Digital Commons Network^™

Culturally Relevant Africultural Coping Moderates The Association Between Discrimination And Antiretroviral Adherence Among Sexual Minority Black Americans Living With Hiv., Glenn J. Wagner, Laura M. Bogart, David J. Klein, Sean J. Lawrence, Kathy Goggin, Mahlet Gizaw, Matt G. Mutchler

Manuscripts, Articles, Book Chapters and Other Papers

Exposure to discrimination has been linked to lower HIV antiretroviral therapy (ART) adherence and poor HIV care outcomes among Black Americans. Coping has been shown to mitigate the harmful effects of discrimination on health behaviors, but the use of cultural relevant Africultural coping strategies is understudied as a moderator of the association between intersectional discrimination and ART adherence among Black Americans. We used adjusted logistic regression to test whether Africultural coping strategies (cognitive/emotional debriefing; collective; spiritual-centered; ritual-centered) moderated associations between multiple forms of discrimination (HIV, sexual orientation, race) and good ART adherence (minimum of 75% or 85% of prescribed doses …

Guidance For Assessment Of The Inflammation Etiologic Criterion For The Glim Diagnosis Of Malnutrition: A Modified Delphi Approach., Gordon L Jensen, Tommy Cederholm, Maria D Ballesteros-Pomar, Renee Blaauw, M Isabel T D Correia, Cristina Cuerda, David C Evans, Ryoji Fukushima, Juan Bernardo Ochoa Gautier, M Cristina Gonzalez, Andre Van Gossum, Leah Gramlich, Joseph Hartono, Steven B Heymsfield, Harriët Jager-Wittenaar, Renuka Jayatissa, Heather Keller, Ainsley Malone, William Manzanares, M Molly Mcmahon, Yolanda Mendez, Kris M Mogensen, Naoharu Mori, Maurizio Muscaritoli, Guillermo Contreras Nogales, Ibolya Nyulasi, Wendy Phillips, Matthias Pirlich, Veeradej Pisprasert, Elisabet Rothenberg, Marian De Van Der Schueren, Han Ping Shi, Alison Steiber, Marion F Winkler, Charlene Compher, Rocco Barazzoni

Ambulatory and Primary Care Articles

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation, and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation.

METHODS: A GLIM-constituted working group with …

Determinants Of Referral Network Size For Screening Colonoscopies In The Veterans Health Administration After The Implementation Of The Mission Act, Chase S Eck, Vivian Ho, Cheng Jiang, Laura A Petersen

Center for Medical Ethics and Health Policy Staff Publications

Objective: To measure key characteristics of the Veterans Health Administration's (VHA) Community Care (CC) referral network for screening colonoscopy and identify market and institutional factors associated with network size.

Data sources: VHA electronic health records, CC claim data, and National Plan and Provider Enumeration System.

Study design: In this retrospective cross-sectional study, we measure the size of the VHA's CC referral networks over time and by VHA parent facility (n = 137). We used a multivariable linear regression to identify factors associated with network size at the market-year level. Network size was measured as the number of physicians who performed …

Calorie Restriction Reduces Biomarkers Of Cellular Senescence In Humans, Zaira Aversa, Susan B Racette, Et Al.

2020-Current year OA Pubs

Calorie restriction (CR) with adequate nutrient intake is a potential geroprotective intervention. To advance this concept in humans, we tested the hypothesis that moderate CR in healthy young-to-middle-aged individuals would reduce circulating biomarkers of cellular senescence, a fundamental mechanism of aging and aging-related conditions. Using plasma specimens from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) phase 2 study, we found that CR significantly reduced the concentrations of several senescence biomarkers at 12 and 24 months compared to an ad libitum diet. Using machine learning, changes in biomarker concentrations emerged as important predictors of the change …

Current Understanding Of The Alzheimer's Disease-Associated Microbiome And Therapeutic Strategies, Dong-Oh Seo, David M Holtzman

2020-Current year OA Pubs

Alzheimer's disease (AD) is a fatal progressive neurodegenerative disease. Despite tremendous research efforts to understand this complex disease, the exact pathophysiology of the disease is not completely clear. Recently, anti-Aβ antibodies have been shown to remove amyloid from the brain and slow the clinical progression of mild dementia by ~30%. However, exploring alternative strategies is crucial to understanding and developing more effective therapeutic interventions. In recent years, the microbiota-gut-brain axis has received significant attention in the AD field. Numerous studies have suggested that alterations in the gut microbiota composition are associated with the progression of AD, and several underlying mechanisms …

Deep Learning-Based H-Score Quantification Of Immunohistochemistry-Stained Images, Zhuoyu Wen, Danni Luo, Shidan Wang, Ruichen Rong, Bret M Evers, Yisheng Fang, Shengjie Yang, Zifan Gu, Emily N Arner, Cheryl M Lewis, Luisa M Solis Soto, Junya Fujimoto, Carmen Behrens, Ignacio I Wistuba, Donghan M Yang, Rolf A Brekken, Kathryn A O'Donnell, Yang Xie, Guanghua Xiao

Faculty, Staff and Student Publications

Immunohistochemistry (IHC) is a well-established and commonly used staining method for clinical diagnosis and biomedical research. In most IHC images, the target protein is conjugated with a specific antibody and stained using diaminobenzidine (DAB), resulting in a brown coloration, whereas hematoxylin serves as a blue counterstain for cell nuclei. The protein expression level is quantified through the H-score, calculated from DAB staining intensity within the target cell region. Traditionally, this process requires evaluation by 2 expert pathologists, which is both time consuming and subjective. To enhance the efficiency and accuracy of this process, we have developed an automatic algorithm for …

The Biology Of Hope: Inflammatory And Neuroendocrine Profiles In Ovarian Cancer Patients, Susan K Lutgendorf, Rachel M Telles, Brendan Whitney, Premal H Thaker, George M Slavich, Frank J Penedo, Steven W Cole, Anil K Sood, Benjamin W Corn

Faculty, Staff and Student Publications

INTRODUCTION: Although the concept of hope is highly relevant for cancer patients, little is known about its association with cancer-relevant biomarkers. Here we examined how hope was related to diurnal cortisol and interleukin-6 (IL-6), a pro-inflammatory cytokine previously associated with tumor biology and survival in ovarian cancer. Secondly, we examined whether hope and hopelessness are distinctly associated with these biomarkers.

METHOD: Participants were 292 high-grade ovarian cancer patients who completed surveys and provided saliva samples 4x/daily for 3 days pre-surgery to assess diurnal cortisol. Blood (pre-surgery) and ascites were assessed for IL-6. Hope and hopelessness were assessed using standardized survey …

Mediators Of Necroptosis: From Cell Death To Metabolic Regulation, Xiaoqin Wu, Laura E Nagy, Jérémie Gautheron

Faculty, Staff and Student Publications

Necroptosis, a programmed cell death mechanism distinct from apoptosis, has garnered attention for its role in various pathological conditions. While initially recognized for its involvement in cell death, recent research has revealed that key necroptotic mediators, including receptor-interacting protein kinases (RIPKs) and mixed lineage kinase domain-like protein (MLKL), possess additional functions that go beyond inducing cell demise. These functions encompass influencing critical aspects of metabolic regulation, such as energy metabolism, glucose homeostasis, and lipid metabolism. Dysregulated necroptosis has been implicated in metabolic diseases, including obesity, diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD), contributing to chronic …

Lfsproshiny: An Interactive R/Shiny App For Prediction And Visualization Of Cancer Risks In Families With Deleterious Germline Tp53 Mutations, Nam H Nguyen, Elissa B Dodd-Eaton, Gang Peng, Jessica L Corredor, Wenwei Jiao, Banu K Arun

Faculty, Staff and Student Publications

Purpose: LFSPRO is an R library that implements risk prediction models for Li-Fraumeni syndrome (LFS), a genetic disorder characterized by deleterious germline mutations in the TP53 gene. To facilitate the use of these models in clinics, we developed LFSPROShiny, an interactive R/Shiny interface of LFSPRO that allows genetic counselors (GCs) to perform risk predictions without any programming components and further visualize the risk profiles of their patients to aid the decision-making process.

Methods: LFSPROShiny implements two models that have been validated on multiple LFS patient cohorts: a competing risk model that predicts cancer-specific risks for the first primary and a …

Glucose Metabolism In Posterior Cingulate Cortex Has Supplementary Value To Predict The Progression Of Cognitively Unimpaired To Dementia Due To Alzheimer’S Disease: An Exploratory Study Of 18f-Fdg-Pet, Qi Zhang, Chunqiu Fan, Luyao Wang, Taoran Li, Min Wang, Jiehui Jiang

Faculty, Staff and Student Publications

Amyloid-β (Aβ) and tau are important biomarkers to predict the progression of cognitively unimpaired (CU) to dementia due to Alzheimer's disease (AD), according to the diagnosis framework from the US National Institute on Aging and the Alzheimer's Association (NIA-AA). However, it is clinically difficult to predict those subjects who were already with Aβ positive (A +) or tau positive (T +). As a typical characteristic of neurodegeneration in the diagnosis framework, the hypometabolism of the posterior cingulate cortex (PCC) has significant clinical value in the early prediction and prevention of AD. In this paper, we proposed the glucose metabolism in …

Circulating Tumor Dna And Radiological Tumor Volume Identify Patients At Risk For Relapse With Resected, Early-Stage Non-Small-Cell Lung Cancer, H T Tran, S Heeke, S Sujit, N Vokes, J Zhang, V K Lam, S G Swisher, M C B Godoy, T Cascone, B Sepesi, D L Gibbons, J Wu, J V Heymach

Faculty, Staff and Student Publications

Background: Predicting relapse and overall survival (OS) in early-stage non-small-cell lung cancer (NSCLC) patients remains challenging. Therefore, we hypothesized that detection of circulating tumor DNA (ctDNA) can identify patients with increased risk of relapse and that integrating radiological tumor volume measurement along with ctDNA detectability improves prediction of outcome.

Patients and methods: We analyzed 366 serial plasma samples from 85 patients who underwent surgical resections and assessed ctDNA using a next-generation sequencing liquid biopsy assay, and measured tumor volume using a computed tomography-based three-dimensional annotation.

Results: Our results showed that patients with detectable ctDNA at baseline or after treatment and …

Experiences Of Patients With Peritoneal Carcinomatosis-Related Complex Care Needs And Their Caregivers, Rachel A Pozzar, Jaclyn A Wall, Anna Tavormina, Embree Thompson, Andrea C Enzinger, Susana Campos, Alexi A Wright

Faculty, Staff and Student Publications

Background: Patients with peritoneal carcinomatosis (PC) frequently undergo palliative procedures, yet these patients and their caregivers report being unprepared to manage ostomies, drains, and other complex care needs at home. The purpose of this study was to characterize the unique needs of these patients and their caregivers during care transitions.

Methods: Patients completed measures of health status and advance care planning, caregivers completed measures of preparedness and burden, and all participants completed measures of depression and anxiety. Participants detailed their experiences in individual, semi-structured interviews. We analyzed data using descriptive statistics and conventional content analysis.

Results: Sixty-one patients and 39 …

Safety And Academic Outcomes Of College Campus-Based Advocacy Services, Leila Wood

Faculty, Staff and Student Publications

Intimate partner violence (IPV), sexual assault, and stalking are consequential public health and safety issues with wide reaching impacts on emerging adults, including those on college campuses in the United States. In response to high rates of violence among college student populations, universities are developing campus-based advocacy (CBA) programs, which aim to support survivors of interpersonal violence through supportive connections, resource acquisition, and safety planning. However, little data exists related to their impact on key student-survivor outcomes. Thus, this study aims to understand (a) the approach CBA programs use to address safety and academic concerns of student-survivors, and (b) the …

Large-Scale Investigation Of White Matter Structural Differences In Bilingual And Monolingual Children: An Adolescent Brain Cognitive Development Data Study

Faculty, Staff and Student Publications

Emerging research has provided valuable insights into the structural characteristics of the bilingual brain from studies of bilingual adults; however, there is a dearth of evidence examining brain structural alterations in childhood associated with the bilingual experience. This study examined the associations between bilingualism and white matter organization in bilingual children compared to monolingual peers leveraging the large-scale data from the Adolescent Brain Cognitive Development (ABCD) Study. Then, 446 bilingual children (ages 9-10) were identified from the participants in the ABCD data and rigorously matched to a group of 446 monolingual peers. Multiple regression models for selected language and cognitive …

Rationale And Design Of The Nephrotic Syndrome Study Network (Neptune) Match In Glomerular Diseases: Designing The Right Trial For The Right Patient, Today, Sean Eddy, Wendy R Uhlmann, Cathie Spino, Lawrence B Holzman, John R Sedor, Crystal Gadegbeku, Lalita Subramanian, Chrysta C Lienczewski, Tina Manieri, Scott J Roberts, Debbie S Gipson, Matthias Kretzler, Neptune Investigators

Faculty, Staff and Student Publications

Glomerular diseases are classified using a descriptive taxonomy that is not reflective of the heterogeneous underlying molecular drivers. This limits not only diagnostic and therapeutic patient management, but also impacts clinical trials evaluating targeted interventions. The Nephrotic Syndrome Study Network (NEPTUNE) is poised to address these challenges. The study has enrolled >850 pediatric and adult patients with proteinuric glomerular diseases who have contributed to deep clinical, histologic, genetic, and molecular profiles linked to long-term outcomes. The NEPTUNE Knowledge Network, comprising combined, multiscalar data sets, captures each participant's molecular disease processes at the time of kidney biopsy. In this editorial, we …

What's Going Well: A Qualitative Analysis Of Positive Patient And Family Feedback In The Context Of The Diagnostic Process, Elizabeth Lowe, Sigall K Bell

Faculty, Staff and Student Publications

OBJECTIVES: Accurate and timely diagnosis relies on close collaboration between patients/families and clinicians. Just as patients have unique insights into diagnostic breakdowns, positive patient feedback may also generate broader perspectives on what constitutes a "good" diagnostic process (DxP).

METHODS: We evaluated patient/family feedback on "what's going well" as part of an online pre-visit survey designed to engage patients/families in the DxP. Patients/families living with chronic conditions with visits in three urban pediatric subspecialty clinics (site 1) and one rural adult primary care clinic (site 2) were invited to complete the survey between December 2020 and March 2022. We adapted the …

Patient Interest In Exploring Nonsurgical Treatment Approaches For Early-Stage Breast Cancer: A Qualitative Study, Maya Guhan, Stacey M Crane, Lillian S Valerius, Denise De La Cruz, Benjamin D Smith, Melissa P Mitchell, Gaiane M Rauch, Savitri Krishnamurthy, Carla L Warnecke, Henry M Kuerer, Simona F Shaitelman

Faculty, Staff and Student Publications

Purpose: Advances in radiation therapy have enabled the ability to deliver ablative treatments, but there has been limited application of these treatments to early-stage breast cancers with a goal of omitting surgery. The purpose of this study was to explore patient interest in pursuing nonsurgical treatment approaches for their early-stage breast cancer.

Methods and materials: We conducted a qualitative study involving interviews with 21 patients with early-stage breast cancer who were eligible for participation in a phase 2 clinical trial offering omission of definitive surgery. Interviews were transcribed and an inductive, thematic analysis was performed by 3 independent reviewers to …

The Role Of Peroxisome Proliferator-Activated Receptors In The Development And Physiology Of Gametes And Preimplantation Embryos, Dev Patel, Maria M Patarroyo-Aponte, Biswajit Kar, Igor D Gregoric, Caroline Ha, Bela Patel

Faculty, Staff and Student Publications

Background: Extracorporeal membrane oxygenation (ECMO) has extended the survivability of critically ill patients beyond their unsupported prognosis and has widened the timeframe for making an informed decision about the goal of care. However, an extended time window for survival does not necessarily translate into a better outcome and the sustaining treatment is ultimately withdrawn in many patients. Emerging evidence has implicated the determining role of palliative care consult (PCC) in direction of the care that critically ill patients receive. Objective: To evaluate the impact of PCC in withdrawal of life-sustaining treatment (WOLST) among critically ill patients, who were placed on …

The Role Of Palliative Care Consultation In Withdrawal Of Life-Sustaining Treatment Among Icu Patients Receiving Veno-Venous Extracorporeal Membrane Oxygenation (Vv-Ecmo): A Retrospective Case-Control Study, Dev Patel, Maria M Patarroyo-Aponte, Biswajit Kar, Igor D Gregoric, Caroline Ha, Bela Patel

Faculty, Staff and Student Publications

Background: Extracorporeal membrane oxygenation (ECMO) has extended the survivability of critically ill patients beyond their unsupported prognosis and has widened the timeframe for making an informed decision about the goal of care. However, an extended time window for survival does not necessarily translate into a better outcome and the sustaining treatment is ultimately withdrawn in many patients. Emerging evidence has implicated the determining role of palliative care consult (PCC) in direction of the care that critically ill patients receive. Objective: To evaluate the impact of PCC in withdrawal of life-sustaining treatment (WOLST) among critically ill patients, who were placed on …

Safety And Academic Outcomes Of College Campus-Based Advocacy Services, Leila Wood

Faculty, Staff and Student Publications

Intimate partner violence (IPV), sexual assault, and stalking are consequential public health and safety issues with wide reaching impacts on emerging adults, including those on college campuses in the United States. In response to high rates of violence among college student populations, universities are developing campus-based advocacy (CBA) programs, which aim to support survivors of interpersonal violence through supportive connections, resource acquisition, and safety planning. However, little data exists related to their impact on key student-survivor outcomes. Thus, this study aims to understand (a) the approach CBA programs use to address safety and academic concerns of student-survivors, and (b) the …

Inspiring New Science To Guide Healthcare In Turner Syndrome: Rationale, Design, And Methods For The Insights Registry, Wendy J Brickman, Iris Gutmark Little, Karen O Klein, Catherina T Pinnaro, Kelly Ranallo, Marybel Good, Shanlee M Davis

Faculty, Staff and Student Publications

Inspiring New Science to Guide Healthcare in Turner Syndrome (InsighTS) Registry is a national, multicenter registry for individuals with Turner syndrome (TS) designed to collect and store validated longitudinal clinical data from a diverse cohort of patients with TS. Herein, we describe the rationale, design, and approach used to develop the InsighTS registry, as well as the demographics of the initial participants to illustrate the registry's diversity and future utility. Multiple stakeholder groups have been involved from project conceptualization through dissemination, ensuring the registry serves the priorities of the TS community. Key features of InsighTS include recruitment strategies to facilitate …

The Differences In Code Status Conversation Approaches Reported By Emergency Medicine And Palliative Care Clinicians: A Mixed-Method Study, Joshua R Lakin, Masaya Higuchi, Shan W Liu, Maura Kennedy, Anna C Revette, Anita N Chary, Jenson Kaithamattam, Brandon Lee, Thanh H Neville, Mohammad A Hasdianda, Rebecca Sudore, Mara A Schonberg, James A Tulsky, Susan D Block

Faculty, Staff and Students Publications

BACKGROUND: During acute health deterioration, emergency medicine and palliative care clinicians routinely discuss code status (e.g., shared decision making about mechanical ventilation) with seriously ill patients. Little is known about their approaches. We sought to elucidate how code status conversations are conducted by emergency medicine and palliative care clinicians and why their approaches are different.

METHODS: We conducted a sequential-explanatory, mixed-method study in three large academic medical centers in the Northeastern United States. Attending physicians and advanced practice providers working in emergency medicine and palliative care were eligible. Among the survey respondents, we purposefully sampled the participants for follow-up interviews. …

Reaction Hijacking Inhibition Of Plasmodium Falciparum Asparagine Trna Synthetase, Stanley C Xie, Eva S Istvan, Daniel E Goldberg, Et Al.

2020-Current year OA Pubs

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein …

Enhancing Antibody Responses By Multivalent Antigen Display On Thymus-Independent Dna Origami Scaffolds, Eike-Christian Wamhoff, James Brett Case, Shilpa Sanapala, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Protein-based virus-like particles (P-VLPs) are commonly used to spatially organize antigens and enhance humoral immunity through multivalent antigen display. However, P-VLPs are thymus-dependent antigens that are themselves immunogenic and can induce B cell responses that may neutralize the platform. Here, we investigate thymus-independent DNA origami as an alternative material for multivalent antigen display using the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, the primary target of neutralizing antibody responses. Sequential immunization of mice with DNA-based VLPs (DNA-VLPs) elicits protective neutralizing antibodies to SARS-CoV-2 in a manner that depends on the valency of the antigen displayed and on T …

Myd88 In Myofibroblasts Enhances Nonalcoholic Fatty Liver Disease-Related Hepatocarcinogenesis Via Promoting Macrophage M2 Polarization, Yu Liu, Haiqiang Chen, Xuanxuan Yan, Jie Zhang, Zhenzhong Deng, Jianchun Gu

Faculty, Staff and Student Publications

Background: Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver diseases and has emerged as the leading factor in the pathogenesis of hepatocellular carcinoma (HCC). MyD88 contributes to the development of HCC. However, the underlying mechanism by which MyD88 in myofibroblasts regulates NAFLD-associated liver cancer development remains unknown.

Results: Myofibroblast MyD88-deficient (SMAMyD88-/-) mice were protected from diet-induced obesity and developed fewer and smaller liver tumors. MyD88 deficiency in myofibroblasts attenuated macrophage M2 polarization and fat accumulation in HCC tissues. Mechanistically, MyD88 signaling in myofibroblasts enhanced CCL9 secretion, thereby promoting macrophage M2 polarization. This process may depend on …

Utility Of Long-Read Sequencing For All Of Us., M Mahmoud, Y Huang, K Garimella, Peter A Audano, W Wan, N Prasad, R E Handsaker, S Hall, A Pionzio, M C Schatz, M E Talkowski, E E Eichler, S E Levy, F J Sedlazeck

Faculty Research 2024

The All of Us (AoU) initiative aims to sequence the genomes of over one million Americans from diverse ethnic backgrounds to improve personalized medical care. In a recent technical pilot, we compare the performance of traditional short-read sequencing with long-read sequencing in a small cohort of samples from the HapMap project and two AoU control samples representing eight datasets. Our analysis reveals substantial differences in the ability of these technologies to accurately sequence complex medically relevant genes, particularly in terms of gene coverage and pathogenic variant identification. We also consider the advantages and challenges of using low coverage sequencing to …

Mosaic Loss Of Y Chromosome Is Associated With Aging And Epithelial Injury In Chronic Kidney Disease, Parker C Wilson, Amit Verma, Yasuhiro Yoshimura, Yoshiharu Muto, Haikuo Li, Nicole P Malvin, Eryn E Dixon, Benjamin D Humphreys

2020-Current year OA Pubs

BACKGROUND: Mosaic loss of Y chromosome (LOY) is the most common chromosomal alteration in aging men. Here, we use single-cell RNA and ATAC sequencing to show that LOY is present in the kidney and increases with age and chronic kidney disease.

RESULTS: The likelihood of a cell having LOY varies depending on its location in the nephron. Cortical epithelial cell types have a greater proportion of LOY than medullary or glomerular cell types, which may reflect their proliferative history. Proximal tubule cells are the most abundant cell type in the cortex and are susceptible to hypoxic injury. A subset of …

Ahp Db: A Reference Database Of Proteins In The Human Aqueous Humor, Tae Jin Lee, Arnav Goyal, Garrett Jones, Joshua Glass, Vishal Doshi, Lane Ulrich, Sai Karthik Kodeboyina, Amy Estes, Marc Töteberg-Harms, Wenbo Zhi, Shruti Sharma, Ashok Sharma

Faculty, Staff and Student Publications

The aqueous humor (AH) is a low-viscosity biofluid that continuously circulates from the posterior chamber to the anterior chamber of the eye. Recent advances in high-resolution mass-spectrometry workflows have facilitated the study of proteomic content in small-volume biofluids like AH, highlighting the potential clinical implications of the AH proteome. Nevertheless, in-depth investigations into the role of AH proteins in ocular diseases have encountered challenges due to limited accessibility to these workflows, difficulties in large-scale AH sample collection and the absence of a reference AH proteomic database. In response to these obstacles, and to promote further research on the involvement of …

Circulating Microrna Expression And Nonalcoholic Fatty Liver Disease In Adolescents With Severe Obesity, Jesse A Goodrich, Hao-Tian Wu, Jing-Xuan He, Yin-Qi Zhao, Max T Aung, Hong-Xu Wang, Sandrah P Eckel, Douglas I Walker, Damaskini Valvi, Michele A La Merrill, Justin R Ryder, Thomas H Inge, Todd Jenkins, Stephanie Sisley, Rohit Kohli, Stavra A Xanthakos, Andrea A Baccarelli, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.

AIM: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.

METHODS: This …

Reconstitution Of Human Pdac Using Primary Cells Reveals Oncogenic Transcriptomic Features At Tumor Onset, Yi Xu, Michael H Nipper, Angel A Dominguez, Zhenqing Ye, Naoki Akanuma, Janice J Deng, Ava Sanchez, Francis E Sharkey, Colin M Court, Aatur D Singhi, Huamin Wang, Martin E Fernandez-Zapico, Lu-Zhe Sun, Siyuan Zheng, Yidong Chen, Jun Liu, Pei Wang

Faculty, Staff and Student Publications

Animal studies have demonstrated the ability of pancreatic acinar cells to transform into pancreatic ductal adenocarcinoma (PDAC). However, the tumorigenic potential of human pancreatic acinar cells remains under debate. To address this gap in knowledge, we expand sorted human acinar cells as 3D organoids and genetically modify them through introduction of common PDAC mutations. The acinar organoids undergo dramatic transcriptional alterations but maintain a recognizable DNA methylation signature. The transcriptomes of acinar organoids are similar to those of disease-specific cell populations. Oncogenic KRAS alone do not transform acinar organoids. However, acinar organoids can form PDAC in vivo after acquiring the …