Digital Commons Network^™

Investigation Of A Global Mouse Methylome Atlas Reveals Subtype-Specific Copy Number Alterations In Pediatric Cancer Models., Melanie Schoof, Tuyu Zheng, Martin Sill, Roland Imle, Alessia Cais, Lea Altendorf, Alicia Fürst, Nina Hofmann, Kati Ernst, Dominik Vonficht, Kenneth Chun-Ho Chan, Tim Holland-Letz, Andreas Postlmayr, Ryo Shiraishi, Wanchen Wang, Alaide Morcavallo, Michael Spohn, Carolin Göbel, Judith Niesen, Levke-Sophie Peter, Franck Bourdeaut, Zhi-Yan Han, Yanxin Pei, Najiba Murad, Fredrik J. Swartling, Jessica Taylor, Monika Yadav, Garrett R. Gibson, Richard J. Gilbertson, Matthias Dottermusch, Rajanya Roy, Kornelius Kerl, Rainer Glass, Jiying Cheng, Martin A. Horstmann, Gerrit Wolters-Eisfeld, Haotian Zhao, Dominik Sturm, Viveka Nand Yadav, Louis Chesler, Simon Haas, William A. Weiss, Paul A. Northcott, Lena M. Kutscher, Ana Guerreiro Stucklin, Olivier Ayrault, Julia E. Neumann, Daisuke Kawauchi, David T W Jones, Kristian Pajtler, Ana Banito, Stefan M. Pfister, Ulrich Schüller, Marc Zuckermann

Manuscripts, Articles, Book Chapters and Other Papers

Copy number alterations (CNAs) are hallmarks of cancer, yet investigation of their oncogenic role has been hindered by technical limitations and missing model systems. Here we generated a genome-wide DNA methylation and CNA atlas of 106 genetic mouse models across 31 pediatric tumor types, including 18 new models for pediatric glioma. We demonstrated their epigenetic resemblance to human disease counterparts and identified entity-specific patterns of immune infiltration. We discovered that mouse tumors harbor highly recurrent CNA signatures that occur distinctly based on the tumor subgroup and driving oncogene and showed that these CNAs share syntenic regions with the matching human …

Pt/Zno-Decorated Laser-Induced Graphene For Nonenzymatic Glucose Monitoring Under Physiological Conditions, Reagan Aviha, Gymama Slaughter

Center for Bioelectronics Publications

Diabetes continues to impose significant global health and economic burdens, driving the demand for robust, enzyme-free glucose sensors capable of reliable operation under physiological conditions. Here, we report the development of a high-performance nonenzymatic glucose sensor based on laser-induced graphene (LIG) modified with zinc oxide (ZnO) and platinum (Pt) nanostructures. ZnO was electrodeposited onto LIG with modulation potential and deposition duration systematically optimized. The ZnO/LIG electrodes were characterized electrochemically using potassium ferricyanide and evaluated for glucose oxidation in phosphate-buffered solution. Subsequent electrodeposition of Pt under analogous optimized conditions yielded a ternary Pt/ZnO/LIG architecture with enhanced electrocatalytic activity. Sensor performance was …

The History We Didn't Hear: An M&M On Communication And Misinformation, Ansh Patel, Anjan Parghi

South Atlantic Division GME Research Days 2026

No abstract provided.

Bop2-Comb: Bayesian Optimal Phase Ii Design For Optimizing Doses And Assessing Contribution Of Components In Drug Combinations, Xiaohan Chi, Ying Yuan, Ruitao Lin

Faculty, Staff and Student Publications

Background: Personalized cancer treatment using combination therapies offers substantial therapeutic benefits over single-agent treatments in most cancers. However, unmet clinical needs and increasing market competition pressure drug developers to quickly optimize combination doses and clearly demonstrate the contribution of each component when developing and evaluating new combination treatments.

Methods: We propose a Bayesian optimal phase II drug-combination (BOP2-Comb) design that optimizes the combination dose and evaluates the proof-of-concept as well as the contribution of each component in two seamless stages. Our optimal calibration scheme minimizes the total trial sample size while controlling incorrect decision rates at nominal levels. This calibration …

Freeze-Dried, Not Frozen: Lyophilized Mesenchymal Stromal Cell-Derived Extracellular Vesicles And Therapeutic Function In Neuroinflammatory Models, Janet R Ashley, Aidan M Collier, Scott D Olson, Charles S Cox

Faculty, Staff and Student Publications

Background: Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) offer a promising acellular therapy for immune modulation, but clinical translation is hindered by variability and storage constraints. Lyophilization (freeze-drying) could enable shelf-stable EV therapeutics, although its effects on biological activity remain incompletely defined.

Study design: We compared the immunomodulatory effects of frozen and lyophilized EVs from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) MSCs using lipopolysaccharide-stimulated rodent splenocytes and microglial models and human peripheral blood mononuclear cells (PBMCs). Variables included batch scale (small vs large), cytokine priming, and MSC source. Tumor necrosis factor alpha (TNF-α) secretion was measured …

Digital Communication Strategies For Culinary Medicine In Cancer Prevention And Survivorship: Information-Seeking Habits And Content Preferences Of Online Cooking Media Among Adults Participating In Four Cancer Prevention And Control Cohort Studies, Margaret Raber, Sara Fares, Maria Vazquez, Larkin Strong, Carrie Daniel-Macdougall, Lorna Mcneill, Karen Basen-Engquist

Faculty, Staff and Student Publications

Introduction

Poor diet and excess weight have been linked to increased risk for at least 13 types of cancer. Culinary medicine utilizes experiential cooking skill development to improve individuals’ capacity for healthy eating. Digital communication strategies offer pathways for scalable culinary medicine interventions, but little research has explored how online cooking tools could be leveraged for cancer prevention messaging. We conducted a cross-sectional survey study exploring online cooking information-seeking habits and content preferences among participants in four cancer prevention and control cohorts to inform future digital culinary medicine interventions.

Methods

A cross-sectional survey study was conducted with a convenience sample …

T Cells Modulate The Development And Maintenance Of Painful Paclitaxel-Induced Peripheral Neuropathy In Rnu Rats, Ahmed Olalekan Bakare, Gerard Limerick, Vasudha Goel, Ratan K Banik, Lei Zheng, Andrew J Shepherd, Kristine Glunde, Qin Zheng, Eellan Sivanesan

Faculty, Staff and Student Publications

The role of T cells in chemotherapy-induced peripheral neuropathy (CIPN) is complex and shaped by biological and experimental factors, including sex, hormonal status, genetic background, and cancer model. This complexity has contributed to inconsistent findings among studies, limiting therapeutic progress. In this study, we investigate how T cells contribute to painful paclitaxel (PTX)-induced peripheral neuropathy (PIPN). Adult male T cell-competent (RNU+/−) and T cell-deficient (RNU−/−) rats were subcutaneously inoculated with tumor cells and subsequently treated with intraperitoneal PTX (8 mg/kg total dose). Reflexive (mechanical, heat, cold) and non-reflexive (burrowing, gait) pain behaviors were assessed from baseline through week 6. Immunohistochemistry …

The Lysine Demethylase Kdm4c Is An Oncogenic Driver And Regulates Erk Activity In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Menna-T-Allah Shaheen, Sarah Dhebat, Kimal I Rajapakshe, Bidyut Ghosh, Benson Chellakkan Selvanesan, Shariq S Ansari, Cara L Haymaker, Dorsay Sadeghian, Huamin Wang, Ching-Fei Li, Haoqiang Ying, Anirban Maitra

Faculty, Staff and Student Publications

Deregulation of proteins involved in chromatin regulation is common in pancreatic ductal adenocarcinoma (PDAC). Lysine demethylase 4C (KDM4C) is one of the chromatin-modifying proteins frequently overexpressed across multiple solid cancers and is linked to chromatin instability, increased cell proliferation, and enhanced stem cell–like behavior. We observed upregulation of KDM4C protein in a panel of human PDAC cell lines and patient samples compared with nonneoplastic controls. CRISPR/Cas9-mediated deletion of KDM4C in human and murine PDAC cells reduced proliferation, clonogenicity, and increased survival of orthotopically implanted murine PDAC allografts. Transcriptomic and proteomic analyses revealed that loss of KDM4C in both human and …

Prickle4 Drives Microenvironmental Remodeling And Resistance To Parp Inhibition In Idh-Mutant Glioma, Ju Yang, Hua Yang, Yifan Yuan, Chenyang Zhang, Ziwei Fu, Yanyan Chen, Yinghong Xiong, Shuyu Chen, Kexin Ling, Ying Liu, Jason T Huse, Bo Chen, Timothy A Chan, Zengxin Qi, Zhao Zhang, Xiuping Liu, Yuxiang Wang

Faculty, Staff and Student Publications

Mutations in isocitrate dehydrogenase (IDH) genes sensitize gliomas to PARP inhibition (PARPi) by inducing epigenetic reprogramming of DNA damage repair circuits. However, tumors treated with PARPi eventually relapse despite initial responsiveness. In this study, it is demonstrated that the anti-angiogenic agent lenvatinib synergizes effectively with PARPi, resulting in substantial tumor regression and significantly extended survival. Genomic analysis of tumors reveals that PARPi induces widespread transcriptomic changes that are predominantly pro-inflammatory, thereby promoting tumor angiogenesis. Prickle4, a planar cell polarity protein, is identified as a critical mediator of PARPi-induced neovascularization. Targeting Prickle4 effectively overcomes PARPi resistance in these tumors. Collectively, these …

Navigating Prediabetes In A Foreign Country: A Qualitative Study Of Self-Management Experiences Among Chinese-Speaking Immigrants In Australia, Min Zhang, Kirsten J. Coppell, Johnny Lo, Lisa Whitehead

Research outputs 2022 to 2026

Aim: Chinese-speaking immigrants in Australia have a higher risk of type 2 diabetes and face more barriers to accessing quality healthcare compared to non-culturally and linguistically diverse populations. This study aimed to explore the self-management experiences of Chinese-speaking Australians with self-reported lived experience of prediabetes following immigration. Design: Qualitative study. Methods: Semi-structured interviews were conducted with 10 purposively selected Australian Chinese-speaking immigrants aged over 40 years. Data collection was undertaken in Perth, Western Australia between April and August 2024. Data were analysed using reflexive thematic analysis. Results: Three themes are presented in this paper: (1) An acculturation journey: Reshaping cultural …

Stim1-Dependent Treg Dysfunction Promotes Cardiometabolic Hfpef: Insights From Patients And Animal Studies, Balaji Srinivas, Alluri Kiran, Hongmei Peng, Jiang Xu, Paula Fortuno, Jennifer May, Ismail El Moudden, Nour-Eddine Rhaleb, John M. Herre, Raymond L. Benza, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Background

Heart failure with preserved ejection fraction (HFpEF) arises from chronic cardiometabolic and vascular stress and is increasingly recognized as an inflammatory syndrome with immune dysregulation. Regulatory T cells (Tregs) are critical modulators of cardiovascular inflammation, yet the mechanisms driving Treg dysfunction in HFpEF remain poorly defined. stromal interaction molecule 1 (STIM1)-dependent calcium signaling is a key stress-responsive pathway in immune cells; however, its role in Treg maladaptation during HFpEF remains unknown.

Methods

Circulating Tregs from patients with and without HFpEF were analyzed for abundance, STIM1 expression, and stress-associated signaling pathways. To establish causality, mice with Treg-specific deletion of STIM1 …

Contribution Of Comorbidities And Pregnancy Complications To Severe Maternal Morbidity In The United States, Tetsuya Kawakita, Sora A. Jones, Natsume Furukawa, George Saade

Department of Obstetrics & Gynecology Faculty Publications

Objective: To quantify the extent to which rising rates of severe maternal morbidity (SMM) in the United States from 2016 to 2022 are attributable to increasing prevalence of maternal risk factors, including advanced maternal age, obesity, pregestational diabetes mellitus, gestational diabetes, chronic hypertension, and hypertensive disorders of pregnancy (HDP).

Methods: We conducted a retrospective cohort study using the Nationwide Readmissions Database from 2016 to 2022, representing more than 25 million weighted delivery hospitalizations. The primary outcome of SMM was identified with the Centers for Disease Control and Prevention's 21-condition algorithm; a secondary outcome excluded transfusion to improve specificity. Temporal trends …

Evaluating The Mediating Role Of Gestational Phthalate And Replacement Biomarkers In The Associations Between Race/Ethnicity And Birthweight, Amir J. Lueth, Danielle R. Stevens, Sarahna A. Moyd, Elena Sinkovskaya, Ann Przybylska, Antonia M. Calafat, Julianne C. Botelho, George Saade, Alfred Abuhamad, Kelly K. Ferguson

Department of Obstetrics & Gynecology Faculty Publications

Background

Gestational exposure to phthalates is higher among non-Hispanic black (NHB) women than non-Hispanic white (NHW) women and may contribute to racial/ethnic differences in birthweight z-scores.

Objective

We aimed to investigate whether gestational phthalate and replacement biomarkers mediate the association between race/ethnicity and birthweight z-scores.

Methods

We analyzed data from 271 pregnancies in the Human Placenta and Phthalates study, a prospective cohort recruited from 2017 to 2020. Urinary phthalate metabolite concentrations were measured at up to eight time points during pregnancy and averaged to represent gestational exposure. Metabolites were grouped by parent compound. Linear regression models estimated associations in phthalate …

Blood Flow Regulates Metabolism In Hematopoietic Development, Pamela L Wenzel

Faculty, Staff and Student Publications

Blood flow modifies oxygen availability and biomechanical forces within the vasculature of the embryo as the hematopoietic system develops. The aorta-gonad-mesonephros (AGM) envelops the largest artery in the body and is a critical site for the emergence of hematopoietic stem cells (HSCs). Herein, I discuss the role of hypoxia-inducible factors (HIFs) and force as determinants of metabolism and fate determination. To address the effects of blood flow on hematopoietic development, I employ mouse embryo models and biomimetic culture. Real-time cell metabolic analyses show that oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) are altered by flow in cultures of …

Engineering Mutation Clones In Mammalian Cells With Crispr/Cas9, Zijun Huo, Jian Tu, Rachel Shoemaker, Dung-Fang Lee, Ruiying Zhao

Faculty, Staff and Student Publications

CRISPR, Clustered Regularly Interspaced Short Palindromic Repeat, as a powerful genome engineering system, has been widely accepted and employed in gene editing of a vast range of cell types. Compared to zinc finger nucleases (ZFNs) or transcription activator-like effector nucleases (TALENs), CRISPR shows a less complicated process and higher efficiency. With the development of different CRISPR systems, it can be used not only to knock out a gene but also to make precise modifications, activate or repress target genes with epigenetic modifications, and even for genome wide screening. Here we will describe the procedure of generating a stable cell line …

Prepregnancy Overweight And Obesity In Kuwait Birth Cohort Study, Abdullah Al-Taiar, Ali H. Ziyab, Eelaf A. Husain, Maryam M.Y. Mohammad, Maryem A. Shamsah, Noor Salah Alali, Reem Sharaf-Alddin, Majeda S. Hammoud

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Objectives: This study aimed to estimate the prevalence of prepregnancy obesity and overweight, and to identify a set of sociodemographic factors that could guide weight management interventions for women prior to conception.

Design, Sample, and Measurements: Pregnant women (N = 989) were recruited in the Kuwait Birth Cohort Study during the period June 2017 to February 2020. Prepregnancy weight and height were self-reported, while current weight and height were measured in a standardized procedure. Data on sociodemographic factors were collected through face-to-face interviews conducted by a trained data collector. Multinomial logistic regression was used to investigate the association between sociodemographic …

Compassionate Communities, Māori Ageing And End-Of-Life: A Systematic Review, Melissa Carey, Kathleen Mason, Levi Fox, Tess Moeke-Maxwell, Merryn Gott

Research outputs 2022 to 2026

Background: Māori people in Aotearoa New Zealand and Australia experience significant healthcare inequity as they age and towards the end of their lives. Compassionate community approaches to ageing and end-of-life care are increasing in popularity throughout the world. However, this approach has arisen from Eurocentric knowledge systems and not from First Nations people and their communities. Objectives: This research aimed to gain insight into what the Compassionate Communities approach means for First Nations people and identify implications for Māori in Aotearoa New Zealand and Australia. A systematic literature review explored the intersection of Compassionate Communities and First Nations peoples’ perspectives …

Rapid Decentralized Prostate Cancer Risk Stratification By Portable Liquid Biopsy Analysis Within A Clinical Biosensor Validation Framework, Kevin M. Koo, Grant Phillips, Sriganesh Srihari, Áine Farrell, Binny Jaradi, Kira J. Fitzpatrick, John W. Yaxley, Hemamali Samaratunga, Paul N. Mainwaring, Ke-Lin Ru, Darren J. Korbie, Scott A. Tomlins, Matthew J. Roberts, Robert A. Gardiner, Matt Trau

Research outputs 2022 to 2026

Clinical liquid biopsy (e.g., blood or urine) specimens, as a minimally invasive source of crucial molecular information, continue to grow in importance for efficacious targeted cancer treatment. Yet, current molecular profiling technologies are still confined to centralized laboratory testing, which escalates testing costs, result turnaround time, and patient anxiety. Crucially, there is also a scarcity of purposeful clinical validation studies to rigorously evaluate emerging liquid biopsy technologies from research settings to facilitate clinical translation. Here, we report liquid biopsy biosensor advancements in achieving rapid, accurate, and decentralized molecular profiling of a clinically accredited prostate cancer (PCa) urinary circulating RNA biomarker …

It Will Only Work If Everyone Is On Board: A Needs And Context Assessment To Inform Exercise Oncology Implementation Within A Public Healthcare Organisation, Georgia L. White, Mary A. Kennedy, Bryan A. Chan, Hattie Wright, Grace L. Rose

Research outputs 2022 to 2026

Introduction: Exercise has well-established benefits across the cancer continuum for people living with and beyond cancer, yet the exercise oncology field faces a research-to-practice gap. Understanding the factors that influence implementation in any given context is essential to ensure implementation strategies have the greatest likelihood of success. The study mapped onsite exercise oncology services, staff-reported implementation barriers and facilitators, organisational readiness, and experiences reported by people living with or beyond cancer, across a large public healthcare organisation.

Methods: Staff and people living with and beyond cancer across cancer care centres within the public healthcare organisation completed an online survey. Data …

Effectiveness, Reach, Uptake, And Feasibility Of Digital Health Interventions For Culturally And Linguistically Diverse Populations Living With Prediabetes Across The Lifespan: Systematic Review And Meta-Analysis, Lisa Whitehead, Min Zhang, Wai Hang Kwok, Diana Arabiat, Amanda Towell Barnard

Research outputs 2022 to 2026

Background: Culturally and linguistically diverse (CaLD) populations are at a higher risk of developing prediabetes; however, the effectiveness and implementation of digital health interventions for prediabetes management in this population are not well understood. Objective: This review aims to evaluate the effectiveness and implementation of digital health interventions (DHIs) versus usual care for glycemic control in CaLD populations living with prediabetes. Methods: This review aimed to include people of any age living with prediabetes who are from a CaLD background. Experimental and quasi-experimental studies that compare digital health interventions to usual care, waitlist, or active control were eligible. The primary …

Evaluating Novel Targeted Combination Therapies For Gastrointestinal Cancers, Joseph A. Goode

Graduate Studies Theses and Dissertations 2026

Gastrointestinal (GI) cancers remain among the leading causes of cancer-related mortality worldwide, with therapeutic resistance continuing to limit the effectiveness of current treatments. Three complementary studies were conducted to identify therapeutic vulnerabilities and evaluate novel combination strategies in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC).  First, dual inhibition of fibroblast growth factor receptor 4 (FGFR4) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling was investigated in PDAC models. A combination of targeted drug treatments reduced viability, clonogenic survival, migration, and suppressed signaling pathways involved in translational control. This supported a functional interaction between FGFR4 and PI3K-mTOR co-activation in …

The Diversity Of Flavivirus Antibody Dependent Enhancement (Ade) Profiles From A Pediatric Cohort In Mexico, Maiesha Samiha Mahmood

Graduate Studies Theses and Dissertations 2026

The Aedes mosquito-borne flaviviruses Zika (ZIKV) and dengue (DENV-1-4) cause an estimated 400 million annual infections globally and pose an increasing threat to public health. Typically, individuals infected with ZIKV or a DENV serotype generate neutralizing serotype-specific antibodies and non-neutralizing, cross-reactive antibodies that bind multiple flaviviruses. Upon secondary heterotypic infection, pre-existing antibodies can either protect or exacerbate disease through antibody dependent enhancement (ADE). ADE occurs when non- or sub-neutralizing concentrations of cross-reactive antibodies facilitate viral uptake into FcγR-bearing myeloid cells, enabling infection of otherwise non-permissive cells and driving severe disease. To date, ADE has not been characterized at a population …

Creating Community Through Walking The Talk For Dementia, Kate Irving, Fernando Aguzzoli Peres, Walter D. Dawson, Jonathan Adrián Zegarra-Valdivia, Lingani Mbakile-Mahlanza, Iracema Leroi, Sherril B. Gelmon

Institute on Aging Publications

Objectives

Creating community is not only therapeutic—it has been described as essential. This study explores a process of community-building among people with lived and professional experience in the dementia field, during Walking the Talk for Dementia (WTD), a week-long, immersive event on the Camino de Santiago in Spain. Absence of community can lead to fragmented support for both people living with dementia and their care partners and for those working in the field. Achieving a sense of community, however, can be complex.

Methods

A qualitative evaluation was conducted with 79 participants from 27 countries, incorporating pre-, during and post-event reflections. …

Tau In Alzheimer’S Disease: Shaping The Future Patient Journey, Catherine J Mummery, Christopher Chen Li-Hsian, Cristian A Lasagna-Reeves, Rik Ossenkoppele, Christopher C Rowe, Douglas W Scharre, Huali Wang, Simon Kyaga, Jeffrey L Cummings

Faculty, Staff and Students Publications

Alzheimer's disease is a complex and multifactorial disease characterized by two key pathological hallmarks: amyloid-beta plaques and tau neurofibrillary tangles. Recent progress has led to the development and approval of disease-targeted therapies for Alzheimer's disease in the form of anti-amyloid-beta monoclonal antibodies. However, findings suggest that amelioration of multiple pathological drivers may be required to maximize clinical effect. An increasing body of evidence suggests that tau is a critical player in Alzheimer's disease pathophysiology, contributing significantly to neurodegeneration and cognitive decline. There are now several tau-targeting drugs in clinical development. In this review, we build on research and advancements in …

Senolytic-Resistant Senescent Cells Have A Distinct Sasp Profile And Functional Impact: The Path To Developing Senosensitizers, Utkarsh Tripathi, Masayoshi Suda, Vagisha Kulshreshtha, Bryan T Piatkowski, Allyson K Palmer, Nino Giorgadze, Christina Inman, Nathan Gasek, Ming Xu, Kurt O Johnson, Tamar Pirtskhalava, Selim Chaib, Larissa P G Langhi Prata, Yi Zhu, Renuka Kandhaya-Pillai, Stefan G Tullius, Saranya P Wyles, Rambabu Majji, Hari Krishna Yalamanchili, David B Allison, Tamar Tchkonia, James L Kirkland

Faculty, Staff and Students Publications

The senescent cell (SC) fate is linked to aging, multiple disorders and diseases, and physical dysfunction. Senolytics, agents that selectively eliminate 30%-70% of SCs, act by transiently disabling the senescent cell antiapoptotic pathways (SCAPs), which defend those SCs that are proapoptotic and pro-inflammatory from their own senescence-associated secretory phenotype (SASP). Consistent with this, a JAK/STAT inhibitor, Ruxolitinib, which attenuates the pro-inflammatory SASP of senescent human preadipocytes, caused them to become "senolytic-resistant". Administering senolytics to obese mice selectively decreased the abundance of the subset of SCs that is pro-inflammatory. In cell cultures, the 30%-70% of human senescent preadipocytes or human umbilical …

Challenges In The Diagnosis Of Concurrent T-Lymphoblastic Leukemia/Lymphoma And Thymic Neuroendocrine Carcinoma: A Case Report, Kristen Oliveira, Mary Doan, Ying Pei, Marwan Yared, Songlin Zhang

Faculty, Staff and Students Publications

The co-occurrence of T-lymphoblastic leukemia/lymphoma and thymic neoplasia is a rare event that can present a diagnostic challenge. In this case report, we describe a 31-year-old man who was found to have thymic neuroendocrine carcinoma and T-lymphoblastic leukemia/lymphoma 2 years after initial treatment for T-lymphoblastic leukemia/lymphoma. The thymic neuroendocrine carcinoma was initially detected in a malignant pleural effusion, and a retrospective review of a preceding lung biopsy suggested the involvement of both tumors within one tissue sample. Immunohistochemical analysis was imperative in highlighting these two elements because despite their unique cytomorphological characteristics, a limited amount of each component was seen …

Integrating A Project-Based Learning Methodology Into A Department-Wide Quality Improvement Curriculum: A Nine-Year Experience In Pediatric Subspecialty Training, Venessa Lynn Pinto, Danny Castro, Constance M Wiemann, Liza Bonin, Cagri Yildirim-Toruner, Nicholas A Ettinger, Sharada Hiranya Gowda, Joyee Vachani, Mehmet Fatih Okcu

Faculty, Staff and Students Publications

Background: Quality improvement (QI) training of subspecialty fellows is an essential component of graduate medical education, yet often delivered in silos within departments through a variety of instructional methodologies.

Objective: We applied project-based learning (PjBL) as a guiding methodology for a QI curriculum for pediatric subspecialty fellows and describe our curriculum development, instructional design, and its implementation.

Methods: We integrated the Institute for Healthcare Improvement (IHI) Model for Improvement with the 6 key features of PjBL: a driving question, defined learning goals, active participation in educational tasks, collaboration among learners, scaffolding with learning technology, and production of tangible artifacts. The …

Pd-L1-Centric Whole Blood-Based Immune Signature Profiles Of Tuberculosis Patients During Therapy, Johanna Eggeling, Martina Sester, Christoph Lange, Jan Heyckendorf, Barbara Kalsdorf, Anna M Mandalakas, Andrew R Dinardo, David Lewinsohn, Dagmar Schaub, Tina Schmidt, Eva Tolosa, Maja Reimann, Patricia M Sánchez Carballo

Faculty, Staff and Students Publications

This prospective study investigated whole blood-based immune cell biomarkers for pulmonary tuberculosis (TB) immunoprofiling. Blood samples from 34 healthy controls and 51 tuberculosis patients were analyzed at three timepoints: Prior to therapy (T0), after 14 days of therapy (T1), and at the end of treatment (Te). Using multiparameter flow cytometry, 386 immune cell populations were analyzed. Predictive models were developed using two machine learning algorithms. A TB5LF change score, which was based on five cell populations, effectively distinguished tuberculosis patients from controls (AUC = 0.89) and tuberculosis patients before and at the end of treatment (AUC = 0.92). Similarly, the …

Cultured Ex Vivo Human Brain Tissue Maintains Cell-Type Transcriptional Identities, J P Mcginnis, Sai Mallannagari, Maria Camila Guevara, Joshua Ortiz-Guzman, Benjamin D W Belfort, Suyang Bao, Snigdha Srivastava, Maria Morkas, Emily Ji, Kalman A Katlowitz, Angela Addison, Evelyne K Tantry, Carrie A Mohila, Melissa M Blessing, Nisha Gadgil, Samuel G Mcclugage, David F Bauer, William E Whitehead, Guillermo Aldave, Omar Tanweer, Naser Jaleel, Ali Jalali, Akash J Patel, Sameer A Sheth, Howard L Weiner, Shankar Gopinath, Ganesh Rao, Akdes Serin Harmanci, Daniel Curry, Benjamin R Arenkiel

Faculty, Staff and Students Publications

There is growing recognition of the need for human-based models of the nervous system and its diseases. Studies have investigated the electrophysiological properties of neurons in ex vivo human brain tissue, but the maintenance of other cell types remains unclear. We therefore used single-nucleus RNA sequencing of six patient samples to determine how well various cell types maintain their transcriptional identities over two weeks in organotypic slice culture (day 0, with 83 501 nuclei, and day 14, with 45 738). For each patient sample (two pediatric temporal lobectomies, one adult frontal cortex, two glioblastomas, and one medulloblastoma), we generated correlations …

Astrocytic Sox9 Overexpression In Alzheimer’S Disease Mouse Models Promotes Aβ Plaque Phagocytosis And Preserves Cognitive Function, Dong-Joo Choi, Sanjana Murali, Wookbong Kwon, Junsung Woo, Eun-Ah Christine Song, Yeunjung Ko, Debosmita Sardar, Brittney Lozzi, Yi-Ting Cheng, Michael R Williamson, Teng-Wei Huang, Kaitlyn Sanchez, Joanna Jankowsky, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes play essential roles in the brain, and their dysfunction is associated with nearly every form of neurological disease. Despite their ubiquity, knowledge of how astrocytes contribute to disease pathogenesis is incomplete; accordingly, harnessing their biology toward therapeutics remains a major challenge. Here we show that the transcription factor Sox9 plays a context-specific role in maintaining astrocyte function and circuit activity in the aging hippocampus and Alzheimer's disease (AD) models. We found that Sox9 overexpression in astrocytes in AD models clears existing amyloid beta (Aβ) plaques and preserves cognitive function. Mechanistically, Sox9 promotes the phagocytosis of Aβ plaques by astrocytes …