Digital Commons Network^™

Editorial: The Impact Of Inflammation On The Oral Microbiome, Chun-Teh Lee, Loreto Abusleme, Thomas E Van Dyke

Faculty, Staff and Student Publications

No abstract provided.

Toward A More Comprehensive Understanding Of Organizational Influences On Implementation: The Organization Theory For Implementation Science Framework, Sarah A Birken, Cheyenne R Wagi, Alexandra G Peluso, Michelle C Kegler, Jure Baloh, Prajakta Adsul, Maria E Fernandez, Manal Masud, Terry T-K Huang, Matthew Lee, Mary Wangen, Per Nilsen, Miriam Bender, Mimi Choy-Brown, Grace Ryan, Aliza Randazzo, Linda K Ko

Faculty, Staff and Student Publications

Introduction: Implementation is influenced by factors beyond individual clinical settings. Nevertheless, implementation research often focuses on factors related to individual providers and practices, potentially due to limitations of available frameworks. Extant frameworks do not adequately capture the myriad organizational influences on implementation. Organization theories capture diverse organizational influences but remain underused in implementation science. To advance their use among implementation scientists, we distilled 70 constructs from nine organization theories identified in our previous work into theoretical domains in the Organization Theory for Implementation Science (OTIS) framework.

Methods: The process of distilling organization theory constructs into domains involved concept mapping and …

Peripheral Calcifying Odontogenic Cyst: A Case Report And Comprehensive Review Of 60 Years Of Literature, Sally Sheng, Nicholas Tipton, Jennifer Chang, Hsiu-Wan Meng, Gena D Tribble

Faculty, Staff and Student Publications

Peripheral Calcifying Odontogenic Cyst (PCOC) is the extraosseous form of calcifying odontogenic cyst that is limited to peripheral soft tissue without bony involvement. This case report presents a case of PCOC manifested as a progressive growth of gingival mass in a young male treated with excisional biopsy. Histological examination confirmed diagnosis of PCOC with presence of characteristic ghost cells and sporadic calcifications. No recurrence of the lesion and no complication were noted at three-year follow-up. Review of available literature on PCOC noted a predilection of occurrence in the mandible (61%) and in the anterior area of the jaws (58%). Mean …

Comorbidity Network Analysis Using Graphical Models For Electronic Health Records, Bo Zhao, Sarah Huepenbecker, Gen Zhu, Suja S Rajan, Kayo Fujimoto, Xi Luo

Faculty, Staff and Student Publications

IMPORTANCE: The comorbidity network represents multiple diseases and their relationships in a graph. Understanding comorbidity networks among critical care unit (CCU) patients can help doctors diagnose patients faster, minimize missed diagnoses, and potentially decrease morbidity and mortality.

OBJECTIVE: The main objective of this study was to identify the comorbidity network among CCU patients using a novel application of a machine learning method (graphical modeling method). The second objective was to compare the machine learning method with a traditional pairwise method in simulation.

METHOD: This cross-sectional study used CCU patients' data from Medical Information Mart for the Intensive Care-3 (MIMIC-3) dataset, …

Ai-Drugnet: A Network-Based Deep Learning Model For Drug Repurposing And Combination Therapy In Neurological Disorders, Xingxin Pan, Jun Yun, Zeynep H Coban Akdemir, Xiaoqian Jiang, Erxi Wu, Jason H Huang, Nidhi Sahni, S Stephen Yi

Faculty, Staff and Student Publications

Discovering effective therapies is difficult for neurological and developmental disorders in that disease progression is often associated with a complex and interactive mechanism. Over the past few decades, few drugs have been identified for treating Alzheimer's disease (AD), especially for impacting the causes of cell death in AD. Although drug repurposing is gaining more success in developing therapeutic efficacy for complex diseases such as common cancer, the complications behind AD require further study. Here, we developed a novel prediction framework based on deep learning to identify potential repurposed drug therapies for AD, and more importantly, our framework is broadly applicable …

Gain-Of-Function Variomics And Multi-Omics Network Biology For Precision Medicine, Mark M Li, Sharad Awasthi, Sumanta Ghosh, Deepa Bisht, Zeynep H Coban Akdemir, Gloria M Sheynkman, Nidhi Sahni, S Stephen Yi

Faculty, Staff and Student Publications

Traditionally, disease causal mutations were thought to disrupt gene function. However, it becomes more clear that many deleterious mutations could exhibit a "gain-of-function" (GOF) behavior. Systematic investigation of such mutations has been lacking and largely overlooked. Advances in next-generation sequencing have identified thousands of genomic variants that perturb the normal functions of proteins, further contributing to diverse phenotypic consequences in disease. Elucidating the functional pathways rewired by GOF mutations will be crucial for prioritizing disease-causing variants and their resultant therapeutic liabilities. In distinct cell types (with varying genotypes), precise signal transduction controls cell decision, including gene regulation and phenotypic output. …

A Novel Bayesian Spatial-Temporal Approach To Quantify Sars-Cov-2 Testing Disparities For Small Area Estimation, Cici Bauer, Xiaona Li, Kehe Zhang, Miryoung Lee, Esmeralda Guajardo, Susan Fisher-Hoch, Joseph Mccormick, Maria E Fernandez, Belinda Reininger

Faculty, Staff and Student Publications

Objectives. To propose a novel Bayesian spatial–temporal approach to identify and quantify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing disparities for small area estimation.

Methods. In step 1, we used a Bayesian inseparable space–time model framework to estimate the testing positivity rate (TPR) at geographically granular areas of the census block groups (CBGs). In step 2, we adopted a rank-based approach to compare the estimated TPR and the testing rate to identify areas with testing deficiency and quantify the number of needed tests. We used weekly SARS-CoV-2 infection and testing surveillance data from Cameron County, Texas, between March 2020 …

Genetic Associations Between Sleep Traits And Cognitive Ageing Outcomes In The Hispanic Community Health Study/Study Of Latinos, Yuan Zhang, Michael Elgart, Einat Granot-Hershkovitz, Heming Wang, Wassim Tarraf, Alberto R Ramos, Ariana M Stickel, Donglin Zeng, Tanya P Garcia, Fernando D Testai, Sylvia Wassertheil-Smoller, Carmen R Isasi, Martha L Daviglus, Robert Kaplan, Myriam Fornage, Charles Decarli, Susan Redline, Hector M González, Tamar Sofer

Faculty, Staff and Student Publications

BACKGROUND: Sleep phenotypes have been reported to be associated with cognitive ageing outcomes. However, there is limited research using genetic variants as proxies for sleep traits to study their associations. We estimated associations between Polygenic Risk Scores (PRSs) for sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnoea (OSA) and measures of cogntive ageing in Hispanic/Latino adults.

METHODS: We used summary statistics from published genome-wide association studies to construct PRSs representing the genetic basis of each sleep trait, then we studied the association of the PRSs of the sleep phenotypes with cognitive outcomes in the Hispanic Community Healthy Study/Study of …

Enabling Structural Resilience Of Street-Involved Children And Youth In Kenya: Reintegration Outcomes And The Flourishing Community Model, Michael L Goodman, Sarah E Seidel, Andrew Springer, Aleisha Elliott, Christine Markham, Hani Serag, Philip Keiser, Ben Raimer, Lauren Raimer-Goodman, Christine Gatwiri, Kelvin Munene, Stanley Gitari

Faculty, Staff and Student Publications

Introduction: Millions of children and youth live on city streets across the globe, vulnerable to substance use, abuse, material and structural neglect. Structural resilience, the re-establishment of access to structural goods within a society such as housing, education, and healthcare following some interruption, provides an orientation for research and interventional efforts with street-involved children and youth (SICY). Further, a structural resilience framework supports organizing interactions between levels and sectors of a socio-ecology.

Methods: Following the expressed interests of Kenyan SICY, and consistent with emerging policy interests at national and global levels, we assess reintegration trajectories of Kenyan SICY (n …

Pregnancy-Related Covid Worry, Depressive Symptom Severity, And Mediation Through Sleep Disturbance In A Low-Income, Primarily Latinx Population In California’S Central Valley, Jennifer N Felder, Patience A Afulani, Kimberly Coleman-Phox, Serwaa S Omowale, Charles E Mcculloch, Lauren Lessard, Miriam Kuppermann

Faculty, Staff and Student Publications

Purpose: This study (1) assessed the psychometric properties of a pregnancy-related COVID worry scale, (2) explored variations in pregnancy-related COVID worry over the course of the pandemic, and (3) examined associations between pregnancy-related COVID worry and depressive symptom severity, and evaluated sleep disturbance as a mediator.

Methods: Data were drawn from an ongoing randomized trial comparing the effectiveness of two enhanced forms of prenatal care. The current analysis includes baseline pre-randomization data collected from participants who enrolled November 2020-November 2021 (n = 201). Participants were pregnant individuals with low income and primarily Latinx.

Results: Our 7-item scale was valid and …

Maternal Perceptions Of Vaccinating Boys Against Human Papillomavirus (Hpv) In Seoul, South Korea: A Descriptive Exploratory Qualitative Study, Jihye Choi, Christine Markham, Irene Tamí-Maury, Sooyoun Kim, Paula Cuccaro

Faculty, Staff and Student Publications

Human Papillomavirus (HPV) vaccination is of paramount importance to reduce HPV-associated cancers in both genders. In South Korea, the prophylactic vaccine is recognized as prevention of cervical cancer with little attention given to male HPV vaccination. The purpose of this study was to explore perceptions of male HPV vaccination and underlying factors for vaccine hesitancy among mothers of unvaccinated boys in Seoul, Korea using a qualitative method. We used a purposive sampling strategy to recruit mothers of unvaccinated middle school-aged boys living in one of the 25 districts in Seoul, supplemented by a snowball sampling approach. We conducted one-on-one telephone …

A Narrative Review Of The Lesser Known Medications For Treatment Of Restless Legs Syndrome And Pathogenetic Implications For Their Use, Paul G Yeh, Karen Spruyt, Lourdes M Delrosso, Arthur S Walters

Faculty, Staff and Student Publications

BACKGROUND: There are several well-known treatments for Restless Legs Syndrome (RLS), including dopamine agonists (pramipexole, ropinirole, rotigotine), anticonvulsants (gabapentin and its analogs, pregabalin), oral or intravenous iron, opioids and benzodiazepines. However, in clinical practice, treatment is sometimes limited due to incomplete response or side effects and it is necessary to be aware of other treatment options for RLS, which is the purpose of this review.

METHODS: We performed a narrative review detailing all of the lesser known pharmacological treatment literature on RLS. The review purposefully excludes well-established, well-known treatments for RLS which are widely accepted as treatments for RLS in …

From The National To The Local: Issues Of Trust And A Model For Community-Academic-Engagement, Olufunmilayo Chinekezi, Lauri Andress, Etsemaye P Agonafer, Susan Massick, Sarah Piepenbrink, Karey M Sutton, Philip M Alberti, Desiree De La Torre, Shannon Guillot-Wright, Marshala Lee

Faculty, Staff and Student Publications

Inequities in health and health care in the United States have persisted for decades, and the impacts on equity from the COVID-19 pandemic were no exception. In addition to the disproportionate burden of the disease across various populations, the pandemic posed several challenges, which exacerbated these existing inequities. This has undoubtedly contributed to deeply rooted public mistrust in medical research and healthcare delivery, particularly among historically and structurally oppressed populations. In the summer of 2020, given the series of social injustices posed by the pandemic and highly publicized incidents of police brutality, notably the murder of George Floyd, the Association …

The Predictive Value Of Coronary Microvascular Dysfunction For Left Ventricular Reverse Remodelling In Dilated Cardiomyopathy, Ao Kan, Yinping Leng, Shuhao Li, Fang Lin, Qimin Fang, Xinwei Tao, Mengyao Hu, Lianggeng Gong

Faculty, Staff and Student Publications

AIMS: to evaluate the degree of coronary microvascular dysfunction (CMD) in dilated cardiomyopathy (DCM) patients by cardiac magnetic resonance (CMR) first-pass perfusion parameters and to examine the correlation between myocardial perfusion and left ventricle reverse remodelling (LVRR).

METHODS: In this study, 94 DCM patients and 35 healthy controls matched for age and sex were included. Myocardial perfusion parameters, including upslope, time to maximum signal intensity (Time

RESULTS: With a median follow-up period of 12 months [interquartile range (IQR), 8-13], 41 DCM patients (44%) achieved LVRR. Compared with healthy controls, DCM patients presented CMD with reduced upslope, SI

CONCLUSIONS: CMD could …

A Case Of Successful Treatment Of Recurrent Urinary Tract Infection By Extended-Spectrum Β-Lactamase Producing, Naomi Bier, Blake Hanson, Zhi-Dong Jiang, Herbert L Dupont, Cesar A Arias, William R Miller

Faculty, Staff and Student Publications

Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producing

Subendocardial And Transmural Myocardial Ischemia: Clinical Characteristics, Prevalence, And Outcomes With And Without Revascularization, K Lance Gould, Tung Nguyen, Richard Kirkeeide, Amanda E Roby, Linh Bui, Danai Kitkungvan, Monica B Patel, Mohammad Madjid, Mary Haynie, Dejian Lai, Ruosha Li, Jagat Narula, Nils P Johnson

Faculty, Staff and Student Publications

BACKGROUND: Subendocardial ischemia is commonly diagnosed but not quantified by imaging.

OBJECTIVES: This study sought to define size and severity of subendocardial and transmural stress perfusion deficits, clinical associations, and outcomes.

METHODS: Regional rest-stress perfusion in mL/min/g, coronary flow reserve, coronary flow capacity (CFC), relative stress flow, subendocardial stress-to-rest ratio and stress subendocardial-to-subepicardial ratio as percentage of left ventricle were measured by positron emission tomography (PET) with rubidium Rb 82 and dipyridamole stress in serial 6,331 diagnostic PETs with prospective 10-year follow-up for major adverse cardiac events with and without revascularization.

RESULTS: Of 6,331 diagnostic PETs, 1,316 (20.7%) had severely …

Corrigendum: Editorial: Period Poverty, Lea Sacca, Christine Margaret Markham, Jhumka Gupta, Melissa Peskin

Faculty, Staff and Student Publications

This corrects the article "Editorial: Period poverty" in volume 5, 1140981.

Novornabreak: Local Assembly For Novel Splice Junction And Fusion Transcript Detection From Rna-Seq Data, Yukun Tan, Vakul Mohanty, Shaoheng Liang, Jinzhuang Dou, Jun Ma, Kun Hee Kim, Marc Jan Bonder, Xinghua Shi, Charles Lee, Zechen Chong, Ken Chen

Faculty, Staff and Student Publications

We present novoRNABreak, a unified framework for cancer specific novel splice junction and fusion transcript detection in RNA-seq data obtained from human cancer samples. novoRNABreak is based on a local assembly model, which offers a tradeoff between the alignment-based and de novo whole transcriptome assembly (WTA) methods. This approach is accurate and sensitive in assembling novel junctions that are difficult to directly align or have multiple alignments. Additionally, it is more efficient due to the strategy that focuses on junctions rather than full length transcripts. The performance of novoRNABreak is demonstrated by a comprehensive set of experiments using synthetic data …

Automated Brain Metastases Segmentation With A Deep Dive Into False-Positive Detection, Hamidreza Ziyaee, Carlos E Cardenas, D Nana Yeboa, Jing Li, Sherise D Ferguson, Jason Johnson, Zijian Zhou, Jeremiah Sanders, Raymond Mumme, Laurence Court, Tina Briere, Jinzhong Yang

Faculty, Staff and Student Publications

Purpose: The clinical management of brain metastases after stereotactic radiosurgery (SRS) is difficult, because a physician must review follow-up magnetic resonance imaging (MRI) scans to determine treatment outcome, which is often labor intensive. The purpose of this study was to develop an automated framework to contour brain metastases in MRI to help treatment planning for SRS and understand its limitations.

Methods and materials: Two self-adaptive nnU-Net models trained on postcontrast 3-dimensional T1-weighted MRI scans from patients who underwent SRS were analyzed. Performance was evaluated by computing positive predictive value (PPV), sensitivity, and Dice similarity coefficient (DSC). The training and testing …

Pathologic And Molecular Insights In Nodal T-Follicular Helper Cell Lymphomas, Mario L Marques-Piubelli, Catalina Amador, Francisco Vega

Faculty, Staff and Student Publications

T-follicular helper (TFH) cells are one of the T-cell subsets with a critical role in the regulation of germinal center (GC) reactions. TFH cells contribute to the positive selection of GC B-cells and promote plasma cell differentiation and antibody production. TFH cells express a unique phenotype characterized by PD-1hi, ICOShi, CD40Lhi, CD95hi, CTLAhi, CCR7lo, and CXCR5hi . Three main subtypes of nodal TFH lymphomas have been described: 1) angioimmunoblastic-type, 2) follicular-type, and 3) not otherwise specified (NOS). The diagnosis of these neoplasms can be challenging, and it is rendered based on a combination of clinical, laboratory, histopathologic, immunophenotypic, and molecular …

When Guilt Works: A Comprehensive Meta-Analysis Of Guilt Appeals, Wei Peng, Qian Huang, Bingjing Mao, Di Lun, Ekaterina Malova, Jazmyne V Simmons, Nick Carcioppolo

Faculty, Staff and Student Publications

Introduction: Guilt appeals are widely used as a persuasive approach in various areas of practice. However, the strength and direction of the persuasive effects of guilt appeals are mixed, which could be influenced by theoretical and methodological factors.

Method: The present study is a comprehensive meta-analysis of 26 studies using a random-effects model to assess the persuasive effects of guilt appeals. In total, 127 effect sizes from seven types of persuasive outcomes (i.e., guilt, attitude, behavior, behavioral intention, non-guilt emotions, motivation, and cognition) were calculated based on 7,512 participants.

Results: The analysis showed a small effect size of guilt appeals …

Sociodemographic Differences In Menthol Cigarette Use In The United States, Rajesh Talluri, Sanjay Shete

Faculty, Staff and Student Publications

Background: Menthol cigarette use is associated with higher smoking initiation and reduced smoking cessation. We investigated sociodemographic differences in menthol and nonmenthol cigarette use in the United States.

Methods: We used the most recent available data from the May 2019 wave of the nationally-representative Tobacco Use Supplement to the Current Population Survey. The survey weights were used to estimate the national prevalence of individuals who currently smoke among individuals who use menthol and nonmenthol cigarettes. Survey-weighted logistic regression methods were used to estimate the association of menthol cigarette use with formerly smoking cigarettes and attempting to quit within the past …

Applying Ht-Saxs To Chemical Ligand Screening, Chris A Brosey, Runze Shen, Davide Moiani, Darin E Jones, Kathryn Burnett, Greg L Hura, John A Tainer

Faculty, Staff and Student Publications

Chemical probes are invaluable tools for investigating essential biological processes. Understanding how small-molecule probes engage biomolecular conformations is critical to developing their functional selectivity. High-throughput solution X-ray scattering is well-positioned to profile target-ligand complexes during probe development, bringing conformational insight and selection to traditional ligand binding assays. Access to high-quality synchrotron SAXS datasets and high-throughput data analysis now allows routine academic users to incorporate conformational information into small-molecule development pipelines. Here we describe a general approach for benchmarking and preparing HT-SAXS chemical screens from small fragment libraries. Using the allosteric oxidoreductase Apoptosis-Inducing Factor (AIF) as an exemplary system, we illustrate …

Adverse Events Of Immune Checkpoint Therapy Alone Versus When Combined With Vascular Endothelial Growth Factor Inhibitors: A Pooled Meta-Analysis Of 1735 Patients, Iuliia Kovalenko, Wern Lynn Ng, Yimin Geng, Yinghong Wang, Pavlos Msaouel, Shailender Bhatia, Petros Grivas, Raed Benkhadra, Omar Alhalabi

Faculty, Staff and Student Publications

Background: Combining immune checkpoint therapy (ICT) and vascular endothelial growth factor inhibitors (VEGFi) may result in increased treatment-related and immune-related adverse events (TRAEs and irAEs) compared to ICT alone. This metanalysis was conducted to identify prospective phase II or III clinical studies that evaluated the toxicity profile of ICT + VEGFi compared to ICT alone.

Methods: A systematic search was performed across all cancer types and major databases until August 10, 2022, and screening was done by two independent investigators. Inclusion criteria included phase 2 or 3 studies with at least one arm of patients treated with combination therapy and …

Cd73-Generated Extracellular Adenosine Promotes Resolution Of Neutrophil-Mediated Tissue Injury And Restrains Metaplasia In Pancreatitis, Baylee J O'Brien, Erika Y Faraoni, Lincoln N Strickland, Zhibo Ma, Victoria Mota, Samantha Mota, Xuebo Chen, Tingting Mills, Holger K Eltzschig, Kathleen E Delgiorno, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatitis is currently the leading cause of gastrointestinal hospitalizations in the US. This condition occurs in response to abdominal injury, gallstones, chronic alcohol consumption or, less frequently, the cause remains idiopathic. CD73 is a cell surface ecto‐5′‐nucleotidase that generates extracellular adenosine, which can contribute to resolution of inflammation by binding adenosine receptors on infiltrating immune cells. We hypothesized genetic deletion of CD73 would result in more severe pancreatitis due to decreased generation of extracellular adenosine. CD73 knockout (CD73 −/−) and C57BL/6 (wild type, WT) mice were used to evaluate the progression and response of caerulein‐induced acute and chronic pancreatitis. …

Positron Emission Tomography Derived Metrics In Relapsed Or Refractory Large B-Cell Lymphoma With Residual Disease Before Autologous Stem Cell Transplant, Hua-Jay J Cherng, Guofan Xu, Lei Feng, Raphael Steiner, Luis Fayad, Paolo Strati, Ranjit Nair, Loretta J Nastoupil, Hun Ju Lee, Sattva S Neelapu, Christopher R Flowers, Maria Rodriguez, Michael Wang, Fredrick Hagemeister, Chelsea C Pinnix, Jeremy Ramdial, Samer Srour, Yago Nieto, Katayoun Rezvani, Richard Champlin, Partow Kebriaei, Jason Westin, Homer A Macapinlac, Elizabeth Shpall, Sairah Ahmed

Faculty, Staff and Student Publications

Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative treatment for patients with relapsed or refractory large B-cell lymphoma (rrLBCL) with chemosensitive disease. A18 F-fluorodeoxyglucose positron emission tomography (PET) scan after salvage chemotherapy is used to assess response and eligibility for ASCT, but metrics for chemosensitivity in patients with residual disease are not well defined. We performed a single-centre retrospective analysis of 92 patients with a partial response or stable disease after salvage chemotherapy for rrLBCL who received ASCT to investigate PET-derived parameters and their prognostic utility. The Deauville 5-point Scale (D-5PS) score, …

The Kynurenine Pathway Presents Multi-Faceted Metabolic Vulnerabilities In Cancer, Ricardo A León-Letelier, Rongzhang Dou, Jody Vykoukal, Ali Hussein Abdel Sater, Edwin Ostrin, Samir Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

The kynurenine pathway (KP) and associated catabolites play key roles in promoting tumor progression and modulating the host anti-tumor immune response. To date, considerable focus has been on the role of indoleamine 2,3-dioxygenase 1 (IDO1) and its catabolite, kynurenine (Kyn). However, increasing evidence has demonstrated that downstream KP enzymes and their associated metabolite products can also elicit tumor-microenvironment immune suppression. These advancements in our understanding of the tumor promotive role of the KP have led to the conception of novel therapeutic strategies to target the KP pathway for anti-cancer effects and reversal of immune escape. This review aims to 1) …

Impact Of Region-Of-Interest Size On Immune Profiling Using Multiplex Immunofluorescence Tyramide Signal Amplification For Paraffin-Embedded Tumor Tissues, Baohua Sun, Caddie Laberiano-Fernández, Ruth Salazar-Alejo, Jiexin Zhang, Jose Luis Solorzano Rendon, Jack Lee, Luisa Maren Solis Soto, Ignacio Ivan Wistuba, Edwin Roger Parra

Faculty, Staff and Student Publications

Introduction: Representative regions of interest (ROIs) analysis from the whole slide images (WSI) are currently being used to study immune markers by multiplex immunofluorescence (mIF) and single immunohistochemistry (IHC). However, the amount of area needed to be analyzed to be representative of the entire tumor in a WSI has not been defined.

Methods: We labeled tumor-associated immune cells by mIF and single IHC in separate cohorts of non-small cell lung cancer (NSCLC) samples and we analyzed them as whole tumor area as well as using different number of ROIs to know how much area will be need to represent the …

Tp53-Pten-Nf1 Depletion In Human Brain Organoids Produces A Glioma Phenotype In Vitro, Sanjay K Singh, Yan Wang, Ahmed Habib, Mamindla Priyadarshini, Chowdari V Kodavali, Apeng Chen, Wencai Ma, Jing Wang, N U Farrukh Hameed, Baoli Hu, Gregory N Fuller, Scott M Kulich, Nduka Amankulor, Rivka R Colen, Lincoln A Edwards, Pascal O Zinn

Faculty, Staff and Student Publications

Glioblastoma (GBM) is fatal and the study of therapeutic resistance, disease progression, and drug discovery in GBM or glioma stem cells is often hindered by limited resources. This limitation slows down progress in both drug discovery and patient survival. Here we present a genetically engineered human cerebral organoid model with a cancer-like phenotype that could provide a basis for GBM-like models. Specifically, we engineered a doxycycline-inducible vector encoding shRNAs enabling depletion of the TP53, PTEN, and NF1 tumor suppressors in human cerebral organoids. Designated as inducible short hairpin-TP53-PTEN-NF1 (ish-TPN), doxycycline treatment resulted in human cancer-like cerebral organoids that effaced the …

Minimax Estimation For Personalized Federated Learning: An Alternative Between Fedavg And Local Training?, Shuxiao Chen, Qinqing Zheng, Qi Long, Weijie J Su

Faculty, Staff and Student Publications

A widely recognized difficulty in federated learning arises from the statistical heterogeneity among clients: local datasets often originate from distinct yet not entirely unrelated probability distributions, and personalization is, therefore, necessary to achieve optimal results from each individual's perspective. In this paper, we show how the excess risks of personalized federated learning using a smooth, strongly convex loss depend on data heterogeneity from a minimax point of view, with a focus on the FedAvg algorithm (McMahan et al., 2017) and pure local training (i.e., clients solve empirical risk minimization problems on their local datasets without any communication). Our main result …