Digital Commons Network^™

A Temperature-Sensitive Crispr-Cas12a System For Sterile Insect Technique, Christina Nguyen, Ahmed Idowu Omotayo, Sara Sanz Juste, Xuechun Feng, Víctor López Del Amo

Faculty, Staff and Student Publications

The sterile insect technique (SIT) reduces population numbers by releasing sterile males that produce non-viable progeny. Specifically, CRISPR/Cas9-based precision-guided SIT (pgSIT) generates sterile males through genetic crosses of two transgenic lines: a Cas9 strain and a guide RNA (gRNA) strain targeting male sterility and female viability or infertility. However, pgSIT requires separate maintenance of the two lines and sorting to obtain sterile males, creating possible challenges for scaling. To overcome this, we propose using Cas12a nuclease, which is inoperative at lower temperatures but active at higher temperatures. Here, we develop a Cas12a-based pgSIT system involving a single strain containing both …

Early Ctdna Dynamics Inform First-Line Therapy In Patients With Extensive-Stage Small Cell Lung Cancer, Carmela Ciardullo, Luis Tobalina, T Hedley Carr, Philip Szekeres, Silvija Kraljevic, Lauren Averett Byers, Giulia Fabbri

Faculty, Staff and Student Publications

Purpose: Small cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis despite initial treatment responses. This study evaluates ctDNA for monitoring disease and assessing the efficacy of first-line therapy in patients with extensive-stage SCLC (1L ES-SCLC).

Experimental design: In the TAZMAN trial, 31 patients with 1L ES-SCLC received standard treatment with durvalumab and etoposide plus carboplatin or cisplatin. We analyzed 228 plasma samples from 27 of 31 patients using a liquid biopsy approach to detect somatic mutations and copy-number aberrations, while also accounting for clonal hematopoiesis mutations.

Results: Baseline ctDNA analysis detected somatic alterations in 96.3% of …

Preclinical Fluorescence-Guided Imaging Leveraging Surrounding Sentinel Tumor Microenvironment Identifies High-Risk Premalignant Pancreatic Lesions, Shilpa Sharma, Xiaoxia Wen, Jianbo Wang, Beibei Huang, Denise A Hernandez, Cong-Dat Pham, Zhiwen Liu, Susanne Je-Han Lin, Aiko Yamaguchi, Dimitra K Georgiou, Ryan P Coll, H Charles Manning

Faculty, Staff and Student Publications

Purpose: Because surgery is the only potential cure for pancreatic cancer, high-risk premalignant pancreatic lesions often evade detection by palpation or white-light visualization, increasing the risk of recurrence. We asked whether near-infrared fluorescence imaging of tumor-associated inflammation could identify high-risk premalignant lesions, leveraging the tumor microenvironment as a sentinel of local disease and, thus, enhance surgery outcomes.

Experimental design: Fluorescence-guided surgery was performed on genetically engineered mice [Ptf1a-Cre; LSL-KrasG12D/+; Smad4flox/flox (KSC)] at discrete stages of disease progression, histologically confirmed high-risk, premalignant lesions in postnatal mice to locally advanced pancreatic tumors in adults, using the imaging agent V-1520, a translocator protein …

Genetic Contribution To Treatment-Related Dyslipidemia In Adult Survivors Of Childhood Cancer: Findings From The Ccss, Sjlife, And Dccss-Later Cohorts, Melissa Bolier, Vincent G Pluimakers, Linda Broer, Sebastian J C M M Neggers, Demi T C De Winter, Fan Wang, Jessica L Baedke, André G Uitterlinden, Kateryna Petrykey, Leontien C M Kremer, Jacqueline J Loonen, Marloes Louwerens, Heleen J Van Der Pal, E Lieke A M Feijen, Kevin C Oeffinger, Rebecca M Howell, Eric J Chow, Wendy M Leisenring, Maria Monica M Gramatges, Lindsay M Morton, Leslie L Robison, Melissa M Hudson, Kirsten K Ness, Yadav Sapkota, Gregory T Armstrong, Smita Bhatia, Yutaka Yasui, Marry M Van Den Heuvel-Eibrink

Faculty, Staff and Student Publications

Background: Dyslipidemia can occur as a long-term side effect of childhood cancer treatment. The difference in prevalence among children receiving comparable treatment suggests a role for genetic variation. We conducted the first genome-wide association study on dyslipidemia in a large childhood cancer survivor cohort, using three additional cohorts for replication.

Methods: Discovery analysis was performed in the original Childhood Cancer Survivor Study (CCSS) cohort (N = 4,332). Replication analyses were carried out in the CCSS expansion (N = 2,212), St. Jude Lifetime (N = 2,829), and Dutch Childhood Cancer Survivor Study (DCCSS-LATER) (N = 1,814) cohorts. In the CCSS cohorts, …

A Clinical Practice Guideline For The Management Of Pregnancy Alloimmunized To Red Blood Cell Antigens\, Kenneth J Moise, Kara B Markham, Philip C Spinella, Molly R Sherwood, Karen A Robinson, Lisa M Wilson, Jay Malone, Jimmy Espinoza, Donna Dizon-Townson, Laura Mercer, Russell Miller, Leonardo Pereira, Anthony Sciscione, Alireza A Shamshirsaz, Kathryn Shanahan, Saul Snowise, Thomas Trevett, Juan M González Vélez, Bethany Weathersby

Faculty, Staff and Student Publications

Importance: Red blood cell alloimmunization is typically associated with the transplacental transfer of incompatible fetal red blood cells into maternal circulation. Subsequent pregnancies can be affected by fetal anemia, hydrops fetalis, and perinatal death. Most cases of Rhesus D (RhD) alloimmunization due to pregnancy can be prevented by the proper administration of Rhesus immune globulin. However, an emerging practice of using low-titer, O, RhD-positive whole blood (LTOWB) in cases of life-threatening hemorrhage has the potential to increase the exposure of the female population to a new source of incompatible red blood cells.

Objective: To establish recommendations for the management of …

A Multi-National Cross-Sectional Exploration Of Rehabilitation Services For Children And Young People Following Brain Injury In Low And Middle Income Countries, Mark A Linden, Leigh Schrieff-Brown, Linda Ewing-Cobbs, R A Leonard, Rajendra Prasad, Juan Carlos Arango-Lasprilla, Sandra Strazzer, Lucia Braga, Consuelo Reyes Payeras, Kim C Davis, Lisa Kalungwana-Mambwe, Flavia Dorrego, Mathilde Chevignard

Faculty, Staff and Student Publications

Background: Brain injury (BI) is the largest cause of mortality and morbidity among children and can lead to significant cognitive, social, emotional and behavioural deficits. There has been an absence of research examining the availability of rehabilitation services for affected children and young people in low and middle income countries (LMICs). This study therefore investigated current rehabilitation provision in LMICs for children and young people with BI.

Methods: An online survey was developed which collected data on funding support for rehabilitation, causes of BI and access to services. The survey was distributed to healthcare professionals known to members of the …

An Annotated Biobank Of Triple-Negative Breast Cancer Patient-Derived Xenografts Features Treatment-Naïve And Longitudinal Samples During Neoadjuvant Chemotherapy, Amanda L Rinkenbaugh, Yuan Qi, Shirong Cai, Jiansu Shao, Faiza Baameur Hancock, Sabrina L Jeter-Jones, Xiaomei Zhang, Emily Powell, Lei Huo, Rosanna Lau, Chunxiao Fu, Rebekah Gould, Petra Den Hollander, Elizabeth E Ravenberg, Jason B White, Gaiane M Rauch, Banu Arun, Clinton Yam, Alastair M Thompson, Gloria V Echeverria, Stacy L Moulder, W Fraser Symmans, Jeffrey T Chang, Helen Piwnica-Worms

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) that fails to respond to neoadjuvant chemotherapy (NACT) can be lethal. Developing effective strategies to eradicate chemoresistant disease requires experimental models that recapitulate the heterogeneity characteristic of TNBC. To that end, we established a biobank of 92 orthotopic patient-derived xenograft (PDX) models of TNBC from the tumors of 75 patients enrolled in the ARTEMIS clinical trial (NCT02276443), including 12 longitudinal sets generated from serial patient biopsies collected throughout NACT treatment and from metastatic disease. Models were established from both chemosensitive and chemoresistant tumors, and nearly 30% of the PDX models were capable of metastasizing …

Proteomic Perspectives On Kras-Driven Cancers And Emerging Therapeutic Approaches, Ramesh Karki, Ru Chen, Sheng Pan

Faculty, Staff and Student Publications

KRAS mutations are implicated in approximately 23% of all human malignancies, with particularly high prevalence in pancreatic ductal adenocarcinoma (PDAC) (~92%), colorectal cancer (CRC) (~49%), and non-small cell lung cancer (NSCLC) (~35%). The recent approval of the KRASG12C-specific inhibitors for NSCLC represents a pivotal advancement in KRAS-targeted therapy. Nevertheless, the emergence of intrinsic and acquired resistance to KRAS-targeted therapies poses a significant clinical obstacle to targeting KRAS, which necessitates a deeper understanding of the resistance mechanisms. Recent progress in proteomic studies has enabled comprehensive profiling of the proteomic alterations driven by KRAS mutations, offering valuable insights into the disrupted KRAS …

Using Artificial Intelligence For Text Screening In A Systematic Review Of Cardiotoxicity, Steven E Canfield, Moez Karim Aziz, Muhammad Imran Omar, James N'Dow, Bob J A Schijvenaars, Jennifer Ghith, Kausar Riaz Ahmed, Donald Molony, Arnulf Stenzl

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVE: Artificial intelligence (AI), capable of analyzing vast volume of data rapidly, presents a promising solution to optimize literature screening for systematic reviews (SRs). Using the INSIDE (artificial INtelligence to Support Informed DEcision making) platform, we compared the performance of AI against the "gold standard" traditional SR method in the context of prostate cancer (PC) to assess whether AI could potentially improve efficiency and quality of screening.

METHODS: Publications from traditional screening of four SRs (focused on PC therapies and potential cardiotoxicity) were compared with the AI-based approach. Publications were ranked based on relevance scores. Work saved over …

Hand Swelling And Other Non-Raynaud Phenomenon Symptoms As The Initial Presentation Of Systemic Sclerosis: Prevalence And Clinical Associations In Two Us Cohorts, Iqtidar Hanif, Shervin Assassi, Maureen D Mayes, Zsuzsanna H Mcmahan, Meng Zhang, Julio Charles, John M Vanburen, Jessica S Alvey, Kimia Ghaffari, Elana J Bernstein, Flavia V Castelino, Lorinda Chung, Luke Evnin, Tracy M Frech, Jessica K Gordon, Faye N Hant, Laura K Hummers, Dinesh Khanna, Kimberly S Lakin, Dorota Lebiedz-Odrobina, Yiming Luo, Ashima Makol, Jerry A Molitor, Duncan F Moore, Carrie Richardson, Nora Sandorfi, Ami A Shah, Ankoor Shah, Victoria K Shanmugam, Virginia D Steen, Elizabeth R Volkmann, Carleigh Zahn, Brian Skaug

Faculty, Staff and Student Publications

Objective: Raynaud phenomenon (RP) is often the initial clinical manifestation of systemic sclerosis (SSc), but some patients develop other manifestations first. To help elucidate the diversity of SSc presentation in its early stages, we describe the initial clinical manifestations and antinuclear antibody (ANA) profiles of patients in two early SSc cohorts.

Methods: All patient data in the Genetics vs Environment in Scleroderma Outcomes Study (GENISOS) and Collaborative National Quality and Efficacy Registry (CONQUER) cohorts were reviewed. Both studies enrolled patients within five years of the first non-RP symptom.

Results: In GENISOS and CONQUER, respectively, 194 (44.2%) of 439 and 292 …

Structural-Level Stigma Within Emergency Food Assistance Programs: Perspectives From Delaware And Pennsylvania, Mckenna M Halverson, Evyn Y Appel, Valerie A Earnshaw, Raquelle Powell, Grace Sands, Nithila Chrisostam, Shreela V Sharma, Allison Karpyn

Faculty, Staff and Student Publications

To characterize the ways in which structural stigma manifests within emergency food program settings.

Methods : We conducted 30-minute semi-structured interviews with 18 emergency food program clients in Pennsylvania and Delaware between August and December of 2024. The discussion guide included open-ended questions regarding client experiences of structural stigma, with an emphasis on issues of access and quality. Demographic data and household food insecurity (Hunger Vital Sign) were also captured. A hybrid inductive and deductive coding approach was used to analyze the data.

Results : Structural stigma is a persistent issue within emergency food program environments, impacting both participant access …

Exploring The Future Of Occupational Safety Research: A Strategic Foresight Approach, Jessica M K Streit, Sarah A Felknor, Nicole T Edwards, John J Howard

Faculty, Staff and Student Publications

A team from the U.S. National Institute for Occupational Safety and Health conducted a strategic foresight project to explore the future of occupational safety research (OSR). Data collected via systematic horizon scanning and key informant interviews were synthesized into six drivers of OSR change: (1) technological advancement, (2) partnerships and public trust, (3) prioritizing research investments, (4) safety and health integration, (5) data and science quality, and (6) worker protections. These drivers served as the basis for envisioning four potential OSR futures. Analysis of the resulting scenarios identified opportunities to enhance and advance OSR methods and approaches, innovation, systems thinking, …

Mitigating Food Insecurity-Related Stigma: A Review Of Intervention Strategies, Evyn Y Appel, Mckenna M Halverson, Valerie A Earnshaw, Tania Cruz Cordero, Maya Rozin, Raquelle Powell, Grace Sands, Nithila Chrisostam, Sarah E Katz, Shreela V Sharma, Allison Karpyn

Faculty, Staff and Student Publications

Objective: To characterize intervention strategies addressing food insecurity-related stigma implemented in federal nutrition programs (e.g. SNAP, WIC) and emergency food programs (e.g. food pantries, food cupboards) within high income countries.

Methods: Six databases (PubMed, PsychINFO, Web of Science, CINAHL, Sociological Abstracts, Dissertations and Theses Global) and the Internet were searched through September 2024. Data on study characteristics and stigma intervention characteristics were extracted with a structured template. Descriptive statistics and thematic analysis were used.

Results: The review found 46 intervention strategies across 18 articles. The majority of articles were based in the United States (89.9%) with the remaining portion from …

Stomach Cancer Incidence In Asians As Compared To Other Ethnic Populations Over Time From 2000 To 2021 In Seer Areas Of The United States, Zhuoyun Li, Xianglin L Du

Faculty, Staff and Student Publications

Background: Stomach cancer is the fourth leading cause of cancer-related deaths globally, but its late-stage detection and its lack of early symptoms are still the main challenges ahead. Limited research has focused on detailed racial and ethnic disparities in stomach cancer incidence within the United States. This study aims to address these gaps by analyzing age-adjusted stomach cancer incidence rates from 2000 to 2021.

Methods: Using data from the US Surveillance, Epidemiology, and End Results (SEER) program (2000-2021), we identified a cohort of 138,628 individuals diagnosed with incident stomach cancer at age ≥ 20. Both crude and age-adjusted models were …

Estimating Daily Air Quality Exposure Of The Aging And Dementia Population, Wan-Tai Michael Au-Yeung, Moiz Usmani, Ryan Ramphul, Chao-Yi Wu, Hiroko Dodge, Joel Steele, Zachary Beattie, Jeffrey Kaye

Faculty, Staff and Student Publications

Background

To understand the effect of air quality on cognition, air quality measurements should reflect real-world exposure. Currently, air quality exposure is derived from outdoor air quality monitors despite older adults spending most of their time indoors.

Objective

To examine if there are discrepancies between indoor particulate matter 2.5 (PM2.5) at older adults’ personal residences, PM2.5 levels measured with nearest outdoor public air monitors, and remotely accessed gridded ensemble air quality data.

Methods

PM2.5 levels collected in older adults’ residences, collected from the nearest outdoor public air quality monitors and ensemble data from Hazardous Air Quality Ensemble System (HAQES) were …

Deciphering Rna Modification And Post-Transcriptional Regulation With Netrnapan, Haodong Xu, Wankun Deng, Ruifeng Hu, Binfeng Liu, Wenchao Zhang, Lujuan Wang, Lin Qi, Xiaolei Ren, Chao Tu, Zhihong Li, Zhongming Zhao

Faculty, Staff and Student Publications

RNA modification, which is evolutionarily conserved, is crucial for modulating various biological functions and disease pathogenesis. High resolution transcriptome-wide mapping of RNA modifications has facilitated both data resources and computational prediction of RNA modification. While these prediction algorithms are promising, they are limited in interpretability or generalizability, or the capacity for discovering novel post-transcriptional regulations. Here, we present NetRNApan, a deep learning framework for RNA modification site prediction, motif discovery and trans-regulatory factor identification. Using m5U profiles generated by FICC-seq and miCLIP-seq technologies and single-base resolution m6A sites from multiple experiments as cases, we demonstrated the accuracy of NetRNApan with …

Nonsteroidal Anti-Inflammatory Drug Use And Acute Kidney Injury In Nephrectomies: A Retrospective Propensity Score-Matched Cohort Study, Chun-Yan Ye, Long-Yan Li, Min-Jing Yang, Xing-Yang Liu, Ning Luo, Jing-Han Wu, Yu-Jie Xiao, Daniel I Sessler, E Wang

Faculty, Staff and Student Publications

Introduction: Nonsteroidal anti-inflammatory drugs (NSAID) are analgesic and spare opioids, but it remains unclear whether perioperative NSAID use worsens renal function after nephrectomy. We therefore tested the hypothesis that perioperative use of NSAID is associated with acute kidney injury (AKI) after nephrectomy surgery.

Methods: This retrospective cohort study included patients ≥18 years old who had partial or radical nephrectomies. Patients who were given intravenous NSAIDs for postoperative analgesia were defined as one group, whereas reference patients did not use any NSAIDs. The primary outcome was the occurrence of postoperative acute kidney injury (AKI), as defined by the Kidney Disease: Improving …

Aligning Surgical Decisions With Older Adults' Outcome Goals, Aanand D Naik, Margaret L Schwarze, Jack Banks, Suha Soni, Salman A Arain, Parag Goyal, Daniel D Matlock, Rachel Lampert, Mary E Tinetti

Faculty, Staff and Student Publications

No abstract provided.

Evaluating Interactions Between National And Subnational Governments In The Czech Republic For Physical Activity Policy Development And Implementation, Michael Pratt, Juliana Mejía-Grueso, Eugen Resendiz, Aleš Jakubec, Zdeněk Hamřík, Deborah Salvo, Andrea Ramírez Varela, Josef Mitáš

Faculty, Staff and Student Publications

Background: Most countries now have physical activity (PA) policies but translating them into action at national and subnational levels remains poor. To better understand the disconnect, the "Interaction between National and Local Government Levels in Development and Implementation of Physical Activity Policies Tool" (INTEGRATE-PA-Pol) was developed by the Global Observatory for Physical Activity (GoPA!).

Methods: The Czech Republic was chosen as a European pilot site based on existing research capacity and relationships. The INTEGRATE-PA-Pol tool was translated and adapted for use in the country. This questionnaire-based tool has 8 components assessing government levels, political system, and sectors across the 5 …

A Longitudinal Study Of The Association Between E-Cigarette Use Contexts And Alcohol Use Problems Among College Students, Tzung-Shiang Ou, Anne Buu, James J Yang, Hsien-Chang Lin

Faculty, Staff and Student Publications

Objective: Previous studies had explored the associations between e-cigarette use and alcohol use problems, yet they did not fully consider e-cigarette use contexts. This longitudinal study conducted a prospective examination of e-cigarette use contexts and alcohol use problems among college students.

Participants: College e-cigarette users at three public universities from Fall 2019 to Fall 2020 were included (N = 377).

Methods: A linear mixed model with a random intercept and random slope was employed to examine the longitudinal associations.

Results: Higher frequencies of e-cigarette use (β = 0.38, p < 0.001), being hooked on e-cigarettes (β = 0.96, p < 0.01), using e-cigarettes for socializing purposes (β = 0.58, p < 0.05), and more occasions of co-using e-cigarettes with alcohol (β …