Medicine and Health Sciences Commons^™

Trends And Challenges: A 15-Year Review Of Imaging And Radiation Oncology Core Anthropomorphic Phantom Audits For Proton Therapy, Lian Duan, Hunter S Mehrens, Stephen F Kry, Jessica R L Lowenstein, Nadia Hernandez, Lucas B Acuna Scafati, Paige A Taylor

Faculty, Staff and Student Publications

Purpose: This study aims to analyze the trends in institutional performance on Imaging and Radiation Oncology Core (IROC) proton phantoms and to investigate the impact of treatment parameters on proton therapy delivery accuracy.

Materials and methods: We analyzed 402 IROC anthropomorphic phantom audits performed by 57 institutions worldwide between 2009 and 2024, including brain, head and neck (H&N), spine, prostate, lung, and liver phantoms. Dosimetric assessments included thermoluminescent dosimeters (TLDs) for dose comparison and gamma analysis of radiochromic film. The lung and liver phantoms were irradiated with simulated motion. Univariate analysis was performed to evaluate the relationships between treatment parameters …

Selective Deletion Of Fgfr1 In Agrp Neurons Impairs Energy Homeostasis Under High-Fat Diet In Mice, Daniel Shookster, Shea O'Connell, Patel Darshan, Taylor Landry, Wyatt Bunner, Zhiying Jiang, Qingchun Tong, Hu Huang

Faculty, Staff and Student Publications

Background: The global obesity crisis and the limited success of current treatments underscore the need to identify novel regulatory pathways. While central administration of α-Klotho exerts anti-obesity effects in rodents through AgRP neurons, the intracellular signaling mechanisms that mediate this process remain undefined.

Methods: To define the role of FGFR1 within the α-Klotho signaling pathway in AgRP neurons, we performed a targeted deletion of the receptor in adult mice using an AAV-mediated CRISPR/Cas9 system alongside transgenic models.

Results: Deletion of FGFR1 in AgRP neurons disrupted energy homeostasis, promoting weight gain induced by a high-fat diet. Electrophysiological recordings revealed that FGFR1 …

Quantifying Rate-Limiting Genetic Variation In Breast And Ovarian Tumourigenesis, Kathleen E Houlahan, Mahad Bihie, Yves Greatti, Julián Grandvallet Contreras, Daniel J Fulop, Gonzalo Lopez, Marc Williams, Hsin-Hsiung Huang, Peter Van Loo, Paul C Boutros, Kuan-Lin Huang

Faculty, Staff and Student Publications

Background: The number and type of genetic alterations required to initiate breast and ovarian cancer remain unclear. While germline BRCA1/2 carriers show markedly elevated cancer risk, it is uncertain whether point mutations or copy number alterations constitute the rate-limiting events of tumourigenesis.

Methods: We developed a statistical framework extending prior incidence-mutation models to estimate the minimal number and type of driver events required for cancer initiation. Somatic mutation and copy-number data from >3000 breast and ovarian cancers in TCGA and METABRIC were compared between germline BRCA1/2 carriers and non-carriers matched on subtypes. Results were validated through analyses of evolutionary timing …

Cd44v9 As A Therapeutic Target For Antibody-Drug Conjugate In Advanced Breast Cancer, Dileep R Reddy, Mckenna E Flynn, Yasuaki Anami, Zhaoxuan Yang, Jayden Aleman, Minji Seo, Kyoji Tsuchikama, Jennifer A Maynard, Naoto T Ueno, Jangsoon Lee

Faculty, Staff and Student Publications

Antibody-drug conjugates (ADCs) have revolutionized breast cancer therapy. HER2 is the only validated biomarker guiding ADC therapy in breast cancer. However, their clinical benefit remains confined to HER2- and TROP2-targeted therapies. Tumor heterogeneity and acquired resistance often limit durable responses, underscoring the need for novel, tumor-specific ADC targets. CD44 variant isoform 9 (CD44v9), a splice variant of the CD44 family, is largely absent in normal tissues but enriched in aggressive breast cancers, where it contributes to stemness, redox regulation, and therapy resistance. In this study, we developed a chimeric monoclonal antibody against CD44v9 (clone SUM24.1, IgG1) and conjugated it to …

Large Language Models For Bioinformatics, Wei Ruan, Yanjun Lyu, Jing Zhang, Jiazhang Cai, Peng Shu, Yang Ge, Yao Lu, Shang Gao, Yue Wang, Peilong Wang, Lin Zhao, Tao Wang, Yufang Liu, Luyang Fang, Ziyu Liu, Zhengliang Liu, Yiwei Li, Zihao Wu, Junhao Chen, Hanqi Jiang, Yi Pan, Zhenyuan Yang, Jingyuan Chen, Shizhe Liang, Wei Zhang, Terry Ma, Yuan Dou, Jianli Zhang, Xinyu Gong, Qi Gan, Yusong Zou, Zebang Chen, Yuanxin Qian, Shuo Yu, Jin Lu, Kenan Song, Xianqiao Wang, Andrea Sikora, Gang Li, Xiang Li, Quanzheng Li, Yingfeng Wang, Lu Zhang, Yohannes Abate, Lifang He, Wenxuan Zhong, Rongjie Liu, Chao Huang, Wei Liu, Ye Shen, Ping Ma, Hongtu Zhu, Yajun Yan, Dajiang Zhu, Tianming Liu

Faculty, Staff and Student Publications

With the rapid advancements in large language model technology and the emergence of bioinformatics-specific language models (BioLMs), there is a growing need for a comprehensive analysis of the current landscape, computational characteristics, and diverse applications. This survey aims to address this need by providing a thorough review of BioLMs, focusing on their evolution, classification, and distinguishing features, alongside a detailed examination of training methodologies, datasets, and evaluation frameworks. We explore the wide-ranging applications of BioLMs in critical areas such as disease diagnosis, drug discovery, and vaccine development, highlighting their impact and transformative potential in bioinformatics. We identify key challenges and …

Tuscan: Tumor Segmentation And Classification Analysis In Spatial Transcriptomics, Chenxuan Zang, Charles C Guo, Yaohong Wang, Peng Wei, Ziyi Li

Faculty, Staff and Student Publications

The identification of tumor cells is pivotal for understanding tumor heterogeneity and the tumor microenvironment. Recent advances in spatially resolved transcriptomics (SRT) have revolutionized the way that transcriptomic profiles are characterized and have enabled the simultaneous quantification of transcript locations in intact tissue samples. SRT is a promising alternative method to study gene expression patterns in spatial domains. Nevertheless, the precise detection of tumor regions within intact tissue remains a great challenge. A common strategy for identifying tumor cells is via tumor-specific marker gene expression signatures, which are highly dependent on marker accuracy. Another effective approach is through aneuploid copy …

Severe Renal Phenotype Across A Multigenerational Tuberous Sclerosis Complex (Tsc) Family, Elena Tuller, Joshua A Samuels, Hope Northrup, Kate Richardson

Faculty, Staff and Student Publications

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by the formation of hamartomas in the brain, kidney, and heart, along with other complex clinical manifestations, including TSC-associated neuropsychiatric disorder (TAND). Development of genotype-phenotype correlations within TSC can aid clinicians in providing prognostic data and improve clinical management. We present here a multigenerational family who has a pathogenic variant in TSC2 displaying a severe renal phenotype.

Methods: A 23-year-old Caucasian male (Patient 1) was determined to have a molecularly confirmed diagnosis of TSC at approximately 2 months of age. The nonsense pathogenic variant (c.1372C>T (p.Arg458*)) in …

Development And Initial Testing Of An Online Security Prime Writing Intervention During Covid-19, Angie S Leroy, Andreas Weyland, Jade Kanemitsu, Arya Tsay-Jones, Vincent D Lai, E Lydia Wu-Chung, Nyla Vela, Amanda Perozo, Valentina I Maza, Sierra Wickline, Katherine Beach, Robert Suchting

Faculty, Staff and Student Publications

Background and objectives: During the COVID-19 pandemic, we tested the efficacy of a one-week online security prime (SP) writing intervention in reducing distress among 254 adults (60+ years and/or having an underlying health condition). The efficacy of writing interventions can depend on several factors. Attachment orientations, characterized by dimensions of anxiety and avoidance, reflect individuals' tendencies in how they seek proximity to and rely on others for support, and influence how people experience and regulate their emotions.

Design and methods: Participants were randomly assigned to one of three conditions: Security Priming (SP), where people wrote about what made them feel …

Defining A Quantitative Threshold For Adaptive Re-Planning Using A Percentile-Based Scoring System, Alexandra O Leone, Christine B Peterson, Anna Lee, Adam S Garden, G Brandon Gunn, Lauren L Mayo, Amy C Moreno, Steven J Frank, C David Fuller, Jay P Reddy, Karen Hoffman, Ivan Vazquez, Ming Yang, Joshua S Niedzielski, Laurence E Court, Thomas J Whitaker

Faculty, Staff and Student Publications

Background: Despite the frequent need for adaptive planning in head and neck proton therapy, no quantitative indicators have been identified to determine when a plan should be adapted. Here, we aimed to determine a quantitative threshold for the change in plan quality between the primary treatment plan and verification plans that correlates with the physician's decision to adapt.

Methods: Primary treatment and verification plans were extracted from the clinical treatment planning system for 167 patients who underwent intensity-modulated proton therapy for base of tongue, tonsillar, or oropharyngeal cancers, with and without nodal involvement, between 2016 and 2021. All plans were …

Optimizing Feasibility And Acceptability Of An Online Expressive Writing Intervention For Survivors Of Adolescent And Young Adult Cancer: A Pilot Randomized Trial Of Iterative Modifications And Outcomes, Eunju Choi, Yusi Aveva Xu, Celia Cy Wong-Meli, Michael E Roth, Yisheng Li, Qian Lu

Faculty, Staff and Student Publications

Objective: To evaluate the feasibility of an online expressive writing (EW) intervention for survivors of adolescent and young adult (AYA) cancer and determine whether iterative, theory-driven modifications can enhance response, adherence, and completion rates.

Methods: In this randomized pilot trial, survivors of AYA cancer were recruited through a hospital-based AYA oncology clinic and an online community. Forty participants were randomly assigned to the EW intervention or control group. To improve on lower-than-expected adherence and completion rates in a previous cohort, the protocol was iteratively revised using the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS). Modifications included …

Intraoperative Ultrasound Imaging Features Guiding Surgical Strategy In Spinal Cord Ependymoma Resection, Esteban Ramirez-Ferrer, Ian E Mccutcheon, Gil Kimchi, Behrang Amini, Romulo Andrade Almeida, Francisco Call-Orellana, Juan Pablo Zuluaga-Garcia, Robert Y North, Christopher A Alvarez-Breckenridge, Jeffrey S Weinberg, Laurence D Rhines, Claudio E Tatsui

Faculty, Staff and Student Publications

Background and objectives: Preoperative imaging provides surgeons with an initial estimate of tumor infiltration and the likelihood of achieving an en-bloc resection in spinal cord ependymomas, yet the definitive decision is made intraoperatively. This study characterizes the intraoperative ultrasound (iUS) features that guide real-time surgical strategy and are associated with successful en-bloc removal.

Methods: A retrospective review of iUS images obtained during resection of spinal cord ependymomas was performed. The presence of a peritumoral halo representing the transition zone between the tumor and the spinal cord, the dorsal sagittal area of the spinal cord overlying the tumoral poles, the presence …

Fgl2-Knockout Tumor Cells Serve As A Vaccine Inducing Long-Duration Brain-Resident Memory T Cells That Reject Subsequent Intracranial Tumor Cell Challenges, Sheng Zhang, Yining Jin, Zhiliang Jia, Xueqing Xia, Yang Li, Qi Wang, Jing Wang, Jian Wang, Joya Chandra, Gregory K Friedman, Shulin Li

Faculty, Staff and Student Publications

The failure to prevent brain tumors, including both recurrent primary and metastatic brain tumors, is the primary cause of patients' mortality. We developed a novel whole tumor-cell vaccine to rapidly induce long-duration brain-resident memory T (TRM) cells that prevent brain tumor progression. Ten Fgl2-KO primary and metastatic tumor cell lines, generated via CRISPR/Cas9, were used to vaccinate mice and for intracranial challenges with the WT tumor cells. Not only did vaccinated mice reject these tumor cell challenges, but also more than half of these mice became long-duration survivors. Transplanting brain immune cells from vaccinated mice into naïve mice enabled this …

Mri Analysis Of The Wrist: Does The Presence Of Palmaris Longus Affect Median Nerve Position?, Victor B Chavez, Dean W Smith

Faculty, Staff and Student Publications

Background: Understanding the median nerve's position relative to surrounding anatomy is essential; however, there are many variations among individuals. This study assesses differences in median nerve position with or without palmaris longus (PL). We hypothesize that PL presence alters median nerve position, resulting in a greater distance to the skin volar surface, a decreased distance to the radius volar surface, and an increased distance to the flexor carpi radialis (FCR).

Methods: 1193 wrist magnetic resonance imaging (MRI) studies were retrospectively reviewed from 2019 to 2023. One hundred adults ages 18 to 50 meeting criteria were included for a power > 80%: …

Generalizability Analyses With A Partially Nested Trial Design: The Necrotizing Enterocolitis Surgery Trial, Sarah E Robertson, Matthew A Rysavy, Martin L Blakely, Jon A Steingrimsson, Issa J Dahabreh

Faculty, Staff and Student Publications

We discuss generalizability analyses under a partially nested trial design, where part of the trial is nested within a cohort of trial-eligible individuals, while the rest of the trial is not nested. This design arises, for example, when only some centers participating in a trial are able to collect data on non-randomized individuals, or when data on non-randomized individuals cannot be collected for the full duration of the trial. Our work is motivated by the Necrotizing Enterocolitis Surgery Trial (NEST), which compared initial laparotomy versus peritoneal drain for infants with necrotizing enterocolitis or spontaneous intestinal perforation. During the first phase …

Potential Missed Opportunities To Administer Intravenous Thrombolysis To Patients With Acute Ischemic Stroke, Babak B Navi, Mengxi Wang, Jose-Miguel Yamal, Suja S Rajan, Alexandra L Czap, Stephanie A Parker, May Nour, Ilana Spokoyny, Saad Mir, Mathew E Fink, Joshua Z Willey, William J Jones, James C Grotta

Faculty, Staff and Student Publications

Background: Recent years have seen improvements in stroke-care pathways, including mobile stroke units (MSUs), and this may have affected the rate, predictors, and outcomes of patients with acute ischemic stroke who qualify for but do not receive treatment with intravenous thrombolysis (IVT).

Methods: This was a secondary observational cohort analysis of the prospective, multicenter BEST-MSU trial (Benefits of Stroke Treatment Delivered by a Mobile Stroke Unit Compared With Standard Management by Emergency Medical Services), conducted in 7 US cities from 2014 to 2020, comparing MSU management versus standard emergency department management for patients with suspected acute ischemic stroke. The analytical …

A Comprehensive Biomechanical Material Characterization Of The Human Breast Fibro-Structural Support System, Aroj Bhattarai, Gregory P Reece, Kristy K Brock, Krishnaswamy Ravi-Chandar

Faculty, Staff and Student Publications

Breast surgery for aesthetic purposes, such as breast augmentation or breast reduction, and breast reconstruction after cancer treatment require an accurate structural (anatomical) and mechanical (functional) understanding of the breast components, including the fascial-ligamentous support system of the breast, to achieve optimal results. This paper aims to provide a comprehensive description of the mechanical behavior of the ligamentous and fascial connective tissues of the human female breast. Fasciae and ligaments obtained from 17 patients between 35 and 85 years of age who were undergoing mastectomy and three female cadavers were tested. Uniaxial tensile tests were conducted, and three constitutive models …

An Adp Getaway Service, Not An Atp Tank: Insights Into The Phosphagen System In Neurons, Madeline P Marques, Kartik Venkatachalam

Faculty, Staff and Student Publications

No abstract provided.

Segmental Tracheal Resection For Thyroid Cancer: Perioperative Morbidity, Locoregional Control, And Survival, Anastasios Maniakas, David C Wilde, Isabelle Fournier, Emily K Hyde, Li Xu, Jennifer R Wang, Neil D Gross, Erich M Sturgis, Victoria Banuchi, Naifa L Busaidy, Maria E Cabanillas, Priyanka Iyer, Ramona Dadu, Steven G Waguespack, Mimi I Hu, G Brandon Gunn, Michael Kwon, Salmaan Ahmed, Michelle D Williams, Mark E Zafereo

Faculty, Staff and Student Publications

Background: Segmental tracheal resection is rarely needed for advanced thyroid cancer but is among the most complex, high-risk thyroid surgeries.

Methods: Retrospective study of patients undergoing segmental tracheal resection for thyroid cancer at MD Anderson Cancer Center (2005-2024).

Results: We identified 120 patients with a median follow-up of 4.6 years (range 0.02-16.38). Papillary thyroid cancer was most common (68%). The median number of tracheal rings resected was 4 (range 1-9). Seventeen (14%) patients had a new tracheostomy placed at the time of surgery, with 11 (9%) remaining trach-dependent at last follow-up. Twenty-six (22%) patients had a return to the operating …

Establishing Proof-Of-Concept For The Feasibility And Implementation Of A Point-Of-Sale Firearm Safety Counseling Program: A Qualitative Case Study, Amanda Koong, Mike Henson-Garcia, Lauren Malthaner, Katelyn Jetelina, Belinda Hernandez, Sandra Mckay

Faculty, Staff and Student Publications

Safe firearm storage is critical for injury prevention, yet there is limited evidence surrounding effective interventions to promote storage behaviors among owners. One potential avenue for intervention is at the point-of-sale, a concept well-proven in the nutrition promotion and tobacco cessation space. This study explored firearm retailer attitudes toward a firearm storage intervention delivered at the point of sale. Seventeen in-depth interviews were conducted with firearm retailers from a suburban gun shop in Fort Bend, USA. This semi-structured interview assessed firearm retailer perceptions of the proposed point-of-sale intervention. Interviews were transcribed and independently coded to identify themes that emerged from …

Terraforming The Kras Lipid Landscape, Yong Zhou, John F Hancock

Faculty, Staff and Student Publications

No abstract provided.

Rab4 Spatially And Functionally Converges With Rab7 In The Degradative Endolysosomal Network, Stephen M Farmer, Shiyu Xu, Yue Yu, Xin Ye, Haoyi Yang, Jing Cai, Beatriz Rios, Wen-Wen Lin, Daniela Covarrubias, Vicky Chuong, Lili Ye, German Zylberberg, Charissa Wang, Erin Furr-Stimming, Qingchun Tong, Oguz Kanca, Hugo J Bellen, Travis I Moore, Sheng Zhang

Faculty, Staff and Students Publications

Rab GTPases are key regulators of endosomal trafficking in eukaryotes. In mammalian cells, Rab4 and Rab7 were shown to localize to distinct compartments, with Rab4 on early endosomes for fast recycling and Rab7 on late endosomes for degradation. Here, we show that in Drosophila, endogenous Rab4 and Rab7 extensively colocalize across tissues and developmental stages. Recruited to the same compartments through mechanisms that do not require the activity of the other, they have opposing effects on endolysosomal size: Rab4 overexpression or Rab7 impairment leads to enlarged endolysosomes, whereas Rab4 loss or constitutively active Rab7 reduces their sizes. Rab4 deficiency suppresses …

Predictive Validity Of The Obsessive-Compulsive Inventory-4 And Florida Obsessive-Compulsive Inventory-Ii Severity Scale, Eric A Storch, Ryan J Mccarty, Maya Zehavi, Mahnoor Ahmad, Vanessa Zavala Cruz, Dayan Berrones, Josselyn S Muñoz, Diana Obando, Servando Rodriguez Barajas, Renee M Frederick, Jacey L Anderberg, Hannah C Moore, Marcos E Ochoa-Panaifo, Mayra C Martinez Mallen, Ogechi C Onyeka, Andrew D Wiese, Melisa N Sagarnaga, Joseph F Mcguire, Ygor Arzeno Ferrão, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Wayne K Goodman, James J Crowley, Brazilian Obsessive-Compulsive Spectrum Disorder Working Group (Gttoc)

Faculty, Staff and Students Publications

Efficient and accurate screening tools are crucial for improving early identification and treatment outcomes among individuals with obsessive-compulsive disorder (OCD). This study evaluated the sensitivity and specificity of two OCD screening measures: the Obsessive-Compulsive Inventory-4 (OCI-4) and the Florida Obsessive-Compulsive Inventory-II (FOCI-II) severity scale. The measures were administered in a large transnational sample of Spanish speaking Latin American adults (N = 1696) with elevated obsessive-compulsive symptomatology. Participants completed diagnostic interviews (MINI and Y-BOCS) and self-report assessments across 23 sites in 11 countries. Both measures significantly distinguished OCD from non-OCD cases, with the FOCI-II demonstrating somewhat better predictive performance (AUC = …

Segmental And Multifocal Isolated Dystonias: Similarities And Differences, Hyder A Jinnah, Vittorio Velucci, Daniele Belvisi, Gamze Kilic-Berkmen, Joel S Perlmutter, Laura J Wright, Christine Klein, Jeanne S Feuerstein, Steven Bellows, Joseph Jankovic, Cynthia Comella, Richard L Barbano, Aparna Wagle Shukla, Stephen G Reich, Mark S Ledoux, Alberto J Espay, Kevin R Duque, Florence C F Chang, Victor S C Fung, Sarah Pirio-Richardson, Carmen Terranova, Emile S Moukheiber, Sarah Idrissi, Barbara Vitucci, Susan H Fox, Samuel Frank, Natividad Stover, Brian D Berman, Rachel Saunders-Pullman, William G Ondo, Christopher L Groth, Marcello Esposito, Laura Avanzino, Francesco Bono, Roberto Erro, Marcello Mario Mascia, Antonella Muroni, Alfredo Berardelli, Giovanni Defazio

Faculty, Staff and Students Publications

Background: Whether the traditional distinction between segmental and multifocal dystonia is clinically or scientifically useful remains unclear.

Objective: To evaluate whether idiopathic isolated adult-onset segmental and multifocal dystonia can be differentiated based on clinical features other than the contiguity of affected body regions.

Methods: We compared data on segmental and multifocal dystonia from two large dystonia databases established in the USA and Italy that used similar criteria for patient recruitment and assessment.

Results: Compared to segmental dystonia, multifocal dystonia was characterized by a higher proportion of men, a younger age at dystonia onset, a greater frequency of upper limb dystonia, …

How Does Frailty Impact Peri-Operative And Speech Recognition Outcomes For Cochlear Implants In Veterans?, Kaitlyn A Brooks, Benjamin D Lovin, Alex D Sweeney, Angela S Peng, Nathan R Lindquist

Faculty, Staff and Students Publications

Objective: To investigate the association of frailty with post-cochlear implant (CI) admission, morbidity, and CI-aided word recognition outcomes in veterans.

Study design: Retrospective cohort.

Setting: Single-institution tertiary care Veterans Health Administration (VHA) hospital.

Methods: Veterans who underwent cochlear implantation between 1998 to 2024 were included. The Modified 5-Item Frailty Index (mFI-5) score was used to characterize preoperative frailty. Outcomes of interest were admission from post-anesthesia care unit (PACU), relative risk (RR) of admission among frail patients, and relationship between frailty and post-CI word recognition score (WRS). Ordinal data were analyzed via logistic regression and Chi square tests; a multivariate linear …

Communicating Across Languages: Experiences Of Spanish-Speaking People With Dementia And Care Partners In The Emergency Department, Anita N Chary, Victor Lara, Sumin Yoon, Annika R Bhananker, Edgar Ordoñez, Michelle I Suh, Manish N Shah

Faculty, Staff and Students Publications

No abstract provided.

Validation And Longitudinal Trajectory Analysis Of An Ai-Based Ecg Model For Aortic Stenosis: From Community Screening To Pre-Ta\Vr Risk Stratification, Matthew W Segar, Kaleb D Lambeth, Alexander Postalian, Stephanie Coulter, Jasen Gilge, Naveed Razvi, Mohammad Saeed, Robert D Paisley, Ambarish Pandey, Mehdi Razavi

Faculty, Staff and Students Publications

Aims: Early aortic stenosis (AS) detection remains challenging, with many patients presenting late when left ventricular dysfunction may be irreversible. We evaluated whether longitudinal AI-enhanced ECG patterns can predict outcomes years before intervention and assessed the community screening potential of the AK-AVS model.

Methods and results: We conducted two complementary analyses: (1) community validation of the AK-AVS model in 3632 cardiovascular disease-free ARIC participants, and (2) longitudinal trajectory analysis of 7860 ECGs from 2040 TAVR recipients collected up to 10 years pre-procedure. Unsupervised clustering identified distinct AK-AVS trajectories, with mortality associations assessed using Cox regression and net reclassification improvement. In …

Application Of A Natural Language Processing Algorithm To Early Asthma Ascertainment For Adults In The Era Of Electronic Health Records, Chung-Il Wi, Thanai Pongdee, Hee Yun Seol, Sunghwan Sohn, Elham Sagheb, Bhavani Singh Agnikula Kshatriya, Shauna M Overgaard, Deepak K Sharma, Sungrim Moon, Elizabeth A Krusemark, Dave Watson, Sergio E Chiarella, Miguel A Park, Jason D Greenwood, Randy M Foss, Zhandong Liu, Meera Gupta, Carla M Davis, Wade Schulz, Hongfang Liu, Young J Juhn

Faculty, Staff and Students Publications

Background: The natural language processing (NLP) algorithm for predetermined asthma criteria (NLP-PAC) was successfully developed and validated for automatically ascertaining pediatric asthma from electronic health record (EHRs) systems. A scalable, efficient, and automated tool for ascertaining adult asthma status from EHRs remains nonexistent.

Objective: We validated NLP-PAC enabling ascertainment and early identification of adult asthma status in their EHRs.

Methods: We applied the validated NLP-PAC to EHRs of a convenient sample (adult cohorts who participated in our previous population-based studies) in which a reference standard (ie, asthma status defined by manual chart review) is available. The performance of NLP-PAC was …

Nasopharyngeal Microbiome-Epigenome-Wide Association Analysis In Infants With Severe Bronchiolitis, Ryohei Shibata, Yijun Li, Anat Yaskolka Meir, Sara Javornik Cregeen, Matthew Clayton Ross, Janice A Espinola, Ashley F Sullivan, Liming Liang, Kohei Hasegawa, Carlos A Camargo, Zhaozhong Zhu

Faculty, Staff and Students Publications

Background: Bronchiolitis exposes infants to both acute burdens (e.g., hospitalization in cases of severe bronchiolitis) and increased risks for chronic respiratory sequelae (e.g., asthma). In severe bronchiolitis, recent evidence suggests distinct pathobiological roles of microbiota (e.g., viruses, bacteria) and host responses influenced by genetic and epigenetic factors. However, the relationship of airway microbiota with host DNA methylation (DNAm) in infants with severe bronchiolitis remains unknown.

Methods: In a multi-center prospective cohort of 504 multi-ethnic infants with severe bronchiolitis (age < 1 year), using nasopharyngeal microbiome (exposure) and blood DNAm (outcome, Infinium MethylationEPIC BeadChip, Illumina) data within 24 h of the hospitalization, we conducted microbiome-epigenome-wide association studies (mbEWAS). We examined microbiota-associated differentially methylated CpGs (mbDMCs, false discovery rate [FDR] < 0.05), regions (mbDMRs, FDR < 0.05), and DNAm age acceleration. We also determined the associations of DNAm age acceleration with asthma development by age 6 years. Furthermore, we focused on asthma-related pathogenic bacteria-Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae-for functional analyses by examining serum mbDMR-related proteins (Proseek Multiplex, Olink) and their enriched pathways (FDR < 0.10).

Results: Across 23 common taxa-observed at least in 25% of the infants, we identified 1 mbDMC (S. pneumoniae, cg16594639, chr20: 39528675) …

Histone Demethylase Jmjd1a Protects Mice From Enteric Bacterial Infection By Upregulating Ccl8 Expression To Recruit Macrophages And Cd4+ T Cells, Guifang Lin, Lichun Yang, Shuyan Jiang, Yong Zhang, Ping Luo, Weihua Li, Jianming Xu, Gongpeng Xiong, Chundong Yu, Wenbo Chen

Faculty, Staff and Students Publications

Jumonji domain-containing 1A (JMJD1A, also known as KDM3A) is a histone demethylase that specifically demethylates H3K9me1/2 to enhance gene expression. The roles of JMJD1A in many physiological and pathological processes have been revealed. However, it is unclear whether JMJD1A is involved in host defense against enteric pathogen infection. In this study, we found that enteric infection with C. rodentium induced JMJD1A expression in colonic epithelial cells at the transcriptional level partly mediated by IRF1. After C. rodentium infection, JMJD1A-/- mice exhibited increased mortality, colonic injury, and C. rodentium load and systemic spread, suggesting that JMJD1A protects host against C. rodentium …

Online Tutorial On Survival Analysis For Biomarker Discovery, Jaka Kokošar, Ela Praznik, Martin Špendl, Nancy P Moreno, Alana Newell, Gad Shaulsky, Blaž Zupan

Faculty, Staff and Students Publications

In biomedicine, survival analysis addresses time-to-event data to study outcomes like patient survival and treatment response, and supports biomarker discovery. Yet, teaching this analysis is often hindered by mathematical and programming barriers. We present a structured, hands-on tutorial that goes beyond a typical online guide-offering integrated video lectures, literature, quizzes, and practical exercises. Built around Orange Data Mining, an open and free no-code visual analytics platform, the tutorial covers key concepts such as censoring, Kaplan-Meier curves, group comparisons, and biomarker discovery through real-world datasets. Organized in four pedagogical units, it progresses from basic survival data analysis to gene and gene-set …