Medicine and Health Sciences Commons^™

A Qualitative Analysis Of The Lived Experience Of Active-Duty Servicewomen Receiving Perinatal Care Within The Military Health System., Caitlin Russell, Emily Balog, Anne Teitelman, Rosemary Polomano

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVES: We explored the lived experiences of active-duty servicewomen (ADSW) accessing and receiving care during the perinatal period (from discovery of pregnancy to 1 year postpartum) within the Military Health System.

STUDY DESIGN: Using qualitative methods, we conducted semi-structured interviews between September 2022 and February 2023 with 23 ADSW participants who were pregnant or within their first year postpartum. Data were analyzed using inductive coding and thematic analysis techniques.

RESULTS: Participants reported bureaucratic hurdles and long wait times for accessing care, too little choice in providers, and inadequate coordination between civilian and military care providers. Those who experienced perinatal complications …

Post-Translational Modifications Of Extracellular Matrix Domains As Prognosticators Of Hepatocellular Carcinoma Via Integrative Serum And Spatial Proteomics, Jade K. Macdonald

MUSC Theses and Dissertations

Hepatocellular carcinoma (HCC) remains a major global health challenge, with rising incidence, high mortality, and a five-year survival rate below 20%. Approximately 90% of HCC cases arise in cirrhosis, a stromal disease characterized by excessive deposition and remodeling of collagenous extracellular matrix (ECM). As HCC progresses, alterations in ECM composition and spatial distribution influence disease progression, emphasizing the potential of the ECM as a biomarker for HCC prognosis and treatment response. However, ECM proteomic analysis is challenging due to complex post-translational modifications, crosslinking, and insolubility. This dissertation molecularly and spatially characterizes the stromal landscape in and around HCC tumors in …

Advanced Robotic Multimodal Imaging With Real-Time Motion Compensation For Dynamic Structural Health Monitoring, George Papaioannou, Christos Mitrogiannis, Mark Schweitzer, Maria Pappa, Pegah Khosravi, Apostolos Karantanas, Chris Ruberg, Shawn Owens, Nikolaos Michailidis

Publications and Research

Modern composite materials promise superior performance and load-bearing capabilities, yet evaluating their structural integrity remains challenging. Current testing methods, such as visual, thermographic, ultrasonic, optical, electromagnetic, terahertz, shearography, X-ray, and neutron imaging, are hampered by long scan durations, limited field of view, suboptimal accuracy, and high costs, particularly when applied to large structures.

This paper addresses these issues by introducing a novel robotic multimodal imaging system that overcomes the limitations of traditional methods. This system dynamically captures both static and dynamic properties of materials using advanced motion compensation techniques. By integrating multiple radiographic modalities into a coordinated robotic platform, it …

Co-Targeting Bcl-Xl With Mcl-1 Induces Lethal Mitochondrial Dysfunction In Diffuse Mesothelioma, Yuan Xu, Cristian G Medina, Deborah R Surman, Lacey E Dobrolecki, Monica Vilchis, Maheshwari Ramineni, Susan G Hilsenbeck, Yanming Li, Naren Li, Siqi Wu, Jaylon C Aggison, Xi Chen, Yi Zhu, Ying H Shen, R Taylor Ripley

Faculty, Staff and Students Publications

Diffuse mesothelioma (DM) is a rare but highly aggressive and treatment resistant neoplasm with low survival rates. Effective therapeutic strategies are limited, and resistance to treatment is a major obstacle. Myeloid Cell Leukemia (MCL)-1 and B-cell leukemia (BCL)-xL are anti-apoptotic B-cell lymphoma 2 (Bcl-2) family proteins that block cell-intrinsic apoptosis through interactions on the mitochondrial outer membrane which contribute to therapeutic resistance.

We investigated whether B-cell homology domain (BH)-3 profiles were consistent between intra-patient fresh tumor sample, patient-derived cells (PDC), and patient-derived xenografts (PDX) by BH3 profiling; we observed striking consistency which enabled cross model comparisons. Next, we co-targeted BCL-xl …

Inter- And Intra-Observer Agreement In Ultrasound Diagnosis Of Steatotic Liver Disease: Implications For Screening In Resource-Limited Settings, Maria Spencer-Sandino, Maya Balakrishnan, David Wynne, Ilona Argirion, Paz Cook, Vanessa Van De Wyngard, Noldy Mardones, Ruth Pfeiffer, Allan Hildesheim, Catterina Ferreccio, Jill Koshiol

Faculty, Staff and Students Publications

Steatotic liver disease (SLD), which is associated with increased risk of cancer-related mortality, needs timely and cost-effective detection. Although liver biopsy remains the diagnostic gold standard, its invasiveness and high-cost limit widespread use. Ultrasound is a practical and affordable alternative. We evaluated inter- and intra-observer agreement for ultrasound-based diagnosis of SLD using images from the Chile Biliary Longitudinal Study (Chile BiLS), a cohort of women with gallstones. These women have a high burden of obesity and related metabolic disorders, putting them at higher risk for SLD. A radiologist (observer 1) reviewed a randomly selected subset of 425 baseline images and …

Beyond Smoking: A Geospatial Investigation Of Factors Associated With Lung And Bronchus Cancer Risk In Pennsylvania, Tesla D. Dubois, Daniel Wiese, Kevin A. Henry, Shannon M. Lynch

Kimmel Cancer Center Faculty Papers

INTRODUCTION: While smoking is the leading cause of lung and bronchus cancer (LBC), additional exposures have been implicated and may explain the rise in LBC among never-smokers. To better understand the spatial distribution of LBC incidence and associated risk factors, this study aims to identify geographic areas with significantly elevated incidence rates in Pennsylvania and investigate the potential underlying risk factors.

METHODS: Using cancer registry data aggregated to the census tract level, spatial scan statistics were applied to detect areas of higher-than-expected LBC incidence across the state. Associations were then tested between census tract inclusion in a high-incidence area and …

Multidimensional Analysis Of B7 Homolog 3 Rna Expression In Small Cell Lung Cancer Molecular Subtypes, Carl M Gay, Taofeek K Owonikoko, Lauren A Byers, Noura J Choudhury, Sajid Ahmed, Zachary Cain, Xiaozhong Qian, Matthew Brentnall, Simon Heeke, Ming Poi, Sharon Wu, Charles M Rudin

Faculty, Staff and Student Publications

Purpose: B7 homolog 3 (B7-H3) is a promising target for antibody-drug conjugates, with ifinatamab deruxtecan demonstrating an objective response rate of 54.8% in previously treated extensive-stage small cell lung cancer (SCLC). This analysis aimed to characterize B7-H3 RNA expression with reference to SCLC molecular subtypes (SCLC-A, SCLC-N, SCLC-P, and SCLC-I) and immune-related parameters.

Experimental design: Tumor RNA expression and mutational burden for 1,721 patients with SCLC were derived from a real-world database (Caris Life Sciences). A predominant molecular subtype was assigned based on RNA expression using a gene-ratio classifier. PD-L1 expression was assessed by IHC (antibody 22C3; positive cutoff: tumor …

Large-Scale Crispr Screening In Primary Human 3d Gastric Organoids Enables Comprehensive Dissection Of Gene-Drug Interactions, Yuan-Hung Lo, Hudson T Horn, Mo-Fan Huang, Wei-Chieh Yu, Chia-Mei Young, Qing Liu, Madeline Tomaske, Martina Towers, Antonia Dominguez, Michael C Bassik, Dung-Fang Lee, Lei S Qi, Jonathan S Weissman, Jin Chen, Calvin J Kuo

Faculty, Staff and Student Publications

Understanding how genes influence drug responses is critical for advancing personalized cancer treatments. However, identifying these gene-drug interactions in a physiologically relevant human system remains a challenge, as it requires a model that reflects the complexity and heterogeneity among individuals. Here we show that large-scale CRISPR-based genetic screens, including knockout, interference (CRISPRi), activation (CRISPRa), and single-cell approaches, can be applied in primary human 3D gastric organoids to systematically identify genes that affect sensitivity to cisplatin. Our screens uncover genes that modulate cisplatin response. By combining CRISPR perturbations with single-cell transcriptomics, we resolve how genetic alterations interact with cisplatin at the …

Iterative Intraoperative 3t Mri (Imri)-Guided Brachytherapy: A Prospective Study On Enhancing Implantation Precision And Dosimetric Gains In Advanced Gynecologic Cancers, Shrikiriti S Rajan, Matthew S Ning, Megan Jacobson, Samantha J Simiele, Teresa Bruno, Ramez Kouzy, Kyoko Yoshida-Court, Tatiana Cisneros-Napravnik, Henry Yu, Jason Stafford, Yusung Kim, Geena Mathew, Rauda Alicia Cordova, Maliah Domingo, Anuja Jhingran, Lilie L Lin, Melissa Joyner, Travis T Sims, Lauren Colbert, Aradhana M Venkatesan, Ann Klopp

Faculty, Staff and Student Publications

Purpose: To report on primary outcomes and dosimetric results of a prospective clinical trial and protocol for use of iterative intraoperative magnetic resonance imaging (iMRI) in gynecologic brachytherapy.

Methods: Patients with locally advanced cervical or vaginal cancer (FIGO stages IB2 - IVA, and stage II-IVA, respectively) undergoing pulsed dose rate (PDR) brachytherapy were enrolled in a prospective clinical trial (NCT03634267) using iterative 3T iMRI during brachytherapy implant placement. Applicator and optional interstitial needles were placed under iMRI guidance in a 3T clinical MRI scanner. Imaging, dosimetry and clinical outcomes (local control (LC), recurrence-free survival (RFS), overall survival (OS)), …

Genome Sequences Of Eight Fusobacterium Watanabei Sp Isolates, Martha A Zepeda-Rivera, Falk Ponath, Kaitlyn N Lewis, Rutika P Gavate, Floyd E Dewhirst, Junko Tomida, Yoshiaki Kawamura, Kaori Tanaka, Susan Bullman, Christopher D Johnston

Faculty, Staff and Student Publications

We report draft genome sequences of eight Fusobacterium watanabei clinical isolates, ranging from 1.95 to 2.09 Mbp. Analysis against the Genome Taxonomy Database indicates that F. watanabei genomes are part of the "Fusobacterium nucleatum_J" group.

Planetary Health: At The Crossroads Of Cvd Prevention, Tasveer Khawaja, Sanjay Rajagopalan

Faculty Scholarship

Purpose of Review: To highlight important recent findings demonstrating the interconnectedness of planetary and human health with a focus on cardiovascular disease. Recent Findings: Data continue to demonstrate a clear interconnectedness between the health of the planet and human health, with cardiovascular disease as an important outcome. The central roles of air pollution, non-optimal temperatures, water/waste management, and food/biodiversity are highlighted. We also highlight the clear opportunity for healthcare organizations to facilitate change that will yield positive environmental and patient outcomes. Summary: The undeniable interconnectedness of the health of the planet and human health serves as a call to action …

Proteomics-Based Aging Clocks In Midlife Or Late-Life And Their Associated Risk Of Dementia, Sanaz Sedaghat, Saeun Park, Rob F Walker, Shuo Wang, Jialing Liu, Timothy M Hughes, Behnam Sabayan, Weihong Tang, Josef Coresh, James S Pankow, Keenan A Walker, Ramon Casanova, Ruth Dubin, Rajat Deo, Jerome I Rotter, Alexis C Wood, Peter Ganz, Pamela L Lutsey, Weihua Guan, Anna Prizment

Children’s Nutrition Research Center Staff Publications

Background: Biological age can be quantified by composite proteomic scores, called proteomics-based aging clocks (PACs). We investigated whether a discrepancy between chronological and biological age in midlife and late-life is associated with cognition and dementia risk.

Methods: We used two longitudinal population-based studies: the Atherosclerosis Risk in Communities (ARIC) Study and the Multi-Ethnic Study of Atherosclerosis (MESA). PACs were created in ARIC at midlife (mean age: 58 years, 57% female, n = 11,758) and late-life (mean age: 77 years, 56% female, n = 4934) using elastic net regression models in two-thirds of dementia-free participants and validated in the remaining one-third …

One Tracer, Dual Platforms: Unlocking Versatility Of Fluorescent Probes In Tr-Fret And Nanobret Target Engagement Assays, Erika Y Monroy, Xin Yu, Dong Lu, Xiaoli Qi, Jin Wang

Faculty, Staff and Students Publications

Target engagement assays are essential for drug discovery, utilizing Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) and Nano Bioluminescence Resonance Energy Transfer (NanoBRET) as complementary methods for biochemical and cellular evaluation. Traditional platforms require distinct fluorescent tracers, increasing costs and complexity. This study systematically evaluates the cross-platform performance of T2-BODIPY-FL and T2-BODIPY-589, tracers developed for receptor-interacting protein kinase 1 (RIPK1) target engagement in TR-FRET and NanoBRET applications, respectively. Our results demonstrate both tracers effectively bridge biochemical and cellular assays, providing reliable measurements. T2-BODIPY-589 demonstrates superior performance in NanoBRET (Z’ up to 0.80) and acceptable functionality in TR-FRET (Z’=0.53). Conversely, T2-BODIPY-FL performs …

Transcriptional Remodeling Shapes Therapeutic Vulnerability To Necroptosis In Acute Lymphoblastic Leukemia, Anna Saorin, Anna Dehler, Bartimée Galvan, Fabio Steffen, Marine Ray, Dong Lu, Xin Yu, James Kim, Aneta Drakul, Samanta Kisele, Jin Wang, Jean-Pierre Bourquin, Beat C Bornhauser

Faculty, Staff and Students Publications

Insufficient eradication of cancer cells and survival of drug tolerant clones are major relapse driving forces. Underlying molecular mechanisms comprise activated prosurvival and antiapoptotic signaling, leading to insufficient apoptosis and drug resistance. The identification of programmed cell death pathways alternative to apoptosis opens up possibilities to antagonize apoptosis escape routes. We have earlier shown that acute lymphoblastic leukemia (ALL) harbors a distinct propensity to undergo cell death by receptor-interacting protein kinase 1 (RIPK1)-dependent necroptosis, activated by small-molecule second mitochondria-derived activators of caspase (SMAC) mimetics. Despite demonstrated safety and tolerability of SMAC mimetics in clinical trials, their efficacy as single agent …

Adherence To Inhaled Corticosteroid Medications After An Asthma Exacerbation And The Risk Of Subsequent Exacerbations, Mina Khezrian, Marjan Kerkhof, Tham T Le, Tim Harrison, Tianshi David Wu, Bill Cook, Jonatan Hedberg, Kirsty Rhodes, Nicole Zubizarreta, Joshua Enxing, Trung N Tran

Faculty, Staff and Students Publications

Background: Data on the duration of improved adherence to controller medications after an exacerbation and its impact on asthma outcomes are inconsistent.

Objective: To describe levels and changes in adherence to inhaled corticosteroid (ICS)-containing medication after a severe exacerbation and the association with future exacerbation risk.

Methods: This retrospective cohort study used data from Optum's deidentified Clinformatics Data Mart Database (October 2015-December 2023). Patients with asthma, 1 or more severe exacerbations, and adherence to ICS-containing therapy (proportion of days covered [PDC]) of less than 80% in the 3 months before an exacerbation were included. Primary and secondary end points were …

Established And Emerging Asthma Biomarkers With A Focus On Biologic Trials: A Narrative Review, Philip F Lavere, Kaitlin M Phillips, Nicola A Hanania, Muhammad Adrish

Faculty, Staff and Students Publications

Chronic airway inflammation with variable airflow obstruction is clinical asthma, and it arises from distinct molecular and pathological mechanisms called endotypes. Biomarkers allow for precise endotype characterization and have been used in clinical trials to design, monitor, and evaluate outcomes for asthma biologic therapies. This review will highlight the central and evolving role of biomarkers for past, present, and future asthma, with a focus on regulatory-approved biologic therapies and emerging biomarkers. Established biomarkers, including serum immunoglobulin E (IgE), blood eosinophils, the fraction of exhaled nitric oxide (FeNO), and serum periostin, helped elucidate the complex pathophysiology of the eosinophilic type 2 …

Prenatal Diagnosis Of An Uncommon Form Of A Hypoplastic Left Heart Syndrome Variant., Anmol Goyal, Abigail Phillips, Kelsey Brattrud, Rita France, Maria Kiaffas

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Mitral valve dysplasia syndrome (MVDS) is a rare cardiac defect requiring accurate prenatal identification and appropriate counseling, delivery planning, and postnatal management.

CASE SUMMARY: A 39-year-old woman underwent fetal echocardiography at 34 weeks' gestation owing to cardiomegaly and hydrops. Biatrial enlargement, mild to moderate atrioventricular valve insufficiency, dysplastic mitral valve apparatus, biventricular dilation with systolic dysfunction, endocardial fibroelastosis, hypoplastic aortic outflow, and severely restrictive atrial septum were attributed to MVDS. The plan for critical (class IV) delivery was modified with premature onset of labor at 36 weeks' gestation, leading to urgent cesarean section. Emergent balloon atrial septostomy was performed …

Gastrointestinal Fistulas-What Gastroenterologists Need To Know In 2025, Monjur Ahmed

Division of Gastroenterology and Hepatology Faculty Papers

Gastrointestinal fistulas are increasingly being encountered in our clinical practice because of the increased burden of Crohn's disease, bariatric surgeries, interventional endoscopic procedures, nonsurgical trauma, and war and disaster zones worldwide. Presentation depends on the location and specific type of the fistula. Symptomatic ones can have a tremendous impact on social life and can cause dehydration, electrolyte imbalance, malnutrition, increased morbidity, and mortality. Different imaging studies and endoscopic procedures are done to establish the diagnosis. Treatment modalities to close the fistula depend on the underlying disease and the type of fistula. They include conservative treatment, medical therapy, endoscopic interventions, and …

Operative Trends In Endovascular And Open Procedures Among Vascular Fellows, Jin Park, Nicola Habash, Dawn Salvatore, Michael Nooromid, Paul J. Dimuzio, Babak Abai

Department of Surgery Faculty Papers

Objective: Over the past decade, there has been a growing adoption of endovascular approaches for treating vascular pathologies. This shift toward minimally invasive techniques has raised concerns about declining open surgical case volumes for vascular surgery fellows, particularly in procedures such as aortic aneurysm repair. This study aimed to analyze trends in both open and endovascular case volumes across major vascular procedure categories, including aortic aneurysm, lower extremity arterial disease, abdominal occlusive disease, and cerebrovascular disease, among graduating vascular surgery fellows. Methods: National case log data from the Accreditation Council for Graduate Medical Education were collected for 5 + 2 …

Clinical Outcomes Following Endoscopic Carpal Tunnel Release With The Arthrex Nanoscopic Release System-A Single Surgeon Experience, Sina Ramtin, Asif M. Ilyas

Department of Orthopaedic Surgery Faculty Papers

PURPOSE: Endoscopic carpal tunnel release (ECTR) is a minimally invasive alternative to open release, offering faster recovery and reduced postoperative discomfort. The Arthrex NanoScopic ECTR system, a novel single-use device using chip-on-tip digital imaging and designed for use under local anesthesia without arthroscopic equipment, may further streamline care and expand surgical access.

METHODS: A retrospective review was conducted of the first 50 consecutive ECTR procedures performed using the Arthrex NanoScopic system by a single hand fellowship-trained hand surgeon. All procedures were completed under wide-awake local anesthesia no tourniquet technique in an outpatient surgical center. Outcomes included operative times, adverse events, …

Ribosome Deficiency Induces Salmonella Filamentation Within Host Cells, Zhihui Lyu, Cierra Wilson, Kalyn Weiss, Spencer Lewis, Kurt Fredrick, William Margolin, Jiqiang Ling

Faculty, Staff and Student Publications

The ribosome is the central hub for protein synthesis and is heavily targeted by antibiotics. Ribosomal mutations, antibiotic treatment, and nutrient starvation can alter translational efficiency and lead to stressed cells. Ribosome deficiency plays a critical role in stress responses and disease progression; yet, how it affects bacteria-host interactions remains poorly understood. In this study, we show that a ribosome-deficient strain exhibits a surprising morphological change from rod shape to filamentous in Salmonella cells growing inside host macrophages. Such filamentation depends on an acidic condition within macrophages and in a defined medium mimicking macrophage conditions. Further genetic analyses revealed that …

Csf-Exosomal Mirnas And Delayed Cerebral Ischemia: Insights Into Pathophysiology But No Definitive Biomarkers, Chathathayil M Shafeeque, Devin W Mcbride, Yuanqing Yan, Hussein A Zeineddine, John P Hagen, H Alex Choi, Jude P Savarraj, Ari Dienel, Spiros L Blackburn, Peeyush Kumar Thankamani

Faculty, Staff and Student Publications

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is notoriously known for its high mortality and morbidity. Approximately one-third of the patients who survive aneurysm rupture are reported to develop delayed cerebral ischemia (DCI), which contributes to a poor clinical outcome. Currently, there are no biomarkers for identifying which aSAH patients are at risk of developing DCI. We aimed to determine the feasibility of cerebrospinal fluid (CSF) exosomal microRNAs (miRNAs) for predicting DCI post-aSAH.

Methods: aSAH patients were prospectively enrolled, and CSF samples were collected at two time points (< 24 h and 72 h post-aSAH) from individuals undergoing external ventricular drainage. Exosomal miRNAs were isolated from the CSF for analysis. In the initial group of patients (discovery cohort), an exploratory analysis was conducted using a CSF panel containing 84 miRNAs, assessed by quantitative real-time PCR (RT-qPCR). Based on this analysis, 27 miRNAs were selected for further evaluation in a second group of patients (validation cohort). Among these, 10 miRNAs had previously been reported in SAH-related CSF studies, supporting their relevance for continued investigation.

Results: In this study, RT-qPCR analysis of 84 miRNAs in CSF samples from …

Reduced Computed Tomography Scan Speed Improves Alignment Errors For Patients Undergoing Thoracic Stereotactic Body Radiation Therapy, Ramaswamy Sadagopan, Rachael M Martin-Paulpeter, Christopher R Peeler, Xiaochun Wang, Paige Nitsch, Julianne M Pollard-Larkin

Faculty, Staff and Student Publications

Objectives: We investigated the performance of a slow computed tomography (CT) protocol to reduce alignment errors arising from motion when using CT-on-rail (CTOR) for image guidance for patients receiving thoracic stereotactic body radiation therapy (SBRT).

Methods: A Quasar lung phantom with a moving tumor was programmed with three breathing rates and three motion amplitudes. MIP and average 4DCT images were used for contouring and alignment, respectively. Ten CTOR images were obtained for each of the breathing rates and amplitudes, under both CT protocols. We used in-house CAT software for image guidance, centering the tumor in the lung window …

Dalbavancin For Treatment Of Staphylococcus Aureus Bacteremia: The Dots Randomized Clinical Trial, Nicholas A Turner, Toshimitsu Hamasaki, Sarah B Doernberg, Thomas P Lodise, Heather A King, Varduhi Ghazaryan, Sara E Cosgrove, Timothy C Jenkins, Catherine Liu, Shrabani Sharma, Smitha Zaharoff, Lana Wahid, Valerie J Renard, Paul Cook, Issam Raad, Ray Hachem, Anne-Marie Chaftari, Matthew Sims, Carmen Demarco, Loren G Miller, Matthew W Mccarthy, Caryn G Morse, Chris Lucasti, Graeme N Forrest, Kartikeya Cherabuddi, Christopher Polk, Tasaduq Fazili, Mark E Rupp, George R Thompson, Kami Kim, Luke Strnad, Amanda E Schnee, James A Mckinnell, Mayur Ramesh, Fernanda P Silveira, Todd P Mccarty, Todd C Lee, Emily G Mcdonald, Kristopher Paolino, Katie Wiegand, Alison Wall, Todd Riccobene, Rinal Patel, Urania Rappo, Scott Evans, Henry F Chambers, Vance G Fowler, Thomas L Holland

Faculty, Staff and Student Publications

Importance: Dalbavancin is a long-acting intravenous lipoglycopeptide that may be effective for treatment of complicated Staphylococcus aureus bacteremia without requiring long-term intravenous access.

Objective: To evaluate the efficacy and safety of dalbavancin vs standard therapy for completion of treatment of complicated S aureus bacteremia.

Design, setting, and participants: Open-label, assessor-masked, randomized clinical trial conducted from April 2021 to December 2023 at 23 medical centers in the US (n = 22) and Canada (n = 1). Participant follow-up lasted 70 days (180 days for participants with osteomyelitis); date of final follow-up was December 1, 2023. Hospitalized adults with complicated S aureus …

Identification Of Alkynyl Nicotinamide Hsn748 As A Ret Solvent-Front Mutant Inhibitor With Intracranial Efficacy, Ujjwol Khatri, Neetu Dayal, Kofi B Owusu, Mandeep Kaur Hunjan, Shriya Pandey, Haley Anne Harper, Carli Mcmahan, Bennett D Elzey, Tao Shen, Xueqing Hu, Kurt W Evans, Ahmed El-Sheikh, Seong Jun Jo, Frederick W Holtsberg, M Javad Aman, Funda Meric-Bernstam, Sukyung Woo, Herman O Sintim, Jie Wu

Faculty, Staff and Student Publications

RET solvent-front G810C/R/S mutations confer resistance to the currently approved RET protein tyrosine kinase inhibitors (TKIs) selpercatinib and pralsetinib. Moreover, RET fusion-positive lung adenocarcinoma frequently metastasizes to the brain. To address these challenges, it is imperative to develop a RET TKI that is effective against solvent-front mutations and exhibits intracranial activity. We synthesized alkynyl nicotinamide-based RET TKIs and tested their efficacy in cell cultures in inhibiting selpercatinib/pralsetinib-resistant RET solvent-front mutants G810C/R/S found in cancer patients, and in BaF3/KIF5B-RET(G810C) cell-derived subcutaneous and intracranial tumors in vivo. We also evaluated alkynyl nicotinamide RET TKIs in KIF5B-RET-induced lung tumors in immune competent …

Defining Treatment-Resistant Bipolar Depression: Recommendations From The Isbd Task Force, Eduard Vieta, Roger S Mcintyre, Trisha Suppes, Tamsyn E Van Rheenen, Balwinder Singh, Kamilla Woznica Miskowiak, Allan H Young, Lakshmi N Yatham, Kyooseob Ha, Michael Berk, Holly A Swartz, Chantal Henry, Maja Pantovic Stefanovic, Gerard Anmella Diaz, Aysegul Ozerdem, Wiesław J Cubała, Diego Hidalgo-Mazzei, Mauricio Tohen, Isabella Pacchiarotti, Paula Villela Nunes, Carlos Lopez-Jaramillo, Ana Gonzalez-Pinto, Paolo Brambilla, Robert Post, Jair C Soares, Michael Bauer, Ana C Andreazza, Xavier Justes Fradera, Montserrat Cosials-Lopez, Giovanna Fico

Faculty, Staff and Student Publications

Objective: Despite the availability of approved treatments, a substantial proportion of patients with bipolar disorder experience treatment-resistant bipolar depression (TRBD), characterized by persistent depressive symptoms unresponsive to standard therapies. However, a universally accepted definition of TRBD is lacking. This consensus document, developed by the International Society for Bipolar Disorders (ISBD) Task Force on TRBD, aims to provide a standardized definition of TRBD to facilitate clinical trials, research, and treatment strategies.

Methods: The Task Force employed a literature review, clinical trials analysis, and expert consensus meetings to define TRBD.

Results: TRBD was defined as the failure to achieve a significant and …

Defining Treatment-Resistant Bipolar Depression: Recommendations From The Isbd Task Force, Eduard Vieta, Roger S Mcintyre, Trisha Suppes, Tamsyn E Van Rheenen, Balwinder Singh, Kamilla Woznica Miskowiak, Allan H Young, Lakshmi N Yatham, Kyooseob Ha, Michael Berk, Holly A Swartz, Chantal Henry, Maja Pantovic Stefanovic, Gerard Anmella Diaz, Aysegul Ozerdem, Wiesław J Cubała, Diego Hidalgo-Mazzei, Mauricio Tohen, Isabella Pacchiarotti, Paula Villela Nunes, Carlos Lopez-Jaramillo, Ana Gonzalez-Pinto, Paolo Brambilla, Robert Post, Jair C Soares, Michael Bauer, Ana C Andreazza, Xavier Justes Fradera, Montserrat Cosials-Lopez, Giovanna Fico

Faculty, Staff and Student Publications

Objective: Despite the availability of approved treatments, a substantial proportion of patients with bipolar disorder experience treatment-resistant bipolar depression (TRBD), characterized by persistent depressive symptoms unresponsive to standard therapies. However, a universally accepted definition of TRBD is lacking. This consensus document, developed by the International Society for Bipolar Disorders (ISBD) Task Force on TRBD, aims to provide a standardized definition of TRBD to facilitate clinical trials, research, and treatment strategies.

Methods: The Task Force employed a literature review, clinical trials analysis, and expert consensus meetings to define TRBD.

Results: TRBD was defined as the failure to achieve a significant and …

An Exciting Future For Microbial Molecular Biology And Physiology, Andrew A Bridges, Leah Guthrie, Mckenzie Lehman, Elizabeth H Kellogg, Samantha Wellington Miranda, Andrew Pountain, Anthony L Shiver, Andrew Varble, Molecular Biology And Physiology Community Of The Council On Microbial Sciences, Heidi B Kaplan, Elizabeth A Shank, Gisela Storz

Faculty, Staff and Student Publications

Continuous advances in technologies ranging from deep sequencing and genetic manipulation to mass spectrometry, single cell imaging, and structural biology have led to previously unimaginable advances in our understanding of microbial physiology and the molecular mechanisms underlying microbial responses in a multitude of environments. Simultaneously, these advances are revealing how much more there is to learn. At the 2024 virtual retreat of the Molecular Biology and Physiology (MBP) Community of the Council on Microbial Sciences (COMS) of the American Society for Microbiology (ASM), eight early-career investigators, along with retreat attendees, discussed some of these astounding advances, as well as the …

Macrophage Phagocytosis Of Human Norovirus-Infected Cells In An Ex Vivo Human Enteroid-Macrophage Coculture Model, Ngan Fung Li, Sue E Crawford, Sydney R Mittiga, Cristian Coarfa, Hoa Nguyen-Phuc, Budi Utama, Sarah E Blutt, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

Human norovirus (HuNoV) causes acute gastroenteritis in immunocompetent hosts and chronic infection in immunocompromised individuals. Many recent studies of replication and innate immune responses following HuNoV infection have utilized epithelium-only human intestinal enteroids (HIEs), which lack immune cells. Here, we utilized an ex vivo enteroid-macrophage coculture model consisting of HIEs and different subtypes of human peripheral blood mononuclear cell-derived macrophages to better recapitulate in vivo gut biology and explore the role of macrophages in HuNoV replication and pathogenesis. We show that HuNoV infection in HIEs polarized on Transwells leads to bilateral release of the viral genome, with predominant apical virus …

Pd-1 Inhibition For Relapse After Allogeneic Transplantation In Acute Myeloid Leukemia And Myelodysplastic Syndrome, John M Magenau, David G Frame, Mary Riwes, John Maciejewski, Sarah Anand, Attaphol Pawarode, Anamarija M Perry, Marcus Geer, Thomas Braun, Monalisa Ghosh, Pavan Reddy

Faculty, Staff and Students Publications

Relapse of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains the primary source of mortality after allogeneic hematopoietic stem cell transplantation (HCT). Targeting programmed death-1 (PD-1) for reversing T-cell exhaustion and restoring the graft-versus-leukemia (GVL) effect may have logistical advantages over donor lymphocyte infusion. In a prospective phase 1B clinical trial, pembrolizumab was administered every 3 weeks to 16 patients with AML (n = 12) and MDS (n = 4) in relapse after HCT to assess graft-versus-host disease (GVHD), clinical response, and survival. The median time to relapse after HCT was 5.5 months and the median pretreatment bone marrow …