Medicine and Health Sciences Commons^™

Using Randomization To Compare Ai And Expert-Generated Formative Assessment Questions In Medical Education, Akshat Kumar, Katie Stinson, Litao Wang, Elizabeth Nugent, Yongsu Lee, Mark Hormann, Latanya Jones Love, Toufeeq Ahmed Syed

Faculty, Staff and Student Publications

Background: AI-generated content is being used across the education spectrum and is beneficial for creating complex multiple-choice questions, such as those used in medical education. However, evaluating AI-generated content is challenging, and existing testing and evaluation methods are falling short. This study uses randomization to compare medical students' performance on and subjective evaluation of AI versus expert-generated questions. We hypothesized that there would be no difference in student performance or subjective evaluation of AI vs expert-generated questions.

Methods: We designed a single-center, randomized study where medical student participants received either one AI- or expert-generated question per day over four weeks. …

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

Impact Of School Nurse Education On Factors Influencing Hpv Vaccine Communication With Parents, Jihye Choi, Efrat K Gabay, Jeanette Deason, Elizabeth Baumler, Diane Santa Maria, Daisy Mullassery, Lara S Savas, Erika Thompson, Sanghamitra M Misra, Paula M Cuccaro

Faculty, Staff and Student Publications

Human papillomavirus (HPV) can cause six cancer types but can be prevented with timely vaccination in early adolescence. However, despite the wide availability of the HPV vaccine, uptake remains suboptimal among US adolescents. School nurses are invaluable resources to students and their families regarding adolescent immunization needs. As part of the All for Them vaccination program, we assessed the impact of the continued nurse education (CNE) intervention on school nurses’ HPV vaccine communication with parents. Seventy-two school nurses and nurse administrators in Texas participated in the study. Using a single-arm study design, we measured participants’ potential barriers to and self-efficacy …

In-Hospital Mortality Patterns And Readmissions In Patients With Chronic Obstructive Pulmonary Disease: An Analysis Of The Role Of Pulmonary Hypertension, Saad Afzal Khan, Trishna Parikh, Adishwar Rao, Akriti Agrawal, Aarohi Parikh, Farah Kazzaz, Sarah Shin, Harry Karmouty-Quintana, Maulin Patel, Kha Dinh, Bela Patel, Bindu Akkanti

Faculty, Staff and Student Publications

Chronic obstructive pulmonary disease (COPD) may be complicated by pulmonary hypertension (PH). We aimed to understand the impact of PH on in-hospital mortality and quantify the 30-day readmission rate among patients with COPD. For this cross-sectional study, we used the Nationwide Readmissions Database from 2017-2020 to identify adults ≥18 years with COPD. Patients were stratified according to PH diagnosis. Baseline characteristics between groups were compared using the Pearson chi-square test and two-sample t-test. Predictors of in-hospital mortality were determined using multivariate logistic regression analysis adjusted for demographics and confounders. The 30-day readmission rate and prevalence of PH subgroups by baseline …

Ambulatory Blood Pressure Variability In Prediction Of Target Organ Injury: The Ship Ahoy Study, Coral D Hanevold, Jang Dong Seo, Stephen R Daniels, Bonita E Falkner, Michael A Ferguson, Joseph T Flynn, Julie R Ingelfinger, Philip R Khoury, Marc B Lande, Kevin E Meyers, Mark Mitsnefes, Joshua Samuels, Elaine M Urbina

Faculty, Staff and Student Publications

Background: Ambulatory hypertension is associated with elevated left ventricular mass index (LVMI), cardiac dysfunction, and increased arterial stiffness in adolescents. Whether the addition of measures of BP variability improves the prediction of subclinical cardiovascular target organ damage (TOD) over mean BP measures is not known.

Methods: We assessed clinic and ambulatory BP (ABP), anthropometrics, and TOD in 397 adolescents. ABP means standard deviation (SD), BP, and heart rate (HR) dipping were calculated; coefficients of variability (CV) were calculated (SD/mean) to assess ABP variabilities. Measures of TOD included LVMI, left ventricular hypertrophy (LVH), LV systolic shortening, LV diastolic function (e'/a'), and …

Use Of Extracorporeal Membrane Oxygenation In Neonates With Congenital Anomalies Of The Kidney And Urinary Tract: A Multicenter Survey Of Current Practices Across Chnc And Pedi-Ecmo Centers., Syed Ahmed, Burhan Mahmood, John M. Daniel Iv, Sandy Johng, Amy Strong, John Ibrahim, June Hu, Kara Short, Kelsey Montgomery, Keri Drake, Kushal Bhakta, Leslie Lusk, Mary Revenis, Pratibha Thakkar, Ruth Seabrook, Samir Pandya, Sarah Keene, Sharada Gowda, Suma Hoffman, Tahagod Mohamed, Tara Beck, Tasnim Najaf, Robert Digeronimo, Natalie Rintoul, Abhishek Makkar

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: This study aimed to characterize practices and decision-making for extracorporeal membrane oxygenation (ECMO) for congenital anomalies of the kidney and urinary tract (CAKUT).

METHODS: General practices (GP) section inquired about institutional practices and barriers, ECMO criteria, and dialysis. The hypothetical cases (HC) illustrated four clinical scenarios with varying degrees of renal severity for ECMO candidacy.

RESULTS: Then, 99 (42 centers) and 91 (38 centers) physicians completed the GP and HC components, respectively. The majority considered ECMO on a case-by-case basis (66%). Bilateral renal agenesis was the most common diagnosis for exclusion (52%). Prenatal markers used for ECMO exclusion included …

Birth Cohort Effects In Adults Associated With Influenza A(H1n1)Pdm09 Vaccine Effectiveness, Feng Liu, Stacey L House, Tamair Curley, Et Al.

2020-Current year OA Pubs

BACKGROUND: In 2023-2024 influenza season, adults in the 1957-1985 birth cohort had the lowest vaccine effectiveness (VE) against A(H1N1)pdm09 viruses than other age groups, including those in the 1986-2005 birth cohort. We investigated A(H1N1)pdm09 antibody levels in sera collected from influenza cases and controls to explain the birth cohort effect of the low VE.

METHODS: Acute and convalescent sera were collected from adults (1986-2005 and 1957-1985 birth cohorts) during 2023-2024. Hemagglutination inhibiting (HI) and binding antibodies were assessed against representative A(H1N1) viruses and hemagglutinin antigens.

RESULTS: A(H1N1)pdm09-infected cases in the 1957-1985 birth cohort had significantly lower HI antibodies in the …

A Phase 2, Open-Label, Multicenter Study Of The Safety And Efficacy Of Tak-007 In Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma, Justin Darrah, Indumathy Varadarajan, Amitkumar Mehta, Jennifer Saultz, Matthew Mckinney, Monalisa Ghosh, Usama Gergis, Andrew Krueger, Kevin Galinsky, Girish Bende, Ajeetha Ramachandran, Varsha Sundaresan, Siddha Kasar, Bradley Hupf, Sharon Chen, Leopold Sellner, Reem Karmali

Department of Medical Oncology Faculty Papers

In relapsed/refractory large B-cell lymphoma (LBCL), chimeric antigen receptor (CAR)-natural killer (NK) cell therapies offer potential advantages over CAR-T-cell therapies, including off-the-shelf availability and scalable manufacturing. We performed a phase 2 study of single-dose TAK-007, a cryopreserved, cord blood-derived, off-the-shelf CD19 CAR-NK cell therapy, in 26 heavily pre-treated patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Adverse events were manageable, with limited grade 1-2 cytokine release syndrome (11.5%). Overall response rate with TAK-007 800 x106 CD19 CAR+ viable NK cells (n=14) was 60.9% (95% CI: 38.5-80.3). Median progression-free survival was 2.0 months (95% CI: 0.99-3.58) in LBCL (n=10) and 5.6 months …

Expanding The Clinical And Molecular Spectrum Of Tubb2b Through Distinct Variants Identified Across Multiple Families, Shaghayegh T Beheshti, Angad Jolly, Ahmed K Saad, Haowei Du, Lauren E Westerfield, Chloe Munderloh, Divya Kalra, Yifan Wu, Yi Chen, Marie-Claude Gingras, Shalini N Jhangiani, Sarenur Yilmaz, Maha S Zaki, Daniel G Calame, Davut Pehlivan, Richard A Gibbs, Richard A Lewis, James R Lupski, Jennifer E Posey

Faculty, Staff and Students Publications

TUBB2B encodes a β-tubulin isotype essential for neuronal proliferation, migration, and organization during brain development. Pathogenic heterozygous variants in TUBB2B are associated with neurodevelopmental disorders including polymicrogyria and corpus callosum abnormalities. However, the phenotypic spectrum remains heterogeneous, most likely reflecting variant-specific effects on microtubule formation and stability. Homozygous TUBB2B variants are exceedingly rare, with one family reported to date. We describe five individuals in four families with rare TUBB2B variants. Four variants are described, including a previously reported de novo missense variant, c.292G>A (GenBank: NM_178012.5) (p.Gly98Arg), with potential phenotypic expansion including panhypopituitarism; a previously reported de novo missense variant, …

Expanding The Clinical And Molecular Spectrum Of Tubb2b Through Distinct Variants Identified Across Multiple Families, Shaghayegh T Beheshti, Angad Jolly, Ahmed K Saad, Haowei Du, Lauren E Westerfield, Chloe Munderloh, Divya Kalra, Yifan Wu, Yi Chen, Marie-Claude Gingras, Shalini N Jhangiani, Sarenur Yilmaz, Maha S Zaki, Daniel G Calame, Davut Pehlivan, Richard A Gibbs, Richard A Lewis, James R Lupski, Jennifer E Posey

Faculty, Staff and Students Publications

TUBB2B encodes a β-tubulin isotype essential for neuronal proliferation, migration, and organization during brain development. Pathogenic heterozygous variants in TUBB2B are associated with neurodevelopmental disorders including polymicrogyria and corpus callosum abnormalities. However, the phenotypic spectrum remains heterogeneous, most likely reflecting variant-specific effects on microtubule formation and stability. Homozygous TUBB2B variants are exceedingly rare, with one family reported to date. We describe five individuals in four families with rare TUBB2B variants. Four variants are described, including a previously reported de novo missense variant, c.292G>A (GenBank: NM_178012.5) (p.Gly98Arg), with potential phenotypic expansion including panhypopituitarism; a previously reported de novo missense variant, …

Real-World Experience Of Hepatitis C Treatment With Glecaprevir-Pibrentasvir During Pregnancy, L Madeline Mccrary, Megan R Curtis, Jeannie C Kelly, Jessica Elrod-Gallegos, Patrick Kojima, Patricia Werner, Jennifer L Mullersman, Tracey Habrock-Bach, Michael J Durkin, Laura R Marks

2020-Current year OA Pubs

Guidelines endorse antenatal hepatitis C virus treatment following shared decision making. No clinical trial or real-world data exist for glecaprevir-pibrentasvir (GLE/PIB). We report our experience with prenatal GLE/PIB in 14 patients. Ten patients completed treatment; all achieved virologic response by or at delivery, with no maternal or neonatal safety concerns.

Translation And Comprehensive Validation Of The Neurological Outcome Scale For Traumatic Brain Injury (Nos-Tbi) Into Brazilian Portuguese, Karina T. Weber, Luciana B. M. Alves, Monica C. Braga, Suleimy C. Mazin, Brunna R. Pileggi, Millene R. Camilo, Viviane A. Guimaraes, Clara M. A. Barreira, Frederico Alessio-Alves, Aline S. Carvalho, Aline C. Pacheco-Castilho, João P. Leite, Dylan J. Edwards, Octavio M. Pontes-Neto, Taiza G. S. Edwards

Moss-Magee Rehabilitation Papers

Background: Traumatic brain injury (TBI) is a leading cause of disability in Brazil and worldwide. National and multinational clinical trials in TBI require global standardization of outcome measures. The original English version of the Neurological Outcome Scale for TBI (NOS-TBI) is a valid and valuable neurological assessment tool. However, NOS-TBI has not yet been validated in Brazilian Portuguese.

Objective: To perform the translation, cultural adaptation, and validation of the NOS-TBI in a Brazilian cohort of individuals with TBI.

Methods: We conducted the translation and cultural adaptation of the NOS-TBI scale to Brazilian Portuguese, followed by an analysis of psychometric properties: …

Study Of Blood Linear Rna Nominates Cd55 And Dld As Early-Stage Biomarkers For Parkinson's Disease, Aleksandra Beric, Sarp Sahin, Santiago Sanchez, Zining Yang, Ravindra Kumar, Isabel Alfradique-Dunham, Jessie Sanford, Daniel Western, Bridget Phillips, John P Budde, Richard J Perrin, Paul T Kotzbauer, Joel S Perlmutter, Scott A Norris, Carlos Cruchaga, Laura Ibanez

2020-Current year OA Pubs

Parkinson's disease (PD) is the second leading neurodegenerative disease, pathologically characterized by the accumulation of alpha-synuclein in the brain and the loss of dopaminergic neurons in the substantia nigra pars compacta. Despite the intensive efforts to identify diagnostic biomarkers for PD and nominating prospective candidates such as such as CSF α-synuclein seed amplification assay or α-/β-synuclein ratio, establishment of minimally invasive biomarkers remains the focus of PD research. We leveraged transcriptomic data from 4343 participants from four independent datasets to robustly identify PD-associated transcripts. Following the differential abundance analyses, we integrated our findings with several brain transcriptomic, CSF proteomic, plasma …

A Framework For Aligning 5-Year And Lifetime Breast Cancer Risk In Women Without High-Penetrance Mutations, Graham A Colditz, Debbie L Bennett, Kala Visvanathan, Bernie A Rosner, Shu Jiang

2020-Current year OA Pubs

OBJECTIVE: Reconciling cutoff thresholds for short-term (5-year) and long-term (lifetime) breast cancer risk could support tailored and evidence-based approaches to supplemental screening and risk management most relevant to short-term clinical actions. This study aims to consistently classify women at increased risk and provide 5-year risk cutoff that corresponds to a 20% lifetime risk.

METHODS: Using U.S. Surveillance, Epidemiology and End Results (SEER) program population incidence data for women 40 to 74 years of age, this study reports both lifetime and 5-year population-based risk estimates controlling for competing risk and age varying breast cancer incidence. A cut point for 5-year risk …

Support For Human And Civil Rights In Physical Disability, Mental Illness, And Substance Use Disorder, Jessica Williams, Mia Kouveliotes, Nev Jones, Morgan C Shields

2020-Current year OA Pubs

IMPORTANCE: While there is much research on stigma toward marginalized populations, public perceptions regarding deservingness of basic human and civil rights of these groups have not been examined in a nationwide sample of US adults.

OBJECTIVE: To understand the US public's perceptions regarding deservingness of basic human and contested civil rights for people with severe physical disabilities (SPDs), severe mental illness (SMI), and substance use disorders (SUDs).

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was a nationwide US internet-based quota panel survey of US adults (aged ≥18 years) who completed the survey. Responses were collected from January 17 to February …

Clinical Presentations, Treatments, And Outcomes Of Pediatric Lupus Nephritis: A Prospective Cohort Study From The Pediatric Nephrology Research Consortium., Melonie Phillips, Mahmoud Kallash, Chloe Tang, Steve Rust, Kia Jubert-Bacon, Scott Wenderfer, Smriti Mohan, Neal Blatt, Don Batisky, Alejandro Quiroga, Tetyana L. Vasylyeva, Nilka Dejesus, Jerome C. Lane

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: There are few prospective studies of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC) for pediatric lupus nephritis (pLN) and none evaluating rituximab (RTX).

METHODS: The Prospective Pediatric Lupus Nephritis Registry (ProPeL-R) enrolled patients <  21 years within 4 weeks of an initial kidney biopsy diagnostic of pLN. Demographic, clinical, and laboratory data were collected prospectively at enrollment, 3 months, 6 months, and then every 6 months thereafter for up to 5 years of follow-up. For this study, we compared patients receiving initial therapy with corticosteroids (CS) and either MMF (n = 33) vs. CYC (n = 18), and those treated with CS, either MMF or CYC, with RTX (n = 20) vs. without RTX (n = 51).

RESULTS: Histology consisted of 18% class III; 35% class IV; 25% mixed class; and 22% pure class V. Eighty-two percent were female. No significant differences in response or infection rates were identified between those receiving MMF or CYC. There was a significant increase in combined complete (CR) and partial response (PR) at 24 months with RTX use. Overall CR rates at 6 and 24 months were 35% …

High-Grade Astrocytoma With Piloid Features: A Clinical And Genomic Analysis Of Prognostic Factors Using A Large Cohort, Shuodan Zhang, Omar H Butt, Sonika Dahiya, Et Al.

2020-Current year OA Pubs

BACKGROUND: High-grade astrocytoma with piloid features (HGAP) is a recently defined tumor type that is not well understood. Prognostic factors of clinical outcomes are not well established.

METHODS: Methylation profiling was performed on tumor samples, many at the National Cancer Institute (NCI) Laboratory of Pathology, and others from publicly available sources. Methylation classifier scores of ≥0.90 to the HGAP class on the NCI-Bethesda classifier version 3 were included. Clinical features were collected from the medical record. Survival analyses were performed using the Kaplan-Meier and Cox-proportional hazards methods.

RESULTS: The cohort comprised 421 patients. There were high rates of ATRX alteration …

Unveiling Functional-Metabolic Synergy In The Healthy Brain: Multivariate Integration Of Dynamic [18f]Fdg-Pet And Resting-State Fmri, Claudia Tarricone, Giulia Vallini, Giorgia Baron, Massimiliano Facca, Erica Silvestri, Tommaso Volpi, Andrei G Vlassenko, Manu S Goyal, Alessandra Bertoldo

2020-Current year OA Pubs

Despite accounting for only 2% of body weight, the human brain requires significant amounts of glucose, even at rest, underscoring the importance of functional-metabolic relationships. Previous studies revealed moderate associations between resting-state fMRI functional connectivity (FC) and local metabolism via [

Ambulatory Blood Pressure Thresholds And Left Ventricular Hypertrophy In Children Aged 6-12 Years: A Pediatric Nephrology Research Consortium Study., Afsana Jahan, Matthew Schuchman, Mahie Abdullah, Meghan Mclaughlin, Emilia Maria Cadiz, Eshanika Manchanda, Aftab Chishti, Maggie Murphy, Sarah Twichell, Alexandra Mazo, Dmitry Samsonov, Aesha Maniar, Hannah Kim, Francis Lomanta, Ashok Chakravarthy Patibandla, Rachel Frank, Tarak Srivastava, Ikuyo Yamaguchi, Christine Sethna

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To evaluate the diagnostic performance of ambulatory blood pressure monitoring (ABPM) thresholds for predicting left ventricular hypertrophy (LVH) in children aged 6-12 years.

STUDY DESIGN: A retrospective, multicenter study was conducted across 11 Pediatric Nephrology Research Consortium sites and included children aged 6-12 years who underwent ABPM and 2-dimensional echocardiography for diagnostic assessment of elevated BP. The diagnostic accuracy of fixed ABPM thresholds and the current 95th percentile for sex and height were assessed using area under the receiver operating characteristic, sensitivity, specificity, and Youden index. Multivariable logistic regression models, adjusted for age, sex, and body mass index z-score, …

Early Prediction Of The Breast Cancer Response To Neoadjuvant Chemotherapy Based On Intratumoral Interstitial Fluid Pressure Using 3-D Subharmonic-Aided Pressure Estimation, Sung In Choi, Basak Dogan, Corinne E. Wessner, Jessica H. Porembka, Priscilla Machado, B. Bersu Ozcan, Nisha Unni, Maysa Abu-Khalaf, Kenneth Hoyt, Flemming Forsberg, Kibo Nam

Department of Radiology Faculty Papers

Elevated intratumoral interstitial fluid pressure (IFP) may negatively impact the efficacy of neoadjuvant chemotherapy (NAC). This study aimed to predict the breast cancer response to NAC based on intratumoral IFP using 3D contrast-enhanced ultrasound (CEUS) with subharmonic-aided pressure estimation (SHAPE). This prospective study enrolled breast cancer patients undergoing NAC from two clinical sites. 3D CEUS was performed at 0%, 10%, and 30% of NAC completion using a GE Logiq E9 with Definity. The pressure gradients between the tumor and adjacent normal tissue were estimated by SHAPE, utilizing the inverse linear relationship between the ultrasound contrast agent’s subharmonic signal amplitude and …

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) …

Efficacy And Safety Of Frail Patients Treated With Ciltacabtagene Autoleucel In The Real World: A Center For International Blood And Marrow Transplant Research Analysis., Hira Mian, Muhammad Salman Faisal, Tiening Chen, Ruta Brazauskas, Temitope Oloyede, Nausheen Ahmed, Aimaz Afrough, Larry D Anderson, Rahul Banerjee, Jesus Berdeja, Aram Bidikian, Jakob Devos, Binod Dhakal, Ajoy Dias, Danai Dima, Yvonne A Efebera, Lohith Gowda, Doris K Hansen, Hamza Hashmi, Heather J Landau, Lazaros Lekakis, Abu-Sayeef Mirza, Ravi Narra, Krina Patel, Ashley E Rosko, Mark Schroeder, Surbhi Sidana, Saad Usmani, Marcelo C Pasquini, Taiga Nishihori, Othman Salim Akhtar, Meera Mohan

Oncology Articles

Background: Ciltacabtagene autoleucel (cilta-cel), an anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy, is approved for relapsed/refractory multiple myeloma (RRMM).

Methods: Using the Center for International Blood and Marrow Transplant Research registry, this study evaluated outcomes of frail patients receiving commercial cilta-cel from March 2022 to December 2023. Frailty was defined by an adapted simplified score incorporating age, performance status, and comorbidities.

Results: Among 541 patients with available frailty status, 183 (33.8%) were frail and 358 (66.2%) were nonfrail. Overall response rates were comparable (frail 82.8% vs. nonfrail 88.5%). However, frail patients had inferior progression-free survival (PFS) (12-month …

The Epidemiology Of Kidney And Urinary Tract Infections In Pediatric Chronic Kidney Disease: Prevalence, Risk Factors And Association With Gfr Decline In The Chronic Kidney Disease In Children Study., Derek K. Ng, Andrea R. Molino, Siyao Zhang, Emily J. Stonebrook, Craig S. Wong, Pratyush Gyawali, Kimberly J. Reidy, Susan L. Furth, Bradley A. Warady, Jeffrey J. Fadrowski, Ckid Study Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Urinary tract and kidney infections are potential complications in pediatric chronic kidney disease (CKD), especially among patients with congenital anomalies of the kidney and urinary tract (CAKUT). We characterized the prevalence of self-reported infections from childhood through young adulthood; evaluated risk factors; and quantified the association with CKD progression.

METHODS: Infections in the past year were self-reported at annual Chronic Kidney Disease in Children (CKiD) study visits. Age-specific infection prevalences were stratified by sex and CKD diagnoses (glomerular, non-glomerular non-CAKUT, CAKUT low-risk for infections, and three CAKUT high-risk categories: reflux nephropathy, obstructive uropathy, and other high-risk). Repeated measures logistic …

Peritoneal Dialysis Catheter Complications In Neonates With Kidney Failure., Shannon Reinert, Maanasa Yarlagadda, Alexander Bondoc, Donna Claes, Stefanie Riddle, Meredith P. Schuh

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Neonates with kidney failure require placement of a peritoneal dialysis catheter (PD-C) shortly after birth. PD-C malfunction and peritonitis, both common in this population, are associated with PD failure. The aim of this study was to describe our center's PD-C-related practices and outcomes in neonates with kidney failure.

METHODS: We performed a retrospective chart review of neonates who required kidney replacement therapy (KRT) within the first 30 days of life from 01/2018-12/2023. We evaluated for PD-C duration, PD-C replacement or revision, and peritonitis.

RESULTS: Twenty-four neonates had PD-C placed for chronic dialysis at a median of 9.7 days and …

Early Hands-On Surgical Exposure: Outcomes Of A Student-Led Surgical Externship Program For Preclinical Students, Meryem C. Guler, Elizabeth Spitz, Jennifer E. Geller, Talar Tatarian, Renee Tholey

Department of Surgery Faculty Papers

Objective: Early surgical exposure may potentially influence medical students' decision to pursue a surgical career. At our urban, academic medical school, senior medical students developed a Surgical Externship Program (SEP) to provide first-years with hands-on OR experience. This program is a structured 1- to 2-week immersive experience in which first-year students scrubbed into operations, participated in rounds, and engaged with surgical teams under resident and attending supervision. This study evaluates the SEP's impact on surgical interest, OR confidence, and clinical exposure.

Setting: Academic tertiary care hospital.

Participants: First-year medical students.

Design: First-year students participated in a 1- or 2-week SEP …

A Rare Recurring Gain-Of-Function Variant In Bmpr2 Causes Neurodevelopmental Phenotypes In Humans And Flies, Jung-Wan Mok, Carrie L Welch, Haley A Dostalik, Zhi Tan, Ariel Brautbar, Maria Descartes, Erica T Gray, Alejandro Iglesias, Scott D Mclean, Morgan Nutter, Olivia Daugherty, Amber Begtrup, Ingrid M Wentzensen, Yufeng Shen, Damian W Young, Martin M Matzuk, Oguz Kanca, Michael F Wangler, Hugo J Bellen, Wendy K Chung, Shinya Yamamoto

Faculty, Staff and Students Publications

Bone morphogenetic protein receptor type 2 (BMPR2) encodes an evolutionarily conserved serine/threonine kinase that phosphorylates type-1 BMP receptors to mediate intercellular communication upon ligand binding. Loss-of-function variants in BMPR2 are known to cause pulmonary arterial hypertension and other cardiovascular disorders. Here, we report a rare recurrent missense variant in BMPR2 (c.1126G>A [GenBank: NM_001204] [p.Glu376Lys]) identified in six individuals, who all present with neurodevelopmental phenotypes including autism spectrum disorder and global developmental delay. Trio analysis demonstrates de novo occurrence of this variant in at least five of the individuals. Using the fruit fly Drosophila melanogaster, we show that this variant …

Nlgn3 Autism Variants Have Distinct Functional Impact On Synapses And Sleep Behavior In Drosophila, Rebekah E Townsley, Jonathan C Andrews, Saurabh Srivastav, Sharayu V Jangam, Shabab B Hannan, Oguz Kanca, Paul C Marcogliese, Shinya Yamamoto, Michael F Wangler

Faculty, Staff and Students Publications

Neuroligin-3 (NLGN3) was first identified as a X-linked risk gene associated with autism spectrum disorder (ASD). Most reported variants are identified in males who inherited their variants from an unaffected mother, but de novo variants have also been identified in both affected heterozygous females and hemizygous males. The p.R451C variant was the initial variant associating NLGN3 with ASD and has been heavily investigated, yet little is known about the functional consequences of other NLGN3 variants. To determine the functional consequences of other NLGN3 variants in vivo, we generated transgenic Drosophila models corresponding to a de novo variant (p.R175W) identified in …

A Genetic Risk Variant Associated With The Risk Of Primary Biliary Cholangitis Is Inherited From Neanderthals, Alessio Gerussi, Chiara Caime, Harold Wang, Heather J Cordell, George F Mells, Richard N Sandford, David E Jones, Gideon Hirschfield, Katherine A Siminovitch, M Eric Gershwin, Brian D Juran, Elizabeth J Atkinson, Angela Cheung, Mariza De Andrade, Aris Baras, Konstantinos N Lazaridis, Rosanna Asselta, Pietro Invernizzi, Manuela Sironi, Sriram Sankararaman, Canadian‐Us Pbc Consortium, Uk‐Pbc Consortium, Italian Pbc Genetics Study Group

Faculty, Staff and Students Publications

Background: Primary Biliary Cholangitis (PBC) is an autoimmune cholangiopathy with polygenic architecture and unknown aetiology. Evidence links Neanderthal-derived genetic variants to autoimmune conditions; however, their contribution to PBC susceptibility remains unexplored.

Objective: We investigate whether archaic alleles influence PBC risk.

Design: Genotype data from four PBC cohorts were analysed: CANUK (4615 cases, 9233 controls), OLD IT (444 cases, 901 controls), NEW IT (255 cases, 579 controls) and MAYO (891 cases, 621 controls). Association testing with 235 592 Neanderthal Informative Markers (NIMs) was performed, adjusting for population stratification. Heritability was estimated using RHE-mc and temporal haplotype dynamics were assessed using ancient …

Engagement And Weight Change In An Online Weight Management Program In Clinical Settings: An Implementation Project, Heather J Baer, Joann Cho, Richard Fay, Caroline M Apovian, Ashley C Mccarthy, Alexander J Blood, Lipika Samal, Naomi D L Fisher, E John Orav, Matthew Wien, Jorge Plutzky, Jason P Block, David W Bates, Ronen Rozenblum, Michela Tucci, Marian Mcpartlin, Michael Oates, Katherine D Mcmanus, Benjamin M Scirica

Faculty, Staff and Students Publications

Background: There is an urgent need for scalable strategies for treatment of overweight and obesity that can be implemented in clinical settings.

Objective: To implement and evaluate an online weight management program in a large, diverse population of patients.

Design: Clinical implementation project in primary care and specialty clinics.

Participants: Eligible patients were ≥ 20 years old, spoke English or Spanish, and had a body mass index (BMI) of ≥ 30 kg/m2 or a BMI of 25-29.9 kg/m2 plus ≥ 1 cardiovascular risk factor or obesity-related condition.

Intervention: Enrolled patients were encouraged to register for a 12-month digital health program …

A Prospective Natural History Study Protocol For Clinical Trial Readiness In Synaptic Disorders, Jillian L Mckee, Sarah M Ruggiero, Kristin Cunningham, Joeylynn Coyne, Ian Mcsalley, Michael C Kaufman, Bintou Bane, Torrey Chisari, Jonathan Toib, Carlyn Glatts, Sarah Tefft, Julie M Orlando, Viveknarayanan Padmanabhan, Alexander K Gonzalez, Alicia Harrison, Charlene Woo, Stephanie A Zbikowski, Rency Dhaduk, Johanna Mercurio, Macie Mccarthy, Jan H Magielski, Zachary Grinspan, Megan Abbott, Juliet Knowles, Hsiao-Tuan Chao, Katherine Xiong, Elizabeth Berry-Kravis, Sepideh Tabarestani, J Michael Graglia, Kathryn Helde, Virginie Mcnamar, Charlene Son Rigby, James Goss, Scott Demarest, Andrea Miele, Benjamin Prosser, Michael J Boland, Samuel R Pierce, Ingo Helbig

Faculty, Staff and Students Publications

Objective: STXBP1-related disorder (STXBP1-RD) and SYNGAP1-related disorder (SYNGAP1-RD) are two common genetic synaptopathies that are associated with epilepsy, developmental delay, intellectual developmental disorder, and behavioral problems. Both STXBP1-RD and SYNGAP1-RD are potential targets for disease-modifying therapies, but there is limited information in the literature describing the natural history of either disorder, which impedes outcome selection for future clinical trials. The objective of this study is to develop a framework to better define and outline the clinical spectrum and longitudinal trajectories of STXBP1-RD and SYNGAP1-RD natural history, including development, behavior, seizure histories, and electrophysiology.

Methods: Here, we describe a protocol, regulatory …