Medicine and Health Sciences Commons^™

Papillary Tumor Of The Pineal Region: Analysis Of Dna Methylation Profiles And Clinical Outcomes In 76 Cases, Zhichao Wu, Sonika Dahiya, Et Al.

2020-Current year OA Pubs

Papillary tumor of the pineal region (PTPR) is an uncommon tumor of the pineal region with distinctive histopathologic and molecular characteristics. Experience is limited with respect to its molecular heterogeneity and clinical characteristics. Here, we describe 39 new cases and combine these with 37 previously published cases for a cohort of 76 PTPR's, all confirmed by methylation profiling. As previously reported, two main methylation groups were identified (PTPR-A and PTPR-B). In our analysis we extended the subtyping into three subtypes: PTPR-A, PTPR-B1 and PTPR-B2 supported by DNA methylation profile and genomic copy number variations. Frequent loss of chromosome 3 or …

Mate Selection And Current Trends In The Prevalence Of Autism, Elizabeth Forsen, Natasha Marrus, Jacqueline Joyce, Yi Zhang, John N Constantino

2020-Current year OA Pubs

BACKGROUND: According to the most recent U.S. CDC surveillance data, the rise in prevalence of childhood autism spectrum disorder among minority children has begun to outpace that of non-Hispanic white children. Since prior research has identified possible differences in the extent of mate selection for autistic traits across families of different ethnicity, this study examined variation in autism related traits in contemporaneous, epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white populations. The purpose was to determine whether discrepancies by ethnicity could contribute to differential increases in prevalence in the current generation of young children.

METHODS: Birth records …

Epigenome-Wide Association Study Of Lung Cancer Among Never Smokers In Two Prospective Cohorts In Shanghai, China, Mohammad L Rahman, Charles E Breeze, Xiao-Ou Shu, Jason Y Y Wong, Batel Blechter, Andres Cardenas, Xuting Wang, Bu-Tian Ji, Wei Hu, Qiuyin Cai, H Dean Hosgood, Gong Yang, Jianxin Shi, Jirong Long, Yu-Tang Gao, Douglas A Bell, Wei Zheng, Nathaniel Rothman, Qing Lan

Faculty, Staff and Student Publications

BACKGROUND: The aetiology of lung cancer among individuals who never smoked remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Epigenetic alterations, particularly DNA methylation (DNAm) changes, have emerged as potential drivers. Yet, few prospective epigenome-wide association studies (EWAS), primarily focusing on peripheral blood DNAm with limited representation of never smokers, have been conducted.

METHODS: We conducted a nested case-control study of 80 never-smoking incident lung cancer cases and 83 never-smoking controls within the Shanghai Women's Health Study and Shanghai Men's Health Study. DNAm was measured in prediagnostic oral rinse …

Hiv/Aids-Associated Knowledge And Attitudes Towards Treating Disadvantaged Communities Among Pre-Community-Based Dental Education Dental Students In The Us, Aditi Tomar, Hannah Balcezak, Shirley Lewis Miranda, Marie C Latortue, Richa Chinchkhandi, Lisa Wigfall

Faculty, Staff and Student Publications

This study examines HIV/AIDS-associated knowledge and attitudes towards treating disadvantaged communities among predoctoral dental students in U.S. dental schools who have not yet commenced their Community-Based Dental Education (CBDE) training. It also compares the difference in the knowledge and attitudes between students with reported community engagement with PLWHA and those without. Our study comprised 89 predoctoral dental students within their D1-D3 years of dental school who had not yet initiated their Community-Based Dental Education (referred to as pre-CBDE dental students). Their responses were collected via an online survey. The participants were 68% females, 94% heterosexual, and with a mean age …

Early Bolus Epinephrine Administration During Pediatric Cardiopulmonary Resuscitation For Bradycardia With Poor Perfusion: An Icu-Resuscitation Study, Amanda J O'Halloran, Stuart H Friess, Arushi Manga, Et Al.

2020-Current year OA Pubs

BACKGROUND: Half of pediatric in-hospital cardiopulmonary resuscitation (CPR) events have an initial rhythm of non-pulseless bradycardia with poor perfusion. Our study objectives were to leverage granular data from the ICU-RESUScitation (ICU-RESUS) trial to: (1) determine the association of early epinephrine administration with survival outcomes in children receiving CPR for bradycardia with poor perfusion; and (2) describe the incidence and time course of the development of pulselessness.

METHODS: Prespecified secondary analysis of ICU-RESUS, a multicenter cluster randomized trial of children (<  19 years) receiving CPR in 18 intensive care units in the United States. Index events (October 2016-March 2021) lasting ≥ 2 min with a documented initial rhythm of bradycardia with poor perfusion were included. Associations between early epinephrine (first 2 min of CPR) and outcomes were evaluated with Poisson multivariable regression controlling for a priori pre-arrest characteristics. Among patients with arterial lines, intra-arrest blood pressure waveforms were reviewed to determine presence of a pulse during CPR interruptions. The temporal nature of progression to pulselessness was described and outcomes were compared between patients according to subsequent pulselessness status.

RESULTS: Of 452 eligible subjects, 322 (71%) received early epinephrine. The early epinephrine group had higher pre-arrest severity of illness …

Social Vulnerability And Surgery Outcomes: A Cross-Sectional Analysis, Mohamed Abdelhack Washington University School Of Medicine In St. Louis, Sandhya Tripathi, Yixin Chen, Michael S Avidan, Christopher R King

2020-Current year OA Pubs

BACKGROUND: Post-operative complications present a challenge to the healthcare system due to the high unpredictability of their incidence. Socioeconomic conditions have been established as social determinants of health. However, their contribution relating to postoperative complications is still unclear as it can be heterogeneous based on community, type of surgical services, and sex and gender. Uncovering these relations can enable improved public health policy to reduce such complications.

METHODS: In this study, we conducted a large population cross-sectional analysis of social vulnerability and the odds of various post-surgical complications. We collected electronic health records data from over 50,000 surgeries that happened …

Dietary Acculturation Is Associated With Altered Gut Microbiome, Circulating Metabolites, And Cardiovascular Disease Risk In Us Hispanics And Latinos: Results From Hchs/Sol, Yi Wang, Guo-Chong Chen, Zheng Wang, Kai Luo, Yanbo Zhang, Yang Li, Amanda C Mcclain, Marta M Jankowska, Krista M Perreira, Josiemer Mattei, Carmen R Isasi, Maria M Llabre, Bharat Thyagarajan, Martha L Daviglus, Linda Van Horn, David Goldsztajn Farelo, Luis E Maldonado, Steven R Levine, Bing Yu, Eric Boerwinkle, Rob Knight, Robert D Burk, Robert C Kaplan, Qibin Qi, Brandilyn A Peters

Faculty, Staff and Student Publications

Background: Dietary acculturation, or adoption of dominant culture diet by migrant groups, influences human health. We aimed to examine dietary acculturation and its relationships with cardiovascular disease (CVD), gut microbiota, and blood metabolites among US Hispanic and Latino adults.

Methods: In the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), US exposure was defined by years in the United States (50 states and Washington, DC) and US nativity. A dietary acculturation pattern was derived from 14 172 participants with two 24-hour dietary recalls at baseline (2008-2011) using least absolute shrinkage and selection operator regression, with food groups as predictors of US …

Clear Thrombectomy Score: An Index To Estimate The Probability Of Good Functional Outcome With Or Without Endovascular Treatment In The Late Window For Anterior Circulation Occlusion, James E Siegler, Manisha Koneru, Muhammad M Qureshi, Mohamed Doheim, Raul G Nogueira, Nicolas Martinez-Majander, Simon Nagel, Mary Penckofer, Jelle Demeestere, Volker Puetz, Marc Ribo, Mohamad Abdalkader, João Pedro Marto, Alhamza R Al-Bayati, Hiroshi Yamagami, Diogo C Haussen, Marta Olive-Gadea, Simon Winzer, Mahmoud H Mohammaden, Robin Lemmens, Kanta Tanaka, Pekka Virtanen, Anne Dusart, Flavio Bellante, Daniel P O Kaiser, Francois Caparros, Hilde Henon, João Nuno Ramos, Santiago Ortega-Gutierrez, Sunil A Sheth, Stefania Nannoni, Lieselotte Vandewalle, Johannes Kaesmacher, Sergio Salazar-Marioni, Liisa Tomppo, Rita Ventura, Syed F Zaidi, Mouhammad Jumaa, Alicia C Castonguay, Milagros Galecio-Castillo, Ajit S Puri, Adnan Mujanovic, Piers Klein, Liqi Shu, Behzad Farzin, Hannah Moomey, Hesham E Masoud, Jessica Jesser, Markus A Möhlenbruch, Peter A Ringleb, Daniel Strbian, Osama O Zaidat, Shadi Yaghi, Davide Strambo, Patrik Michel, Daniel Roy, Shinichi Yoshimura, Kazutaka Uchida, Jean Raymond, Thanh N Nguyen

Faculty, Staff and Student Publications

Background: With the expanding eligibility for endovascular therapy (EVT) of patients presenting in the late window (6-24 hours after last known well), we aimed to derive a score to predict favorable outcomes associated with EVT versus best medical management.

Methods and results: A multinational observational cohort of patients from the CLEAR (Computed Tomography for Late Endovascular Reperfusion) study with proximal intracranial occlusion (2014-2022) was queried (n=58 sites). Logistic regression analyses were used to derive a 9-point score for predicting good functional outcome (modified Rankin Scale score 0-2 or return to premorbid modified Rankin Scale score) at 90 days, with sensitivity …

Early Bolus Epinephrine Administration During Pediatric Cardiopulmonary Resuscitation For Bradycardia With Poor Perfusion: An Icu-Resuscitation Study, Amanda O'Halloran, Ron Reeder, Robert Berg, Tageldin Ahmed, Michael Bell, Robert Bishop, Matthew Bochkoris, Candice Burns, Joseph Carcillo, Todd Carpenter, J. Michael Dean, J. Wesley Diddle, Myke Federman, Richard Fernandez, Ericka Fink, Deborah Franzon, Aisha Frazier, Stuart Friess, Kathryn Graham, Mark Hall, David Hehir, Christopher M Horvat, Leanna Huard, Martha Kienzle, Todd Kilbaugh, Tensing Maa, Arushi Manga, Patrick Mcquillen, Kathleen Meert, Peter Mourani, Vinay Nadkarni, Maryam Naim, Daniel Notterman, Murray Pollack, Anil Sapru, Carleen Schneiter, Matthew Sharron, Neeraj Srivastava, Bradley Tilford, Alexis Topjian, Shirley Viteri, David Wessel, Heather Wolfe, Andrew Yates, Athena Zuppa, Robert Sutton, Ryan Morgan

Department of Pediatrics Faculty Papers

BACKGROUND: Half of pediatric in-hospital cardiopulmonary resuscitation (CPR) events have an initial rhythm of non-pulseless bradycardia with poor perfusion. Our study objectives were to leverage granular data from the ICU-RESUScitation (ICU-RESUS) trial to: (1) determine the association of early epinephrine administration with survival outcomes in children receiving CPR for bradycardia with poor perfusion; and (2) describe the incidence and time course of the development of pulselessness.

METHODS: Prespecified secondary analysis of ICU-RESUS, a multicenter cluster randomized trial of children (< 19 years) receiving CPR in 18 intensive care units in the United States. Index events (October 2016-March 2021) lasting ≥ 2 min with a documented initial rhythm of bradycardia with poor perfusion were included. Associations between early epinephrine (first 2 min of CPR) and outcomes were evaluated with Poisson multivariable regression controlling for a priori pre-arrest characteristics. Among patients with arterial lines, intra-arrest blood pressure waveforms were reviewed to determine presence of a pulse during CPR interruptions. The temporal nature of progression to pulselessness was described and outcomes were compared between patients according to subsequent pulselessness status.

RESULTS: Of 452 eligible subjects, 322 (71%) received early epinephrine. The early epinephrine group had higher pre-arrest severity of illness …

Associations Of Ambulatory Blood Pressure Measurements With High-Sensitivity Troponin And Natriuretic Peptide Levels In Sprint, Nikit Venishetty, Jarett D Berry, James A De Lemos, Elaine Wu, Minjae Lee, Paul E Drawz, Vijay Nambi, Christie M Ballantyne, Anthony A Killeen, Joachim H Ix, Michael G Shlipak, Simon B Ascher

Faculty, Staff and Students Publications

Background: Nighttime blood pressure (BP) has greater prognostic importance for cardiovascular disease (CVD) than daytime BP, but less is known about nighttime and daytime BP associations with measures of subclinical CVD.

Methods: Among 897 Systolic Blood Pressure Intervention Trial Study (SPRINT) participants with 24-hour ambulatory BP monitoring obtained near the 27-month study visit, 849 (95%) had N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) measured at the 24-month study visit. Multivariable linear regression analyses were performed to evaluate the associations of nighttime and daytime BP with cardiac biomarker levels.

Results: The mean age was 69 ± 12 …

Beta Activity In Human Anterior Cingulate Cortex Mediates Reward Biases, Jiayang Xiao, Joshua A Adkinson, John Myers, Anusha B Allawala, Raissa K Mathura, Victoria Pirtle, Ricardo Najera, Nicole R Provenza, Eleonora Bartoli, Andrew J Watrous, Denise Oswalt, Ron Gadot, Adrish Anand, Ben Shofty, Sanjay J Mathew, Wayne K Goodman, Nader Pouratian, Xaq Pitkow, Kelly R Bijanki, Benjamin Hayden, Sameer A Sheth

Faculty, Staff and Students Publications

The rewards that we get from our choices and actions can have a major influence on our future behavior. Understanding how reward biasing of behavior is implemented in the brain is important for many reasons, including the fact that diminution in reward biasing is a hallmark of clinical depression. We hypothesized that reward biasing is mediated by the anterior cingulate cortex (ACC), a cortical hub region associated with the integration of reward and executive control and with the etiology of depression. To test this hypothesis, we recorded neural activity during a biased judgment task in patients undergoing intracranial monitoring for …

Tractography-Based Modeling Explains Treatment Outcomes In Patients Undergoing Deep Brain Stimulation For Obsessive-Compulsive Disorder, Ron Gadot, Ningfei Li, Ben Shofty, Michelle Avendano-Ortega, Sarah Mckay, Kelly R Bijanki, Meghan E Robinson, Garrett Banks, Nicole Provenza, Eric A Storch, Wayne K Goodman, Andreas Horn, Sameer A Sheth

Faculty, Staff and Students Publications

BACKGROUND: Deep brain stimulation (DBS) is an established and expanding therapy for treatment-refractory obsessive-compulsive disorder. Previous work has suggested that a white matter circuit providing hyperdirect input from the dorsal cingulate and ventrolateral prefrontal regions to the subthalamic nucleus could be an effective neuromodulatory target.

METHODS: We tested this concept by attempting to retrospectively explain through predictive modeling the ranks of clinical improvement as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) in 10 patients with obsessive-compulsive disorder who underwent DBS to the ventral anterior limb of internal capsule with subsequent programming uninformed by the putative target tract.

RESULTS: Rank …

Transcriptomic Analysis Reveals The Anti-Cancer Effect Of Gestational Mesenchymal Stem Cell Secretome, Salvatore Vaiasicca, Gianmarco Melone, David W James, Marcos Quintela, Jing Xiao, Seydou Yao, Richard H Finnell, Robert S Conlan, Lewis W Francis, Bruna Corradetti

Faculty, Staff and Students Publications

The environment created during embryogenesis contributes to reducing aberrations that drive structural malformations and tumorigenesis. In this study, we investigate the anti-cancer effect of mesenchymal stem cells (MSCs) derived from 2 different gestational tissues, the amniotic fluid (AF) and the chorionic villi (CV), with emphasis on their secretome. Transcriptomic analysis was performed on patient-derived AF- and CV-MSCs collected during prenatal diagnosis and identified both mRNAs and lncRNAs, involved in tissue homeostasis and inhibiting biological processes associated with the etiology of aggressive cancers while regulating immune pathways shown to be important in chronic disorders. Secretome enrichment analysis also identified soluble moieties …

Early Depletion Of Gut Microbiota Shape Oligodendrocyte Response After Traumatic Brain Injury, Kirill Shumilov, Allen Ni, Maria Garcia-Bonilla, Marta Celorrio, Stuart H Friess

2020-Current year OA Pubs

BACKGROUND: This study is a cost-effectiveness study of two implementation strategies designed to train therapists in college and university counseling centers to deliver interpersonal psychotherapy. Costs of implementing a train-the-trainer (TTT) strategy versus an expert consultation strategy were estimated, and their relative effects upon therapist outcomes were calculated and compared.

METHODS: Twenty four counseling centers were recruited across the United States. These centers were randomized to either a TTT (experimental) condition, in which an in-house therapist trained other center therapists, or an expert consultation condition, in which center therapists participated in a workshop and received 12 months of ongoing supervision. …

Implementation, Enrollment, And Engagement In An Opt-Out Telehealth Pharmacist-Assisted Tobacco Treatment Program For Patients Seen In Oncology Outpatient Clinics, K. Michael Cummings, Benjamin A. Toll, Vincent Talbot, Avery Roberson, Dianne Wilson, Martha Dunlap, Emily C. Ware, Amanda M. Palmer, Asia A. Bliss, Vincent S. Anokye, Graham Warren

Markey Cancer Center Faculty Publications

OBJECTIVE: To describe the workflow, reach, cost, and self-reported quit rates for an opt-out tobacco treatment program (TTP) for patients seen in 43 oncology outpatient clinics.

METHODS: Between May 25, 2021, and December 31, 2022, adult patients (≥18 years) visiting clinics affiliated with the Medical University of South Carolina Hollings Cancer Center were screened for smoking status. Those currently smoking were referred to a telehealth pharmacy-assisted TTP. An attempt was made to contact referred patients by phone. Patients reached were offered free smoking cessation counseling and a 2-week starter kit of nicotine replacement medication. A random sample of 420 patients …

Specific Patterns Of Endogenous Functional Connectivity Are Associated With Harm Avoidance In Obsessive-Compulsive Disorder, Merage Ghane, Lucas Trambaiolli, Michele A Bertocci, Freddyson J Martinez-Rivera, Henry W Chase, Tyler Brady, Alex Skeba, Simona Graur, Lisa Bonar, Satish Iyengar, Gregory J Quirk, Steven A Rasmussen, Suzanne N Haber, Mary L Phillips

Faculty, Staff and Student Publications

Background: Individuals with obsessive-compulsive disorder (OCD) show persistent avoidance behaviors, often in the absence of actual threat. Quality-of-life costs and heterogeneity support the need for novel brain-behavior intervention targets. Informed by mechanistic and anatomical studies of persistent avoidance in rodents and nonhuman primates, our goal was to test whether connections within a hypothesized persistent avoidance-related network predicted OCD-related harm avoidance (HA), a trait measure of persistent avoidance. We hypothesized that 1) HA, not an OCD diagnosis, would be associated with altered endogenous connectivity in at least one connection in the network; 2) HA-specific findings would be robust to comorbid symptoms; …

Brain-Age Prediction: Systematic Evaluation Of Site Effects, And Sample Age Range And Size, Yuetong Yu, Hao-Qi Cui, Shalaila S Haas, Faye New, Nicole Sanford, Kevin Yu, Denghuang Zhan, Guoyuan Yang, Jia-Hong Gao, Dongtao Wei, Jiang Qiu, Nerisa Banaj, Dorret I Boomsma, Alan Breier, Henry Brodaty, Randy L Buckner, Jan K Buitelaar, Dara M Cannon, Xavier Caseras, Vincent P Clark, Patricia J Conrod, Fabrice Crivello, Eveline A Crone, Udo Dannlowski, Christopher G Davey, Lieuwe De Haan, Greig I De Zubicaray, Annabella Di Giorgio, Lukas Fisch, Simon E Fisher, Barbara Franke, David C Glahn, Dominik Grotegerd, Oliver Gruber, Raquel E Gur, Ruben C Gur, Tim Hahn, Ben J Harrison, Sean Hatton, Ian B Hickie, Hilleke E Hulshoff Pol, Alec J Jamieson, Terry L Jernigan, Jiyang Jiang, Andrew J Kalnin, Sim Kang, Nicole A Kochan, Anna Kraus, Jim Lagopoulos, Luisa Lazaro, Brenna C Mcdonald, Colm Mcdonald, Katie L Mcmahon, Benson Mwangi, Fabrizio Piras, Raul Rodriguez-Cruces, Jessica Royer, Perminder S Sachdev, Theodore D Satterthwaite, Andrew J Saykin, Gunter Schumann, Pierluigi Sevaggi, Jordan W Smoller, Jair C Soares, Gianfranco Spalletta, Christian K Tamnes, Julian N Trollor, Dennis Van't Ent, Daniela Vecchio, Henrik Walter, Yang Wang, Bernd Weber, Wei Wen, Lara M Wierenga, Steven C R Williams, Mon-Ju Wu, Giovana B Zunta-Soares, Boris Bernhardt, Paul Thompson, Sophia Frangou, Ruiyang Ge, Enigma‐Lifespan Working Group

Faculty, Staff and Student Publications

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain‐age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain‐age has highlighted the need for robust and publicly available brain‐age models pre‐trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain‐age model. Here we expand this work to develop, empirically validate, and disseminate a pre‐trained brain‐age model to cover most of the human lifespan. To achieve this, we selected the …

Bayesian Varying-Effects Vector Autoregressive Models For Inference Of Brain Connectivity Networks And Covariate Effects In Pediatric Traumatic Brain Injury, Yangfan Ren, Nathan Osborne, Christine B Peterson, Dana M Demaster, Linda Ewing-Cobbs, Marina Vannucci

Faculty, Staff and Student Publications

In this article, we develop an analytical approach for estimating brain connectivity networks that accounts for subject heterogeneity. More specifically, we consider a novel extension of a multi-subject Bayesian vector autoregressive model that estimates group-specific directed brain connectivity networks and accounts for the effects of covariates on the network edges. We adopt a flexible approach, allowing for (possibly) nonlinear effects of the covariates on edge strength via a novel Bayesian nonparametric prior that employs a weighted mixture of Gaussian processes. For posterior inference, we achieve computational scalability by implementing a variational Bayes scheme. Our approach enables simultaneous estimation of group-specific …

Clinical And Genomic Landscape Of Ras Mutations In Gynecologic Cancers, Ji Son, Yingao Zhang, Heather Lin, Oriol Mirallas, Pablo Alvarez Ballesteros, Mirella Nardo, Natalie Clark, R Tyler Hillman, Erick Campbell, Vijaykumar Holla, Amber M Johnson, Amadeo B Biter, Ying Yuan, Lauren P Cobb, David M Gershenson, Amir A Jazaeri, Karen H Lu, Pamela T Soliman, Shannon N Westin, Elizabeth D Euscher, Barrett C Lawson, Richard K Yang, Funda Meric-Bernstam, David S Hong

Faculty, Staff and Student Publications

Purpose: We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications.

Experimental design: Gynecologic cancers with available somatic molecular profiling data at our institution between February 2010 and August 2022 were included and grouped by RAS mutation status. Overall survival was estimated by the Kaplan-Meier method, and multivariable analysis was performed using the Cox proportional hazard model.

Results: Of 3,328 gynecologic cancers, 523 (15.7%) showed any RAS mutation. Patients with RAS-mutated tumors were younger (57 vs. 60 years nonmutated), had a higher prevalence of endometriosis (27.3% vs. 16.9%), and …

Intratumoral Microbiome Of Adenoid Cystic Carcinomas And Comparison With Other Head And Neck Cancers, Tatiana V Karpinets, Yoshitsugu Mitani, Chia-Chi Chang, Xiaogang Wu, Xingzhi Song, Ivonne I Flores, Lauren K Mcdaniel, Yasmine M Hoballah, Fabiana J Veguilla, Renata Ferrarotto, Lauren E Colbert, Nadim J Ajami, Robert R Jenq, Jianhua Zhang, Andrew P Futreal, Adel K El-Naggar

Faculty, Staff and Student Publications

Adenoid cystic carcinoma (ACC) is a rare, usually slow-growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited. We investigated the intratumoral microbiomes of 50 ACC tumor tissues and 33 adjacent normal tissues using 16S rRNA gene sequencing. This allowed us to characterize the bacterial communities within the ACC and explore potential associations between the bacterial community structure, patient clinical characteristics, and tumor molecular features obtained through RNA sequencing. The bacterial composition in the ACC was significantly different from that in adjacent normal salivary tissue, and the …

Impact Of Efavirenz On Hormone-Positive Breast Cancer Survival In Women Living With Hiv, Arthur T Johnson, Taolo Ntloedibe, Jose Euberto Mendez Reyes, Mogomotsi S Matshaba, Scott L Dryden-Peterson, Elizabeth Y Chiao

Center for Medical Ethics and Health Policy Staff Publications

Women living with HIV and breast cancer have poorer survival than HIV-negative women. Efavirenz-estrogen interactions are documented; however, the survival impact is unknown. Survival between women with estrogen-receptor positive breast cancer taking efavirenz (n = 38) and nonefavirenz regimens (n = 51) were compared. The 5-year overall-survival was 48.9% [95% confidence interval (CI) 33.0-72.2 and 51.1% (95% CI 34.0-76.8)] in the efavirenz and nonefavirenz groups, respectively suggesting efavirenz is unlikely driving poorer survival in women living with HIV and estrogen-receptor positive breast cancer.

The Effect Of Cesarean Delivery On The Neonatal Gut Microbiome In An Under-Resourced Population In The Bronx, Ny, Usa, Sandra E Reznik, Ayodele J Akinyemi, David Harary, Mariam S Latuga, Mamta Fuloria, Maureen J Charron

SKMC Student Presentations and Publications

BACKGROUND: Neonatal and early-life gut microbiome changes are associated with altered cardiometabolic and immune development. In this study, we explored Cesarean delivery effects on the gut microbiome in our high-risk, under-resourced Bronx, NY population.

RESULTS: Fecal samples from the Bronx MomBa Health Study (Bronx MomBa Health Study) were categorized by delivery mode (vaginal/Cesarean) and analyzed via 16 S rRNA gene sequencing at four timepoints over the first two years of life. Bacteroidota organisms, which have been linked to decreased risk for obesity and type 2 diabetes, were relatively reduced by Cesarean delivery, while Firmicutes organisms were increased. Organisms belonging to …

27-Hydroxycholesterol Acts On Estrogen Receptor Α Expressed By Pomc Neurons In The Arcuate Nucleus To Modulate Feeding Behavior, Hui Ye, Xiaohua Yang, Bing Feng, Pei Luo, Valeria C Torres Irizarry, Leslie Carrillo-Sáenz, Meng Yu, Yongjie Yang, Benjamin P Eappen, Marcos David Munoz, Nirali Patel, Sarah Schaul, Lucas Ibrahimi, Penghua Lai, Xinyue Qi, Yuliang Zhou, Maya Kota, Devin Dixit, Madeline Mun, Chong Wee Liew, Yuwei Jiang, Chunmei Wang, Yanlin He, Pingwen Xu

Faculty, Staff and Students Publications

Oxysterols are metabolites of cholesterol that regulate cholesterol homeostasis. Among these, the most abundant oxysterol is 27-hydroxycholesterol (27HC), which can cross the blood-brain barrier. Because 27HC functions as an endogenous selective estrogen receptor modulator, we hypothesize that 27HC binds to the estrogen receptor α (ERα) in the brain to regulate energy balance. Supporting this view, we found that delivering 27HC to the brain reduced food intake and activated proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (POMCARH) in an ERα-dependent manner. In addition, we observed that inhibiting brain ERα, deleting ERα in POMC neurons, or chemogenetic inhibition of …

Monoallelic De Novo Ajap1 Loss-Of-Function Variants Disrupt Trans-Synaptic Control Of Neurotransmitter Release, Simon Früh, Sami Boudkkazi, Peter Koppensteiner, Vita Sereikaite, Li-Yuan Chen, Diego Fernandez-Fernandez, Pascal D Rem, Daniel Ulrich, Jochen Schwenk, Ziyang Chen, Elodie Le Monnier, Thorsten Fritzius, Sabrina M Innocenti, Valérie Besseyrias, Luca Trovò, Michal Stawarski, Emanuela Argilli, Elliott H Sherr, Bregje Van Bon, Erik-Jan Kamsteeg, Maria Iascone, Alba Pilotta, Maria R Cutrì, Mahshid S Azamian, Andrés Hernández-García, Seema R Lalani, Jill A Rosenfeld, Xiaonan Zhao, Tiphanie P Vogel, Herda Ona, Daryl A Scott, Peter Scheiffele, Kristian Strømgaard, Mehdi Tafti, Martin Gassmann, Bernd Fakler, Ryuichi Shigemoto, Bernhard Bettler

Faculty, Staff and Students Publications

Adherens junction–associated protein 1 (AJAP1) has been implicated in brain diseases; however, a pathogenic mechanism has not been identified. AJAP1 is widely expressed in neurons and binds to γ-aminobutyric acid type B receptors (GBRs), which inhibit neurotransmitter release at most synapses in the brain. Here, we show that AJAP1 is selectively expressed in dendrites and trans-synaptically recruits GBRs to presynaptic sites of neurons expressing AJAP1. We have identified several monoallelic AJAP1 variants in individuals with epilepsy and/or neurodevelopmental disorders. Specifically, we show that the variant p.(W183C) lacks binding to GBRs, resulting in the inability to recruit them. Ultrastructural analysis revealed …

Pulmonary Osteoclast-Like Cells In Silica Induced Pulmonary Fibrosis, Yoshihiro Hasegawa, Steven L Teitelbaum, Et Al.

2020-Current year OA Pubs

The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored mechanisms of silica-induced pulmonary fibrosis in human lung samples collected from patients with occupational exposure to silica and in a longitudinal mouse model of silicosis using multiple modalities including whole-lung single-cell RNA sequencing and histological, biochemical, and physiologic assessments. In addition to pulmonary inflammation and fibrosis, intratracheal silica challenge induced osteoclast-like differentiation of alveolar macrophages and recruited monocytes, driven by induction of the osteoclastogenic cytokine, receptor activator of nuclear factor κΒ ligand (RANKL) in pulmonary lymphocytes, and …

Multiparametric Mri-Based Radiomic Models For Early Prediction Of Response To Neoadjuvant Systemic Therapy In Triple-Negative Breast Cancer, Rania M Mohamed, Bikash Panthi, Beatriz E Adrada, Medine Boge, Rosalind P Candelaria, Huiqin Chen, Mary S Guirguis, Kelly K Hunt, Lei Huo, Ken-Pin Hwang, Anil Korkut, Jennifer K Litton, Tanya W Moseley, Sanaz Pashapoor, Miral M Patel, Brandy Reed, Marion E Scoggins, Jong Bum Son, Alastair Thompson, Debu Tripathy, Vicente Valero, Peng Wei, Jason White, Gary J Whitman, Zhan Xu, Wei Yang, Clinton Yam, Jingfei Ma, Gaiane M Rauch

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is often treated with neoadjuvant systemic therapy (NAST). We investigated if radiomic models based on multiparametric Magnetic Resonance Imaging (MRI) obtained early during NAST predict pathologic complete response (pCR). We included 163 patients with stage I-III TNBC with multiparametric MRI at baseline and after 2 (C2) and 4 cycles of NAST. Seventy-eight patients (48%) had pCR, and 85 (52%) had non-pCR. Thirty-six multivariate models combining radiomic features from dynamic contrast-enhanced MRI and diffusion-weighted imaging had an area under the receiver operating characteristics curve (AUC) > 0.7. The top-performing model combined 35 radiomic features of relative difference between …

Patient-Reported Quality Of Life At Diagnosis In Adolescent And Young Adults With Cancer, Goldy C George, Clark Andersen, Xiaohui Tang, Elizabeth Rodriguez, Midhat Jafry, Maria C Swartz, Sairah Ahmed, Carlos H Barcenas, J Andrew Livingston, Michael E Roth, Michelle A T Hildebrandt

Faculty, Staff and Student Publications

Background: The overall landscape of health-related quality of life (HRQoL) has not been thoroughly investigated in adolescents and young adults (AYAs) with cancer. Data are also lacking on how well HRQoL at the time of cancer diagnosis can prognosticate long-term survival in AYA survivors.

Patients and methods: We included 3,497 survivors of AYA cancer (age 15-39 years at diagnosis) who completed the Short-Form 12 Health Survey (SF-12) HRQoL questionnaire at diagnosis. Physical component summary (PCS) and mental component summary (MCS) scores were generated, with scores < 50 representing poor HRQoL. Differences in HRQoL by patient characteristics and tumor type were investigated using violin plots and t tests/analysis of variance. The effect of HRQoL on overall survival was assessed using Kaplan-Meier plots and Cox proportional hazards models.

Results: Overall mean PCS and MCS scores in this racially/ethnically diverse cohort (64% White, 19% …

A Hybrid Epithelial/Mesenchymal State In Head And Neck Cancer: A Biomarker For Survival With Differential Prognosis By Self-Reported Race, Angela L Mazul, Thomas F Barrett, Graham Colditz, Anuraag S Parikh, Salma Ramadan, Jose P Zevallos, Jason T Rich, R Alex Harbison, Ryan S Jackson, Patrik Pipkorn, Paul Zolkind, Itay Tirosh, Sidharth V Puram

2020-Current year OA Pubs

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the 6

METHODS: Given the overlap in gene expression between hybrid E/M malignant cells and cancer-associated fibroblasts, we utilized deconvolution of bulk RNA sequencing data from oral cavity and laryngeal squamous cell carcinoma tumors from The Cancer Genome Atlas. We utilized our previously collected single-cell profiles to generate inferred malignant profiles and then scored these for hybrid E/M. We then conducted a survival analysis on overall and disease-free survival among self-reported Black and White Americans.

FINDINGS: The hybrid E/M state was differentially associated with head and neck cancer survival by self-reported …

Msl2 Variants Lead To A Neurodevelopmental Syndrome With Lack Of Coordination, Epilepsy, Specific Dysmorphisms, And A Distinct Episignature, Remzi Karayol, Maria Carla Borroto, Sadegheh Haghshenas, Anoja Namasivayam, Jack Reilly, Michael A Levy, Raissa Relator, Jennifer Kerkhof, Haley Mcconkey, Maria Shvedunova, Andrea K Petersen, Kari Magnussen, Christiane Zweier, Georgia Vasileiou, André Reis, Juliann M Savatt, Meghan R Mulligan, Louise S Bicknell, Gemma Poke, Aya Abu-El-Haija, Jessica Duis, Vickie Hannig, Siddharth Srivastava, Elizabeth Barkoudah, Natalie S Hauser, Myrthe Van Den Born, Uri Hamiel, Noa Henig, Hagit Baris Feldman, Shane Mckee, Ingrid P C Krapels, Yunping Lei, Albena Todorova, Ralitsa Yordanova, Slavena Atemin, Mihael Rogac, Vivienne Mcconnell, Anna Chassevent, Kristin W Barañano, Vandana Shashi, Jennifer A Sullivan, Angela Peron, Maria Iascone, Maria P Canevini, Jennifer Friedman, Iris A Reyes, Janell Kierstein, Joseph J Shen, Faria N Ahmed, Xiao Mao, Berta Almoguera, Fiona Blanco-Kelly, Konrad Platzer, Ariana-Berenike Treu, Juliette Quilichini, Alexia Bourgois, Nicolas Chatron, Louis Januel, Christelle Rougeot, Deanna Alexis Carere, Kristin G Monaghan, Justine Rousseau, Kenneth A Myers, Bekim Sadikovic, Asifa Akhtar, Philippe M Campeau

Faculty, Staff and Students Publications

Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition of histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent multi-subunit epigenetic regulator of gene expression and is responsible for histone 4 lysine 16 acetylation (H4K16ac). Using exome sequencing, here we identify a cohort of 25 individuals with heterozygous de novo variants in MSL complex member MSL2. MSL2 variants were associated with NDD phenotypes including global developmental delay, intellectual disability, hypotonia, and motor issues such as coordination problems, feeding …

Psmd11 Loss-Of-Function Variants Correlate With A Neurobehavioral Phenotype, Obesity, And Increased Interferon Response, Wallid Deb, Cory Rosenfelt, Virginie Vignard, Jonas Johannes Papendorf, Sophie Möller, Martin Wendlandt, Maja Studencka-Turski, Benjamin Cogné, Thomas Besnard, Léa Ruffier, Bérénice Toutain, Léa Poirier, Silvestre Cuinat, Amy Kritzer, Amy Crunk, Janette Dimonda, Jaime Vengoechea, Sandra Mercier, Lotte Kleinendorst, Mieke M Van Haelst, Linda Zuurbier, Telma Sulem, Hildigunnur Katrínardóttir, Rún Friðriksdóttir, Patrick Sulem, Kari Stefansson, Berglind Jonsdottir, Shimriet Zeidler, Margje Sinnema, Alexander P A Stegmann, Natali Naveh, Cara M Skraban, Christopher Gray, Jill R Murrell, Sedat Isikay, Davut Pehlivan, Daniel G Calame, Jennifer E Posey, Mathilde Nizon, Kirsty Mcwalter, James R Lupski, Bertrand Isidor, François V Bolduc, Stéphane Bézieau, Elke Krüger, Sébastien Küry, Frédéric Ebstein

Faculty, Staff and Students Publications

Primary proteasomopathies have recently emerged as a new class of rare early-onset neurodevelopmental disorders (NDDs) caused by pathogenic variants in the PSMB1, PSMC1, PSMC3, or PSMD12 proteasome genes. Proteasomes are large multi-subunit protein complexes that maintain cellular protein homeostasis by clearing ubiquitin-tagged damaged, misfolded, or unnecessary proteins. In this study, we have identified PSMD11 as an additional proteasome gene in which pathogenic variation is associated with an NDD-causing proteasomopathy. PSMD11 loss-of-function variants caused early-onset syndromic intellectual disability and neurodevelopmental delay with recurrent obesity in 10 unrelated children. Our findings demonstrate that the cognitive impairment observed in these individuals could be …