Medical Specialties Commons^™

Expanding The Clinical And Molecular Spectrum Of Tubb2b Through Distinct Variants Identified Across Multiple Families, 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, 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, …

Mapping Long-Read Sequences To A Complete Reference Genome Reveals Uncaptured Variants Across The Β-Globin Cluster In Africans With Sickle Cell Disease, Pamela Lurie, Medhat Mahmoud, Aparna Haldipur, Yixing Han, Qing Li, Edmond Wonkam Tingang, Natalie Asmus, Emilyn Banfield, Nancy J Hall, Bamidele Tayo, Richard Cooper, Titilola Akingbola, George Ayodo, Stephen Obaro, Guillaume Lettre, Qing Meng, Shalini Jhangiani, R Alan Harris, Kim C Worley, Juyhun Kim, Arang Rhie, Adam M Phillippy, Fritz Sedlazeck, Ambroise Wonkam, Neil A Hanchard

Faculty, Staff and Students Publications

African genomes are marked by extensive complexity in the number and distribution of variants yet remain under-represented in genetic databases and the human reference genome. This gap in representation limits the broad application of genomic medicine. Sickle cell disease (SCD)-one of the most common monogenic diseases-has its highest prevalence in Africa, and variation in disease severity has consistently been linked to the β-globin locus, including levels of fetal hemoglobin (HbF). Modulation of HbF is central to current SCD gene therapies; however, the inherent complexity and variation at the locus in African genomes present a challenge to translating these advances to …

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: …

Immune Hallmarks Of Recurrent Immune Checkpoint Inhibitor-Mediated Inflammatory Arthritis, Synat Keam, Yuanteng Jeff Li, Yanshuo Chu, Jean H Tayar, Huifang Lu, Michael Wu, Sandeep K Agarwal, Nitin Jain, Pavlos Msaouel, Adi Diab, Linghua Wang, Cara Haymaker, Roza Nurieva, Sang T Kim

Faculty, Staff and Students Publications

Immune checkpoint inhibitor (ICI) therapy is often associated with immune-related adverse events including inflammatory arthritis (IA). However, the mechanisms underlying ICI-mediated IA (ICI-IA), especially its recurrence, are not well understood. In this study, we sought to elucidate mechanisms of recurrent ICI-IA by analyzing longitudinal synovial fluid (SF) samples from patients with ICI-IA. SF samples were collected from six patients with ICI-IA at the first and second occurrences of ICI-IA and analyzed with single-cell RNA sequencing (n = 3), single-cell T-cell receptor sequencing (n = 3), single-cell B-cell receptor sequencing (n = 3), and flow cytometry (n = 6). SF samples …

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 …

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 …

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% …

Holding Hope: Maternal Experiences Of Kangaroo Mother Care Within Sociocultural Contexts In Ethiopia., Miraj Fuad Alemar, Betelehem B. Kassa, Mahlet Abayneh, Hanan N. Mohammed, Stephanie Kukora

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Kangaroo mother care (KMC) is a crucial method for improving the health outcomes of preterm and low birth weight (LBW) infants, particularly in resource-limited settings. However, barriers hinder mothers from effectively practicing KMC. This study aims to explore mothers' perceptions, hopes, and buy-in regarding KMC in a tertiary care center in Ethiopia.

METHODS: A semistructured interview guide was developed on the basis of a literature review. In-depth interviews were conducted with a purposive sample of mothers who had practiced KMC within the past two years at Saint Paul's Hospital Millennium Medical College (SPHMMC), Addis Ababa, Ethiopia. The interviews, which …

Ceftaroline Pharmacokinetics On Ecmo, A Pediatric Case Report., Kathryn Pavia, Ashton Bellamy, Alaina Burns, Allison Scott, Ethan A. Poweleit

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In-vitro studies suggest that patients on extracorporeal membrane oxygenation (ECMO) may struggle to achieve therapeutic ceftaroline exposure to treat infections due to antibiotic sequestration within the ECMO oxygenator; however, there are no published data regarding ceftaroline concentrations from patients supported by ECMO.

PATIENT PRESENTATION: Here we present an analysis of ceftaroline pharmacokinetics in a 5-y-old patient supported on ECMO due to influenza-associated necrotizing pneumonia.

RESULTS: A total of nine concentrations were analyzed, including three concentrations prior to cannulation and six on ECMO. ECMO cannulation was associated with a relatively small change in the volume of distribution (0.17 L/kg to …

A Rare Recurring Gain-Of-Function Variant In Bmpr2 Causes Neurodevelopmental Phenotypes In Humans And Flies, 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 …

Engagement And Weight Change In An Online Weight Management Program In Clinical Settings: An Implementation Project, 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 Genetic Risk Variant Associated With The Risk Of Primary Biliary Cholangitis Is Inherited From Neanderthals, 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 …

Training Apart, Together: Team Dynamics In Individual Sports And Surgical Residency, W. Jack Palmer, Dylan Bertoni, Elizabeth E. Cottrill, Colin T. Huntley

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Surgeons in training share notable parallels with competitive athletes, including rigorous training, skill specialization, and functioning under pressure. Surgical educators have leveraged this comparison, incorporating techniques from sports psychology, such as mental imagery and mindfulness, to improve trainees' individual performance and well-being. Surgical trainees and athletes both rely on effective teamwork for optimal outcomes, suggesting that residency leaders can glean valuable team-level insights from sports psychology. This article examines how the structure of surgical residency influences team dynamics, using concepts from sports psychology to identify evidence-based strategies for improving program cohesion and resident well-being. The surgical literature typically conceptualizes surgery …

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 …

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 Prospective Natural History Study Protocol For Clinical Trial Readiness In Synaptic Disorders, 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 …

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, …

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 …

Clinical Decision Support For Fall Prevention In Primary Care: The Esteps Cluster Randomized Clinical Trial, Nancy K Latham, Erin Hommel, Mackenzie Kiesman, Stuart R Lipsitz, David W Bates, Diane L Carroll, Alexandra C Frost, Pamela M Garabedian, Julia V Loewenthal, Michael Sainlaire, Lipika Samal, Wenyu Song, Matthew Wien, Patricia C Dykes

Faculty, Staff and Students Publications

Importance: Falls are a leading cause of injury among older adults. Although exercise reduces fall risk, implementation in primary care remains limited.

Objective: To assess whether an electronic health record-integrated clinical decision support intervention, Electronic Strategies for Tailored Exercise to Prevent Falls (eSTEPS), reduces falls among older primary care patients at increased risk.

Design, setting, and participants: This matched-pair cluster randomized clinical trial was conducted from June 9, 2023, to May 8, 2025, with 12 to 23 months of follow-up at primary care practices within an integrated health system in the US. Adults aged 65 years or older with a …

Spell: A Scalable Nlp Method Using Regular Expressions And Large Language Models For Clinical Information Extraction, Kathryn J Gray, Vesela P Kovacheva

Faculty, Staff and Students Publications

Background and objectives: Electronic health records (EHRs) contain valuable information for research and decision-making, but much resides in unstructured notes that are challenging to analyze at scale. We developed SPELL (Snippet-Primed rEgex LLM Pipeline), a scalable natural language processing workflow that combines regular-expression-based snippet retrieval with locally hosted large language model (LLM) inference to extract structured variables from large collections of clinical narratives.

Methods: SPELL uses task-specific regular expressions to retrieve short context windows ("snippets") from unstructured texts and applies task-prompted LLM inference on snippets rather than full documents. All processing occurs within institutional computing environments. Accuracy was evaluated on …

Social Responsiveness As A Mediator In Adapted Cognitive Behavioral Therapy For Autistic Youth With Maladaptive And Interfering Anxiety, 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) …

Cadherin-11 Regulation Of Type Ii Alveolar Epithelial Cells During Pulmonary Fibrosis, Mesias Pedroza, Sarah To, Jennifer Smith, Tingting W Mills, Thandiwe Chavula, Harry Karmouty-Quintana, Sandeep K Agarwal

Faculty, Staff and Students Publications

Type II alveolar epithelial cell (AT2) injury has been hypothesized to contribute to pulmonary fibrosis. Cadherin-11 (CDH11) is a mediator of fibrosis and is upregulated on AT2s during lung fibrosis. Herein, the regulation of AT2 by CDH11 during pulmonary fibrosis was investigated. CDH11 levels were increased in lung samples from patients with idiopathic pulmonary fibrosis compared with those from healthy controls. CDH11 expression was inversely correlated with lung function. Cdh11-deficient mice were compared with wild-type mice in the intraperitoneal bleomycin model (IP BLM), and the role of AT2 was investigated using Cdh11 floxed-SPC-Cre mice and in vitro techniques. In …

A Spatial Atlas Of Muscle-Invasive Bladder Cancer Reveals Lineage-Specific Vulnerabilities And Immune Architecture, Sajith Nair, Emanuele Crupi, Elshad Hasanov, Ying Mei, Xueshuai Han, Yang Liu, Yunhe Liu, Guangsheng Pei, Fuduan Peng, Jianlong Liao, Enyu Dai, Tian Chu, Kyung Serk Cho, Jiahui Jiang, Xinmiao Yan, Yibo Dai, Jun Wang, Baifeng Zhang, Giannicola Genovese, Nagireddy Putluri, Livia Eberlin, Liuqing Yang, Chunru Lin, Lawrence N Kwong, Diana Shamsutdinova, Khalida M Wani, Bogdan A Czerniak, Wendong Yu, Jianping Zhao, Charles C Guo, Donna Hansel, Curtis Pettaway, Louis Pisters, Kelly Bree, Neema Navai, Byron H Lee, Ashish M Kamat, Padmanee Sharma, Paul Corn, Cindy Y Jiang, Amishi Y Shah, Omar Alhalabi, Pavlos Msaouel, Arlene O Siefker-Radtke, Christopher J Logothetis, Matthew T Campbell, Alexander J Lazar, Jianjun Gao, Linghua Wang

Faculty, Staff and Students Publications

Muscle-invasive bladder cancer (MIBC) is clinically heterogeneous, and current molecular subtyping does not capture the spatial organization of tumor states and microenvironmental context. In this study, we construct a spatial atlas of MIBC by integrating spatial transcriptomics from 22 tumors with matched bulk RNA and whole-exome sequencing data. We identify a continuous, spatially organized luminal-to-basal axis within individual tumors that is associated with greater chromosomal instability and transcriptional plasticity. Luminal tumor cores are enriched for FGFR3 and NECTIN4, whereas basal-like states localize toward invasive margins and are associated with elevated EGFR signaling, epithelial-mesenchymal transition, genomic instability, immune infiltration, and greater …

Nlgn3 Autism Variants Have Distinct Functional Impact On Synapses And Sleep Behavior In Drosophila, 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 …

Cytogenetic And Molecular Findings In Hydrops-Related Mirror Syndrome, Brian A Burnett, Christian M Parobek, Jessian L Munoz, Lauren E Westerfield, Kristi Poling, Cara Buskmiller, Amir A Shamshirsaz, Roopali V Donepudi, Ignatia B Van Den Veyver, Magdalena Sanz Cortes, Michael A Belfort, Ahmed A Nassr

Faculty, Staff and Students Publications

Objective: Mirror syndrome is a rare, life-threatening condition in which maternal fluid overload mirrors fetal hydrops. Data on genetic findings in affected pregnancies are limited. We compared genetic diagnoses in hydrops cases with and without mirror syndrome.

Methods: We conducted a retrospective cohort study (2012-2023) of pregnancies with non-immune hydrops at a single fetal center. Clinical data along with prenatal and postnatal genetic testing results were analyzed. Mirror syndrome was defined as fetal hydrops with new or worsening hypertension and significant maternal edema. Genetic testing rates and diagnostic yields were compared between the groups.

Results: Of the 192 cases, 140 …

Understanding Gender Wage Disparities In Dermatology., Danielle Duffle, Ramiro Rodriguez, Benjamin Brooks, Robert Dellavalle

Ambulatory and Primary Care Articles

Differences in compensation between men and women exist, despite having similar experiences. Here, we present data from the Association of American Medical Colleges (AAMC) from 2022 of self-reported compensation rates of academic dermatologists. Women dermatologists comprised 36.95% (75/203) of full professors, 61.54% (152/247) of associate professors, and 63.47% (311/490) of assistant professors; among these, 52.17% (12/23) were service chiefs and 35.48 % (22/62) were department chairs. The data shows that, except for department chairs, women are reporting being paid less relative to men at all academic ranks. Division chiefs had the most significant (45.52%) wage difference (45.52%) between men and …

Individual Host Variation In Single-Cell Responses To Enteroaggregative Escherichia Coli Infection Modeled With Human Colon Organoids, Cristian Coarfa, Anthony W Maresso

Faculty, Staff and Students Publications

Enteroaggregative Escherichia coli (EAEC) is a leading cause of diarrhea worldwide. Interestingly, EAEC disease outcomes vary dramatically among infected individuals, ranging from asymptomatic colonization to acute and chronic diarrhea. While previous research has focused on EAEC virulence factors, emerging evidence suggests that host genetic and cellular background may be equally important in determining disease susceptibility. To understand host-driven disease heterogeneity, we performed single-cell RNA sequencing on human colon organoids (HCOs) derived from three healthy adult donors following EAEC 042 infection. Surprisingly, despite comparable EAEC adherence across donors, we observed striking donor-specific responses to infection at multiple levels. A total of …

Palopegteriparatide For Adults With Chronic Hypoparathyroidism: Skeletal Dynamics Through 3 Years Of The Phase 2 Path Forward Trial, Mishaela Rubin, Bart Clarke, Lorenz Hofbauer, Aliya Khan, Peter Schwarz, Tamara Vokes, Intekhab Ahmed, Andrea Palermo, Filomena Cetani, Uberto Pagotto, Carol Zhao, Michael Ominsky, Bryant Lai, Jenny Ukena, Aimee Shu, Lars Rejnmark

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

Hypoparathyroidism is an endocrine disease caused by insufficient levels of PTH, which acts directly on bone and kidney and indirectly on the intestine to regulate calcium and phosphate balance. In clinical trials, palopegteriparatide (TransCon PTH) treatment enabled independence from conventional therapy (no active vitamin D, ≤600 mg/d calcium) and maintained serum biochemistries within normal ranges. The current analyses describe patterns of change in BMD, serum bone turnover markers, and serum and urine calcium in adults with chronic hypoparathyroidism treated with palopegteriparatide through 3 years of the PaTH Forward trial. Baseline BMD Z-scores for the LS, TH, FN, and 1/3 distal …

Endothelial Perk Restricts Lymphoid Regeneration By Reducing Dll4-Notch3 Signaling At The Pre-B Niche, Yimin Ma, Jay Myers, Yinghui Shang, Mofei Huang, Paul Christensen, Stanley Adoro, Chih-Hang Anthony Tang, Chih-Chi Andrew Hu, Sai Ravi Kiran Pingali, Wei Xin, Keith Syson Chan, Stephen Wong, Youli Zu, Hamed Jafar-Nejad, Lan Zhou

Faculty, Staff and Students Publications

Delayed immune recovery after hematopoietic stem cell (HSC) transplantation is associated with a poor clinical outcome. We study the role of unfolded protein response (ER stress) in hematopoietic regeneration within the bone marrow (BM) microenvironment. We reveal that BM endothelium PERK activation is a prominent feature of patients with leukemia and is a hallmark response in mice following ionizing irradiation. Ablating endothelial Perk boosts NOTCH ligand DLL4 expression and promotes DLL4-dependent early HSC and B progenitor regeneration. Single-cell analysis reveals that endothelial DLL4 activates NOTCH3 expressed by mesenchymal stroma cells, and that the PERK-DLL4 axis coordinates the regulation of lymphoid …