Medicine and Health Sciences Commons^™

The Distribution Of The Number Of Mutations In The Genealogy Of A Sample From A Single Population, Yun-Xin Fu

Faculty, Staff and Student Publications

The number K of mutations in the genealogy of a sample of n sequences from a single population is one essential summary statistic in molecular population genetics and is equal to the number of segregating sites in the sample under the infinite-sites model. Although its expectation and variance are the most widely utilized properties, its sampling formula (i.e., probability distribution) is the foundation for all explorations related to K. Despite existence of an analytic sampling formula, its numerical application is limited due to susceptibility to error propagation. This paper presents a new sampling formula for K in a random sample …

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 …

Disentangling Unobserved Heterogeneity: Novel Application Of A Statistical Method To Evaluate A Multilevel Healthcare Intervention For Hispanic Individuals Living On The United States-Mexico Border With Comorbid Diabetes And Hypertension, Minjae Lee, Juliana Z Lopez, Natalia I Heredia, Maria Zolezzi, Soo Kyung Park, Paul G Yeh, Lisa Mitchell-Bennett, Belinda M Reininger

Faculty, Staff and Student Publications

Objective: Individuals with diabetes and hypertension represent a high-risk population with poor prognosis and high healthcare costs. Clinicians recognize the complexities of treating patients with multiple chronic conditions; however, the research literature shows little attention to characterizing change patterns in hypertension outcomes for participants of health interventions. The aim of this study was to characterize individual-level longitudinal trajectories of heterogeneity in blood pressure among a Hispanic population with uncontrolled type II diabetes and hypertension enrolled in a multi-level intervention.

Methods: This study was implemented along the US-Mexico border. Using blood pressure results collected longitudinally between 2013 and 2020 from 2476 …

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 …

Optimization Of A Mobile Imaging System To Aid In Evaluating Patients With Oral Lesions In A Dental Care Setting, Ruchika Mitbander, Jennifer Carns, Richard A Schwarz, Sean Anderson, Geethanjali Vipulanandan, Miriam Hernandez, Amelia E Hartzell, Jun Jiao, Ilona Rutkowska, Safia Durab, Sahar Sadeghi, Ashlee D Clayton, Nancy Bass, Loganayaki Anandasivam, Rachel A Giese, Ann M Gillenwater, Nadarajah Vigneswaran, Rebecca Richards-Kortum

Faculty, Staff and Student Publications

Significance: Oral cancer is often diagnosed at an advanced stage even though the oral cavity is easily accessible for examination. There is a need for tools to support early detection and help non-expert clinicians make appropriate referral recommendations.

Aim: We aim to evaluate a mobile detection of oral cancer (mDOC) smartphone-based autofluorescence imaging system by collecting data in a representative, low-prevalence population and optimizing a referral algorithm suitable for deployment in community dental settings.

Approach: Data were collected from patients at a community dental clinic using the mDOC system, which captures white light and autofluorescence images. A multi-input deep learning …

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 …

Mechanisms For The Age-Related Increase In Fatigability Of The Elbow Flexor Muscles In Healthy Adults, Blaine E. Arney, Andrew Kuplic, Mitchell D. Adam, Christopher W. Sundberg, Sandra Hunter

Exercise Science Faculty Research and Publications

The mechanisms for the age-related increase in fatigability of the elbow flexor muscles during dynamic contractions are unknown. The purpose of this study was to determine the contribution of supraspinal and contractile mechanisms for the age-related increase in fatigability of the elbow flexor muscles. Twenty-eight young (23.2 ± 2.6 years; 14 females) and 32 older adults (72.6 ± 5.6 years; 15 females) performed 80 maximal velocity contractions at 20% of maximal isometric strength. Voluntary activation and muscle contractile properties were assessed before and immediately following the fatiguing exercise using transcranial magnetic stimulation (TMS) and electrical stimulation. Fatigability (% reduction in …

Ambient Artificial Intelligence In Health Care Documentation: A Review Of Tools, Integration, And Clinical Implications, Jasmin Hundal, Molly Jain Md, Joseph Mccollom Do

PCI Publications and Projects

Introduction: Ambient artificial intelligence (AAI) is increasingly being integrated into clinical workflows to address the documentation burden contributing to clinician burnout. AAI systems use automatic speech recognition and natural language processing to capture real-time clinician–patient dialogue and generate structured documentation within the electronic health record. Methods: This review examines AAI’s technical foundations, clinical applications, and implementation considerations in oncology practice. We describe how current AAI tools extract, classify, and populate relevant clinical content, such as the history of present illness, physical examination findings, and assessment and plan, while adhering to established US coding standards (e.g., International Classification of Diseases [ICD-10]). …

Endoscopic Submucosal Dissection For Previously Attempted Colorectal Lesions: An International Multicenter Experience., Suchapa Arayakarnkul, Hiroyuki Aihara, Alessandro Repici, Roberta Maselli, Antonio Capogreco, Leonardo Da Rio, Fabio Shiguehissa Kawaguti, Fauze Maluf-Filho, Makoto Nishimura, Sera Satoi, Sayaka Nagao, Shai Friedland, Robert Bechara, Norio Fukami, Sonmoon Mohapatra, Amit Bhatt, Abel Joseph, Alex Schlachterman, Anand Kumar, Andrew Y Wang, Ross C D Buerlein, Louis M Wong Kee Song, Fnu Deepali, Dennis Yang, Muhammad K Hasan, Nikhil A Kumta, David L Diehl, Edward J Despott, Alberto Murino, Alessandro Rimondi, Laura Lucaciu, Neil R Sharma, Christina Zelt, Ashley Rumple Rn, Bsn, David Leslie Carr-Locke, Reem Z Sharaiha, Srihari Mahadev, Kamal M Hassan, Mohamad-Noor Abu-Hammour, Carlos Robles-Medranda, Martha Arevalo-Mora, Juan Alcivar-Vasquez, Vivek Kumbhari, Jongkyu Park, Salmaan Jawaid, Mai A Khalaf, Kasenee Tiankanon, Sarah S Al Ghamdi, Mohamed O Othman, Saowanee Ngamruengphong

PCI Publications and Projects

BACKGROUND & AIMS: Salvage endoscopic submucosal dissection (ESD) has been proposed for previously attempted colorectal lesions (PACLs), yet the extensive submucosal fibrosis impacts procedural difficulty and resection outcomes. The aim of this study was to evaluate the efficacy and safety of salvage ESD for the treatment of PACLs.

METHODS: This international, multicenter study enrolled consecutive patients who underwent ESD to manage PACLs. Rates of en bloc, R0 resection, and local recurrence were assessed for efficacy. Safety was assessed by adverse events (AEs), procedure-related mortality, and the need for surgical management.

RESULTS: Of 415 lesions, en bloc rate was 83.4%, the …

Engagement In And Correlates Of Total Cutaneous Exams And Skin Self-Exams Among Young Melanoma Survivors And Their Family, Sharon L Manne, Deborah A Kashy, Sherry Pagoto, Susan K Peterson, Carolyn J Heckman, Joseph Gallo, Adam Berger, David B Buller, Alexandria Kulik, Sara Frederick, Morgan Pesanelli

Faculty, Staff and Student Publications

Young adult melanoma survivors and their close family (first degree relatives/FDRs) are at increased risk for developing a melanoma, but little is known about engagement in and correlates of their clinical skin exam (CSE) and skin self-examination (SSE) behaviors. Five hundred and seventy-four YA survivors and their FDRs completed an online survey assessing engagement in CSE and SSE, as well as measures of background factors, cognitive and psychosocial factors, CSE and SSE planning, and family influences. Approximately 90% of YAs had a CSE and 90% performed SSE in the last year, but engagement in CSE among FDRs was lower (63.2%, …

Teaching Ai For Radiology Applications: A Multisociety‑Recommended Syllabus From The Aapm, Acr, Rsna, And Siim, Felipe Kitamura, Timothy Kline, Daniel Warren, Linda Moy, Roxana Daneshjou, Farhad Maleki, Igor Santos, Judy Gichoya, Walter Wiggins, Brian Bialecki, Kevin O’Donnell, Adam Flanders, Matt Morgan, Nabile Safdar, Katherine P. Andriole, Raym Geis, Bibb Allen, Keith Dreyer, Matt Lungren, Monica J. Wood, Marc Kohli, Steve Langer, George Shih, Eduardo Farina, Charles E. Kahn Jr., Ingrid Reiser, Maryellen Giger, Christoph Wald, John Mongan, Tessa Cook, Neil Tenenholtz

Department of Radiology Faculty Papers

No abstract provided.

A Comparative Evaluation Of Two Subharmonic-Aided Pressure Estimation (Shape) Analysis Methods, Hailee Mayer, Priscilla Machado, Trang Vu, Annalisa Berzigotti, Jaume Bosch, Elton Dajti, Antonina Antonenko, Kirk Wallace, Flemming Forsberg

Department of Radiology Faculty Papers

Pressure measurement in clinical practice is a valuable tool for diagnostic evaluation, especially in diseases such as portal hypertension. Currently, portal pressures are measured by invasive hepatic vein catheterization, posing risks to patients, and limiting how often measurements can be obtained. Subharmonic-aided pressure estimation (SHAPE) is an ultrasound-based technique that leverages ultrasound contrast agents (UCAs) to estimate changes in hydrostatic pressure. UCAs act as nonlinear oscillators when exposed to high enough acoustic pressures (typically > 200 kPa) and produce significant energy components ranging from subharmonics to higher harmonics. Tissues do not generate significant subharmonic components, thus making it the optimal component …

Influence Of Institutional Support And Organisational Culture On Hiv And Ncd Integration, David Njuguna, Caroline Kyalo, Eunice Muthoni, Daniel Mwai, Elvis Kirui, Wesley Rotich, Joy Mugambi, James Waweru, Nelson Muriu, Easter Olwanda

Population Health, East Africa

Background: The integration of services for human immunodeficiency virus (HIV) and noncommunicable diseases (NCDs) has gained increasing attention in recent years because of the overlapping prevalence and shared risk factors between these health conditions. However, successful integration requires more than just the alignment of clinical practices. The role of institutional support and organisational culture in promoting effective integration remains an underexplored area.

Aim: This study aims to fill this gap by examining how institutional structures and organisational values influence the integration of HIV and NCD care.

Setting: The study setting was Nakuru County in Kenya.

Methods: …

Gender Trends In Professional Advancement Among Academic Pediatric Neurologists., Juliet K. Knowles, Angela L. Hewitt, Prathyusha Teeyagura, Bren Botzheim, Derek Boothroyd, Ria Pal, Chrisoula Cheronis, Shermila Pia, Rebecca Macrae, Christine Shrock, Taelor Hancock, Rayann Solidum, Jaclyn Peraino, Amy Hill, Laura Owlett, Sara N. Moss, Catherine Tran, Daniel A. Castillo, Mark S. Wainwright, Renée A. Shellhaas, Nomazulu Dlamini, Mustafa Sahin, Rose N. Gelineau-Morel, Joshua L. Bonkowsky

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Wellness Newsletter (Wellness Connection) October 2025, Roger Williams University School Of Law

Life of the Law School (1993- )

No abstract provided.

Recommended Best Practices For Construct-Centered Adaptation Of The Harmonized Cognitive Assessment Protocol, Emily Briceño, Darina Bassil, Pranali Khobragade, Anthony Ngugi, Martine Bejjani, Eric Ochieng, Silvia Mejia-Arango, Salima Douhou, Kazione Kulisewa, Miguel Rentería

Population Health, East Africa

Objectives The Harmonized Cognitive Assessment Protocol (HCAP) neuropsychological assessment approach aims to support the collection of harmonizable data on cognitive function for cross-national cognitive aging and dementia research. As the measurement of cognition is sensitive to differences in contextual, cultural, educational, linguistic, social, and other factors that may influence cognitive test performance, HCAP requires adaptation to be appropriate for the contexts in which it is administered. We aim to provide methodological recommendations for the adaptation and implementation of the HCAP and other cognitive data collection tools in novel settings.

Methods We drew from existing guidelines on cross-cultural psychological test adaptation …

The Colchicine-Sodium-Glucose Cotransporter Two Inhibitors Conundrum: Promise, Pitfalls, And Next Steps, Ali Bin Jabbar, Asma Ahmed, Salim S. Virani

Population Health, East Africa

No abstract provided.

Fifth Edition Who Classification: Mature B-Cell Neoplasms, Kikkeri Naresh, Kennosuke Karube, Anita Borges, Wah Cheuk, Sumeet Gujral, Shahin Sayed, Aliyah Sohani, Stefano Lazzi, German Ott, Ming-Qing Du

Pathology, East Africa

We present a review of mature B-cell neoplasms as described in the fifth edition of the WHO classification of haematolymphoid tumours (WHO-HAEM5). Entities have expanded, and definitions are increasingly reliant on genomic and other technologies. However, the WHO-HAEM5 employs a hierarchical structure with family (class)-level definitions that group several specific entities. This approach enables the assignment of a family-level diagnosis when criteria for specific entities cannot be met due to resource constraints. To facilitate application in resource-limited settings, WHO-HAEM5 divides diagnostic criteria into ‘essential’ and desirable criteria for most entities. This review focuses on changes and updates in B-cell lymphoma …

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 …

Ethical Sourcing In The Context Of Health Data Supply Chain Management: A Value Sensitive Design Approach, Camille Nebeker, Jean Christophe Bélisle-Pipon, Benjamin X Collins, Ashley Cordes, Kadija Ferryman, Brian J Mcinnis, Shannon K Mcweeney, Laurie L Novak, Susannah Rose, Joseph M Yracheta, Ishan C Williams, Xiaoqian Jiang, Ellen W Clayton, Bradley A Malin, Bridge2ai Ethical, Legal And Social Implications Ai Working Group

Faculty, Staff and Student Publications

Objective: The Bridge2AI program is establishing rules of practice for creating ethically sourced health data repositories to support the effective use of ML/AI in biomedical and behavioral research. Given the initially undefined nature of ethically sourced data, this work concurrently developed definitions and guidelines alongside repository creation, grounded in a practical, operational framework.

Materials and methods: A Value Sensitive Design (VSD) approach was used to explore ethical tensions across stages of health data repository development. The conceptual investigation drew from supply chain management (SCM) processes to (1) identify actors who would interact with or be affected by the data repository …

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 …

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 …

Multiomic Random Forest Toxicity Modeling Of Radiation Esophagitis, Saurabh S Nair, Ramon M Salazar, Ting Xu, Alexandra O Leone, Zhongxing Liao, Laurence E Court, Joshua S Niedzielski

Faculty, Staff and Student Publications

Background and purpose: Radiation esophagitis (RE) is a major dose-limiting toxicity resulting from radiotherapy for non-small-cell lung cancer (NSCLC). Multiomic features may provide additional predictive value for high-grade RE compared to traditionally used clinical and dose-volume histogram (DVH) parameters. We aimed to investigate the utility of multiomic features in improving RE toxicity prediction models.

Materials and methods: Of the 179 NSCLC patients considered, 27 patients (15.08 %) were found to have toxicity ≥grade 3 RE per CTCAE v5.0. A total of 343 CT- and PET- based radiomic and dosiomic features were extracted. Four toxicity prediction models were created using clinical …

Multiplexed Imaging Mass Cytometry Reveals Tumor-Immune Microenvironment-Dependent Hormone Receptor Expression In Adult-Type Ovarian Granulosa Cell Tumors, Eleonora Y Khlebus, Veena K Vuttaradhi, Sammy Ferri-Borgogno, Allison L Brodsky, Barrett C Lawson, Samuel C Mok, R Tyler Hillman

Faculty, Staff and Student Publications

Adult-type granulosa cell tumors (AGCT) are rare ovarian tumors with few effective treatments for recurrent disease. To elucidate spatial features and cellular interactions within the AGCT tumor microenvironment, we applied imaging mass cytometry using a 34-marker panel on 130 regions from 24 AGCT samples, profiling more than 900,000 single cells. Analysis confirmed the immune “cold” phenotype of AGCTs and showed higher macrophage abundance in recurrent compared with primary tumors. We observed substantial heterogeneity in tissue architecture across samples, including variable presence of FOXL2+ cells embedded in collagen-rich regions (FOXL2+COL1A1+ cells). Based on tumor microenvironment composition, we defined two AGCT subtypes: …