Digital Commons Network^™

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 …

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 …

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%, …

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 …

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: …

Evaluating Dimensionality Reduction For Patient-Reported Outcome-Based Survival Modeling In Patients With Head And Neck Cancer, Eric Ababio Anyimadu, Yaohua Wang, Amy C Moreno, Clifton David Fuller, Xinhua Zhang, G Elisabeta Marai, Guadalupe M Canahuate

Faculty, Staff and Student Publications

Purpose: This study aims to improve survival modeling in head and neck cancer (HNC) by integrating patient-reported outcomes (PROs) using dimensionality reduction techniques. PROs capture symptom severity across the treatment timeline and offer key insights for personalized care. However, their high dimensionality poses challenges such as overfitting and computational complexity. This work focuses on transforming and incorporating PRO data to enhance model performance in HNC.

Materials and methods: We analyzed retrospective data of 923 patients with HNC treated at the University of Texas MD Anderson Cancer Center between 2010 and 2021. Baseline clinical data including demographic, treatment, and disease characteristics …

Surgical And Blood-Based Minimal Residual Disease In Patients With Ovarian Cancer After First-Line Therapy: Clinical Outcomes And Translational Opportunities, Anne Knisely, Yibo Dai, Graham L Barlow, Sanghoon Lee, Barrett Lawson, Helen Clark, Bryan Fellman, Ying Yuan, Wei Lu, Idania Carolina Lubo Julio, Rossana N Lazcano, Manoj Chelvanambi, Brenda Melendez, Bharat Singh, Bhavana Singh, Khalida Wani, Jianfeng Chen, Chih-Chen Yeh, Jianjun Gao, Sean Barnes, Ou Shi, Khaja B Khan, Alejandra G Serrano, Lorena I Gomez-Bolanos, Carly Bess Scalise, Samantha K Cheung, Punashi Dutta, Sharlene Velichko, Adam C Elnaggar, Minetta C Liu, Roni N Wilke, Jeffrey How, Lois M Ramondetta, David M Boruta, Gwyn Richardson, Aaron Shafer, Shannon N Westin, Travis Sims, Anil K Sood, Pedro T Ramirez, Alexander J Lazar, Pamela T Soliman, Karen Lu, Cara L Haymaker, Luisa M Solis Soto, Jennifer A Wargo, Rachel Grisham, Kai W Wucherpfennig, Linghua Wang, Amir A Jazaeri

Faculty, Staff and Student Publications

Purpose: Minimal residual disease (MRD) after first-line treatment of advanced-stage ovarian cancer remains a long-standing barrier to cure. We investigated the prognostic and translational value of MRD detection by second-look laparoscopy (SLL) and ctDNA at the completion of first-line therapy.

Experimental design: Patients with high-grade epithelial ovarian cancer who had a complete clinical response to first-line therapy and underwent SLL and plasma collection for ctDNA were included. Progression-free survival (PFS) and overall survival (OS) were estimated based on MRD and clinicopathologic status. Spatial transcriptomics (GeoMx and Visium) and proteomics (CODEX) profiling were performed on serial samples from select patients.

Results: …

Factors Associated With Medication Adherence Among Patients With Attention-Deficit/Hyperactivity Disorder (Adhd), Linh Nguyen, Yen-Chi L Le, Hannah Reygaerts, Todd R Johnson, Cesar A Soutullo

Faculty, Staff and Student Publications

Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common behavioral health condition that impacts 5% to 8% of children and 2.5% of adults worldwide. The symptoms of ADHD are effectively managed with medication, yet patients with ADHD may inconsistently take their medication. We assessed medication adherence among patients with ADHD and identified factors associated with medication adherence that may be utilized to optimize adherence.

Method: This is a retrospective, observational study among patients aged 4 years and older with a diagnosis of ADHD at primary care and multispecialty outpatient clinics during May 2021 to May 2023. We assessed sociodemographic characteristics, stratified by …

Transfer Learning Via Distributed Brain Recordings Enables Reliable Speech Decoding, Aditya Singh, Tessy Thomas, Jinlong Li, Greg Hickok, Xaq Pitkow, Nitin Tandon

Faculty, Staff and Student Publications

Speech brain-computer interfaces (BCIs) combine neural recordings with large language models to achieve real-time intelligible speech. However, these decoders rely on dense, intact cortical coverage and are challenging to scale across individuals with heterogeneous brain organization. To derive scalable transfer learning strategies for neural speech decoding, we used minimally invasive stereo-electroencephalography recordings in a large cohort performing a demanding speech motor task. A sequence-to-sequence model enabled decoding of variable-length phonemic sequences prior to and during articulation. This enabled development of a cross-subject transfer learning framework to isolate shared latent manifolds while enabling individual model initialization. The group-derived decoder significantly outperformed …

Engaging Chinese And Korean American Communities In Dementia Research: A Journey Of Inclusivity And Partnership, Jing Wang, Xiang Qi, Mary S Mittelman, Eunjung Ko, Yaolin Pei, I Tek Leong, Sungji Park, Katherine Wang, Weiyu Mao, Cynthia Epstein, Bei Wu

Faculty, Staff and Student Publications

Introduction: The New York University Caregiver Intervention plus Enhanced Support Project is a randomized controlled trial of a family-based psychosocial intervention to enhance social support and reduce cardiometabolic risk for Chinese and Korean American dementia caregivers, using culturally tailored recruitment strategies.

Methods: We reviewed reflections from research staff, weekly meeting minutes, debriefing sessions, and progress reports, to identify key challenges and approaches to engaging participants.

Results: Key challenges included reluctance to involve family members, dementia stigma, and resistance to involving family. In response, we engaged online communities, partnered with local organizations, participated in events, and adapted recruitment messages to cultural …

Performance Characteristics For Physiological Measures Of Progressive Pulmonary Fibrosis, Chad A Newton, Ashwatha Thenappan, Gabrielle Y Liu, Leda Yazbeck, Cathryn T Lee, Janelle Vu Pugashetti, Jennifer M Wang, Ethan White, Kevin R Flaherty, Elizabeth A Belloli, Jamie S Sheth, Nisha Mohan, Nazanin Nazemi, Andrew R Yu, Sahand Ghodrati, Kerri A Johannson, Veronica Marcoux, Jolene H Fisher, Deborah Assayag, Helene Manganas, Nasreen Khalil, Martin Kolb, Julie Morisset, Christine Kim Garcia, Felix Chua, Mary E Strek, Yet H Khor, Ayodeji Adegunsoye, Christopher J Ryerson, Philip L Molyneaux, Justin M Oldham

Faculty, Staff and Student Publications

Rationale: Clinical measures of progressive pulmonary fibrosis (PPF) have been proposed, but their clinical utility remains unclear.

Objectives: To determine performance characteristics of lung function-based PPF measures, including new guideline criteria for discriminating clinically relevant outcomes.

Methods: A multicenter retrospective cohort analysis was performed to assess the performance characteristics of eight categorical measures of FVC and DlCO decline, together with PPF guideline criteria (requiring two of the following: worsening respiratory symptoms, absolute decline in FVC ⩾5% or DlCO ⩾15%, or radiological progression) for discriminating 2-year death or lung transplant among patients fibrotic interstitial lung disease from the United States, United …

Precemtabart Tocentecan, An Anti-Ceacam5 Antibody-Drug Conjugate, In Metastatic Colorectal Cancer: A Phase 1 Trial, Scott Kopetz, Valentina Boni, Ken Kato, Kanwal P S Raghav, Maria Vieito, Athanasios Pallis, Christina Habermehl, Abdul Siddiqui, Perrine Courlet, Willem Sloot, Sabine Raab-Westphal, Felix Hart, Ildefonso Rodriguez-Rivera

Faculty, Staff and Student Publications

CEACAM5, a cell surface protein, is overexpressed in colorectal cancer (CRC). Precemtabart tocentecan (Precem-TcT, previously M9140) is an anti-CEACAM5 antibody–drug conjugate with the topoisomerase 1 inhibitor exatecan as payload. Precem-TcT demonstrated strong antitumor activity and potent bystander activity in preclinical models. Its toxicity profile in cynomolgus monkeys was consistent with that of exatecan. In the dose-escalation stage of the phase 1 trial of Precem-TcT (PROCEADE-CRC-01), 40 heavily pretreated patients with irinotecan-refractory metastatic CRC received Precem-TcT every 3 weeks across seven dose levels (DLs, 0.6–3.2 mg kg−1). Primary endpoints were dose-limiting toxicities (DLTs), adverse events and preliminary clinical activity to establish …

Updated Estimates Of Patients With Oropharyngeal Cancer In The Us, Caineng Cao, Anna Lee, Jung Julie Kang, Irini Yacoub, Kaveh Zakeri, Edward Christopher Dee, Nadeem Riaz, Achraf Shamseddine, Yao Yu, Jennifer Ma, Teeradon Treechairusame, Marc A Cohen, Jennifer R Cracchiolo, Richard J Wong, Winston Wong, Lara A Dunn, Eric J Sherman, Nancy Y Lee

Faculty, Staff and Student Publications

Importance: Updated estimates of oropharyngeal cancer (OPC) in the US are needed.

Objective: To calculate the most recent epidemiologic estimates of OPC in the US and provide projections for future trends up to 2040.

Design, setting, and participants: This cross-sectional epidemiological analysis used data from the recent National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. The SEER-22 (excluding Illinois and Massachusetts) database provided data for incidence, prevalence, survival, and initial treatment by OPC stage. Patients with OPC diagnosed according to International Classification of Diseases for Oncology, Third Edition morphology codes were included. The analysis was conducted from September …

Natural History Of Primary Retroperitoneal Extra-Visceral Perivascular Epithelioid Cell Tumors (Pec): A Study From Transatlantic And Australasian Retroperitoneal Sarcoma Working Group (Tarpswg), Eyal Mor, Sameer Apte, Catherine Mitchell, Carolyn Nessim, Max Almond, Bruno Vincenzi, Jose Antonio Gonzalez Lopez, Lee Cranmer, Michael J Wagner, Aviram Nissan, Miguel Henriques Abreu, Markus Albertsmeier, Mathilda Knoblauch, Adam Barlow, Emily Z Keung, Giovanni Grignani, Jason L Hornick, Alessandro Gronchi, David E Gyorki

Faculty, Staff and Student Publications

Background: Perivascular epithelioid cell tumors (PEComa) are a rare family of mesenchymal tumors that include several subtypes. There are very limited data describing the natural history of patients with extra-visceral retroperitoneal PEComas of the retroperitoneum. The aim of this study is to describe the clinical features, treatment patterns, outcomes, and diagnostic challenges of primary extra-visceral retroperitoneal or abdominopelvic PEComa over the past decade.

Patients and methods: This is a retrospective analysis of all extra-visceral, non-renal, retroperitoneal, or abdominopelvic PEComas treated at participating centers over the past 10 years.

Results: A total of 77 patients from 13 centers were included. The …

Cancer-Induced Nerve Injury Promotes Resistance To Anti-Pd-1 Therapy, Erez N Baruch, Frederico O Gleber-Netto, Priyadharsini Nagarajan, Xiayu Rao, Shamima Akhter, Tuany Eichwald, Tongxin Xie, Mohammad Balood, Adebayo Adewale, Shorook Naara, Hinduja N Sathishkumar, Shajedul Islam, William Mccarthy, Brandi J Mattson, Renata Ferrarotto, Michael K Wong, Michael A Davies, Sonali Jindal, Sreyashi Basu, Karine Roversi, Amin Reza Nikpoor, Maryam Ahmadi, Ali Ahmadi, Catherine Harwood, Irene Leigh, Dennis Gong, Paulino Tallón De Lara, Derrick L Tao, Tara M Davidson, Nadim J Ajami, Andrew Futreal, Kunal Rai, Veena Kochat, Micah Castillo, Preethi Gunaratne, Ryan P Goepfert, Sharia D Hernandez, Nikhil I Khushalani, Jing Wang, Stephanie S Watowich, George A Calin, Michael R Migden, Mona Yuan, Naijiang Liu, Yi Ye, William L Hwang, Paola D Vermeer, Nisha J D'Silva, Yuri L Bunimovich, Dan Yaniv, Jared K Burks, Javier Gomez, Patrick M Dougherty, Kenneth Y Tsai, James P Allison, Padmanee Sharma, Jennifer A Wargo, Jeffrey N Myers, Sebastien Talbot, Neil D Gross, Moran Amit

Faculty, Staff and Student Publications

Perineural invasion (PNI) is a well-established factor of poor prognosis in multiple cancer types1, yet its mechanism remains unclear. Here we provide clinical and mechanistic insights into the role of PNI and cancer-induced nerve injury (CINI) in resistance to anti-PD-1 therapy. Our study demonstrates that PNI and CINI of tumour-associated nerves are associated with poor response to anti-PD-1 therapy among patients with cutaneous squamous cell carcinoma, melanoma and gastric cancer. Electron microscopy and electrical conduction analyses reveal that cancer cells degrade the nerve fibre myelin sheets. The injured neurons respond by autonomously initiating IL-6- and type I interferon-mediated …

Imaging- And Tumor Biomarker-Based Multivariable Model For Early Prediction Of Pathologic Complete Response To Neoadjuvant Systemic Therapy In Triple-Negative Breast Cancer, Beatriz E Adrada, Mary S Guirguis, Lei Huo, Clinton Yam, Debu Tripathy, Rosalind Candelaria, Wei Yang, Miral Patel, Tanya Moseley, Gary J Whitman, Jessica W T Leung, Huong Le-Petross, Deanna L Lane, Nour Abuhadra, Jennifer Litton, Vicente Valero, Kelly K Hunt, Banu Arun, Rania Mohamed, Jia Sun, Anil Korkut, Sanaz Pashapoor, Jason White, Alastair Thompson, Peng Wei, Jingfei Ma, Stacy Moulder, Gaiane M Rauch

Faculty, Staff and Student Publications

Purpose: The response of triple-negative breast cancer (TNBC) to neoadjuvant therapy (NAT) varies widely. This study aimed to determine the performance of clinicopathologic biomarkers and volumetric changes on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting pathologic complete response (pCR) to NAT in patients with TNBC.

Patients and methods: This study included 264 patients with stage I to III TNBC enrolled in a prospective clinical trial. These patients underwent DCE-MRI at baseline and after two and/or after four cycles of dose-dense anthracycline and cyclophosphamide. Tumor volume (TV) was calculated by measuring three tumor dimensions at each time point. Clinicopathologic markers …

Grpa-Prs: A Risk Stratification Method To Identify Genetically-Regulated Pathways In Polygenic Diseases, Xiaoyang Li, Brisa S Fernandes, Andi Liu, Jingchun Chen, Xiangning Chen, Zhongming Zhao, Yulin Dai

Faculty, Staff and Student Publications

Introduction: Polygenic risk score (PRS) assesses genetic risk for diseases, yet some high-risk individuals avoid illness while low-risk individuals develop it. We hypothesize that unknown counterfactors may reverse PRS predictions, offering insights into disease mechanisms and interventions.

Methods: We developed a novel framework to identify genetically-regulated pathways (GRPas) using PRS-based stratification in Alzheimer's disease (AD) and schizophrenia (SCZ) cohorts. We calculated PRS models, stratified individuals by risk and diagnosis, and analyzed differential GRPas. For AD, analyses were further conducted with and without apolipoprotein E (APOE) effects, and across APOE haplotype.

Results: In AD, we identified several well-known AD-related pathways, including …

Design And Development Of An Intervention To Improve The Quality And Safety Of Pediatric Dental Sedation: A Human-Centered Design Approach, Kawtar Zouaidi, Jan Yeager, Suhasini Bangar, Sayali Tungare, Urvi Mehta, Janelle Urata, Alfa-Ibrahim Yansane, Thomas Tanbonliong, Jungsoo Kim, Emily Sedlock, Krishna Kumar Kookal, Yan Xiao, Tokede Oluwabunmi, Heiko Spallek, Amy Franklin, Gregory W Olson, Joel White, Elsbeth Kalenderian, Muhammad F Walji

Faculty, Staff and Student Publications

Background: There are gaps in understanding the experiences of children, parents, and providers during dental conscious sedation. This study aimed to capture and analyze these experiences to identify opportunities for improvement and enhance the quality and safety of pediatric dental conscious sedation.

Methods: A human-centered design approach was used to examine the conscious sedation experience in 2 US advanced education pediatric dental clinics. Researchers conducted field observations, interviews with providers and parents, and providers focus groups to explore experiential factors. Data were transcribed and analyzed using content thematic analysis. Insights from the data were used to explore and generate new …

Relationship Between Quantitative Mri Ute T2* Of Acl Autografts And Bmi-Normalized Knee Laxity Within The First Year After Acl Reconstruction, Alonso Figueroa, Tomasz Bugajski, Dillon Humpal, Manickam Kumaravel, Walter Lowe, Payam Zandiyeh

Faculty, Staff and Student Publications

Background: The anterior cruciate ligament reconstruction (ACLR) graft undergoes a remodeling process that affects its structural properties. Ultrashort echo time T2* (UTE-T2*) imaging has been instrumental in examining this process. However, more research is needed on the postoperative relationship between UTE-T2* of the graft and its mechanical properties.

Purpose: To longitudinally examine ACL graft changes after ACLR using UTE-T2* decay coefficients and knee laxity and explore their relationship.

Study design: Case series; Level of evidence, 4.

Methods: A total of 31 patients who underwent ACLR had magnetic resonance imaging of their knees at 1, 6, and 12 months after surgery …

Bipolar Spinal Correction Reduces Transfusion Rate And Hospital Stay Compared With Traditional Posterior Spinal Fusion In Children With Scoliosis Secondary To Cerebral Palsy, Kristopher Lundine, Matthias Lu, Timothy C Borden, Samuel Yoon, Mia Percival, Michael B Johnson

Faculty, Staff and Student Publications

Purpose: Patients with neuromuscular scoliosis due to Cerebral Palsy (CP) are complex due to their curve severity and associated medical comorbidities. Spinal fusion is associated with high risk of peri-operative complications and large blood loss requiring allogenic red blood cell (RBC) transfusion. In June 2017, our tertiary paediatric institution implemented a new minimally-invasive approach for the treatment of neuromuscular scoliosis, Bipolar Spinal Correction (Bipolar), a technique first published by Miladi et al. in 2018. This study represents an analysis of the initial experience of this technique to see if it achieves the goal of minimally invasive surgery by decreasing surgical …

Morphometric Analysis Of Spina Bifida After Fetal Repair Shows New Subtypes With Associated Outcomes, L K Mann, S Pandiri, N Agarwal, H Northrup, K S Au, E Grundberg, E P Bergh, M T Austin, R Patel, B Miller, S Zhu, J S Feinberg, D Lai, K Tsao, S A Fletcher, R Papanna

Faculty, Staff and Student Publications

Objectives: The binary classification of spina bifida lesions as myelomeningocele (with sac) or myeloschisis (without sac) belies a spectrum of morphologies. This study aimed to characterize types of spina bifida lesion and correlate them with preoperative presentation and postoperative outcome.

Methods: This was a secondary analysis of a prospective cohort of patients referred for fetal spina bifida who underwent fetoscopic repair between 2020 and 2023 at a single center. We evaluated lesion morphology on high-resolution intraoperative images and videos to categorize lesions based on placode exposure and nerve root stretching. The reproducibility of lesion classification was assessed using the Kappa …

Herthena-Pantumor01: A Phase Ii Study Of Patritumab Deruxtecan (Her3-Dxd) In Previously Treated Advanced Solid Tumors, Thomas Powles, Aarti Bhatia, Barbara Burtness, Takahiro Kogawa, Tomohiro Nishina, Izuma Nakayama, Christos Fountzilas, Dani R Castillo, Meredith Mckean, Funda Meric-Bernstam, Nicoletta Colombo, James W Smithy, Jérome Fayette, Sunandana Chandra, David W Sternberg, Fan Jin, Kendall Sullivan, Sue Yueh, Graham Clinthorne, Ariel E Aguilo, Ragini Kudchadkar, Hidetoshi Hayashi

Faculty, Staff and Student Publications

Human epidermal growth factor receptor 3 (HER3) is a receptor tyrosine kinase that is expressed in numerous solid tumors. Higher levels of HER3 expression in multiple tumor types are associated with adverse clinical outcomes, such as reduced survival. However, there is currently no HER3-directed antibody-drug conjugate approved for the treatment of any cancer. Improved treatment options are needed, in particular for patients who progress on standard therapies. HER3-DXd is an investigational HER3-directed antibody-drug conjugate composed of an anti-HER3 monoclonal antibody linked to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. In previous clinical trials, HER3-DXd demonstrated a …

Pka-Driven Spp1 Activation As A Novel Mechanism Connecting The Bone Microenvironment To Prostate Cancer Progression, Pablo Sanchis, Agustina Sabater, Julia Lechuga, Jimena Rada, Rocio Seniuk, Gaston Pascual, Mora Gatti, Juan Bizzotto, Peter D A Shepherd, Jun Yang, Javier Cotignola, Elba Vazquez, Joaquin Mateo, Pia Valacco, Estefania Labanca, Christopher Logothetis, Geraldine Gueron, Nicolas Anselmino

Faculty, Staff and Student Publications

Prostate cancer (PCa) bone metastasis (BM) poses a significant clinical challenge due to the heterogeneity of treatment responses and patient outcomes. In this study, we examined the role of Protein Kinase A (PKA) signaling in modulating the expression of osteopontin (SPP1/OPN), a protein associated with poor prognosis, within a subset of PCa BM patients. By integrating multi-omics results we identified a novel mechanism in which bone-derived type-I collagen (Col1a1) and fibronectin (Fn1) stimulate SPP1 expression in PCa cells through the activation of PKA signaling. This bone-induced regulation of SPP1 was confirmed both in vitro, using PCa-bone co-culture systems (PC3 or …

Tirzepatide For The Maintenance Of Body Weight Reduction: Rationale, Design, And Baseline Characteristics Of Surmount-Maintain, Deborah B Horn, Louis J Aronne, Sean Wharton, Harold E Bays, Elisa Gomez-Valderas, Avigdor D Arad, Palash Sharma, Julia P Dunn, Cagri Senyucel, Clare J Lee

Faculty, Staff and Student Publications

Objective: SURMOUNT-MAINTAIN aims to evaluate the efficacy and safety of reducing the tirzepatide dose and/or continuing the maximum tolerated dose (MTD) versus placebo in maintaining body weight (BW) reduction achieved with tirzepatide MTD.

Methods: This Phase 3b, multicenter, randomized, parallel-arm, double-blinded, placebo-controlled, 52-week clinical trial is in progress comparing treatment with once weekly tirzepatide (5 mg and/or MTD of 15 mg or 10 mg) versus placebo in achieving BW reduction maintenance from the initial 60-week open-label weight-loss period on tirzepatide MTD, in adults with obesity (BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with ≥ 1 obesity-related comorbidity, excluding type …

Family History Of Substance Use And Stressful Life Events Impact Adolescent Maturation Of Cerebral White Matter, Yizhou Ma, Ashley Acheson, Corneliu Bolbocean, Mustafa N Mithaiwala, Si Gao, Neda Jahanshad, Paul M Thompson, Bhim M Adhikari, Xiaoming Du, A Ankeeta, Alia Warner, Antonio F Pagán, L Elliot Hong, Peter Kochunov

Faculty, Staff and Student Publications

Family history (FH) of substance use disorders (SUDs) and stressful life events (SLEs) are known risk factors for SUDs in adolescents and young adults. Cross‐sectional studies suggest that FH and SLEs affect adolescent white matter (WM) development and form abnormal WM patterns. Here, we examined the effects of FH, SLEs and their interaction on WM integrity in youths in the Adolescent Cognitive Brain Development (ABCD) study at baseline and 2‐ and 4‐year follow‐ups. ABCD youths (N = 8939, age ± SD = 9.9 ± 0.6 years, 4302 female) completed baseline diffusion tensor imaging, of which 5661 repeated the scan …