Medical Specialties Commons^™

Preliminary Findings From The Gulf War Women’S Cohort: Reproductive And Children’S Health Outcomes Among Women Veterans, Alexa Friedman, Patricia A Janulewicz Lloyd, Jeffrey Carlson, Emily Quinn, Dylan Keating, Rosemary Toomey, Timothy Heeren, Steven S Coughlin, Glenn Markenson, Maxine Krengel, Kimberly Sullivan

Faculty, Staff and Student Publications

Reproductive outcomes, such as preterm birth, miscarriage/stillbirth, and pre-eclampsia, are understudied in veterans, particularly among Gulf War veterans (GWVs). During deployment, women GWVs were exposed to toxicant and nontoxicant exposures that may be associated with adverse reproductive and developmental outcomes. The data come from a survey of 239 participants from northeastern and southern U.S. cohorts of women veterans. The questionnaire collected information about the service history, current and past general health, reproductive and family health, demographic information, and deployment exposures. Odds ratios were computed with 95% confidence intervals between exposures in theater and reproductive/children's health outcomes. GWVs experienced adverse reproductive …

Metabolic Requirement For Got2 In Pancreatic Cancer Depends On Environmental Context, Samuel A Kerk, Lin Lin, Amy L Myers, Damien J Sutton, Anthony Andren, Peter Sajjakulnukit, Li Zhang, Yaqing Zhang, Jennifer A Jiménez, Barbara S Nelson, Brandon Chen, Anthony Robinson, Galloway Thurston, Samantha B Kemp, Nina G Steele, Megan T Hoffman, Hui-Ju Wen, Daniel Long, Sarah E Ackenhusen, Johanna Ramos, Xiaohua Gao, Zeribe C Nwosu, Stefanie Galban, Christopher J Halbrook, David B Lombard, David R Piwnica-Worms, Haoqiang Ying, Marina Pasca Di Magliano, Howard C Crawford, Yatrik M Shah, Costas A Lyssiotis

Faculty, Staff and Student Publications

Mitochondrial glutamate-oxaloacetate transaminase 2 (GOT2) is part of the malate-aspartate shuttle, a mechanism by which cells transfer reducing equivalents from the cytosol to the mitochondria. GOT2 is a key component of mutant KRAS (KRAS*)-mediated rewiring of glutamine metabolism in pancreatic ductal adenocarcinoma (PDA). Here, we demonstrate that the loss of GOT2 disturbs redox homeostasis and halts proliferation of PDA cells in vitro. GOT2 knockdown (KD) in PDA cell lines in vitro induced NADH accumulation, decreased Asp and α-ketoglutarate (αKG) production, stalled glycolysis, disrupted the TCA cycle, and impaired proliferation. Oxidizing NADH through chemical or genetic means resolved the redox imbalance …

Immunophenotypic And Molecular Features Of Acute Myeloid Leukemia With Plasmacytoid Dendritic Cell Differentiation Are Distinct From Blastic Plasmacytoid Dendritic Cell Neoplasm, Wei Wang, Jie Xu, Joseph D Khoury, Naveen Pemmaraju, Hong Fang, Roberto N Miranda, C Cameron Yin, Siba El Hussein, Fuli Jia, Zhenya Tang, Shimin Hu, Marina Konopleva, L Jeffrey Medeiros, Sa A Wang

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with ≥2% plasmacytoid dendritic cells (pDC) has been recently described as AML with pDC differentiation (pDC-AML) characterized by pDC expansion with frequent RUNX1 mutations. In this study, we investigated a cohort of 53 pDC-AML cases representing about 3% of all AML cases. We characterized their immunophenotype and genetic profiles and compared these findings with blastic plasmacytoid dendritic cell neoplasm (BPDCN). pDC-differentiation/expansion was preferentially observed in AML with an immature myeloid or myelomonocytic immunophenotype, where myeloblasts were frequently positive for CD34 (98%), CD117 (94%), HLA-DR (100%) and TdT (79%), with increased CD123 (89%) expression. The median number …

Multi-Modal Molecular Programs Regulate Melanoma Cell State, Miles C Andrews, Junna Oba, Chang-Jiun Wu, Haifeng Zhu, Tatiana Karpinets, Caitlin A Creasy, Marie-Andrée Forget, Xiaoxing Yu, Xingzhi Song, Xizeng Mao, A Gordon Robertson, Gabriele Romano, Peng Li, Elizabeth M Burton, Yiling Lu, Robert Szczepaniak Sloane, Khalida M Wani, Kunal Rai, Alexander J Lazar, Lauren E Haydu, Matias A Bustos, Jianjun Shen, Yueping Chen, Margaret B Morgan, Jennifer A Wargo, Lawrence N Kwong, Cara L Haymaker, Elizabeth A Grimm, Patrick Hwu, Dave S B Hoon, Jianhua Zhang, Jeffrey E Gershenwald, Michael A Davies, P Andrew Futreal, Chantale Bernatchez, Scott E Woodman

Faculty, Staff and Student Publications

Melanoma cells display distinct intrinsic phenotypic states. Here, we seek to characterize the molecular regulation of these states using multi-omic analyses of whole exome, transcriptome, microRNA, long non-coding RNA and DNA methylation data together with reverse-phase protein array data on a panel of 68 highly annotated early passage melanoma cell lines. We demonstrate that clearly defined cancer cell intrinsic transcriptomic programs are maintained in melanoma cells ex vivo and remain highly conserved within melanoma tumors, are associated with distinct immune features within tumors, and differentially correlate with checkpoint inhibitor and adoptive T cell therapy efficacy. Through integrative analyses we demonstrate …

Optical Control Of Protein Delivery And Partitioning In The Nucleolus, Peng Tan, Tingting Hong, Xiaoli Cai, Wenbo Li, Yun Huang, Lian He, Yubin Zhou

Faculty, Staff and Student Publications

The nucleolus is a subnuclear membraneless compartment intimately involved in ribosomal RNA synthesis, ribosome biogenesis and stress response. Multiple optogenetic devices have been developed to manipulate nuclear protein import and export, but molecular tools tailored for remote control over selective targeting or partitioning of cargo proteins into subnuclear compartments capable of phase separation are still limited. Here, we report a set of single-component photoinducible nucleolus-targeting tools, designated pNUTs, to enable rapid and reversible nucleoplasm-to-nucleolus shuttling, with the half-lives ranging from milliseconds to minutes. pNUTs allow both global protein infiltration into nucleoli and local delivery of cargoes into the outermost layer …

Tp53 Copy Number And Protein Expression Inform Mutation Status Across Risk Categories In Acute Myeloid Leukemia, Mehrnoosh Tashakori, Tapan Kadia, Sanam Loghavi, Naval Daver, Rashmi Kanagal-Shamanna, Sherry Pierce, Dawen Sui, Peng Wei, Farnoosh Khodakarami, Zhenya Tang, Mark Routbort, Carol A Bivins, Elias J Jabbour, L Jeffrey Medeiros, Kapil Bhalla, Hagop M Kantarjian, Farhad Ravandi, Joseph D Khoury

Faculty, Staff and Student Publications

Mutant TP53 is an adverse risk factor in acute myeloid leukemia (AML), but large-scale integrated genomic-proteomic analyses of TP53 alterations in patients with AML remain limited. We analyzed TP53 mutational status, copy number (CN), and protein expression data in AML (N = 528) and provide a compilation of mutation sites and types across disease subgroups among treated and untreated patients. Our analysis shows differential hotspots in subsets of AML and uncovers novel pathogenic variants involving TP53 splice sites. In addition, we identified TP53 CN loss in 70.2% of TP53-mutated AML cases, which have more deleterious TP53 mutations, as well as …

Lncrna-Associated Genetic Etiologies Are Shared Between Type 2 Diabetes And Cancers In The Uae Population, Roberta Giordo, Rida Gulsha, Sarah Kalla, George A Calin, Leonard Lipovich

Faculty, Staff and Student Publications

Numerous epidemiological studies place patients with T2D at a higher risk for cancer. Many risk factors, such as obesity, ageing, poor diet and low physical activity, are shared between T2D and cancer; however, the biological mechanisms linking the two diseases remain largely unknown. The advent of genome wide association studies (GWAS) revealed large numbers of genetic variants associated with both T2D and cancer. Most significant disease-associated variants reside in non-coding regions of the genome. Several studies show that single nucleotide polymorphisms (SNPs) at or near long non-coding RNA (lncRNA) genes may impact the susceptibility to T2D and cancer. Therefore, the …

Small Rna Signatures Of Acute Ischemic Stroke In L1cam Positive Extracellular Vesicles, Michael A Lopez, Ying Si, Xianzhen Hu, Valentyna Williams, Fuad Qushair, Jackson Carlyle, Lyndsy Alesce, Michael Conklin, Shawn Gilbert, Marcas M Bamman, Matthew S Alexander, Peter H King

Faculty, Staff and Student Publications

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by skeletal muscle instability, progressive muscle wasting, and fibrosis. A major driver of DMD pathology stems from aberrant upregulation of transforming growth factor β (TGFβ) signaling. In this report, we investigated the major transducers of TGFβ signaling, i.e., receptor Smads (R-Smads), in DMD patient skeletal muscle and observed a 48-fold increase in Smad8 mRNA. Smad1, Smad2, Smad3, and Smad5 mRNA were only minimally increased. A similar pattern was observed in the muscle from the mdx5cv mouse. Western blot analysis showed upregulation of phosphorylated Smad1, Smad5, and Smad8 …

Dissecting The Treatment-Naive Ecosystem Of Human Melanoma Brain Metastasis, Jana Biermann, Johannes C Melms, Amit Dipak Amin, Yiping Wang, Lindsay A Caprio, Alcida Karz, Somnath Tagore, Irving Barrera, Miguel A Ibarra-Arellano, Massimo Andreatta, Benjamin T Fullerton, Kristjan H Gretarsson, Varun Sahu, Vaibhav S Mangipudy, Trang T T Nguyen, Ajay Nair, Meri Rogava, Patricia Ho, Peter D Koch, Matei Banu, Nelson Humala, Aayushi Mahajan, Zachary H Walsh, Shivem B Shah, Daniel H Vaccaro, Blake Caldwell, Michael Mu, Florian Wünnemann, Margot Chazotte, Simon Berhe, Adrienne M Luoma, Joseph Driver, Matthew Ingham, Shaheer A Khan, Suthee Rapisuwon, Craig L Slingluff, Thomas Eigentler, Martin Röcken, Richard Carvajal, Michael B Atkins, Michael A Davies, Albert Agustinus, Samuel F Bakhoum, Elham Azizi, Markus Siegelin, Chao Lu, Santiago J Carmona, Hanina Hibshoosh, Antoni Ribas, Peter Canoll, Jeffrey N Bruce, Wenya Linda Bi, Praveen Agrawal, Denis Schapiro, Eva Hernando, Evan Z Macosko, Fei Chen, Gary K Schwartz, Benjamin Izar

Faculty, Staff and Student Publications

Melanoma brain metastasis (MBM) frequently occurs in patients with advanced melanoma; yet, our understanding of the underlying salient biology is rudimentary. Here, we performed single-cell/nucleus RNA-seq in 22 treatment-naive MBMs and 10 extracranial melanoma metastases (ECMs) and matched spatial single-cell transcriptomics and T cell receptor (TCR)-seq. Cancer cells from MBM were more chromosomally unstable, adopted a neuronal-like cell state, and enriched for spatially variably expressed metabolic pathways. Key observations were validated in independent patient cohorts, patient-derived MBM/ECM xenograft models, RNA/ATAC-seq, proteomics, and multiplexed imaging. Integrated spatial analyses revealed distinct geography of putative cancer immune evasion and evidence for more abundant …

Macrophage Migration Inhibitory Factor (Mif) Makes Complex Contributions To Pain-Related Hyperactivity Of Nociceptors After Spinal Cord Injury, Alexis Bavencoffe, Emily A Spence, Michael Y Zhu, Anibal Garza-Carbajal, Kerry E Chu, Ona E Bloom, Carmen W Dessauer, Edgar T Walters

Faculty, Staff and Student Publications

Neuropathic pain is a major, inadequately treated challenge for people with spinal cord injury (SCI). While SCI pain mechanisms are often assumed to be in the CNS, rodent studies have revealed mechanistic contributions from primary nociceptors. These neurons become chronically hyperexcitable after SCI, generating ongoing electrical activity that promotes ongoing pain. A major question is whether extrinsic chemical signals help to drive ongoing electrical activity after SCI. People living with SCI exhibit acute and chronic elevation of circulating levels of macrophage migration inhibitory factor (MIF), a cytokine implicated in preclinical pain models. Probable nociceptors isolated from male rats and exposed …

Vitamin E Enhances Cancer Immunotherapy By Reinvigorating Dendritic Cells Via Targeting Checkpoint Shp1, Xiangliang Yuan, Yimin Duan, Yi Xiao, Kai Sun, Yutao Qi, Yuan Zhang, Zamal Ahmed, Davide Moiani, Jun Yao, Hongzhong Li, Lin Zhang, Arseniy E Yuzhalin, Ping Li, Chenyu Zhang, Akosua Badu-Nkansah, Yohei Saito, Xianghua Liu, Wen-Ling Kuo, Haoqiang Ying, Shao-Cong Sun, Jenny C Chang, John A Tainer, Dihua Yu

Faculty, Staff and Student Publications

Despite the popular use of dietary supplements during conventional cancer treatments, their impacts on the efficacies of prevalent immunotherapies, including immune-checkpoint therapy (ICT), are unknown. Surprisingly, our analyses of electronic health records revealed that ICT-treated patients with cancer who took vitamin E (VitE) had significantly improved survival. In mouse models, VitE increased ICT antitumor efficacy, which depended on dendritic cells (DC). VitE entered DCs via the SCARB1 receptor and restored tumor-associated DC functionality by directly binding to and inhibiting protein tyrosine phosphatase SHP1, a DC-intrinsic checkpoint. SHP1 inhibition, genetically or by VitE treatment, enhanced tumor antigen cross-presentation by DCs and …

Synthetic Essentiality Of Tryptophan 2,3-Dioxygenase 2 In Apc-Mutated Colorectal Cancer, Rumi Lee, Jiexi Li, Jun Li, Chang-Jiun Wu, Shan Jiang, Wen-Hao Hsu, Deepavali Chakravarti, Peiwen Chen, Kyle A Labella, Jing Li, Denise J Spring, Di Zhao, Y Alan Wang, Ronald A Depinho

Faculty, Staff and Student Publications

Inactivation of adenomatous polyposis coli (APC) is common across many cancer types and serves as a critical initiating event in most sporadic colorectal cancers. APC deficiency activates WNT signaling, which remains an elusive target for cancer therapy, prompting us to apply the synthetic essentiality framework to identify druggable vulnerabilities for APC-deficient cancers. Tryptophan 2,3-dioxygenase 2 (TDO2) was identified as a synthetic essential effector of APC-deficient colorectal cancer. Mechanistically, APC deficiency results in the TCF4/β-catenin-mediated upregulation of TDO2 gene transcription. TDO2 in turn activates the Kyn-AhR pathway, which increases glycolysis to drive anabolic cancer cell growth and CXCL5 secretion to recruit …

A Spatiotemporal Map Of Reading Aloud, Oscar Woolnough, Cristian Donos, Aidan Curtis, Patrick S Rollo, Zachary J Roccaforte, Stanislas Dehaene, Simon Fischer-Baum, Nitin Tandon

Faculty, Staff and Student Publications

Reading words aloud is a fundamental aspect of literacy. The rapid rate at which multiple distributed neural substrates are engaged in this process can only be probed via techniques with high spatiotemporal resolution. We probed this with direct intracranial recordings covering most of the left hemisphere in 46 humans (26 male, 20 female) as they read aloud regular, exception and pseudo-words. We used this to create a spatiotemporal map of word processing and to derive how broadband γ activity varies with multiple word attributes critical to reading speed: lexicality, word frequency, and orthographic neighborhood. We found that lexicality is encoded …

Novel Markers For Liquid Biopsies In Cancer Management: Circulating Platelets And Extracellular Vesicles, Sara Corvigno, Anna Maria Johnson, Kwong-Kwok Wong, Min Soon Cho, Vahid Afshar-Kharghan, David G Menter, Anil K Sood

Faculty, Staff and Student Publications

Although radiologic imaging and histologic assessment of tumor tissues are classic approaches for diagnosis and monitoring of treatment response, they have many limitations. These include challenges in distinguishing benign from malignant masses, difficult access to the tumor, high cost of the procedures, and tumor heterogeneity. In this setting, liquid biopsy has emerged as a potential alternative for both diagnostic and monitoring purposes. The approaches to liquid biopsy include cell-free DNA/circulating tumor DNA, long and micro noncoding RNAs, proteins/peptides, carbohydrates/lectins, lipids, and metabolites. Other approaches include detection and analysis of circulating tumor cells, extracellular vesicles, and tumor-activated platelets. Ultimately, reliable use …

Arrhythmia Monitoring And Outcomes In Patients With Cardiac Sarcoidosis: Insights From The Cardiac Sarcoidosis Consortium, Edoardo Bressi, Thomas C Crawford, Frank M Bogun, Xiaokui Gu, Kenneth A Ellenbogen, Alexandra B Chicos, Henri Roukoz, Peter J Zimetbaum, Steven J Kalbfleisch, Francis D Murgatroyd, David A Steckman, Lynda E Rosenfeld, Ann C Garlitski, Kyoko Soejima, Adarsh K Bhan, Vasanth Vedantham, Timm M Dickfeld, David B De Lurgio, Pyotr G Platonov, Matthew M Zipse, Suguru Nishiuchi, Matthew L Ortman, Calambur Narasimhan, Kris K Patton, David G Rosenthal, Siddharth S Mukerji, Jarieke C Hoogendoorn, Katja Zeppenfeld, William H Sauer, Jordana Kron

Faculty, Staff and Student Publications

No abstract provided.

Modeling The Prognostic Impact Of Circulating Tumor Cells Enumeration In Metastatic Breast Cancer For Clinical Trial Design Simulation, Lorenzo Gerratana, Jean-Yves Pierga, James M Reuben, Andrew A Davis, Firas H Wehbe, Luc Dirix, Tanja Fehm, Franco Nolé, Rafael Gisbert-Criado, Dimitrios Mavroudis, Salvatore Grisanti, Jose A Garcia-Saenz, Justin Stebbing, Carlos Caldas, Paola Gazzaniga, Luis Manso, Rita Zamarchi, Marta Bonotto, Angela Fernandez De Lascoiti, Leticia De Mattos-Arruda, Michail Ignatiadis, Maria-Teresa Sandri, Daniele Generali, Carmine De Angelis, Sarah-Jane Dawson, Wolfgang Janni, Vicente Carañana, Sabine Riethdorf, Erich-Franz Solomayer, Fabio Puglisi, Mario Giuliano, Klaus Pantel, François-Clément Bidard, Massimo Cristofanilli

Faculty, Staff and Student Publications

Despite the strong prognostic stratification of circulating tumor cells (CTCs) enumeration in metastatic breast cancer (MBC), current clinical trials usually do not include a baseline CTCs in their design. This study aimed to generate a classifier for CTCs prognostic simulation in existing datasets for hypothesis generation in patients with MBC. A K-nearest neighbor machine learning algorithm was trained on a pooled dataset comprising 2436 individual MBC patients from the European Pooled Analysis Consortium and the MD Anderson Cancer Center to identify patients likely to have CTCs ≥ 5/7 mL blood (StageIVaggressive vs StageIVindolent). The model had a 65.1% accuracy and …

The Use Of Second-Generation Antipsychotics And The Changes In Physical Growth In Children And Adolescents With Perinatally Acquired Hiv, Nan Xin, Jenni Durieux, Chunxia Yang, Suzanne Wolff, Hyun-Eui Kim, Andrew Dillin

Faculty, Staff and Student Publications

The mitochondrial unfolded protein response (UPRmt) is dedicated to promoting mitochondrial proteostasis and is linked to extreme longevity. The key regulator of this process is the transcription factor ATFS-1, which, upon UPRmt activation, is excluded from the mitochondria and enters the nucleus to regulate UPRmt genes. However, the repair proteins synthesized as a direct result of UPRmt activation must be transported into damaged mitochondria that had previously excluded ATFS-1 owing to reduced import efficiency. To address this conundrum, we analyzed the role of the import machinery when the UPRmt was induced. Using in vitro and in vivo analysis of mitochondrial …

Pd-1/Pd-L1 Pathway: A Therapeutic Target In Cd30+ Large Cell Lymphomas, Wei Xie, L Jeffrey Medeiros, Shaoying Li, Guilin Tang, Guang Fan, Jie Xu

Faculty, Staff and Student Publications

The programmed death-ligands, PD-L1 and PD-L2, reside on tumor cells and can bind with programmed death-1 protein (PD-1) on T-cells, resulting in tumor immune escape. PD-1 ligands are highly expressed in some CD30+ large cell lymphomas, including classic Hodgkin lymphoma (CHL), primary mediastinal large B-cell lymphoma (PMBL), Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL), and anaplastic large cell lymphoma (ALCL). The genetic alteration of the chromosome 9p24.1 locus, the location of

Heart Transplant Recipient 1-Year Outcomes During The Covid-19 Pandemic, Gabriel Esmailian, Nikhil Patel, Jignesh K Patel, Lawrence Czer, Matthew Rafiei, Dominick Megna, Dominic Emerson, Danny Ramzy, Alfredo Trento, Joanna Chikwe, Fardad Esmailian, Jon A Kobashigawa

Faculty, Staff and Student Publications

The COVID-19 pandemic initially brought forth considerable challenges to the field of heart transplantation. To prevent the spread of the virus and protect immunocompromised recipients, our center made the following modifications to post-transplant outpatient management: eliminating early coronary angiograms, video visits for postoperative months 7, 9, and 11, and home blood draws for immunosuppression adjustments. To assess if these changes have impacted patient outcomes, the current study examines 1-year outcomes for patients transplanted during the pandemic. Between March and September 2020, we assessed 50 heart transplant patients transplanted during the pandemic. These patients were compared to patients who were transplanted …

Effects Of Combined Gentamicin And Furosemide Treatment On Cochlear Macrophages, Liana Sargsyan, Austin R Swisher, Alisa P Hetrick, Hongzhe Li

Faculty, Staff and Student Publications

Combining aminoglycosides and loop diuretics often serves as an effective ototoxic approach to deafen experimental animals. The treatment results in rapid hair cell loss with extended macrophage presence in the cochlea, creating a sterile inflammatory environment. Although the early recruitment of macrophages is typically neuroprotective, the delay in the resolution of macrophage activity can be a complication if the damaged cochlea is used as a model to study subsequent therapeutic strategies. Here, we applied a high dose combination of systemic gentamicin and furosemide in

Assessment Of Electronic Health Record For Cancer Research And Patient Care Through A Scoping Review Of Cancer Natural Language Processing, Liwei Wang, Sunyang Fu, Andrew Wen, Xiaoyang Ruan, Huan He, Sijia Liu, Sungrim Moon, Michelle Mai, Irbaz B Riaz, Nan Wang, Ping Yang, Hua Xu, Jeremy L Warner, Hongfang Liu

Faculty, Staff and Student Publications

Purpose: The advancement of natural language processing (NLP) has promoted the use of detailed textual data in electronic health records (EHRs) to support cancer research and to facilitate patient care. In this review, we aim to assess EHR for cancer research and patient care by using the Minimal Common Oncology Data Elements (mCODE), which is a community-driven effort to define a minimal set of data elements for cancer research and practice. Specifically, we aim to assess the alignment of NLP-extracted data elements with mCODE and review existing NLP methodologies for extracting said data elements.

Methods: Published literature studies were searched …

Potential Impact Of Revised Nci Eligibility Criteria Guidance: Prior Malignancy Exclusion In Breast Cancer Clinical Trials, Matthew Perez, Caitlin C Murphy, Sandi L Pruitt, Sawsan Rashdan, Asal Rahimi, David E Gerber

Faculty, Staff and Student Publications

BACKGROUND: Many individuals with cancer have survived a prior cancer and for this reason may have been excluded from clinical trials. Recent NCI guidance recommends including these individuals, especially when the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low. Using breast cancer as an example, we determined the potential effect this policy change may have on clinical trial accrual.

PATIENTS AND METHODS: We reviewed protocols of NCI-sponsored breast cancer clinical trials activated in 1991 through 2016. We quantified prevalence of prior cancer-related exclusion criteria and assessed the association with trial characteristics using Fisher's …

Vaccine Hesitancy And Betrayal Aversion, Abdelaziz Alsharawy, Esha Dwibedi, Jason Aimone, Sheryl Ball

Faculty, Staff and Student Publications

The determinants of vaccine hesitancy remain complex and context specific. Betrayal aversion occurs when an individual is hesitant to risk being betrayed in an environment involving trust. In this pre-registered vignette experiment, we show that betrayal aversion is not captured by current vaccine hesitancy measures despite representing a significant source of unwillingness to be vaccinated. Our survey instrument was administered to 888 United States residents via Amazon Mechanical Turk in March 2021. We find that over a third of participants have betrayal averse preferences, resulting in an 8-26% decline in vaccine acceptance, depending on the betrayal source. Interestingly, attributing betrayal …

Pirtobrutinib Inhibits Wild-Type And Mutant Bruton’S Tyrosine Kinase-Mediated Signaling In Chronic Lymphocytic Leukemia, Sarah Tettamanti, Maria Caterina Rotiroti, Greta Maria Paola Giordano Attianese, Silvia Arcangeli, Ronghua Zhang, Priyanka Banerjee, Giovanni Galletti, Sheighlah Mcmanus, Massimiliano Mazza, Fabio Nicolini, Giovanni Martinelli, Cristina Ivan, Tania Veliz Rodriguez, Federica Barbaglio, Lydia Scarfò, Maurilio Ponzoni, William Wierda, Varsha Gandhi, Michael Keating, Andrea Biondi, Federico Caligaris-Cappio, Ettore Biagi, Paolo Ghia, Maria Teresa Sabrina Bertilaccio

Faculty, Staff and Student Publications

Chimeric antigen receptors (CAR)-modified T cells are an emerging therapeutic tool for chronic lymphocytic leukemia (CLL). However, in patients with CLL, well-known T-cell defects and the inhibitory properties of the tumor microenvironment (TME) hinder the efficacy of CAR T cells.

We explored a novel approach combining CARs with lenalidomide, an immunomodulatory drug that tempers the immunosuppressive activity of the CLL TME. T cells from patients with CLL were engineered to express a CAR specific for CD23, a promising target antigen. Lenalidomide preserves CD23.CAR T cells in vitro effector functions in terms of antigen-specific cytotoxicity, cytokine release and proliferation. Overall, lenalidomide …

Maternal Obesity, Pregnancy Weight Gain, And Birth Weight And Risk Of Colorectal Cancer, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Minjae Lee, Timothy Zaki, Ezra Burstein, Barbara A Cohn

Faculty, Staff and Student Publications

Objective: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Obesity is a well-established risk factor for CRC, and fetal or developmental origins of obesity may underlie its effect on cancer in adulthood. We examined associations of maternal obesity, pregnancy weight gain, and birth weight and CRC in adult offspring.

Design: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California (N=18 751 live births among 14 507 mothers). Clinical information was abstracted from mothers' medical records 6 months prior to pregnancy through delivery. Diagnoses of …

Hypertension In Pregnancy And Adverse Outcomes Among Low-Risk Nulliparous People Expectantly Managed At Or After 39 Weeks: A Secondary Analysis Of A Randomized Controlled Trial, Michal Fishel Bartal, Ashish Premkumar, Madeline Murguia Rice, Uma M Reddy, Alan T N Tita, Robert M Silver, Yasser Y El-Sayed, Ronald J Wapner, Dwight J Rouse, George R Saade, John M Thorp, Maged M Costantine, Edward K Chien, Brian M Casey, Sindhu K Srinivas, Geeta K Swamy, Hyagriv N Simhan, Eunice Kennedy Shriver National Institute Of Child Health And Human Development (Nichd) Maternal-Fetal Medicine Units (Mfmu) Network

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate whether hypertensive disorders of pregnancy (HDP) among low-risk nulliparous women expectantly managed at or after 39 weeks of gestation are associated with adverse outcomes.

DESIGN: Secondary analysis of a randomised trial.

SETTING: Multicentre, USA.

POPULATION: Individuals in the expectantly managed group who delivered on or after 39 weeks.

METHODS: Multivariable analysis to estimate adjusted relative risks (aRR) for binomial outcomes, adjusted odds ratios (aOR) for multinomial outcomes and 95% CI.

MAIN OUTCOME MEASURES: Composite adverse maternal outcome including placental abruption, pulmonary oedema, postpartum haemorrhage, postpartum infection, venous thromboembolism or intensive care unit admission. Secondary outcomes included a …

Minimal Clinically Important Differences Of Promis Pf In Ankle Fracture Patients, Luke Myhre, Patrick Kellam, Graham Dekeyser, Haojia Li, Yue Zhang, Amy M Cizik, Justin Haller

Faculty, Staff and Student Publications

BACKGROUND: Evaluating the minimal clinically important differences (MCIDs) in patient-reported outcome scores is essential for use of clinical outcomes data. The purpose of the current study was to calculate MCID of Patient Reported Outcome Information System Physical Function (PROMIS PF) scores for ankle fracture patients.

METHODS: All patients who underwent operative fixation for ankle fractures at a single level 1 trauma center were identified by

RESULTS: A total of 331 patients were included in the distribution-based analysis, and 195 patients were included in the anchor-based analysis. Mean age was 45.3 years (SD 17.5), and 59.4% of participants were female. MCID …

A Pilot Study To Determine The Incidence, Type, And Severity Of Non-Routine Events In Neonates Undergoing Gastrostomy Tube Placement, Daniel J France, Emma Schremp, Evan B Rhodes, Jason Slagle, Sarah Moroz, Peter H Grubb, Leon D Hatch, Matthew Shotwell, Amanda Lorinc, Jamie Robinson, Marlee Crankshaw, Timothy Newman, Matthew B Weinger, Martin L Blakely

Faculty, Staff and Student Publications

BACKGROUND: Non-routine events (NRE) are defined as any suboptimal occurrences in a process being measured in the opinion of the reporter and comes from the field of human factors engineering. These typically occur well up-stream of an adverse event and NRE measurement has not been applied to the complex context of neonatal surgery. We sought to apply this novel safety event measurement methodology to neonates in the NICU undergoing gastrostomy tube placement.

METHODS: A prospective pilot study was conducted between November 2016 and August 2020 in the Level IV NICU and the pediatric operating rooms of an urban academic children's …

Infant Prostatic Rhabdomyosarcoma: A Diagnostic And Therapeutic Challenge, Sohail Dhanji, Leonardo D Borregales, Nicolette K Janzen, Guilherme Godoy, Maren Y Fuller, Jason K Au

Faculty, Staff and Student Publications

The following case report describes a case of prostatic rhabdomyosarcoma in a 6-month-old male who presented with urinary retention and constipation. MRI showed a prostatic mass that was displacing the rectum and bladder, leading to bladder outlet obstruction. A suprapubic tube was placed for urinary diversion and a transvesical approach was used for tissue diagnosis. Biopsy confirmed the diagnosis of prostatic rhabdomyosarcoma. Patient underwent chemotherapy regiment with VAC (vincristine, actinomycin D and cyclophosphamide) and subsequently ifosfamide and doxorubicin. Eventually, due to tumor progression, the patient underwent a radical cystoprostatectomy with pelvic lymph node dissection and ileal conduit.

Platelet Function In Trauma: Is Current Technology In Function Testing Missing The Mark In Injured Patients?, Jacob B Schriner, Mitchell J George, Jessica C Cardenas, Scott D Olson, Kimberly A Mankiewicz, Charles S Cox, Brijesh S Gill, Charles E Wade

Faculty, Staff and Student Publications

Platelets are subcellular anucleate components of blood primarily responsible for initiating and maintaining hemostasis. Following injury to a blood vessel, platelets can be activated via several pathways, resulting in changed shape, adherence to the injury site, aggregation to form a plug, degranulation to initiate activation in other nearby platelets, and acceleration of thrombin formation to convert fibrinogen to fibrin before contracting to strengthen the clot. Platelet function assays use agonists to induce and measure 1 or more of these processes to identify alterations in platelet function that increase the likelihood of bleeding or thrombotic events. In severe trauma, these assays …