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The Effects Of Supplemental Dietary Chitosan On Broiler Performance And Myopathic Features Of White Striping, Mary F Love, Andrea Nicole Brooks, Sonya D Cox, Munachi Okpala, Gail Cooksey, Audrey Sarah Cohen, Anjail Z Sharrief

Faculty, Staff and Student Publications

Introduction

Stroke, a life-threatening stressor, often negatively impacts stroke-survivor (SS) quality of life (QoL). Annual age-adjusted incidence and death rates for stroke are significantly higher among Black Americans than among White Americans. Racism, a significant stressor, occurs at structural, cultural, and interpersonal levels and contributes to health disparities for Black SS. Resilience, a dynamic process of positive adaptation to significant stress, is impacted by factors or resources both internal and external to the individual. This study aims to examine the effects of experiences of racism and resilience on Black SS QoL during early stroke recovery. This article presents the study …

Adipose Tissue-Specific Ablation Of Ces1d Causes Metabolic Dysregulation In Mice, Gang Li, Xin Li, Li Yang, Shuyue Wang, Yulin Dai, Baharan Fekry, Lucas Veillon, Lin Tan, Rebecca Berdeaux, Kristin Eckel-Mahan, Philip L Lorenzi, Zhongming Zhao, Richard Lehner, Kai Sun

Faculty, Staff and Student Publications

Carboxylesterase 1d (Ces1d) is a crucial enzyme with a wide range of activities in multiple tissues. It has been reported to localize predominantly in ER. Here, we found that Ces1d levels are significantly increased in obese patients with type 2 diabetes. Intriguingly, a high level of Ces1d translocates onto lipid droplets where it digests the lipids to produce a unique set of fatty acids. We further revealed that adipose tissue-specific Ces1d knock-out (FKO) mice gained more body weight with increased fat mass during a high fat-diet challenge. The FKO mice exhibited impaired glucose and lipid metabolism and developed exacerbated liver …

Preventing Cholesterol-Induced Perk (Protein Kinase Rna-Like Endoplasmic Reticulum Kinase) Signaling In Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation, Abhijnan Chattopadhyay, Pujun Guan, Suravi Majumder, Kaveeta Kaw, Zhen Zhou, Chen Zhang, Siddharth K Prakash, Anita Kaw, L Maximillian Buja, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

BACKGROUND: Vascular smooth muscle cells (SMCs) undergo complex phenotypic modulation with atherosclerotic plaque formation in hyperlipidemic mice, which is characterized by de-differentiation and heterogeneous increases in the expression of macrophage, fibroblast, osteogenic, and stem cell markers. An increase of cellular cholesterol in SMCs triggers similar phenotypic changes in vitro with exposure to free cholesterol due to cholesterol entering the endoplasmic reticulum, triggering endoplasmic reticulum stress and activating Perk (protein kinase RNA-like endoplasmic reticulum kinase) signaling.

METHODS: We generated an SMC-specific

RESULTS: SMC-specific deletion of Perk reduces atherosclerotic plaque formation in male hyperlipidemic mice by 80%. Single-cell transcriptomic data identify 2 …

Clinical Research In Ovarian Cancer: Consensus Recommendations From The Gynecologic Cancer Intergroup, Ignace Vergote, Antonio Gonzalez-Martin, Domenica Lorusso, Charlie Gourley, Mansoor Raza Mirza, Jean-Emmanuel Kurtz, Aikou Okamoto, Kathleen Moore, Frédéric Kridelka, Iain Mcneish, Alexander Reuss, Bénédicte Votan, Andreas Du Bois, Sven Mahner, Isabelle Ray-Coquard, Elise C Kohn, Jonathan S Berek, David S P Tan, Nicoletta Colombo, Rongyu Zang, Nicole Concin, Dearbhaile O'Donnell, Alejandro Rauh-Hain, C Simon Herrington, Christian Marth, Andres Poveda, Keiichi Fujiwara, Gavin C E Stuart, Amit M Oza, Michael A Bookman, Participants Of The 6th Gynecologic Cancer Intergroup (Gcig) Ovarian Cancer Consensus Conference On Clinical Research

Faculty, Staff and Student Publications

The Gynecologic Cancer InterGroup (GCIG) sixth Ovarian Cancer Conference on Clinical Research was held virtually in October, 2021, following published consensus guidelines. The goal of the consensus meeting was to achieve harmonisation on the design elements of upcoming trials in ovarian cancer, to select important questions for future study, and to identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and adoption of 20 statements within four topic groups on clinical research in ovarian cancer including first line treatment, recurrent disease, disease subgroups, and future trials. Unanimous consensus was obtained for 14 of 20 statements, with …

Novel Mitochondria-Targeting Compounds Selectively Kill Human Leukemia Cells, Svetlana B Panina, Jingqi Pei, Natalia Baran, Elissa Tjahjono, Shraddha Patel, Gheath Alatrash, Sergej Konoplev, Leonid A Stolbov, Vladimir V Poroikov, Marina Konopleva, Natalia V Kirienko

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is a heterogeneous group of aggressive hematological malignancies commonly associated with treatment resistance, high risk of relapse, and mitochondrial dysregulation. We identified six mitochondria-affecting compounds (PS compounds) that exhibit selective cytotoxicity against AML cells in vitro. Structure-activity relationship studies identified six analogs from two original scaffolds that had over an order of magnitude difference between LD50 in AML and healthy peripheral blood mononuclear cells. Mechanistically, all hit compounds reduced ATP and selectively impaired both basal and ATP-linked oxygen consumption in leukemic cells. Compounds derived from PS127 significantly upregulated production of reactive oxygen species (ROS) in AML …

Advances In Head And Neck Cancer Pain, Y Ye, D D Jensen, C T Viet, H L Pan, W M Campana, M Amit, M D Boada

Faculty, Staff and Student Publications

Head and neck cancer (HNC) affects over 890,000 people annually worldwide and has a mortality rate of 50%. Aside from poor survival, HNC pain impairs eating, drinking, and talking in patients, severely reducing quality of life. Different pain phenotype in patients (allodynia, hyperalgesia, and spontaneous pain) results from a combination of anatomical, histopathological, and molecular differences between cancers. Poor pathologic features (e.g., perineural invasion, lymph node metastasis) are associated with increased pain. The use of syngeneic/immunocompetent animal models, as well as a new mouse model of perineural invasion, provides novel insights into the pathobiology of HNC pain. Glial and immune …

Preventing Cholesterol-Induced Perk (Protein Kinase Rna-Like Endoplasmic Reticulum Kinase) Signaling In Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation, Abhijnan Chattopadhyay, Pujun Guan, Suravi Majumder, Kaveeta Kaw, Zhen Zhou, Chen Zhang, Siddharth K Prakash, Anita Kaw, L Maximillian Buja, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

BACKGROUND: Vascular smooth muscle cells (SMCs) undergo complex phenotypic modulation with atherosclerotic plaque formation in hyperlipidemic mice, which is characterized by de-differentiation and heterogeneous increases in the expression of macrophage, fibroblast, osteogenic, and stem cell markers. An increase of cellular cholesterol in SMCs triggers similar phenotypic changes in vitro with exposure to free cholesterol due to cholesterol entering the endoplasmic reticulum, triggering endoplasmic reticulum stress and activating Perk (protein kinase RNA-like endoplasmic reticulum kinase) signaling.

METHODS: We generated an SMC-specific

RESULTS: SMC-specific deletion of Perk reduces atherosclerotic plaque formation in male hyperlipidemic mice by 80%. Single-cell transcriptomic data identify 2 …

Unilateral Radiation Therapy For Tonsillar Cancer: Treatment Outcomes In The Era Of Human Papillomavirus, Positron-Emission Tomography, And Intensity Modulated Radiation Therapy, Nicolette Taku, Gregory Chronowski, G Brandon Gunn, William H Morrison, Neil D Gross, Amy C Moreno, Renata Ferrarotto, Steven J Frank, C David Fuller, Ryan P Goepfert, Jack Phan, Stephen Y Lai, Jay P Reddy, David I Rosenthal, Adam S Garden

Faculty, Staff and Student Publications

Purpose: The goal of this study was to evaluate disease, survival, and toxic effects after unilateral radiation therapy treatment for tonsillar cancer.

Methods and materials: A retrospective study was performed of patients treated at our institution within the period from 2000 to 2018. Summary statistics were used to assess the cohort by patient characteristics and treatments delivered. The Kaplan-Meier method was used to determine survival outcomes.

Results: The cohort comprised 403 patients, including 343 (85%) with clinical and/or radiographic evidence of ipsilateral cervical nodal disease and 181 (45%) with multiple involved nodes. Human papillomavirus was detected in 294 (73%) tumors. …

Anesthesia For Echocardiography And Magnetic Resonance Imaging In The African Clawed Frog (Xenopus Laevis), Antonio F Corno, Noelia E Flores, Wen Li, Thomas H Gomez, Jorge D Salazar

Faculty, Staff and Student Publications

This report describes an anesthesia technique that we used to study cardiovascular anatomy and physiology with echocardiography and cardiac magnetic resonance (CMR) in 46 African clawed frogs (Xenopus laevis) (n = 24 for electrocardiography and n = 22 for CMR). For administration of anesthesia, 3 holding tanks, one each for transportation, sedation, and recovery, were filled with filtered water, with 0.05% buffered tricaine methasulfonate solution (MS-222) added into the sedation tank. Fifteen minutes after the frog was placed in the sedation tank, a paper towel was soaked in MS-222 solution, and the frog was placed in a …

Hepatic Recruitment Of Eosinophils And Their Protective Function During Acute Liver Injury, Long Xu, Yang Yang, Yankai Wen, Jong-Min Jeong, Christoph Emontzpohl, Constance L Atkins, Zhaoli Sun, Kyle L Poulsen, David R Hall, J Steve Bynon, Bin Gao, William M Lee, Jody Rule, Elizabeth A Jacobsen, Hua Wang, Cynthia Ju

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Beyond the classical description of eosinophil functions in parasite infections and allergic diseases, emerging evidence supports a critical role of eosinophils in resolving inflammation and promoting tissue remodeling. However, the role of eosinophils in liver injury and the underlying mechanism of their recruitment into the liver remain unclear.

METHODS: Hepatic eosinophils were detected and quantified using flow cytometry and immunohistochemical staining. Eosinophil-deficient (ΔdblGata1) mice were used to investigate the role of eosinophils in 3 models of acute liver injury. In vivo experiments using Il33

RESULTS: Hepatic accumulation of eosinophils was observed in patients with acetaminophen (APAP)-induced liver …

Pulmonary Fibrosis Model Using Micro-Ct Analyzable Human Psc-Derived Alveolar Organoids Containing Alveolar Macrophage-Like Cells, Seri Choi, Jiwoong Choi, Seongmin Cheon, Jihong Song, Seung-Yeon Kim, Ji-Eun Kim, Dae-Hwan Nam, Gohar Manzar, Su-Man Kim, Hyung-Sik Kang, Kee K Kim, Sang Hoon Jeong, Ju-Han Lee, Eun-Kee Park, Minseob Lee, Hyang-Ae Lee, Ki-Suk Kim, Han-Jin Park, Won Keun Oh, Chungoo Park, Chang Hyun Lee, Eun-Mi Kim

Faculty, Staff and Student Publications

Human lung organoids (hLOs) are useful for disease modelling and drug screening. However, a lack of immune cells in hLOs limits the recapitulation of in vivo cellular physiology. Here, we generated hLOs containing alveolar macrophage (AMφ)-like cells derived from pluripotent stem cells (PSC). To bridge hLOs with advanced human lung high-resolution X-ray computed tomography (CT), we acquired quantitative micro-CT images. Three hLO types were observed during differentiation. Among them, alveolar hLOs highly expressed not only lung epithelial cell markers but also AMφ-specific markers. Furthermore, CD68

Changes Of Brain Function In Patients With Type 2 Diabetes Mellitus Measured By Different Analysis Methods: A New Coordinate-Based Meta-Analysis Of Neuroimaging, Ze-Yang Li, Teng Ma, Ying Yu, Bo Hu, Yu Han, Hao Xie, Min-Hua Ni, Zhu-Hong Chen, Yang-Ming Zhang, Yu-Xiang Huang, Wen-Hua Li, Wen Wang, Lin-Feng Yan, Guang-Bin Cui

Faculty, Staff and Student Publications

OBJECTIVE: Neuroimaging meta-analysis identified abnormal neural activity alterations in patients with type 2 diabetes mellitus (T2DM), but there was no consistency or heterogeneity analysis between different brain imaging processing strategies. The aim of this meta-analysis was to determine consistent changes of regional brain functions in T2DM

METHODS: Since the indicators obtained using varied post-processing methods reflect different neurophysiological and pathological characteristics, we further conducted a coordinate-based meta-analysis (CBMA) of the two categories of neuroimaging literature, which were grouped according to similar data processing methods: one group included regional homogeneity (ReHo), independent component analysis (ICA), and degree centrality (DC) studies, while …

Mir-103-3p Promotes Hepatic Steatosis To Aggravate Nonalcoholic Fatty Liver Disease By Targeting Of Acox1, Jiexia Ding, Caixia Xia, Panpan Cen, Siying Li, Lifei Yu, Jing Zhu, Jie Jin

Faculty, Staff and Student Publications

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major risk factor for hepatocellular carcinoma, and alterations in miRNA expression are related to the development of NAFLD. However, the role of miRNAs in regulating the development of NAFLD is still poorly understood.

METHODS: We used qRT-PCR to detect the level of miR-103-3p in both cell and mouse models of NAFLD. Biochemical assays, DCF-DA assays, Oil red O staining and HE staining were used to detect the role of miR-103-3p in NAFLD development. Target genes of miR-103-3p were predicted using the TargetScan database and verified by qRT-PCR, western blot and dual-luciferase assays. …

Geriatric Cardiology: Coming Of Age, Parag Goyal, Min Ji Kwak, Christina Al Malouf, Manish Kumar, Namit Rohant, Abdulla A Damluji, Quin E Denfeld, Kim K Bircher, Ashok Krishnaswami, Karen P Alexander, Daniel E Forman, Michael W Rich, Nanette K Wenger, James N Kirkpatrick, Jerome L Fleg

Faculty, Staff and Student Publications

Older adults with cardiovascular disease (CVD) contend with deficits across multiple domains of health due to age-related physiological changes and the impact of CVD. Multimorbidity, polypharmacy, cognitive changes, and diminished functional capacity, along with changes in the social environment, result in complexity that makes provision of CVD care to older adults challenging. In this review, we first describe the history of geriatric cardiology, an orientation that acknowledges the unique needs of older adults with CVD. Then, we introduce 5 essential principles for meeting the needs of older adults with CVD: 1) recognize and consider the potential impact of multicomplexity; 2) …

Antibody Evasion By Sars-Cov-2 Omicron Subvariants Ba2121, Ba4 And Ba5, Qian Wang, Yicheng Guo, Sho Iketani, Manoj S Nair, Zhiteng Li, Hiroshi Mohri, Maple Wang, Jian Yu, Anthony D Bowen, Jennifer Y Chang, Jayesh G Shah, Nadia Nguyen, Zhiwei Chen, Kathrine Meyers, Michael T Yin, Magdalena E Sobieszczyk, Zizhang Sheng, Yaoxing Huang, Lihong Liu, David D Ho

Faculty, Staff and Student Publications

SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged notably to become dominant in the United States and South Africa, respectively1,2. These new subvariants carrying further mutations in their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike …

Insulin Resistance In Depression: A Large Meta-Analysis Of Metabolic Parameters And Variation, Brisa S Fernandes, Estela Salagre, Nitesh Enduru, Iria Grande, Eduard Vieta, Zhongming Zhao

Faculty, Staff and Student Publications

Increased insulin resistance is recognized in psychiatric disorders, such as schizophrenia and bipolar disorder, but its occurrence in depression is less clear. Our aims were to verify if insulin resistance is altered in depression, to test the metabolic subgroup hypothesis of depression and if there are changes with antidepressants. Inclusion criteria were studies including adult subjects with depression and either a control group or follow-up after treatment with antidepressants, and assessing fasting insulin or glucose levels or the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index. Seventy studies with 240,704 participants were included. Both insulin levels and the HOMA-IR index …

Strategy For Generating Blinded Evidence For Single-Arm Trials With External Controls Using Expert Review Of Home Video, Bharti Manwani, Carson Finger, Lynda Lisabeth

Faculty, Staff and Student Publications

Stroke risk and prevalence increase with advanced age and women tend to be older than men at the time of their first stroke. Advanced age in women confers unique stroke risks that are beyond reproductive factors. Previous reviews and guidelines have largely focused on risk factors specific to women, with a predominant focus on reproductive factors and, therefore, younger to middle-aged women. This review aims to specifically describe stroke risk factors in elderly women, the population of women where the majority of strokes occur, with a focus on atrial fibrillation, hormone therapy, psychosocial risk factors, and cognitive impairment. Our review …

Tp53-Altered Chronic Lymphocytic Leukemia Treated With Firstline Bruton’S Tyrosine Kinase Inhibitor-Based Therapy: A Retrospective Analysis, Hua-Jay J Cherng, Raamis Khwaja, Rashmi Kanagal-Shamanna, Guilin Tang, Jan Burger, Philip Thompson, Alessandra Ferrajoli, Zeev Estrov, Koji Sasaki, Deepa Sampath, Xuemei Wang, Hagop Kantarjian, Michael Keating, William G Wierda, Nitin Jain

Faculty, Staff and Student Publications

Long-term follow up of prospective studies has shown that continuous Bruton's tyrosine kinase inhibitor (BTKi) therapy leads to durable remissions in previously untreated patients with TP53-altered chronic lymphocytic leukemia (CLL); however, it is unknown how variant allele frequency (VAF) of TP53 mutation (TP53-m) or percentage of cells with deletion of chromosome 17p [del(17p)] influences efficacy of firstline BTKi. We performed a retrospective analysis of 130 patients with CLL with baseline del(17p) and/or TP53-m treated with BTKi with or without the BCL2 inhibitor venetoclax (VEN) and with or without CD20 antibody in the firstline setting. A total of 104/130 (80%) patients …

Spatial Charting Of Single-Cell Transcriptomes In Tissues, Runmin Wei, Siyuan He, Shanshan Bai, Emi Sei, Min Hu, Alastair Thompson, Ken Chen, Savitri Krishnamurthy, Nicholas E Navin

Faculty, Staff and Student Publications

Single-cell RNA sequencing methods can profile the transcriptomes of single cells but cannot preserve spatial information. Conversely, spatial transcriptomics assays can profile spatial regions in tissue sections, but do not have single-cell resolution. Here, we developed a computational method called CellTrek that combines these two datasets to achieve single-cell spatial mapping through coembedding and metric learning approaches. We benchmarked CellTrek using simulation and in situ hybridization datasets, which demonstrated its accuracy and robustness. We then applied CellTrek to existing mouse brain and kidney datasets and showed that CellTrek can detect topological patterns of different cell types and cell states. We …

Artificial Intelligence-Assisted Mapping Of Proliferation Centers Allows The Distinction Of Accelerated Phase From Large Cell Transformation In Chronic Lymphocytic Leukemia, Siba El Hussein, Pingjun Chen, L Jeffrey Medeiros, John D Hazle, Jia Wu, Joseph D Khoury

Faculty, Staff and Student Publications

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is characterized morphologically by numerous small lymphocytes and pale nodules composed of prolymphocytes and paraimmunoblasts known as proliferation centers (PCs). Patients with CLL can undergo transformation to a more aggressive lymphoma, most often diffuse large B-cell lymphoma (DLBCL), known as Richter transformation (RT). An accelerated phase of CLL (aCLL) also may be observed which correlates with subsequent transformation to DLBCL, and may represent an early stage of transformation. Distinguishing PCs in CLL from aCLL or RT can be diagnostically challenging, particularly in small needle biopsy specimens. Available guidelines pertaining to distinguishing CLL from its' …

Generation Of A Homozygous Knock-In Human Embryonic Stem Cell Line Expressing Meos4b-Tagged Ctr1, Yi-Hung Chen, Pei-San Huang, Meng-Hsuan Wen, Manhua Pan, Dung-Fang Lee, Tai-Yen Chen

Faculty, Staff and Student Publications

Copper transporter 1 (CTR1) is the major membrane protein responsible for cellular copper (Cu) uptake and mediates cellular copper homeostasis. To elucidate CTR1's behavior using imaging approaches, we generated a homozygous knock-in human embryonic stem cell (hESC) clone expressing photoconvertible fluorescence protein mEos4b-tagged endogenous CTR1 using CRISPR-Cas9 mediated homologous recombination. The engineered cells express functional CTR1-mEos4b fusion and have normal stem cell morphology. They remain pluripotent and can be differentiated into all three germ layers in vitro. This resource allows the study of CTR1 at an endogenous level in different cellular contexts using microscopy.

Plasma Metabolomics Analysis Of Aspirin Treatment And Risk Of Colorectal Adenomas, Elizabeth L Barry, Veronika Fedirko, Yutong Jin, Ken Liu, Leila A Mott, Janet L Peacock, Michael N Passarelli, John A Baron, Dean P Jones

Faculty, Staff and Student Publications

Despite substantial observational and experimental evidence that aspirin use can provide protection against the development of colorectal neoplasia, our understanding of the molecular mechanisms involved is inadequate and limits our ability to use this drug effectively and safely for chemoprevention. We employed an untargeted plasma metabolomics approach using liquid chromatography with high-resolution mass spectroscopy to explore novel metabolites that may contribute to the chemopreventive effects of aspirin. Associations between levels of metabolic features in plasma and aspirin treatment were investigated among 523 participants in a randomized placebo-controlled clinical trial of two doses of aspirin (81 or 325 mg/day) and were …

Microbiome Dynamics During Chemoradiation Therapy For Anal Cancer, Daniel Lin, Molly B El Alam, Joseph Abi Jaoude, Ramez Kouzy, Jae L Phan, Jacob H Elnaggar, Brianna Resendiz, Andrea Y Delgado Medrano, Erica J Lynn, Nicholas D Nguyen, Sonal S Noticewala, Geena G Mathew, Emma B Holliday, Bruce D Minsky, Prajnan Das, Van K Morris, Cathy Eng, Melissa P Mezzari, Joseph F Petrosino, Nadim J Ajami, Ann H Klopp, Cullen M Taniguchi, Lauren E Colbert

Faculty, Staff and Student Publications

Purpose: Patients with localized squamous cell carcinoma of the anus (SCCA) who experience treatment toxicity or recurrences have few therapeutic options. Investigation into the microbiome's influence on treatment toxicity and its potential use as a predictive biomarker could improve these patients' outcomes. Our study presents the first longitudinal characterization of the SCCA tumor microbiome and its associations with treatment-related toxicities.

Methods and materials: This prospective cohort study included patients with nonmetastatic SCCA receiving standard-of-care chemoradiation therapy. Anorectal swabs of the tumor site were collected before, during, and after treatment. Patient-reported quality-of-life metrics were collected at similar time points. 16S rRNA …

Proteomes Of Extracellular Vesicles From Pancreatic Cancer Cells And Cancer-Associated Fibroblasts, Sharon Pan, Lisa A Lai, Diane M Simeone, David W Dawson, Yuanqing Yan, Tatjana Crnogorac-Jurcevic, Ru Chen, Teresa A Brentnall

Faculty, Staff and Students Publications

OBJECTIVES: Extracellular vesicles (EVs) are lipid bound vesicles secreted by cells into the extracellular environment. Studies have implicated EVs in cell proliferation, epithelial-mesenchymal transition, metastasis, angiogenesis, and mediating the interaction of tumor cells and microenvironment. A systematic characterization of EVs from pancreatic cancer cells and cancer-associated fibroblasts (CAFs) would be valuable for studying the roles of EV proteins in pancreatic tumorigenesis.

METHODS: Proteomic and functional analyses were applied to characterize the proteomes of EVs released from 5 pancreatic cancer lines, 2 CAF cell lines, and a normal pancreatic epithelial cell line (HPDE).

RESULTS: More than 1400 nonredundant proteins were identified …

Cell Plasticity In Regeneration In The Stomach And Beyond, Mahliyah Adkins-Threats, Jason C Mills

Faculty, Staff and Students Publications

Recent studies using cell lineage-tracing techniques, organoids, and single-cell RNA sequencing analyses have revealed: 1) adult organs use cell plasticity programs to recruit progenitor cells to regenerate tissues after injury, and 2) plasticity is far more common than previously thought, even in homeostasis. Here, we focus on the complex interplay of normal stem cell differentiation and plasticity in homeostasis and after injury, using the gastric epithelium as a touchstone. We also examine common features of regenerative programs and discuss the evolutionarily conserved, stepwise process of paligenosis which reprograms mature cells into progenitors that can repair damaged tissue. Finally, we discuss …

Deep Brain Stimulation For Depression Informed By Intracranial Recordings, Sameer A Sheth, Kelly R Bijanki, Brian Metzger, Anusha Allawala, Victoria Pirtle, Joshua A Adkinson, John Myers, Raissa K Mathura, Denise Oswalt, Evangelia Tsolaki, Jiayang Xiao, Angela Noecker, Adriana M Strutt, Jeffrey F Cohn, Cameron C Mcintyre, Sanjay J Mathew, David Borton, Wayne Goodman, Nader Pouratian

Staff and Researcher Publications

The success of deep brain stimulation (DBS) for treating Parkinson's disease has led to its application to several other disorders, including treatment-resistant depression. Results with DBS for treatment-resistant depression have been heterogeneous, with inconsistencies largely driven by incomplete understanding of the brain networks regulating mood, especially on an individual basis. We report results from the first subject treated with DBS for treatment-resistant depression using an approach that incorporates intracranial recordings to personalize understanding of network behavior and its response to stimulation. These recordings enabled calculation of individually optimized DBS stimulation parameters using a novel inverse solution approach. In the ensuing …

Randomized Placebo-Controlled Trial Of Losartan For Pediatric Nafld, Miriam B Vos, Mark L Van Natta, Niviann M Blondet, Srinivasan Dasarathy, Mark Fishbein, Paula Hertel, Ajay K Jain, Saul J Karpen, Joel E Lavine, Saeed Mohammad, Laura A Miriel, Jean P Molleston, Marialena Mouzaki, Arun Sanyal, Emily P Sharkey, Jeffrey B Schwimmer, James Tonascia, Laura A Wilson, Stavra A Xanthakos, Nash Clinical Research Network

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects.

APPROACH AND RESULTS: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT …

Is Detection Of Relapse By Surveillance Imaging Associated With Longer Survival In Patients With Rhabdomyosarcoma?, Stephanie Fetzko, Adriana Fonseca, Mary Frances Wedekind, Abha A Gupta, Bhuvana A Setty, Jeremy Schraw, Philip J Lupo, Robert P Guillerman, Anish A Butala, Heidi Russell, Lauren Nicholls, David Walterhouse, Douglas S Hawkins, Mehmet F Okcu

Center for Medical Ethics and Health Policy Staff Publications

Background: We investigated whether surveillance imaging had an impact on post-relapse survival in patients with rhabdomyosarcoma (RMS). We hypothesized that relapse detected by imaging (group IM) would be associated with longer survival compared with relapse detected with a clinical sign or symptom (group SS).

Materials and methods: We performed an observational multi-institutional study in 127 patients with relapsed RMS comparing overall survival (OS) after relapse using Kaplan-Meier and Cox proportional hazards analyses.

Results: Relapse was detected in 60 (47%) group IM and 67 (53%) SS patients. Median follow-up in survivors was 4 years (range 1.0 to 16.7 y). Four-year OS …

De Novo Heterozygous Variants In Slc30a7 Are A Candidate Cause For Joubert Syndrome, Monica Penon-Portmann, Mohammad K Eldomery, Lorraine Potocki, Dana Marafi, Jennifer E Posey, Zeynep Coban-Akdemir, Tamar Harel, Christopher M Grochowski, Hailey Loucks, Walter Patrick Devine, Jessica Van Ziffle, Dan Doherty, James R Lupski, Joseph T Shieh

Center for Medical Ethics and Health Policy Staff Publications

Joubert syndrome (JS), a well-established ciliopathy, is characterized by the distinctive molar tooth sign on brain MRI, ataxia, and neurodevelopmental features. Other manifestations can include polydactyly, accessory frenula, renal, or liver disease. Here, we report individuals meeting criteria for JS with de novo heterozygous variants in SLC30A7 (Chr1p21.2). The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. Exome sequencing detected a de novo heterozygous missense variant in SLC30A7: NM_133496.5: c.407 T > C, (p.Val136Ala). The second individual had bilateral postaxial polydactyly, molar …

Circulating Trophoblast Numbers As A Potential Marker For Pregnancy Complications, Brielle Crovetti, Mohamad Ali Maktabi, Hadi Erfani, Tachjaree Panchalee, Qun Wang, Liesbeth Vossaert, Ignatia Van Den Veyver

Center for Medical Ethics and Health Policy Staff Publications

Objective: To explore the potential of circulating trophoblasts (TBs) as a non-invasive tool to assess placental health and predict obstetric complications.

Methods: We retrospectively reviewed maternal characteristics and pregnancy outcomes of 369 women who enrolled in our original cell-based NIPT (cbNIPT) study. The number of circulating TBs recovered from the maternal blood samples was recorded and expressed as fetal cell concentration (FCC). We evaluated if FCC can be used to predict pregnancy outcomes such as hypertensive disorders of pregnancy (HDP), fetal growth restriction, placental abruption, preterm labor, and pregnancy loss.

Results: Receiver operating characteristic (ROC) analysis was performed to find …