Medicine and Health Sciences Commons^™

Trajectories Of Attention Problems In Preschoolers Born Very Preterm., Marie Camerota, Francisco Xavier Castellanos, Brian S. Carter, Jennifer Check, Jennifer Helderman, Julie A. Hofheimer, Elisabeth C. Mcgowan, Charles R. Neal, Steven L. Pastyrnak, Lynne M. Smith, Thomas Michael O'Shea, Carmen J. Marsit, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Children born preterm are at heightened risk for neurodevelopmental impairment, including specific deficits in attention. Few studies have investigated change over time in attention problems prior to school entry. The current study aims to describe trajectories of attention problems from age 2 through 5 years in a cohort of children born(GA), identify sociodemographic, medical, and neurobehavioral characteristics associated with attention trajectories, and test whether attention problem trajectories predict the risk of a reported attention-deficit/hyperactivity disorder (ADHD) diagnosis.

METHODS: We studied 608 infants from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a prospective, multisite study of …

Automated Extraction Of Functional Biomarkers Of Verbal And Ambulatory Ability From Multi-Institutional Clinical Notes Using Large Language Models, Levi Kaster, Ethan Hillis, Inez Y Oh, Bhooma R Aravamuthan, Virginia C Lanzotti, Casey R Vickstrom, Brain Gene Registry Consortium, Christina A Gurnett, Philip R O Payne, Aditi Gupta

2020-Current year OA Pubs

BACKGROUND: Functional biomarkers in neurodevelopmental disorders, such as verbal and ambulatory abilities, are essential for clinical care and research activities. Treatment planning, intervention monitoring, and identifying comorbid conditions in individuals with intellectual and developmental disabilities (IDDs) rely on standardized assessments of these abilities. However, traditional assessments impose a burden on patients and providers, often leading to longitudinal inconsistencies and inequities due to evolving guidelines and associated time-cost. Therefore, this study aimed to develop an automated approach to classify verbal and ambulatory abilities from EHR data of IDD and cerebral palsy (CP) patients. Application of large language models (LLMs) to clinical …

Synergies, Partnership Outcomes, And Lessons Learned: A Qualitative Evaluation Of Cancer Center-Coalition Engagement, Aubrey Villalobos, Sarah Chavez, Bettina Drake, Et Al.

2020-Current year OA Pubs

BACKGROUND: Nine National Cancer Institute-Designated Cancer Centers received supplemental funding to expand community outreach and engagement activities through a partnership with Centers for Disease Control and Prevention-funded comprehensive cancer control coalitions. This article reports on an evaluation of these awards focused on organizational relationships and partnership outcomes.

METHODS: The National Cancer Institute, community outreach and engagement, and coalition representatives co-designed the evaluation, which involved document review and 18 semistructured interviews with 16 community outreach and engagement and 19 coalition representatives. Artificial intelligence-generated interview transcripts were dual-coded in NVivo, version 20/R1, software.

RESULTS: The funding generated a diverse collection of projects …

New Performance Measurement Framework For Realizing Patient-Centered Clinical Decision Support: Qualitative Development Study, Prashila Dullabh, Courtney Zott, Nicole Gauthreaux, James Swiger, Edwin Lomotan, Dean F Sittig

Faculty, Staff and Student Publications

Background: Patient-centered clinical decision support (PC CDS) exists on a continuum that reflects the degree to which its knowledge base, data, delivery, and use focus on patient needs and experiences. A new focus on value-based, whole-person care has resulted in broader development of PC CDS technologies, yet there is limited information on how to measure their performance and effectiveness. To address these gaps, there is a need for more measurement guidance to assess PC CDS interventions.

Objective: This paper presents a new framework that incorporates patient-centered principles into traditional health IT and clinical decision support (CDS) evaluation frameworks to create …

Development Of A Reference Standard To Assign Bacterial Versus Viral Infection Etiology Using An All-Inclusive Methodology For Comparison Of Novel Diagnostic Tool Performance, Coburn Allen, J Kate Deanehan, Yaniv Dotan, Matthew A Eisenberg, Andrew M Fine, Jonathan Isenberg, Ann Kane, Dani Kirshner, Todd W Lyons, Yasmin Maor, Ami Neuberger, Daniel G Ostermayer, Sharona Paz, Oded Scheuerman, Shachaf Shiber, Victoria A Statler, Michal Stein, Renata Yakubov, Shirly Yanai, Roy Navon, Lior Kellerman, Tanya M Gottlieb, Eran Eden

Faculty, Staff and Student Publications

Background: Diagnostic test evaluation requires a reference standard. We describe an approach for creating a reference standard for acute infection using unrestricted adjudication and apply it to compare biomarker tools.

Methods: Adults and children with suspected acute infection enrolled in three prospective studies at emergency departments and urgent cares were included. Adjudicators, blinded to C-reactive protein, procalcitonin, and MeMed BV (MMBV), labeled each case (bacterial/viral/non-infectious/indeterminate). Initial adjudication involved 3 adjudicators. Reference standard cohorts were defined: Microbiologically confirmed (3/3 adjudicators concur with high confidence and a concordant microbiological finding), unanimous (3/3 adjudicators concur with high confidence), suspected (3/3 adjudicators concur with …

Neurotransmitter Power Plays: The Synaptic Communication Nexus Shaping Brain Cancer, Jayanta Mondal, Jason T Huse

Faculty, Staff and Student Publications

Gliomas and brain metastases are notorious for their dismal prognosis and low survival rates, a challenge exacerbated by our incomplete grasp of the complex dynamics that govern brain cancers. Recently, a groundbreaking paradigm shift has emerged, highlighting the crucial role of synaptic communication between neurons and brain tumor cells in reshaping neuronal signaling to favor tumor growth. This review delves into the pivotal interplay of synaptic mechanisms, focusing on excitatory glutamatergic and inhibitory GABAergic pathways. Glutamatergic synapses utilize glutamate to propagate excitatory signals, while GABAergic synapses employ gamma-aminobutyric acid (GABA) to inhibit neuronal firing. Glutamatergic signaling can be broadly classified …

Use Of Natural Language Processing To Identify Patients With Inflammatory Breast Cancer Across A Health-Care System, Ramez Kouzy, Megumi Kai, Huong T Le-Petross, Sadia Saleem, Wendy A Woodward

Faculty, Staff and Student Publications

Early identification and referral of inflammatory breast cancer remains challenging within large health-care systems, limiting access to specialized care. We developed and evaluated an artificial intelligence-driven platform integrating natural language processing (NLP) with electronic health records to systematically identify potential inflammatory breast cancer patients across 5 campuses. Our platform analyzed 8 623 494 clinical notes, implementing a sequential review process: NLP screening followed by human validation and multidisciplinary confirmation. Initial NLP screening achieved 55.4% positive predictive value, improving to 78.4% with human-in-the-loop review. Notably, among 255 confirmed patients with inflammatory breast cancer, our system demonstrated 92.2% sensitivity, identifying 57 patients …

Bilateral Germ Cell Tumor Of The Testis: Biological And Clinical Implications For A Stem Versus Genetic Origin Of Cancers, Jamaal C Jackson, Darren Sanchez, Aron Y Joon, Marcos R Estecio, Andrew C Johns, Amishi Y Shah, Matthew Campbell, John F Ward, Louis L Pisters, Charles C Guo, Miao Zhang, Niki M Zacharias, Shi-Ming Tu

Faculty, Staff and Student Publications

Germ cell tumors of the testis (GCTs) provide an ideal tumor model to investigate the cellular versus genetic origin of cancers. In this single institutional study, we evaluated 38 patients with bilateral GCT, including tumors that occurred simultaneously (synchronous) and those occurring at different times (metachronous). For nine of these patients, DNA was isolated from the right and left GCT to determine the genomic and epigenetic differences between tissues using whole-exome sequencing (WES) and reduced representation bisulfite sequencing (RRBS). We found that seminomas and non-seminomas are molecularly distinct based on DNA methylation and not due to synchronous or metachronous disease. …

Trends In Medicare Payments Within The First Year Of Cervical Cancer Diagnosis, 2010–2019, Mohammad A Karim, Ning Zhang, Hui Zhao, Ya-Chen Tina Shih, Lakshmi S M Kodali, Sharon H Giordano, Sanjay Shete

Faculty, Staff and Student Publications

Assessing Medicare payment trends for cervical cancer care is important to mitigate the financial impact on Medicare. This multiyear cross-sectional study included 65 years and older cervical cancer patients in SEER registries diagnosed between 2010 and 2019 who had continuous Part A and B Medicare coverage at least 6 months before diagnosis and at least within the first year of diagnosis and were not enrolled in any Health Maintenance Organization (HMO) in this duration. The main outcomes were trends in total and service-specific mean monthly Medicare payments within the first year of a cervical cancer diagnosis. This study included 2147 …

Network-Based Clustering Unveils Interconnected Landscapes Of Genomic And Clinical Features Across Myeloid Malignancies, Fritz Bayer, Marco Roncador, Giusi Moffa, Kiyomi Morita, Koichi Takahashi, Niko Beerenwinkel, Jack Kuipers

Faculty, Staff and Student Publications

Myeloid malignancies exhibit considerable heterogeneity with overlapping clinical and genetic features among subtypes. We present a data-driven approach that integrates mutational features and clinical covariates at diagnosis within networks of their probabilistic relationships, enabling the discovery of patient subgroups. A key strength is its ability to include presumed causal directions in the edges linking clinical and mutational features, and account for them aptly in the clustering. In a cohort of 1323 patients, we identify subgroups that outperform established risk classifications in prognostic accuracy. Our approach generalises well to unseen cohorts with classification based on our subgroups similarly offering advantages in …

The Effects Of Prescribed Medications On Depressive Symptoms And Neurocognitive Performance In People With Hiv, Asante R Kamkwalala, Avery Matthews, Ankita Garg, Upal Roy, Qing Ma, Maile Karris, Erin Sundermann, Ronald J Ellis, Patricia K Riggs, Mattia Trunfio, Jennifer Blanchard, David J Moore, Leah H Rubin, Scott L Letendre

Faculty, Staff and Student Publications

Background: Alterations in brain function and structure, such as depression and neurocognitive impairment, continue to occur in people with human immunodeficiency virus (HIV, PWH) taking suppressive antiretroviral therapy (ART). The lifespan of PWH has improved but the healthspan remains worse than people without HIV, in part because of aging-related diseases. As a result, polypharmacy is common and increases the risk of drug-drug interactions and adverse reactions.

Methods: This cross-sectional project investigated the relationship between 7 medication-related metrics (including anticholinergic burden), depressive symptoms, and neurocognitive performance in 491 PWH at a single center in the United States. All participants were taking …

Nutrition Provision In Pediatric Extracorporeal Membrane Oxygenation: Evidence, Challenges, And Clinical Considerations, Marwa Mansour, Nicole Knebusch, Andrea Ontaneda, Stephanie Vazquez, Jennifer Daughtry, Katri Typpo, Jorge A Coss-Bu

Faculty, Staff and Students Publications

Background/objectives: Nutritional support is a critical yet challenging aspect of care for pediatric patients requiring extracorporeal membrane oxygenation (ECMO). Malnutrition is prevalent in this population and is associated with worse clinical outcomes. This review synthesizes current evidence on nutritional strategies for pediatric ECMO patients, emphasizing assessment methods, feeding routes, challenges, and clinical outcomes.

Methods: A literature review was conducted using PubMed, Scopus, and Web of Science to identify relevant studies published between January 2010 and 2025. Keywords included "pediatric ECMO", "nutrition", "enteral feeding", and "parenteral nutrition". Studies addressing nutritional assessment, enteral and parenteral feeding practices, and their impact on clinical …

Effect Of A Digital Health Exercise Program On The Intention For Spinal Surgery In Adult Spinal Deformity: Exploratory Cross-Sectional Survey, Marsalis Christian Brown, Christopher Quincy Lin, Christopher Jin, Matthew Rohde, Brett Rocos, Jonathan Belding, Barrett I. Woods, Stacey J. Ackerman

Rothman Institute Papers

BACKGROUND: Adult spinal deformity (ASD) is a prevalent condition estimated at 38%. Symptomatic ASD is associated with substantial health care costs. The role of nonoperative interventions in the management of ASD remains elusive. The National Scoliosis Clinic's (NSC) scoliosis realignment therapy (SRT) is a personalized digital health exercise program for the nonoperative management of ASD.

OBJECTIVE: This exploratory study had two objectives: (1) to evaluate the effect of the SRT program on users' intention of having spinal fusion; and (2) from a US payer perspective, to estimate the annual cost savings per 100,000 beneficiaries by averting spinal surgery.

METHODS: Individuals …

A Secretome Atlas Of Cardiac Fibroblasts From Healthy And Infarcted Mouse Hearts, Jasmin Bahr, Junedh M Amrute, Kory J Lavine, Et Al.

2020-Current year OA Pubs

Cardiac fibroblasts (CF) are key players after myocardial infarction (MI), but their signaling is only incompletely understood. Here we report a first secretome atlas of CF in control (cCF) and post-MI mouse hearts (miCF), combining a rapid cell isolation technique with SILAC and click chemistry. In CF, numerous paracrine factors involved in immune homeostasis are identified. Comparing secretome, transcriptome (SLAMseq), and cellular proteome disclose protein turnover. In miCF at day 5 post-MI, significantly upregulated proteins include SLIT2, FN1, and CRLF1 in mouse and human samples. Comparing the miCF secretome at days 3 and 5 post-MI reveals the dynamic nature of …

An Intranasally Administered Igm Protects Against Antigenically Distinct Subtypes Of Influenza A Viruses, Ashwin Kumar Ramesh, Jwala Priyadarsini Sivaccumar, Xiaohua Ye, Luona Yang, Hailong Guo, Chen-Ni Chin, Sha Ha, John W Shiver, William R Strohl, Yan Xu, Haijuan Du, Tongqing Zhou, Ningyan Zhang, Kai Xu, Xinli Liu, Tong-Ming Fu, Zhiqiang An

Faculty, Staff and Student Publications

Engineering broadly neutralizing monoclonal antibodies (mAbs) targeting the hemagglutinin (HA) of Influenza A virus (IAV) is a promising approach for intervention of seasonal flu. However, HA plasticity often leads to resistant strains that compromise mAb potency as bivalent IgGs. Here we hypothesize that multimerization of anti-IAV antibodies as IgMs can enhance coverage and neutralization potency. Here, we construct 18 IgM antibodies from known broadly neutralizing IgGs targeting different IAV HA epitopes and evaluate their breadth and potency of neutralization against distinct H1N1 and H3N2 IAVs. The IgM version of receptor binding site-specific IgG F045-092 shows increased breadth and antiviral potency …

#Genderaffirminghormonetherapy And Health Information On Tiktok: Thematic Content Analysis, Julia Beatini, Nora Yanyi Sun, Julianna K. Coleman, Maetal E. Haas-Kogan, Andrea Pelletier, Deborah Bartz, Alex Sogomon Keuroghlian

Student Papers, Posters & Projects

BACKGROUND: Transgender and gender diverse people often turn to online platforms for information and support regarding gender-affirming hormone therapy (GAHT); however, analysis of this social media content remains scarce.

OBJECTIVE: We characterized GAHT-related videos on TikTok to highlight the implications relevant to GAHT prescribers.

METHODS: We used a web scraper to identify TikTok videos posted under the hashtags #genderaffirminghormonetherapy and #genderaffirminghormones as of November 2023. We identified recurrent themes via qualitative content analysis and assessed health education videos with the Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT-A/V) scale and a modified Currency, Relevance, Authority, Accuracy, and Purpose (CRAAP) …

Immune Cells And Arrhythmias, Joshua A Keefe, Jian Wang, Jiangping Song, Li Ni, Xander H T Wehrens

Faculty, Staff and Students Publications

Cardiac arrhythmias are a significant cause of morbidity and mortality worldwide. Emerging evidence has demonstrated that resident and infiltrating cardiac immune cells play direct, mechanistic roles in arrhythmia onset and progression. In this review, we provide a comprehensive summary and expert commentary on the role of each immune cell subtype in the pathogenesis of atrial and ventricular arrhythmias.

Percutaneous Transluminal Angioplasty And Stenting (Ptas) In Patients With Symptomatic Intracranial Vertebrobasilar Artery Stenosis (Ivbs), Ramtin Pourahmad, Kiarash Saleki, Sina Zoghi, Ramtin Hajibeygi, Hamed Ghorani, Amin Javanbakht, Sina Goodarzi, Parsa Alijanizadeh, Kelly Trinh, Ravi Shastri, Mohammad Ghasemi-Rad

Faculty, Staff and Students Publications

Background: Approximately 20% of all transient ischaemic attacks (TIAs) and ischaemic strokes occur within the posterior circulation, with vertebrobasilar stenosis identified as the cause in roughly 25% of the cases. Studies have shown that about a quarter of these patients have atherosclerotic stenosis of at least 50% of the vertebrobasilar artery. Stenosis has been shown to be associated with an increased risk of 90-day recurrent vertebrobasilar stroke, particularly in the first few weeks, which is significantly higher when compared with patients with stenosis of the anterior circulation. Therefore, aggressive treatment is important for the patient's prognosis. Stenting is emerging as …

Mapping The Developmental Profile Of Ventricular Zone-Derived Neurons In The Human Cerebellum, Anders W Erickson, Henry Tan, Liam D Hendrikse, Jake Millman, Zachary Thomson, Joseph Golser, Omar Khan, Guanyi He, Kathleen Bach, Arpit Suresh Mishra, Janja Kopic, Zeljka Krsnik, Ferechte Encha-Razavi, Giulia Petrilli, Fabien Guimiot, Evelina Silvestri, Kimberly A Aldinger, Michael D Taylor, Kathleen J Millen, Parthiv Haldipur

Faculty, Staff and Students Publications

The cerebellar ventricular zone (VZ) is the primary source of progenitors that generate cerebellar GABAergic neurons, including Purkinje cells (PCs) and interneurons (INs). This study provides detailed characterization of human cerebellar GABAergic neurogenesis using transcriptomic and histopathological analyses and reveals conserved and unique features compared to rodents. We show that the sequential progression of neurogenesis is conserved and occurs before 8 postconception weeks. Notably, PC differentiation occurs in the outer subventricular zone (SVZ), a region absent in the mouse cerebellum. Human PCs are generated during a compact two-week period before the onset of cerebral cortex histogenesis. A subset of human …

Heavy Metals In Spices From Lancaster, Pa: Arsenic, Cadmium, And Lead Exposure Risks And The Need For Regulation, Andrew Huff, Hoi Lam, Anuj Ghimirey, Jay Goldring, Michelle Pimentel, Harriet Okatch

College of Population Health Faculty Papers

Heavy metal exposure is associated with adverse health effects in children including impaired cognitive functioning. Studies have identified spices as a potential source of heavy metals. However, in Lancaster, PA no such studies have been conducted. Hence the aim of this study was to quantify arsenic (As), cadmium (Cd) and lead (Pb) in spices from Lancaster, PA. Spices were either purchased from stores in Lancaster or obtained as donations from families in Lancaster. As, Cd, and Pb were quantified using inductively coupled plasma-mass spectrometry. The Wilcoxon rank sum test was used to compare the median heavy metal concentrations in store-purchased …

Functional Connectivity Between The Visual And Salience Networks And Autistic Social Features At School-Age, Jessica B Girault, Tomoyuki Nishino, Muhamed Talović, Margaret Reynolds, Abraham Z Snyder, Kelly N Botteron, Natasha Marrus, Robert C Mckinstry, Alexandre A Todorov, John R Pruett Jr, Et Al.

2020-Current year OA Pubs

BACKGROUND: Autism spectrum disorder (ASD) is highly heritable and phenotypically variable. Neuroimaging markers reflecting variation in behavior will provide insights into circuitry subserving core features. We examined functional correlates of ASD symptomology at school-age, while accounting for associated behavioral and cognitive domains, in a longitudinal sample followed from infancy and enriched for those with a genetic liability for ASD.

METHODS: Resting state functional connectivity MRIs (fcMRI) and behavioral data were analyzed from 97 school-age children (8.1-12.0 years, 55 males, 15 ASD) with (n = 63) or without (n = 34) a family history of ASD. fcMRI enrichment analysis (EA) was …

Place-Based Harms And Hidden Strengths: A Qualitative Study Exploring Facets Of Neighborhood Disinvestment Driving Opioid Overdose Among Black Individuals, Kaytryn D Campbell, Rachel P Winograd, Maria E Paschke, Alex Duello, Devin E Banks

2020-Current year OA Pubs

BACKGROUND: Despite significant efforts to address the opioid overdose crisis, Black people who use drugs (PWUD) face unabating, disproportionate increases in opioid overdose death (OOD) rates. These inequities persist in treatment admissions, utilization of medication for opioid use disorder, and treatment retention. Research has linked neighborhood disinvestment - a process of urban decline driven by policy-related changes in neighborhood demand and desirability leading to decreased population, physical and economic erosion, and poorer quality of life for residents - to increased rates of OOD. However, given recent increases in OOD inequities, more research is needed to determine the specific aspects of …

The Potential Of Brain Organoids In Addressing The Heterogeneity Of Synucleinopathies, Xiao-Jun Diao, Claudio Soto, Fei Wang, Yu Wang, Yun-Cheng Wu, Abhisek Mukherjee

Faculty, Staff and Student Publications

Synucleinopathies are a group of diseases characterized by neuronal and glial accumulation of α-synuclein (aSyn) linked with different clinical presentations, including Parkinson's disease (PD), Parkinson's disease with dementia (PDD), Dementia with Lewy Bodies (DLB) and Multiple system atrophy (MSA). Interestingly, the structure of the aSyn aggregates can vary across different synucleinopathies. Currently, it is unclear how the aSyn protein can aggregate into diverse structures and affect distinct cell types and various brain regions, leading to different clinical symptoms. Recent advances in induced pluripotent stem cells (iPSCs)-based brain organoids (BOs) technology provide an unprecedented opportunity to define the etiology of synucleinopathies …

Investigative Needle Core Biopsies Support Multimodal Deep-Data Generation In Glioblastoma, Kenny K H Yu, Sreyashi Basu, Gerard Baquer, Ryuhjin Ahn, Jennifer Gantchev, Sonali Jindal, Michael S Regan, Zaki Abou-Mrad, Michael C Prabhu, Marc J Williams, Alicia D D'Souza, Seth W Malinowski, Kelsey Hopland, Yuval Elhanati, Sylwia A Stopka, Alexei Stortchevoi, Charles Couturier, Zhong He, Jingjing Sun, Yulong Chen, Alexsandra B Espejo, Kin Hoe Chow, Smitha Yerrum, Pei-Lun Kao, Brittany Parker Kerrigan, Lisa Norberg, Douglas Nielsen, Vinay K Puduvalli, Jason Huse, Rameen Beroukhim, Betty Y S Kim, Sangeeta Goswami, Adrienne Boire, Sarah Frisken, Michael J Cima, Matthias Holdhoff, Calixto-Hope G Lucas, Chetan Bettegowda, Stuart S Levine, Tejus A Bale, Cameron Brennan, David A Reardon, Frederick F Lang, E Antonio Chiocca, Keith L Ligon, Forest M White, Padmanee Sharma, Viviane Tabar, Nathalie Y R Agar

Faculty, Staff and Student Publications

Glioblastoma (GBM) is an aggressive primary brain cancer with few effective therapies. Stereotactic needle biopsies are routinely used for diagnosis; however, the feasibility and utility of investigative biopsies to monitor treatment response remains ill-defined. Here, we demonstrate the depth of data generation possible from routine stereotactic needle core biopsies and perform highly resolved multi-omics analyses, including single-cell RNA sequencing, spatial transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics on standard biopsy tissue obtained intra-operatively. We also examine biopsies taken from different locations and provide a framework for measuring spatial and genomic heterogeneity. Finally, we investigate the …

Rural-Urban Disparities In Hospitalisation For Myocardial Infarction In Systemic Lupus Erythematosus In The Usa, Jasvinder A Singh, Sumanth Chandrupatla

Faculty, Staff and Students Publications

Objective: To assess whether rural-urban disparities exist in people with SLE for hospitalisation with myocardial infarction (MI).

Methods: We used the 2016-2019 US National Inpatient Sample data that contain all hospitalisation data. In people with a diagnosis of SLE, we assessed the multivariable adjusted ORs (aORs) to examine the association of rural patient residence with MI hospitalisation, while adjusting for demographics, payer, income, hospital characteristics and the Deyo-Charlson Comorbidity Index.

Results: We found that the crude rates of patients hospitalised with MI per 100 000 area specific SLE hospitalisations were higher in rural versus urban residents with SLE, 2265 versus …

Improved Overall Survival In An Anti-Pd-L1 Treated Cohort Of Newly Diagnosed Glioblastoma Patients Is Associated With Distinct Immune, Mutation, And Gut Microbiome Features: A Single Arm Prospective Phase I/Ii Trial, Shiao-Pei Weathers, Xiqi Li, Haifeng Zhu, Ashish V Damania, Mark Knafl, Brian Mckinley, Heather Lin, Rebecca A Harrison, Nazanin K Majd, Barbara J O'Brien, Marta Penas-Prado, Monica Loghin, Carlos Kamiya-Matsuoka, W K Alfred Yung, Luisa M Solis Soto, Dipen M Maru, Ignacio Wistuba, Edwin R Parra Cuentas, Sharia Hernandez, Andrew Futreal, Jennifer A Wargo, Katja Schulze, Walter C Darbonne, Nadim J Ajami, Scott E Woodman, John F De Groot

Faculty, Staff and Student Publications

This phase I/II trial aims to evaluate the efficacy of concurrent atezolizumab with radiation therapy and temozolomide (TMZ) followed by adjuvant atezolizumab and TMZ in newly diagnosed glioblastoma (GBM) patients and to identify pre-treatment correlates with outcome (N = 60). Trial number: NCT03174197. The primary outcome was overall survival (OS) whereas secondary outcomes were retrospective global-omics analyses to identify pre-treatment immune and genetic tumor features that correlated with survival. Concurrent use of atezolizumab with radiation and TMZ demonstrated OS in line with published trials for newly diagnosed GBM. Tumor genomic (WES and/or targeted NGS panel), transcriptomic (RNAseq) and tissue microenvironment …

Building A Pre-Surgical Multiparametric-Mri-Based Morphologic, Qualitative, Semiquantitative, First And High-Order Radiomic Predictive Treatment Response Model For Undifferentiated Pleomorphic Sarcoma To Replace Recist, Raul F Valenzuela, Elvis Duran-Sierra, Mathew Antony, Behrang Amini, Sam Lo, Keila E Torres, Robert S Benjamin, Jingfei Ma, Ken-Pin Hwang, R Jason Stafford, Dejka Araujo, Andrew J Bishop, Ravin Ratan, Wei-Lien Wang, Jossue Espinoza, Pia V Valenzuela, Chengyue Wu, John E Madewell, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Background: Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft-tissue sarcomas. It demonstrates post-therapeutic hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. Our research aims to establish the multiparametric MRI (mp-MRI) value for predicting UPS treatment response.

Methods: An IRB-approved retrospective study included 33 extremity UPS patients with pre-operative mp-MRI, including diffusion-weighted imaging (DWI), contrast-enhanced susceptibility-weighted imaging (CE-SWI), and perfusion-weighted imaging with dynamic contrast-enhancement (PWI/DCE), and surgical resection between February 2021 and May 2023. Lesions were visually classified on CE-SWI into one of 6 morphology patterns. On PWI/DCE, lesions were classified into one of 6 patterns, and time-intensity curves …

The Impact Of Epac2-Associated Junction Plakoglobin On Respiratory Syncytial Virus Infection, Chaitra A Takle, Eun-Jin Choi, Eun Seok Choi, Devang Deepak, Kashish Khatkar, Jong Min Choi, Ke Zhang, Sung Yun Jung, Tian Wang, Wenzhe Wu, Xiaoyong Bao

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants, young children, and immunocompromised individuals. Currently, FDA-approved monoclonal antibody therapies are limited to infants and young children with severe RSV disease. As a result, there is an urgent need for comprehensive studies of RSV pathogenesis to support the development of new therapeutic strategies. Exchange proteins directly activated by cAMP (EPAC) have recently emerged as key regulators in various viral infections. Our previous work identified EPAC isoform 2 (EPAC2) as a critical factor in RSV replication and host innate immune responses. However, …

Perspectives On The Current Diagnostic And Treatment Paradigms In Secondary Hemophagocytic Lymphohistiocytosis (Hlh), Leonard Naymagon, Jeffrey Bednarski, Et Al.

2020-Current year OA Pubs

Improved awareness of hemophagocytic lymphohistiocytosis (HLH) among clinicians has led to an increase in its diagnosis. Often diagnosis is made based on the HLH- 2004 criteria. While these criteria have considerable strengths, they lack specificity and may be fulfilled in the setting of many pro-inflammatory disorders. Genetic defects affecting cellular cytotoxicity cause familial (primary) HLH. On the other hand, secondary HLH is more a pathophysiologic process common to many conditions, rather than a singular disease entity. Improved genetic, immunologic, and functional testing have changed not only the way we diagnose HLH, but also how we treat it. In 2004, there …

Structural Insights Into The Function, Dysfunction And Modulation Of Kv3 Channels, Manuel Covarrubias, Qiansheng Liang, Linh Nguyen-Phuong, Kyle J. Kennedy, Tyler D. Alexander, Ms, Andrew Sam

Department of Neuroscience Faculty Papers

The third subfamily of voltage-gated K⁺ (Kv) channels includes four members, Kv3.1, Kv3.2, Kv3.3 and Kv3.4. Fast gating and activation at relatively depolarized membrane potentials allows Kv3 channels to be major drivers of fast action potential repolarization in the nervous system. Consequently, they help determine the fast-spiking phenotype of inhibitory interneurons and regulate fast synaptic transmission at glutamatergic synapses and the neuromuscular junction. Recent studies from our group and a team of collaborators have used cryo-EM to demonstrate the surprising gating role of the Kv3.1 cytoplasmic T1 domain, the structural basis of a developmental epileptic encephalopathy caused by the …