Biomedical Informatics Commons^™

Galectin-3 Cooperates With Cd47 To Suppress Phagocytosis And T-Cell Immunity In Gastric Cancer Peritoneal Metastases, Yibo Fan, Shumei Song, Yuan Li, Shilpa S Dhar, Jiankang Jin, Katsuhiro Yoshimura, Xiaodan Yao, Ruiping Wang, Ailing W Scott, Melissa Pool Pizzi, Jingjing Wu, Lang Ma, George A Calin, Samir Hanash, Linghua Wang, Michael Curran, Jaffer A Ajani

Faculty, Staff and Student Publications

UNLABELLED: The peritoneal cavity is a common site of gastric adenocarcinoma (GAC) metastasis. Peritoneal carcinomatosis (PC) is resistant to current therapies and confers poor prognosis, highlighting the need to identify new therapeutic targets. CD47 conveys a "don't eat me" signal to myeloid cells upon binding its receptor signal regulatory protein alpha (SIRPα), which helps tumor cells circumvent macrophage phagocytosis and evade innate immune responses. Previous studies demonstrated that the blockade of CD47 alone results in limited clinical benefits, suggesting that other target(s) might need to be inhibited simultaneously with CD47 to elicit a strong antitumor response. Here, we found that …

Dissociable Effects Of Alzheimer's Disease-Related Cognitive Dysfunction And Aging On Functional Brain Network Segregation, Ziwei Zhang, Micaela Y Chan, Liang Han, Claudia A Carreno, Ezra Winter-Nelson, Gagan S Wig

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is associated with changes in large-scale functional brain network organization. Individuals with AD exhibit less segregated resting-state brain networks compared with individuals without dementia. However, declines in brain network segregation are also evident as adult individuals grow older. Determining whether these observations reflect unique or overlapping alterations on the functional connectome of the brain is essential for understanding the impact of AD on network organization and incorporating measures of functional brain network organization toward AD characterization. Relationships between AD dementia severity and participant's age on resting-state brain system segregation were examined in 326 cognitively healthy and 275 …

Baseline Extracellular Vesicle Mirna-30c And Autophagic Ctcs Predict Chemoradiotherapy Resistance And Outcomes In Patients With Lung Cancer, Diego De Miguel-Perez, Francisco Gabriel Ortega, Rosario Guerrero Tejada, Antonio Martínez-Única, Christine B Peterson, Alessandro Russo, Muthukumar Gunasekaran, Andres F Cardona, Victor Amezcua, Jose Antonio Lorente, Jose Expósito Hernández, Christian Rolfo, Maria Jose Serrano

Faculty, Staff and Student Publications

Concurrent chemoradiotherapy (cCRT) is the mainstay of treatment for patients diagnosed with locally advanced non-small cell lung cancer (NSCLC). One significant challenge in the effectiveness of this therapy is the potential development of resistance mechanisms, where autophagy up-regulation has been proposed as a key contributing factor. However, there is a lack of reliable biomarkers to predict outcomes on these patients. Interestingly, for addressing this gap, extracellular vesicles (EVs) and circulating tumor cells (CTCs) have emerged as potential sources of such biomarkers. In this study, we investigated EV-associated miRNAs and presence of autophagic CTCs in prospectively collected serial samples from 38 …

Novel Clinical Trial Designs With Dose Optimization To Improve Long-Term Outcomes, Peter F Thall, Yong Zang, Andrew G Chapple, Ying Yuan, Ruitao Lin, David Marin, Pavlos Msaouel

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Conventional designs for choosing a dose for a new therapy may select doses that are unsafe or ineffective and fail to optimize progression-free survival time, overall survival time, or response/remission duration. We explain and illustrate limitations of conventional dose-finding designs and make four recommendations to address these problems. When feasible, a dose-finding design should account for long-term outcomes, include screening rules that drop unsafe or ineffective doses, enroll an adequate sample size, and randomize patients among doses. As illustrations, we review three designs that include one or more of these features. The first illustration is a trial that randomized patients …

Phase 1 Study Of Vibecotamab Identifies An Optimized Dose For Treatment Of Relapsed/Refractory Acute Myeloid Leukemia, Farhad Ravandi, Asad Bashey, James Foran, Wendy Stock, Raya Mawad, Nicholas Short, Musa Yilmaz, Hagop Kantarjian, Olatoyosi Odenike, Anand Patel, Raman Garcha, William Barrett Ainsworth, Raphael Clynes, Jitendra Kanodia, Ying Ding, Huajiang Li, Steve Kye, Alice Mims

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML), an aggressive malignancy with unmet medical need, lacks immunotherapeutic options. CD123, the cellular receptor for interleukin-3, expressed in AML is an attractive target for tumor-specific therapy. Vibecotamab (XmAb14045), a humanized bispecific antibody, monovalently binds both CD3 and CD123 to recruit cytotoxic T cells to kill CD123+ tumor cells. This phase 1 study's primary objectives were safety and tolerability and identification of a maximum tolerated dose/recommended dose for use as monotherapy in patients with relapsed/refractory AML. Identification of a recommended phase 2 vibecotamab dose comprised 3 step-up doses (Week 1), which were noted to reduce cytokine response …

Dhodh: A Promising Target In The Treatment Of T-Cell Acute Lymphoblastic Leukemia, Amy N Sexauer, Gabriela Alexe, Karin Gustafsson, Elizabeth Zanetakos, Jelena Milosevic, Mary Ayres, Varsha Gandhi, Yana Pikman, Kimberly Stegmaier, David B Sykes

Faculty, Staff and Student Publications

Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) have a poor prognosis with few therapeutic options. With the goal of identifying novel therapeutic targets, we used data from the Dependency Map project to identify dihydroorotate dehydrogenase (DHODH) as one of the top metabolic dependencies in T-ALL. DHODH catalyzes the fourth step of de novo pyrimidine nucleotide synthesis. Small molecule inhibition of DHODH rapidly leads to the depletion of intracellular pyrimidine pools and forces cells to rely on extracellular salvage. In the absence of sufficient salvage, this intracellular nucleotide starvation results in the inhibition of DNA and RNA synthesis, …

The Landscape Of Alterations From 1407 Ultra-Rare Sarcomas From The Aacr Genie Database: Clinical Implications, Ryan A Denu, Justin T Moyers, Mohamed A Gouda, Anthony P Conley, Alexander J Lazar, Vivek Subbiah

Faculty, Staff and Student Publications

Purpose: Ultra-rare sarcomas (URS) comprise a group of orphan diseases with an incidence of ≤1/1,000,000 people per year. We aimed to assess clinically actionable genomic alterations in URS.

Experimental design: Data were extracted from the GENIE database using cBioPortal. OncoKB was used to assess for clinical actionability of mutations. Tumor mutational burden (TMB) was inferred from clinical sequencing data.

Results: Soft tissue (ST) URS made up 23.5% of ST sarcoma cases, and bone URS made up 16.5% of bone sarcoma cases. The most commonly mutated gene in all four groups was TP53. The most common fusions involved EWSR1. The most …

A Phase 1 Study Of Prophylactic Anakinra To Mitigate Icans In Patients With Large B-Cell Lymphoma, Paolo Strati, Andrew Jallouk, Qing Deng, Xubin Li, Lei Feng, Ryan Sun, Sherry Adkins, Swapna Johncy, Taylor Cain, Raphael E Steiner, Sairah Ahmed, Dai Chihara, Luis E Fayad, Swaminathan P Iyer, Sandra Horowitz, Loretta J Nastoupil, Ranjit Nair, Ahmed Hassan, Taher E Daoud, Misha Hawkins, Maria A Rodriguez, Elizabeth J Shpall, Jeremy L Ramdial, Partow Kebriaei, David S Hong, Jason R Westin, Sattva S Neelapu, Michael R Green

Faculty, Staff and Student Publications

No abstract provided.

Gasdermin D Permeabilization Of Mitochondrial Inner And Outer Membranes Accelerates And Enhances Pyroptosis, Rui Miao, Cong Jiang, Winston Y Chang, Haiwei Zhang, Jinsu An, Felicia Ho, Pengcheng Chen, Han Zhang, Caroline Junqueira, Dulguun Amgalan, Felix G Liang, Junbing Zhang, Charles L Evavold, Iva Hafner-Bratkovič, Zhibin Zhang, Pietro Fontana, Shiyu Xia, Markus Waldeck-Weiermair, Youdong Pan, Thomas Michel, Liron Bar-Peled, Hao Wu, Jonathan C Kagan, Richard N Kitsis, Peng Zhang, Xing Liu, Judy Lieberman

Faculty, Staff and Student Publications

Gasdermin D (GSDMD)-activated inflammatory cell death (pyroptosis) causes mitochondrial damage, but its underlying mechanism and functional consequences are largely unknown. Here, we show that the N-terminal pore-forming GSDMD fragment (GSDMD-NT) rapidly damaged both inner and outer mitochondrial membranes (OMMs) leading to reduced mitochondrial numbers, mitophagy, ROS, loss of transmembrane potential, attenuated oxidative phosphorylation (OXPHOS), and release of mitochondrial proteins and DNA from the matrix and intermembrane space. Mitochondrial damage occurred as soon as GSDMD was cleaved prior to plasma membrane damage. Mitochondrial damage was independent of the B-cell lymphoma 2 family and depended on GSDMD-NT binding to cardiolipin. Canonical and …

Cigarette Smoke Exposure Accelerates Aml Progression In Flt3-Itd Models, Mary Figueroa, Huaxian Ma, Mansour Alfayez, Daniel Enrique Morales-Mantilla, Fei Wang, Yue Lu, Marcos R Estecio, Katherine Y King, Eugenie Kleinerman, Seyed Javad Moghaddam, Naval Daver, Michael Andreeff, Marina Konopleva, Courtney Dinardo, Joya Chandra

Faculty, Staff and Student Publications

No abstract provided.

Beyond Bacteria: How The Intratumor Mycobiome Modulates Lung Adenocarcinoma Progression, Zahraa Rahal, Humam Kadara

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Increasing evidence suggests that tumors harbor diverse microbiomes, adding complexity to the tumor microenvironment. In this issue of Cancer Cell, Liu et al. highlight the role of the intratumor mycobiome, specifically Aspergillus sydowii, in promoting lung adenocarcinoma progression. A. sydowii enhances the recruitment and activation of myeloid-derived suppressor cells via IL-1β signaling driven by the β-glucan-mediated Dectin-1/CARD9 pathway.

A Single-Cell Atlas Of Cd19 Chimeric Antigen Receptor T Cells, Xubin Li, Jared Henderson, Max J Gordon, Irtiza Sheikh, Loretta J Nastoupil, Jason Westin, Christopher Flowers, Sairah Ahmed, Linghua Wang, Sattva S Neelapu, Paolo Strati, Qing Deng, Michael R Green

Faculty, Staff and Student Publications

Li et al. present a resource of single-cell RNA sequencing (scRNA-seq) data from the infusion products of relapsed or refractory large B cell lymphoma (rrLBCL) patients treated with standard-of-care axicabtagene ciloleucel and identify features that are significantly different between products from responders and non-responders at 3-month followup by PET/CT, an important landmark for long-term outcomes.

Tumor-Resident Lactobacillus Iners Confer Chemoradiation Resistance Through Lactate-Induced Metabolic Rewiring, Lauren E Colbert, Molly B El Alam, Rui Wang, Tatiana Karpinets, David Lo, Erica J Lynn, Timothy A Harris, Jacob H Elnaggar, Kyoko Yoshida-Court, Katarina Tomasic, Julianna K Bronk, Julie Sammouri, Ananta V Yanamandra, Adilene V Olvera, Lily G Carlin, Travis Sims, Andrea Y Delgado Medrano, Tatiana Cisneros Napravnik, Madison O'Hara, Daniel Lin, Chike O Abana, Hannah X Li, Patricia J Eifel, Anuja Jhingran, Melissa Joyner, Lilie Lin, Lois M Ramondetta, Andrew M Futreal, Kathleen M Schmeler, Geena Mathew, Stephanie Dorta-Estremera, Jianhua Zhang, Xiaogang Wu, Nadim J Ajami, Matthew Wong, Cullen Taniguchi, Joseph F Petrosino, K Jagannadha Sastry, Pablo C Okhuysen, Sara A Martinez, Lin Tan, Iqbal Mahmud, Philip L Lorenzi, Jennifer A Wargo, Ann H Klopp

Faculty, Staff and Student Publications

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other …

Usp38 Exacerbates Atrial Inflammation, Fibrosis, And Susceptibility To Atrial Fibrillation After Myocardial Infarction In Mice, Yang Gong, Tingting Yu, Wei Shuai, Tao Chen, Jingjing Zhang, He Huang

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BACKGROUND: Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear.

METHODS: In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms.

RESULTS: Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, …

Microplastics In Different Tissues Of A Commonly Consumed Fish, Mohammad Belal Hossain, Farjana Haque Pingki, Md Abdus Samad Azad, As-Ad Ujjaman Nur, Partho Banik, Bilal Ahamad Paray, Takaomi Arai, Jimmy Yu

Faculty, Staff and Student Publications

Microplastics (MPs) ingestion by fish signifies a worldwide threat to human health but limited research has examined their existence within the consumable portions (muscle) of fish. Thus, this study was undertaken to unveil the prevalence, characterization, and contamination extent of MPs across various body tissues, including the muscle of the king mackerel (S. guttatus) from the lower Meghna estuary in Bangladesh-a pioneering investigation in this region. In our analysis, we identified a total of 487 MPs, with an average abundance of 48.7 ± 20.3 MPs/individual. These MPs were distributed across different tissues, with respective concentrations of 0.84 ± …

Single-Cell Analysis Differentiates The Effects Of P53 Mutation And P53 Loss On Cell Compositions Of Oncogenic Kras-Driven Pancreatic Cancer, Xinlei Sun, Daowei Yang, Yang Chen

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Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignant disease with a dismal prognosis. In the past decades, a plethora of genetically engineered mouse models (GEMMs) with autochthonous pancreatic tumor development have greatly facilitated studies of pancreatic cancer. Commonly used GEMMs of PDAC often harbor the oncogenic KRAS driver mutation (KrasG12D), in combination with either p53 mutation by knock-in strategy (Trp53R172H) or p53 loss by conditional knockout (Trp53cKO) strategy, in pancreatic cell lineages. However, the systematic comparison of the tumor microenvironment between KrasG12D; Trp53R172H (KPmut) mouse models and KrasG12D; Trp53cKO (KPloss) mouse models …

The Importance Of A Healthy Microbiome In Pregnancy And Infancy And Microbiota Treatment To Reverse Dysbiosis For Improved Health, Herbert L Dupont, Madeleine Mary Hines Salge

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BACKGROUND: The microbiome of newborn infants during the first 1000 days, influenced early on by their mothers' microbiome health, mode of delivery and breast feeding, orchestrates the education and programming of the infant's immune system and determines in large part the general health of the infant for years.

METHODS: PubMed was reviewed for maternal infant microbiome health and microbiota therapy in this setting with prebiotics, probiotics, vaginal seeding and fecal microbiota transplantation (FMT).

RESULTS: A healthy nonobese mother, vaginal delivery and strict breast feeding contribute to microbiome health in a newborn and young infant. With reduced microbiome diversity (dysbiosis) during …

An Overview Of The Immune Modulatory Properties Of Long Non-Coding Rnas And Their Potential Use As Therapeutic Targets In Cancer, Moises Martinez-Castillo, Abdelrahman M Elsayed, Gabriel López-Berestein, Paola Amero, Cristian Rodríguez-Aguayo

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) play pivotal roles in regulating immune responses, immune cell differentiation, activation, and inflammatory processes. In cancer, they are gaining prominence as potential therapeutic targets due to their ability to regulate immune checkpoint molecules and immune-related factors, suggesting avenues for bolstering anti-tumor immune responses. Here, we explore the mechanistic insights into lncRNA-mediated immune modulation, highlighting their impact on immunity. Additionally, we discuss their potential to enhance cancer immunotherapy, augmenting the effectiveness of immune checkpoint inhibitors and adoptive T cell therapies. LncRNAs as therapeutic targets hold the promise of revolutionizing cancer treatments, inspiring further research in this field …

Endoscopic Ultrasound-Guided Fiducial Placement For Stereotactic Body Radiation Therapy In Patients With Pancreatic Cancer, Irina M Cazacu, Ben S Singh, Rachael M Martin-Paulpeter, Sam Beddar, Stephen Chun, Emma B Holliday, Albert C Koong, Prajnan Das, Eugene J Koay, Cullen Taniguchi, Joseph M Herman, Manoop S Bhutani

Faculty, Staff and Student Publications

Accurate delivery of stereotactic body radiotherapy (SBRT) to pancreatic tumors relies on successful EUS-guided placement of fiducial markers. The aim of this study is to report the technical feasibility and safety of EUS-guided fiducial placement and to evaluate the characteristics and technical benefit of SBRT in a cohort of patients with pancreatic cancer (PC). A retrospective chart review was performed for all (n = 82) PC patients referred for EUS-guided fiducial placement by a single endosonographer at a tertiary cancer center. Data regarding EUS-related technical details, SBRT characteristics, adverse events, and continuous visibility of fiducials were recorded and analyzed. …

Helpful, Unnecessary, Or Harmful: A Systematic Review Of The Effects Of Prescription Drug Monitoring Program Use On Opioid Prescriptions, Nina Z.Y. Smith, J. Douglass Thornton, Susan H. Fenton, Debora Simmons, Tiffany Champagne-Langabeer

Faculty, Staff and Student Publications

Prescription drug misuse is a global problem, especially in the United States (US). Clinician involvement is necessary in this crisis, and prescription drug monitoring programs (PDMPs) are a recommended tool for the prevention, recognition, and management of prescription opioid misuse. However, because of the plethora of differences between different PDMPs, research on their effects is mixed. Yet, despite varied evidence, policy on PDMP use is trending stricter and more comprehensive. We aimed to identify patterns in the research to inform clinicians and policy. Through a systematic review of four literature databases (CINAHL, Cochrane Database, Embase, and Medline/OVID), we found 56 …

Biom-55. Targeted Gene Expression Profiling Predicts Meningioma Outcomes And Radiotherapy Responses, William Chen, Abrar Choundhury, Narj W. Youngblood, Mei-Yin Polly, Calixto-Hope Lucas, Kanish Mirchia, Sybren Maas, Abigail Suwala, Minhee Won, James Bayley, Akdes Harmanci, Arif Marmanci, Tiemo Kilsch, Minh Nguyen, Harish Vasudevan, Katy Mccortney, Tai-Chung Lam, Jenny Kan-Suen Pu, Lai-Fung Li, Gilberto Ka-Kit Leung, Jason Chan, Haley Perlow, Joshua Palmer, Anna Berghoff, Matthias Preusser, Theodore Nicolaides, Christian Mawrin, Jacob Young, Lauren Boreta, Steve Braunstein, Jessica Schulte, Nicolas Butowski, Sandro Santagatta, Nancy Ann Oberheim Bush, Javier Vallaneuva-Meyer, James P. Chandler, David Solomon, Leland Rogers, Stephanie Pugh, Minesh Mehta, Penny Sneed, Michael Berger, Craig Horbinski, Michael Mcdrmott, Arie Perry, Wenya Linda Bi, Akash Patel, Felix Sahm, Stephen Magill, David Raleigh

Faculty, Staff and Student Publications

INTRODUCTION

Improvements in meningioma risk stratification are needed and current indications for postoperative radiotherapy are controversial. Here we report multicenter clinical and analytical validation of a gene expression biomarker using clinical and genomic data from 1856 meningiomas from 12 institutions across 3 continents. METHODS

A previously-developed 34-gene expression biomarker was applied to 3 validation cohorts: (1) a multicenter retrospective clinical validation cohort (N = 6 centers, N = 866 meningiomas, median follow-up 5.2 years), (2) a prospective investigator-blinded clinical validation cohort from RTOG 0539 (N = 103 meningiomas, median follow-up 8.4 years), and (3) an analytical validation cohort for test/re-test …

A Longitudinal Study Of Polygenic Score And Cognitive Function Decline Considering Baseline Cognitive Function, Lifestyle Behaviors, And Diabetes Among Middle-Aged And Older Us Adults, Tingting Liu, Changwei Li, Ruiyuan Zhang, Eugenia Flores Millender, Hongyu Miao, Michael Ormsbee, Jinzhen Guo, Adrianna Westbrook, Yang Pan, Jing Wang, Tanika N Kelly

Faculty, Staff and Student Publications

Background: Genomic study of cognition decline while considering baseline cognition and lifestyle behaviors is scarce. We aimed to evaluate the impact of a polygenic score for general cognition on cognition decline rate, while considering baseline cognition and lifestyle behaviors, among the general population and people with diabetes, a patient group commonly affected by cognition impairment.

Methods: We tested associations of the polygenic score for general cognition with annual changing rates of cognition measures in 8 years of follow-up among 12,090 White and 3100 Black participants of the Health and Retirement Study (HRS), a nationally representative sample of adults aged 50 …

Recurrent Somatic Copy Number Alterations And Their Association With Oncogene Expression Levels In High-Grade Ovarian Serous Carcinoma, Hillary P Esplen, Richard K Yang, Awdhesh Kalia, Zhenya Tang, Guilin Tang, L Jeffrey Medeiros, Gokce A Toruner

Faculty, Staff and Student Publications

Somatic copy number alterations (SCNAs) are frequently observed in high-grade ovarian serous carcinoma (HGOSC). However, their impact on gene expression levels has not been systematically assessed. In this study, we explored the relationship between recurrent SCNA and gene expression using The Cancer Genome Atlas Pan Cancer dataset (OSC, TCGA, PanCancer Atlas) to identify cancer-related genes in HGOSC. We then investigated any association between highly correlated cancer genes and clinicopathological parameters, including age of diagnosis, disease stage, overall survival (OS), and progression-free survival (PFS). A total of 772 genes with recurrent SCNAs were observed. SCNA and mRNA expression levels were highly …

Transforming Ovarian Cancer Care By Targeting Minimal Residual Disease, Amir A Jazaeri, Rachel Grisham, Anne Knisely, Stefani Spranger, Dmitriy Zamarin, R Tyler Hillman, Barrett C Lawson, Kathleen H Burns, Sanghoon Lee, Shannon N Westin, Enrico Moiso, Marc J Williams, Neelkanth M Bardhan, Thomas Pisanic, Ursula Matulonis, Britta Weigelt, Ieming Shih, Panagiotis A Konstantinopoulos, Stephanie Gaillard, Linghua Wang, Carol Aghajanian, Alan D D'Andrea, Paula Hammond, Sohrab Shah, Kai W Wucherpfennig, Karen H Lu

Faculty, Staff and Student Publications

Frontline treatment and resultant cure rates in patients with advanced ovarian cancer have changed little over the past several decades. Here, we outline a multidisciplinary approach aimed at gaining novel therapeutic insights by focusing on the poorly understood minimal residual disease phase of ovarian cancer that leads to eventual incurable recurrences.

Comparative Performance Analysis Of Binary Variants Of Fox Optimization Algorithm With Half-Quadratic Ensemble Ranking Method For Thyroid Cancer Detection, Rohit Sharma, Gautam Kumar Mahanti, Ganapati Panda, Adyasha Rath, Sujata Dash, Saurav Mallik, Zhongming Zhao

Faculty, Staff and Student Publications

Thyroid cancer is a life-threatening condition that arises from the cells of the thyroid gland located in the neck's frontal region just below the adam's apple. While it is not as prevalent as other types of cancer, it ranks prominently among the commonly observed cancers affecting the endocrine system. Machine learning has emerged as a valuable medical diagnostics tool specifically for detecting thyroid abnormalities. Feature selection is of vital importance in the field of machine learning as it serves to decrease the data dimensionality and concentrate on the most pertinent features. This process improves model performance, reduces training time, and …

Cd46-Adc Reduces The Engraftment Of Multiple Myeloma Patient-Derived Xenografts, Michael J Vanwyngarden, Zachary J Walker, Yang Su, Olivia Perez De Acha, Brett M Stevens, Peter A Forsberg, Tomer M Mark, William Matsui, Bin Liu, Daniel W Sherbenou

Faculty, Staff and Student Publications

An antibody-drug conjugate (ADC) targeting CD46 conjugated to monomethyl auristatin has a potent anti-myeloma effect in cell lines in vitro and in vivo, and patient samples treated ex vivo. Here, we tested if CD46-ADC may have the potential to target MM-initiating cells (MM-ICs). CD46 expression was measured on primary MM cells with a stem-like phenotype. A patient-derived xenograft (PDX) model was implemented utilizing implanted fetal bone fragments to provide a humanized microenvironment. Engraftment was monitored via serum human light chain ELISA, and at sacrifice via bone marrow and bone fragment flow cytometry. We then tested MM regeneration in PDX by …

Is The Direct Fixation Of Displaced Quadrilateral Plates In Acetabular Fractures Necessary?, Beom-Soo Kim, Ki-Cheor Bae, Chul-Hyun Cho, Kyung-Jae Lee, In Gyu Lee, Min-Gyu Lee, Byung-Woo Min

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Quadrilateral plate fractures represent a heterogeneous group of acetabular fractures. Accurate reduction is required to prevent post-traumatic arthritis. The purpose of this study is to determine the reduction effect of the direct fixation of quadrilateral plates in acetabular fractures, and to evaluate the strength of direct fixation compared to indirect fixation. Between 2005 and 2021, 49 patients underwent surgery for open reduction and internal fixation in acetabular fractures with severely displaced quadrilateral plates. Twenty-nine patients comprised the indirect fixation group, and twenty patients comprised the direct fixation group. In a comparison of primary outcome between two groups, 10 out of …

Venetoclax Abrogates The Prognostic Impact Of Splicing Factor Gene Mutations In Newly Diagnosed Acute Myeloid Leukemia, Jayastu Senapati, Samuel Urrutia, Sanam Loghavi, Nicholas J Short, Ghayas C Issa, Abhishek Maiti, Hussein A Abbas, Naval G Daver, Naveen Pemmaraju, Sherry Pierce, Kelly S Chien, Koji Sasaki, Tapan M Kadia, Danielle E Hammond, Gautam Borthakur, Keyur Patel, Farhad Ravandi, Hagop M Kantarjian, Guillermo Garcia-Manero, Courtney D Dinardo

Faculty, Staff and Student Publications

Mutations in splicing factor (SF) genes SRSF2, U2AF1, SF3B1, and ZRSR2 are now considered adverse risk in the European LeukemiaNet 2022 acute myeloid leukemia (AML) risk stratification. The prognostic impact of SF mutations in AML has been predominantly derived from younger patients treated with intensive (INT) therapy. We evaluated 994 patients with newly diagnosed AML, including 266 (27%) with a SFmut. Median age was 67 years overall, with patients with SFmut being older at 72 years. SRSF2 (n = 140, 53%) was the most common SFmut. In patients treated with INT, median relapse-free survival (RFS) (9.6 vs 21.4 months, P …

Voltage- And Calcium-Gated Membrane Currents Tune The Plateau Potential Properties Of Multiple Neuron Types, Curtis L Neveu, Paul Smolen, Douglas A Baxter, John H Byrne

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Many neurons exhibit regular firing that is limited to the duration and intensity of depolarizing stimuli. However, some neurons exhibit all-or-nothing plateau potentials that, once elicited, can lead to prolonged activity that is independent of stimulus intensity or duration. To better understand this diversity of information processing, we compared the voltage-gated and Ca2+-gated currents of three identified neurons from hermaphroditic Aplysia californica Two of these neurons, B51 and B64, generated plateau potentials and a third neuron, B8, exhibited regular firing and was incapable of generating a plateau potential. With the exception of the Ca2+-gated potassium current (I KCa), all …

The Cancer Moonshot Immuno-Oncology Translational Network At 5: Accelerating Cancer Immunotherapies, Ananth Annapragada, Andrew G Sikora, Himangi Marathe, Song Liu, Michael Demetriou, Lawrence Fong, Jinming Gao, Donald Kufe, Zachary S Morris, Eduardo Vilar, Elad Sharon, Alan Hutson, Kunle Odunsi

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The Immuno-Oncology Translational Network (IOTN) was established in 2018 as part of the Cancer Moonshot. In 2022, President Joe Biden set new goals to reduce the cancer death rate by half within 25 years and improve the lives of people with cancer and cancer survivors. The IOTN is focused on accelerating translation of cancer immunology research, from bench to bedside, and improving immunotherapy outcomes across a wide array of cancers in the adult population. The unique structure and team science approach of the IOTN is designed to accelerate discovery and evaluation of novel immune-based therapeutic and prevention strategies. In this …