Digital Commons Network^™

Concurrent Bone Marrow Acute Undifferentiated Leukemia And Mediastinal T‐Lymphoblastic Lymphoma With Identical Set::Nup214 Fusion And Phf6 And Ezh2 Mutations, Qing Wei, Fatima Z Jelloul, Sa A Wang, Guilin Tang, Shaoying Li, Sanam Loghavi, L Jeffrey Medeiros, Jie Xu

Faculty, Staff and Student Publications

Acute undifferentiated leukemia (AUL) is a rare hematologic malignancy lacking lineage‐specific markers. Concurrent, clonally related AUL and T‐lymphoblastic lymphoma (T‐LBL) has not been reported previously. Here we describe a patient who was diagnosed with AUL in the bone marrow and T‐LBL in the mediastinum after a thorough immunophenotyping by flow cytometry and immunohistochemistry. Despite their immunophenotypic differences, the AUL and T‐LBL showed identical genetic alterations: SET::NUP214 fusion, PHF6, and EZH2 mutations. The patient achieved and remained in complete remission after chemotherapy and stem cell transplantation. This case underscores the value of comprehensive immunophenotyping and genetic analysis in rare hematologic …

Lesion Classification By Model-Based Feature Extraction: A Differential Affine Invariant Model Of Soft Tissue Elasticity In Ct Images, Weiguo Cao, Marc J Pomeroy, Zhengrong Liang, Yongfeng Gao, Yongyi Shi, Fangfang Han, Jianhua Ma, Hongbin Lu, Almas F Abbasi, Perry J Pickhardt

Faculty, Staff and Student Publications

The elasticity of soft tissues has been widely considered a characteristic property for differentiation of healthy and lesions and, therefore, motivated the development of several elasticity imaging modalities, for example, ultrasound elastography, magnetic resonance elastography, and optical coherence elastography to directly measure the tissue elasticity. This paper proposes an alternative approach of modeling the elasticity for prior knowledge-based extraction of tissue elastic characteristic features for machine learning (ML) lesion classification using computed tomography (CT) imaging modality. The model describes a dynamic non-rigid (or elastic) soft tissue deformation in differential manifold to mimic the tissues’ elasticity under wave fluctuation in vivo. …

Immunotherapy Targeting A Leader Sequence Cathepsin G-Derived Peptide, Chunhua Shi, Ze Tian, Jun Yan, Mao Zhang, Pariya Sukhumalchandra, Guojun Yang, Meng Cui, Qing Shi, Celine Kerros, Anne Philips, Na Qiao, Hiroki Torikai, Sathvik Patchametla, Anna Sergeeva, Lisa St John, Helen He, Dmitri Wiederschain, Benjamin H Lee, Geraldine L C Paulus, Dongxing Zha, Jeffrey Molldrem, Gheath Alatrash

Faculty, Staff and Student Publications

Myeloid azurophil granules provide a rich source of intracellular leukemia antigens. Cathepsin G (CG) is a serine protease that has higher expression in acute myeloid leukemia (AML) blasts in comparison to normal myeloid progenitors. Based on the unique biology of HLA-A*0201 (HLA-A2), in which presentation of leader sequence (LS)-derived peptides is favored, we focused on the LS-CG-derived peptide CG1 (FLLPTGAEA). We previously detected CG1/HLA-A2 complexes on the surface of primary HLA-A2+ AML blasts and cell lines, and immunity targeting CG1/HLA-A2 in leukemia patients. T cell receptor (TCR)-mimic (m) antibodies are immunotherapeutic antibodies that target peptide-HLA (pHLA) complexes. Here we report …

Nicotinic Acetylcholine Receptor Expression In Merkel Cell Carcinoma Is Associated With Clinical And Histopathologic Parameters, Christopher R Cunningham, Yiannis P Dimopoulos, Ian M García-Quiñones, Denái R Milton, Manuel Delgado-Vélez, Victor G Prieto, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics.

Methods: The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7-234.1). We performed immunohistochemistry using antibodies against the …

Il13rα2-Targeting Antibodies For Immuno-Pet In Solid Malignancies, Leah Gajecki, Irina V Lebedeva, Yu-Rou Liao, Daisy Ambriz, Lukas M Carter, Samantha Lovibond, Maya S Graham, Michael Postow, Jason S Lewis, David P Andrew, Manuel Baca, Heiko Schöder, Steven M Larson, Darren R Veach, Simone Krebs

Faculty, Staff and Student Publications

Interleukin-13 receptor α-2 (IL13Rα2) is a cell surface receptor frequently expressed in solid malignancies, such as glioblastoma and melanoma, with limited expression in healthy tissue, rendering it an ideal target for noninvasive and specific tumor delineation. In this study, we report the development of 5 novel IL13Rα2-targeted human monoclonal antibodies (mAbs) KLG-1-5; in subsequent in vitro and in vivo studies after radiolabeling with 89Zr, we evaluate their performance to identify a lead candidate.

Methods: Five novel human anti-IL13Rα2 mAbs KLG-1-5 were developed and in vitro binding properties and target specificity assessed. In vivo 89Zr-immuno-PET using KLG-1-5 was conducted in a …

The Effect Of Alzheimer's Disease Genetic Factors On Limbic White Matter Microstructure, Anna Lorenz, Aditi Sathe, Dimitrios Zaras, Yisu Yang, Alaina Durant, Chenyu Gao, Karthik Ramadass, Praitayini Kanakaraj, Nazirah Mohd Khairi, Zhiyuan Li, Tianyuan Yao, Yuankai Huo, Logan Dumitrescu, Niranjana Shashikumar, Kimberly R Pechman, Trevor Bryan Jackson, Abigail W Workmeister, Shannon L Risacher, Lori L Beason-Held, Yang An, Konstantinos Arfanakis, Guray Erus, Christos Davatzikos, Mohamad Habes, Di Wang, Duygu Tosun, Arthur W Toga, Paul M Thompson, Elizabeth C Mormino, Panpan Zhang, Kurt Schilling, Marilyn Albert, Walter Kukull, Sarah A Biber, Bennett A Landman, Sterling C Johnson, Barbara Bendlin, Julie Schneider, Lisa L Barnes, David A Bennett, Angela L Jefferson, Susan M Resnick, Andrew J Saykin, Timothy J Hohman, Derek B Archer

Faculty, Staff and Student Publications

Introduction: White matter (WM) microstructure is essential for brain function but deteriorates with age and in neurodegenerative conditions such as Alzheimer's disease (AD). Diffusion MRI, enhanced by advanced bi-tensor models accounting for free water (FW), enables in vivo quantification of WM microstructural differences.

Methods: To evaluate how AD genetic risk factors affect limbic WM microstructure - crucial for memory and early impacted in disease - we conducted linear regression analyses in a cohort of 2,614 non-Hispanic White aging adults (aged 50.12 to 100.85 years). The study evaluated 36 AD risk variants across 26 genes, the association between AD polygenic scores …

Staged Screening Identifies People With Biomarkers Related To Neuronal Alpha-Synuclein Disease, Ethan G Brown, Lana M Chahine, Andrew Siderowf, Caroline Gochanour, Ryan Kurth, Chelsea Caspell-Garcia, Craig E Stanley, Monica Korell, Bridget Mcmahon, Maggie Kuhl, Kimberly Fabrizio, Laura Heathers, Luis Concha-Marambio, Claudio Soto, Sohini Chowdhury, Christopher S Coffey, Tatiana M Foroud, Tanya Simuni, Kenneth Marek, Caroline M Tanner

Faculty, Staff and Student Publications

Objective: Remote identification of individuals with severe hyposmia may enable scalable recruitment of participants with underlying alpha-synuclein aggregation. We evaluated the performance of a staged screening paradigm using remote smell testing to enrich for abnormal dopamine transporter single-photon emission computed tomography imaging (DAT-SPECT) and alpha-synuclein aggregation.

Methods: The Parkinson's Progression Markers Initiative (PPMI) recruited participants for the prodromal cohort who were 60-years and older without a Parkinson's disease diagnosis. Participants were invited to complete a University of Pennsylvania Smell Identification Test (UPSIT) independently through an online portal. Hyposmic participants were invited to complete DAT-SPECT, which determined eligibility for enrollment in …

Receptor Tyrosine Kinase Fusion-Mediated Resistance To Egfr Tki In Egfr-Mutant Nsclc: A Multi-Center Analysis And Literature Review, Yang Xia, Kaiwen Wang, Jing Zhao, Zhaohui Arter, Yongchang Zhang, Yuefei Lu, Robyn Du, Jennifer A Owens, Yasir Y Elamin, Carl M Gay, Ferdinandos Skoulidis, Anne S Tsao, Charles Lu, Tina Cascone, Don L Gibbons, Jianjun Zhang, Olivia Chen, Kevin K S Mok, Misako Nagasaka, Wen Li, John V Heymach, Sai-Hong Ignatius Ou, Molly Li, Xiuning Le

Faculty, Staff and Student Publications

Introduction: Drug resistance remains a major clinical challenge in EGFR-mutant NSCLC tumors owing to pathway reactivation, pathway bypass, and pathway indifference resistance mechanisms to evade tyrosine kinase inhibitor (TKI) suppression. Fusion of receptor tyrosine kinases (RTKs), such as RET, ALK, and FGFR3, has been reported to mediate EGFR TKI resistance. Given the rarity of these fusions and the heterogeneous nature of the condition, no prospective clinical trials evaluated the incidence, safety, and therapeutic benefit of dual EGFR-RTK inhibition.

Methods: We queried clinical databases from multiple institutions to identify patients who had RTK fusions detected on next-generation sequencing testing results from …

Pediatric Myeloid Neoplasms With Ubtf Tandem Duplications: Morphologic, Immunophenotypic, And Clinical Characterization, Mahsa Khanlari, Wei Wang, Yonghui Ni, Paul E Mead, Masayuki Umeda, Jing Ma, Juan M Barajas, Stanley Pounds, Jeffery M Klco

Faculty, Staff and Student Publications

Tandem duplications (TDs) in exons of upstream binding transcription factor (UBTF-TD) are a rare recurrent alteration in pediatric and adult acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)/neoplasm. Although recently identified, AML with UBTF-TD is now considered a distinct subtype of AML. To further our understanding of myeloid neoplasms with UBTF-TD, we analyzed clinical, morphologic, and immunophenotypic characteristics of 27 pediatric patients with UBTF-TD-positive myeloid neoplasm, including 21 diagnosed as AML and 6 as MDS. Our data demonstrated that UBTF-TD is frequently associated with cytopenia, hypercellular marrow with erythroid hyperplasia, and trilineage dysplasia. Blasts …

Efficacy And Safety Of Denileukin Diftitox-Cxdl, An Improved Purity Formulation Of Denileukin Diftitox, In Patients With Relapsed Or Refractory Cutaneous T-Cell Lymphoma, Francine M Foss, Youn H Kim, H Miles Prince, Oleg E Akilov, Christiane Querfeld, David C Fisher, Costas K Yannakou, Larisa J Geskin, Tatyana Feldman, Lubomir Sokol, Pamela Blair Allen, Nam Hoang Dang, Fernando Cabanillas, Henry K Wong, Chean Eng Ooi, Dongyuan Xing, Nicholas Sauter, Preeti Singh, Myron Czuczman, Madeleine Duvic

Faculty, Staff and Student Publications

Purpose: Denileukin diftitox (DD)-cxdl is a fusion protein comprising diphtheria toxin fragments A and B and human interleukin-2. This phase III, multicenter, open-label, single-arm registrational trial evaluated the efficacy and safety of DD-cxdl in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL).

Patients and methods: In the main study, which followed a dose-finding lead-in, DD-cxdl was administered intravenously daily (5 days; 9 µg/kg/d once daily) every 21 days for up to eight cycles. Patients in the primary efficacy analysis set (PEAS) were required to have stage IA-IIIB CTCL (mycosis fungoides and/or Sézary syndrome) and at least ≥one previous systemic therapy. …

Correction To: Selinexor In Combination With Carboplatin And Paclitaxel In Patients With Advanced Solid Tumors: Results Of A Single-Center, Multi-Arm Phase Ib Study, Kyaw Z Thein, Daniel D Karp, Apostolia Tsimberidou, Jing Gong, Selma Sulovic, Denái R Milton, Filip Janku, Lacey Mcquinn, Bettzy A Stephen, Rivka Colen, Brett W Carter, Timothy A Yap, Sarina A Piha-Paul, Siqing Fu, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

No abstract provided.

Self-Reported Cognitive Function In Older Breast Cancer Survivors After Chemotherapy Treatment, Rachel Kim, Julia Peña, Kai-Ping Liao, Susan K Peterson, Liang Li, Holly M Holmes, Sharon H Giordano

Faculty, Staff and Student Publications

Purpose: This study evaluated self-reported cognitive function in older breast cancer survivors and its association with prior chemotherapy.

Materials and methods: Breast cancer survivors aged 65-years and older, diagnosed 2012-2013, with local and regional stage disease, were identified through the linked Texas Cancer Registry-Medicare dataset. Survivors completed the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-CogV3) instrument and provided demographic and clinical data. A PCI--sub-score of less than 54 was used to identify cognitive impairment. Linear regression models were used to examine the FACT-CogV3 primary score, and logistic regression models evaluated the PCI--sub-score.

Results: Of 4448 eligible survivors, 1594 (35.8 %) …

Circulating Short-Chain And Branched Short-Chain Fatty Acids And The Risk Of Incident Type 2 Diabetes: Findings From The 4c Study, Shuangyuan Wang, Hong Lin, Xiaojing Jia, Yiting Lin, Chunyan Hu, Yu Xu, Jie Zheng, Xinjie Zhao, Yanli Li, Lulu Chen, Tianshu Zeng, Ruying Hu, Zhen Ye, Lixin Shi, Qing Su, Yuhong Chen, Xuefeng Yu, Li Yan, Tiange Wang, Zhiyun Zhao, Guijun Qin, Qin Wan, Gang Chen, Meng Dai, Di Zhang, Bihan Qiu, Xiaoyan Zhu, Ruixin Liu, Xiao Wang, Xulei Tang, Zhengnan Gao, Feixia Shen, Xuejiang Gu, Zuojie Luo, Yingfen Qin, Li Chen, Xinguo Hou, Yanan Huo, Qiang Li, Guixia Wang, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Jiajun Zhao, Yiming Mu, Guowang Xu, Shenghan Lai, Donghui Li, Guang Ning, Weiqing Wang, Yufang Bi, Jieli Lu

Faculty, Staff and Student Publications

Previous studies suggested that fecal short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) are associated with glucose regulation. However, the potential relationship between circulating SCFAs and BCFAs with incident diabetes risk in both men and women remains unidentified in prospective cohort studies. In this study, we examined a panel of nine serum SCFAs and BCFAs in 3414 subjects with incident diabetes, and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort study. In fully adjusted conditional logistic regression models, total SCFAs, total BCFAs, and isovaleric acid were significantly associated with incident type 2 diabetes mellitus (T2DM) …

Real-World Effectiveness Of Chemoimmunotherapy And Novel Therapies For Patients With Relapsed/Refractory Aggressive Large B-Cell Lymphoma, Loretta J Nastoupil, Clark R Andersen, Amy Ayers, Yucai Wang, Thomas M Habermann, Brad S Kahl, Jean L Koff, Jonathon B Cohen, Peter Martin, Izidore S Lossos, Michele Stanchina, Sara Haddadi, Carla Casulo, Sabarish Ayyappan, Ruitao Lin, Ziyi Li, Melissa A Larson, Matthew J Maurer, Lynn Huynh, Chi Gao, Ramya Ramasubramanian, Mei Sheng Duh, Alex Mutebi, Tongsheng Wang, Monika Jun, Anthony Wang, Rajesh Kamalakar, Anupama Kalsekar, James R Cerhan, Christopher R Flowers

Faculty, Staff and Student Publications

Introduction: Clinical trials provide meaningful data regarding the safety and efficacy of novel therapies but there is often a lag between the time of new drug approval and information on posttreatment clinical outcomes in real-world practice. This study evaluated clinical outcomes in a large real-world population of patients with relapsed and/or refractory large B-cell lymphoma (r/r LBCL) treated with chemoimmunotherapy or novel therapies in second or later lines of therapy (2L+).

Materials and methods: Data from the Lymphoma Epidemiology of Outcomes (LEO) Consortium of Real-World Evidence (CReWE) cohort (1/1/2015-2/15/2023) were analyzed. Patients' demographic and clinical characteristics were described and response …

An Examination Of Ambulatory Care Code Specificity Utilization In Icd-10-Cm Compared To Icd-9-Cm: Implications For Icd-11 Implementation, Valerie Watzlaf

Faculty, Staff and Student Publications

Objective: The ICD-10-CM classification system contains more specificity than its predecessor ICD-9-CM. A stated reason for transitioning to ICD-10-CM was to increase the availability of detailed data. This study aims to determine whether the increased specificity contained in ICD-10-CM is utilized in the ambulatory care setting and inform an evidence-based approach to evaluate ICD-11 content for implementation planning in the United States.

Materials and methods: Diagnosis codes and text descriptions were extracted from a 25% random sample of the IQVIA Ambulatory EMR-US database for 2014 (ICD-9-CM, n = 14 327 155) and 2019 (ICD-10-CM, n = 13 062 900). Code …

Whole-Body Hypothermia For Neonatal Encephalopathy In Preterm Infants 33 To 35 Weeks' Gestation: A Randomized Clinical Trial, Roger G Faix, Abbot R Laptook, Seetha Shankaran, Barry Eggleston, Dhuly Chowdhury, Roy J Heyne, Abhik Das, Claudia Pedroza, Jon E Tyson, Courtney Wusthoff, Sonia L Bonifacio, Pablo J Sánchez, Bradley A Yoder, Matthew M Laughon, Diana M Vasil, Krisa P Van Meurs, Margaret M Crawford, Rosemary D Higgins, Brenda B Poindexter, Tarah T Colaizy, Shannon E G Hamrick, Lina F Chalak, Robin K Ohls, Michele E Hartley-Mcandrew, Kevin Dysart, Carl T D'Angio, Ronnie Guillet, Stephen D Kicklighter, Waldemar A Carlo, Gregory M Sokol, Sara B Demauro, Anna Maria Hibbs, C Michael Cotten, Stephanie L Merhar, Roopali V Bapat, Heidi M Harmon, Elizabeth Sewell, Sarah Winter, Girija Natarajan, Ricardo Mosquera, Susan R Hintz, Nathalie L Maitre, Kristen L Benninger, Myriam Peralta-Carcelen, Abbey C Hines, Andrea F Duncan, Deanne E Wilson-Costello, Andrea Trembath, William F Malcolm, Michele C Walsh

Faculty, Staff and Student Publications

Importance: Hypothermia begun less than 6 hours after birth reduces death or disability in infants with encephalopathy due to hypoxia-ischemia at 36 or more weeks' gestation. Trials of hypothermia for infants younger than 36 weeks' gestation are lacking.

Objective: To assess the probability that hypothermia at less than 6 hours after birth decreases death or disability in infants 33 to 35 weeks' gestation with moderate or severe hypoxic-ischemic encephalopathy.

Design, setting, and participants: This randomized clinical trial was conducted between July 2015 and December 2022 for infants 33 to 35 weeks' gestation with moderate or severe hypoxic-ischemic encephalopathy at less …

Changes In Patent Ductus Arteriosus Management And Outcomes In Infants Born At 26-28 Weeks' Gestation, Dinushan C Kaluarachchi, Matthew A Rysavy, Barbara T Do, Valerie Y Chock, Matthew M Laughon, Carl H Backes, Tarah T Colaizy, Edward F Bell, Patrick J Mcnamara

Faculty, Staff and Student Publications

Objective: To investigate the association between the secular decrease in treatment of patent ductus arteriosus (PDA) and trends in neonatal mortality and morbidity in infants born at 26 0/7-28 6/7 weeks' gestation.

Study design: A retrospective cohort study including infants born between 2012 and 2021 in continually participating hospitals in the National Institute of Child Health and Human Development Neonatal Research Network. The primary composite outcome was defined as surgical necrotizing enterocolitis, grade 2-3 bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage, or death. Relationships of temporal trends in PDA treatment with the primary composite outcome and its components were analyzed using …

Nichd Magnetic Resonance Brain Imaging Score In Term Infants With Hypoxic-Ischemic Encephalopathy: A Secondary Analysis Of A Randomized Clinical Trial, Seetha Shankaran, Abbot R Laptook, Carolina Guimaraes, Johnathan Murnick, Scott A Mcdonald, Abhik Das, Carolyn M Petrie Huitema, Athina Pappas, Rosemary D Higgins, Susan R Hintz, Kristin M Zaterka-Baxter, Krisa P Van Meurs, Gregory M Sokol, Lina F Chalak, Tarah T Colaizy, Uday Devaskar, Jon E Tyson, Anne Marie Reynolds, Sara B Demauro, Pablo J Sánchez, Matthew M Laughon, Waldemar A Carlo, Kristi Watterberg, Karen M Puopolo, Anna Maria Hibbs, Shannon E G Hamrick, C Michael Cotten, John Barks, Brenda B Poindexter, William E Truog, Carl T D'Angio

Faculty, Staff and Student Publications

Importance: The neonatal brain injury score on magnetic resonance imaging following moderate or severe hypoxic-ischemic encephalopathy developed by the National Institute of Child Health and Human Development Neonatal Research Network has been revised to separate watershed and basal ganglia or thalamic injury and their associated outcomes.

Objective: To evaluate the association of the injury score with outcomes of death or moderate or severe disability among all infants, and with neurodevelopment among survivors in a trial of deeper and longer cooling.

Design, setting, and participants: In this secondary analysis of a multicenter randomized clinical trial, brain imaging was obtained from infants …

Challenges And Opportunities In Using Cognitive Screeners For Adolescents And Young Adults With Bipolar Disorder, Rebekah S Huber, Sally Weinstein, Aimee E Sullivan, Melissa M Batt, Jennifer Vande Voort, Melinda Westlund Schreiner, Funlola Are, Ioanna Douka, Melissa Delbello, Manpreet K Singh, Leslie Hulvershorn, Ramnarine Boodoo, Christopher J Hammond, James R Brasic, Neera Ghaziuddin, Richard Dopp, Leslie Miller

Faculty, Staff and Student Publications

Adolescents and young adults with bipolar disorder often experience cognitive deficits that hinder academic performance and social interactions, affecting long-term outcomes. Identifying cognitive impairments is crucial for improving clinical management of bipolar disorder. Use of cognitive screeners is recommended to identify cognitive difficulties and for ongoing assessment. Although cognitive screeners are effective with adults, their use with adolescents and young adults is limited. This project assessed clinicians' attitudes and practices regarding cognitive screening of adolescents and young adults with bipolar disorder. The National Network of Depression Centers (NNDC) Child and Adolescent Mood Disorders Task Group developed a survey for clinicians …

The Relationship Between Physical Activity And Telomere Length In Women: A Systematic Review, Jeni Page, Catherine Stephens, Melissa Richard, Elizabeth Lyons, Elizabeth Baumler, M Terese Verklan, Elizabeth Lorenzo

Faculty, Staff and Student Publications

Telomere length (TL) is a biomarker of cellular aging with variations observed by sex, age, race, and ethnicity. Prior studies have suggested that physical activity (PA) may positively impact TL by potentially elongating telomeres and slowing cellular aging. However, research examining the optimal type and intensity of PA needed to elicit these changes specific to women remains limited. This systematic review aimed to investigate variations in TL in response to PA among women, exploring how these effects differ by age, race, or ethnicity. Following PRISMA guidelines, searches across five databases identified 17 relevant studies published from 2008 to 2022. A …

A New Multiple Imputation Method For High-Dimensional Neuroimaging Data, Tong Lu, Peter Kochunov, Chixiang Chen, Hsin-Hsiung Huang, L Elliot Hong, Shuo Chen

Faculty, Staff and Student Publications

Missing data are a prevalent challenge in neuroimaging, with significant implications for downstream statistical analysis. Neglecting this issue can introduce bias and lead to erroneous inferential conclusions, making it crucial to employ appropriate statistical methods for handling missing data. Although the multiple imputation is a widely used technique, its application in neuroimaging is severely hindered by the high dimensionality of neuroimaging data, and the substantial computational demands. To tackle the critical computational challenges, we propose a novel approach, High dimensional Multiple Imputation (HIMA), based on Bayesian models specifically designed for large-scale neuroimaging datasets. HIMA introduces a new computational strategy to …

The Impact Of Atlas Parcellation On Functional Connectivity Analysis Across Six Psychiatric Disorders, Xiaoya Wu, Chuang Liang, Juan Bustillo, Peter Kochunov, Xuyun Wen, Jing Sui, Rongtao Jiang, Xiao Yang, Zening Fu, Daoqiang Zhang, Vince D Calhoun, Shile Qi

Faculty, Staff and Student Publications

Neuropsychiatric disorders are associated with altered functional connectivity (FC); however, the reported regional patterns of functional alterations suffered from low replicability and high variability. This is partly because of differences in the atlas and delineation techniques used to measure FC-related deficits within/across disorders. We systematically investigated the impact of the brain parcellation approach on the FC-based brain network analysis. We focused on identifying the replicable FCs using three structural brain atlases, including Automated Anatomical Labeling (AAL), Brainnetome atlas (BNA) and HCP_MMP_1.0, and four functional brain parcellation approaches: Yeo-Networks (Yeo), Gordon parcel (Gordon) and two Schaefer parcelletions, among correlation, group difference, …

Fungal Infections In People Who Use Drugs, Jose Portugal Gonzales, Luis Ostrosky-Zeichner

Faculty, Staff and Student Publications

Illicit drug use in the United States continues to rise, alongside an increasing number of severe infections associated with drug use. Surveillance studies report that 28%–34% of candidemia cases are linked to intravenous drug use, with Candida albicans being the most commonly isolated species, followed by Candida parapsilosis and Candida glabrata. Marijuana use is associated with lung infections caused by Aspergillus and the Mucorales, showing a 3.5-fold increased risk of mold infections and a 2.2-fold increased risk for other fungal infections. Intravenous drug use also presents a recognized risk factor for Aspergillus and Mucorales infections. Additionally, substances like …

Uric Acid Stroke Cerebroprotection Transcended Sex, Age, And Comorbidities In A Multicenter Preclinical Trial, Rakesh B Patel, Mariia Kumskova, Hanish Kodali, Ivan Budnik, Vitalii Kuznetsov, Aditi Jain, Abhishek Jha, Daniel Thedens, Nirav Dhanesha, Brijesh Sutariya, Karisma A Nagarkatti, Jessica Lamb, Pradip Kamat, Yanrong Shi, Brooklyn Avery, Takahiko Imai, Xuyan Jin, Anjali Chauhan, Ligia S B Boisserand, Mohammad B Khan, Krishnan Dhandapani, Basavaraju G Sanganahalli, Lauren H Sansing, David C Hess, Raymond C Koehler, Louise D Mccullough, Jaroslaw Aronowski, Cenk Ayata, Márcio A Diniz, Patrick D Lyden, Anna M Planas, Angel Chamorro, Anil K Chauhan, Enrique C Leira, Span Investigators

Faculty, Staff and Student Publications

Background: Past failures in translating stroke cerebroprotection provoked calls for a more rigorous methodological approach, leading to the stroke preclinical assessment network SPAN (Stroke Preclinical Assessment Network), where uric acid (UA) treatment exceeded a prespecified efficacy boundary for the primary functional outcome. Still, successful translation to humans requires confirmation of the effect of UA across key biological variables relevant to patients with stroke.

Methods: We measured the effects of intravenous UA treatment (16 mg/kg) versus intravenous saline in groups of animals enrolled in the SPAN network with diverse comorbidities, sex, and age. The masked study drug or placebo was administered …

Opportunities In Stroke Care At Safety Net Hospitals: A Socioecological Perspective, Anjail Sharrief, Joshua Wollen, Maha Almohamad, M Carter Denny, Erica Jones, Aardhra M Venkatachalam, Digvijaya Navalkele, Shivika Chandra, Mariam Ahmed, Robert Pratt, Bradley D Shy, John Mcmenamy, Chigozirim Izeogu, Lesli E Skolarus, Nneka L Ifejika, Nicole R Gonzales

Faculty, Staff and Student Publications

Safety net hospitals (SNHs) provide care to patients regardless of their insurance status or ability to pay, serving populations at the highest risk for poor stroke outcomes. These include historically marginalized racial and ethnic groups, and individuals disproportionately affected by adverse social drivers of health, including lower socioeconomic status, housing instability, and limited access to preventive care. Improving stroke care at SNHs presents a critical opportunity to strengthen care delivery for individuals with the greatest need. However, such efforts require a clear understanding of the barriers across all levels of the healthcare system. In this Perspective, the authors adopt a …

Safety Outcomes Of Antiplatelet Therapy During Endovascular Treatment Of Tandem Lesions In Acute Ischemic Stroke Patients, Mudassir Farooqui, Afshin A Divani, Milagros Galecio-Castillo, Ameer E Hassan, Mouhammad A Jumaa, Marc Ribo, Michael Abraham, Nils Petersen, Johanna Fifi, Waldo R Guerrero, Amer M Malik, James E Siegler, Thanh N Nguyen, Sunil A Sheth, Albert J Yoo, Guillermo Linares, Nazli Janjua, Darko Quispe-Orozco, Asad Ikram, Wondewossen G Tekle, Syed F Zaidi, Cynthia B Zevallos, Federica Rizzo, Tiffany Barkley, Reade De Leacy, Jane Khalife, Mohamad Abdalkader, Sergio Salazar-Marioni, Jazba Soomro, Weston Gordon, Aaron Rodriguez-Calienes, Juan Vivanco-Suarez, Charoskhon Turabova, Maxim Mokin, Dileep R Yavagal, Santiago Ortega-Gutierrez

Faculty, Staff and Student Publications

Risk of hemorrhage remains with antiplatelet medications required with carotid stenting during endovascular therapy (EVT) for tandem lesion (TLs). We evaluated the safety of antiplatelet regimens in EVT of TLs. This multicenter study included anterior circulation TL patients from 2015 to 2020, stratified by periprocedural EVT antiplatelet strategy: (1) no antiplatelets, (2) single oral, (3) dual oral, and (4) intravenous IV (in combination with single or dual oral). Primary outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were any hemorrhage, favorable functional status (mRS 0-2) at 90 days, successful reperfusion (mTICI score ≥ 2b), in-stent thrombosis, and mortality at 90 …

Prediction Of Hepatitis C Virus Perinatal Transmission In Pregnant Individuals With Hepatitis C Virus Infection, Grecio J Sandoval, George R Saade, Brenna L Hughes, Rebecca G Clifton, Uma M Reddy, Anna Bartholomew, Ashley Salazar, Edward K Chien, Alan T N Tita, John M Thorp, Torri D Metz, Ronald J Wapner, Vishakha Sabharwal, Hyagriv N Simhan, Geeta K Swamy, Kent D Heyborne, Baha M Sibai, William A Grobman, Yasser Y El-Sayed, Brian M Casey, Samuel Parry, George A Macones, Mona Prasad

Faculty, Staff and Student Publications

Our objective was to develop a prediction model for hepatitis C virus (HCV) infection perinatal transmission to improve triage for neonatal follow-up. This was a secondary analysis of HCV antibody-positive participants who were enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network multicenter observational study of HCV infection in pregnancy. Among 432 participants, the perinatal transmission rate was 6.0% (95% CI, 4.0-8.7%). The prediction model was developed and included two factors: maternal HCV RNA titer greater than 10 6 international units/mL and having had any antepartum bleeding. Using this model, the …

Acute Pain Trajectories In Elderly Patients With Fragility Hip Fractures, Paul Potnuru, Christina Goehl, Katherine S Becker, Alejandro Juul, Madison Aycock, Johanna Blair De Haan, Sudipta Sen, Michelle Ge, Stephen J Warner, Nadia Hernandez

Faculty, Staff and Student Publications

Background: Pain management for hospitalized elderly patients with fragility hip fractures (FHF) remains challenging. This study aims to distinguish acute pain trajectories in FHF patients that can inform personalized analgesia management.

Methods: We conducted a prospective observational study of patients aged 65 and older with FHF at a Level I trauma center. The primary outcome was daily average pain assessed for five days post-injury using the Brief Pain Inventory (BPI). We used group-based trajectory modeling (GBTM) to distinguish acute pain trajectories. Then, factors and secondary outcomes (opioid use and hospital length of stay [LOS]) associated with more severe pain trajectories …

Pulmonary Disease Caused By Mycobacterium Marseillense In Colombia, Martha Isabel Murcia-Aranguren

Faculty, Staff and Student Publications

No abstract provided.

Selected Social And Lifestyle Correlates Of Brain Health Markers: The Cross-Cohort Collaboration Consortium, Jeannette Simino, Jan Bressler, Robin Bülow, Charles S Decarli, Alison E Fohner, Laura B Harrington, Catherine Helmer, M Arfan Ikram, Rozenn N Lemaitre, Oscar L Lopez, W T Longstreth, Julia Neitzel, Michelle C Odden, Priya Palta, Carsten O Schmidt, Rajesh Talluri, Meike W Vernooij, Henry Völzke, Trudy Voortman, Quest Whalen, Katharina Wittfeld, Hans J Grabe, Thomas H Mosley, Bruce M Psaty, Frank J Wolters, Sudha Seshadri, Carole Dufouil

Faculty, Staff and Student Publications

Introduction: To investigate the associations of education level, marital status, and physical activity with dementia risk and brain MRI markers.

Methods: Data from six community-based samples from the Cross-Cohort Collaboration Consortium were analyzed. Self-reported education level, marital status, and physical activity at age 60 to 75 years were harmonized. Subsamples of participants with brain MRI markers at time of exposure were selected. Associations with dementia risk and cross-sectional MRI markers were meta-analyzed.

Results: Higher education level was associated with lower dementia risk (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.59; 0.72 vs low level) but not significantly …