Medicine and Health Sciences Commons^™

Preclinical Efficacy Of Cdk7 Inhibitor-Based Combinations Against Myeloproliferative Neoplasms Transformed To Aml, Warren Fiskus, Christopher P Mill, Prithviraj Bose, Lucia Masarova, Naveen Pemmaraju, Andrew Dunbar, Christine E Birdwell, John A Davis, Kaberi Das, Hanxi Hou, Taghi Manshouri, Antrix Jain, Anna Malovannaya, Kevin Philip, Noor Alhamadani, Alicia Matthews, Katie Lin, Lauren B Flores, Sanam Loghavi, Courtney Dinardo, Xiaoping Su, Raajit K Rampal, Kapil N Bhalla

Faculty, Staff and Student Publications

Rising blast percentage or secondary acute myeloid leukemia (sAML) transformation in myeloproliferative neoplasms (MPNs) leads to JAK1/2 inhibitor (JAKi) therapy resistance and poor survival. Here, we demonstrate that treatment with the CDK7 inhibitor (CDK7i) SY-5609 depletes phenotypically characterized post-MPN sAML stem/progenitor cells. In cultured post-MPN sAML SET2, HEL and patient-derived (PD) post-MPN sAML cells, SY-5609 treatment inhibited growth and induced lethality while sparing normal cells. RNA-sequencing analysis after SY-5609 treatment reduced mRNA expression of MYC, MYB, CDK4/6, PIM1, and CCND1 but increased expression of CDKN1A and BCL2L1. Mass spectrometry of SY-5609-treated MPN-sAML cells also reduced c-Myc, c-Myb, PIM1, and CDK4/6 …

Characterizing Features Affecting Local Ancestry Inference Performance In Admixed Populations, Jessica Honorato-Mauer, Nirav N Shah, Adam X Maihofer, Clement C Zai, Sintia Belangero, Caroline M Nievergelt, Marcos Santoro, Elizabeth G Atkinson

Faculty, Staff and Students Publications

In recent years, significant efforts have been made to improve methods for genomic studies of admixed populations using local ancestry inference (LAI). Accurate LAI is crucial to ensure that downstream analyses accurately reflect the genetic ancestry of research participants. Here, we test analytic strategies for LAI to provide guidelines for optimal accuracy, focusing on admixed populations reflective of Latin America's primary continental ancestries-African (AFR), Amerindigenous (AMR), and European (EUR). Simulating linkage-disequilibrium-informed admixed haplotypes under a variety of 2- and 3-way admixture models, we implemented a standard LAI pipeline, testing the impact of reference panel composition, DNA data type, demography, and …

Dna-Binding Affinity And Specificity Determine The Phenotypic Diversity In Bcl11b-Related Disorders, Ivana Lessel, Anja Baresic, Ivan K Chinn, Jonathan May, Anu Goenka, Kate E Chandler, Jennifer E Posey, Alexandra Afenjar, Luisa Averdunk, Maria Francesca Bedeschi, Thomas Besnard, Rae Brager, Lauren Brick, Melanie Brugger, Theresa Brunet, Susan Byrne, Oscar De La Calle-Martín, Valeria Capra, Paul Cardenas, Céline Chappé, Hey J Chong, Benjamin Cogne, Erin Conboy, Heidi Cope, Thomas Courtin, Wallid Deb, Robertino Dilena, Christèle Dubourg, Magdeldin Elgizouli, Erica Fernandes, Kristi K Fitzgerald, Silvana Gangi, Jaya K George-Abraham, Muge Gucsavas-Calikoglu, Tobias B Haack, Medard Hadonou, Britta Hanker, Irina Hüning, Maria Iascone, Bertrand Isidor, Irma Järvelä, Jay J Jin, Alexander A L Jorge, Dragana Josifova, Ruta Kalinauskiene, Erik-Jan Kamsteeg, Boris Keren, Elena Kessler, Heike Kölbel, Mariya Kozenko, Christian Kubisch, Alma Kuechler, Suzanne M Leal, Juha Leppälä, Sharon M Luu, Gholson J Lyon, Suneeta Madan-Khetarpal, Margherita Mancardi, Elaine Marchi, Lakshmi Mehta, Beatriz Menendez, Chantal F Morel, Sue Moyer Harasink, Dayna-Lynn Nevay, Vincenzo Nigro, Sylvie Odent, Renske Oegema, John Pappas, Matthew T Pastore, Yezmin Perilla-Young, Konrad Platzer, Nina Powell-Hamilton, Rachel Rabin, Aisha Rekab, Raissa C Rezende, Leema Robert, Ferruccio Romano, Marcello Scala, Karin Poths, Isabelle Schrauwen, Jessica Sebastian, John Short, Richard Sidlow, Jennifer Sullivan, Katalin Szakszon, Queenie K G Tan, Undiagnosed Diseases Network, Matias Wagner, Dagmar Wieczorek, Bo Yuan, Nicole Maeding, Dirk Strunk, Amber Begtrup, Siddharth Banka, James R Lupski, Eva Tolosa, Davor Lessel

Faculty, Staff and Students Publications

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive. To dissect these, we performed genotype-phenotype correlations of 92 affected individuals harboring a pathogenic or likely pathogenic BCL11B variant, followed by immune phenotyping, analysis of chromatin immunoprecipitation DNA-sequencing data, dual-luciferase reporter assays, and molecular modeling. These integrative analyses enabled us to define three clinical subtypes of BCL11B-related disorders. …

Design And Implementation Of An Action Plan For Justice, Equity, Diversity, And Inclusion Within The Clinical Genome Resource, Alice B Popejoy, Deborah I Ritter, Danielle Azzariti, Jonathan S Berg, Joanna E Bulkley, Mildred Cho, Claudia Gonzaga-Jauregui, Teri E Klein, Daphne O Martschenko, Akinyemi Oni-Orisan, Erin M Ramos, Heidi L Rehm, Erin R Riggs, Matthew W Wright, Michael Yudell, Sharon E Plon, Joannella Morales

Faculty, Staff and Students Publications

How might members of a large, multi-institutional research and resource consortium foster justice, equity, diversity, and inclusion as central to its mission, goals, governance, and culture? These four principles, often referred to as JEDI, can be aspirational-but to be operationalized, they must be supported by concrete actions, investments, and a persistent long-term commitment to the principles themselves, which often requires self-reflection and course correction. We present here the iterative design process implemented across the Clinical Genome Resource (ClinGen) that led to the development of an action plan to operationalize JEDI principles across three major domains, with specific deliverables and commitments …

Differentiating Between Renal Medullary And Clear Cell Renal Carcinoma With A Machine Learning Radiomics Approach, Rahim Jiwani, Koustav Pal, Iwan Paolucci, Bruno Odisio, Kristy Brock, Nizar M Tannir, Daniel D Shapiro, Pavlos Msaouel, Rahul A Sheth

Faculty, Staff and Student Publications

Background: The objective of this study was to develop and validate a radiomics-based machine learning (ML) model to differentiate between renal medullary carcinoma (RMC) and clear cell renal carcinoma (ccRCC).

Methods: This retrospective Institutional Review Board -approved study analyzed CT images and clinical data from patients with RMC (n = 87) and ccRCC (n = 93). Patients without contrast-enhanced CT scans obtained before nephrectomy were excluded. A standard volumetric software package (MIM 7.1.4, MIM Software Inc.) was used for contouring, after which 949 radiomics features were extracted with PyRadiomics 3.1.0. Radiomics analysis was then performed with RadAR for differential radiomics …

Proceedings Of The 1st Biannual Bridging The Gaps In Lung Cancer Conference, Narjust Florez, Sandip P Patel, Heather Wakelee, Lyudmila Bazhenova, Erminia Massarelli, Ravi Salgia, Brendon Stiles, Solange Peters, Jyoti Malhotra, Shirish M Gadgeel, Jorge J Nieva, Michelle Afkhami, Fred R Hirsch, Matthew Gubens, Tina Cascone, Benjamin Levy, Joshua Sabari, Hatim Husain, Patrick C Ma, Leah M Backhus, Puneeth Iyengar, Percy Lee, Russell Miller, Jacob Sands, Edward Kim

Faculty, Staff and Student Publications

Lung cancer is the leading cause of cancer death in the US and globally. The mortality from lung cancer has been declining, due to a reduction in incidence and advances in treatment. Although recent success in developing targeted and immunotherapies for lung cancer has benefitted patients, it has also expanded the complexity of potential treatment options for health care providers. To aid in reducing such complexity, experts in oncology convened a conference (Bridging the Gaps in Lung Cancer) to identify current knowledge gaps and controversies in the diagnosis, treatment, and outcomes of various lung cancer scenarios, as described here. Such …

Oncogenic Kras Mutations Confer A Unique Mechanotransduction Response To Peristalsis In Colorectal Cancer Cells, Abigail J Clevenger, Claudia A Collier, John Paul M Gorley, Sarah Colijn, Maygan K Mcfarlin, Spencer C Solberg, Scott Kopetz, Amber N Stratman, Shreya A Raghavan

Faculty, Staff and Student Publications

Colorectal cancer tumors start as polyps on the inner lining of the colorectum, in which they are exposed to the mechanics of peristalsis. Our previous work leveraged a custom-built peristalsis bioreactor to demonstrate that colonic peristalsis led to cancer stem cell enrichment in colorectal cancer cells. However, this malignant mechanotransductive response was confined to select colorectal cancer lines that harbored an oncogenic mutation in the Kirsten rat sarcoma virus (KRAS) gene. In this study, we explored the involvement of activating KRAS mutations on peristalsis-associated mechanotransduction in colorectal cancer. Peristalsis enriched cancer stem cell marker Leucine-rich repeat-containing G protein-coupled receptor 5 …

Differences In Provider Beliefs And Delivery Of The 5as For Cigarette And Non-Cigarette Tobacco Use Between Two Types Of Healthcare Centers Serving Rural And/Or Medically Underserved Areas Of Texas, Us, Ammar D Siddiqi, Brian J Carter, Maggie Britton, Tzuan A Chen, Isabel Martinez Leal, Asfand B Moosa, Teresa Williams, Kathleen Casey, Hector Sanchez, Lorraine R Reitzel

Faculty, Staff and Student Publications

Background/objectives: Rural populations in the US bear a disproportionate burden of cancer mortality, which may be partly due to their elevated tobacco use and the limited receipt of tobacco use interventions in rural healthcare settings. Here, we examine providers' use of the 5As (Ask, Advise, Assess, Assist, and Arrange), a brief tobacco cessation intervention, with their patients to assess intervention gaps.

Methods: Provider practices in substance use treatment centers (SUTCs) and medical healthcare centers (MHCs), each serving rural and/or medically underserved areas (MUAs) of Texas, were compared. In total, 347 providers from 10 SUTCs (n = 174) and 9 …

Heterogeneous Clinical Phenotypes Of Sporadic Early-Onset Alzheimer's Disease: A Neuropsychological Data-Driven Approach, Deepti Putcha, Erik Musiek, Kyle Womack, Et Al.

2020-Current year OA Pubs

BACKGROUND: The clinical presentations of early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease are distinct, with EOAD having a more aggressive disease course with greater heterogeneity. Recent publications from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) described EOAD as predominantly amnestic, though this phenotypic description was based solely on clinical judgment. To better understand the phenotypic range of EOAD presentation, we applied a neuropsychological data-driven method to subtype the LEADS cohort.

METHODS: Neuropsychological test performance from 169 amyloid-positive EOAD participants were analyzed. Education-corrected normative comparisons were made using a sample of 98 cognitively normal participants. Comparing the relative levels of …

Subtalar Dislocation With Isolated Talonavicular Dislocation – A Unique Case, Yaser J. Rahim, Naveen J. Pattisapu, Maxwell C. Alley

The Lahey Journal

Subtalar joint dislocations are infrequent injuries of the foot involving interruption of the articulations in the subtalar joint complex. These injuries involve dislocation of the talocalcaneal and talonavicular joints simultaneously with or without associated fractures. Subtalar joint dislocations are classified as medial or lateral, with medial dislocations occurring more commonly. Medial subtalar dislocations are generally not associated with other injuries whereas lateral subtalar dislocations are more frequently accompanied by fractures of talus, calcaneus or navicular. Prompt recognition of this dislocation and other injuries prevent negative sequelae associated with delayed treatment, and patients typically have a good outcome and return to …

Antidiabetic Properties Of Prickly Pear (Opuntia Ficus-Indica) Fruit Extract, Kenzy Aidan Joseph Mckay

The Undergraduate Research Journal

Diabetes mellitus is a metabolic disorder that claims 1.5 million lives annually. Opuntia ficus-indica, commonly known as the prickly pear, has been commonly used in traditional folk medicine for its hypoglycemic properties. It has been claimed that it has antimicrobial and antioxidant properties as well. The plant is native to Mexico and is commonly found in the middle east and India and folk medicine from all of these areas have been using prickly pear medicinally for years. To test these claims an extract of locally sourced Opuntia ficus-indica was prepared using the flesh and seeds of the fruit. The …

The Experiences Of Older Adults With Vascular Anomalies: An Oral History, Anna Kerr

Primary Care Faculty Data

Older adults who have navigated care for vascular anomalies (VAs) their entire lives can help clinicians and researchers understand the most significant experiences for patients across multiple life stages. Their insights can also reveal gaps in care and supportive resources that can inform the development of tailored interventions across age groups. We explored the experiences of older adults with rare VAs. Data were collected using in-depth oral history interviews with 9 older adults (Mean age = 69.4 years; SD = 4.1) with VAs recruited from advocacy organizations. The interviews were conducted over the phone or using Zoom.

February 5, 2025 — Letter To The House Ways And Means Committee On Tax, American Dental Association

Advocacy in Action letters

No abstract provided.

Rectus Abdominis Repair Compared To Posterior Wall Mesh Reinforcement In Athletes With Sportsman's Hernia: A Systematic Review, Jonathan Mckeeman, Benjamin Johnson, Jessica C. Rivera

School of Medicine Faculty Publications

Athletic pubalgia is a relatively uncommon injury that is not fully understood. There are few high-level studies comparing treatments of athletic pubalgia, and this investigation seeks to utilize original articles to compare two common techniques for treatment of athletic pubalgia. The purpose of this study is to compare two prominent procedures, i.e., rectus abdominus repair and posterior wall reinforcement, through a systematic review. Inclusion/exclusion criteria were identified and then applied to search strategies in PubMed and MEDLINE. Two reviewers screened articles based on the agreed-upon criteria in a primary screen of titles and abstracts and a secondary screen of full-text …

Comparing In-Person, Standard Telehealth, And Remote Musculoskeletal Examination With A Novel Augmented Reality Exercise Game System: Pilot Cross-Sectional Comparison Study, Richard Wu, Keerthana Chakka, Sara Belko, Ninad Khargonkar, Kevin Desai, Balakrishnan Prabhakaran, Thiru Annaswamy

SKMC Student Presentations and Publications

BACKGROUND: Current telemedicine technologies are not fully optimized for conducting physical examinations. The Virtual Remote Tele-Physical Examination (VIRTEPEX) system, a novel proprietary technology platform using a Microsoft Kinect-based augmented reality game system to track motion and estimate force, has the potential to assist with conducting asynchronous, remote musculoskeletal examinations.

OBJECTIVE: This pilot study evaluated the feasibility of the VIRTEPEX system as a supplement to telehealth musculoskeletal strength assessments.

METHODS: In this cross-sectional pilot study, 12 study participants with upper extremity pain and/or weakness underwent strength evaluations for four upper extremity movements using in-person, telehealth, VIRTEPEX, and composite (telehealth plus VIRTEPEX) …

Deeper Than Disease: Uncovering Health-Related Social Needs Through Screening And Reporting, Rebecca Cammy, Msw, Lcsw

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Introduction

Identification of cancer patients’ unmet health-related social needs (HRSNs) is key to overcoming barriers, improving well-being and outcomes in oncologic care. Numerous national organizations have called for integration of HRSN screening into routine practice.¹

Objective

Results from the implementation of HRSN electronic health record-integrated screening into the ambulatory oncology setting.

Methods

A sample of 3,617 cancer patients in active treatment from April – June 2024 were screened, utilizing the Health Leads tool,² across eight HRSN domains: (1) transportation, (2) food, (3) housing, (4) utilities, (5) social isolation, (6) interpersonal safety, financial resource strain related to (7) appointments …

Classification Of Schizophrenia, Bipolar Disorder And Major Depressive Disorder With Comorbid Traits And Deep Learning Algorithms, Xiangning Chen, Yimei Lu, Joan Manuel Cue, Mira V Han, Vishwajit L Nimgaonkar, Daniel R Weinberger, Shizhong Han, Zhongming Zhao, Jingchun Chen

Faculty, Staff and Student Publications

Many psychiatric disorders share genetic liabilities, but whether these shared liabilities can be utilized to classify and differentiate psychiatric disorders remains unclear. In this study, we use polygenic risk scores (PRSs) of 42 traits comorbid with schizophrenia (SCZ), bipolar disorder (BIP), and major depressive disorder (MDD) to evaluate their utilities. We found that combining target specific PRS with PRSs of comorbid traits can improve the classification of the target disorders. Importantly, without inclusion of PRSs from targeted disorders, we can still classify SCZ (accuracy 0.710 ± 0.008, AUC 0.789 ± 0.011), BIP (accuracy 0.782 ± 0.006, AUC 0.852 ± 0.004), …

An Open-Label Study To Determine The Maximum Tolerated Dose Of Oral Esk-440 Administered As A Single Agent In Patients With Advanced Or Metastatic Solid Tumors, Russell J. Schilder, Drew Rasco, Manish R. Sharma

Kimmel Cancer Center Faculty Papers

PURPOSE: Anaplastic lymphoma kinase (ALK) dysregulation is implicated in numerous cancers. Tyrosine kinase inhibitors (TKIs) targeting ALK have improved disease outcomes, but resistance mechanisms are common. This first-in-human trial evaluates ESK-440, a dual inhibitor of ALK and focal adhesion kinase, as a novel strategy for cancers with resistance to ALK-targeting TKIs.

METHODS: This phase 1, open-label, dose-finding study evaluated the maximum tolerated dose (MTD), safety, efficacy, and pharmacokinetics of ESK-440 in participants with advanced or metastatic solid tumors (ClinicalTrials.gov: NCT01922752). A 3 + 3 dose-escalation design, with daily doses ranging from 25 to 700 mg/day of ESK-440 for each 28-day …

How Health Literacy Influences Rural West Virginians Knowledge Of Chronic Disease Prevention And Management, Summer Mitchell

Walden Dissertations and Doctoral Studies

Health literacy can be described as the understanding of own’s own health and understanding of health-related information (Shadid, 2022). In rural communities, health literacy is typically at a lower level than in urban communities. West Virginia is a mostly rural state and in addition to lower health literacy, chronic diseases are high in West Virginia. The target area for this study was rural Greenbrier County, West Virginia. The purpose of the study was to examine perceived barriers to health literacy in Greenbrier County, West Virginia, and how this affects understanding of chronic disease. Research questions focused on participants’ knowledge of …

Targeting Tiam1 Enhances Hippocampal-Dependent Learning And Memory In The Adult Brain And Promotes Nmda Receptor-Mediated Synaptic Plasticity And Function, Francisco A Blanco, Md Ali Bin Saifullah, Jinxuan X Cheng, Carlota Abella, Federico Scala, Karen Firozi, Sanyong Niu, Jin Park, Jeannie Chin, Kimberley F Tolias

Faculty, Staff and Students Publications

Excitatory synapses and the actin-rich dendritic spines on which they reside are indispensable for information processing and storage in the brain. In the adult hippocampus, excitatory synapses must balance plasticity and stability to support learning and memory. However, the mechanisms governing this balance remain poorly understood. Tiam1 is an actin cytoskeleton regulator prominently expressed in the dentate gyrus (DG) throughout life. Previously, we showed that Tiam1 promotes dentate granule cell synapse and spine stabilization during development, but its role in the adult hippocampus remains unclear. Here, we deleted Tiam1 from adult forebrain excitatory neurons (Tiam1^fKO) and assessed …

Snap Participation As A Moderator Of Food And Nutrition Security And Combined Cardiometabolic Conditions: A Mixed Regression Approach, Maha Almohamad, Ruosha Li, Natalia I Heredia, Jayna M Dave, Eric E Calloway, Anjail Sharrief, Shreela V Sharma

Faculty, Staff and Student Publications

Objectives: To examine the relationships between food security, nutrition security, Supplemental Nutrition Assistance Program (SNAP) participation, and cardiometabolic outcomes, including hypertension, hyperlipidemia, or diabetes, among low-income U.S. individuals.

Methods: A cross-sectional survey of 486 participants (April–June 2021) assessed food and nutrition security and cardiometabolic outcomes. Mixed-effects logistic regression models adjusted for covariates and included a random effect for state of residence. Moderation analyses evaluated SNAP participation’s impact.

Results: Very low food security was associated with higher odds of having at least one cardiometabolic condition, such as hypertension, hyperlipidemia, or diabetes (AOR = 1.96; 95% CI: 1.04–3.69; p = 0.04). SNAP …

Neutralizing Antibody Immune Correlates For A Recombinant Protein Vaccine In The Covail Trial, Youyi Fong, Lauren Dang, Bo Zhang, Jonathan Fintzi, Shiyu Chen, Jing Wang, Nadine G Rouphael, Angela R Branche, David J Diemert, Ann R Falsey, Cecilia Losada, Lindsey R Baden, Sharon E Frey, Jennifer A Whitaker, Susan J Little, Satoshi Kamidani, Emmanuel B Walter, Richard M Novak, Richard Rupp, Lisa A Jackson, Chenchen Yu, Craig A Magaret, Cindy Molitor, Bhavesh Borate, Tara M Babu, Angelica C Kottkamp, Anne F Luetkemeyer, Lilly C Immergluck, Rachel M Presti, Martín Bäcker, Patricia L Winokur, Siham M Mahgoub, Paul A Goepfert, Dahlene N Fusco, Robert L Atmar, Christine M Posavad, Jinjian Mu, Mat Makowski, Mamodikoe K Makhene, Seema U Nayak, Paul C Roberts, Dean Follmann, Peter B Gilbert

Faculty, Staff and Students Publications

For COVAIL recipients of a coronavirus disease 2019 (COVID-19) Sanofi booster vaccine, neutralizing antibody titers were assessed as a correlate of risk (CoR) of COVID-19. Peak and exposure-proximal titers were inverse CoRs with covariate-adjusted hazard ratios (95% confidence intervals) 0.30 (0.11, 0.78) and 0.25 (0.07, 0.85) per 10-fold increase in weighted average titer.

Advanced External Beam Stereotactic Radiotherapy For Skull Base Reirradiation, He Wang, Fahed M Alsanea, Dong Joo Rhee, Xiaodong Zhang, Wei Liu, Jinzhong Yang, Zhifei Wen, Yao Zhao, Tyler D Williamson, Rachel A Hunter, Peter A Balter, Tina M Briere, Ronald X Zhu, Anna Lee, Amy C Moreno, Jay P Reddy, Adam S Garden, David I Rosenthal, Gary B Gunn, Jack Phan

Faculty, Staff and Student Publications

Background/objectives: Stereotactic body radiation therapy (SBRT) for skull base reirradiation is particularly challenging, as patients have already received substantial radiation doses to the region, and nearby normal organs may have approached their tolerance limit from prior treatments. In this study, we reviewed the characteristics and capabilities of four advanced external beam radiation delivery systems and four modern treatment planning systems and evaluated the treatment plan quality of each technique using skull base reirradiation patient cases.

Methods: SBRT plans were generated for sixteen skull base reirradiation patients using four modalities: the GK plan for the Elekta Leksell Gamma Knife Perfexion/ICON, the …

Detection Of Parasite Dna In Soil Samples From Rural Yucatan, Mexico, Liliana E Villanueva-Lizama, Angela Cruz-Coral, Christian Teh-Poot, Julio Vladimir Cruz-Chan, Rojelio Mejia

Faculty, Staff and Students Publications

The soil is the primary environmental reservoir for many parasites transmitted to humans that cause disease. Our environmental study used a multiparallel real-time quantitative polymerase chain reaction assay to detect parasite DNA in soil collected from the outdoor built environments of 34 houses in rural Yucatan, Mexico. The number of positive houses (n, %) per parasite species was 18 (53%) for Acanthamoeba spp.; four (12%) for Blastocystis spp. and Ascaris lumbricoides; three (9%) for Toxocara canis; and one (3%) for Ancylostoma spp., Trichuris trichiura, Entamoeba histolytica, and Giardia intestinalis. No DNA from Necator americanus, Strongyloides stercoralis, Toxocara cati, or Cryptosporidium …

Distributed Cross-Learning For Equitable Federated Models – Privacy-Preserving Prediction On Data From Five California Hospitals, Tsung-Ting Kuo, Rodney A Gabriel, Jejo Koola, Robert T Schooley, Lucila Ohno-Machado

Faculty, Staff and Student Publications

Quality improvement, clinical research, and patient care can be supported by medical predictive analytics. Predictive models can be improved by integrating more patient records from different healthcare centers (horizontal) or integrating parts of information of a patient from different centers (vertical). We introduce Distributed Cross-Learning for Equitable Federated models (D-CLEF), which incorporates horizontally- or vertically-partitioned data without disseminating patient-level records, to protect patients' privacy. We compared D-CLEF with centralized/siloed/federated learning in horizontal or vertical scenarios. Using data of more than 15,000 patients with COVID-19 from five University of California (UC) Health medical centers, surgical data from UC San Diego, and …

Vasa Previa: Prenatal Diagnosis And The Rationale Behind Using A 5 Cm Distance From Internal Os, Claudio V Schenone, Faezeh Aghajani, Ali Javinani, Eyal Krispin, Yinka Oyelese, Ramesha Papanna, Ramen H Chmait, Alireza A Shamshirsaz

Faculty, Staff and Student Publications

In pregnancies with vasa previa, prenatal diagnosis and pre-labor cesarean delivery are associated with significantly improved perinatal outcomes compared to undetected cases. However, a universally accepted ultrasonographic definition of vasa previa is lacking. Specifically, the distance from the cervical internal os beyond which vaginal delivery can be safely recommended remains to be determined. Field experts and recently published societal guidelines agree that a 2 cm cut-off is suboptimal, given that complete cervical dilation during labor risks unprotected fetal vessels within a 5 cm radius from the internal os. Thus, in the setting of a scarcity of evidence and case reports …

Acute Mecp2 Loss In Adult Mice Reveals Transcriptional And Chromatin Changes That Precede Neurological Dysfunction And Inform Pathogenesis, Sameer S Bajikar, Jian Zhou, Ryan O'Hara, Harini P Tirumala, Mark A Durham, Alexander J Trostle, Michelle Dias, Yingyao Shao, Hu Chen, Wei Wang, Hari Krishna Yalamanchili, Ying-Wooi Wan, Laura A Banaszynski, Zhandong Liu, Huda Y Zoghbi

Faculty, Staff and Students Publications

Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene cause Rett syndrome, a severe childhood neurological disorder. MeCP2 is a well-established transcriptional repressor, yet upon its loss, hundreds of genes are dysregulated in both directions. To understand what drives such dysregulation, we deleted Mecp2 in adult mice, circumventing developmental contributions and secondary pathogenesis. We performed time series transcriptional, chromatin, and phenotypic analyses of the hippocampus to determine the immediate consequences of MeCP2 loss and the cascade of pathogenesis. We find that loss of MeCP2 causes immediate and bidirectional progressive dysregulation of the transcriptome. To understand what drives gene downregulation, we …

Novel Intraoperative Applications Of Fluorescence Imaging Using Indocyanine Green In Pediatric Urology, Albert S T Lee, Ching Man Carmen Tong

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Near-infrared fluorescence imaging (NIRF) with the use of indocyanine green (ICG) has been recently adopted in pediatric urology after its well-published use in the adult population. As a powerful tool that can help delineate complex anatomy and congenital anomalies, we discuss the various applications of this imaging in minimally invasive and open surgery in pediatric urology.

RECENT FINDINGS: The most reported applications of ICG in pediatric urology are within minimally invasive surgery, particularly varicoceles, renal surgery such as nephrectomies and renal tumor excision, mimicking its use in adult urology. ICG has also been applied to reconstructive urology …

Brd7 Loss Reawakens Dormant Metastasis Initiating Cells In Lung By Forging An Immunosuppressive Niche, Jayanta Mondal, Junfeng Zhang, Feng Qing, Shunping Li, Dhiraj Kumar, Jason T Huse, Filippo G Giancotti

Faculty, Staff and Student Publications

Metastasis in cancer is influenced by epigenetic factors. Using an in vivo screen, we demonstrate that several subunits of the polybromo-associated BAF (PBAF) chromatin remodeling complex, particularly Brd7, are required for maintaining breast cancer metastatic dormancy in the lungs of female mice. Brd7 loss induces metastatic reawakening, along with modifications in epigenomic landscapes and upregulated oncogenic signaling. Breast cancer cells harboring Brd7 inactivation also reprogram the surrounding immune microenvironment by downregulating MHC-1 expression and promoting a pro-metastatic cytokine profile. Flow cytometric and single-cell analyses reveal increased levels of pro-tumorigenic inflammatory and transitional neutrophils, CD8+ exhausted T cells, and CD4+ stress …

Braf Mutant Appendiceal Adenocarcinoma Differs From Colorectal Cancer But Responds To Braf-Targeted Therapy, Vinay K Pattalachinti, Emaan Haque, Mahmoud Yousef, Abdelrahman Yousef, Saikat Chowdhury, Michael Overman, Christine M Parseghian, Van K Morris, Bryan Kee, Ryan W Huey, Kanwal Raghav, Colin M Court, John Paul Shen

Faculty, Staff and Student Publications

Appendiceal Adenocarcinoma (AA) is a rare gastrointestinal cancer with no FDA-approved targeted therapies. Here, we retrospectively compare BRAF-mutant AA and colorectal cancer (CRC). BRAF mutation is rare in AA (3%). Unlike CRC, BRAFV600E AA is not associated with poor prognosis, female sex, microsatellite instability, mucinous histology, or poor differentiation. In both cancers, BRAFV600E but not atypical BRAF mutations are mutually exclusive with other Ras-activating mutations. BRAFV600E + EGFR inhibition shows efficacy in BRAFV600E AA (disease control rate = 80%, median progression-free survival = 7.1 months).