Digital Commons Network^™

Steroid Receptor Coactivator 3-Deficient Regulatory T Cells Eradicate Multiple Solid Tumors In Syngeneic Mouse Models, Nuri Sung, Eunsu Kim, Yosef Gilad, Yuri Park, Adam M Dean, Yan Xia, Jianming Xu, Clifford C Dacso, David M Lonard, Sang Jun Han

Faculty, Staff and Students Publications

Steroid receptor coactivator 3 (SRC-3) is highly expressed in regulatory T cells (Tregs) and is important for their immunosuppressive activity. Recently, we demonstrated that disrupting SRC-3 expression in Tregs eliminates triple-negative breast cancer (TNBC) and prostate cancer in syngeneic animal models by generating an anti-tumor immune microenvironment without inducing immune-related adverse events (irAEs). Further analysis of these mice revealed that SRC-3 knockout (KO) Tregs infiltrated breast tumors and facilitated the infiltration of CD8

When Probiotics Guidelines Differ: A Practical Guide For Clinicians And Researchers, Geoffrey A Preidis, Hania Szajewska, Marla Cunningham, Howard Bauchner, Daniel J Merenstein

Faculty, Staff and Students Publications

Many professional organizations publish clinical practice guidelines for the use of probiotics in gastrointestinal disorders. Generally, no two guidelines align perfectly, and some differ markedly. These discrepancies occur because clinical practice guidelines are not purely mechanical outputs of data synthesis. They are shaped by structured interpretation, value judgments, and predefined thresholds for uncertainty. These elements become particularly visible when effect sizes are small, heterogeneity is high, and outcomes vary in clinical relevance-as is the case with probiotic research. This article examines why discordance among probiotic guidelines is predictable and provides practical guidance for clinicians who must decide among conflicting recommendations …

Limosilactobacillus Reuteri Promotes Melatonin Release From Human Intestinal Organoids Via 5′Ectonucleotidase Activity, Micah D Forshee, Erika J Nachman, Esha R Shenoy, Heather A Danhof, Ludwig Ermann Lundberg, Stefan Roos, Robert A Britton

Faculty, Staff and Students Publications

Strains of Limosilactobacillus reuteri have been used to prevent or treat various conditions; however, the mechanisms by which they exert beneficial effects are not completely understood. Infant colic is one example in which L. reuteri DSM 17938 reduces clinical symptoms. While the etiology of colic is unknown, abnormal melatonin levels in infants have been suggested as a possible contributor. L. reuteri DSM 17938 has been shown to produce adenosine from AMP via production of the extracellular enzyme 5′ectonucleotidase (5′NT). Adenosine is a potent signaling molecule that impacts several important aspects of host physiology, including the release of melatonin from the …

Mtorc2-Nav1.2 Signaling Drives Early Hyperexcitability In Alzheimer’S Disease Mouse Model, Nolan M Dvorak, Jeffrey L Noebels

Faculty, Staff and Students Publications

Hyperexcitability is a biomarker of early-stage Alzheimer’s Disease (AD) and hastens cognitive decline later in its course. Mechanistic target of rapamycin (mTOR) signaling contributes to the slope of this trajectory, as evidenced by early increased brain expression and the rescue of hyperexcitability by genetic deletion of mTOR complex 2 (mTORC2); however, a molecular mechanism directly linking mTOR signaling to membrane hyperexcitability in early-stage AD remains elusive. Here, we show that hyperactive mTOR signaling stimulates the voltage-gated Na+ channel 1.2 (Nav1.2), a previously identified downstream phosphorylation target of mTORC2 and a key regulator of membrane electrogenesis. Augmented Nav1.2 channel function induced …

Corrigendum To “Characterizing The Metabolites Of The Tyrosine-Kinase Inhibitor Pexidartinib In Mouse Feces, Urine, Plasma, And Liver” [J. Pharm. Biomed. Anal. 265 (2025) 117034], Xuan Qin, Si Chen, John M Hakenjos, Jian Wang, Lei Guo, Ashish Dogra, Zhaoyong Hu, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

No abstract provided.

Adjunctive Embolization Of Target Vessel Dissections To Improve Suitability For Fenestrated-Branched Endovascular Aortic Repair, Zemia C Ferreira, Hannah V Oden-Brunson, Ying Huang, Steven Maximus, Naveed Saqib, Erin Greenleaf, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Students Publications

Suitability of renal-mesenteric target arteries is an essential criterion for fenestrated-branched endovascular aortic repair (FB-EVAR). We describe a staged adjunctive technique of target vessel false lumen (FL) embolization to improve suitability for FB-EVAR in patients with chronic postdissection thoracoabdominal aortic aneurysms (PD-TAAA) and dissection extension into the superior mesenteric artery (SMA). Three patients with SMA dissection and ectasia (diameter > 12-14 mm) underwent staged FL embolization with pre-emptive stent placement to optimize SMA incorporation. Using bilateral transfemoral access with intravascular ultrasound guidance, the proximal SMA true lumen was stented with an 8 L × 39 mm VBX balloon-expandable stent graft (W. …

Considering Access And Methodological Rigor In Framing Results Of The Bergen 4 Day Treatment Program For Obsessive-Compulsive Disorder, Eric A Storch, Benjamin J Chang

Faculty, Staff and Students Publications

No abstract provided.

Social Responsiveness As A Mediator In Adapted Cognitive Behavioral Therapy For Autistic Youth With Maladaptive And Interfering Anxiety, Jeffrey J Wood, Eric A Storch, Katherine Sung, Karen S Wood, Philip C Kendall

Faculty, Staff and Students Publications

Numerous adaptations to interventions have been included in cognitive behavioral therapy (CBT) for autistic youth. This study examines the degree to which CBT adapted to the social needs of autistic youth confers significant benefit by promoting social responsiveness. A secondary analysis was conducted on a multisite randomized clinical trial (Wood et al. in JAMA Psychiatry 77:474-483, 2020) comparing adapted CBT with standard-of-practice CBT and treatment-as-usual (TA). Autistic youth (N = 167; aged 7-13) with maladaptive and interfering anxiety participated. The adapted CBT (BIACA) uses a modular format, with an emphasis on supplementing common CBT practice elements (reframing and graded exposure) …

Newborn Screening Reduces Survival Disparities In Scid After Stem Cell Transplant: A Pidtc Report, Lena E Winestone, Brent R Logan, Xuerong Liu, Olatundun Williams, Elizabeth A Dunn, Monica S Thakar, Sharon A Kidd, Talal Mousallem, Morna J Dorsey, Richard J O'Reilly, Neena Kapoor, Lisa Forbes Satter, Malika Kapadia, Soma C Jyonouchi, Sharat Chandra, Christen L Ebens, Deepakbabu Chellapandian, Sonali Chaudhury, Karin Chen, Blachy J Dávila Saldaña, Ahmad Rayes, Troy C Quigg, Shanmuganathan Chandrakasan, Jeffrey J Bednarski, Kenneth B Desantes, Pierre Teira, Alfred P Gillio, Hesham Eissa, Alan P Knutsen, Victor M Aquino, Evan B Shereck, Theodore B Moore, Emi H Caywood, Mark T Vander Lugt, Jacob Rozmus, Larisa Broglie, Lolie C Yu, Ami J Shah, Avni Y Joshi, Rebecca H Buckley, Jasmeen Dara, Joseph H Oved, Hisham Abdel Azim, Caridad A Martinez, Susan Prockop, Kathleen E Sullivan, Jack J Bleesing, Michael D Keller, Lisa M Madden, Suhag Parikh, Shalini Shenoy, Christine M Seroogy, Tamar Rubin, Jennifer Licata, Jeffrey R Andolina, Donald B Kohn, Lauri Burroughs, Jennifer W Leiding, Rebecca A Marsh, Luigi D Notarangelo, Sung-Yun Pai, Troy R Torgerson, Michael A Pulsipher, Jennifer Heimall, Geoffrey D E Cuvelier, Linda M Griffith, Jennifer M Puck, Christopher C Dvorak, Morton J Cowan, Elie Haddad

Faculty, Staff and Students Publications

Black race and Hispanic ethnicity are associated with higher mortality in severe combined immunodeficiency (SCID) following hematopoietic cell transplantation (HCT), though mechanisms remain unclear. We evaluated 796 children with SCID who received nonsibling HCT between 1982 and 2020 using data from the Primary Immune Deficiency Treatment Consortium. Overall survival for Black (aHR 2.47, 95%CI 1.64, 3.71) and Asian/Pacific Islander patients (aHR 1.82, 95%CI 1.00, 3.30) was significantly lower compared with non-Hispanic White patients, while Hispanic patients had lower event-free survival (aHR 1.83, 95%CI 1.27, 2.63) compared with non-Hispanic White patients. Even after adjusting for age and infection, Black patients with …

Cerebellar Atrophy In Pediatric-Onset Opsoclonus-Myoclonus-Ataxia Syndrome: A Large International Cohort Study, Rebecca Macrae, Kierstin Hederstedt, Christopher Cortina, Kumaran Deiva, Andrea Klein, Ming Lim, Thomas Rossor, Elizabeth A Sokol, Yasmin Khakoo, Nikita Malani Shukla, Timothy E Lotze, Wendy G Mitchell, Sarah Hopkins, Bo Zhang, Mark P Gorman

Faculty, Staff and Students Publications

Background and objectives: Pediatric-onset opsoclonus-myoclonus-ataxia syndrome (POOMAS) is a rare, neuroinflammatory syndrome that targets the cerebellum and can cause irreversible cerebellar structural changes, namely cerebellar atrophy. We investigated the frequency of cerebellar atrophy, as well as associated risk factors and functional outcome measures, using the largest active POOMAS registry.

Methods: This was a retrospective observational study of participants with POOMAS with disease onset from 1995 to 2025 using data from the multinational, multicenter POOMAS registry. Variables were compared between the cerebellar atrophy subgroups using the Fisher exact test or Wilcoxon rank-sum test.

Results: Of participants with follow-up imaging, cerebellar atrophy …

Bivip: A Competitive Neural Network For Bilateral Visuo-Haptic Processing, Eleonore Federica Di Rosa, Aaisha Sheth, Jeffrey Min-In Yau, Laura Astolfi, Cristiano Cuppini

Faculty, Staff and Students Publications

Visuo-haptic interactions are gaining interest in perception research because of their relevance to robotics and rehabilitation. While the benefits of integrating concurrent visuo-tactile cues are well-documented, the temporal dynamics of competitive interactions between vision and touch remain less understood. Building on extant empirical evidence of unilateral intersensory switching, we ask whether bilateral detection of visual and tactile stimuli can be explained by cross-sensory competition and explore the underlying sensorineural dynamics via a multi-level neural network model. Tested against results from a speeded reaction time task to unilateral and bilateral visual, tactile, and visuo-tactile targets, the network successfully predicts higher switch …

Cigarette Smoke Induces Fasn-Dependent Fatty Acid Metabolic Rewiring To Drive Bladder Cancer Progression, Chandra Sekhar Amara, Danthasinghe Waduge Badrajee Piyarathna, Abu Hena Mostafa Kamal, Yuen San Chan, Karthik Reddy Kami Reddy, Chandra Shekar R Ambati, Mohammed Khurshidul Hassan, Pratik Shriwas, Tanmay Gandhi, Antrix Jain, Tanja Gangnus, Pooja Popli, Roshan Borkar, Sung Wook Kang, Silvia L Summers, Vasanta Putluri, Sandra L Grimm, Sharan Venkatesh, Ningxin Song, Erin H Seeley, Jenna Hedlich-Dwyer, Shu-Hsia Chen, Nupam P Mahajan, Abhinav K Jain, Lacey Elizabeth Dobrolecki, Gabrielle A Wells, Hugo Villanueva, Jenny Li, Xuefeng Liu, Roni J Bollag, Anna Malovannaya, Sung Yun Jung, Hyun-Sung Lee, Irfan A Asangani, Martha K Terris, Chad J Creighton, Leomar Y Ballester, Balasubramanyam Karanam, Suyu Liu, Minjae Lee, Rajeeva R Raju, M Minhaj Siddiqui, Livia S Eberlin, Ramakrishna Kommagani, Arun Sreekumar, Jianjun Gao, Nicolas L Young, H Courtney Hodges, Cristian Coarfa, Natalie R Gassman, Seth P Lerner, Yair Lotan, Nagireddy Putluri

Faculty, Staff and Students Publications

Cigarette smoke promotes bladder tumor growth by enhancing cancer cell survival and proliferation through smoke mediated carcinogens. FASN, a key enzyme in fatty acid synthesis, is dysregulated in many cancers and correlates with aggressive phenotypes. In this study, we demonstrate elevated fatty acid levels and FASN specifically in smokers with bladder cancer. Elevated FASN under smoke exposure imparted epigenetic alterations, particularly histone acetylation, impacts DNA repair and DNA-binding transcription factors which regulate metabolic pathways. Under cigarette smoke, bladder cancer cells undergo a metabolic shift, utilizing glutamine as a major carbon source through reductive carboxylation to fuel fatty acid biosynthesis via …

Quantitative Imaging Of Pyruvate Metabolism In A Patient With Anaplastic Thyroid Cancer, James A Bankson, Joshua S Niedzielski, Collin J Harlan, 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. …

Multi-Level Disparities In Survival Among Patients Diagnosed With Oral Cavity Cancer In Texas Between 1995 And 2020, Guillermo A Tortolero, Erich M Sturgis, Jose-Miguel Yamal, 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: …

Nutrition Considerations In Youth With Type 2 Diabetes Using Glucagon-Like Peptide-1 Receptor Agonists: A Commentary, Maria E Diaz, Grace Kim, Mili Vakharia

Faculty, Staff and Students Publications

No abstract provided.

Cost-Effectiveness Of Hes V2.0 And Galad For Hepatocellular Carcinoma Surveillance In Patients With Cirrhosis, Mert Sahinkoc, Gizem S Nemutlu, Hashem B El-Serag, 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 …

Dupilumab Versus Placebo In Adults And Adolescents With Eosinophilic Gastritis (Degas): A Double-Blind, Placebo-Controlled, Phase 2, Multicentre, Randomised Controlled Trial, Nirmala P Gonsalves, Evan S Dellon, Kara L Kliewer, 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 …

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 …

Future Prospects Of Pediatric Lung Transplantation, Ernestina Melicoff, David Moreno Mcneill, Christian Benden

Faculty, Staff and Students Publications

This special issue of the Journal of Heart Transplantation Open is dedicated to Pediatric Thoracic Transplantation. The authors will discuss subjects related to pediatric lung transplantation such as access to donor organs, allograft dysfunction and role of functional status in outcomes.

Indications, Techniques, And Safety Of Cryotherapy And Cryobiopsy Via Flexible Bronchoscopy In Pediatric Patients, Alex J Katz, Haley Haskett, Kubra M Bozkanat, 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. …

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, …

Rates Of, Reasons For, And Reactions To Discontinuation Of Glp-1 Receptor Agonists: A Narrative Review, Henry D Heisey, L Parker Gregg, Christopher D Verrico, 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 …

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 …

De Novo Complex Genomic Rearrangement Spanning 2q31.1 In A Proband With Congenital Malformations: Genotype-Phenotype Correlation And Development Of A Cgr Detection Pipeline, Katherine Helle, Jesse D Bengtsson, Mira Gandhi, 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 …

Obsessive-Compulsive Training Experiences In United States (Us) Medical School Education Programs, Carlos Valenzuela-Flores, Leanne Maduka, Dale Shepherd, 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 …

The Kdm-Family Inhibitor Jib-04 Sensitizes Aml Cells To Venetoclax By Inducing A Ferroptosis-Like Phenotype, Katharina Wohlan, Dandan Fan, Anna G Guzman, Alexis Quezada, Hyunji Park, Elmira Khabusheva, Farzane Sivandzade, Matthew Wither, Amber Alcorn, Tamara Thevarajah, Steven M Kornblau, Courtney D Dinardo, Jianzhong Su, Margaret A Goodell, Rachel E Rau

Faculty, Staff and Students Publications

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with various molecular and cytogenetic subtypes. Treatment options for older adult patients are limited due to high toxicity of conventional chemotherapy. The B-cell leukemia/lymphoma 2 inhibitor venetoclax is effective in combination with hypomethylating agents or low-dose cytarabine, but ∼30% of patients do not respond to the initial combination treatment. Thus, alternative combinations are needed to sensitize AML cells to venetoclax and overcome resistance mechanisms. Here, we report that targeting histone lysine-specific demethylases induces a ferroptosis-like phenotype driven by oxidative stress in various AML subtypes. In both patient samples and cell lines, …

"It Doesn't Matter Where Ocd Comes From," Or Does It?, Caitlin M Pinciotti, Ryan J Mccarty, Gabriella T Ponzini

Faculty, Staff and Students Publications

Purpose of review: This review critically evaluates the claim that etiology is not relevant to cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD). Research on the clinical presentation and treatment outcomes associated with traumatic/stressor and biological etiologies is presented.

Recent findings: The extant literature demonstrates varying clinical utility across the reviewed etiologies. Traumatic/stressor etiologies show the most consistent and robust evidence of clinical utility, demonstrating compelling associations with clinical presentation and treatment outcomes, while also being amenable to existing evidence-based approaches. Medical conditions (e.g., Pediatric Acute onset Neuropsychiatric Syndrome) and neurobiological factors also demonstrate considerable associations with OCD presentation, yet …

Tic-Related Functional Impairment Drives The Relationship Between Tics And Depression In Youth With Tourette Syndrome, Benjamin J Mitchell, Emily I Braley, Erika S Trent, Steve Barash, Mark F Gordon, Jordan Stiede, Eric A Storch

Faculty, Staff and Students Publications

Although many youth with Tourette syndrome (TS) have at least 1 comorbid psychiatric condition (eg, obsessive-compulsive disorder), the extent to which TS is associated with depression remains unclear. This cross-sectional study examined relationships among tic severity, tic-related functional impairment, and depressive symptoms in 277 youth with TS. Tic-related impairment, but not tic severity, was associated with both self- and parent-reported depressive symptoms. An age × sex interaction emerged, such that among younger participants, females reported higher depressive symptoms than males; however, this effect was observed only for self-report, not parent report. Additionally, both depressive symptoms and tic severity were associated …

Obsessive-Compulsive Disorder In Three Understudied Populations: A Review Of Latino, Black, And Sexual & Gender Minority Individuals, Ryan J Mccarty, Ogechi C Onyeka, Caitlin M Pinciotti, Andrew D Wiese, Eric A Storch

Faculty, Staff and Students Publications

Purpose of review: This review overviews the research base for obsessive-compulsive disorder (OCD) among three historically understudied populations; Latino/Latin Americans, Black/African Americans, and Sexual and Gender Minority individuals.

Recent findings: Findings suggest that while core OCD symptoms are broadly similar across groups, sociocultural factors such as discrimination, minority stress, stigma, family context, spirituality, and access to care significantly influence symptom presentation, severity, and treatment utilization. Recent studies have evaluated assessment tools and provided evidence supporting exposure and response prevention, while emphasizing the importance of culturally responsive assessment and treatment. Large-scale initiatives are also improving representation in OCD research and addressing …

Segmented Profile Analysis (Sepa): Plane-Wise Decomposition Of Within-Person Variation Via Ipsatized Singular Value Decomposition, Se-Kang Kim, Joe Grochowalski

Faculty, Staff and Students Publications

Traditional profile analyses summarize multivariate person data with overall mean levels and relative patterns, but existing methods often blur these sources of variation or reduce each individual to a single best-fitting profile. Segmented Profile Analysis (SEPA) offers a unified, ipsatized singular-value decomposition (SVD) framework that decomposes individual profiles into orthogonal level (LE) and pattern (PE) effects and, crucially, introduces plane-wise segment profiles (summaries of each person's response pattern within each variable-contrast dimension) as primary person-oriented objects. Within each low-dimensional plane, SEPA defines a projected response pattern (segment profile), domain-person cosines that index variable-by-variable alignment, and plane-fit correlations that summarize how …