Digital Commons Network^™

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 …

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, …

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 …

Racial And Ethnic Disparities In Pediatric Autoimmune Encephalitis: A Systematic Review, Jennifer H Yang, Kristen S Fisher, Julia Dumcum, Sophie Zacharek, Alexandra B Kornbluh, Kelsey Poisson, Mary C Karalius, Leigh Sepeta

Faculty, Staff and Students Publications

Objectives: Health disparities and social determinants of health are increasingly recognized as important predictors for clinical outcomes in autoimmune disease. However, this is poorly studied in pediatric autoimmune encephalitis (AE).

Methods: We conducted a systematic literature review in accordance with PRISMA guidelines. Searches included Medline (Pubmed), EMBASE, and Web of Science databases from inception years to October 4, 2024. Inclusion criteria were: 1) Patients diagnosed with AE ≤ 18 years old; 2) any report of race and/or ethnicity, 3) report of specific diagnostics and disease outcomes, 4) observational cohort studies, epidemiological studies or case series/ cohort studies of n ≥ …

Benchmarking Empirical Severity For The Yale-Brown Obsessive Compulsive Scale-Second Edition, Caitlin M Pinciotti, Juliana Avery, Chencheng Zhang, Josselyn S Muñoz, Dayan Berrones, Vanessa Zavala Cruz, Andrew D Wiese, Jacey L Anderberg, Renee M Frederick, Tomás Miño, Nuria Lanzagorta, Juan Camilo Restrepo, Marcos E Ochoa-Panaifo, Wayne K Goodman, James J Crowley, Eric A Storch, Matti Cervin

Faculty, Staff and Students Publications

The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is considered the primary instrument for assessing the presence and severity of obsessive-compulsive disorder (OCD). Conceptual and empirical critiques inspired the development of an updated version of the instrument, the Yale-Brown Obsessive Compulsive Scale-Second Edition (Y-BOCS-II), with a higher ceiling of OCD severity to better differentiate between severe and the most debilitating OCD presentations, among other revisions. The Y-BOCS-II has demonstrated sound psychometric properties across diverse samples. Empirically derived severity benchmarks have been proposed for the original Y-BOCS, yielding somewhat different ranges than what has been commonly used in clinical and research settings, yet …

Transoral Robotic-Assisted Removal Of A Submucosal Pyriform Sinus Foreign Body, Elisabeth Wenneker, Rebecca Doctor, Ari Schuman, Adam Szymanowski, Ray Wang

Faculty, Staff and Students Publications

Background: Submucosal foreign bodies of the medial pyriform sinus represent a challenge given limited visualization and difficult retraction with endoscopic approaches, and risk of injury to the recurrent laryngeal nerve with open approaches. Transoral robotic surgery (TORS) offers improved visualization and multiple working arms to facilitate retraction. We present a novel case utilizing the Da Vinci SP system for removal of an embedded fishbone of the medial pyriform sinus.

Results: An 84-year-old woman presented with five days of odynophagia and globus sensation after swallowing a fish bone. Non-contrast computed tomography scan revealed a 3.0 cm submucosal object within the post-cricoid …

Bridging The Gap: From Early Recognition To Timely Referral For Cardiac Implantable Electronic Devices Infections, M Rizwan Sohail, Sarwat Khalil, Molly L Paras, Christopher B Granger, Andrew Uehlin, Yu-Rong Gao, Zerelda Esquer Garrigos

Faculty, Staff and Students Publications

An increasing number of patients are living with cardiac implantable electronic devices (CIEDs). When a patient with a CIED is hospitalized with concern for infection or positive blood cultures from any source, recognizing and managing a possible CIED infection is critical due to its significant morbidity and mortality risk. Internists are often the first to evaluate these patients and must consider the possibility of an underlying device infection. Gram-positive bacteremia carries a high risk of CIED infection, often necessitating cardiac imaging. In contrast, hematogenous seeding with gram-negative bacteremia is infrequent. Patients with clinical or imaging evidence of device infection should …

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 …

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 …

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 …

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 …

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 …

Group Concept Mapping To Develop A Salon-Based Hpv Self-Collection Intervention, Kelly N B Palmer, Namoonga M Mantina, Adebola Adegboyega, Itunu O Sokale, Kathleen Pryor, Azaria Suero-Davis, Trevon Brooks, Jennifer Hatcher

Faculty, Staff and Students Publications

Background: Black women in the US face higher cervical cancer mortality rates due to delayed diagnoses linked to lower screening rates. Contributing factors include provider bias, costs, and limited access, particularly affecting women aged 40-64. While innovative approaches like clinical and home-based HPV self-collection exist, equitable dissemination remains challenging. Distributing HPV self-collection kits in unconventional sites like hair salons may offer a solution. Using concept mapping, we gathered community insights to design a salon-based cervical cancer screening intervention.

Methods: We employed groupwisdom™ and REDCap platforms for community-based participatory intervention development. Participants included members of the Black Community Advisory Council of …

The Association Between Condom Use Self-Efficacy And Condom-Decision Abdication Among College Students, Mikaela Gjoka, Madison K Firkey, Alan Z Sheinfil, Sarah E Woolf-King

Faculty, Staff and Students Publications

Objective: Condomless sex and its related consequences are a persistent problem on college campuses in the United States. This study aimed to examine the association between condom use self-efficacy and condom-decision abdication among college students, and whether this association was moderated by gender.

Participants & methods: Undergraduate college students (N = 212; 50.5% female) were recruited via Amazon Mechanical Turk as part of a larger online study that examined normative feedback for condom use.

Results: The association between condom use self-efficacy and condom-decision abdication was significantly moderated by gender (B = -0.07, p < .001), such that condom use self-efficacy was associated with condom-decision abdication in college women (B = -0.05, p < .005) but not in college men (B = .02, p = .18).

Conclusion: Findings from this study suggest that …

Fast And Accurate Measurement Of Small Field Dosimetry Using A Novel Scintillation Detector, Yiding Han, Jingzhu Xu, Yao Hao, Baozhou Sun

Faculty, Staff and Students Publications

Background: The most used instruments for small-field dosimetry have notable limitations, including the need for correction of output factors, limited scanning speeds, and challenges in alignment for percentage depth dose (PDD) measurements, particularly for extremely small fields. However, plastic scintillation detectors (PSDs) are an attractive alternative for small-field dosimetry due to their correction-free nature, linear dose response, and fast response time.

Purpose: This study evaluates the robustness and accuracy of the dosimetric measurements using a new water-equivalent PSD in small-field dosimetry. The study also aims to report accurate measurements of output factors, profiles, and an indirect method for measuring PDD …

Generation Of Ipscs (Rfsci007-A, Rfsci008-A) From A Patient With Early-Onset Bilateral Drusen And A Healthy Sibling For Retinal Disease Modeling, Sonali Singh, Wendy Runyon, Sam Hu, Paige Grona Kennedy, Ajeet Singh, Rinki Ratnapriya, Ritu Kumar, Karl Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Drusen are extracellular deposits between the retinal pigment epithelium and Bruch's membrane, commonly linked to age-related macular degeneration (AMD). However, their presence in younger individuals offers a unique opportunity to study early disease mechanisms before extensive degeneration. We generated two human induced pluripotent stem cell (hiPSC) lines from siblings' peripheral blood mononuclear cells-one with early-onset bilateral drusen and the other unaffected. This genetically matched iPSC pair enables investigation of early drusen associated pathological changes driving retinal disease development.

Soluble C5b-9 (Sc5b-9) In Pediatrics-A Clinical Assessment, Ridwan B Ibrahim, Radwa Almamoun, Sarah E Sartain, Sridevi Devaraj

Faculty, Staff and Students Publications

Background: The soluble C5b-9 (sC5b-9) is a soluble form of the Terminal Complement Complex (TCC) that is released into the circulation with elevated levels, associated with increased morbidity and mortality in patients with complement-mediated inflammatory conditions. With the advent of eculizumab and ravulizumab, proper testing for diagnoses and therapeutic monitoring is warranted.

Methods: We evaluated both the analytical and clinical performance of the Quidel Microvue sC5b-9 Plus enzyme immunoassay. Analytical performance was evaluated with precision, linearity, interference studies, and correlation with a reference laboratory. Reference intervals were established using control donor samples [n = 26; median age 18.5 years (range …

Transcriptional Coregulator Zmiz1 Modulates Estrogen Responses That Are Essential For Healthy Endometrial Function, Sylvia C Hewitt, Frank Orellana, Ryan M Marquardt, Myeongjin Yi, Cynthia J Willson, Mark Y Chiang, Yong Song, Goutham Venkata Naga Davuluri, Christopher Day, Ramakrishna Kommagani, Joseph Rodriguez, Asgerally T Fazleabas, John P Lydon, Francesco J Demayo

Faculty, Staff and Students Publications

Estrogen is a critical regulator of endometrial health. Aberrant estrogen stimulation can result in infertility, endometrial cancer, and endometriosis. Here, we identified Zinc Finger MIZ-Type Containing 1 (Zmiz1) as a coregulator of uterine estrogen signaling. ZMIZ1 is colocalized with an estrogen receptor α–binding (ESR1-binding) super enhancer. ZMIZ1 mutations are found in endometrial cancer and its RNA levels trend toward reduction in endometrium of patients with endometriosis. ZMIZ1 is dynamically expressed in human endometrial tissues during the menstrual cycle. Disrupting ZMIZ1 in cultured human endometrial stromal cells resulted in impaired cell proliferation and decidual differentiation. Ablation of Zmiz1 using …

Lilrb4 Regulates Circadian Disruption-Induced Mammary Tumorigenesis Via Non-Canonical Wnt Signaling Pathway, Olajumoke Ogunlusi, Mrinmoy Sarkar, Kayla Carter, Arhit Chakrabarti, Devon J Boland, Tristan Nguyen, James Sampson, Christian Nguyen, Danielle Fails, Yava Jones-Hall, Loning Fu, Gus Wright, Da Mi Kim, James J Cai, Bani Mallick, Alex C Keene, Jeff R Jones, Tapasree Roy Sarkar

Faculty, Staff and Students Publications

Epidemiological studies have shown that circadian rhythm disruption (CRD) is associated with the risk of breast cancer. However, the role of CRD in mammary gland morphology and aggressive basal mammary tumorigenesis and the molecular mechanism underlying CRD-induced carcinogenesis remain unknown. To investigate the effect of CRD on aggressive tumorigenesis, a genetically engineered mouse model of aggressive breast cancer was used. The impact of CRD on the tumor microenvironment was investigated using the tumors from LD12:12 and CRD mice via scRNA-seq, flow cytometry, multiplexing immunostaining, and realtime PCR. The effect of LILRB4-immunotherapy on CRD-induced tumorigenesis was also investigated. Here we investigated …

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 …

Cross-Species Standardised Cortico-Subcortical Tractography, Stephania Assimopoulos, Shaun Warrington, Davide Folloni, Katherine Bryant, Ali-Reza Mohammadi-Nejad, Wei Tang, Saad Jbabdi, Sarah R Heilbronner, Rogier B Mars, Stamatios N Sotiropoulos

Faculty, Staff and Students Publications

Despite their importance for brain function, cortico-subcortical white matter tracts are under-represented in diffusion magnetic resonance imaging tractography studies. Their non-invasive mapping is more challenging and less explored compared to other major cortico-cortical bundles. We introduce a set of standardised tractography protocols for delineating tracts between the cortex and various deep subcortical structures, including the caudate, putamen, amygdala, thalamus, and hippocampus. To enable comparative studies, our protocols are designed for both human and macaque brains. We demonstrate how tractography reconstructions follow topographical principles obtained from tracers in the macaque and how these translate to humans. We show that the proposed …

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 …

Evaluating Covid-19 Severity Prediction And Immune Dynamics With Nulisaseq: Insights From The Impacc Study, Koji Abe, Tyson H Holmes, Tran T Nguyen, Seunghee Kim-Schulze, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren I R Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, Ruth R Montgomery, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez-Sesma, Viviana Simon, Monica Kraft, Chris Bime, Carolyn S Calfee, David J Erle, Joanna Schaenman, Elaine F Reed, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Holden T Maecker

Faculty, Staff and Students Publications

The National Institutes of Health-funded IMPACC (IMmunoPhenotyping Assessment in a COVID-19 Cohort) evaluated longitudinal clinical and immunological features of human patients hospitalized for COVID-19. This study focuses on comparing the novel NULISAseq assay with the Olink platform using a subset of participants to assess their efficacy in predicting COVID-19 severity and understanding immune response dynamics. Our findings reveal that NULISAseq could provide superior detectability and dynamic range across various targets. Elastic net analysis demonstrated that specific proteins, including amphiregulin, effectively predict COVID-19 severity from sera at admission (samples drawn within 96 h of admission), with a test area under the …

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 …

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 …

Application Of The Surgical Apgar Score To Predict Intensive Care Unit Admission And Post-Operative Outcomes In Cesarean Hysterectomy For Placenta Accreta Spectrum, Emily Root, Jacqueline Curbelo, Patrick Ramsey, Jessian L Munoz

Faculty, Staff and Students Publications

Background and Objective: Placenta Accreta Spectrum (PAS) encompasses a continuum of abnormal placentation conditions associated with significant maternal and fetal morbidity. Management of PAS requires coordinated cesarean hysterectomy. Associated morbidities include blood transfusion, coagulopathy, and intensive care unit (ICU) admission. Accurate prediction of ICU admission allows for enhanced multidisciplinary management, coordination of care and utilization of resources. Scoring systems exist in other surgical specialties that can predict the likelihood of ICU admission, but these have not been applied to an obstetric population. The SAS is a 10-point scale that has been validated for the prediction of ICU-level care requirements within …

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 …

Benchmarking Dna Foundation Models For Genomic And Genetic Tasks, Haonan Feng, Lang Wu, Bingxin Zhao, Chad Huff, Jianjun Zhang, Jia Wu, Lifeng Lin, Peng Wei, Chong Wu

Faculty, Staff and Student Publications

The rapid evolution of DNA foundation models promises to revolutionize genomics, yet comprehensive evaluations are lacking. Here, we present a comprehensive, unbiased benchmark of five models (DNABERT-2, Nucleotide Transformer V2, HyenaDNA, Caduceus-Ph, and GROVER) across diverse genomic and genetic tasks including sequence classification, gene expression prediction, variant effect quantification, and topologically associating domain (TAD) region recognition, using zero-shot embeddings. Our analysis reveals that mean token embedding consistently and significantly improves sequence classification performance, outperforming other pooling strategies. Model performance varies among tasks and datasets; while general purpose DNA foundation models showed competitive performance in pathogenic variant identification, they were less …

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 …