Digital Commons Network^™

Dna Methylation Patterns In Umbilical Cord Blood From Infants Of Methadone Maintained Opioid Dependent Mothers, Oluwatobi Adegboyega, Suhita Gayen Nee' Betal, Pedro Urday, Rachel Huang, Katherine Bodycot, Huda Al-Kouatly, Kolawole Solarin, Joanna Chan, Sankar Addya, Rupsa Boelig, Zubair Aghai

Department of Pediatrics Faculty Papers

Methadone maintenance treatment for opioid dependent mothers is standard of care. Infants of methadone maintained opioid dependent (MMOD) mothers have better outcomes compared to infants of opioid dependent mothers without treatment. However, when compared to non-exposed infants, infants of MMOD mothers are associated with worse outcomes. We conducted a pilot study to examine genome wide differential DNA methylation using cord blood samples from sixteen term and near-term infants of MMOD and opioid naïve mothers, excluding Infants with chorioamnionitis. A total of 152 differentially methylated loci were identified at a difference >  + 2, < - 2 and p-value < 0.05. There were 90 hypermethylated loci (59 annotated genes) and 62 hypomethylated loci (38 annotated genes) observed. The hypermethylated and hypomethylated DNA changes involved multiple genes, pathways and networks that may explain some of the changes seen in infants of MMOD mothers. Top hypermethylated and hypomethylated genes involved areas of cell growth, neurodevelopment, vision and xenobiotic metabolism functions. Our data may explain the role of key pathways and genes relevant to neonatal outcomes seen from methadone exposure in pregnancy. Functional studies on the identified pathways and genes could lead to improved understanding of the mechanisms and identify areas for intervention.

Detection Of Diffusely Abnormal White Matter In Multiple Sclerosis On Multiparametric Brain Mri Using Semi-Supervised Deep Learning, Benjamin C Musall, Refaat E Gabr, Yanyu Yang, Arash Kamali, John A Lincoln, Michael A Jacobs, Vi Ly, Xi Luo, Jerry S Wolinsky, Ponnada A Narayana, Khader M Hasan

Faculty, Staff and Student Publications

In addition to focal lesions, diffusely abnormal white matter (DAWM) is seen on brain MRI of multiple sclerosis (MS) patients and may represent early or distinct disease processes. The role of MRI-observed DAWM is understudied due to a lack of automated assessment methods. Supervised deep learning (DL) methods are highly capable in this domain, but require large sets of labeled data. To overcome this challenge, a DL-based network (DAWM-Net) was trained using semi-supervised learning on a limited set of labeled data for segmentation of DAWM, focal lesions, and normal-appearing brain tissues on multiparametric MRI. DAWM-Net segmentation performance was compared to …

An Analysis Of The Genus Aleyrodes Latreille (Hemiptera: Sternorrhyncha: Aleyrodidae) In California, With Three Synonymies, Natalia Von Ellenrieder, Raymond J. Gill

Insecta Mundi

Abstract

Based on the examination of an extensive series of specimens and available type material, three out of the six species of Aleyrodes Latreille (Hemiptera: Sternorrhyncha: Aleyrodidae) described from California, A. diasemus Bemis, 1904, A. essigi Penny, 1922, and A. osmaroniae Sampson, 1945, are newly synonymized under A. spiraeoides Quaintance, 1900. The species of Aleyrodes reported from California are keyed and diagnosed based on characters from puparia and male genitalia, and character variability is documented and illustrated.

Resumen

Basado en el examen de una extensa serie de especímenes y material tipo disponible, tres de las seis …

Blinatumomab For Mrd-Negative Acute Lymphoblastic Leukemia In Adults, Mark R Litzow, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

BACKGROUND: Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission.

METHODS: In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with

RESULTS: The data and safety monitoring committee reviewed the results from the third efficacy interim analysis and recommended that they be reported. Complete remission with or without full …

First-In-Human Dose Escalation Trial To Evaluate The Clinical Safety And Efficacy Of An Anti-Magea1 Autologous Tcr-Transgenic T Cell Therapy In Relapsed And Refractory Solid Tumors, Martin Wermke, Tobias A W Holderried, Jason John Luke, Van K Morris, Winfried H Alsdorf, Katrin Wetzko, Borje S Andersson, Ignacio I Wistuba, Edwin R Parra, Mohammad B Hossain, Sandra Grund-Gröschke, Katrin Aslan, Arun Satelli, Anantha Marisetty, Swapna Satam, Mamta Kalra, Jens Hukelmann, M Alper Kursunel, Karine Pozo, Andreas Acs, Linus Backert, Melissa Baumeister, Sebastian Bunk, Claudia Wagner, Oliver Schoor, Ali S Mohamed, Andrea Mayer-Mokler, Norbert Hilf, Delfi Krishna, Steffen Walter, Apostolia M Tsimberidou, Cedrik M Britten

Faculty, Staff and Student Publications

RATIONALE OF THE TRIAL: Although the use of engineered T cells in cancer immunotherapy has greatly advanced the treatment of hematological malignancies, reaching meaningful clinical responses in the treatment of solid tumors is still challenging. We investigated the safety and tolerability of IMA202 in a first-in-human, dose escalation basket trial in human leucocyte antigen A*02:01 positive patients with melanoma-associated antigen A1 (MAGEA1)-positive advanced solid tumors.

TRIAL DESIGN: The 2+2 trial design was an algorithmic design based on a maximally acceptable dose-limiting toxicity (DLT) rate of 25% and the sample size was driven by the algorithmic design with a maximum of …

Targeted Sequencing For Hereditary Breast And Ovarian Cancer In Brca1/2-Negative Families Reveals Complex Genetic Architecture And Phenocopies, Jocelyn N Plowman, Evanjalina J Matoy, Lavanya V Uppala, Samantha B Draves, Cynthia J Watson, Bridget A Sefranek, Mark L Stacey, Samuel P Anderson, Michael A Belshan, Elizabeth E Blue, Chad D Huff, Yusi Fu, Holly A F Stessman

Faculty, Staff and Student Publications

Approximately 20% of breast cancer cases are attributed to increased family risk, yet variation in BRCA1/2 can only explain 20%-25% of cases. Historically, only single gene or single variant testing were common in at-risk family members, and further sequencing studies were rarely offered after negative results. In this study, we applied an efficient and inexpensive targeted sequencing approach to provide molecular diagnoses in 245 human samples representing 134 BRCA mutation-negative (BRCAX) hereditary breast and ovarian cancer (HBOC) families recruited from 1973 to 2019 by Dr. Henry Lynch. Sequencing identified 391 variants, which were functionally annotated and ranked based on their …

Mucosal Signatures Of Pathogenic T Cells In Hla-B*27+ Anterior Uveitis And Axial Spondyloarthritis, Michael A. Paley, Lynn M. Hassman, Grace L. Paley, Nicole Linskey, Ryan Agnew, Paulo Henrique Arantes De Faria, Annie Feng, Sophia Y. Li, Elisha D. O. Roberson, Philip A. Ruzycki, Ekaterina Esaulova, Jennifer Laurent, Lacey Feigl-Lenzen, Luke E. Springer, Chang Liu, Wayne M. Yokoyama, Et Al.

2020-Current year OA Pubs

HLA-B*27 was one of the first HLA alleles associated with an autoimmune disease, i.e., axial spondyloarthritis (axSpA) and acute anterior uveitis (B27AAU), which cause joint and eye inflammation, respectively. Gastrointestinal inflammation has been suggested as a trigger of axSpA. We recently identified a bacterial peptide (YeiH) that can be presented by HLA-B*27 to expanded public T cell receptors in the joint in axSpA and the eye in B27AAU. While YeiH is present in enteric microbiota and pathogens, additional evidence that pathogenic T cells in HLA-B*27-associated autoimmunity may have had a prior antigenic encounter within the gastrointestinal tract remains lacking. Here, …

Changing Neighborhood Income Deprivation Over Time, Moving In Childhood, And Adult Risk Of Depression, Clive E Sabel, Carsten Bøcker Pedersen, Sussie Antonsen, Roger T Webb, Henriette Thisted Horsdal

School of Geography, Earth and Environmental Sciences

IMPORTANCE: Complex biological, socioeconomic, and psychological variables combine to cause mental illnesses, with mounting evidence that early-life experiences are associated with adulthood mental health.

OBJECTIVE: To evaluate whether changing neighborhood income deprivation and residential moves during childhood are associated with the risk of receiving a diagnosis of depression in adulthood.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included the whole population of 1 096 916 people born in Denmark from January 1, 1982, to December 31, 2003, who resided in the country during their first 15 years of life. Individuals were followed up from 15 years of age until either …

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 …

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 …

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 …

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 …

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% …

Clonal Hematopoiesis Driven By Mutated Dnmt3a Promotes Inflammatory Bone Loss, Hui Wang, Kimon Divaris, Bohu Pan, Xiaofei Li, Jong-Hyung Lim, Gundappa Saha, Marko Barovic, Danai Giannakou, Jonathan M Korostoff, Yu Bing, Souvik Sen, Kevin Moss, Di Wu, James D Beck, Christie M Ballantyne, Pradeep Natarajan, Kari E North, Mihai G Netea, Triantafyllos Chavakis, George Hajishengallis

Faculty, Staff and Student Publications

Clonal hematopoiesis of indeterminate potential (CHIP) arises from aging-associated acquired mutations in hematopoietic progenitors, which display clonal expansion and produce phenotypically altered leukocytes. We associated CHIP-DNMT3A mutations with a higher prevalence of periodontitis and gingival inflammation among 4,946 community-dwelling adults. To model DNMT3A-driven CHIP, we used mice with the heterozygous loss-of-function mutation R878H, equivalent to the human hotspot mutation R882H. Partial transplantation with Dnmt3a

The Impact Of Clinical Genome Sequencing In A Global Population With Suspected Rare Genetic Disease, Erin Thorpe, Taylor Williams, Chad Shaw, Evgenii Chekalin, Julia Ortega, Keisha Robinson, Jason Button, Marilyn C Jones, Miguel Del Campo, Donald Basel, Julie Mccarrier, Laura Davis Keppen, Erin Royer, Romina Foster-Bonds, Milagros M Duenas-Roque, Nora Urraca, Kerri Bosfield, Chester W Brown, Holly Lydigsen, Henry J Mroczkowski, Jewell Ward, Fabio Sirchia, Elisa Giorgio, Keith Vaux, Hildegard Peña Salguero, Aimé Lumaka, Gerrye Mubungu, Prince Makay, Mamy Ngole, Prosper Tshilobo Lukusa, Adeline Vanderver, Kayla Muirhead, Omar Sherbini, Melissa D Lah, Katelynn Anderson, Jeny Bazalar-Montoya, Richard S Rodriguez, Mario Cornejo-Olivas, Karina Milla-Neyra, Marwan Shinawi, Pilar Magoulas, Duncan Henry, Kate Gibson, Samuel Wiafe, Parul Jayakar, Daria Salyakina, Diane Masser-Frye, Arturo Serize, Jorge E Perez, Alan Taylor, Shruti Shenbagam, Ahmad Abou Tayoun, Alka Malhotra, Maren Bennett, Vani Rajan, James Avecilla, Andrew Warren, Max Arseneault, Tasha Kalista, Ali Crawford, Subramanian S Ajay, Denise L Perry, John Belmont, Ryan J Taft

Center for Medical Ethics and Health Policy Staff Publications

There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds …

Costs And Impact Of Disease In Adults With Sickle Cell Disease: A Pilot Study, Sophie Lanzkron, Nicole Crook, Joanne Wu, Sarah Hussain, Randall G. Curtis, Derek Robertson, Judith R. Baker, Diane Nugent, Amit Soni, Jonathan C. Roberts, Megan M. Ullman, Julie Kanter, Michael B. Nichol

Cardeza Foundation for Hematologic Research

We assessed the feasibility to estimate illness burden in adults with SCD, investigated factors associated with health-related quality of life (HRQoL), and estimated societal burden. We recruited 32 participants and collected data on fatigue, HRQoL, and work productivity and activity impairment via patient survey. Health care utilization was abstracted for the 12 months before enrollment using medical chart review. Mean age was 36.7 years; 84.4% of participants had hemoglobin SS or Sβthal0 disease, and 81.3% reported chronic pain (experiencing pain on ≥3 days per week in the past 6 months). Mean EQ-5D-3L visual analogue scale score was 63.4 and the …

Phase Ib Study Of Unesbulin (Ptc596) Plus Dacarbazine For The Treatment Of Locally Recurrent, Unresectable Or Metastatic, Relapsed Or Refractory Leiomyosarcoma, Brian A Van Tine, Matthew A Ingham, Steven Attia, Christian F Meyer, John D Baird, Esther Brooks-Asplund, Dhiren D'Silva, Ronald Kong, Anthony Mwatha, Kylie O'Keefe, Marla Weetall, Robert Spiegel, Gary K Schwartz

2020-Current year OA Pubs

PURPOSE: This multicenter, single-arm, open-label, phase Ib study was designed to determine the recommended phase II dose (RP2D) and to evaluate the safety and preliminary efficacy of unesbulin plus dacarbazine (DTIC) in patients with advanced leiomyosarcoma (LMS).

PATIENTS AND METHODS: Adult subjects with locally advanced, unresectable or metastatic, relapsed or refractory LMS were treated with escalating doses of unesbulin orally twice per week in combination with DTIC 1,000 mg/m

RESULTS: Unesbulin 300 mg administered orally twice per week in combination with DTIC 1,000 mg/m

CONCLUSION: Unesbulin 300 mg twice per week plus DTIC 1,000 mg/m

Incidence And Types Of Cardiac Arrhythmias In The Peri-Ictal Period In Patients Having A Generalized Convulsive Seizure, Laura Vilella, Christina Y Miyake, Ganne Chaitanya, Johnson P Hampson, Shirin Jamal Omidi, Manuela Ochoa-Urrea, Blanca Talavera, Oscar Mancera, Norma J Hupp, Jaison S Hampson, M R Sandhya Rani, Nuria Lacuey, Shiqiang Tao, Rup K Sainju, Daniel Friedman, Maromi Nei, Catherine A Scott, Brian Gehlbach, Stephan U Schuele, Jennifer A Ogren, Ronald M Harper, Beate Diehl, Lisa M Bateman, Orrin Devinsky, George B Richerson, Guo-Qiang Zhang, Samden D Lhatoo

Faculty, Staff and Students Publications

Background and objectives: Generalized convulsive seizures (GCSs) are the main risk factor of sudden unexpected death in epilepsy (SUDEP), which is likely due to peri-ictal cardiorespiratory dysfunction. The incidence of GCS-induced cardiac arrhythmias, their relationship to seizure severity markers, and their role in SUDEP physiopathology are unknown. The aim of this study was to analyze the incidence of seizure-induced cardiac arrhythmias, their association with electroclinical features and seizure severity biomarkers, as well as their specific occurrences in SUDEP cases.

Methods: This is an observational, prospective, multicenter study of patients with epilepsy aged 18 years and older with recorded GCS during …

Ai-Assisted Segmentation Tool For Brain Tumor Mr Image Analysis, Myungeun Lee, Jong Hyo Kim, Wookjin Choi, Ki Hong Lee

Department of Radiation Oncology Faculty Papers

TumorPrism3D software was developed to segment brain tumors with a straightforward and user-friendly graphical interface applied to two- and three-dimensional brain magnetic resonance (MR) images. The MR images of 185 patients (103 males, 82 females) with glioblastoma multiforme were downloaded from The Cancer Imaging Archive (TCIA) to test the tumor segmentation performance of this software. Regions of interest (ROIs) corresponding to contrast-enhancing lesions, necrotic portions, and non-enhancing T2 high signal intensity components were segmented for each tumor. TumorPrism3D demonstrated high accuracy in segmenting all three tumor components in cases of glioblastoma multiforme. They achieved a better Dice similarity coefficient (DSC) …

Contributions Of Brain Microstructures And Metabolism To Visual Field Loss Patterns In Glaucoma Using Archetypal And Information Gain Analyses, Yueyin Pang, Ji Won Bang, Anisha Kasi, Jeremy Li, Carlos Parra, Els Fieremans, Gadi Wollstein, Joel S. Schuman, Mengyu Wang, Kevin C Chan

Wills Eye Hospital Papers

PURPOSE: To investigate the contributions of the microstructural and metabolic brain environment to glaucoma and their association with visual field (VF) loss patterns by using advanced diffusion magnetic resonance imaging (dMRI), proton magnetic resonance spectroscopy (MRS), and clinical ophthalmic measures.

METHODS: Sixty-nine glaucoma and healthy subjects underwent dMRI and/or MRS at 3 Tesla. Ophthalmic data were collected from VF perimetry and optical coherence tomography. dMRI parameters of microstructural integrity in the optic radiation and MRS-derived neurochemical levels in the visual cortex were compared among early glaucoma, advanced glaucoma, and healthy controls. Multivariate regression was used to correlate neuroimaging metrics with …

Efficacy, Safety, And Tolerability Of Tivozanib In Heavily Pretreated Patients With Advanced Clear Cell Renal Cell Carcinoma, Andrew C Johns, Matthew T Campbell, Mamie Gao, Andrew W Hahn, Zita Lim, Emily Wang, Jianjun Gao, Amishi Y Shah, Pavlos Msaouel, Nizar M Tannir

Faculty, Staff and Student Publications

BACKGROUND: Tivozanib has been approved as a third-line or later therapy for advanced renal cell carcinoma based on the TIVO-3 trial, which was conducted before immune checkpoint therapies (ICT), cabozantinib, and lenvatinib/everolimus became incorporated in the current sequential treatment paradigm for advanced clear cell RCC (ccRCC).

METHODS: We performed a retrospective study of patients with advanced ccRCC treated with tivozanib at MD Anderson Cancer Center during 6/2021-7/2023. A blinded radiologist assessed tumor response by RECIST v1.1. We assessed overall response rate (ORR), clinical benefit rate (CBR) [percentage of all treated patients who achieved radiologic response or stable disease (SD) for …

Reverse Phase Proteomic Array Profiling Of Asparagine Synthetase Expression In Newly Diagnosed Acute Myeloid Leukemia, Nisha Narayanan, Jennifer Marvin-Peek, Mohamad K Abouelnaaj, Dhabya Majid, Bofei Wang, Brandon D Brown, Yihua Qiu, Steven M Kornblau, Hussein A Abbas

Faculty, Staff and Student Publications

Asparaginase-based therapy is a cornerstone in acute lymphoblastic leukemia (ALL) treatment, capitalizing on the methylation status of the asparagine synthetase (ASNS) gene, which renders ALL cells reliant on extracellular asparagine. Contrastingly, ASNS expression in acute myeloid leukemia (AML) has not been thoroughly investigated, despite studies suggesting that AML with chromosome 7/7q deletions might have reduced ASNS levels. Here, we leverage reverse phase protein arrays to measure ASNS expression in 810 AML patients and assess its impact on outcomes. We find that AML with inv(16) has the lowest overall ASNS expression. While AML with deletion 7/7q had ASNS levels slightly lower …

Olaparib For Childhood Tumors Harboring Defects In Dna Damage Repair Genes: Arm H Of The Nci-Cog Pediatric Match Trial, Julia L Glade Bender, Kerice Pinkney, Paul M Williams, Sinchita Roy-Chowdhuri, David R Patton, Brent D Coffey, Joel M Reid, Jin Piao, Lauren Saguilig, Todd A Alonzo, Stacey L Berg, Nilsa C Ramirez, Elizabeth Fox, Brenda J Weigel, Douglas S Hawkins, Margaret M Mooney, Naoko Takebe, James V Tricoli, Katherine A Janeway, Nita L Seibel, Donald W Parsons

Center for Medical Ethics and Health Policy Staff Publications

Background: The National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice (MATCH) precision oncology platform trial enrolled children aged 1-21 years with treatment-refractory solid tumors and predefined actionable genetic alterations. Patients with tumors harboring alterations in DNA damage repair (DDR) genes were assigned to receive olaparib.

Methods: Tumor and blood samples were submitted for centralized molecular testing. Tumor and germline sequencing were conducted in parallel. Olaparib was given twice daily for 28-day cycles starting at a dose 30% lower than the adult recommended phase 2 dose (RP2D). The primary endpoint was the objective response.

Results: Eighteen patients matched …

Task And Stimulus Coding In The Multiple-Demand Network, Sneha Shashidhara, Moataz Assem, Matthew F Glasser, John Duncan

2020-Current year OA Pubs

In the human brain, a multiple-demand (MD) network plays a key role in cognitive control, with core components in lateral frontal, dorsomedial frontal and lateral parietal cortex, and multivariate activity patterns that discriminate the contents of many cognitive activities. In prefrontal cortex of the behaving monkey, different cognitive operations are associated with very different patterns of neural activity, while details of a particular stimulus are encoded as small variations on these basic patterns (Sigala et al, 2008). Here, using the advanced fMRI methods of the Human Connectome Project and their 360-region cortical parcellation, we searched for a similar result in …

Individual And Joint Associations Of High-Sensitivity Troponin I And High-Sensitivity Troponin T With Cardiac Phenotypes And Outcomes In The General Population: An Analysis From The Dallas Heart Study, Rebecca Vigen, Colby Ayers, Jarett Berry, Anand Rohatgi, Vijay Nambi, Christie M Ballantyne, Torbjorn Omland, Christopher R De Filippi, James De Lemos

Faculty, Staff and Students Publications

Background: High-sensitivity troponin I (hs-cTnI) and T (hs-cTnT) provide complementary information regarding cardiovascular disease risk. The explanation for their distinct risk profiles is incompletely understood.

Methods and results: hs-cTnI and hs-cTnT were measured in Dallas Heart Study participants. Associations of hs-cTnI and hs-cTnT with demographics and phenotypes were assessed using linear regression. Associations with incident heart failure, atherosclerotic cardiovascular disease, global cardiovascular disease, and cardiovascular and all-cause mortality were assessed using Cox models. Among 3276 participants (56% women, 50% Black persons, median age 43 years), the correlation between hs-cTnI and hs-cTnT was modest (Spearman rho=0.35). Variables associated with hs-cTnI but …

Tumor-Immune Signatures Of Treatment Resistance To Brentuximab Vedotin With Ipilimumab And/Or Nivolumab In Hodgkin Lymphoma, Edgar Gonzalez-Kozlova, Brad S Kahl, Et Al.

2020-Current year OA Pubs

UNLABELLED: To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (>75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed …

Risk Factors For Postpartum Depression And Severe Distress Among Mothers Of Very Preterm Infants At Nicu Discharge., Julie A. Hofheimer, Elisabeth C. Mcgowan, Lynne M. Smith, Samantha Meltzer-Brody, Brian S. Carter, Lynne M. Dansereau, Steven Pastyrnak, Jennifer B. Helderman, Charles R. Neal, Sheri A. Dellagrotta, Thomas Michael D O'Shea, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE:  To identify psychological, medical, and socioenvironmental risk factors for maternal postpartum depression (PPD) and severe psychological distress (SPD) at intensive care nursery discharge among mothers of very preterm infants.

STUDY DESIGN:  We studied 562 self-identified mothers of 641 infants born(NOVI) conducted in nine university-affiliated intensive care nurseries. Enrollment interviews collected socioenvironmental data, depression, and anxiety diagnoses prior to and during the study pregnancy. Standardized medical record reviews ascertained prenatal substance use, maternal and neonatal medical complications. The Edinburgh Postnatal Depression Scale and Brief Symptom Inventory were administered at nursery discharge to screen for PPD and SPD symptoms, respectively.

RESULTS: …

Financial Incentives For Smoking Cessation Among Socioeconomically Disadvantaged Adults: A Randomized Clinical Trial, Darla Kendzor, Michael Businelle, Summer Frank-Pearce, Joseph Waring, Sixia Chen, Emily Hébert, Michael Swartz, Adam Alexander, Munjireen Sifat, Laili Kharazi Boozary, David Wetter

Kimmel Cancer Center Faculty Papers

IMPORTANCE: Socioeconomically disadvantaged individuals (ie, those with low socioeconomic status [SES]) have difficulty quitting smoking and may benefit from incentive-based cessation interventions.

OBJECTIVES: To evaluate the impact of incentivizing smoking abstinence on smoking cessation among adults with low SES.

DESIGN, SETTING, AND PARTICIPANTS: This study used a 2-group randomized clinical trial design. Data collection occurred between January 30, 2017, and February 7, 2022. Participants included adults with low SES who were willing to undergo smoking cessation treatment. Data were analyzed from April 18, 2023, to April 19, 2024.

INTERVENTIONS: Participants were randomized to usual care (UC) for smoking cessation (counseling …