Digital Commons Network^™

Health-Related Quality Of Life After Neonatal Treatment Of Symptomatic Tetralogy Of Fallot: Insights From The Congenital Cardiac Research Collaborative, George T Nicholson, Jeffrey D Zampi, Andrew C Glatz, Bryan H Goldstein, Christopher J Petit, Yun Zhang, Courtney E Mccracken, Athar M Qureshi, Caren S Goldberg, Jennifer C Romano, Mark A Law, Jeffery J Meadows, Shabana Shahanavaz, Sarosh P Batlivala, Shiraz A Maskatia, Asaad Beshish, Michael L O'Byrne, R Allen Ligon, Kathryn O Stack, Hala Q Khan, Shalin Parekh, Dawn L Ilardi

Faculty, Staff and Students Publications

To evaluate the association between initial management strategy of neonatal symptomatic Tetralogy of Fallot (sTOF) and later health-related quality of life (HRQOL) outcomes. We performed a multicenter, cross-sectional evaluation of a previously assembled cohort of infants with sTOF who underwent initial intervention at ≤ 30 days of age, between 2005 and 2017. Eligible patients’ parents/guardians completed an age-appropriate Pediatric Quality of Life Inventory, a Pediatric Quality of Life Inventory Cardiac Module Heart Disease Symptoms Scale, and a parental survey. The association between treatment strategy and HRQOL was evaluated, and the entire sTOF cohort was compared to published values for the …

Resilience And Childhood Trauma In Mood Disorders: Psychopathological Implications And Treatment Response, Giovanni Camardese, Antonio Maria D'Onofrio, Francesca Bardi, Alessio Simonetti, Alexia Koukopoulos, Delfina Janiri, Lorenzo Moccia, Marianna Mazza, Mauro Pettorruso, Giovanni Martinotti, Gabriele Sani

Faculty, Staff and Students Publications

Background and aim: Childhood trauma is a key risk factor for mood disorders and is associated with greater clinical severity, while resilience may act as a protective factor. This study investigates how childhood trauma and resilience interact to shape psychopathology and treatment response in patients with major depressive disorder (MDD) and bipolar disorder (BD).

Methods: The study included 669 participants: 569 patients (380 MDD, 189 BD) and 100 healthy controls (HC). Symptom severity was assessed using standardized scales, with follow-up evaluations of depressive symptoms at six months. All participants completed the Childhood Trauma Questionnaire (CTQ) and Connor-Davidson Resilience Scale (CD-RISC). …

Cerebellar Purkinje Cell Stripe Patterns Reveal A Differential Vulnerability And Resistance To Cell Loss During Normal Aging In Mice, Sarah G Donofrio, Cheryl Brandenburg, Amanda M Brown, Tao Lin, Hsiang-Chih Lu, Roy V Sillitoe

Faculty, Staff and Students Publications

Age-related neurodegenerative diseases involve reduced cell numbers and impaired behavioral capacity. Neurodegeneration and behavioral deficits also occur during aging, and notably in the absence of disease. The cerebellum, which modulates movement and cognition, is susceptible to cell loss in both aging and disease. Here, we demonstrate that cerebellar Purkinje cell loss in aged mice is not spatially random but rather occurs in a pattern of parasagittal stripes. We also find that aged mice exhibit impaired motor coordination and more severe tremor compared to younger mice. However, the relationship between patterned Purkinje cell loss and motor dysfunction is not straightforward. Examination …

Fibroblasts Are The Primary Contributors To A Disrupted Micro-Environment In End-Stage Pediatric Hypertrophic Cardiomyopathy, Hanna J Tadros, Diwakar Turaga, Yi Zhao, Chang-Ru Tsai, Iki A Adachi, Xiao Li, James F Martin

Faculty, Staff and Students Publications

Background: Hypertrophic cardiomyopathy (HCM) is a relatively rare but debilitating diagnosis in the pediatric population, and patients with end-stage HCM require heart transplantation. Here, we have examined the transcriptome in ventricular tissue from this patient group to identify cell states and underlying cellular processes unique to pediatric HCM.

Methods: We performed single-nucleus RNA sequencing (snRNA-seq) on explanted hearts at transplant in 3 pediatric patients with end-stage HCM and compared findings to pediatric control and adult HCM.

Results: We identified distinct underlying cellular processes in cardiomyocytes, fibroblasts, endothelial cells, and myeloid cells compared with controls. Pediatric HCM was enriched in cardiomyocytes …

Insights From A Survey Of School Nurses: Assessing The Challenges Of Constipation In Schools, Andrew S Chu, Eric H Chiou

Faculty, Staff and Students Publications

Objectives: School nurses are key responders to students with constipation, yet their experiences are underreported. This study surveyed their observations regarding constipation, identified barriers to student restroom access, and assessed educational needs.

Methods: In this descriptive, cross-sectional survey study, an anonymous online survey was distributed to school nurses participating in a virtual education series. The survey assessed nurse demographics, frequency of encounters with constipation and encopresis, school restroom policies, barriers to restroom use, accommodation requests, and training in constipation management.

Findings: Of 125 respondents, 95% encountered students with constipation at least monthly and 55% reported ≥ 6 encounters monthly. Commonly …

Rationale And Design Of The Rembrandt Trial: A Phase 3 Study To Evaluate The Effect Of Obicetrapib/Ezetimibe On Coronary Plaque Characteristics, Cian P Mccarthy, Christie M Ballantyne, Ron Blankstein, Matthew J Budoff, Marc Ditmarsch, C Michael Gibson, John J P Kastelein, Ann Marie Navar, Stephen J Nicholls, Kausik K Ray, Cheerag Shirodaria, Michelle C Williams, James L Januzzi

Faculty, Staff and Students Publications

Background: Obicetrapib is a potent, selective cholesteryl ester transfer protein (CETP) inhibitor that significantly lowers low-density lipoprotein cholesterol (LDL-C). Additive reductions in LDL-C occur when obicetrapib is combined with ezetimibe. The impact of obicetrapib and ezetimibe fixed-dose combination (FDC) on coronary plaque burden is unknown. Favorable changes in noncalcified coronary atherosclerotic plaque volume (NCPV) may indicate a potential beneficial effect on atherosclerotic cardiovascular disease (ASCVD) events.

Methods: REMBRANDT is a placebo-controlled, double-blind, randomized trial designed to assess the efficacy of obicetrapib and ezetimibe FDC on coronary plaque burden. Individuals aged 45 years or older with ASCVD (imaging evidence of vascular …

Where, How, And How Much? A Multicenter Cohort Study Of The Relationship Across Lupus Decision-Aid Modality, Place Of Administration, Interruption And Viewing Completeness, And Patient-Reported Outcomes, Jasvinder A Singh, Mark Beasley, Larry R Hearld

Faculty, Staff and Students Publications

Objective: We assessed whether shared decision-making (SDM) and patient acceptability, feasibility, and overall satisfaction with a computerized patient decision aid (PtDA) for patients with systemic lupus erythematosus (SLE) differs by PtDA setting, modality, and the viewing experience.

Methods: Patients with SLE were invited to view a self-administered computerized SLE PtDA during regular clinic visits at 15 rheumatology clinics in an implementation trial. Patients completed a survey that included SDM measures including the decision conflict scale (DCS), Preparation for Decision Making (PDM) scale, and CollaboRATE scale, and we measured perceived patient acceptability, feasibility, and satisfaction. Patients viewed the SLE PtDA in …

Net Clinical Benefit Of Patiromer For Acute Hyperkalemia: A Post-Hoc Analysis Of The Reduce Trial, Robert Mcarthur, W Frank Peacock, Jeff Budden, Zubaid Rafique

Faculty, Staff and Students Publications

Introduction: Hyperkalemia (HK) is a common and potentially life-threatening electrolyte disturbance managed with potassium (K)-shifting medications and potassium binders. The use of K-shifting agents is a confounder when assessing the effects of K-binding treatments in clinical trials. Patiromer is a K-binding agent with demonstrated efficacy for the management of chronic hyperkalemia. As both changes in sK level and the number of interventions required to lower potassium are clinically relevant, we propose an evaluation using Net Clinical Benefit (NCB), defined as the number of K shifting interventions less the numerical change in K.

Methods: We conducted a post-hoc analysis of the …

Derivation Of Pluripotent Stem Cell Lines (Rfsci005-A, Rfsci006-A) From Siblings Harboring Identical High-Risk Complement Variants With Discordant Age-Related Macular Degeneration, Naresh Rajendran, Ajeet Singh, Wendy Runyon, Sam Hu, Ritu Kumar, Rinki Ratnapriya, Karl Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Age-related macular degeneration (AMD) is a complex disease influenced by genetic and environmental factors. Variants in the complement pathway, especially in the CFH gene, increase AMD risk, yet disease severity can differ among individuals with identical high-risk genotypes. We generated induced pluripotent stem cell (iPSC) lines from siblings carrying identical high-risk complement variants but displaying discordant AMD phenotypes. These lines provide a unique platform to study epigenetic, transcriptomic, and environmental factors driving AMD heterogeneity. By comparing differentiated retinal cells, we aim to reveal mechanisms behind variable disease susceptibility and inform personalized therapies for AMD.

Clinical Exome Sequencing Efficacy And Phenotypic Expansions Involving Non-Isolated Congenital Anomalies Of Kidney And Urinary Tract (Cakut+), E Andres Rivera-Munoz, Xiaonan E Zhao, Jill A Rosenfeld, Pamela N Luna, Chad A Shaw, Jennifer E Posey, Daryl A Scott

Faculty, Staff and Students Publications

Congenital Anomalies of Kidney and Urinary Tract (CAKUT) can occur in isolation or in conjunction with one or more non-CAKUT associated congenital anomalies or neurodevelopmental disorders (CAKUT+). A molecular cause is not identified in most individuals with CAKUT+. This is due, in part, to uncertainty regarding the efficacy of genetic testing and an incomplete understanding of the genes that cause CAKUT+. Here, we use data from 515 individuals with CAKUT+ (n = 500) or isolated CAKUT (n = 15) to determine the efficacy of clinical exome sequencing (cES) and to identify new phenotype expansions that involve CAKUT. We determined that …

Gene Therapy Cm-Yapon Protects The Mouse Heart From Myocardial Infarction, Fansen Meng, Jeffrey D Steimle, Elizabeth Straight, Rich G Li, Yuka Morikawa, Zohaib Iqbal, Bing Xie, Jun Wang, Wyatt G Paltzer, Yi Zhao, Chang-Ru Tsai, Lin Liu, Maggie Lim, Rita A Schack, Daniel Ramirez, Katherine Carlson, Vaibhav Deshmukh, Jason M Karch, Robia G Pautler, Xiao Li, James F Martin

Faculty, Staff and Students Publications

Myocardial infarction (MI) affects millions of people worldwide, causing irreversible injury to the heart and impairing cardiac function1. In both mouse and pig MI models, activating YAP in cardiomyocytes (CMs) stimulates regenerative repair2,3. Here we developed an adeno-associated virus 9 (AAV9)-based therapy, termed CM-YAPon, which enables transient expression of an active YAP variant (YAP5SA) in CMs following exposure to the small molecule LMI070. A single LMI070 dose in mice triggers YAP5SA expression, CM cell cycle re-entry, and reprogramming of the cardiac microenvironment. YAP5SA induction after MI rapidly improves cardiac function while pre-MI induction confers …

How Well Can Commonly Used Anxiety Scales Detect Treatment Outcomes In The Context Of Autism?, Huilin Chen, Jeffrey J Wood, Connor M Kerns, Eric A Storch, Philip C Kendall, Gaia Scerif, Cathy Creswell

Faculty, Staff and Students Publications

Anxiety is one of the most prevalent mental health challenges in autistic children, yet there is limited evidence on effective tools to measure treatment outcomes. Previous research with non-autistic children has found that the Child Anxiety Impact Scale, Parent Version achieved good diagnostic accuracy when measuring treatment outcomes and performed better than a commonly used symptom measure. However, this has not been evaluated for autistic children. The present study examined the psychometric properties of the Child Anxiety Impact Scale, Parent Version in autistic children and compared its utility against other anxiety symptom measures, to detect treatment outcomes as assessed by …

Implications Of Cooccurring Adhd For The Cognitive Behavioural Treatment Of Anxiety In Autistic Children, Elise Ng-Cordell, Eric A Storch, Philip C Kendall, Jeffrey J Wood, Amori Yee Mikami, Connor M Kerns

Faculty, Staff and Students Publications

Background: Childhood mental health conditions commonly cooccur, with potential treatment implications. Autistic children frequently experience anxiety and attention deficit/hyperactivity disorder (ADHD). We investigated the implications of this cooccurrence for Cognitive Behavioural Therapy (CBT), a front-line treatment for anxiety in autistic children. We tested whether (1) ADHD predicts anxiety treatment response, (2) ADHD improves in response to anxiety treatment and (3) ADHD improvement is related to reductions in anxiety.

Method: Autistic children with elevated anxiety (N = 167) enrolled in a multisite, randomised controlled trial comparing standard CBT, autism-adapted CBT and treatment as usual. ADHD symptoms and severity were assessed via …

Abca4-Mutant Human Retinal Organoids Sequencing Reveals Organoids Application In Inherited Retinal Diseases, Yourong Bao, Sujung Soh, Jean Li, Zhen Zuo, Salma Ferdous, Xinye Qian, Jin Li, Jiaxiong Lu, Xuesen Cheng, Anna Matynia, Yumei Li, Rui Chen

Faculty, Staff and Students Publications

In the studies of Inherited Retinal Diseases (IRDs), the knockout of traditional animal models like mice often fails to accurately replicate human phenotypes due to genetic and anatomical differences. Human retinal organoids (ROs) derived from stem cells have emerged as promising developmental models in retinal studies to delineate cell growth, but their ability to represent the characteristics of late-onset IRDs remains unclear. This study aims to validate ROs as a disease model for Stargardt's Disease (STGD) caused by ABCA4 mutations. Using single-cell RNA sequencing, ROs from 2 STGD patients were compared with healthy control-derived ROs at two developmental stages on …

Vaccine Hesitancy At Nine Community Sites Across The United States, Early In Covid-19 Vaccine Rollout, Aneeka Ratnayake, Julie H Hernandez, Jessica Justman, Jason E Farley, Yael Hirsch-Moverman, Ken Ho, Stockton Mayer, Abiodun Oluyomi, Magdalena E Sobieszczyk, Shobha Swaminathan, Timothy Skalland, Jean De Dieu Tapsoba, Patricia J Kissinger

Faculty, Staff and Students Publications

Background: Vaccine hesitancy has been a significant concern throughout the COVID-19 pandemic. Vaccine hesitancy can be attributed to lack of confidence in vaccines, complacency about the health threat, or lack of convenience of vaccination. To date, few studies have used methods designed to include populations underrepresented in research when identifying factors associated with vaccine hesitancy.

Methods: Between January and July 2021, potential participants were recruited from community venues selected through time-location sampling in 15 defined communities in the United States. Study staff administered a questionnaire on demographics, COVID-19 behaviors and attitudes, and vaccination status or intention to consenting individuals. Vaccine …

Functional Head Tremor: Contrasting Features With Other Tremor Etiologies, José Fidel Baizabal-Carvallo, Joseph Jankovic

Faculty, Staff and Students Publications

Background: Functional tremor (FT) is considered the most common phenomenology among patients with functional movement disorders (FMDs). Most patients have limb tremor, but they can also present with tremor involving the head and trunk.

Objectives and methods: We aimed to assess the clinical phenomenology of functional head tremor (FHT) and contrast it with features of HT observed in 125 patients with other tremor etiologies (OTE), including 71 patients with essential tremor (ET).

Results: There were 101 consecutive patients (68.3% females) with FT from which n = 36 (35.6%) had FHT. Yes-yes tremor was the most common directionality (47.2%). Functional trunk …

Exploration Of Zileuton Protective Mechanisms Against Vancomycin-Associated Nephrotoxicity, Cole S Hudson, James E Smith, Rongjin Sun, Linh T Vuong, Luan D Truong, David Sheikh-Hamad, Masayuki Nigo, Ming Hu, Vincent H Tam

Faculty, Staff and Students Publications

Vancomycin is one of the most commonly used parenteral antibiotics for treating drug-resistant bacterial infections, however, it is hindered by nephrotoxicity. We previously demonstrated that zileuton could delay the onset of vancomycin-associated nephrotoxicity in rats. Here, we sought to understand the mechanism(s) of zileuton renal protection. Sprague-Dawley rats were administered vancomycin (200 mg/kg) and zileuton (1 and 4 mg/kg) daily for 10 days. After 3 days, kidneys were collected from select animals for histopathological analysis of renal injury. Single-dose vancomycin serum pharmacokinetics and renal tissue spatial distribution with adjuvant zileuton were evaluated. In vitro, proximal tubular cells were exposed …

Plasma Metabolomic And Proteomic Signatures Of Blood Pressure Management After Bariatric Surgery Among Adolescents, Shudi Pan, Zhenjiang Li, Juan Pablo Lewinger, Jesse A Goodrich, Hongxu Wang, Sarah Rock, Carmen Chen, Todd M Jenkins, Stephanie Sisley, Stephen R Daniels, Douglas I Walker, Max T Aung, Erika Garcia, Rob Mcconnell, Sandrah P Eckel, Michele A La Merrill, Tanya L Alderete, Zhuanghua Chen, Frank D Gilliland, Thomas H Inge, David V Conti, Justin R Ryder, Lida Chatzi

Faculty, Staff and Students Publications

Background: Emerging omics approaches, including metabolomics and proteomics, can be integrated into obesity treatment for better blood pressure management. We tested whether preoperative metabolomic and proteomic profiles predict long-term elevated blood pressure (EBP) changes better than known risk factors in adolescents undergoing bariatric surgery.

Methods: We included 108 participants from the Teen-LABS (Teen-Longitudinal Assessment of Bariatric Surgery). Plasma untargeted metabolomics (via liquid chromatography with high-resolution mass spectrometry) and Olink proteomics were assessed pre surgery. An elastic net model with stability selection was used to identify features predictive of EBP reductions 5 years post surgery. Models including identified metabolites, proteins, and …

Differential Microrna Profiling Of Blood L1cam And Bulk Extracellular Vesicles In Bipolar Disorder, Gabriel R Fries, Salahudeen Mirza, Jun Wang, Camila N C Lima, Wei Zhang, Marcela Carbajal Tamez, Giselli Scaini, Jair C Soares, Joao Quevedo

Faculty, Staff and Students Publications

Objective: This preliminary study aimed to identify microRNA (miRNA) signatures associated with bipolar disorder (BD) by profiling blood-derived extracellular vesicles (EVs) of both putative neuronal origin and from all sources.

Method: In two parallel studies of individuals with BD and controls (CON), we characterized miRNA expression profiles of blood EVs selected for L1CAM, a putative marker of neuronal origin (n = 20 BD/20 CON), as well as bulk EVs (n = 21 BD/20 CON). For each study, analyses identified miRNAs differentially expressed between groups, followed by functional interrogation and testing for associations with clinical features.

Results: Results of …

Common Severity-Based Definitions Of Bronchopulmonary Dysplasia Are Not Associated With Outpatient Morbidities, Robin L Mckinney, Antonia P Popova, Milenka Cuevas Guaman, Matthew J Kielt, Paul E Moore, Sharon A Mcgrath-Morrow, Joseph M Collaco

Faculty, Staff and Students Publications

Objectives: Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth, which can have life-long effects. Commonly used definitions of BPD severity are based on respiratory support at 36 weeks post-menstrual age. The utility of these definitions for tertiary referral centers outside the initial birth hospitalization is unclear.

Study design: Retrospective cohort study of infants born < 34 weeks gestation in the BPD Collaborative registry using three common definitions of BPD severity at 36 weeks post menstrual age and associated their severity with outpatient respiratory outcomes during the first 3 years of life.

Results: BPD severity by all three definitions was applied to 608 patients. Although the definitions had different distributions of BPD severity for the cohort, a majority of participants (75.7%) had moderate/Grade 2 or severe/Grade 3 BPD irrespective of the definition. Using clustered logistic …

Decreasing Barriers To The Utilization Of Cryopreserved Sperm In Male Cancer Survivors: An Expert Review And Guide, Megan V Alexander, Hailie Ciomperlik, Anna Claire Reynolds, Allyson Nevins, Luwam Ghidei, Jordan Kassab, Kevin Campbell, John Sullivan, Michael D Jochum, Laura Detti, Terri L Woodard, Larry I Lipshultz, Laurie J Mckenzie

Faculty, Staff and Students Publications

Background: Sperm cryopreservation offers male cancer patients a critical opportunity to preserve fertility prior to gonadotoxic therapy, yet utilization of banked sperm remains modest, typically under 10%. A structured understanding of barriers across the cancer survivorship continuum is needed to support patients in utilization of cryopreserved sperm in alignment with their reproductive goals.

Materials and methods: This expert review synthesizes current evidence and clinical experience to explore the multifaceted barriers to cryopreserved sperm use and propose specific solutions. Key intervention timepoints are examined, including the post-treatment fertility return visit, long-term cryopreservation while remote from family building, readiness for family building, …

Impact Of Common Variants On Brain Gene Expression From Rna To Protein To Schizophrenia Risk, Qiuman Liang, Yi Jiang, Annie W Shieh, Dan Zhou, Rui Chen, Feiran Wang, Meng Xu, Mingming Niu, Xusheng Wang, Dalila Pinto, Yue Wang, Lijun Cheng, Ramu Vadukapuram, Chunling Zhang, Kay Grennan, Gina Giase, Kevin P White, Junmin Peng, Bingshan Li, Chunyu Liu, Chao Chen, Sidney H Wang

The Brown Foundation: Institute of Molecular Medicine

Genetic variants influencing gene expression have been extensively studied at the transcriptional level. How these variants affect downstream processes remains unclear. We quantitated ribosome occupancy in prefrontal cortex samples from the BrainGVEX cohort and integrated these data with transcriptomic and proteomic profiles from the same individuals. Through cis-QTL mapping, we identified genetic variants associated with transcript level (eQTLs), ribosome occupancy (rQTLs), and protein level (pQTLs). Notably, only 34% of eQTLs have their effects propagated to the protein levels, suggesting widespread post-transcriptional attenuation. Using both a gene-based approach and a variant-based approach we identified omics-specific QTLs that associated with brain disorder …

The Impact Of Extramedullary And Paraskeletal Plasmacytomas On Treatment Outcomes In Multiple Myeloma Treated With Teclistamab: U.S. Myeloma Immunotherapy Consortium Real-World Experience, Aimaz Afrough, Danai Dima, Beatrice Razzo, Utkarsh Goel, Aishwarya Sannareddy, Oren Pasvolsky, Mariola Vazquez-Martinez, Christopher Ferreri, Rahul Banerjee, Jack Khouri, James Davis, Mahmoud Gaballa, Alex Lieberman-Cribbin, Masooma Rana, Kelley Julian, Faiz Anwer, Leyla Shune, Shaun Dejarnette, Ariel Grajales-Cruz, Evguenia Ouchveridze, Gabriel De Avila, Sandra Susanibar-Adaniya, Andrew Portuguese, Daniel Schrum, Erin Eberwein, Hitomi Hosoya, Lekha Mikkilineni, Gurbakhash Kaur, Joseph Mcguirk, Adriana Rossi, Megan Herr, Omar Castaneda, Frederick Locke, Shahzad Raza, Yi Lin, Shebli Atrash, Douglas Sborov, Peter Voorhees, Shambavi Richard, Alfred Garfall, Surbhi Sidana, Krina Patel, Doris Hansen, Andrew Cowan, Larry Anderson, Hans Lee

Department of Medical Oncology Faculty Papers

Teclistamab, a bispecific antibody targeting B-cell maturation antigen (BCMA), is effective in relapsed or refractory multiple myeloma (RRMM), but its impact on patients with soft tissue plasmacytomas is unclear. We studied 385 RRMM patients treated with teclistamab at 13 U.S. centers through September 2023, with follow-up to April 2024. Soft tissue plasmacytomas were classified as true extramedullary disease (EMD; not contiguous with bone) or paraskeletal plasmacytomas (PSK; contiguous with bone). Patients with the simultaneous presence of both were classified as true-EMD, reflecting its adverse prognosis. Of those, 109 (28%) had true EMD, 33 (9%) had PSK, and 243 (63%) had …

Developmental Stage-Dependent Transcriptomic Responses To Neonatal Intraventricular Hemorrhage, Elizabeth Wallace-Anthony, Miriam Zamorano, Hemendra J Vekaria, Braden B Oldham, Kiara P Umpornpun, Scott D Olson, Stefano Berto, Brandon A Miller

Faculty, Staff and Student Publications

Neonatal intraventricular hemorrhage (IVH) is a major complication of preterm birth, yet how developmental stage influences the brain's response to injury remains unclear. We performed single-nucleus RNA sequencing on rat brains 24 h after IVH at postnatal day 2 (PND2) or day 5 (PND5) to define transcriptional responses across cell types. We identified 42 distinct cell populations and found that PND5 brains exhibited a markedly stronger immune and inflammatory response to IVH, with a threefold increase in differentially expressed genes compared to PND2. Microglia were the most perturbed cell type at both stages, showing increased oxidative stress and polarization toward …

Microbial Associations And Viruses On The Risk Of Celiac Disease (Mavric): A Longitudinal Post-Hoc Case-Cohort Study, Kristian F Lynch, Eric W Triplett, Heikki Hyöty, Angelica P Ahrens, Jutta E Laiho, Joseph F Petrosino, Richard E Lloyd, Daniel Agardh

Faculty, Staff and Students Publications

Celiac disease etiopathogenesis requires genetic predisposition and exposure to gluten, yet these factors alone are not sufficient. Larger longitudinal studies are needed to determine the role of time-varying infections and gut microorganisms. The aim was to design a celiac disease case-cohort longitudinal study using The Environmental Determinants of Diabetes in the Young (TEDDY) study. By age 3-years, persistent tissue transglutaminase autoantibodies (tTGA), i.e., celiac disease autoimmunity (CDA), was confirmed in 704 of the 6132 genetically at-risk TEDDY children. Celiac disease onset (CD-onset) was defined as the age CDA developed when followed by a biopsy-proven diagnosis. A competing risk analysis on …

“I Missed My Other Oncologist”: Established Relationships As Barriers And Facilitators To Accessing Car-T And Autologous Transplantation, Zachary A. K. Frosch, Clark Meshack, Caitlin Meeker, Asya Varshavsky-Yanovsky, Rashmi Khanal, Michael Bromberg, Ashwin Chandar, Emmanuel Quien, Jordan Carter, Shazia K. Nakhoda, Marcus Messmer, Charissa Montgomery, Jason A. Incorvati, Nadia D. Ali, Michael J. Styler, Carolyn Y. Fang

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Autologous stem cell transplantation (ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) can provide significant clinical benefit, but are not equally available to all patients. Oncologist continuity and trust are important to patients, and may act as barriers to receipt of therapy. However, detailed data are lacking on the mechanism by which these might affect receipt of therapy, or how this barrier may be overcome.

METHODS: We conducted a qualitative interview study with patients with non-Hodgkin lymphoma (NHL), classic Hodgkin lymphoma (cHL) or multiple myeloma (MM) eligible for or treated with ASCT/CAR-T. Participants were recruited from a multi-site academic …

Feasibility And Acceptability Of An Implementation Strategy To Enhance Use Of Classroom-Based Physical Activity Approaches In Elementary Schools: A Mixed Methods Study, Timothy J Walker, Derek W Craig, Christopher D Pfledderer, Matthew Lee, Kempson Onadeko, Emma E Saving, John B Bartholomew, Maria E Fernández

Faculty, Staff and Student Publications

Background: Classroom-based approaches are an evidence-based way to improve children's physical activity; however, they are inconsistently implemented in schools. We developed MAGIC (Movement for Academic Growth In Classrooms), a multifaceted implementation strategy that consists of leadership training, teacher training, and a monthly newsletter to improve use of classroom-based physical activity approaches. The purpose of this study is to examine the feasibility and acceptability of MAGIC among elementary school teachers and leaders.

Methods: We used an embedded, convergent mixed methods design. We provided the MAGIC implementation strategy to a partner elementary school. We then administered surveys to teachers to quantitatively examine …

Developing Ehealth Interventions To Improve Diabetes Management In Emerging Adulthood: Qualitative Formative Study, April Idalski Carcone, Deepika Baskar, Aishah Mahmood, Karen Macdonell, Susan Eggly, Samiran Ghosh, Colleen Buggs-Saxton, Steven J Ondersma, Deborah A Ellis

Faculty, Staff and Student Publications

Background: Emerging adulthood is a high-risk period during which many with type 1 diabetes demonstrate suboptimal diabetes management and glycemic control. There is a need for effective, scalable interventions designed specifically for this population. Technology-based approaches are readily accessible to this age group. Furthermore, interventions consistent with self-determination theory-which posits that the fulfillment of psychological needs for autonomy, self-efficacy, and relatedness promotes intrinsic motivation for change-may resonate well with emerging adults' developmental needs for establishing independence and autonomy, and growing their social network.

Objective: This study aimed to enhance the potential relevance, sustainability, and efficacy of 3 self-determination theory-informed mobile …

Brain Power Comparison Between Microgravity And Head-Down Tilt Bed Rest: An Electroencephalography Approach, María Sevilla-García, Adrián Quivira-Lopesino, Pablo Cuesta, Sandra Pusil, Ricardo Bruña, Patrique Fiedler, Fernando Maestu, Ana Maria Cebolla, Guy Cheron, Katharina Brauns, Alexander C Stahn, Michael E Funke

Faculty, Staff and Student Publications

This study examines neurophysiological changes in microgravity by comparing EEG data from two ground analog 60-day head-down tilt bed rest (HDBR) experiments (ESA/DLR “Cocktail” and “RSL”) and the NEUROSPAT experiment in space. The primary objective was to determine whether HDBR could effectively model spaceflight’s impact on the human brain’s EEG signal. In the HDBR dataset, increases in relative delta (2–4 Hz) (p <  0.01) and theta (4–8 Hz) (p <  0.001) power bands were observed during a two-month HDBR experiment, predominantly in the left temporal and parieto-occipital regions. Conversely, the NEUROSPAT dataset showed a significant increase in beta (12–30 Hz) (p <  0.05) power in the left somatosensory cortex during in-flight conditions, suggesting a potential adaptation to disrupted proprioceptive input and motor control in microgravity. The contrasting findings between the two datasets indicate that while HDBR can simulate some aspects of microgravity, it may not serve as a model for all central nervous system changes, especially those related to proprioception and motor functions. This highlights the need for further research, including larger sample sizes, consistent EEG recording conditions, and integration of additional physiological and cognitive markers to fully understand the effects of prolonged microgravity.

A Phase 1/2 Study Of Ds-1594 Menin Inhibitor In Relapsed/Refractory Acute Leukemias, Jayastu Senapati, Marina Konopleva, Ghayas C Issa, Elias Jabbour, Tapan Kadia, Courtney Dinardo, Gautam Borthakur, Naveen Pemmaraju, Nicholas J Short, Musa Yilmaz, Indraneel Deshmukh, Joie Alvarez, Sanam Loghavi, Guilin Tang, Hussein A Abbas, Michael Andreeff, Kapil Bhalla, Narasimha M Midde, Nabil Said, Amy Noyalis, Derek E Mires, Jing Ning, Lianchun Xiao, Farhad Ravandi, Guillermo Garcia-Manero, Hagop M Kantarjian, Naval G Daver

Faculty, Staff and Student Publications

Several menin inhibitors are in development targeting menin dependent leukemias, however available preclinical results show variable level of activity. We report the phase 1 portion (to establish a recommended phase 2 dose [RP2D]) and pharmacokinetic analysis of a phase 1/2 first-in-human clinical trial of DS-1594b menin inhibitor. Eligible patients included adults (≥ 18 years of age) with relapsed/refractory (R/R) acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) including but not restricted to those with KMT2A-rearrangement (r) or NPM1 mutation. Seventeen patients at a median of age 56 years (range, 19-82 years) were treated, 15 (88%) had R/R AML, and …