Digital Commons Network^™

Nonexposed Endoscopic Full Thickness Resection Of Residual Disease After Definitive Chemoradiation For Locally Advanced Gastric Cancer, Brennan W Gioe, Bryan C Luu, Michael M Ittmann, George Chen, Yvonne H Sada, Wasseem Skef

Faculty, Staff and Students Publications

Salvage endoscopic resection of residual esophageal neoplasia for patients that prefer to avoid surgery or are poor surgical candidates has been reported. We report a case of gastric signet ring cell carcinoma with residual disease after definitive chemoradiotherapy, that was treated with nonexposed endoscopic full thickness resection. This endoscopic resection achieved negative margins, with postresection surveillance endoscopy and imaging showing no evidence of disease. This case highlights the potential use of salvage endoscopic resection as a therapy for residual gastric cancer after chemoradiation in patients where surgery is not an option.

Endoglin-Directed Car T Cells Comprehensively Target Tumors In Advanced Sarcomas, Harrison R Berger, Malina Maharana, Jeneffer Mirabal, Lyazat Kurenbekova, Alberto Delaidelli, Atreyi Dasgupta, Ahmed Z Gad, Mohamed F Sheha, Sybrina S Kerr, Ada I Ozcan, Jessica S Morris, Angela M Major, M John Hicks, Mary K Mckenna, Ben K Seon, Matthew L Baker, Poul H Sorensen, Meenakshi Hegde, Jason T Yustein, Nabil Ahmed, Sujith K Joseph

Faculty, Staff and Students Publications

There are limited therapeutic options for patients with advanced sarcomas, which leads to dismal outcomes for children and adults. Although chimeric antigen receptor (CAR) T cells hold promise for treating advanced sarcomas, this approach is constrained by a paucity of effective targets. Our previous clinical study identified endoglin (ENG/CD105), a TGFβ coreceptor, as a target of the endogenous immune response in a patient with sarcoma who exhibited an exceptional response to HER2-targeted CAR T-cell therapy. ENG is expressed on various sarcomas, cancer-associated fibroblasts, and neoangiogenic vessels and therefore offers comprehensive tumor targeting. Furthermore, ENG knockout in sarcoma cells reduces their …

Fructose And Glucose From Sugary Drinks Enhance Colorectal Cancer Metastasis Via Sord, Tianshi Feng, Qin Luo, Yanlin Liu, Zeyu Jin, David Skwarchuk, Rumi Lee, Miso Nam, John M Asara, Daya R Adye, Philip L Lorenzi, Lin Tan, Guangsheng Pei, Zhongming Zhao, Neda Zarrin-Khameh, Adriana Paulucci-Holthauzen, Brian W Simons, Ju-Seog Lee, Scott Kopetz, Jihye Yun

Faculty, Staff and Students Publications

The consumption of sugar-sweetened beverages (SSBs), which contain high levels of fructose and glucose, has been causally and mechanistically linked to an increased risk of colorectal cancer (CRC). However, the effects of SSB consumption on advanced stages of disease progression, including metastasis, remain poorly understood. Here we show that exposure of CRC cells to a glucose and fructose formulation-reflecting the composition of both high-fructose corn syrup and sucrose found in SSBs-enhances cellular motility and metastatic potential compared to glucose alone. Given that CRC cells grow poorly in fructose alone, and cells in vivo are not physiologically exposed to fructose without …

Neuroleukemiosis Masquerading As Drug Toxicity In An Adolescent With Refractory Aml, Nia Choi, Deborah Schady, Tim Lotze, Jill Ann Jarrell, Alexandra Rodriguez-Hernandez, Sandra Aziz, Karen K Moeller, Joanna S Yi, Suzanne Woodbury, Andrea N Marcogliese, Zoann E Dreyer, Eric S Schafer

Faculty, Staff and Students Publications

No abstract provided.

Molecular And Genetic Landscapes Of Retina And Brain Microglia In Neurodegenerative Diseases, Khang Ma, Rinki Ratnapriya

Faculty, Staff and Students Publications

Microglia-driven dysregulation has emerged as a significant underlying mechanism in many neurodegenerative diseases, such as age-related macular degeneration (AMD) and Alzheimer's disease (AD). Although both brain and retinal microglia originate from the yolk sac, it is uncertain whether they share molecular similarities or genetic and molecular foundations related to neurodegenerative diseases. In this study, we examine the transcriptomic and epigenetic profiles of retina and brain microglia through integrative analyses of single-nucleus RNA sequencing (snRNA-seq) and single-nucleus ATAC sequencing (snATAC-seq) from 97 independent human samples across 11 different studies. Our findings reveal that retina and brain microglia share similar expression and …

Protein Kinase Rock1 Activates Mitochondrial Fission Linking To Oxidative Stress And Muscle Atrophy, Meijun Si, Jihong Chen, Rizhen Yu, Hongchun Lin, Feng Li, Sungyun Jung, Sandhya S Thomas, Farhard R Danesh, Yanlin Wang, Hui Peng, Zhaoyong Hu

Faculty, Staff and Students Publications

Introduction: Chronic kidney disease (CKD) is associated with protein-energy wasting, characterized by a reduction in muscle mass and strength. Although mitochondrial dysfunction and oxidative stress are implicated in the pathogenesis of muscle wasting, underlying mechanisms remain unclear.

Methods: Here, we used transcriptomic analysis, metabolomics analyses, and mouse gene manipulation to investigate the effects of mitochondrial plasticity and oxidative stress on muscle wasting the subtotal nephrectomy mouse models of CKD. The mice with CKD were age- and sex-matched to sham-operated controls.

Results: Through these approaches, Rho-associated kinase ROCK1 emerged as a key molecule responsible for the observed mitochondrial fission and oxidative …

Pfas Exposure And Postoperative Weight Regain In Adolescents After Bariatric Surgery: Findings From The Teen-Labs Study, Brittney O Baumert, Elizabeth Costello, Zhenjiang Li, Justin R Ryder, Thomas Inge, Todd Jenkins, Stephanie Sisley, Stavra A Xanthakos, Douglas I Walker, Nikos Stratakis, Damaskini Valvi, Scott M Bartell, Angela L Slitt, Rohit Kohli, Sarah Rock, Michele A La Merrill, Sandrah P Eckel, Max T Aung, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

Objective: Weight regain following bariatric surgery remains a clinical challenge, with limited understanding of contributing environmental factors. Per- and polyfluoroalkyl substances (PFAS), persistent chemicals linked to metabolic dysfunction, may influence long-term weight trajectories. This study aimed to evaluate associations between PFAS exposure and changes in BMI, percent weight loss, and waist circumference among adolescents after bariatric surgery.

Methods: We included 186 adolescents (mean age: 17.1 years; 76.3% female; 72.0% White) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort who underwent surgery between 2007 and 2012. Anthropometric measurements were collected at baseline and 6, 12, 36, and 60 months post …

From Assistance To Autonomy: Evaluating Procedural Competency In Pediatric Emergency Medicine, Richard Barber, Marideth Rus, Elizabeth Moran, Esther M Sampayo, Deborah Hsu, Corrie E Chumpitazi, Elizabeth A Camp, Nidhi V Singh

Faculty, Staff and Students Publications

Objective: Pediatric emergency medicine (PEM) physicians require expertise in numerous procedural skills to manage emergencies in children. Fellows require hands-on experience, expert supervision, and standardized feedback to build procedural competency. Our objective was to develop and gather validity evidence for an evaluation tool to assess PEM fellows' ability to perform procedures.

Methods: We conducted a retrospective study of PEM fellows' procedural performance within a children's hospital system. Faculty evaluated fellows using a one-item, five-point entrustment/level of supervision scale. We focused on three frequently performed procedures: laceration repair, intubation, and procedural sedation. To assess changes in supervision scores by training year, …

Carbonic Anhydrase Inhibition Sensitizes Group 3 Medulloblastoma To Radiotherapy, Cory M Richman, Alexandra Rasnitsyn, Borja L Holgado, Maria Vladoiu, Namal Abeysundara, Sandra Majo, Sara Chabi, Lucie J Taunay, Hiromichi Suzuki, Ichiyo Shibahara, Joonas Haapasalo, Jonelle G Pallotta, Tajana Douglas, Kaitlin Kharas, Kyle Juraschka, Oliver Ocsenas, Sachin A Kumar, Kristiina Nordfors, Ana Guerreiro Stücklin, Raul A Suarez, Jiao Zhang, Xiaochong Wu, Craig Daniels, Livia Garzia, Jüri Reimand, Olivier Saulnier, Thomas E Merchant, Celio Pouponnot, David R Raleigh, Michael D Taylor, Pasqualino De Antonellis

Faculty, Staff and Students Publications

Group 3 (G3) medulloblastoma constitutes the most aggressive molecular subgroup, and nearly all patients present with metastases upon recurrence. Treatment for newly diagnosed medulloblastoma relies on a combination of maximal safe surgical resection, followed by chemotherapy and ionizing radiation, and no therapies have been shown to confer a survival benefit at the time of recurrence. Given the limited therapeutic options available for patients with medulloblastoma, especially at recurrence, and the incomplete understanding of the molecular mechanisms underlying resistance to treatment, we sought to uncover actionable targets and biomarkers that could help refine patient selection and treatment of newly diagnosed medulloblastoma …

Alternative Polyadenylation Contributes To Fibroblast Senescence In Pulmonary Fibrosis, Jingjing Huang, Maria Jose Gacha-Garay, Yu Wang, Scott D Collum, Rene A Girard, Hydia Puente, Seung-Hee Yoo, Rahat Hussain, Jayeshkumar Patel, Manish Patel, Eric J Wagner, Hari Krishnayalamanchili, Harry Karmouty-Quintana, Zheng Chen, Tingting Mills

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a prevalent and deadly age-related disease characterized by chronic, progressive, and irreversible fibrosis. A key effector cell population in the fibroproliferative response is the fibroblasts. Fibroblast cell senescence gradually worsens during aging, and the acquisition of a senescence-associated secretory phenotype (SASP) turns senescent fibroblasts into pro-inflammatory cells. However, the mechanism promoting senescence in IPF, especially at the post-transcriptional level, is poorly understood. We recently discovered that Nudix Hydrolase 21 (NUDT21, also named CFIm25), an RNA-binding protein, plays a critical role in regulating the expression of SASP factors through alternative polyadenylation (APA). APA allows adding poly(A) …

A Narrative Review Of The Ileal Pouch In Pediatric Inflammatory Bowel Disease And Familial Adenomatous Polyposis, Anitta Philip, Allyson Wyatt, Jose R Rodriguez, Brad Pasternak, Lisa Mcmahon, Kalyani Patel, Richard Kellermayer

Faculty, Staff and Students Publications

Ileal pouch-anal anastomosis is a surgical intervention in patients with medically refractory inflammatory bowel disease and familial adenomatous polyposis syndrome. Reported outcomes in children have been limited by both the retrospective nature and sample size of the investigations. In addition, there is a lack of consensus on surveillance guidelines in this patient population. Delay or lack of surveillance may increase the risk of complications (pouchitis, Crohn's disease-like inflammation, dysplasia, etc.). This narrative review aims to summarize the most recent literature (2013-2023) on short-term, long-term, and quality of life (QoL) outcomes in pediatric ileal pouch (J-pouch) patients. A proposed surveillance guidance …

Functional Importance Of Bile Acid-Fxr Signaling In Neonatal Immunity And Disease, Douglas G Burrin, Greg Guthrie, Caitlin Vonderohe

Faculty, Staff and Students Publications

No abstract provided.

Clinical Profiles And Outcomes Of Adult Congenital Heart Disease Patients In The Cardiac Intensive Care Unit, Luke J Burchill, Viral K Desai, Maan Jokhadar, Cameron Dezfulian, Heidi M Connolly, Alexander C Egbe, William R Miranda, C Charles Jain, Jacob C Jentzer

Faculty, Staff and Students Publications

Background: There is limited evidence to guide care and improve outcomes among critically ill adult congenital heart disease (ACHD) patients.

Objectives: The purpose of this study was to examine the clinical profile and outcomes of ACHD patients admitted to an academic cardiac intensive care unit (CICU).

Methods: Retrospective cohort study of Mayo Clinic CICU admissions (2007-2018), including those who had been evaluated in our ACHD clinic. Critical care diagnoses (CCD) at the time of admission and critical care therapies (CCT) during the CICU stay were examined. Logistic regression and Cox proportional hazards regression were used to evaluate in-hospital and 1-year …

Using Latent Patient-Centered Fear Extinction Profiles To Guide Treatment In Pediatric Ocd, Katherine M Ingram, Eric A Storch, Daniel A Geller, Brent J Small, Sabine Wilhelm, Joseph F Mcguire

Faculty, Staff and Students Publications

Background: While exposure with response prevention (ERP) is the frontline treatment for pediatric obsessive-compulsive disorder (OCD), not all patients benefit. Impairments in extinction learning are implicated in pediatric OCD's etiology and treatment, with impaired pre-treatment extinction learning associated with worse ERP outcomes. However, available methods for assessing patients' difficulties with fear extinction are costly and underdeveloped. In response, we used person-centered profiles to characterize latent fear extinction patterns among youth with OCD, and investigated the degree to which scores on common rating scales correspond to profile membership.

Methods: Youth with OCD (n=98) completed a diagnostic clinical battery followed by a …

Picalm Alzheimer’S Risk Allele Causes Aberrant Lipid Droplets In Microglia, Alena Kozlova, Siwei Zhang, Ari Sudwarts, Hanwen Zhang, Stanislau Smirnou, Seul Kee Byeon, Christina Thapa, Xiaotong Sun, Kimberley Stephenson, Xiaojie Zhao, Brendan Jamison, Moorthi Ponnusamy, Xin He, Julie A Schneider, Akhilesh Pandey, David A Bennett, Zhiping P Pang, Alan R Sanders, Hugo J Bellen, Gopal Thinakaran, Jubao Duan

Faculty, Staff and Students Publications

Despite genome-wide association studies (GWAS) of late-onset Alzheimer’s disease (LOAD) having identified many genetic risk loci1–3, the underlying disease mechanisms remain largely unclear. Determining causal disease variants and their LOAD-relevant cellular phenotypes has been a challenge. Here, using our approach for identifying functional GWAS risk variants showing allele-specific open chromatin, we systematically identified putative causal LOAD-risk variants in human induced pluripotent stem (iPS)-cell-derived neurons, astrocytes and microglia, and linked a PICALM LOAD-risk allele to a microglial-specific role of PICALM in lipid droplet (LD) accumulation. Allele-specific open-chromatin mapping revealed functional risk variants for 26 LOAD-risk loci, mostly …

Liver-Specific Expression Of Hiv-1 Viral Protein R Causes Hepatic Steatosis And Glucose Intolerance In Male Mice, Neeti Agarwal, Pradip Saha, Claudia E Ramirez Bustamante, Sean M Hartig, Mark A Herman, Ashok Balasubramanyam, Jordan E Lake

Faculty, Staff and Students Publications

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized in people with HIV (PWH), with both HIV and antiretroviral therapy contributing to liver damage and glucose intolerance. However, the role of viral proteins derived from reservoirs in this process remains unclear.

Methods: Adeno-associated virus (AAV) constructs encoding a control protein or HIV-1 viral protein R (Vpr) driven by the thyroxine-binding globulin promoter were administered to male mice (n = 5 per group) fed regular chow or a high-fat diet (HFD). Young adult mice underwent intraperitoneal glucose tolerance testing and magnetic resonance imaging, followed by euthanasia. Liver and adipose tissues …

Prostaglandin E2 As A Mechanistic Biomarker Of Chronic Pancreatitis, Jami L Saloman, Bahiyyah Jefferson, Samuel Han, William E Fisher, Evan L Fogel, Phil A Hart, Liang Li, Walter G Park, Santhi Swaroop Vege, Dhiraj Yadav, Mark D Topazian, Darwin L Conwell

Faculty, Staff and Students Publications

Introduction: Chronic pancreatitis (CP) is a disease associated with chronic inflammation, fibrosis, and pain. There is a lack of tools available that facilitate early diagnosis, when intervention could prevent irreversible damage. Pilot data suggested prostaglandin E2 (PGE2) as a candidate biomarker for early CP. PGE2 activates signaling pathways that promote inflammation, pain, and fibrosis.

Methods: We assessed PGE2, metabolites, and downstream targets in pancreatic fluid collected endoscopically 0-10 (n = 110) and 10-20 (n = 111) minutes after intravenous secretin administration. PGE2 and metabolites were measured in plasma (n = 75) and urine (n = 71) from the same subjects. …

Exploring The Transformative Effects Of Calorie Restriction On The Lacrimal Gland In Adult Mice, Olivier Mauduit, Prashant Kumar, Kaitlin K Scholand, Emre Aksan, Laura Schaefer, Anmar Abu-Romman, Vanessa Delcroix, Zhiyuan Yu, Aude I Sindikubwabo, Ron Korstanje, Helen P Makarenkova, Cintia S De Paiva

Faculty, Staff and Students Publications

Advanced age is one of the most recognizable risk factors for dry eye. Dry eye disease affects millions worldwide and can result from age-related lacrimal gland dysfunction, which correlates with a decline in lacrimal gland secretory cell function and chronic inflammation. This study investigated the potential of calorie restriction to maintain lacrimal gland and ocular surface health. Adult female C57BL/6 J mice were subjected to a 40% calorie restriction for 4 months, starting at 6-7 months and continuing until 10-11 months. These mice were compared to controls fed ad libitum. Bulk RNA sequencing of lacrimal glands, conjunctiva, and cornea subjected …

Author Correction: Clonal Dynamics And Somatic Evolution Of Haematopoiesis In Mouse, Chiraag D Kapadia, Nicholas Williams, Kevin J Dawson, Caroline Watson, Matthew J Yousefzadeh, Duy Le, Kudzai Nyamondo, Sreeya Kodavali, Alex Cagan, Sarah Waldvogel, Xiaoyan Zhang, Josephine De La Fuente, Daniel Leongamornlert, Emily Mitchell, Marcus A Florez, Krzysztof Sosnowski, Rogelio Aguilar, Alejandra Martell, Anna Guzman, David Harrison, Laura J Niedernhofer, Katherine Y King, Peter J Campbell, Jamie Blundell, Margaret A Goodell, Jyoti Nangalia

Faculty, Staff and Students Publications

No abstract provided.

Examining The Relationship Between Dysphagia, Eating-Related Symptoms, And Diet Quality Among Oropharyngeal Cancer Patients During Critical Stages Of Cancer Survivorship: The U-Dine Study, Beatrice Manduchi, Vlad C Sandulache, Ji Yun Tark, Shreela Sharma, Ruosha Li, Emily Roller, Andrew Bevelhimer, Katherine A Hutcheson, Marcia C De Oliveira Otto

Faculty, Staff and Students Publications

Background: Diet quality is a modifiable factor impacting treatment outcomes in oropharyngeal cancer (OPC), yet the effect of dysphagia and self-reported eating-related symptoms remains unclear. This study examined their associations with diet quality in OPC patients.

Methods: A cross-sectional analysis was conducted with two parallel cohorts from MD Anderson Cancer Center and Michael E. DeBakey Veterans Affairs Medical Center as part of the Uncovering the Long-Term Impact of OPC and Dysphagia on Dietary Quality and Nutrition Among Cancer Survivors (U-DINE) Study. Participants at varying survivorship stages (prediagnosis, 3-6 and 18+ months posttreatment) were assessed for dysphagia (DIGEST scale) and six …

Nrf2 Hyperactivation As A Driver Of Radiotherapy Resistance And Suppressed Antitumor Immunity In Head And Neck Squamous Cell Carcinoma, Rutulkumar Patel, Kalil Saab, Lixia Luo, Yan Ma, Rashid Abdullah Osman, Nerissa T Williams, Jeffrey Everitt, Maciej J Zelazowski, Patricia Castro, William K Decker, William H Hudson, Jeffrey N Myers, Vlad C Sandulache, Mitchell J Frederick, Yvonne M Mowery, David G Kirsch

Faculty, Staff and Students Publications

Purpose: Alterations in the KEAP1/NFE2L2 (NRF2)/CUL3 pathway occur in ∼20% of human head and neck squamous cell carcinomas (HNSCC) and are associated with resistance to standard-of-care therapy. However, this pathway's role in radiotherapy resistance in HNSCC has not been well studied.

Experimental design: We generated genetically engineered mouse models and developed primary murine cancer cell lines harboring mutations commonly observed in human HNSCC, including inducible activation of PIK3CA and deletion of Trp53, with or without Keap1 loss. Primary tumors were initiated via 4-hydroxytamoxifen injection ± the tobacco carcinogen benzo[a]pyrene (BAP) into the oral buccal mucosa. Tumors were analyzed by Western …

Dissecting The Effects Of 223radium On The Bone Microenvironment, Sergio Barrios, Elisa Serafini, Ludovica La Posta, D Nicole Meyers, Nicholas J Dunbar, Paul G Corn, Florent Elefteriou, Catherine G Ambrose, Stefano Casarin, Antonios G Mikos, Eleonora Dondossola

Faculty, Staff and Students Publications

Radium-223 (223Ra) is a bone-seeking, alpha-particle-emitting radionuclide that is approved for the treatment of patients with metastatic prostate cancer and is currently being tested in clinical trials for primary and metastatic cancers to the bone. 223Ra accumulates in mineralized bone areas with high bone turnover, where its effects are confined within 100 μm of the bone–marrow interface due to the short tissue penetrance of the alpha particles. A recent clinical study has shown a significantly increased fracture rate associated with the administration of 223Ra, mostly in tumor-free bones. Importantly, the biological mechanisms underlying this bone fragility remain unclear. In this …

Dominant Negative Atp5f1a Variants Disrupt Oxidative Phosphorylation Causing Neurological Disorders, Sara M Fielder, Marisa W Friederich, Daniella H Hock, Jessie R Zhang, Liana M Valin, Jill A Rosenfeld, Kevin T A Booth, Natasha J Brown, Rocio Rius, Tanavi Sharma, Liana N Semcesen, Kim C Worley, Lindsay C Burrage, Kayla Treat, Tara Samson, Sarah Govert, Sara Dacunha, Weimin Yuan, Jian Chen, Jacob Lesinski, Hieu Hoang, Stephanie A Morrison, Farah A Ladha, Roxanne A Van Hove, Cole R Michel, Richard Reisdorph, Eric Tycksen, Dustin Baldridge, Gary A Silverman, Claudia Soler-Alfonso, Erin Conboy, Francesco Vetrini, Lisa Emrick, William J Craigen, Undiagnosed Diseases Network, Stephen M Sykes, David A Stroud, Johan L K Van Hove, Tim Schedl, Stephen C Pak

Faculty, Staff and Students Publications

ATP5F1A encodes the α-subunit of complex V of the respiratory chain, which is responsible for mitochondrial ATP synthesis. We describe 6 probands with heterozygous de novo missense ATP5F1A variants that presented with developmental delay, intellectual disability, and movement disorders. All variants were located at the contact points between the α- and β-subunits. Functional studies in C. elegans revealed that the variants were damaging via a dominant negative genetic mechanism. Biochemical and proteomics studies of proband-derived cells showed a marked reduction in complex V abundance and activity. Mitochondrial physiology studies revealed increased oxygen consumption, yet decreased mitochondrial membrane potential and ATP …

Stratifying Lung Adenocarcinoma Risk With Multi-Ancestry Polygenic Risk Scores In East Asian Never-Smokers, Batel Blechter, Xiaoyu Wang, Juncheng Dai, Christiana Karsonaki, Jianxin Shi, Kouya Shiraishi, Jiyeon Choi, Keitaro Matsuo, Tzu-Yu Chen, Rayjean J Hung, Kexin Chen, Xiao-Ou Shu, Young Tae Kim, Parichoy Pal Choudhury, Jacob Williams, Maria Teresa Landi, Dongxin Lin, Wei Zheng, Zhihua Yin, Baosen Zhou, Jiucun Wang, Wei Jie Seow, Lei Song, I-Shou Chang, Wei Hu, Li-Hsin Chien, Qiuyin Cai, Yun-Chul Hong, Hee Nam Kim, Yi-Long Wu, Maria Pik Wong, Brian Douglas Richardson, Shilan Li, Tongwu Zhang, Charles Breeze, Zhaoming Wang, Bryan A Bassig, Jin Hee Kim, Demetrius Albanes, Jason Yy Wong Sm, Min-Ho Shin, Lap Ping Chung, Yang Yang, Hong Zheng, Hongji Dai, Yasushi Yatabe, Xu-Chao Zhang, Young-Chul Kim, Neil E Caporaso, Jiang Chang, James Chung Man Ho, Yataro Daigo, Yukihide Momozawa, Yoichiro Kamatani, Masashi Kobayashi, Kenichi Okubo, Takayuki Honda, H Dean Hosgood, Hideo Kunitoh, Shun-Ichi Watanabe, Yohei Miyagi, Shingo Matsumoto, Hidehito Horinouchi, Masahiro Tsuboi, Ryuji Hamamoto, Koichi Goto, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Megumi Hara, Yuichiro Nishida, Kenji Takeuchi, Kenji Wakai, Koichi Matsuda, Yoshinori Murakami, Kimihiro Shimizu, Hiroyuki Suzuki, Motonobu Saito, Yoichi Ohtaki, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Mitchell J Machiela, Yeul Hong Kim, In-Jae Oh, Victor Ho Fun Lee, Gee-Chen Chang, Kuan-Yu Chen, Wu-Chou Su, Yuh-Min Chen, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Yu-Tang Gao, Jianjun Liu, Ann G Schwartz, Richard Houlston, Ivan P Gorlov, Xifeng Wu, Ping Yang, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, Bu-Tian Ji, H-Erich Wichmann, David C Christiani, Gad Rennert, Susanne M Arnold, Paul Brennan, James Mckay, John K Field, Michael P A Davies, Sanjay S Shete, Loïc Le Marchand, Geoffrey Liu, Angeline S Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Kjell Grankvist, Angela Cox, Fiona Taylor, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Hyo-Sung Jeon, Shih Sheng Jiang, Chung-Hsing Chen, Chin-Fu Hsiao, Zhibin Hu, Laura Burdett, Meredith Yeager, Amy Hutchinson, Belynda Hicks, Jia Liu, Sonja I Berndt, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Chang Hyun Kang, Wen-Chang Wang, Jun Xu, Peng Guan, Wen Tan, Chong-Jen Yu, Gong Yang, Alan Dart Loon Sihoe, Yi Young Choi, In Kyu Park, Hsiao-Han Hung, Roel C H Vermeulen, Iona Cheng, Junjie Wu, Fang-Yu Tsai, John K C Chan, Jihua Li, Hsien-Chih Lin, Jie Liu, Bao Song, Norie Sawada, Taiki Yamaji, Kathleen Wyatt, Hongxia Ma, Meng Zhu, Yifan Wang, Tianchen Qi, Xuelian Li, Yangwu Ren, Ann Chao, Motoki Iwasaki, Junjie Zhu, Guoping Wu, Chih-Yi Chen, Chien-Jen Chen Scd, Pan-Chyr Yang, Victoria L Stevens, Joseph F Fraumeni, Kuang Lin, Robin G Walters, Zhengming Chen, Nilanjan Chatterjee, Olga Y Gorlova, Christopher I Amos, Hongbing Shen, Chao Agnes Hsiung, Stephen J Chanock, Nathaniel Rothman, Takashi Kohno, Qing Lan, Haoyu Zhang

Faculty, Staff and Students Publications

Background: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction.

Methods: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the …

Bi-Allelic Loss-Of-Function Variants In Poc5 Cause A Syndromic Retinal, Endocrine, And Neuromuscular Ciliopathy, Anneke T Vulto-Van Silfhout, Ingrid M Jazet, Suzanne Yzer, Jeroen Pas, Serwet Demirdas, Elisabeth F C Van Rossum, Alberta A H J Thiadens, Ronald Van Beek, Lonneke Haer-Wigman, Daniela Q C M Barge-Schaapveld, Charlotte Brasch-Andersen, Simon Frost, Miriam Bauwens, Elfride De Baere, Irina Balikova, Filip Van Den Broeck, Monika Weisz-Hubshman, Pascal Joset, Peter Miny, Isabel Filges, Susanne Kohl, Pietro De Angeli, Laura Kühlewein, Jan-Philipp Bodenbender, Tobias Haack, Karin Poths, Lidia Fernandez-Caballero, Marta Corton, Fiona Blanco Kelly, Carmen Ayuso, Peggy Martínez-Esteban, John Vissing, Jordi Díaz-Manera, Volker Straub, Ana Töpf, Siying Lin, Gavin Arno, William L Macken, Jennifer Spillane, Radha Ramachandran, Erik De Vrieze, Tjakko Van Ham, Susanne Roosing, Machteld M Oud

Faculty, Staff and Students Publications

Purpose: A homozygous loss-of-function (LoF) variant in POC5 was previously described in an individual with retinitis pigmentosa. We identified POC5 variants in 12 probands with a syndromic phenotype. We aim to define the phenotype spectrum and molecular mechanism associated with biallelic POC5 LoF variants.

Methods: We studied a cohort of 12 families with bi-allelic LoF POC5 variants and performed detailed phenotype analysis. POC5 localization studies were performed in 3 proband-derived fibroblast cell lines.

Results: Detailed phenotyping of probands with POC5 variants expands the phenotype spectrum beyond ocular manifestations. This syndrome causes not only rod-cone dystrophy but also diabetes mellitus with …

Associations Of High Attenuation Area-Related Proteomic Biomarkers With Fibrotic Or Subpleural Interstitial Lung Abnormalities, John S Kim, Catherine L Debban, Daniel E Guzman, Riley T Hannan, Mary Salvatore, Claire Mcgroder, David Zhang, Anna J Podolanczuk, Daniel A Duprez, Shwu-Fan Ma, Yong Huang, Jeffrey M Sturek, Stephen S Rich, Jerome I Rotter, Rajat Deo, Ruth F Dubin, Janelle Vu Pugashetti, Jennifer M Wang, Meilan K Han, Justin M Oldham, Imre Noth, Prescott G Woodruff, Victor E Ortega, Julie C Fanburg-Smith, Edward B Stelow, Christopher A Moskaluk, Eric A Hoffman, Christine Kim Garcia, Russell P Bowler, Peter Ganz, R Graham Barr, Ani Manichaikul

Faculty, Staff and Student Publications

No abstract provided.

Enhancing Stemm Education Through Advanced Technologies And Collaborative Programs, Zhongcheng Shi, Michael Nguyen, Yuan Yao, Debra D Murray, Rayne H Rouce, Veronica Ajewole, Huan Xie, Shixia Huang

Faculty and Staff Publications

Integrating advanced technologies into STEMM (Science, Technology, Engineering, Mathematics, and Medicine) education is essential for preparing a future-ready, diverse scientific workforce capable of addressing complex global challenges. This paper presents three interconnected programs-BRITE (Biotechnology Research Incubator for Teachers), ASPIRATION (AI-guided Scientist-Mentored Primary Literature Adaptation for STEMM Education), and C-REP (Cancer Research Education Program)-developed through collaborations with Advanced Technology Cores and multi-institutional participation, involving mentors ranging from core directors to graduate and medical students. While initially supported by internal funding, two of these initiatives have since secured NIH grant support. These initiatives provide immersive, hands-on training in genomics, proteomics, metabolomics, flow …

Observational Activation Of Anterior Cingulate Cortical Neurons Coordinates Hippocampal Replay In Social Learning, Xiang Mou, Daoyun Ji

Faculty, Staff and Students Publications

Social learning enables a subject to make decisions by observing the actions of another. How neural circuits acquire relevant information during observation to guide subsequent behavior is unknown. Utilizing an observational spatial working memory task, we show that neurons in the rat anterior cingulate cortex (ACC) associated with spatial trajectories during self-running in a maze are reactivated when observing another rat running the same maze. The observation-induced ACC activities are reduced in error trials and are correlated with activities of hippocampal place cells representing the same trajectories. The ACC activities during observation also predict subsequent hippocampal place cell activities during …

Clinically Significant Neuroimaging Findings Among Pediatric Patients Presenting To The Emergency Department With Symptoms Of Psychosis: A Multicenter Retrospective Study, Jennifer A Hoffmann, Tapan K Parikh, Doug Lorenz, Michael P Goldman, Emily M Powers, Shilpa J Patel, Ilana S Lavina, Theodore W Heyming, Jasmin T England, Mohsen Saidinejad, Ilene Claudius, Pallavi Ghosh, Daniel J Shapiro, Tricia B Swan, Kamali L Bouvay, Eileen Murtagh Kurowski, Nadine M Smith, Justin R Davis, Alexander B Moxam, Eli J Muhrer, Rohit P Shenoi, Elyse N Portillo, Ron L Kaplan, Neil G Uspal, Robert M Lapus, Andrea T Vo, Daniel B Fenster, Danielle B Barrocas, Deborah R Liu, Pradip P Chaudhari, Rachel Cafferty, Stephen B Freedman, Jerri A Rose, Megan F Evers, Ashley M Metcalf, Fareed Saleh, Jennifer Dunnick, Raymond D Pitetti, Yashas R Nathani, Muhammad Waseem, Todd A Florin

Faculty, Staff and Students Publications

Background: The clinical utility of diagnostic neuroimaging for pediatric patients presenting to the emergency department (ED) for psychosis remains unclear. We sought to estimate the prevalence of and characteristics associated with clinically significant neuroimaging findings among pediatric patients presenting to the ED with symptoms of psychosis who had neuroimaging performed.

Methods: This retrospective cross-sectional study included visits by patients 5 to < 18 years old presenting with symptoms of psychosis to 28 EDs affiliated with the Pediatric Emergency Medicine Collaborative Research Committee from 2016 to 2019 and had neuroimaging performed. We estimated the rate of clinically significant neuroimaging findings, defined as those resulting in further testing, treatment, or medical admission, overall and by imaging modality. Multivariable logistic regression models examined presenting features associated with clinically significant findings.

Results: Clinically significant neuroimaging findings were identified in 5.4% (95% CI 4.2%, 6.9%) of 1118 ED visits (54% male, median [IQR] 14 [11-16] years old). Clinically significant findings occurred in 4.9% (34/699) of head computed tomography scans and 7.5% …

Cyp1b1 Mediates Cigarette Smoke-Induced Lipid Accumulation In Alveolar Type 2 Cells, Yin Zhu, Siddhika Gamare, Francesca Polverino, Caroline A Owen, Payaningal R Somanath, Xiaoyun Wang, Duo Zhang

Faculty, Staff and Students Publications

Alterations in lipid profiles have been shown in patients with chronic obstructive pulmonary disease (COPD), but the underlying molecular mechanisms remain unclear. In this study, we aimed to investigate the role of cytochrome P450 family-1 subfamily B member 1 (CYP1B1) in cigarette smoke (CS)-induced lipid accumulation in alveolar type II epithelial (AT2) cells. We observed a steady increase in CYP1B1 protein levels in AT2 cells from COPD patients. Additionally, CS exposure induced CYP1B1 expression in AT2 cells of murine lungs. In vitro, treatment with cigarette smoke extract (CSE) not only upregulated CYP1B1 expression but also triggered lipid accumulation in AT2-like …