Digital Commons Network^™

Keratin 17 Is A Prognostic And Predictive Biomarker In Pancreatic Ductal Adenocarcinoma, Lyanne Delgado-Coka, Lucia Roa-Peña, Sruthi Babu, Michael Horowitz, Emanuel Petricoin, Lynn Matrisian, Edik Blais, Natalia Marchenko, Felicia Allard, Ali Akalin, Wei Jiang, Md, Phd, Brent Larson, Andrew Hendifar, Vincent Picozzi, Minsig Choi, Kenneth Shroyer, Luisa Escobar-Hoyos

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVES: To determine the role of keratin 17 (K17) as a predictive biomarker for response to chemotherapy by defining thresholds of K17 expression based on immunohistochemical tests that could be used to optimize therapeutic intervention for patients with pancreatic ductal adenocarcinoma (PDAC).

METHODS: We profiled K17 expression, a hallmark of the basal molecular subtype of PDAC, by immunohistochemistry in 2 cohorts of formalin-fixed, paraffin-embedded PDACs (n = 305). We determined a K17 threshold of expression to optimize prognostic stratification according to the lowest Akaike information criterion and explored the potential relationship between K17 and chemoresistance by multivariate predictive analyses.

RESULTS: …

Prognostic Significance And Biologic Associations Of Senescence-Associated Secretory Phenotype Biomarkers In Heart Failure, Oday Salman, Ali Javaheri, Douglas L Mann, Et Al.

2020-Current year OA Pubs

BACKGROUND: The role of cellular senescence in human heart failure (HF) remains unclear. The senescence-associated secretory phenotype (SASP) is composed of proteins released by senescent cells. We assessed the prognostic significance and biologic pathways associated with the SASP in human HF using a plasma proteomics approach.

METHODS AND RESULTS: We measured 25 known SASP proteins among 2248 PHFS (Penn HF Study) participants using the SOMAScan V4 assay. We extracted the common variance in these proteins to generate SASP factor scores and assessed the relationship between these SASP factor scores and (1) all-cause death and (2) the composite of death or …

Use Of Palliative Care Among Adults With Newly Diagnosed Heart Failure: Insights From A Us National Insured Patient Sample, Zidong Zhang, Divya S Subramaniam, Steven W Howard, Kenton J Johnston, William H Frick, Kimberly Enard, Leslie Hinyard

2020-Current year OA Pubs

BACKGROUND: Despite the known benefits for individuals with heart failure (HF), incomplete data suggest a low use of palliative care (PC) for HF in the United States. We aimed to investigate the national PC use for adults with HF by determining when they received their first PC consultation (PCC) and the associations with clinical factors following diagnosis of HF.

METHODS AND RESULTS: We conducted a retrospective cohort study in a national all-payer electronic health record database to identify adults (aged ≥18 years) with newly diagnosed HF between 2011 and 2018. The proportion of those who received PCC within 5 years …

Proteomic Correlates And Prognostic Significance Of Kidney Injury In Heart Failure With Preserved Ejection Fraction, Oday Salman, Ali Javaheri, Douglas L Mann, Et Al.

2020-Current year OA Pubs

BACKGROUND: Kidney disease is common in heart failure with preserved ejection fraction (HFpEF). However, the biologic correlates and prognostic significance of kidney injury (KI), in HFpEF, beyond the estimated glomerular filtration rate (eGFR), are unclear.

METHODS AND RESULTS: Using baseline plasma samples from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, we measured the following KI biomarkers: cystatin-C, fatty acid-binding protein-3, Beta-2 microglobulin, neutrophil gelatinase-associated lipocalin, and kidney-injury molecule-1. Factor analysis was used to extract the common variability underlying these biomarkers. We assessed the relationship between the KI-factor score and the risk of death …

Concurrent Ependymal And Ganglionic Differentiation In A Subset Of Supratentorial Neuroepithelial Tumors With Ewsr1-Plagl1 Rearrangement, Julieann C Lee, Sonika Dahiya, Kaleigh Roberts, Et Al.

2020-Current year OA Pubs

Neuroepithelial tumors with fusion of PLAGL1 or amplification of PLAGL1/PLAGL2 have recently been described often with ependymoma-like or embryonal histology respectively. To further evaluate emerging entities with PLAG-family genetic alterations, the histologic, molecular, clinical, and imaging features are described for 8 clinical cases encountered at St. Jude (EWSR1-PLAGL1 fusion n = 6; PLAGL1 amplification n = 1; PLAGL2 amplification n = 1). A histologic feature observed on initial resection in a subset (4/6) of supratentorial neuroepithelial tumors with EWSR1-PLAGL1 rearrangement was the presence of concurrent ependymal and ganglionic differentiation. This ranged from prominent clusters of ganglion cells within ependymoma/subependymoma-like areas, …

Folate Metabolism And Risk Of Childhood Acute Lymphoblastic Leukemia: A Genetic Pathway Analysis From The Childhood Cancer And Leukemia International Consortium, Catherine Metayer, Logan G Spector, Michael E Scheurer, Soyoung Jeon, Rodney J Scott, Masatoshi Takagi, Jacqueline Clavel, Atsushi Manabe, Xiaomei Ma, Elleni M Hailu, Philip J Lupo, Kevin Y Urayama, Audrey Bonaventure, Motohiro Kato, Aline Meirhaeghe, Charleston W K Chiang, Libby M Morimoto, Joseph L Wiemels

Faculty, Staff and Students Publications

BACKGROUND: Prenatal folate supplementation has been consistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Previous germline genetic studies examining the one carbon (folate) metabolism pathway were limited in sample size, scope, and population diversity and led to inconclusive results.

METHODS: We evaluated whether ∼2,900 single-nucleotide polymorphisms (SNP) within 46 candidate genes involved in the folate metabolism pathway influence the risk of childhood ALL, using genome-wide data from nine case-control studies in the Childhood Cancer and Leukemia International Consortium (n = 9,058 cases including 4,510 children of European ancestry, 3,018 Latinx, and 1,406 Asians, and 92,364 controls). …

Exoskeletal-Assisted Walking In Veterans With Paralysis: A Randomized Clinical Trial, Ann M Spungen, Ellen J Dematt, Kousick Biswas, Karen M Jones, Zhibao Mi, Amanda J Snodgrass, Kel Morin, Pierre K Asselin, Christopher M Cirnigliaro, Steven Kirshblum, Peter H Gorman, Lance L Goetz, Katherine Stenson, Kevin T White, Alice Hon, Sunil Sabharwal, B Jenny Kiratli, Doug Ota, Bridget Bennett, Joseph E Berman, Denis Castillo, Kenneth K Lee, Byron W Eddy, M Kristi Henzel, Michelle Trbovich, Sally A Holmes, Felicia Skelton, Michael Priebe, Stephen L Kornfeld, Grant D Huang, William A Bauman

Faculty, Staff and Students Publications

IMPORTANCE: Robotic exoskeletons leverage technology that assists people with spinal cord injury (SCI) to walk. The efficacy of home and community exoskeletal use has not been studied in a randomized clinical trial (RCT).

OBJECTIVE: To examine whether use of a wheelchair plus an exoskeleton compared with use of only a wheelchair led to clinically meaningful net improvements in patient-reported outcomes for mental and physical health.

DESIGN, SETTING, AND PARTICIPANTS: This RCT of veterans with SCI was conducted at 15 Veterans Affairs medical centers in the US from September 6, 2016, to September 27, 2021. Data analysis was performed from March …

Socioeconomic And Urban-Rural Disparities In Genome-Matched Treatment Receipt And Survival After Genomic Tumor Testing., Jessica F Dibiase, Elizabeth Scharnetzki, Emily A Edelman, Kate Reed, Petra Helbig, Jens Rueter, Susan Miesfeldt, Cara L Frankenfeld, Paul K J Han, Elizabeth A Jacobs, Eric C Anderson, Maine Cancer Genomics Initiative Working Group

Faculty Research 2024

BACKGROUND: Emerging cancer treatments are often most available to socially advantaged individuals. This study examines the relationship of patient educational attainment, income level, and rurality to the receipt of genome-matched treatment and overall survival.

METHODS: Survey and clinical data were collected from patients with cancer (n = 1258) enrolled in the Maine Cancer Genomics Initiative. Logistic regression models examined whether receipt of genome-matched treatment differed by patient education, income, and rurality. Kaplan-Meier curves and Cox regression were conducted to evaluate 12-month mortality. We completed additional exploratory analyses using Kaplan-Meier curves and Cox models stratified by receipt of genome-matched treatment. Logistic …

Setrusumab For The Treatment Of Osteogenesis Imperfecta: 12-Month Results From The Phase 2b Asteroid Study, Francis H Glorieux, Bente Langdahl, Roland Chapurlat, Suzanne Jan De Beur, Vernon Reid Sutton, Kenneth E S Poole, Kathryn M Dahir, Eric S Orwoll, Bettina M Willie, Nicholas Mikolajewicz, Elizabeth Zimmermann, Seyedmahdi Hosseinitabatabaei, Michael S Ominsky, Chris Saville, James Clancy, Alastair Mackinnon, Arun Mistry, Muhammad K Javaid

Faculty, Staff and Students Publications

Osteogenesis imperfecta (OI) is a rare genetic disorder commonly caused by variants of the type I collagen genes COL1A1 and COL1A2. OI is associated with increased bone fragility, bone deformities, bone pain, and reduced growth. Setrusumab, a neutralizing antibody to sclerostin, increased areal bone mineral density (aBMD) in a 21-week phase 2a dose escalation study. The phase 2b Asteroid (NCT03118570) study evaluated the efficacy and safety of setrusumab in adults. Adults with a clinical diagnosis of OI type I, III, or IV, a pathogenic variant in COL1A1/A2, and a recent fragility fracture were randomized 1:1:1:1 to receive 2, 8, or …

Skin Tone Discrimination And Birth Control Avoidance Among Women In Harris County, Texas: A Cross-Sectional Study, Kimberly Baker, Susan Tortolero Emery, Evelyn Spike, Jazmyne Sutton, Eran Ben-Porath

Faculty, Staff and Student Publications

INTRODUCTION: Structural racism plays a major role in reproductive health inequities. Colorism, discrimination based on skin color, may profoundly impact reproductive health access and service delivery. However, quantitative research in this area is limited.

METHODS: We administered an online survey of women (n = 1,299) aged 18-44 from Harris County, Texas to assess the relationship between skin color discrimination and reproductive health service avoidance. The survey included questions on demographics, self-reported skin tone, and dichotomous measures of previous discrimination experiences and avoidance of care because of perceived discrimination. Binary logistic regression was used to examine whether race/ethnicity, skin tone, and …

Glycemic Control In Diabetic Patients Improved Overall Lung Cancer Survival Across Diverse Populations, Wayne Y Wu, Brian Luke, Xiao-Cheng Wu, J Jack Lee, Yong Yi, Samuel C Okpechi, Barry Gause, Paras Mehta, Steven I Sherman, Augusto Ochoa, Ethan Dmitrovsky, Xi Liu

Faculty, Staff and Student Publications

Background: The consequence of diabetes on lung cancer overall survival (OS) is debated. This retrospective study used 2 large lung cancer databases to assess comprehensively diabetes effects on lung cancer OS in diverse demographic populations, including health disparity.

Methods: The University of Texas MD Anderson Cancer Center database (32 643 lung cancer patients with 11 973 patients with diabetes) was extracted from electronic health records (EHRs) using natural language processing (NLP). Associations were between diabetes and lung cancer prognostic features (age, sex, race, body mass index [BMI], insurance status, smoking, stage, and histopathology). Hemoglobin A1C (HgbA1c) and glucose levels assessed …

Fetal Mavs And Type I Ifn Signaling Pathways Control Zikv Infection In The Placenta And Maternal Decidua, Yael Alippe, Leran Wang, Reyan Coskun, Stéfanie P Muraro, Fang R Zhao, Michelle Elam-Noll, J Michael White, Daiana M Vota, Vanesa C Hauk, Jeffrey I Gordon, Scott A Handley, Michael S Diamond

2020-Current year OA Pubs

The contribution of placental immune responses to congenital Zika virus (ZIKV) syndrome remains poorly understood. Here, we leveraged a mouse model of ZIKV infection to identify mechanisms of innate immune restriction exclusively in the fetal compartment of the placenta. ZIKV principally infected mononuclear trophoblasts in the junctional zone, which was limited by mitochondrial antiviral-signaling protein (MAVS) and type I interferon (IFN) signaling mechanisms. Single nuclear RNA sequencing revealed MAVS-dependent expression of IFN-stimulated genes (ISGs) in spongiotrophoblasts but not in other placental cells that use alternate pathways to induce ISGs. ZIKV infection of Ifnar1-/- or Mavs-/- placentas was associated with greater …

Analysis Of Ductal Carcinoma In Situ By Self-Reported Race Reveals Molecular Differences Related To Outcome, Siri H Strand, Graham A Colditz, Et Al.

2020-Current year OA Pubs

BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive breast cancer (IBC). Studies have indicated differences in DCIS outcome based on race or ethnicity, but molecular differences have not been investigated.

METHODS: We examined the molecular profile of DCIS by self-reported race (SRR) and outcome groups in Black (n = 99) and White (n = 191) women in a large DCIS case-control cohort study with longitudinal follow up.

RESULTS: Gene expression and pathway analyses suggested that different genes and pathways are involved in diagnosis and ipsilateral breast outcome (DCIS or IBC) after DCIS treatment in White versus …

Factors Associated With Recanalization And Reintervention Following Below Knee Polidocanol Endovenous Microfoam Ablation For Great Saphenous And Small Saphenous Veins, John Fang, Christian Fang, Andy Moyal, Enrico Ascher, Anil Hingorani, Natalie Marks

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Polidocanol endovenous microfoam (PEM) has been used to treat lower extremity venous reflux for almost one decade with specific advantages for below knee (BK) truncal veins where thermal ablation poses a risk of injury to adjacent nerves. The current literature of the BK segment often examines short-term outcomes with modest sample sizes. We aim to identify factors associated with recanalization and reintervention in this subset of patients.

METHODS: We performed a retrospective study of a prospectively maintained database of patients from a single institution who underwent 1% PEM ablation for BK great saphenous vein (GSV) and small saphenous vein …

Proactive Psychiatry: Innovating The Delivery Of Consultation-Liaison Services In A Pediatric Hospital, Elizabeth Schindler, Katherine Winner, Ramzi W. Nahhas, Gianni Maione, Aisha Jamison, Kelly Blankenship

Population and Public Health Sciences Faculty Publications

Background: The benefits of a proactive consultation-liaison psychiatry service have been well documented in the adult population, including decreased length of stay (LOS), increased satisfaction among physicians, and enhanced collaborative care. However, there is no available research on the effectiveness of this model in pediatric hospitals. Objective: This study compared patients aged 5–18 years on a general medical floor receiving a proactive psychiatry consult to concurrent controls receiving no consult and to historical controls receiving traditional reactive consults. Methods: New admissions to two pediatric general medical hospital teams were reviewed on weekday mornings to identify those with active psychiatric concerns. …

Trifarotene Alleviates Skin Photoaging Injury By Inhibition Of Jnk/C-Jun/Mmps, Xuan Fei, Lele Zixin Yang, Jingjing Zhang, Xiang Li, Mengtian Pan, Guangchen Xu, Cuixia Zhang, Fei Liu, Weirong Fang

Student Papers, Posters & Projects

Long-term exposure to ultraviolet (UV) radiation induces skin photoaging, which manifests as oxidative stress, inflammation, and collagen degradation. Multiple approaches (topical or systemic retinoids, antioxidants, alpha-hydroxy acids, laser, surgery) are used in the treatment of photoaged skin, and the use of topical retinoids is currently a primary clinical treatment. Previous studies revealed that retinoic acid promotes keratinocyte proliferation and reduces melanin deposition and matrix metalloproteinase (MMP) secretion; it also causes potential allergic and inflammatory damage to the skin. This study aimed to investigate the therapeutic effects and mechanisms of trifarotene, a functional retinoic acid analog, on UV-irradiated photoaging ICR and …

Toward Reliable Symptom Coding In Electronic Health Records For Symptom Assessment And Research: Identification And Categorization Of International Classification Of Diseases, Ninth Revision, Clinical Modification Symptom Codes, Tru Cao, Veronica Brady, Meagan Whisenant, Xueying Wang, Yuxuan Gu, Hulin Wu

Faculty, Staff and Student Publications

To date, symptom documentation has mostly relied on clinical notes in electronic health records or patient-reported outcomes using disease-specific symptom inventories. To provide a common and precise language for symptom recording, assessment, and research, a comprehensive list of symptom codes is needed. The International Classification of Diseases, Ninth Revision or its clinical modification ( International Classification of Diseases, Ninth Revision, Clinical Modification ) has a range of codes designated for symptoms, but it does not contain codes for all possible symptoms, and not all codes in that range are symptom related. This study aimed to identify and categorize the first …

Low-Acuity Pediatric Emergency Department Utilization, Lisa Ziemnik, Noah Parker, Kyra Bufi, Kristen Waters, Jacob Almeda, Adrienne Stolfi

Medical Education Faculty Publications

Objectives: Proper emergency department (ED) utilization is a hallmark of population health. Emergency department overcrowding due to nonurgent visits causes increased stress to healthcare staff, higher costs, and longer wait times for more urgent cases. This study sought to better understand post pandemic reasons caregivers have when bringing in their children for nonurgent visits and devise effective interventions to improve caregiver choice for non-ED care for nonurgent conditions.

Methods: Surveys were conducted at an urban pediatric hospital for Emergency Severity Index (ESI) level 3 to 5 visits. A total of 602 surveys were completed with 8 being excluded from analysis. …

Targeting Undruggable Phosphatase Overcomes Trastuzumab Resistance By Inhibiting Multi-Oncogenic Kinases., Lu Wang, Yusheng Lin, Zhimeng Yao, Nipun Babu, Wan Lin, Chaoying Chen, Liang Du, Songwang Cai, Yunlong Pan, Xiao Xiong, Qiantao Ye, Hongzheng Ren, Dianzheng Zhang, Yexi Chen, Sai-Ching Jim Yeung, Edwin Bremer, Hao Zhang

PCOM Scholarly Works

AIMS: Resistance to targeted therapy is one of the critical obstacles in cancer management. Resistance to trastuzumab frequently develops in the treatment for HER2

METHODS: Four public datasets were used to screen PTP candidates in relation to trastuzumab responsiveness in HER2

RESULTS: PTPRO was identified as the key PTP which influences trastuzumab responsiveness and patient survival. PTPRO de-phosphorated several TKs, including the previously overlooked substrate ERBB3, thereby inhibiting multiple oncogenic pathways associated with drug resistance. Notably, PTPRO, previously deemed "undruggable," was effectively upregulated by saRNA-loaded nanoparticles. The upregulated PTPRO simultaneously inhibited ERBB3, ERBB2, and downstream SRC signaling pathways, thereby counteracting …

Systematically Assessing The Quality Of Dental Electronic Health Record Data For An Investigation Into Oral Health Care Disparities, Krishna Kumar Kookal, Muhammad F Walji, Ryan Brandon, Ferit Kivanc, Elizabeth Mertz, Aubri Kottek, Joanna Mullins, Shuang Liang, Larry E Jenson, Joel M White

Faculty, Staff and Student Publications

Objectives: This work describes the process by which the quality of electronic health care data for a public health study was determined. The objectives were to adapt, develop, and implement data quality assessments (DQAs) based on the National Institutes of Health Pragmatic Trials Collaboratory (NIHPTC) data quality framework within the three domains of completeness, accuracy, and consistency, for an investigation into oral health care disparities of a preventive care program.

Methods: Electronic health record data for eligible children in a dental accountable care organization of 30 offices, in Oregon, were extracted iteratively from January 1, 2014, through March 31, 2022. …

Early Therapeutic Drug Monitoring Of Methotrexate And Its Association With Acute Kidney Injury: A Retrospective Cohort Study., Nicolás Tentoni, Miriam Hwang, Gabriela Villanueva, Ryan Combs, Jennifer Lowe, Laura Ramsey, Zachary L. Taylor, Thais Murciano Carrillo, María Dolores Aumente, Teresa López-Viñau López, Carmelo Rizzari, Scott C. Howard

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: High-dose methotrexate (HDMTX) use can be limited by the development of acute kidney injury (AKI). Early AKI detection is paramount to prevent further renal injury and irreversible toxicities. This study sought to determine whether early elimination patterns of MTX would be useful as a biomarker of AKI in HDMTX treatment.

METHODS: This retrospective cohort study included two sites that collected ≥2 MTX levels within 16 h from completion of MTX infusion. Early levels were tagged and MTX elimination half-life (t_½) were calculated from combinations of two of three different early time periods. Receiver operating characteristic (ROC) curves …

Utilization Of Geospatial Distribution In The Measurement Of Study Cohort Representativeness., Keith Feldman, Natalie J. Kane, Stacey Daniels-Young, Bruce Reed, Jessica Welch, Lauren Fitzpatrick, Mark A. Hoffman, Andrea Bradley-Ewing, Elin Grundberg

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: The ability to apply results from a study to a broader population remains a primary objective in translational science. Distinct from intrinsic elements of scientific rigor, the extrinsic concept of generalization requires there be alignment between a study cohort and population in which results are expected to be applied. Widespread efforts have been made to quantify representativeness of study cohorts. These techniques, however, often consider the study and target cohorts as monolithic collections that can be directly compared. Overlooking known impacts to health from socio-demographic and environmental factors tied to individual's geographical location, and potentially obfuscating misalignment in underrepresented …

Utilization Of Blood Flow Restriction Therapy With A Former Triathlete After Total Knee Arthroplasty: A Case Report, Christopher Keating, Stephanie Muth, Pt, Phd, Cameron Hui, Lisa T. Hoglund

Department of Physical Therapy Faculty Papers

INTRODUCTION AND PURPOSE: Knee osteoarthritis (OA) is a common condition that limits function and reduces quality of life. Total knee arthroplasty (TKA) is a surgical procedure that replaces the joint surfaces to address anatomical changes due to knee OA. While TKA improves symptoms and function, postoperative impairments are common, including reduced quadriceps strength. Blood flow restriction (BFR) may be a viable option for patients following TKA, as it can improve strength with a minimal amount of joint loading compared to traditional strength training. The purpose of this case report is to describe the impact of BFR use in an individual …

Ataxia Telangiectasia And Rad3-Related (Atr) Inhibitor Camonsertib Dose Optimization In Patients With Biomarker-Selected Advanced Solid Tumors (Tresr Study), Elisa Fontana, Ezra Rosen, Elizabeth K Lee, Martin Højgaard, Niharika B Mettu, Stephanie Lheureux, Benedito A Carneiro, Gregory M Cote, Louise Carter, Ruth Plummer, Devalingam Mahalingam, Adrian J Fretland, Joseph D Schonhoft, Ian M Silverman, Marisa Wainszelbaum, Yi Xu, Danielle Ulanet, Maria Koehler, Timothy A Yap

Faculty, Staff and Student Publications

BACKGROUND: Camonsertib is a selective oral inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase with demonstrated efficacy in tumors with DNA damage response gene deficiencies. On-target anemia is the main drug-related toxicity typically manifesting after the period of dose-limiting toxicity evaluation. Thus, dose and schedule optimization requires extended follow-up to assess prolonged treatment effects.

METHODS: Long-term safety, tolerability, and antitumor efficacy of 3 camonsertib monotherapy dosing regimens were assessed in the TRESR study dose-optimization phase: 160 mg once daily (QD) 3 days on, 4 days off (160 3/4; the preliminary recommended Phase II dose [RP2D]) and two step-down groups of …

Target Engagement And Immunogenicity Of An Active Immunotherapeutic Targeting Pathological Α-Synuclein: A Phase 1 Placebo-Controlled Trial, Pepijn Eijsvogel, Pinaki Misra, Luis Concha-Marambio, Justin D Boyd, Shuang Ding, Lauren Fedor, Yueh-Ting Hsieh, Yu Shuang Sun, Madeline M Vroom, Carly M Farris, Yihua Ma, Marieke L De Kam, Igor Radanovic, Maurits F J M Vissers, Dario Mirski, Ghazal Shareghi, Mohammad Shahnawaz, Wolfgang Singer, Philip Kremer, Geert Jan Groeneveld, Hui Jing Yu, Jean-Cosme Dodart

Faculty, Staff and Student Publications

Investigational therapeutics that target toxic species of α-synuclein (αSyn) aim to slow down or halt disease progression in patients with Parkinson's disease (PD). Here this 44-week, randomized, placebo-controlled, double-blind, single-center phase 1 study investigated safety, tolerability and immunogenicity of UB-312, an active immunotherapeutic targeting pathological αSyn, in patients with PD. The primary outcome measures were adverse event frequency and change in anti-αSyn antibody titers in blood and cerebrospinal fluid (CSF). Exploratory outcomes were changes in clinical scales and biomarker-based target engagement as measured by seed amplification assays. Twenty patients were randomized 7:3 (UB-312:placebo) into 300/100/100 μg or 300/300/300 μg (weeks …

Automatic Vessel Attenuation Measurement For Quality Control Of Contrast-Enhanced Ct: Validation On The Portal Vein, Kevin Mccoy, Sujay Marisetty, Dominique Tan, Corey T Jensen, Jeffrey H Siewerdsen, Christine B Peterson, Moiz Ahmad

Faculty, Staff and Student Publications

Background: Adequate image enhancement of organs and blood vessels of interest is an important aspect of image quality in contrast-enhanced computed tomography (CT). There is a need for an objective method for evaluation of vessel contrast that can be automatically and systematically applied to large sets of CT exams.

Purpose: The purpose of this work was to develop a method to automatically segment and measure attenuation Hounsfield Unit (HU) in the portal vein (PV) in contrast-enhanced abdomen CT examinations.

Methods: Input CT images were processed by a vessel enhancing filter to determine candidate PV segmentations. Multiple machine learning (ML) classifiers …

Artificial Intelligence-Based Segmentation Of Residual Pancreatic Cancer In Resection Specimens Following Neoadjuvant Treatment (Isgpp-2): International Improvement And Validation Study, Boris V Janssen, Bart Oteman, Mahsoem Ali, Pieter A Valkema, Volkan Adsay, Olca Basturk, Deyali Chatterjee, Angela Chou, Stijn Crobach, Michael Doukas, Paul Drillenburg, Irene Esposito, Anthony J Gill, Seung-Mo Hong, Casper Jansen, Mike Kliffen, Anubhav Mittal, Jas Samra, Marie-Louise F Van Velthuysen, Aslihan Yavas, Geert Kazemier, Joanne Verheij, Ewout Steyerberg, Marc G Besselink, Huamin Wang, Caroline Verbeke, Arantza Fariña, Onno J De Boer, Pancreatobiliary And Hepatic Artificial Intelligence Research (Phair) Consortium, International Study Group Of Pancreatic Pathologists (Isgpp);

Faculty, Staff and Student Publications

Neoadjuvant therapy (NAT) has become routine in patients with borderline resectable pancreatic cancer. Pathologists examine pancreatic cancer resection specimens to evaluate the effect of NAT. However, an automated scoring system to objectively quantify residual pancreatic cancer (RPC) is currently lacking. Herein, we developed and validated the first automated segmentation model using artificial intelligence techniques to objectively quantify RPC. Digitized histopathological tissue slides were included from resected pancreatic cancer specimens from 14 centers in 7 countries in Europe, North America, Australia, and Asia. Four different scanner types were used: Philips (56%), Hamamatsu (27%), 3DHistech (10%), and Leica (7%). Regions of interest …

A Pilot Study Of The Cd38 Antagonist Daratumumab In Patients With Metastatic Renal Cell Carcinoma Or Muscle-Invasive Bladder Cancer, Matthew T Campbell, Amishi Y Shah, Pavlos Msaouel, Nizar M Tannir, Arlene O Siefker-Radtke, Ashish M Kamat, Neema Navai, Colin P N Dinney, Priya Rao, Charles C Guo, Rahul A Sheth, Aradhana M Venkatesan, Rebecca S Tidwell, Shalini S Yadav, Aidi Gu, Hong Chen, Marc Macaluso, Fei Duan, Sreyashi Basu, Sonali Jindal, Padmanee Sharma

Faculty, Staff and Student Publications

PURPOSE: We performed a pilot study of daratumumab (an mAb directed against CD38) in muscle-invasive bladder cancer (MIBC) and treatment-refractory metastatic renal cell carcinoma (mRCC).

EXPERIMENTAL DESIGN: Patients with MIBC underwent baseline transurethral resection of the bladder tumor followed by four weekly doses of daratumumab prior to cystectomy. Patients with mRCC underwent baseline and sequential biopsies after eight weekly doses. The primary endpoint was safety. The secondary endpoints were pathologic complete response rate for the MIBC cohort and objective response rate and progression-free survival for the mRCC cohort. Exploratory analyses included immune monitoring and overall survival. A Bayesian sequential monitoring …

Mechanisms That Clear Mutations Drive Field Cancerization In Mammary Tissue, Marta Ciwinska, Hendrik A Messal, Hristina R Hristova, Catrin Lutz, Laura Bornes, Theofilos Chalkiadakis, Rolf Harkes, Nathalia S M Langedijk, Stefan J Hutten, Renée X Menezes, Jos Jonkers, Stefan Prekovic, Grand Challenge Precision Consortium, Benjamin D Simons, Colinda L G J Scheele, Jacco Van Rheenen

Faculty, Staff and Student Publications

Oncogenic mutations are abundant in the tissues of healthy individuals, but rarely form tumours1-3. Yet, the underlying protection mechanisms are largely unknown. To resolve these mechanisms in mouse mammary tissue, we use lineage tracing to map the fate of wild-type and Brca1-/-;Trp53-/- cells, and find that both follow a similar pattern of loss and spread within ducts. Clonal analysis reveals that ducts consist of small repetitive units of self-renewing cells that give rise to short-lived descendants. This offers a first layer of protection as any descendants, including oncogenic mutant cells, are constantly lost, thereby limiting the spread of mutations to …

Admixture Mapping Of Cognitive Function In Diverse Hispanic And Latino Adults: Results From The Hispanic Community Health Study/Study Of Latinos, Rui Xia, Xueqiu Jian, Amanda L Rodrigue, Jan Bressler, Eric Boerwinkle, Biqi Cui, Martha L Daviglus, Charles Decarli, Linda C Gallo, David C Glahn, Emma E M Knowles, Jee-Young Moon, Thomas H Mosley, Claudia L Satizabal, Tamar Sofer, Wassim Tarraf, Fernando Testai, John Blangero, Sudha Seshadri, Hector M González, Myriam Fornage

Faculty, Staff and Student Publications

INTRODUCTION: We conducted admixture mapping and fine-mapping analyses to identify ancestry-of-origin loci influencing cognitive abilities.

METHODS: We estimated the association of local ancestry intervals across the genome with five neurocognitive measures in 7140 diverse Hispanic and Latino adults (mean age 55 years). We prioritized genetic variants in associated loci and tested them for replication in four independent cohorts.

RESULTS: We identified nine local ancestry-associated regions for the five neurocognitive measures. There was strong biological support for the observed associations to cognitive function at all loci and there was statistical evidence of independent replication at 4q12, 9p22.1, and 13q12.13.

DISCUSSION: Our …