Medicine and Health Sciences Commons^™

Accurate Chromatin Marks Peak Calling With Omnipeak, Oleg Shpynov, Maxim N Artyomov

2020-Current year OA Pubs

Chromatin immunoprecipitation sequencing (ChIP-seq) is a widely used technique for identifying transcription-factor binding and histone modifications across the genome. Peaks in ChIP-seq data vary in length depending on the biological context, from narrow transcription factor binding sites to broad histone modification domains. However, commonly used peak-calling tools are tailored to the specific types of data and struggle to consistently handle various peak lengths, datasets of varying quality, and missing control tracks-common issues in comparative or meta-analyses. These limitations are addressed with Omnipeak, a universal unsupervised peak-calling algorithm based on a constrained three-state hidden Markov model. Omnipeak accurately models global genomic …

Towards A Unified Gating Scheme For The Cnbd Ion Channel Family, Jenna L Lin, Baron Chanda

2020-Current year OA Pubs

Cyclic nucleotide-binding domain (CNBD) channels are critical components of numerous bioelectrical processes, including cardiac pacemaking, neuronal signaling, phototransduction in the eye, and stomatal regulation in plants. While members of this channel family share a conserved overall structure, they exhibit striking differences in voltage sensitivity. Hyperpolarization-activated cyclic nucleotide-gated channels are activated by membrane hyperpolarization, whereas ether-à-go-go channels open upon depolarization. Mutagenesis and chimeragenesis studies have revealed that some mutants display bipolar gating behavior-remaining closed at intermediate membrane potentials but capable of opening in response to both hyperpolarization and depolarization. Remarkably, in certain cases, just a few mutations are sufficient to reverse …

Environmental Enteric Dysfunction In Well-Nourished And Undernourished Women In Bangladesh, Mustafa Mahfuz, Md Shabab Hossain, Ar-Rafi Khan, Mehjabin Tishan Mahfuz, Rumana Sharmin, A H M Rezwan, Musarrat Tasnim, S M Tafsir Hasan, S M Khodeza Nahar Begum, M Masudur Rahman, Michael J Barratt, Jeffrey I Gordon, Tahmeed Ahmed

2020-Current year OA Pubs

INTRODUCTION: Environmental Enteric Dysfunction (EED) is a subacute inflammation of the small intestinal (SI) mucosa associated with undernutrition and perturbation of the SI microbiota. Its diagnosis relies on histopathological assessment of small intestinal biopsies, with a lack of validated biomarkers contributing to underdiagnosis. This study assessed the prevalence and histological features of EED in undernourished Bangladeshi women living in an urban slum in Dhaka, compared to well-nourished women from slum and non-slum areas, and examined the factors associated with histologically confirmed EED.

METHODS: This analysis included non-pregnant, non-lactating Bangladeshi women aged 18-45 years classified by location of residence and nutritional …

Integrating Clinical Reasoning Into Mental Health Diagnosis: A Conceptual Framework For Counseling Practice, Ashley F. Waddington, Alexander M. Fields, Haley Ault

Journal of Human Services Scholarship and Interprofessional Collaboration

Clinical reasoning has long guided diagnostic accuracy in nursing and medical fields, but its application in mental health counseling remains limited. This paper presents a conceptual diagnostic decision-making (DDM) process to embed clinical reasoning into the diagnostic process for counselors, incorporating two vital constructs: counselor self-efficacy and counselor bias (implicit and explicit). Grounded in Bandura’s theory of self-efficacy (1977) and Carvalho et al.’s (2017) clinical reasoning model, the framework highlights the cognitive, behavioral, and contextual factors that shape diagnostic decision-making in early-career counselors, including counselor biases. The paper calls for reform in counselor training, emphasizing curriculum enhancements as pathways to …

Micrornas In Prostate Cancer Liquid Biopsies: Early Detection, Prognosis, And Treatment Monitoring, Seyyed Mohammad Yaghoubi, Erfan Zare, Sina Jafari Dargahlou, Maryam Jafari, Mahdiye Azimi, Maedeh Khoshnazar, Solmaz Shirjang, Behzad Mansoori

Student Papers, Posters & Projects

Prostate cancer (PCa) is a common malignancy in men worldwide, with incidence projected to rise in the coming years. Traditional screening and diagnostic methods, such as prostate-specific antigen (PSA) testing and biopsy, face limitations in specificity and invasiveness. Circulating microRNAs (miRNAs) have emerged as stable, non-invasive biomarkers obtainable via liquid biopsies (blood, urine, semen) that could transform PCa management. These small regulatory RNAs reflect underlying tumor biology and are detectable at early disease stages, enabling improved early detection when used alongside or in place of PSA. Distinct miRNA expression patterns correlate with tumor aggressiveness. For example, miR-141 and miR-375 are …

Assessment Of Non-Clinical Time Expenditures By Academic Emergency Medicine Faculty, Barry J. Knapp, Charles S. Graffeo, Francis L. Counselman, Donald V. Byars, Martin D. Klinkhammer, Jondavid D. Landon

Eastern Virginia Medical Journal

Introduction: In 2020, the Accreditation Council for Graduate Medical Education (ACGME) approved the Residency Review Committee for Emergency Medicine (RRC-EM) revisions to the program requirements. Revisions mandated that Program Directors (PDs) receive 50% full-time equivalent (FTE) non-clinical time, and Associate Program Directors (APDs) receive 35% FTE non-clinical time for administrative and teaching responsibilities for a program our size at the Department of Emergency Medicine, Macon & Joan Brock Virginia Health Sciences Eastern Virginia Medical School at Old Dominion University. Objective: To quantify the actual administrative time our residency leadership team— including the PD, APD, Department Chair, and core faculty— used …

Asian Reference Values For Handgrip Strength, Gait Speed, Five-Times-Sit-To-Stand Test, Muscle Mass And Calf Circumference, Jozo Grgic, Siew Ling Tey, Dieu Thi Thu Huynh, Yen Ling Low, Zeljko Pedisic, Nina Schaller, Vanessa Kristina Wazny, Weilan Wang, Yasuhiko Saito, Ravindra P Rannan-Eliya, Hala Ghattas Ph.D., Monique Chaaya, Carlos Mendes De Leon, Preeti Gupta, Ecosse L Lamoureux, Mythily Subramaniam, Edimansyah Abdin, Rahul Malhotra, Angelique Chan, Bayasgalan Tumenbayar, Oyunbileg Luvsandavaajav, Bolormaa Enkhtuvshin, Norma Mansor, Halimah Awang, Andrea B Maier

Faculty Publications

Background:Handgrip strength, gait speed, Five-Times-Sit-to-Stand Test (FTSST) performance, skeletal muscle mass and calf circumference are important health outcomes, particularly useful for diagnosing sarcopenia. The aim of this study was to establish reference (normative) values for handgrip strength, gait speed, FTSST performance, skeletal muscle mass and calf circumference by pooling individual participant data from national cohorts in Asia.

>Methods:We conducted a pooled analysis of individual participant data from 20 national cohorts representing 12 Asian countries (China, India, Indonesia, Israel, Japan, Lebanon, Malaysia, Mongolia, Philippines, Republic of Korea, Singapore and Sri Lanka). We included cohorts with data on at least …

Celltra: Aligning Cell Names With Gene Expression Via A Pathway-Informed Transformer, Zhao Li, Zaiyi Zheng, Rongbin Li, Wenbo Chen, Yuntao Yang, Meer A Ali, Jundong Li, W Jim Zheng

Faculty, Staff and Student Publications

Motivation: Single-cell RNA sequencing (scRNA-Seq) technology enables detailed exploration of gene expression at the individual cell level, crucial for annotating cell types and understanding cellular diversity. Traditional methods for cell type annotation often rely on marker genes and manual labeling, posing challenges due to low data quality and incomplete reference datasets.

Results: We developed CeLLTra, a novel contrastive learning framework that leverages a Transformer-based model integrating biological pathway information to group genes into super tokens, effectively capturing comprehensive gene expression from scRNA-Seq data. By combining this pathway-informed Transformer with a pretrained domain-specific language model, CeLLTra accurately aligns cell-type annotations with …

Disease Burden Attributable To Intimate Partner Violence Against Females And Sexual Violence Against Children In 204 Countries And Territories, 1990–2023: A Systematic Analysis For The Global Burden Of Disease Study 2023, Luisa S. Flor, Cory N. Spencer, Jack Cagney, Gabriela Fernanda Gil, Hasan Aalruz, Samar Abd Elhafeez, Siddig Ibrahim Abdelwahab, Meriem Abdoun, Mesfin Abebe, Yonas Abebe, Armita Abedi, Roberto Ariel Abeldaño Zuñiga, Alemwork Abie, Olumide Abiodun, Richard Gyan Aboagye, Lucas Guimarães Abreu, Rana Kamal Abu Farha, Bilyaminu Abubakar, Sawsan Abuhammad, Meshack Achore, Lisa C. Adams, Babatope Oluwadamilare Adebiyi, Kamoru Ademola Adedokun, Oluwatobi E. Adegbile, Nurudeen A. Adegoke, Olumide Thomas Adeleke, Makinde Adebayo Adeniyi, Zahir Vally

All Works

Background Violence against women and against children are human rights violations with lasting harms to survivors and societies at large. Intimate partner violence (IPV) and sexual violence against children (SVAC) are two major forms of such abuse. Despite their wide-reaching effects on individual and community health, these risk factors have not been adequately prioritised as key drivers of global health burden. Comprehensive x§and reliable estimates of the comparative health burden of IPV and SVAC are urgently needed to inform investments in prevention and support for survivors at both national and global levels. Methods We estimated the prevalence and attributable burden …

Anti-Csf-1r Therapy With Combined Immuno-Chemotherapy Coordinate An Adaptive Immune Response To Eliminate Macrophage Enriched Triple Negative Breast Cancers, Diego A Pedroza, Xueying Yuan, Fengshuo Liu, Hilda L Chan, Christina Zhang, William Bowie, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Weiguo Wu, Paul Porter, Poonam Sarkar, Na Zhao, Constanze V Oehler, Ondrej Peller, M Waleed Gaber, Qian Zhu, Charles M Perou, Xiang H-F Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Women diagnosed with metastatic triple negative breast cancer (mTNBC) have limited treatment options, are more prone to develop resistance and are associated with high mortality. A cold tumor immune microenvironment (TIME) characterized by low T cells and high tumor associated macrophages (TAMs) in mTNBC is associated with the failure of standard-of-care chemotherapy and immune checkpoint blockade (ICB) treatment. We demonstrate that the combination of immunomodulatory low-dose Cyclophosphamide (CTX) coupled with anti-CSF-1R antibody targeted therapy (SNDX-ms6352) and anti-PD-1 (ICB), was highly effective against aggressive metastatic Trp53 null TNBC transplantable syngeneic models that present with high macrophage infiltration. Mechanistically, CSF-1R inhibition along …

Machine Learning Models Predict Long Covid Outcomes Based On Baseline Clinical And Immunologic Factors, Naresh Doni Jayavelu, Hady Samaha, Sonia Tandon Wimalasena, Annmarie Hoch, Jeremy P Gygi, Gisela Gabernet, Al Ozonoff, Shanshan Liu, Carly E Milliren, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren I R Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Joanna Schaenman, Albert C Shaw, David A Hafler, Ruth R Montgomery, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuit, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Linda N Gen, Ana Fernandez Sesma, Viviana Simon, Florian Krammer, Monica Kraft, Chris Bime, Carolyn S Calfee, David J Erle, Charles R Langelier, Leying Guan, Holden T Maecker, Bjoern Peters, Steven H Kleinstein, Elaine F Reed, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Matthew C Altman

Faculty, Staff and Students Publications

Background: The post-acute sequelae of SARS-CoV-2 (PASC), also known as long COVID, remain a significant health issue that is incompletely understood. Predicting which acutely infected individuals will develop long COVID is challenging due to the absence of established biomarkers, clear disease mechanisms, or well-defined sub-phenotypes. Machine learning (ML) models may address this gap by leveraging clinical data to enhance diagnostic precision.

Methods: Clinical data, including antibody titers and viral load measurements collected at the time of hospital admission, are used to predict the likelihood of acute COVID-19 progressing to long COVID. Machine learning models are trained and evaluated for predictive …

A Probabilistic Modeling Analysis Of The Longitudinal Immune Response To Infection And Vaccination Across Demographic Groups And Pulmonary Symptoms, James O'Hanlon, Kaitlyn Sullivan, Lyndsey M. Muehling, Glenda Canderan, Jie Sun, Judith A. Woodfolk, Jeffrey M. Wilson, Rayanne A. Luke

Spora: A Journal of Biomathematics

Antibody and cytokine kinetics describe the dynamic response to immune events such as infection and vaccination. These dynamics are not fully understood, and mathematical characterization may help explain variability across demographic groups and pulmonary symptoms post-acute infection. We fit time-dependent probability models to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) data to obtain distributions of longitudinal antibody response and cytokine values. To assess differences between groups, an overlap metric is applied to the modeled response curves. Our antibody models suggest significant differences between male and female populations and demonstrate deficient antibody responses of less-healthy groups such as smokers. Our cytokine …

Optimal Intervention Strategies In Age-Structured Sirvd Model: Epidemiological And Economic Analysis Of Covid-19 In Korea, Joon Chun, Melisa Hendrata

Spora: A Journal of Biomathematics

This study employed an age-structured Susceptible-Infected-Recovered-Vaccinated-Deceased (SIRVD) model to design optimal COVID‑19 intervention strategies by integrating epidemiological dynamics with economic costs. Using empirical data from South Korea, we estimated transmission parameters and analyzed quarantine-based non-pharmaceutical interventions (NPIs) alongside targeted vaccination scenarios. Our results indicated that a stronger form of mild NPI (upper range of Level I), when combined with targeted vaccination that prioritized seniors, achieved substantial reductions in infection peaks and overall economic burden. These findings underscore the effectiveness of age-specific strategies in epidemic management and offer critical insights for policymakers seeking balanced, resource-efficient approaches.

Sheep Umbilical Cord Mesenchymal Stem Cells: Biological Characteristics, Ethical Considerations, And Translational Applications, Hasan M. Agha, Mohammed A. Abdalqader, Oh Chin Kin Michelle, Sabaa M. Agha, Jantson Hoh, Abdulmutalib Alabeed Allaq, Amjad Abdulhadi Mohammed, Muneer Mohammed Saleh Alsayadi

AUIQ Complementary Biological System

Mesenchymal stem cells (MSCs) are widely used in regenerative medicine due to their self-renewal capacity, multilineage differentiation potential, and paracrine activity. Limitations associated with the sourcing and scalability of human MSCs have increased interest in xenogeneic alternatives, particularly sheep umbilical cord–derived MSCs (sUC-MSCs). These cells display high proliferative capacity, stable karyotypes, and a typical MSC immunophenotype (CD44, CD73, CD90, CD105), with low basal immunogenicity. sUC-MSCs exhibit osteogenic, chondrogenic, and adipogenic differentiation potential and secrete angiogenic and immunomodulatory factors, including VEGF, HGF, IGF-1, TGF-β, and IL-10. Owing to their biological similarities to human MSCs and accessibility from perinatal tissue, …

Deep-Learning Serial Ct Prediction Of Survival In Immunotherapy-Treated Non-Small Cell Lung Cancer., Chiharu Sako, Brenda F Kurland, Taly G Schmidt, Jing He, Marius De Groot, Arpan A Patel, Dwight H Owen, Arya Amini, Brendan D Curti, Ronan J Kelly, Ray D Page, Aurelie Swalduz, Jean-Paul Beregi, Jan Chrusciel, Stephane Sanchez, Jakob Weiss, An Liu, Olivier Gevaert, Alma Hart, George R Simon, Ravi B Parikh, Jasper Van Der Aart, Petr Jordan

Oncology Articles

IMPORTANCE: Reliable early response biomarkers for overall survival (OS) are lacking for patients receiving immune checkpoint inhibitor (ICI) therapy for advanced non-small cell lung cancer (NSCLC). Existing imaging-based measures, such as Response Evaluation Criteria in Solid Tumors (RECIST) and tumor volume change (TVC), have limited predictive value for long-term outcomes, and advanced imaging-based biomarkers may enhance decision-making in clinical practice and clinical trials.

OBJECTIVE: To develop and validate a fully automated deep-learning imaging-based biomarker using pretherapy and 12-week follow-up computed tomography (CT) scans.

DESIGN, SETTING, AND PARTICIPANTS: This prognostic study used retrospectively collected HER data from routine clinical practice (RCP) …

Dual Challenges, Shared Wins: Unlocking Climate Financing For Nutrition, Chiara Dell’Aira, Natalia Rovelo-Velazquez, Sarah Lahaye, Xiu Xin Catherine Lok, Stella Nordhagen, Stephen Dorey, Mireya Vilar-Compte

Department of Public Health Scholarship and Creative Works

Background

The intertwined challenges of climate change and malnutrition amplify each other, with climate change exacerbating malnutrition, particularly in vulnerable populations; and food systems significantly contributing to emissions and environmental degradation. Addressing these issues together offers opportunities for shared gains, yet funding streams for these sectors remain siloed and misaligned.

Objective

This study developed a scoring methodology to assess the compatibility of climate funds with financing nutrition-related actions where synergies align with climate funds’ primary goals, referred to as the “scope for nutrition integration”.

Methods

Using the Climate Funds Update database, 18 active climate funds were systematically reviewed …

Multisystem Challenges In Reproductive Medicine: A Case Report Of Bicornuate Uterus, Fibroadenoma, And Postpartum Thyroiditis, Fatima Faisal, Aiman Javed, Faisal Muzaffar, Tirath Patel, Ahmed Ibrahim, Fathimathul Henna, Hafiza Tooba Siddiqui, Bhumi Patel, Nana Sardarova, Nikhilesh Anand

School of Medicine Publications

Rationale: A bicornuate uterus is an uncommon mullerian duct malformation strongly associated with recurrent early pregnancy loss and adverse obstetric outcomes. When combined with endocrine disturbances such as hyperprolactinemia and postpartum thyroid dysfunction, fertility becomes even more challenging. This case highlights how coordinated reproductive-endocrine management can overcome multiple intersecting barriers to conception and successful pregnancy.

Patient concerns: A 24-year-old woman presented with a history of 3 first-trimester miscarriages, difficulty conceiving, and prior breast fibroadenoma excision. Following the birth of her first child, she later developed symptoms of palpitations, weight loss, and anxiety suggestive of thyroid dysfunction.

Diagnoses: Pelvic ultrasonography identified …

Etoposide-Associated Severe Rhabdomyolysis In A Patient With Diffuse Large B-Cell Lymphoma: A Case Report And Review Of The Literature, Ibrahim Al Nabhani, Ruquiya Al Dhuhli, Farah Al Kindy, Mahmood Al Abri, Khalil Al Farsi, Almundher Al Oraimi

Sultan Qaboos University Medical Journal

Rhabdomyolysis is a clinical syndrome characterised by skeletal muscle necrosis with subsequent release of intracellular constituents into the circulation. Although multifactorial in aetiology, chemotherapeutic agents, including etoposide, are rarely implicated. We report a 62-year-old male who presented to a tertiary care hospital in Muscat, Oman, in 2023 with severe rhabdomyolysis and advanced-stage diffuse large B-cell lymphoma following the first cycle of R-CEOP chemotherapy. Extensive evaluation excluded infectious, inflammatory and structural neuromuscular aetiologies. Work-up for metabolic myopathy suggested, but did not confirm, multiple acyl-CoA dehydrogenase deficiency. The patient’s clinical course was complicated by acute kidney injury necessitating dialysis, followed by gradual …

Career Plans Among Graduating Us Emergency Medicine Residents, Dave W. Lu, Bo Gu, D. Mark Courtney, Bryan G. Kane, Michelle D. Lall, Michael Gottlieb, Yvette Calderon, Christopher Bennett

Department of Emergency Medicine Faculty Papers

IMPORTANCE: The emergency medicine (EM) workforce is undergoing complex change, including a potential projected physician surplus, the volatile and evolving interests of medical students, and the continued high rates of burnout. Understanding the career intentions of graduating residents is critical to inform workforce planning.

OBJECTIVE: To examine the career plans, anticipated career durations, and key factors associated with the career decisions of graduating US EM residents.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey study, which sampled graduating residents from all Accreditation Council for Graduate Medical Education-accredited categorical EM programs, was conducted after the 2023 American Board of Emergency Medicine In-Training …

Circadian-Shaped Immune Variability Predicts Infection Outcome, Jonathan Lalsiamthara, Mariko Locke, Alejandro Aballay

Faculty, Staff and Student Publications

Disease risk and severity are influenced by genetics, epigenetics, and environmental factors. However, immune responses vary even among genetically similar or related individuals, shaped by inherited and noninherited factors. Using Caenorhabditis elegans, we found that pathogen susceptibility can be predicted by preinfection biomarkers. Individuals with high-basal expression of irg-5, an infection response gene regulated by the p38 mitogen-activated protein kinase-1 (PMK-1) pathway, were more susceptible to Pseudomonas aeruginosa infection. A genome-wide screen identified the myeloid ecotropic viral integration site-1 (MEIS) homeobox protein UNC-62 as a regulator of irg-5 expression, acting through PMK-1 and GATA binding erythroid-like transcription factor …

Career Plans Among Graduating Us Emergency Medicine Residents, Dave W. Lu, Bo Gu, D. Mark Courtney, Bryan G. Kane, Michelle D. Lall, Michael Gottlieb, Yvette Calderon, Christopher Bennett

Department of Emergency Medicine Faculty Papers

IMPORTANCE: The emergency medicine (EM) workforce is undergoing complex change, including a potential projected physician surplus, the volatile and evolving interests of medical students, and the continued high rates of burnout. Understanding the career intentions of graduating residents is critical to inform workforce planning.

OBJECTIVE: To examine the career plans, anticipated career durations, and key factors associated with the career decisions of graduating US EM residents.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey study, which sampled graduating residents from all Accreditation Council for Graduate Medical Education-accredited categorical EM programs, was conducted after the 2023 American Board of Emergency Medicine In-Training …

Cost-Effectiveness Of Home-Based Self-Sampling Vs Clinician Sampling For Anal Precancer Screening, Haluk Damgacioglu, Timothy L Mcauliffe, Timothy J Ridolfi, Elizabeth Chiao, Maria E Fernandez, Vanessa Schick, Jennifer S Smith, Bridgett Brzezinski, Jenna Nitkowski, Ashish A Deshmukh, Alan G Nyitray

Faculty, Staff and Student Publications

Importance: Anal cancer screening is recommended for high-risk populations, particularly sexual and gender minority (SGM) individuals. However, the cost-effectiveness of home-based self-sampling in increasing anal cancer screening uptake has not yet been evaluated in the US.

Objective: To evaluate the cost-effectiveness of home-based anal self-sampling compared with clinic-based screening among SGM individuals.

Design, setting, and participants: This economic evaluation used data from a 2-group randomized clinical trial conducted in Milwaukee, Wisconsin, from January 2020 to August 2022, enrolling SGM individuals aged 25 years or older. Participants were randomized to home-based self-sampling or clinic-based screening. Costs for home-based screening were obtained …

Type Iv Secretion Systems: Reconciling Diversity Through A Unified Nomenclature, Peter J Christie, Gabriel Waksman, Ronnie Per-Arne Berntsson, Nicolas Soler, Nathalie Leblond-Bourget, Badreddine Douzi

Faculty, Staff and Student Publications

Type IV secretion systems (T4SS) are versatile nanomachines responsible for the transfer of DNA and proteins across cell envelopes. From their ancestral role in conjugation, these systems have diversified into a superfamily with functions ranging from horizontal gene transfer to the delivery of toxins to eukaryotic and prokaryotic hosts. Recent structural and functional studies have uncovered unexpected architectural variations not only among Gram-negative systems but also between Gram-negative and Gram-positive systems. Despite this diversity, a conserved set of core proteins is maintained across the superfamily. To facilitate cross-system comparisons, we propose in this review a unified nomenclature for conserved T4SS …

Cholesterol Efflux Protein, Abca1, Supports Anticancer Functions Of Myeloid Immune Cells, Shruti V Bendre, Yu Wang, Basel Hajyousif, Rajendra K C, Shounak G Bhogale, Dhanya Pradeep, Natalia Krawczynska, Claire P Schane, Erin Weisser, Avni Singh, Simon Han, Hannah Kim, Lara Kockaya, Anasuya Das Gupta, Adam T Nelczyk, Hashni Epa Vidana Gamage, Yifan Fei, Desirée Rodríguez-Casiano, Xingyu Guo, Haoyun Li, Ryan J Deaton, Fei Mo, Maria Sverdlov, Peter H Gann, Saurabh Sinha, Sahil Sahni, Kun Wang, Kevin Van Bortle, Emad Tajkorshid, Wendy A Woodward, Wonhwa Cho, Erik R Nelson

Faculty, Staff and Student Publications

Breast and other solid tumors respond poorly to immune therapy. Myeloid cells (MCs) such as macrophages contribute to resistance. Established clinical evidence links cholesterol to cancer outcomes, with MC function being regulated by cholesterol metabolism. We screened MC-expressed regulators of cholesterol homeostasis linked to survival and identified the cholesterol efflux protein ABCA1. ABCA1 activity increases anticancer functions of macrophages: enhancing tumor infiltration, decreasing angiogenic potential, reducing efferocytosis, and improving support of CD8+ T cell activity. Mechanistically, different AKT isoforms are involved, through both PI3K-dependent and PI3K-independent mechanisms. Highlighting the clinical relevance of our findings are correlations between ABCA1 in macrophages …

Nf2 Loss Malignantly Transforms Human Pancreatic Acinar Cells And Enhances Cell Fitness Under Environmental Stress, Yi Xu, Michael H Nipper, Angel A Dominguez, Chenhui He, Francis E Sharkey, Sajid Khan, Han Xu, Daohong Zhou, Lei Zheng, Yu Luan, Jun Liu, Pei Wang

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) occurs as a complex, multifaceted event driven by the interplay of tumor-permissive genetic mutations, the nature of the cellular origin, and microenvironmental stress. In this study, using primary human pancreatic acinar 3D organoids, we performed a CRISPR-KO screen targeting 199 potential tumor suppressors curated from clinical PDAC samples. Our data revealed significant enrichment of a list of candidate genes, with neurofibromatosis type 2 associated gene (NF2) emerging as the top target. Functional validation confirmed that loss of NF2 promoted the transition of PDAC to an invasive state, potentially through extracellular matrix modulation. NF2 inactivation …

Racial, Ethnic, And Socioeconomic Survival Disparities In Early-Onset Metastatic Colorectal Cancer, Jennifer S Wang, Benny Johnson, Caitlin C Murphy

Faculty, Staff and Student Publications

Importance: Rates of metastatic colorectal cancer (mCRC) are rising among young adults. Disparities by race and ethnicity and neighborhood-level socioeconomic status (SES) among this population are understudied.

Objective: To examine the association of race and ethnicity and neighborhood-level SES with mortality among a community-based sample of young adults with mCRC.

Design, setting, and participants: This cohort study used a large electronic health record-derived database of young adults with cancer treated at 280 community-based US clinics between 2013 and 2021. Eligible patients were young adults aged 18 to 49 years diagnosed with de novo or recurrent mCRC. Patients were followed up …

Public Support For Alcohol-Control Policies And Political Ideology In The Us, Joël Fokom Domgue, Robert Yu, Ernest Hawk, Sanjay Shete

Faculty, Staff and Student Publications

This cross-sectional study examines the role of US adults’ political affiliation, perception about alcohol use and cancer, and sociodemographic and behavioral factors in banning outdoor alcohol advertising and adding cancer warnings on alcohol containers.

Peroxisomal Integrity In Demyelination-Associated Microglia Enables Cellular Debris Clearance And Myelin Renewal In Mice, Joseph A Barnes-Vélez, Xiaohong Zhang, Yaren L Peña Señeriz, Kiersten A Scott, Yinglu Guan, Jian Hu

Faculty, Staff and Student Publications

Demyelination associated microglia (DMAM) orchestrate the regenerative response to demyelination by clearing myelin debris and promoting oligodendrocyte maturation. Peroxisomal metabolism has emerged as a candidate regulator of DMAMs, though the cell-intrinsic contribution in microglia remains undefined. Here we elucidate the role of peroxisome integrity in DMAMs, using cuprizone-mediated demyelination coupled with conditional KO of peroxisome biogenesis factor 5 (PEX5) in microglia. Absent demyelination, PEX5 conditional KO (PEX5cKO) had minimal impact on homeostatic microglia. However, during cuprizone-induced demyelination, the emergence of DMAMs unmasked a critical requirement for peroxisome integrity. At peak demyelination, PEX5cKO DMAMs exhibited increased lipid droplet burden and reduced …

Medicaid Expansion And Breast Cancer Care And Outcomes-What Lies Ahead?, Meghan H. Maceyko, Oluwadamilola M. Fayanju

Department of Surgery Faculty Papers

No abstract provided.

Person-Centered Care In Adult Auditory Rehabilitation: A Scoping Review, Marien Alet Graham, Nannette Nicholson, Rachel Glade, Sonja Delport, Faheema Mahomed-Asmail

Communication Disorders and Occupational Therapy Faculty Publications and Presentations

Objective To scrutinise the efficacy of person-centered care (PCC) in enhancing outcomes for adults navigating hearing loss through a comprehensive examination of literature on PCC in auditory rehabilitation (AR). Design A scoping review was conducted following Joanna Briggs Institute guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) reporting standards. A context framework guided the research question. Study Sample Structured searches across multiple databases identified 36 records which were categorised by research design, mapped by the first author's country, and depicted by number of publications per year. Six identified elements of PCC were anaylzed …