Digital Commons Network^™

Dna Methyltransferase Inhibitors In Hematological Malignancies And Solid Tumors, Valentin Wenger, Guillermo Garcia-Manero, Robert Zeiser, Michael Lübbert

Faculty, Staff and Student Publications

Epigenetic modifications such as DNA methylation play a fundamental role in oncogenesis and the progression of neoplasms neoplasias. DNA methyltransferase inhibitors (DNMTi) constitute a family of therapeutic agents that impede the methylation at the 5-position on cytosine nucleotides, thereby modulating the epigenetic regulation of tumor suppressor genes, oncogenes, and other key regulatory genes. The first-generation DNMTi azacitidine and decitabine have demonstrated substantial efficacy in the treatment of medically non-fit, older patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy (IC), by virtue of their favorable safety profile. Despite these clinical achievements, however, single-agent DNMTi treatment …

Bdcd: A Comprehensive Brain Disease Cell-Cell Communication Database, Xinyi Liu, Citu Citu, Gang Qu, Wendao Liu, Nitesh Enduru, Andi Liu, Chia-Hao Tung, Zhongming Zhao

Faculty, Staff and Student Publications

Dysregulated cell–cell communication (CCC) is increasingly recognized as a driver of brain disease pathology, contributing to neuroinflammation, synaptic dysfunction, and neurodegeneration. Nevertheless, existing resources remain limited in brain specificity, regional coverage, and functional annotation. To address this gap, we develop the Brain Disease Cell-cell communication Database (BDCD), the first comprehensive resource focused on CCC networks across major brain diseases. BDCD integrates 38 manually curated datasets, comprising 8 519 425 single cells from single-cell RNA-seq studies and 140 744 spots from spatial transcriptomic maps, spanning 14 brain regions and 13 canonical cell types covering Alzheimer’s disease, Parkinson’s disease, schizophrenia, bipolar disorder, …

Bridging Hypoxia And Vision Loss: The Emerging Role Of Connexins In Local And Systemic Eye Diseases, Xianping Zhang, Yalong Cheng, Jean X Jiang, Yuting Li

Faculty, Staff and Student Publications

Hypoxic eye diseases represent a pivotal yet often underappreciated contributor to the onset and progression of many retinal disorders. When hypoxia persists or exceeds the tissue's compensatory capacity, it triggers pathological retinal neovascularization, blood-retinal barrier disruption, and neuronal apoptosis, ultimately resulting in irreversible visual impairment. Connexins (Cxs) form gap junction channels and hemichannels and regulate retinal cell proliferation, differentiation, and survival, thereby playing a central regulatory role in the pathogenesis of hypoxic ocular diseases. In addition to gap junctions, Cx hemichannels promote transmission of molecules between intra- and extracellular environments, further influencing retinal homeostasis under hypoxic stress. This review synthesizes …

Epilepsy Disease Classification: A Community Effort To Enhance The Mondo Disease Ontology, Nicole Vasilevsky, Sarah Gehrke, Kathleen Mullen, Subit Barua, Ian Braun, Tobias Brünger, Curtis Coughlin, Alina Ivaniuk, Daniel Korn, Dennis Lal, Stephanie Marsh, Elaine O'Loughlin, Daniel Olson, Yousif Shwetar, Christalena Sofocleous, Vanessa Vogel-Farley, Heidi Grabenstatter, Melissa Haendel, Christopher Mungall, Sabrina Toro

Faculty, Staff and Student Publications

Motivation: Epilepsy is a diverse group of neurological disorders affecting over 50 million people worldwide. While common epilepsy types are well studied, rare epilepsies-often severe and genetically complex-pose significant challenges in diagnosis, research, and treatment. Accurate and interoperable etiology and disease classifications are critical for improving data sharing, supporting clinical decision-making, and advancing rare disease research.

Results: To enhance the accuracy of epilepsy-related disease concept representation within the Mondo Disease Ontology (Mondo), we conducted a series of expert-driven workshops in collaboration with the team from the Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP). Specialists in epileptology, genetics, neurodevelopment, biomedical …

Whole Genome Sequence Analysis Of Pulmonary Function And Copd In 44,287 Multi-Ancestry Participants, Wonji Kim, Lucinda Antonacci-Fulton, Susan K Dutcher, Et Al.

2020-Current year OA Pubs

BACKGROUND: Whole genome sequence (WGS) data in multi-ancestry samples supports discovery of low-frequency or population-specific genetic variants associated with chronic obstructive pulmonary disease (COPD) and lung function.

RESULTS: We performed single variant, structural variant, and gene-based analysis of pulmonary function (FEV

CONCLUSIONS: Large-scale multi-ancestry WGS analysis improves variant discovery and fine-mapping resolution for lung function and COPD and highlights biologically relevant genes and pathways.

The Impact Of Indigenous American-Like Ancestry On The Risk Of Acute Lymphoblastic Leukemia In Hispanic/Latino Children, Jalen Langie, Tsz Fung Chan, Wenjian Yang, Alice Y Kang, Libby Morimoto, Daniel O Stram, Nicholas Mancuso, Xiaomei Ma, Catherine Metayer, Philip J Lupo, Karen R Rabin, Michael E Scheurer, Joseph L Wiemels, Jun J Yang, Adam J De Smith, Charleston W K Chiang

Faculty, Staff and Students Publications

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with Hispanic/Latino children having a higher incidence of ALL than other racial/ethnic groups. Among the genetic variants previously implicated in ALL risk, a number of them were found to be enriched in Indigenous American (IA)-like ancestries and inherited by many Hispanic/Latino individuals. However, due to potential confounding from environmental factors, the association between IA-like ancestry and risk for ALL has remained unclear. In this study, we characterized the impact of IA-like ancestry on overall ALL risk and on the frequency and effect size of known risk alleles, while accounting for …

The Effects Of Bone-Remodeling Therapy On Survival, Pain, And Skeletal Related Events In The Setting Of Renal Cell Carcinoma With Bone Metastases: A Multicenter Investigation From A Large Global Health Research Network (Trinetx), Brian H. Im, Kevin K. Zarrabi, Aaron R. Hochberg, Mihir M. Shah, Md, James R. Mark, Joseph K. Izes, Patrick T. Gomella, Costas D. Lallas, Leonard G. Gomella, Adam R. Metwalli

Department of Urology Faculty Papers

INTRODUCTION: Renal cell carcinoma (RCC) is the most common renal malignancy-bone metastases (BM) are indicative of aggressive disease with a poor prognosis. We aim to evaluate the overall mortality of patients with RCC with and without BM, and to elucidate the effects of bone-remodeling therapy on mortality, incidence of skeletal-related events, and opioid usage patterns in patients with BM.

METHODS: A retrospective cohort study was conducted using TriNetX, a large, collaborative network sourced from electronic medical records of over 110 million patients from over 100 healthcare organizations. All adult patients with RCC and RCC with BM were queried.

RESULTS: There …

The Impact Of Skin Tone On Performance Of Pulse Oximeters Used By Nhs England Covid Oximetry @Home Scheme: Measurement And Diagnostic Accuracy Study, Exakt Study Investigators, Daniel S Martin, James C Doidge, Doug Gould, Tasnin Shahid, Alex Cowden, Walton N Charles, Amelia Francis Johnson, Roger Garrett, Catherine Mbema, Olusegun Olusanya, Eugene Healy, Kathryn Rowan, Paul Mouncey, David A Harrison

Peninsula Medical School

OBJECTIVES: To assess the impact of skin tone on the measurement and diagnostic accuracy of five fingertip pulse oximeters used by patients in the NHS (National Health Service) England COVID Oximetry @home scheme.

DESIGN: Measurement and diagnostic accuracy study (exploring pulse oximeter accuracy across skin tones-EXAKT).

SETTING: Twenty four intensive care units in England between June 2022 and August 2024.

PARTICIPANTS: 903 critically ill adults admitted to intensive care units screened for or enrolled into a trial evaluating different approaches to oxygen therapy.

INTERVENTIONS: Pulse oximetry derived peripheral oxygen saturation (SpO2) measurements were compared with paired arterial oxygen saturation (SaO2) …

Egfr Inhibitor-Resistant Lung Cancers Exhibit Collateral Sensitivity To A Covalent, Cysteine-Independent Keap1 Oligomerizing Molecular Bridge, Christopher F Bassil, Kerry Dillon, Gray R Anderson, Benjamin Mayro, Kayleigh N Askin, Peter S Winter, Stefan Harry, Samuel Gruber, Tierney M Hall, Jacob P Hoj, Christian Cerda-Smith, Haley M Hutchinson, Shane T Killarney, Ava Heffernan, Caroline Teddy, Katherine R Singleton, Li Qin, Kévin Jubien-Girard, Cécile Favreau, Guillaume Robert, Barr Tivon, Ella Livnah, Nir London, Rachid Benhida, Patrick Auberger, Ann Marie Pendergast, Liron Bar-Peled, David M Lonard, Anthony R Martin, Alexandre Puissant, Kris C Wood

Faculty, Staff and Students Publications

Targeted therapies have revolutionized cancer care. Unfortunately, most patients develop refractory, multifocal resistance to these therapies within a matter of months. Here, we demonstrate that the evolution of resistance to EGFR inhibitors in EGFR-mutant non-small cell lung cancer endows cells with hypersensitivity to a PAINS-like small molecule, MCB-613. Systematic proteomic, functional genomic, and biochemical studies revealed that MCB-613 binds KEAP1 in a covalent, cysteine-independent fashion, acting as a divalent molecular bridge that relies upon lysine residues in the KEAP1 dimerization domain to join monomers of KEAP1 together. Oligomerization of KEAP1 by MCB-613 sets into motion a fatal cascade of KEAP1 …

Resolution Of A Human Chromosomal Mystery: Evolutionary Complexity Revealed, Jeffrey Rogers

Faculty, Staff and Students Publications

The human complement of chromosomes differs from our closest primate relatives by virtue of a unique chromosome fusion event. In this issue of Cell Genomics, Yang et al. provide the first detailed analysis of the site of chromosome fusion and reconstruct the complex evolutionary relationships among the genomic elements within the human fusion site and their related sequences in our great ape relatives.

Africa's Digital Health Revolution: The Digital Fit-Viability Model To Move From Innovation To Scaled Implementation, Afra Jiwa, Antony Ngatia, Karim Benali, Niclas Boehmer, Sangu Delle, Patrick Emedom-Nnamdi, Chris Opoku Fofie, Christine M O'Brien, Tobi Olatunji, Kate Obayabgona, Milind Tambe, Richard Ribon Fletcher, Adeline Adwoa Boatin, Bethany Hedt-Gauthier

2020-Current year OA Pubs

Digital innovations hold immense potential to transform health care delivery, particularly in sub-Saharan Africa, where financial, geographical, and infrastructural constraints continue to hinder progress toward universal health care delivery. Although a growing health tech sector offers creative solutions, few digital health interventions reach scaled implementation. In this paper, we present the digital fit/viability model-an adapted determinant framework to describe facilitators and barriers to moving from digital tools to integrated digital health implementation. We then use this model to describe the specific challenges and recommended solutions when developing digital health tools for health systems in sub-Saharan Africa.

Primate Gut Microbiota Induce Evolutionarily Salient Changes In Mouse Neurodevelopment., Alex R Decasien, Jacob E Aronoff, Elizabeth K Mallott, Sahana Kuthyar, Sriram Chitta, Brian T Layden, Maria L Savo Sardaro, Stanton Gray, Lawrence E Williams, Emma R Liechty, Hyo M Lee, Won Lee, James P Curley, Christopher W Kuzawa, Katherine R Amato

Faculty Research 2026

Multiple primate species, including humans, evolved brains that are exceptionally large relative to their body sizes. These large brains coevolved with metabolic adaptations that enhance cerebral energy supply, including increased circulating glucose levels. While the gut microbiota (GM) is known to influence host metabolism, its potential role in primate brain evolution remains unclear. To investigate this, we inoculated germ-free mice with the GMs of primate species selected to separate the effects of brain size (encephalization) from phylogenetic relatedness: humans (large-brained, Catarrhini), macaques (smaller-brained, Catarrhini), and squirrel monkeys (large-brained, Platyrrhini). We first show that differences in brain gene expression between mice …

Safety And Effectiveness Of Bolt-Mounted Versus Tunnelled External Ventricular Drains: A Systematic Review, Meta-Analysis And Trial-Sequential Analysis, Shaan Patel, Shiva A. Nischal, Ayush Sinha, Kush Kale, Pious D. Patel, Jack Jallo, Srinivas K. Prasad

Department of Neurosurgery Faculty Papers

BACKGROUND: External ventricular drains (EVDs) are fundamental to neurocritical care, yet substantial procedural heterogeneity persists, particularly regarding bolt-mounted versus tunnelled catheter fixation. The relative safety and effectiveness of these approaches remain unclear, with conflicting data from observational studies and a lack of trial-level evidence.

OBJECTIVE: To compare bolt-mounted and tunnelled EVDs across accuracy, reoperation, and key safety outcomes using systematic review, meta-analysis, and trial-sequential analysis.

METHODS: Following PRISMA guidelines, PubMed, Embase, and CENTRAL databases were searched (November 2025) for randomised or observational studies comparing bolt-mounted with tunnelled EVDs in adults. Two reviewers independently screened studies, extracted data, and assessed risk …

A Novel Vision Transformer Model Produces Clock Drawing Test Scores As Accurate As Expert Human Coders, Mengyao Hu, Tian Qin, Richard Gonzalez, Vicki A Freedman, Laura B Zahodne, Edmundo R Melipillán, Yi Lu Murphey

Faculty, Staff and Student Publications

Alzheimer's disease and related dementias is a growing public health concern. The clock-drawing test, where subjects draw a clock, typically with hands showing 11:10, has been widely used for dementia screening. A limitation of including the clock-drawing test in large-scale studies is that it requires manual coding, which could result in biases if coders interpret and implement coding rules differently. This study created and evaluated an intelligent Clock Scoring system built with deep learning neural networks to automatically code clock-drawing images. We used a large, publicly available repository of clock-drawing images from the 2011-2019 National Health and Aging Trends Study …

Genome-Wide Gene By Sleepiness Interaction Analysis For Sleep Apnea, Pavithra Nagarajan, Nuzulul Kurniansyah, Jiwon Lee, Sina A Gharib, Yushan Xu, Yiyan Zhang, Brian Spitzer, Tariq Faquih, Hufeng Zhou, Eric Boerwinkle, Han Chen, Daniel J Gottlieb, Xiuqing Guo, Nancy L Heard-Costa, Bertha A Hidalgo, Daniel Levy, Peter Y Liu, Hao Mei, Rebecca Montalvan, Sutapa Mukherjee, Kari E North, George T O'Connor, Lyle J Palmer, Sanjay R Patel, Bruce M Psaty, Shaun M Purcell, Laura M Raffield, Stephen S Rich, Jerome I Rotter, Richa Saxena, Albert V Smith, Katie L Stone, Xiaofeng Zhu, Topmed Sleep Trait Working Group, Brian E Cade, Tamar Sofer, Susan Redline, Heming Wang

Faculty, Staff and Student Publications

Study objectives: Excessive daytime sleepiness (EDS), influenced by environmental and social-behavioral factors, is reported by a subset of patients with sleep apnea-a group that may be at elevated cardiovascular risk. However, it is unclear whether sleep apnea with and without EDS have distinct genetic underpinnings. In this study, we perform gene-by-EDS interaction analyses for apnea hypopnea index, a diagnostic marker of sleep apnea severity, to understand EDS's influence on its underlying genetic risk.

Methods: Discovery interaction analyses for common variants and gene-based rare variants were conducted respectively using multi-ethnic Trans-Omics for Precision Medicine (N = 11 619) data, followed by …

Workflow Improvements From Automated Large Vessel Occlusion Detection Algorithms Are Dependent On Care Team Engagement, Emmanuel C Ebirim, Ngoc Mai Le, Joseph N Samaha, Hussain Azeem, Ananya Iyyangar, Anjan N Ballekere, Saagar Dhanjani, Luca Giancardo, Eunyoung Lee, Sunil A Sheth

Faculty, Staff and Student Publications

Background: Automated machine learning (ML)-based large vessel occlusion (LVO) detection algorithms have been shown to improve in-hospital workflow metrics including door-to-groin time (DTG). The degree to which care team engagement and interaction are required for these benefits remains incompletely characterized.

Methods: This analysis was conducted as a pre-planned post-hoc analysis of a randomized prospective clinical trial. ML-based LVO detection software was implemented at four comprehensive stroke centers (CSCs) from January 1, 2021, to February 27, 2022. Patients were included if they underwent endovascular thrombectomy for LVO acute ischemic stroke. ML software utilization was quantified as the total number of active …

Perioperative Fluid Management In Pancreaticoduodenectomy In The Era Of Goal-Directed Fluid Therapy: A Review Of The Literature, Meghan D Grim, Richard Zheng, Nader Hanna, Harish Lavu, Charles J. Yeo, Avinoam Nevler

Department of Surgery Faculty Papers

BACKGROUND: Pancreaticoduodenectomy (PD) is the only curative option for localized pancreatic head and periampullary malignancies. However, PD is associated with significant perioperative morbidity. Perioperative fluid management has emerged as an important modifiable factor influencing surgical outcomes in PD.

METHODS: In this qualitative review, PubMed/Medline searches were performed between March and August 2025 to review the terms "pancreaticoduodenectomy," "fluid management," "Enhanced Recovery After Surgery," "complications," and related terms.

RESULTS: Historically, liberal fluid administration was favored to compensate for third-space losses, but contemporary evidence has linked excessive fluid volumes to complications, such as postoperative pancreatic fistula, anastomotic edema, and increased inflammatory responses. …

Efficacy And Safety Of Oral Pcsk9 Inhibitor Enlicitide In Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial, Christie M Ballantyne, Laura Gellis, Jean-Claude Tardif, Puja Banka, Ann Marie Navar, Emil Andreas Asprusten, Russell Scott, Erik S G Stroes, Samar Froman, Geraldine Mendizabal, Fan Wang, Alberico L Catapano

Faculty, Staff and Students Publications

Importance: Persons with heterozygous familial hypercholesterolemia (HeFH) are at increased risk of atherosclerotic cardiovascular disease due to lifelong elevated levels of low-density lipoprotein cholesterol (LDL-C). Many patients with HeFH do not achieve guideline-recommended LDL-C goals with the currently available lipid-lowering therapies.

Objective: To evaluate the efficacy of enlicitide decanoate (an oral proprotein convertase subtilisin/kexin type 9 inhibitor) vs placebo in adults with HeFH requiring further lowering of LDL-C levels despite use of statin therapy.

Design, setting, and participants: This phase 3, randomized clinical trial included persons aged 18 years or older with HeFH currently using lipid-lowering therapy (taking at least …

Matched Unrelated Vs Haploidentical Donor Hematopoietic Cell Transplantation Using Posttransplant Cyclophosphamide, Dipenkumar Modi, Ramzi Abboud, Et Al.

2020-Current year OA Pubs

Posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is now standard for matched unrelated donor (MUD) hematopoietic cell transplantation (HCT). Previous studies comparing MUD and haploidentical donor HCT using PTCy were limited in size and follow-up. We therefore performed a registry-based analysis examining the impact of donor type on HCT with PTCy. Adult patients (n = 5873) receiving MUD (n = 1973) or haploidentical (n = 3900) HCT with PTCy for acute leukemia (74.2%) or myelodysplastic syndrome (MDS; 25.8%) reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021 were included. Primary end points were 3-year …

Induction Of Moderate Dna Damage Enhances Megakaryopoiesis And Platelet Production, Virginia Camacho, Luis Francisco Zirnberger Batista, Et Al.

2020-Current year OA Pubs

Megakaryocytes (MKs) are large, hematopoietic cells with a polyploid, multilobulated nucleus. Although DNA replication in MKs (endomitosis) is well studied, limited investigations have examined the impact of DNA instability on megakaryopoiesis. Poly-adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitors are chemotherapeutics that result in accumulation of DNA damage and are commonly associated with thrombocytopenia, presumably mediated through platelet progenitors, MKs. To explore PARP inhibitor-induced thrombocytopenia, we treated mice with the PARP inhibitor niraparib. Although high-dose niraparib treatment led to thrombocytopenia, consistent with clinical observations, lower-dose treatment led to a significant increase in bone marrow MKs, MK progenitors (MkPs), and circulating platelets. …

A Chemogenetic Approach For Temporal And Cell-Specific Activation Of Endogenous Gpcrs In Vivo, Gwendolyn Shingles, Qianqian Pang, Jian Weng, Ryan Singer, Waleed Babar, Jiaqi Shen, Luis Vazquez-Rivera, Yao Chen, Peng Li, Wenjing Wang

2020-Current year OA Pubs

Cell-specific regulation of endogenous G protein-coupled receptors (GPCRs) is crucial for understanding their roles in physiological processes. We present chemogenetic tools using shield-1-dependent irreversible protein switches to regulate peptide agonist activity. To demonstrate this platform, we engineered chemogenetically regulated pituitary adenylate cyclase activating polypeptide (cPACAP), which exhibited >15-fold chemical-dependent regulation of endogenous receptor activity. In vivo application of cPACAP allowed neuronal activation via the endogenous receptor for PACAP, engaging neural circuits that control respiratory and feeding behaviors. By integrating cPACAP with transgenic mice, we selectively activated endogenous PACAP receptor signaling in hypocretin-expressing neurons of the lateral hypothalamic area (LHA), revealing …

Identifying Priority Research Questions For Decentralized Wastewater, Bryan W Brooks, Timothy Callahan, Jacob K Stanley, Jamie Holodak, Kevin M Stroski, Alissa H Cox, Thomas W Groves, Anish Jantrania, Jeff C Moeller, Kris Neset, Christopher Walker, Harry Zhang, Amal Bakchan, Kelly D Alley, Jim Bell, Allison Blodig, Eric Casey, Donna Cosper, Victor D'Amato, Mark A Elliott, Greg Graves, Roxanne Groover, Robert Himschoot, Mary G Lusk, Jillian Maxcy-Brown, David Meints, Rojelio Mejia, Matt Pace, Benjamin J Ryan, Brian Scheffe, Tom Schimelfenig, June E Wolfe, Sara F Heger

Faculty, Staff and Students Publications

Decentralized wastewater treatment and reuse represent critical infrastructure across the rural-periurban-urban continuum around the world. Effective, efficient, resilient, and equitable implementation of on-premise technologies and management systems is part of a One Water approach and necessary to protect public health and the environment, yet inconsistent delivery of essential public health services persists in many regions, including across states, tribes, and territories of the United States. We initiated a groundbreaking effort to understand challenges and to identify research opportunities related to the science and practice of decentralized wastewater. A horizon scanning exercise using a bottom up and transparent key questions approach …

Self-Efficacy Change Among Diverse Family Caregivers In Dementia Care, Deborah M Oyeyemi, Erich J Greene, Yunshan Xu, David R Lee, Rafael Samper-Ternent, Maya L Lichtenstein, Alan Stevens, Jeff D Williamson, Arun S Karlamangla, Debra Saliba, David B Reuben

Faculty, Staff and Student Publications

Objectives: To determine whether changes in caregiver self-efficacy (beliefs about one's ability to manage dementia-related problems and access help) differed by caregiver race and ethnicity across all participants enrolled in a large pragmatic trial of comprehensive dementia care.

Methods: In the Dementia Care Study (D-CARE), community-dwelling older adults with dementia and their unpaid family caregivers were randomized to receive usual care, community-based, or health system-based comprehensive dementia care. Caregiver self-efficacy was assessed at baseline, 6 months, and 18 months using a 4-item scale (range 4-20, higher scores indicate greater self-efficacy). Among all caregivers, we compared least squares means for overall …

Tumor-Infiltrating Bacteria Disrupt Cancer Epithelial Cell Interactions And Induce Cell-Cycle Arrest, Jorge Luis Galeano Niño, Falk Ponath, Victor A Ajisafe, Clara R Becker, Andrew G Kempchinsky, Martha A Zepeda-Rivera, Javier A Gomez, Hanrui Wu, Jessica G Terrazas, Heather Bouzek, Elizabeth Cromwell, Pritha Chanana, Matthew Wong, Ashish Damania, Michael G White, Y Nancy You, Scott Kopetz, Nadim J Ajami, Jennifer A Wargo, Christopher D Johnston, Susan Bullman

Faculty, Staff and Student Publications

Tumor-infiltrating bacteria are increasingly recognized as modulators of cancer progression and therapy resistance. We describe a mechanism by which extracellular intratumoral bacteria, including Fusobacterium, modulate cancer epithelial cell behavior. Spatial imaging and single-cell spatial transcriptomics show that these bacteria predominantly localize extracellularly within tumor microniches of colorectal and oral cancers, characterized by reduced cell density, transcriptional activity, and proliferation. In vitro, Fusobacterium nucleatum disrupts epithelial contacts, inducing G0-G1 arrest and transcriptional quiescence. This state confers 5-fluorouracil resistance and remodels the tumor microenvironment. Findings were validated by live-cell imaging, spatial profiling, mouse models, and a 52-patient colorectal cancer cohort. Transcriptomics reveals …

Spatial Omics At The Forefront: Emerging Technologies, Analytical Innovations, And Clinical Applications, Yunhe Liu, Yibo Dai, Linghua Wang

Faculty, Staff and Student Publications

Spatial omics transforms our understanding of cancer by revealing how tumor cells and the microenvironment are organized, interact, and evolve within tissues. Here, we synthesize advances in spatial technologies that map tumor ecosystems with unprecedented fidelity. We highlighted analytical breakthroughs-including multimodal integration and emerging spatial foundation models-that resolve functional niches and spatial communities, converting spatial patterns into mechanistic insights. We summarize how spatially organized features, from immune hubs to microbiota and neural interfaces, shape tumor evolution and clinical outcomes. We then outline how spatial approaches illuminate precancer biology, metastatic adaptation, and therapy response. Bridging discovery and translation, we provide a …

Tet2-Mutant Clonal Hematopoiesis Enhances Macrophage Antigen Presentation And Improves Immune Checkpoint Therapy In Solid Tumors, Shelley Herbrich, Mehdi Chaib, Swetha Anandhan, Samuel W Andrewes, Ashwat Nagarajan, Baoxiang Guan, Nishant Gandhi, Jared Gilliam, Milan Radovich, Padmanee Sharma

Faculty, Staff and Student Publications

Clonal hematopoiesis (CH) is detectable in upwards of 20% of patients with solid tumors and is associated with worsened prognosis; however, its role in tumor immunology and immune checkpoint therapy (ICT) is unknown. Using a bone marrow chimera model of Tet2+/mut CH in mice with solid tumors, we found the Tet2-mutant myeloid cells are abundant in the tumor microenvironment and contributed to an improved response to ICT. Mechanistically, Tet2+/mut macrophages inside the tumor act as immunogenic antigen-presenting cells that more effectively cross-prime naive CD8+ T cells in response to IFNγ. In human cohorts of 35,971 non-small cell lung cancer patients …

Social Prescribing Within Five European Countries: A Protocol Of A Cross-Country Qualitative Analysis, Stephanie Tierney, Debra Westlake, Farhad Rezvani, Daniela Rojatz, Juliane Köberlein-Neu, Trutz Bommhardt, Sónia Dias, Maria João Marques, Donata Kurpas, Hendrik Napierala, Wolfram Herrmann, K Husk

Peninsula Medical School

Introduction Social prescribing is an approach to addressing non-medical issues affecting people’s health and well-being (eg, loneliness, housing or financial problems). It has gained international traction over recent years as complementary to medical care. A larger research project, comparing social prescribing across European countries, is considering how to tailor provision for the following groups: (a) LGBTIQ+persons, (b) refugees and first-generation immigrants and (c) older adults living alone. As part of this research, a qualitative study will address the question: What are the enabling and limiting factors associated with implementing social prescribing, across different European countries, from the perspective of key …

Neighborhood-Level Deprivation Measures In The United States: A Scoping Review And Reference Guide For Investigators, Jaesung Choi, Madeline R Horan, Mary G Nusloch, Yikyung Park, Gregory T Armstrong, Melissa M Hudson, Kirsten K Ness, I-Chan Huang

2020-Current year OA Pubs

PURPOSE: The extent to which existing measures cover the spectrum of neighborhood-level social determinants of health (SDOH) has not yet been assessed. This review compared the content of U.S.-based neighborhood-level SDOH measures and summarized the use of these measures in empirical research. METHODS: We conducted a comprehensive search on PubMed and Google Scholar, identifying review articles published from 1990–2023, and complemented this search by manually examining the original articles on measure development. We identified 85 measures and categorized them into two groups (42 with a specific name and 43 with no name) and used a framework including 14 domains of …

Characteristics And Effectiveness Of Maternal Health Interventions To Prevent Mother-To-Child Transmission (Pmtct) Of Syphilis In A Global Setting: A Scoping Review Using Intervention Mapping As A Framework, Jinni Tang, Anusha Sajja, Christine Markham, Emily T Hebert, Irene Stafford, Sheryl Dacso, Melissa F Peskin

Faculty, Staff and Student Publications

Background: Despite the availability of cost-effective treatments, maternal syphilis continues to contribute significantly to preventable stillbirths and congenital syphilis cases worldwide. This scoping review aimed to identify and characterize maternal health interventions designed to prevent mother-to-child transmission (PMTCT) of syphilis globally, using a modified Intervention Mapping (IM) framework.

Methods: We conducted a scoping review of maternal health interventions targeting PMTCT of syphilis published between January 2010 and August 2023. Searches were performed in PubMed, Medline Ovid, and Embase, supplemented by manual reference screening. Eligible studies described at least one maternal health intervention addressing syphilis PMTCT and were analyzed using a …

Flipi24: A Modern Prognostic Model And Clinical Trial Enrichment Tool For Newly Diagnosed Follicular Lymphoma, Matthew J Maurer, Vit K Prochazka, Tarec Christoffer El-Galaly, Christopher R Flowers, Diego Villa, Emmanuel Bachy, Elliot J Cahn, Marguerite Fournier, Melissa C Larson, Caroline E Dietrich, Lasse Hjort Jakobsen, Hervé Ghesquières, Robert Kridel, Maher K Gandhi, Chan Y Cheah, Eliza A Hawkes, John F Seymour, Ciara L Freeman, Michael R Clausen, Björn E Wahlin, Jonathan W Friedberg, Carla Casulo, Thomas M Habermann, Yucai Wang, Loretta J Nastoupil, Peter De Nully Brown, David Belada, Andrea Janíková, Heidi Mocikova, Tomáš Fürst, Pierre Feugier, Hervé Tilly, Corinne Haioun, Andrew J Davies, Guillaume Cartron, Richard Burack, Dai Chihara, Peter Martin, Jonathon B Cohen, Izidore S Lossos, Brad S Kahl, Laurie H Sehn, Karin E Smedby, Gilles Salles, Marek Trneny, Brian K Link, Franck Morschhauser, James R Cerhan

Faculty, Staff and Student Publications

Purpose: Although most patients with follicular lymphoma (FL) can expect an indolent course, progressive lymphoma remains the primary cause of death during the first decade after diagnosis. Progression of disease within 24 months (POD24) of starting first-line (1L) immunochemotherapy defines a high-risk population with poor survival, but better risk stratification at diagnosis is needed.

Methods: The FLIPI24 model was developed and internally validated to predict 24-month event rates using individual data from 4,485 patients treated with 1L immunochemotherapy from 10 observational cohorts of FL. Overall and cause-specific survival was further evaluated in FLIPI24 risk groups. External validation in the 1L …