Digital Commons Network^™

Sleep-Disordered Breathing Subtypes And Future Diet Quality In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Cecilia Castro-Diehl, Tianyi Huang, Alexis C Wood, Jerome I Rotter, Stephen S Rich, Tamar Sofer, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Objectives: Sleep-disordered breathing (SDB) and diet quality impact cardiometabolic disease, but few studies have examined if SDB influences diet quality. This study estimated the association between SDB subtypes (with and without sleepiness) and future diet quality in the Multi-Ethnic Study of Atherosclerosis.

Methods: Probable SDB was characterized by self-reported physician-diagnosed sleep apnea (PDSA) or habitual snoring and subtyped by presence or absence of sleepiness. A food frequency questionnaire measured diet 1.6 years before, and 7.8 years after SDB assessment. Diet quality was measured with the Alternate Healthy Eating Index-2010 (AHEI). Mean differences in AHEI at follow-up by SDB subtypes were …

Definition Of The 3d Position And Motion Status Of The Moving Heart Based On 2d Projections, Lawrence D. Orijuela

Electronic Theses, Projects, and Dissertations

This thesis presents a novel application of deep learning to the estimation of pulmonary vein coordinates using X-ray image pairs from a FORBILD Thorax phantom derived motion dataset. A Siamese neural network was developed to predict the 3D coordinates of one pulmonary vein at a time, specifically the Right Superior Pulmonary Vein (RSPV), Left Superior Pulmonary Vein (LSPV), Left Inferior Pulmonary Vein (LIPV), or Right Inferior Pulmonary Vein (RIPV), based on two-dimensional projection images.

The input data consisted of over 1.6 million grayscale X-ray image pairs across 1331 virtual patients, each annotated with ground truth 3D coordinates. To manage memory …

Comparative Value Of Echocardiography Vs. Right Heart Catheterization In Heart Failure With Preserved Ejection Fraction, Nathanael Tran, Mohammad Shaar, Hussein Al-Sudani, Ramy Sedhom, Hamza Akhtar, Kevin Bryan Lo, Gregg S. Pressman

Einstein Health Papers

BACKGROUND: Echocardiography and right heart catheterization (RHC) are useful in the evaluation of heart failure with preserved ejection fraction (HFpEF). We compared the two among decompensated HFpEF patients to determine their relative value in predicting all-cause mortality and a composite of cardiovascular (CV) death and heart failure (HF) readmission at 1 year.

METHODS: One hundred seventy-eight decompensated HFpEF patients who underwent both procedures and survived to hospital discharge were retrospectively identified. Hospital records and the National Death Index were queried to determine outcomes. Echocardiographic and invasive parameters were tested for significant associations with each outcome. Additionally, three predictive models were …

Improved Model For Neurodegeneration In C. Elegans, Jean-Pierre Arditi

Graduate Theses and Dissertations (2019 - present)

During Alzheimer's disease (AD), insoluble amyloid beta (AP) peptides accumulate to form extracellular aggregates (plaques). The direct cause of neuronal dysfunction observed in AD has been broadly investigated. The amyloid hypothesis states that AP plaques are neurotoxic, but recent studies support the AP oligomer hypothesis, which states that intracellular AP (iAP) is neurotoxic. To test this hypothesis, I used CRISPR-Cas9 gene editing to generate two transgenic Caenorhabditis elegans (C. elegans) strains. I generated a strain (RSLl 11) using the rab-3 promoter to co-express GFP in neurons, which showed no gross behavioral changes but had a 50% reduced egglaying rate. RSLl …

Detection Of Phase-Binning And Interpolation Artifacts In 4-Dimensional Computed Tomography Imaging Using Deep Learning And Rule-Based Approaches, Jorge Cisneros, Nathan H. Feldt, Yevgeniy Vinogradskiy, Richard Castillo, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Four-dimensional computed tomography (4DCT) imaging is a crucial component to lung cancer radiotherapy planning and enables CT-ventilation-based functional avoidance planning to mitigate radiation toxicity. However, 4DCT scans are frequently impaired by acquisition artifacts that corrupt downstream analyses that depend on lung segmentation and deformable image registration, such as CT-ventilation and dose accumulation.

PURPOSE: This study develops 3D deep learning models to identify phase-binning artifacts at the voxel level and a heuristic, rule-based method to identify interpolation slices within 4DCT images.

METHODS: We introduce a generator that systematically inserts synthetic phase-binning and interpolation artifacts into any artifact-free breathing phase obtained …

Advancing Trypanosoma Cruzi N-Myristoyltransferase As A Drug Target For Chagas Disease Through In Silico Discovery And Biochemical Evaluation, Diana Citlali González García

Open Access Theses & Dissertations

Chagas disease remains one of the most persistent and neglected parasitic infections in the Americas, advancing silently through the intracellular replication of Trypanosoma cruzi amastigotes and the invasive spread of trypomastigotes. The survival of the parasite is critically reliant on protein N-myristoylation, a lipid modification catalyzed by N-myristoyltransferase (NMT). This dissertation aims to advance beyond prior studies by systematically investigating NMT inhibition across multiple biological levels, spanning from the characterization of the purified enzyme, through cellular infection models, to the global proteomic remodeling induced within the parasite, thereby evaluating TcNMT as a potential therapeutic vulnerability in T.cruzi.Recombinant TcNMT was expressed, …

Perceived Utility Of Genetic Carrier Screening In A Diverse Patient Population, Jack A Colleran, Meagan Choates, Syed Hashmi, Brittanie Shelton, Aranza Gonzalez Cendejas, Angela Haynes Burgess, Blair K Stevens

Faculty, Staff and Student Publications

Current reproductive guidelines call for offering expanded carrier screening (ECS) for genetic conditions. Currently available panels can include screening for carrier status of tens to hundreds of autosomal recessive and/or X-linked conditions. Clinical utility is based on alterations to reproductive decision-making, but study cohorts supporting the utility of ECS largely consist of individuals of European ancestry who are highly educated, of high income, and who often receive preconception counseling. There is a lack of research on the views of patients from diverse backgrounds. Therefore, we aimed to assess and compare perceptions of the utility of ECS and targeted carrier screening …

Kras Inhibition Activates An Actionable Cd24 "Do Not Eat Me" Signal In Pancreatic Cancer, Yongkun Wei, Minghui Liu, Er-Yen Yen, Jun Yao, Zhenzhen Xun, Phuoc T Nguyen, Xiaofei Wang, Zecheng Yang, Abdelrahman Yousef, Dean Pan, Yanqing Jin, Ching-Fei Li, Madelaine S Theardy, Jangho Park, Yiming Cai, Mitsunobu Takeda, Matthew Vasquez, Elizabeth M Park, David H Peng, Yong Zhou, Hong Zhao, Timothy P Heffernan, Andrea Viale, Huamin Wang, Stephanie S Watowich, Han Liang, Dan Zhao, Ronald A Depinho, Wantong Yao, Haoqiang Ying

Faculty, Staff and Student Publications

KRASG12C inhibitors (G12Ci) have produced encouraging, albeit modest and transient, clinical benefit in pancreatic ductal adenocarcinoma (PDAC). Identifying and targeting resistance mechanisms to G12Ci treatment is therefore crucial. To better understand the function of KRASG12C and possible G12Ci bypass mechanisms, we developed an autochthonous KRASG12C-driven PDAC model. Compared to the classical KRASG12D PDAC model, the G12C model exhibits slower tumor growth, yet similar histopathological and molecular features. Aligned with clinical experience, G12Ci treatment of KRASG12C tumors produced modest impact despite stimulating a ‘hot’ tumor immune microenvironment. Immunoprofiling revealed that CD24, a ‘don’t eat me’ signal, is significantly upregulated on cancer …

Author Correction: Evidence For Improved Dna Repair In The Long-Lived Bowhead Whale, Denis Firsanov, Max Zacher, Xiao Tian, Todd L Sformo, Yang Zhao, Gregory Tombline, J Yuyang Lu, Zhizhong Zheng, Luigi Perelli, Enrico Gurreri, Li Zhang, Jing Guo, Anatoly Korotkov, Valentin Volobaev, Seyed Ali Biashad, Zhihui Zhang, Johanna Heid, Alexander Y Maslov, Shixiang Sun, Zhuoer Wu, Jonathan Gigas, Eric C Hillpot, John C Martinez, Minseon Lee, Alyssa Williams, Abbey Gilman, Nicholas Hamilton, Ekaterina Strelkova, Ena Haseljic, Avnee Patel, Maggie E Straight, Nalani Miller, Julia Ablaeva, Lok Ming Tam, Chloé Couderc, Michael R Hoopmann, Robert L Moritz, Shingo Fujii, Amandine Pelletier, Dan J Hayman, Hongrui Liu, Yuxuan Cai, Anthony K L Leung, Zhengdong Zhang, C Bradley Nelson, Lisa M Abegglen, Joshua D Schiffman, Vadim N Gladyshev, Carlo C Maley, Mauro Modesti, Giannicola Genovese, Mirre J P Simons, Jan Vijg, Andrei Seluanov, Vera Gorbunova

Faculty, Staff and Student Publications

No abstract provided.

Evidence For Improved Dna Repair In The Long-Lived Bowhead Whale, Denis Firsanov, Max Zacher, Xiao Tian, Todd L Sformo, Yang Zhao, Gregory Tombline, J Yuyang Lu, Zhizhong Zheng, Luigi Perelli, Enrico Gurreri, Li Zhang, Jing Guo, Anatoly Korotkov, Valentin Volobaev, Seyed Ali Biashad, Zhihui Zhang, Johanna Heid, Alexander Y Maslov, Shixiang Sun, Zhuoer Wu, Jonathan Gigas, Eric C Hillpot, John C Martinez, Minseon Lee, Alyssa Williams, Abbey Gilman, Nicholas Hamilton, Ekaterina Strelkova, Ena Haseljic, Avnee Patel, Maggie E Straight, Nalani Miller, Julia Ablaeva, Lok Ming Tam, Chloé Couderc, Michael R Hoopmann, Robert L Moritz, Shingo Fujii, Amandine Pelletier, Dan J Hayman, Hongrui Liu, Yuxuan Cai, Anthony K L Leung, Zhengdong Zhang, C Bradley Nelson, Lisa M Abegglen, Joshua D Schiffman, Vadim N Gladyshev, Carlo C Maley, Mauro Modesti, Giannicola Genovese, Mirre J P Simons, Jan Vijg, Andrei Seluanov, Vera Gorbunova

Faculty, Staff and Student Publications

At more than 200 years, the maximum lifespan of the bowhead whale exceeds that of all other mammals. The bowhead is also the second-largest animal on Earth1, reaching over 80,000 kg. Despite its very large number of cells and long lifespan, the bowhead is not highly cancer-prone, an incongruity termed Peto’s paradox2. Here, to understand the mechanisms that underlie the cancer resistance of the bowhead whale, we examined the number of oncogenic hits required for malignant transformation of whale primary fibroblasts. Unexpectedly, bowhead whale fibroblasts required fewer oncogenic hits to undergo malignant transformation than human fibroblasts. …

Bayesian Integrated Learning Of Longitudinal Dose-Response Relationships Via Decentralized Clinical Trials, Jingyi Zhang, Tuo Wang, Yongming Qu, Fangrong Yan, Suyu Liu, Ruitao Lin

Faculty, Staff and Student Publications

Decentralized clinical trials (DCTs) extend trial activities beyond traditional sites, enhancing access, convenience, efficiency, and result generalizability. They are particularly promising for chronic conditions like diabetes and obesity, which require longer study durations to evaluate drug effects. However, decentralized data collection raises concerns about increased variability and potential biases. This paper presents a novel Bayesian integrated learning procedure to analyze dose-response relationships using longitudinal data from a phase II DCT that combines centralized and decentralized data collection. We generalize a parametric exponential decay model to handle mixed data sources and apply Bayesian spike-and-slab priors to address biases and uncertainties from …

Individualizing Nsaid Therapy In Axial Spondyloarthritis: N-Of-1 Trials With Bayesian Analysis, Mark C Hwang, Seokhun Kim, Shervin Assassi, Reyna Chavez, Joyce Samuel, Charles Green, Jon Tyson, John Reveille

Faculty, Staff and Student Publications

Objective: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly affecting the spine and sacroiliac joints. NSAIDs are first-line therapy, but individual responses vary widely. We evaluated the efficacy and patient preference of three NSAIDs (celecoxib, meloxicam and naproxen) through Bayesian N-of-1 clinical trials to optimize axSpA management.

Methods: We conducted N-of-1 trials with 42 patients meeting ASAS criteria for axSpA. Each patient was asked to complete two cycles of randomized double-blind crossover comparisons of the three NSAIDs, each for 4 weeks. The primary end point was the change in the Ankylosing Spondylitis Disease Activity Score (ASDAS). Bayesian analysis assessed …

Personalized Risk Prediction For Cancer Survivors: A Generalized Bayesian Semi-Parametric Model Of Recurrent Events With Competing Outcomes, Nam Hoai Nguyen, Seung Jun Shin, Elissa Dodd-Eaton, Jing Ning, Wenyi Wang

Faculty, Staff and Student Publications

Multiple primary cancers are increasingly more frequent due to improved survival of cancer patients. Characteristics of the first primary cancer largely impact the risk of developing subsequent primary cancers. Hence, model-based risk characterization of cancer survivors that captures patient-specific variables is needed for healthcare policy making. We propose a Bayesian semi-parametric framework, where the occurrence processes of the competing cancer types follow independent non-homogeneous Poisson processes and adjust for covariates including the type and age at diagnosis of the first primary. Applying this framework to a historically collected cohort with families presenting a highly enriched history of multiple primary tumors …

Evaluation Of Renal Masses With Cest Mri: Protocol Optimization And Preliminary Results, Xiaojing Wang, Jochen Keupp, Ivan E Dimitrov, Ananth Madhuranthakam, Durga Udayakumar, Mahsa Taherzadeh, Emin Albayrak, Orson W Moe, Payal Kapur, Robert E Lenkinski, Ivan Pedrosa, Elena Vinogradov

Faculty, Staff and Student Publications

Purpose: This study investigates the application of CEST MRI in human kidneys, with the overarching goal of developing CEST MRI for renal mass characterization. Here, the focus is on the development of a protocol and the proof-of-principle evaluation of CEST for the characterization of clear cell renal cell carcinoma (ccRCC).

Methods: Ten healthy volunteers and five patients diagnosed with ccRCC underwent CEST MRI scans at 3 T. The sequence performance was characterized in healthy volunteers and tested using three saturation power levels, B1rms = 0.7, 1.2, and 1.6 μT. We compared the magnetization transfer ratio asymmetry (MTRasym) values at 1.0, …

Forecasting Chemoradiation Response Midtreatment For High-Grade Gliomas Through Patient-Specific Biology-Based Modeling, David A Hormuth, Maguy Farhat, Bikash Panthi, Holly Langshaw, Mihir D Shanker, Wasif Talpur, Sara Thrower, Jodi Goldman, Sophia Ty, Calliope Custer, Jeanne Kowalski, Thomas E Yankeelov, Caroline Chung

Faculty, Staff and Student Publications

Purpose: The entire course of radiation therapy (RT) for high-grade glioma (HGG) is currently derived from pre-RT magnetic resonance imaging (MRI). Although it is possible to adapt RT during the course of treatment, it is often guided only by anatomical changes to the tumor. This study seeks to determine if a biology-based mathematical model, parameterized by patient-specific, multiparametric MRI (mpMRI) data, can accurately forecast HGG response during RT.

Methods and materials: Twenty one patients with HGG planned for 6 weeks of concurrent RT and chemotherapy were imaged weekly with mpMRI during RT and at 1, 2, and 3 months post-RT. …

Representation Of Neuro-Oncology In American Neurology Departments: An Analysis Of Grand Rounds And Perspectives From Faculty And Residents, Elizabeth C Neil, Aubree Bruhnding, Zubair A Ahmed, Priya U Kumthekar, Nicholas A Blondin, Christian Grommes, Chirag B Patel, Sigmund Hsu, Feng Wang, Hongyu Miao, Noah L Rosen, Rashmi B Halker Singh, Mark J Burish, Zachary A Corbin

Faculty, Staff and Student Publications

Background: Neuro-oncology education in American neurology departments is highly variable, with no clear guidelines on appropriate practices. To better understand its current state, we focus on the perspective of departmental Grand Rounds (GR), views of adult neurology residency program directors (ANRPD), neuro-oncologists, and residents.

Methods: First, we obtained GR series from academic years 2017-2018 and 2018-2019 via an online search and direct emails to neurology residency programs. Second, two online surveys were dispensed to ANRPD and neuro-oncologists. Third, a cohort of neurology residents completed surveys with pre/post-didactic tests.

Results: Neuro-oncology consisted of 7% (28/ 411) GR in 2017-2018 and 6% …

Standardized Research Electronic Cigarette Acceptability Among Adult Men And Women Who Smoke Combustible Cigarettes, Jason D Robinson, Yong Cui, Maher Karam-Hage, Janice A Blalock, Sanjay Shete, George Kypriotakis, Peiying Yang, Paul M Cinciripini

Faculty, Staff and Student Publications

Objective: The U.S. electronic cigarette marketplace is diverse and has evolved rapidly. To provide a standardized research model, the U.S. National Institute on Drug Abuse developed the Standard Research E-Cigarette (SREC). This study characterized potential gender differences in product use, acceptability, reinforcement, and nicotine dependence symptoms when switching from combustible cigarettes (CCs) to nicotine and placebo SRECs.

Method: In total, 169 adults (82 women) who smoke were enrolled in this all-remote randomized double-blind crossover trial. During Weeks 1-2, participants used their usual brand cigarettes (UBCs). During Weeks 3-4 and 5-6, they were instructed to use the tobacco-flavored SREC (either nicotine …

Experimental Design And Control Methods For Dose Rate Optimization In A Synchrotron-Based Proton Therapy Beamline, Jason Tang, Daniel Liu, Jacob Mathew, Sabrina Campelo, Lawrence Bronk, Paige Taylor, Yuting Li, Fada Guan

Faculty, Staff and Student Publications

Background: Ultra-high dose rate radiotherapy (typically defined >40 Gy/s) has shown promise for enhanced normal tissue sparing while maintaining tumor control, termed the FLASH effect when this biological response is observed. However, precise dose rate control remains a technical challenge in proton therapy systems, particularly for research applications investigating dose rate effects.

Purpose: To develop and validate a passive beam modulation technique using tungsten scatterers for controllable dose rate adjustment in a synchrotron-based proton therapy beamline without modifying accelerator parameters.

Methods: We investigated dose rate modulation using tungsten foils of varying thicknesses (0.1-3.5 mm) positioned upstream in an 87.2 MeV …

Activity-Dependent Transit Dose Assessment In 192ir High-Dose-Rate Brachytherapy Surface Applicator Using Gafchromictm Ebt4 Film, Daniel Liu, Emily Draeger, Christopher J Tien, Fada Guan

Faculty, Staff and Student Publications

Purpose: To characterize the newly released GafChromicTM EBT4 film for transit dose measurement in high-dose rate brachytherapy (HDR-BT) surface applicators and to systematically investigate the relationship between transit dose and 192Ir source activity.

Methods: EBT4 film was used to measure dose at 3 mm depth from a horizontally oriented Leipzig-style surface applicator connected to a 192Ir HDR-BT remote afterloading unit. Transit dose was systematically characterized across eight different source activities ranging from 3.372 to 9.716 Ci (13,724 U to 39,544 U) using measurements with seven nominal dwell times (5-100 seconds, scaled to 10 Ci (40,700 U)). Transit dose was derived …

Utility Of Serum Matrix Metalloproteinase-7 As A Biomarker In Cholestatic Infants With Congenital Heart Disease, Sindhu Pandurangi, Michael E Kim, Nicolas Noriega, Bradley Conant, Jangdong Seo, Reena Mourya, Pranavkumar Shivakumar, Anna L Peters, Andrew Misfeldt, Meghan Chlebowski

Faculty, Staff and Student Publications

Background: Matrix metalloproteinase 7 (MMP-7) is a novel biomarker for diagnosis of biliary atresia (BA), the most common cholestatic liver disease in infancy. There is a pressing need to determine the utility of MMP-7 levels in infants with congenital heart disease (CHD) to avoid unnecessary invasive diagnostic procedures in this high-risk population. We investigated the utility of MMP-7 in discriminating BA from non-BA cholestasis in infants with CHD and whether MMP-7 elevation was present in infants requiring treatment for clinically significant PH.

Methods: This is a single-center cross-sectional study including infants < 180 days of age with cholestasis and serum MMP-7 levels collected from 2019 to 2023. Demographic data and descriptive statistics were summarized with medians with interquartile ranges and frequencies with percentages. Median MMP-7 levels were assessed via Wilcoxon rank-sum test.

Results: A total of 149 patients were included. Patients …

Pancreatic Cancer-Related Diabetes And Type 2 Diabetes Differ In Multiple Aspects Of Glucose Homeostasis, Frederico G S Toledo, Yisheng Li, Fuchenchu Wang, Melena D Bellin, Randall Brand, Kenneth Cusi, William Fisher, Yogish C Kudva, Walter G Park, Zeb I Saeed, Dhiraj Yadav, Robert V Considine, Sarah C Graham, Dana K Andersen, Jose Serrano, Mark O Goodarzi, Phil A Hart

Faculty, Staff and Student Publications

Aims/hypothesis: Pancreatic ductal adenocarcinoma-related diabetes mellitus (PDAC-DM) is a paraneoplastic syndrome with a poorly understood pathophysiology. PDAC-DM is often clinically confused with type 2 diabetes, resulting in delayed cancer detection and poorly individualised hyperglycaemia treatment. We investigated whether these forms of diabetes can be distinguished at the metabolic level.

Methods: Adults with either cancer treatment-naive PDAC-DM (n=28) or type 2 diabetes (n=97), and with diabetes onset within 3 years, underwent mixed-meal tolerance tests to investigate glucose metabolism. Outcomes included insulin sensitivity (Matsuda index), insulin secretion (insulinogenic index), beta cell function (oral disposition index), insulin clearance, and postprandial glucagon, glucagon-like peptide-1 …

Sars-Cov-2 Rna-Binding Protein Suppresses Extracellular Mirna Release, Hyejin Mun, Chang Hoon Shin, Qingxuan Fei, Andrea Estefania Lopez Giraldo, Kyoung-Min Choi, Ji Won Lee, Kyungmin Kim, Kyung-Won Min, Leilei Shi, Mark T Bedford, Dong-Chan Kim, Yoo Lim Chun, Seonghyun Ryu, Dongin Kim, Jeong Ho Chang, Ryan T Westrope, Michelle Shay, Edward Nguyen, Junho K Hur, Abigail Agyenda, Nam Chul Kim, Sung-Ung Kang, Woonghee Lee, Je-Hyun Yoon

Faculty, Staff and Student Publications

SARS-CoV-2 is the betacoronavirus causing the COVID-19 pandemic. Although the SARS-CoV-2 genome and transcriptome were reported previously, the function of individual viral proteins is largely unknown. Utilizing biochemical and molecular biology methods, we identified that four SARS-CoV-2 RNA-binding proteins (RBPs) regulate the host RNA metabolism by direct interaction with mature miRNA let-7b revealed by Nuclear Magnetic Resonance spectroscopy (NMR). SARS-CoV-2 RBP Nsp9 primarily binds mature miRNA let-7b, a direct ligand of the Toll-like Receptor 7 (TLR7), one of the potential SARS-CoV-2 therapeutics. Nsp9 suppresses host gene expression possibly by promoting let-7b-mediated silencing of a cellular RNA polymerase, POLR2D. In addition, …

Normalization Of Temperature Effects For Quality Assurance Of Quantitative Prostate Apparent Diffusion Coefficient Imaging Across Multiple Sites, Ken-Pin Hwang, Joshua Yung, R Jason Stafford, Caroline Chung, Aradhana M Venkatesan

Faculty, Staff and Student Publications

Background: Apparent Diffusion Coefficient (ADC) as measured by diffusion weighted imaging is known to negatively correlate with prostate tumor aggressiveness. Heterogeneity in system and protocol performance causes potential variability in ADC acquired across a large scanner network, prompting a need to evaluate quantitative ADC from a prostate-specific MR diffusion protocol as part of quality assurance (QA). Due to the temperature dependence of ADC, repeatability and reproducibility assessments typically require phantoms to maintain a temperature of 0°C, imposing a considerable burden when assessing large numbers of scanners.

Purpose: To develop a QA procedure at room temperature for assessing the reproducibility of …

Fusobacterium Sphaericum Sp Nov, Isolated From A Human Colon Tumor Adheres To Colonic Epithelial Cells And Induces Il-8 Secretion, Martha A Zepeda-Rivera, Yannick Eisele, Alexander Baryiames, Hanrui Wu, Claudia Mengoni, Gianmarco Piccinno, Elsa F Mcmahon, Kaitlyn D Lacourse, Dakota S Jones, Hans Hauner, Samuel S Minot, Nicola Segata, Floyd E Dewhirst, Christopher D Johnston, Susan Bullman

Faculty, Staff and Student Publications

Cancerous tissue is a largely unexplored microbial niche that provides a unique environment for the colonization and growth of specific bacterial communities, and with it, the opportunity to identify novel bacterial species. Here, we report distinct features of a novel Fusobacterium species, F. sphaericum sp. nov. (Fs), isolated from primary colon adenocarcinoma tissue. We acquire the complete closed genome and associated methylome of this organism and phylogenetically confirm its classification into the Fusobacterium genus, with F. perfoetens as its closest neighbor. Fs is phenotypically and genetically distinct, with morphological analysis revealing its coccoid shape, that while similar to …

A Human Factors Analysis And Classification System (Hfacs) Approach To Compare Cardiovascular, Orthopedics, Trauma Care, And Neurosurgery, Asfandyar Khan

Doctoral Dissertations and Master's Theses

Background: Despite significant progress in patient safety, human error continues to occur at high rates in procedural settings. Traditional safety models tend to focus on retrospective incident analysis, often overlooking the systemic conditions that allow errors to occur. The Human Factors Analysis and Classification System (HFACS) offers a proactive lens to understand how and where errors emerge and is useful for identifying active and latent failures.

Objective: To evaluate the utility and reliability of the Human Factors Analysis and Classification System (HFACS) in categorizing and comparing the pattern of frequencies (events) in cardiovascular, orthopedic, trauma care, and neurosurgical procedure.

Design, …

Benzodioxane-Benzamides Targeting Bacterial Cell Division Protein Ftsz Potentially Disrupt Slma-Mediated Nucleoid Occlusion And Reversible Biomolecular Condensation, Marta Sobrinos-Sanguino, Inés Barros-Medina, Lorenzo Suigo, Alessia Lanzini, Ermanno Valoti, William Margolin, Valentina Straniero, Begoña Monterroso, Silvia Zorrilla

Faculty, Staff and Student Publications

New strategies are urgently needed against antimicrobial resistance, a major health threat, and the different mechanisms regulating the bacterial cell division machinery offer multiple opportunities for developing novel therapeutics. FtsZ, an essential protein of this process, is targeted by multiple small molecules, and benzodioxane-benzamides (BDOBs) are among the most potent inhibitors in several bacterial species. BDOBs mechanisms are however poorly understood, particularly their impact on FtsZ's interplay with partners and ability to assemble phase-separated biomolecular condensates potentially involved in stress sensing. We show that certain BDOBs shielded FtsZ against depolymerization induced by the nucleoprotein complexes of SlmA, which inhibit Z-ring …

Impact Of Peripheral Circadian Misalignment And Alcohol On The Resiliency Of Intestinal Barrier And Microbiota, Laura Tran, Maliha Shaikh, Phillip A Engen, Ankur Naqib, Dulce M Frausto, Vivian Ramirez, Malia Gasteier, Zlata Bogin, Kristi Lawrence, Lijuan Zhang, Shiwen Song, Stefan J Green, Faraz Bishehsari, Christopher B Forsyth, Ali Keshavarzian, Garth R Swanson

Faculty, Staff and Student Publications

Circadian organization is involved in many gastrointestinal tract (GIT) functions such as the maintenance of intestinal barrier integrity. There is compelling evidence that perturbation of the circadian clock decreases intestinal epithelial cells' resiliency to alcohol-induced injury. One of the most common causes of circadian misalignment is wrong-time eating (largest meal at dinner) in modern societies. Yet, few studies have examined the importance of peripheral circadian rhythms of the GIT to alcohol consumption. Eating patterns during physiologic rest time, defined as wrong-time eating (WTE), misalign the peripheral circadian clock of the GIT and the body's central clock. This study aims to …

Molecular And Immunological Features Associated With Long-Term Benefits In Metastatic Nsclc Patients Undergoing Immune Checkpoint Blockade, Pedro Rocha, Rafael Bach, Laura Masfarré, Sharia Hernandez, Nil Navarro-Gorro, Adrià Rossell, Xavier Villanueva, Mario Giner, Ignacio Sanchéz, Miguel Galindo, Raúl Del Rey-Vergara, Albert Iñañez, Beatriz Sanchéz-Espiridion, Wei Lu, Ariadna Acedo-Terrades, Pau Berenguer-Molins, Albert Sánchez-Font, Roberto Chalela, Victor Curull, Álvaro Taus, Max Hardy-Werbin, Mark Sausen, Andrew Georgiadis, James White, Jennifer B Jackson, Laura Moliner, Sergi Clavé, Beatriz Bellosillo, Ana Rovira, Ignacio Wistuba, Luisa M Solis Soto, Júlia Perera-Bel, Edurne Arriola

Faculty, Staff and Student Publications

Introduction: Immunotherapy is firmly established as a treatment regimen in various solid tumors, driven by its exceptional benefits in a selected group of patients. Despite widespread adoption of immune checkpoint blockade (ICB) across diverse solid tumors, the quest for a clinically informative biomarker for long-term benefit remains unmet.

Methods: A total of 49 patients with metastatic NSCLC treated with ICB were included. Long-term (LTR) and short-term responders (STR) were defined as those with a response to ICB lasting more than 24 months or less than 6 months, respectively. Longitudinal blood specimens were collected before ICB treatment initiation and early-on treatment. …

Tubulin Regulates Stability And Localization Of Stmn2 By Binding Preferentially To Its Soluble Form, Xiang Deng, Gary A Bradshaw, Marian Kalocsay, Timothy Mitchison

Faculty, Staff and Student Publications

The small, tubulin-binding protein STMN2 is highly expressed in neurons and is implicated in amyotrophic lateral sclerosis. STMN2 degrades rapidly and accumulates at axotomy sites, suggesting fast turnover is crucial for its neuroprotective function. We show that STMN2 was primarily degraded by the ubiquitin-proteasome system. Its membrane-targeting N-terminal domain promoted fast turnover, whereas its tubulin-binding domain promoted stabilization. Proximity labeling and imaging showed that tubulin binding reduced STMN2 targeting to trans-Golgi network membranes. Pull-down assays showed that tubulin binds preferentially to soluble over membrane-bound STMN2. Our observations suggest that STMN2 interconverts between a soluble, tubulin-bound form and a membrane-bound, tubulin-free …

Smags-Lasso: A Novel Feature Selection Method For Sensitivity Maximization In Early Cancer Detection, Hamid Khoshfekr Rudsari, Sara Khorami-Sarvestani, Johannes F Fahrmann, James P Long, Samir Hanash, Kim-Anh Do, Ehsan Irajizad

Faculty, Staff and Student Publications

Background: Sensitivity and specificity are foundational metrics for cancer detection tools. However, most machine learning algorithms prioritize overall accuracy during optimization, which fails to align with clinical priorities of early detection. We aim to develop a feature selection machine learning algorithm while maximizing sensitivity at a given specificity.

Methods: We developed SMAGS-LASSO, a machine learning algorithm that combines our developed Sensitivity Maximization at a Given Specificity (SMAGS) framework with L1 regularization for feature selection. This approach simultaneously optimizes sensitivity at user-defined specificity thresholds while performing feature selection. SMAGS-LASSO utilizes a custom loss function with L1 regularization and multiple parallel optimization …