Digital Commons Network^™

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 …

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 …

Structured Telehealth Community Health Worker-Clinician Feedback And Diabetes Outcomes: A Randomized Clinical Trial, Elizabeth M Vaughan, Xiaoying Yu, Amber B Amspoker, Aanand D Naik, Ashok Balasubramanyam, Craig A Johnston, Christi M Ballantyne, Salim S Virani, H Shelton Brown, Kristina Mena, Laura R Porterfield

Faculty, Staff and Students Publications

Importance: Community health workers (CHWs) improve chronic disease management in underserved populations, but scalable integration strategies are limited.

Objective: To evaluate whether a multidimensional intervention incorporating telementored CHWs and a structured participant-CHW-clinician feedback loop can improve diabetes outcomes.

Design, setting, and participants: This 12-month randomized clinical trial was conducted at 3 institutionally and geographically diverse community clinics in Texas between September 1, 2023, and April 30, 2025, and included low-income, uninsured White Hispanic adults with type 2 diabetes identified through clinic databases. Data were analyzed between May 1 and July 31, 2025.

Intervention: Individuals were randomized 1:1 to the intervention …

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 …

Targeted Reflex Rna Sequencing For Enhanced Variant Classification On Exome And Genome Sequencing Improves Patient Outcomes, Xiaonan Zhao, Robert Rigobello, Morgan Driver, Sydney Lau, Mei Ling Chong, Jason Chibuk, Hongzheng Dai, Wilson C W Wu, Christina Peroutka, Laura Famularo, Alexander Y Kim, Bailey Hummel, Sarah Dugan, Tinsley Douglas, Linyan Meng, Fan Xia, Christine M Eng

Faculty, Staff and Students Publications

RNA sequencing (RNA-seq) has been utilized to provide functional evidence regarding the impact of splicing variants. This study explores the utility of targeted reflex RNA-seq to inform classification of predicted splicing variants identified through clinical exome sequencing (ES) and genome sequencing (GS). A retrospective analysis was conducted on consecutive ES/GS cases completed at a single center in which targeted reflex RNA-seq was performed following identification of eligible variants. There were 131 cases (4.1%) that had at least one RNA-seq eligible variant reported, with eight of these cases having two unique eligible variants. Of the 139 eligible variants, 125 were classified …

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%) …

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 …

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 …

The Aggregated Latent Profile Index: Measuring Person Profile Differentiation Within A Bootstrap-Validated Latent Profile Space, Se-Kang Kim

Faculty, Staff and Students Publications

Multivariate assessment profiles contain two conceptually distinct sources of variation: overall level and profile shape. Existing approaches recover some aspects of this structure, but none jointly establishes the replicability of latent pattern dimensions and provides a principled, population-referenced summary of person profile differentiation independent of overall level. We introduce the Aggregated Latent Profile Index (ALPI), a variance-weighted Euclidean distance that quantifies the degree to which an individual’s profile departs from a flat population reference within a bootstrap-validated latent profile space. ALPI is derived from the Aggregated Latent Profile Space (ALPS), a framework that combines parallel analysis with bootstrap stability diagnostics …

Impact Of Lumen Origin And Gap Distance On Target Vessel Outcomes Following Fenestrated-Branched Endovascular Aortic Repair Of Postdissection Thoracoabdominal Aortic Aneurysms, Armin Tabiei, Jesse Chait, Andrea Vacirca, Randall R Demartino, Emanuel R Tenorio, Fahad Shuja, Dora Babocs, Guilherme B B Lima, Naveed Saqib, Gustavo S Oderich, Bernardo C Mendes

Faculty, Staff and Students Publications

Background: This study evaluated the role of target vessel (TV) lumen origin and fenestration gap (FG) distance between the endograft and the aortic wall on TV outcomes following fenestrated-branched endovascular aortic repair (FB-EVAR) for postdissection thoracoabdominal aortic aneurysms (PD-TAAAs).

Methods: A multicenter review of prospectively and retrospectively collected data of patients undergoing FB-EVAR for PD-TAAAs between 2013 and 2023 was performed. Lumen origin was retrospectively analyzed on preoperative imaging studies and classified as true lumen (TL) only, false lumen (FL) only, or both TL and FL. The FG distance was retrospectively measured on postoperative imaging studies and included as a …

The Omeract Core Domain Sets For Calcium Pyrophosphate Deposition Disease, Nicola Dalbeth, Yiling Zhang, Owen Hensey, David Grossberg, Ken Cai, Amy Fuller, Geraldine M Mccarthy, Tristan Pascart, Augustin Latourte, Edoardo Cipolletta, William J Taylor, Cesar Diaz-Torne, Tim L Jansen, Lih En Hong, Silvia Sirotti, Fabio Becce, Georgios Filippou, Beverley Shea, Robin Christensen, Jasvinder A Singh, Abhishek Abhishek, Sara K Tedeschi

Faculty, Staff and Students Publications

Objectives: To develop OMERACT core domain sets for chronic and recurrent calcium pyrophosphate deposition (CPPD) disease and acute calcium pyrophosphate (CPP) crystal arthritis.

Methods: Following OMERACT methodology, the CPPD Working Group (comprising of patient research partners, fellows, clinicians, and methodologists) defined the core domain sets. The development of the core sets occurred through a scoping review, qualitative study, Delphi surveys, and ranking exercises to identify the most relevant domains. A virtual e-module was developed to enable members of the OMERACT community to discuss and vote for endorsement of the OMERACT CPPD core domain sets.

Results: The core domains for chronic …

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 …

Complement Activation In Maternal And Placental Pathology Of Preeclampsia, Manu T Banadakoppa, Madhulatha S Chauhan, Moises J Tacam, Allyson W Nevins, Antonio H Ruano, Simone H Ruano, Jon A Fuson, Chandra Yallampalli

Faculty, Staff and Students Publications

Background: Preeclampsia is a multifactorial, pregnancy-related disorder characterized by new-onset hypertension and proteinuria, with distinct early- and late-onset forms. Although complement dysregulation has been implicated in the pathogenesis of preeclampsia, its causal role remains unclear. In mice, Crry (complement receptor 1-related protein Y) functions as a critical complement regulator at the fetal-maternal interface. Because complete Crry deficiency is embryonically lethal, direct in vivo investigation of complement activation in pregnancy has been challenging.

Methods: We generated a placenta-specific, doxycycline-inducible short hairpin RNA mouse model in which Crry expression can be downregulated in a dose-dependent manner. This system employs Cyp19-driven Cre recombinase …

Impact (Immune Monitoring And Phenotype Assessment Of Clinical Trajectory) For Patients With Inborn Errors Of Immunity From The Primary Immune Deficiency Treatment Consortium (Pidtc), Danielle E Arnold, Hesham Eissa, Elizabeth Dunn, Geoffrey D E Cuvelier, Nicola A M Wright, Rebecca A Marsh, Suhag Parikh, Blachy Davila Saldana, Mark T Vander Lugt, Rosa Bacchetta, Lisa Forbes Satter, Shanmuganathan Chandrakasan, Erinn Kellner, Eric J Allenspach, Erica G Schmitt, Brent Logan, Lauri Burroughs, Morton J Cowan, Linda M Griffith, Luigi Notarangelo, Sung-Yun Pai, Michael A Pulsipher, Christopher C Dvorak, Elie Haddad, Jennifer M Puck, Troy R Torgerson, Jennifer W Leiding, Jennifer Heimall, Alice Y Chan

Faculty, Staff and Students Publications

Background: Evaluating natural history and outcomes of rare inborn errors of immunity (IEIs) has been challenging due to the diverse disease manifestations and lack of standardized data.

Objective: To develop a set of standardized, quantitative, generalizable data collection modules to measure organ dysfunction in IEIs, modeled on the previously validated Common Terminology Criteria for Adverse Event system for grading treatment toxicity.

Methods: Disease conditions were organized by organ system. Experts from the Primary Immune Deficiency Treatment Consortium identified essential features of severe combined immunodeficiency, chronic granulomatous disease, Wiskott-Aldrich syndrome, and primary immune regulatory disorders and compared these to Common Terminology …

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, …

A Novel Qa Method For Adaptive Aperture Position Verification Of Proton Therapy System, Shuxin Fan, Tiezhi Zhang, Xiandong Zhao, Winter Green, Baozhou Sun, Tianyu Zhao, Yao Hao

Faculty, Staff and Students Publications

Accurate Adaptive Aperture (AA) leaf positioning is essential for some proton therapy systems to ensure precise dose delivery and patient safety. However, conventional quality assurance (QA) methods can be suboptimal or inefficient for routinely assessing the dynamic nature of AA in the Mevion S250i HYPERSCAN system. This study introduces a novel automated QA method to verify AA positions utilizing a scintillation detector. A specialized QA plan consisting of 7 rectangular fields was generated in the RayStation treatment planning system (TPS) and delivered using the Mevion S250i HYPERSCAN proton therapy system. Dose distributions were measured with an IBA Lynx PT scintillation …

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 …

Reducing Cardiovascular Disease Risk In Obesity: An Unexpected But Welcome Fourier Transformation, Layla A Abushamat, Arsalan Hamid, Vijay Nambi, Huaizhu Wu, Christie M Ballantyne

Faculty, Staff and Students Publications

No abstract provided.

A Multi-Country Community Of Practice To Strengthen Quality Improvement In Low- And Middle-Income Countries: A Quality Improvement Program Description, Samhita Bhargava, Heather A Haq, Brodus A Franklin, Elizabeth Davis, Florence Anabwani-Richter, Thobile Bhembe, Lindokuhle P Dlamini, Makhosazana Dlamini, Andy Chapola, Nomsa Kafumba, Chisomo Mzandu Zinyemba, Menard Bvumbwe, Kyakuwa Richard Jjuuko, Jacqueline Balungi Kanywa, Dithan Kiragga, Andreas Boy Isaac, Esther Makhalanyane, Lwamba Nyembo, Retselisitoe Mahlaha, John T Farirai, Eunice W Ketang'enyi, Andrea E M Imsen, Iuliana Costas, Susan B Torrey

Faculty, Staff and Students Publications

Background/objectives: Quality improvement (QI) is widely used in global health to improve patient outcomes, reduce costs, and strengthen service delivery. The Texas Children's Global Health Network (TCGHN) includes nine independent non-governmental organizations supporting healthcare in low- and middle-income countries (LMICs), with pediatric HIV clinical centers of excellence in six countries in sub-Saharan Africa (SSA), supported technically by Baylor College of Medicine. We describe the development of a virtual QI Community of Practice (QICoP) to connect geographically dispersed teams and strengthen local QI capacity.

Methods: In 2022, QI and global health experts convened to design the QICoP and assess site readiness. …

Paid Employment And Ability To Work Among People Receiving Dialysis: A Systematic Review Of Qualitative Studies, Ao Zhang, Adam Martin, Karine Manera, Chandana Guha, Martin Howell, Patrizia Natale, Nicole Scholes-Robertson, Dharshana Sabanayagam, Adeera Levin, Wolfgang Winkelmayer, Kevin F Erickson, Germaine Wong, Allison Jaure, Anita Van Zwieten

Faculty, Staff and Students Publications

Rationale & objective: People receiving dialysis have reduced workforce participation, which can affect mental well-being and exacerbate the financial burden of dialysis. This study describes the experiences and perspectives of people receiving dialysis on employment and their ability to work.

Study design: Systematic review and thematic synthesis of qualitative studies.

Setting & study populations: Adults aged 16 years and over receiving dialysis.

Search strategy & sources: MEDLINE, Embase, and PsycINFO were searched to May 2025 for qualitative and mixed-methods studies that reported the perspectives of people receiving dialysis on employment or ability to work.

Data extraction: Text from results and …

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 …

Kidney Disease And Heart Failure: Recent Advances And Current Challenges: Conclusions From A Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference, Carolyn S P Lam, Biykem Bozkurt, David Z I Cherney, Justin A Ezekowitz, Meg J Jardine, Sadiya S Khan, Magdalena Madero, Mark J Sarnak, Jozine M Ter Maaten, Michael Cheung, Jennifer M King, Morgan E Grams, Michel Jadoul, Nisha Bansal

Faculty, Staff and Students Publications

Heart failure (HF) and chronic kidney disease (CKD) frequently coexist, which elevates the risks of hospitalization, disease progression, and death. Despite advances in treating each condition independently, many challenges remain in diagnosing and managing them in combination. In March 2024, Kidney Disease: Improving Global Outcomes (KDIGO) held the Controversies Conference on Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Discussions highlighted the complex, bidirectional relationship between HF and CKD, including shared risk factors and overlapping pathophysiology as well as nuances in interpreting biomarkers such as natriuretic peptides and serum creatinine. Sodium-glucose cotransporter-2 inhibitors, renin-angiotensin-aldosterone system inhibitors, and emerging …

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 …

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 …

Identification Of A Persistent Ascaris-Derived Kalirin Epitope Associated With Chronic T Cell Activation In The Lung, Yifan Wu, Leroy Versteeg, Meng-Chih Wu, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis remains a dominant global health burden due to its vast prevalence and associated morbidity. The obligatory migration of Ascaris larvae through pulmonary tissue triggers intense type-2 inflammation which typically presents as acute allergic airway disease. Even after the parasite is eliminated, a single episode of larval migration can result in chronic lung damage and dysfunction, which may be driven by the long-term retention of helminth antigens in macrophages. However, the molecular identity of these retained antigens, and the mechanisms by which they sustain chronic T cell responses, remain unknown. In this study, we utilized immunopeptidomics to identify a retained …

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 …

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, …

Mindful Self-Compassion To Reduce Pain Interference Among Adults With Osteogenesis Imperfecta, Amena Sediqi, Roya Al-Khalili, Saunya Dover, Corien Peeters, Adam Khalif, V Reid Sutton, Frank Rauch, Brendan Lee, Eric A Storch, Marie-Eve Robinson

Faculty, Staff and Students Publications

Between 60 and 80% of adults with osteogenesis imperfecta (OI) experience chronic pain and associated interference. Currently available pain therapies often provide marginal efficacy. Mindful self-compassion (MSC) has emerged as a promising intervention for coping with chronic pain. We conducted a single-center 8-week pilot intervention study to assess the feasibility and acceptability of a MSC program among adults with OI and co-occurring chronic pain. Individuals attended the validated MSC course consisting of 8 weekly virtual 2-h sessions. Participants completed a battery of validated questionnaires assessing pain, various aspects of well-being, and physical function at baseline and post-intervention. Participants wore the …