Medicine and Health Sciences Commons^™

Cd70 Is A Therapeutic Target Upregulated In Emt-Associated Egfr Tyrosine Kinase Inhibitor Resistance, Monique B Nilsson, Yan Yang, Simon Heeke, Sonia A Patel, Alissa Poteete, Hibiki Udagawa, Yasir Y Elamin, Cesar A Moran, Yukie Kashima, Thiruvengadam Arumugam, Xiaoxing Yu, Xiaoyang Ren, Lixia Diao, Li Shen, Qi Wang, Minying Zhang, Jacqulyne P Robichaux, Chunhua Shi, Allyson N Pfeil, Hai Tran, Don L Gibbons, Jason Bock, Jing Wang, John D Minna, Susumu S Kobayashi, Xiuning Le, John V Heymach

Faculty, Staff and Student Publications

Effective therapeutic strategies are needed for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations that acquire resistance to EGFR tyrosine kinase inhibitors (TKIs) mediated by epithelial-to-mesenchymal transition (EMT). We investigate cell surface proteins that could be targeted by antibody-based or adoptive cell therapy approaches and identify CD70 as being highly upregulated in EMT-associated resistance. Moreover, CD70 upregulation is an early event in the evolution of resistance and occurs in drug-tolerant persister cells (DTPCs). CD70 promotes cell survival and invasiveness, and stimulation of CD70 triggers signal transduction pathways known to be re-activated with acquired TKI resistance. …

Automated Contouring And Planning In Radiation Therapy: What Is 'Clinically Acceptable'?, Hana Baroudi, Kristy K Brock, Wenhua Cao, Xinru Chen, Caroline Chung, Laurence E Court, Mohammad D El Basha, Maguy Farhat, Skylar Gay, Mary P Gronberg, Aashish Chandra Gupta, Soleil Hernandez, Kai Huang, David A Jaffray, Rebecca Lim, Barbara Marquez, Kelly Nealon, Tucker J Netherton, Callistus M Nguyen, Brandon Reber, Dong Joo Rhee, Ramon M Salazar, Mihir D Shanker, Carlos Sjogreen, Mckell Woodland, Jinzhong Yang, Cenji Yu, Yao Zhao

Faculty, Staff and Student Publications

Developers and users of artificial-intelligence-based tools for automatic contouring and treatment planning in radiotherapy are expected to assess clinical acceptability of these tools. However, what is 'clinical acceptability'? Quantitative and qualitative approaches have been used to assess this ill-defined concept, all of which have advantages and disadvantages or limitations. The approach chosen may depend on the goal of the study as well as on available resources. In this paper, we discuss various aspects of 'clinical acceptability' and how they can move us toward a standard for defining clinical acceptability of new autocontouring and planning tools.

Machine Learning Methods For Computational Phenotyping Using Patient Healthcare Data With Noisy Labels, Praveen Kumar

Computer Science ETDs

Positive and Unlabeled (PU) learning problems abound in many real-world applications. In healthcare informatics, diagnosed patients are considered labeled positive for a specific disease, but being undiagnosed does not mean they can be labeled negative. PU learning can improve classification performance, and estimate the positive fraction, α, among unlabeled samples. However, algorithms based on the Selected Completely At Random (SCAR) assumption are inadequate when the SCAR assumption fails (e.g., severe cases overrepresented), and when class imbalance is substantial. This dissertation presents and evaluates new algorithms to overcome these limitations. The proposed methods outperform the state-of-art for α-estimation, enhance classification performance, …

Phase Ib Study Of Telisotuzumab Vedotin In Combination With Erlotinib In Patients With C-Met Protein-Expressing Non-Small-Cell Lung Cancer, D Ross Camidge, Fabrice Barlesi, Jonathan W Goldman, Daniel Morgensztern, Rebecca Heist, Everett Vokes, Alex Spira, Eric Angevin, Wu-Chou Su, David S Hong, John H Strickler, Monica Motwani, Martin Dunbar, Apurvasena Parikh, Elysa Noon, Vincent Blot, Jun Wu, Karen Kelly

Faculty, Staff and Student Publications

Purpose: Overexpression of c-Met protein and epidermal growth factor receptor (EGFR) mutations can co-occur in non-small-cell lung cancer (NSCLC), providing strong rationale for dual targeting. Telisotuzumab vedotin (Teliso-V), a first-in-class antibody-drug conjugate targeting c-Met, has shown a tolerable safety profile and antitumor activity as monotherapy. Herein, we report the results of a phase Ib study (ClinicalTrials.gov identifier: NCT02099058) evaluating Teliso-V plus erlotinib, an EGFR tyrosine kinase inhibitor (TKI), in patients with c-Met-positive (+) NSCLC.

Patients and methods: This study evaluated Teliso-V (2.7 mg/kg once every 21 days) plus erlotinib (150 mg once daily) in adult patients (age …

Associations Of Financial Toxicity With Symptoms And Unplanned Healthcare Utilization Among Cancer Patients Taking Oral Chemotherapy At Home: A Prospective Observational Study, Yongfeng Chen, Zhenxiang Chen, Haiyun Jin, Yanrong Chen, Jinbing Bai, Guifen Fu

Faculty, Staff and Student Publications

Background: Cancer patients with financial toxicity experience psychological distress and often miss medical appointments and quit treatments early, which could be a barrier to the effective management of oral chemotherapy drugs at home. This study explores whether financial toxicity predicts symptoms and unplanned healthcare utilization among cancer patients taking oral chemotherapy at home, which will contribute to the safe management of oral chemotherapy.

Methods: Data in this study was from a prospective observational study, which was conducted between October 2018 and December 2019. 151 patients completed the Comprehensive Score for Financial Toxicity at discharge and completed the MD Anderson Symptom …

Deep Learning For Detecting And Elucidating Human T-Cell Leukemia Virus Type 1 Integration In The Human Genome, Haodong Xu, Johnathan Jia, Hyun-Hwan Jeong, Zhongming Zhao

Faculty, Staff and Student Publications

Human T-cell leukemia virus type 1 (HTLV-1), a retrovirus, is the causative agent for adult T cell leukemia/lymphoma and many other human diseases. Accurate and high throughput detection of HTLV-1 virus integration sites (VISs) across the host genomes plays a crucial role in the prevention and treatment of HTLV-1-associated diseases. Here, we developed DeepHTLV, the first deep learning framework for VIS prediction de novo from genome sequence, motif discovery, and cis-regulatory factor identification. We demonstrated the high accuracy of DeepHTLV with more efficient and interpretive feature representations. Decoding the informative features captured by DeepHTLV resulted in eight representative clusters …

Fgl2-Targeting T Cells Exhibit Antitumor Effects On Glioblastoma And Recruit Tumor-Specific Brain-Resident Memory T Cells, Qingnan Zhao, Jiemiao Hu, Lingyuan Kong, Shan Jiang, Xiangjun Tian, Jing Wang, Rintaro Hashizume, Zhiliang Jia, Natalie Wall Fowlkes, Jun Yan, Xueqing Xia, Sofia F Yi, Long Hoang Dao, David Masopust, Amy B Heimberger, Shulin Li

Faculty, Staff and Student Publications

Although tissue-resident memory T (TRM) cells specific for previously encountered pathogens have been characterized, the induction and recruitment of brain TRM cells following immune therapy has not been observed in the context of glioblastoma. Here, we show that T cells expressing fibrinogen-like 2 (FGL2)–specific single-chain variable fragments (T-αFGL2) can induce tumor-specific CD8+ TRM cells that prevent glioblastoma recurrence. These CD8+ TRM cells display a highly expanded T cell receptor repertoire distinct from that found in peripheral tissue. When adoptively transferred to the brains of either immunocompetent or T cell-deficient naïve mice, these CD8+ TRM cells reject glioma cells. Mechanistically, T-αFGL2 …

Health Benefits And Cost-Effectiveness Of Children's Oncology Group Breast Cancer Screening Guidelines For Chest-Irradiated Hodgkin Lymphoma Survivors, F Lennie Wong, Janie M Lee, Wendy M Leisenring, Joseph P Neglia, Rebecca M Howell, Susan A Smith, Kevin C Oeffinger, Chaya S Moskowitz, Tara O Henderson, Ann Mertens, Paul C Nathan, Yutaka Yasui, Wendy Landier, Gregory T Armstrong, Leslie L Robison, Smita Bhatia

Faculty, Staff and Student Publications

Purpose: To evaluate the outcomes and cost-effectiveness of the Children's Oncology Group Guideline recommendation for breast cancer (BC) screening using mammography (MAM) and breast magnetic resonance imaging (MRI) in female chest-irradiated childhood Hodgkin lymphoma (HL) survivors. Digital breast tomosynthesis (DBT), increasingly replacing MAM in practice, was also examined.

Methods: Life years (LYs), quality-adjusted LYs (QALYs), BC mortality, health care costs, and false-positive screen frequencies of undergoing annual MAM, DBT, MRI, MAM + MRI, and DBT + MRI from age 25 to 74 years were estimated by microsimulation. BC risks and non-BC mortality were estimated from female 5-year survivors of …

A Phase Ib/Ii Study Of Lenvatinib And Pembrolizumab In Advanced Endometrial Carcinoma (Study 111/Keynote-146): Long-Term Efficacy And Safety Update, Vicky Makker, Carol Aghajanian, Allen L Cohn, Margarita Romeo, Raquel Bratos, Marcia S Brose, Mark Messing, Lea Dutta, Corina E Dutcus, Jie Huang, Emmett V Schmidt, Robert Orlowski, Matthew H Taylor

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The open-label phase Ib/II Study 111/KEYNOTE-146 of daily lenvatinib 20 mg plus pembrolizumab 200 mg once every 3 weeks showed promising efficacy and tolerable safety in patients with previously treated advanced endometrial carcinoma (EC; primary data cutoff …

Editorial: Precision Medicine In Obstetrics: Pregnancy Complication, Serena Bertozzi, Bruna Corradetti, Arrigo Fruscalzo, Ambrogio P Londero

Faculty, Staff and Students Publications

No abstract provided.

Early Restrictive Or Liberal Fluid Management For Sepsis-Induced Hypotension, Nathan I Shapiro, Ivor S Douglas, Roy G Brower, Samuel M Brown, Matthew C Exline, Adit A Ginde, Michelle N Gong, Colin K Grissom, Douglas Hayden, Catherine L Hough, Weixing Huang, Theodore J Iwashyna, Alan E Jones, Akram Khan, Poying Lai, Kathleen D Liu, Chadwick D Miller, Katherine Oldmixon, Pauline K Park, Todd W Rice, Nancy Ringwood, Matthew W Semler, Jay S Steingrub, Daniel Talmor, B Taylor Thompson, Donald M Yealy, Wesley H Self

Faculty, Staff and Student Publications

BACKGROUND: Intravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are limited.

METHODS: In an unblinded superiority trial conducted at 60 U.S. centers, we randomly assigned patients to either a restrictive fluid strategy (prioritizing vasopressors and lower intravenous fluid volumes) or a liberal fluid strategy (prioritizing higher volumes of intravenous fluids before vasopressor use) for a 24-hour period. Randomization occurred within 4 hours after a patient met the criteria for sepsis-induced hypotension refractory to initial treatment with 1 to 3 liters of intravenous fluid. We hypothesized that …

The Landscape Of Immunotherapy For Retroperitoneal Sarcoma, Alicia A Gingrich, Elise F Nassif, Christina L Roland, Emily Z Keung

Faculty, Staff and Student Publications

Significant multidisciplinary scientific effort has been undertaken to understand the heterogeneous family of neoplasms that comprise soft tissue sarcomas. Within this family of neoplasms, outcomes for retroperitoneal sarcomas (RPS) are currently limited given a lack of effective therapies. In this review, we focus on immunotherapy and its relationship with the common RPS histologic subtypes. Although initial outcomes for RPS patients with immune checkpoint inhibition alone have been somewhat disappointing, subsequent analyses on histologies, the tumor microenvironment, sarcoma immune class, tumor infiltrating lymphocytes and genetic analysis for tumor mutational burden have yielded insight into the interplay between sarcomas and immunotherapy. Such …

North American Blastic Plasmacytoid Dendritic Cell Neoplasm Consortium: Position On Standards Of Care And Areas Of Need, Naveen Pemmaraju, Hagop Kantarjian, Kendra Sweet, Eunice Wang, Jayastu Senapati, Nathaniel R Wilson, Marina Konopleva, Arthur E Frankel, Vikas Gupta, Ruben Mesa, Matthew Ulrickson, Edward Gorak, Sumeet Bhatia, Tulin Budak-Alpdogan, James Mason, Maria Teresa Garcia-Romero, Norma Lopez-Santiago, Gabriela Cesarman-Maus, Pankit Vachhani, Sangmin Lee, Vijaya Raj Bhatt, William Blum, Roland B Walter, Dale Bixby, Ivana Gojo, Madeleine Duvic, Raajit K Rampal, Marcos De Lima, James Foran, Amir T Fathi, Aric Cameron Hall, Meagan A Jacoby, Jeffrey Lancet, Gabriel Mannis, Anthony S Stein, Alice Mims, David Rizzieri, Rebecca Olin, Alexander Perl, Gary Schiller, Paul Shami, Richard M Stone, Stephen Strickland, Matthew J Wieduwilt, Naval Daver, Farhad Ravandi, Sumithira Vasu, Monica Guzman, Gail J Roboz, Joseph Khoury, Muzaffar Qazilbash, Phyu P Aung, Branko Cuglievan, Yazan Madanat, Mohamed A Kharfan-Dabaja, Anna Pawlowska, Justin Taylor, Martin Tallman, Prajwal Dhakal, Andrew A Lane

Faculty, Staff and Student Publications

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with historically poor outcomes and no worldwide consensus treatment approach. Unique among most hematologic malignancies for its frequent cutaneous involvement, BPDCN can also invade other extramedullary compartments, including the central nervous system. Generally affecting older adults, many patients are unfit to receive intensive chemotherapy, and although hematopoietic stem cell transplantation is preferred for younger, fit individuals, not all are eligible. One recent therapeutic breakthrough is that all BPDCNs express CD123 (IL3Rα) and that this accessible surface marker can be pharmacologically targeted. The first-in-class agent for BPDCN, tagraxofusp, which targets …

Efficacy And Clinicogenomic Correlates Of Response To Immune Checkpoint Inhibitors Alone Or With Chemotherapy In Non-Small Cell Lung Cancer, Lingzhi Hong, Muhammad Aminu, Shenduo Li, Xuetao Lu, Milena Petranovic, Maliazurina B Saad, Pingjun Chen, Kang Qin, Susan Varghese, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, Amy Spelman, Yasir Y Elamin, Marcelo V Negrao, Ferdinandos Skoulidis, Carl M Gay, Tina Cascone, Saumil J Gandhi, Steven H Lin, Percy P Lee, Brett W Carter, Carol C Wu, Mara B Antonoff, Boris Sepesi, Jeff Lewis, Don L Gibbons, Ara A Vaporciyan, Xiuning Le, J Jack Lee, Sinchita Roy-Chowdhuri, Mark J Routbort, Justin F Gainor, John V Heymach, Yanyan Lou, Jia Wu, Jianjun Zhang, Natalie I Vokes

Faculty, Staff and Student Publications

The role of combination chemotherapy with immune checkpoint inhibitors (ICI) (ICI-chemo) over ICI monotherapy (ICI-mono) in non-small cell lung cancer (NSCLC) remains underexplored. In this retrospective study of 1133 NSCLC patients, treatment with ICI-mono vs ICI-chemo associate with higher rates of early progression, but similar long-term progression-free and overall survival. Sequential vs concurrent ICI and chemotherapy have similar long-term survival, suggesting no synergism from combination therapy. Integrative modeling identified PD-L1, disease burden (Stage IVb; liver metastases), and STK11 and JAK2 alterations as features associate with a higher likelihood of early progression on ICI-mono. CDKN2A alterations associate with worse long-term outcomes …

Identifying Flow Patterns In A Narrow Channel Via Feature Extraction Of Conductivity Measurements With A Support Vector Machine, Kai Yang, Jiajia Liu, Min Wang, Hua Wang, Qingtai Xiao

Faculty, Staff and Student Publications

In this work, a visualization experiment for rectangular channels was carried out to explore gas-liquid two-phase flow characteristics. Typical flow patterns, including bubble, elastic and mixed flows, were captured by direct imaging technology and the corresponding measurements with fluctuation characteristics were recorded by using an electrical conductivity sensor. Time-domain and frequency-domain characteristics of the corresponding electrical conductivity measurements of each flow pattern were analyzed with a probability density function and a power spectral density curve. The results showed that the feature vectors can be constructed to reflect the time-frequency characteristics of conductivity measurements successfully by introducing the quantized characteristic parameters, …

Improving Traditional Registrational Trial End Points: Development And Application Of A Desirability Of Outcome Ranking End Point For Complicated Urinary Tract Infection Clinical Trials, Jessica Howard-Anderson, Toshimitsu Hamasaki, Weixiao Dai, Deborah Collyar, Daniel Rubin, Sumathi Nambiar, Tori Kinamon, Carol Hill, Steven P Gelone, David Mariano, Takamichi Baba, Thomas L Holland, Sarah B Doernberg, Henry F Chambers, Vance G Fowler, Scott R Evans, Helen W Boucher

Faculty, Staff and Student Publications

BACKGROUND: Traditional end points used in registrational randomized, controlled trials (RCTs) often do not allow for complete interpretation of the full range of potential clinical outcomes. Desirability of outcome ranking (DOOR) is an approach to the design and analysis of clinical trials that incorporates benefits and risks of novel treatment strategies and provides a global assessment of patient experience.

METHODS: Through a multidisciplinary committee of experts in infectious diseases, clinical trial design, drug regulation, and patient experience, we developed a DOOR end point for infectious disease syndromes and demonstrated how this could be applied to 3 registrational drug trials (ZEUS, …

Association Of Circulating Mtdna With Cvd In Hemodialysis Patients And In Vitro Effect Of Exogenous Mtdna On Cardiac Microvascular Inflammation, Zhen Fan, Ya Feng, Li Zang, Yi Guo, Xiao-Yi Zhong

Faculty, Staff and Student Publications

BACKGROUND: Chronic kidney disease (CKD) patients sustain a fairly high prevalence of cardiovascular disease (CVD). Microvascular inflammation is an early manifestation of CVD, and the released mitochondrial DNA (MtDNA) has been proposed to be a crucial integrator of inflammatory signals. Herein, the aim of this study was to determine the relationship between CVD, microvessel, and circulating MtDNA in the settings of uremia.

METHODS: Forty-two maintenance hemodialysis (MHD) patients and 36 health controls were enrolled in this study. Plasma cell-free MtDNA was detected by TaqMan-based qPCR assay. CVD risk markers including high-sensitive C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), fibrinogen, and …

Clinical And Molecular Analyses Of Recurrent Gram-Negative Bloodstream Infections, Andrew Bock, Blake M Hanson, Felicia Ruffin, Joshua B Parsons, Lawrence P Park, Batu Sharma-Kuinkel, Michael Mohnasky, Cesar A Arias, Vance G Fowler, Joshua T Thaden

Faculty, Staff and Student Publications

Background: The causes and clinical characteristics of recurrent gram-negative bacterial bloodstream infections (GNB-BSI) are poorly understood.

Methods: We used a cohort of patients with GNB-BSI to identify clinical characteristics, microbiology, and risk factors associated with recurrent GNB-BSI. Bacterial genotyping (pulsed-field gel electrophoresis [PFGE] and whole-genome sequencing [WGS]) was used to determine whether episodes were due to relapse or reinfection. Multivariable logistic regression was used to identify risk factors for recurrence.

Results: Of the 1423 patients with GNB-BSI in this study, 60 (4%) had recurrent GNB-BSI. Non-White race (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.38-4.01; P = .002), admission …

An Epithelial-Immune Circuit Amplifies Inflammasome And Il-6 Responses To Sars-Cov-2, Katherine C Barnett, Yuying Xie, Takanori Asakura, Dingka Song, Kaixin Liang, Sharon A Taft-Benz, Haitao Guo, Shuangshuang Yang, Kenichi Okuda, Rodney C Gilmore, Jennifer F Loome, Thomas H Oguin Iii, Gregory D Sempowski, Scott H Randell, Mark T Heise, Yu Leo Lei, Richard C Boucher, Jenny P-Y Ting

Faculty, Staff and Student Publications

Elevated levels of cytokines IL-1β and IL-6 are associated with severe COVID-19. Investigating the underlying mechanisms, we find that while primary human airway epithelia (HAE) have functional inflammasomes and support SARS-CoV-2 replication, they are not the source of IL-1β released upon infection. In leukocytes, the SARS-CoV-2 E protein upregulates inflammasome gene transcription via TLR2 to prime, but not activate, inflammasomes. SARS-CoV-2-infected HAE supply a second signal, which includes genomic and mitochondrial DNA, to stimulate leukocyte IL-1β release. Nuclease treatment, STING, and caspase-1 inhibition but not NLRP3 inhibition blocked leukocyte IL-1β release. After release, IL-1β stimulates IL-6 secretion from HAE. Therefore, …

Incidence And Clearance Of Anal Human Papillomavirus Infection In 16 164 Individuals, According To Human Immunodeficiency Virus Status, Sex, And Male Sexuality: An International Pooled Analysis Of 34 Longitudinal Studies, Feixue Wei, Marc T Goodman, Ningshao Xia, Jun Zhang, Anna R Giuliano, Gypsyamber D'Souza, Nancy A Hessol, Maarten F Schim Van Der Loeff, Jianghong Dai, Karin Neukam, Alexandra De Pokomandy, I Mary Poynten, Ronald B Geskus, Joaquin Burgos, Isabelle Etienney, Anna-Barbara Moscicki, Maria Gabriella Donà, Maura L Gillison, Alan G Nyitray, Rebecca G Nowak, Evy Yunihastuti, Huachun Zou, Carmen Hidalgo-Tenorio, Nittaya Phanuphak, Jean-Michel Molina, Alice M Schofield, Stephen Kerr, Song Fan, Yong Lu, Jason J Ong, Admire T Chikandiwa, Sirinya Teeraananchai, Nicola Squillace, Dorothy J Wiley, Joel M Palefsky, Damien Georges, Catharina J Alberts, Gary M Clifford

Faculty, Staff and Student Publications

Background: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized.

Methods: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their …

Life-Threatening Complications Of Influenza Vs Coronavirus Disease 2019 (Covid-19) In Us Children, Natasha B Halasa, Andrew J Spieker, Cameron C Young, Samantha M Olson, Margaret M Newhams, Justin Z Amarin, Kristin L Moffitt, Mari M Nakamura, Emily R Levy, Vijaya L Soma, Rana Talj, Scott L Weiss, Julie C Fitzgerald, Elizabeth H Mack, Aline B Maddux, Jennifer E Schuster, Bria M Coates, Mark W Hall, Stephanie P Schwartz, Adam J Schwarz, Michele Kong, Philip C Spinella, Laura L Loftis, Gwenn E Mclaughlin, Charlotte V Hobbs, Courtney M Rowan, Melania M Bembea, Ryan A Nofziger, Christopher J Babbitt, Cindy Bowens, Heidi R Flori, Shira J Gertz, Matt S Zinter, John S Giuliano, Janet R Hume, Natalie Z Cvijanovich, Aalok R Singh, Hillary A Crandall, Neal J Thomas, Melissa L Cullimore, Manish M Patel, Adrienne G Randolph, Pediatric Intensive Care Influenza, Overcoming Covid-19 Investigators

Faculty, Staff and Student Publications

Background: Clinical differences between critical illness from influenza infection vs coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients.

Methods: We compared demographics, clinical characteristics, and outcomes of US children (aged 8 months to 17 years) admitted to the intensive care or high-acuity unit with influenza or COVID-19. Using mixed-effects models, we assessed the odds of death or requiring life support for influenza vs COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity.

Results: Children with influenza (n = 179) were younger than those with COVID-19 (n = 381; median, 5.2 …

Bintrafusp Alfa: A Bifunctional Fusion Protein Targeting Pd-L1 And Tgf-Β, In Patients With Pretreated Colorectal Cancer: Results From A Phase I Trial, Alexander Spira, Michael S Wertheim, Edward J Kim, Benjamin Tan, Heinz-Josef Lenz, Petros Nikolinakos, Patricia L Rich, Genevieve Jehl, Andreas Machl, Rena Ito, James L Gulley, Scott Kopetz

Faculty, Staff and Student Publications

Colorectal cancer (CRC) is a heterogeneous and complex disease with limited treatment options. Targeting transforming growth factor β (TGF-β) and programmed death ligand 1 pathways may enhance antitumor efficacy. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-β receptor II (a TGF-β "trap") fused to a human IgG1 monoclonal antibody blocking programmed cell death ligand 1. We report results from an expansion cohort of a phase I study (NCT02517398) in patients with heavily pretreated advanced CRC treated with bintrafusp alfa. As of May 15, 2020, 32 patients with advanced CRC had received …

2d Respiratory Sound Analysis To Detect Lung Abnormalities, Rafia Sharmin Alice, Kc Santosh

SDSU Data Science Symposium

Abstract. In this paper, we analyze deep visual features from 2D data representation(s) of the respiratory sound to detect evidence of lung abnormalities. The primary motivation behind this is that visual cues are more important in decision-making than raw data (lung sound). Early detection and prompt treatments are essential for any future possible respiratory disorders, and respiratory sound is proven to be one of the biomarkers. In contrast to state-of-the-art approaches, we aim at understanding/analyzing visual features using our Convolutional Neural Networks (CNN) tailored Deep Learning Models, where we consider all possible 2D data such as Spectrogram, Mel-frequency Cepstral Coefficients …

Production Of A Monoclonal Antibody For The Detection Of Forchlorfenuron: Application In An Indirect Enzyme-Linked Immunosorbent Assay And Immunochromatographic Strip, Xingmei Lei, A M Abd El-Aty, Lingyuan Xu, Jing Zhao, Jia Li, Song Gao, Yun Zhao, Yongxin She, Fen Jin, Jing Wang, Lufei Zheng, Maojun Jin, Bruce D Hammock

Faculty, Staff and Student Publications

In this study, a monoclonal antibody (mAb) specific to forchlorfenuron (CPPU) with high sensitivity and specificity was produced and designated (9G9). To detect CPPU in cucumber samples, an indirect enzyme-linked immunosorbent assay (ic-ELISA) and a colloidal gold nanobead immunochromatographic test strip (CGN-ICTS) were established using 9G9. The half-maximal inhibitory concentration (IC50) and the LOD for the developed ic-ELISA were determined to be 0.19 ng/mL and 0.04 ng/mL in the sample dilution buffer, respectively. The results indicate that the sensitivity of the antibodies prepared in this study (9G9 mAb) was higher than those reported in the previous literature. On the other …

Intestinal Toxicity To Ctla-4 Blockade Driven By Il-6 And Myeloid Infiltration, Yifan Zhou, Yusra B Medik, Bhakti Patel, Daniel B Zamler, Sijie Chen, Thomas Chapman, Sarah Schneider, Elizabeth M Park, Rachel L Babcock, Taylor T Chrisikos, Laura M Kahn, Allison M Dyevoich, Josue E Pineda, Matthew C Wong, Aditya K Mishra, Samuel H Cass, Alexandria P Cogdill, Daniel H Johnson, Sarah B Johnson, Khalida Wani, Debora A Ledesma, Courtney W Hudgens, Jingjing Wang, Md Abdul Wadud Khan, Christine B Peterson, Aron Y Joon, Weiyi Peng, Haiyan S Li, Reetakshi Arora, Ximing Tang, Maria Gabriela Raso, Xuegong Zhang, Wai Chin Foo, Michael T Tetzlaff, Gretchen E Diehl, Karen Clise-Dwyer, Elizabeth M Whitley, Matthew M Gubin, James P Allison, Patrick Hwu, Nadim J Ajami, Adi Diab, Jennifer A Wargo, Stephanie S Watowich

Faculty, Staff and Student Publications

Immune checkpoint blockade (ICB) has revolutionized cancer treatment, yet quality of life and continuation of therapy can be constrained by immune-related adverse events (irAEs). Limited understanding of irAE mechanisms hampers development of approaches to mitigate their damage. To address this, we examined whether mice gained sensitivity to anti-CTLA-4 (αCTLA-4)–mediated toxicity upon disruption of gut homeostatic immunity. We found αCTLA-4 drove increased inflammation and colonic tissue damage in mice with genetic predisposition to intestinal inflammation, acute gastrointestinal infection, transplantation with a dysbiotic fecal microbiome, or dextran sodium sulfate administration. We identified an immune signature of αCTLA-4–mediated irAEs, including colonic neutrophil accumulation …

Assessment Of Response To Neoadjuvant Systemic Treatment In Triple-Negative Breast Cancer Using Functional Tumor Volumes From Longitudinal Dynamic Contrast-Enhanced Mri, Bikash Panthi, Beatriz E Adrada, Rosalind P Candelaria, Mary S Guirguis, Clinton Yam, Medine Boge, Huiqin Chen, Kelly K Hunt, Lei Huo, Ken-Pin Hwang, Anil Korkut, Deanna L Lane, Huong C Le-Petross, Jessica W T Leung, Jennifer K Litton, Rania M Mohamed, Benjamin C Musall, Sanaz Pashapoor, Miral M Patel, Frances Perez, Jong Bum Son, Alastair Thompson, Vicente Valero, Peng Wei, Jason White, Zhan Xu, Lawrence Pinsky, Debu Tripathy, Wei Yang, Jingfei Ma, Gaiane M Rauch

Faculty, Staff and Student Publications

Early assessment of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) is critical for patient care in order to avoid the unnecessary toxicity of an ineffective treatment. We assessed functional tumor volumes (FTVs) from dynamic contrast-enhanced (DCE) MRI after 2 cycles (C2) and 4 cycles (C4) of NAST as predictors of response in TNBC. A group of 100 patients with stage I-III TNBC who underwent DCE MRI at baseline, C2, and C4 were included in this study. Tumors were segmented on DCE images of 1 min and 2.5 min post-injection. FTVs were measured using the optimized percentage enhancement …

Patient-Reported Symptoms At Discharge And Risk Of Complications After Gynecologic Surgery, Xin Shelley Wang, Pedro T Ramirez, Qiuling Shi, Mona Kamal, Araceli Garcia-Gonzalez, Maria D Iniesta, Charles S Cleeland, Larissa A Meyer

Faculty, Staff and Student Publications

Objective: Current gaps in knowledge limit clinicians from fully implementing patient-reported outcomes in routine post-operative care.

Methods: This prospective study assessed symptoms via the gynecologic module of the MD Anderson Symptom Inventory (MDASI-PeriOp-GYN) in patients who underwent open laparotomy.

Results: At discharge, patient-reported moderate to severe (≥4 on a 0-10 scale) abdominal bloating or abdominal cramping, combined with length of stay of ≥4 days, were found to be associated with a higher risk of 30-day post-operative grade II-IV complications by the Clavien-Dindo system (all p values < 0.01). Also, length of stay of ≥4 days and moderate to severe urinary urgency at discharge were found to be associated with the need for re-admission (all p values < 0.01).

Conclusion: This study defined the clinically meaningful symptoms that related to the risk of …

Dynamic Cone-Beam Ct Reconstruction Using Spatial And Temporal Implicit Neural Representation Learning (Stinr), You Zhang, Hua-Chieh Shao, Tinsu Pan, Tielige Mengke

Faculty, Staff and Student Publications

Objective. Dynamic cone-beam CT (CBCT) imaging is highly desired in image-guided radiation therapy to provide volumetric images with high spatial and temporal resolutions to enable applications including tumor motion tracking/prediction and intra-delivery dose calculation/accumulation. However, dynamic CBCT reconstruction is a substantially challenging spatiotemporal inverse problem, due to the extremely limited projection sample available for each CBCT reconstruction (one projection for one CBCT volume).

Approach. We developed a simultaneous spatial and temporal implicit neural representation (STINR) method for dynamic CBCT reconstruction. STINR mapped the unknown image and the evolution of its motion into spatial and temporal multi-layer perceptrons (MLPs), and …

Loci On Chromosome 12q132 Encompassing Erbb3, Pa2g4 And Rab5b Are Associated With Polycystic Ovary Syndrome, R Alan Harris, Kellie J Archer, Mark O Goodarzi, Timothy P York, Jeffrey Rogers, Andrea Dunaif, Jan M Mcallister, Jerome F Strauss

Faculty, Staff and Students Publications

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenemia of ovarian theca cell origin. We report significant association of androgen production with 15 single nucleotide variants (SNVs) identified by exome sequencing of theca cells from women with PCOS and normal ovulatory women. Ten SNVs are located within a 150 kbp region on 12q13.2 which encompasses loci identified in PCOS genome-wide association studies (GWAS) and contains PCOS candidate genes ERBB3 and RAB5B. The region also contains PA2G4 which encodes a transcriptional corepressor of androgen receptor and androgen receptor-regulated genes. PA2G4 has not previously been recognized as related to PCOS in published …

Long And Short Duration Exposures To The Selective Serotonin Reuptake Inhibitors (Ssris) Fluoxetine, Paroxetine And Sertraline At Environmentally Relevant Concentrations Lead To Adverse Effects On Zebrafish Behaviour And Reproduction, Ananda Baskaran Venkatachalam, Bailey Levesque, John C Achenbach, Jane J Pappas, Lee D Ellis

Faculty, Staff and Student Publications

Selective serotonin reuptake inhibitors (SSRIs) are currently the most prescribed class of psychotropic medications. Their increased global manufacture and use have become growing concerns for aquatic toxicologists and environmental biologists, who assess both the direct and indirect effects of substances on the environment and on human health. In order to assess the potential impact of environmentally relevant levels of SSRIs on fish development, behaviour and reproduction, we exposed juvenile and adult zebrafish to a select group of SSRIs using two separate exposure paradigms. In the first paradigm, juvenile zebrafish were exposed to Fluoxetine (Prozac), Paroxetine (Paxil), Sertraline (Zoloft) or a …