertainments. Additional analysis of …

Glycoside Hydrolase-Mediated Glucomannan Catabolism In Segatella Copri, A Target Of Microbiota-Directed Foods For Malnourished Children, Cyrus Zhou, Matthew C Hibberd, Evan M Lee, Suzanne Henrissat, Marie A Crane, Jiye Cheng, Michael J Barratt, Jeffrey I Gordon, Et Al.

2020-Current year OA Pubs

Evidence is emerging that perturbed postnatal gut microbiota development is causally related to childhood undernutrition. Clinical trials in undernourished Bangladeshi children found that a polysaccharide-rich, microbiota-directed complementary food (MDCF-2) designed to repair this perturbation produced superior ponderal and linear growth compared to a standard ready-to-use supplementary food. Subsequent analyses disclosed several candidate bioactive polysaccharides in the MDCF and their bacterial targets, notably strains of

Artem-Is For Erp: Agreed Reporting Template For Eeg Methodology-International Standard For Event-Related Potential Experiments, Giorgio Ganis

School of Psychology

The choices we make during the recording, preprocessing and analysis of event-related potentials (ERP) data can affect study outcomes. As such, it is critical that they are transparently reported to allow for reproducibility. Yet, systematic reviews of reporting practices in the field have shown that journal articles often do not meet this goal and that existing reporting guidelines have not resulted in a sufficient improvement in reporting transparency. An easier workflow for transparently documenting pipelines used in regular journal articles is needed. The ARTEM-IS (Agreed Reporting Template for EEG Methodology—International Standard) initiative is working towards addressing this issue by building …

Synergistic Potential Of Sipuleucel-T In Enhancing Immunotherapy For Metastatic Castration-Resistant Prostate Cancer, Kavita Rawat, Varnika Punia, Parker Mathews, Sara Mccoy, Wilbur Song, Muhammad A Saeed, Russell K Pachynski

2020-Current year OA Pubs

Clinical trials of immunotherapy in metastatic castration-resistant prostate cancer (mCRPC) have largely been unsuccessful despite promising preclinical studies and proven efficacy in other solid tumors. These disappointing clinical outcomes have been attributed to an immunosuppressive tumor microenvironment, a relative lack of infiltrating immune effector cells, and tumor-related and host-related factors, which collectively render prostate cancer a relatively immunologically "cold" tumor. Sipuleucel-T (Provenge), an autologous cellular immunotherapy, induces an immune response targeted against prostatic acid phosphatase. It received approval from the US Food and Drug Administration in 2010, marking the first immunotherapy to show an overall survival benefit in patients with …

Hsp90 Buffers Deleterious Genetic Variations In Brca1, Brant Gracia, Xing-Han Zhang, Patricia Montes, Tin Chanh Pham, Min Huang, Junjie Chen, Georgios Ioannis Karras

Faculty, Staff and Student Publications

Protein-folding chaperone heat shock protein 90 (HSP90) buffers genetic variation in diverse organisms, but the clinical significance of HSP90 buffering in human disease remains unclear. Here, we show that HSP90 buffers mutations in the BRCT domain of BRCA1. HSP90-buffered BRCA1 mutations result in protein variants that retain interactions with partner proteins and strongly rely on HSP90 for protein stability and function in cell survival. Moreover, HSP90-buffered BRCA1 variants confer poly (ADP-ribose) polymerase (PARP) inhibitor resistance in cancer cells. Low-level HSP90 inhibition overcomes this resistance, revealing a cryptic and mutant-specific HSP90-contingent synthetic lethality. Furthermore, by stabilizing metastable variants across the entirety …

Discovery Of A Small Molecule Tlr3 Agonist Adjuvant, Branden Lee, Danica Dong, Etsuro Nanishi, John Mark Awad, Kimia Abedi, Yoshine Saito, Francesco Borriello, Soumik Barman, Byron Brook, Aisling Kelly, Manisha Menon, Constance Marques-Mourlet, Maansi Gupta, Ida Lister, Chiwoo Oh, Kevin Lyskawa, Morgan Goetz, Kristina Walker, Wing Ki Cheng, Spencer Brightman, Pankaj Sharma, Timothy O'Meara, Katherine Chew, Daniel Vieira, Kevin Ryff, Cali Sweitzer, Sanya Thomas, Simon Van Haren, Matthew Pettengill, Hyuk-Soo Seo, Sirano Dhe-Paganon, Wei Zhang, Ofer Levy, David Dowling

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Pattern-recognition receptor (PRR) agonists are valuable agents across multiple medical applications, from vaccinology to immune-oncology. However, well-defined and potent small molecule agonists for many PRRs still await discovery and development. Screening of chemical libraries of ~200,000 small molecules for maturation of human monocytic cells by quantifying NF-κB activation and cell adherence was completed. From this screen, we selected a thiazole benzamide derivative, PVP-057, for its robust immunomodulatory properties, low toxicity profile, and concentration-dependent activity. In vitro investigation of pathway and receptor activation reveals that PVP-057 is a Toll-like receptor 3 (TLR3) agonist. As a single-component adjuvant, administered intramuscularly or intradermally …

Unconventional Binding Of Calmodulin To Chk2 Kinase Inhibits Catalytic Activity, Christopher R Horne, Tingting Wang, Samuel N Young, Toby A Dite, Hunter G Nyvall, Sushant Suresh, Katherine A Davies, Abner Gonzalez Castro, Vineet Vaibhav, Lucy J Mather, Laura F Dagley, Matthew J Belousoff, Gerard Manning, Anthony R Means, John E Burke, Janni Petersen, John W Scott, James M Murphy

Faculty, Staff and Students Publications

Calmodulin (CaM) serves an essential role in eukaryotic cells as a Ca2+ sensor. Ca2+ binding leads to conformation changes in CaM that enable engagement of a repertoire of enzymes and the regulation of their catalytic activities. Classically, Ca2+-CaM binds to an inhibitory pseudosubstrate sequence C-terminal to the kinase domain in members of the Ca2+-CaM-dependent protein kinase (CAMK) family and relieves inhibition to promote catalytic activity. Here, we report an unexpected mechanism by which CaM can bind CHK2 kinase to inhibit its kinase activity. Using biochemical, biophysical and structural mass spectrometry, we identify a direct interaction of Ca2+-CaM with the CHK2 …

Integrated Phenotypic And Proteomic Screening Identifies Top-Tier Alzheimer's Disease Therapeutic Targets., Gregory Cary, Qianjin Li, Jesse C Wiley, Carolyn Paisie, Yuhong Du, Elizabeth L Zoeller, Duc Duong, Haian Fu, Nicholas T Seyfried, Allan I Levey, Ranjita Betarbet, Gregory W. Carter, The Emory-Sage-Sgc-Jax Treat-Ad Center

Faculty Research 2025

INTRODUCTION: Alzheimer's disease (AD) is a complex neurodegenerative disorder. Hundreds of therapeutic targets have been nominated through genetic and multi-omic studies, but effective prioritization remains a major bottleneck.

METHODS: We applied an integrative screening framework to assess 29 candidate targets from risk-enriched biological domains. Using disease-relevant murine BV2 microglial cell lines with stable Psen2 knockdown, we performed small interfering RNA-mediated perturbations followed by cellular phenotypic assays and quantitative proteomics.

RESULTS: Twenty-five candidate targets significantly altered at least one phenotype, with stronger effects in Psen2 knockdown cells. Integrated proteomic analyses identified several perturbations that reversed AD-associated molecular patterns. Five targets-Ap2a2, Pdhb, …

Left And Right Ventricular Strain Mechanics In Fetal Tachyarrhythmia., Rukmini Komarlu, Janelle R. Noel-Macdonnell Phd, Neha Chellu, Geetha Haligheri

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: Assessment of myocardial function in fetuses with supraventricular tachyarrhythmia is challenging. Speckle-tracking echocardiography (STE) is a newer sensitive method to assess ventricular systolic function. We sought to assess left (LV) and right (RV) ventricular myocardial strain mechanics in fetuses with tachyarrhythmia and hypothesized that strain mechanics are impaired in this patient population even after conversion to sinus rhythm.

METHODS: This was a single-center retrospective review. LV and RV strain parameters were assessed using STE in tachyarrhythmia and after conversion to sinus rhythm and, compared to gestational age (GA), matched control fetuses in sinus rhythm.

RESULTS: Eighteen fetuses with tachyarrhythmia …

A Class Of Benzofuranoindoline-Bearing Heptacyclic Fungal Ripps With Anticancer Activities, Qiuyue Nie, Fanglong Zhao, Xuerong Yu, Mithun C Madhusudhanan, Caleb Chang, Siting Li, Sandipan Roy Chowdhury, Bryce Kille, Andy Xu, Rory Sharkey, Chunxiao Sun, Hongzhi Zeng, Shuai Liu, Dishu Zhou, Xin Yu, Kevin Yang, Sandra A C Figueiredo, Maria Zotova, Zichen Hu, Alan Y Du, Dongyin Guan, Rui Tang, Todd Treangen, Jin Wang, Pedro N Leão, Yang Gao, Junjie Chen, Peng Liu, Hans Renata, Xue Gao

Children’s Nutrition Research Center Staff Publications

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a promising source of new pharmaceuticals, yet the therapeutic potential of fungal RiPPs remains largely underexplored. Here, we report asperigimycins as a distinct class of fungal RiPPs, featuring a unique heptacyclic scaffold consisting of a benzofuranoindoline core and three additional macrocycles, primarily assembled by six distinct fungi-specific DUF3328 oxidases. Inspired by the enhancement of anticancer activity through the N-terminal pyroglutamate in naturally occurring asperigimycins C and D, we chemically modify the inactive asperigimycin B with a series of lipid substitutions at its N-terminus. A derivative with a C-11 linear fatty …

Understanding Dental Hygienists’ Knowledge, Attitudes, And Practices Regarding Hpv Vaccination, Paula M Cuccaro, Jihye Choi, Kawtar Zouaidi, Efrat K Gabay, Michael Mackert, Josefine Ortiz Wolfe

Faculty, Staff and Student Publications

The American Dental Association and American Academy of Pediatric Dentistry encourage oral health professionals to strongly recommend human papillomavirus (HPV) vaccination to prevent HPV-associated oropharyngeal cancer. This study examined oral health professionals' knowledge, attitudes, and practices regarding HPV vaccination. We used purposive sampling to recruit participants through state and national oral health societies and social media platforms. Flyers outlining eligibility criteria were distributed, and eligible participants completed an online survey. Primary measures included participants' HPV-related knowledge, attitudes, and practices, and willingness to receive HPV-related training and recommend HPV vaccination to patients, including parents of adolescents. Only responses from dental hygienists …

The Use Of Alcohol-Free And Low-Alcohol Drinks In Pregnancy In The Uk, Kate Maslin, Heather Hopper, Jill Shawe

School of Nursing and Midwifery

Alcohol-free drinks [beers, ciders, wines, and spirits containing <0.05% alcohol by volume (ABV)], and lowalcohol drinks (between 0.05% and 1.2% ABV) are increasingly available and may be used as a harm reduction measure. However, it is not known what pregnant women think and feel about these drinks and how regularly they are consumed before and during pregnancy. A cross-sectional online survey was developed and piloted. Women ≥18 years in the UK who were pregnant, or recently pregnant, were recruited via targeted social media advertising. Of the 2092 respondents, 47.8% (n ¼ 1001) were currently pregnant; 55.7% (n ¼ 1167) were between 25 and 34 years, 90.0% were White (n ¼ 1881); 6.1% (n ¼ 128) were drinking alcohol at “increasing risk” levels (>14 units/week) before pregnancy. During pregnancy, 13.5% (n ¼ 282) consumed alcohol, which was more common in the increasing risk category (P < .01). Alcohol-free or low-alcohol drinks were consumed by 71.3% (n ¼ 1491) of respondents during pregnancy; 91.4% of the increasing risk category versus 69.9% of the lower risk category (P < .01). The most common reasons for consuming alcohol-free or low-alcohol drinks were “to choose a safer alternative” (71.9%, n ¼ 1073) and “to feel included in social events involving alcohol” (68.8%, n ¼ 1026). More than half of respondents (56.7%) thought there was insufficient information available about consuming alcohol-free and low-alcohol drinks during pregnancy, with internet searching the primary source of information. Although alcohol-free and low-alcohol drinks are commonly consumed during pregnancy, there are some safety concerns. Their role as a harm reduction measure in those who are drinking alcohol at increasing risk levels prepregnancy needs further investigation.

Does Reducing Videofluoroscopy Frame Rate Affect Dige/St Grades In Modified Barium Swallow Studies?, Shitong Mao, Carla L Warneke, Sheila N Buoy, Ariana J Sahli, Brinda Rao Korivi, Carly E A Barbon, Kristy K Brock, Katherine A Hutcheson

Faculty, Staff and Student Publications

Understanding the effects of reduced frame rates on the reliability of Modified Barium Swallow (MBS) ratings for swallowing safety and efficiency is essential for clinical practice. While previous research has examined frame rate (simulated pulse rates) implications concerning penetration, aspiration, and residue ratings, the impact on summary grading systems like the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) remains unclear. This study analyzed a total of 315 full MBS videos collected from 278 patients, and 76.25% of patients were diagnosed with head and neck cancer (mean age 62.51 years, SD 8.53; 12.23% female). We performed pairwise comparisons of DIGEST grades …

Periostin Promotes Sarcoma Growth By Promoting Tumor-Associated Macrophage Migration And Differentiation, Jin-Fen Xiao, Kristin Ishaya, Emily Y Ko, Annaliese Fowler, Marina T Broz, Jlenia Guarnerio

Faculty, Staff and Student Publications

Soft-tissue sarcomas (STS) are characterized by abundant extracellular matrix (ECM) deposition, yet the functional contribution of specific ECM components remains poorly understood. In this study, we identify periostin (POSTN), a matricellular protein, as a regulator of sarcoma progression and the tumor immune microenvironment. Analysis of human sarcoma datasets revealed that high POSTN expression correlates with poor prognosis and elevated expression of ECM-related and myeloid cell–associated genes. In murine genetic models of sarcoma, tumors expressing high levels of Postn displayed enhanced expression of ECM genes and monocyte-recruiting cytokines. Functional silencing of Postnin vivo reduced tumor growth without altering tumor cell …

Bayesian Integrated Learning Of Longitudinal Dose-Response Relationships Via Decentralized Clinical Trials, Jingyi Zhang, Tuo Wang, Yongming Qu, Fangrong Yan, Suyu Liu, Ruitao Lin

Faculty, Staff and Student Publications

Decentralized clinical trials (DCTs) extend trial activities beyond traditional sites, enhancing access, convenience, efficiency, and result generalizability. They are particularly promising for chronic conditions like diabetes and obesity, which require longer study durations to evaluate drug effects. However, decentralized data collection raises concerns about increased variability and potential biases. This paper presents a novel Bayesian integrated learning procedure to analyze dose-response relationships using longitudinal data from a phase II DCT that combines centralized and decentralized data collection. We generalize a parametric exponential decay model to handle mixed data sources and apply Bayesian spike-and-slab priors to address biases and uncertainties from …

Artificial Intelligence Biomarker Detects High-Risk Childhood Asthma Subgroup For Respiratory Infections And Exacerbations, Young J Juhn, Chung-Il Wi, Euijung Ryu, Katherine S King, Sunghwan Sohn, Elham Sagheb, Greg Jenkins, David Watson, Miguel A Park, Sergio E Chiarella, Hirohito Kita, Mir Ali, W Charles Huskins, Elizabeth H Ristagno, Imad Absah, Charles Grose, Kathy Ihrke, Elizabeth A Krusemark, Thanai Pongdee, Björn Nordlund, Carla M Davis, Robert J Pignolo, Hongfang Liu

Faculty, Staff and Student Publications

Background: Asthma is associated with an increased risk of acute respiratory infections (ARI). Little is known about whether natural language processing (NLP)-powered digital biomarkers can identify a high-risk asthma subgroup for ARI during early childhood.

Objective: We assessed whether a digital biomarker could identify a high-risk subgroup of childhood asthma for ARI.

Methods: We applied validated NLP algorithms for Predetermined Asthma Criteria (NLP-PAC) and Asthma Predictive Index (NLP-API) to electronic health records of the 1997-2016 Mayo Clinic Birth Cohort. We categorized the cohort into 4 subgroups: both criteria positive (NLP-PAC+/NLP-API+), PAC positive only (NLP-PAC+), API positive only (NLP-API+), and both …

The Longitudinal Impact Of Radiotherapy On Osseointegrated Hearing Aid Outcomes And Complications, Benjamin D Lovin, Mike Hernandez, Paul W Gidley, Karine Al Feghali, Jack Phan, Catherine Wang, Congjun Wang, Dianna Roberts, Marc-Elie Nader

Faculty, Staff and Student Publications

Objective: To evaluate the impact of radiotherapy on osseointegrated hearing aids (OIHA) complications.

Methods: Retrospective review of percutaneous OIHA performed from 2006 to 2021 at an academic institution. Implant and abutment-related complications were evaluated and stratified by radiation parameters. Main outcome measures were abutment, implant, and major complications assessed using the modified Holgers and IPS grading scales.

Results: Total of 190 OIHA were included; 124 (65%) were placed in bones that previously or subsequently received radiation. Total of 84 (44%) OIHA experienced at least one complication at mean 43.3 months. Radiation cohort had greater rates of having any complication (p …

Adherence To Breast Cancer Screening Guidelines Among Age-Eligible Us Women: Findings From Nhis 2021, Monalisa Chandra, Joël Fokom Domgue, Robert Yu, Sanjay Shete

Faculty, Staff and Student Publications

Background: Despite the proven benefits of early breast cancer detection in reducing mortality, adherence to breast cancer screening guidelines in the United States is suboptimal. In this study, we assessed the prevalence and factors associated with adherence to breast cancer screening guidelines.

Methods: Using nationally representative data from the National Health Interview Survey 2021, we included breast cancer screening-eligible women (aged 50-74). Descriptive statistics and population-weighted multivariable logistic regression were employed to examine breast cancer screening adherence per the United States Preventive Services Task Force guidelines, and its determinants in this population.

Results: Of the 6814 screening-eligible women included in …

Lymphodepletion, Tumor-Infiltrating Lymphocytes, And High Versus Low Dose Il-2 Followed By Pembrolizumab In Patients With Metastatic Melanoma, Merve Hasanov, Simin Kiany, Marie-Andrée Forget, Roland Bassett, Michael A Davies, Adi Diab, Jeffrey E Gershenwald, Isabella C Glitza, Jeffrey E Lee, Anthony Lucci, Jennifer L Mcquade, Sapna P Patel, Merrick I Ross, Hussein A Tawbi, Jennifer A Wargo, Michael K Wong, Chantale Bernatchez, Patrick Hwu, Cara Haymaker, Rodabe N Amaria

Faculty, Staff and Student Publications

This study evaluated the efficacy and safety of unengineered tumor-infiltrating lymphocytes (TILs) combined with pembrolizumab and either high (HD, Arm-1) or low (LD, Arm-2) doses of IL-2 in patients with metastatic melanoma (MM). Patients were lymphodepleted with cyclophosphamide and fludarabine, followed by TIL infusion and IL-2 (Arm-1: 720,000 IU/kg IV q 8 hrs up to 15 doses; Arm-2: 2 million IU SC for 14 days). Patients received pembrolizumab 200 mg IV starting 21 days post-TIL infusion, and every 3 weeks for up to 2 years. The primary endpoint was overall response rate (ORR) per RECIST 1.1. Blood samples were collected …

Sars-Cov-2 Rna-Binding Protein Suppresses Extracellular Mirna Release, Hyejin Mun, Chang Hoon Shin, Qingxuan Fei, Andrea Estefania Lopez Giraldo, Kyoung-Min Choi, Ji Won Lee, Kyungmin Kim, Kyung-Won Min, Leilei Shi, Mark T Bedford, Dong-Chan Kim, Yoo Lim Chun, Seonghyun Ryu, Dongin Kim, Jeong Ho Chang, Ryan T Westrope, Michelle Shay, Edward Nguyen, Junho K Hur, Abigail Agyenda, Nam Chul Kim, Sung-Ung Kang, Woonghee Lee, Je-Hyun Yoon

Faculty, Staff and Student Publications

SARS-CoV-2 is the betacoronavirus causing the COVID-19 pandemic. Although the SARS-CoV-2 genome and transcriptome were reported previously, the function of individual viral proteins is largely unknown. Utilizing biochemical and molecular biology methods, we identified that four SARS-CoV-2 RNA-binding proteins (RBPs) regulate the host RNA metabolism by direct interaction with mature miRNA let-7b revealed by Nuclear Magnetic Resonance spectroscopy (NMR). SARS-CoV-2 RBP Nsp9 primarily binds mature miRNA let-7b, a direct ligand of the Toll-like Receptor 7 (TLR7), one of the potential SARS-CoV-2 therapeutics. Nsp9 suppresses host gene expression possibly by promoting let-7b-mediated silencing of a cellular RNA polymerase, POLR2D. In addition, …

Real-World Disease Burden And Health Care Resource Utilization For Patients With Barth Syndrome, Lindsay Marjoram, Yonglin Huang, Mary Kay Koenig, Bruce H Cohen, Eric Anderson

Faculty, Staff and Student Publications

Background: Barth syndrome (BTHS) is an ultra-rare, X-linked genetic disorder for which there is limited economic data. Because compiling such data that target rare indications is difficult, we assessed real-world data to increase understanding of the cost of BTHS based on disease burden and health care resource utilization (HCRU).

Methods: A search of the published medical literature identified individual case studies and registry data used to assess the burden of disease and potential costs associated with BTHS, including the potential ability of developing treatments to positively impact those costs. In addition, a claims database analysis was conducted to assess HCRU …

Social Media Listening Study To Understand The Journey And Unmet Needs Of Patients Living With Post-Stroke Spasticity, Stefano Carda, Jörg Wissel, Damon Hoad, Gerard E Francisco, Monica Verduzco-Gutierrez, Daniela Gallardo, Matteo Vacchelli, Jorge Jacinto

Faculty, Staff and Student Publications

Purpose: Stroke survivors may develop spasticity (post-stroke spasticity [PSS]) that can challenge activity and participation. Recognising the needs and expectations of people with PSS is crucial for enhancing care. This study is the first to employ social media listening to explore the experiences, unmet needs, and quality of life (QoL) of people with PSS.

Materials and methods: A subset of 417 patient-centric PSS-related posts published on major social media platforms was identified for analysis from 31 600 retrieved.

Results: Posts mainly discussed patient journey (centred around treatment options and management techniques), the impact of PSS on QoL, and patient interactions …

Tubulin Regulates Stability And Localization Of Stmn2 By Binding Preferentially To Its Soluble Form, Xiang Deng, Gary A Bradshaw, Marian Kalocsay, Timothy Mitchison

Faculty, Staff and Student Publications

The small, tubulin-binding protein STMN2 is highly expressed in neurons and is implicated in amyotrophic lateral sclerosis. STMN2 degrades rapidly and accumulates at axotomy sites, suggesting fast turnover is crucial for its neuroprotective function. We show that STMN2 was primarily degraded by the ubiquitin-proteasome system. Its membrane-targeting N-terminal domain promoted fast turnover, whereas its tubulin-binding domain promoted stabilization. Proximity labeling and imaging showed that tubulin binding reduced STMN2 targeting to trans-Golgi network membranes. Pull-down assays showed that tubulin binds preferentially to soluble over membrane-bound STMN2. Our observations suggest that STMN2 interconverts between a soluble, tubulin-bound form and a membrane-bound, tubulin-free …