Digital Commons Network^™

Mapping Burdens And Inequalities Of Polycystic Ovary Syndrome In Young Females Across 953 Locations 1990–2040 With Deep Learning Forecasts, Yaling Wu, Wenxiang Cai, Mao Chen, Susu Luo, Robert J Norman, Mahnaz Bahri Khomami, Lisa Moran, Heping Zhang, Suhaniya N S Samarasinghe, Salman Rawaf, Davd A Ehrmann, Liming Pan, Kexin Ding, Shuxian Ma, Lili Zheng, Xian Shao, You Zuo, Baozhen Huang, Fei Li, Mingyang Xue, Tongrui Shang, Guangyao Cai, Yuanyuan Chen, Ying Wang, Yutong Lu, Dong Wang, Yuanyuan Wan, Ningning Wu, Ciqing Lin, Wei Pan, Rui Zhang, Tingting Yao, Yiming Xiong, Kai Chen, Jianli Zhao, Shunrong Li, Liling Zhu, Luyuan Tan, Yinduo Zeng, You Zeng, Lukasz Szarpak, Nadia M Hamdy, Claire Chenwen Zhong, Fa Yuan, Yihang Chu, Xiao Jia, Peng Wu, Linjiang Wei, Yanfang Ye, João Conde, Zimeng Wu, Jinjin Zhang, Yamei Tang, Pengpeng Ye, Dongzi Yang, Shixuan Wang, Azeem Majeed, Helena Teede, Wenyi Jin, Queran Lin

Faculty, Staff and Students Publications

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder impacting the health of young female populations. Using harmonized estimates from 953 locations, we assessed temporal trends, geographic inequalities, and forecasts of PCOS among individuals aged 10-24 years from 1990 to 2040. Between 1990 and 2021, global prevalence and disability burden increased by more than 30%, with the highest burden observed among those aged 20-24 years. Substantial geographic heterogeneity was identified, with particularly high prevalence in Europe and East Asia. While high-income regions carried the greatest absolute burden, low- and middle-income regions showed the fastest growth, accompanied by widening …

Neuropathological Hallmarks During The Chronic Phase Of Ischemic Stroke In Mice And Humans, Romeesa Khan, Gary Guzman, Trang Do, Patrick Devlin, John Ahn, Chunfeng Tan, Venugopal Reddy Venna, Sean P Marrelli, Haniyeh Koochak, Claudia M Di Gesù, Anthony Flores, Louise D Mccullough, Rodney M Ritzel

Faculty, Staff and Student Publications

Background: Advances in acute stroke care, including endovascular thrombectomy and improved neurocritical management, have increased survival after ischemic stroke. However, stroke remains a leading cause of long-term disability, with many survivors experiencing persistent neurological and cognitive impairments. The chronic neurological consequences of stroke, particularly its potential to accelerate brain aging, remain poorly understood.

Methods: We examined chronic neurobehavioral changes at 2 and 6 months after middle cerebral artery occlusion in male C57Bl/6 mice. Behavioral assessments included the open field test (OFT), novel object recognition test (NORT), fear conditioning (FC), nesting activity, and tail suspension testing. Transcriptomic profiling was performed using …

Prmt5 Inhibition Impairs Fanconi Anemia Pathway-Mediated Homologous Recombination And Enhances The Antitumor Efficacy Of Temozolomide In Glioblastoma, Shumpei Onishi, Sridharan Jayamohan, Ashis Chowdhury, Sarah Rivas, Yoshihiro Otani, Celine Ertekin, Jean-Paul Bryant, Sara A Murphy, Kimberly A Rivera-Caraballo, Stuart Walbridge, Bayu Sisay, Dragan Maric, Abdel Elkahloun, Kory Johnson, Desmond A Brown, John D Heiss, Ashish H Shah, Tae Jin Lee, Sangamesh G Kumbar, Ji Young Yoo, Andrew J Brenner, Balveen Kaur, Gangadhara R Sareddy, Yeshavanth Kumar Banasavadi-Siddegowda

Faculty, Staff and Student Publications

Despite multimodal therapy of surgical resection, radiation, and chemotherapy, glioblastoma patients show a dismal prognosis. Protein Arginine Methyltransferase 5 (PRMT5) is overexpressed in glioblastoma, and its inhibition imparts an anti-tumor effect. Tumor cells invariably develop resistance to Temozolomide (TMZ), the standard chemotherapeutic agent for glioblastoma. However, the mechanistic role of PRMT5 in treatment-resistant glioblastoma is unknown. Patient-derived glioma stem-like cells (GSCs), treated with PRMT5 inhibitor (LLY-283) or transfected with PRMT5-target-specific siRNA, were treated with TMZ and subjected to in vitro functional and mechanistic studies. The intracranial mouse xenograft model was used to test the in vivo antitumor efficacy of combination …

Sex-Specific Autosomal Susceptibility Loci In Systemic Sclerosis: A Genome-Wide Association Study, Inmaculada Rodriguez-Martin, Martin Kerick, Carlos Rangel-Peláez, Carlos Rosa-Baez, Gonzalo Borrego-Yaniz, Lourdes Ortiz-Fernández, Alfredo Guillen-Del-Castillo, Carmen P Simeón-Aznar, José Luis Callejas, Oliver Distler, Susanna M Proudman, Mandana Nikpour, Nicolas Hunzelmann, Jeska K De Vries-Bouwstra, Ariane L Herrick, Yannick Allanore, Marta E Alarcón-Riquelme, Lorenzo Beretta, Shervin Assassi, Christopher P Denton, Maureen D Mayes, Javier Martin, Marialbert Acosta-Herrera

Faculty, Staff and Student Publications

Background: Systemic sclerosis is an immune-mediated inflammatory disease with marked sex differences in prevalence and severity. Although genome-wide association studies (GWAS) have advanced the understanding of systemic sclerosis genetics, sex-aware approaches remain scarce. We aimed to address this gap by examining autosomal sex-specific genetic factors in systemic sclerosis.

Methods: Based on a chromosomal definition of sex, we conducted a sex-stratified autosomal meta-analysis of GWAS in systemic sclerosis. We retrieved patient-level and control data from a previous GWAS for systemic sclerosis and newly recruited participants from an international multicentre collaboration (data cutoff June 1, 2024). Adult patients (aged ≥18 years) were …

Ftsz Forms Biomolecular Condensates In A Polar-Growing Alphaproteobacterium, Todd A Cameron, Miguel Ángel Robles-Ramos, Lorenzo Suigo, Silvia Zorrilla, William Margolin

Faculty, Staff and Student Publications

The conserved tubulin homolog FtsZ assembles into GTP-dependent protofilaments that organize the bacterial cell division machinery. Purified Escherichia coli FtsZ (FtsZEc) can form biomolecular condensates in the absence of GTP in macromolecular crowding conditions, but FtsZ condensates have not yet been confirmed in vivo. FtsZ from the Alphaproteobacterium Agrobacterium tumefaciens (FtsZAt) localizes to distinct polar foci during growth and contains an intrinsically disordered region much longer than FtsZEc, suggesting a greater tendency to form condensates. Here, we show that purified FtsZAt readily formed dynamic condensates in vitro under molecular crowding conditions, and the addition of GTP induced the formation …

Single-Nucleus Brain Transcriptomics Reveals Microglia Dysfunction In Multiple System Atrophy, Rasmus Rydbirk, Frederik Nørby Friis Sørensen, Jonas Folke, Henriette Haukedal, Andrea Asenjo Martinez, Irene Lisa Vargas, Simone Mcgarry, Oline Chantell Hollmann, Camila Gherardelli, Sofia Sepulveda, Adam T Szafran, Michael A Mancini, Sanne Simone Kaalund, Tomasz Brudek, Lisette Salvesen, Sara Bech, Justyna Okarmus, Peter Kharchenko, Morten Meyer, Claudio Soto, Kristine Freude, Abhisek Mukherjee, Susana Aznar, Konstantin Khodosevich

Faculty, Staff and Student Publications

Multiple system atrophy (MSA) is a rare, age-related neurodegenerative disease that shares clinical and pathological features with Parkinson's disease (PD) but presents a more devastating disease course. To elucidate the distinct cellular pathophysiology, we performed single-nucleus RNA sequencing on postmortem striatal brain tissue from 7 MSA and 12 PD patients, and 10 non-neurological cases. Here, we show significant compositional differences in astroglia and microglia subtypes, while oligodendroglia and neurons are comparable. PD brains show abundant microglia expressing MHC class II HLA haplotypes, indicative of a proinflammatory state, alongside more homeostatic astrocytes. In contrast, MSA lack activated microglia but has more …

Decoding Immunotherapy Response Through Computational Modeling, Bingrui Li, Ruihan Luo, Kexin Huang, Jiajia Liu, Weiling Zhao, Xiaobo Zhou

Faculty, Staff and Student Publications

Immunotherapy has seen success in treating patients with cancer, but variable responses underscore the need for effective patient stratification and therapy planning. Computational tools integrating multi-omics, imaging and machine learning have advanced, yet reliable personalized predictions remain challenging. This review analyzes the field through four converging paradigms: classical machine learning, deep learning, graph and network modeling, and mechanistic systems biology. We examine the evolution from correlational features to representation learning, relational inference, and causal simulation of tumor-immune dynamics, highlighting the shift towards multi-modal fusion and interpretable, clinically deployable models. By providing an integrated review of these computational tools, we hope …

Inflammation- And Resolution-Programmed Myeloid Circuits Govern Therapeutic Resistance In Epithelial And Mesenchymal Triple-Negative Breast Cancer, Liqun Yu, Charlotte Rivas, Fengshuo Liu, Yichao Shen, Ling Wu, Zhan Xu, Yunfeng Ding, Xiaoxin Hao, Weijie Zhang, Hilda L Chan, Jun Liu, Bo Wei, Yang Gao, Luis Becerra-Dominguez, Yi-Hsuan Wu, Siyue Wang, Tobie D Lee, Xuan Li, Xiang Chen, David G Edwards, Xiang H-F Zhang

Faculty, Staff and Students Publications

Single-cell analysis of human triple-negative breast cancer revealed heterogeneous macrophage populations with opposing phenotypes - proinflammatory and proresolution of inflammation. Paradoxically, both subsets accumulated in therapy-refractory residual tumors but showed inverse correlations across patients, suggesting mutually exclusive resistance mechanisms. Inflammatory macrophages localized preferentially to epithelial-like tumors, whereas proresolution macrophages were enriched in mesenchymal-like tumors. Mouse models faithfully recapitulated these patterns. After chemoimmunotherapy, mesenchymal-like tumors expanded proresolution macrophages through phagocytosis/efferocytosis, ω-3 fatty acid uptake, and resolvin production. Macrophage-secreted C1q emerged as a principal antagonist of T cell function by targeting mitochondria and inducing metabolic dysfunction. By contrast, epithelial-like tumors accumulated inflammatory …

To Seize Or Not To Seize? That Is The (Epigenetic) Question, Corey St Romain, Jeannie Chin

Faculty, Staff and Students Publications

No abstract provided.

A Digital Diabetes Prevention Program For Hispanic Adolescents (Fit24+): Protocol For A Feasibility Randomized Controlled Trial, Erica G Soltero, Marbelly Partida, Sandra Mihail, Lizette Villanueva, Callie Lopez, Salma M Musaad, Teresia M O'Connor, Maria J Redondo, Matthew Buman, Debbe Thompson

Faculty, Staff and Students Publications

Background: Hispanic youth are disproportionately impacted by obesity and subsequent type 2 diabetes (T2D) yet remain underrepresented in diabetes prevention research. Digital health interventions hold promise for increasing the accessibility to and engagement in disease prevention programming, particularly among high-risk populations. However, there is a significant gap in the literature regarding digital T2D prevention programs for adolescents or Hispanic youth.

Objective: The objective of this article is to describe the protocol for examining the feasibility of a 12-week digital diabetes prevention program among Hispanic adolescents with obesity.

Methods: Participants (N=40; aged 12-16 years) will be randomized (1:1) to a 12-week …

Acute Compartment Syndrome Following Lower Leg Vascular Injury: A Big-Data Approach To Estimating Incidence And Risk Factors, Harry Moroz, Edward J. Harvey, Yasser C. Bouklouch

Journal of Shock and Hemodynamics

Acute Compartment Syndrome (ACS) is a limb- and life-threatening complication of lower leg fractures. Rapid recognition and fasciotomy can prevent irreversible ischemic injury, but ACS is often under-recognized. Vascular injury may increase the risk of ACS by impairing perfusion and exacerbating swelling. This study aimed to determine the incidence, risk factors, and outcomes of ACS in patients with lower leg fractures, with particular emphasis on the impact of vascular injury. This retrospective cohort study used data from the 2017 American College of Surgeons Trauma Quality Programs database to perform a multicenter analysis of patients with lower leg fractures. Patients were …

Global Impact Of Germline Structural Variation On The Cancer Proteome, Fengju Chen, Yiqun Zhang, Luis F Paulin, Darshan S Chandrashekar, Sooryanarayana Varambally, Fritz J Sedlazeck, Chad J Creighton

Faculty, Staff and Students Publications

Proteome and transcriptome data combined can help assess the relevance of non-coding germline variants. Here, we combine germline Structural Variants (SVs) with mass spectrometry-based proteomics on tumors from 1637 cancer patients spanning various tumor tissues of origin to determine the extent SV breakpoint patterns involve differential protein expression of nearby genes. Rare and singleton SVs disrupting protein expression of known cancer susceptibility genes collectively involve 6% of patients. About 24% of the hundreds of genes with SV-associated non-coding cis-regulatory alterations at the mRNA level are similarly associated at the protein level. Both rare and common SVs may associate with differential …

Dapk2 Regulates Pkm2 Phosphorylation At Threonine 45 To Facilitate Disturbed Flow-Induced Atherosclerosis, Shuai Guo, Long Xu, Yixin Chen, Yuan Zhao, Yuting Zhang, Runfa Yu, Kaixiang Cao, Litao Wang, Wenjia Ai, Jiang-Yun Luo, Lu Lu, Jun He, Yuan Zhou, Li Wang, Andrew H Baker, Yuqing Huo, Yiming Xu

Faculty, Staff and Students Publications

Background: Oscillatory shear stress (OSS), resulting from disturbed blood flow, is implicated in atherosclerotic plaque formation by incompletely understood mechanisms. This study aims to elucidate the involvement of death-associated protein kinase (DAPK) 2 in OSS-induced endothelial cell (EC) activation and atherosclerosis.

Methods: Publicly available resources, including genome-wide microarray, RNA sequencing, and single-cell RNA sequencing, were utilized to identify key OSS-sensitive regulatory factors. Techniques such as mass spectrometry, immunoprecipitation, proximity ligation assay, and RNA sequencing were employed to identify pyruvate kinase M2 (PKM2) as the binding protein of DAPK2 and determine the specific site of PKM2 phosphorylation by DAPK2. To assess …

International Consensus On The Evaluation And Management Of Hypothalamic Hamartomas: Results From A Modified Delphi Survey, Nathan T Cohen, Xiaotong Li, Madison M Berl, Chima O Oluigbo, Hiroshi Shirozu, Samuel F Berkovic, Margaret Zacharin, Wirginia Maixner, Andreas Schulze-Bonhage, Kerstin Klotz, Nicola Specchio, Sarah Ferrand-Sorbets, Christine Bulteau, Alexis A Arzimanoglou, Jean Regis, J Helen Cross, Martin M Tisdall, Hanna Richardson, Arthur Cukiert, Cristine Cukiert, Julia Jacobs, Elizabeth J Donner, Phillip L Pearl, John F Kerrigan, Angus A Wilfong, Kevin C J Yuen, Dennis J Dlugos, Daniel Curry, Irfan Ali, John Ragheb, Lisa Soeby, Erica Webster, William D Gaillard

Faculty, Staff and Students Publications

Background and objectives: Hypothalamic hamartomas (HH) are rare brain lesions associated with epilepsy and numerous comorbidities. Worldwide treatment is varied. There is a paucity of high-quality evidence to guide treatment. This study aimed to establish expert consensus on the evaluation and management of HH.

Methods: A modified Delphi survey was designed by the Medical Advisory Board of Hope for Hypothalamic Hamartomas and was conducted among 17 International League Against Epilepsy level II epilepsy surgery centers. The survey included 257 questions in round 1 and 81 refined questions in round 2, covering domains of diagnosis, imaging, medical and surgical treatment, neuropsychological …

Adoptive Cell Therapies For Glioblastoma: A Quest For Cures From Within, Jia-Shiun Leu, Xin Ge, Charles Robin Yu, Guang Peng, Jiyong Liang

The Brown Foundation: Institute of Molecular Medicine

Glioblastomas (GBMs) are the most aggressive form of brain cancer recalcitrant to both current standard-of-care and immune checkpoint therapies that benefit other cancer patients. Adoptive cell therapies (ACT) using patients' own immune cells have long been explored as a treatment strategy, including the historically studied lymphokine-activated killer (LAK) cells, the evolving chimeric antigen receptor (CAR) directed immune cells, the newly emerging tumor-infiltrating T lymphocyte (TIL) therapies, and others. Preclinical and clinical studies have shown promise but also highlighted significant challenges. In this review, we summarize these findings, highlight recent developments, discuss current limitations, and emphasize how ACT may benefit from …

Engineering Of Genetically Encoded Programmable Calcium Channel Inhibitory Binders, Xiaoxuan Liu, Sher Ali, Tien-Hung Lan, Decheng Wang, Brendan Mckee, Tatsuki Nonomura, Siyao Liu, Feng Zhao, Michael X Zhu, Yun Huang, Qing Deng, Guolin Ma, Yubin Zhou

Faculty, Staff and Student Publications

Store-operated Ca2+ release-activated Ca2+ (CRAC) channels, composed of STIM and ORAI, are essential for immune and developmental processes, and their dysregulation underlies channelopathies such as Stormorken syndrome. Here, we report the engineering of genetically encoded CRAC channel inhibitory binders (CRABs) derived from the ORAI C-terminal tail. Guided by deep mutational scanning, we optimize a membrane-anchored CRAB variant that potently inhibits Ca2+ influx and NFAT signaling, and rescues thrombocytopenia-like phenotypes in a zebrafish model of Stormorken syndrome. To enable tunable inhibition, we further design oligomeric, optogenetic (Opto-CRAB), and chemogenetic (Chemo-CRAB) variants, providing graded and real-time control of CRAC activity. Chemo-CRAB further …

Acute Traumatic Aortic Injury: What The Radiologist Needs To Know, Kristina Ramirez-Garcia, Catalina Jaramillo, Emma Ferguson, Jason Au, Erika Odisio, Gustavo S Oderich, Daniel Ocazionez, Cihan Duran, Thanila Macedo

Faculty, Staff and Students Publications

Acute traumatic aortic injury (ATAI) is a rare but life-threatening consequence of blunt trauma that requires prompt diagnosis and accurate imaging assessment. This review presents an imaging-based approach to ATAI, with emphasis on computed tomography angiography (CTA) as the first-line modality for diagnosis, grading, treatment planning, and follow-up. CTA enables the detection of both direct and indirect signs while also allowing for the assessment of lesion severity, extent, and associated findings that may influence management. Familiarity with common mimics and anatomic variants improves diagnostic confidence and helps avoid false positive interpretations. Careful protocol optimization, including multiphasic acquisition, bolus timing, and …

Computer, Diagnose This Paper: Ai Tools For Student Health Information Research, Brandon Kennedy

Library Class: Lunch & Learn

Discover how to harness the power of artificial intelligence to navigate the rapidly expanding landscape of medical literature in this bite sized 30-minute session. You will learn how to utilize relevant AI tools like ChatGPT, Gemini, and Consensus to enhance your ability to develop effective search strategies and interpret information while strictly adhering to academic and ethical standards. Perfect for students who want to incorporate AI within their research workflow.

A Rare Case Of Cutaneous Extramedullary Hematopoiesis In Chronic Myeloid Leukemia, Bennett Christie-Nguyen, Hanadi El Achi, Levani Iashvili, Amer Wahed, Brenda Mai, Jacob Armstrong

Faculty, Staff and Student Publications

Cutaneous extramedullary hematopoiesis (CEH) is a rare manifestation of extramedullary hematopoiesis (EMH), a process typically associated with fetal development or myeloproliferative neoplasms. EMH most commonly involves the spleen, liver, and lymph nodes, with CEH being exceedingly rare in chronic myeloid leukemia (CML). Here, we present a 34-year-old Hispanic male with multiple bilateral lower extremity lesions, right buttock and leg pain, fatigue, and splenomegaly, who was found to have chronic-phase CML. Punch biopsy of one of the skin lesions demonstrated dermal infiltration by maturing hematopoietic elements, including granulocytes, megakaryocytes, and erythroid precursors, with fluorescence in situ hybridization (FISH) testing confirming a …

A Multidomain Peptide Hydrogel-Liposome Composite For Controlled Release Of A Cyclic Dinucleotide In Oral Cancer, Joseph W R Swain, Andrea H Molina, Gemalene M Sunga, Danielle Chew-Martinez, Neeraja Dharmaraj, Alejandra Cobos Perez, Arghadip Dey, Ephraim J Vázquez-Rosado, Simon Young, Jeffrey D Hartgerink

Faculty, Staff and Student Publications

While immunotherapy is a promising treatment strategy for cancer, the majority of head and neck squamous cell carcinoma (HNSCC) patients treated with single-agent immunotherapy do not respond. Therefore, researchers are investigating combination treatments with immunostimulatory molecules that can maximize anti-tumor responses. Cyclic dinucleotides (CDNs) are STING agonists that hold promise in combination approaches, but they require frequent intratumoral administration when used in both preclinical models of HNSCC and clinical trials. To reduce administration frequency, we have created a peptide hydrogel–liposome composite system, K2-Lip(CDN), for local and prolonged availability of CDN. We investigated the loading limits of cationic liposomes in both …

Therapeutic Potential Of Glp-1 Receptor Agonists For Smoking Cessation, Christian S Hendershot, W Kyle Simmons, Manish K Jha, Sherry A Mckee, Luba Yammine

Faculty, Staff and Student Publications

Glucagon-like peptide-1 (GLP-1) therapies are under investigation for a growing number of neuropsychiatric conditions, including substance use disorders. Cigarette smoking accounts for the largest proportion of substance use-related morbidity and mortality, in part reflecting increased risk for cardiometabolic disease among people who smoke. Given modest quit rates with approved smoking cessation therapies, medications with novel mechanisms of action are needed to expand the available monotherapy and combination treatment options. Treatments that prevent post-cessation weight gain could further reduce relapse and cardiometabolic risks following smoking cessation. Preclinical findings show that GLP-1 receptor agonists (GLP-1RA) modulate nicotine reward, reduce nicotine self-administration, and …

A Machine-Learning-Based Tool For Stroke Risk Prediction In Blunt Cerebrovascular Injury: Development And Preliminary Evaluation, Victoria Wagner, Joshua D Preston, Alejandro De Leon Castro, William F Mueller, Jonathan Nguyen, Manuel Garcia-Toca, Elizabeth R Benjamin, S Rob Todd, Jason D Sciarretta

Faculty, Staff and Student Publications

Purpose: Stroke risk correlates with the Biffl grading system in blunt cerebrovascular injury (BCVI). Although anti-thrombotic therapy is the mainstay of stroke prevention, no point-of-care clinical decision-support tool exists to guide timing for therapy. We sought to develop an interactive online calculator that incorporates patient-specific demographic and injury characteristics to estimate stroke risk and risk reduction with anti-thrombotic (AT) administration.

Methods: Data from BCVI patients (n = 1,197) at a Level I Trauma Center were retrospectively collected. Six machine learning methods were employed to predict stroke risk with and without AT therapy. Class imbalance was addressed using downsampling and/or class …

Loss Of Znrf3/Rnf43 Unleashes Egrfr In Cancer, Fei Yue, Amy T Ku, Payton D Stevens, Megan N Michalski, Weiyu Jiang, Jianghua Tu, Zhongcheng Shi, Yongchao Dou, Yi Wang, Xin-Hua Feng, Galen Hostetter, Xiangwei Wu, Shixia Huang, Noah F Shroyer, Bing Zhang, Bart O Williams, Qingyun Liu, Xia Lin, Yi Li

Faculty, Staff and Students Publications

ZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development and cancer. Conventionally, their biological functions have been associated with regulating WNT signaling receptor ubiquitination and degradation. However, our proteogenomic studies have revealed EGFR as the protein most negatively correlated with ZNRF3/RNF43 mRNA levels in multiple human cancers. Through biochemical investigations, we demonstrate that ZNRF3/RNF43 interact with EGFR via their extracellular domains, leading to EGFR ubiquitination and subsequent degradation facilitated by the E3 ligase RING domain. Overexpression of ZNRF3 reduces EGFR levels and suppresses cancer cell growth in vitro and in vivo, whereas knockout of …

Single-Cell Tcr Mapping Reveals Spatially Coordinated T Cell States In Head And Neck Cancer, Kelli A Mccord, Emerald Kan, Sean Hyslop, Amanda Y Xia, Colby J Hofferek, James S Lewis, Andreas Wieland, David J Hernandez, Vlad C Sandulache, William H Hudson

Faculty, Staff and Students Publications

Current spatial T cell receptor (TCR) profiling approaches lack the resolution needed to link clonal identity, transcriptional state, and spatial positioning of individual T cells in the tumor microenvironment. Here, we introduce a spatial TCR profiling strategy that resolves individual T cell clones together with their transcriptional states at single-cell resolution and applied the method to human head and neck squamous cell carcinoma. Presumed tumor-specific T cells were broadly dispersed throughout the tumor microenvironment, and cells of the same clone occupied distinct transcriptional states in different locations: Immune-rich regions contained more plastic or progenitor cells, whereas tumor-dense regions were enriched …

A Tv-Bm3d Iterative Algorithm For Vmat-Ct Reconstruction, Chia-Lung Chien, Beibei Guo, Rui Zhang

Faculty, Staff and Students Publications

Volumetric modulated arc therapy-computed tomography (VMAT-CT), which is the CT reconstructed using the portal images collected during VMAT, can potentially be an effective onsite imaging tool. The goal of this study was to propose an iterative reconstruction algorithm that can further improve the image quality of VMAT-CT and reduce the number of failed reconstructions. An iterative algorithm combining total variation (TV) with block-matching and 3D filtering (BM3D) was proposed, addressing the L1-L2 regularization problem using the split Bregman method. We collected portal images from 67 VMAT cases including 50 phantom and 17 real-patient cases. Both Feldkamp-Davis-Kress (FDK) and TV-BM3D iterative …

Constitutive Ampk Activation Prevents Hepatocellular Carcinoma Development Through Inhibition Of Hnf4Α Activity, Zhen Sun, Bernard Linares, Cassidy Urdiales, Fiyad Alsarmi, Boyuan Sang, Nagireddy Putluri, Jeanine L Van Nostrand

Faculty, Staff and Students Publications

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality and is largely driven by metabolic disorders such as obesity and type 2 diabetes. The AMP-activated protein kinase (AMPK) is a master regulator of metabolism, and its activation has been proposed as a therapeutic strategy for treating metabolic disorders. However, although AMPK activity is down-regulated in HCC, the precise role of AMPK in HCC development has not been clearly delineated. Here, we investigated the ability of constitutive AMPK activation to prevent HCC development using a constitutively active AMPK transgenic mouse model and a pharmacological AMPK activator. We observed that AMPK …

Epigenome-Wide Association Study Of Blood Proteome In The Atherosclerosis Risk In Communities Study, Yang Li, Aditya Surapaneni, Zulema Rodriguez-Hernandez, Pascal Schlosser, Eugene P Rhee, Eric Boerwinkle, Bing Yu, Megan L Grove, Kelly V Ruggles, Josef Coresh, Morgan Grams

Faculty, Staff and Student Publications

Characterizing the relationship between DNA methylation and circulating proteins is critical to understanding the epigenetic regulation of the human plasma proteome. Here, we performed an epigenome-wide association study of 5,032 circulating proteins in 1,449 White and 315 Black participants from the Atherosclerosis Risk in Communities cohort. We identified 12,500 significant protein quantitative trait methylation (pQTM)-protein associations involving 1,647 proteins. Among 7,796 unique pQTMs, 14.7% were classified as cis-pQTMs, which were enriched for fundamental cellular processes, whereas trans-pQTMs were predominantly linked to immune-related functions. Trans-pQTMs also exhibited stronger associations with demographic, lifestyle, and clinical traits as compared with cis-pQTMs. We identified …

Bi-Allelic Variants In Ap5z1 And Ap5b1 Lead To Retinal Degeneration, Hafiz Muhammad Jafar Hussain, Meng Wang, Paul Yang, Behnoosh Tasharrofi, Yumei Li, Rebecca Lynn Clark, Emma Fale-Olsen, Grace Waldow, Mohammad Keramatipour, Mostafa Asadollahi, Mark E Pennesi, Rui Chen

Faculty, Staff and Students Publications

Inherited retinal diseases (IRDs) comprise a diverse group of disorders that frequently lead to progressive vision impairment and blindness. Despite advances in genetic testing, a significant number of IRD cases remain genetically unsolved, often due to unidentified disease-associated genes or variants. This study reports additional cases for the newly discovered IRD genes of the AP-5 complex. A comprehensive ophthalmological evaluation was performed for all patients, including retinal imaging (multimodal imaging), visual field testing, and electroretinogram (ERG) testing. Whole-genome and -exome sequencing (WGS and WES) were performed for clinically unsolved IRD patients, and data were analyzed to identify underlying causal variants. …

Evapecognition: An 18-Year Dataset Of Great Ape Cognition, Alejandro Sánchez-Amaro, Sonja J Ebel Van Wijk, Carin Molenaar, Akzira Abuova, Lizbeth Mujica-Manrique, Sarah M Leisterer-Peoples, Bret Beheim, Luke Maurits, Anna Albiach-Serrano, Matthias Allritz, Nazli Altınok, Federica Amici, Alice Mi Auersperg, Filippo Aureli, Elisa Bandini, Jochen Barth, Leïla Benziad, Bettina E Bläsing, Manuel Bohn, Marie Bourjade, Juliane Bräuer, Marie-Hélène Broihanne, Sarah F Brosnan, Nereida Bueno-Guerra, Thomas Bugnyar, David Buttelmann, Frances Buttelmann, Trix Cacchione, Malinda Carpenter, Fernando Colmenares, Catherine Crockford, Katherine A Cronin, África De Las Heras, Arianna De Marco, Sarah E Detroy, Valérie Dufour, Shona Duguid, Robin I M Dunbar, Johanna Eckert, Jan M Engelmann, Joel Fagot, Julia Fischer, Sofia Ingrid Fredrika Forss, Martina Funk, György Gergely, Julia R Greenberg, Johannes Großmann, Sebastian Grüneisen, Marta Halina, Daniel Hanus, Sarah R Heilbronner, Christophe Heintz, Robert Hepach, Esther Herrmann, Satoshi Hirata, Alenka Hribar, Gabriele Janzen, Juliane Kaminski, Patricia Kanngiesser, Fumihiro Kano, Katharina C Kirchhofer, Hagen Knofe, Kathrin S Kopp, Christopher Krupenye, Isabelle Barbara Laumer, Stephen C Levinson, Ulf Liszkowski, Héctor M Manrique, Gema Martin-Ordas, Emma Suvi Mcewen, Richard T Moore, Enric Munar, Marcos Nadal, Christian Nawroth, Suska Nolte, Marie Pelé, Patrizia Potì, Hannes Rakoczy, Julia Riedel, Amélie Romain, Federico Rossano, Yvan I Russell, Gloria Sabbatini, Marie Schäfer, Marina Scheumann, Martin Schmelz, Benjamin Schmid, Vanesa Schmitt, Carla Sebastián-Enesco, Amanda Madeleine Seed, Chikako Suda-King, Tibor Tauzin, Sebastian Tempelmann, Claudio Tennie, Valentina Truppa, Jana Uher, Amrisha Vaish, Edwin J C Van Leeuwen, Elisabetta M Visalberghi, Christoph J Völter, Victoria Vonau, Claudia A F Wascher, Roman M Wittig, Wouter Wolf, Michael Tomasello, Katja Liebal, Josep Call, Daniel B M Haun

Faculty, Staff and Students Publications

The study of great ape cognition offers insights into the evolutionary origins of human intelligence, but is hindered by small sample sizes and restricted access to data. To address this, we present the EVApeCognition Dataset, a publicly available resource comprising 262 experimental datasets from 150 scientific publications from the Wolfgang Köhler Primate Research Center (2004-2021) in Leipzig, Germany. Eighty-one apes participated in 150 studies, with a majority (N = 78) participating in more than one study. Publication of the dataset aims to make these unique datasets accessible for future meta-analyses and correlational analyses, helping us better understand how our great …

Contributing Factors Of Contralateral Breast Cancer In Patients With Brca Mutation (On-Brca Ii Study, Korea-Bsg 11), Seon-Hi Shin, Sung Gwe Ahn, Jai Min Ryu, Sae Byul Lee, Hyung Seok Park, Eun-Shin Lee, Janghee Lee, Byeongju Kang, Sanghwa Kim, Eun Young Kim, Young-Joon Kang, Sun Young Min, Moohyun Lee, Se-Kang Kim, Hong-Kyu Kim, Chihwan David Cha

Faculty, Staff and Students Publications

Background: The cumulative risk of contralateral breast cancer (CBC) in BRCA1/2 carriers is remarkably higher than in non-carriers. This study aimed to investigate the clinicopathological predictors associated with the risk of metachronous CBC among breast cancer patients with BRCA1/2 mutations using correspondence analysis.

Methods: This retrospective study included patients who underwent BRCA testing between January 2008 and December 2018. The inclusion criterion was patients being between 20 and 80-years-old with invasive breast cancer (pT1-3, N0-3). We performed univariate and multivariate survival analyses to assess the risks associated with BRCA mutations, and conducted correspondence analysis to identify contributing factors for CBC …