Digital Commons Network^™

A Plain Language Summary Of The Ascertain Trial: Oral Decitabine And Cedazuridine Versus Intravenous Decitabine For Mds Or Cmml, Guillermo Garcia-Manero, James Mccloskey, Elizabeth A Griffiths, Karen W L Yee, Amer M Zeidan, Aref Al-Kali, H Joachim Deeg, Mitchell Sabloff, Mary-Margaret Keating, Nancy Zhu, Nashat Y Gabrail, Salman Fazal, Joseph Maly, Olatoyosi Odenike, Amy E Dezern, Casey L O'Connell, Gail J Roboz, Lambert Busque, Rena Buckstein, Harshad Amin, Brian Leber, Aditi Shastri, Aram Oganesian, Harold N Keer, Mohammad Azab, Michael R Savona

Faculty, Staff and Student Publications

What is this summary about?This summary describes results from a phase 3 clinical trial called ASCERTAIN.Researchers compared two treatments in people with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML), either of which can develop into acute myeloid leukemia (AML). One group was treated with oral decitabine and cedazuridine (oral DEC-C) and the other with intravenous decitabine.Treatment was given in a series of cycles. In the first cycle, people were randomly assigned to receive oral DEC-C or intravenous decitabine and then switched to the other treatment in the second cycle. After the first two cycles, everyone …

Differentiation Stage Predicts Radiosensitivity In Mesenchymal-Like Pancreatic Cancer, Tingshi Su, Xinjian Yu, Mojtaba Hoseini-Ghahfarokhi, David B Flint, Scott J Bright, Joana I D S Antunes, David K J Martinus, Mandira Manandhar, Mariam Ben Kacem, Poliana C Marinello, Eurico J G Pereira, Hua-Sheng Chiu, Uwe Titt, David R Grosshans, Jan Schuemann, Henning Willers, Harald Paganetti, Pavel Sumazin, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Purpose: To derive a genomic classifier to predict radiosensitivity of pancreatic cancer cell lines and patients with pancreatic cancer to allow genomic-guided radiation therapy.

Methods and materials: We collected a comprehensive data set of full clonogenic cell survival curves of 45 pancreatic cancer cell lines irradiated with clinical photon and proton beams. We derived classifiers based on data from human embryonic and fetal pancreas single-cell RNA-sequencing to distinguish between epithelial and mesenchymal cells and to predict pancreas cell-line differentiation stage. Independent testing was done with an embryonic mouse pancreas single-cell RNA-sequencing data set. We then used bulk RNA-seq profiles from …

Correction To: Selinexor In Combination With Carboplatin And Paclitaxel In Patients With Advanced Solid Tumors: Results Of A Single-Center, Multi-Arm Phase Ib Study, Kyaw Z Thein, Daniel D Karp, Apostolia Tsimberidou, Jing Gong, Selma Sulovic, Jatin Shah, Denái R Milton, David S Hong, Filip Janku, Lacey Mcquinn, Bettzy A Stephen, Rivka Colen, Brett W Carter, Timothy A Yap, Sarina A Piha-Paul, Siqing Fu, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

No abstract provided.

External Validation Of An Algorithm To Detect Vertebral Level Mislabeling And Autocontouring Errors, Tucker J Netherton, Didier Duprez, Tina Patel, Gizem Cifter, Laurence E Court, Christoph Trauernicht, Ajay Aggarwal

Faculty, Staff and Student Publications

Background and purpose: This work performs external validation of a previously developed vertebral body autocontouring tool and investigates a post-processing method to increase performance to clinically acceptable levels.

Materials and methods: Vertebral bodies within CT scans from two separate institutions (40 from institution A and 41 from institution B) were automatically 1) localized and enumerated, 2) contoured, and 3) screened as a means of quality assurance (QA) for errors. Identification rate, contour acceptability rate, and QA accuracy were calculated to assess the tool's performance. These metrics were compared to those calculated on CTs from the model's original training dataset, and …

Evaluation Of A Comprehensive Set Of Normal Tissue Complication Probability Models For Patients With Head And Neck Cancer In An International Cohort, Suzanne P M De Vette, Maria I Van Rijn-Dekker, Lisa Van Den Bosch, Kylie Keijzer, Hendrike Neh, Hung Chu, Yan Li, Mark L Frederiks, Hans Paul Van Der Laan, Jolien Heukelom, Peter Van Luijk, Arjen Van Der Schaaf, Roel J H M Steenbakkers, Nanna M Sijtsema, Katherine A Hutcheson, Clifton D Fuller, Johannes A Langendijk, Amy C Moreno, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Background/purpose: Normal tissue complication probability (NTCP) models can be used to guide radiation therapy (RT) decisions by estimating side-effect risks pretreatment to minimize (late) side-effects. Recently, a comprehensive individual toxicity risk (CITOR) profile of NTCP models addressing common side-effects in head and neck cancer (HNC) patients was developed. This study investigates the generalizability of these models in an international setting, with different treatment approaches and side-effect assessments, promoting their integration into more widespread clinical practice.

Materials/methods: From a prospective registry study, 407 HNC patients were included who were treated with definitive RT with or without systemic therapy between 2015 and …

Insulin-Like Growth Factor 2 As A Driving Force For Exponential Expansion And Differentiation Of The Neonatal Thymus, Seung Woo Kang, Bryan R Helm, Yu Wang, Shiyun Xiao, Wen Zhang, Anusha Vasudev, Ken S Lau, Qi Liu, Ellen R Richie, Laura P Hale, Nancy R Manley

Faculty, Staff and Student Publications

Like all organs, the thymus grows in size and function rapidly during development, but this growth comes to a halt after birth. However, the molecular mechanisms behind such a transition in the thymus remain obscure. Using single-cell RNA sequencing (scRNA-seq) of the murine thymic stroma, we identified that major transcriptomic changes occur in the endothelium and mesenchyme across the transition to homeostasis. Differentially expressed gene and intercellular network analyses of temporally resolved scRNA-seq data revealed fibroblast-derived insulin-like growth factor 2 (IGF2) as a candidate driving neonatal thymic expansion. We demonstrated that IGF2 activity promotes a cortical thymic epithelial cell-specific proliferation …

Concurrent Bone Marrow Acute Undifferentiated Leukemia And Mediastinal T‐Lymphoblastic Lymphoma With Identical Set::Nup214 Fusion And Phf6 And Ezh2 Mutations, Qing Wei, Fatima Z Jelloul, Sa A Wang, Guilin Tang, Shaoying Li, Pei Lin, Sanam Loghavi, Huan-You Wang, L Jeffrey Medeiros, Jie Xu

Faculty, Staff and Student Publications

Acute undifferentiated leukemia (AUL) is a rare hematologic malignancy lacking lineage‐specific markers. Concurrent, clonally related AUL and T‐lymphoblastic lymphoma (T‐LBL) has not been reported previously. Here we describe a patient who was diagnosed with AUL in the bone marrow and T‐LBL in the mediastinum after a thorough immunophenotyping by flow cytometry and immunohistochemistry. Despite their immunophenotypic differences, the AUL and T‐LBL showed identical genetic alterations: SET::NUP214 fusion, PHF6, and EZH2 mutations. The patient achieved and remained in complete remission after chemotherapy and stem cell transplantation. This case underscores the value of comprehensive immunophenotyping and genetic analysis in rare hematologic …

Characterization Of A Time-Resolved, Real-Time Scintillation Dosimetry System For Ultra-High Dose-Rate Radiation Therapy Applications, Alexander Baikalov, Daline Tho, Kevin Liu, Stefan Bartzsch, Sam Beddar, Emil Schüler

Faculty, Staff and Student Publications

Purpose: Scintillation dosimetry has promising qualities for ultra-high-dose-rate (UHDR) radiation therapy (RT), but no system has shown compatibility with mean dose rates (DR¯) above 100 Gy/s and doses per pulse (Dp) exceeding 1.5 Gy typical of UHDR (FLASH)-RT. The aim of this study was to characterize a novel scintillation dosimetry system with the potential of accommodating UHDRs.

Methods and materials: We undertook a thorough dosimetric characterization of the system on an UHDR electron beamline. The system's response as a function of dose, DR¯, Dp, and the pulse dose-rate (DRp) was investigated, as was the system's dose sensitivity (signal per unit …

Vitamin D-Related Genetic Variants And Prostate Cancer Risk In Black Men, Tracy M Layne, Joseph H Rothstein, Xiaoyu Song, Shaneda Warren Andersen, Emma K T Benn, Weiva Sieh, Robert J Klein

Faculty, Staff and Student Publications

Background: The relationship between vitamin D and prostate cancer has primarily been characterized among White men. Black men, however, have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine critical genes in the vitamin D pathway and prostate cancer risk in Black men.

Methods: We assessed a total of 73 candidate variants in genes (namely GC, CYP27A1, CYP27B1, CYP24A1, VDR, and RXRA) including functional variants previously associated with prostate cancer and circulating 25(OHD) in White men. Associations with prostate cancer risk were examined using genome-wide …

Imaging Considerations For Patients With Chronic Low Back Pain: A Case Report, Kennedy Kirkpatrick, Jay D Shah, Krishna Shah

Faculty, Staff and Students Publications

Background: The incidence of low back pain, a leading cause of global disability, has increased significantly. Spinal cord stimulation (SCS) is US Food and Drug Administration-approved for treating intractable back pain, particularly in patients with prior surgical interventions.

Case report: A 43-year-old woman was referred for SCS implantation following 3 prior lumbar spinal surgeries with continued, right-sided radicular back pain. Additional diagnostic imaging was obtained, and a magnetic resonance imaging with and without contrast revealed a recurrent disc despite 3 lumbar microdiscectomies. The patient was then referred for lumbar spinal fusion, specifically anterior lumbar interbody fusion.

Conclusions: This case underscores …

A Multipronged Effort To Incorporate Professionalism Into Campuswide Programming Through A Center For Professionalism, Kyler M Godwin, Asma Ali, Larry Laufman, Ellen M Friedman

Faculty, Staff and Students Publications

Background Professionalism, a core competency for graduate medical education accreditation, has a clear educational mandate. However, the pathway to successful incorporation of professionalism within organizational culture has not been established. Integration of professionalism within the learning environment requires intentional design and formal education. Objective To describe the integration of professionalism in the learning environment through formal education and programming and report feasibility and acceptability data.

Methods The Center for Professionalism (Center) was developed in 2013 to align with the learning and clinical environments of our academic medical center. Primary drivers of a culture of professionalism were identified through input from …

Atrial Cardiomyocyte-Restricted Cleavage Of Gasdermin D Promotes Atrial Arrhythmogenesis, Yue Yuan, Pascal Martsch, Xiaohui Chen, Enrique Martinez, Luge Li, Jia Song, Theresa Poppenborg, Florian Bruns, Jong Hwan Kim, Markus Kamler, James F Martin, Issam Abu-Taha, Dobromir Dobrev, Na Li

Faculty, Staff and Students Publications

Background and aims: Enhanced inflammatory signalling causally contributes to atrial fibrillation (AF) development. Gasdermin D (GSDMD) is an important downstream effector of several inflammasome pathways. However, the role of GSDMD, particularly the cleaved N-terminal (NT)-GSDMD, in non-immune cells remains elusive. This study aimed to elucidate the function of NT-GSDMD in atrial cardiomyocytes (ACMs) and determine its contribution to atrial arrhythmogenesis.

Methods: Human atrial appendages were used to assess the protein levels and localization. A modified adeno-associated virus 9 was employed to establish ACM-restricted overexpression of NT-GSDMD in mice.

Results: The cleavage of GSDMD was enhanced in ACMs of AF patients. …

Intestinal Epithelial Serotonin As A Novel Target For Treating Disorders Of Gut-Brain Interaction And Mood, Lin Y Hung, Nuno D Alves, Andrew Del Colle, Ardesheer Talati, Sarah A Najjar, Virginie Bouchard, Virginie Gillet, Yan Tong, Zixing Huang, Kirsteen N Browning, Jialiang Hua, Ying Liu, James O Woodruff, Daniel Juarez, Melissa Medina, Jonathan Posner, Raquel Tonello, Nazli Yalcinkaya, Narek Israelyan, Roey Ringel, Letao Yang, Kam W Leong, Mu Yang, Ji Ying Sze, Tor Savidge, Jay Gingrich, Robert J Shulman, Michael D Gershon, Annie Ouellet, Larissa Takser, Mark S Ansorge, Kara Gross Margolis

Faculty, Staff and Students Publications

Background & aims: Mood disorders and disorders of gut-brain interaction (DGBI) are highly prevalent, commonly comorbid, and lack fully effective therapies. Although selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for these disorders, they may impart adverse effects, including anxiety, anhedonia, dysmotility, and, in children exposed in utero, an increased risk of cognitive, mood, and gastrointestinal disorders. SSRIs act systemically to block the serotonin reuptake transporter and enhance serotonergic signaling in the brain, intestinal epithelium, and enteric neurons. Yet, the compartments that mediate the therapeutic and adverse effects of SSRIs are unknown, as is whether gestational SSRI exposure directly …

Correction To: Active Versus Passive Learning In Large-Group Sessions In Medical School: A Randomized Cross-Over Trial Investigating Effects On Learning And The Feeling Of Learning, Peter Boedeker, Tobias Schlingmann, Joshua Kailin, Ajith Nair, Cara Foldes, David Rowley, Katherine Salciccioli, Ronald Maag, Nancy Moreno, Nadia Ismail

Faculty, Staff and Students Publications

This corrects the article "Active Versus Passive Learning in Large-Group Sessions in Medical School: A Randomized Cross-Over Trial Investigating Effects on Learning and the Feeling of Learning" on page 459.

Postoperative Intraocular Lens Tilt From Preoperative Full Crystalline Lens Geometry Using Machine Learning, Eduardo Martinez-Enriquez, Gonzalo Velarde-Rodríguez, Nicolás Alejandre-Alba, Derick Ansah, Sindhu Kishore, Álvaro De La Peña, Ramya Natarajan, Pravin Vaddavalli, Yue Zhao, Joseph O Okudolo, Dylan B Mcbee, Ugur Celik, Mujdat Cetin, Jen-Li Dong, Yuli Lim, Li Wang, Douglas Donald Koch, Scott Macrae, Susana Marcos

Faculty, Staff and Students Publications

In cataract surgery, the opacified crystalline lens is replaced by an artificial intraocular lens (IOL), requiring precise preoperative selection of parameters to optimize postoperative visual quality. Three-dimensional customized eye models, which can be constructed using quantitative data from anterior segment optical coherence tomography, provide a robust platform for virtual surgery. These models enable simulations and predictions of the optical outcomes for specific patients and selected IOLs. A critical step in building these models is estimating the IOL's tilt and position preoperatively based on the available preoperative geometrical information (ocular parameters). In this study, we present a machine learning model that, …

Most Elderly Patients With Subclinical Hypothyroidism Do Not Need To Be Treated, Risheng Xu, Nicola Abate, Nalini Ram, Kristina Little

Faculty, Staff and Students Publications

Whether subclinical hypothyroidism should be treated in elderly patients (≥ 65 years) is controversial. The authors argue for a personalized, wait-and-see approach rather than universal treatment, pointing out that randomized clinical trials have not shown that levothyroxine treatment makes any difference in terms of hard clinical end points, quality of life, or hypothyroid symptom relief in elderly patients with this condition.

“Everything Is Electronic Health Record-Driven”: The Role Of The Electronic Health Record In The Emergency Department Diagnostic Process, Tyler G James, Courtney W Mangus, Sarah J Parker, P Paul Chandanabhumma, C M Cassady, Fernanda Bellolio, Kalyan Pasupathy, Milisa Manojlovich, Hardeep Singh, Prashant Mahajan

Faculty, Staff and Students Publications

Objectives: There is limited knowledge on how providers and patients in the emergency department (ED) use electronic health records (EHRs) to facilitate the diagnostic process. While EHRs can support diagnostic decision-making, EHR features that are not user-centered may increase the likelihood of diagnostic error. We aimed to identify how EHRs facilitate or impede the diagnostic process in the ED and to identify opportunities to reduce diagnostic errors and improve care quality.

Materials and methods: We conducted semistructured interviews with 10 physicians, 15 nurses, and 8 patients across 4 EDs. Data were analyzed using a hybrid thematic analysis approach, which blends …

Suppression Of Hypothalamic Oestrogenic Signal Sustains Hyperprolactinemia And Metabolic Adaptation In Lactating Mice, Meng Yu, Bing Feng, Jonathan C Bean, Qianru Zhao, Yongjie Yang, Hailan Liu, Yongxiang Li, Benjamin P Eappen, Hesong Liu, Longlong Tu, Kristine M Conde, Mengjie Wang, Xi Chen, Na Yin, Darah Ave Threat, Nathan Xu, Junying Han, Peiyu Gao, Yi Zhu, Darryl L Hadsell, Yang He, Pingwen Xu, Yanlin He, Chunmei Wang

Faculty, Staff and Students Publications

17β-oestradiol (E2) inhibits overeating and promotes brown adipose tissue (BAT) thermogenesis, whereas prolactin (PRL) does the opposite. During lactation, the simultaneous decline in E2 and surge in PRL contribute to maternal metabolic adaptations, including hyperphagia and suppressed BAT thermogenesis. However, the underlying neuroendocrine mechanisms remain unclear. Here, we find that oestrogen receptor alpha (ERα)-expressing neurons in the medial basal hypothalamus (MBH), specifically the arcuate nucleus of the hypothalamus and the ventrolateral subdivision of the ventromedial hypothalamus (vlVMH), are suppressed during lactation. Deletion of ERα from MBH neurons in virgin female mice induces metabolic phenotypes characteristic of lactation, including hyperprolactinemia, hyperphagia …

Il-12-Producing Cytokine Factories Induce Precursor Exhausted T Cells And Elimination Of Primary And Metastatic Tumors, Amanda Nash, Jonathon Debonis, Danna Murungi, Bertha Castillo, Boram Kim, Fangheng Hu, Courtney Chambers, Annie Nguyen, Andrea Hernandez, Zeshi Wang, Peter D Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Ningbo Zheng, Weiyi Peng, Oleg A Igoshin, Jose Oberholzer, H Courtney Hodges, Nathan Reticker-Flynn, Omid Veiseh

Faculty, Staff and Students Publications

Background: Curative responses to immunotherapy require the generation of robust systemic immunity with limited toxicity. Recruitment of T cell populations such as precursor exhausted T cells (Tpex) from lymphoid tissues to tumors is a hallmark of effective treatment. However, the ability to efficiently induce this recruitment is lacking in current immunotherapy approaches. Furthermore, systemic administration of immunotherapies frequently results in dose-limiting toxicities, yielding an inadequate therapeutic window for eliciting durable responses.

Methods: In this investigation, we evaluated the safety and antitumor efficacy of locally administered interleukin 12 (IL-12) using a clinically translatable cytokine delivery platform (NCT05538624) to identify …

Inhibitory Specificity From A Connectomic Census Of Mouse Visual Cortex, Casey M Schneider-Mizell, Agnes L Bodor, Derrick Brittain, Joann Buchanan, Daniel J Bumbarger, Leila Elabbady, Clare Gamlin, Daniel Kapner, Sam Kinn, Gayathri Mahalingam, Sharmishtaa Seshamani, Shelby Suckow, Marc Takeno, Russel Torres, Wenjing Yin, Sven Dorkenwald, J Alexander Bae, Manuel A Castro, Akhilesh Halageri, Zhen Jia, Chris Jordan, Nico Kemnitz, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Eric Mitchell, Shanka Subhra Mondal, Shang Mu, Barak Nehoran, Sergiy Popovych, William Silversmith, Nicholas L Turner, William Wong, Jingpeng Wu, Jacob Reimer, Andreas S Tolias, H Sebastian Seung, R Clay Reid, Forrest Collman, Nuno Maçarico Da Costa

Faculty, Staff and Students Publications

Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties1. Synaptic connectivity shapes how each cell type participates in the cortical circuit, but mapping connectivity rules at the resolution of distinct cell types remains difficult. Here we used millimetre-scale volumetric electron microscopy2 to investigate the connectivity of all inhibitory neurons across a densely segmented neuronal population of 1,352 cells spanning all layers of mouse visual cortex, producing a wiring diagram of inhibition with more than 70,000 synapses. Inspired by classical neuroanatomy, we classified inhibitory neurons based on targeting of …

Correction: Citation Issues In The American Academy Of Pediatrics Policy Statement On Transgender And Gender-Diverse Children And Adolescents (Rafferty, 2018), Kathleen Mcdeavitt

Faculty, Staff and Students Publications

No abstract provided.

Citation Issues In The American Academy Of Pediatrics Policy Statement On Transgender And Gender-Diverse Children And Adolescents (Rafferty, 2018), Kathleen Mcdeavitt

Faculty, Staff and Students Publications

No abstract provided.

Dysregulation Of Mirna Expression And Excitation In Mef2c Autism Patient Hipsc-Neurons And Cerebral Organoids, Dorit Trudler, Swagata Ghatak, Michael Bula, James Parker, Maria Talantova, Melissa Luevanos, Sergio Labra, Titas Grabauskas, Sarah Moore Noveral, Mayu Teranaka, Emily Schahrer, Nima Dolatabadi, Clare Bakker, Kevin Lopez, Abdullah Sultan, Parth Patel, Agnes Chan, Yongwook Choi, Riki Kawaguchi, Pawel Stankiewicz, Ivan Garcia-Bassets, Piotr Kozbial, Michael G Rosenfeld, Nobuki Nakanishi, Daniel H Geschwind, Shing Fai Chan, Wei Lin, Nicholas J Schork, Rajesh Ambasudhan, Stuart A Lipton

Faculty, Staff and Students Publications

MEF2C is a critical transcription factor in neurodevelopment, whose loss-of-function mutation in humans results in MEF2C haploinsufficiency syndrome (MHS), a severe form of autism spectrum disorder (ASD)/intellectual disability (ID). Despite prior animal studies of MEF2C heterozygosity to mimic MHS, MHS-specific mutations have not been investigated previously, particularly in a human context as hiPSCs afford. Here, for the first time, we use patient hiPSC-derived cerebrocortical neurons and cerebral organoids to characterize MHS deficits. Unexpectedly, we found that decreased neurogenesis was accompanied by activation of a micro-(mi)RNA-mediated gliogenesis pathway. We also demonstrate network-level hyperexcitability in MHS neurons, as evidenced by excessive synaptic …

Ethics Of Learning Surgical Autonomy In Safety-Net Hospital Systems With Patients Who Are Incarcerated, Kala T Pham, Rachel W Davis

Faculty, Staff and Students Publications

Safety-net hospitals care for patients who are incarcerated and are key environments in which surgical trainees learn to wield their professional autonomy. This article explores ethical questions raised by surgical trainees' participation in carceral care and canvasses possible responses to those questions.

Klf4 Enhances Transplantation-Induced Hematopoiesis By Inhibiting Tlrs And Noncanonical Nfκb Signaling At A Steady State, Chun Shik Park, Cory S Bridges, Andrew H Lewis, Taylor J Chen, Saptarsi Shai, Wa Du, Monica Puppi, Barry Zorman, Sumazin Pavel, H Daniel Lacorazza

Faculty, Staff and Students Publications

The transcription factor Krüppel-like factor 4 (KLF4) acts as a transcriptional activator and repressor. KLF4 plays a role in various cellular processes, including the dedifferentiation of somatic cells into induced pluripotent stem cells. Although it has been shown to enhance self-renewal in embryonic and leukemia stem cells, its role in adult hematopoietic stem cells (HSCs) remains underexplored. We demonstrate that conditional deletion of the Klf4 gene in hematopoietic cells led to an increased frequency of immunophenotypic HSCs in the bone marrow, along with a normal distribution of lymphoid and myeloid progenitor cells. Noncompetitive bone marrow transplants showed normal engraftment and …

Words Matter: Destigmatizing The Language Of Medicine Through Research, Training, And Future Directions For Emergency Medicine, Natalie Strokes, Richard Sapp, Meta Carroll, Elizabeth Maxwell Hovis, Mary Mclean, Shannon Markus, Aaryn Hammond, Rosemarie Diaz, Ryan E Tsuchida, Marcia Perry, Edgardo Ordonez

Faculty, Staff and Students Publications

Background: In emergency medicine (EM), language choice significantly impacts patient care and can potentially cause harm, dehumanize patients, and introduce bias. Stigmatizing language in medical settings can affect patient dignity, trust, and outcomes. Despite its importance, there is limited education on avoiding stigmatizing language in EM. This concept paper addresses the need to raise awareness and develop strategies for use of inclusive language in the emergency department (ED).

Methods: A didactic session titled "Words Matter: Destigmatizing the Language of Medicine" was developed and presented at the 2024 Society for Academic Emergency Medicine (SAEM) Annual Meeting. The session involved a collaborative …

Galectin-1 Inhibition As A Strategy For Malignant Peripheral Nerve Sheath Tumor Treatment, Hsiao-Chi Wang, Keila E Torres, Roger Xia, Marcio H Malogolowkin, Ssu-Wei Hsu, Ching-Hsien Chen, Tsung-Chieh Shih

Faculty, Staff and Student Publications

Neurofibromatosis type 1 (NF1) is an inherited disorder that predisposes individuals to malignant peripheral nerve sheath tumors (MPNSTs), a highly aggressive sarcoma with limited treatment options and poor prognosis. This study explores the potential of targeting the interaction between Galectin-1 and Ras as a novel therapeutic strategy for MPNSTs. Through molecular docking, we identified critical residues involved in the Galectin-1 and H-Ras interaction. We developed LLS30, a compound designed to target this Ras-binding pocket on Galectin-1, and tested its efficacy. LLS30 effectively disrupted the Galectin-1/Ras interaction, causing Ras delocalization from the plasma membrane and inhibiting Ras signaling. In vitro experiments …

Limosilactobacillus Reuteri Promotes The Expression And Secretion Of Enteroendocrine- And Enterocyte-Derived Hormones, Sara C Di Rienzi, Heather A Danhof, Micah D Forshee, Ari Roberts, Robert A Britton

Faculty, Staff and Students Publications

Intestinal microbes can beneficially impact host physiology, prompting investigations into the therapeutic usage of such microbes in a range of diseases. For example, human intestinal microbe Limosilactobacillus reuteri strains ATCC PTA 6475 and DSM 17938 are being considered for use for intestinal ailments, including colic, infection, and inflammation, as well as for non-intestinal ailments, including osteoporosis, wound healing, and autism spectrum disorder. While many of their beneficial properties are attributed to suppressing inflammatory responses, we postulated that L. reuteri may also regulate intestinal hormones to affect physiology within and outside of the gut. To determine if L. reuteri secreted factors …

Video Discharge Instructions Increase Patient Understanding For Office-Based Procedures: A Randomized Controlled Study, Jenna Bates Maffei, Jeffrey J Song, Gal Saffati, Mohit Khera

Faculty, Staff and Students Publications

Background: Health literacy significantly influences healthcare outcomes, with poor literacy leading to worse quality of life, increased mortality, and higher readmission rates. Recent efforts to improve post-encounter education include structured teach-back methods, patient preference assessments, and standardized discharge instructions. Studies in emergency departments have shown that incorporating video discharge instructions enhances patient understanding and retention of care information. To address the gap in urology, this study aims to evaluate patient comprehension and satisfaction with video discharge instructions following clinic-based vasectomy procedures.

Methods: We performed an Institutional Review Board approved (#H-51614) unblinded randomized controlled study with written consent from each participant. …

Assessing Cancer Therapeutic Efficacy In Vivo Using [2h7]Glucose Deuterium Metabolic Imaging, Mario C Chang, Vinay R Malut, Rohit Mahar, Anna Rushin, Marc A Mcleod, Geraldine L Pierre, Indu R Malut, Stephen J Staklinski, Max E Glanz, Mukundan Ragavan, Gaurav Sharma, Manoj Madheswaran, Arshee Badar, Aparna D Rao, Brian K Law, Michael S Kilberg, James H P Collins, Vikram D Kodibagkar, James A Bankson, Ralph J Deberardinis, Matthew E Merritt

Faculty, Staff and Student Publications

Metabolic imaging produces powerful visual assessments of organ function in vivo. Current techniques can be improved by safely increasing metabolic contrast. The gold standard, 2-[18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging, is limited by radioactive exposure and sparse assessment of metabolism beyond glucose uptake and retention. Deuterium magnetic resonance imaging (DMRI) with [6,6-2H2]glucose is nonradioactive, achieves tumor metabolic contrast, but can be improved by enriched contrast from deuterated water (HDO) based imaging. Here, we developed a DMRI protocol employing [2H7]glucose. Imaging 2H-signal and measuring HDO production in tumor-bearing mice detected differential glucose utilization across baseline tumors, tumors treated with vehicle control or …