Medicine and Health Sciences Commons^™

High Throughput Single Cell Long-Read Sequencing Analyses Of Same-Cell Genotypes And Phenotypes In Human Tumors, Cheng-Kai Shiau, Lina Lu, Rachel Kieser, Kazutaka Fukumura, Timothy Pan, Hsiao-Yun Lin, Jie Yang, Eric L Tong, Gahyun Lee, Yuanqing Yan, Jason T Huse, Ruli Gao

Faculty, Staff and Student Publications

Single-cell nanopore sequencing of full-length mRNAs transforms single-cell multi-omics studies. However, challenges include high sequencing errors and dependence on short-reads and/or barcode whitelists. To address these, we develop scNanoGPS to calculate same-cell genotypes (mutations) and phenotypes (gene/isoform expressions) without short-read nor whitelist guidance. We apply scNanoGPS onto 23,587 long-read transcriptomes from 4 tumors and 2 cell-lines. Standalone, scNanoGPS deconvolutes error-prone long-reads into single-cells and single-molecules, and simultaneously accesses both phenotypes and genotypes of individual cells. Our analyses reveal that tumor and stroma/immune cells express distinct combination of isoforms (DCIs). In a kidney tumor, we identify 924 DCI genes involved in …

A Global Study For Acute Myeloid Leukemia With Rarg Rearrangement, Hong-Hu Zhu, Ya-Zhen Qin, Zhang-Lin Zhang, Yong-Jing Liu, Li-Jun Wen, M James You, Cheng Zhang, Esperanza Such, Hong Luo, Hong-Jian Yuan, Hong-Sheng Zhou, Hong-Xing Liu, Reng Xu, Ji Li, Jian-Hu Li, Jian-Ping Hao, Jie Jin, Liang Yu, Jing-Ying Zhang, Li-Ping Liu, Le-Ping Zhang, Rui-Bin Huang, Shu-Hong Shen, Su-Jun Gao, Wei Wang, Xiao-Jing Yan, Xin-You Zhang, Xin Du, Xiao-Xia Chu, Yan-Fang Yu, Yi Wang, Ying-Chang Mi, Ying Lu, Zhen Cai, Zhan Su, David Christopher Taussig, Suzanne Macmahon, Edward D Ball, Huan-You Wang, John S Welch, C Cameron Yin, Gautam Borthakur, Miguel A Sanz, Hagop M Kantarjian, Jin-Yan Huang, Jiong Hu, Su-Ning Chen

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and …

A Global Study For Acute Myeloid Leukemia With Rarg Rearrangement, Hong-Hu Zhu, John S Welch, Et Al.

2020-Current year OA Pubs

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and …

Building Capacity Of Community Nurses To Strengthen The Management Of Uncomplicated Hypertension In Persons Living With Hiv In Low- And Middle-Income Countries, Dike Ojji, Daphne Lew, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Poor training of non-physician healthcare workers (especially community nurses) could hinder the successful integration of cardiovascular disease (CVD) management into HIV chronic care in primary healthcare facilities in low- and middle-income countries. To address this limitation, we included a holistic training programme with a robust module for both practice facilitators and community nurses as part of the formative stages of the managing hypertension among people living with HIV: an integrated model (MAP-IT), which is a study that is evaluating the effectiveness of practice facilitation on the integration of a task-strengthening strategy for hypertension control (TASSH) into primary healthcare centres …

Randomized, Double-Blinded, Placebo-Controlled Trial Of Allogeneic Cord Blood T-Regulatory Cells For Treatment Of Covid-19 Ards, Douglas E Gladstone, Franco D'Alessio, Christopher Howard, Mi-Ae Lyu, Jason R Mock, Kevin W Gibbs, Darryl Abrams, Meixian Huang, Ke Zeng, James P Herlihy, Sergio T Castillo, Roland Bassett, Tara Sadeghi, Simrit Parmar, Christopher R Flowers, Siddhartha Mukherjee, David Schoenfeld, Peter F Thall, Arthur S Slutsky

Faculty, Staff and Students Publications

No abstract provided.

The Medical Institutional Repositories In Libraries (Mirl) Symposium: A Blueprint Designed In Response To A Community Of Practice Need., Brenda Fay, Lisa M Buda, Anthony J Dellureficio, Sara Hoover, Ramune K Kubilius, Steven J Moore, Lisa A Palmer

Himmelfarb Library Faculty Publications

BACKGROUND: Health sciences libraries in medical schools, academic health centers, health care networks, and hospitals have established institutional repositories (IRs) to showcase their research achievements, increase visibility, expand the reach of institutional scholarship, and disseminate unique content. Newer roles for IRs include publishing open access journals, tracking researcher productivity, and serving as repositories for data sharing. Many repository managers oversee their IR with limited assistance from others at their institution. Therefore, IR practitioners find it valuable to network and learn from colleagues at other institutions.

CASE PRESENTATION: This case report describes the genesis and implementation of a new initiative specifically …

Real-Time Environmental Surveillance Of Sars-Cov-2 Aerosols, Joseph V Puthussery, Kevin R Mcbrearty, Brookelyn M Doherty, Woodrow D Gardiner, Jordan P Magrecki, Traci L Bricker, Adrianus C M Boon, Carla M Yuede, John R Cirrito, Et Al.

2020-Current year OA Pubs

Real-time surveillance of airborne SARS-CoV-2 virus is a technological gap that has eluded the scientific community since the beginning of the COVID-19 pandemic. Offline air sampling techniques for SARS-CoV-2 detection suffer from longer turnaround times and require skilled labor. Here, we present a proof-of-concept pathogen Air Quality (pAQ) monitor for real-time (5 min time resolution) direct detection of SARS-CoV-2 aerosols. The system synergistically integrates a high flow (~1000 lpm) wet cyclone air sampler and a nanobody-based ultrasensitive micro-immunoelectrode biosensor. The wet cyclone showed comparable or better virus sampling performance than commercially available samplers. Laboratory experiments demonstrate a device sensitivity of …

Developing A National-Scale Exposure Index For Combined Environmental Hazards And Social Stressors And Applications To The Environmental Influences On Child Health Outcomes (Echo) Cohort., Sheena E. Martenies, Mingyu Zhang, Anne E. Corrigan, Anton Kvit, Timothy Shields, William Wheaton, Deana Around Him, Judy Aschner, Maria M. Talavera-Barber, Emily S. Barrett, Theresa M. Bastain, Casper Bendixsen, Carrie V. Breton, Nicole R. Bush, Ferdinand Cacho, Carlos A. Camargo, Kecia N. Carroll, Brian S. Carter, Andrea E. Cassidy-Bushrow, Whitney Cowell, Lisa A. Croen, Dana Dabelea, Cristiane S. Duarte, Anne L. Dunlop, Todd M. Everson, Rima Habre, Tina V. Hartert, Jennifer B. Helderman, Alison E. Hipwell, Margaret R. Karagas, Barry M. Lester, Kaja Z. Lewinn, Sheryl Magzamen, Rachel Morello-Frosch, Thomas G. O'Connor, Amy M. Padula, Michael Petriello, Sheela Sathyanarayana, Joseph B. Stanford, Tracey J. Woodruff, Rosalind J. Wright, Amii M. Kress, Program Collaborators For Environmental Influences On Child Health Outcomes

Manuscripts, Articles, Book Chapters and Other Papers

Tools for assessing multiple exposures across several domains (e.g., physical, chemical, and social) are of growing importance in social and environmental epidemiology because of their value in uncovering disparities and their impact on health outcomes. Here we describe work done within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study to build a combined exposure index. Our index considered both environmental hazards and social stressors simultaneously with national coverage for a 10-year period. Our goal was to build this index and demonstrate its utility for assessing differences in exposure for pregnancies enrolled in the ECHO-wide Cohort Study. Our unitless …

Propensity Score Analysis With Local Balance, Yan Li, Liang Li

Faculty, Staff and Student Publications

Most propensity score (PS) analysis methods rely on a correctly specified parametric PS model, which may result in biased estimation of the average treatment effect (ATE) when the model is misspecified. More flexible nonparametric models for treatment assignment alleviate this issue, but they do not always guarantee covariate balance. Methods that force balance in the means of covariates and their transformations between the treatment groups, termed global balance in this article, do not always lead to unbiased estimation of ATE. Their estimated propensity scores only ensure global balance but not the balancing property, which is defined as the conditional independence …

Accumulation Of Chronic Disease Among Survivors Of Childhood Cancer Predicts Early Mortality, Adam J Esbenshade, Lu Lu, Debra L Friedman, Kevin C Oeffinger, Gregory T Armstrong, Kevin R Krull, Joseph P Neglia, Wendy M Leisenring, Rebecca Howell, Robyn Partin, Amy Sketch, Leslie L Robison, Kirsten K Ness

Faculty, Staff and Student Publications

Purpose: Cancer survivors develop cancer and treatment-related morbidities at younger than normal ages and are at risk for early mortality, suggestive of an aging phenotype. The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) is specifically designed to describe the accumulation of comorbidities over time with estimates of severity such as total score (TS) which is a sum of possible conditions weighted by severity. These severity scores can then be used to predict future mortality.

Methods: CIRS-G scores were calculated in cancer survivors and their siblings from Childhood Cancer Survivor Study cohort members from two time points 19 years apart and …

Effect Of Reduced Versus Usual Lipid Emulsion Dosing On Bilirubin Neurotoxicity And Neurodevelopmental Impairment In Extremely Preterm Infants: Study Protocol For A Randomized Controlled Trial, Lindsay F Holzapfel, Cody Arnold, Jon E Tyson, Steven M Shapiro, Eric W Reynolds, Claudia Pedroza, Emily K Stephens, Alan Kleinfeld, Andrew H Huber, Matthew A Rysavy, Maria Del Mar Romero Lopez, Amir M Khan

Faculty, Staff and Student Publications

BACKGROUND: Bilirubin neurotoxicity (BN) occurs in premature infants at lower total serum bilirubin levels than term infants and causes neurodevelopmental impairment. Usual dose lipid infusions in preterm infants may increase free fatty acids sufficiently to cause bilirubin displacement from albumin, increasing passage of unbound bilirubin (UB) into the brain leading to BN and neurodevelopmental impairment not reliably identifiable in infancy. These risks may be influenced by whether cycled or continuous phototherapy is used to control bilirubin levels.

OBJECTIVE: To assess differences in wave V latency measured by brainstem auditory evoked responses (BAER) at 34-36 weeks gestational age in infants born …

Myc Regulates Csf1 Expression Via Microrna 17/20a To Modulate Tumor-Associated Macrophages In Osteosarcoma, Bikesh K Nirala, Tajhal D Patel, Lyazat Kurenbekova, Ryan Shuck, Atreyi Dasgupta, Nino Rainusso, Cristian Coarfa, Jason T Yustein

Faculty, Staff and Students Publications

Osteosarcoma (OS) is the most common primary bone tumor of childhood. Approximately 20%-30% of OSs carry amplification of chromosome 8q24, which harbors the oncogene c-MYC and correlates with a poor prognosis. To understand the mechanisms that underlie the ability of MYC to alter both the tumor and its surrounding tumor microenvironment (TME), we generated and molecularly characterized an osteoblast-specific Cre-Lox-Stop-Lox-c-MycT58A p53fl/+ knockin genetically engineered mouse model (GEMM). Phenotypically, the Myc-knockin GEMM had rapid tumor development with a high incidence of metastasis. MYC-dependent gene signatures in our murine model demonstrated significant homology to the human hyperactivated MYC OS. We established that …

Differentials And Predictors Of Food Insecurity Among Federally Qualified Health Center Target Populations In Philadelphia: A Cross-Sectional Study, Galicano Kai Inguito, Brandon Joa, James Gardner, Eric N Fung, Laura Layer, Karen Fritz

Department of Medicine Faculty Papers

BACKGROUND: Over the past decade, the prevalence of food insecurity declined in the United States but curiously climbed in Philadelphia, Pennsylvania, a sizable metropolitan area where many households experience food insecurity and are dependent on programs like SNAP. Therefore, we aimed to determine the burden of food insecurity among populations near Philadelphia Federally Qualified Health Center (FQHC) clinic sites.

METHODS: This cross-sectional study was conducted in North Philadelphia, a populous and impoverished section of Philadelphia with many zip codes reporting 30-45% or more of the population below the federal poverty line. Students and clinicians affiliated with a local FQHC conducted …

Roving Methyltransferases Generate A Mosaic Epigenetic Landscape And Influence Evolution In Bacteroides Fragilis Group, Michael J Tisza, Derek D N Smith, Andrew E Clark, Jung-Ho Youn, Pavel P Khil, John P Dekker

Faculty, Staff and Students Publications

Three types of DNA methyl modifications have been detected in bacterial genomes, and mechanistic studies have demonstrated roles for DNA methylation in physiological functions ranging from phage defense to transcriptional control of virulence and host-pathogen interactions. Despite the ubiquity of methyltransferases and the immense variety of possible methylation patterns, epigenomic diversity remains unexplored for most bacterial species. Members of the Bacteroides fragilis group (BFG) reside in the human gastrointestinal tract as key players in symbiotic communities but also can establish anaerobic infections that are increasingly multi-drug resistant. In this work, we utilize long-read sequencing technologies to perform pangenomic (n = …

The Neutralization Of The Eosinophil Peroxidase Antibody Accelerates Eosinophilic Mucin Decomposition, Panagiotis Doukas, Jan Paul Frese, Thorsten Eierhoff, Gabriel Hellfritsch, Ben Raude, Michael J Jacobs, Andreas Greiner, Alexander Oberhuber, Alexander Gombert

Faculty, Staff and Student Publications

Acute kidney injury (AKI) is a common complication after complex aortic procedures and it is associated with relevant mortality and morbidity. Biomarkers for early and specific AKI detection are lacking. The aim of this work is to investigate the reliability of the NephroCheck bedside system for diagnosing stage 3 AKI following open aortic surgery. In this prospective, multicenter, observational study,- https://clinicaltrials.gov/ct2/show/NCT04087161 -we included 45 patients undergoing open thoracoabdominal aortic repair. AKI risk (AKIRisk-Index) was calculated from urine samples at 5 timepoints: baseline, immediately postoperatively and at 12, 24, 48, and 72 h post-surgery. AKIs were classified according to the KDIGO …

A Phase 1/2 Study Of Azacitidine, Venetoclax And Pevonedistat In Newly Diagnosed Secondary Aml And In Mds Or Cmml After Failure Of Hypomethylating Agents, Nicholas J Short, Muharrem Muftuoglu, Faustine Ong, Lewis Nasr, Walid Macaron, Guillermo Montalban-Bravo, Yesid Alvarado, Mahesh Basyal, Naval Daver, Courtney D Dinardo, Gautam Borthakur, Nitin Jain, Maro Ohanian, Elias Jabbour, Ghayas C Issa, Wei Qiao, Xuelin Huang, Rashmi Kanagal-Shamanna, Keyur P Patel, Prithviraj Bose, Farhad Ravandi, Ricardo Delumpa, Regina Abramova, Guillermo Garcia-Manero, Michael Andreeff, Jorge Cortes, Hagop Kantarjian

Faculty, Staff and Student Publications

BACKGROUND: Pevonedistat is a first-in-class, small molecular inhibitor of NEDD8-activating enzyme that has clinical activity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Preclinical data suggest synergy of pevonedistat with azacitidine and venetoclax.

METHODS: This single-center, phase 1/2 study evaluated the combination of azacitidine, venetoclax and pevonedistat in older adults with newly diagnosed secondary AML or with MDS or chronic myelomonocytic leukemia (CMML) after failure of hypomethylating agents. Patients received azacitidine 75 mg/m

FINDINGS: Forty patients were enrolled (32 with AML and 8 with MDS/CMML). In the AML cohort, the median age was 74 years (range 61-86 years), and …

Overactive Bladder Syndrome Symptoms In Youth With Abdominal Pain-Associated Disorders Of Gut-Brain Interaction., Hunter J. Friesen, Pierce Thompson, Jennifer Verrill Schurman, Jennifer Colombo, Craig A. Friesen

Manuscripts, Articles, Book Chapters and Other Papers

The purpose of the current study was to assess the frequency of overactive bladder syndrome (OBS) symptoms and their relationship to gastrointestinal symptoms in youth with abdominal pain-associated disorders of gut-brain interaction (AP-DGBI). This is a retrospective study of 226 youth diagnosed with an AP-DGBI. As part of standard care, all patients completed a symptom questionnaire regarding gastrointestinal and non-gastrointestinal symptoms including increased urinary frequency, nighttime urination, and urinary urgency. Overall, 54% of patients reported at least one OBS symptom. Increased frequency of urination was reported by 19%, urinary urgency by 34%, and nighttime urination by 36%. Increased frequency of …

A Phase 1/2 Study Of Azacitidine, Venetoclax And Pevonedistat In Newly Diagnosed Secondary Aml And In Mds Or Cmmlafter Failure Of Hypomethylating Agents, Nicholas J Short, Muharrem Muftuoglu, Faustine Ong, Lewis Nasr, Walid Macaron, Guillermo Montalban-Bravo, Yesid Alvarado, Mahesh Basyal, Naval Daver, Courtney D Dinardo, Gautam Borthakur, Nitin Jain, Maro Ohanian, Elias Jabbour, Ghayas C Issa, Wei Qiao, Xuelin Huang, Rashmi Kanagal-Shamanna, Keyur P Patel, Prithviraj Bose, Farhad Ravandi, Ricardo Delumpa, Regina Abramova, Guillermo Garcia-Manero, Michael Andreeff, Jorge Cortes, Hagop Kantarjian

Faculty, Staff and Student Publications

BACKGROUND: Pevonedistat is a first-in-class, small molecular inhibitor of NEDD8-activating enzyme that has clinical activity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Preclinical data suggest synergy of pevonedistat with azacitidine and venetoclax.

METHODS: This single-center, phase 1/2 study evaluated the combination of azacitidine, venetoclax and pevonedistat in older adults with newly diagnosed secondary AML or with MDS or chronic myelomonocytic leukemia (CMML) after failure of hypomethylating agents. Patients received azacitidine 75 mg/m

FINDINGS: Forty patients were enrolled (32 with AML and 8 with MDS/CMML). In the AML cohort, the median age was 74 years (range 61-86 years), and …

Self-Administered Intranasal Etripamil Using A Symptom-Prompted, Repeat-Dose Regimen For Atrioventricular-Nodal-Dependent Supraventricular Tachycardia (Rapid): A Multicentre, Randomised Trial, Bruce S Stambler, A John Camm, Marco Alings, Paul Dorian, Hein Heidbuchel, Jaco Houtgraaf, Peter R. Kowey, Jose L Merino, Blandine Mondésert, Jonathan P Piccini, Sean D Pokorney, Philip T Sager, Atul Verma, J Marcus Wharton, David B Bharucha, Francis Plat, Silvia Shardonofsky, Michael Chen, James E Ip

Department of Medicine Faculty Papers

BACKGROUND: Etripamil is a fast-acting, intranasally administered calcium-channel blocker in development for on-demand therapy outside a health-care setting for paroxysmal supraventricular tachycardia. We aimed to evaluate the efficacy and safety of etripamil 70 mg nasal spray using a symptom-prompted, repeat-dose regimen for acute conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm within 30 min.

METHODS: RAPID was a multicentre, randomised, placebo-controlled, event-driven trial, conducted at 160 sites in North America and Europe as part 2 of the NODE-301 study. Eligible patients were aged at least 18 years and had a history of paroxysmal supraventricular tachycardia with sustained, symptomatic episodes …

Measuring The Effect Of Newborn Screening On Survival After Haematopoietic Cell Transplantation For Severe Combined Immunodeficiency: A 36-Year Longitudinal Study From The Primary Immune Deficiency Treatment Consortium, Monica S Thakar, Brent R Logan, Jennifer M Puck, Elizabeth A Dunn, Rebecca H Buckley, Morton J Cowan, Richard J O'Reilly, Neena Kapoor, Lisa Forbes Satter, Sung-Yun Pai, Jennifer Heimall, Sharat Chandra, Christen L Ebens, Deepak Chellapandian, Olatundun Williams, Lauri M Burroughs, Blachy Davila Saldana, Ahmad Rayes, Lisa M Madden, Shanmuganathan Chandrakasan, Jeffrey J Bednarski, Kenneth B Desantes, Geoffrey D E Cuvelier, Pierre Teira, Alfred P Gillio, Hesham Eissa, Alan P Knutsen, Frederick D Goldman, Victor M Aquino, Evan B Shereck, Theodore B Moore, Emi H Caywood, Mark T Vander Lugt, Jacob Rozmus, Larisa Broglie, Lolie C Yu, Ami J Shah, Jeffrey R Andolina, Xuerong Liu, Roberta E Parrott, Jasmeen Dara, Susan Prockop, Caridad A Martinez, Malika Kapadia, Soma C Jyonouchi, Kathleen E Sullivan, Jack J Bleesing, Sonali Chaudhury, Aleksandra Petrovic, Michael D Keller, Troy C Quigg, Suhag Parikh, Shalini Shenoy, Christine Seroogy, Tamar Rubin, Hélène Decaluwe, John M Routes, Troy R Torgerson, Jennifer W Leiding, Michael A Pulsipher, Donald B Kohn, Linda M Griffith, Elie Haddad, Christopher C Dvorak, Luigi D Notarangelo

Faculty, Staff and Students Publications

Background: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18.

Methods: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18. Categorical variables were compared by χ2 test and continuous outcomes by …

Development Of A Covid-19 Vulnerability Index (Cvi) For The Counties And Residents Of New Jersey, Usa., Remo Disalvatore, Sarah K Bauer, Jeong Eun Ahn, Kauser Jahan

Henry M. Rowan College of Engineering Departmental Research

The coronavirus disease 2019, or COVID-19, has impacted countless aspects of everyday life since it was declared a global pandemic by the World Health Organization in March of 2020. From societal to economic impacts, COVID-19 and its variants will leave a lasting impact on our society and the world. During the height of the pandemic, it became increasingly evident that indices, such as the Center for Disease Control's (CDC) Social Vulnerability Index (SVI), were instrumental in predicting vulnerabilities within a community. The CDC's SVI provides important estimates on which communities will be more susceptible to 'hazard events' by compiling a …

Proportion Of Physicians Who Treat Patients With Greater Social And Clinical Risk And Physician Inclusion In Medicare Advantage Networks, Jung Ho Gong, Kenton J Johnston, David J Meyers

2020-Current year OA Pubs

IMPORTANCE: Medicare Advantage (MA) plans are expanding rapidly, now serving 50% of all Medicare enrollees. Little is known about how inclusion rates of physicians in MA plan networks vary by the social and clinical risks of their patients.

OBJECTIVE: To examine the association of physicians caring for patients with higher levels of social and clinical risk in traditional Medicare (TM) with the likelihood of inclusion in MA plan networks.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study evaluated the number of patients of physicians participating in TM Part B in 2019. The data analysis was conducted between June 2022 and March …

Opportunistic Detection Of Type 2 Diabetes Using Deep Learning From Frontal Chest Radiographs, Ayis Pyrros, Stephen M. Borstelmann, Ramana Mantravadi, Zachary Zaiman, Kaesha Thomas, Brandon Price, Eugene Greenstein, Nasir Siddiqui, Melinda Willis, Ihar Shulhan, John Hines-Shah, Jeanne M. Horowitz, Paul Nikolaidis, Matthew P. Lungren, Jorge Mario Rodríguez-Fernández, Judy Wawira Gichoya, Sanmi Koyejo, Adam E. Flanders, Nishith Khandwala, Amit Gupta, John W. Garrett, Joseph Paul Cohen, Brian T. Layden, Perry J. Pickhardt, William Galanter

Department of Radiology Faculty Papers

Deep learning (DL) models can harness electronic health records (EHRs) to predict diseases and extract radiologic findings for diagnosis. With ambulatory chest radiographs (CXRs) frequently ordered, we investigated detecting type 2 diabetes (T2D) by combining radiographic and EHR data using a DL model. Our model, developed from 271,065 CXRs and 160,244 patients, was tested on a prospective dataset of 9,943 CXRs. Here we show the model effectively detected T2D with a ROC AUC of 0.84 and a 16% prevalence. The algorithm flagged 1,381 cases (14%) as suspicious for T2D. External validation at a distinct institution yielded a ROC AUC of …

Comutations And Krasg12c Inhibitor Efficacy In Advanced Nsclc, Marcelo V Negrao, Haniel A Araujo, Giuseppe Lamberti, Alissa J Cooper, Neal S Akhave, Teng Zhou, Lukas Delasos, J Kevin Hicks, Mihaela Aldea, Gabriele Minuti, Jacobi Hines, Jacqueline V Aredo, Michael J Dennis, Turja Chakrabarti, Susan C Scott, Paolo Bironzo, Matthias Scheffler, Petros Christopoulos, Albrecht Stenzinger, Jonathan W Riess, So Yeon Kim, Sarah B Goldberg, Mingjia Li, Qi Wang, Yun Qing, Ying Ni, Minh Truong Do, Richard Lee, Biagio Ricciuti, Joao Victor Alessi, Jing Wang, Blerina Resuli, Lorenza Landi, Shu-Chi Tseng, Mizuki Nishino, Subba R Digumarthy, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, Ara A Vaporciyan, George R Blumenschein, Jianjun Zhang, Dwight H Owen, Collin M Blakely, Giannis Mountzios, Catherine A Shu, Christine M Bestvina, Marina Chiara Garassino, Kristen A Marrone, Jhanelle E Gray, Sandip Pravin Patel, Amy L Cummings, Heather A Wakelee, Juergen Wolf, Giorgio Vittorio Scagliotti, Federico Cappuzzo, Fabrice Barlesi, Pradnya D Patil, Leylah Drusbosky, Don L Gibbons, Funda Meric-Bernstam, J Jack Lee, John V Heymach, David S Hong, Rebecca S Heist, Mark M Awad, Ferdinandos Skoulidis

Faculty, Staff and Student Publications

Molecular modifiers of KRASG12C inhibitor (KRASG12Ci) efficacy in advanced KRASG12C-mutant NSCLC are poorly defined. In a large unbiased clinicogenomic analysis of 424 patients with non-small cell lung cancer (NSCLC), we identified and validated coalterations in KEAP1, SMARCA4, and CDKN2A as major independent determinants of inferior clinical outcomes with KRASG12Ci monotherapy. Collectively, comutations in these three tumor suppressor genes segregated patients into distinct prognostic subgroups and captured ∼50% of those with early disease progression (progression-free survival ≤3 months) with KRASG12Ci. Pathway-level integration of less prevalent coalterations in functionally related genes nominated PI3K/AKT/MTOR pathway and additional baseline RAS gene alterations, including amplifications, …

Mitophagy Promotes Resistance To Bh3 Mimetics In Acute Myeloid Leukemia, Christina Glytsou, Xufeng Chen, Emmanouil Zacharioudakis, Wafa Al-Santli, Hua Zhou, Bettina Nadorp, Soobeom Lee, Audrey Lasry, Zhengxi Sun, Dimitrios Papaioannou, Michael Cammer, Kun Wang, Tomasz Zal, Malgorzata Anna Zal, Bing Z Carter, Jo Ishizawa, Raoul Tibes, Aristotelis Tsirigos, Michael Andreeff, Evripidis Gavathiotis, Iannis Aifantis

Faculty, Staff and Student Publications

BH3 mimetics are used as an efficient strategy to induce cell death in several blood malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 antagonist, is used clinically in combination with hypomethylating agents for the treatment of AML. Moreover, MCL1 or dual BCL-2/BCL-xL antagonists are under investigation. Yet, resistance to single or combinatorial BH3-mimetic therapies eventually ensues. Integration of multiple genome-wide CRISPR/Cas9 screens revealed that loss of mitophagy modulators sensitizes AML cells to various BH3 mimetics targeting different BCL-2 family members. One such regulator is MFN2, whose protein levels positively correlate with drug resistance in patients with AML. MFN2 …

Using Predictive Validity To Compare Associations Between Brain Damage And Behavior, John F Magnotti, Jaclyn S Patterson, Tatiana T Schnur

Faculty, Staff and Student Publications

Lesion-behavior mapping (LBM) provides a statistical map of the association between voxel-wise brain damage and individual differences in behavior. To understand whether two behaviors are mediated by damage to distinct regions, researchers often compare LBM weight outputs by either the Overlap method or the Correlation method. However, these methods lack statistical criteria to determine whether two LBM are distinct versus the same and are disconnected from a major goal of LBMs: predicting behavior from brain damage. Without such criteria, researchers may draw conclusions from numeric differences between LBMs that are irrelevant to predicting behavior. We developed and validated a predictive …

The Relationship Between Changes In Neighborhood Physical Environment And Changes In Physical Activity Among Children: A Prospective Cohort Study, Francesco Acciai, Robin S Deweese, Kristen Lloyd, Michael J Yedidia, Michelle Kennedy, Katherine Isselmann Disantis, David Tulloch, Punam Ohri-Vachaspati

College of Population Health Faculty Papers

BACKGROUND: Physical activity (PA) is associated with positive health outcomes over the entire life course. Many community-based interventions that promote PA focus on implementing incremental changes to existing facilities and infrastructure. The objective of this study was to determine if such upgrades were associated with increases in children's PA.

METHODS: Two cohorts of 3- to 15-year-old children (n = 599) living in 4 low-income New Jersey cities were followed during 2- to 5-year periods from 2009 to 2017. Data on children's PA were collected at 2 time points (T1 and T2) from each cohort using telephone survey of parents; data …

Evaluating Approaches For Constructing Polygenic Risk Scores For Prostate Cancer In Men Of African And European Ancestry, Burcu F Darst, Jiayi Shen, Ravi K Madduri, Alexis A Rodriguez, Yukai Xiao, Xin Sheng, Edward J Saunders, Tokhir Dadaev, Mark N Brook, Thomas J Hoffmann, Kenneth Muir, Peggy Wan, Loic Le Marchand, Lynne Wilkens, Ying Wang, Johanna Schleutker, Robert J Macinnis, Cezary Cybulski, David E Neal, Børge G Nordestgaard, Sune F Nielsen, Jyotsna Batra, Judith A Clements, Australian Prostate Cancer Bioresource, Henrik Grönberg, Nora Pashayan, Ruth C Travis, Jong Y Park, Demetrius Albanes, Stephanie Weinstein, Lorelei A Mucci, David J Hunter, Kathryn L Penney, Catherine M Tangen, Robert J Hamilton, Marie-Élise Parent, Janet L Stanford, Stella Koutros, Alicja Wolk, Karina D Sørensen, William J Blot, Edward D Yeboah, James E Mensah, Yong-Jie Lu, Daniel J Schaid, Stephen N Thibodeau, Catharine M West, Christiane Maier, Adam S Kibel, Géraldine Cancel-Tassin, Florence Menegaux, Esther M John, Eli Marie Grindedal, Kay-Tee Khaw, Sue A Ingles, Ana Vega, Barry S Rosenstein, Manuel R Teixeira, Nc-La Pcap Investigators, Manolis Kogevinas, Lisa Cannon-Albright, Chad Huff, Luc Multigner, Radka Kaneva, Robin J Leach, Hermann Brenner, Ann W Hsing, Rick A Kittles, Adam B Murphy, Christopher J Logothetis, Susan L Neuhausen, William B Isaacs, Barbara Nemesure, Anselm J Hennis, John Carpten, Hardev Pandha, Kim De Ruyck, Jianfeng Xu, Azad Razack, Soo-Hwang Teo, Canary Pass Investigators, Lisa F Newcomb, Jay H Fowke, Christine Neslund-Dudas, Benjamin A Rybicki, Marija Gamulin, Nawaid Usmani, Frank Claessens, Manuela Gago-Dominguez, Jose Esteban Castelao, Paul A Townsend, Dana C Crawford, Gyorgy Petrovics, Graham Casey, Monique J Roobol, Jennifer F Hu, Sonja I Berndt, Stephen K Van Den Eeden, Douglas F Easton, Stephen J Chanock, Michael B Cook, Fredrik Wiklund, John S Witte, Rosalind A Eeles, Zsofia Kote-Jarai, Stephen Watya, John M Gaziano, Amy C Justice, David V Conti, Christopher A Haiman

Faculty, Staff and Student Publications

Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and …

Changes In Outcomes And Factors Associated With Survival In Melanoma Patients With Brain Metastases, Merve Hasanov, Denái R Milton, Alicia Bea Davies, Elizabeth Sirmans, Chantal Saberian, Eliza L Posada, Sylvia Opusunju, Jeffrey E Gershenwald, Carlos A Torres-Cabala, Elizabeth M Burton, Rivka R Colen, Jason T Huse, Isabella C Glitza Oliva, Caroline Chung, Mary Frances Mcaleer, Susan L Mcgovern, Debra N Yeboa, Betty Y S Kim, Sujit S Prabhu, Ian E Mccutcheon, Jeffrey S Weinberg, Frederick F Lang, Hussein A Tawbi, Jing Li, Lauren E Haydu, Michael A Davies, Sherise D Ferguson

Faculty, Staff and Student Publications

BACKGROUND: Treatment options for patients with melanoma brain metastasis (MBM) have changed significantly in the last decade. Few studies have evaluated changes in outcomes and factors associated with survival in MBM patients over time. The aim of this study is to evaluate changes in clinical features and overall survival (OS) for MBM patients.

METHODS: Patients diagnosed with MBMs from 1/1/2009 to 12/31/2013 (Prior Era; PE) and 1/1/2014 to 12/31/2018 (Current Era; CE) at The University of Texas MD Anderson Cancer Center were included in this retrospective analysis. The primary outcome measure was OS. Log-rank test assessed differences between groups; multivariable …

Targeting Gbm With An Oncolytic Picornavirus Svv-001 Alone And In Combination With Fractionated Radiation In A Novel Panel Of Orthotopic Pdx Models, Huiyuan Zhang, Yuchen Du, Lin Qi, Sophie Xiao, Frank K Braun, Mari Kogiso, Yulun Huang, Frank Huang, Aalaa Abdallah, Milagros Suarez, Sekar Karthick, Nabil M Ahmed, Vita S Salsman, Patricia A Baxter, Jack M Su, Daniel J Brat, Paul L Hellenbeck, Wan-Yee Teo, Akash J Patel, Xiao-Nan Li

Faculty, Staff and Students Publications

BACKGROUND: Animal models representing different molecular subtypes of glioblastoma multiforme (GBM) is desired for developing new therapies. SVV-001 is an oncolytic virus selectively targeting cancer cells. It's capacity of passing through the blood brain barrier makes is an attractive novel approach for GBM.

MATERIALS AND METHODS: 23 patient tumor samples were implanted into the brains of NOD/SCID mice (1 × 105 cells/mouse). Tumor histology, gene expression (RNAseq), and growth rate of the developed patient-derived orthotopic xenograft (PDOX) models were compared with the originating patient tumors during serial subtransplantations. Anti-tumor activities of SVV-001 were examined in vivo; and therapeutic efficacy validated …