Digital Commons Network^™

Proteomic Signatures Of 3-Year Progression From Impaired Fasting Glucose To Diabetes: The Atherosclerosis Risk In Communities (Aric) Study, Mary R Rooney, Justin B Echouffo Tcheugui, Jingsha Chen, Keenan A Walker, Christie M Ballantyne, Eric Boerwinkle, Tanika N Kelly, Chiadi E Ndumele, James S Pankow, Morgan E Grams, Wendy S Post, Peter J Ganz, Alexis C Wood, Jerome I Rotter, Elizabeth Selvin, Josef Coresh

Faculty, Staff and Students Publications

Objective: To identify proteomic signatures underlying 3-year progression from impaired fasting glucose (IFG) to diabetes.

Research design and methods: We examined IFG progression in the Atherosclerosis Risk in Communities (ARIC) study from visit 2 (1990-1992) to visit 3 (1993-1995). We tested associations of 4,955 plasma proteins (SomaScan version 4.0) with ∼3-year progression from IFG (FG 100-125 mg/dL without diabetes) to diabetes (diagnosis, medication, or FG ≥126 mg/dL) using logistic regression models adjusted for demographics, cardiometabolic risk factors, and baseline glucose with Bonferroni correction (P < 10-5). We explored biological pathways enriched among the top proteins and calculated improvements in prediction (ΔAUC and net reclassification using 3-year risk thresholds of 6% and 15% in 80% training and 20% internal validation subsamples). We validated results in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.

Results: There were 3,786 ARIC participants with IFG (mean [SD] age 57 [6] years, 52% female, …

Decision-Making Criteria In Polygenic Embryo Screening: A Survey Of Reproductive Medicine Physicians, Rémy A Furrer, Aayushi Gandhi, Dorit Barlevy, Shai Carmi, Todd Lencz, Stacey Pereira, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Polygenic embryo screening (PES) examines embryos for their genetic likelihood of developing complex conditions and traits. The commercialization of PES places reproductive endocrinologists and infertility specialists (REIs) as the primary decision-makers in its use, despite professional guidelines cautioning that PES is not ready for clinical use.

Methods: This survey examines how 152 US REIs perceive and approach potential clinical decision-making scenarios regarding the use of PES.

Results: REIs were more likely to offer PES for medical conditions (up to 62% for cancer) than for traits (eg, 0% for skin color, 10% for body mass index). When evaluating 11 potential …

All-Cause And Cause-Specific Mortality In Gambling Disorder: Evidence From A Nation-Wide Matched And Sibling Cohort Study In Taiwan, Yang-Chieh Brian Chen, Chih-Wei Hsu, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Background and aims: Gambling disorder (GD) has been linked to suicidal ideation and suicide deaths; however, evidence on all-cause and cause-specific mortality-particularly in Asian populations-remains limited. Using a retrospective cohort study based on nationwide matched and sibling cohort, we investigated all-cause and cause-specific mortality risk in patients with GD.

Design, setting and participants: A retrospective cohort study was conducted using 2000-2022 data from Taiwan's National Health Insurance Research Database. A cohort of 961 individuals diagnosed with GD was identified. An age- and sex-matched control cohort (n = 3,844) and an unaffected sibling cohort (n = 675) were constructed. Cumulative survival …

Reduced Lower Extremity Strength, Altered Muscle Activation, And Unchanged Kinetics During Single-Leg Squatting In Males With Patellofemoral Pain Versus Pain-Free Males: A Cross-Sectional Analysis, Lisa T. Hoglund, Amy H. Amabile, Thomas Alexander Hulcher, Victoria K. Polansky, Erin L. Dopke

Department of Physical Therapy Faculty Papers

BACKGROUND: Patellofemoral pain is frequently a cause of reduced quality of life in physically active males. The cause of patellofemoral pain is theorized to include aberrant biomechanics during weight-bearing activities. Altered biomechanics of females with patellofemoral pain have been reported, but there is a dearth of research for males with this condition. This study aimed to compare males with and without patellofemoral pain for hip and knee joint moments and muscle activation during single-leg-squatting and proximal muscle strength.

METHODS: Twenty males with patellofemoral pain and 20 pain-free males aged 20-39 years performed single-leg-squatting while motion, ground reaction force, and proximal …

Assessing The Feasibility Of A Self-Management Intervention For Individuals With Advanced Prostate Cancer And Comorbid Type Ii Diabetes Mellitus, Amy L. Shaver, Christina Steinbock-Malfer, William Tester, Patrick Mille, William K. Kelly, Kevin K. Zarrabi, Costas D. Lallas, Mihir M. Shah, Rose Dimarco, Emily Brand, Shawntel Brown, Swapnil Sharma, Nikita Nikita, Cindy Cogen, Scott W. Keith, Grace Lu-Yao

Kimmel Cancer Center Faculty Papers

BACKGROUND: Many older adults with cancer have at least one comorbidity. Type II diabetes mellitus (T2DM) is a common comorbidity among patients with prostate cancer (PC) and represents an important consideration in this population. Comorbid T2DM can negatively impact cancer-specific outcomes for patients, suggesting the need for better glycemic management, especially for patients on active cancer treatment. The goal of this modified Diabetes Self-Management Education Services (mDSMES) pilot study was to provide patients with the opportunity to learn methods of diabetes self-management, including how to manage their glucose levels, improve their understanding and utilization of medication to promote improvements in …

Diabetter Together: Outcomes Of A Randomized Controlled Trial Evaluating A Peer Mentor Behavioral Intervention For Young Adults With Type 1 Diabetes During The Transfer From Pediatric To Adult Care, Marisa E Hilliard, Charles G Minard, Samantha A Carreon, Wendy L Levy, Sarah K Lyons, Randi Streisand, Tricia S Tang, Siripoom V Mckay, Sridevi Devaraj, Barbara J Anderson

Faculty, Staff and Students Publications

Objective: Transition between pediatric and adult health care is complex, with high risk for loss to follow-up and suboptimal health outcomes for young adults with type 1 diabetes. This trial evaluated the efficacy of DiaBetter Together, a 12-month strengths-based behavioral intervention delivered by trained peer mentors. The intervention aimed to help young adults navigate the transfer process to promote optimal glycemic outcomes, shorten time to adult care follow-up, and improve psychosocial outcomes.

Research design and methods: Using a single-site randomized clinical trial design, we compared the 12-month intervention to usual care among n = 100 young adults aged 17-25 years …

Adamts13 And Von Willebrand Factor In Relation To Vascular Cognitive Impairment And Cerebral Small Vessel Disease: The Heart-Brain Connection Study, Amos C Pomp, Mathijs T Rosbergen, Moniek P M De Maat, Paul S De Vries, M Arfan Ikram, Mat J A P Daemen, Imo E Hoefer, Wiro J Niessen, Jeroen De Bresser, Esther E Bron, Charlotte E Teunissen, Geert Jan Biessels, Robert J Van Oostenbrugge, Frank J Wolters

Faculty, Staff and Student Publications

Background: Reduced activity of a disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13 (ADAMTS13) is associated with an increased risk of dementia, independent of Von Willebrand factor (VWF) levels. Pathways underlying this association remain poorly understood.

Objectives: Investigate the associations of VWF levels and ADAMTS13 activity with vascular cognitive impairment (VCI) and cerebral small vessel disease (CSVD).

Methods: In this cross-sectional study, we included 147 participants with VCI and 120 reference subjects (mean age: 67.5 years, 41% women). Using multivariable logistic regression, we determined the cross-sectional association of ADAMTS13 activity and VWF levels in plasma with VCI. Additionally, across …

Kirschner Wire Skeletal Fixation In The Hand And Wrist: Risk Of Infection And Predictors Of Progression To Major Complications, Mitchell S Mologne, Julia M Perugini, Nicholas A Calotta, Lindley B Wall, Charles A Goldfarb

2020-Current year OA Pubs

PURPOSE: Kirschner wire (K-wire) infections continue to be a challenge in hand surgery. Our purpose was to quantify the frequency of K-wire site infections of the hand and wrist, to tabulate major and minor infectious manifestations, to identify factors that may predispose a patient to major complications, and to generate an updated algorithm for prognostication and treatment of K-wire site infections.

METHODS: Patients treated with K-wires in the fingers, hand, and wrist who developed infections between 2018 and 2024 at our institution were identified. Information regarding patient factors, injury, treatment, and subsequent infectious complications was collected. Variables from single variable …

Language And Sound Exposure Across Neonatal Intensive Care Hospitalization And Relationships With Early Outcome, R Pineda, L J Woodward, Z A Vesoulis, C D Smyser, T E Inder, A M Mathur, B L Schlaggar

2020-Current year OA Pubs

OBJECTIVES: Examine relationships between quantitative measures of language and sound exposure in the NICU and infant neurobehavior.

STUDY DESIGN: Sixty-four preterm infants (≤28 weeks of gestation) had language and sound exposure measured across four time points: within two weeks of birth and at 30, 34, and 35-41 weeks postmenstrual age (PMA). Neurobehavior was assessed at 35-41 weeks PMA using the NICU Network Neurobehavioral Scales.

RESULTS: Higher average decibel levels in the NICU environment were associated with lower infant orientation scores (p = 0.04, β = -0.33). Higher peak decibel levels were associated with greater hypertonia (p = 0.01, β = …

Effects Of Concurrent Neuropathologies With Alzheimer Disease Neuropathologic Change On Cognitive Decline: Minimal Impact Of Vascular Brain Injury Compared With Other Combinations, Sarah M Yasuda, Charles Mock, Kathryn Gauthreaux, Kwun C G Chan, C Dirk Keene, Jessica E Culhane, Yen-Chi Chen, Walter Kukull

2020-Current year OA Pubs

We examined cognitive changes associated with several neuropathologic entities, alone and in combination. We studied 808 participants from the National Alzheimer's Coordinating Center to assess associations between neuropathologic diagnoses (from autopsy) and neuropsychologic test scores (trajectories over time for 5 domains: overall cognition, episodic memory, attention, language, executive function). Neuropathologies included: Alzheimer disease neuropathologic change (ADNC), Lewy body disease (LBD), vascular brain injury (VBI), and limbic-predominant age-related TDP43 encephalopathy neuropathologic change (LATE-NC). Using linear mixed-effects models, we examined trajectories of cognitive decline for ADNC alone compared to ADNC plus LBD, VBI, or LATE-NC. We also examined differences between observed trajectories …

A Cooking Skills Intervention For Long-Term Weight Loss In Young Adults With Intellectual Disabilities: Rationale And Design For A Randomized Trial., Lauren T. Ptomey, Jessica C. Danon, Delwyn Catley, Richard A. Washburn, Amy Bodde, Francisco J. Diaz, Brian C. Helsel, Anna M. Rice, Joseph R. Sherman, Madison Koester, Walker S. Mckinney Ph.D., Joseph E. Donnelly

Manuscripts, Articles, Book Chapters and Other Papers

Young adults with intellectual disability (ID) are an underserved population with a high prevalence of obesity, obesity-related health conditions, and reduced ability to complete instrumental and basic activities of daily living (I/ADLs). After leaving the structured environment of public school, many young adults with ID spend more time at home or in day programs, begin living more independently, or enter the workforce. These transitions may increase reliance on fast or processed foods and reduce opportunities for physical activity, contributing to accelerated weight gain. Previous research has demonstrated clinically meaningful short- and long-term weight loss (18-24 months) in adults with mild-to-moderate …

Impact Of Trisomy 21 On Post Pull-Through Enterocolitis And Bowel Function In Children With Hirschsprung Disease: A Pcplc Analysis., Marshall W. Wallace, Scott S. Short, Rachel C. Crady, Ron W. Reeder, Hira Ahmad, Kelly Austin, Andrea Badillo, Casey M. Calkins, Megan M. Durham, Julie R. Fuchs, Christopher Gayer, Julia E. Grabowski, Jamie C. Harris, Charles R. Hong, Ankur Rana, Rebecca M. Rentea, Nelson Rosen, Payam Saadai, Caitlin A. Smith, K Elizabeth Speck, Cristine S. Velazco, Richard J. Wood, Michael D. Rollins

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: We evaluated whether Trisomy 21 (T21) affected bowel management use, ability to toilet train for stool, and rates of Hirschsprung-Associated Enterocolitis (HAEC) in children with Hirschsprung disease (HD). We hypothesized that T21 would be associated with increased rates of HAEC, bowel management program (BMP) use, and delayed toilet training for stool.

METHODS: Children with HD in the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) database who underwent primary pull-through were included and stratified by T21 status: HD only versus HD + T21. Children requiring a redo pull-through, initially managed with a stoma, or those who had inadequate follow-up were …

Are We Winning At Twinning? Persistent Cni Use In Identical Kidney Transplants., Nicholas S. Herrera, Shivani Wadnerkar, Diane M. Cibrik

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Calcineurin inhibitors (CNIs) revolutionized kidney transplantation by reducing acute rejection rates. Identical twin kidney transplantation is the only setting in which the allograft is immunologically indistinguishable from self, yet CNI use persists. We characterized CNI utilization across end-stage kidney disease etiologies and examined whether CNI exposure was associated with reduced rejection or improved death-censored graft survival (DCGS).

METHODS: We performed a retrospective cohort study using scientific registry of transplant recipients data (January 2000-August 2025). Among 255 adult identical twin kidney transplant recipients, discharge regimens were categorized by CNI use; Firth penalized Cox regression was the primary method for 10-year …

Select Plasma Oxylipins As Potential Biomarkers Of Effective Indomethacin Treatment Response In Preterm Infants With Patent Ductus Arteriosus., Khanh C K Nguyen, Cindy H T Yeung, Allison Scott, Thomas J. Velenosi, Tamorah Lewis

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Patent ductus arteriosus (PDA) is one of the most common heart conditions in preterm infants, and indomethacin treatment is used for PDA closure. However, its efficacy varies among patients. This pilot study aimed to identify novel metabolic biomarkers to predict effective indomethacin response in infants with PDA.

METHODS: Preterm infants with PDA <  34 weeks gestational age were recruited and treated with indomethacin. Plasma and urine samples were collected before and 2-7 days after initial treatment. Longitudinal targeted oxylipin and untargeted metabolomics analysis were performed on plasma and urine samples.

RESULTS: Among 17 infants, 12 were responders and 5 non-responders to indomethacin treatment. Before the treatment, four plasma oxylipins: 12,13-DiHOME, 9,10-DiHOME, 15,16-DiHODE, and 9,10-DiHODE were significantly higher in responders compared to non-responders (P <  0.05). Following treatment, these oxylipins decreased in responders but remained stable in non-responders. Urinary 12,13-DiHOME showed an opposite trend, with lower baseline concentrations in the responders.

CONCLUSIONS: Pre-treatment plasma levels of four oxylipins were associated with effective PDA response to …

Under Pressure: Negative Urgency And Disordered Eating In The Context Of Parental Differential Support, Hamide Gozu, Jenna K. Rieder

College of Humanities and Sciences Faculty Papers

Disordered eating behaviors are prevalent in emerging adulthood and may be shaped by family dynamics. This study examined associations among maternal and paternal differential support, weight-shape concerns, and binge eating and compensatory behaviors in emerging adulthood, while testing the moderating role of negative urgency. Participants were 517 emerging adults from across the United States (ages 18-29; M = 22.60, SD = 3.81; 76% female). Participants reported on parental differential support, weight-shape concerns, eating behaviors, and negative urgency. Using moderated-mediation analyses, we found that weight-shape concerns mediated associations between differential support and eating behaviors. Unequal maternal support and paternal favoritism showed …

Acalabrutinib Monotherapy As A First-Line Treatment For Cll: 3 Years Follow-Up Of The Real-World Epic Study: 3-Year Follow-Up Of The Real-World Epic Study, Toby A. Eyre, Nicolás Martínez-Calle, Shankara Paneesha, Mohsen Norouzi, David L Tucker, Harriet Sarah Walter, Alison Boden, Mari Kilner, Neil Phillips, Piers Em Patten, Nimish Shah, Meghna Ruparelia, Sharon Oddy, Tan Tsawayo, Francesco Forconi, Helen Wardle, Tobore Gbemre, Chris Gregory, Lucy B. M. Cook, David J Allsup, Anna Morris, Christopher J C Knechtli, Jenni Davies, Joy Galani, Helen Marr, Claire Hutchinson, Stella Williams, Joe Hickey, Hannah Harding, Sukhjit Hunjan

Peninsula Medical School

Clinical trials indicate that acalabrutinib, a second-generation Bruton tyrosine kinase inhibitor, is safe and effective for treating patients with chronic lymphocytic leukemia (CLL), but real-world evidence on its clinical effectiveness is limited. This ongoing multicenter retrospective chart review included UK adults with previously untreated CLL who received acalabrutinib monotherapy as part of a UK-wide early access program. These patients received their first dose of acalabrutinib between 1 April 2020 and 1 April 2021. Data from 282 patients (male patients, n = 156 [55%]) collected from 29 sites across the United Kingdom revealed a median age of 73.9 years (interquartile range …

Adverse Childhood Experiences And Well-Being In Middle-Aged Korean Men: Mediating Role Of Andropause, Jeongok Park, Hyunju Lee, Gyeryung Park

International Nursing Research Congress (INRC)

Adverse childhood experiences (ACEs) can impact midlife well-being, however, their impact on middle-aged men is understudied. (1-5). This study aimed to examine the relationship between ACEs and well-being in middle-aged men, focusing on the mediating role of andropause symptoms to help develop strategies for improving men’s well-being.

This descriptive cross-sectional study included 444 community-dwelling men between the ages of 40 and 64 in Korea. Data were collected through an online survey. Individuals with psychological conditions impairing cognitive functions were excluded. Measures included PERMA-Profiler for well-being, ACEs International Questionnaire, and Androgen Deficiency in the Aging Males Questionnaire. SAS 9.4 was used …

Effects Of Non-Surgical Periodontal Therapy On Dental Plaque Microbiome, Qingguo Wang, Bing-Yan Wang, Derek Wilus, Hua Xie

Faculty, Staff and Student Publications

Periodontitis, a chronic inflammatory disease affecting approximately 40% of U.S. adults aged 30 years and older, is characterized by dysbiosis of the dental plaque microbiome. However, although scaling and root planing (SRP) is the cornerstone of periodontal treatment, its effects on the taxonomic composition and functional potential of the dental plaque microbiome remain incompletely understood. In this study, we used whole-metagenome shotgun sequencing to characterize taxonomic composition and functional potential in dental plaque microbiomes collected from 39 patients with Stage II or III generalized periodontitis before and 3–4 months after SRP. Consistent with clinical improvement, periodontal therapy significantly reduced probing …

Barriers To Recommendation Of Integrative Oncology Modalities In Supportive Care: A Mascc/Sio Survey, Alexandre Chan, Dalia Kagramanov, Reem Nasr, Chioma Asuzu, Ting Bao, Yin Ting Cheung, Jung Hye Kwon, Judith Lacey, Richard T. Lee, Maryam Lustberg, Beatrice M. Ohaeri, Santosh Rao, Enrique Soto-Perez-De-Celis, Claudia M. Witt, Ana M. Lopez

Kimmel Cancer Center Faculty Papers

PURPOSE: Integrative oncology (IO) modalities aim to improve the quality of life of persons with cancer, including strategies to manage treatment and disease-related symptoms. As evidence increases to include IO in supportive care, interest grows globally. Understanding barriers to IO recommendation is key to facilitating its uptake.

METHODS: Members of the Multinational Association of Supportive Care in Cancer (MASCC) and the Society for Integrative Oncology (SIO) were invited to complete an online survey in Fall 2023 assessing barriers to IO recommendation on a 5-point scale. Descriptive statistics assessed demographic data and general counts of scaled agreement, while logistic regression analysis …

Loss Of Atp-Dependent Citrate Lyase Drives Left Ventricular Dysfunction By Metabolic Remodeling, Shijie Liu, Seth T Gammon, Lin Tan, Yaqi Gao, Kyoungmin Kim, Mahmoud H Elbatreek, Adrian Arrieta, Ian K Williamson, Rebecca L Salazar, Janet Pham, Angela Davidian, Radhika Khanna Neicheril, Benjamin D Gould, Heidi Vitrac, Alia Sadiq, An Q Dinh, Evan C Lien, Francisca N De Luna Vitorino, Joanna M Gongora, Sara A Martinez, Melanie T Odenkirk, Anna K Boatman, Jessie R Chappel, Lawrence S C Czer, Evan P Kransdorf, David J Lefer, Blake M Hanson, Benjamin A Garcia, Erin M Baker, Matthew G Vander Heiden, Philip L Lorenzi, Heinrich Taegtmeyer, David Piwnica-Worms, James F Martin, Anja Karlstaedt

Faculty, Staff and Student Publications

Background: Metabolic adaptation and maladaptation are hallmarks of the failing heart and may be a target for therapeutic interventions. For example, sustained glucose oxidation during cardiac stress is associated with increased activity and abundance of ACL (ATP-dependent citrate lyase, Acly), which produces acetyl-coenzyme A (CoA) from citrate and CoA and supports de novo lipid synthesis. However, our understanding of how ACL supports cardiac metabolic adaptation and its potential to modulate disease pathophysiology has not yet been investigated.

Methods: We used human heart tissue samples from healthy donors and patients with nonischemic cardiomyopathy. Next, we used CRISPR (clustered, regularly interspaced …

Molecular Mechanism Leading To Human Coronary Atherosclerosis Assessed By Proteomic Analysis And Rna Sequences, Sarah J Parker, Chunhong Mao, David L Caudell, Austin Lyle Seals, Yizhi Wang, Thomas D Green, Joseph M Mcclung, Joshua T Maxwell, Jacolby T Roddey, Kiarash Shakeriastani, Chiung-Ting Wu, Yingzhou Lu, Do-Kyun Kim, Justyna Fert-Bober, Dongping Du, Archana Bhat, Niveda Sundararaman, Matthew Ayres, Rakhi Pandey, Saurabh Bhardwaj, Genesio M Karere, Dana Troxclair, Fannie Jackson, Gordon L Love, Richard Vander Heide, James Hixson, Jennifer E Van Eyk, Yue Wang, David Herrington

Faculty, Staff and Student Publications

Background and aims: Atherosclerosis results from cellular and extracellular changes in the arterial wall, preceded by molecular shifts that initiate disease and drive tissue conversion, yet these changes are not yet fully described. More data are needed concerning these early changes in the coronary artery molecular landscape that signify the initiation of atherosclerosis and the subsequent tissue pheno-conversion to atherosclerotic plaque. This report summarizes results from a large biorepository of human coronary artery tissue, applying state-of-the-art omics technology, advanced data analytic methods, and an arterial organoid model system to predict molecular dynamics and identify potential regulatory mechanisms that could interrupt …

Neurofilament Light Chain (Nfl) As A Surrogate Outcome Measure For Gm2 Gangliosidoses., Kyriakos Martakis, Nicolas J. Abreu, Joshua J. Baker, Peter R. Baker Ii, Ian Billington, T Andrew Burrow, Mallory Factor, Taylor Fields, Cassandra Fields, Jennifer L. Gannon, Megan Grosso, Jorgji Kerthi, Marc C. Patterson, Brian J. Shayota, Michael Strupp, Lennard Strupp, Tatiana Bremova-Ert

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The GM2 gangliosidoses (GM2) are ultra-rare neurodegenerative disorders caused by deficient hexosaminidase A and/or B activity, leading to lysosomal GM2 ganglioside accumulation. Disease onset ranges from infancy to adulthood, with earlier onset associated with more rapid progression. Neurofilament light chain (NfL), a sensitive marker of axonal injury, has been extensively investigated as a biomarker for neurodegenerative disorders, including GM2.

METHODS: To evaluate its clinical utility as a biomarker for GM2, NfL was measured in patients with GM2 enrolled in a Phase 2b, multinational, rater-blinded study of levacetylleucine [NCT03759665], and in its open-label Extension Phase (EP).

RESULTS: Nineteen participants had …

Tau Seeds Induce Neurofibrillary Tangle Formation Across Brain Regions Via Individual-Specific Connectivity, Audrey J Weber, Bernard Ng, Kelsey M Greathouse, David A Bennett, Shinya Tasaki, Chris Gaiteri, Jeremy H Herskowitz

Faculty, Staff and Student Publications

The spread of tau pathology across the cerebral cortex is closely tied to cognitive decline in Alzheimer's disease (AD). To investigate mechanisms underlying tau spread, we measured bioactivity of tau seeds from inferior temporal gyrus (ITG) and superior frontal gyrus (SFG) synaptosomes in 128 individuals and demonstrated that tau seed bioactivity associates with tau phosphorylation, neurofibrillary tangles (NFTs), and cognitive impairment. Incorporating genotype data from the same individuals within a Mendelian randomization framework showed that tau seeds in ITG induce NFTs locally as well as drive tau seeds and NFTs in SFG. Integrating antemortem functional magnetic resonance imaging data from …

Aberrant Stat Signaling And T Cell Dysregulation Define A Targetable Pediatric Sepsis Endotype, Robert B. Lindell, Samir U. Sayed, Jose S. Campos Duran, Sydney A. Sheetz, Apoorva Babu, Montana S. Knight, Andrea A. Mauracher, Ceire A. Hay, Peyton E. Conrey, Julie C. Fitzgerald, Nadir Yehya, Stephen T. Famularo, Teresa Arroyo, Richard Tustin, Hossein Fazelinia, Edward M. Behrens, David T. Teachey, Lisa R. Forbes Satter, Alexandra F. Freeman, Jenna Re Bergerson, Steven M. Holland, Jennifer W. Leiding, Scott L. Weiss, Mark W. Hall, Deanne M. Taylor, Rui Feng, E. John Wherry, Nuala J. Meyer, Sarah E. Henrickson

Department of Pediatrics Faculty Papers

BACKGROUNDSepsis is a leading cause of morbidity and mortality in critically ill children, yet heterogeneous immune responses complicate the development of targeted therapies and the host immune factors driving sepsis pathobiology remain unclear.METHODSWe integrated deep immune phenotyping, plasma proteomics, single-cell transcriptomics, and phosphoflow cytometry in a prospective cohort of 88 critically ill children to elucidate the mechanisms underlying immune heterogeneity.RESULTSUnsupervised clustering of plasma cytokines identified 3 immunologic subgroups, including a high-severity group ("Group C") characterized by hypercytokinemia driven by IL-6 and IFN-γ. Group C exhibited distinct alterations in immune cell frequency and activation, with a strong association between hyperinflammatory cytokine …

A Systematic Literature Review Of Cvid Reveals Pervasive Detrimental Noninfectious Manifestations, Robert B Lindell, Samir U Sayed, Jose S Campos Duran, Sydney A Sheetz, Apoorva Babu, Montana S Knight, Andrea A Mauracher, Ceire A Hay, Peyton E Conrey, Julie C Fitzgerald, Nadir Yehya, Stephen T Famularo, Teresa Arroyo, Richard Tustin, Hossein Fazelinia, Edward M Behrens, David T Teachey, Lisa R Forbes Satter, Alexandra F Freeman, Jenna Re Bergerson, Steven M Holland, Jennifer W Leiding, Scott L Weiss, Mark W Hall, Deanne M Taylor, Rui Feng, E John Wherry, Nuala J Meyer, Sarah E Henrickson

Faculty, Staff and Students Publications

BACKGROUND

Sepsis is a leading cause of morbidity and mortality in critically ill children, yet heterogeneous immune responses complicate the development of targeted therapies and the host immune factors driving sepsis pathobiology remain unclear.

METHODS

We integrated deep immune phenotyping, plasma proteomics, single-cell transcriptomics, and phosphoflow cytometry in a prospective cohort of 88 critically ill children to elucidate the mechanisms underlying immune heterogeneity.

RESULTS

Unsupervised clustering of plasma cytokines identified 3 immunologic subgroups, including a high-severity group (“Group C”) characterized by hypercytokinemia driven by IL-6 and IFN-γ. Group C exhibited distinct alterations in immune cell frequency and activation, with a …

Exploring Factors Associated With High Frequency Emergency Department Use By Children And Young People: A Retrospective Cohort Study, Akshay Kumar, Rebecca M Simpson, Kerryn Husk, Graham D Johnson, Chris Burton

Peninsula Medical School

Objective To explore drivers of high frequency emergency department (ED) use by children and young people, particularly among those attending EDs most often.Design A population-based retrospective cohort study using routinely collected linked healthcare data.Setting EDs in the Yorkshire and Humber region of the UK.Patients 288 545 children and young people aged 17 and under making at least one ED attendance in the year period 1 April 2016 to 31 March 2017.Main outcome measures ED attendances made by individuals in the year period.Results Of the 288 545 distinct children and young people making at least one attendance to an ED, 27 …

Leveraging Health Information Exchange (Hie) Data To Demonstrate The Impact On Health Outcomes Of Community Based Organization Interventions: Case Studies Of Housing Placement And Medically Tailored Meal Program, Kevin Kramer, Harm Scherpbier, William Marella

College of Population Health Faculty Papers

Objective

Methods

Association Between Author Specialty And Reported Outcomes In Non-Randomized Comparisons Of Prostatectomy Versus Radiation, Zakaria El Kouzi, Mohammed A Mohammed, Michael Kevin Rooney, Ramez Kouzy, Jie Jane Chen, Shalin Shah, Tarek Al Bitar, Sherif M Gadoue, Comron Hassanzadeh, Steven Frank, Phuoc Tho Tran, Chad Tang, Seungtaek Choi, Ryan Jin-Hyung Park, Karen Hoffman, Sean Eric Mcguire, Henry Mok, Quynh-Nhu Nguyen, Adam B Samman, Zain Rahman, Mohamed Shelan, Toufic Eid, Osama Mohamad

Faculty, Staff and Students Publications

Background: While the ProtecT randomized trial demonstrated comparable oncologic outcomes between radical prostatectomy (RP) and radiation therapy (RT) for localized prostate cancer, several retrospective studies have reported mixed findings. In this study, we investigated whether non-randomized studies tend to favor RP or RT and assessed whether the specialty of leading authors-urologists or radiation oncologists-correlates with study conclusions.

Methods: We identified non-randomized clinical studies published between 1993 and 2024 that compared RP and RT for localized prostate cancer and reported oncologic outcomes including biochemical, metastasis, and/or survival outcomes. Author specialty was determined based on whether the first and senior authors were …

Association Between Trainee Involvement During Pediatric And Congenital Cardiac Catheterization And Procedural Outcomes., Natalie Jayaram, John A. Spertus, Kevin F. Kennedy, Andrew C. Glatz

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Participation in the cardiac catheterization laboratory is a requirement of cardiology fellowship training. We sought to determine whether trainee presence is associated with outcomes during pediatric and congenital cardiac catheterization.

METHODS: We identified catheterizations between January 2011 and September 2020 within the IMPACT (Improving Pediatric and Adult Congenital Treatment) Registry. Multivariable multilevel regression was used to determine the association between trainee presence and procedural outcomes.

RESULTS: Of 122 760 catheterizations at 107 academic hospitals, a trainee was present in 71 651 (58.4%) cases. Rates of major adverse events were similar between trainee and nontrainee cases (9.0% versus 8.0%). Contrast …

Multiple Event Segmentation Mechanisms In The Human Brain, Tan T Nguyen, Joset A Etzel, Matthew A Bezdek, Jeffrey M Zacks

2020-Current year OA Pubs

The human brain segments continuous experience into discrete events, with theoretical accounts proposing two distinct mechanisms: creating boundaries at points of high