Digital Commons Network^™

Airway Management In Emergency Department Thoracotomy: A Narrative Review, Aaron J Lacy, Adam Liebendorfer, Sarah M Guess, Rami S Al-Aref, Anthony P Kronfli, Rachel E Armstrong, Amelia W Maiga, Alexander Bracey, Ryan N Barnicle

2020-Current year OA Pubs

INTRODUCTION: Emergency department thoracotomy (EDT) is a high-risk, life-saving intervention for patients in traumatic cardiac arrest. A critical component of EDT is airway management, typically performed by emergency physicians, yet formal guidance regarding optimal strategies remains limited. Airway management in this setting is uniquely complex due to concurrent anatomic injury, physiologic instability, and the procedural demands of thoracotomy.

DISCUSSION: Endotracheal intubation (ETI) during EDT presents multiple challenges. Anatomic difficulties may arise from facial or cervical trauma, restricted positioning, and the presence of cervical collars. Cognitive load is heightened by the chaotic, multidisciplinary environment, requiring strategies such as pre-briefing, checklists, and …

A Single-Cell Atlas Characterizes Dysregulation Of The Bone Marrow Immune Microenvironment Associated With Outcomes In Multiple Myeloma, William C Pilcher, Lijun Yao, Yizhe Song, Kazuhito Sato, Julia T Wang, Reyka G Jayasinghe, Jennifer A Foltz, Mark A Fiala, Chiang I-Ling, Julie Fortier, Michael Slade, Stephen T Oh, Michael P Rettig, John F Dipersio, Shaji Kumar, Ravi Vij, Li Ding, Et Al.

2020-Current year OA Pubs

Multiple myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We developed an Immune Atlas of MM by generating profiles of 1,397,272 single cells from the bone marrow (BM) of 337 newly diagnosed participants and characterized immune and hematopoietic cell populations. Cytogenetic risk-based analysis revealed heterogeneous associations with T cells of BM, with 17p13 deletion showing distinct enrichment of a type 1 interferon signature. The disease progression-based analysis revealed the presence of a proinflammatory immune …

The Impact Of Pasifikas In Medicine On Pacific Islander Medical Student Experiences, Devon Hori Harvey, Micah Ngatuvai, Siale Vaitohi, Paige E. Faasuamalie, Maegan Tupinio, Lisa H. Smith

Student Papers, Posters & Projects

BACKGROUND: Pacific Islanders experience significant health disparities. One contributing aspect to these disparities is the lack of racial concordance as Pacific Islanders are underrepresented in the U.S. physician work force. Several factors contribute to this underrepresentation including lack of support systems for Pacific Islander premed and medical students. Pasifikas in Medicine (PiM) is a recently established national student organization founded to provide support for Pacific Islander premed students, medical students, residents, fellows and attending physicians. This study seeks to understand the impact of PiM on medical student experiences.

METHODS: An anonymous survey was distributed to the PiM listserv and to …

Co-Developing Strategies For Leprosy Management In Malaysia: A Transdisciplinary Research Approach Involving Individuals Affected By Leprosy And Other Stakeholders, Norana Abdul Rahman, Vaikunthan Rajaratnam, Ruth Mh Peters, Marjolein Bm Zweekhorst, Pamela Wright Phd, Ms, Med, Rn, Cen, Karen Morgan, Mohamed Rusli Abdullah

Publications

Despite Malaysia's low leprosy prevalence, new cases continue to emerge in rural and Indigenous communities. National strategies often prioritise elimination and surveillance, while overlooking the needs and challenges of individuals affected by leprosy and those managing their care. This study employed a transdisciplinary research approach, guided by the Dialogue Model, to co-develop context-specific strategies to improve the lives of those affected through participatory engagement with both groups. Conducted across three high-burden states in Peninsular Malaysia, the research involved a desk review and stakeholder mapping, followed by 40 in-depth interviews with affected individuals and other stakeholders. These were complemented by a …

Gut Microbiome Metagenomics In Clinical Practice: Bridging The Gap Between Research And Precision Medicine, Henok Ayalew Tegegne, Tor C Savidge

Faculty, Staff and Students Publications

Gut microbiome metagenomics is emerging as a cornerstone of precision medicine, offering exceptional opportunities for improved diagnostics, risk stratification, and therapeutic development. Advances in high-throughput sequencing have uncovered robust microbial signatures linked to infectious, inflammatory, metabolic, and neoplastic diseases. Clinical applications now include pathogen detection, antimicrobial resistance profiling, microbiota-based therapies, and enterotype-guided patient stratification. However, translation into routine care is hindered by significant barriers including methodological variability, limited functional annotation, lack of bioinformatics standardization, and underrepresentation of global populations. This review synthesizes current translational strategies, emphasizing the need for hypothesis-driven designs, multi-omic integration, longitudinal and multi-center cohorts, and mechanistic validation. …

Eata Mediated Degradation Of Intestinal Mucus Is Species-Specific And Driven By Muc2 Structural Features, Sergio Trillo-Muyo, Brendan Dolan, Frida Svensson, Tim J Vickers, Liisa Arike, Maria-Jose García-Bonete, Jenny K Gustafsson, Mathias I Nielsen, Hans H Wandall, James M Fleckenstein, Gunnar C Hansson, Sjoerd Van Der Post

2020-Current year OA Pubs

Enterotoxigenic Escherichia coli (ETEC) infections are a leading cause of diarrheal illness, responsible for an estimated 100,000 deaths annually. ETEC pathogenesis is driven by various virulence factors, including toxins, adhesins, and noncanonical factors such as the protease EatA. The first line of host defense against intestinal pathogenic bacterial infections is the protective intestinal mucus layer. Here, we demonstrate the mechanism by which EatA degrades the core mucus component MUC2, thereby facilitating access to the epithelial cell surface and promoting infection. We identify the specific cleavage site region localized at the C-terminal of MUC2. EatA's protease activity depends on the interaction …

Membrane Il-18 Identifies A Human Macrophage Subset With Distinct Proteomic And Functional Traits, Chiara Vitale, Marco Colonna, Et Al.

2020-Current year OA Pubs

This study contributes to the characterization of human macrophages in normal and pathological conditions such as cancer. We characterized a macrophage population expressing membrane-associated IL-18 (mIL-18) that shows peculiar proteomic, phenotypic, ultrastructural, and functional properties. mIL-18+ macrophages exhibit increased levels of key proteins involved in pathogen recognition, activation, migration, and endocytosis. They also display specialized functions in vesicle and actin filament transport and lipid metabolism, and have typical mitochondrial traits. Importantly, mIL-18+ cells dominate the peritoneal fluid of adult cancer patients and are present in the bone marrow of children with neuroblastoma. They express high levels of TREM2 but display …

Mental Health And Beliefs About Abortion Access Following Changes To Reproductive Healthcare Laws In 2022: Findings From Oklahoma, Munjireen Sifat, Laili K. Boozary, Tina N. Le, Julia Mcquoid, Brittany Zaring-Hinkle, Sarah Tonkin, Lizbeth Benson, Bingjing Mao, Motolani Ogunsanya, Ruosi Shao, Amy M. Cohn, Allyson Shortle, Darla E. Kendzor

Department of Medical Oncology Faculty Papers

INTRODUCTION: A secondary analysis of cross-sectional survey data was conducted to characterize beliefs about abortion access in Oklahoma, measure stress associated with the overturn of Roe vs. Wade (2022), and evaluate the potential relationship between post-Roe stress (PR stress) and mental health.

METHODS: From August through September 2022, adult Oklahomans (N = 1793) were surveyed about their sociodemographic characteristics, beliefs about abortion access, frequency of past-month stress related to the overturn of Roe vs. Wade, and mental health. Beliefs about abortion access were characterized overall and within sociodemographic groups. The relationship between PR stress and mental health was evaluated, and …

Chemotherapy-Induced Adipo-Lineage Cell Senescence Drives Bone Loss, Ganesh Kumar Raut, Taylor Malachowski, Anupama Melam, Renata Ramalho-Oliveira, Taylor Holt, Xianmin Luo, Zhangting Yao, Douglas V Faget, Qihao Ren, David G Denardo, Sheila A Stewart

2020-Current year OA Pubs

Chemotherapy-induced bone loss is a debilitating and common side effect of cancer treatment, though its underlying mechanisms remain poorly understood. Here, we show that, despite the systemic administration of chemotherapy, cellular senescence is restricted to bone marrow adipo-lineage cells specifically Cxcl12-abundant reticular (CAR) cells and bone marrow adipocytes (BMAds). Induction of senescence within these populations promotes RANK ligand (RANKL)-mediated osteoclastogenesis, leading to significant bone loss. Notably, we find that inhibition of the p38MAPK-MK2 pathway suppresses the senescence-associated secretory phenotype (SASP), including RANKL production abrogating bone loss. Furthermore, treatment with the senolytic combination dasatinib and quercetin (D + Q) selectively eliminates …

Batf2 Is A Glutamine-Responsive Tumour Suppressor Required For Type-I Interferon-Dependent Anti-Tumour Immunity, Wang Gong, Hülya F Taner, Yuesong Wu, Yumin He, Xingwu Zhou, Zaiye Li, Xin Hu, Charisse Ursin, Kala Chand Debnath, Kohei Okuyama, Qiang Hu, Christopher R Donnelly, Felipe Nör, Chamila D Perera, Emily Bellile, Arash Yunesi, Zhiqian Zhai, Mei Zhao, Wanqing Cheng, Zackary R Fitzsimonds, Luke Broses, Jiaqian Li, Shadmehr Demehri, Deepak Nagrath, Gregory T Wolf, Andrew G Sikora, Yanbao Yu, Haitao Wen, Lei Wei, Steven B Chinn, Jeffrey N Myers, Shizuo Akira, Yuying Xie, James J Moon, Yu Leo Lei

Faculty, Staff and Student Publications

Recent evidence highlights the significance of a new type of tumour suppressors, which are not frequently mutated but inhibited by metabolic cues in cancers. Here, we identify BATF2 as a tumour suppressor whose expression is epigenetically silenced by glutamine in Head and Neck Squamous Cell Carcinomas (HNSCC). BATF2 correlates with type-I interferon and Th1 signatures in human HNSCC, with correlation coefficients even stronger than those of the positive control, STING. The phosphorylation of BATF2 at serine 227 promotes the oligomerization of STING. BATF2 deficiency or high glutamine levels result in higher oxygen consumption rates and metabolic profiles unfavorable for …

The Concise Guide To Pharmacology 2025/26: Catalytic Receptors, Stephen P. H. Alexander, Doriano Fabbro, Chloe J. Peach, Alasdair J. Gibb, Eamonn Kelly, Alistair A. Mathie, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Christopher Southan, Jamie A. Davies, Annie Beuve, Peter Brouckaert, Clare Bryant, John C. Burnett, Richard W. Farndale, Andreas Friebe, John Garthwaite, Adrian J. Hobbs, Gavin E. Jarvis, Laura Kilpatrick, Doris Koesling, Michaela Kuhn, Birgit Leitinger, David Macewan, Tom P. Monie, Lincoln R. Potter, Michael Russwurm, Harald H. H. W. Schmidt, Johannes-Peter Stasch, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The Concise Guide to Pharmacology 2025/26 marks the seventh edition in this series of biennial publications in the British Journal of Pharmacology. Presented in landscape format, the guide provides a comparative overview of the pharmacology of drug target families. The concise nature of the Concise Guide refers to the style of presentation, being clear, accessible, and well-structured, rather than the scope of the content, which spans approximately 500 pages. The Concise Guide summarises the key pharmacological properties of around 1900 human drug targets, and nearly 7000 interactions, involving around 4400 ligands. While the content is a substantially condensed version of …

A Spatiotemporal Model Of Cxcl10 As A Master Regulator Of Immune Evasion And Metastasis In Osteosarcoma, Benjamin B Gyau, Tsz-Kwong Man

Faculty, Staff and Students Publications

The C-X-C motif chemokine ligand 10 (CXCL10) is implicated in the progression of osteosarcoma (OS), the most aggressive pediatric bone malignancy. However, its role often presents a profound clinical paradox: although high circulating levels are strongly linked to poor prognosis, its canonical function is to recruit anti-tumor immune cells. This review unravels these contrasting roles by proposing a novel spatiotemporal model. We argue that in the early stages, immune-evading OS cells initiate the formation of a pre-metastatic niche (PMN) in the lungs, creating a localized inflammatory environment that becomes the primary source of elevated circulating CXCL10. As the disease progresses, …

Distinct Populations Of Lung Capillary Endothelial Cells And Their Functional Significance, Joel James, Dan Yi, Zhiyu Dai, Et Al.

2020-Current year OA Pubs

The role of the lung's microcirculation and capillary endothelial cells in normal physiology and the pathobiology of pulmonary diseases is obviously vital. The recent discovery of molecularly distinct aerocytes and general capillary (gCaps) endothelial cells by single-cell transcriptomics (scRNAseq) advanced the field in understanding microcirculatory milieu and cellular communications. However, increasing evidence from different groups indicated the possibility of a more heterogeneous nature of lung capillaries. Therefore, we investigated enriched lung endothelial cells by scRNAseq and identified five novel populations of gCaps with distinct molecular signatures and roles. Our analysis suggests that two major populations of gCaps that express Scn7a(Na

Using A Heuristic Tool To Improve Symptom Self-Management In Adolescents And Young Adults With Cancer: Protocol For A Randomized Controlled Trial., Suzanne Ameringer, Grace Hodges, R K Elswick, Lauri Linder, Catherine Fiona Macpherson, Kristin Stegenga

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Adolescents and young adults (AYAs) with cancer experience multiple distressing symptoms during treatment, yet few developmentally relevant resources have been developed to help them self-manage their symptoms. Empowering patients to have a more active role in self-management during cancer treatment may lessen their symptom severity and distress.

OBJECTIVE: The aim of this study is to test an intervention designed to improve symptom self-management, the Computerized Symptom Capture Tool (C-SCAT), by helping AYAs understand their unique symptom experience and discuss it with their health care providers.

METHODS: We are conducting a multisite, 2-group randomized controlled trial to evaluate the effects …

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

Faculty, Staff and Student Publications

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

Predictive Modeling Of Hematoma Expansion From Non-Contrast Computed Tomography In Spontaneous Intracerebral Hemorrhage Patients, Natasha Ironside, Shinjini Kundu, Et Al.

2020-Current year OA Pubs

Hematoma expansion is a consistent predictor of poor neurological outcome and mortality after spontaneous intracerebral hemorrhage (ICH). An incomplete understanding of its biophysiology has limited early preventative intervention. Transport-based morphometry (TBM) is a mathematical modeling technique that uses a physically meaningful metric to quantify and visualize discriminating image features that are not readily perceptible to the human eye. We hypothesized that TBM could discover relationships between hematoma morphology on initial Non-Contrast Computed Tomography (NCCT) and hematoma expansion. 170 spontaneous ICH patients enrolled in the multi-center international Virtual International Trials of Stroke Archive (VISTA-ICH) with time-series NCCT data were used for …

Clair3-Rna: A Deep Learning-Based Small Variant Caller For Long-Read Rna Sequencing Data, Zhenxian Zheng, Xian Yu, Lei Chen, Yan-Lam Lee, Cheng Xin, Angel On Ki Wong, Miten Jain, Rupesh K Kesharwani, Fritz J Sedlazeck, Ruibang Luo

Faculty, Staff and Students Publications

Variant calling with long-read RNA sequencing (lrRNA-seq) helps to analyze full-length isoforms and gene expression but is complicated by high error rates, transcript diversity, RNA editing events, etc. Here, we propose Clair3-RNA, the first deep learning-based variant caller tailored for lrRNA-seq data. Building upon Clair series' pipelines, Clair3-RNA enhances lrRNA-seq variant calling using optimized techniques, such as uneven coverage normalization, refined training data, editing site discovery, and haplotype phasing to enhance performance. Clair3-RNA supports various platforms, including PacBio, ONT complementary DNA sequencing (cDNA), and ONT direct RNA sequencing (dRNA). Clair3-RNA achieved a ~ 91% SNP F1-score on the ONT platform …

Implementation Of Single-Pill Combination Medication For Hypertension Treatment By Nonphysician Health Care Workers At Primary Healthcare Facilities In Nigeria: An Explanatory Mixed Methods Study, Emmanuel I Okpetu, Chisom Obiezu-Umeh, Boni M Ale, Abigail S Baldridge, Rosemary C B Okoli, Grace J Shedul, Gabriel L Shedul, Nanna R Ripiye, Ikechukwu A Orji, Lisa R Hirschhorn, Dike B Ojji, Mark D Huffman, Hypertension Treatment In Nigeria Program Investigators

2020-Current year OA Pubs

BACKGROUND: Single-pill combination (SPC) therapy improves hypertension control; however, its implementation in primary care settings remains limited. In Nigeria, there is insufficient evidence on factors influencing SPC uptake, particularly from the perspective of healthcare workers (HCWs). This study examined the implementation of SPC medications for hypertension treatment by nonphysician HCWs at primary healthcare facilities (PHCs) in Nigeria.

METHODS: An explanatory sequential mixed methods study was conducted, building on a cluster randomized controlled trial embedded within the Hypertension Treatment in Nigeria Program. The trial compared SPC medications with free-equivalent combination therapies across 60 PHCs (January-June 2021). A subsequent qualitative component (September-December …

Society For Immunotherapy Of Cancer: Standards For Reporting Of Multiplex Immunohistochemistry/Immunofluorescence Assays (Stormi), Sam Sater, Carlo B Bifulco, Jaime Rodriguez-Canales, Joe Yeong, Guray Akturk, Michael Angelo, Carmen Ballesteros-Merino, Peter Bankhead, Subham Basu, Jorge M Blando, Saska Brajkovic, Marco Cassano, Benjamin J Chen, Ahmet F Coskun, Tricia R Cottrell, Carlos E De Andrea, Robin H Edwards, Colt Egelston, Logan L Engle, Marc S Ernstoff, Rong Fan, Michael Feldman, Bernard A Fox, Jerome Galon, Robyn Gartrell, Sacha Gnjatic, Benjamin F Green, James L Gulley, Anne Hellebust, Stephen Hewitt, Travis J Hollmann, Lucas A Horn, William J Howat, Clifford C Hoyt, Shawn M Jensen, Arutha Kulasinghe, Wiem Lassoued, Steven Lott, James Mansfield, Sebastian Marwitz, George Netto, David B Page, Edwin Parra, David L Rimm, Scott J Rodig, Roberto Salgado, Denis Schapiro, Kurt A Schalper, Joel C Sunshine, Michael J Surace, Alexander S Szalay, Magdalena Thurin, Jose C Villasboas, Keith Wharton, Ignacio I Wistuba, Jennifer H Yearley, Yinyin Yuan, Geroge Zaki, James Ziai, Janis M Taube

Faculty, Staff and Student Publications

Multiplex immunofluorescence and immunohistochemistry (mIF/IHC) are increasingly employed antibody-based technologies that use tissue sparingly and facilitate the detection of co-localized or neighboring biomarkers. Specifically, these platforms enable spatial analyses of the tumor microenvironment as well as extended applications, for example, describing normal tissue anatomy, autoimmunity, infectious diseases, etc. mIF/IHC has greatly enhanced biomarker discovery efforts, and a growing number of studies suggest superiority to traditional IHC. Standardization of staining approaches, reporting of image analysis strategies and resultant data is critical for facilitating cross-study comparisons, validation, deployment, and generalization of findings. To address this challenge, The Society for Immunotherapy of Cancer …

A Protein Complex In The Extreme Distal Tip Of Vertebrate Motile Cilia Controls Their Organization, Length, And Function, Juyeon Hong, Jiehong Pan, Amjad Horani, Steven L Brody, Et Al.

2020-Current year OA Pubs

The beating of cilia on multi-ciliated cells (MCCs) is essential for normal development and homeostasis in animals. But while the structure and function of basal bodies and axonemes have received significant attention recently, the distal tips of MCC cilia remain relatively poorly defined. Here, we characterize the molecular organization of the distal tip of vertebrate MCC cilia, characterizing two distinct domains occupied by distinct protein constituents. Using frog, mouse, and human MCCs, we find that two largely uncharacterized proteins, Ccdc78 and Ccdc33, occupy a previously undefined region at the extreme distal tip, and these are required for the normal organization …

Trait-Like Visual Cortical Hyperactivity In Trait Anxiety, Zhaohan Wu, Yuqi You, Joshua A Brown, Raymond J Dolan, Wen Li

Faculty, Staff and Student Publications

Sensory processing varies across individuals, with some traits-particularly sensory hypersensitivity to basic non-valenced stimuli-linked to emotional traits and psychiatric risk. Traditional accounts attribute this sensory-emotion linkage to limbic or prefrontal modulation, but empirical support is limited. Growing evidence suggests sensory cortex itself flexibly encodes value beyond labeled-line analysis. Across four high-density EEG experiments with multi-wave assessments, we identified reliable visual cortical hyperactivity in high trait anxiety. The effect emerged as early as 46 ms, localized to V1/V2, and was specific to the parvocellular pathway. It was reproducible across arousal states, stimulus valence, extended intervals, and paradigms, and evident for both …

Single-Nucleus Multiomics Reveals The Disrupted Regulatory Programs In Three Brain Regions Of Sporadic Early-Onset Alzheimer’S Disease, Andi Liu, Citu Citu, Nitesh Enduru, Xian Chen, Chia-Hao Tung, Tirthankar Sinha, Sofia E Sepulveda, Astrid M Manuel, Damian Gorski, Brisa S Fernandes, Meifang Yu, Paul E Schulz, Lukas M Simon, Claudio Soto, Zhongming Zhao

Faculty, Staff and Student Publications

Sporadic early-onset Alzheimer’s disease (sEOAD) represents a substantial but less-studied subtype of Alzheimer’s disease (AD). Here, we generated a single-nucleus multiome atlas derived from the postmortem prefrontal cortex, entorhinal cortex, and hippocampus of nine individuals with or without sEOAD. Comprehensive analyses were conducted to delineate cell type–specific transcriptomic changes and linked candidate cis-regulatory elements (cCREs) across brain regions. We prioritized eight conservative transcription factors in glial cells in multiple brain regions, including RFX4 in astrocytes and IKZF1 in microglia, which are implicated in regulating sEOAD-associated genes. Moreover, we identified the top 25 altered intercellular signaling between glial cells …

Adaptive Neuromodulation Dialogues: Navigating Current Challenges And Emerging Innovations In Neuromodulation System Development, Frederik Lampert, Matthew R Baker, Michael A Jensen, Amir H Ayyoubi, Christian Bentler, Jessica L Bowersock, Rosana Esteller, Jeffrey A Herron, Graham W Johnson, Daryl R Kipke, Christopher K Kovach, Vaclav Kremen, Filip Mivalt, Joseph S Neimat, Theoden I Netoff, Enrico Opri, Alexander Rockhill, Joshua M Rosenow, Kristin K Sellers, Nathan P Staff, Chandra Prakash Swamy, Ashwin Viswanathan, Gerwin Schalk, Timothy Denison, Dora Hermes, Nuri F Ince, Peter Brunner, Gregory A Worrell, Kai J Miller

Faculty, Staff and Students Publications

Adaptive neuromodulation systems and implantable brain-computer interfaces have made notable strides in recent years, translating experimental prototypes into clinical applications and garnering substantial attention from the public. This surge in interest is accompanied by increased scrutiny related to the safety, efficacy, and ethical implications of these systems, all of which must be directly addressed as we introduce new neurotechnologies. In response, we have synthesized the insights resulting from discussions between groups of experts in the field and summarized them into five key domains essential to therapeutic device development: (1) analyzing current landscape of neuromodulation devices and translational platforms (2) identifying …

Surgical Revision In The Presence Of An S. Aureus Infection Increases Virulence Factor Expression And Activates A Multi-Tissue Inflammatory Response, Carly J. Smith, Arianna J. Moniodes, Amanda R. Watkins, Autumn G. Melvage, Thomas P. Thompson, Eirene Choi, Abigail A. Lucas, Brendan F. Gilmore, Thomas P. Schaer, Noreen J. Hickok, Theresa A. Freeman

Department of Orthopaedic Surgery Faculty Papers

Replacing implanted medical hardware due to infection often requires one or more revision surgeries. Each surgery triggers a tissue injury response and disrupts the established bacterial biofilm. However, the complex tissue response to reinjury and biofilm disturbance is not well understood. Our results show that with an existing infection, immunological niches such as the bone marrow, lymph nodes, and circulating blood further upregulate pro-inflammatory programs in response to revision. Rather than reducing bacterial burden, this heightened inflammation provokes virulence factor expression and tissue damage, including bone osteolysis and muscle fibrosis. While muscle fibrosis appears transient and begins resolving by 14 …

Investigating The Polygenic Relationship Between Heavy Cannabis Use And Schizophrenia In The All Of Us Research Program, Isabelle Austin-Zimmerman, Hayley H A Thorpe, John J Meredith, Jibran Y Khokhar, Tian Ge, Marta Di Forti, Arpana Agrawal, Emma C Johnson, Sandra Sanchez-Roige

2020-Current year OA Pubs

BACKGROUND: Decades of research have identified a strong association between heavy cannabis use and schizophrenia (SCZ), with evidence of correlated genetic factors. However, many studies on the genetic relationship between cannabis use and psychosis have lacked data on both phenotypes within the same individuals, creating challenges due to unmeasured confounding. We aimed to address this by using multimodal data from the All of Us Research Program, which contains genetic data as well as information on SCZ diagnosis and cannabis use.

METHODS: We tested the association between cannabis use disorder (CUD) and SCZ polygenic scores (PGSs) with SCZ and heavy cannabis …

Adjudicated Cardiovascular Events In Patients With Covid-19: Association With Vaccination Status And Changes Over Time, Behnood Bikdeli, Darsiya Krishnathasan, Antoine Bejjani, Candrika D. Khairani, Nada Hamade, Umberto Campia, Julia Davies, Nicole Porio, Ali Assi, Andre Armero, Anthony Tristani, Marcos D. Ortiz-Rios, Victor Nauffal, Zaid I. Almarzooq, Eric Q. Wei, Bridget Mcgonagle, Mariana Pfeferman, Sina Rashedi, Alyssa Sato, Giovanni Scimeca, Valeria Zuluaga-Sánchez, Mehrdad Zarghami, Aditya Achanta, Sirus Jesudasen, Bruce C. Tiu, Geno J. Merli, Orly Leiva, John Fanikos, Aditya M. Sharma, Samantha M. Rizzo, Ruth B. Morrison, Alec Vishnevsky, Shiavax J. Rao, Sivan Naveh, Abdelghani El Rafei, James Welker, Marc P. Bonaca, Brett J. Carroll, Samuel Z. Goldhaber, Zhou Lan, Gregory Piazza, The Corona-Vte Network Investigators

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Patients with COVID-19 are at risk of thrombotic and cardiovascular complications. Existing risk estimates derive from early COVID-19 experiences. More recent event rates, temporal trends, and the association between vaccination status and cardiovascular outcomes remain unclear.

METHODS: The CORONA-VTE Network (COVID-19 Registry to Assess Frequency, Risk Factors, Management, and Outcomes of Arterial and Venous Thromboembolic Complications) multicenter registry included patients with COVID-19 from March 2020 to February 2024. A composite of venous and arterial thrombotic events and a composite of adjudicated cardiovascular events were assessed at 90 days after COVID-19 diagnosis. Time-to-first-event analyses were stratified by inpatients and outpatients …

Accurate Imputation Of Pathway-Specific Gene Expression In Spatial Transcriptomics With Pasta, Ruoxing Li, Peng Yang, Mauro Di Pilato, Jianjun Zhang, Christopher R Flowers, Lulu Shang, Ziyi Li

Faculty, Staff and Student Publications

Mapping the entire transcriptome at single-cell resolution under its natural spatial context is essential for investigating the oncogenesis and progression of diseases. The recently emerged targeted in-situ technologies retain the spatial organization of cells at high resolution, although they remain limited in the number of genes that can be simultaneously measured. To overcome this obstacle, numerous computational methods have been developed to predict unmeasured gene expression in spatial transcriptomics data by leveraging scRNA-seq data. Most of these methods focus on the expression of individual genes and usually generate highly variable predictions. In this study, we introduce PASTA (PAthway-oriented Spatial gene …

A Proteogenomic Gene Signature Defines Prognostic Subgroups Highlighting Pi3k/Akt/Mtor Signaling Pathway As A Therapeutic Vulnerability In Myeloid Malignancies, Fan He, Shuyang Lin, Bei Gao, Varun Ramesh, Alexander B Kim, Tim Kong, Daniel A C Fisher, Christopher T Letson, Molly Brakhane, Mary Fulbright, Yanbo Yu, Marco Sardiello, Jorge Di Paola, Stephen M Sykes, Stephen T Oh

2020-Current year OA Pubs

INTRODUCTION: Myeloid malignancies, including acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN), exhibit overlapping pathophysiology. Chronic MPNs can transform into secondary AML (sAML), which is associated with poor prognosis and limited treatment options. However, the process and prognostic significance of leukemic transformation remain incompletely understood.

METHOD: Through a two-sample bidirectional Mendelian randomization (MR) analysis, we showed that genetic liability to MPN significantly predicts the risk of developing AML, establishing MPN as the precursor to leukemia. To identify mediators of this risk, we integrated population-level plasma proteomics data, identifying 55 proteins associated with MPN. Upon integrative analysis with the BEAT-AML cohort, …

Structural Basis For Genome-Wide Site-Specific Dna Recognition By Nuclear Factor Ia, Ci Zhu, Ding Xiao, Zhipu Luo, Jie Zhang, Shuang Liu, Yueyu Wang, Xi Chen, Hejin Xiao, Xiaofeng Li, Juyu Tang, Xianyang Fang, Jie Shen, He Song

2020-Current year OA Pubs

Nuclear Factor IA, a member of the long-studied Nuclear Factor I family of DNA-binding proteins, plays pivotal roles in development and metabolism. Dysregulation or loss of Nuclear Factor IA is associated with severe neurological defects in humans and disruptions in fatty acid metabolism linked to conditions such as osteoarthritis. Despite extensive study, the DNA recognition mechanism of Nuclear Factor I family proteins remains unresolved. Previous studies have proposed that these proteins dimerize via their DNA-binding domains to bind TGGCA-containing dyad sequences. In this study, we demonstrate that both full-length Nuclear Factor IA and its isolated DNA-binding domain are monomeric in …

A Long Non-Coding Rna Leat1 Mediates The Hormone Responsiveness Of Efnb2 During Male Urogenital Development, Deidre Mattiske, Pascal Bernard, Paul E Gradie, Richard R Behringer, Paul A Overbeek, Rachel J O'Neill, Tiffany Phillips, Melanie Stewart, Neil Youngson, Gerard Tarulli, Andrew J Pask

Faculty, Staff and Students Publications

The novel long non-coding RNA (lncRNA) Leat1 is extraordinarily conserved in both its location (syntenic with EfnB2, an essential gene in anogenital patterning) and sequence. Here we show that Leat1 is upregulated following the production of testosterone from the developing testis in mice and interacts with EfnB2, positively regulating its expression. Leat1 expression is suppressed by estrogen, which in turn suppresses the expression of EfnB2. Moreover, the loss of Leat1 leads to reduced EfnB2, resulting in a severe hypospadias phenotype. The human LEAT1 gene is also co-expressed with EFNB2 in the developing human penis, suggesting a conserved function for this …