Digital Commons Network^™

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

Faculty, Staff and Students Publications

Introduction

Methods

Sex-Related Measurement Bias In Autism Spectrum Disorder Symptoms In The Baby Siblings Research Consortium, Catherine A Burrows, Natasha Marrus, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Disparities exist in age of diagnosis and prevalence of autism spectrum disorder (ASD) for female compared with male children. Correcting for sources of bias is critical for improving equitable ASD identification.

OBJECTIVE: To determine whether sex differences exist in measurement of ASD symptoms using the Autism Diagnostic Observation Schedule (ADOS) among young children at high familial likelihood (HFL) and low familial likelihood (LFL) of ASD.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study collected longitudinal, prospective data from the Baby Siblings Research Consortium between January 1, 2003, and December 31, 2021. Participants included 3106 children who had an older sibling …

Disruption Of The Cerebrospinal Fluid-Plasma Protein Balance In Cognitive Impairment And Aging, Amelia Farinas, Daniel Western, Jigyasha Timsina, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

The brain barrier system, including the choroid plexus, meninges and brain vasculature, regulates substrate transport and maintains differential protein concentrations between blood and cerebrospinal fluid (CSF). Aging and neurodegeneration disrupt brain barrier function, but proteomic studies of the effects on blood-CSF protein balance are limited. Here we used SomaScan proteomics to characterize paired CSF and plasma samples from 2,171 healthy or cognitively impaired older individuals from multiple cohorts, including the Global Neurodegeneration Proteomics Consortium. We identified proteins with correlated CSF and plasma levels that are produced primarily outside the brain and are enriched for structural domains that may enable their …

Longer Scans Boost Prediction And Cut Costs In Brain-Wide Association Studies, Leon Qi Rong Ooi, Scott Marek, Nico U F Dosenbach, Timothy O Laumann, Evan M Gordon, Et Al.

2020-Current year OA Pubs

A pervasive dilemma in brain-wide association studies

High-Density Lipoprotein-Associated Cholesterol Abnormalities In A Clinical Outcomes Study Of Dysferlin-Deficient Limb-Girdle Muscular Dystrophy Type R2, Zoe White, Alan Pestronk, Et Al.

2020-Current year OA Pubs

BACKGROUND: Limb-girdle muscular dystrophy (MD) type R2 (LGMDR2, formerly LGMD2B) is an autosomal recessive form of MD caused by variants in the dysferlin gene, DYSF. It leads to slow proximal and distal muscle weakening that generally results in loss of ambulation around early adulthood but without the lethal cardiorespiratory dysfunction observed in the more severe Duchenne MD. How loss of dysferlin causes muscle fibre death is poorly understood, but recent evidence suggests a link between muscle wasting and loss of muscle cholesterol homeostasis with circulating lipoprotein abnormalities in many forms of MD.

METHODS: Cross-sectional circulating total cholesterol (CHOL), high-density lipoprotein-associated …

Domains Of Housing Instability And Intimate Partner Violence Risk Among U.S. Tenants, Anairany Zapata, Leila G Wood, Annalynn M Galvin, Wenyaw Chan, Timothy A Thomas, Jack Tsai, Heather K Way, Elizabeth J Mueller, Daphne C Hernandez

Faculty, Staff and Student Publications

While IPV is often studied as a predictor of housing insecurity, few U.S. studies explore how different forms of housing instability may contribute to intimate partner violence (IPV) risk. Using a mixed-methods approach and a cross-sectional design, this study examined the association between four housing instability domains and IPV among a sample of tenants that had either experienced eviction or were at high risk for eviction. Tenants in Harris and Travis counties (Texas, USA) completed an online survey (n = 1085; March–July 2024). Housing instability was assessed across four domains: homelessness, lease violations, utility hardship, and poor housing quality. …

Neighborhood Environment And Incident Diabetes, A Neighborhood Environment-Wide Association Study ('Ne-Was'): Results From The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol)., Cara M. Smith, Elizabeth W. Spalt, Linda C. Gallo, Jordan A. Carlson, Matthew Allison, Daniela Sotres-Alvarez, Christina Cordero, Qibin Qi, Earle C. Chambers, Martha Daviglus, Amber Pirzada, Gregory A. Talavera, Robert Kaplan, Joel D. Kaufman, Stephen J. Mooney

Manuscripts, Articles, Book Chapters and Other Papers

The prevalence of type 2 diabetes is increasing among the Hispanic/Latino population. Type 2 diabetes incidence rates vary between neighborhoods, but no single aspect of the neighborhood environment is known to cause type 2 diabetes. Using data from the Hispanic Community Health Study/Study of Latinos cohort of 16,415 Hispanic/Latino adults in four major US cities, we conducted a neighborhood environment-wide association study to identify neighborhood measures or clusters of measures associated with diabetes incidence. Two-hundred and four neighborhood measures were calculated at the census tract level or within a 1-km buffer of participants' residential addresses. Independent covariate-adjusted and survey-weighted Poisson …

Do Gender-Related Characteristics Impact Female Faculty Career Progression In Academic Doctor Of Physical Therapy Programs?, Bridget Eubanks

Internet Journal of Allied Health Sciences and Practice

Purpose: This study explored the experiences of female faculty in academic Doctor of Physical Therapy (DPT) programs in the US and if gender, or more specifically any gender-related characteristics such as pregnancy or motherhood, impacts female faculty career progression. Evidence has demonstrated that several challenges disproportionately affect women in academia, but there is currently no research available related to female faculty experiences in academic DPT programs. Methods: This study used a qualitative research design with a descriptive statistics component. It utilized a descriptive, cross-sectional design with a nonexperimental survey methodology. The Culture Conducive to Women’s Academic Success instrument was used …

Use Of A Shoulder-Mounted Wearable Sensor Prototype Designed To Detect Opioid-Related Overdose: A Qualitative User Experience Study, Alexis M. Roth, Ally K. D'Angelo, David Gordon, Benjamin Cocchiaro, Anush Lingamoorthy, Rose Laurano, Matthew Salzman, Jacob S. Brenner, Cameron Baston

SKMC Student Presentations and Publications

BACKGROUND: For over a decade, drug overdose has been the leading cause of injury and accidental death in the United States. Most fatal overdoses involve opioids and occur during solitary drug use events when no one is available to initiate lifesaving responses (eg, naloxone). While there is a growing interest in devices providing early overdose detection and automated responses, little research has engaged end users in a device design process.

OBJECTIVE: This study aimed to describe user experience, perceived harms and benefits, and the acceptability of a shoulder-mounted wearable sensor among people who inject drugs who wore a device prototype …

Pilot Study Of [11c]Hy-2-15: A Mixed Alpha-Synuclein And Tau Pet Radiotracer, Chia-Ju Hsieh, Dinahlee Saturnino Guarino, Anthony J Young, Andrew D Siderowf, Ilya Nasrallah, Alexander Schmitz, Carol Garcia, Ho Young Kim, Erin K Schubert, Hsiaoju Lee, Joel S Perlmutter, Robert H Mach

2020-Current year OA Pubs

A novel brain positron emission tomography (PET) radioligand, [

Replication Of Sensor-Based Categorization Of Upper-Limb Performance In Daily Life In People Post Stroke And Generalizability To Other Populations, Chelsea E Macpherson, Marghuretta D Bland, Christine Gordon, Allison E Miller, Caitlin Newman, Carey L Holleran, Christopher J Dy, Lindsay Peterson, Keith R Lohse, Catherine E Lang

2020-Current year OA Pubs

BACKGROUND: Wearable movement sensors can measure upper limb (UL) activity, but single variables may not capture the full picture. This study aimed to replicate prior work identifying five multivariate categories of UL activity performance in people with stroke and controls and expand those findings to other UL conditions.

METHODS: Demographic, self-report, and wearable sensor-based UL activity performance variables were collected from 324 participants (stroke

RESULTS: Two PCs explained 70-90% variance: PC1 (overall UL activity performance) and PC2 (preferred-limb use). A five-variable, five-cluster model was optimal across samples. In comparison to clusters, two PCs and individual accelerometry variables showed higher convergent …

Physician And Hospital Performance In Medicare’S Updated Bundled-Payment Model For Joint Replacement, Aidan P. Crowley, Austin S. Kilaru, Qian Erin Huang, Erkuan Wang, Jingsan Zhu, Ayush Arora, Torrey Shirk, Deborah S. Cousins, Kristin A. Linn, Said A. Ibrahim, Joshua M. Liao, Amol S. Navathe

Department of Medicine Faculty Papers

IMPORTANCE: Independent evaluations of Bundled Payments for Care Improvement Advanced (BPCI-A) have focused on hospitals and have not assessed the performance of physicians in participating physician group practices (PGPs). However, PGPs are accountable for a larger proportion of surgical procedures, including for lower-extremity joint replacement, in the BPCI-A model than are hospitals.

OBJECTIVE: To evaluate the association of treatment by BPCI-A-participating physicians and hospitals with health care spending, quality, and utilization for joint replacement procedures compared to nonparticipants.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used Medicare claims of beneficiaries receiving lower-extremity joint replacement between April 2016 and September 2019 …

Phase 1b/2 Study Evaluating Safety, Efficacy And Immune Effects Of Tlr9 Agonist Cavrotolimod With Anti-Pd-1 Antibodies Among Patients With Advanced Solid Tumors, Mohammed M Milhem, George Ansstas, Et Al.

2020-Current year OA Pubs

BACKGROUND: There is an unmet need for novel immunotherapies to overcome immune evasion in patients with advanced skin cancers resistant to programmed death (PD)-1 / PD-ligand 1 (PD-L1) blockade. Cavrotolimod is a novel spherical nucleic acid configuration of a toll-like receptor 9 agonist oligonucleotide, designed to trigger innate and adaptive immune responses to tumors.

PATIENTS AND METHODS: The safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of intratumoral cavrotolimod, first dosed alone and then in combination with anti-PD-1 antibodies (pembrolizumab or cemiplimab), were assessed in a combined Phase 1b/2 dose escalation/dose expansion study in patients with advanced skin cancers, including melanoma, Merkel …

Machine-Learning Driven Strategies For Adapting Immunotherapy In Metastatic Nsclc, Maliazurina B Saad, Qasem Al-Tashi, Lingzhi Hong, Vivek Verma, Wentao Li, Daniel Boiarsky, Shenduo Li, Milena Petranovic, Carol C Wu, Brett W Carter, Girish S Shroff, Tina Cascone, Xiuning Le, Yasir Y Elamin, Mehmet Altan, Simon Heeke, Ajay Sheshadri, Joe Y Chang, Percy P Lee, Zhongxing Liao, Don L Gibbons, Ara A Vaporciyan, J Jack Lee, Ignacio I Wistuba, Cara Haymaker, Seyedali Mirjalili, David Jaffray, Justin F Gainor, Yanyan Lou, Alessandro Di Federico, Federica Pecci, Mark Awad, Biagio Ricciuti, John V Heymach, Natalie I Vokes, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs), either as monotherapy (ICI-Mono) or combined with chemotherapy (ICI-Chemo), improves survival in advanced non-small cell lung cancer (NSCLC). However, prospective guidance for choosing between these options remains limited, and single-feature biomarkers like PD-L1 prove inadequate. We develop a machine learning model using clinicogenomic data from four cohorts (MD Anderson n = 750; Mayo Clinic n = 80; Dana-Farber n = 1077; Stand Up To Cancer n = 393) to predict individual benefit from adding chemotherapy. Benefit scores are calculated using five distinct functions derived from 28 genomic and 6 clinical features. Our integrated model, A-STEP (Attention-based …

Effects Of Oxygen Manipulation On Myofibroblast Phenotypic Transformation In Patients With Radiation-Induced Fibrosis, Eric Mastrolonardo, Sarah Sussman, Bo Yun, Victor Jegede, Dev Amin, Joel Rosenbloom, Andrew P. South, Voichita Bar-Ad, Peter J Wermuth, Adam J. Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

We tested if hyperoxic conditions can reduce the proportion of active myofibroblasts, which are assumed to be a major driver of head and neck radiation-induced fibrosis, as measured by expression levels of pro-fibrotic genes. Radiated, non-cancerous soft tissue from the head and neck and skin/soft tissue from non-radiated flap donor site were collected from each patient. Myofibroblast density was quantified using immunofluorescence staining with α-SMA and DAPI and visualisation under confocal microscopy and compared between baseline non-radiated and radiated tissue from the same patient. From each tissue specimen, fibroblast cell lines were cultured and exposed to either normoxic, hypoxic, or …

Macrophage-T Cell Interactions Promote Slamf1 Expression For Enhanced Tb Defense, G V R Krishna Prasad, Steven J Grigsby, Gideon A Erkenswick, Cynthia Portal-Celhay, Ekansh Mittal, Guozhe Yang, Samuel M Fallon, Fengyixin Chen, Thais Klevorn, Neharika Jain, Yuanyuan Li, Makedonka Mitreva, Amanda J Martinot, Joel D Ernst, Jennifer A Philips

2020-Current year OA Pubs

CD4+ T cells are crucial for protective immunity to intracellular pathogens. In addition to secreting cytokines, CD4+ T cells promote control of Mycobacterium tuberculosis infection through cognate interactions with macrophages, but the mechanism has been unclear. Here, we show that SLAMF1/CD150 is highly and uniquely induced in macrophages by antigen-specific interactions with CD4+ T cells. In macrophages, SLAMF1 enhances the generation of reactive oxygen species and restricts Mtb replication. Mtb-infection of mice promotes SLAMF1 expression specifically on infected macrophages, not uninfected bystanders. SLAMF1 expression depends on adaptive immunity and also autophagy. Moreover, Slamf1

Participant Engagement In A National Longitudinal Study Of Covid-19: Insights From The Inspire Study, Kris Pui Kwan Ma, Tracy Stober, Michael Gottlieb, Rachel E. Geyer, Kristin L. Rising, Sharon Saydah, Michelle Santangelo, Kristyn Gatling, Dylan Grau, Ralph C. Wang, Juan Carlos Montoy, Ahamed Idris, Samuel Macdonald, Mandy J. Hill, Ryan Huebinger, Maria G. Prado, Nicole L. Gentile, Erica Spatz, Caitlin Maliki, Jocelyn Dorney, Joann G. Elmore, Michelle L'Hommedieu, Robert A Weinstein, Arjun K. Venkatesh, Kari A. Stephens

Department of Emergency Medicine Faculty Papers

OBJECTIVE: To examine participants' motivations and their experiences throughout a decentralized, longitudinal COVID-19 study in the U.S.

METHODS: We recruited 355 participants from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) between November 2022 - March 2023 to answer five qualitative survey questions anonymously. We used an inductive content analysis approach to analyze the data.

RESULTS: We identified five key themes from the analysis, which reflected participants' a) motivations to join the study, b) study benefits, c) perceptions of survey questions, d) experiences with the research process, and e) preferences for disseminating research findings. Participants were motivated to …

Timing Of Nodal Metastasis In Patients With Eyelid Sebaceous Carcinoma And Implications For Surveillance And Survival, Tracy Lu, Casey Anthony, Xinyang Jiang, Jing Ning, Ryan Goepfert, Bita Esmaeli

Faculty, Staff and Student Publications

Background/aims: Sebaceous carcinoma (SC) is a rare cancer with periocular predilection. Studies focused on patterns and timing of nodal metastasis are scarce.Our aim is to report patterns of regional nodal metastasis in patients with eyelid SC, including results of sentinel lymph node biopsy (SLNB).

Methods: All consecutive patients with eyelid SC treated during 1999-2023 were retrospectively reviewed.All subjects had standard of care surgery for eyelid SC and regional lymph node evaluation using physical examination and ultrasonography (US) at baseline and during the surveillance period. 38 patients with negative findings on US had SLNB to rule out microscopic metastasis.The frequency and …

A Whole-Brain Voxel-Based Analysis Of Structural Abnormalities In Ptsd: An Enigma-Pgc Study, Cheryl R Z See, Shuqing Si, C Lexi Baird, Courtney C Haswell, Ahmed Hussain, Miranda Olff, Dick J Veltman, Jessie L Frijling, Mirjam Van Zuiden, Saskia B J Koch, Laura Nawijn, Li Wang, Ye Zhu, Gen Li, Yuval Neria, Xi Zhu, Benjamin Suarez-Jimenez, Sigal Zilcha-Mano, Amit Lazarov, Jennifer S Stevens, Kerry Ressler, Negar Fani, Tanja Jovanovic, Sanne J H Van Rooij, Milissa L Kaufman, Lauren A M Lebois, Isabelle M Rosso, Elizabeth A Olson, Justin T Baker, Scott R Sponheim, Seth G Disner, Nicholas D Davenport, Amit Etkin, Adi Maron-Katz, Murray B Stein, Martha E Shenton, Dan J Stein, Jonathan Ipser, Sheri-Michelle Koopowitz, Soraya Seedat, Stefan Du Plessis, Leigh L Van Den Heuvel, Shmuel Lissek, Hannah Berg, Thomas Straube, David Hofman, Lee A Baugh, Gina L Forster, Raluca M Simons, Jeffrey S Simons, Vincent A Magnotta, Kelene A Fercho, Xin Wang, Andrew S Cotton, Erin N O'Leary, Hong Xie, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine L Larson, Terri A Deroon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Jennifer Urbano Blackford, Bunmi O Olatunji, Evan M Gordon, Geoffrey May, Steven M Nelson, Ruth Lanius, Jean Théberge, Maria Densmore, Richard W J Neufeld, Chadi G Abdallah, Christopher L Averill, Ilan Harpaz-Rotem, Ifat Levy, John H Krystal, Elbert Geuze, Remko Van Lutterveld, Emily L Dennis, David F Tate, David X Cifu, William C Walker, Elisabeth A Wilde, Nic J A Van Der Wee, Robert R J M Vermeiren, Steven J A Van Der Werff, Katie Mclaughlin, Kelly Sambrook, Matthew Peverill, Joaquim Radua, Lauren E Salminen, Neda Jahanshad, Sophia I Thomopoulos, Anthony James, Lucia Valmaggia, Paul M Thompson, Rajendra A Morey, Matthew J Kempton

Faculty, Staff and Students Publications

Background: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

Methods: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and …

A Whole-Brain Voxel-Based Analysis Of Structural Abnormalities In Ptsd: An Enigma-Pgc Study, Cheryl R Z See, Evan M Gordon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

METHODS: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD

RESULTS: PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges'

CONCLUSIONS: PTSD patients exhibited widespread, regional differences in brain volumes where greater regional …

Investigating The Necessity Of Adaptive Radiotherapy In Tomotherapy Of Head And Neck Cancer Patients, Ali Chaparian, Mahsa Kianinia, Mahnaz Roayaei, Nadia Najafizade, Abolfazl Kanani, Leili Mahani, Hamidreza Nourzadeh

Department of Radiation Oncology Faculty Papers

BACKGROUND: Anatomical variations that occur during radiation therapy in head and neck cancer (HNC) patients can lead to significant dosimetric changes. The purpose of this study is to evaluate dosimetric and volume changes in key anatomical structures for different treatment sites in HNC patients, and to determine the percentage of patients who need adaptive radiotherapy (ART) per treatment site.

METHODS: A total of 1,740 megavoltage computed tomography (MVCT) images from 58 HNC patients treated with helical tomotherapy (HT) were exported to the PreciseART™ (Accuray) software. Volume changes in the planning target volume (PTV) and the organs at risk (OARs) in …

Smartboot: Real-Time Monitoring Of Patient Activity Via Remote Edge Computing Technologies, Gozde Cay, Myeounggon Lee, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

Diabetic foot ulcers (DFUs) are a serious complication of diabetes, associated with high recurrence and amputation rates. Adherence to offloading devices is critical for wound healing but remains inadequately monitored in real-world settings. This study evaluates the SmartBoot edge-computing system-a wearable, real-time remote monitoring solution integrating an inertial measurement unit (Sensoria Core) and smartwatch-for its validity in quantifying cadence and step count as digital biomarkers of frailty, and for detecting adherence. Twelve healthy adults wore two types of removable offloading boots (Össur and Foot Defender) during walking tasks at varied speeds; system outputs were validated against a gold-standard wearable and …

Impact Of Sars-Cov-2 On Healthcare And Essential Workers: A Longitudinal Study Of Promis-29 Outcomes, Jocelyn Dorney, Imtiaz Ebna Mannan, Caitlin Malicki, Lauren E. Wisk, Joann Elmore, Kelli N. O'Laughlin, Dana Morse, Kristyn Gatling, Michael Gottlieb, Michelle Santangelo, Michelle L'Hommedieu, Nicole L. Gentile, Sharon Saydah, Mandy J. Hill, Ryan Huebinger, Katherine Riley Martin, Ahamed H. Idris, Efrat Kean, Kevin Schaeffer, Robert M. Rodriguez, Robert A. Weinstein, Erica S. Spatz, Inspire Group

Department of Emergency Medicine Faculty Papers

IMPORTANCE: The mandatory service of essential workers during the COVID-19 pandemic was associated with high job stress, increased SARS-CoV-2 exposure, and limited time for recovery following infection. Understanding outcomes for frontline workers can inform planning for future pandemics.

OBJECTIVE: To compare patient-reported outcomes by employment type and SARS-CoV-2 status.

DESIGN: Data from the INSPIRE registry, which enrolled COVID-positive and COVID-negative adults between 12/7/2020-8/29/2022 was analyzed. Patient-reported outcomes were collected quarterly over 18 months.

SETTING: Participants were recruited across eight US sites.

PARTICIPANTS: Employed INSPIRE participants who completed a short (3-month) and long-term (12-18 month) survey.

EXPOSURE: SARS-CoV-2 index status and …

A Two-Stage Dual-Task Learning Strategy For Early Prediction Of Pathological Complete Response To Neoadjuvant Chemotherapy For Breast Cancer Using Dynamic Contrast-Enhanced Magnetic Resonance Images, Bowen Jing, Jing Wang

Faculty, Staff and Student Publications

Early prediction of treatment response can facilitate personalized treatment for breast cancer patients. Studies on the I-SPY 2 clinical trial demonstrate that multi-time point dynamic contrast-enhanced magnetic resonance (DCEMR) imaging improves the accuracy of predicting pathological complete response (pCR) to chemotherapy. However, previous image-based prediction models usually rely on mid- or post-treatment images to ensure the accuracy of prediction, which may outweigh the benefit of response-based adaptive treatment strategy. Accurately predicting the pCR at the early time point is desired yet remains challenging. To improve prediction accuracy at the early time point of treatment, we proposed a two-stage dual-task learning …

Patient-Centered, Theory-Based, Online Intervention To Promote A Physically Active Lifestyle For People With Multiple Sclerosis: Protocol For A Randomized Controlled Trial, Chungyi Chiu, Vaishnavi Sridharan, Mojtaba Khaliji, Md Refat Uz Zaman Sajib, Xiaotian Gao, Kathleen Zackowski

Children’s Nutrition Research Center Staff Publications

Background: People with multiple sclerosis (MS) experience life challenges due to the nature of disease progression. Although an active lifestyle has been shown effective for symptom and relapse management, most people with MS lead a sedentary lifestyle and do not reach the recommended physical activity (PA) guidelines.

Objective: This study aims to test the preliminary efficacy of a codeveloped, online self-management intervention based on the health action process approach (HAPA) adapted for people with MS to cultivate a physically active lifestyle.

Methods: The 8-week intervention program was developed using community-based participatory research based on the HAPA. The program includes increasing …

Serum Metabolomic Profiling Of Incident Type 2 Diabetes Mellitus In The Multi-Ethnic Study Of Atherosclerosis And Rotterdam Study, Xuanwei Jiang, Fang Zhu, Gonçalo Graça, Xihao Du, Jinjun Ran, Fariba Ahmadizar, Alexis C Wood, Yanqiu Zhou, Denise M Scholtens, Ali Farzaneh, M Arfan Ikram, Alan Kuang, Carel W Le Roux, Meghana D Gadgil, Marilyn C Cornelis, Kent D Taylor, Xiuqing Guo, Mohsen Ghanbari, Laura J Rasmussen-Torvik, Russell P Tracy, Alain G Bertoni, Jerome I Rotter, David M Herrington, Philip Greenland, Maryam Kavousi, Victor W Zhong

Children’s Nutrition Research Center Staff Publications

Objective: This study aimed to investigate serum metabolomic biomarkers associated with incident type 2 diabetes mellitus (T2DM) and evaluate their performance in improving T2DM risk prediction.

Methods: Untargeted proton nuclear magnetic resonance (1H NMR) spectroscopy-based metabolomics analyses were conducted in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 3460; discovery cohort) and The Rotterdam Study (RS; n = 1556; replication cohort). Multivariable cause-specific hazards models were used to analyze the associations between 23 571 serum metabolomic spectral variables and incident T2DM. Replicated metabolites required an false discovery rate-adjusted P < .01 in MESA, P < .05 in RS, and consistent direction of association. Pathway and network analyses were conducted to elucidate biological mechanisms underlying T2DM development. The utility of the replicated metabolites in improving T2DM risk prediction was assessed based on the Framingham Diabetes Risk Score. A 2-sample Mendelian randomization was conducted to assess causal associations.

Results: Nineteen metabolites were significantly associated with incident T2DM. Pathway analyses …

Predictors Of Final Visual Outcome In Patients With Leber Hereditary Optic Neuropathy Treated With Lenadogene Nolparvovec Gene Therapy, Robert C Sergott, Valerio Carelli, Nancy Newman, Valérie Biousse, Patrick Yu-Wai-Man, Catherine Vignal-Clermont, Constant Josse, Magali Taiel, José-Alain Sahel, Piero Barboni

Wills Eye Hospital Papers

PURPOSE: This exploratory analysis aimed to identify predictive factors of final best-corrected visual acuity (BCVA) in patients with Leber hereditary optic neuropathy (LHON) harboring the m.11778G>A mutation who received lenadogene nolparvovec gene therapy.

METHODS: The following covariates were individually evaluated as possible factors associated with improved final BCVA: age, gender, timing of treatment, baseline BCVA value, and baseline optical coherence tomography (OCT) parameters. Univariate analyses were performed from three phase 3 studies (RESCUE, REVERSE, and REFLECT), using BCVA at 1.5 years post-treatment as the dependent variable.

RESULTS: In 113 eyes treated at least 6 months after disease onset, the …

Fgfr3-Induced Y158 Parp1 Phosphorylation Promotes Parp Inhibitor Resistance Via Brg1/Mre11-Mediated Dna Repair In Breast Cancer Models, Mei-Kuang Chen, Hirohito Yamaguchi, Yuan Gao, Weiya Xia, Jeffrey T Chang, Yu-Chun Hsiao, Tewodros W Shegute, Zong-Shin Lin, Chen-Shiou Wu, Yu-Han Wang, Jennifer K Litton, Qingqing Ding, Yongkun Wei, Yu-Yi Chu, Funda Meric-Bernstam, Helen Piwnica-Worms, Banu Arun, Jordi Rodon Ahnert, Jinsong Liu, Jun Yao, Wei-Chao Chang, Hung-Ling Wang, Coya Tapia, Constance T Albarracin, Khandan Keyomarsi, Shao-Chun Wang, Ying-Nai Wang, Gabriel N Hortobagyi, Chunru Lin, Liuqing Yang, Dihua Yu, Mien-Chie Hung

Faculty, Staff and Student Publications

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) are used to treat BRCA-mutated (BRCAm) cancer patients; however, resistance has been observed. Therefore, biomarkers to indicate PARPi resistance and combination therapy to overcome that are urgently needed. We identified a high prevalence of activated FGF receptor 3 (FGFR3) in BRCAm triple-negative breast cancer (TNBC) cells with intrinsic and acquired PARPi resistance. FGFR3 phosphorylated PARP1 at tyrosine 158 (Y158) to recruit BRG1 and prolong chromatin-loaded MRE11, thus promoting homologous recombination (HR) to enhance PARPi resistance. FGFR inhibition prolonged PARP trapping and synergized with PARPi in vitro and in vivo. High-level PARP1 Y158 phosphorylation (p-Y158) positively …

Synergistic Activity Of Combined Flt3-Itd And Mdm2 Inhibition With Quizartinib And Milademetan In Flt3-Itd Mutant/Tp53 Wild-Type Acute Myeloid Leukemias, Weiguo Zhang, Li Li, Muharrem Muftuoglu, Mahesh Basyal, Noriko Togashi, Koichi Iwanaga, Fumie Tanzawa, Masashi Numata, Dale L Bixby, Harry P Erba, Nikolai Podoltsev, Gary J Schiller, Prasanna Kumar, Arnaud Lesegretain, Takeshi Isoyama, Takahiko Seki, Naval Daver, Michael Andreeff

Faculty, Staff and Student Publications

Purpose: Acute myeloid leukemia (AML) is characterized by frequent mutations in FMS-like tyrosine kinase 3 (FLT3), overexpression of murine double minute 2 (MDM2), and TP53 wild-type (WT). Monotherapies targeting FLT3 frequently result in the development of resistant disease. In this study, we investigated the antileukemic efficacy of co-targeting FLT3 and MDM2 with quizartinib and milademetan (Q/M) in FLT3 internal tandem duplication (FLT3-ITD) AML cell lines, xenograft and patient-derived xenograft (PDX) models, and a phase I clinical trial.

Experimental design: Preclinical studies used human and murine cell lines carrying FLT3-ITD and/or tyrosine kinase domain mutations, TP53 WT/knockdown, leukemia cell xenograft models, …

Hepatitis Patients Undergoing Cardiac Surgery: A Single-Center Retrospective Study, Jin-Long Ju, Yun-Tai Yao, Jun Li, Zhi Cheng, Ling-Ling Fan, Yu-Long Zhong

Faculty, Staff and Student Publications

This study aimed to investigate whether there is difference among various clinical variables, especially blood loss and total drainage volume, among patients with different types of hepatitis undergoing cardiac surgery. A retrospective study was performed on 150 hepatitis patients (127 hepatitis B and 23 hepatitis C) who underwent cardiac surgery at a single cardiovascular center in 2020. Data on their preoperative, intraoperative, and postoperative variables were collected and statistically analyzed to assess the inter-group differences in the following variables: intraoperative blood loss, postoperative drainage volume, proportion of patients treated with blood transfusion, proportion of patients treated with vasoactive drugs, and …