Digital Commons Network^™

Latent Factor Modeling Reveals Unexpected Spatial Heterogeneity In Human Alzheimer's Disease Brain Transcriptomes, Rami Al-Ouran, Chaozhong Liu, Linhua Wang, Zhijian Yu, Ying-Wooi Wan, Chaohao Gu, Xiqi Li, Gerarda Cappuccio, Mirjana Maletic-Savatic, Aleksandar Milosavljevic, Joshua M Shulman, Hu Chen, Zhandong Liu

Faculty, Staff and Students Publications

Alzheimer's disease is characterized by complex molecular and cellular heterogeneity, which complicates efforts to identify consistent biomarkers and therapeutic targets. To better characterize the heterogeneity, we applied latent factor modeling to RNA sequencing data from approximately 2,500 human Alzheimer's disease brain samples, uncovering underlying patterns in gene expression. These transcriptional groups demonstrated unique gene expression profiles related to synaptic and neuronal pathways, vasculature development, and protein folding and antigen processing. Notably, this latent factor reflects variation in spatial sampling. Adjusting for the latent factor improved the identification of differentially expressed genes in disease samples. This finding suggests that spatial heterogeneity …

Rare But Relevant? Assessing Variants In Dystonia-Linked Genes In Parkinson's Disease, Lara M Lange, Zih-Hua Fang, Laurel Screven, Ai Huey Tan, Roy N Alcalay, Rim Amouri, Roberta Bovenzi, Matilda Fenn, Joshua L I Frost, Joseph Jankovic, Simona Jasaityte, Zane Jaunmuktane, Beomseok Jeon, Ignacio Juan Keller Sarmiento, Rejko Krüger, Gregor Kuhlenbäumer, Chin-Hsien Lin, Lukas Pavelka, Maria Teresa Periñan, Samia Ben Sassi, Tommaso Schirinzi, Jung Hwan Shin, Joshua M Shulman, Yi Wen Tay, Ryan Uitti, Tom Warner, Zbigniew K Wszolek, Lesley Wu, Ruey-Meei Wu, Kirsten E Zeuner, Cornelis Blauwendraat, Andrew Singleton, Niccolò E Mencacci, Huw R Morris, Shen-Yang Lim, Katja Lohmann, Christine Klein

Faculty, Staff and Students Publications

Background: Dystonia and Parkinson's disease (PD) exhibit clinical and genetic overlap, but the relevance of dystonia gene variants in PD remains unclear.

Objective: The aim was to assess the frequency of dystonia-linked pathogenic variants in PD.

Methods: We screened sequencing data from 15,684 individuals (8272 PD, 3200 atypical parkinsonism, and 4212 unaffected) from the Global Parkinson's Genetics Program (GP2) and Accelerating Medicines Partnership-Parkinson's Disease (AMP-PD) for variants in genes linked to isolated dystonia, dystonia-parkinsonism, and myoclonus-dystonia.

Results: Pathogenic variants were identified only in PD patients. Forty-five PD individuals (0.54%) carried 26 distinct (likely) pathogenic variants in nine dystonia-linked genes, most …

Highly Variable Expressivity Of A Cnv Deletion Involving Tbx4 In Three Deceased Siblings With Lung Developmental Disorder And Their Mildly Affected Mother And Grandfather, Przemyslaw Szafranski, Tomasz Gambin, Michal Kadlof, Michał Denkiewicz, Dariusz Plewczynski, Hyun Jeong Kim, Gail Deutsch, Nahir Cortes-Santiago, Salmo Raskin, Paweł Stankiewicz

Faculty, Staff and Students Publications

Single nucleotide variants (SNVs) and copy-number variant (CNV) deletions involving TBX4 have been associated with pulmonary arterial hypertension, ischiocoxopodopatellar syndrome, and lethal lung developmental disorders (LLDDs). Thus far, all large CNV deletions encompassing entire TBX4 have been found to have arisen de novo. Here, we present a three-generation family with three neonate siblings who died within 35-66 days due to histopathologically diagnosed LLDD. Whole-genome sequencing identified an ~108-kb CNV deletion encompassing TBX4 in all three infants. The deletion was also found in their mother with a history of pneumonia and persistent thick upper airway secretions and in the maternal grandfather …

Mapping The Structural Connections Between The Anterior Cingulate Cortex And The Insula/Ventrolateral Prefrontal Cortex.Mapping The Structural Connections Between The Anterior Cingulate Cortex And The Insula/Ventrolateral Prefrontal Cortex, Wei Tang, Javier Guaje, Shreyas Fadnavis, Sarah R Heilbronner, Eleftherios Garyfallidis

Faculty, Staff and Students Publications

The anterior cingulate cortex (ACC) is functionally closely related with the insula and the ventral lateral prefrontal cortex (vlPFC). The ACC and insula are the main hubs of the salience network, a set of functionally related brain regions involved in detecting salient stimuli and coordinating inter-network communication, while communication between ACC and vlPFC is closely linked to inhibitory control. However, despite strong indirect evidence from nonhuman primate (NHP) tract tracing, the structural connections between the ACC and the insula/vlPFC remain poorly understood in the human brain, in part because standard approaches fail to capture this projection. In this study, we …

Surgical Outcomes And Learning Curve Of Robotic Single-Port Vaginal Natural Orifice Transluminal Endoscopic Surgery (Vnotes) Hysterectomy Using The Da Vinci Single-Port System, Qiannan Yang, Daniel Y Lovell, Xiaoming Guan

Faculty, Staff and Students Publications

Objective: This study aims to assess the surgical outcomes and learning curve of robotic single-port vaginal natural orifice transluminal endoscopic surgery (RSP-vNOTES) for hysterectomy in benign gynecologic conditions.

Materials and methods: A retrospective observational analysis was conducted of 97 consecutively enrolled patients who underwent RSP-vNOTES hysterectomy using the da Vinci (single-port) SP system between December 2023 and July 2025 at a single tertiary care center.

Results: Median procedural durations included a total operative time of 151 minutes, a port placement time of five minutes, a docking time of two minutes, a robotic console time of 78 minutes, and a hysterectomy …

School-Level Gaps In Mmr Coverage As The Fuel For Measles Outbreaks, Meagan C Fitzpatrick, Chad R Wells, Abhishek Pandey, Lamia Ayaz, Peter J Hotez, Seyed M Moghadas, Alison P Galvani

Faculty, Staff and Students Publications

No abstract provided.

Point-Of-Care Ultrasound Foundations In Physics And Image Acquisition: An Innovative Hands-On Active Learning Workshop, Cherie Tator, Saul Flores, Alan Riley, Kiyetta Alade

Faculty, Staff and Students Publications

Introduction: We developed an innovative, active learning workshop to introduce foundations of point-of-care ultrasound (POCUS) physics and instrumentation. The workshop design aimed to reduce cognitive load and encourage learner-centered engagement through hands-on exploration that reinforces key principles and connects theory to practice.

Methods: First-year medical students participated in small-group, student-driven exercises to explore POCUS machine controls, transducers, and image acquisition skills. Each group was supported by a faculty member to guide activities and ensure accuracy. Students scanned pickles, hard-boiled eggs, and olives with pits; these items were selected for their low cost, sonographic characteristics, and recognizability. Later in the semester, …

A Strategy To Identify Biliary Atresia Efficiently: A Perspective From A Texas Center, Sanjiv Harpavat, Tebyan A Rabbani, Ashley M Upton, Sridevi Devaraj, Jose A Hernandez, Benjamin L Shneider

Faculty, Staff and Students Publications

Infants with biliary atresia are often diagnosed after 60 days of life because the disease is difficult to detect in its early stages. However, infants treated before 30-45 days of life have the best long-term outcomes. To help accelerate the biliary atresia diagnosis, we have developed a streamlined strategy that involves two sequential tests: (1) direct or conjugated bilirubin measurements and (2) a feeding abdominal ultrasound exam. In this review, the strategy is shared to encourage others to provide feedback as well as to consider incorporating portions into their own clinical workflows.

Wnt4 Deficiency Impacts Heart, Diaphragm, And Palate Development: Insights From Human Genetics, Machine Learning, And Mouse Models, Andrés Hernández-García, Bum Jun Kim, David Chitayat, Patrick Shannon, Stephanie Hedges, Maria Al Bandari, Maria J Guillen Sacoto, Emily Anne Bates, Yunus H Ozekin, Victor Faundes, Pamela N Luna, Chad A Shaw, Tara L Rasmussen, Chih-Wei Hsu, Daryl A Scott

Faculty, Staff and Students Publications

WNT4 is a secreted protein that plays a critical role in the regulation of cell fate and embryogenesis. Biallelic variants in WNT4 have been linked to SERKAL syndrome, an autosomal recessive disorder characterized by 46,XX sex reversal and dysgenesis of the kidneys, adrenals, and lungs. SERKAL syndrome has only been described in a single consanguineous kindred with four affected fetuses. Additional features seen in a subset of affected fetuses included ventricular septal defect (VSD), congenital diaphragmatic hernia (CDH), and orofacial clefting (OFC). To determine if these additional features were likely to be caused by WNT4 deficiency, we used machine learning …

Phase I Study Of Niraparib With Radiotherapy For Treatment Of Metastatic And Locally Advanced Invasive Carcinoma Of The Cervix (Nivix), Piyush Pathak, Eunji Jo, Susan Hilsenbeck, Matthew L Anderson, Alfredo Echeverria, Shelly Sharma, Jan Sunde, Tracilyn Hall, Anthony Costales, Claire Hoppenot, Michelle Ludwig

Faculty, Staff and Students Publications

Introduction: This Phase I study evaluated the safety and tolerability of concurrent niraparib, an oral poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, with definitive radiotherapy in women with locally advanced or platinum-sensitive metastatic cervical cancer. Dose escalation followed a Bayesian Optimal Interval (BOIN) design with a target dose-limiting toxicity (DLT) rate of 30%.

Methods: Women ≥18 years with FIGO stage IIIC2 (bulky nodes >1 cm) or stage IV cervical cancer demonstrating response to platinum-based induction chemotherapy were eligible. Niraparib 100 mg was administered daily concurrent with pelvic radiotherapy (45-57.5 Gy via IMRT with nodal boosts) and brachytherapy, continuing 28 days post-radiation. Per …

Immune-Mediated Diarrhea And Colitis With Normal Biochemical, Endoscopic And Histologic Findings: A Retrospective Study, Malek Shatila, Sharada Wali, Carolina Colli Cruz, Kei Takigawa, Andres Caleb Urias Rivera, Kian Abdul-Baki, Tanvi Gupta, Elliot Baerman, Linfeng Lu, Irene Jeong-Ah Lee, Raakhi Menon, Hamza Salim, Andrew Sullivan, Varun Vemulapalli, Cristina Natha, Ayesha Khan, Krishnavathana Varatharajalu, Stephane Champiat, Kerry L Reynolds, Lucy B Kennedy, Katy Tsai, Anusha Shirwaiker Thomas, Yinghong Wang

Faculty, Staff and Students Publications

Background: Immune-mediated diarrhea and colitis (IMDC) due to checkpoint inhibition infrequently presents with normal stool biomarkers and no endoscopic or histologic evidence of inflammation. Little is known about the treatment needs and outcomes of this subset of patients. We aimed to describe this entity and clarify the role of immunosuppressive treatments in its management.

Method: This was a single-center, retrospective study of patients treated with immune checkpoint inhibitors who developed clinical symptoms of IMDC, with no evidence of inflammation based on fecal calprotectin or endoscopic/histologic evaluation, between January 2010 and February 2024.

Results: Of 1151 patients with IMDC, 131 (11.4%) …

Hemispherotomy For Drug-Resistant Epilepsy In A Low-Resource Setting: Surgical Outcomes And Quality Of Life In 23 Children Treated In A Hybrid Program In Panama, Emmajane G Rhodenhiser, David Bonda, Carmen Baez, Hannah K Weiss, Yosef Dastagirzada, Guzman Aranda, Laurent Bruggeman, Ameeta Grover, Shaun D Rodgers, Ruben Kuzniecky, Yvonne Zelenka-Kuzniecky, Howard L Weiner, Eveline Teresa Hidalgo

Faculty, Staff and Students Publications

Introduction: Hemispherotomy is an effective treatment for children with drug-resistant epilepsy (DRE). While hemispherotomy techniques and indications have evolved, access remains predominantly constrained to high-resource settings.

Methods: We performed a retrospective analysis of children who underwent hemispherotomy from 2011 to 2023 by a hybrid team, including local Panamanian and US neurologists, neurosurgeons, and EEG technicians and analyzed surgical, epilepsy, and quality of life (QoL) parameters. Follow-up data were collected according to the International Consortium for Health Outcomes Measurement (ICHOM) guidelines for children with epilepsy.

Results: Twenty-three children underwent hemispherotomy. The median age at surgery was 10 years (range 2-20). The …

Intercornual Distance And Postoperative Reproductive Outcomes In Moderate-To-Severe Intrauterine Adhesions: A Retrospective Cohort Study, Yifu He, Xingping Zhao, Huan Huang, Changfa Shu, Xiaoming Guan, Jia Guo, Dabao Xu

Faculty, Staff and Students Publications

Study question: Does intercornual distance (ICD), as reflected by intrauterine stent size during hysteroscopic adhesiolysis, have an association with reproductive outcomes and provide information for postoperative risk stratification in women with moderate-to-severe intrauterine adhesions?

Summary answer: A smaller ICD was independently associated with a lower likelihood of clinical pregnancy within 1 year of the final hysteroscopy and may offer additional information for postoperative risk stratification in women with moderate-to-severe intrauterine adhesions.

What is known already: Reproductive outcomes following treatment for moderate-to-severe intrauterine adhesions vary considerably. Existing severity classifications offer limited discrimination within this group. The potential association between ICD and …

Dynamic Progression Of Ectopic Lymphoid Structure Formation In Lacrimal Glands Of A Sjögren’S Disease Murine Model, Sara Abdelhamid, Alison V Ramirez, Emre Aksan, Elizaveta A Demianova, Cintia S De Paiva, Maria C Edman, J Andrew Mackay, Sarah F Hamm-Alvarez

Faculty, Staff and Students Publications

Background: Sjögren's Disease (SjD) is a chronic autoimmune condition characterized by lymphocytic infiltration of lacrimal glands (LG) and salivary glands (SG). In SG, these immune structures have properties of ectopic lymphoid structures (ELS) and appear to play a critical role in disease pathology. While the presence of ELS in patients' SG biopsies is linked to disease severity, their presence and composition in LG has not been well characterized.

Methods: The properties and time course of apparent ELS development in LG from the male non-obese diabetes free (NOR) sub-strain of the Non-Obese Diabetic (NOD) mice was investigated at stages encompassing early …

Disrupted Intrathalamic And Thalamocortical Structural Covariance Networks In Posttraumatic Stress Disorder, Nick Steele, Ahmed Hussain, Delin Sun, C Lexi Baird, Courtney Russell, Neda Jahanshad, Lauren E Salminen, Miranda Olff, Jessie L Frijling, Dick J Veltman, Saskia B J Koch, Laura Nawijn, Mirjam Van Zuiden, Li Wang, Ye Zhu, Gen Li, Dan J Stein, Jonathan Ipser, Sheri Koopowitz, Yuval Neria, Xi Zhu, Orren Ravid, Sigal Zilcha-Mano, Amit Lazarov, Benjamin Suarez-Jimenez, Ashley A Huggins, Jennifer Stevens, Kerry Ressler, Tanja Jovanovic, Sanne J H Van Rooij, Negar Fani, Emily L Dennis, David F Tate, David X Cifu, William C Walker, Elisabeth A Wilde, Ivan Rektor, Pavel Říha, Milissa L Kaufman, Lauren A M Lebois, Justin T Baker, Anthony King, Israel Liberzon, Mike Angstadt, Nicholas D Davenport, Seth G Disner, Scott R Sponheim, Thomas Straube, David Hofmann, Guang Ming Lu, Rongfeng Qi, Amit Etkin, Adi Maron-Katz, Xin Wang, Austin Kunch, Hong Xie, Yann Quidé, Wissam El-Hage, Shmuel Lissek, Hannah Berg, Steven E Bruce, Josh Cisler, Marisa Ross, Ryan Herringa, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine Larson, Terri A Deroon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Brandee Feola, Jennifer U Blackford, Bunmi O Olatunji, Geoffrey May, Steven M Nelson, Evan M Gordon, Chadi G Abdallah, Ruth Lanius, Maria Densmore, Jean Théberge, Richard W J Neufeld, Paul M Thompson, Rajendra A Morey

Faculty, Staff and Students Publications

The thalamus is a heterogeneous structure crucial for corticocortical communication, affective–perceptual integration, motor preparation, and memory-related functions. Posttraumatic stress disorder (PTSD) is characterized by various symptoms that likely relate to thalamic functions. Group-level and individual differential structural covariance (SC) analyses were conducted on intrathalamic, thalamocortical, and thalamosubcortical volumetric networks by segmenting structural MRI data from 2,784 subjects (PTSD n = 1,306; controls n = 1,478) into 25 thalamic nuclei per hemisphere. We found that PTSD was associated with stronger intrathalamic and thalamocortical network strength and stronger SC between the limbic thalamus and the somatomotor and auditory thalamus. PTSD severity was …

Updates In Mycobacterial Keratitis Diagnosis And Treatment, Uma L Balakrishnan, Ryan T Wallace, Patricia Chévez-Barrios, Alejandro Arboleda, Masih U Ahmed

Faculty, Staff and Students Publications

Mycobacterial keratitis is an uncommon but challenging form of infectious keratitis, often associated with postsurgical eyes. Clinical presentation is variable and may be difficult to recognize, resulting in delays in diagnosis and challenges in management. Traditional diagnostic techniques from corneal scrapings are limited by slow organism growth and may yield negative results. Treatment is challenging due to antimicrobial resistance and typically requires prolonged multidrug therapy. Advances in diagnostic modalities, antimicrobial therapies, surgical approaches, and adjunctive treatments such as corneal crosslinking have improved clinicians' ability to mitigate or avoid severe visual consequences. Despite these developments, optimal management strategies remain incompletely defined, …

Professionalism In Practice: A Novel Approach To Integrating Small Doses Of Case-Based Professionalism Education Into Monthly Grand Rounds., Allison H Taylor, Andrew Caruso, Kelley Arredondo, Ellen M Friedman, Stacey R Rose

Faculty, Staff and Students Publications

Introduction: Professionalism is a critical construct across the health professions, though learners and faculty report feeling underprepared to navigate difficult situations; education in professionalism is challenged by the absence of a universal definition, time constraints due to overcrowded curricula, and the lack of consistent messaging to learners and faculty.

Methods: Professionalism in Practice (PiP) was developed to provide small doses (∼5 minutes) of case-based professionalism education as part of an existing educational forum (Grand Rounds) to optimize attendance of both learners and faculty. Each vignette highlighted a common professionalism challenge and was aligned with an AAMC professional competency. Sessions were …

Challenges In The Diagnosis Of Concurrent T-Lymphoblastic Leukemia/Lymphoma And Thymic Neuroendocrine Carcinoma: A Case Report, Kristen Oliveira, Mary Doan, Ying Pei, Marwan Yared, Songlin Zhang

Faculty, Staff and Students Publications

The co-occurrence of T-lymphoblastic leukemia/lymphoma and thymic neoplasia is a rare event that can present a diagnostic challenge. In this case report, we describe a 31-year-old man who was found to have thymic neuroendocrine carcinoma and T-lymphoblastic leukemia/lymphoma 2 years after initial treatment for T-lymphoblastic leukemia/lymphoma. The thymic neuroendocrine carcinoma was initially detected in a malignant pleural effusion, and a retrospective review of a preceding lung biopsy suggested the involvement of both tumors within one tissue sample. Immunohistochemical analysis was imperative in highlighting these two elements because despite their unique cytomorphological characteristics, a limited amount of each component was seen …

When Targeted Gene Testing Falls Short: Case Report Of A Novel Slc4a3 F347s Genetic Variant Associated With Short Qt Syndrome, Chelsea A Boyd, Tyler J Novy, Taylor A Beecroft-Dawson, Connor A Bell, Emily M Bland, Christina Y Miyake

Faculty, Staff and Students Publications

No abstract provided.

Host- And Pathogen-Related Determinants Of Pulmonary Versus Extrapulmonary Tuberculosis, Begna Tulu, Thomas Theo Brehm, Reinout Van Crevel, Tobias Dallenga, Andrew R Dinardo, Keertan Dheda, Johanna Eggeling, Wendemagegn Enbiale, Matthias I Gröschel, Jialun Hao, Vinod Kumar, Arjan Van Laarhoven, Rolanda Londt, Gareth Prosser, Philippa Randall, Norbert Reiling, Jan Rybniker, Ulrich E Schaible, Erwin Schurr, Isabelle Suarez, Sebastian J Theobald, Robert J Wilkinson, Christoph Lange

Faculty, Staff and Students Publications

Tuberculosis (TB) primarily manifests as pulmonary TB (PTB), but extrapulmonary TB (EPTB) remains a major clinical challenge. Distinct diagnostic and therapeutic difficulties arise from differences in immune responses, pathogen behaviour and host susceptibility. However, the factors driving disease localisation are still incompletely understood. We conducted a comprehensive narrative review of studies examining differences between PTB and EPTB in terms of epidemiology, mycobacterial factors, genetic and epigenetic determinants, host immune responses, transcriptomic profiles, cytokine and chemokine patterns, and immunophenotypes. EPTB is more common among females, children, older adults and immunocompromised individuals with deficient granuloma formation. This review is intended to provide …

Improving Compliance With Safe Sleep Guidelines For Vulnerable Patients In A Community Safety Net Hospital Neonatal Intensive Care Unit, Andrew Beverstock, Samantha Carlton, Hillary Lee, Thomas Lu, Kelsi Morgan, Ashlee Smith-Patel, Kelli Phillips, Joseph Hagan, Pablo Lohmann, Caraciolo Fernandes, Lisa Owens, Daniela Dinu

Faculty, Staff and Students Publications

Objectives: Congenital diaphragmatic hernia (CDH) often coexists with fetal growth restriction (FGR). The observed-to-expected (O/E) total fetal lung volume (TFLV) is used to assess CDH severity, predict outcomes, and direct fetal interventions. Expected TFLV measurements traditionally rely only on gestation age (GA). This simulation assesses how incorporating weight-adjusted GA norms affects O/E TFLV calculations in patients with isolated CDH and FGR.

Methods: A simulated dataset (n=1,005) utilized published mean fetal weight and TFLV references. Computer-generated variables included observed weights (3rd-10th %ile), O/E TFLV (10-65 %), and percent liver herniation (0-42 %). GA estimates were corrected by weight and used to …

Use Of A Medication Management Algorithm In Depressed Youth Living With Hiv: Secondary Analysis Of A Multisite Randomized Controlled Trial, Graham J Emslie, Beth D Kennard, Kristin Baltrusaitis, Sophia M Jones, Jessica M Jones, Jaime G Deville, Kathleen Pitts, David E Shapiro, Allison Eliscu, Larry K Brown

Faculty, Staff and Students Publications

Objectives: Depression is a prevalent co-occurring condition in youth living with HIV. This report is a secondary analysis of a multisite cluster randomized trial evaluating the efficacy of a health and wellness cognitive behavioral therapy (CBT) combined with a medication management algorithm utilizing measure-based care (COMB-R) compared with enhanced standard of care (ESC). We describe and compare antidepressant prescribing strategies (i.e., antidepressant treatment, type of antidepressant) for youth living with HIV at COMB-R sites to those at ESC sites over the 24-week intervention. We also describe self-reported adherence to antidepressants.

Methods: Participants (12-24 years) were youth living with HIV diagnosed …

Injuries In Children Undergoing Subspecialty Abuse Evaluations Because Of Intimate Partner Violence, M Katherine Henry, Gunjan Tiyyagura, Joanne N Wood, Jan Leonard, Kristine A Campbell, Daniel M Lindberg, Angela N Bachim, Farah W Brink, Lori D Frasier, Nancy S Harper, Claire Hickey, Natalie Laub, John D Melville, Hannah Sahud, Philip V Scribano

Faculty, Staff and Students Publications

Background and objectives: Intimate partner violence (IPV) and child physical abuse often co-occur, but the frequency and risk factors for abusive injuries in IPV-exposed children remain unknown. Our objectives were to (1) determine frequency of skeletal surveys (SSs) and neuroimaging use because of IPV and their diagnostic value in children aged less than 24 months evaluated by a child abuse pediatrics specialist (CAP) and (2) identify factors associated with performance of and findings on SS and neuroimaging.

Methods: We conducted a retrospective study of children aged less than 24 months undergoing CAP consultations because of IPV exposure from February 2021 …

Tracheobronchial Mucoepidermoid Carcinoma In Four Pediatric Patients, Kalen Hendra, Muhammad Ijlal Khan, Mitali Thanawala, Manuel Silva-Carmona, Eric D Zee

Faculty, Staff and Students Publications

Pediatric tracheobronchial mucoepidermoid carcinoma (MEC), also called pulmonary MEC, is a rare malignant primary lung neoplasm that is typically found in the large airways. Patients may present with symptoms such as cough, pneumonia, fever, hemoptysis, dyspnea, wheezing, chest pain, weight loss, and fatigue. These nonspecific symptoms (or lack of symptoms in some cases) often result in a delayed diagnosis. Chest CT typically demonstrates findings consistent with bronchial obstruction and diagnosis is made via histopathology. Surgical resection is the mainstay of treatment and children often have favorable outcomes. Here we present four cases of tracheobronchial MEC in children treated at three …

Left Atrial Appendage Closure Devices: A Contemporary Review Of Techniques, Tips And Tricks, Kamran Namjouyan, Hafeez Ul Hassan Virk, Affan Rizwan, Muzamil Khawaja, Mahboob Alam, Markus Strauss, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Atrial fibrillation (AF) affects approximately 3%-5% of adults and is projected to double in prevalence by 2060, significantly increasing the burden of thromboembolic stroke. This risk is largely attributed to thrombus formation within the left atrial appendage (LAA), particularly in nonvalvular AF, where the LAA's trabeculated anatomy, diverse morphologies (e.g., chicken wing, windsock, cactus, cauliflower), and impaired contractility allows for blood stasis and thrombogenesis. As a result, the LAA has become a focus for stroke prevention strategies. This review demonstrates current evidence on LAA closure by discussing patient selection, anatomical feasibility, procedural workflow, imaging guidance (transesophageal echocardiography vs. intracardiac echocardiography), …

A Practical Approach To The Management Of Percutaneous Coronary Intervention Complications, Tanawat Attachaipanich, Hafeez Ul Hassan Virk, Muzamil Khawaja, Mahboob Alam, Ravi S Hira, Jacob A Doll, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Introduction: Despite advances in stent design, pharmacotherapy, and procedural techniques that have improved percutaneous coronary intervention (PCI) outcomes and reduced PCI-related complications, these events still occur and are associated with adverse outcomes. Moreover, complex PCI procedures, which predispose to increased risk of complications, are increasingly performed. Understanding risk factors, underlying mechanisms, evidence-based management, and preventive strategies are essential to optimize procedural outcomes. This review aims to summarize current evidence and highlight gaps in knowledge related to PCI-associated complications.

Methods: This narrative review used a focused PubMed search through October 2025, prioritizing randomized trials, large observational studies, guidelines, and consensus statements. …

Assessment Of In-Frame Indel Variants In An Unsolved Cohort Of Inherited Retinal Diseases Using Machine Learning, David E Rauch, Meng Wang, Muhammad Jafar Hussain Hafiz, Daniel C Brock, Yumei Li, Molly Marra, Mark E Pennesi, Paul Yang, Everett Lesley, Irma Lopez, Robert Koenekoop, Edward Ryan Collantes, Joanne Bolinao, Rui Chen

Faculty, Staff and Students Publications

The standard for in silico pathogenicity prediction of in-frame insertions and deletions (indels) is less established compared to other types of variations. We aimed to systematically assess the performance of in silico machine learning (ML) tools on a patient cohort with inherited retinal diseases (IRDs). The performance of four ML tools (CADD, FATHMM-indel, VEST4, and MetaRNN-indel) was compared. Among them, MetaRNN-indel showed the best overall results. MetaRNN-indel was then applied to 1013 unsolved IRD patients, identifying two likely pathogenic causal variants in two unrelated IRD patients by confirming clinical phenotypes. Hence, our findings indicate that reliable prediction of the pathogenicity …

Editorial: Advances In Phage Applications: Deciphering Phage Biological And Ecological Mechanisms Through Metagenomics, Tasha M Santiago-Rodriguez, Gary A Toranzos

Faculty, Staff and Students Publications

No abstract provided.

Discovery Of Genetic Susceptibility Variants In Pediatric And Adult Ependymoma, Joshua D Strauss, Priya B Shetty, Spiridon Tsavachidis, Jinyoung Byun, Stephen C Mack, Xiao Xiangjun, Terri S Armstrong, Mark R Gilbert, (On Behalf Of Nci-Connect);, Lisa Mirabello, Smita Bhatia, Wendy M Leisenring, Lindsay M Morton, Gregory T Armstrong, Jon Foss-Skiftesvik, Christian Munch Hagen, Jonas Bybjerg-Grauholm, (On Behalf Of Gicc), Manel Ghozal, Audrey Bonaventure, Jacqueline Clavel, Melissa L Bondy, Christopher I Amos, Thanh T Hoang, Michael E Scheurer

Faculty, Staff and Students Publications

Background: Ependymoma is a malignancy of the neuroepithelium-derived ependyma that lines the spinal cord and ventricles of the brain, occurring most frequently in young children and older adults. Genetic susceptibility to ependymoma has proven difficult to assess due to disease rarity.

Methods: We performed genome-wide association studies (GWAS) of 478 ependymoma patients and 4,841 disease-free controls of European ancestry. Ependymoma patients consisted of 117 children (< 18 years old) with whole-genome sequencing (WGS), 142 children with genotyping, and 219 adults (≥18 years old) with genotyping. Genotyped samples were imputed using the 1,000 Genomes Project as the reference panel and underwent quality control filtering. The GWAS was performed separately by age group and technology (genotyped or WGS). GWAS variants were considered significant at P < 5 × 10-8.

Results: Among pediatric subjects with WGS data, we identified a significant intronic variant in EDIL3 (rs149378, P = 1.9 × 10-8) and a nearly significant intronic variant in LHX4 (rs79008224, P = 7.2 …

Acmg Medical Directors’ Special Interest Group Survey: Current Challenges For Medical Genetics Clinics, Mark Dulchavsky, Catherine E Keegan, Nathaniel H Robin, Chad Haldeman-Englert, Shweta U Dhar, Fuki M Hisama

Faculty, Staff and Students Publications

Purpose: The American College of Medical Genetics and Genomics Medical Directors' Special Interest Group (SIG) began in 2021 as a forum for directors of medical genetics clinical groups to share questions, concerns, current practices, and solutions regarding clinical operations. We report on the first 4 years of the SIG-its membership growth and SIG activities. We also present quantitative and qualitative results of a nationwide survey of 66 SIG members addressing recurrent questions from members regarding: wait times, volume of referrals, clinical workload expectations, and independent practice of genetic counselors (GCs) and advanced practice providers.

Methods: Cross-sectional survey of American College …