Digital Commons Network^™

Targeting Inequities: Addressing Lung Cancer Care Challenges In Africa Through Drug Access, Radiotherapy, And Surgical Innovations, Elvis Obomanu, Chidiebube Ugwu, Muluken Megiso, Tarfa Verinumbe, Colton Jones, Verna Vanderpuye, Nazik Hammad

Division of Internal Medicine Faculty Papers & Presentations

Lung cancer remains one of the leading causes of cancer-related mortality in Africa, with survival rates starkly lagging behind global benchmarks because of systemic inequities in prevention, diagnosis, and treatment access. Despite representing only 6% of global smokers, the continent faces a disproportionate burden driven by environmental and occupational carcinogens, aggressive tobacco marketing, and fragmented health care infrastructure. Key challenges include prohibitive delays in accessing targeted therapies like epidermal growth factor receptor inhibitors and immunotherapies, a dire shortage of radiotherapy infrastructure-0.12 megavoltage units per million people versus the International Atomic Energy Agency's recommended five megavoltage units per million, and a …

The Effect Of Hunger On The Likelihood Of Glucose Excursions In Adults With Overweight Or Obesity: Continuous Glucose Monitoring And Ecological Momentary Assessment Observational Study, Byunggul Lim, Phrashiah Githinji, Yue Liao, Jacob Szeszulski, Alexandra L Macmillan Uribe, Rebecca A Seguin-Fowler, Jane Anderson, Chad D Rethorst

Faculty, Staff and Students Publications

Background: Maintaining stable glucose levels is important for metabolic health. Glucose excursions (GEs), which are marked increases in glucose following food intake, have been associated with a higher risk for cardiovascular disease and metabolic dysfunction. Individuals with overweight or obesity who do not have diabetes may still show impaired glucose regulation, as reflected in increased glucose variability. Hunger, as a real-time physiological cue, may be associated with subsequent glucose changes and represents a potential target for just-in-time adaptive interventions.

Objective: This study aimed to investigate the temporal relationship between self-reported hunger and subsequent glucose dynamics, including the likelihood of GE …

Cure Sickle Cell Initiative Recommendations On Common Data Elements For Sickle Cell Disease Gene Therapy Trials, Sophie Lanzkron, Victoria H. Coleman-Cowger, Alexis A. Thompson, C. Patrick Carroll, Traci Clemons, Michael Debaun, Julie Kanter, Punam Malik, Deepa Manwani, Francis John Pierciey, Mark C. Walters, Sherita Alai

Cardeza Foundation for Hematologic Research

The Cure Sickle Cell Initiative (CureSCi), created by the National Heart, Lung, and Blood Institute, has developed data standards to increase interoperability and meta-analysis of studies specifically investigating gene therapy for sickle cell disease (SCD). The aims of the CureSCi Common Data Elements (CDE) initiative are to facilitate the development of safe, effective, and accessible gene therapies. Five working groups (WGs) comprising people living with SCD, stakeholders, clinicians, and researchers reviewed current definitions used for SCD clinical studies, including those from the American Society of Hematology, US Food and Drug Administration, PhenX catalog of consensus measures for phenotypes and exposures, …

Text Messaging Support For Patients Diagnosed With Impaired Glucose Tolerance During Pregnancy: Nonrandomized Pre-Post Implementation Study Assessing Impact On Postpartum Transitions Of Care, Natasha R. Kumar, Whitney Bender, Celeste Durnwald

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Patients with impaired glucose tolerance (IGT) identified during pregnancy who do not develop gestational diabetes mellitus (GDM) often do not receive additional interventions for their long-term metabolic risks.

OBJECTIVE: This nonrandomized pre-post implementation study reports the design process and initial program evaluation for Better Follow-up of Impaired Glucose Tolerance (BRIDGE), a 12-week text-based postpartum support program promoting hemoglobin A1c (HbA1c) completion and primary care provider (PCP) visit scheduling for patients diagnosed with IGT during pregnancy, assessing improvement in desired postpartum transition milestones. The 19-month program was divided into 2 arms lasting 9.5 months each, BRIDGE- (SMS text messaging support …

In Vivo Orf Overexpression Screening Identifies Ccn4 As A Regulator Of Glioblastoma Growth Validated Across Multiple Models, Pushan Dasgupta

Faculty, Staff and Students Publications

Despite current multimodal therapies for glioblastoma (GBM), its prognosis remains grim. Thus, a tremendous need exists to identify new genetic drivers that may serve as potential therapeutic targets in glioblastoma (GBM). We describe an in vivo overexpression screening strategy to identify drivers of glioblastoma where we have leveraged TCGA datasets to conduct a functional genomics screen of prioritized open reading frames (ORFs) that are overexpressed and/or amplified in GBM. To interrogate these potential drivers within a more relevant physiological context, the screening was accomplished in vivo in an orthotopic patient-derived glioma stem-like cell (GSC) model. Among 5 positive "hits" from …

Impact Of Dolutegravir-Based Regimens On Patient Satisfaction And Quality Of Life Among People Living With Hiv: A Systematic Review And Meta-Analysis, Mustapha Muhammed Abubakar, Christabel Ogechukwu Okoye, Ruth Jeminiwa, Ifeanyi Kanayo Ifeorah, Lotanna Ezeja, Yusuf Dauran, Sahabi Musa, Silas Usen Joel, Abdurrahman Murtala Bello, Amauche Pearl Ngige, Gabriel Ezenri, Abdulmuminu Isah, Ifunanya Ikhile, Blessing Onyinye Ukoha-Kalu

College of Pharmacy Faculty Papers

Background: Despite the global scale up of dolutegravir (DTG)-based regimens as the preferred first-line therapy for persons living with HIV (PLHIV), no comprehensive evidence exists on its effect on patient-reported outcomes such as Quality of Life (QoL) and patient satisfaction (PS). We conducted a systematic review and meta-analysis to provide the first comprehensive quantitative synthesis of the effect of DTG-based regimens on QoL and PS among PLHIV.

Method: We conducted literature search on PubMed, Scopus, Embase and Cochrane Library databases for peer-reviewed, primary studies published from January 2015 to January 2025. Studies using validated tools to evaluate QoL and PS …

Auricular Point Acupressure Self-Management (Apa-Sm) Program For Chronic Musculoskeletal Pain Among Rural Populations: A Protocol For A Pragmatic, Randomized Controlled Trial, Jennifer Kawi, Jane Bolin, Hulin Wu, Jungkyung Min, Rupsikha Bora, Sarah Pace, Idara N Akpan, Alee Lockman, Tonychris Nnaka

Faculty, Staff and Student Publications

Introduction: Chronic musculoskeletal pain (CMP) is a leading cause of incurred personal healthcare costs and disability in the USA. It disproportionately affects rural populations, who are more likely to be uninsured, lack access to a regular healthcare provider and experience a higher prevalence of CMP. As a result of reduced access to non-pharmacological care, there is greater reliance on opioids. The Auricular Point Acupressure - Self-Management (APA-SM) program is a simple, needleless, evidence-based therapy that empowers individuals to self-manage their pain. Preliminary studies, including a recent UG3 pilot testing, demonstrated feasibility, safety and significant improvements in pain and function. Guided …

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 …

Notch1 Acts As A Tumor Suppressor That Induces Early Differentiation In Head And Neck Cancer, Chenfei Huang, Shhyam Moorthy, Qiuli Li, Kazi M Ahmed, Kalil Saab, Defeng Deng, Jiping Wang, Xiayu Rao, Jiexin Zhang, Yuanxin Xi, Jing Wang, Zhiyi Liu, Noriaki Tanaka, David A Wheeler, Eve Shinbrot, Rami Saade, Curtis R Pickering, Tong-Xin Xie, Adel K El-Naggar, Abdullah A Osman, Kunal Rai, Patrick A Zweidler-Mckay, John V Heymach, Lauren A Byers, Faye M Johnson, Vlad C Sandulache, Jeffrey N Myers, Pedram Yadollahi, Mitchell J Frederick

Faculty, Staff and Students Publications

Inactivating NOTCH1 mutations in head and neck squamous cell carcinoma (HNSCC) were described over a decade ago, suggesting a tumor suppressor function - unlike its oncogenic role in other tumors. Today, much debate persists regarding a putative oncogenic role in HNSCC as well, with reports that NOTCH1 signaling drives tumor growth and a cancer stem cell (CSC) phenotype. In this work, comprehensive experiments unequivocally demonstrate that NOTCH1 is a tumor suppressor in HNSCC regardless of mutation or activation status and that it reduces CSC frequency. We developed a signature of NOTCH1 activation showing the pathway is associated with very early …

Recent Antibiotic Exposure And Response To Treatment Of Juvenile Idiopathic Arthritis: A Retrospective Cohort Study, Daniel Horton, Charu Verma, Sanika Rege, Stephen Crystal, Tobias Gerhard, Alicia Iizuka, Matthew Iozzio, Dawn Koffman, Lauren Parlett, Julianne Varga, Carlos Rose, Brian Strom

Department of Medicine Faculty Papers

BACKGROUND: Juvenile idiopathic arthritis (JIA) has been tied to microbiome disruption and antibiotic exposure. Gut microbiota may affect how adults with rheumatoid arthritis respond to methotrexate. We tested if exposure to antibiotics was associated with response to methotrexate for JIA.

METHODS: We conducted a retrospective cohort study using national US public and private insurance claims data (2001-2023). We included children ages 1-17 continuously enrolled for ≥ 10 months and diagnosed with JIA who initiated methotrexate monotherapy or, for comparison, tumor necrosis factor inhibitor (TNFi) monotherapy without prior disease-modifying antirheumatic drug (DMARD) exposure. Antibiotic exposure during the 10-month baseline period was …

Why Are Some Children Under 24 Months Still Undernourished In Urban And Peri-Urban Vientiane? A Mixed-Methods Study, Kethmany Ratsavong, Dirk Essink, Pamela J. Wright Phd, Ms, Med, Rn, Cen, Somphou Sayasone, Sengchanh Kounnavong, Jacqueline E. Broerse

Publications

Child undernutrition remains a significant public health challenge in many low and middle-income countries (LMICs), including Lao PDR, where high levels persist even in urban areas with generally available and accessible food. This study aimed to explore factors underlying the persistently high rates of undernutrition among young children in urban (Saysetha) and peri-urban (Pakgneum) districts of the Vientiane Capital in Lao PDR. A cross-sectional survey employed a sequential explanatory mixed-methods approach, combining a structured questionnaire of 333 mother-child pairs for quantitative analysis with semi-structured interviews of 47 caregivers for qualitative insights. The prevalence of malnutrition among children under 24 months …

Recommendations For Disclosure Of Artificial Intelligence In Scientific Writing And Publishing: A Regional Anesthesia And Pain Medicine Modified Delphi Study, Michael R Fettiplace, Anuj Bhatia, Yian Chen, Steven L Orebaugh, Michael Gofeld, Rodney A Gabriel, Daniel I Sessler, Hannah Lonsdale, Brittani Bungart, Christopher P Cheng, Garrett W Burnett, Lichy Han, Matthew Wiles, Steve Coppens, Thomas Joseph, Kristin L Schreiber, Thomas Volk, Richard D Urman, Vesela P Kovacheva, Christopher L Wu, Edward R Mariano, Vivian H Y Ip

Faculty, Staff and Student Publications

Introduction: The use of artificial intelligence (AI) in the scientific process is advancing at a remarkable speed, thanks to continued innovations in large language models. While AI provides widespread benefits, including editing for fluency and clarity, it also has drawbacks, including fabricated content, perpetuation of bias, and lack of accountability. The editorial board of Regional Anesthesia & Pain Medicine (RAPM) therefore sought to develop best practices for AI usage and disclosure.

Methods: A steering committee from the American Society of Regional Anesthesia and Pain Medicine used a modified Delphi process to address definitions, disclosure requirements, authorship standards, and editorial oversight …

Monoclonal Antibodies Targeting Pcdh7 Inhibit Tumor Growth And Enhance Immune Responses In Kras-Mutant Non-Small Cell Lung Cancer, Nicole Novaresi, Poorva Ghosh, Shayna Thomas-Jardin, Hui Deng, Xuejun Fan, Zhiqiang Ku, Wei Xiong, Xiaorong Zhou, Jingfei Zhu, Huiyu Li, Mahesh S Padanad, Bethany Smith, Chul Ahn, John D Minna, Zhiqiang An, Ningyan Zhang, Kathryn A O'Donnell

The Brown Foundation: Institute of Molecular Medicine

We identified an important oncogenic role for protocadherin 7 (PCDH7), a cell surface protein frequently overexpressed in lung adenocarcinoma and associated with poor clinical outcome. Pcdh7 depletion reduces tumor burden and prolongs survival in KrasLSL-G12D; Tp53fl/fl mice. These findings nominate this cell surface protein as an actionable therapeutic target and highlight the therapeutic potential of PCDH7 inhibition for non–small cell lung cancer. We report the development and characterization of high-affinity anti-PCDH7 monoclonal antibodies (mAbs) that inhibit downstream mitogen-activated protein kinase (MAPK) pathway activation and suppress tumor growth in multiple mutant KRAS–driven models. A lead mAb (mAb7) sensitized tumors …

Disease-Causing Mfn2 Mutants Impair Mitochondrial Fission Dynamics By Distinct Drp1 Dysregulation, Daniel Lagos, Pamela R. De Santiago, Nicolás Pérez-Bravo, Benjamín Cartes-Saavedra, Josefa Vial-Brizzi, Diego Troncoso-Chandía, Oliver Podmanicky, Rita Horvath, Verónica Eisner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondria undergo fusion and fission. While DRP1 regulates fission, fusion is controlled by OPA1, MFN1, and MFN2. The balance between these processes and the crosstalk between machineries remains poorly understood. MFN2 mutations cause Charcot-Marie-Tooth disease type 2 A (CMT2A), affecting mitochondrial fusion and morphology. However, their role in fission is unclear. Using skin fibroblasts from CMT2A patients (L248H and M376V MFN2 mutations) and wild-type mouse embryonic fibroblasts expressing these variants, we studied how MFN2 mutations impact mitochondrial dynamics beyond fusion. We analyzed mitochondrial morphology and dynamics by live-cell confocal microscopy and tested fusion/fission protein levels, oxygen consumption rate (OCR), extracellular …

Histone Deacetylase Enzyme Activity Is Not The Universal Anticancer Target Of Hdac Inhibitors, Chaitra Rai, Hang Ruan, Xue Li, Wenbo Li, Hyun-Hwan Jeong, Chengchuang Song, Panpan Liu, Yingjie Chang, Hao Fang, Udhaya Kumar S, Yuxiang Sun, M James You, Dongyin Guan, Zhandong Liu, Leng Han, Xuben Hou, Zheng Sun

Faculty, Staff and Students Publications

Histone deacetylase inhibitors (HDIs) are approved for treating hematologic cancers and are currently being evaluated in hundreds of clinical trials for various cancers and other diseases, although their mechanisms of action remain poorly understood. Here, our unbiased bioinformatics analyses found that, for most cancer types, expression levels or genetic variants of histone deacetylase (HDACs) do not consistently correlate with carcinogenesis, do not predict cancer patient survival, and do not associate with cellular responses to HDIs. Whole-genome CRISPR library screens did not identify HDACs as genes affecting cellular responses to HDIs. Overexpression of dominant-negative Class I HDACs causes similar protein hyperacetylation …

Relationship Between Sleep And Meal Timing With Glycemia Parameters In Individuals With Obesity Participating In A Randomized Time-Restricted Eating Study., Sirimon Reutrakul, Stacey L. Simon, Qi Wang, Emily N C Manoogian, Satchindananda Panda, Suryeon Ryu, Zan Gao, Caleb Griffiths, Erika Helgeson, Douglas G. Mashek, Niki Oldenburg, Lisa Senye Chow

Manuscripts, Articles, Book Chapters and Other Papers

Background/Objectives: Circadian misalignment, including mistimed sleep or eating, is associated with altered glucose metabolism. The importance of eating window timing for time-restricted eating (TRE) is increasingly recognized. This secondary analysis examined associations between meal to sleep timing intervals and glycemic parameters in individuals with obesity across three dietary interventions [TRE, CR: caloric restriction, and UE: unrestricted eating]. Methods: Participants aged 18-65 years with obesity were randomized to a 12-week intervention: TRE (8 h eating window), CR (15% reduction in daily caloric intake), or UE (usual eating habits). CGM and actigraphy were assessed over two weeks at baseline and end-intervention. Mixed …

Evaluating Chest-Worn Light Logger Adherence: Development And Application Of A Wear/Non-Wear Model, Carlyn Patterson Gentile, Adah Thomas, Ryan Shah, Blanca Marquez De Prado, Nichelle Raj, Christina Szperka, Geoffrey Aguirre

Student Papers, Posters & Projects

Light exposure plays an important role in overall health because it entrains circadian rhythms. Recent technological advances in wearable light loggers allow measurement daily light exposure habits. Using a chest-worn light logger, our goal was to (1) develop methodology for differentiating adherent versus non-adherent use, and (2) define differences in lighting intensity in indoor and outdoor environments, to improve data reliability in future clinical studies using this technology. Four testers used a 10-channel chest worn light logging device under different conditions of wear and non-wear (experiment 1), and another tester made measurements with the light logger across a variety of …

‘Wala Kaming Alam Sa Stroke Care’ (We Don’T Know Anything About Stroke Care): Experiences Of Care Providers Delivering Stroke Rehabilitation Care In The Philippines, Fiona Leggat, Sarah Ann Buckingham, Aira Patrice Rueda Ong, Bridie Kent, Nena Marie Santos, Annah Teves, Vergil Boac, Paula Melizza Valera, Elda Anota, Maria Mercedes Barba, Myrna Estrada, Neil Bryan Pita, Alyssa Dar Juan, Lorraine Faeldon, Fiona Jones

School of Nursing and Midwifery

BackgroundIn the Philippines, rising stroke prevalence and healthcare inequalities present a concerning outlook. While acute stroke care is prioritised, rehabilitation remains undervalued. The experiences of healthcare providers who deliver stroke support are also under-researched.Objective(s)Our study aimed to explore the experiences and needs of care providers across multiple regions of the Philippines to inform the development of stroke support initiatives and programmes.MethodsForming part of the Tulong, Ugnayan ng Lingap At gabaY (TULAY) project, a qualitative descriptive design involving semi-structured interviews was used. Care providers with professional or voluntary community healthcare service delivery roles were recruited. Data were analysed using reflexive thematic …

Intrathecal Antibody Synthesis - Reiber Method Revisited, John J. Halperin, Dane Granger

Department of Neurology Faculty Papers

BACKGROUND: CSF immunoglobulin (IgG) often informs diagnosis in CNS inflammatory disease- qualitatively (oligoclonal bands; OCBs), or quantitatively (CSF: serum IgG: albumin, e.g. IgG index). Most US laboratories estimate excess CSF IgG using linear models, most in Europe, Reiber's hyperbolic model - the latter often also incorporated into CSF pathogen-specific immunoreactivity calculations. We compared Reiber hyperbolic and linear approaches.

METHODS: Required data were available for 1,872 samples, Lyme-specific data for 1,365. We compared linear and Reiber's hyperbolic models to determine which better describes normal CSF: serum IgG/albumin, assessed correlations with OCBs using ROC analysis and compared Lyme-specific antibody indices (AI) by …

Continuous Glucose Monitoring Use In The Management Of Type 2 Diabetes In Primary Care: Cross-Sectional Survey Of Provider Comfort, Ryley Harris, Catherine Guariglia, Amy Cunningham

Department of Family & Community Medicine Faculty Papers

This study assessed primary care providers’ comfort with prescribing and using continuous glucose monitoring technology for type 2 diabetes management, identifying key barriers and educational needs.

Screen-Based Simulation Assessment For Emergency Medicine Learners: A Rapid Review, Patrick Zeniecki, Rebecca Kamens, Jared Kilpatrick, Dimitrios Papanagnou, Xiao C. Zhang

Department of Emergency Medicine Faculty Papers

BACKGROUND: Simulation has played a vital role in training medical professionals. The COVID-19 Pandemic has highlighted the need for physically distant educational assessment methods. Screen-based simulation (SBS) demonstrates one alternative to traditional in-person simulation methods to assess learners clinical reasoning and communication skills. This study aims to compare in-person simulation to SBS as assessment methods in Emergency Medicine (EM).

METHODS: A rapid review literature search methodology of an electronic database (PubMed) was performed in February 2022 with search terms such as "Computer Simulation," "Patient Simulation," "Simulation Training," "Education, Distance," "Virtual OSCE," "Academic Performance," or "Emergency Medicine." Reference lists of relevant …

Genetic Architecture Of White Matter Microstructure Captured By Unsupervised Deep Representation Learning Of Fractional Anisotropy Maps, Xingzhong Zhao, Ziqian Xie, Wei He, Hyun Yong Koh, Bohong Guo, Han Chen, Myriam Fornage, Degui Zhi

The Brown Foundation: Institute of Molecular Medicine

Fractional anisotropy (FA) from diffusion MRI is a widely used marker of white matter (WM) integrity, but conventional FA-based genetic studies typically rely on tract- or atlas-defined averages that may obscure spatially distributed WM variation and limit genetic discovery. Here, we propose a deep learning framework, termed unsupervised deep representation of WM (UDR-WM), which uses voxel-wise FA maps to derive brain-wide unsupervised deep imaging phenotypes (UDIP-FA) without prior anatomical assumptions. Compared with traditional FA phenotypes, UDIP-FA shows greater sensitivity to aging and substantially higher SNP-based heritability. Multivariate GWAS identified 939 lead SNPs across 586 loci, mapping to 3,480 UDIP-FA-associated genes. …

The Influence Of Social Media Messaging On Human Papillomavirus Vaccine Attitudes And Confidence Among Adolescent Males: Group Discussion Study, Neha Trivedi, Rachel Van Vleet, Czesia Eid, Amelia Burke-Garcia, Amy Leader

Department of Medical Oncology Faculty Papers

BACKGROUND: Despite the human papillomavirus (HPV) vaccine being available to males for the past 12 years, adolescent males continue to lag in HPV vaccine uptake due to a variety of factors. With the ubiquitous nature of social media use among this population, further research is needed to improve HPV vaccine confidence among young adolescent males using these platforms.

OBJECTIVE: Using the Elaboration Likelihood Model (ELM), this study sought to better understand knowledge, attitudes, and beliefs about HPV and HPV vaccination among male adolescents aged 14-17 years and examine how social media messaging influences vaccine perceptions and explore the characteristics of …

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 …

The Relationship Between Psychological Stress And Sars-Cov-2 Nucleocapsid-Antibody Response Following Natural Infection: Longitudinal Findings From The Aegis Study, Erika T Beidelman, Ashley Judge, David B Allison, Stephanie Dickinson, Lilian Golzarri Arroyo, Anna L M Macagno, Michael J Ricciardi, Jon Macy, Stanley Perlman, Christina Ludema, Kevin C Maki, Molly Rosenberg

Faculty, Staff and Students Publications

Psychological stress can cause diminished immune response to infectious challenges. The extent this holds true during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the modifying effect of vaccination status is untested. We explored these relationships in a non-random sample standardized to the US adult population. Across 2178 participants in the Aegis study (2021-2022), we identified 507 eligible laboratory-confirmed SARS-CoV-2 infections. We estimated the natural log of nucleocapsid-binding antibody absorbance (N-antibody) at study visits up to 225 days following a positive SARS-CoV-2 test. Linear mixed effects models were fit to estimate the association of baseline perceived stress and, separately, …

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 …

Optimizing The Sensitivity Of Detection Of Respiratory Syncytial Virus Infections In Longitudinal Studies Using The Combination Of Weekly Sample Testing And Biannual Serology., Shannon C. Conrey, Daniel C. Payne, Maria Deza Leon, Monica Epperson, Melissa M. Coughlin, Allison R. Burrell, Claire P. Mattison, Rachel M. Burke, Julia M. Baker, Natalie J. Thornburg, Meredith L. Mcmorrow, Mary Allen Staat, Ardythe L. Morrow

Manuscripts, Articles, Book Chapters and Other Papers

Cohort studies are often challenged by incomplete adherence to sampling regimens, limiting the full capture of disease burden. We describe the detection of respiratory syncytial virus (RSV) infections achieved in a birth cohort using a combination of weekly nasal sample testing and serology. The Pediatric Respiratory and Enteric Viral Acquisition and Immunogenesis Longitudinal Cohort followed 245 maternal-child dyads from birth to age 18 to 24 months. Weekly mid-turbinate nasal swabs were tested for RSV using real-time polymerase chain reaction (RT-qPCR). Serum was tested for RSV pre-fusion F IgG and IgA antibody at age 6 weeks and biannually from 6 to …

Body Mass Index, Clinical Outcomes, And Mortality In Heart Failure: A Mendelian Randomization Study, Nicholas Sunderland, Douglas L Mann, Et Al.

2020-Current year OA Pubs

BACKGROUND: Excess adiposity, most commonly indexed through body mass index (BMI), is strongly associated with the development of heart failure (HF). Weight loss therapies improve outcomes in patients with obesity and HF with preserved left ventricular ejection fraction (LVEF), but their effects in HF with reduced LVEF remain unclear.

OBJECTIVES: The aim of this work is to determine whether higher BMI is associated with adverse clinical outcomes in patients with HF and whether there is effect modification by LVEF subgroup.

METHODS: Two-sample Mendelian randomization (MR) was used, with genome-wide significant loci associated with BMI as instrumental variables and outcome data …

Garlic-Derived Metabolite Activates Lkb1, Promotes Adipose Enampt Secretion, And Improves Age-Related Muscle Function Via Hypothalamic Signaling, Jun-Ichiro Suzuki, Kiyoshi Yoshioka, Masahiro Kurita, Takumi Sugimoto, Takahiro Eguchi, Naoki Ito, Aoi Kodama, Yasutomi Kamei, Masahiro Ohtani, Toshiaki Matsutomo, Shin-Ichiro Imai

2020-Current year OA Pubs

Garlic (Allium sativum L.) and its aged extract contain many bioactive compounds that can bring health benefits to humans. Among them, S-1-propenyl-L-cysteine (S1PC) has recently drawn significant attention in the field of nutriceutical research. However, the mechanism of its molecular action has remained poorly understood. Here, we show that S1PC significantly activates liver kinase B1 (LKB1) through enhancing its tertiary complex formation with STRAD and MO25, leading to stimulating the phosphorylation of a mammalian NAD

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 …