Medical Specialties Commons^™

A Statistical Approach For Systematic Identification Of Transition Cells From Scrna-Seq Data, Yuanxin Wang, Merve Dede, Vakul Mohanty, Jinzhuang Dou, Ziyi Li, Ken Chen

Faculty, Staff and Student Publications

Decoding cellular state transitions is crucial for understanding complex biological processes in development and disease. While recent advancements in single-cell RNA sequencing (scRNA-seq) offer insights into cellular trajectories, existing tools primarily study expressional rather than regulatory state shifts. We present CellTran, a statistical approach utilizing paired-gene expression correlations to detect transition cells from scRNA-seq data without explicitly resolving gene regulatory networks. Applying our approach to various contexts, including tissue regeneration, embryonic development, preinvasive lesions, and humoral responses post-vaccination, reveals transition cells and their distinct gene expression profiles. Our study sheds light on the underlying molecular mechanisms driving cellular state transitions, …

Pharmacologic Blockade Of A Pioneer Transcription Factor, Katerina Cermakova, H Courtney Hodges

Faculty, Staff and Students Publications

Cancers frequently co-opt lineage-specific transcription factors (TF) utilized in normal development to sustain proliferation. However, the effects of these TFs on tumor development depend considerably on where in the genome they bind. A new article by Taylor and colleagues expands on previously developed diamidine compounds that obstruct the DNA binding sites of the pioneer TF PU.1 (SPI1) in acute myeloid leukemia. Immobilization and sequencing of genomic DNA targeted by these compounds revealed that these inhibitors alter the genomic binding patterns of PU.1. The authors report that their strategy constrains the genomic binding preferences of PU.1, leading to redistribution of PU.1 …

Whispers In The Wind: Face Mask Sampling For Mycobacterium Tuberculosis Detection In Children With Pulmonary Tuberculosis, Lennard Meiwes, Irina Kontsevaya, Dumitru Chesov, Stela Kulciţkaia, Viola Dreyer, Doris Hillemann, Qiniso Dlamini, Caroline Williams, Michael Barer, Folke Brinkmann, Renate Krüger, Stephanie Thee, Alexander Kay, Anna Maria Mandalakas, Christoph Lange

Faculty, Staff and Students Publications

Background: Recently, face mask sampling (FMS) confirmed detection of Mycobacterium tuberculosis DNA from exhaled breath in adults with tuberculosis. To date, no study has evaluated the use of FMS to detect pulmonary tuberculosis in children. We developed a method for FMS of M. tuberculosis-specific DNA in children and performed a clinical exploration to assess feasibility in children.

Methods: Face masks were spiked, analyzed on GeneXpert-Ultra, quantitative polymerase chain reaction, and targeted next-generation sequencing. Children with pulmonary tuberculosis were asked to wear 3 modified FFP2 masks for 30 minutes as part of an exploratory clinical study.

Results: Experiments with H37Ra M. …

Cutaneous Nodules Secondary To Mycobacterium Avium Complex In A Patient With Human Immunodeficiency Virus, Jay Patel, Shannon Sayyadioskoie, Hanna Siatecka, Theodore Rosen

Faculty, Staff and Students Publications

We present a patient with human immunodeficiency virus who developed multiple painful lesions that previously in the past had speciated as Cryptococcus neoformans cutaneously, and in the lung. Despite induction therapy for presumed re-infection, the patient did not improve so a biopsy was performed and this was speciated as Mycobacterium avium complex, with final diagnosis being disseminated Mycobacterium avium complex. This case highlights the importance of considering a broad differential diagnosis for any new lesions regardless of prior culture data.

Development Of A Ripk1 Degrader To Enhance Antitumor Immunity, Xin Yu, Dong Lu, Xiaoli Qi, Rishi Ram Paudel, Hanfeng Lin, Bryan L Holloman, Feng Jin, Longyong Xu, Lang Ding, Weiyi Peng, Meng C Wang, Xi Chen, Jin Wang

Faculty, Staff and Students Publications

The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and emerges as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain of RIPK1, here we harness proteolysis targeting chimera (PROTAC) technology to develop a RIPK1 degrader, LD4172. LD4172 exhibits potent and selective RIPK1 degradation both in vitro and in vivo. Degradation of RIPK1 by LD4172 triggers immunogenic cell death, enhances tumor-infiltrating lymphocyte responses, and sensitizes tumors to anti-PD1 therapy in female C57BL/6J mice. This work reports …

The American Cancer Society National Lung Cancer Roundtable Strategic Plan: Methods For Improving Turnaround Time Of Comprehensive Biomarker Testing In Non-Small Cell Lung Cancer, Sinchita Roy-Chowdhuri, Haresh Mani, Adam H Fox, Anne Tsao, Lynette M Sholl, Farhood Farjah, Bruce E Johnson, Raymond U Osarogiagbon, M Patricia Rivera, Gerard A Silvestri, Robert A Smith, Ignacio I Wistuba

Faculty, Staff and Student Publications

Comprehensive biomarker testing for patients with non-small cell lung cancer is critical for selecting appropriate targeted therapy or immunotherapy. Ensuring timely ordering, processing, and reporting is key to optimizing patient outcomes. However, various factors can prevent or delay patients from being offered the option of treatment selection based on comprehensive biomarker testing. These factors include problems with access to testing, tissue adequacy, turnaround time, and health insurance coverage and billing practices. Turnaround time depends on several logistical and tissue handling factors, which involve institutional policies, processes, resources, testing methodology, and testing algorithms that vary across different practices. In this article, …

The American Cancer Society National Lung Cancer Roundtable Strategic Plan: Advancing Comprehensive Biomarker Testing In Non-Small Cell Lung Cancer, Adam H Fox, Raymond U Osarogiagbon, Farhood Farjah, James R Jett, Bruce E Johnson, M Patricia Rivera, Robert A Smith, Ignacio I Wistuba, Gerard A Silvestri

Faculty, Staff and Student Publications

Comprehensive biomarker testing is a crucial requirement for the optimal treatment of advanced-stage non-small cell lung cancer (NSCLC), with emerging relevance in the adjuvant treatment setting. To advance its goal of ensuring optimal therapy for persons diagnosed with lung cancer, the American Cancer Society National Lung Cancer Roundtable (ACS NLCRT) held The Summit on Optimizing Lung Cancer Biomarkers in Practice in September 2020 to align its partners toward the goal of ensuring comprehensive biomarker testing for all eligible patients with NSCLC. The ACS NLCRT's Strategic Plan for Advancing Comprehensive Biomarker Testing in NSCLC, a product of the summit, comprises actions …

Global Impact Of Aging On The Hemodynamic Response Function In The Gray Matter Of Human Cerebral Cortex, Nooshin J Fesharaki, Amanda Taylor, Keisjon Mosby, Ruosha Li, Jung Hwan Kim, David Ress

Faculty, Staff and Students Publications

In functional magnetic resonance imaging, the hemodynamic response function (HRF) is a stereotypical response to local changes in cerebral hemodynamics and oxygen metabolism due to briefly (< 4 s) evoked neural activity. Accordingly, the HRF is often used as an impulse response with the assumption of linearity in data analysis. In cognitive aging studies, it has been very common to interpret differences in brain activation as age-related changes in neural activity. Contrary to this assumption, however, evidence has accrued that normal aging may also significantly affect the vasculature, thereby affecting cerebral hemodynamics and metabolism, confounding interpretation of fMRI cognitive aging studies. In this study, use was made of a multisensory task to evoke the HRF in ~87% of cerebral cortex in cognitively intact adults with ages ranging from 22 to 75 years. This widespread activation enabled us to investigate age trends in the spatial distributions of HRF characteristics within the majority of cortical gray matter, which we termed as global age trends. The task evoked both positive and negative HRFs, which were characterized using model-free parameters in native-space coordinates. We found significant global age trends in the distributions of HRF parameters in terms of both amplitudes (e.g., peak amplitude and contrast-to-noise ratio) and temporal dynamics (e.g., full-width-at-half-maximum). Our findings offer insight into how age-dependent changes affect neurovascular coupling and show promise for use of HRF parameters as non-invasive indicators for age-related pathology.

Parent And Primary Care Clinician Perceptions About Pediatric Hypertension, Abbas H. Zaidi, Erica Sood, Sarah De Ferranti, Samuel Gidding, Varsha Zadokar, Jonathan Miller, Anne Kazak

Department of Pediatrics Faculty Papers

IMPORTANCE: Despite published guidelines and a prevalence of pediatric hypertension of approximately 3%, less than 25% of affected children are identified, with 60% not receiving any intervention despite detection. Understanding the knowledge and perceptions of parents or caregivers and health care teams is crucial to identify factors that may contribute to these unacceptably low detection rates.

OBJECTIVE: To examine the knowledge and perceptions of parents and health care teams regarding pediatric hypertension to identify common themes contributing to low hypertension detection.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study, interviewed parents of children diagnosed with hypertension who did not follow up …

The Rise, Fall, And Resurgence Of Phage Therapy For Urinary Tract Infection, Jacob J Zulk, Kathryn A Patras, Anthony W Maresso

Faculty, Staff and Students Publications

In the face of rising antimicrobial resistance, bacteriophage therapy, also known as phage therapy, is seeing a resurgence as a potential treatment for bacterial infections including urinary tract infection (UTI). Primarily caused by uropathogenic Escherichia coli, the 400 million UTI cases annually are major global healthcare burdens and a primary cause of antibiotic prescriptions in the outpatient setting. Phage therapy has several potential advantages over antibiotics including the ability to disrupt bacterial biofilms and synergize with antimicrobial treatments with minimal side effects or impacts on the microbiota. Phage therapy for UTI treatment has shown generally favorable results in recent …

Ire1Α Silences Dsrna To Prevent Taxane-Induced Pyroptosis In Triple-Negative Breast Cancer, Longyong Xu, Fanglue Peng, Qin Luo, Yao Ding, Fei Yuan, Liting Zheng, Wei He, Sophie S Zhang, Xin Fu, Jin Liu, Ayse Sena Mutlu, Shuyue Wang, Ralf Bernd Nehring, Xingyu Li, Qianzi Tang, Catherine Li, Xiangdong Lv, Lacey E Dobrolecki, Weijie Zhang, Dong Han, Na Zhao, Eric Jaehnig, Jingyi Wang, Weiche Wu, Davis A Graham, Yumei Li, Rui Chen, Weiyi Peng, Yiwen Chen, Andre Catic, Zhibin Zhang, Bing Zhang, Anthony M Mustoe, Albert C Koong, George Miles, Michael T Lewis, Meng C Wang, Susan M Rosenberg, Bert W O'Malley, Thomas F Westbrook, Han Xu, Xiang H-F Zhang, C Kent Osborne, Jin Billy Li, Matthew J Ellis, Mothaffar F Rimawi, Jeffrey M Rosen, Xi Chen

Faculty, Staff and Students Publications

Chemotherapy is often combined with immune checkpoint inhibitor (ICI) to enhance immunotherapy responses. Despite the approval of chemo-immunotherapy in multiple human cancers, many immunologically cold tumors remain unresponsive. The mechanisms determining the immunogenicity of chemotherapy are elusive. Here, we identify the ER stress sensor IRE1α as a critical checkpoint that restricts the immunostimulatory effects of taxane-chemotherapy and prevents the innate immune recognition of immunologically cold triple-negative breast cancer (TNBC). IRE1α RNase silences taxane-induced dsRNA through RIDD (Regulated IRE1-Dependent Decay) to prevent NLRP3 inflammasome–dependent pyroptosis. Inhibition of IRE1α in Trp53−/− TNBC allows taxane to induce extensive dsRNAs that are sensed …

Nomenclature For Human And Animal Fungal Pathogens And Diseases: A Proposal For Standardized Terminology, Sybren De Hoog, Thomas J Walsh, Sarah A Ahmed, Ana Alastruey-Izquierdo, Maiken Cavling Arendrup, Andrew Borman, Sharon Chen, Anuradha Chowdhary, Robert C Colgrove, Oliver A Cornely, David W Denning, Philippe J Dufresne, Laura Filkins, Jean-Pierre Gangneux, Josepa Gené, Andreas H Groll, Jaques Guillot, Gerhard Haase, Catriona Halliday, David L Hawksworth, Roderick Hay, Martin Hoenigl, Vit Hubka, Tomasz Jagielski, Hazal Kandemir, Sarah E Kidd, Julianne V Kus, June Kwon-Chung, Shawn R Lockhart, Jacques F Meis, Leonel Mendoza, Wieland Meyer, M Hong Nguyen, Yinggai Song, Tania C Sorrell, J Benjamin Stielow, Rachel Vilela, Roxana G Vitale, Nancy L Wengenack, P Lewis White, Luis Ostrosky-Zeichner, Sean X Zhang

Faculty, Staff and Student Publications

Medically important pathogenic fungi invade vertebrate tissue and are considered primary when part of their nature life cycle is associated with an animal host and are usually able to infect immunocompetent hosts. Opportunistic fungal pathogens complete their life cycle in environmental habitats or occur as commensals within or on the vertebrate body, but under certain conditions can thrive upon infecting humans. The extent of host damage in opportunistic infections largely depends on the portal and modality of entry as well as on the host's immune and metabolic status. Diseases caused by primary pathogens and common opportunists, causing the top approximately …

Staphylococcus Epidermidis St2 Strains Associated With Bloodstream Infections Contain A Unique Mobile Genetic Element Encoding A Plasmin Inhibitor, Amy A Gomez, Clara Kjerfve, Minseo Choi, Wen Liu, Kelly Churion, Sheila Thomas, Holger Rohde, Sam Shelburne, Jon T Skare, Magnus Hook, Srishtee Arora

Faculty, Staff and Student Publications

Staphylococcus epidermidis, a common commensal bacterium, is a leading cause of nosocomial catheter-associated bloodstream infections. S. epidermidis sequence type 2 (ST2) is specifically recognized globally for causing invasive disease. In this study, we identified a novel putative integrated conjugative element, pICE-Sepi-ST2, unique to the genomes of S. epidermidis ST2. Our investigation identified pICE-Sepi-ST2 in all ST2 isolates from bloodstream infections. Meanwhile, ST2 isolates from other infection sources, such as catheters, prosthetic joints, and fracture fixations, showed variable pICE-Sepi-ST2 prevalence. pICE-Sepi-ST2 encodes two putative cell wall anchored proteins that we have designated SesX and SesY. Biochemical characterization of SesY revealed …

Guideline-Directed Medical Therapy After Hospitalization For Acute Heart Failure: Insights From The Connect-Hf, Satoshi Shoji, Lisa Kaltenbach, Bradi B. Granger, Gregg C. Fonarow, Hussein R. Al-Khalidi, Nancy M. Albert, Javed Butler, Larry A. Allen, David E. Lanfear, Jennifer T. Thibodeau, Brittany M. Chapman, Sandra M. Oliver-Mcneil, G. Michael Felker, Ileana L. Piña, Christopher B. Granger, Adrian F. Hernandez, Adam D. Devore

Division of Cardiology Faculty Papers

BACKGROUND: Significant gap remains in the implementation of guideline-directed medical therapy (GDMT) in patients with heart failure after a hospitalization. We aimed to evaluate the use and titration of GDMT at discharge and over a 12-month period after hospital discharge and to identify factors associated with GDMT use and titration.

METHODS AND RESULTS: The CONNECT-HF (Care Optimization Through Patient and Hospital Engagement Clinical Trial for Heart Failure) trial evaluated the effect of a hospital and postdischarge quality improvement intervention in participants with heart failure with reduced ejection fraction. In this secondary analysis, we examined use and titration to at least …

An Empirical Model Of Carbon-Ion Relative Biological Effectiveness Based On The Linear Correlation Between Radiosensitivity To Photons And Carbon Ions, David B Flint, Scott J Bright, Conor Mcfadden, Teruaki Konishi, David K J Martinus, Mandira Manandhar, Mariam Ben Kacem, Lawrence Bronk, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Objective.To develop an empirical model to predict carbon ion (C-ion) relative biological effectiveness (RBE).Approach.We used published cell survival data comprising 360 cell line/energy combinations to characterize the linear energy transfer (LET) dependence of cell radiosensitivity parameters describing the dose required to achieve a given survival level, e.g. 5% (D5%), which are linearly correlated between photon and C-ion radiations. Based on the LET response of the metrics D5%and D37%, we constructed a model containing four free parameters that predicts cells' linear quadratic model (LQM) survival curve parameters for C-ions,αCandβC, from the reference LQM parameters …

Impact Of Prior Inotuzumab Ozogamicin Treatment On Brexucabtagene Autoleucel Outcomes In Adults With B-Cell All, Ibrahim Aldoss, Gregory W Roloff, Rawan Faramand, Noam E Kopmar, Chenyu Lin, Anjali S Advani, Simone E Dekker, Vishal K Gupta, Timothy E O'Connor, Nikeshan Jeyakumar, Ibrahim N Muhsen, Yannis Valtis, Amy Zhang, Katharine Miller, Katherine Sutherland, Kaitlyn C Dykes, Mohamed Ahmed, Evan Chen, Hector Zambrano, Danielle Bradshaw, Santiago Mercadal, Marc Schwartz, Sean Tracy, Bhagirathbhai Dholaria, Michal Kubiak, Akash Mukherjee, Navneet Majhail, Minoo Battiwalla, Luke Mountjoy, Shahbaz A Malik, John Mathews, Paul Shaughnessy, Aaron C Logan, Abdullah Ladha, Maryann Stefan, Caitlin Guzowski, Rasmus T Hoeg, Talal Hilal, Jozal Moore, Matthew Connor, Kristen M O'Dwyer, Laquisa C Hill, Stephanie B Tsai, Joshua Sasine, Melhem M Solh, Catherine J Lee, Vamsi K Kota, Divya Koura, Muthu Veeraputhiran, Betsy Blunk, Caspian Oliai, Jessica T Leonard, Noelle V Frey, Jae H Park, Marlise R Luskin, Veronika Bachanova, Ahmed Galal, Michael R Bishop, Wendy Stock, Ryan D Cassaday, Vinod Pullarkat, Bijal D Shah, Lori S Muffly

Faculty, Staff and Students Publications

The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed). InO-exposed patients were more heavily pretreated (P = .02) and frequently had active marrow disease before apheresis (P = .03). Response rate and toxicity profile after brexu-cel were comparable for InO-exposed and InO-naïve patients; however, consolidation therapy after brexu-cel response was used at a higher rate in InO-naïve patients (P = .005). …

Wearable Surface Electromyography System To Predict Freeze Of Gait In Parkinson's Disease Patients., Anna Moore, Jinxing Li, Christopher H Contag, Luke J Currano, Connor O Pyles, David A Hinkle, Vivek Shinde Patil

Neuroscience Articles

Freezing of gait (FOG) is a disabling yet poorly understood paroxysmal gait disorder affecting the vast majority of patients with Parkinson's disease (PD) as they reach advanced stages of the disorder. Falling is one of the most disabling consequences of a FOG episode; it often results in injury and a future fear of falling, leading to diminished social engagement, a reduction in general fitness, loss of independence, and degradation of overall quality of life. Currently, there is no robust or reliable treatment against FOG in PD. In the absence of reliable and effective treatment for Parkinson's disease, alleviating the consequences …

Factors Associated With Receipt Of Tobacco Treatment Integrated With Nurse Navigation In A Centralized Lung Cancer Screening Program At An Urban Academic Medical Center, Christine S. Shusted, Sarah Mukhtar, James Lee, Brooke Ruane, Emily Muse, Lawrence Emeigh-Mcbride, Eboni Gatson-Anderson, Gregory C. Kane, Kuang-Yi Wen, Hee-Soon Juon, Julie A. Barta

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

PURPOSE: Optimal approaches for tobacco treatment counseling among individuals who currently smoke and are undergoing shared decision-making (SDM) and lung cancer screening (LCS) are unknown. The objective of this cross-sectional study was to determine the rate of reported interest in tobacco treatment counseling and pharmacotherapy among individuals who currently smoke and are receiving integrated nurse navigation for LCS and tobacco treatment in a centralized LCS Program.

METHODS: We identified individuals undergoing SDM through our centralized LCS Program between March 2021 and March 2022. The LCS Program tobacco treatment protocol includes counseling both in-person and via telephone during SDM, LCS results …

Automated Segmentation Of Mri White Matter Hyperintensities In 8421 Patients With Acute Ischemic Stroke, Hosung Kim, Wi-Sun Ryu, Dawid Schellingerhout, Jonghyeok Park, Jinyong Chung, Sang-Wuk Jeong, Dong-Seok Gwak, Beom Joon Kim, Joon-Tae Kim, Keun-Sik Hong, Kyung Bok Lee, Tai Hwan Park, Jong-Moo Park, Kyusik Kang, Yong-Jin Cho, Byung-Chul Lee, Kyung-Ho Yu, Mi Sun Oh, Soo Joo Lee, Jae-Kwan Cha, Dae-Hyun Kim, Jun Lee, Man Seok Park, Hee-Joon Bae, Dong-Eog Kim

Faculty, Staff and Student Publications

Background and purpose: To date, only a few small studies have attempted deep learning-based automatic segmentation of white matter hyperintensity (WMH) lesions in patients with cerebral infarction; this issue is complicated because stroke-related lesions can obscure WMH borders. We developed and validated deep learning algorithms to segment WMH lesions accurately in patients with cerebral infarction using multisite data sets involving 8421 patients with acute ischemic stroke.

Materials and methods: We included 8421 patients with stroke from 9 centers in Korea. 2D UNet and squeeze-and-excitation (SE)-UNet models were trained using 2408 FLAIR MRIs from 3 hospitals and validated using 6013 FLAIR …

Additional Expression Of T-Cell Engager In Clinically Tested Oncolytic Adeno-Immunotherapy Redirects Tumor-Infiltrated, Irrelevant T Cells Against Cancer Cells To Enhance Antitumor Immunity, Daisuke Morita, Amanda Rosewell Shaw, Greyson Biegert, Caroline Porter, Mae Woods, Spyridoula Vasileiou, Bora Lim, Masataka Suzuki

Faculty, Staff and Student Publications

Background: Oncolytic adenoviruses (OAds) are the most clinically tested viral vectors for solid tumors. However, most clinically tested "Armed" OAds show limited antitumor effects in patients with various solid tumors even with increased dosages and multiple injections. We developed a binary oncolytic/helper-dependent adenovirus system (CAdVEC), in which tumors are coinfected with an OAd and a non-replicating helper-dependent Ad (HDAd). We recently demonstrated that a single low-dose CAdVEC expressing interleukin-12, programmed death-ligand 1 blocker, and HSV thymidine kinase safety switch (CAdTrio) induces significant antitumor effects in patients, including complete response. Similar to previous OAd studies, all patients primarily amplified Ad-specific T …

Clinical And Radiologic Findings In Children With Anomalous Pontine Cranial Nerves, Karen K Moeller, Brandon H Tran, Thierry A G M Huisman, Nilesh K Desai, Marcia K Kukreja, Rajan P Patel, Uma S Ramaswamy, Carol Liu, Stephen F Kralik

Faculty, Staff and Students Publications

We retrospectively reviewed the clinical and radiologic findings in 17 children with an aberrant cisternal cranial nerve 7 (CN7), and found that these patients had additional anomalies involving other pontine cranial nerves (CNs). The hallmark imaging feature identified in all patients was an aberrant cisternal segment of an enlarged-appearing CN7. The abnormal nerve coursed anteriorly toward the Gasserian ganglion, where it fanned out toward the internal auditory canal, Meckel cave, or both. This finding was accompanied by a small cisternal CN5, which often had a lateral bowed appearance. CN5 and CN7 were abnormally close to each other. Meckel's cave appeared …

Benefits Of Multisensory Rooms In Schools To Control Behaviors In Children With Disabilities, Kye Smith, Cassandra Nelson

Fall 2024 OTD Capstone Symposium

This project explores the benefits of implementing multisensory rooms in schools to manage challenging behaviors in children with disabilities. Conducted at the Barack and Michelle Obama Ninth Grade Center in Lancaster, TX, the program involved participants aged 13-15 diagnosed with disabilities. A comprehensive needs assessment identified gaps in behavior management and overstimulation challenges. The program was designed using evidence-based strategies, including the Person-Environment-Occupation-Performance (PEOP) model, and incorporated techniques such as the Take Five Breathing Strategy, deep pressure input, chair yoga, and meditation.

Through pre- and post-surveys with students, parents, and teachers, the study evaluated the program's impact on functional independence …

Antimicrobial Susceptibility Trends In E. Coli Causing Pediatric Urinary Tract Infections In The United States, Simren Mahajan, Neena Kanwar, Gina M. Morgan, Rodrigo E. Mendes, Brian R. Lee, Dithi Banerjee, Rangaraj Selvarangan

Manuscripts, Articles, Book Chapters and Other Papers

Urinary tract infections (UTIs) are among the most common pediatric infections. This study evaluated the antimicrobial susceptibility patterns of 3511 uropathogenic E. coli (UPEC) isolated from pediatric patients in the United States from 2014 to 2023. The database from the SENTRY antimicrobial surveillance program from 89 medical centers was utilized as a data source. The antimicrobial susceptibility was tested using the microbroth dilution technique against 24 antimicrobial agents. MICs were determined using the CLSI/EUCAST/FDA breakpoint criteria. All the antimicrobials reported susceptibility rates above 80% except for tetracycline (76.2%), trimethoprim-sulfamethoxazole (69.7%), and ampicillin-sulbactam (55.7%). During the study period, the susceptibility rates …

Mutation- And Mrd-Informed Treatments For Transplant-Ineligible Patients, Curtis A Lachowiez, Courtney D Dinardo

Faculty, Staff and Student Publications

The ongoing development of molecularly targeted therapies in addition to the new standard of care combination of azacitidine and venetoclax (AZA-VEN) has transformed the prognostic outlook for older, transplant-ineligible patients with acute myeloid leukemia (AML). While conventional treatments, such as standard anthracycline and cytarabine- based chemotherapy or hypomethylating agent (HMA) monotherapy, are associated with a generally poor prognosis in this patient population, the use of these novel regimens can result in long-lasting, durable remissions in select patient subgroups. Furthermore, the simultaneous discovery of resistance mechanisms to targeted therapies and AZA-VEN has enabled the identification of patient subgroups with inferior outcomes, …

Transplant-Associated Tma: The Conundrum Of Diagnosis And Treatment, Ang Li, Sarah E Sartain

Faculty, Staff and Students Publications

Transplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic cell transplantation is characterized by microangiopathic hemolytic anemia (MAHA) with persistent schistocytosis, elevated markers of hemolysis, thrombocytopenia, and microvascular thrombosis leading to ischemic injuries in the kidneys and other organs. The initial evaluation of the disease requires confirmation of non-immune MAHA and careful examination of known secondary causes of TMA. Due to increased likelihood of long-term renal failure and overall mortality, a rapid diagnosis and treatment of the underlying trigger is needed. However, the diagnostic criteria proposed to define TA-TMA remain insufficient. sC5b9, the soluble form of the membrane attack complex of the terminal …

Integrative Multi-Omics Analysis Uncovers Tumor-Immune-Gut Axis Influencing Immunotherapy Outcomes In Ovarian Cancer, Spencer R Rosario, Mark D Long, Shanmuga Chilakapati, Eduardo Cortes Gomez, Sebastiano Battaglia, Prashant K Singh, Jianmin Wang, Katy Wang, Kristopher Attwood, Suzanne M Hess, A J Robert Mcgray, Kunle Odunsi, Brahm H Segal, Gyorgy Paragh, Song Liu, Jennifer A Wargo, Emese Zsiros

Faculty, Staff and Student Publications

Recurrent ovarian cancer patients, especially those resistant to platinum, lack effective curative treatments. To address this, we conducted a phase 2 clinical trial (NCT02853318) combining pembrolizumab with bevacizumab, to increase T cell infiltration into the tumor, and oral cyclophosphamide, to reduce the number of regulatory T cells. The trial accrued 40 heavily pretreated recurrent ovarian cancer patients. The primary endpoint, progression free survival, was extended to a median of 10.2 months. The secondary endpoints demonstrated an objective response rate of 47.5%, and disease control in 30% of patients for over a year while maintaining a good quality of life. We …

Clonal Landscape And Clinical Outcomes Of Telomere Biology Disorders: Somatic Rescue And Cancer Mutations, Fernanda Gutierrez-Rodrigues, Emma M Groarke, Natthakan Thongon, Juan Jose Rodriguez-Sevilla, Luiz Fernando B Catto, Marena R Niewisch, Ruba Shalhoub, Lisa J Mcreynolds, Diego V Clé, Bhavisha A Patel, Xiaoyang Ma, Dalton Hironaka, Flávia S Donaires, Nina Spitofsky, Barbara A Santana, Tsung-Po Lai, Lemlem Alemu, Sachiko Kajigaya, Ivana Darden, Weiyin Zhou, Paul V Browne, Subrata Paul, Justin Lack, David J Young, Courtney D Dinardo, Abraham Aviv, Feiyang Ma, Michel Michels De Oliveira, Ana Paula De Azambuja, Cynthia E Dunbar, Malgorzata Olszewska, Emmanuel Olivier, Eirini P Papapetrou, Neelam Giri, Blanche P Alter, Carmem Bonfim, Colin O Wu, Guillermo Garcia-Manero, Sharon A Savage, Neal S Young, Simona Colla, Rodrigo T Calado

Faculty, Staff and Student Publications

Telomere biology disorders (TBDs), caused by pathogenic germ line variants in telomere-related genes, present with multiorgan disease and a predisposition to cancer. Clonal hematopoiesis (CH) as a marker of cancer development and survival in TBDs is poorly understood. Here, we characterized the clonal landscape of a large cohort of 207 patients with TBD with a broad range of age and phenotype. CH occurred predominantly in symptomatic patients and in signature genes typically associated with cancers: PPM1D, POT1, TERT promoter (TERTp), U2AF1S34, and/or TP53. Chromosome 1q gain (Chr1q+) was the commonest karyotypic abnormality. Clinically, multiorgan involvement and CH in TERTp, TP53, …

Immune Landscape Of Isocitrate Dehydrogenase-Stratified Primary And Recurrent Human Gliomas, Pravesh Gupta, Minghao Dang, Shivangi Oberai, Simona Migliozzi, Rakesh Trivedi, Gayatri Kumar, Mekenzie Peshoff, Nancy Milam, Aml Ahmed, Krishna Bojja, Tuan M Tran, Joy Gumin, Carlos Kamiya-Matsuoka, Jason Huse, Kathryn Cox, Jianzhuo Li, Huma Shehwana, Sameer A Sheth, Rodriguez Saxon, Sun Baohua, Brittany Parker Kerrigan, Atul Maheshwari, Edwin Roger Parra Cuentas, Nicholas E Navin, Amy B Heimberger, Frederick F Lang, Antonio Iavarone, Karen Clise-Dwyer, Linghua Wang, Krishna P Bhat

Faculty, Staff and Student Publications

Background: Human gliomas are classified using isocitrate dehydrogenase (IDH) status as a prognosticator; however, the influence of genetic differences and treatment effects on ensuing immunity remains unclear.

Methods: In this study, we used sequential single-cell transcriptomics on 144 678 and spectral cytometry on over 2 million immune cells encompassing 48 human gliomas to decipher their immune landscape.

Results: We identified 22 distinct immune cell types that contribute to glioma immunity. Specifically, brain-resident microglia (MG) were reduced with a concomitant increase in CD8+ T lymphocytes during glioma recurrence independent of IDH status. In contrast, IDH-wild type-associated patterns, such as an abundance …

Amniotic Fluid-Derived Stem Cells: Potential Factories Of Natural And Mimetic Strategies For Congenital Malformations, Cristiane S R Fonteles, Julia Enterria-Rosales, Ying Lin, John W Steele, Ramiro A Villarreal-Leal, Jing Xiao, Daniel I Idowu, Beck Burgelin, Bogdan J Wlodarczyk, Richard H Finnell, Bruna Corradetti

Faculty, Staff and Students Publications

BACKGROUND: Mesenchymal stem cells (MSCs) derived from gestational tissues offer a promising avenue for prenatal intervention in congenital malformations although their application is hampered by concerns related to cellular plasticity and the need for invasive, high-risk surgical procedures. Here, we present naturally occurring exosomes (EXOs) isolated from amniotic fluid-derived MSCs (AF-MSCs) and their mimetic analogs (MIMs) as viable, reproducible, and stable alternatives. These nanovesicles present a minimally invasive therapeutic option, addressing the limitations of MSC-based treatments while retaining therapeutic efficacy.

METHODS: MIMs were generated from AF-MSCs by combining sequential filtration steps through filter membranes with different porosity and size exclusion …

Exploration Of The Tunability Of Brd4 Degradation By Dcaf16 Trans-Labelling Covalent Glues, Muhammad Murtaza Hassan, Yen-Der Li, Michelle W Ma, Mingxing Teng, Woong Sub Byun, Kedar Puvar, Ryan Lumpkin, Brittany Sandoval, Justine C Rutter, Cyrus Y Jin, Michelle Y Wang, Shawn Xu, Anna M Schmoker, Hakyung Cheong, Brian J Groendyke, Jun Qi, Eric S Fischer, Benjamin L Ebert, Nathanael S Gray

Faculty, Staff and Students Publications

Chemically induced proximity modalities such as targeted protein degradation (TPD) hold promise for expanding the number of proteins that can be manipulated pharmacologically. However, current TPD strategies are often limited to proteins with preexisting ligands. Molecular glues (e.g. glutarimide ligands for CUL4CRBN), offer the potential to target undruggable proteins. Yet, their rational design is largely unattainable due to the unpredictability of the ‘gain-of-function’ nature of the glue interaction upon chemical modification of ligands. We recently reported a covalent trans-labelling glue mechanism which we named ‘Template-assisted covalent modification’, where an electrophile decorated BRD4 inhibitor was effectively delivered to …