Medical Specialties Commons^™

A Phase 2 Trial Of Niraparib Plus Bevacizumab Maintenance Therapy Following First-Line Platinum-Based Chemotherapy With Bevacizumab In Advanced Ovarian Cancer: Final Analysis And Overall Survival Results From Ovario., Melissa M Hardesty, Thomas C Krivak, Gail S Wright, Erika Hamilton, Evelyn L Fleming, Jimmy Belotte, Shelby Gorman, Natalie Compton, Aine Clements, Heidi J Gray, Gottfried E Konecny, Richard G Moore, Debra L Richardson

Oncology Articles

OBJECTIVE: To report long-term outcomes from the OVARIO trial of niraparib plus bevacizumab maintenance following first-line platinum-based chemotherapy with bevacizumab in advanced ovarian cancer.

METHODS: The phase 2, single-arm, open-label trial enrolled adult patients with stage IIIB-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (NCT03326193). Patients were required to have attempted debulking surgery and have a complete or partial response or no evidence of disease following first-line, platinum-based chemotherapy with ≥3 cycles of bevacizumab. The primary endpoint was 18-month progression-free survival (PFS) rate, per RECIST. Secondary endpoints included PFS, overall survival (OS), safety, and health-related quality of life (HRQOL) …

The Impact Of Gender, Training Year, Medical Specialty And The Covid-19 Pandemic On Resident Wellness, Sara Beachy, Jessica Luzier, Chantel Weisenmuller, Kathleen Bors, Mary Ann Maurer, Amna Anees, Tiffany Lasky, Lisa Calderwood

Department of Family & Community Medicine Faculty Papers

INTRODUCTION: Data are limited as to which factors most strongly impact medical trainees' well-being, and few studies have assessed trainee's wellness at multiple time points during the COVID-19 pandemic. Additionally, much research has not taken an intersectional approach to understanding the ways in which different facets of a resident's identity impact their wellness. Thus, more person-centred, probability-driven statistical approaches that can produce distinct heterogenous groups of individuals are warranted to understand the way in which different identities are associated with resident wellness scores.

METHODS: A latent profile analysis was conducted using institutional data from resident surveys administered from 2019 to …

High Risk Of Drug-Resistant Tuberculosis In Igra-Negative Contacts: Should Preventive Treatment Be Considered?, Thomas Theo Brehm, Niklas Köhler, Hans-Peter Grobbel, Jürgen Welling, Anna Maria Mandalakas, Vinicius Fava, Erwin Schurr, Christoph Lange

Faculty, Staff and Students Publications

Purpose: Deciding whether to provide preventive treatment to contacts of individuals with multidrug-resistant (MDR) tuberculosis is complex.

Methods: We present the diagnostic pathways, clinical course and outcome of tuberculosis treatment in eight siblings from a single family. Tuberculosis disease was diagnosed by Mycobacterium tuberculosis culture and molecular detection of M. tuberculosis-specific DNA from bronchopulmonary specimens using GeneXpert® MTB/RIF. M. tuberculosis infection was diagnosed by an interferon-gamma release assay (IGRA; QuantiFERON®-TB Gold Plus). Whole exome sequencing for genetic predisposition to mycobacterial infection was performed in one patient.

Results: Six of eight siblings aged 16-20 years from a migrant family of Somali …

Semaphorin 3e-Plexin-D1 Pathway Downstream Of The Luteinizing Hormone Surge Regulates Ovulation, Granulosa Cell Luteinization, And Ovarian Angiogenesis In Mice, Hanxue Zhang, Jimmy Dhillon, Paul D Soloway, Bo Shui, Seoyeon Lee, Jennifer K Grenier, Paul R Munn, M Cecilia Ljungberg, Rebecca B Williams, Rainer B Lanz, Yu-Hsiang Liao, Yi A Ren

Faculty, Staff and Students Publications

Ovulation is induced by the luteinizing hormone (LH) surge and accompanied by granulosa cell luteinization and ovarian angiogenesis. Semaphorin 3E (Sema3E)-Plexin-D1 pathway regulates angiogenesis in other tissues, but its role in the ovary is unknown. Evidence indicates that Sema3E-Plexin-D1 pathway plays an important role in the mouse ovary. The expression of Sema3E and its receptor, Plexin-D1, is dynamically regulated in the mouse ovary downstream of the LH surge. This regulation requires the modulation of chromatin accessibility by CCAAT/enhancer-binding proteins α and β. Intraovarian injection of recombinant Sema3E results in reduced ovulation, impaired corpus luteum formation, and aberrant ovarian angiogenesis. These …

Measuring The Impact Of A Delay In Care On Pediatric Otolaryngologic Surgery Completion, Geethanjeli N Mahendran, Ching Siong Tey, Mary Frances Musso, Grace Shebha Anand, Jeffrey Larson, Mitesh Mehta, Lara Reichert, Kara Prickett, Nikhila Pinnapureddy Raol

Faculty, Staff and Students Publications

Objective: To determine if postponement of elective pediatric otorhinolaryngology surgeries results in a change in overall healthcare utilization and if there is any commensurate impact on disease progression.

Methods: We identified patients ≤18 years of age whose surgeries were postponed at the onset of the COVID-19 pandemic-related shutdown. We then tracked patients' rate of and patterns of rescheduling surgery. Surveys were also sent to caregivers to better characterize his/her decision regarding moving forward with his/her child's surgery during COVID-19.

Results: A total of 1915 pediatric patients had elective surgeries canceled, of which 992 (51.8%) were rescheduled within 4 months. No …

Mood And Sleep In Young Adults With Type 1 Diabetes, Samantha A Carreon, Marissa N Baudino, Charles G Minard, Sarah K Lyons, Randi Streisand, Barbara J Anderson, Siripoom V Mckay, Tricia S Tang, Sara Nowakowski, Ashley M Butler, Sridevi Devaraj, Marisa E Hilliard

Faculty, Staff and Students Publications

Objective: Depression is associated with sleep problems, and both are associated with higher HbA1c in people with type 1 diabetes (T1D). However, little is known about depressed mood and sleep in young adults with T1D. The aims of this secondary analysis were to provide descriptive statistics of multiple aspects of mood and sleep in young adults with T1D and evaluate associations of depressed mood, diabetes distress, and sleep quality and duration.

Methods: At baseline of a behavioral intervention trial, young adults with T1D completed self-report measures of sleep, diabetes distress, and depressive symptoms. We described sleep metrics across racial/ethnic groups …

Characterization Of Visual Field Loss Over 4 Years In The Rate Of Progression In Ush2a-Related Retinal Degeneration (Rush2a) Study, Jacque L Duncan, Maureen G Maguire, Lee S Mcdaniel, Nicole R Doucet, Isabelle Audo, Allison R Ayala, Janet K Cheetham, Peiyao Cheng, Todd A Durham, Rachel M Huckfeldt, Robert B Hufnagel, K Thiran Jayasundera, Naheed Khan, Brett Malbin, Ramiro S Maldonado, Michel Michaelides, Mark E Pennesi, Christina Y Weng, Alex Zmejkoski, Shobana Aravind, Hiroshi Ishikawa, David G Birch

Faculty, Staff and Students Publications

Purpose: To report visual field loss using static perimetry (SP) and kinetic perimetry (KP) over 4 years in the Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) study.

Design: Prospective, observational cohort study.

Subjects, participants, and/or controls: Participants had USH2A-related rod-cone degeneration, visual acuity ≥20/80, and KP III4e ≥10° at baseline in the study eye. Preserved cohorts with baseline visual fields sufficient to detect progression were identified.

Methods: Participants were examined annually through 4 years. Mixed-effects models were used to estimate the annual, standardized rate, and percentage rates of change.

Main outcome measures: SP measures included hill of vision (total: …

Data-Driven Approach To Dynamic Resting State Functional Connectivity In Post-Traumatic Stress Disorder: An Enigma-Pgc Ptsd Study, Carissa W Tomas, Jacklynn M Fitzgerald, C Lexi Baird, Courtney C Haswell, Chadi G Abdallah, Michael Angstadt, Justin T Baker, Hannah Berg, Jennifer U Blackford, Josh Cisler, Andrew S Cotton, Judith K Daniels, Nicholas D Davenport, Richard J Davidson, Terri A Deroon-Cassini, Seth G Disner, Wissam El Hage, Negar Fani, Jessie L Frijling, Evan M Gordon, Daniel W Grupe, Xiaofu He, Ryan Herringa, David Hofmann, Ashley A Huggins, Ahmed Hussain, Jonathan Ipser, Neda Jahanshad, Tanja Jovanovic, Milissa L Kaufman, Yoojean Kim, Anthony King, Saskia B J Koch, Sheri Koopowitz, Amit Lazarov, Lauren A M Lebois, Isreal Liberzon, Shmuel Lissek, Antje Manthey, Geoffrey May, Katie A Mclaughlin, Laura Nawijn, Steven M Nelson, Yuval Neria, Jack B Nitschke, Bunmi O Olatunji, Miranda Olff, Matthew Peverill, Yann Quidé, Orren Ravid, Kerry Ressler, Marisa Ross, Lauren E Salminen, Kelly Sambrook, Chiahao Shih, Anika Sierk, Scott R Sponheim, Dan J Stein, Jennifer Stevens, Thomas Straube, Benjamin Suarez-Jimenez, Paul M Thompson, Nic J A Van Der Wee, Steven J A Van Der Werff, Sanne J H Van Rooij, Mirjam Van Zuiden, Dick J Veltman, Robert R J M Vermeiren, Henrik Walter, Xin Wang, Hong Xie, Xi Zhu, Sigal Zilcha-Mano, Christine L Larson, Rajendra Morey

Faculty, Staff and Students Publications

Using functional magnetic resonance imaging (fMRI), symptoms of posttraumatic stress disorder (PTSD) have been associated with aberrations in brain networks in the absence of a given cognitive demand or task, called resting-state networks. Prior work has focused on disruption in the static functional connectivity (FC) among specific regions constrained by a priori hypotheses. However, dynamic FC, an approach that examines brain network characteristics over time, may provide a more sensitive measure to understand the network properties underlying dysfunction in PTSD. Further, using a data-driven analytic approach may reveal the contribution of other larger network disturbances beyond those revealed by hypothesis-driven …

Integrative Exome Sequencing And Machine Learning Identify Micb And Interferon Pathway Genes As Contributors To Ssc Risk, Shamika Ketkar, Hongzheng Dai, Lindsay Burrage, David Murdock, Brian Dawson, Marialbert Acosta-Herrera, Martin Kerick, Javier Martin, Kevin Wilhelm, Jennifer Kay Asmussen, Olivier Lichtarge, Regeneron Genetics Center, Shervin Assassi, Maureen D Mayes, Brendan H Lee

Faculty, Staff and Students Publications

Objectives: Systemic sclerosis (SSc) is a complex autoimmune disease with both known and unidentified genetic contributors. While genome-wide association studies (GWAS) have implicated multiple loci, many reside in noncoding regions. We aimed to identify novel protein-coding variants and pathogenic pathways using exome sequencing (ES) integrated with an Evolutionary Action-Machine Learning (EAML) framework, single-cell RNA sequencing (scRNA-seq), and expression quantitative trait locus (eQTL) analysis.

Methods: GWAS was conducted in 2,559 SSc cases and 893 controls of Caucasian ancestry, with replication in 9,846 cases and 18,333 controls of European ancestry. EAML prioritized genes with high-impact missense variants predictive of disease. Public scRNA-seq …

Notice-Ed: Nurse Or Technician Insights Into Cognitive Evaluations In The Emergency Department, Sarah J Nessen, Anita N Chary, Annika R Bhananker, K Jane Muir, Lauren T Southerland, Kyra O'Brien, Ari B Friedman

Faculty, Staff and Students Publications

Background: Several strategies have been proposed to increase chronic cognitive impairment (CI) screening in the emergency department (ED). Our goal was to assess the feasibility and acceptability of implementing specific CI screening tools and strategies in the ED from an ED registered nurse and technician perspective.

Methods: We performed a qualitative study using semi-structured interviews with a purposive sample of ED nurses and ED technicians (EDTs). Participants worked at an urban academic hospital and were interviewed between November 2023 and March 2024. Interviews assessed participants' opinions on the feasibility and acceptability of CI screening and the use of machine learning …

A Simple, Interpretable Machine Learning Model Based On Clinical Factors Accurately Predicts Incident Dysplasia Or Malignancy In Barrett's Esophagus, Ashwin Rao, Jasmine Haydel, Samuel Ma, Aaron P Thrift, Theresa Nguyen-Wenker, Hashem B El-Serag

Faculty, Staff and Students Publications

Purpose: Identifying patients likely to develop dysplasia or malignancy is critical for effective surveillance in patients with Barrett's Esophagus (BE). However, current predictive models are limited. We evaluated the performance of machine learning (ML) models in predicting incident dysplasia or malignancy in a cohort of veteran patients with BE.

Methods: We analyzed data from 598 patients newly diagnosed with non-dysplastic BE (NDBE), BE indefinite for dysplasia (BE-IND), and BE with non-persistent low-grade dysplasia (LGD) at the Michael DeBakey Veterans Affairs Medical Center from November 1990 to January 2019 with follow-up through January 2024. Progressors were patients who developed persistent LGD, …

An Electronic Trigger To Detect Telemedicine-Related Diagnostic Errors, Daniel R Murphy, Himabindu Kadiyala, Li Wei, Hardeep Singh

Faculty, Staff and Students Publications

Introduction

Methods

Racial And Ethnic Disparity For Cancer Mortality In General And Single-Payer Healthcare Systems In The United States, Rock Bum Kim, Emily Zhou, Kaitlin N Swinnerton, Jennifer La, Shengling Ma, Mrinal Ranjan, Nhan V Do, Mary T Brophy, Nathanael R Fillmore, Ang Li

Faculty, Staff and Students Publications

Background: It remains unclear what factors significantly drive racial disparity in cancer survival in the United States (US). We compared adjusted mortality outcomes in cancer patients from different racial and ethnic groups on a population level in the US and a single-payer healthcare system.

Patients and methods: We selected adult patients with incident solid and hematologic malignancies from the Surveillance, Epidemiology, and End Results (SEER) 2011-2020 and Veteran Affairs national healthcare system (VA) 2011-2021. We classified the self-reported NIH race and ethnicity into non-Hispanic White (NHW), non-Hispanic Black (NHB), non-Hispanic Asian Pacific Islander (API), and Hispanic. Cox regression models for …

Are There Rural-Urban Disparities In Cardiovascular Disease Hospitalization And Other Outcomes In People With Gout? A Nationwide Us Study, Jasvinder A Singh, Sumanth R Chandrupatla

Faculty, Staff and Students Publications

Objective: The objective of this study was to assess whether rural vs urban patient residence is associated with the risk of myocardial infarction (MI) hospitalization and other outcomes in people with gout.

Methods: We used the 2016-2019 U.S. National Inpatient Sample (NIS) database to assess whether rural patient residence is associated with a higher risk of MI hospitalizations in gout, while adjusting for demographics (age, sex, race), comorbidity, median household income, insurance payer, and hospital characteristics (location and teaching status, bed size, hospital control, and hospital region). We calculated adjusted odds ratios (aORs) and 95% CIs (CIs).

Results: We found …

Rest-Activity Rhythm Phenotypes In Adults With Epilepsy And Intellectual Disability, Nandani Adhyapak, Grace E Cardenas, Mark A Abboud, Vaishnav Krishnan

Faculty, Staff and Students Publications

Objective: Rest-activity rhythms (RARs) are perturbed in many forms of neuropsychiatric illness. In this study, we applied wrist actigraphy to describe RAR perturbations in intellectually disabled adults with epilepsy ("E + ID"), using a cross-sectional case-control design. We examined whether RAR phenotypes correlated with epilepsy severity, deficits in adaptive function, and/or comorbid psychopathology.

Methods: Caregivers of E + ID subjects provided informed consent during routine ambulatory clinic visits and were asked to complete standardized surveys of overall epilepsy severity (GASE, Global Assessment of Severity of Epilepsy), adaptive function (ABAS-3, Adaptive Behavior Assessment System-3) and psychopathology (ABCL, Adult Behavior Checklist). Caregivers …

Genetic Diversity And Expanded Phenotypes In Dystonia: Insights From Large-Scale Exome Sequencing, Mirja Thomsen, Fabian Ott, Sebastian Loens, Gamze Kilic-Berkmen, Ai Huey Tan, Shen-Yang Lim, Ebba Lohmann, Kaja M Schröder, Lea Ipsen, Lena A Nothacker, Linn Welzel, Alexandra S Rudnik, Frauke Hinrichs, Thorsten Odorfer, Kirsten E Zeuner, Friederike Schumann, Andrea A Kühn, Simone Zittel, Marius Moeller, Robert Pfister, Christoph Kamm, Anthony E Lang, Yi Wen Tay, Ana Luísa De Almeida Marcelino, Marie Vidailhet, Emmanuel Roze, Joel S Perlmutter, Jeanne S Feuerstein, Victor S C Fung, Florence Chang, Richard L Barbano, Steven Bellows, Aparna A Wagle Shukla, Alberto J Espay, Mark S Ledoux, Brian D Berman, Stephen Reich, Andres Deik, Andre Franke, Michael Wittig, Sören Franzenburg, Jens Volkmann, Norbert Brüggemann, H A Jinnah, Tobias Bäumer, Christine Klein, Hauke Busch, Katja Lohmann

Faculty, Staff and Students Publications

Objective: Dystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%), the etiology in most patients remains elusive. Moreover, understanding correlations between clinical manifestations and genetic variants has become increasingly complex.

Methods: Exome sequencing was conducted on 1924 genetically unsolved, mainly late-onset isolated dystonia patients, recruited primarily from two dystonia registries (DysTract and the Dystonia Coalition). Rare variants in genes previously linked to dystonia (n = 406) were examined, confirmed via Sanger sequencing, and analyzed for segregation when possible.

Results: We identified 137 distinct likely pathogenic/pathogenic variants (according to ACMG …

Ruptured Arteriovenous Malformation Mortality: Incidence, Risk Factors, And Inpatient Outcome Score, Eric Feldstein, Allison Zhong, Kevin Clare, Bridget Nolan, Smit Patel, Nir Lavi-Romer, Zehavya Stadlan, Alis Dicpinigaitis, Jose Dominguez, Haris Kamal, Steven D Shapiro, Arundhati Biswas, Omar Tanweer, Ketan Bulsara, Carrie Muh, Jared Pisapia, Simon Hanft, Stephan Mayer, Chirag D Gandhi, Fawaz Al-Mufti

Faculty, Staff and Students Publications

Background

Limited literature exists on the morbidity and mortality of AVM associated intracerebral hemorrhage (ICH) compared with non-AVM ICH.

Objective

We examine morbidity and mortality in cAVM in a large nationwide inpatient sample to create a prognostic inpatient ruptured AVM mortality score.

Methods

This retrospective cohort study from 2008 to 2014 compares outcomes in cAVM related hemorrhages and ICH utilizing the National Inpatient Sample database. Diagnostic codes for ICH and AVM underlying ICH were identified. We compared case fatality according to medical complications. Multivariate analysis was used to derive hazard ratios and 95% confidence intervals to assess odds of mortality. …

Implementation Outcomes Of A Patient Decision-Aid In A Diverse Population With Systemic Lupus Erythematosus In 15 Us Rheumatology Clinics, Jasvinder A Singh, Larry R Hearld, Seth Eisen, W Winn Chatham, Sonali Narain, Narender Annapureddy, Diane L Kamen, Kimberly Trotter, Vikas Majithia, Cathy Lee Ching, Zineb Aouhab, Swamy Venuturupalli, Daniel J Wallace, Rosalind Ramsey-Goldman, Alfred Kim, Maureen Mcmahon, S Sam Lim, Kalpana Bhairavarasu, Alexa Meara, Kenneth Kalunian, T Mark Beasley

Faculty, Staff and Students Publications

Objective: The objective of this study was to examine the clinical outcomes during the implementation of a self-administered patient decision-aid (PtDA) for lupus.

Methods: We provided an effective computerized lupus PtDA in 15 rheumatology outpatient clinics 2019-2024 (including the COVID pandemic). We undertook Organizational Readiness to Implement Change Surveys (ORICs) and Team Learning and Psychological Safety Surveys (TLPSSs) at baseline. The primary study outcome objective measure, percent penetration/reach, was defined as the number of patients who viewed the lupus PtDA at the end of the study, divided by the total number of eligible patients (times 100). We used validated clinical …

Work Impairment And Financial Outcomes Among Adults With Vs Without Long Covid, Michael Gottlieb, Ji Chen, Huihui Yu, Michelle Santangelo, Erica S. Spatz, Nicole L. Gentile, Rachel E. Geyer, Caitlin Malicki, Kristyn Gatling, Kelli N. O'Laughlin, Kari A. Stephens, Joann G. Elmore, Lauren E. Wisk, Michelle L'Hommedieu, Robert Rodriguez, Juan Carlos C. Montoy, Ralph C. Wang, Kristin L. Rising, Efrat Kean, Jonathan W. Dyal, Mandy J. Hill, Arjun K. Venkatesh, Robert A. Weinstein

Department of Emergency Medicine Faculty Papers

IMPORTANCE: While much of the focus on long COVID (LC; defined as developing new, persistent symptoms lasting 3 months or longer after SARS-CoV-2 infection) has been on health status and quality of life, the impact on individual work productivity and financial distress are less well established.

OBJECTIVES: To assess differences in work and financial outcomes among individuals with current, resolved, and no LC up to 3 years after initial infection.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, multisite, longitudinal cohort study enrolled adult participants (age ≥18 years) with at least 1 reported SARS-CoV-2 infection from December 7, 2020, to August 29, …

Multicenter Span Trial Of Fasudil In Ischemic Stroke, Takahiko Imai, Andreia Lopes De Morais, Xuyan Jin, Tao Qin, Jessica Lamb, Karisma A Nagarkatti, Mu-Hsun Chen, Ligia S B Boisserand, Rakesh B Patel, Mariia Kumskova, Anjali Chauhan, Krishnan M Dhandapani, Mohammad B Khan, Pradip K Kamat, Yanrong Shi, Suyi Cao, Basavaraju G Sanganahalli, Joseph B Mandeville, Patrick D Lyden, David C Hess, Enrique C Leira, Anil K Chauhan, Jaroslaw Aronowski, Louise D Mccullough, Raymond C Koehler, Lauren H Sansing, Márcio A Diniz, Cenk Ayata

Children’s Nutrition Research Center Staff Publications

Background: The SPAN (Stroke Preclinical Assessment Network) is a confirmatory multicenter trial network to test cerebroprotective interventions in experimental acute stroke. In a first-of-its-kind trial, SPAN tested 6 interventions in a rodent model of transient focal ischemic stroke. Here, we report the efficacy of fasudil, an isoform-nonselective rho-associated kinase inhibitor, on primary and secondary outcomes in the SPAN trial.

Methods: Fasudil was administered at 10 mg/kg intraperitoneally every 12 hours for 6 doses starting 5 minutes before reperfusion in a 60-minute endovascular filament middle cerebral artery occlusion model. The active treatment arm (n=345) was compared with the pooled intraperitoneal and …

Family-Level Factors That Influence Physical Activity Among Hispanic Adolescents At Risk For Type 2 Diabetes, Sandra Mihail, Ayleen A Hernandez, Erica G Soltero

Children’s Nutrition Research Center Staff Publications

Objective: Family-based health promotion and disease prevention strategies are recommended as best practice; however, there is limited knowledge regarding the family-level factors that influence modifiable behavior risk factors like physical activity (PA) among Latinx adolescents. This study addressed this knowledge gap by using qualitative methods to identify perceptions of family-level factors that influence PA among Hispanic youth.

Methods: We conducted semistructured, open-ended interviews with 20 Latinx adolescents (14-16 years) with obesity (body mass index ≥95th percentile) to identify their perceptions of how family influences PA. Content analysis was used to identify emergent themes, which were then compared across demographic factors, …

Nerve-To-Cancer Transfer Of Mitochondria During Cancer Metastasis, Gregory Hoover, Shila Gilbert, Olivia Curley, Clémence Obellianne, Mike T Lin, William Hixson, Terry W Pierce, Joel F Andrews, Mikhail F Alexeyev, Yi Ding, Ping Bu, Fariba Behbod, Daniel Medina, Jeffrey T Chang, Gustavo Ayala, Simon Grelet

Faculty, Staff and Students Publications

The nervous system has a pivotal role in cancer biology, and pathological investigations have linked intratumoural nerve density to metastasis1. However, the precise impact of cancer-associated neurons and the communication channels at the nerve–cancer interface remain poorly understood. Previous cancer denervation models in rodents and humans have highlighted robust cancer dependency on nerves, but the underlying mechanisms that drive nerve-mediated cancer aggressivity remain unknown2,3. Here we show that cancer-associated neurons enhance cancer metabolic plasticity by transferring mitochondria to cancer cells. Breast cancer denervation and nerve–cancer coculture models confirmed that neurons significantly improve tumour energetics. …

Experiences Of The Emergency Department Environment: A Qualitative Study With Caregivers Of People With Dementia, Anita N Chary, Michelle Suh, Annika Bhananker, Norvin Hernandez, Ana Paulina Rivera, Ed Boyer, Mark E Kunik, Manish N Shah, Christine Ritchie, Aanand D Naik, Shan W Liu, Maura Kennedy

Faculty, Staff and Students Publications

ED crowding and boarding adversely impact older patients' care and outcomes. Little is known about how ED crowding impacts persons living with dementia, a vulnerable population. This study sought to explore ED experiences of caregivers of people with dementia during a period of ED crowding and boarding. We performed semi-structured interviews with caregivers of people with dementia with an ED visit during a period of ED crowding and boarding at two public hospitals experiencing a threefold increase in boarding from pre-pandemic levels. Participants were recruited via chart review. We coded data using an inductive approach. Three themes emerged from 29 …

Bridging Psychiatry And Rare Genetic Diseases: A Scoping Review Of Therapeutic Strategies And Diagnostic Delay Paired With Healthcare Economic Burden Analysis, Sheldon R Garrison, Isaac J Siegel, Christopher R Takala, Sarah L Vaithilingam, Gene W Yang, Anthony W Zoghbi, Madeline M Hartig, Sreya Vadapalli, Margaret E Anderson

Duncan NRI Faculty and Staff Publications

Rare genetic diseases (RDs) with primary neuropsychiatric symptoms pose unique challenges for diagnosis and management. While the majority of these RDs have neuropsychiatric symptoms that are secondary to the RD, a subset presents with primary neuropsychiatric symptoms directly linked to their underlying pathophysiology. This subset has significant unmet medical need with delayed diagnoses leading to prolonged delays in treatment optimization and the trialing of medications that fail to target the underlying pathophysiology. This comprehensive review identifies 108 RDs with central neuropsychiatric symptoms that have a 7.7-year average diagnostic delay. Optimal management strategies for these RDs typically includes non-psychotropic medications, dietary …

De Novo And Inherited Variants In Ddx39b Cause A Novel Neurodevelopmental Syndrome, Kevin T A Booth, Sharayu V Jangam, Martin M C Chui, Kayla Treat, Lorenzo Graziani, Alessia Soldano, Yao Ruan, Jeffrey Wan-Hei Hui, Kerry White, Celanie K Christensen, Ty Lynnes, Shinya Yamamoto, Oguz Kanca, Mandy H Y Tsang, Sally A Lynch, Sureni V Mullegama, Julia Baptista, Daniela Iancu, Shelagh K Joss, Sandra Y Y Wong, Christopher C Y Mak, Anna K Y Kwong, Hugo J Bellen, Erin Conboy, Remo Sanges, Anskar Yu-Hung Leung, Michael F Wangler, Brian H Y Chung, Francesco Vetrini

Duncan NRI Faculty and Staff Publications

DDX39B is a conserved member of the DEAD-box family of ATP-dependent RNA helicases, critical in mRNA metabolism across eukaryotes. DDX39B is also a core component of the TRanscription-EXport (TREX) super protein complex, and recent studies have highlighted the important role of its subunits in neurodevelopmental disorders. Here, we describe six individuals from five families, four harbouring de novo missense variants in DDX39B and one with an inherited splicing variant, presenting with variable developmental delay, congenital hypotonia, epilepsy, short stature, skeletal abnormalities, dysmorphic features and microcephaly in three patients.

3D molecular modelling predicts these variants would alter protein structure. In vitro …

Folliculin Depletion Results In Liver Cell Damage And Cholangiocarcinoma Through Mit/Tfe Activation, Bruno Maria Custode, Francesco Annunziata, Felipe Dos Santos Matos, Valentina Schiano, Veronica Maffia, Milena Lillo, Rita Colonna, Rossella De Cegli, Andrea Ballabio, Nunzia Pastore

Duncan NRI Faculty and Staff Publications

Mutations in the tumor suppressor gene Folliculin (FLCN) are responsible for Birt-Hogg-Dube’ (BHD) syndrome, a rare inherited condition that predisposes affected individuals to skin tumors, pulmonary cysts, and kidney tumors. FLCN regulates key cellular pathways, including TFEB, TFE3, and mTORC1, which are critical for maintaining cell homeostasis. Loss of FLCN leads to both hyperactivation of mTORC1 and constitutive activation of TFEB and TFE3, contributing to tumorigenesis. While previous studies showed that Flcn liver-specific conditional knockout (FlcnLiKO) mice are protected from developing liver fibrosis and damage upon high-fat diet exposure, the potential role of FLCN loss in liver carcinogenesis …

Diagnostic Value Of Cell-Free Dna Fetal Fraction In Patients With Prenatally Suspected Placenta Accreta Spectrum Disorder, Danielle Chirumbole, Christian M Parobek, Alex Tai, Haleh Sangi-Haghpeykar, Yamely H Mendez, Spoorthi Kamepalli, Christina C Reed, Arthur Ladron De Guevara, Keneshia Lane, Claire Hoppenot, Amir A Shamshirsaz, Michael A Belfort, Jessian L Munoz, Hendrik A Lombaard

Faculty, Staff and Students Publications

Objective: The purpose of this study was to investigate the relationship between fetal fraction (FF) and placenta accreta spectrum (PAS) pathology in patients with prenatally suspected PAS.

Methods: This was a case-control study utilizing a database of pregnancies with suspected or proven PAS delivered between 6/2012 and 7/2024 at a single institution. Pregnancies were excluded if FF was not reported. The primary outcome was mean FF in pregnancies with a final clinical diagnosis of low FIGO grade (no PAS or FIGO1-2) versus high FIGO grade (FIGO3) placenta accreta. Results were reported as mean FF ± standard error of the mean. …

Efficacy And Safety Of Oral Decitabine/Cedazuridine In The Chronic Myelomonocytic Leukaemia Subpopulations From Phase 2 And 3 Studies, Michael R Savona, Olatoyosi Odenike, Gail J Roboz, Harshad Amin, Amy E Dezern, Elizabeth A Griffiths, Kim-Hien Dao, Amer M Zeidan, Bhavana Bhatnagar, Rena Buckstein, Brian Leber, Mary-Margaret Keating, Somedeb Ball, Aram Oganesian, Yuri Sano, Harold N Keer, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

DNA methyltransferase inhibitors (DNMTis) are commonly used in treating chronic myelomonocytic leukaemia (CMML); however, data from prospective studies of DNMTis in CMML are limited. The present analysis evaluated the efficacy, safety and pharmacodynamics of the oral DNMTi decitabine/cedazuridine in the subset of patients with CMML from the phase 2 and 3 trials, which led to the approval of this agent for myelodysplastic syndromes and CMML in the United States and Canada. Potential prognostic factors also were analysed. In all, 34 patients with CMML were screened and 33 were treated. Most patients (76% [n = 25]) had myelodysplastic type-CMML and 77% …

Bayesian Counterfactual Machine Learning Individualizes Radiation Modality Selection To Mitigate Immunosuppression, Duo Yu, Michael J Kane, Yiqing Chen, Steven H Lin, Radhe Mohan, Brian P Hobbs

Faculty, Staff and Student Publications

Purpose: Lymphocytes play critical roles in cancer immunity and tumor surveillance. Radiation-induced lymphopenia (RIL) is a common side effect observed in patients with cancer undergoing chemoradiation therapy (CRT), leading to impaired immunity and worse clinical outcomes. Although proton beam therapy (PBT) has been suggested to reduce RIL risk compared with intensity-modulated radiation therapy (IMRT), this study used Bayesian counterfactual machine learning to identify distinct patient profiles and inform personalized radiation modality choice.

Methods: A novel Bayesian causal inferential technique is introduced and applied to a matched retrospective cohort of 510 patients with esophageal cancer undergoing CRT to identify patient profiles …

12/15-Lipooxygenase Inhibition Reduces Microvessel Constriction And Microthrombi After Subarachnoid Hemorrhage In Mice, Ari Dienel, Sung Ha Hong, Hussein A Zeineddine, Sithara Thomas, Shafeeque C M, Dania A Jose, Kiara Torres, Jose Guzman, Andrew Dunn, P Kumar T, Gadiparthi N Rao, Spiros L Blackburn, Devin W Mcbride

Faculty, Staff and Student Publications

Impaired cerebral circulation, induced by blood vessel constrictions and microthrombi, leads to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). 12/15-Lipooxygenase (12/15-LOX) overexpression has been implicated in worsening early brain injury outcomes following SAH. However, it is unknown if 12/15-LOX is important in delayed pathophysiological events after SAH. Since 12/15-LOX produces metabolites that induce inflammation and vasoconstriction, we hypothesized that 12/15-LOX leads to microvessel constriction and microthrombi formation after SAH, and thus, 12/15-LOX is an important target to prevent delayed cerebral ischemia. SAH was induced in C57BL/6 and 12/15-LOX−/− mice of both sexes by endovascular perforation. Expression of 12/15-LOX was assessed …