Digital Commons Network^™

Pan-Uk Biobank Genome-Wide Association Analyses Enhance Discovery And Resolution Of Ancestry-Enriched Effects, Konrad J Karczewski, Rahul Gupta, Masahiro Kanai, Wenhan Lu, Kristin Tsuo, Ying Wang, Raymond K Walters, Patrick Turley, Shawneequa Callier, Nirav N Shah, Nikolas Baya, Duncan S Palmer, Jacqueline I Goldstein, Gopal Sarma, Matthew Solomonson, Nathan Cheng, Sam Bryant, Claire Churchhouse, Caroline M Cusick, Timothy Poterba, John Compitello, Daniel King, Wei Zhou, Cotton Seed, Hilary K Finucane, Mark J Daly, Benjamin M Neale, Elizabeth G Atkinson, Alicia R Martin

Faculty, Staff and Students Publications

Large biobanks, such as the UK Biobank (UKB), enable massive phenome by genome-wide association studies that elucidate genetic etiology of complex traits. However, individuals from diverse genetic ancestry groups are often excluded from association analyses due to concerns about population structure introducing false positive associations. Here, we generate mixed model associations and meta-analyses across genetic ancestry groups, inclusive of a larger fraction of the UKB than previous efforts, to produce freely-available summary statistics for 7,266 traits. We build a quality control and analysis framework informed by genetic architecture. Overall, we identify 14,676 significant loci (p < 5 × 10−8) in the meta-analysis that were not found in the EUR genetic ancestry group alone, including novel associations for example between CAMK2D and triglycerides. We also …

Pfas Exposure And Postoperative Weight Regain In Adolescents After Bariatric Surgery: Findings From The Teen-Labs Study, Brittney O Baumert, Elizabeth Costello, Zhenjiang Li, Justin R Ryder, Thomas Inge, Todd Jenkins, Stephanie Sisley, Stavra A Xanthakos, Douglas I Walker, Nikos Stratakis, Damaskini Valvi, Scott M Bartell, Angela L Slitt, Rohit Kohli, Sarah Rock, Michele A La Merrill, Sandrah P Eckel, Max T Aung, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

Objective: Weight regain following bariatric surgery remains a clinical challenge, with limited understanding of contributing environmental factors. Per- and polyfluoroalkyl substances (PFAS), persistent chemicals linked to metabolic dysfunction, may influence long-term weight trajectories. This study aimed to evaluate associations between PFAS exposure and changes in BMI, percent weight loss, and waist circumference among adolescents after bariatric surgery.

Methods: We included 186 adolescents (mean age: 17.1 years; 76.3% female; 72.0% White) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort who underwent surgery between 2007 and 2012. Anthropometric measurements were collected at baseline and 6, 12, 36, and 60 months post …

Nrf2 Hyperactivation As A Driver Of Radiotherapy Resistance And Suppressed Antitumor Immunity In Head And Neck Squamous Cell Carcinoma, Rutulkumar Patel, Kalil Saab, Lixia Luo, Yan Ma, Rashid Abdullah Osman, Nerissa T Williams, Jeffrey Everitt, Maciej J Zelazowski, Patricia Castro, William K Decker, William H Hudson, Jeffrey N Myers, Vlad C Sandulache, Mitchell J Frederick, Yvonne M Mowery, David G Kirsch

Faculty, Staff and Students Publications

Purpose: Alterations in the KEAP1/NFE2L2 (NRF2)/CUL3 pathway occur in ∼20% of human head and neck squamous cell carcinomas (HNSCC) and are associated with resistance to standard-of-care therapy. However, this pathway's role in radiotherapy resistance in HNSCC has not been well studied.

Experimental design: We generated genetically engineered mouse models and developed primary murine cancer cell lines harboring mutations commonly observed in human HNSCC, including inducible activation of PIK3CA and deletion of Trp53, with or without Keap1 loss. Primary tumors were initiated via 4-hydroxytamoxifen injection ± the tobacco carcinogen benzo[a]pyrene (BAP) into the oral buccal mucosa. Tumors were analyzed by Western …

What Community Members With Chronic Illness Teach Future Healthcare Professionals In A Longitudinal Interprofessional Education Program: A Focus Group Study, Rachel White, Maria Brucato, Amber King, Anne B. Mitchell, Nethra S. Ankam

Department of Medicine Faculty Papers

INTRODUCTION: Nearly 50% of Americans have at least one chronic illness. Preparing future healthcare providers for interprofessional collaborative practice (IPCP) and person-centred care through community-based interprofessional education (IPE) can improve outcomes for this growing population. Partial programme theories predict that patients' participation as teachers in health professions education contributes to students' development of patient-centredness. Role theory asserts that behaviours are shaped by assigned roles; therefore, community members with chronic illness who assume roles of health mentors in an IPE curriculum are predicted to teach students about their patient experiences. Yet, this teaching outcome and the lessons health mentors teach in …

Enhancing Stemm Education Through Advanced Technologies And Collaborative Programs, Zhongcheng Shi, Michael Nguyen, Yuan Yao, Debra D Murray, Rayne H Rouce, Veronica Ajewole, Huan Xie, Shixia Huang

Faculty and Staff Publications

Integrating advanced technologies into STEMM (Science, Technology, Engineering, Mathematics, and Medicine) education is essential for preparing a future-ready, diverse scientific workforce capable of addressing complex global challenges. This paper presents three interconnected programs-BRITE (Biotechnology Research Incubator for Teachers), ASPIRATION (AI-guided Scientist-Mentored Primary Literature Adaptation for STEMM Education), and C-REP (Cancer Research Education Program)-developed through collaborations with Advanced Technology Cores and multi-institutional participation, involving mentors ranging from core directors to graduate and medical students. While initially supported by internal funding, two of these initiatives have since secured NIH grant support. These initiatives provide immersive, hands-on training in genomics, proteomics, metabolomics, flow …

Life-Moms: Effects Of Multicomponent Lifestyle Randomized Control Trial On Physical Activity During Pregnancy In Women With Overweight And Obesity, Hannah E Cabre, Debra Haire-Joshu, Alison G Cahill, Samuel Klein, Et Al.

2020-Current year OA Pubs

BACKGROUND: This report details the effect of LIFE-Mom's multicomponent lifestyle interventions on physical activity (PA) and inactivity time across pregnancy (2nd and 3rd trimesters) and their effect on gestational weight gain (GWG) and maternal/neonatal outcomes, a pre-specified secondary analysis.

METHODS: Pregnant people with BMI ≥ 25 kg/m

RESULTS: Although there were statistically significant differences in vigorous activity between the intervention and control group (p = .024), there were no clinically meaningful differences in PA. In the combined sample, moderate to vigorous PA (MVPA) significantly decreased across pregnancy (mean ± SD: 72.9 ± 29.1 min/day vs 63.9 ± 28.1 min/day; p …

Ebola Virus Vp35 Nnlns Motif Modulates Viral Rna Synthesis And Mib2-Mediated Signaling, Grace Uwase, Priya Luthra, Olivia A Vogel, Jyoti Batra, Bruno A La Rosa, Kathleen C F Sheehan, Oam Khatavkar, Jacqueline E Payton, Robert A Davey, Nevan J Krogan, Christopher F Basler, Daisy W Leung, Gaya K Amarasinghe

2020-Current year OA Pubs

Ebola virus (EBOV) is a nonsegmented, negative-sense virus (NNSV) with a single-stranded RNA genome. EBOV encodes for a limited number of proteins and thus depends on host factors to facilitate viral replication and pathogenesis. Of the virus-encoded proteins, multifunctional EBOV VP35 (eVP35) is necessary for host immune evasion and viral RNA synthesis. Previous proteomics studies identified an interaction between eVP35 and the host E3 ubiquitin ligase Mindbomb 2 (MIB2). Here, we show how an NNLNS (Asn-Asn-Leu-Asn-Ser) motif (residues 201 to 205) within eVP35 serves as a binding site for MIB2. This motif is critical for eVP35-dependent inhibition of MIB2-mediated interferon …

Development Of A Leucine-Rich Repeat-Containing Protein 15-Targeted Radio-Immunotheranostic Approach To Deplete Pro-Tumorigenic Mechanisms And Immunotherapy Resistance, Claire M Storey, Abbie Hasson, Diane Abou, Daniel Thorek, Et Al.

2020-Current year OA Pubs

Leucine-rich repeat containing 15 (LRRC15) has emerged as an attractive biomarker and target for cancer therapy. Transforming growth factor-β (TGFβ) induces the expression of this plasma membrane protein specifically in aggressive and treatment resistant tumor cells derived from mesenchymal stem cells, with minimal expression observed in non-neoplastic tissues. We have developed a humanized monoclonal antibody, DUNP19, that specifically binds with high affinity to a phylogenetically conserved LRRC15 epitope and is rapidly internalized upon LRRC15 binding. In multiple subcutaneous and orthotopic tumor xenograft mouse models, Lutetium-177 labeled DUNP19 ([

The Critical Human Pathogen Acinetobacter Baumannii Exhibits Light-Regulated Circadian Rhythms, Valentín Permingeat, Bárbara Edith Perez Mora, María Laura Migliori, Natalia Arana, Julia Fernández, María Belén Allasia, Melisa Luciana Lamberti, Gisela Di Venanzio, Ramiro Esteban Rodriguez, Mario Federico Feldman, Diego Andrés Golombek, María Alejandra Mussi

2020-Current year OA Pubs

Acinetobacter baumannii is recognized as the paradigm of multidrug-resistant superbug, topping the WHO priority list of critical human pathogens. Interestingly, it senses and responds to blue light, which modulates global aspects of its physiology, including pathogenicity. We hypothesized that light could serve as a signal to synchronize the bacterial physiology to the host's behavior and/or to the environment. At environmental temperatures, light regulation is mainly governed by the photoreceptor BlsA. In this work, we identified the existence of daily rhythms in blsA promoter activity displaying a robust response to light, as well as endogenous circadian rhythms in A. baumannii. In …

Htlv-1 And Atll: Epidemiology, Oncogenesis, And Opportunities For Community-Informed Research In The United States, Adrian D. Altieri, Sean P. Reilly, Abu Mansalay, Alan Khoo, Nettie Johnson, Zafar K. Khan, Amy Leader, Pooja Jain, Pierluigi Porcu

Kimmel Cancer Center Faculty Papers

Human T-cell leukemia virus type 1 (HTLV-1), the first oncogenic human retrovirus, causes adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm of mature CD4+ T-cells that is incurable in most patients and is associated with a median survival of less than 1 year. HTLV-1 also causes inflammatory disorders, including HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and uveitis. The estimated lifetime risks of ATLL and HAM/TSP in HTLV-1 carriers are 3-5% and 0.25-1.8%, respectively. Although there is uncertainty about other health effects of HTLV-1, a recent meta-analysis showed an association between HTLV-1 and cardiovascular, cerebrovascular, and metabolic diseases and a 57% increased risk …

Current States In Understanding Oligodendroglia-Mediated Neurological Issues In Neurofibromatosis Type 1 (Nf1), Benjamin E Aghoghovwia, Cheng-En Shen, Sabiha Bano, Nandini Shyamala, Alesandra Echeandia Marrero, Khushboo Irshad, Samer Sharafaldin, Nicole M Brossier, Yuan Pan

2020-Current year OA Pubs

Neurofibromatosis type 1 (NF1) is among the most common neurogenetic disorders and is associated with an increased risk of developing tumors in the nervous system. Additionally, up to 80% of patients with NF1 experience neurological complications, including deficits in attention, memory, and executive function. Significant effort has been dedicated to studying how NF1 mutations autonomously dysregulate neuronal function. Increasing evidence indicates that NF1 mutations also dysregulate the oligodendroglial lineage that contributes to neurological issues in NF1. Here, we summarize our current understanding of how NF1 mutations impact the oligodendroglial lineage homeostasis and plasticity. We also discuss gaps in knowledge, potential …

In Vivo Crispr Screening In Head And Neck Cancer Reveals Uchl5 As An Immunotherapy Target, Cong Fu, Zahra Alipour, Douglas R Adkins, Rebecca D Chernock, Et Al.

2020-Current year OA Pubs

Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with a significant unmet need for enhancing immunotherapy response given current modest efficacy. Here, we perform an in vivo CRISPR screen in an HNSCC mouse model to identify immune evasion genes. We identify several regulators of immune checkpoint blockade (ICB) response, including the ubiquitin C-terminal hydrolase 5 (UCHL5). Loss of Uchl5 in tumors increases CD8

Motion Impact Score For Detecting Spurious Brain-Behavior Associations, Benjamin P Kay, David F Montez, Scott Marek, Joshua S Siegel, Babatunde Adeyemo, Timothy O Laumann, Athanasia Metoki, Roselyne J Chauvin, Andrew N Van, Vahdeta Suljic, Samuel R Krimmel, Ryland L Miller, Dillan J Newbold, Annie Zheng, Nicole A Seider, Kristen M Scheidter, Julia S Monk, Jarod L Roland, Evan M Gordon, Abraham Z Snyder, Deanna M Barch, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

In-scanner head motion introduces systematic bias to resting-state fMRI functional connectivity (FC) not completely removed by denoising algorithms. Researchers studying traits associated with motion (e.g. psychiatric disorders) need to know if their trait-FC relationships are impacted by residual motion to avoid reporting false positive results. We devised Split Half Analysis of Motion Associated Networks (SHAMAN) to assign a motion impact score to specific trait-FC relationships. SHAMAN distinguishes between motion causing overestimation or underestimation of trait-FC effects. We assessed 45 traits from n = 7270 participants in the Adolescent Brain Cognitive Development (ABCD) Study. After standard denoising with ABCD-BIDS and without …

Uncovering The Pml::Rara Fusion In Cytogenetically Cryptic And Fish-Negative Acute Promyelocytic Leukemia-A Case Report And Comprehensive Literature Review, Busra Delikkaya, Jaime Eberle-Singh, Arianna Morton, Jerald Gong, Jinglan Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The PML::RARA fusion resulting from t(15;17) is the genetic hallmark of acute promyelocytic leukemia (APL), typically detected by cytogenetics and/or fluorescence in situ hybridization (FISH) studies. Rarely, APL patients present with normal cytogenetics and FISH findings, complicating diagnosis and delaying life-saving therapy. We report a 23-year-old male with clinical, morphologic and immunophenotypic features consistent with APL but negative for FISH studies. Despite prompt initiation of all-trans retinoic acid (ATRA) based on clinical suspicion, the patient succumbed to intracranial hemorrhage. Quantitative reverse transcriptase PCR (qRT-PCR) confirmed a long isoform PML::RARA fusion. A review of 34 published cytogenetics- and FISH-negative cases since …

Economics Of Corneal Cross-Linking For Keratoconus Treatment, Christopher J. Rapuano, Richard L. Lindstrom, Eric Donnenfeld, John P. Berdahl, Vance Thompson, David Kratochvil, John Carter

Wills Eye Hospital Papers

AIM: To optimize the real-world applicability of a health economic model estimating the cost-effectiveness of corneal cross-linking for the treatment of keratoconus in the United States.

MATERIALS AND METHODS: A previously reported discrete-event simulation (DES) model was adapted to reassess the cost-effectiveness of corneal cross-linking (CXL) from the US payer perspective. The simulation of keratoconus progression, which is a key driver of model outcomes, was remodeled to more accurately reflect the real-world relationship between age and the rate of disease progression. All costs were updated to reflect 2025 values. We simulated 4,000 eyes of 2,000 patients diagnosed with keratoconus to …

Comparison Of Authentic Urine N-Ethylpentedrone Metabolites To Predicted In Silico And In Vitro Human Hepatocyte Metabolism, Gloria Daziani, Omayema Taoussi, Diletta Berardinelli, Giulia Bambagiotti, Marilyn A. Huestis, Francesco P. Busardò, Jeremy Carlier

Institute of Emerging Health Professions Faculty Papers

Synthetic cathinones are the second most common class of substances belonging to the category of new psychoactive substances (NPS). N-ethylpentedrone (NEPD) self-administration was reported, making it important to elucidate its metabolic pathway to improve its detection. NEPD is often taken together with other substances; confidently identifying its intake is important for accurate toxicological analysis and understanding its toxicity. NEPD metabolism was studied following incubation with human hepatocytes and analysis by liquid chromatography-high-resolution mass spectrometry paired with Compound Discoverer software (Thermo Fisher Scientific). Prediction of possible metabolites was performed with the online software GLORYx. In vivo NEPD metabolism was evaluated by …

Growth Plate Skeletal Stem Cells And Their Actions Within The Stem Cell Niche, Natalie Kiat-Amnuay Cheng, Shion Orikasa, Noriaki Ono

Faculty, Staff and Student Publications

The growth plate is a specialized cartilage structure near the ends of long bones that orchestrates longitudinal bone growth during fetal and postnatal stages. Within this region reside a dynamic population of growth plate skeletal stem cells (gpSSCs), primarily located in the resting zone, which possess self-renewal and multilineage differentiation capacity. Recent advances in cell-lineage tracing, single-cell transcriptomics, and in vivo functional studies have revealed distinct subpopulations of gpSSCs, which are defined by markers such as parathyroid hormone-related protein (PTHrP), CD73, axis inhibition protein 2 (Axin2), forkhead box protein A2 (FoxA2), and apolipoprotein E (ApoE). These stem cells interact intricately …

Acute Care Of Patients With Moderate Respiratory Distress: Recommendations From An American College Of Emergency Physicians Expert Panel., Christopher W Baugh, Jim F Neuenschwander, Jesslyn Lenox, Jennifer Hoh, Kara Ward, Sara Muramoto, John Casey, Antonio Anzueto, Hajirah Ishaq, Jared Mount, Peter M Deblieux

Ambulatory and Primary Care Articles

INTRODUCTION: Patients with respiratory distress are frequently encountered in the emergency department (ED). Efforts to assess, initiate treatments, and stabilize these patients require a systematic and rapid response. Emergency physicians need a comprehensive and efficient approach for evaluating, treating, and managing patients presenting to the ED with moderate respiratory distress.

METHODS: The American College of Emergency Physicians convened an expert panel of academic and community emergency physicians, critical care specialists, respiratory therapists, hospitalists, and pharmacists to develop and subsequently disseminate consensus recommendations regarding the diagnosis and treatment of patients with moderate respiratory distress presenting to the ED.

RESULTS: A digital …

Genetic Susceptibility To Oral And Atherosclerotic Cardiovascular Diseases Based On Dental And Heart Score Studies, Mariana Bezamat, Dylan J Baxter, Nandita Mukhopadhyay, Anum Saeed, Lei Liu, Lisa De Las Fuentes, Betsy Foxman, John R Shaffer, Daniel W Mcneil, Steven E Reis, Mary L Marazita

2020-Current year OA Pubs

Periodontal disease and dental caries are two oral conditions that have been associated with atherosclerotic cardiovascular disease (ASCVD). However, it is unclear if one of the key mechanisms involved in this association could be a shared genetic susceptibility. The goal of this study was to explore whether there is an intersection of genetic loci among individuals with comprehensive oral examinations and subclinical ASCVD screenings. We leveraged data from oral and medical examinations obtained from the Dental and Heart Strategies Concentrating on Risk Evaluation (Dental/Heart SCORE) projects. Genome-wide association studies (GWASs) were performed independently in 552 participants (aged 45-75 years). The …

A Protein-Proximity Screen Reveals Ebola Virus Co-Opts The Mrna Decapping Complex Through The Scaffold Protein Edc4, Callie J Donahue, Aditi S Kesari, Naveen Thakur, Ling Wang, Sarah Hulsey Stubbs, Caroline G Williams, Sandhya Bharti Sharma, Cara D Kirby, Daisy W Leung, Uma K Aryal, Christopher F Basler, Douglas J Lacount, Robert A Davey

2020-Current year OA Pubs

The interaction of host and Ebola virus (EBOV) proteins is required for establishing infection. In this study, we use proximity-dependent biotinylation to identify cellular proteins that bind to EBOV proteins encoded by six of the seven viral genes. Hits are computationally mapped onto a human protein-protein interactome and annotated with viral proteins, confirming known EBOV-host protein interactions and revealing previously undescribed interactions and processes. This approach efficiently arranges proteins into functional complexes associated with single viral proteins. Focused characterization of interactions between EBOV VP35 and the mRNA decapping complex shows that VP35 binds the scaffold protein EDC4 through the C-terminal …

Lysosomal Lrrc8 Complex Impacts Lysosomal Ph, Morphology, And Systemic Glucose Metabolism, Ashutosh Kumar, Yonghui Zhao, Litao Xie, Rahul Chadda, John D Tranter, Ryan T Mikami, Nihil Abraham, Juan Hong, Ethan Feng, David R Rawnsley, Haiyan Liu, Gretchen Meyer, Abhinav Diwan, Rajan Sah, Et Al.

2020-Current year OA Pubs

The lysosome integrates anabolic signaling and nutrient sensing to regulate intracellular growth pathways. The leucine-rich repeat-containing 8 (LRRC8) channel complex forms a lysosomal anion channel and regulates PI3K-AKT-mTOR signaling, skeletal muscle differentiation, growth, and systemic glucose metabolism. Here, we define the endogenous LRRC8 subunits localized to a subset of lysosomes in differentiated myotubes. We show that LRRC8A affects leucine-stimulated mTOR; lysosome size; number; pH; expression of lysosomal proteins LAMP2, P62, and LC3B; and lysosomal function. Mutating an LRRC8A lysosomal targeting dileucine motif sequence (LRRC8A-L706A;L707A) in myotubes recapitulates the abnormal AKT signaling and altered lysosomal morphology and pH observed in LRRC8A …

Aggrebots: Configuring Ciliabots Through Guided, Modular Tissue Aggregation, Dhruv Bhattaram, Kian Golestan, Xuanshuo Zhang, Shihong Yang, Zhuowei Gong, Steven L Brody, Amjad Horani, Victoria A Webster-Wood, Amir Barati Farimani, Xi Ren

2020-Current year OA Pubs

Ciliated biobots (CiliaBots) are engineered tissues capable of self-actuated propulsion via exterior motile cilia. While correlations have been observed between CiliaBot motility and morphology, direct control of morphological features to deliver desired motility outcomes remains unexplored. Here, we describe the engineering of aggregated CiliaBots (AggreBots) to augment control over CiliaBot structural parameters and, consequently, motility patterns through guided, modular aggregation of human airway epithelial spheroids [referred to as CiliaBot building blocks (CBBs)]. Multi-CBB aggregation generated rod-, triangle-, and diamond-shaped AggreBots, altering tissue geometry without sacrificing surface cilia density or inter-CBB boundary fidelity. The further introduction of

Bedside Small-Bowel Challenge Vs. Fluoroscopic Series For Sbo: A Cost Effectiveness Analysis, Aravinda Krishna Ganapathy, Liam Cunningham, M Hunter Lanier, Selasi Nakhaima, Madelyn Thiel, Daniel Hoffman, Obeid Ilahi, David H Ballard, Vincent M Mellnick

2020-Current year OA Pubs

BACKGROUND: Small bowel obstruction (SBO) accounts for 12-16% of surgical hospital admissions and can lead to complications such as bowel ischemia. Traditional management requires transporting patients to the Radiology Department (RD) for a fluoroscopic small bowel series, occupying resources and time. This study evaluates the efficacy and efficiency of the Small Bowel Challenge Exam, a bedside alternative.

METHODS: A retrospective analysis was performed on 85 SBO patients from January 2018 to December 2023 at an academic tertiary care facility, comparing the traditional fluoroscopic series (37 patients) to the bedside Small Bowel Challenge Exam (48 patients). Key metrics analyzed included hospital …

Effects Of Olfactory Enrichment On Perioperative Neurocognitive Disorders In Elderly Patients Undergoing Orthopedic Surgery: A Study Protocol Of A Multi-Center Randomized Controlled Trial, Xinchun Mei, Jiayi Wang, Zihan Ni, Yanyan Wang, Binglei Zhao, Daniel I Sessler, Zhongcong Xie, Yuan Shen

Faculty, Staff and Student Publications

Background: Neurocognitive disorders are prevalent among older surgical patients, yet their underlying mechanisms and effective interventions remain largely unknown. Studies in rodents and patients suggest a connection between olfactory impairment and perioperative neurocognitive disorder (PND). Previous work in mice demonstrates that anesthesia and surgery can lead to both olfactory impairment and cognitive deficits. Olfactory enrichment, which is also referred to as olfactory training (i.e., daily exposure to multiple odorants), may prove helpful. For example, olfactory enrichment appears to reduce PND-like behaviors in mice, possibly by mitigating anesthesia- and surgery-induced reductions in olfactory receptor neurons. Additionally, olfactory enrichment increases the volume …

Comparison Of Imaging Based Single-Cell Resolution Spatial Transcriptomics Profiling Platforms Using Formalin-Fixed Paraffin-Embedded Tumor Samples, Nejla Ozirmak Lermi, Max Molina Ayala, Sharia Hernandez, Wei Lu, Khaja Khan, Alejandra Serrano, Idania Lubo, Leticia Hamana, Katarzyna Tomczak, Sean Barnes, Jinzhuang Dou, Qingnan Liang, Rti Team, Maria Gabriela Raso, Ximing Tang, Mei Jiang, Beatriz Sanchez-Espiridion, Annikka Weissferdt, John Heymach, Jianjun Zhang, Boris Sepesi, Tina Cascone, Anne Tsao, Mehmet Altan, Reza Mehran, Don Gibbons, Ignacio Wistuba, Cara Haymaker, Ken Chen, Luisa M Solis Soto

Faculty, Staff and Student Publications

Imaging-based spatial transcriptomics (ST) is evolving as a pivotal technology in studying tumor biology and associated microenvironments. However, the strengths of the commercially available ST platforms in studying spatial biology have not been systematically evaluated using rigorously controlled experiments. We use serial 5 μm sections of formalin-fixed, paraffin-embedded surgically resected lung adenocarcinoma and pleural mesothelioma samples in tissue microarrays to compare the performance of the ST platforms (CosMx, MERFISH, and Xenium (uni/multi-modal)) in reference to bulk RNA sequencing, multiplex immunofluorescence, GeoMx, and hematoxylin and eosin staining data. In addition to an objective assessment of automatic cell segmentation and phenotyping, we …

Fusion: A Web-Based Application For In-Depth Exploration Of Multi-Omics Data With Brightfield Histology, Samuel P Border, Sanjay Jain, Et Al.

2020-Current year OA Pubs

Spatial technologies examining the cell and tissue microenvironment at near single-cell resolution are revealing important molecular insights. However, few tools enable integrated, interactive analysis of spatial-omics with tissue morphology in the same functional tissue unit. Here, we present FUSION (Functional Unit State Identification in Whole Slide Images), a web-based platform for visualizing and analyzing spatial-omics data with high-resolution histology. FUSION provides workflows for assessing cell compositions, quantitative morphometrics, and comparative tissue analyses. We demonstrate applicability across spatial assays, including 10x Visium, Visium HD, 10x Xenium, Cell DIVE, and PhenoCycler, applied to healthy and diseased tissues from kidney, small intestine, lung, …

Evolutionary Loss Of An Antibiotic Efflux Pump Increases Pseudomonas Aeruginosa Quorum Sensing Mediated Virulence In Vivo, Sheryl E Fernandes, Humberto Ortega, Mylene Vaillancourt, Anna Clara M Galdino, Aleksandr Stotland, Kyu Shik Mun, Diane Aguilar, Yohei Doi, Janet S Lee, Elizabeth B Burgener, Jeffrey E Barrick, Jeffrey W Schertzer, Peter Jorth

2020-Current year OA Pubs

Antibiotic resistance is a threat to human health, yet recent work highlights how loss of resistance may drive pathogenesis in some bacteria. In two recent studies, we found that β-lactam antibiotics and nutrient stresses faced during infection selected for genetic inactivation of the Pseudomonas aeruginosa antibiotic efflux pump mexEFoprN. Unexpectedly, efflux pump mutations increased P. aeruginosa virulence during infection; however, neither the prevalence of mexEFoprN inactivating mutations in real human infections, nor the mechanisms driving increased virulence of efflux pump mutants are known. We hypothesized that human infection would select for virulence enhancing mutations. Using genome sequencing of clinical isolates, …

Health And Climate At Cop29: Advancing Integration And Bridging Research Gaps, Rupa R Patel, Yevheniia Varyvoda, Hiba Baroud, Philip J Landrigan, Aminata Kilungo

2020-Current year OA Pubs

Climate and health science is a rapidly growing, interdisciplinary field and holds importance during intergovernmental climate adaptation and mitigation policy negotiations. The 29th session of the Conference of the Parties (COP) to the United Nations Framework Convention on Climate Change (UNFCCC) convened stakeholders for negotiations and scientific discourse. This viewpoint presents insights gained by the authors' participation at COP29 focused on health and climate. The authors analyze the evolving integration of health into the UNFCCC process, dissect the contributions and the role of the Research and Independent Non‑Governmental Organizations (RINGOs), a constituency to achieve this endeavor, and identify the key …

Association Of Chronic Conditions With Bladder Health In Women: Cross-Sectional Results From The Rise For Health Study, Camille P Vaughan, Gerald Mcgwin, Jean F Wyman, Siobhan Sutcliffe, Diane K Newman, Ariana L Smith, Colleen M Fitzgerald, Todd Rockwood, James Griffith, Sheila Gahagan, Alayne D Markland, Prevention Of Lower Urinary Tract Symptoms (Plus) Research Consortium

2020-Current year OA Pubs

INTRODUCTION: Women with multiple chronic conditions are more likely than women without them to report lower urinary tract symptoms (LUTS); understanding the association of common and coexisting chronic conditions with bladder health across adulthood may inform prevention efforts.

METHODS: Data were collected from May 2022 through December 2023 from a regionally representative cohort of community-dwelling adult women in the US. Chronic conditions were assessed by self-report and bladder health, and LUTS were measured using validated questionnaires. Analyses were limited to women aged 40 years or older and included multivariable linear and logistic regression models, adjusted for age, body mass index, …

Synthesis, Structure-Activity Relationships, And Antitumor Activities Of Quinoxiline-Containing Inhibitors Of The Protein-Protein Interactions Between Transcription Coactivator Af9/Enl And Dot1l/Af4, Chandra Bhushan Mishra, Xin Li, Bala Krishna Moku, Sehun Kwak, Dnyaneshwar N Garad, Yongcheng Song

Faculty, Staff and Students Publications

Mixed lineage leukemia (MLL) gene rearrangements cause ~75% of acute leukemia in infants and 5-10% in children and adults with poor clinical outcomes. Protein-protein interactions (PPI) between frequent MLL fusion partners AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Sixty-seven quinoxiline compounds were synthesized and tested for their ability to inhibit such PPIs. Compounds 16, 17, 59 and 63 were found to be potent inhibitors with IC50 values of 0.35-1.5 μM. Structure-activity relationships are discussed. Potent inhibitors can suppress expression of MLL target genes Myc and Meis1 and selectively block proliferation of MLL-r and …