Digital Commons Network^™

Trigeminal Neuralgia As A Primary Demyelinating Disease: Potential Multimodal Evidence And Remaining Controversies, Seyed H Mousavi, John W Lindsey, Karin N Westlund, Sascha R A Alles

Faculty, Staff and Student Publications

Trigeminal neuralgia is a heterogeneous disorder with likely multifactorial and complex etiology; however, trigeminal nerve demyelination and injury are observed in almost all patients with trigeminal neuralgia. The current management strategies for trigeminal neuralgia primarily involve anticonvulsants and surgical interventions, neither of which directly address demyelination, the pathological hallmark of trigeminal neuralgia, and treatments targeting demyelination are not available. Demyelination of the trigeminal nerve has been historically considered a secondary effect of vascular compression, and as a result, trigeminal neuralgia is not recognized nor treated as a primary demyelinating disorder. In this article, we review the evolution of our understanding …

Bloodstream Infections After Solid Organ Transplantation: Clinical Epidemiology And Antimicrobial Resistance (2016–21), Max W Adelman, Ashton A Connor, Enshuo Hsu, Ashish Saharia, Constance M Mobley, David W Victor, Mark J Hobeika, Jiejian Lin, Kevin A Grimes, Elizabeth Ramos, Claudia Pedroza, Elizabeth W Brombosz, R Mark Ghobrial, Cesar A Arias

Faculty, Staff and Student Publications

Background: Solid organ transplant (SOT) recipients are at risk of bloodstream infections (BSIs) with MDR organisms (MDROs).

Objectives: To describe the epidemiology of BSI in the year after several types of SOT, as well as the prevalence of MDRO infections in this population.

Methods: We conducted a single-centre, retrospective study of kidney, liver, heart, and multi-organ transplantation patients. We examined BSIs ≤1 year from SOT and classified MDRO phenotypes for Staphylococcus aureus, enterococci, Enterobacterales, Pseudomonas aeruginosa and Candida spp. We compared BSI characteristics between SOT types and determined risk factors for 90 day mortality.

Results: We included 2293 patients …

Pulmonary Alveolar Microlithiasis In A Middle-Aged Man Presenting With Respiratory Failure: A Case Report And Review Of The Literature, Allen C Omo-Ogboi, Joyce Ederhion, Asad Ur Rehman, Olanrewaju Ogunleye, Jaiyeola Thomas-Ogunniyi

Faculty, Staff and Student Publications

Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive disease of the lung, characterized by diffuse deposits of intra-alveolar calcium phosphate microliths. It usually affects both sexes, presenting mostly in the second and third decades. The clinical course is highly variable, ranging from being asymptomatic to respiratory failure. PAM is usually diagnosed after careful clinical, radiological, and pathological evaluation, usually when patients present for other medical purposes. Here, a case of PAM in a middle-aged man presenting with acute-on-chronic hypoxemic respiratory failure is reported, with a review of the literature.

The Role Of Palliative Care Consultation In Withdrawal Of Life-Sustaining Treatment Among Icu Patients Receiving Veno-Venous Extracorporeal Membrane Oxygenation (Vv-Ecmo): A Retrospective Case-Control Study, Gabriel Patarroyo-Aponte, Saeed Shoar, Deptmer M Ashley, Ali Noorbaksh, Dev Patel, Alisha Y Young, Bindu H Akkanti, Mark T Warner, Maria M Patarroyo-Aponte, Biswajit Kar, Igor D Gregoric, Caroline Ha, Bela Patel

Faculty, Staff and Student Publications

Background: Extracorporeal membrane oxygenation (ECMO) has extended the survivability of critically ill patients beyond their unsupported prognosis and has widened the timeframe for making an informed decision about the goal of care. However, an extended time window for survival does not necessarily translate into a better outcome and the sustaining treatment is ultimately withdrawn in many patients. Emerging evidence has implicated the determining role of palliative care consult (PCC) in direction of the care that critically ill patients receive. Objective: To evaluate the impact of PCC in withdrawal of life-sustaining treatment (WOLST) among critically ill patients, who were placed on …

The Role Of Peroxisome Proliferator-Activated Receptors In The Development And Physiology Of Gametes And Preimplantation Embryos, Gabriel Patarroyo-Aponte, Saeed Shoar, Deptmer M Ashley, Ali Noorbaksh, Dev Patel, Alisha Y Young, Bindu H Akkanti, Mark T Warner, Maria M Patarroyo-Aponte, Biswajit Kar, Igor D Gregoric, Caroline Ha, Bela Patel

Faculty, Staff and Student Publications

Background: Extracorporeal membrane oxygenation (ECMO) has extended the survivability of critically ill patients beyond their unsupported prognosis and has widened the timeframe for making an informed decision about the goal of care. However, an extended time window for survival does not necessarily translate into a better outcome and the sustaining treatment is ultimately withdrawn in many patients. Emerging evidence has implicated the determining role of palliative care consult (PCC) in direction of the care that critically ill patients receive. Objective: To evaluate the impact of PCC in withdrawal of life-sustaining treatment (WOLST) among critically ill patients, who were placed on …

Knowledge And Attitudes On Contraception And Reproductive Health In Women With Hiv, Anna Henricks, Samantha Singal, Dana Hughes, Sean Kelly, Jessica L Castilho, Jamison Norwood

Faculty, Staff and Student Publications

BACKGROUND: For reasons not fully explained to date, contraception usage among women with HIV remains low. The aim of our study was to understand attitudes toward and lifetime use of contraception among women with HIV.

METHODS: We administered an anonymous, community-informed, voluntary survey to cisgender, English-speaking women with HIV (≥18 years of age) at a Southern urban HIV clinic. It included multiple choice and Likert-scale questions on reproductive health. Participants reported contraception use, recollection of provider conversations about contraception, and perceived empowerment and knowledge regarding reproductive health. We used chi-square and Fisher exact tests to compare attitudes and prior conversations …

A Kinesin-13 Family Kinesin In Trypanosoma Brucei Regulates Cytokinesis And Cytoskeleton Morphogenesis By Promoting Microtubule Bundling, Huiqing Hu, Yasuhiro Kurasawa, Qing Zhou, Ziyin Li

Faculty, Staff and Student Publications

The early branching eukaryote Trypanosoma brucei divides uni-directionally along the longitudinal cell axis from the cell anterior toward the cell posterior, and the cleavage furrow ingresses along the cell division plane between the new and the old flagella of a dividing bi-flagellated cell. Regulation of cytokinesis in T. brucei involves actomyosin-independent machineries and trypanosome-specific signaling pathways, but the molecular mechanisms underlying cell division plane positioning remain poorly understood. Here we report a kinesin-13 family protein, KIN13-5, that functions downstream of FPRC in the cytokinesis regulatory pathway and determines cell division plane placement. KIN13-5 localizes to multiple cytoskeletal structures, interacts …

Gut Microbiome Of Patients With Breast Cancer In Vietnam, Sang M Nguyen, Huong T T Tran, Jirong Long, Martha J Shrubsole, Hui Cai, Yaohua Yang, Lan M Nguyen, Giang H Nguyen, Chu V Nguyen, To V Ta, Jie Wu, Qiuyin Cai, Wei Zheng, Thuan V Tran, Xiao-Ou Shu

Faculty, Staff and Student Publications

PURPOSE: Gut microbiota play an important role in human health, including cancer. Cancer and its treatment, in turn, may alter the gut microbiome. To understand this complex relationship, we profiled the gut microbiome of 356 Vietnamese patients with breast cancer.

MATERIALS AND METHODS: Stool samples were collected before chemotherapy, with 162 pre- and 194 postsurgery. The gut microbiome was measured by shotgun metagenomic sequencing. Associations of gut microbial diversity, taxa abundance, and gut microbiome health index (GMHI) with sociodemographic, clinical factors, and tumor characteristics were evaluated.

RESULTS: Postsurgery samples were associated with significantly lower α- and β-diversities (

CONCLUSION: Our …

Does Coding Internal Working Models Of Attachment Have To Be So Hard?, Amanda Venta, Veronica Mclaren, Carla Sharp, Anna Abate, Madeleine Allman, Breana Cervantes, Sophie Kerr, Jessica Hernandez Ortiz, Eric Sumlin, Jesse Walker, Kiana Wall

Faculty, Staff and Student Publications

The Child Attachment Interview (CAI) has demonstrated promise in youth, yet widespread use is thwarted by the need for interview transcription, face-to-face training, and reliability certification. The present study sought to examine the empirical basis for these barriers. Thirty-five archival CAIs were re-coded by: (1) expert coders (i.e., trained and reliable) without access to transcripts, (2) trained coders who had not completed reliability training, and (3) novice coders who had no formal training. Agreement with consensus classifications was computed with the expectation of moderate agreement. Results supported coding by experts without transcription of the interview. Near-moderate agreement preliminarily supported the …

Artificial Intelligence Model Predicts Sudden Cardiac Arrest Manifesting With Pulseless Electric Activity Versus Ventricular Fibrillation, Lauri Holmstrom, Bryan Bednarski, Harpriya Chugh, Habiba Aziz, Hoang Nhat Pham, Arayik Sargsyan, Audrey Uy-Evanado, Damini Dey, Angelo Salvucci, Jonathan Jui, Kyndaron Reinier, Piotr J Slomka, Sumeet S Chugh

Faculty, Staff and Student Publications

BACKGROUND: There is no specific treatment for sudden cardiac arrest (SCA) manifesting as pulseless electric activity (PEA) and survival rates are low; unlike ventricular fibrillation (VF), which is treatable by defibrillation. Development of novel treatments requires fundamental clinical studies, but access to the true initial rhythm has been a limiting factor.

METHODS: Using demographics and detailed clinical variables, we trained and tested an AI model (extreme gradient boosting) to differentiate PEA-SCA versus VF-SCA in a novel setting that provided the true initial rhythm. A subgroup of SCAs are witnessed by emergency medical services personnel, and because the response time is …

What's Going Well: A Qualitative Analysis Of Positive Patient And Family Feedback In The Context Of The Diagnostic Process, Stephen K Liu, Fabienne Bourgeois, Joe Dong, Kendall Harcourt, Elizabeth Lowe, Liz Salmi, Eric J Thomas, Natalie Riblet, Sigall K Bell

Faculty, Staff and Student Publications

OBJECTIVES: Accurate and timely diagnosis relies on close collaboration between patients/families and clinicians. Just as patients have unique insights into diagnostic breakdowns, positive patient feedback may also generate broader perspectives on what constitutes a "good" diagnostic process (DxP).

METHODS: We evaluated patient/family feedback on "what's going well" as part of an online pre-visit survey designed to engage patients/families in the DxP. Patients/families living with chronic conditions with visits in three urban pediatric subspecialty clinics (site 1) and one rural adult primary care clinic (site 2) were invited to complete the survey between December 2020 and March 2022. We adapted the …

The Artificial Intelligence-Based Model Anorak Improves Histopathological Grading Of Lung Adenocarcinoma, Xiaoxi Pan, Khalid Abduljabbar, Jose Coelho-Lima, Anca-Ioana Grapa, Hanyun Zhang, Alvin Ho Kwan Cheung, Juvenal Baena, Takahiro Karasaki, Claire Rachel Wilson, Marco Sereno, Selvaraju Veeriah, Sarah J Aitken, Allan Hackshaw, Andrew G Nicholson, Mariam Jamal-Hanjani, Charles Swanton, Yinyin Yuan, John Le Quesne, David A Moore

Faculty, Staff and Student Publications

The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant …

Increased Prevalence Of Clostridioides Difficile Infection Among Pediatric Oncology Patients: Risk Factors For Infection And Complications, Brianna R Murphy, Natalie J Dailey Garnes, Hyunsoo Hwang, Christine B Peterson, Kevin W Garey, Pablo Okhuysen

Faculty, Staff and Student Publications

Background: Pediatric oncology patients, who are typically immunosuppressed, exposed to medications associated with increased Clostridioides difficile infection (CDI) risk and hospitalized, are expected to be at substantial risk for infection and complications. Although certain C. difficile ribotypes have been associated with more severe infection in adults, such an association has not been described in children.

Methods: To characterize CDI epidemiology, including risk factors and complications among pediatric oncology patients, we retrospectively reviewed charts of patients 1-18 years old treated at a designated cancer center during 2000-2017. We used fluorescence-based polymerase chain reaction to identify ribotypes causing disease at our institution. …

Deep Learning-Based Automatic Segmentation Of Cardiac Substructures For Lung Cancers, Xinru Chen, Raymond P Mumme, Kelsey L Corrigan, Yuki Mukai-Sasaki, Efstratios Koutroumpakis, Nicolas L Palaskas, Callistus M Nguyen, Yao Zhao, Kai Huang, Cenji Yu, Ting Xu, Aji Daniel, Peter A Balter, Xiaodong Zhang, Joshua S Niedzielski, Sanjay S Shete, Anita Deswal, Laurence E Court, Zhongxing Liao, Jinzhong Yang

Faculty, Staff and Student Publications

Purpose: Accurate and comprehensive segmentation of cardiac substructures is crucial for minimizing the risk of radiation-induced heart disease in lung cancer radiotherapy. We sought to develop and validate deep learning-based auto-segmentation models for cardiac substructures.

Materials and methods: Nineteen cardiac substructures (whole heart, 4 heart chambers, 6 great vessels, 4 valves, and 4 coronary arteries) in 100 patients treated for non-small cell lung cancer were manually delineated by two radiation oncologists. The valves and coronary arteries were delineated as planning risk volumes. An nnU-Net auto-segmentation model was trained, validated, and tested on this dataset with a split ratio of 75:5:20. …

Genomic Staging Of Multifocal Lung Squamous Cell Carcinomas Is Independent Of The Comprehensive Morphologic Assessment, Sanja Dacic, Xuanye Cao, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridion, Sabina Berezowska, Yuchen Han, Jin-Haeng Chung, Mary Beth Beasley, Lin Dongmei, David Hwang, Mari Mino-Kenudson, Yuko Minami, Mauro Papotti, Natasha Rekhtman, Anja C Roden, Erik Thunnissen, Ming-Sound Tsao, Yasushi Yatabe, Akihiko Yoshida, Linghua Wang, Douglas J Hartman, Jacob A Jerome, Humam Kadara, Teh-Ying Chou, Ignacio I Wistuba

Faculty, Staff and Student Publications

Introduction: Morphologic and molecular data for staging of multifocal lung squamous cell carcinomas (LSCCs) are limited. In this study, whole exome sequencing (WES) was used as the gold standard to determine whether multifocal LSCC represented separate primary lung cancers (SPLCs) or intrapulmonary metastases (IPMs). Genomic profiles were compared with the comprehensive morphologic assessment.

Methods: WES was performed on 20 tumor pairs of multifocal LSCC and matched normal lymph nodes using the Illumina NovaSeq6000 S4-Xp (Illumina, San Diego, CA). WES clonal and subclonal analysis data were compared with histologic assessment by 16 thoracic pathologists. In addition, the immune gene profiling of …

Transmission Of Amyloid-Β Pathology In Humans: A Perspective On Clinical Evidence, Celso S G Catumbela, Rodrigo Morales

Faculty, Staff and Student Publications

No abstract provided.

Azithromycin Reduces Hemoglobin-Induced Innate Neuroimmune Activation, Chirayu D Pandya, Hemendra J Vekaria, Miriam Zamorano, Amanda L Trout, Rodney M Ritzel, Gary U Guzman, Christopher Bolden, Patrick G Sullivan, John C Gensel, Brandon A Miller

Faculty, Staff and Student Publications

Neonatal intraventricular hemorrhage (IVH) releases blood products into the lateral ventricles and brain parenchyma. There are currently no medical treatments for IVH and surgery is used to treat a delayed effect of IVH, post-hemorrhagic hydrocephalus. However, surgery is not a cure for intrinsic brain injury from IVH, and is performed in a subacute time frame. Like many neurological diseases and injuries, innate immune activation is implicated in the pathogenesis of IVH. Innate immune activation is a pharmaceutically targetable mechanism to reduce brain injury and post-hemorrhagic hydrocephalus after IVH. Here, we tested the macrolide antibiotic azithromycin, which has immunomodulatory properties, to …

Phase 2 Study Of Inotuzumab Ozogamicin For Measurable Residual Disease In Acute Lymphoblastic Leukemia In Remission, Elias Jabbour, Fadi G Haddad, Nicholas J Short, Jayastu Senapati, Nitin Jain, Koji Sasaki, Jeffrey Jorgensen, Sa A Wang, Yesid Alvarado, Xuemei Wang, Courtney Dinardo, Lucia Masarova, Tapan Kadia, Rebecca S Garris, Farhad Ravandi, Hagop Kantarjian

Faculty, Staff and Student Publications

The detection of measurable residual disease (MRD) is the strongest predictor of relapse in acute lymphoblastic leukemia (ALL). Using inotuzumab ozogamicin in the setting of MRD may improve outcomes. Patients with ALL in first complete remission (CR1) or beyond (CR2+) with MRD ≥ 1 × 10-4 were enrolled in this phase 2 trial. Inotuzumab was administered at 0.6 mg/m2 on day 1 and 0.3 mg/m2 on day 8 of cycle 1, then at 0.3 mg/m2 on days 1 and 8 of cycles 2-6. Twenty-six consecutive patients with a median age of 46 years (range, 19-70 years) were treated. Nineteen (73%) …

Acquisition Of Tp63 Rearrangement In Large Cell Transformation Of Mycosis Fungoides, Karen A Nahmod, Guilin Tang, Shaoying Li, Carlos Torres-Cabala, Jie Xu

Faculty, Staff and Student Publications

No abstract provided.

Minimal Information For Studies Of Extracellular Vesicles (Misev2023): From Basic To Advanced Approaches, Joshua A Welsh, Deborah C I Goberdhan, Lorraine O'Driscoll, Edit I Buzas, Cherie Blenkiron, Benedetta Bussolati, Houjian Cai, Dolores Di Vizio, Tom A P Driedonks, Uta Erdbrügger, Juan M Falcon-Perez, Qing-Ling Fu, Andrew F Hill, Metka Lenassi, Sai Kiang Lim, Mỹ G Mahoney, Sujata Mohanty, Andreas Möller, Rienk Nieuwland, Takahiro Ochiya, Susmita Sahoo, Ana C Torrecilhas, Lei Zheng, Andries Zijlstra, Sarah Abuelreich, Reem Bagabas, Paolo Bergese, Esther M Bridges, Marco Brucale, Dylan Burger, Randy P Carney, Emanuele Cocucci, Rossella Crescitelli, Edveena Hanser, Adrian L Harris, Norman J Haughey, An Hendrix, Alexander R Ivanov, Tijana Jovanovic-Talisman, Nicole A Kruh-Garcia, Vroniqa Ku'ulei-Lyn Faustino, Diego Kyburz, Cecilia Lässer, Kathleen M Lennon, Jan Lötvall, Adam L Maddox, Elena S Martens-Uzunova, Rachel R Mizenko, Lauren A Newman, Andrea Ridolfi, Eva Rohde, Tatu Rojalin, Andrew Rowland, Andras Saftics, Ursula S Sandau, Julie A Saugstad, Faezeh Shekari, Simon Swift, Dmitry Ter-Ovanesyan, Juan P Tosar, Zivile Useckaite, Francesco Valle, Zoltan Varga, Edwin Van Der Pol, Martijn J C Van Herwijnen, Marca H M Wauben, Ann M Wehman, Sarah Williams, Andrea Zendrini, Alan J Zimmerman, Clotilde Théry, Kenneth W Witwer

Faculty, Staff and Student Publications

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional …

Tumor Treating Fields Increases Blood-Brain Barrier Permeability And Relative Cerebral Blood Volume In Patients With Glioblastoma, Michael Iv, Lewis Naya, Sajal Sanan, Samuel L Van Buskirk, Seema Nagpal, Reena P Thomas, Lawrence D Recht, Chirag B Patel

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVE: 200 kHz tumor treating fields (TTFields) is clinically approved for newly-diagnosed glioblastoma (nGBM). Because its effects on conventional surveillance MRI brain scans are equivocal, we investigated its effects on perfusion MRI (pMRI) brain scans.

METHODS: Each patient underwent institutional standard pMRI: dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) pMRI at three time points: baseline, 2-, and 6-months on-adjuvant therapy. At each timepoint, the difference between T1 pre- versus post-contrast tumor volume (ΔT1) and these pMRI metrics were evaluated: normalized and standardized relative cerebral blood volume (nRCBV, sRCBV); fractional plasma volume (V

RESULTS: Among 13 pMRI datasets …

Transcription-Replication Interactions Reveal Bacterial Genome Regulation, Andrew W Pountain, Peien Jiang, Tianyou Yao, Ehsan Homaee, Yichao Guan, Kevin J C Mcdonald, Magdalena Podkowik, Bo Shopsin, Victor J Torres, Ido Golding, Itai Yanai

Faculty, Staff and Student Publications

Organisms determine the transcription rates of thousands of genes through a few modes of regulation that recur across the genome1. In bacteria, the relationship between the regulatory architecture of a gene and its expression is well understood for individual model gene circuits2,3. However, a broader perspective of these dynamics at the genome scale is lacking, in part because bacterial transcriptomics has hitherto captured only a static snapshot of expression averaged across millions of cells4. As a result, the full diversity of gene expression dynamics and their relation to regulatory architecture remains unknown. Here we present a novel genome-wide classification of …

Allogeneic Stem Cell Therapy For Acute Ischemic Stroke: The Phase 2/3 Treasure Randomized Clinical Trial, Kiyohiro Houkin, Toshiya Osanai, Shinichiro Uchiyama, Kazuo Minematsu, Akihiko Taguchi, Katsuhiko Maruichi, Yoshimasa Niiya, Katsuyuki Asaoka, Yoshihiro Kuga, Katsumi Takizawa, Koichi Haraguchi, Shinichi Yoshimura, Kazumi Kimura, Koji Tokunaga, Atsuo Aoyama, Fusao Ikawa, Chikanori Inenaga, Tatsuya Abe, Atsushi Tominaga, Shinichi Takahashi, Kohsuke Kudo, Miki Fujimura, Taku Sugiyama, Masaki Ito, Masahito Kawabori, David C Hess, Sean I Savitz, Teruyuki Hirano

Faculty, Staff and Student Publications

IMPORTANCE: Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke.

OBJECTIVE: To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset.

DESIGN, SETTING, AND PARTICIPANTS: The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were …

From Primary Myelofibrosis To Chronic Myeloid Leukemia, Bcr::Abl1+ B-Lymphoblastic Leukemia, And Back To Primary Myelofibrosis: An Illustration Of Dynamic Clonal Evolution, Devin Wang, Wataru Kamata, Fengxi Ye, M James You

Faculty, Staff and Student Publications

The simultaneous detection of BCR::ABL1 and JAK2 V617F was rarely reported and their clonal relationship and dynamic clonal shift were not characterized. Here, we described a unique case with the initial presentation as JAK2 V617F+ primary myelofibrosis, followed by the emergence of BCR::ABL1+ chronic myeloid leukemia. The patient then developed BCR::ABL1+ B-lymphoblastic leukemia. Treatment for B-lymphoblastic leukemia prompted a regression to the state of primary myelofibrosis. In light of these observations, we proposed a clonal evolution model for this case.

Deep Learning-Based H-Score Quantification Of Immunohistochemistry-Stained Images, Zhuoyu Wen, Danni Luo, Shidan Wang, Ruichen Rong, Bret M Evers, Liwei Jia, Yisheng Fang, Elena V Daoud, Shengjie Yang, Zifan Gu, Emily N Arner, Cheryl M Lewis, Luisa M Solis Soto, Junya Fujimoto, Carmen Behrens, Ignacio I Wistuba, Donghan M Yang, Rolf A Brekken, Kathryn A O'Donnell, Yang Xie, Guanghua Xiao

Faculty, Staff and Student Publications

Immunohistochemistry (IHC) is a well-established and commonly used staining method for clinical diagnosis and biomedical research. In most IHC images, the target protein is conjugated with a specific antibody and stained using diaminobenzidine (DAB), resulting in a brown coloration, whereas hematoxylin serves as a blue counterstain for cell nuclei. The protein expression level is quantified through the H-score, calculated from DAB staining intensity within the target cell region. Traditionally, this process requires evaluation by 2 expert pathologists, which is both time consuming and subjective. To enhance the efficiency and accuracy of this process, we have developed an automatic algorithm for …

Epigenetic Regulation In Cancer, Minzhi Gu, Bo Ren, Yuan Fang, Jie Ren, Xiaohong Liu, Xing Wang, Feihan Zhou, Ruiling Xiao, Xiyuan Luo, Lei You, Yupei Zhao

Faculty, Staff and Student Publications

Epigenetic modifications are defined as heritable changes in gene activity that do not involve changes in the underlying DNA sequence. The oncogenic process is driven by the accumulation of alterations that impact genome's structure and function. Genetic mutations, which directly disrupt the DNA sequence, are complemented by epigenetic modifications that modulate gene expression, thereby facilitating the acquisition of malignant characteristics. Principals among these epigenetic changes are shifts in DNA methylation and histone mark patterns, which promote tumor development and metastasis. Notably, the reversible nature of epigenetic alterations, as opposed to the permanence of genetic changes, positions the epigenetic machinery as …

Brief Report: Comprehensive Clinicogenomic Profiling Of Small Cell Transformation From Egfr-Mutant Nsclc Informs Potential Therapeutic Targets, Bingnan Zhang, Whitney Lewis, C Allison Stewart, Benjamin B Morris, Luisa M Solis, Alejandra Serrano, Yuanxin Xi, Qi Wang, Elyse R Lopez, Kyle Concannon, Simon Heeke, Ximing Tang, Gabriela Raso, Robert J Cardnell, Natalie Vokes, George Blumenschein, Yasir Elamin, Frank Fosella, Anne Tsao, Ferdinandos Skoulidis, Celyne Bueno Hume, Koji Sasak, Jeff Lewis, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, Jack Lee, Hai Tran, Jianjun Zhang, Don Gibbons, Ara Vaporciyan, Jing Wang, Keunchil Park, John V Heymach, Lauren A Byers, Carl M Gay, Xiuning Le

Faculty, Staff and Student Publications

INTRODUCTION: NSCLC transformation to SCLC has been best characterized with

METHODS: In this study, we conducted a single-center retrospective analysis of clinical and genomic characteristics of patients with

RESULTS: A total of 34 patients were identified in our study. Median age at initial diagnosis was 58, and median time to SCLC transformation was 24.2 months. 68% were female and 82% were never smokers. 79% of patients were diagnosed as stage IV disease, and over half had brain metastases at baseline. Median overall survival of the entire cohort was 38.3 months from initial diagnoses and 12.4 months from time of SCLC …

Metabolism, Fibrosis, And Apoptosis: The Effect Of Lipids And Their Derivatives On Keloid Formation, Chen-Yu Li, Ru-Xin Xie, Shi-Wei Zhang, Jiao Yun, Ai Zhong, Ying Cen, Jun-Jie Chen

Faculty, Staff and Student Publications

Keloids, pathological scars resulting from skin trauma, have traditionally posed significant clinical management challenges due to their persistence and high recurrence rates. Our research elucidates the pivotal roles of lipids and their derivatives in keloid development, driven by underlying mechanisms of abnormal cell proliferation, apoptosis, and extracellular matrix deposition. Key findings suggest that abnormalities in arachidonic acid (AA) synthesis and non-essential fatty acid synthesis are integral to keloid formation. Further, a complex interplay exists between lipid derivatives, notably butyric acid (BA), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and the regulation of hyperfibrosis. Additionally, combinations of docosahexaenoic acid (DHA) with BA …

Locoregional Therapies In Immunologically "Cold" Tumors: Opportunities And Clinical Trial Design Considerations, Pavlos Msaouel, Rahul A Sheth

Faculty, Staff and Student Publications

Immunotherapy has revolutionized cancer management, but many tumors, particularly immunologically "cold" tumors, remain resistant to the therapy. The combination of conventional systemic immunotherapies and locoregional interventional radiology approaches is being explored to transform these cold tumors into immunologically active "hot" ones. The present article uses the example of chromophobe renal cell carcinoma (ChRCC), a renal cell carcinoma subtype resistant to current systemic immunotherapies, to address practical and conceptual challenges that have prevented the activation of clinical trials specifically designed for this malignancy to date. The practical framework discussed herein can help overcome logistic and funding limitations and facilitate the development …

The Future Of Targeting Cytotoxic T-Lymphocyte-Associated Protein-4: Is There A Role?, Anna Maria Di Giacomo, Michael Lahn, Alexander Mm Eggermont, Bernard Fox, Ramy Ibrahim, Padmanee Sharma, James P Allison, Michele Maio

Faculty, Staff and Student Publications

The 2022 yearly Think Tank Meeting in Siena, Tuscany (Italy), organized by the Italian Network for Tumor Biotherapy (NIBIT) Foundation, the Parker Institute for Cancer Immunotherapy and the World Immunotherapy Council, included a focus on the future of integrating and expanding the use of targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). The conference members exchanged their views on the lessons from targeting CTLA-4 and compared the effect to the impact of blocking Programmed cell death protein 1 (PD1) or its ligand (PDL1). The increasing experience with both therapeutic approaches and their combination suggests that targeting CTLA-4 may lead to more durable …