Digital Commons Network^™

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 …

Systemic Corticosteroids In The Management Of Sinonasal Disease: An Evidence-Based Expert Review, Andrew Thamboo, Deanna Gigliotti, Eugenio De Corso, Stella Lee, Benjamin S Bleier, Christopher J Chin, Marie-Noelle Corriveau, Valerie Hox, Claire Hopkins, Peter H Hwang, Arif Janjua, Ludger Klimek, Daniel Lee, John Lee, Amber Luong, Geoffrey Mortuaire, Joaquim Mullol, Zara M Patel, John Scott, Doron Sommer, Leigh Sowerby, Marc Tewfik, Beatrice Voizard, Martin Wagenmannm, Sarah K Wise, Jonathan Yip, Quirina Thompson, Martin Desrosiers, Yvonne Chan

The Brown Foundation: Institute of Molecular Medicine

Background: Chronic rhinosinusitis (CRS) is a prevalent, heterogeneous inflammatory disease associated with significant morbidity. Systemic corticosteroids (SCS) are commonly prescribed for their anti-inflammatory effects, but cumulative exposure carries risks, including metabolic, cardiovascular, and skeletal complications. Despite widespread use, evidence-based guidance on optimal indications, timing, and duration of SCS in CRS remains inconsistent.

Methodology/principal: An evidence-based review was performed using MEDLINE, EMBASE, and Cochrane databases (2013-2023). Studies were screened and categorized into two primary groups: CRS with (CRSwNP) or without (CRSsNP) nasal polyps. Within CRSwNP, evidence was subcategorized by indication, including (1) polyp size reduction, (2) olfactory dysfunction, (3) comorbid disease, …

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 …

Fuimos Olvidados Y Descuidados [Forgotten And Neglected]: Lessons Learned And Findings From On-Farm Covid-19 Education And Vaccine Clinics For Agricultural Workers And Their Multigenerational Families In Texas, Lus Chavez, Annie J Keeney, Nora Hernandez, Brenda Berumen-Flucker, Eva M Shipp, Matthew W Nonnenmann, Shannon P Guillot-Wright, Bethany Boggess Alcauter, G Lopez Ixta, Paula M Cuccaro, Higinio Fernandez-Sanchez, David Gimeno Ruiz De Porras

Faculty, Staff and Student Publications

Background: Despite being deemed essential non-healthcare workers, agricultural workers were excluded from COVID-19 vaccine prioritization in Texas. This professional practice report describes the multifaceted worker health and safety approaches to protecting agricultural workers and their families during the COVID-19 pandemic.

Methods: Between March 2020 and January 2025, several outreach, education, and training grants from various funding agencies were leveraged to deliver training, personal protective equipment, vaccines, and economic relief to agricultural workers in partnership with community-based organizations, industry, local public health departments, and academic institutions.

Findings: Timely funding efforts led to the distribution of 1,000 PPE kits, with more than …

Clinical Machine Learning Model For Predicting Pathological Complete Response In Patients With Esophageal And Gastroesophageal Junction Adenocarcinoma After Trimodality Therapy, Katsuhiro Yoshimura, Jenny J Li, Rebecca E Waters, Mariela Blum Murphy, Masaaki Iwatsuki, Wayne L Hofstetter, Aileen Chen, Ying Yuan, Jaffer A Ajani

Faculty, Staff and Student Publications

Background: Accurate prediction of pathological complete response (pCR) after preoperative chemoradiation therapy, followed by surgery (trimodality therapy) in esophageal adenocarcinoma (EAC) and gastroesophageal junction adenocarcinoma (GEJAC) may improve clinical decision-making and patient counseling before esophagectomy. This study aimed to develop predictive models for pCR after trimodality using machine learning (ML) approaches.

Patients and methods: A total of 569 patients with EAC and GEJAC who received trimodality therapy at MD Anderson Cancer Center between 2002 and 2022 were included. Clinicopathological characteristics and survival benefit of patients who achieved a pCR were reviewed via descriptive and survival analyses. Subsequently, ML models based …

Safety And Efficacy Of Tranexamic Acid In Urologic Surgery: Results From The International, Randomized, Placebo-Controlled Poise-3 Trial, Flavia K Borges, Farhad Tondroanamag, Tuomas P Kilpeläinen, Sara V Tornberg, Thomas W Painter, David Conen, Vladimir Lomivorotov, Daniel I Sessler, Matthew T V Chan, Maria Jose Martinez-Zapata, Chew Y Wang, Denis B Xavier, Michael K Wang, Wojciech Szczeklik, Kate Leslie, Luke T Lavallee, Rodney H Breau, Kumar Balasubramanian

Faculty, Staff and Student Publications

Background and objective: Perioperative bleeding is common. Evidence for tranexamic acid (TXA) in urology remains limited and conflicting, and major urologic guidelines provide no recommendations. In an a priori planned analysis, we evaluated TXA among patients undergoing urologic surgery in POISE-3.

Methods: POISE-3 was an international randomized trial of patients undergoing surgery with bleeding and cardiovascular risk factors. Participants received TXA (1 g intravenous bolus at surgery start and end) or placebo. The primary efficacy outcome was a 30-day bleeding composite (life-threatening/major/critical organ), and the primary safety outcome was a 30-day thrombosis composite (myocardial injury after noncardiac surgery [MINS], nonhemorrhagic …

Language Serving Hospitals And Their Impact On Readmission For Surgical Patients With A Non-English Primary Language: A Retrospective Cohort Study, Jesus Mejia, Bryan S Torres, Rachel E Murphy, Nayeli Magana, Regan W Bergmark, Andrea L Pusic, Alicia Fernandez, David W Bates, Gregory L Peck, Gezzer Ortega

Faculty, Staff and Students Publications

Objective: To assess postoperative readmission for patients with non-English primary language (NEPL) at language-serving hospitals (LSHs) versus non-LSH.

Background: Patients with NEPL have worse surgical outcomes compared to patients with an English primary language. Hospital-level language access resources vary, potentially leading to disparate health outcomes.

Methods: We performed a retrospective cohort study from 2010 to 2022 using the New Jersey AHRQ-Healthcare Cost and Utilization Project State Inpatient Database. Patients with a primary language variable seen at a hospital that met LSH or non-LSH criteria were identified. Patients with NEPL who underwent appendectomy, breast surgery, cholecystectomy, colectomy, or lower extremity arterial …

Rates Of, Reasons For, And Reactions To Discontinuation Of Glp-1 Receptor Agonists: A Narrative Review, Dennis T Villareal, Terri L Fletcher

Faculty, Staff and Students Publications

GLP-1RAs are increasingly used for their glucose-lowering and weight-management effects, but many patients discontinue them. In this narrative review we aim to review real-world, quantitative and qualitative GLP-1RA discontinuation, adherence, and persistence evidence as it aligns with an established conceptual framework for understanding medication adherence in noncommunicable chronic disease. Many inconsistencies exist in how discontinuation, adherence, and persistence are studied in this literature. Few qualitative studies have focused on discontinuation of GLP-1RAs. Quantitative approaches often focus on medication-related factors and more superficial aspects of socioeconomic and condition-related factors. Very few studies encompass all 5 dimensions of the medication adherence conceptual …

Vitamin B6 Predicts Poor Outcomes In Geographically Distinct Populations With Primary Sclerosing Cholangitis, 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 …

Beyond Language: Generative Artificial Intelligence As A General Computing Model For Medicine

Faculty, Staff and Students Publications

In this Viewpoint, we advocate for direct tokenisation of medical data by breaking them into discrete units, such as laboratory results, medications, and vital signs, similar to word tokenisation in language models. This approach enables transformer-based models to learn from the temporal structure of patient health timelines without relying on textual translation, potentially leading to more accurate and personalised care. Enhanced Transformer for Health Outcome Simulation, an example of a model that uses tokenisation, forecasts health timelines and supports clinical decision making using tokenised medical records. We outline a privacy-preserving model-sharing framework, in which models are trained locally and only …

De Novo Complex Genomic Rearrangement Spanning 2q31.1 In A Proband With Congenital Malformations: Genotype-Phenotype Correlation And Development Of A Cgr Detection Pipeline, Christopher M Grochowski, Ming Yin Lun, Neha Sudhir, Shalini N Jhangiani, Fritz J Sedlazeck, Seema R Lalani, Neil A Hanchard, Claudia M B Carvalho

Faculty, Staff and Students Publications

The 2q31 region is commonly associated with pathogenic alleles of the HOXD cluster leading to various clinical phenotypes related to skeletal development. We present a proband with tetralogy of Fallot and multiple congenital anomalies. Genomic variant screening including an in-house CGR detection pipeline pairing genome sequencing (GS) structural variant calls with read-depth data revealed a de novo complex genomic rearrangement (CGR) spanning 2.7 Mb across 2q31 characterized by a series of duplications and triplications including the HOXD gene cluster. The genomic structure was assembled by applying combined methodologies including short-read and long-read GS, and optical genome mapping (OGM). This in-house …

Multi-Level Disparities In Survival Among Patients Diagnosed With Oral Cavity Cancer In Texas Between 1995 And 2020, Melissa F Peskin, Cici Bauer, Caitlin C Murphy

Faculty, Staff and Students Publications

Background: Multi-level factors, including demographic and neighborhood social conditions, related to disparities in oral cavity cancer (OCC) are not fully understood. We examined the association between these factors and survival outcomes among patients diagnosed with OCC.

Methods: We identified 14,416 patients diagnosed with OCC from 1995 to 2020 using population-based data from the Texas Cancer Registry. Neighborhood-level social vulnerability was measured using the 2010 US Centers for Disease Control and Prevention's Neighborhood Social Vulnerability Index (CDC-SVI). We examined race and ethnicity, CDC-SVI (as sample-based quintiles), and their joint effects with survival outcomes.

Results: Five-year survival probability was 38.6% (95% CI: …

Indications, Techniques, And Safety Of Cryotherapy And Cryobiopsy Via Flexible Bronchoscopy In Pediatric Patients, Aoife Corcoran, Lauren M C Grant, Antoinette Wannes Daou, Sin Tran, Esra Caylan, Alfin Vicencio, Dan T Benscoter, Cherie A Torres-Silva, Sara M Zak, Gregory Burg, Lisa R Young, Pelton Phinizy, Shailendra Das, Richard Paul Boesch, Erik B Hysinger, Joseph Piccione

Faculty, Staff and Students Publications

Rationale: Cryotherapy and its diagnostic analogue, cryobiopsy, are emerging techniques via bronchoscopy with a wide range of clinical applications. While the use of cryotherapy and cryobiopsy has been established in adult pulmonary medicine, pediatric data describing the indications, procedural specifics, outcomes, and complications are limited.

Objective: To describe the indications, procedural specifics, outcomes, and complications of cryotherapy and cryobiopsy use in pediatric bronchoscopy.

Methods: A multicenter retrospective observational study was conducted at 5 pediatric hospitals in the United States. Patients aged 0 to 21 years who underwent cryotherapy or cryobiopsy via bronchoscopy between January 2017 and January 2025 were included. …

Cost-Effectiveness Of Hes V2.0 And Galad For Hepatocellular Carcinoma Surveillance In Patients With Cirrhosis, Mary Linton B Peters, Ali Hajjar, Anthony E Samir, Leigh Anne Dageforde, Fasiha Kanwal, Jagpreet Chhatwal

Faculty, Staff and Students Publications

Background: Ultrasound-based surveillance for HCC is limited by suboptimal sensitivity and low adherence. Blood-based biomarkers are potential alternatives for routine HCC surveillance. We aimed to define optimal sensitivity, specificity, and cost parameters under which blood-based biomarkers could serve as cost-effective alternatives in patients with cirrhosis.

Methods: We developed a microsimulation model of the natural history of HCC in individuals with compensated cirrhosis. We compared the cost-effectiveness of biannual surveillance using 2 blood-based biomarkers-HES V2.0 and GALAD-versus ultrasound-based surveillance across a range of sensitivity, specificity, test costs, and adherence levels. Outcomes included quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios …

Proteomic Signatures Of 3-Year Progression From Impaired Fasting Glucose To Diabetes: The Atherosclerosis Risk In Communities (Aric) Study, 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, …

Adamts13 And Von Willebrand Factor In Relation To Vascular Cognitive Impairment And Cerebral Small Vessel Disease: The Heart-Brain Connection Study, M Arfan Ikram, 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 …

Long-Term Outcomes In Seronegative Rheumatoid Arthritis, 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 …

Increased Risk Of Sarcomas In Children With Congenital Anomalies: Findings From The Genetic Overlap Between Anomalies And Cancer In Kids (Goback) Registry Linkage Study, Tania A Desrosiers, Michael E Scheurer, Charles Shumate, Wendy N Nembhard, Mahsa M Yazdy, Eirini Nestoridi, Amanda E Janitz, Jean Paul Tanner, Russell S Kirby, Jason L Salemi, Yao Yu, Chad D Huff, Sharon E Plon, Philip J Lupo, Jeremy M Schraw

Faculty, Staff and Students Publications

Background: Pediatric sarcomas are a heterogeneous group of tumors that contribute disproportionately to cancer mortality in children. Although congenital anomalies are among the strongest known risk factors for childhood cancer, the risk of specific sarcoma subtypes among affected individuals has not yet been thoroughly evaluated.

Procedure: We obtained data on maternal and perinatal characteristics, congenital anomalies, and pediatric sarcoma diagnoses for all live births in nine states. We used Cox proportional hazards regression to estimate the hazard ratio (HR) and 95% confidence interval (CI) of sarcoma (overall and by subtype) among children with non-syndromic congenital anomalies. We considered all non-syndromic …

Dupilumab Versus Placebo In Adults And Adolescents With Eosinophilic Gastritis (Degas): A Double-Blind, Placebo-Controlled, Phase 2, Multicentre, Randomised Controlled Trial, Tetsuo Shoda, Regina Yearout, Seema S Aceves, Nicoleta C Arva, John A Besse, Julie M Caldwell, Mirna Chehade, Amaziah Coleman, Margaret H Collins, Sara Anvari, Gary W Falk, Sandeep K Gupta, Girish Hiremath, David A Katzka, Paneez Khoury, John Leung, Calies Menard-Katcher, Paul Menard-Katcher, Kathryn A Peterson, Maria A Pletneva, Amanda K Rudman Spergel, Jonathan M Spergel, Tatyana Vaysman, Joshua B Wechsler, Benjamin L Wright, Guang-Yu Yang, Xue Zhang, Meijian Zhou, Ashish Bansal, Bram P Raphael, Amr Radwan, Jennifer Maloney, Antonio Martin, Yamo Deniz, Glenn T Furuta, Lisa J Martin, Marc E Rothenberg

Faculty, Staff and Students Publications

Background: Eosinophilic gastritis currently has no approved treatments and is postulated to be driven by type 2 inflammation. Dupilumab blocks type 2 cytokines IL-4 and IL-13 and has efficacy in multiple diseases characterised by type 2 inflammation, including eosinophilic oesophagitis. We aimed to assess the efficacy and safety of dupilumab in patients with eosinophilic gastritis.

Methods: DEGAS was a proof-of-concept, phase 2, multicentre, randomised controlled trial consisting of a 12-week, double-blind, placebo-controlled period, followed by a 24-week open-label extension period. Patients aged 12-70 years from 11 hospitals in the USA with histologically active eosinophilic gastritis (≥30 eosinophils per high-power field …

The Crisis Of Adolescent Firearm Reinjury: A 14-Year Retrospective Cohort Analysis, Zoe M Miller, Taylor Kaser, Benjamin P Cooper, Christopher Behr, Lindsay Clukies, Joseph Finney, Marguerite W Spruce, Lindsay M Kranker, Michael A Mancini, Melissa Kroll, Erin G Dawson, Matt Vogel, Rachel M Ancona, Vicki Moran, Melik Coffey, Kateri-Chapman Kramer, Doug J E Schuerer, Elvin Geng, Megan L Ranney, Randi E Foraker

Faculty, Staff and Students Publications

Background: Firearm injuries are the leading cause of death among US adolescents. Adolescents are among the highest risk, and those with nonfatal injuries experience high rates of reinjury. Identifying factors that predict firearm reinjury among adolescents may support tailored prevention strategies. This study sought to identify factors associated with firearm reinjury among adolescents who presented with acute nonfatal firearm injury in the St. Louis, Missouri region.

Methods: We conducted a multicenter observational cohort study of youth aged 15 to 17 years presenting to 2 adult and 2 pediatric trauma centers from 2010 through 2023. We collected data on firearm-injured patient …

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, 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 …

Targeting Oncogenic Flt3 Uncovers A Ferroptosis Vulnerability Through Selenocysteine Recoding In Acute Myeloid Leukaemia, Ken Furudate, Ayumi Kitano, Taotao Tan, Mengdie Feng, Jing Zhou, Tao Wang, Robert J Taylor, Alexandra M Stevens, Md Abul Hassan Samee, Jeffrey A Magee, Koichi Takahashi, Daisuke Nakada

Faculty, Staff and Students Publications

Ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation, has emerged as a potential therapeutic strategy for therapy-resistant cancers. Glutathione peroxidase 4 and the selenoprotein biosynthesis pathway essential for its translation are key regulators of ferroptosis but lack effective therapeutic targeting. In a drug screening using a selenoprotein translation reporter, here we identify FMS-like tyrosine kinase 3 (FLT3) inhibitors as suppressors of selenoprotein translation that induce ferroptosis in FLT3-mutant acute myeloid leukaemia. Mechanistically, FLT3 inhibition disrupts selenocysteine recoding, in which a UGA stop codon is recoded as selenocysteine via the SECIS element and associated binding proteins. Notably, the …

Deep Learning-Based Comparison Of Knee Minimum Joint Space Width In Patients With Rheumatoid Arthritis And Osteoarthritis Before Total Knee Arthroplasty, Kellen L Mulford, Cassondra A Hulshizer, Elizabeth J Atkinson, Cody C Wyles, John M Davis, Gavin A Mckenzie, Cynthia S Crowson

Faculty, Staff and Students Publications

Objective: Although both osteoarthritis (OA) and rheumatoid arthritis (RA) can necessitate total knee arthroplasty (TKA), their mechanisms and radiographic patterns of joint space narrowing (JSN) differ. Deep learning (DL) enables compartment-specific measurement of minimum joint space width (mJSW). This study compared JSN patterns between patients with RA and OA undergoing TKA and evaluated the associations between mJSW and RA disease activity.

Methods: In this retrospective study, 409 patients with RA undergoing TKA (2000-2021) were age- and sex-matched with OA patients. A validated DL model quantified medial and lateral mJSW from anteroposterior knee radiographs at 2 timepoints: early (> 2 years …

Obsessive-Compulsive Training Experiences In United States (Us) Medical School Education Programs, Megan C Alam, Juliana E Avery, Hannah C Moore, Gian Depamphilis, Megan M Dailey, Caitlin M Pinciotti, Andrew D Wiese, Wayne K Goodman, Eric A Storch

Faculty, Staff and Students Publications

Objective: To evaluate the content and structure of OCD-specific training within United States osteopathic (D.O.) and allopathic (M.D.) medical schools. Although many physicians encounter patients with obsessive-compulsive disorder (OCD) in clinical practice, limited familiarity with the full range of OCD presentations, including typical and atypical forms, may contribute to misdiagnosis and delays in accurate diagnosis and treatment.

Methods: Respondents from 35 of the 154 (22.73%) medical schools within the United States (28 (80%) allopathic, 7 (20%) osteopathic schools) completed a survey assessing demographics, school information, and OCD-focused training within medical school curriculums. Descriptives were gathered to characterize the level of …

Epidemiology, Predictors Of Antimicrobial Resistance And Empiric Treatment Strategies For Spontaneous Bacterial Peritonitis In Cirrhosis: A Multicentre Sbp-India Study, Pratibha Garg, Rohit Kumar Nadda, Shilpa Prasad, Anand Sharma, Rohit Gupta, Balram Ji Omar, Naga Srikanth Darla, Roshan Agarwala, Mrinal Deb Barma, Mandira Sarma, Ameet Mandot, Wasim Khot, Shalimar, Akash Shukla, Arun Vaidya, Mithra Prasad, Dibyalochan Praharaj, Anil C Anand, Radha Krishan Dhiman, Surender Singh, Narendra Singh Choudhary, Anand Kulkarni, Sandeep Satsangi, Sahaj Rathi, Arka De, Madhumita Premkumar, Sunil Taneja, Virendra Singh, Archana Angrup, Neelam Taneja, Nusrat Shafiq, Ajay Duseja

Faculty, Staff and Students Publications

Background and aims: The rising burden of multidrug-resistant (MDRO) and carbapenem-resistant organisms (CRO) among patients with cirrhosis and spontaneous bacterial peritonitis (SBP) is compromising the effectiveness of standard empiric therapy. This multicentre study evaluated resistance patterns, independent predictors of MDRO and CRO infection, and clinical outcomes to inform risk-based empiric therapy and antimicrobial stewardship in ascitic infections.

Methods: We analysed clinical characteristics and outcomes of hospitalized patients with cirrhosis and culture-positive ascitic fluid infections from 13 centres across India. SBP was defined as ascitic neutrophil count (ANC) ≥ 250/mm3; culture-positive cases with ANC < 250/mm3 were classified as non-neutrocytic bacterascites (NNBA). Predictors of MDRO, CRO and mortality were assessed through regression models.

Results: Among 319 patients (median age 49 …

Clingen Variant Curation Interface Workshops: Training Variant Scientists On An International Platform, Marina Distefano, Sahia M Bryant, Nadia Carstens, Rolanda S Julius, Aimé Lumaka, Madhuri Hegde, Joanne Ngeow, Joannella Morales, Matt W Wright, Heidi L Rehm, Sharon E Plon

Faculty, Staff and Students Publications

Purpose: The Clinical Genome Resource (ClinGen) is creating a central resource of clinically relevant genetic knowledge to improve genomic medicine. Dissemination and use of the ClinGen Resource is essential to ensure broad community uptake. We report on experiences and sustained use of ClinGen tools through engaging international genetics groups based in India, Africa, and Singapore in variant classification training workshops using the ClinGen Variant Curation Interface (VCI).

Methods: We developed pre- and postworkshop questionnaires and analyzed ClinGen tool use following the workshops. We evaluated organizational aspects and costs of creating a dedicated ClinGen VCI instance for each workshop.

Results: The …

Impact Of Prematurity On Nutrient Signaling And Protein Synthesis In Skeletal Muscle, Teresa A Davis

Faculty, Staff and Students Publications

Preterm birth disrupts nutrient-responsive signaling pathways critical for skeletal muscle growth and long-term metabolic health. Despite improvements in neonatal care, preterm infants often experience postnatal growth failure marked by impaired lean mass accretion. This review examines how prematurity intrinsically alters insulin and amino acid signaling to mechanistic target of rapamycin complex 1 (mTORC1), a central regulator of translation initiation and protein synthesis. Evidence from translational models reveals blunted activation of mTORC1 and its downstream effectors, independent of birth weight or comorbidities. Defects in insulin-PDK1/mTORC2-Akt signaling and amino acid sensing, particularly leucine sensing, contribute to impaired mTORC1-dependent translation initiation and reduced …

Quantitative Assessment Of Aortic Arch Conformability And Clinical Outcomes Following Thoracic Endovascular Aortic Repair, Celia Riga, Richard Gibbs, Colin Bicknell, Michael Jenkins, Mohamad Hamady

Faculty, Staff and Students Publications

Purpose: Thoracic stent graft conformability is believed to provide mechanical advantages during thoracic endovascular aortic repair (TEVAR); however, quantitative evidence and associated clinical outcomes remain limited. This study aimed to assess stent graft conformability across varying aortic arch configurations and pathologies, and to evaluate short- and mid-term technical and clinical outcomes.

Materials and methods: A retrospective, single-centre review was conducted of TEVAR procedures performed using the GORE cTAG stent graft over a seven-year period. Pre- and post-deployment anatomical measurements were obtained using Endosize® software to assess conformability across a range of aortic arch morphologies and aortic syndromes. Conformability was defined …

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, 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 …

Quantitative Imaging Of Pyruvate Metabolism In A Patient With Anaplastic Thyroid Cancer, Yunyun Chen, Christopher M Walker, Philip L Lorenzi, Lin Tan, Vikas Kundra, Matthew E Merritt, Mukundan Ragavan, Dawid Schellingerhout, Renjie He, Yao Ding, Sahana Datar, Qing Wang, Christine B Peterson, Clifton D Fuller, Vlad C Sandulache, Stephen Y Lai

Faculty, Staff and Students Publications

Purpose: Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate.

Methods: A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. …