Medical Specialties Commons^™

Tdp43 Negtively Regulates Tbk1-Medicated Ifn1 Production Through Irf7 Pathway In Neurodegenerative Diseases, Wenjuan Zhang, Zhen Yi, Daihe Yang, Yifan Hao, Feng Zhou, Guohua Song, Cao Huang, Yun Zhou, Bo Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mutations in the genes encoding TAR DNA-binding protein 43 (TDP43) or TANK- binding kinase 1 (TBK1) have been strongly associated with neurological disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. TDP43 is a key component of pathological protein aggregates found in more than 90% of ALS cases, while TBK1 plays a critical role in innate immune signaling and autophagy. Despite these associations, the precise molecular mechanisms linking TDP43 or TBK1 dysfunction to neurodegeneration remain poorly understood. The present study examined the impact of TDP43 on TBK1-mediated type I interferon (IFN1) production in HEK-293T cells. The findings demonstrated that co-expression …

Lifestyle Attitudes And Habits In A Case Series Of Patients With Cancer And Metabolic Syndrome, Kimberly Siu, Isabel Martinez Leal, Natalia I Heredia, Jessica T Foreman, Jessica P Hwang

Faculty, Staff and Student Publications

Metabolic syndrome (MetS) is associated with increased cancer risk and poor cancer prognosis. The current study applied a mixed methods approach to better understand attitudes about making lifestyle changes and current dietary and physical activity behaviors among cancer patients with MetS at a cancer center and to explore the suitability of brief lifestyle questionnaires to help providers understand their patients' lifestyle attitudes and habits. Qualitative interviews were used to obtain patients' perspectives about lifestyle changes, and 3 quantitative questionnaires-the Readiness Ruler, Rate Your Plate, and the International Physical Activity Questionnaire-Short Form (IPAQ-SF)-were used to measure patients' readiness for lifestyle change, …

A Rare Case Of Adolescent Epiglottitis Secondary To Streptococcus Dysgalactiae Septicemia., Kedar Tilak, Mohamed Aashiq Abdul Ghayum, Douglas Swanson, Rana El Feghaly

Manuscripts, Articles, Book Chapters and Other Papers

Streptococcus dysgalactiae (S. dysgalactiae)is a relatively uncommon pathogen in the pediatric populations, often overshadowed by Streptococcus pyogenes (S. pyogenes)in causing diseases such as cellulitis, severe seep tissue necrotizing infections, and streptococcal toxic shock syndrome. This case report presents the case of a 15-year-old recent immigrant male patient from Egypt who developed an extensive neck infection with complications from S. dysgalactiae septicemia. Initially misdiagnosed as viral pharyngitis, the patient was later admitted with high fevers, dysphagia, and progressive respiratory distress. Imaging revealed widespread inflammatory changes, including cellulitis, epiglottitis, and lymphadenopathy. Despite prompt antibiotic therapy, the patient required …

Therapeutic Targeting Of The Janus Kinase/Signal Transducer And Activator Of Transcription Pathway In Cutaneous T-Cell Lymphoma, Alisha Kashyap, Julia Dai, Xiao Ni

Faculty, Staff and Student Publications

Background/Objectives: Cutaneous T-cell lymphoma (CTCL) is a rare group of non-Hodgkin lymphomas characterized by the clonal expansion of malignant T cells. While current treatments can alleviate symptoms and significant progress has been made in treating leukemic CTCL, a definitive cure remains elusive. Dysregulation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is a key driver of CTCL pathogenesis. As a result, therapeutic strategies targeting JAK/STAT signaling have gained momentum, with the increasing use of JAK inhibitors and other agents that effectively suppress this pathway. These immune-modulating therapies have broad effects on physiological processes, inflammation, and …

Effectiveness Of Empagliflozin In Treating Patients With Heart Failure With Preserved Ejection Fraction: A Systematic Review, Sara Abou Al-Saud

Journal of the Saudi Heart Association

Aim

The goal of this systematic review is to determine the effectiveness of empagliflozin in managing patients with heart failure with preserved ejection fraction (HFpEF) as compared with a placebo

Methods

Web of Science, Cochrane, PubMed, and Scopus databases were searched for articles from 2000 to 2023. Reference lists of articles were manually screened. Trials that recruited patients with HFpEF and reported the effects of empagliflozin were included. Endnote X9 software was used for the study screening process.

Results

1029 non-duplicate articles were identified from the literature and 9 were selected for inclusion in this review. The included papers were …

Applications Of Machine Learning-Driven Molecular Models For Advancing Ophthalmic Precision Medicine, Rahul Kumar, Joshua Ong, Ethan Waisberg, Ryung Lee, Tuan Nguyen, Phani Paladugu, Maria C. Rivolta, Chirag Gowda, John V. Janin, Jeremy Saintyl, Dylan Amiri, Ansh Gosain, Ram Jagadeesan

SKMC Student Presentations and Publications

Ophthalmic diseases such as glaucoma, age-related macular degeneration (ARMD), and optic neuritis involve complex molecular and cellular disruptions that challenge current diagnostic and therapeutic approaches. Advanced artificial intelligence (AI) and machine learning (ML) models offer a novel lens to analyze these diseases by integrating diverse datasets, identifying patterns, and enabling precision medicine strategies. Over the past decade, applications of AI in ophthalmology have expanded from imaging-based diagnostics to molecular-level modeling, bridging critical gaps in understanding disease mechanisms. This paper systematically reviews the application of AI-driven methods, including reinforcement learning (RL), graph neural networks (GNNs), Bayesian inference, and generative adversarial networks …

Bi-Allelic Kics2 Mutations Impair Kicstor Complex-Mediated Mtorc1 Regulation, Causing Intellectual Disability And Epilepsy, Rebecca Buchert, Martin D Burkhalter, Chrisovalantou Huridou, Linda Sofan, Timo Roser, Kirsten Cremer, Javeria Raza Alvi, Stephanie Efthymiou, Tawfiq Froukh, Sughra Gulieva, Ulviyya Guliyeva, Moath Hamdallah, Muriel Holder-Espinasse, Rauan Kaiyrzhanov, Doreen Klingler, Mahmoud Koko, Lars Matthies, Joohyun Park, Marc Sturm, Ana Velic, Stephanie Spranger, Tipu Sultan, Hartmut Engels, Holger Lerche, Henry Houlden, Alistair T Pagnamenta, Ingo Borggraefe, Yvonne Weber, Penelope E Bonnen, Reza Maroofian, Olaf Riess, Jonasz J Weber, Melanie Philipp, Tobias B Haack

Faculty, Staff and Students Publications

Nutrient-dependent mTORC1 regulation upon amino acid deprivation is mediated by the KICSTOR complex, comprising SZT2, KPTN, ITFG2, and KICS2, recruiting GATOR1 to lysosomes. Previously, pathogenic SZT2 and KPTN variants have been associated with autosomal recessive intellectual disability and epileptic encephalopathy. We identified bi-allelic KICS2 variants in eleven affected individuals presenting with intellectual disability and epilepsy. These variants partly affected KICS2 stability, compromised KICSTOR complex formation, and demonstrated a deleterious impact on nutrient-dependent mTORC1 regulation of 4EBP1 and S6K. Phosphoproteome analyses extended these findings to show that KICS2 variants changed the mTORC1 proteome, affecting proteins that function in translation, splicing, and …

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 …

Efficacy Of Zenocutuzumab In Nrg1 Fusion-Positive Cancer, Alison M Schram, Koichi Goto, Dong-Wan Kim, Teresa Macarulla, Antoine Hollebecque, Eileen M O'Reilly, Sai-Hong Ignatius Ou, Jordi Rodon, Sun Young Rha, Kazumi Nishino, Michaël Duruisseaux, Joon Oh Park, Cindy Neuzillet, Stephen V Liu, Benjamin A Weinberg, James M Cleary, Emiliano Calvo, Kumiko Umemoto, Misako Nagasaka, Christoph Springfeld, Tanios Bekaii-Saab, Grainne M O'Kane, Frans Opdam, Kim A Reiss, Andrew K Joe, Ernesto Wasserman, Viktoriya Stalbovskaya, Jim Ford, Shola Adeyemi, Lokesh Jain, Shekeab Jauhari, Alexander Drilon, Enrgy Investigators

Faculty, Staff and Student Publications

Background: Neuregulin 1 (NRG1) fusions are recurrent oncogenic drivers found in multiple solid tumors. NRG1 binds to human epidermal growth factor receptor 3 (HER3), leading to heterodimerization with HER2 and activation of downstream growth and proliferation pathways. The efficacy and safety of zenocutuzumab, a bispecific antibody against HER2 and HER3, in patients with NRG1 fusion-positive solid tumors are unclear.

Methods: In this registrational, phase 2 clinical study, we assigned patients with advanced NRG1 fusion-positive cancer involving any tumor type to receive zenocutuzumab at a dose of 750 mg intravenously every 2 weeks. The primary end point was overall …

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 …

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 …

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 …

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 …

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 …

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 …

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).

The Usefulness Of 3d Heart Models As A Tool Of Congenital Heart Disease Education: A Narrative Review, Raghad Abdulaziz Alhojailan, Reghd Husain M Alkhalifah, Bana Albani, Majed Wadi

Journal of the Saudi Heart Association

Objectives: The objective of this review is to evaluate the effectiveness of three-dimensional (3D) heart models as teaching tools for congenital heart disease (CHD), addressing the limitations of traditional medical education methods. Methods: A thorough literature review was conducted using PubMed, Google Scholar, Scientific Direct and Scopus databases. Relevant articles were screened and selected based on their discussion of the application of 3D models in CHD education. Results: The comprehensive review of 19 studies revealed that 3D heart models provide students, healthcare professionals, and patients with meaningful experiences that significantly enhance understanding and learning outcomes. These models improve …

Monroe County Medical Society Abstract Competition, Janine Fogarty

Advances in Clinical Medical Research and Healthcare Delivery

Established in 1821 in Rochester, New York, Monroe County Medical Society is a non-profit, professional organization whose 1,200 members are physicians, residents, and medical students. The society advocates for physicians and patients for the betterment of the medical profession and the health of the community. Monroe County Medical Society encompasses the 7th District Branch of the Medical Society of the State of New York and serves the New York State counties of Monroe, Livingston, Ontario, Seneca, Steuben, Wayne & Yates Counties

A call for abstracts was requested for the Monroe County Medical Society 203rd Anniversary Gala held on September 25th, …