Medicine and Health Sciences Commons^™

Single-Cell Analysis Of Age-Related Changes In Leukocytes Of Diabetic Mouse Hindpaws, James M Nichols, Hoang Vu Pham, Eric F Lee, Rajasekaran Mahalingam, Andrew J Shepherd

Faculty, Staff and Student Publications

Complications associated with Type 1 and Type 2 diabetes, such as diabetic peripheral neuropathy and diabetic foot ulcers, are a growing health-care concern. In addition, this concern increases as diabetic patients age due to their increased susceptibility to complications. To address this growing problem, it is important to understand fluctuations in physiology which lead to pathological changes associated with the metabolic disturbances of diabetes. Our study explores dysregulation of immune cell populations in the hindpaws of healthy and diabetic mice at 12 and 21 weeks of age using single-cell RNA sequencing to provide insight into immune disruptions occurring in the …

Visual Outcome And Ocular Complications In Patients With Lacrimal Gland Carcinoma After Eye-Sparing Surgery And Adjuvant Radiation Therapy, Zhenyang Zhao, Steven Jay Frank, Jing Ning, Jiawei Zhao, Xinyang Jiang, Xin A Wang, Amy C Schefler, Ehab Hanna, Amy Moreno, Brandon Gunn, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

Background: We report visual outcomes and ocular complications in patients with lacrimal gland carcinoma who had eye-sparing surgery followed by radiotherapy.

Methods: This review included consecutive patients with lacrimal gland carcinoma who underwent eye-sparing surgery and adjuvant radiotherapy or concurrent chemoradiation therapy between 2007 and 2018. Clinical data, including details of ophthalmological examinations and radiation treatment were reviewed.

Results: The study included 23 patients, 15 males and 8 females, with median age 51 years. Twenty patients (87%) received intensity-modulated proton therapy; 3 (13%) received intensity-modulated radiotherapy. Nineteen patients (83%) received concurrent chemotherapy. After a median follow-up time of 37 months …

Polyamine-Mediated Ferroptosis Amplification Acts As A Targetable Vulnerability In Cancer, Guoshu Bi, Jiaqi Liang, Yunyi Bian, Guangyao Shan, Yiwei Huang, Tao Lu, Huan Zhang, Xing Jin, Zhencong Chen, Mengnan Zhao, Hong Fan, Qun Wang, Boyi Gan, Cheng Zhan

Faculty, Staff and Student Publications

Targeting ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal overload of lipid peroxides, in cancer therapy is impeded by our limited understanding of the intersection of tumour’s metabolic feature and ferroptosis vulnerability. In the present study, arginine is identified as a ferroptotic promoter using a metabolites library. This effect is mainly achieved through arginine’s conversion to polyamines, which exerts their potent ferroptosis-promoting property in an H2O2-dependent manner. Notably, the expression of ornithine decarboxylase 1 (ODC1), the critical enzyme catalysing polyamine synthesis, is significantly activated by the ferroptosis signal——iron overload——through WNT/MYC signalling, as well as the subsequent …

Durvalumab And Tremelimumab Before Surgery In Patients With Hormone Receptor Positive, Her2-Negative Stage Ii-Iii Breast Cancer, Haven R Garber, Sreyashi Basu, Sonali Jindal, Zhong He, Khoi Chu, Akshara Singareeka Raghavendra, Clinton Yam, Lumarie Santiago, Beatriz E Adrada, Padmanee Sharma, Elizabeth A Mittendorf, Jennifer K Litton

Faculty, Staff and Student Publications

A clinical trial was conducted to assess the feasibility of enrolling patients with Stage II or III hormone receptor positive (HR+)/HER2-negative breast cancer to pre-operative dual PD-L1/CTLA-4 checkpoint inhibition administered prior to neoadjuvant chemotherapy (NACT). Eight eligible patients were treated with upfront durvalumab and tremelimumab for two cycles. Patients then received NACT prior to breast surgery. Seven patients had baseline and interval breast ultrasounds after combination immunotherapy and the responses were mixed: 3/7 patients experienced a ≥30% decrease in tumor volume, 3/7 a ≥30% increase, and 1 patient had stable disease. At the time of breast surgery, 1/8 patients had …

Three-Dimensional Optothermal Manipulation Of Light-Absorbing Particles In Phase-Change Gel Media, Pavana Siddhartha Kollipara, Zilong Wu, Kan Yao, Dongdong Lin, Zhengyu Ju, Xiaotian Zhang, Taizhi Jiang, Hongru Ding, Jie Fang, Jingang Li, Brian A Korgel, Joan M Redwing, Guihua Yu, Yuebing Zheng

Faculty, Staff and Student Publications

Rational manipulation and assembly of discrete colloidal particles into architected superstructures have enabled several applications in materials science and nanotechnology. Optical manipulation techniques, typically operated in fluid media, facilitate the precise arrangement of colloidal particles into superstructures by using focused laser beams. However, as the optical energy is turned off, the inherent Brownian motion of the particles in fluid media impedes the retention and reconfiguration of such superstructures. Overcoming this fundamental limitation, we present on-demand, three-dimensional (3D) optical manipulation of colloidal particles in a phase-change solid medium made of surfactant bilayers. Unlike liquid crystal media, the lack of fluid flow …

Synthetic Pet From Ct Improves Diagnosis And Prognosis For Lung Cancer: Proof Of Concept, Morteza Salehjahromi, Tatiana V Karpinets, Sheeba J Sujit, Mohamed Qayati, Pingjun Chen, Muhammad Aminu, Maliazurina B Saad, Rukhmini Bandyopadhyay, Lingzhi Hong, Ajay Sheshadri, Julie Lin, Mara B Antonoff, Boris Sepesi, Edwin J Ostrin, Iakovos Toumazis, Peng Huang, Chao Cheng, Tina Cascone, Natalie I Vokes, Carmen Behrens, Jeffrey H Siewerdsen, John D Hazle, Joe Y Chang, Jianhua Zhang, Yang Lu, Myrna C B Godoy, Caroline Chung, David Jaffray, Ignacio Wistuba, J Jack Lee, Ara A Vaporciyan, Don L Gibbons, Gregory Gladish, John V Heymach, Carol C Wu, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

[18F]Fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) are indispensable components in modern medicine. Although PET can provide additional diagnostic value, it is costly and not universally accessible, particularly in low-income countries. To bridge this gap, we have developed a conditional generative adversarial network pipeline that can produce FDG-PET from diagnostic CT scans based on multi-center multi-modal lung cancer datasets (n = 1,478). Synthetic PET images are validated across imaging, biological, and clinical aspects. Radiologists confirm comparable imaging quality and tumor contrast between synthetic and actual PET scans. Radiogenomics analysis further proves that the dysregulated cancer hallmark pathways of …

Remodeling Anaplastic Thyroid Cancer's Aggressive Profile And Metabolic Signature By Natural Alkaloid Berberine, Tara Elizabeth Jarboe

NYMC Student Theses and Dissertations

Anaplastic thyroid cancer is a rare, fatal cancer with a five-year survival of 4%. Universally diagnosed at stage IV, anaplastic thyroid cancer is characterized by its lack of differentiation, rapid proliferative rate, highly inflammatory tumor microenvironment, and metabolic dysregulation. Refractory to all established therapies, anaplastic thyroid cancer requires a novel therapeutic approach that targets all of these drivers of anaplastic thyroid cancer carcinogenesis. We propose natural alkaloid berberine as a therapeutic with multitarget efficacy to alter mitochondrial metabolism and reprogram anaplastic thyroid cancer’s aggressive phenotype. Our in vitro model uses monocyte cell line U937, anaplastic thyroid cancer cell lines T238 …

Fungi Of The Order Mucorales Express A “Sealing-Only” Trna Ligase, Khondakar Sayef Ahammed, Ambro Van Hoof

Faculty, Staff and Student Publications

Some eukaryotic pre-tRNAs contain an intron that is removed by a dedicated set of enzymes. Intron-containing pre-tRNAs are cleaved by tRNA splicing endonuclease, followed by ligation of the two exons and release of the intron. Fungi use a "heal and seal" pathway that requires three distinct catalytic domains of the tRNA ligase enzyme, Trl1. In contrast, humans use a "direct ligation" pathway carried out by RTCB, an enzyme completely unrelated to Trl1. Because of these mechanistic differences, Trl1 has been proposed as a promising drug target for fungal infections. To validate Trl1 as a broad-spectrum drug target, we show that …

Hematopoietic Stem Cells With Granulo-Monocytic Differentiation State Overcome Venetoclax Sensitivity In Patients With Myelodysplastic Syndromes, Juan Jose Rodriguez-Sevilla, Irene Ganan-Gomez, Feiyang Ma, Kelly Chien, Monica Del Rey, Sanam Loghavi, Guillermo Montalban-Bravo, Vera Adema, Bethany Wildeman, Rashmi Kanagal-Shamanna, Alexandre Bazinet, Helen T Chifotides, Natthakan Thongon, Xavier Calvo, Jesús María Hernández-Rivas, Maria Díez-Campelo, Guillermo Garcia-Manero, Simona Colla

Faculty, Staff and Student Publications

The molecular mechanisms of venetoclax-based therapy failure in patients with acute myeloid leukemia were recently clarified, but the mechanisms by which patients with myelodysplastic syndromes (MDS) acquire secondary resistance to venetoclax after an initial response remain to be elucidated. Here, we show an expansion of MDS hematopoietic stem cells (HSCs) with a granulo-monocytic-biased transcriptional differentiation state in MDS patients who initially responded to venetoclax but eventually relapsed. While MDS HSCs in an undifferentiated cellular state are sensitive to venetoclax treatment, differentiation towards a granulo-monocytic-biased transcriptional state, through the acquisition or expansion of clones with STAG2 or RUNX1 mutations, affects HSCs' …

Neoadjuvant Chemotherapy Alone Or Combined With Egfr-Directed Targeted Therapy Or Anti-Pd-1 Immunotherapy For Locally Advanced Lacrimal Sac And Nasolacrimal Duct Carcinomas, Jeremy Goldfarb, Janet Fan, Luana Guimaraes De Sousa, Neal Akhave, Jeffrey Myers, Ryan Goepfert, Krish Manisundaram, Jiawei Zhao, Steven J Frank, Amy Moreno, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

Background/aims: We describe our findings in patients with locally advanced lacrimal sac and nasolacrimal duct (NLD) carcinoma who received neoadjuvant systemic therapy.

Methods: We identified patients with locally advanced primary lacrimal sac/NLD carcinoma treated with neoadjuvant systemic intravenous therapy at our institution during 2017-2019.

Results: The study included seven patients, four men and three women; the mean age was 60.4 years (range: 43-76). All patients had locally advanced disease with significant orbital soft tissue invasion with or without skull base invasion making eye-sparing surgery not feasible as an initial step. Three patients had poorly differentiated squamous cell carcinoma; two, invasive …

Ultrasound Biomicroscopy As A Novel, Potential Modality To Evaluate Anterior Segment Ophthalmic Structures During Spaceflight: An Analysis Of Current Technology, Benjamin Soares, Joshua Ong, Daniela Osteicoechea, Cihan Mehmet Kadipasaoglu, Ethan Waisberg, Prithul Sarker, Nasif Zaman, Alireza Tavakkoli, Gianmarco Vizzeri, Andrew G Lee

Faculty, Staff and Student Publications

Ocular health is currently a major concern for astronauts on current and future long-duration spaceflight missions. Spaceflight-associated neuro-ocular syndrome (SANS) is a collection of ophthalmic and neurologic findings that is one potential physiologic barrier to interplanetary spaceflight. Since its initial report in 2011, our understanding of SANS has advanced considerably, with a primary focus on posterior ocular imaging including fundus photography and optical coherence tomography. However, there may be changes to the anterior segment that have not been identified. Additional concerns to ocular health in space include corneal damage and radiation-induced cataract formation. Given these concerns, precision anterior segment imaging …

Long Noncoding Rna Malat1 Protects Against Osteoporosis And Bone Metastasis, Yang Zhao, Jingyuan Ning, Hongqi Teng, Yalan Deng, Marisela Sheldon, Lei Shi, Consuelo Martinez, Jie Zhang, Annie Tian, Yutong Sun, Shinichi Nakagawa, Fan Yao, Hai Wang, Li Ma

Faculty, Staff and Student Publications

MALAT1, one of the few highly conserved nuclear long noncoding RNAs (lncRNAs), is abundantly expressed in normal tissues. Previously, targeted inactivation and genetic rescue experiments identified MALAT1 as a suppressor of breast cancer lung metastasis. On the other hand, Malat1-knockout mice are viable and develop normally. On a quest to discover the fundamental roles of MALAT1 in physiological and pathological processes, we find that this lncRNA is downregulated during osteoclastogenesis in humans and mice. Remarkably, Malat1 deficiency in mice promotes osteoporosis and bone metastasis of melanoma and mammary tumor cells, which can be rescued by genetic add-back of Malat1. Mechanistically, …

Downregulation Of Irf8 In Alveolar Macrophages By G-Csf Promotes Metastatic Tumor Progression, Stephanie L Tzetzo, Elliot D Kramer, Hemn Mohammadpour, Minhyung Kim, Spencer R Rosario, Han Yu, Melissa R Dolan, Chetan C Oturkar, Brian G Morreale, Paul N Bogner, Aimee B Stablewski, Fernando J Benavides, Craig M Brackett, John M L Ebos, Gokul M Das, Mateusz Opyrchal, Michael J Nemeth, Sharon S Evans, Scott I Abrams

Faculty, Staff and Student Publications

Tissue-resident macrophages (TRMs) are abundant immune cells within pre-metastatic sites, yet their functional contributions to metastasis remain incompletely understood. Here, we show that alveolar macrophages (AMs), the main TRMs of the lung, are susceptible to downregulation of the immune stimulatory transcription factor IRF8, impairing anti-metastatic activity in models of metastatic breast cancer. G-CSF is a key tumor-associated factor (TAF) that acts upon AMs to reduce IRF8 levels and facilitate metastasis. Translational relevance of IRF8 downregulation was observed among macrophage precursors in breast cancer and a

A Self-Supervised Learning Approach For Registration Agnostic Imaging Models With 3d Brain Cta, Yingjun Dong, Samiksha Pachade, Xiaomin Liang, Sunil A Sheth, Luca Giancardo

Faculty, Staff and Student Publications

Deep learning-based neuroimaging pipelines for acute stroke typically rely on image registration, which not only increases computation but also introduces a point of failure. In this paper, we propose a general-purpose contrastive self-supervised learning method that converts a convolutional deep neural network designed for registered images to work on a different input domain, i.e., with unregistered images. This is accomplished by using a self-supervised strategy that does not rely on labels, where the original model acts as a teacher and a new network as a student. Large vessel occlusion (LVO) detection experiments using computed tomographic angiography (CTA) data from 402 …

Validation Of A Multiomic Model Of Plasma Extracellular Vesicle Pd-L1 And Radiomics For Prediction Of Response To Immunotherapy In Nsclc, Diego De Miguel-Perez, Murat Ak, Priyadarshini Mamindla, Alessandro Russo, Serafettin Zenkin, Nursima Ak, Vishal Peddagangireddy, Luis Lara-Mejia, Muthukumar Gunasekaran, Andres F Cardona, Aung Naing, Fred R Hirsch, Oscar Arrieta, Rivka R Colen, Christian Rolfo

Faculty, Staff and Student Publications

BACKGROUND: Immune-checkpoint inhibitors (ICIs) have showed unprecedent efficacy in the treatment of patients with advanced non-small cell lung cancer (NSCLC). However, not all patients manifest clinical benefit due to the lack of reliable predictive biomarkers. We showed preliminary data on the predictive role of the combination of radiomics and plasma extracellular vesicle (EV) PD-L1 to predict durable response to ICIs.

MAIN BODY: Here, we validated this model in a prospective cohort of patients receiving ICIs plus chemotherapy and compared it with patients undergoing chemotherapy alone. This multiparametric model showed high sensitivity and specificity at identifying non-responders to ICIs and outperformed …

Case Report: Molecular Profiling Facilitates The Diagnosis Of A Challenging Case Of Lung Cancer With Choriocarcinoma Features, Hui Li, Xin Hu, Matthew S Ning, Gregory N Fuller, John M Stewart, Jared C Gilliam, Jia Wu, Xiuning Le, Ara A Vaporciyan, J Jack Lee, Don L Gibbons, John V Heymach, Andrew Futreal, Jianjun Zhang

Faculty, Staff and Student Publications

Accurate diagnoses are crucial in determining the most effective treatment across different cancers. In challenging cases, morphology-based traditional pathology methods have important limitations, while molecular profiling can provide valuable information to guide clinical decisions. We present a 35-year female with lung cancer with choriocarcinoma features. Her disease involved the right lower lung, brain, and thoracic lymph nodes. The pathology from brain metastasis was reported as "metastatic choriocarcinoma" (a germ cell tumor) by local pathologists. She initiated carboplatin and etoposide, a regimen for choriocarcinoma. Subsequently, her case was assessed by pathologists from an academic cancer center, who gave the diagnosis of …

The Digital Transition: Are Adults Aged 65 Years Or Older Willing To Complete Online Forms And Questionnaires In Patient Portals?, Nancy P Gordon, Sherry Zhang, Joan C Lo, Christina F Li

Faculty, Staff and Student Publications

INTRODUCTION: Patients are being encouraged to complete forms electronically using patient portals rather than on paper, but willingness of older adults to make this transition is uncertain.

METHODS: The authors analyzed data for 4105 Kaiser Permanente Northern California 2020 Member Health Survey respondents aged 65-85 years who answered a question about willingness to complete online forms and questionnaires using a patient portal. Data weighted to the Kaiser Permanente Northern California membership were used to estimate percentages of older adults willing to complete patient portal forms and questionnaires. Chi-square tests and log-Poisson regression models that included sociodemographic, internet use, and patient …

Sabr For Sarcoma Lung Metastases: Indications For Treatment And Guidance For Patient Selection, Ahsan S Farooqi, Alison K Yoder, Heather Y Lin, Dario Pasalic, Jeremy Erasmus, Sonia Betancourt, Cort Wernz, Devarati Mitra, Maria A Zarzour, Neeta Somaiah, Anthony Conley, Ravin Ratan, Andrew Livingston, Dejka M Araujo, Christina Roland, Christopher Scally, Emily Keung, Saumil N Gandhi, B Ashleigh Guadagnolo, Quynh-Nhu Nguyen, Andrew J Bishop

Faculty, Staff and Student Publications

Purpose: The lungs are the most common site of metastasis for patients with soft tissue sarcoma. SABR is commonly employed to treat lung metastases among select patients with sarcoma with limited disease burden. We sought to evaluate outcomes and patterns of failure among patients with sarcoma treated with SABR for their lung metastases.

Methods and materials: We performed a retrospective review of patients treated at a tertiary cancer center between 2006 and 2020. Patient disease status at the time of SABR was categorized as either oligorecurrent or oligoprogressive. The Kaplan-Meier method was used to estimate disease outcomes. Uni- and multivariable …

Phase I Study Of Oric-101, A Glucocorticoid Receptor Antagonist, In Combination With Enzalutamide In Patients With Metastatic Castration-Resistant Prostate Cancer Progressing On Enzalutamide, Wassim Abida, Andrew W Hahn, Neal Shore, Neeraj Agarwal, Paul Sieber, Matthew R Smith, Tanya Dorff, Paul Monk, Matthew Rettig, Rupal Patel, Anne Page, Maureen Duff, Rongda Xu, Jian Wang, Shravani Barkund, Aleksandr Pankov, Amber Wang, Melissa R Junttila, Pratik S Multani, Anneleen Daemen, Edna Chow Maneval, Christopher J Logothetis, Michael J Morris

Faculty, Staff and Student Publications

Purpose: Increased glucocorticoid receptor (GR) signaling is a proposed compensatory mechanism of resistance to androgen receptor (AR) inhibition in metastatic castration-resistant prostate cancer (mCRPC). ORIC-101 is a potent and selective orally-bioavailable GR antagonist.

Patients and methods: Safety, pharmacokinetic/pharmacodynamic, and antitumor activity of ORIC-101 in combination with enzalutamide were studied in patients with mCRPC progressing on enzalutamide. ORIC-101 doses ranging from 80 to 240 mg once daily were tested in combination with enzalutamide 160 mg once daily. Pharmacokinetics/pharmacodynamics was assessed after a single dose and at steady state. Disease control rate (DCR) at 12 weeks was evaluated at the recommended phase …

Toward Clinical-Grade Evaluation Of Large Language Models, Amy C Moreno, Danielle S Bitterman

Faculty, Staff and Student Publications

No abstract provided.

Clonal Dominance Defines Metastatic Dissemination In Pancreatic Cancer, I-Lin Ho, Chieh-Yuan Li, Fuchenchu Wang, Li Zhao, Jingjing Liu, Er-Yen Yen, Charles A Dyke, Rutvi Shah, Zhaoliang Liu, Ali Osman Çetin, Yanshuo Chu, Francesca Citron, Sergio Attanasio, Denise Corti, Faezeh Darbaniyan, Edoardo Del Poggetto, Sara Loponte, Jintan Liu, Melinda Soeung, Ziheng Chen, Shan Jiang, Hong Jiang, Akira Inoue, Sisi Gao, Angela Deem, Ningping Feng, Haoqiang Ying, Michael Kim, Virginia Giuliani, Giannicola Genovese, Jianhua Zhang, Andrew Futreal, Anirban Maitra, Timothy Heffernan, Linghua Wang, Kim-Anh Do, Gaetano Gargiulo, Giulio Draetta, Alessandro Carugo, Ruitao Lin, Andrea Viale

Faculty, Staff and Student Publications

Tumors represent ecosystems where subclones compete during tumor growth. While extensively investigated, a comprehensive picture of the interplay of clonal lineages during dissemination is still lacking. Using patient-derived pancreatic cancer cells, we created orthotopically implanted clonal replica tumors to trace clonal dynamics of unperturbed tumor expansion and dissemination. This model revealed the multifaceted nature of tumor growth, with rapid changes in clonal fitness leading to continuous reshuffling of tumor architecture and alternating clonal dominance as a distinct feature of cancer growth. Regarding dissemination, a large fraction of tumor lineages could be found at secondary sites each having distinctive organ growth …

Safety And Efficacy Of Ibrutinib In Combination With Rituximab And Lenalidomide In Previously Untreated Follicular And Marginal Zone Lymphoma: An Open Label, Phase 2 Study, Max J Gordon, Lei Feng, Paolo Strati, Hun Ju Lee, Fredrick B Hagemeister, Jason R Westin, Felipe Samaniego, Mario L Marques-Piubelli, Francisco Vega Vazquez, Edwin R Parra Cuentas, Luisa M Solis-Soto, Wencai Ma, Jing Wang, Linda Claret, Barbara Averill, Karina Ibanez, Luis E Fayad, Christopher R Flowers, Michael R Green, R Eric Davis, Sattva S Neelapu, Nathan H Fowler, Loretta J Nastoupil

Faculty, Staff and Student Publications

Background: Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent non-Hodgkin lymphomas (iNHL). Median survival for iNHL is approximately 20 years. Because standard treatments are not curative, patients often receive multiple lines of therapy with associated toxicity-rationally designed, combination therapies with curative potential are needed. The immunomodulatory drug lenalidomide was evaluated in combination with rituximab for the frontline treatment of FL in the phase 3 RELEVANCE study. Ibrutinib, an oral Bruton tyrosine kinase inhibitor, is active in NHL and was evaluated in combination with lenalidomide, rituximab, and ibrutinib (IRR) in a phase 1 study.

Methods: The authors conducted an …

Effect Of Neutralizing Monoclonal Antibody Treatment On Early Trajectories Of Virologic And Immunologic Biomarkers In Patients Hospitalized With Covid-19, Tomas O Jensen, Greg A Grandits, Mamta K Jain, Thomas A Murray, Birgit Grund, Kathryn Shaw-Saliba, Michael A Matthay, Mahsa Abassi, Magdalena Ardelt, Jason V Baker, Peter Chen, Robin L Dewar, Anna L Goodman, Timothy J Hatlen, Helene C Highbarger, Mark Holodniy, Perrine Lallemand, Sylvain Laverdure, Bradley G Leshnower, David Looney, Charalampos D Moschopoulos, Henry Mugerwa, Daniel D Murray, Eleftherios Mylonakis, Stephanie Nagy-Agren, M Tauseef Rehman, Adam Rupert, Randy A Stevens, Stuart Turville, Amy Weintrob, Katherine Wick, Jens Lundgren, Emily R Ko, Activ-3/Tico Study Group

Faculty, Staff and Student Publications

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood.

METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models.

RESULTS: Analysis included 2149 participants enrolled between …

Label-Aware Distance Mitigates Temporal And Spatial Variability For Clustering And Visualization Of Single-Cell Gene Expression Data, Shaoheng Liang, Jinzhuang Dou, Ramiz Iqbal, Ken Chen

Faculty, Staff and Student Publications

Clustering and visualization are essential parts of single-cell gene expression data analysis. The Euclidean distance used in most distance-based methods is not optimal. The batch effect, i.e., the variability among samples gathered from different times, tissues, and patients, introduces large between-group distance and obscures the true identities of cells. To solve this problem, we introduce Label-Aware Distance (LAD), a metric using temporal/spatial locality of the batch effect to control for such factors. We validate LAD on simulated data as well as apply it to a mouse retina development dataset and a lung dataset. We also found the utility of our …

A Road Map Of Relapse In Mds After Allo-Hsct, Juan Jose Rodriguez-Sevilla, Simona Colla

Faculty, Staff and Student Publications

No abstract provided.

Btn1a1 Is A Novel Immune Checkpoint Mutually Exclusive To Pd-L1, Young-Seung Kim, Seung-Hoon Lee, Andrew H Park, Chunai Wu, Bong-Ki Hong, Hyunjin Jung, Steven H Lin, Stephen S Yoo

Faculty, Staff and Student Publications

BACKGROUND: While Programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) blockade is a potent antitumor treatment strategy, it is effective in only limited subsets of patients with cancer, emphasizing the need for the identification of additional immune checkpoints. Butyrophilin 1A1 (BTN1A1) has been reported to exhibit potential immunoregulatory activity, but its ability to function as an immune checkpoint remains to be systematically assessed, and the mechanisms underlying such activity have yet to be characterized.

METHODS: BTN1A1 expression was evaluated in primary tumor tissue samples, and its ability to suppress T-cell activation and T cell-dependent tumor clearance was examined. …

An Exposome Atlas Of Serum Reveals The Risk Of Chronic Diseases In The Chinese Population, Lei You, Jing Kou, Mengdie Wang, Guoqin Ji, Xiang Li, Chang Su, Fujian Zheng, Mingye Zhang, Yuting Wang, Tiantian Chen, Ting Li, Lina Zhou, Xianzhe Shi, Chunxia Zhao, Xinyu Liu, Surong Mei, Guowang Xu

Faculty, Staff and Student Publications

Although adverse environmental exposures are considered a major cause of chronic diseases, current studies provide limited information on real-world chemical exposures and related risks. For this study, we collected serum samples from 5696 healthy people and patients, including those with 12 chronic diseases, in China and completed serum biomonitoring including 267 chemicals via gas and liquid chromatography-tandem mass spectrometry. Seventy-four highly frequently detected exposures were used for exposure characterization and risk analysis. The results show that region is the most critical factor influencing human exposure levels, followed by age. Organochlorine pesticides and perfluoroalkyl substances are associated with multiple chronic diseases, …

Genomic Evolution Shapes Prostate Cancer Disease Type, Dan J Woodcock, Atef Sahli, Ruxandra Teslo, Vinayak Bhandari, Andreas J Gruber, Aleksandra Ziubroniewicz, Gunes Gundem, Yaobo Xu, Adam Butler, Ezequiel Anokian, Bernard J Pope, Chol-Hee Jung, Maxime Tarabichi, Stefan C Dentro, J Henry R Farmery, Cruk Icgc Prostate Group, Peter Van Loo, Anne Y Warren, Vincent Gnanapragasam, Freddie C Hamdy, G Steven Bova, Christopher S Foster, David E Neal, Yong-Jie Lu, Zsofia Kote-Jarai, Michael Fraser, Robert G Bristow, Paul C Boutros, Anthony J Costello, Niall M Corcoran, Christopher M Hovens, Charlie E Massie, Andy G Lynch, Daniel S Brewer, Rosalind A Eeles, Colin S Cooper, David C Wedge

Faculty, Staff and Student Publications

The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype …

Cytoplasmic Genome Contributions To Domestication And Improvement Of Modern Maize, Shuai Cao, Huanhuan Zhang, Yang Liu, Yi Sun, Z Jeffrey Chen

Faculty, Staff and Student Publications

Background: Studies on maize evolution and domestication are largely limited to the nuclear genomes, and the contribution of cytoplasmic genomes to selection and domestication of modern maize remains elusive. Maize cytoplasmic genomes have been classified into fertile (NA and NB) and cytoplasmic-nuclear male-sterility (CMS-S, CMS-C, and CMS-T) groups, but their contributions to modern maize breeding have not been systematically investigated.

Results: Here we report co-selection and convergent evolution between nuclear and cytoplasmic genomes by analyzing whole genome sequencing data of 630 maize accessions modern maize and its relatives, including 24 fully assembled mitochondrial and chloroplast genomes. We show that the …

Ursapgx: A New R Package To Annotate Pharmacogenetic Star Alleles Using Phased Whole-Genome Sequencing Data., Gennaro Calendo, Dara Kusic, Josef Madzo, Neda Gharani, Laua Scheinfeldt

Cooper Medical School of Rowan University Departmental Research

Long-read sequencing technologies offer new opportunities to generate high-confidence phased whole-genome sequencing data for robust pharmacogenetic annotation. Here, we describe a new user-friendly R package, ursaPGx, designed to accept multi-sample phased whole-genome sequencing data VCF input files and output star allele annotations for pharmacogenes annotated in PharmVar.