Digital Commons Network^™

Patient And Dentist Perspectives On Collecting Patient Reported Outcomes After Painful Dental Procedures In The National Dental Pbrn, Elsbeth Kalenderian, Sayali Tungare, Urvi Mehta, Sharmeen Hamid, Rahma Mungia, Alfa-Ibrahim Yansane, David Holmes, Kim Funkhouser, Ana M Ibarra-Noriega, Janelle Urata, D Brad Rindal, Heiko Spallek, Joel White, Muhammad F Walji

Faculty, Staff and Student Publications

BACKGROUND: Dental Patient Reported Outcomes (PROs) relate to a dental patient's subjective experience of their oral health. How practitioners and patients value PROs influences their successful use in practice.

METHODS: Semi-structured interviews were conducted with 22 practitioners and 32 patients who provided feedback on using a mobile health (mHealth) platform to collect the pain experience after dental procedures. A themes analysis was conducted to identify implementation barriers and facilitators.

RESULTS: Five themes were uncovered: (1) Sense of Better Care. (2) Tailored Follow-up based on the dental procedure and patient's pain experience. (3) Effective Messaging and Alerts. (4) Usable Digital Platform. …

Androgen Drives Melanoma Invasiveness And Metastatic Spread By Inducing Tumorigenic Fucosylation, Qian Liu, Emma Adhikari, Daniel K Lester, Bin Fang, Joseph O Johnson, Yijun Tian, Andrea T Mockabee-Macias, Victoria Izumi, Kelly M Guzman, Michael G White, John M Koomen, Jennifer A Wargo, Jane L Messina, Jianfei Qi, Eric K Lau

Faculty, Staff and Student Publications

Melanoma incidence and mortality rates are historically higher for men than women. Although emerging studies have highlighted tumorigenic roles for the male sex hormone androgen and its receptor (AR) in melanoma, cellular and molecular mechanisms underlying these sex-associated discrepancies are poorly defined. Here, we delineate a previously undisclosed mechanism by which androgen-activated AR transcriptionally upregulates fucosyltransferase 4 (FUT4) expression, which drives melanoma invasiveness by interfering with adherens junctions (AJs). Global phosphoproteomic and fucoproteomic profiling, coupled with in vitro and in vivo functional validation, further reveal that AR-induced FUT4 fucosylates L1 cell adhesion molecule (L1CAM), which is required for FUT4-increased metastatic …

[Summary: International Consensus Statement On Nomenclature And Classification Of The Congenital Bicuspid Aortic Valve And Its Aortopathy, For Clinical, Surgical, Interventional And Research Purposes], Hector I Michelena, Alessandro Della Corte, Arturo Evangelista, Joseph J Maleszewski, William D Edwards, Mary J Roman, Richard B Devereux, Borja Fernández, Federico M Asch, Alex J Barker, Lilia M Sierra, Laurent De Kerchove, Susan M Fernandes, Paul W M Fedak, Evaldas Girdauskas, Victoria Delgado, Suhny Abbara, Emmanuel Lansac, Siddharth K Prakash, Malenka M Bissell, Bogdan A Popescu, Michael D Hope, Marta Sitges, Vinod H Thourani, Phillippe Pibarot, Krishnaswamy Chandrasekaran, Patrizio Lancellotti, Michael A Borger, John K Forrest, John Webb, Dianna M Milewicz, Raj Makkar, Martin B Leon, Stephen P Sanders, Michael Markl, Victor A Ferrari, William C Roberts, Jae-Kwan Song, Philipp Blanke, Charles S White, Samuel Siu, Lars G Svensson, Alan C Braverman, Joseph Bavaria, Thoralf M Sundt, Gebrine El Khoury, Ruggero De Paulis, Maurice Enriquez-Sarano, Jeroen J Bax, Catherine M Otto, Hans-Joachim Schäfers

Faculty, Staff and Student Publications

This consensus of nomenclature and classification for congenital bicuspid aortic valve and its aortopathy is evidence-based and intended for universal use by physicians (both pediatricians and adults), echocardiographers, advanced cardiovascular imaging specialists, interventional cardiologists, cardiovascular surgeons, pathologists, geneticists, and researchers spanning these areas of clinical and basic research. In addition, as long as new key and reference research is available, this international consensus may be subject to change based on evidence-based data1.

Examining Associations Between School-Level Determinants And The Implementation Of Physical Activity Opportunities, Derek W Craig, Timothy J Walker, Shreela V Sharma, Paula Cuccaro, Natalia I Heredia, Andjelka Pavlovic, Laura F Defina, Harold W Kohl, Maria E Fernandez

Faculty, Staff and Student Publications

School-based physical activity (PA) opportunities can help students engage in greater amounts of daily PA, meet PA guidelines, and lead to improved health and educational outcomes. However, we do not completely understand the organizational challenges to implementing these opportunities successfully. This exploratory study examined associations between school-level determinants and the implementation of school-based PA opportunities. We analyzed cross-sectional survey data from schools (n = 46) participating in the Healthy Zone School Program (HZSP) (Dallas, Texas, USA) during 2019-2020. Respondents completed an electronic survey that included measures of school-level determinants (e.g. culture, leadership, priority) and the implementation of school-based PA opportunities. …

Rapid Anti-Myeloma Activity By T Cells Expressing An Anti-Bcma Car With A Human Heavy-Chain-Only Antigen-Binding Domain, Lekha Mikkilineni, Danielle A Natrakul, Norris Lam, Elisabet E Manasanch, Jennifer Mann, Katherine A Weissler, Nathan Wong, Jennifer N Brudno, Stephanie L Goff, James C Yang, Micaela Ganaden, Rashmika Patel, Zhili Zheng, Jared J Gartner, Kathryn R Martin, Hao-Wei Wang, Constance M Yuan, Tyler Lowe, Irina Maric, Lipei Shao, Ping Jin, David F Stroncek, Steven L Highfill, Steven A Rosenberg, James N Kochenderfer

Faculty, Staff and Student Publications

Multiple myeloma (MM) is a rarely curable malignancy of plasma cells. MM expresses B cell maturation antigen (BCMA). We developed a fully human anti-BCMA chimeric antigen receptor (CAR) with a heavy-chain-only antigen-recognition domain, a 4-1BB domain, and a CD3ζ domain. The CAR was designated FHVH33-CD8BBZ. We conducted the first-in-humans clinical trial of T cells expressing FHVH33-CD8BBZ (FHVH-T). Twenty-five patients with relapsed MM were treated. The stringent complete response rate (sCR) was 52%. Median progression-free survival (PFS) was 78 weeks. Of 24 evaluable patients, 6 (25%) had a maximum cytokine-release syndrome (CRS) grade of 3; no patients had CRS of greater …

Aspscr1-Tfe3 Reprograms Transcription By Organizing Enhancer Loops Around Hexameric Vcp/P97, Amir Pozner, Li Li, Shiv Prakash Verma, Shuxin Wang, Jared J Barrott, Mary L Nelson, Jamie S E Yu, Gian Luca Negri, Shane Colborne, Christopher S Hughes, Ju-Fen Zhu, Sydney L Lambert, Lara S Carroll, Kyllie Smith-Fry, Michael G Stewart, Sarmishta Kannan, Bodrie Jensen, Cini M John, Saif Sikdar, Hongrui Liu, Ngoc Ha Dang, Jennifer Bourdage, Jinxiu Li, Jeffery M Vahrenkamp, Katelyn L Mortenson, John S Groundland, Rosanna Wustrack, Donna L Senger, Franz J Zemp, Douglas J Mahoney, Jason Gertz, Xiaoyang Zhang, Alexander J Lazar, Martin Hirst, Gregg B Morin, Torsten O Nielsen, Peter S Shen, Kevin B Jones

Faculty, Staff and Student Publications

The t(X,17) chromosomal translocation, generating the ASPSCR1::TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCCs), frustrating efforts to identify therapeutic targets for these rare cancers. Here, proteomic analysis identifies VCP/p97, an AAA+ ATPase with known segregase function, as strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1::TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1::TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology. Specifically, VCP co-distributes with ASPSCR1::TFE3 across chromatin in association with enhancers genome-wide. VCP presence, its hexameric assembly, and its …

Antibody-Conjugated Polymersomes With Encapsulated Indocyanine Green J-Aggregates And High Near-Infrared Absorption For Molecular Photoacoustic Cancer Imaging, Mohammed R Kawelah, Sangheon Han, Ceren Atila Dincer, Jongyeong Jeon, Joel Brisola, Aasim F Hussain, Ananthakrishnan S Jeevarathinam, Richard Bouchard, Alexander E Marras, Thomas M Truskett, Konstantin V Sokolov, Keith P Johnston

Faculty, Staff and Student Publications

Imaging plays a critical role in all stages of cancer care from early detection to diagnosis, prognosis, and therapy monitoring. Recently, photoacoustic imaging (PAI) has started to emerge into the clinical realm due to its high sensitivity and ability to penetrate tissues up to several centimeters deep. Herein, we encapsulated indocyanine green J (ICGJ) aggregate, one of the only FDA-approved organic exogenous contrast agents that absorbs in the near-infrared range, at high loadings up to ∼40% w/w within biodegradable polymersomes (ICGJ-Ps) composed of poly(lactide-

The Hsp90-Myc-Cdk9 Network Drives Therapeutic Resistance In Mantle Cell Lymphoma, Fangfang Yan, Vivian Jiang, Alexa Jordan, Yuxuan Che, Yang Liu, Qingsong Cai, Yu Xue, Yijing Li, Joseph Mcintosh, Zhihong Chen, Jovanny Vargas, Lei Nie, Yixin Yao, Heng-Huan Lee, Wei Wang, Johnnelson R Bigcal, Maria Badillo, Jitendra Meena, Christopher Flowers, Jia Zhou, Zhongming Zhao, Lukas M Simon, Michael Wang

Faculty, Staff and Student Publications

Brexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton's tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma. However, many patients relapse post CAR-T therapy with dismal outcomes. To dissect the underlying mechanisms of sequential resistance to BTKi and CAR-T therapy, we performed single-cell RNA sequencing analysis for 66 samples from 25 patients treated with BTKi and/or CAR-T therapy and conducted in-depth bioinformatics™ analysis. Our analysis revealed that MYC activity progressively increased with sequential resistance. HSP90AB1 (Heat shock protein 90 alpha family class B member 1), a MYC target, was identified as early driver of CAR-T resistance. CDK9 …

Shewanella Phage Encoding A Putative Anti-Crispr-Like Gene Represents A Novel Potential Viral Family, Hongmin Wang, Kaiyang Zheng, Min Wang, Keran Ma, Linyi Ren, Ruizhe Guo, Lina Ma, Hong Zhang, Yundan Liu, Yao Xiong, Miaolan Wu, Hongbing Shao, Yeong Yik Sung, Wen Jye Mok, Li Lian Wong, Andrew Mcminn, Yantao Liang

Faculty, Staff and Student Publications

Shewanella is a prevalent bacterial genus in deep-sea environments including marine sediments, exhibiting diverse metabolic capabilities that indicate its significant contributions to the marine biogeochemical cycles. However, only a few Shewanella phages were isolated and deposited in the NCBI database. In this study, we report the isolation and characterization of a novel Shewanella phage, vB_SbaS_Y11, that infects Shewanella KR11 and was isolated from the sewage in Qingdao, China. Transmission electron microscopy revealed that vB_SbaS_Y11 has an icosahedral head and a long tail. The genome of vB_SbaS_Y11 is a linear, double-stranded DNA with a length of 62,799 bp and a G+C …

Dynamic Prognosis Prediction For Patients On Dapt After Drug-Eluting Stent Implantation: Model Development And Validation, Fang Li, Laila Rasmy, Yang Xiang, Jingna Feng, Ahmed Abdelhameed, Xinyue Hu, Zenan Sun, David Aguilar, Abhijeet Dhoble, Jingcheng Du, Qing Wang, Shuteng Niu, Yifang Dang, Xinyuan Zhang, Ziqian Xie, Yi Nian, Jianping He, Yujia Zhou, Jianfu Li, Mattia Prosperi, Jiang Bian, Degui Zhi, Cui Tao

Faculty, Staff and Student Publications

BACKGROUND: The rapid evolution of artificial intelligence (AI) in conjunction with recent updates in dual antiplatelet therapy (DAPT) management guidelines emphasizes the necessity for innovative models to predict ischemic or bleeding events after drug-eluting stent implantation. Leveraging AI for dynamic prediction has the potential to revolutionize risk stratification and provide personalized decision support for DAPT management.

METHODS AND RESULTS: We developed and validated a new AI-based pipeline using retrospective data of drug-eluting stent-treated patients, sourced from the Cerner Health Facts data set (n=98 236) and Optum's de-identified Clinformatics Data Mart Database (n=9978). The 36 months following drug-eluting stent implantation were …

Unsatisfactory Fecal Immunochemical Tests For Colorectal Cancer Screening: Prevalence, Reasons, And Subsequent Testing, Po-Hong Liu, Rasmi G Nair, Celette Sugg Skinner, Caitlin C Murphy, Eric J Kim, Cynthia Ortiz, Lei Wang, Ellen Hu, Jacquelyn M Lykken, Theodore R Levin, Beverly B Green, Erin E Hahn, Noel Santini, Ethan A Halm

Faculty, Staff and Student Publications

BACKGROUND: Fecal immunochemical test (FIT) is an effective colorectal cancer screening modality. Little is known about prevalence, reasons, and testing after unsatisfactory FIT, or a FIT that cannot be processed by the laboratory due to inadequate stool specimen or incomplete labeling.

METHODS: Our retrospective cohort study examined unsatisfactory FIT among average-risk individuals aged 50-74 years in a large, integrated, safety-net health system who completed an index FIT from 2010 to 2019. We determined prevalence of unsatisfactory FIT and categorized reasons hierarchically. We used multivariable logistic regression models to identify factors associated with: (i) unsatisfactory FIT; and (ii) subsequent testing within …

Oral Microbiome Associated With Differential Ratios Of Porphyromonas Gingivalis And Streptococcus Cristatus, Qingguo Wang, Bing-Yan Wang, Siddharth Pratap, Hua Xie

Faculty, Staff and Student Publications

Periodontitis has recently been defined as a dysbiotic disease caused by an imbalanced oral microbiota. The transition from commensal microbial communities to periodontitis-associated ones requires colonization by specific pathogens, including Porphyromonas gingivalis. We previously reported an antagonistic relationship between Streptococcus cristatus and P. gingivalis. To determine the role of S. cristatus in altering the interactions of P. gingivalis with other oral bacteria in a complex context, we collected dental plaque samples from patients with periodontitis and assigned them to two groups based on the ratios of S. cristatus and P. gingivalis. We then characterized the microbial profiles …

Parenting Influences On Frontal Lobe Gray Matter And Preterm Toddlers' Problem-Solving Skills, Josselyn S Muñoz, Megan E Giles, Kelly A Vaughn, Ying Wang, Susan H Landry, Johanna R Bick, Dana M Demaster

Faculty, Staff and Student Publications

Children born preterm often face challenges with self-regulation during toddlerhood. This study examined the relationship between prematurity, supportive parent behaviors, frontal lobe gray matter volume (GMV), and emotion regulation (ER) among toddlers during a parent-assisted, increasingly complex problem-solving task, validated for this age range. Data were collected from preterm toddlers (n = 57) ages 15–30 months corrected for prematurity and their primary caregivers. MRI data were collected during toddlers’ natural sleep. The sample contained three gestational groups: 22–27 weeks (extremely preterm; EPT), 28–33 weeks (very preterm; VPT), and 34–36 weeks (late preterm; LPT). Older toddlers became more compliant as …

Large-Scale Proteomics Identifies Novel Biomarkers And Circulating Risk Factors For Aortic Stenosis, Khaled Shelbaya, Victoria Arthur, Yimin Yang, Pranav Dorbala, Leo Buckley, Brian Claggett, Hicham Skali, Line Dufresne, Ta-Yu Yang, James C Engert, George Thanassoulis, James Floyd, Thomas R Austin, Anna Bortnick, Jorge Kizer, Renata C C Freitas, Sasha A Singh, Elena Aikawa, Ron C Hoogeveen, Christie Ballantyne, Bing Yu, Josef Coresh, Michael J Blaha, Kunihiro Matsushita, Amil M Shah

Faculty, Staff and Student Publications

Background: Limited data exist regarding risk factors for aortic stenosis (AS). The plasma proteome is a promising phenotype for discovery of novel biomarkers and potentially causative mechanisms.

Objectives: The aim of this study was to discover novel biomarkers with potentially causal associations with AS.

Methods: We measured 4,877 plasma proteins (SomaScan aptamer-affinity assay) among ARIC (Atherosclerosis Risk In Communities) study participants in mid-life (visit 3 [V3]; n = 11,430; age 60 ± 6 years) and in late-life (V5; n = 4,899; age 76 ± 5 years). We identified proteins cross-sectionally associated with aortic valve (AV) peak velocity (AVmax) and dimensionless …

Real-World Trends, Rural-Urban Differences, And Socioeconomic Disparities In Utilization Of Narrow Versus Broad Next-Generation Sequencing Panels, Yiqing Zhao, Anastasios Dimou, Zachary C Fogarty, Jun Jiang, Hongfang Liu, William B Wong, Chen Wang

Faculty, Staff and Student Publications

UNLABELLED: Advances in genetic technology have led to the increasing use of genomic panels in precision oncology practice, with panels ranging from a couple to hundreds of genes. However, the clinical utilization and utility of oncology genomic panels, especially among vulnerable populations, is unclear. We examined the association of panel size with socioeconomic status and clinical trial matching. We retrospectively identified 9,886 eligible adult subjects in the Mayo Clinic Health System who underwent genomic testing between January 1, 2016 and June 30, 2020. Patient data were retrieved from structured and unstructured data sources of institutional collections, including cancer registries, clinical …

Serum Tumor Markers And Outcomes In Patients With Appendiceal Adenocarcinoma, Abdelrahman Yousef, Mahmoud Yousef, Mohammad A Zeineddine, Aditya More, Mohammad Fanaeian, Saikat Chowdhury, Mark Knafl, Paul Edelkamp, Ichiaki Ito, Yue Gu, Vinay Pattalachinti, Zahra Alavi Naini, Fadl A Zeineddine, Jennifer Peterson, Kristin Alfaro, Wai Chin Foo, Jeff Jin, Neal Bhutiani, Victoria Higbie, Christopher P Scally, Bryan Kee, Scott Kopetz, Drew Goldstein, Madeleine Strach, Andrew Williamson, Omer Aziz, Jorge Barriuso, Abhineet Uppal, Michael G White, Beth Helmink, Keith F Fournier, Kanwal P Raghav, Melissa W Taggart, Michael J Overman, John Paul Shen

Faculty, Staff and Student Publications

IMPORTANCE: Serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA125) have been useful in the management of gastrointestinal and gynecological cancers; however, there is limited information regarding their utility in patients with appendiceal adenocarcinoma.

OBJECTIVE: To assess the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes and pathologic and molecular features in patients with appendiceal adenocarcinoma.

DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective cohort study at a single tertiary care comprehensive cancer center. The median (IQR) follow-up time was 52 (21-101) months. Software was used to query the MD …

Impact Of Individual Level Uncertainty Of Lung Cancer Polygenic Risk Score (Prs) On Risk Stratification, Xinan Wang, Ziwei Zhang, Yi Ding, Tony Chen, Lorelei Mucci, Demetrios Albanes, Maria Teresa Landi, Neil E Caporaso, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, Gadi Rennert, Susanne Arnold, Paul Brennan, James D Mckay, John K Field, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Angeline S Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Annelie Behndig, Mikael Johansson, Angie Cox, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Rayjean J Hung, Christopher I Amos, Xihong Lin, David C Christiani

Faculty, Staff and Student Publications

BACKGROUND: Although polygenic risk score (PRS) has emerged as a promising tool for predicting cancer risk from genome-wide association studies (GWAS), the individual-level accuracy of lung cancer PRS and the extent to which its impact on subsequent clinical applications remains largely unexplored.

METHODS: Lung cancer PRSs and confidence/credible interval (CI) were constructed using two statistical approaches for each individual: (1) the weighted sum of 16 GWAS-derived significant SNP loci and the CI through the bootstrapping method (PRS-16-CV) and (2) LDpred2 and the CI through posteriors sampling (PRS-Bayes), among 17,166 lung cancer cases and 12,894 controls with European ancestry from the …

Teaching And Safety-Net Hospital Penalization In The Hospital-Acquired Condition Reduction Program, Jose A Serpa, Gretchen Gemeinhardt, Cesar A Arias, Robert O Morgan, Heidi Russell, Hongyu Miao, Cecilia M Ganduglia Cazaban

Faculty, Staff and Student Publications

IMPORTANCE: The Hospital-Acquired Condition Reduction Program (HACRP) evaluates acute care hospitals on the occurrence of patient safety events and health care-associated infections. Since its implementation, several studies have raised concerns about the overpenalization of teaching and safety-net hospitals, and although several changes in the program's methodology have been applied in the last few years, whether these changes reversed the overpenalization of teaching and safety-net hospitals is unknown.

OBJECTIVE: to determine hospital characteristics associated with HACRP penalization and penalization reversal.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study assessed data from 3117 acute care hospitals participating in the HACRP. The HACRP …

Teaching And Safety-Net Hospital Penalization In The Hospital-Acquired Condition Reduction Program, Jose A Serpa, Gretchen Gemeinhardt, Cesar A Arias, Robert O Morgan, Heidi Russell, Hongyu Miao, Cecilia M Ganduglia Cazaban

Faculty, Staff and Student Publications

IMPORTANCE: The Hospital-Acquired Condition Reduction Program (HACRP) evaluates acute care hospitals on the occurrence of patient safety events and health care-associated infections. Since its implementation, several studies have raised concerns about the overpenalization of teaching and safety-net hospitals, and although several changes in the program's methodology have been applied in the last few years, whether these changes reversed the overpenalization of teaching and safety-net hospitals is unknown.

OBJECTIVE: to determine hospital characteristics associated with HACRP penalization and penalization reversal.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study assessed data from 3117 acute care hospitals participating in the HACRP. The HACRP …

Fluvoxamine Inhibits Th1 And Th17 Polarization And Function By Repressing Glycolysis To Attenuate Autoimmune Progression In Type 1 Diabetes, Yuan Zou, Jing Zhang, Fei Sun, Qianqian Xu, Longmin Chen, Xi Luo, Ting Wang, Qing Zhou, Shu Zhang, Fei Xiong, Wen Kong, Ping Yang, Qilin Yu, Shiwei Liu, Cong-Yi Wang

Faculty, Staff and Student Publications

BACKGROUND: Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on autoimmune diseases, particularly type 1 diabetes (T1D) and the related cellular and molecular mechanisms, are yet to be addressed.

METHOD: Herein in this report, we treated NOD mice with fluvoxamine for 2 weeks starting from 10-week of age to dissect the impact of fluvoxamine on the prevention of type 1 diabetes. We compared the differences of immune …

Health Economic Consequences Associated With Covid-19-Related Delay In Melanoma Diagnosis In Europe, Lara V Maul, Dagmar Jamiolkowski, Rebecca A Lapides, Alina M Mueller, Axel Hauschild, Claus Garbe, Paul Lorigan, Jeffrey E Gershenwald, Paolo Antonio Ascierto, Georgina V Long, Michael Wang-Evers, Richard A Scolyer, Babak Saravi, Matthias Augustin, Alexander A Navarini, Stefan Legge, István B Németh, Ágnes J Jánosi, Simone Mocellin, Anita Feller, Dieter Manstein, Alexander Zink, Julia-Tatjana Maul, Alessandra Buja, Kaustubh Adhikari, Elisabeth Roider

Faculty, Staff and Student Publications

IMPORTANCE: The COVID-19 pandemic resulted in delayed access to medical care. Restrictions to health care specialists, staff shortages, and fear of SARS-CoV-2 infection led to interruptions in routine care, such as early melanoma detection; however, premature mortality and economic burden associated with this postponement have not been studied yet.

OBJECTIVE: To determine the premature mortality and economic costs associated with suspended melanoma screenings during COVID-19 pandemic lockdowns by estimating the total burden of delayed melanoma diagnoses for Europe.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter economic evaluation used population-based data from patients aged at least 18 years with invasive primary cutaneous …

Efficacy Of Novel Agents Against Cellular Models Of Familial Platelet Disorder With Myeloid Malignancy (Fpd-Mm), Christopher P Mill, Warren C Fiskus, Courtney D Dinardo, Patrick Reville, John A Davis, Christine E Birdwell, Kaberi Das, Hanxi Hou, Koichi Takahashi, Lauren Flores, Xinjia Ruan, Xiaoping Su, Sanam Loghavi, Joseph D Khoury, Kapil N Bhalla

Faculty, Staff and Student Publications

Germline, mono-allelic mutations in RUNX1 cause familial platelet disorder (RUNX1-FPD) that evolves into myeloid malignancy (FPD-MM): MDS or AML. FPD-MM commonly harbors co-mutations in the second RUNX1 allele and/or other epigenetic regulators. Here we utilized patient-derived (PD) FPD-MM cells and established the first FPD-MM AML cell line (GMR-AML1). GMR-AML1 cells exhibited active super-enhancers of MYB, MYC, BCL2 and CDK6, augmented expressions of c-Myc, c-Myb, EVI1 and PLK1 and surface markers of AML stem cells. In longitudinally studied bone marrow cells from a patient at FPD-MM vs RUNX1-FPD state, we confirmed increased chromatin accessibility and mRNA expressions of MYB, MECOM and …

Evaluation Of A Tiered Opioid Prescription Algorithm In An Eras Pathway: Exploring Opportunities For Further Refinement, M Sol Basabe, Tina S Suki, Mark F Munsell, Maria D Iniesta, Juan E Garcia Lopez, Robert Tyler Hillman, Katherine Cain, Sarah Huepenbecker, Gabriel Mena, Jolyn S Taylor, Pedro T Ramirez, Larissa A Meyer

Faculty, Staff and Student Publications

Background: Opioid over-prescription is wasteful and contributes to the opioid crisis. We implemented a personalized tiered discharge opioid protocol and education on opioid disposal to minimize over-prescription.

Objective: To evaluate the intervention by investigating opioid use post-discharge for women undergoing abdomino-pelvic surgery, and patient adherence to opioid disposal education.

Methods: We analyzed post-discharge opioid consumption among 558 patients. Eligible patients included those who underwent elective gynecologic surgery, were not taking scheduled opioids pre-operatively, and received discharge opioids according to a tiered prescribing algorithm. A survey assessing discharge opioid consumption and disposal safety knowledge was distributed on post-discharge day 21. Over-prescription …

Neonatal Intensive Care Unit Resource Use For Infants At 22 Weeks' Gestation In The Us, 2008-2021, Matthew A Rysavy, Monica M Bennett, Kaashif A Ahmad, Ravi M Patel, Zubin S Shah, Dan L Ellsbury, Reese H Clark, Veeral N Tolia

Faculty, Staff and Student Publications

IMPORTANCE: During the past decade, clinical guidance about the provision of intensive care for infants born at 22 weeks' gestation has changed. The impact of these changes on neonatal intensive care unit (NICU) resource utilization is unknown.

OBJECTIVE: To characterize recent trends in NICU resource utilization for infants born at 22 weeks' gestation compared with other extremely preterm infants (≤28 weeks' gestation) and other NICU-admitted infants.

DESIGN, SETTING, AND PARTICIPANTS: This is a serial cross-sectional study of 137 continuously participating NICUs in 29 US states from January 1, 2008, through December 31, 2021. Participants included infants admitted to the NICU. …

Hospital-Level Nicu Capacity, Utilization, And 30-Day Outcomes In Texas, David C Goodman, Patrick Stuchlik, Cecilia Ganduglia-Cazaban, Jon E Tyson, Joanna Leyenaar, Elenir B C Avritscher, Mathew Rysavy, Kanekal S Gautham, David Lynch, Therese A Stukel

Faculty, Staff and Student Publications

IMPORTANCE: Risk-adjusted neonatal intensive care unit (NICU) utilization and outcomes vary markedly across regions and hospitals. The causes of this variation are poorly understood.

OBJECTIVE: To assess the association of hospital-level NICU bed capacity with utilization and outcomes in newborn cohorts with differing levels of health risk.

DESIGN, SETTING, AND PARTICIPANTS: This population-based retrospective cohort study included all Medicaid-insured live births in Texas from 2010 to 2014 using linked vital records and maternal and newborn claims data. Participants were Medicaid-insured singleton live births (LBs) with birth weights of at least 400 g and gestational ages between 22 and 44 weeks. …

Author Correction: A Ck2 And Sumo-Dependent, Pml Nb-Involved Regulatory Mechanism Controlling Blm Ubiquitination And G-Quadruplex Resolution, Shichang Liu, Erin Atkinson, Adriana Paulucci-Holthauzen, Bin Wang

Faculty, Staff and Student Publications

No abstract provided.

Aneuploid Embryonic Stem Cells Drive Teratoma Metastasis, Rong Xiao, Deshu Xu, Meili Zhang, Zhanghua Chen, Li Cheng, Songjie Du, Mingfei Lu, Tonghai Zhou, Ruoyan Li, Fan Bai, Yue Huang

Faculty, Staff and Student Publications

Aneuploidy, a deviation of the chromosome number from euploidy, is one of the hallmarks of cancer. High levels of aneuploidy are generally correlated with metastasis and poor prognosis in cancer patients. However, the causality of aneuploidy in cancer metastasis remains to be explored. Here we demonstrate that teratomas derived from aneuploid murine embryonic stem cells (ESCs), but not from isogenic diploid ESCs, disseminated to multiple organs, for which no additional copy number variations were required. Notably, no cancer driver gene mutations were identified in any metastases. Aneuploid circulating teratoma cells were successfully isolated from peripheral blood and showed high capacities …

Nivolumab Monotherapy Or Combination With Ipilimumab With Or Without Cobimetinib In Previously Treated Patients With Pancreatic Adenocarcinoma (Checkmate 032), Margaret Callahan, Asim Amin, Frederic J Kaye, Michael A Morse, Matthew H Taylor, Katriina J Peltola, Padmanee Sharma, Eileen M O'Reilly, Stephanie Meadows Shropshire, Shaun O'Brien, Marina Tschaika, Dung T Le

Faculty, Staff and Student Publications

BACKGROUND: Pancreatic cancer is one of the deadliest cancer types and represents a major unmet medical need. CheckMate 032 investigated safety and efficacy of nivolumab monotherapy and nivolumab plus ipilimumab with/without cobimetinib in advanced/metastatic solid tumors, including pancreatic cancer.

METHODS: In the original pancreatic cancer cohort, previously treated patients (≥1 prior regimen) with advanced/metastatic pancreatic adenocarcinoma were assigned to nivolumab 3 mg/kg every 2 weeks (monotherapy arm) or nivolumab 1 mg/kg and ipilimumab 1 mg/kg or 3 mg/kg every 3 weeks for four doses, followed by nivolumab 3 mg/kg every 2 weeks (combination arm). A subsequent modified pancreatic cohort (one …

The Novel Phosphatase Nudt5 Is A Critical Regulator Of Triple-Negative Breast Cancer Growth, Jing Qian, Yanxia Ma, William M Tahaney, Cassandra L Moyer, Amanda Lanier, Jamal Hill, Darian Coleman, Negar Koupaei, Susan G Hilsenbeck, Michelle I Savage, Brent D G Page, Abhijit Mazumdar, Powel H Brown

Faculty, Staff and Student Publications

BACKGROUND: The most aggressive form of breast cancer is triple-negative breast cancer (TNBC), which lacks expression of the estrogen receptor (ER) and progesterone receptor (PR), and does not have overexpression of the human epidermal growth factor receptor 2 (HER2). Treatment options for women with TNBC tumors are limited, unlike those with ER-positive tumors that can be treated with hormone therapy, or those with HER2-positive tumors that can be treated with anti-HER2 therapy. Therefore, we have sought to identify novel targeted therapies for TNBC. In this study, we investigated the potential of a novel phosphatase, NUDT5, as a potential therapeutic target …

Identification Of New Egfr Inhibitors By Structure-Based Virtual Screening And Biological Evaluation, Shuyi Wang, Xiaotian Xu, Chuxin Pan, Qian Guo, Qinlan Li, Shanhe Wan, Zhonghuang Li, Jiajie Zhang, Xiaoyun Wu

Faculty, Staff and Student Publications

Epidermal growth factor receptor (EGFR) inhibitors have been used in clinical for the treatment of non-small-cell lung cancer for years. However, the emergence of drug resistance continues to be a major problem. To identify potential inhibitors, molecular docking-based virtual screening was conducted on ChemDiv and Enamine commercial databases using the Glide program. After multi-step VS and visual inspection, a total of 23 compounds with novel and varied structures were selected, and the predicted ADMET properties were within the satisfactory range. Further molecular dynamics simulations revealed that the reprehensive compound ZINC49691377 formed a stable complex with the allosteric pocket of EGFR …