Digital Commons Network^™

Development Of A Structurally Distinct Topbp1 Inhibitor That Enhances Parp Blockade And Reverses Osimertinib Resistance, Fang-Tsyr Lin, Shwu-Jiuan Lin, Kang Liu, Yang Xiao, Lidija A Wilhelms Garan, Helena Folly-Kossi, Weei-Chin Lin

Faculty, Staff and Students Publications

Therapeutic resistance remains a major challenge in cancer treatment, driven by compensatory signaling and stress response pathways that sustain tumor survival. Topoisomerase IIβ-binding protein 1 (TopBP1), a multifunctional scaffold protein with nine BRCT domains, integrates replication stress signaling with oncogenic networks and is frequently overexpressed in aggressive cancers. Its BRCT7/8 domains mediate critical interactions with E2F1, mutant p53, MIZ1, PLK1, and CIP2A, making TopBP1-BRCT7/8 an attractive therapeutic target. Using docking-guided screening and structure-activity relationship–driven optimization, we developed CS18 as a potent and selective BRCT7/8 inhibitor that disrupts oncogenic TopBP1 complexes without interfering with DNA replication. CS18 suppresses MYC transcriptional programs, …

Young-Onset Stroke In The Uae: A Single-Centre Retrospective Analysis Of Risk Factors And Outcomes, Sobia Siddiq, Saryia Adra, Kamel A. Samara, Batool Aldaher, Mohamad Emad Aldeen Mahfouz, Nour Sakan, Fathima Musfira, Roomiyah Riyaz Assadi, Ahlam Mohamed Almarzooqi, Hiba Jawdat Barqawi, Eman Abu-Gharbieh

Abington Jefferson Health Papers

BACKGROUND: Young-onset stroke represents a growing public health concern, yet data from the United Arab Emirates (UAE) remain limited. This study aimed to examine the risk factors and clinical outcomes associated with young-onset stroke in the UAE.

METHODS: A retrospective chart review was conducted on 419 patients aged below 50 years who were admitted at Al Qassimi Hospital, Sharjah, UAE, with a diagnosis of stroke between 2016 and 2022. Data on demographics, comorbidities, stroke subtype, management, and outcomes were collected and analyzed using Python-based statistical libraries.

RESULTS: The study population comprised predominantly of male individuals (78.28%), with most patients originating …

An Online Epilepsy Self-Management Tool For Patients With Epilepsy: A Formative Usability Study, Katarzyna Czerniak, Ross Shegog, Refugio Sepulveda, Robert Addy, Youngran Kim, Sahiti Myneni, Alejandra Garcia-Quintana, Kimberly Martin, David M Labiner

Faculty, Staff and Student Publications

Background: Epilepsy is a serious chronic neurological condition with no permanent cure. Continual self-management is important to mitigate seizure frequency and optimize quality of life in people with epilepsy who have greater disparities in accessing epilepsy care. The Management Information & Decision Support Epilepsy Tool (MINDSET [UTHealth, University of Arizona, and Radiant Digital]) was developed to enhance accessibility to epilepsy self-management (ESM) assessment and treatment. The purpose of this formative usability pilot study was to assess the user experience and functionality of MINDSET 2.0, an enhanced cross-platform online version of MINDSET, among a sample of patients with epilepsy prior to …

Larotrectinib In Trk Fusion Differentiated Thyroid Carcinoma: Updated Trial Data, Steven Waguespack, Marcia Brose, Jessica J Lin, Ray Mcdermott, Mohammed Almubarak, Jessica Bauman, Michela Casanova, Shivaani Kummar, Se-Hoon Lee, Damian Rieke, Do-Youn Oh, Changsong Qi, Natascha Neu, Domnita-Ileana Burcoveanu, Chiara Mussi, Alexander Drilon, David Hong, Maria Cabanillas

Department of Medical Oncology Faculty Papers

Larotrectinib is a first-in-class, highly selective, central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for tumour-agnostic use in TRK fusion cancer. It has previously demonstrated rapid and durable disease control and favourable safety in patients with advanced TRK fusion thyroid carcinoma (TC). After an additional 4 years of follow-up with the inclusion of two additional patients, and utilising an independent review committee (IRC) to assess overall response rate (ORR), we report updated pooled analyses from three phase 1-2 larotrectinib clinical trials, focusing only on patients with TRK fusion differentiated TC (DTC). The primary endpoint was the IRC-determined ORR per …

Childhood Cancer Predisposition Study: A Prospective Registry And Biorepository Protocol, Melissa R Perrino, Suzanne P Macfarland, Luke Maese, Jennie Vagher, Junne Kamihara, Surya Rednam, Philip J Lupo, Garrett M Brodeur, Joshua Schiffman, Lisa Diller, Lauren Desrosiers-Battu, Sharon E Plon, Kim E Nichols, Samuel L Volchenboum, David Malkin, Anita Villani, Christopher C Porter

Faculty, Staff and Students Publications

Introduction: Cancer is the most common cause of disease-related mortality in children, highlighting the urgent need for improved care in this population. It is estimated that >15% of children diagnosed with cancer harbour a germline pathogenic variant in a cancer predisposition gene which confers an increased risk to develop cancer. There are over 100 genes associated with cancer predisposition syndromes (CPSs) and greater availability and acceptability of genetic testing in the last decade has facilitated their recognition in childhood. However, individually, each of these CPSs is rare, impeding robust research and advancement of clinical care. Once a specific CPS is …

Conceptual Framework And Key Considerations For Field-Based Infrastructure In Food Is Medicine Research, Shreela V Sharma, Colleen Tewksbury, Christopher R Long, Colleen Spees, Ronit A Ridberg, Reshma Gupta, Erin P Ferranti, Naomi Tice, Eric Peterson, Brian Levine

Faculty, Staff and Student Publications

In 2023, the American Heart Association launched the Healthcare by Food (HCXF) initiative to establish a rigorous evidence base for Food Is Medicine (FIM) programs, so that patients with acute or chronic disease could access FIM programs as a covered benefit under their health insurance. The HCXF initiative is engaging in research, advocacy, and education to support the development and testing of interventions that improve health outcomes. The HCXF initiative launched 9 task forces aligned with research progress, including the Field-Based Infrastructure task force designed to examine broader questions to help support either earlier or later stages of the HCXF …

Reinterpreting The Frequency Dependence Of Cortical Auditory-Evoked Response Amplitudes In Light Of Current Understanding Of Cortical Tonotopic Organization, Carl Rushworth, Alexander J. Hardy, Magdalena Sereda, Ben J. Gurer, Julien Besle, Susan T. Francis, Rebecca S. Dewey, Denis Schluppeck, Justin M. Ales, Vassilis Pelekanos, Michael A. Akeroyd, Katrin Krumbholz

School of Psychology

Tonotopy is a fundamental feature of auditory cortical organization, yet its influence on cortical auditory-evoked responses (AERs) remains unclear. Consequently, key properties of cortical AERs—such as their marked amplitude reduction with increasing stimulus frequency—still lack a coherent mechanistic explanation. To address this gap, we combined a meta-analysis of frequency-specific AER amplitudes with forward simulations of AERs informed by current knowledge of auditory cortical tonotopic layout and functional organization. The meta-analysis used a semi-systematic search covering all known automatic cortical AER components—both transient-evoked and steady-state—along with selected subcortical components for comparison. Forward simulations were based on a functional parcellation of the …

The Utility Of Fret/Flim-Based Bioassays For Monitoring Nrf2 Activation In Single Live Cells, Dina Dikovskaya, Albena T Dinkova-Kostova

Peninsula Medical School

The Kelch-like ECH-associated protein 1 - Nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) partnership is vital for protection against oxidative stress, and its dysregulation has been linked to the pathogenesis of numerous chronic diseases. Under homeostatic conditions, Keap1 targets Nrf2 for ubiquitination and proteasomal degradation. When Keap1 is inactivated by electrophiles or Keap1-Nrf2 protein-protein interaction (PPI) inhibitors (termed inducers), Nrf2 accumulates and, in association with a small musculoaponeurotic fibrosarcoma (sMaf) protein, induces the transcription of networks of genes encoding cytoprotective proteins. To understand the PPIs between Nrf2 and Keap1 and the effect of inducers in the cellular context, we expressed …

Mir155, Triplicated In Down Syndrome, Regulates The Development Of Neural Stem Cells And Gabaergic Interneurons In Alzheimer's Disease Mouse And Human Ipsc Models., Xiaodong Zhu, Jean-Vianney Haure-Mirande, Mesude Bicak, Pengfei Dong, Ilya Kruglikov, Aiqun Li, Aisha Al-Subaie, Valentina Fossati, Scott Noggle, Sam Gandy, Michelle E Ehrlich

Faculty Research 2026

INTRODUCTION: Dysfunctional microRNAs and GABAergic interneurons are features of Alzheimer's disease (AD). The role of neuronal microRNA155 (miR155), elevated in both AD and Down syndrome (DS), remains unknown.

METHODS: We utilized in silico analyses of published databases, MIR155-deleted and -overexpressing human induced pluripotent stem cell (hiPSC)-derived cells, cortical organoids, and amyloid beta precursor protein (APP)/PS1-miR155 knockout mouse.

RESULTS: MIR155HG (miR155 host gene) colocalizes with APP in a neuron-specific, topologically associated domain (TAD) in chromosome 21. In human neural stem cells (NSCs), neurons, and cortical organoids, MIR155 deletion enhanced NSC proliferation and GABAergic interneuron generation. MIR155 overexpression inhibited NSC marker expression …

The Past, The Present, And The Future Of Preclinical Mouse Models For Alzheimer's Disease And Related Dementias., Adrian L Oblak, Michael Sasner, Gregory W. Carter, Gareth R Howell, Stacey J Sukoff Rizzo, Karina Leal, Paul R Territo, Bruce T Lamb

Faculty Research 2026

Over the past decade, the Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease (MODEL-AD) consortium has transformed preclinical Alzheimer's disease (AD) research by addressing critical limitations in traditional mouse models that failed to translate to human disease. By leveraging human genetic discoveries, MODEL-AD has developed > 70 genetically informed mouse models, standardized phenotyping pipelines, and an open-access data infrastructure aligned with late-onset AD biology. These models incorporate human risk variants, environmental factors, and aging to better capture disease complexity, including emerging recognition of mixed pathologies such as vascular contributions, Lewy body disease, and TDP-43 proteinopathy. Despite substantial progress, key challenges …

A Collaborative Framework For Uncovering Molecular And Cellular Drivers Of Vcid: Foundations For Future Interventions In Dementia., M Luisa Iruela-Arispe, Jason D Hinman, Andrew C Yang, Fabrice Dabertrand, Jin-Moo Lee, Gareth R Howell, The Vcid Centers Without Walls Network

Faculty Research 2026

Vascular-related factors are now considered major contributors to most forms of dementia, including Alzheimer's disease. However, the degree to which vascular deficits contribute to risk, onset, and progression of cognitive impairment and dementia has only recently been appreciated. Our understanding of the mechanisms by which vascular deficits drive cognitive decline in dementia is still limited. Further, the testing of therapeutic approaches to prevent vascular deficits to treat dementia are few. These factors motivated the establishment of the Vascular Contributions to Cognitive Impairment and Dementia (VCID) Center Without Walls (CWOW) network, comprising institutes across the United States. We describe the current …

Worldwide Innovative Network Consortium: Building A Common Global Cancer Database., Farhood Farahnak, Wafik S El-Deiry, Yves A Lussier, Razelle Kurzrock, Shai Magidi, Catherine Bresson, Shirin A Enger, Jia Liu, Jair Bar, Jeremy L Warner, Tobias Meissner, Eitan Rubin, Jens Rueter, Himabindu Gaddipati, Mandar Kulkarni, Zhen Chen, Sewanti Limaye, Rachel Elsey, Brenda M Rubenstein, Anthony M Joshua, Humaid O Al-Shamsi, Khaled M Musallam, Fanny Wunder, Jacques Raynaud, Guy Berchem, Manon Gantenbein, Amal Al Omari, Said Dermime, Hikmat Abdel-Razeq, Pierre Saintigny, Andrés Cervantes, Roger R Reddel, Adel T Aref, Juan Martin-Liberal, Conxi Lázaro, David Cordero Romera, Marina Sekacheva, Raanan Berger, C S Pramesh, Ioana Berindan-Neagoe, Eugenia Girda, Alejandro Piris-Gimenez, Carol J Farhangfar, Mohammed E Salem, Rodrigo Dienstmann, Ramon Salazar, Naftali Z Frankel, Zachary Batist, Yuri Quintana, Gerald Batist

Faculty Research 2026

This review shares the ongoing work of the global Worldwide Innovative Network (WIN) Consortium for Precision Medicine to synthesize emerging cancer treatment data and to define the requirements for a common global cancer database that can truly support precision oncology. We performed a narrative review of emerging cancer treatment data, molecular profiling technologies, and existing clinicogenomic databases, focusing on how tumors are characterized, how subgroups are defined, and how demographic, lifestyle, and environmental factors are captured. The growth in molecular profiling technologies and the development of new targeted therapies are transforming cancer care. Tumors, regardless of tissue origin, are increasingly …

Inhibition Of Moesin And Cd44 In Stem Cell-Derived Neurons Affects The Pathological Genetic Signature Associated With Alzheimer's Disease., Eiden H Brewer, Charles A Williams, Gregory Cary, Ranjita Betarbet, Inez K A Pranoto, Elizabeth L Zoeller, Haian Fu, Allan I Levey, Jesse C Wiley, Gregory W. Carter, Jessica E Young, Treat-Ad Consortium

Faculty Research 2026

INTRODUCTION: Post mortem proteomic analysis of Alzheimer's disease (AD) brain tissue has identified novel target genes and proteins for potential therapeutic development. Moesin (MSN) and CD44 were identified as candidate targets. Using human induced pluripotent stem cells (hiPSCs)-derived neurons, we assayed how reducing gene expression of MSN and CD44 affected amyloid beta secretion, tau phosphorylation, and transcriptional state.

METHODS: Knockdown of MSN and CD44 in hiPSC-derived neurons was performed using short hairpin RNA (shRNA). Amyloid precursor protein processing and intracellular tau phosphorylation was measured using chemiluminescent ELISA assays. Global gene expression was analyzed by bulk RNA sequencing (RNA-seq).

RESULTS: Knockdown …

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 …

An Update On The Role Of Multimodal Analgesia In Perioperative Pain Management, Whitney N. Kuwamoto, Grace C. Eddy, Edward R. Mariano, Eric S. Schwenk

Department of Anesthesiology Faculty Papers

Multimodal analgesia has become a foundational principle of acute perioperative pain management and enhanced recovery and involves the application of nonpharmacologic, pharmacologic, and/or interventional techniques. The overall goal of this approach is to apply a combination of different modalities that target discrete points along the pain pathway and thereby avoid the overreliance on opioids and associated side effects. Since our review in 2018, there have been significant developments that have prompted an updated review of multimodal analgesia. In this article, we identify and summarize important trends that influence the current approach to acute perioperative pain management as well as provide …

Ecmo Use In Infants With Bronchopulmonary Dysplasia: A Literature Review., John Ibrahim, Nicholas Carr, Franscesca Miquel Verges, Natalie Rintoul, Robert Digeronimo, John M. Daniel Iv, Sarah Keene, Burhan Mahmood

Manuscripts, Articles, Book Chapters and Other Papers

Bronchopulmonary dysplasia (BPD) is a leading cause of chronic respiratory failure in infants. Severe BPD is associated with prolonged mechanical ventilation, pulmonary hypertension, and high morbidity and mortality. As disease severity increases, extracorporeal membrane oxygenation (ECMO) is being reconsidered as a potential rescue therapy. Historically, ECMO has been reserved for neonates with reversible respiratory failure and those who required mechanical ventilation for less than 14 days, while infants with BPD were excluded. However, advancements in ECMO technology, anticoagulation strategies, and ventilatory management have led to a reassessment of its role in this population. Emerging reports suggest ECMO may serve as …

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 …

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 …

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 = …

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 …

Hyperadhesive Von Willebrand Factor Contributes To Pathogenesis Of Preeclampsia, Yajuan Wang, Chenyu Wang, Katie L Houck, Xiaoli Gao, Yuanyuan Chen, Xin Xu, Xue Zhao, Miguel A Cruz, Shu Zhang, Chester Q Li, Fengxia Xue, Min Li, Swati Shree, Jing-Fei Dong, Cha Han

Children’s Nutrition Research Center Staff Publications

Background: Preeclampsia is the most common complication of pregnancy, significantly affecting maternal and fetal health, and is characterized by placental and systemic endotheliopathy. Patients with preeclampsia have elevated levels of VWF (von Willebrand Factor), which is associated with poor clinical outcomes. However, whether VWF serves as a marker for endotheliopathy or contributes to the pathogenesis of preeclampsia remains poorly understood.

Methods: We investigated the role of hyperadhesive VWF in the development of preeclampsia by studying patients, evaluating mouse models, and performing in vitro experiments.

Results: We show that patients develop VWF- and fibrin-rich thrombosis in the placenta and have significantly …

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 …

Defining The Value Of Elective Lumbar Fusion: A Systematic Review Of Existing Methodologies And Framework For The Operative Value Index, Advith Sarikonda, Anthony Chen, Theo S. Biddle, Danyal A. Quraishi, Preston Carey, Arbaz A. Momin, Matthews Lan, Dwight Mitchell Self, Ashmal S. Kabani, Ahilan Sivaganesan

Department of Neurosurgery Faculty Papers

BACKGROUND: Despite wide variation in the outcomes and costs of lumbar fusion, few studies have integrated these domains together within a single metric to assess "value" (outcomes achieved per dollar spent). In this review, we sought to 1) characterize existing metrics of cost-effectiveness for lumbar fusion, 2) evaluate all applications of time-driven activity-based costing (TDABC) in spine surgery, and 3) outline the conceptual foundation for a standardized Operative Value Index (OVI).

METHODS: Two PRISMA-concordant systematic reviews were performed on PubMed and Scopus databases. The first review examined all studies which reported a cost-effectiveness metric for lumbar fusion. The second review …

Small But Mighty: How Can Pediatric Psychologists Harness The Power Of Digital Single-Session Interventions?, Christina Amaro, Alexandra Monzon, Melissa Alderfer, Kimberly Canter, Michael Amylon, Stephanie Fooks-Parker, Jessica Schleider, Susana Patton, Katie Devine

Department of Pediatrics Faculty Papers

OBJECTIVE: Single-session interventions (SSIs) are an innovative, scalable approach for addressing the unmet behavioral and mental health needs of pediatric patients and their families. Specifically, digital SSIs, which are self-guided and delivered online, offer a low-cost and accessible approach but are currently underutilized in pediatric psychology.

METHODS: This topical review aims to describe SSIs broadly and the specific need for digital SSIs, explore potential applications within pediatric psychology, outline future directions and considerations, and present two examples of community-engaged digital SSI design.

RESULTS: SSIs evidence small to medium effects across a range of mental health concerns, including distress, anxiety, and …

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 …

Vitamin B6 Predicts Poor Outcomes In Geographically Distinct Populations With Primary Sclerosing Cholangitis, Peder R Braadland, Ahmad H Ali, Philip Puchas, Brian D Juran, Elizabeth J Atkinson, Erik M Schlicht, Jackie K Bianchi, Bryan M Mccauley, Sara K V Tjønnfjord, Hólmfríður Helgadottir, Per M Ueland, Arve Ulvik, Peter Sauer, Trine Folseraas, Tom H Karlsen, Mette Vesterhus, Michael T Dill, Konstantinos N Lazaridis, Johannes R Hov

Faculty, Staff and Students Publications

Background & aims: Primary sclerosing cholangitis (PSC) has a variable disease course, complicating patient counseling and the timing of liver transplantation. Vitamin B6 deficiency predicts reduced liver transplantation-free survival in Scandinavian PSC cohorts. Here, we aimed to validate this observation in US and German PSC cohorts and to expand our analyses to include hepatic decompensation as a clinical outcome.

Methods: Serum active vitamin B6 (pyridoxal 5'-phosphate [PLP]) was analyzed using liquid chromatography-tandem mass spectrometry in retrospective cohorts of people with PSC from Norway (n = 315), the USA (n = 756), and Germany (n = 149). Cox proportional hazards and …

Long-Term Outcomes In Seronegative Rheumatoid Arthritis, Bradly A Kimbrough, Roslin Jose George, Cynthia S Crowson, Sara J Achenbach, Elizabeth J Atkinson, Vanessa L Kronzer, John M Davis, Elena Myasoedova

Faculty, Staff and Students Publications

Objective: The purpose of this study was to determine the cumulative incidence of diagnosis switching, drug-free remission, and initiation of a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) in individuals with seronegative rheumatoid arthritis (RA).

Methods: Adult residents of Olmsted County, Minnesota, with incident seronegative (rheumatoid factor negative/anti-cyclic citrullinated peptide antibody negative) RA meeting the 1987 and/or 2010 American College of Rheumatology classification criteria were included. Data were collected from January 1, 2005, to December 31, 2023, through manual chart review. Drug-free remission was defined as a period of at least six months where the individual was no longer …

Colocalization Of Eqtls With Type 2 Diabetes And Glycemic Traits Using Whole-Genome Sequences In Diverse Populations From The Nhlbi Trans-Omics In Precision Medicine (Topmed) Program, Ningyuan Wang, Daniel A Dicorpo, Yixin Zhang, Erica Kleinbrink, Donna K Arnett, John Barnard, John Blangero, Donald W Bowden, April P Carson, Yii-Der Ida Chen, Mina K Chung, Joanne E Curran, Dawood Darbar, Ravindranath Duggirala, Patrick T Ellinor, Diane Fatkin, Myriam Fornage, Nancy Heard-Costa, Jiang He, Lifang Hou, Sharon L R Kardia, Charles Kooperberg, Ruth J F Loos, David D Mcmanus, Braxton D Mitchell, Ryan L Minster, Kari E North, Bruce M Psaty, Laura M Raffield, Susan Redline, Stephen S Rich, Dan Roden, Jerome I Rotter, Moore B Shoemaker, Jonathan D Smith, David R Van Wagoner, Francois Aguet, Kristin Ardlie, Joshua C Bis, Jennifer A Brody, Brian E Cade, Clary B Clish, Paul S De Vries, James S Floyd, Barry I Freedman, Stacey Gabriel, Robert E Gerzsten, Mark O Goodarzi, Charles Gu, Xiuqing Guo, Namrata Gupta, Susan R Heckbert, Sarah Hsu, Yi-Jen Hung, Rita R Kalyani, Tanika N Kelly, Gregory L Kinney, Changwei Li, Simin Liu, Yongmei Liu, Donald M Lloyd-Jones, Joann E Manson, Rasika A Mathias, Josep M Mercader, Alanna C Morrison, Take Naseri, Suna Onengut, Nicholette D Palmer, Patricia A Peyser, Qibin Qi, Sridharan Raghavan, Alex P Reiner, Mary R Rooney, Magdalena Sevilla-Gonzalez, Chloe Sarnowski, Joshua D Smith, Jennifer A Smith, Nicole L Spartano, Usman Tahir, Kent D Taylor, Deirdre K Tobias, Russel P Tracy, Satupa'itea Viali, Heming Wang, Alexis C Wood, Lisa R Yanek, Wei Zhao, Yinan Zheng, Josée Dupuis, Ching-Ti Liu, Robert Sladek, Jennifer Wessel, James B Meigs, Alisa K Manning, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium

Faculty, Staff and Students Publications

Large-scale multiancestry genome-wide association studies have identified hundreds of loci associated with type 2 diabetes (T2D) and glycemic traits, yet imputed genotyping arrays limit the detection of low-frequency and rare variants. Whole-genome sequencing (WGS) offers a more complete view of genetic variation, especially across diverse populations. We analyzed high-coverage (38×) WGS data from 21,913 T2D case subjects, 61,036 control subjects, and up to 50,011 individuals with no diabetes with fasting glucose, fasting insulin, and HbA1c from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine Program. We performed single-variant association testing, conditional analysis, fine-mapping, and Bayesian colocalization to …