Medicine and Health Sciences Commons^™

Integrative Genetic Approach Facilitates Precision Strategies For Acute Myocardial Infarction, Muzamil Khawaja, Rehma Siddiqui, Salim S Virani, Christopher I Amos, Dhrubajyoti Bandyopadhyay, Hafeez Ul Hassan Virk, Mahboob Alam, Hani Jneid, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Acute myocardial infarction remains a significant cause of mortality worldwide and its burden continues to grow. Its pathophysiology is known to be complex and multifactorial, with several acquired and inherited risk factors. As advances in technology and medical therapy continue, there is now increasing recognition of the role that genetics play in the development and management of myocardial infarction. The genetic determinants of acute coronary syndrome are still vastly understudied, but the advent of whole-genome scanning and genome-wide association studies has significantly expanded the current understanding of genetics and simultaneously fostered hope that genetic profiling and gene-guided treatments could substantially …

Outcomes And Institutional Variation In Arterial Access Among Patients With Ami And Cardiogenic Shock Undergoing Pci, Dhruv Mahtta, Pratik Manandhar, Zachary K Wegermann, Daniel Wojdyla, Michael Megaly, Ajar Kochar, Salim S Virani, Sunil V Rao, Islam Y Elgendy

Faculty, Staff and Students Publications

Background: Contemporary data comparing the outcomes of transradial access (TRA) vs transfemoral access (TFA) among patients presenting with acute myocardial infarction and cardiogenic shock (AMI-CS) undergoing percutaneous coronary intervention (PCI) are limited.

Objectives: This study examines in-hospital outcomes and institutional variation among patients with AMI-CS undergoing TRA-PCI vs TFA-PCI.

Methods: Patients admitted with AMI-CS from the NCDR CathPCI registry between April 2018 and June 2021 were included. Multivariable logistic regression and inverse probability weighting models were used to assess the association between access site and in-hospital outcomes. A falsification analysis using non-access site-related bleeding was performed.

Results: Among 35,944 patients …

The Reliability And Validity Of The Tbi-Careqol System In Four Diverse Caregiver Groups, Noelle E Carlozzi, Sung Won Choi, Zhenke Wu, Srijan Sen, Jonathan Troost, Angela K Lyden, Jennifer A Miner, Christopher Graves, Angelle M Sander

Faculty, Staff and Students Publications

PURPOSE: Establishing the psychometric reliability and validity of new measures is an ongoing process. More work is needed in to confirm the clinical utility of the TBI-CareQOL measurement development system in both an independent cohort of caregivers of traumatic brain injury (TBI), as well as in additional caregiver groups.

METHODS: An independent cohort of caregivers of people with TBI (n = 139), as well as three new diverse caregiver cohorts (n = 19 caregivers of persons with spinal cord injury, n = 21 caregivers for persons with Huntington disease, and n = 30 caregivers for persons with cancer), completed 11 …

Diagnostic Accuracy Of Whole Heart Coronary Magnetic Resonance Angiography: A Systematic Review And Meta-Analysis, Shingo Kato, Mai Azuma, Naoki Nakayama, Kazuki Fukui, Masanori Ito, Naka Saito, Nobuyuki Horita, Daisuke Utsunomiya

Faculty, Staff and Student Publications

BACKGROUND: The purpose of this meta-analysis was to comprehensively investigate the diagnostic ability of 1.5 T and 3.0 T whole heart coronary angiography (WHCA) to detect significant coronary artery disease (CAD) on X-ray coronary angiography.

METHODS: A literature search of electronic databases, including PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE, was performed to retrieve and integrate articles showing significant CAD detectability of 1.5 and 3.0 T WHCA.

RESULTS: Data from 1899 patients from 34 studies were included in the meta-analysis. 1.5 T WHCA had a summary area under ROC of 0.88 in the patient-based analysis, 0.90 …

Design And Validation Of A Low-Cost Mobile Eeg-Based Brain-Computer Interface, Alexander Craik, Juan José González-España, Ayman Alamir, David Edquilang, Sarah Wong, Lianne Sánchez Rodríguez, Jeff Feng, Gerard E Francisco, Jose L Contreras-Vidal

Faculty, Staff and Student Publications

Objective: We designed and validated a wireless, low-cost, easy-to-use, mobile, dry-electrode headset for scalp electroencephalography (EEG) recordings for closed-loop brain–computer (BCI) interface and internet-of-things (IoT) applications.

Approach: The EEG-based BCI headset was designed from commercial off-the-shelf (COTS) components using a multi-pronged approach that balanced interoperability, cost, portability, usability, form factor, reliability, and closed-loop operation.

Main Results: The adjustable headset was designed to accommodate 90% of the population. A patent-pending self-positioning dry electrode bracket allowed for vertical self-positioning while parting the user’s hair to ensure contact of the electrode with the scalp. In the current prototype, five EEG electrodes were incorporated …

The Long Non-Coding Rna Neat1 Is A Δnp63 Target Gene Modulating Epidermal Differentiation, Claudia Fierro, Veronica Gatti, Veronica La Banca, Sara De Domenico, Stefano Scalera, Giacomo Corleone, Maurizio Fanciulli, Francesca De Nicola, Alessandro Mauriello, Manuela Montanaro, George A Calin, Gerry Melino, Angelo Peschiaroli

Faculty, Staff and Student Publications

The transcription factor ΔNp63 regulates epithelial stem cell function and maintains the integrity of stratified epithelial tissues by acting as transcriptional repressor or activator towards a distinct subset of protein-coding genes and microRNAs. However, our knowledge of the functional link between ∆Np63 transcriptional activity and long non-coding RNAs (lncRNAs) expression is quite limited. Here, we show that in proliferating human keratinocytes ∆Np63 represses the expression of the lncRNA NEAT1 by recruiting the histone deacetylase HDAC1 to the proximal promoter of NEAT1 genomic locus. Upon induction of differentiation, ∆Np63 down-regulation is associated by a marked increase of NEAT1 RNA levels, resulting …

The Effects Of Covid-19 Lockdown On Social Connectedness And Psychological Distress In Us Adults With Chronic Diseases, Ben King, Omolola E Adepoju, Lechauncy Woodard, Abiodun O Oluyomi, Xiaotao Zhang, Christopher I Amos, Hoda Badr

Faculty, Staff and Students Publications

Lockdown measures enacted in 2020 to control the spread of COVID-19 led to increases in the prevalence of mental health problems. Due to their high-risk status, individuals with chronic diseases may be at increased risk and disproportionately adversely affected by the COVID-19 pandemic. The investigators examined associations between having a high-risk chronic condition, social connectedness, and general distress and COVID-19-specific distress among U.S. adults during the COVID-19 lockdown. Baseline measures of a longitudinal survey collected at the beginning of the pandemic (April to June 2020) were analyzed to identify factors associated with loss of social connectedness from pre- to post-lockdown. …

On The Dependent Recognition Of Some Long Zinc Finger Proteins, Zheng Zuo, Timothy Billings, Michael Walker, Petko M Petkov, Polly M Fordyce, Gary D Stormo

2020-Current year OA Pubs

The human genome contains about 800 C2H2 zinc finger proteins (ZFPs), and most of them are composed of long arrays of zinc fingers. Standard ZFP recognition model asserts longer finger arrays should recognize longer DNA-binding sites. However, recent experimental efforts to identify in vivo ZFP binding sites contradict this assumption, with many exhibiting short motifs. Here we use ZFY, CTCF, ZIM3, and ZNF343 as examples to address three closely related questions: What are the reasons that impede current motif discovery methods? What are the functions of those seemingly unused fingers and how can we improve the motif discovery algorithms based …

Researching Covid To Enhance Recovery (Recover) Adult Study Protocol: Rationale, Objectives, And Design, Leora I Horwitz, Tanayott Thaweethai, Shari B Brosnahan, Mine S Cicek, Megan L Fitzgerald, Jason D Goldman, Rachel Hess, S L Hodder, Vanessa L Jacoby, Michael R Jordan, Jerry A Krishnan, Adeyinka O Laiyemo, Torri D Metz, Lauren Nichols, Rachel E Patzer, Anisha Sekar, Nora G Singer, Lauren E Stiles, Barbara S Taylor, Shifa Ahmed, Heather A Algren, Khamal Anglin, Lisa Aponte-Soto, Hassan Ashktorab, Ingrid V Bassett, Brahmchetna Bedi, Nahid Bhadelia, Christian Bime, Marie-Abele C Bind, Lora J Black, Andra L Blomkalns, Hassan Brim, Mario Castro, James Chan, Alexander W Charney, Benjamin K Chen, Li Qing Chen, Peter Chen, David Chestek, Lori B Chibnik, Dominic C Chow, Helen Y Chu, Rebecca G Clifton, Shelby Collins, Maged M Costantine, Sushma K Cribbs, Steven G Deeks, John D Dickinson, Sarah E Donohue, Matthew S Durstenfeld, Ivette F Emery, Kristine M Erlandson, Julio C Facelli, Rachael Farah-Abraham, Aloke V Finn, Melinda S Fischer, Valerie J Flaherman, Judes Fleurimont, Vivian Fonseca, Emily J Gallagher, Jennifer C Gander, Maria Laura Gennaro, Kelly S Gibson, Minjoung Go, Steven N Goodman, Joey P Granger, Frank L Greenway, John W Hafner, Jenny E Han, Michelle S Harkins, Kristine S P Hauser, James R Heath, Carla R Hernandez, On Ho, Matthew K Hoffman, Susan E Hoover, Carol R Horowitz, Harvey Hsu, Priscilla Y Hsue, Brenna L Hughes, Prasanna Jagannathan, Judith A James, Janice John, Sarah Jolley, S E Judd, Joy J Juskowich, Diane G Kanjilal, Elizabeth W Karlson, Stuart D Katz, J Daniel Kelly, Sara W Kelly, Arthur Y Kim, John P Kirwan, Kenneth S Knox, Andre Kumar, Michelle F Lamendola-Essel, Margaret Lanca, Joyce K Lee-Lannotti, R Craig Lefebvre, Bruce D Levy, Janet Y Lin, Brian P Logarbo, Jennifer K Logue, Michele T Longo, Carlos A Luciano, Karen Lutrick, Shahdi K Malakooti, Gail Mallett, Gabrielle Maranga, Jai G Marathe, Vincent C Marconi, Gailen D Marshall, Christopher F Martin, Jeffrey N Martin, Heidi T May, Grace A Mccomsey, Dylan Mcdonald, Hector Mendez-Figueroa, Lucio Miele, Murray A Mittleman, Sindhu Mohandas, Christian Mouchati, Janet M Mullington, Girish N Nadkarni, Erica R Nahin, Robert B Neuman, Lisa T Newman, Amber Nguyen, Janko Z Nikolich, Igho Ofotokun, Princess U Ogbogu, Anna Palatnik, Kristy T S Palomares, Tanyalak Parimon, Samuel Parry, Sairam Parthasarathy, Thomas F Patterson, Ann Pearman, Michael J Peluso, Priscilla Pemu, Christian M Pettker, Beth A Plunkett, Kristen Pogreba-Brown, Athena Poppas, J Zachary Porterfield, John G Quigley, Davin K Quinn, Hengameh Raissy, Candida J Rebello, Uma M Reddy, Rebecca Reece, Harrison T Reeder, Franz P Rischard, Johana M Rosas, Clifford J Rosen, Nadine G Rouphael, Dwight J Rouse, Adam M Ruff, Christina Saint Jean, Grecio J Sandoval, Jorge L Santana, Shannon M Schlater, Frank C Sciurba, Caitlin Selvaggi, Sudha Seshadri, Howard D Sesso, Dimpy P Shah, Eyal Shemesh, Zaki A Sherif, Daniel J Shinnick, Hyagriv N Simhan, Upinder Singh, Amber Sowles, Vignesh Subbian, Jun Sun, Mehul S Suthar, Larissa J Teunis, John M Thorp, Amberly Ticotsky, Alan T N Tita, Robin Tragus, Katherine R Tuttle, Alfredo E Urdaneta, P J Utz, Timothy M Vanwagoner, Andrew Vasey, Suzanne D Vernon, Crystal Vidal, Tiffany Walker, Honorine D Ward, David E Warren, Ryan M Weeks, Steven J Weiner, Jordan C Weyer, Jennifer L Wheeler, Sidney W Whiteheart, Zanthia Wiley, Natasha J Williams, Juan P Wisnivesky, John C Wood, Lynn M Yee, Natalie M Young, Sokratis N Zisis, Andrea S Foulkes

Faculty, Staff and Student Publications

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. …

Female Athlete Health Domains: A Supplement To The International Olympic Committee Consensus Statement On Methods For Recording And Reporting Epidemiological Data On Injury And Illness In Sport., Isabel S Moore, Kay M Crossley, Kari Bo, Margo Mountjoy, Kathryn E Ackerman, Juliana Da Silva Antero, Jorunn Sundgot Borgen, Wendy J Brown, Caroline S Bolling, Benjamin Clarsen, Wayne Derman, Paul Dijkstra, Amber Donaldson, Kirsty J Elliott-Sale, Carolyn A Emery, Lene Haakstad, Astrid Junge, Nonhlanhla S Mkumbuzi, Sophia Nimphius, Debbie Palmer, Mireille Van Poppel, Jane S Thornton, Rita Tomás, Phathokuhle C Zondi, Evert Verhagen

Family Medicine Publications

The IOC made recommendations for recording and reporting epidemiological data on injuries and illness in sports in 2020, but with little, if any, focus on female athletes. Therefore, the aims of this supplement to the IOC consensus statement are to (i) propose a taxonomy for categorisation of female athlete health problems across the lifespan; (ii) make recommendations for data capture to inform consistent recording and reporting of symptoms, injuries, illnesses and other health outcomes in sports injury epidemiology and (iii) make recommendations for specifications when applying the Strengthening the Reporting of Observational Studies in Epidemiology-Sport Injury and Illness Surveillance (STROBE-SIIS) …

Heterogeneity In The Effect Of Marked Weight Loss On Metabolic Function In Women With Obesity, Bettina Mittendorfer, Brandon D. Kayser, Mihoko Yoshino, Jun Yoshino, Jeramie D. Watrous, Mohit Jain, J. Christopher Eagon, Bruce W. Patterson, Samuel Klein

2020-Current year OA Pubs

BACKGROUNDThere is considerable heterogeneity in the effect of weight loss on metabolic function in people with obesity.METHODSWe evaluated muscle and liver insulin sensitivity, body composition, and circulating factors associated with insulin action before and after approximately 20% weight loss in women identified as "Responders" (n = 11) or "Non-responders" (n = 11), defined as the top (>75% increase) and bottom (<5% increase) quartiles of the weight loss-induced increase in glucose disposal rate (GDR) during a hyperinsulinemic-euglycemic clamp procedure, among 43 women with obesity (BMI: 44.1 ± 7.9 kg/m2).RESULTSAt baseline, GDR, which provides an index of muscle insulin sensitivity, and the hepatic insulin sensitivity index were more than 50% lower in Responders than Non-responders, but both increased much more after weight loss in Responders than Non-responders, which eliminated the differences between groups. Weight loss also caused greater decreases in intrahepatic triglyceride content and plasma adiponectin and PAI-1 concentrations in Responders than Non-responders and greater insulin-mediated suppression of plasma free fatty acids, branched-chain amino acids, and C3/C5 acylcarnitines in Non-responders than Responders, so that differences between groups at baseline were no longer present after weight loss. The effect of weight loss on total body fat mass, intra-abdominal adipose tissue volume, adipocyte size, and circulating inflammatory markers were not different between groups.CONCLUSIONThe results from our study demonstrate that the heterogeneity in the effects of marked weight loss on muscle and hepatic insulin sensitivity in people with obesity is determined by baseline insulin action, and reaches a ceiling when "normal" insulin action is achieved.TRIAL REGISTRATIONNCT00981500, NCT01299519, NCT02207777.FUNDINGNIH grants P30 DK056341, P30 DK020579, P30 DK052574, UL1 TR002345, and T32 HL13035, the American Diabetes Association (1-18-ICTS-119), the Longer Life Foundation (2019-011), and the Atkins Philanthropic Trust.

Β Cell Function After Roux-En-Y Gastric Bypass Surgery Or Reduced Energy Intake Alone In People With Obesity, Bettina Mittendorfer, Bruce W. Patterson, Faidon Magkos, Mihoko Yoshino, David P. Bradley, J. Christopher Eagon, Samuel Klein

2020-Current year OA Pubs

BackgroundThe effects of diet-induced weight loss (WL) and WL after Roux-en-Y gastric bypass (RYGB) surgery on β cell function (BCF) are unclear because of conflicting results from different studies, presumably because of differences in the methods used to measure BCF, the amount of WL between treatment groups, and baseline BCF. We evaluated the effect of WL after RYGB surgery or reduced energy intake alone on BCF in people with obesity with and without type 2 diabetes.MethodsBCF (insulin secretion in relationship to plasma glucose) was assessed before and after glucose or mixed-meal ingestion before and after (a) progressive amounts (6%, 11%, …

A Simplified Method To Correct Saturation Of Arterial Input Function For Cardiac Magnetic Resonance First-Pass Perfusion Imaging: Validation With Simultaneously Acquired Pet, Ran Li, Masoud Edalati, David Muccigrosso, Jeffrey M C Lau, Richard Laforest, Pamela K Woodard, Jie Zheng

2020-Current year OA Pubs

BACKGROUND: First-pass perfusion imaging in magnetic resonance imaging (MRI) is an established method to measure myocardial blood flow (MBF). An obstacle for accurate quantification of MBF is the saturation of blood pool signal intensity used for arterial input function (AIF). The objective of this project was to validate a new simplified method for AIF estimation obtained from single-bolus and single sequence perfusion measurements. The reference MBF was measured simultaneously on

METHODS: Sixteen patients with clinically confirmed myocardial ischemia were imaged in a clinical whole-body PET-MRI system. PET perfusion imaging was performed in a 10-min acquisition after the injection of 10 …

Using Three-Dimensional Printed Models For Trainee Orbital Fracture Education, Martina Rama, Lauren Schlegel, Douglas M. Wisner, Robert S. Pugliese, Sathyadeepak Ramesh, Robert Penne, Alison Watson

Wills Eye Hospital Papers

BACKGROUND: Three-dimensional printing is an underutilized technology in ophthalmology training; its use must be explored in complex educational scenarios. This study described a novel approach to trainee education of orbital fracture repair utilizing three-dimensional (3D) printed models as a teaching tool.

METHODS: Ophthalmology residents and oculoplastic fellows from multiple training institutions underwent an educational session on orbital fractures, learning through four different models. Participants analyzed orbital fractures through computerized tomography (CT) imaging alone and then utilizing CT imaging with the aid of a 3D printed model. Participants completed a questionnaire assessing their understanding of the fracture pattern and surgical approach. …

An Integrated Isothermal Nucleic Acid Amplification Test To Detect Hpv16 And Hpv18 Dna In Resource-Limited Settings, Kathryn A Kundrod, Maria Barra, Alexis Wilkinson, Chelsey A Smith, Mary E Natoli, Megan M Chang, Jackson B Coole, Akshaya Santhanaraj, Cesaltina Lorenzoni, Celda Mavume, Hira Atif, Jane Richards Montealegre, Michael E Scheurer, Philip E Castle, Kathleen M Schmeler, Rebecca R Richards-Kortum

Center for Medical Ethics and Health Policy Staff Publications

High-risk human papillomavirus (HPV) DNA testing is widely acknowledged as the most sensitive cervical cancer screening method but has limited availability in resource-limited settings, where the burden of cervical cancer is highest. Recently, HPV DNA tests have been developed for use in resource-limited settings, but they remain too costly for widespread use and require instruments that are often limited to centralized laboratories. To help meet the global need for low-cost cervical cancer screening, we developed a prototype, sample-to-answer, point-of-care test for HPV16 and HPV18 DNA. Our test relies on isothermal DNA amplification and lateral flow detection, two technologies that reduce …

An Improved Reporter Identifies Ruxolitinib As A Potent And Cardioprotective Camkii Inhibitor, Oscar E Reyes Gaido, Nikoleta Pavlaki, Jonathan M Granger, Olurotimi O Mesubi, Bian Liu, Brian L Lin, Alan Long, David Walker, Joshua Mayourian, Kate L Schole, Chantelle E Terrillion, Lubika J Nkashama, Mohit M Hulsurkar, Lauren E Dorn, Kimberly M Ferrero, Richard L Huganir, Frank U Müller, Xander H T Wehrens, Jun O Liu, Elizabeth D Luczak, Vassilios J Bezzerides, Mark E Anderson

Faculty, Staff and Students Publications

Ca2+/calmodulin-dependent protein kinase II (CaMKII) hyperactivity causes cardiac arrhythmias, a major source of morbidity and mortality worldwide. Despite proven benefits of CaMKII inhibition in numerous preclinical models of heart disease, translation of CaMKII antagonists into humans has been stymied by low potency, toxicity, and an enduring concern for adverse effects on cognition due to an established role of CaMKII in learning and memory. To address these challenges, we asked whether any clinically approved drugs, developed for other purposes, were potent CaMKII inhibitors. For this, we engineered an improved fluorescent reporter, CaMKAR (CaMKII activity reporter), which features superior sensitivity, kinetics, and …

Blm Overexpression As A Predictive Biomarker For Chk1 Inhibitor Response In Parp Inhibitor-Resistant Brca-Mutant Ovarian Cancer, Nitasha Gupta, Tzu-Ting Huang, Jayakumar R Nair, Daniel An, Grant Zurcher, Erika J Lampert, Ann Mccoy, Ashley Cimino-Mathews, Elizabeth M Swisher, Marc R Radke, Christina M Lockwood, Jonathan B Reichel, Chih-Yuan Chiang, Kelli M Wilson, Ken Chih-Chien Cheng, Darryl Nousome, Jung-Min Lee

Faculty, Staff and Student Publications

Poly(ADP-ribose) polymerase inhibitors (PARPis) have changed the treatment paradigm in breast cancer gene (BRCA)–mutant high-grade serous ovarian carcinoma (HGSC). However, most patients eventually develop resistance to PARPis, highlighting an unmet need for improved therapeutic strategies. Using high-throughput drug screens, we identified ataxia telangiectasia and rad3-related protein/checkpoint kinase 1 (CHK1) pathway inhibitors as cytotoxic and further validated the activity of the CHK1 inhibitor (CHK1i) prexasertib in PARPi-sensitive and -resistant BRCA-mutant HGSC cells and xenograft mouse models. CHK1i monotherapy induced DNA damage, apoptosis, and tumor size reduction. We then conducted a phase 2 study (NCT02203513) of prexasertib …

Impact Of Food Environments On Obesity Rates: A State-Level Analysis., Elizabeth Cerceo, Elena Sharma, Anne Boguslavsky, Jean-Sebastian Rachoin

Cooper Medical School of Rowan University Departmental Research

INTRODUCTION: Limited access to healthy food in areas that are predominantly food deserts or food swamps may be associated with obesity. Other unhealthy behaviors may also be associated with obesity and poor food environments.

METHODS: We calculated Modified Retail Food Environment Index (mRFEI) to assess food retailers. Using data collected from the Behavioral Risk Factor Surveillance System (BRFSS) survey, the NJ Department of Health (NJDOH), and the US Census Bureau, we conducted a cross-sectional analysis of the interaction of obesity with the food environment and assessed smoking, leisure-time physical activity (LPA), and poor sleep.

RESULTS: There were 17.9% food deserts …

Using Ai-Generated Suggestions From Chatgpt To Optimize Clinical Decision Support, Siru Liu, Aileen P Wright, Barron L Patterson, Jonathan P Wanderer, Robert W Turer, Scott D Nelson, Allison B Mccoy, Dean F Sittig, Adam Wright

Faculty, Staff and Student Publications

OBJECTIVE: To determine if ChatGPT can generate useful suggestions for improving clinical decision support (CDS) logic and to assess noninferiority compared to human-generated suggestions.

METHODS: We supplied summaries of CDS logic to ChatGPT, an artificial intelligence (AI) tool for question answering that uses a large language model, and asked it to generate suggestions. We asked human clinician reviewers to review the AI-generated suggestions as well as human-generated suggestions for improving the same CDS alerts, and rate the suggestions for their usefulness, acceptance, relevance, understanding, workflow, bias, inversion, and redundancy.

RESULTS: Five clinicians analyzed 36 AI-generated suggestions and 29 human-generated suggestions …

Immune Microenvironment Remodeling After Radiation Of A Progressing Brain Metastasis, William H Hudson, Jeffrey J Olson, Lisa J Sudmeier

Faculty, Staff and Students Publications

Radiation is commonly used in the treatment of many cancers. However, its effects on anti-tumor immune responses are incompletely understood. Here, we present a detailed immunological analysis of two tumors from a patient with multiple non-small cell lung cancer metastases to the brain. One tumor was resected without treatment; the second was irradiated to a total dose of 30 Gy and resected following further progression. Comprehensive single-cell analysis reveals a substantially reduced immune cell fraction in the irradiated tumor, including the depletion of tissue-resident macrophages and infiltration of pro-inflammatory monocytes. Despite the presence of similar somatic mutations in both tumors, …

Long-Term Outcomes And Molecular Correlates Of Sotorasib Efficacy In Patients With Pretreated Kras G12c-Mutated Non-Small-Cell Lung Cancer: 2-Year Analysis Of Codebreak 100, Grace K Dy, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

No abstract provided.

Striatal Dopamine Synthesis And Cognitive Flexibility Differ Between Hormonal Contraceptive Users And Nonusers, Caitlin M Taylor, Daniella J Furman, Anne S Berry, Robert L White, William J Jagust, Mark D'Esposito, Emily G Jacobs

2020-Current year OA Pubs

In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine (DA) neurotransmission. Yet less is known about hormonal regulation of the DA system in the human brain. Using positron emission tomography (PET), we address this gap by comparing hormonal contraceptive users and nonusers across multiple aspects of DA function: DA synthesis capacity via the PET radioligand 6-[18F]fluoro-m-tyrosine ([18F]FMT), baseline D2/3 receptor binding potential using [11C]raclopride, and DA release using methylphenidate-paired [11C]raclopride. Participants consisted of 36 healthy women (n = 15 hormonal contraceptive users; n = 21 naturally cycling/non users of hormonal contraception), and men (n = 20) as …

Robust Acoustic Trapping And Perturbation Of Single-Cell Microswimmers Illuminate Three-Dimensional Swimming And Ciliary Coordination, Mingyang Cui, Susan K Dutcher, Philip V Bayly, J Mark Meacham

2020-Current year OA Pubs

We report a label-free acoustic microfluidic method to confine single, cilia-driven swimming cells in space without limiting their rotational degrees of freedom. Our platform integrates a surface acoustic wave (SAW) actuator and bulk acoustic wave (BAW) trapping array to enable multiplexed analysis with high spatial resolution and trapping forces that are strong enough to hold individual microswimmers. The hybrid BAW/SAW acoustic tweezers employ high-efficiency mode conversion to achieve submicron image resolution while compensating for parasitic system losses to immersion oil in contact with the microfluidic chip. We use the platform to quantify cilia and cell body motion for wildtype biciliate …

Healthy Lifestyle Index And Risk Of Cardiovascular Disease Among Postmenopausal Women With Normal Body Mass Index, Rita Peila, Xiaonan Xue, Qibin Qi, Andrew J Dannenberg, Matthew A Allison, Karen C Johnson, Michael J Lamonte, Robert A Wild, Bernhard Haring, Kathy Pan, Hilary A Tindle, Randi Foraker, Nazmus Saquib, Ana Barac, Thomas E Rohan

2020-Current year OA Pubs

Background A lifestyle comprising a healthy diet, light alcohol consumption, no smoking, and moderate or intense physical activity has been associated with reduced risk of cardiovascular disease (CVD). We examined the association of a healthy lifestyle index (HLI), derived from scores for each of these components plus waist circumference, with the risk of incident CVD and CVD subtypes in postmenopausal women with normal body mass index (18.5-<25.0 kg/m

Tumor Biology And Immune Infiltration Define Primary Liver Cancer Subsets Linked To Overall Survival After Immunotherapy, Anuradha Budhu, Erica C Pehrsson, Aiwu He, Lipika Goyal, Robin Kate Kelley, Hien Dang, Changqing Xie, Cecilia Monge, Mayank Tandon, Lichun Ma, Mahler Revsine, Laura Kuhlman, Karen Zhang, Islam Baiev, Ryan Lamm, Keyur Patel, David E Kleiner, Stephen M Hewitt, Bao Tran, Jyoti Shetty, Xiaolin Wu, Yongmei Zhao, Tsai-Wei Shen, Sulbha Choudhari, Yuliya Kriga, Kris Ylaya, Andrew C Warner, Elijah F Edmondson, Marshonna Forgues, Tim F Greten, Xin Wei Wang

Kimmel Cancer Center Faculty Papers

Primary liver cancer is a rising cause of cancer deaths in the US. Although immunotherapy with immune checkpoint inhibitors induces a potent response in a subset of patients, response rates vary among individuals. Predicting which patients will respond to immune checkpoint inhibitors is of great interest in the field. In a retrospective arm of the National Cancer Institute Cancers of the Liver: Accelerating Research of Immunotherapy by a Transdisciplinary Network (NCI-CLARITY) study, we use archived formalin-fixed, paraffin-embedded samples to profile the transcriptome and genomic alterations among 86 hepatocellular carcinoma and cholangiocarcinoma patients prior to and following immune checkpoint inhibitor treatment. …

Arginine Depletion Attenuates Renal Cystogenesis In Tuberous Sclerosis Complex Model, Athar Amleh, Hadass Pri Chen, Lana Watad, Ifat Abramovich, Bella Agranovich, Eyal Gottlieb, Iddo Z Ben-Dov, Morris Nechama, Oded Volovelsky

Faculty, Staff and Student Publications

Cystic kidney disease is a leading cause of morbidity in patients with tuberous sclerosis complex (TSC). We characterize the misregulated metabolic pathways using cell lines, a TSC mouse model, and human kidney sections. Our study reveals a substantial perturbation in the arginine biosynthesis pathway in TSC models with overexpression of argininosuccinate synthetase 1 (ASS1). The rise in ASS1 expression is dependent on the mechanistic target of rapamycin complex 1 (mTORC1) activity. Arginine depletion prevents mTORC1 hyperactivation and cell cycle progression and averts cystogenic signaling overexpression of c-Myc and P65. Accordingly, an arginine-depleted diet substantially reduces the TSC cystic load in …

Comparative Outcomes Of Interventions For Femoropopliteal Chronic Total Occlusion Versus Non-Chronic Total Occlusion Lesions From The Multicenter Xlpad Registry, Shirling Tsai, Yulun Liu, Lawrence Hoang, Michael Vu, Hua Lu, Bala Ramanan, David Fernandez Vazquez, Zachary Rosol, Sameh Sayfo, Mohamad Amer Alaiti, Panagiotis Koutakis, Emmanouil S Brilakis, Mehdi H Shishehbor, Subhash Banerjee

Faculty, Staff and Student Publications

Background Endovascular intervention of femoropopliteal chronic total occlusions (CTOs) is technically more complex. However, there is lack of comparative analysis between CTO and non-CTO femoropopliteal interventions. Methods and Results We report procedural details and outcomes of patients treated for femoropopliteal CTO and non-CTO lesions in the XLPAD (Excellence in Peripheral Artery Disease) registry (NCT01904851) between 2006 and 2019. Primary outcomes were procedural success and 1-year major adverse limb events, a composite of all-cause death, target limb revascularization, or major amputation. Analysis included 2895 patients (CTO: n=1516 patients; non-CTO: n=1379 patients) with 3658 lesions (CTO: n=1998 lesions; non-CTO: n=1660 lesions). Conventional …

Long-Term Outcomes And Molecular Correlates Of Sotorasib Efficacy In Patients With Pretreated Kras G12c-Mutated Non–Small-Cell Lung Cancer: 2-Year Analysis Of Codebreak 100, Grace K Dy, Ramaswamy Govindan, Vamsidhar Velcheti, Gerald S Falchook, Antoine Italiano, Jürgen Wolf, Adrian G Sacher, Toshiaki Takahashi, Suresh S Ramalingam, Christophe Dooms, Dong-Wan Kim, Alfredo Addeo, Jayesh Desai, Martin Schuler, Pascale Tomasini, David S Hong, Piro Lito, Qui Tran, Simon Jones, Abraham Anderson, Antreas Hindoyan, Wendy Snyder, Ferdinandos Skoulidis, Bob T Li

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

In the longest follow-up, to our knowledge, for a KRAS^G12C inhibitor, we assessed the long-term efficacy, safety, and biomarkers of sotorasib in patients with KRAS G12C-mutated advanced non–small-cell lung cancer (NSCLC) from the CodeBreaK 100 clinical …

Pentoxifylline For Treatment Of Sepsis And Necrotising Enterocolitis In Neonates, Mohan Pammi, Khalid N Haque

Faculty, Staff and Students Publications

BACKGROUND: Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015.

OBJECTIVES: To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC.

SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We …

Scutellaria Baicalensis Enhances 5-Fluorouracil-Based Chemotherapy Via Inhibition Of Proliferative Signaling Pathways, Haizhou Liu, Hui Liu, Zhiyi Zhou, Jessica Chung, Guojing Zhang, Jin Chang, Robert A Parise, Edward Chu, John C Schmitz

Abington Jefferson Health Papers

Fluoropyridine-based chemotherapy remains the most widely used treatment for colorectal cancer (CRC). In this study, we investigated the mechanism by which the natural product Scutellaria baicalensis (Huang Qin; HQ) and one of its main components baicalin enhanced 5-fluorouracil (5-FU) antitumor activity against CRC. Cell proliferation assays, cell cycle analysis, reverse-phase protein array (RPPA) analysis, immunoblot analysis, and qRT-PCR were performed to investigate the mechanism(s) of action of HQ and its active components on growth of CRC cells. HQ exhibited in vitro antiproliferative activity against drug resistant human CRC cells, against human and mouse CRC cells with different genetic backgrounds and …