Medicine and Health Sciences Commons^™

Protein Biomarkers Of Ultra-Processed Food Consumption And Risk Of Coronary Heart Disease, Chronic Kidney Disease, And All-Cause Mortality, Shutong Du, Jingsha Chen, Hyunju Kim, Alice H Lichtenstein, Bing Yu, Lawrence J Appel, Josef Coresh, Casey M Rebholz

Faculty, Staff and Student Publications

Background: There is a need to understand the underlying biological mechanisms through which ultra-processed foods negatively affect health. Proteomics offers a valuable tool with which to examine different aspects of ultra-processed foods and their impact on health.

Objectives: The aim of this study was to identify protein biomarkers of usual ultra-processed food consumption and assess their relation to the incidence of coronary heart disease (CHD), chronic kidney disease (CKD), and all-cause mortality risk.

Methods: A total of 9361 participants from the Atherosclerosis Risk in Communities visit 3 (1993-1995) were included. Dietary intake was assessed using a 66-item food-frequency questionnaire and …

Trends In The Use Of Biologic Disease-Modifying Antirheumatic Drugs In Patients With Rheumatoid Arthritis And Recently Diagnosed Colorectal, Lung, Or Prostate Cancer, Maria E Suarez-Almazor, Juan I Ruiz, Xiudong Lei, Chi-Fang Wu, Hui Zhao, Suja S Rajan, Sharon H Giordano

Faculty, Staff and Student Publications

INTRODUCTION: Biologic disease-modifying antirheumatic drugs (bDMARD) are often discontinued when a patient with rheumatoid arthritis (RA) is diagnosed with cancer. Our aim was to determine trends in bDMARD utilization in patients with RA and recently diagnosed cancer.

METHOD: We examined two national claims databases to identify adults with RA and recently diagnosed colorectal, lung, or prostate cancer (Optum's de-identified Clinformatics® Data Mart Database 2008-2022, and Surveillance, Epidemiology, and End Results Program (SEER) Medicare-linked 2008-2017). We determined time trends in bDMARD and tumor necrosis factor inhibitor (TNFi) prescriptions during the first 3 years after cancer with Cochram-Armitage tests and multivariable logistic …

Association Between Risk Of Alzheimer’S Disease And Related Dementias And Angiotensin Receptor Ⅱ Blockers Treatment For Individuals With Hypertension In High-Volume Claims Data, Sori Kim Lundin, Xinyue Hu, Jingna Feng, Karl Kristian Lundin, Lu Li, Yong Chen, Paul Ernest Schulz, Cui Tao

Faculty, Staff and Student Publications

Background: Findings regarding the protective effect of Angiotensin II receptor blockers (ARBs) against Alzheimer's disease and related dementias (AD/ADRD) and cognitive decline have been inconclusive.

Methods: Individuals with hypertension who do not have any prior ADRD diagnosis were included in this retrospective cohort study from Optum's de-identified Clinformatics® Data Mart. We identified antihypertensive medication (AHM) drug classes and subclassified ARBs by blood-brain barrier (BBB) permeability. We compared baseline characteristics and used the Kaplan-Meier (KM) survival curve and adjusted Cox proportional hazards (PH) model for survival analyses.

Findings: From 6,390,826 individuals with hypertension, there were 1,839,176 ARB users, 3,366,841 non-ARB AHM …

History Of Incarceration And Dental Care Use Among Older Adults In The United States, Alexander Testa, Dylan B Jackson, Carmen Gutierrez, Chantal Fahmy, Vahed Maroufy, Rafael Samper-Ternent, Ana C Neumann

Faculty, Staff and Student Publications

INTRODUCTION: Dental care is a critical component of healthy aging; however, emerging evidence suggests that having been previously incarcerated is a risk factor for not using dental care services. This study investigates the relationship between prior incarceration and dental care among older adults and assesses whether wealth and dental insurance explain this relationship.

METHODS: Data are from the Health and Retirement Study, a nationally representative sample of community-dwelling older adults in the United States, collected in 2012 and 2014. Multivariable logistic regression is used to assess the relationship between a history of incarceration and dental care. Mediation analyses were conducted …

Incorporating External Controls In The Design Of Randomized Clinical Trials: A Case Study In Solid Tumors, Emily M Damone, Jiawen Zhu, Herbert Pang, Xiao Li, Yinqi Zhao, Evan Kwiatkowski, Lisa A Carey, Joseph G Ibrahim

Faculty, Staff and Student Publications

BACKGROUND: The use of historical external control data in clinical trials has grown in interest and needs when considering the design of future trials. Hybrid control designs can be more efficient to achieve the same power with fewer patients and limited resources. The literature is sparse on appropriate statistical methods which can account for the differences between historical external controls and the control patients in a study. In this article, we illustrate the analysis framework of a clinical trial if a hybrid control design was used after determining an RCT may not be feasible.

METHODS: We utilize two previously completed …

Participation Of Behavioral Health Facilities In Medicare Accountable Care Organizations, Yucheng Hou, Susan H Busch, Helen Newton

Faculty, Staff and Student Publications

This cross-sectional study examines temporal trends in behavioral health facility inclusion in accountable care organizations (ACOs) and beneficiary characteristics of such ACOs.

Genomic Analysis Of Intracranial And Subcortical Brain Volumes Yields Polygenic Scores Accounting For Variation Across Ancestries, Luis M García-Marín, Adrian I Campos, Santiago Diaz-Torres, Jill A Rabinowitz, Zuriel Ceja, Brittany L Mitchell, Katrina L Grasby, Jackson G Thorp, Ingrid Agartz, Saud Alhusaini, David Ames, Philippe Amouyel, Ole A Andreassen, Konstantinos Arfanakis, Alejandro Arias-Vasquez, Nicola J Armstrong, Lavinia Athanasiu, Mark E Bastin, Alexa S Beiser, David A Bennett, Joshua C Bis, Marco P M Boks, Dorret I Boomsma, Henry Brodaty, Rachel M Brouwer, Jan K Buitelaar, Ralph Burkhardt, Wiepke Cahn, Vince D Calhoun, Owen T Carmichael, Mallar Chakravarty, Qiang Chen, Christopher R K Ching, Sven Cichon, Benedicto Crespo-Facorro, Fabrice Crivello, Anders M Dale, George Davey Smith, Eco J C De Geus, Philip L De Jager, Greig I De Zubicaray, Stéphanie Debette, Charles Decarli, Chantal Depondt, Sylvane Desrivières, Srdjan Djurovic, Stefan Ehrlich, Susanne Erk, Thomas Espeseth, Guillén Fernández, Irina Filippi, Simon E Fisher, Debra A Fleischman, Evan Fletcher, Myriam Fornage, Andreas J Forstner, Clyde Francks, Barbara Franke, Tian Ge, Aaron L Goldman, Hans J Grabe, Robert C Green, Oliver Grimm, Nynke A Groenewold, Oliver Gruber, Vilmundur Gudnason, Asta K Håberg, Unn K Haukvik, Andreas Heinz, Derrek P Hibar, Saima Hilal, Jayandra J Himali, Beng-Choon Ho, David F Hoehn, Pieter J Hoekstra, Edith Hofer, Wolfgang Hoffmann, Avram J Holmes, Georg Homuth, Norbert Hosten, M Kamran Ikram, Jonathan C Ipser, Clifford R Jack, Neda Jahanshad, Erik G Jönsson, Rene S Kahn, Ryota Kanai, Marieke Klein, Maria J Knol, Lenore J Launer, Stephen M Lawrie, Stephanie Le Hellard, Phil H Lee, Hervé Lemaître, Shuo Li, David C M Liewald, Honghuang Lin, W T Longstreth, Oscar L Lopez, Michelle Luciano, Pauline Maillard, Andre F Marquand, Nicholas G Martin, Jean-Luc Martinot, Karen A Mather, Venkata S Mattay, Katie L Mcmahon, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Nazanin Mirza-Schreiber, Yuri Milaneschi, Thomas H Mosley, Thomas W Mühleisen, Bertram Müller-Myhsok, Susana Muñoz Maniega, Matthias Nauck, Kwangsik Nho, Wiro J Niessen, Markus M Nöthen, Paul A Nyquist, Jaap Oosterlaan, Massimo Pandolfo, Tomas Paus, Zdenka Pausova, Brenda W J H Penninx, G Bruce Pike, Bruce M Psaty, Benno Pütz, Simone Reppermund, Marcella D Rietschel, Shannon L Risacher, Nina Romanczuk-Seiferth, Rafael Romero-Garcia, Gennady V Roshchupkin, Jerome I Rotter, Perminder S Sachdev, Philipp G Sämann, Arvin Saremi, Muralidharan Sargurupremraj, Andrew J Saykin, Lianne Schmaal, Helena Schmidt, Reinhold Schmidt, Peter R Schofield, Markus Scholz, Gunter Schumann, Emanuel Schwarz, Li Shen, Jean Shin, Sanjay M Sisodiya, Albert V Smith, Jordan W Smoller, Hilkka S Soininen, Vidar M Steen, Dan J Stein, Jason L Stein, Sophia I Thomopoulos, Arthur W Toga, Diana Tordesillas-Gutiérrez, Julian N Trollor, Maria C Valdes-Hernandez, Dennis Van T Ent, Hans Van Bokhoven, Dennis Van Der Meer, Nic J A Van Der Wee, Javier Vázquez-Bourgon, Dick J Veltman, Meike W Vernooij, Arno Villringer, Louis N Vinke, Henry Völzke, Henrik Walter, Joanna M Wardlaw, Daniel R Weinberger, Michael W Weiner, Wei Wen, Lars T Westlye, Eric Westman, Tonya White, A Veronica Witte, Christiane Wolf, Jingyun Yang, Marcel P Zwiers, M Arfan Ikram, Sudha Seshadri, Paul M Thompson, Claudia L Satizabal, Sarah E Medland, Miguel E Rentería

Faculty, Staff and Student Publications

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse …

Feasibility, Acceptability, And Initial Efficacy Of A Wheelchair Exercise Training Program In Persons With Multiple Sclerosis: Study Protocol For A Parallel Group Randomized Controlled Trial, Stephanie L Silveira, Robert W Motl, Katherine Froehlich-Grobe, Mitch Kay

Faculty, Staff and Student Publications

Purpose: This study is a randomized controlled trial (RCT) that examines the feasibility, acceptability, and initial efficacy of a home-based, remotely supported and supervised exercise training program that was developed using a three-step community engaged research process for persons with multiple sclerosis (MS) who are wheelchair users.

Materials and methods: The study design is a parallel group RCT (NCT05888727). We aim to enroll 24 wheelchair users with MS who will be randomly assigned using REDCap randomization module into exercise training or attention/contact wellness control conditions. The conditions will be delivered remotely over 16 weeks and supported using online, …

Sex Differences In Hypertension And Its Management Throughout Life, Wan-Jin Yeo, Rahul Abraham, Aditya L Surapaneni, Pascal Schlosser, Shoshana H Ballew, Bige Ozkan, Carina M Flaherty, Bing Yu, Joseph V Bonventre, Chirag R Parikh, Paul L Kimmel, Ramachandran S Vasan, Josef Coresh, Morgan E Grams

Faculty, Staff and Student Publications

Background: The prevalence of hypertension and uncontrolled hypertension may differ by age and sex.

Methods: We included participants in the Atherosclerosis Risk in Communities study at seven study visits over 33 years (visit 1: 15 636 participants; mean age, 54 years; 55% women), estimating sex differences in prevalence of hypertension (systolic blood pressure ≥130 mm Hg; diastolic blood pressure ≥80 mm Hg; or self-reported antihypertension medication use) and uncontrolled hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) using unadjusted and comorbidity-adjusted models.

Results: The prevalence of hypertension increased with age from 40% (ages, 43-46 …

Serum Metabolomic Markers Of Artificially Sweetened Beverage Consumption, Hejingzi Jia, Lauren Bernard, Jingsha Chen, Shutong Du, Lyn M Steffen, Kari E Wong, Bing Yu, Valerie K Sullivan, Casey M Rebholz

Faculty, Staff and Student Publications

BACKGROUND: The consumption of artificially sweetened beverages is on the rise. Use of artificial sweeteners has been associated with adverse health outcomes. There is a need to identify novel objective biomarkers of artificially sweetened beverages in order to improve dietary assessment and to provide insight into their metabolic impact.

OBJECTIVES: We aimed to identify serum metabolites that are associated with artificially sweetened beverage consumption.

METHODS: In the Atherosclerosis Risk in Communities (ARIC) study, consumption of artificially sweetened beverages was assessed using a food frequency questionnaire and fasting serum samples were collected during the first study visit (1987-1989). Participants were categorized …

Loss Of Sc5d Results In Micrognathia Due To A Failure In Osteoblast Differentiation, Chihiro Iwaya, Akiko Suzuki, Junichi Iwata

Faculty, Staff and Student Publications

INTRODUCTION: Mutations in genes related to cholesterol metabolism, or maternal diet and health status, affect craniofacial bone formation. However, the precise role of intracellular cholesterol metabolism in craniofacial bone development remains unclear.

OBJECTIVE: The aim of this study is to determine how cholesterol metabolism aberrations affect craniofacial bone development.

METHODS: Mice with a deficiency in Sc5d, which encodes an enzyme involved in cholesterol synthesis, were analyzed with histology, micro computed tomography (microCT), and cellular and molecular biological methods.

RESULTS: Sc5d null mice exhibited mandible hypoplasia resulting from defects in osteoblast differentiation. The activation of the hedgehog and WNT/β-catenin signaling pathways, …

Change Of Ownership And Quality Of Home Health Agency Care, Zhanji Zhang, Kun Li, Siyi Wang, Shekinah Fashaw-Walters, Yucheng Hou

Faculty, Staff and Student Publications

IMPORTANCE: The home health agency (HHA) market has seen increasingly more change in ownership transactions. Little is known about the organizational characteristics and quality of care of HHAs after ownership has changed.

OBJECTIVE: To examine whether an HHA change in ownership was associated with different quality-of-care outcomes, patient volume, and staffing levels.

DESIGN, SETTING, AND PARTICIPANTS: Using current HHA change of ownership files linked to publicly available Medicare HHA data, this staggered difference-in-differences analysis evaluated ownership change transactions of Medicare-certified HHAs from quarter 1 of 2016 to quarter 4 of 2019. Pretransaction and posttransaction HHA characteristics and quality-of-care outcomes were …

Survival In Patients With Rheumatoid Arthritis And Early Breast Cancer Treated With Tumor Necrosis Factor Inhibitors, Juan I Ruiz, Xiudong Lei, Wu Chi-Fang, Sharon H Giordano, Hui Zhao, Suja S Rajan, Heather Lin, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

Background: There have been concerns about the use of tumor necrosis factor inhibitors (TNFi) for autoimmune disease in patients with recently diagnosed cancer. We assessed the survival of patients with rheumatoid arthritis (RA) and newly diagnosed early breast cancer (BC) treated with TNFi in the first two years after BC diagnosis.

Methods: We identified patients in two datasets: (1) Optum's de-identified Clinformatics® Data Mart Database (CDM), (2) Surveillance, Epidemiology, and End Results program (SEER) and Texas Cancer Registry (TCR) Medicare-linked cohort. We grouped patients according to whether they received TNFi, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) only, or no DMARDs …

Impact Of Racial, Ethnic, And Socioeconomic Disparities On Presentation And Survival Of Hcc: A Multicenter Study, Nicole E Rich, Patricia D Jones, Hong Zhu, Tanushree Prasad, Amy Hughes, Sandi Pruitt, Caitlin C Murphy, Karim Seif-El-Dahan, Darine Daher, Gloria Figueroa, Stephanie Castaneda, Lisa Quirk, Michael Gonzales, Osiris Carranza, Samantha Bourque, Nargis Baset, Adam C Yopp, Amit G Singal

Faculty, Staff and Student Publications

BACKGROUND: Racial and ethnic disparities have been reported for HCC prognosis, although few studies fully account for clinically important factors and social determinants of health, including neighborhood socioeconomic status.

METHODS: We conducted a retrospective multicenter cohort study of patients newly diagnosed with HCC from January 2010 through August 2018 at 4 large health systems in the United States. We used multivariable logistic regression and cause-specific Cox proportional hazard models to identify factors associated with early-stage HCC presentation and overall survival.

RESULTS: Of 2263 patients with HCC (37.6% non-Hispanic White, 23.5% non-Hispanic Black, 32.6% Hispanic, and 6.4% Asian/other), 42.0% of patients …

Increased Expression Of Cd70 In Relapsed Acute Myeloid Leukemia After Hypomethylating Agents, Mario L Marques-Piubelli, Bijender Kumar, Rafet Basar, Siler Panowski, Surabhi Srinivasan, Kevin Norwood, Sacha Prashad, Victoria Szenes, Arun Balakumaran, Akanksha Arandhya, Wei Lu, Khaja Khan, Daniela Duenas, Salome Mcallen, Javier A Gomez, Jared K Burks, Sunil Acharyal, Gautam Borthakur, Wei-Lien Wang, Wei Wang, Sa Wang, Luisa M Solis, David Marin, Katayoun Rezvani, May Daher, Francisco Vega

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While induction chemotherapy leads to remission in most patients, a significant number will experience relapse. Therefore, there is a need for novel therapies that can improve remission rates in patients with relapsed and refractory AML. CD70 is the natural ligand for CD27 (a member of the TNF superfamily) and appears to be a promising therapeutic target. Consequently, there is considerable interest in developing chimeric antigen receptor (CAR) T-cell therapy products that can specifically target CD70 in various neoplasms, including AML. In this study, we employed routine diagnostic techniques, …

Assessing Radiology And Radiation Therapy Needs For Cancer Care In Low-And-Middle-Income Countries: Insight From A Global Survey Of Departmental And Institutional Leaders, Stephanie A Parker, Joseph Weygand, Beata Gontova Bernat, Amanda M Jackson, Osama Mawlawi, Izabella Barreto, Yao Hao, Rao Khan, Afua A Yorke, William Swanson, Mohammed Saiful Huq, Eugene Lief, Cesar Della Biancia, Christopher F Njeh, Ahmad Al-Basheer, Oi Wai Chau, Stephen Avery, Wilfred Ngwa, Peter A Sandwall

Faculty, Staff and Student Publications

Purpose: The global cancer burden and mortality rates are increasing, with significant disparities in access to care in low- and middle-income countries (LMICs). This study aimed to identify radiology and radiation therapy needs in LMICs from the perspective of departmental and institutional leaders.

Methods and materials: A survey was developed and conducted by the American Association of Physicists in Medicine Global Needs Assessment Committee and the American Association of Physicists in Medicine International Council. The survey, organized into 5 sections (Introduction, Infrastructure Needs, Education Needs, Research Needs, and General Information), was open to respondents from March 1, to August 16, …

Real-World Use Patterns, Effectiveness, And Tolerability Of Sacituzumab Govitecan For Second-Line And Later-Line Treatment Of Metastatic Triple-Negative Breast Cancer In The United States, Kevin Kalinsky, Laura Spring, Clinton Yam, Manali Ajay Bhave, Ioanna Ntalla, Catherine Lai, Nikoleta Sjekloca, Brian Stwalley, Michael Stokes, Aliki Taylor, Rita Nanda

Faculty, Staff and Student Publications

Purpose: Patients with metastatic triple-negative breast cancer (mTNBC) have poor prognosis and limited treatment options. Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, is approved for patients with mTNBC who have received ≥ 2 systemic therapies (≥ 1 in the metastatic setting) based on the ASCENT study (NCT02574455). The current study describes real-world SG use and outcomes in patients with mTNBC in the United States.

Methods: This retrospective, observational study included adult patients with mTNBC from the ConcertAI Patient360™ database who received SG in the second line (2L) and later from April 2020 to May 2022. SG use patterns, …

Microrna-1307-3p Contributes To Breast Cancer Progression Through Prm2, José Roberto Estupiñan-Jiménez, Valeria Villarreal-García, Vianey Gonzalez-Villasana, Pablo E Vivas-Mejia, Jose Manuel Vazquez-Guillen, Patricio Adrián Zapata-Morin, Marienid Flores-Colón, Claudia Altamirano-Torres, Ezequiel Viveros-Valdez, Cristina Ivan, Mohammed H Rashed, Recep Bayraktar, Cristina Rodríguez-Padilla, Gabriel Lopez-Berestein, Diana Resendez-Perez

Faculty, Staff and Student Publications

Background: Despite advances in screening and therapy, breast cancer (BC) remains the predominant cancer in women globally. Dysregulation of microRNAs (miRNAs) is pivotal in carcinogenesis across various cancers, including BC. Evidence indicates that miR-1307-3p is upregulated in BC tumors, yet its target genes are not fully elucidated. This study aimed to explore how miR-1307-3p regulates BC proliferation, migration, invasion, and angiogenesis and to identify potential target genes.

Methods: Basal miR-1307-3p levels were quantified in BC cell lines MDA-MB-231 and MCF-7, as well as MCF-10A using quantitative real-time reverse transcription-PCR (RT-qPCR). The impact of miR-1307-3p inhibition on BC cell proliferation, migration, …

Exploring Latent Clusters In Pediatric Ocd Based On Symptoms, Severity, Age, Gender, And Comorbidity, Orri Smárason, Robert R Selles, Davíð R M A Højgaard, John R Best, Karin Melin, Tord Ivarsson, Per Hove Thomsen, Bernhard Weidle, Nicole Michelle Mcbride, Eric A Storch, Daniel Geller, Sabine Wilhelm, Lara J Farrell, Allison M Waters, Sharna Mathieu, Noam Soreni, S Evelyn Stewart, Gudmundur Skarphedinsson

Center for Medical Ethics and Health Policy Staff Publications

Given diverse symptom expression and high rates of comorbid conditions, the present study explored underlying commonalities among OCD-affected children and adolescents to better conceptualize disorder presentation and associated features. Data from 830 OCD-affected participants presenting to OCD specialty centers was aggregated. Dependent mixture modeling was used to examine latent clusters based on their age- and gender adjusted symptom severity (as measured by the Children's Yale-Brown Obsessive-Compulsive Scale; CY-BOCS), symptom type (as measured by factor scores calculated from the CY-BOCS symptom checklist), and comorbid diagnoses (as assessed via diagnostic interviews). Fit statistics favored a four-cluster model with groups distinguished primarily by …

Integration Across Biophysical Scales Identifies Molecular And Cellular Correlates Of Person-To-Person Variability In Human Brain Connectivity, Bernard Ng, Shinya Tasaki, Kelsey M Greathouse, Courtney K Walker, Ada Zhang, Sydney Covitz, Matt Cieslak, Audrey J Weber, Ashley B Adamson, Julia P Andrade, Emily H Poovey, Kendall A Curtis, Hamad M Muhammad, Jakob Seidlitz, Ted Satterthwaite, David A Bennett, Nicholas T Seyfried, Jacob Vogel, Chris Gaiteri, Jeremy H Herskowitz

Faculty, Staff and Student Publications

Brain connectivity arises from interactions across biophysical scales, ranging from molecular to cellular to anatomical to network level. To date, there has been little progress toward integrated analysis across these scales. To bridge this gap, from a unique cohort of 98 individuals, we collected antemortem neuroimaging and genetic data, as well as postmortem dendritic spine morphometric, proteomic and gene expression data from the superior frontal and inferior temporal gyri. Through the integration of the molecular and dendritic spine morphology data, we identified hundreds of proteins that explain interindividual differences in functional connectivity and structural covariation. These proteins are enriched for …

A Site-Wise Reliability Analysis Of The Abcd Diffusion Fractional Anisotropy And Cortical Thickness: Impact Of Scanner Platforms, Yezhi Pan, L Elliot Hong, Ashley Acheson, Paul M Thompson, Neda Jahanshad, Alyssa H Zhu, Jiaao Yu, Chixiang Chen, Tianzhou Ma, Ho-Ling Liu, Jelle Veraart, Els Fieremans, Nicole R Karcher, Peter Kochunov, Shuo Chen

Faculty, Staff and Student Publications

The Adolescent Brain and Cognitive Development (ABCD) project is the largest study of adolescent brain development. ABCD longitudinally tracks 11,868 participants aged 9-10 years from 21 sites using standardized protocols for multi-site MRI data collection and analysis. While the multi-site and multi-scanner study design enhances the robustness and generalizability of analysis results, it may also introduce nonbiological variances including scanner-related variations, subject motion, and deviations from protocols. ABCD imaging data were collected biennially within a period of ongoing maturation in cortical thickness and integrity of cerebral white matter. These changes can bias the classical test-retest methodologies, such as intraclass correlation …

Single-Cell Integration Reveals Metaplasia In Inflammatory Gut Diseases, Amanda J Oliver, Ni Huang, Raquel Bartolome-Casado, Ruoyan Li, Simon Koplev, Hogne R Nilsen, Madelyn Moy, Batuhan Cakir, Krzysztof Polanski, Victoria Gudiño, Elisa Melón-Ardanaz, Dinithi Sumanaweera, Daniel Dimitrov, Lisa Marie Milchsack, Michael E B Fitzpatrick, Nicholas M Provine, Jacqueline M Boccacino, Emma Dann, Alexander V Predeus, Ken To, Martin Prete, Jonathan A Chapman, Andrea C Masi, Emily Stephenson, Justin Engelbert, Sebastian Lobentanzer, Shani Perera, Laura Richardson, Rakeshlal Kapuge, Anna Wilbrey-Clark, Claudia I Semprich, Sophie Ellams, Catherine Tudor, Philomeena Joseph, Alba Garrido-Trigo, Ana M Corraliza, Thomas R W Oliver, C Elizabeth Hook, Kylie R James, Krishnaa T Mahbubani, Kourosh Saeb-Parsy, Matthias Zilbauer, Julio Saez-Rodriguez, Marte Lie Høivik, Espen S Bækkevold, Christopher J Stewart, Janet E Berrington, Kerstin B Meyer, Paul Klenerman, Azucena Salas, Muzlifah Haniffa, Frode L Jahnsen, Rasa Elmentaite, Sarah A Teichmann

Faculty, Staff and Student Publications

The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics and a surge in gastrointestinal diseases1,2 has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease3. Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy gastrointestinal tract in development and in adulthood. We uniformly processed 385 samples from 189 healthy controls using a newly developed automated quality control approach (scAutoQC), leading to a healthy reference atlas with approximately 1.1 million cells and 136 fine-grained cell states. We anchor 12 gastrointestinal disease datasets spanning …

A Rigorous Multi-Laboratory Study Of Known Pdac Biomarkers Identifies Increased Sensitivity And Specificity Over Ca19-9 Alone, Brian Haab, Lu Qian, Ben Staal, Maneesh Jain, Johannes Fahrmann, Christine Worthington, Denise Prosser, Liudmila Velokokhatnaya, Camden Lopez, Runlong Tang, Mark W Hurd, Gopalakrishnan Natarajan, Sushil Kumar, Lynette Smith, Sam Hanash, Surinder K Batra, Anirban Maitra, Anna Lokshin, Ying Huang, Randall E Brand

Faculty, Staff and Student Publications

A blood test that enables surveillance for early-stage pancreatic ductal adenocarcinoma (PDAC) is an urgent need. Independent laboratories have reported PDAC biomarkers that could improve biomarker performance over CA19-9 alone, but the performance of the previously reported biomarkers in combination is not known. Therefore, we conducted a coordinated case/control study across multiple laboratories using common sets of blinded training and validation samples (132 and 295 plasma samples, respectively) from PDAC patients and non-PDAC control subjects representing conditions under which surveillance occurs. We analyzed the training set to identify candidate biomarker combination panels using biomarkers across laboratories, and we applied the …

Astct And Usclc Clinical Practice Recommendations For Allogeneic Stem Cell Transplant In Mycosis Fungoides And Sézary Syndrome, Amrita Goyal, Daniel O'Leary, Bouthaina Dabaja, Wen-Kai Weng, Jasmine Zain, Corey Cutler, Joan Guitart, Youn H Kim, Larisa J Geskin, Richard T Hoppe, Lynn D Wilson, Anne W Beaven, Steve Horwitz, Pamela B Allen, Stefan K Barta, Kimberly Bohjanen, Jonathan E Brammer, Joi B Carter, Nneka Comfere, Jennifer A Desimone, Kathryn Dusenbery, Madeleine Duvic, Auris Huen, Deepa Jagadeesh, Chris R Kelsey, Michael S Khodadoust, Mary Jo Lechowicz, Neha Mehta-Shah, Alison J Moskowitz, Elise A Olsen, Christina Poh, Barbara Pro, Christiane Querfeld, Craig Sauter, Lubomir Sokol, Olayemi Sokumbi, Ryan A Wilcox, John A Zic, Mehdi Hamadani, Francine Foss

Faculty, Staff and Student Publications

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). While MF generally follows an indolent course, a subset of patients will experience progressive and/or treatment-refractory disease; Sézary syndrome is an aggressive lymphoma associated with high morbidity and mortality. Although allogeneic hematopoietic cell transplant (allo-HCT) is the only currently available potentially curative treatment modality for MF/SS there is no published guidance on referral criteria, transplant timing orallo-HCT approach. To develop consensus clinical practice recommendations, we performed a Delphi survey of 32 specialists in dermatology (n = 9), transplant hematology/oncology (n = 10), non-transplant …

Epigenomic And Transcriptomic Profiling Of Solitary Fibrous Tumors Identifies Site-Specific Patterns And Candidate Genes Regulated By Dna Methylation, Hannah C Beird, Jeffrey M Cloutier, Nalan Gokgoz, Christopher Eeles, Anthony M Griffin, Davis R Ingram, Khalida M Wani, Rossana Lazcano Segura, Luca Cohen, Carl Ho, Jay S Wunder, Irene L Andrulis, P Andrew Futreal, Benjamin Haibe-Kains, Alexander J Lazar, Wei-Lien Wang, Joanna Przybyl, Elizabeth G Demicco

Faculty, Staff and Student Publications

A solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that can arise at any anatomical site and is characterized by recurrent NAB2::STAT6 fusions and metastatic progression in 10% to 30%. The cell of origin has not been identified. Despite some progress in understanding the contribution of heterogeneous fusion types and secondary mutations to SFT biology, epigenetic alterations in extrameningeal SFT remain largely unexplored, and most sarcoma research to date has focused on the use of methylation profiling for tumor classification. We interrogated genome-wide DNA methylation in 79 SFTs to identify informative epigenetic changes. RNA-seq data from targeted panels and …

Intra-Tumoral And Peripheral Blood Tigit And Pd-1 As Immune Biomarkers In Nodular Lymphocyte Predominant Hodgkin Lymphoma, Jay Gunawardana, Soi C Law, Muhammed B Sabdia, Éanna Fennell, Aoife Hennessy, Ciara I Leahy, Paul G Murray, Karolina Bednarska, Sandra Brosda, Judith Trotman, Leanne Berkahn, Andreea Zaharia, Simone Birch, Melinda Burgess, Dipti Talaulikar, Justina N Lee, Emily Jude, Eliza A Hawkes, Sanjiv Jain, Karthik Nath, Cameron Snell, Fiona Swain, Joshua W D Tobin, Colm Keane, Mohamed Shanavas, Emily Blyth, Christian Steidl, Kerry Savage, Pedro Farinha, Merrill Boyle, Barbara Meissner, Michael R Green, Francisco Vega, Maher K Gandhi

Faculty, Staff and Student Publications

In classical Hodgkin lymphoma (cHL), responsiveness to immune-checkpoint blockade (ICB) is associated with specific tumor microenvironment (TME) and peripheral blood features. The role of ICB in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is not established. To gain insights into its potential in NLPHL, we compared TME and peripheral blood signatures between HLs using an integrative multiomic analysis. A discovery/validation approach in 121 NLPHL and 114 cHL patients highlighted >2-fold enrichment in programmed cell death-1 (PD-1) and T-cell Ig and ITIM domain (TIGIT) gene expression for NLPHL versus cHL. Multiplex imaging showed marked increase in intra-tumoral protein expression of PD-1+ (and/or …

Genomic Alterations In Dna Mismatch Repair Genes Across Different Cancer Types, Vijaykumar R Holla, Michael P Kahle, Sun-Hee Kim, Arash Ronaghy, Richard K Yang, Keyur P Patel, Mark J Routbort, Michael J Overman, Ecaterina E Dumbrava, Kenna R Mills Shaw, Daniel D Karp, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Purpose: PD-1 inhibition is effective in patients with mismatch repair deficient (dMMR) solid tumors in a tumor-agnostic fashion. However, dMMR testing by immunohistochemistry (IHC) is not routinely performed across tumor types. By contrast, next-generation sequencing (NGS) for somatic genomic alterations is frequently performed across tumor types. We hypothesized that NGS would identify patients with alterations in mismatch repair (MMR) genes and that these patients would have higher rates of MMR protein loss by IHC. This would support the utility of IHC reflex testing after NGS and potential matching to approved therapeutic options.

Methods: From January 2016 to December 2021, 15,701 …

A Complementary Metaproteomic Approach To Interrogate Microbiome Cultivated From Clinical Colon Biopsies, Van-An Duong, Altai Enkhbayar, Nobel Bhasin, Lakmini Senavirathna, Eva C Preisner, Kristi L Hoffman, Richa Shukla, Robert R Jenq, Kai Cheng, Mary P Bronner, Daniel Figeys, Robert A Britton, Sheng Pan, Ru Chen

Faculty, Staff and Student Publications

The human gut microbiome plays a vital role in preserving individual health and is intricately involved in essential functions. Imbalances or dysbiosis within the microbiome can significantly impact human health and are associated with many diseases. Several metaproteomics platforms are currently available to study microbial proteins within complex microbial communities. In this study, we attempted to develop an integrated pipeline to provide deeper insights into both the taxonomic and functional aspects of the cultivated human gut microbiomes derived from clinical colon biopsies. We combined a rapid peptide search by MSFragger against the Unified Human Gastrointestinal Protein database and the taxonomic …

Self-Management Intervention Improves Patient Adherence To Swallowing Exercises During Radiation For Head And Neck Cancer, Eileen H Shinn, Adam S Garden, Minxing Chen, Karen Basen-Engquist, Bryan Fellman, Kate Hutcheson, William H Morrison, Susan Peterson, Liang Li

Faculty, Staff and Student Publications

Background: While preventive swallowing exercises reduce the risk of radiation-associated dysphagia in patients with head and neck cancer, strategies are needed to improve patient adherence.

Methods: Before radiation, all participants were taught preventive swallowing exercises and randomized to either an adherence intervention or enhanced usual care. During radiation, all participants met twice with a speech pathologist for swallowing assessment and reinforcement of exercises. Intervention participants met weekly with a counselor in-person or by phone. At 6-week post-radiation follow-up, all participants completed a follow-up assessment of self-reported adherence, which was then corroborated with medical record documentation.

Results: Newly diagnosed pharyngeal and …

Boosting Acetylcholine Signaling By Cannabidiol In A Murine Model Of Alzheimer's Disease, Hesam Khodadadi, Évila Lopes Salles, Sahar Emami Naeini, Bidhan Bhandari, Hannah M Rogers, Jules Gouron, William Meeks, Alvin V Terry, Anilkumar Pillai, Jack C Yu, John C Morgan, Kumar Vaibhav, David C Hess, Krishnan M Dhandapani, Lei P Wang, Babak Baban

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is a challenging medical issue that requires efficacious treatment options to improve long-term quality of life. Cannabidiol (CBD) is a cannabis-derived phytocannabinoid with potential health benefits, including reports from our laboratory and others showing a therapeutic role in the pre-clinical treatment of AD; however, the mechanisms whereby CBD affects AD progression remain undefined. Innate lymphoid cells (ILCs) are recently discovered immune cells that initiate and orchestrate inflammatory responses. ILC2, a sub-class of ILCs, is proposed to have a role in cognitive function via unknown mechanisms. In this present study, we explored whether CBD ameliorates AD symptoms via …