Medicine and Health Sciences Commons^™

Neuronal Activity-Dependent Gene Dysregulation In C9orf72 I3neuronal Models Of Als/Ftd Pathogenesis, Layla T. Ghaffari, Emily A. Welebob, Sarah E. Bond Newton, Ashley V. Boehringer, Kelly L. Cyliax, Piera Pasinelli, Davide Trotti, Aaron R. Haeusler

Farber Institute for Neuroscience Faculty Papers

The GGGGCC nucleotide repeat expansion (NRE) mutation in the C9ORF72 (C9) gene is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Neuronal activity plays an essential role in shaping biological processes within both healthy and neurodegenerative disease scenarios. Here, we show that at baseline conditions, C9-NRE-induced pluripotent stem cell-cortical neurons display aberrations in several pathways, including synaptic signaling and transcriptional machinery, potentially priming diseased neurons for an altered response to neuronal stimulation. Indeed, exposure to two pathophysiologically relevant stimulation modes, prolonged membrane depolarization or a blockade of K⁺ channels, followed by RNA sequencing, induces …

Migraine-Related Disability According To Headache Frequency Subclassifications: A Systematic Review And Meta-Analysis, Manjit Singh Matharu, Stephen Silberstein, Hsiangkuo Yuan, Deborah Edgar, Roos Colman, Todd Schwedt, Michel Lanteri-Minet, Mark Obermann

Department of Jefferson Headache Center Papers and Presentations

BackgroundThis systematic review and meta-analysis synthesized migraine-related disability outcomes according to headache frequency subclassifications, including low-frequency episodic migraine (LFEM), high-frequency episodic migraine (HFEM) and chronic migraine (CM).MethodsWe searched the PubMed and Cochrane Library (CENTRAL) up to 16 October 2024 for peer-reviewed non-interventional studies reporting migraine-related disability outcomes in CM and subclassifications of episodic migraine (e.g. LFEM and HFEM). Eligible studies with an HFEM subgroup were grouped by headache frequency measure (monthly migraine days [MMD] or monthly headache days [MHD]), HFEM subgroup, disability parameter and study setting. Random-effects meta-analyses were conducted on groups with three or more studies, with the results …

What Community Members With Chronic Illness Teach Future Healthcare Professionals In A Longitudinal Interprofessional Education Program: A Focus Group Study, Rachel White, Maria Brucato, Amber King, Anne B. Mitchell, Nethra S. Ankam

Department of Medicine Faculty Papers

INTRODUCTION: Nearly 50% of Americans have at least one chronic illness. Preparing future healthcare providers for interprofessional collaborative practice (IPCP) and person-centred care through community-based interprofessional education (IPE) can improve outcomes for this growing population. Partial programme theories predict that patients' participation as teachers in health professions education contributes to students' development of patient-centredness. Role theory asserts that behaviours are shaped by assigned roles; therefore, community members with chronic illness who assume roles of health mentors in an IPE curriculum are predicted to teach students about their patient experiences. Yet, this teaching outcome and the lessons health mentors teach in …

Concurrent Local Therapy Extends Clinical Benefit Of Tebentafusp In Metastatic Uveal Melanoma Patients, Tristan L. Lim, Kamaneh Montazeri, Eric Wehrenberg-Klee, Antoine Desilets, Rino S. Seedor, Marlana Orloff, Takami Sato, Michael Caplan, Mariam El-Ashmawy, Benjamin Izar, Shaheer Khan, Inderjit Mehmi, Aleigha Lawless, Theodore S. Hong, Omid Hamid, Richard D. Carvajal, Alexander Shoushtari, Ryan J. Sullivan

Kimmel Cancer Center Faculty Papers

BACKGROUND: Tebentafusp has significantly improved overall survival in HLA-A*02:01+ metastatic uveal melanoma (mUM) patients even in those with a best objective response of progressive disease. Thus, strategies to maintain tebentafusp therapy are critical. Here, we examine the efficacy and safety of adding concurrent local therapy (CLT) to tebentafusp upon radiological progression with tebentafusp alone.

PATIENTS AND METHODS: This multicenter retrospective study included mUM patients treated with tebentafusp and CLT, consisting of extrahepatic soft tissue irradiation and liver-directed therapies (LDTs). Efficacy of target and nontarget sites were assessed per RECIST version 1.1. PFS with tebentafusp alone (PFS1) was compared to that …

Concussion Knowledge, Attitudes, And Behaviors: A Comparison Study Of Youth Athletes And Their Parents, Summer D Ott, Sukhnandan K Cheema, Holden Axel, Seema S Aggarwal, Natalie R Parks, Nikhil Gattu, Philip Schatz

Faculty, Staff and Student Publications

Objective: Given the rising participation in high school athletics and the concerning trend of underreporting concussions, this study aims to identify and compare factors influencing sports-related concussion (SRC) awareness and reporting among youth athletes to their parents.'

Methods: Surveys were completed by 239 student-athletes (ages 13-19) and their parents, using a modified Rosenbaum Concussion Knowledge and Attitudes Survey-Student Version (RoCKAS-ST) and demographic questionnaires. Statistical analyses, including paired sample t-tests, ANOVAs, and Spearman's correlations, compared knowledge and attitudes between groups and examined demographic influences.

Results: Parents showed significantly higher concussion knowledge (CKI: t(230) = 5.18, p < .001) and safer attitudes (CAI: t(230) = 10.62, p < .001) than their children. Knowledge scores varied significantly by race and socioeconomic status, with White parents scoring higher than Hispanic and African American parents (F(3,224) = 8.97, p < .001). Child knowledge scores also differed by race (F(4,223) = 3.73, p = .006) …

Associations Among Human Milk Polyunsaturated Fatty Acids And Infant Sleep Patterns: A Cross-Sectional Study, Ana M Palacios, Dominick J Lemas, Bridget E Young, Erik Parker, Stephanie Dickinson, Nandi Marshall, Kelly L Sullivan, Haley Wilt, Michelle I Cardel, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Infant sleep is critical for cognitive, emotional, and long-term health outcomes. Although diet-sleep relationships are established, limited research has explored how polyunsaturated fatty acids (PUFAs) in human milk (HM) relate to infant sleep.

Objectives: This study aims to examine associations between PUFAs in HM and sleep patterns in 2-mo-old infants exclusively fed with HM.

Methods: This cross-sectional secondary analysis used data from a lactation cookie trial involving 131 parents of healthy, term infants. Participants provided a fasting HM sample and completed sociodemographic and Brief Infant Sleep Questionnaire surveys. Multivariate linear models were adjusted for infant sex assigned at birth, …

All-Cause And Cause-Specific Mortality Among Patients With Narcolepsy., Chih-Wei Hsu, Yen-Shan Yang, Yang-Chieh Brian Chen, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Importance: Narcolepsy is a sleep disorder potentially affecting mortality, yet evidence on this association remains sparse.

Objective: To examine whether narcolepsy is associated with an increased risk of all-cause and cause-specific mortality.

Design, setting, and participants: This retrospective cohort study used data from the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2021, with patients followed up until death or December 31, 2022. Patients were aged 6 years or older with 2 or more narcolepsy diagnoses from psychiatrists or neurologists. Controls were selected from the NHIRD as a population-based sample. Controls without narcolepsy were matched in a 1:4 …

Menopause Factors And Alterations In Gut Microbiota And Insulin Homeostasis: A Cross-Sectional Analysis Of The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Vincent J Maffei, Alain G Bertoni, Alexis C Wood, Jerome I Rotter, Osa Crago, Yii-Der I Chen, Joseph F Petrosino, Kristi L Hoffman, Mark O Goodarzi, Elizabeth T Jensen

Children’s Nutrition Research Center Staff Publications

Aim: To assess the risk for impaired insulin homeostasis as a function of menopause-related factors and gut microbiota dysbiosis in non-diabetic, post-menopausal women.

Materials and methods: Baseline data (n = 175 women) from the Microbiome and Insulin Longitudinal Evaluation Study (MILES) were used, including insulin and dysglycaemia indices calculated from a 2-h oral glucose tolerance test, untargeted peripheral metabolomics, targeted peripheral short chain fatty-acid levels and faecal bacterial microbiota surveyed by whole-metagenomic sequencing.

Results: After adjustment for covariates, menopause age < 50 years and use of hormone replacement therapy (HRT) were associated with lower Matsuda et al. insulin sensitivity index levels (β = -0.232, confidence interval (CI) = [-0.450, -0.014] and β = -0.275, CI = [-0.444, -0.107], respectively) but not pre-menopausal gynaecologic surgery. Pre-menopausal gynaecologic surgery was significantly associated with faecal microbiota beta diversity driven by a relative increase in diabetogenic Ruminococcus gnavus and Clostridium species and a decrease in protective Alistipes species and Akkermansia muciniphila relative abundances. A reduction in two glycerophospholipids in the plasmalogen class significantly statistically mediated an inverse association between gynaecologic surgery before menopause and insulin sensitivity.

Conclusions: Menopause age and history of HRT are more strongly associated with insulin resistance than gynaecologic surgery before menopause. However, …

Hydroxocobalamin For Vasoplegia In Cardiac Surgery: A Retrospective Cohort Analysis, Luai Zakaria, Karan Shah, Dongsheng Yang, Marta Kelava, Haytham Elgharably, Ashish K Khanna, Sanchit Ahuja, Benjamin Hohlfelder, Andrej Alfirevic, Andra E Duncan, Nikolaos J Skubas, Daniel I Sessler

Faculty, Staff and Student Publications

Background: Vasoplegia during cardiac surgery is common and associated with perioperative mortality. Hydroxocobalamin is a catecholamine-sparing approach for treating vasoplegia. However, there is currently limited evidence to inform its use.

Methods: We conducted a single-centre retrospective propensity-matched cohort study of patients who developed vasoplegia after cardiopulmonary bypass. Our primary outcome was vasopressor requirement, expressed as norepinephrine equivalents (NEE), at 1, 4, 24, and 48 h after treatment. Our secondary outcome was a collapsed composite of in-hospital complications comprising stroke, sternal wound infection, mesenteric ischaemia, renal failure, and death.

Results: We identified 2727 (11%) patients with vasoplegia from 2018 to 2024. …

The Effect Of Chronic Azithromycin Use In Winter On Health Care Utilization For Children With Bronchopulmonary Dysplasia: A Double Blind Randomized Controlled Study (Rct), Ricardo A Mosquera, Aravind Yadav, Maria Del Mar Romero-Lopez, Ivan G Magana-Ceballos, S Shahrukh Hashmi, Wilfredo De Jesus Rojas, Maria E Tellez, Kaleigh Riggs-Harpur, Fatima M Boricha, Tina S Reddy, Janice L John, Tomika S Harris, Carlos E Rodriguez-Martinez, Jefferson Buendia, Katrina E Mcbeth, Cindy K Jon, James M Stark, Giuseppe N Colasurdo

Faculty, Staff and Student Publications

Background: Bronchopulmonary dysplasia (BPD), a chronic lung disease in preterm infants, often leads to acute respiratory exacerbations triggered by infections. Our previous mouse study suggested that azithromycin's anti-inflammatory properties may benefit virus-induced respiratory illnesses prophylactically.

Methods: In this single-center, double-blind RCT, 60 children (6 months to 6 years) with BPD received azithromycin (5 mg/kg three times weekly; n = 30) or placebo (n = 30) for one winter season (October to March). Primary outcome was the total number of days of unscheduled healthcare clinic visits, ER visits, and hospital days. Secondary outcomes comprised clinic visits, ER visits, hospital admissions, hospital …

Bone Marrow Endosteum In Homeostasis And Metastasis, Yuta Nakai, Wanida Ono, Noriaki Ono

Faculty, Staff and Student Publications

The endosteum is a thin layer of connective tissue lining the inner surfaces of bones adjoining the medullary cavity. The endosteum houses a variety of cells crucial for bone growth, repair and remodelling, including bone-forming osteoblasts, bone-resorbing osteoclasts and their precursor cells. Historically, the endosteum has been extensively studied as a key site for haematopoiesis by which blood cells are incessantly produced. However, recent studies have defined the endosteum as a niche for skeletal stem cells, underscoring the importance of the harmony between the inner endosteum and the outer periosteum in maintaining bone homeostasis. The endosteum also plays a significant …

Sexual Health Education For Behavior Change: Revisiting How Much Is Enough, Ross Shegog, Elizabeth R Baumler, Robert C Addy, Christine M Markham, Melissa F Peskin, Susan Tortolero Emery, Melanie A Thiel, Shehla Sadruddin, Dennis Reidy, Jeff R Temple

Faculty, Staff and Student Publications

Purpose: Successful implementation of school sexual health curricula relies on students receiving sufficient exposure to lesson content. This large replication study assesses the longitudinal association between exposure to sexual health lesson frequency and content domains and delayed sexual initiation of middle school students.

Methods: Post hoc data analysis was conducted using a large harmonized dataset from 3 randomized controlled trials evaluating It's Your Game curricula in the South Central United States. The sample comprised 1,022 sexually inexperienced middle school students (grades 7 and 8) who completed grade 9 follow-up after using either a 24-lesson hybrid (classroom and computer-based) (It's Your …

Slb-Mssim: A Spectral Library-Based Multiplex Segmented Sim Platform For Single-Cell Proteomic Analysis, Lakmini Senavirathna, Cheng Ma, Van-An Duong, Hong-Yuan Tsai, Ru Chen, Sheng Pan

The Brown Foundation: Institute of Molecular Medicine

Mass spectrometry (MS)-based single-cell proteomics, while highly challenging, offers unique potential for a wide range of applications to interrogate cellular heterogeneity, trajectories, and phenotypes at a functional level. We report here the development of the spectral library-based multiplex segmented selected ion monitoring (SLB-msSIM) method, a conceptually unique approach with significantly enhanced sensitivity and robustness for single-cell analysis. The single-cell MS data is acquired by a multiplex segmented selected ion monitoring (msSIM) technique, which sequentially applies multiple isolation cycles with the quadrupole using a wide isolation window in each cycle to accumulate and store precursor ions in the C-trap for a …

Sleep Eeg And Respiratory Biomarkers Of Sudden Unexpected Death In Epilepsy (Sudep): A Case-Control Study, Oman Magana-Tellez, Rama Maganti, Norma J Hupp, Xi Luo, Sandhya Rani, Johnson P Hampson, Manuela Ochoa-Urrea, Sudha S Tallavajhula, Rup K Sainju, Daniel Friedman, Maromi Nei, Brian K Gehlbach, Stephan Schuele, Ronald M Harper, Beate Diehl, Lisa M Bateman, Orrin Devinsky, George B Richerson, Samden D Lhatoo, Nuria Lacuey

Faculty, Staff and Student Publications

Background: Sudden unexpected death in epilepsy (SUDEP) is the most common category of epilepsy-related mortality. Centrally mediated respiratory dysfunction has been observed to lead to death in the majority of cases of SUDEP. SUDEP also mainly occurs during nighttime sleep. This study seeks to identify sleep EEG and sleep-related respiratory biomarkers of SUDEP risk.

Methods: In this case-control study, we compared demographic, clinical, EEG, and respiratory data from people with epilepsy who later died of SUDEP (the SUDEP group) with data from age and sex-matched living people with epilepsy, classified as high risk of SUDEP (with ≥1 generalised tonic-clonic seizure …

Wire-In-Needle Versus Conventional Syringe-On-Needle Technique For Ultrasound-Guided Central Venous Catheter Insertion In The Internal Jugular Vein: The Win Randomized Trial, Kristen K Thomsen, Jovana Stekovic, Felix Köster, Alina Bergholz, Karim Kouz, Moritz Flick, Daniel I Sessler, Christian Zöllner, Bernd Saugel, Leonie Schulte-Uentrop

Faculty, Staff and Student Publications

Purpose: There are different techniques for ultrasound-guided central venous catheter (CVC) insertion. When using the conventional syringe-on-needle technique, the syringe needs to be removed from the needle after venous puncture to pass the guidewire through the needle into the vein. When, alternatively, using the wire-in-needle technique, the needle is preloaded with the guidewire, and the guidewire-after venous puncture-is advanced into the vein under real-time ultrasound guidance. We tested the hypothesis that the wire-in-needle technique reduces the time to successful guidewire insertion in the internal jugular vein compared with the syringe-on-needle technique in adults.

Methods: We randomized 250 patients to the …

Continuous Versus Bolus Norepinephrine Administration And Arterial Blood Pressure Stability During Induction Of General Anaesthesia In High-Risk Noncardiac Surgery Patients: A Randomised Trial, Christina Vokuhl, Karim Kouz, Moritz Flick, Linda Krause, Alina Kröker, Parisa Moll-Khosrawi, Christian Zöllner, Daniel I Sessler, Bernd Saugel, Kristen K Thomsen

Faculty, Staff and Student Publications

Background: Hypotension after induction of general anaesthesia is common in high-risk patients having noncardiac surgery. Anaesthesiologists often give manual boluses of vasopressors repeatedly to maintain blood pressure during induction of general anaesthesia, including the fast-acting vasopressor norepinephrine which has a short half-life. We tested the hypothesis that giving norepinephrine continuously during induction of general anaesthesia, compared with giving it as repeated manual boluses, improves blood pressure stability in high-risk noncardiac surgery patients.

Methods: In this single-centre trial, 72 participants undergoing noncardiac surgery were randomised to continuous norepinephrine infusion or manual bolus norepinephrine administration during induction of general anaesthesia. Blood pressure …

Mitochondrial Haplogroups, But Not Heteroplasmy, Are Associated With Midlife Cognitive Function, Nien Yeh Daphne Yu, Shea J Andrews, Lifang Hou, Myriam Fornage, Kristine Yaffe

Faculty, Staff and Student Publications

Introduction: Mitochondrial DNA (mtDNA) variation may influence cognitive performance, but prior findings are inconsistent.

Methods: We analyzed data from 2308 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, assessing heteroplasmy (mtHz) burden and haplogroups (mtHg) from blood-derived mtDNA at three timepoints and cognitive function across multiple domains. Multivariate linear regression models and multivariate linear mixed models adjusted for age, sex, education, and race.

Results: MtDNA heteroplasmy burden and count were not associated with cognitive performance. However, mtHgs in macro-mtHg L were linked to poorer cognitive outcomes, particularly in processing speed and global cognition in cross-sectional and …

Development And Feasibility Testing Of An Implementation Evaluation Tool: Recommendations From The Managing Epilepsy Well (Mew) Network Research Collaborative, Martha Sajatovic, Ross Shegog, Elaine Kiriakopoulos, Clara Adeniyi, Jessie Black, Barbara C Jobst, Erica K Johnson, Robin Mcgee, Tanya M Spruill, Cam Escoffery

Faculty, Staff and Student Publications

Aims: The Managing Epilepsy Well (MEW) Network has led the development, testing and scale-up of epilepsy self-management (ESM). The MEW Integrated Database (MEW DB) is a pooled repository of archival studies that facilitates aggregate analysis. This report describes an implementation evaluation tool for ESM adopters.

Methods: Publicly available materials on program implementation, adoption and sustainability as well as readiness surveys used by the MEW Network were reviewed, as were content domains and format styles relevant to ESM implementation. Requirements for data Tiers included: 1) survey Tier should be short (≤6 items) and completed quickly (< 3 min), 2) question and response format should be consistent, 3) data elements are relevant to ESM adopters and 4) the tool should be applicable across ESM programs. Iterative review, discussion and item-ranking yielded a final set of 3 distinct data element Tiers.

Results: Implementation data elements assess …

Engaging And Empowering Future Female Surgeons: Development Of The Medical Student Section Of The Society Of Women In Urology, Allison G Booher, Sasha J Vereecken, Erin Kim, Neharika Penmatcha, Alexandra Aponte, Eman N Chaudhri, Meghana Noonavath, Ibukunoluwa Omole, Joanna Orzel, Leigh Martin, Gina Demeo, Tyler L Overholt, Akanksha Mehta

Faculty, Staff and Student Publications

Objective: To describe a replicable model for a large-scale, cross-institutional, and student-driven initiative to promote gender equity within surgical fields.

Methods: To address the lack of a national infrastructure to support female medical students pursuing careers in Urology, a historically male-dominated specialty, the society of women in urology (SWIU) established its medical student section, called SWIUdents, as a student-led initiative to offer mentorship, education, and networking resources for future female urologists. In 2022, SWIUdents convened its first medical student leadership board, comprised of two co-chairs and four subcommittees focused on membership, program implementation, mentorship, and community relations. SWIUdents membership was …

Three-Dimensional Human Mucopolysaccharidosis Iva Chondrocyte Culture Reveals Significant Impairments In The Lysosomal-Mitochondrial Crosstalk, Andrés Felipe Leal, Sampurna Saikia, Shaukat A. Khan, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disorder (LSD) caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase enzyme. MPS IVA patients suffer from skeletal dysplasia due to the abnormal function of chondrocytes. Given the interactions of lysosomes with various intracellular organelles, it is not surprising that lysosomal dysfunction can lead to improper functioning of lysosome-interacting organelles such as mitochondria. Mitochondrial alterations have been evaluated in several LSDs; nevertheless, they have not been fully addressed in MPS IVA. In this study, we assessed the mitochondrial alterations in MPS IVA chondrocytes using a three-dimensional culture approach. Our findings revealed that MPS IVA …

Changes In Antiviral Prescribing For Children With Influenza In Us Emergency Departments., Tess Stopczynski, Olla Hamdan, Justin Z. Amarin, James W. Antoon, Laura S. Stewart, Haya Hayek, James Chappell, Andrew J. Spieker, Eileen J. Klein, Janet A. Englund, Geoffrey A. Weinberg, Peter G. Szilagyi, John V. Williams, Marian G. Michaels, Julie A. Boom, Leila C. Sahni, Mary Allen Staat, Elizabeth P. Schlaudecker, Jennifer E. Schuster, Rangaraj Selvarangan, Ayzsa Tannis, Heidi L. Moline, Samantha M. Olson, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Despite national recommendations, antiviral prescribing in emergency departments (EDs) for children at higher risk of severe influenza, such as those younger than 5 years and those with specific underlying conditions, remains low.

OBJECTIVE: To assess whether there were changes in antiviral prescribing for children at higher risk of severe influenza in academic pediatric EDs before the COVID-19 pandemic (2016-2020) vs the late pandemic period (2021-2023).

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, cross-sectional study included influenza-positive children younger than 18 years presenting to the ED at 1 of 7 US pediatric academic hospitals participating in the Centers for Disease Control …

Recapitulating The Immune Microenvironment In Pediatric Brain Cancer: Preclinical Modeling Strategies., Adip G. Bhargav, Joseph S. Domino, David Akhavan, Jo Ling Goh

Manuscripts, Articles, Book Chapters and Other Papers

Primary brain and CNS tumors comprise the most common tumors in children and are the most common cause of cancer deaths in this population. Pediatric primary malignant brain tumors including high-grade glioma and medulloblastoma account for a significant proportion of these cancer deaths. Advances in the surgical management and adjuvant treatment paradigms have improved the prognosis of many patients with these tumors, but there remains a subset of treatment-resistant tumors or tumors with unique genetics aberrations and aggressive phenotypes that confer a poor prognosis. Immunotherapeutic strategies have demonstrated promise in pre-clinical studies and early clinical trials. However, high-fidelity evaluation of …

Consensus Recommendations For Hyperpolarized [1- 13c]Pyruvate Mri Multi-Center Human Studies, Shonit Punwani, Peder E Z Larson, Christoffer Laustsen, Jan Vandermeulen, Jan Henrik Ardenkjær-Larsen, Adam W Autry, James A Bankson, Jenna Bernard, Robert Bok, Lotte Bonde Bertelsen, Jenny Che, Albert P Chen, Rafat Chowdhury, Arnaud Comment, Charles H Cunningham, Duy Dang, Ferdia A Gallagher, Adam Gaunt, Yangcan Gong, Jeremy W Gordon, Ashley Grimmer, James Grist, Esben Søvsø Szocska Hansen, Mathilde Hauge Lerche, Richard L Hesketh, Jan-Bernd Hoevener, Ching-Yi Hsieh, Kayvan R Keshari, Sebastian Kozerke, Titus Lanz, Dirk Mayer, Mary Mclean, Jae Mo Park, Jim Slater, Damian Tyler, Jean-Luc Vanderheyden, Cornelius Von Morze, Fulvio Zaccagna, Vlad Zaha, Duan Xu, Daniel Vigneron

Faculty, Staff and Student Publications

MRI of hyperpolarized (HP) [1‐13C]pyruvate allows in vivo assessment of metabolism and has translated into human studies across diseases at 15 centers worldwide. To determine consensus on best practice for multi‐center studies for development of clinical applications. This paper presents the results of a two‐round formal consensus building exercise carried out by experts with HP [1‐13C]pyruvate human study experience. Twenty‐nine participants from 13 sites brought together expertise in pharmacy methods, MR physics, translational imaging, and data analysis with the goal of providing recommendations and best practice statements on conduct of multi‐center human studies of HP [1‐13C]pyruvate MRI. Overall, the group …

Single-Cell And Bulk Transcriptome Analysis Identifies B-Cell Subpopulations And Associated Cancer Subtypes With Distinct Clinical And Molecular Characteristics, Yin He, Li Zhao, Yufen Zheng, Xiaosheng Wang

Faculty, Staff and Student Publications

Backgroud: Previous studies have identified B cell subpopulations with pro- and anti-tumoral activities, while the clinical relevance of B cell subpopulations-specific markers in pan-cancer remains understudied.

Methods: We integrated 14 scRNA-seq datasets (102,504 cells from 424 patients, 15 cancer types) to identify B cell subpopulations via unsupervised clustering. We characterized their functional dynamics and prognostic relevance through analyzing single-cell, bulk and spatial transcriptomic data. Moreover, using B cell subpopulations-specific gene signatures, we constructed models for predicting cancer prognosis and immunotherapy response.

Results: We identified eight B cell subpopulations (b00-b07) which were classified into naive, plasma, memory, germinal center (GC), and …

Feasibility And Usage Of A Virtual Assistant Device In Cognitively Impaired Homebound Older Adults, Matthew Nunez, Prisha Patel, Lindsey Ulin, Leslie Kian, Martin Cominsky, Jason Burnett, Jessica L Lee

Faculty, Staff and Student Publications

Social technology in older adults can improve self-rated health; however, there can also be difficulties using it. Our study aimed to evaluate the feasibility and acceptance of virtual assistant device (VAD) use in cognitively impaired homebound older adults. 52 newly referred Meals on Wheels clients aged 60 and older were recruited for a three-phase study: 6 weeks of meals alone (control), followed by 6 weeks of meals+Alexa Echo Show 8 (AES8) basic usage, and lastly 6 weeks of meals+AES8 advanced usage. Technology acceptance with the AES8 was significantly higher by the end of the study and participants anecdotally enjoyed playing …

Carotenoids As Neuroprotective Agents In Multiple Sclerosis: Pathways, Mechanisms, And Clinical Prospects, Elham Nadimi, Shirin Jamal Omidi, Mahshad Ghasemi, Mohammad Hashem Hashempur, Aida Iraji

Faculty, Staff and Student Publications

Multiple sclerosis (MS) is a chronic autoimmune andneurodegenerative disorder affecting the central nervous system (CNS), characterized by demyelination and neuroinflammatory responses, oxidative stress, and immune dysregulation. The global incidence of MS is rising, demonstrating the necessity for new therapeutic agents against its complex pathophysiology. Carotenoids, naturally pigments with strong antioxidant, anti-inflammatory, immunomodulatory, and neuroprotective activities, have been recognized as promising candidates to target MS.The antioxidant effect of astaxanthin, lycopene, β-carotene, crocin, and lutein resulted from the deactivation of reactive oxygen species (ROS), preservation of mitochondrial integrity, and prevention of lipid peroxidation. Additionally, carotenoids regulate inflammatory pathways by suppressing NF-κB activation, …

Hypoperfusion Intensity Ratio Is Associated With Follow-Up Infarct Volume In Medium Vessel Occlusions: A Multicenter Multinational Study, Vivek Yedavalli, Hamza Adel Salim, Dhairya Lakhani, Basel Musmar, Nimer Adeeb, Davide Simonato, Yan-Lin Li, Orabi Hajjeh, Muhammed Amir Essibayi, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Leonard Ll Yeo, Benjamin Yq Tan, Robert W Regenhardt, Jeremy J Heit, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Takahiro Ota, Ashkan Mowla, Kareem El Naamani, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Gaultier Marnat, Hamza Shaikh, Christoph J Griessenauer, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Tobias D Faizy, Illario Tancredi, Erwah Kalsoum, Boris Lubicz, Aman B Patel, Maurizio Fuschi, Max Wintermark, Adrien Guenego, Adam A Dmytriw

Faculty, Staff and Student Publications

Medium vessel occlusion (MeVO) contributes significantly to acute ischemic stroke (AIS). The hypoperfusion intensity ratio (HIR), reflecting collateral circulation via the ratio of Tmax >10s to Tmax >6s volumes, predicts infarct progression in large-vessel occlusions but is unstudied in MeVOs. In this multicenter, multinational retrospective study, we evaluated consecutive patients with MeVO who underwent mechanical thrombectomy with or without intravenous thrombolysis. Inclusion required available follow-up imaging and pretreatment CT perfusion. Follow-up infarct volume (FIV) was measured on CT or MRI 12-36 h post-procedure. Univariable and multivariable linear regression models were used to identify predictors of FIV, with HIR as the …

Isoform-Level Analyses Of 6 Cancers Uncover Extensive Genetic Risk Mechanisms Undetected At The Gene-Level, Yung-Han Chang, Sean T Bresnahan, S Taylor Head, Tabitha A Harrison, Yao Yu, Chad D Huff, Bogdan Pasaniuc, Sara Lindström, Arjun Bhattacharya

Faculty, Staff and Student Publications

Background: Integrating genome-wide association study (GWAS) and transcriptomic datasets can identify mediators for genetic risk of cancer. Traditional methods often are insufficient as they rely on total gene expression measures and overlook alternative splicing, which generates different transcript-isoforms with potentially distinct effects.

Methods: We integrate multi-tissue isoform expression data from the Genotype Tissue-Expression Project with GWAS summary statistics (all N > ~20,000 cases) to identify isoform- and gene-level associations with six cancers (breast, endometrial, colorectal, lung, ovarian, prostate) and six related cancer subtype classifications (N = 12 total).

Results: Directly modeling isoforms using transcriptome-wide association studies (isoTWAS) significantly improves discovery of …

Ideate-Lung02: A Phase 3 Study Of Second-Line Ifinatamab Deruxtecan In Patients With Relapsed Small Cell Lung Cancer, Taofeek K Owonikoko, Lauren Byers, Ying Cheng, Hidetoshi Hayashi, Luis Paz-Ares, Maurice Pérol, Haichuan Hu, Meng Qian, Cecilio Roi Garcia, Juliette Godard, Mei Tang, Charles M Rudin

Faculty, Staff and Student Publications

Patients with small cell lung cancer (SCLC) have poor prognosis and limited treatment options beyond first-line therapy. B7 homolog 3 (B7-H3) is minimally expressed in normal tissues but highly expressed in SCLC. Ifinatamab deruxtecan (I-DXd), a B7-H3-directed antibody-drug conjugate, has demonstrated promising efficacy and a manageable safety profile in various tumours, including SCLC. IDeate-Lung02 is a global, randomized, open-label Phase 3 study of ~540 patients with relapsed SCLC. Adults with one prior line of platinum-based systemic therapy, ECOG performance status 0-1, and ≥1 measurable lesion (per RECIST 1.1) are eligible for study participation. Patients with asymptomatic untreated or previously treated …

Cervical And Tumor-Associated Microbiomes In Botswana Women With And Without Hiv With Carcinoma Of The Cervix Before And After Definitive Chemoradiation, Travis T Sims, Kyoko Yoshida-Court, Molly B El Alam, Pleasure Ramatlho, Rebecca Ketlametswe, Matthew S Ning, Erle S Robertson, Kathleen M Schmeler, Lauren E Colbert, Ann H Klopp, Surbhi Grover

Faculty, Staff and Student Publications

Purpose: Cervical cancer remains a significant public health concern globally and particularly in sub-Saharan Africa, where high rates of HIV infection exacerbate cervical cancer incidence. Understanding the cervical microbiome and its role in cancer progression is essential, especially in regions where both cervical cancer incidence and HIV prevalence are high. This study aimed to characterize the cervical microbiome in women living with HIV (WLWH) and HIV-negative women with squamous cell carcinoma of the cervix in Botswana, compare the microbiome between before and after chemoradiation therapy (CRT) in WLWH, and assess the prognostic value of specific microbial taxa for overall survival …