Biomedical Informatics Commons^™

Preliminary Examination Of Orexin Receptor Antagonism With Suvorexant In Individuals With Methamphetamine Use Disorder: A Case Series Study, Heather Webber, Jessica Badawi, Douglas Calvillo, Jin Yoon, Michael Weaver, Scott Lane, Joy Schmitz

Faculty, Staff and Student Publications

No abstract provided.

Evolving Molecular Subtypes Of Gastric Cancer: From Past Classifications To Present Consensus And Future Directions For Precision Therapy, Ju-Seog Lee

Faculty, Staff and Student Publications

Gastric cancer is a biologically heterogeneous disease. The advent of high-throughput multi-omic technologies has revolutionized our understanding of gastric cancer by deconstructing this heterogeneous entity into distinct and more homogeneous molecular subtypes. Early classifications based on gene expression, methylation, and histology have laid the groundwork for multi-omic frameworks proposed by The Cancer Genome Atlas and Asian Cancer Research Group, which established the foundation of modern molecular taxonomy. Subsequent integrative efforts, particularly the Consensus Genomic Subtypes (Super 6) model, have unified this collected information into clinically relevant subtypes that bridge prognostic stratification with treatment strategies. Established biomarkers such as human epidermal …

Bop2-Te: Bayesian Optimal Phase 2 Design For Jointly Monitoring Efficacy And Toxicity With Application To Dose Optimization, Kai Chen, Heng Zhou, J Jack Lee, Ying Yuan

Faculty, Staff and Student Publications

We propose a Bayesian optimal phase 2 design for jointly monitoring efficacy and toxicity, referred to as BOP2-TE, to improve the operating characteristics of the BOP2 design proposed by Zhou et al. (2017). BOP2-TE utilizes a Dirichlet-multinomial model to jointly model the distribution of toxicity and efficacy endpoints, making go/no-go decisions based on the posterior probability of toxicity and futility. In comparison to the original BOP2 and other existing designs, BOP2-TE offers the advantage of providing rigorous type I error control in cases where the treatment is toxic and futile, effective but toxic, or safe but futile, while optimizing …

A Combinatorial Approach To Synthetic Data Generation For Machine Learning, Krishna Khadka, Jaganmohan Chandrasekaran, Yu Lei, Raghu Kacker, D Richard Kuhn

Faculty, Staff and Student Publications

Datasets used in machine learning often contain sensitive information, including personally identifiable health and financial details. A common challenge faced by organizations and researchers is the risk of privacy breaches when using real-world data. Synthetic data can be used as an alternative to the real-world data. In existing synthetic data generation techniques, an encoder processes the real-world data to map it into a lower-dimensional latent space. Random sampling is then performed in this latent space. Subsequently, a decoder network is utilized to generate synthetic data from these sampled points in the latent space. Such approaches typically require generating a large …

Prickle4 Drives Microenvironmental Remodeling And Resistance To Parp Inhibition In Idh-Mutant Glioma, Ju Yang, Hua Yang, Yifan Yuan, Chenyang Zhang, Ziwei Fu, Yanyan Chen, Yinghong Xiong, Shuyu Chen, Kexin Ling, Ying Liu, Jason T Huse, Bo Chen, Timothy A Chan, Zengxin Qi, Zhao Zhang, Xiuping Liu, Yuxiang Wang

Faculty, Staff and Student Publications

Mutations in isocitrate dehydrogenase (IDH) genes sensitize gliomas to PARP inhibition (PARPi) by inducing epigenetic reprogramming of DNA damage repair circuits. However, tumors treated with PARPi eventually relapse despite initial responsiveness. In this study, it is demonstrated that the anti-angiogenic agent lenvatinib synergizes effectively with PARPi, resulting in substantial tumor regression and significantly extended survival. Genomic analysis of tumors reveals that PARPi induces widespread transcriptomic changes that are predominantly pro-inflammatory, thereby promoting tumor angiogenesis. Prickle4, a planar cell polarity protein, is identified as a critical mediator of PARPi-induced neovascularization. Targeting Prickle4 effectively overcomes PARPi resistance in these tumors. Collectively, these …

A Gut-Activated Nhr-86-Cyp Pathway Mediates The Neuroprotective Effects Of Enterococcus Faecium Probiotics In A Nematode Model Of Amyotrophic Lateral Sclerosis, Yu Sang, Jie Ren, Alejandro Aballay

Faculty, Staff and Student Publications

Neurodegenerative diseases are often associated with oxidative stress, and while probiotics may influence neuronal health, the underlying mechanisms remain poorly understood. Using the sod-1 A4VM amyotrophic lateral sclerosis (ALS) model in Caenorhabditis elegans, we investigated the protective effects of the probiotic Enterococcus faecium against oxidative stress-induced neurodegeneration. Animals fed E. faecium showed reduced motor neuron degeneration under oxidative stress compared to those maintained on a standard Escherichia coli diet. Transcriptome analysis revealed a significant enrichment of oxidoreductase genes, including cytochrome P450 (cyp) genes. RNAi-mediated knockdown of cyp genes impaired E. faecium-mediated neuroprotection, and this loss correlated with increased reactive oxygen …

Guadecitabine Improved Relapse-Free Survival In High-Risk Acute Myeloid Leukemia And Myelodysplastic Syndrome Patients After Transplant: Phase Ii Results From A Single Center, Betül Oran, Peter Thall, Amin Alousi, Gheath Al-Atrash, Rohtesh Mehta, David Marin, Partow Kebriaei, Uday Popat, Roland Bassett, Qaiser Bashir, Jin Im, Amanda Olson, Jessica Jewell, Portia Smallbone, Elizabeth Shpall, Richard Champlin

Faculty, Staff and Student Publications

This phase II, single-center clinical trial evaluated the efficacy and safety of guadecitabine, with or without donor lymphocyte infusion, following allogeneic stem cell transplantation in adult patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The study had three treatment cohorts based on post-transplant disease status. Cohort 1 included patients with hematologic relapse after transplant (N=13). Cohort 2 consisted of patients with minimal residual disease (MRD) detected after transplant (N=18). Cohort 3 compromised patients in remission without MRD within 100 days after transplant (N=24). The primary objectives were achievement of morphological complete remission in cohort 1 and MRD eradication …

Endogenous Processes Underlying Clock-Like Mutational Signatures, Teresa Druck, Rami I Aqeilan, C Marcelo Aldaz, Nicola Zanesi, Kay Huebner

Faculty, Staff and Student Publications

Wellcome Trust scientists have shown that “mutational signatures” in specific nucleotide contexts accumulate in genomes of mammalian tissues, providing clues to underlying causes of specific signatures. Analysis of cancer genomes has identified more than 50 single‐base substitution (SBS) signatures, with SBS1, SBS5, and SBS40 linked to aging and present in normal tissues. SBS1 results from cytosine demethylation, whereas SBS5 and SBS40 arise from unknown endogenous mechanisms. We hypothesized that loss of fragile‐site genes drives these two signatures. FHIT, located at FRA3B, is frequently deleted in cancers, and Fhit‐deficient mouse tissues exhibit a mutation profile resembling human SBS5. Data mining of …

Preclinical Ischemic Stroke Multicenter Trials (Prism) Collective Statement: Opportunities, Challenges, And Recommendations For A New Era, Cenk Ayata, Philip M Bath, Anna M Planas, Stuart M Allan, Johannes Boltze, Ryan P Cabeen, Claire L Gibson, Marilyn J Cipolla, Marcio A Diniz, Stefano Fumagalli, Fahmeed Hyder, Raymond C Koehler, Arthur Liesz, Sarah K Mccann, Tim Magnus, Louise D Mccullough, Emily S Sena, Simone Beretta, Jaroslaw Aronowski, Francesca Bosetti, Clinton B Wright, Patrick D Lyden, Lauren H Sansing

Faculty, Staff and Student Publications

Preclinical stroke research faces a critical translational gap, with animal studies failing to reliably predict clinical efficacy. To address this, the field is moving toward rigorous, multicenter preclinical randomized controlled trials (mpRCTs) that mimic phase 3 clinical trials in several key components. This collective statement, derived from experts involved in mpRCTs, outlines considerations for designing and executing such trials. mpRCTs offer advantages such as increased sample sizes, robust statistical design, incorporation of heterogeneity, and standardized protocols, but they face challenges in finding the right balance between standardization and heterogeneity, appropriate stroke model selection, and outcome measures, as well as the …

Intratumoral Bacteria Are Immunosuppressive And Promote Immunotherapy Resistance In Head And Neck Squamous Cell Carcinoma, Natalie L Silver, Jin Dai, Travis D Kerr, Jessica Altemus, Rekha Garg, Hannah Simmons, Tyler Alban, Laura Noel-Romas, Vladimir Makarov, David J H Shih, Shwetha V Kumar, Akeem Santos, Rehan Akbani, Adam Burgener, Mohammed Dwidar, Neil Gross, Andrew G Sikora, Elias J Sayour, Apollo Stacy, Christian Jobin, Timothy A Chan, Renata Ferrarotto, Daniel J Mcgrail

Faculty, Staff and Student Publications

Despite the promise of immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma (HNSCC), mediators of response are poorly understood. To address this, here we analyzed oropharyngeal HNSCCs treated with neoadjuvant durvalumab (anti-PDL1) alone or in combination with tremelimumab (anti-CTLA4) from the CIAO clinical trial ( NCT03144778 ). We found that only the total abundance of intratumoral bacteria predicted ICB response, which was validated in multiple independent cohorts. High intratumoral bacteria abundance was associated with an immunosuppressive tumor microenvironment, characterized by an accumulation of neutrophils coupled with depletion of T cells and other adaptive immune cells. Experimental elevation …

Developing Provider Digital Twins For Personalized Provider-Patient Communication Via A Rag-Based Conversational Framework, Pengze Li, Yutong Hu, Jianfu Li, Garit Gemeinhardt, Fang Li, Muhammad Amith, Licong Cui, Antonio J Forte, Cui Tao

Faculty, Staff and Student Publications

Digital twins have emerged as a paradigm in precision and personalized medicine, enabling data-driven modeling of individuals to support tailored interventions. While most existing work focuses on patient-oriented twins, little attention has been given to modeling the provider’s role, particularly in clinical communication. In this study, we present GRACE (Generalized RAG-Enhanced Conversation Framework), a framework for constructing a provider digital twin (ProDT) that emulates key aspects of clinicians’ communicative and cognitive behavior. GRACE integrates three modules: a physician-informed dialog script generation and optimization module for provider-patterned conversation, a Retrieval-Augmented Generation (RAG) pipeline for factual grounding and timely knowledge updating, and …

Genomic Determinants Of Response And Resistance To Pirtobrutinib In Relapsed/Refractory Chronic Lymphocytic Leukemia, Jennifer R Brown, Bastien Nguyen, Sai Prasad Desikan, Helen Won, Shady I Tantawy, Samuel C Mcneely, Narasimha Marella, Hetal S Randeria, Lauren M Hanson, Andrew Parker, Salomé Calado Botelho, Jennifer A Woyach, Krish Patel, Constantine S Tam, Toby A Eyre, Chan Y Cheah, Nirav N Shah, Paolo Ghia, Wojciech Jurczak, Minna Balbas, Binoj Nair, Paolo Abada, Chunxiao Wang, Denise Wang, Lindsey E Roeker, Varsha Gandhi, William G Wierda

Faculty, Staff and Student Publications

Pirtobrutinib, a noncovalent, reversible Bruton tyrosine kinase inhibitor (BTKi), demonstrated efficacy in patients with chronic lymphocytic leukemia (CLL), resistant to covalent BTKi (cBTKi). We analyzed genomic correlations with response and resistance to pirtobrutinib in relapsed/refractory (R/R) patients with CLL pretreated with cBTKi enrolled in the phase 1/2 BRUIN trial. DNA sequencing was performed on peripheral blood mononuclear cells at baseline, on treatment, and at progressive disease (PD). Common alterations at baseline included mutations in BTK (43%), TP53 (38%), SF3B1 (25%), NOTCH1 (23%), ATM (19%), XPO1 (11%), PLCG2 (9%), BCL2 (8%), and 17p deletion (28%). Common baseline BTK mutations included C481S …

Integrative Multi-Omics Profiling Identifies Infiltrative Hepatocellular Carcinoma As An Immunotherapy-Resistant Subtype With Distinct Molecular Features, Won Suk Lee, Seonjeong Woo, Sung Hwan Lee, Gae Hoon Jo, Ilhwan Kim, Hyeyeong Kim, Chansik An, Sanghoon Jung, Gwangil Kim, Haeyoun Kang, Beodeul Kang, Jung Sun Kim, Ho Yeong Lim, Incheon Kang, Hannah Yang, So Jung Kong, Dahyeon Son, Dong Jun Shin, Woo Young Kwon, Da-Yeon Lee, Ju-Seog Lee, Junho Park, Youngsoo Kim, Sohyun Hwang, Chan Kim, Hong Jae Chon

Faculty, Staff and Student Publications

Background/aims: Hepatocellular carcinoma (HCC) exhibits substantial morphological and biological heterogeneity. Clinical and molecular relevance of the infiltrative subtype remains poorly defined in the context of cancer immunotherapy. We aimed to evaluate the prognostic impact and molecular features of infiltrative HCC in patients treated with first-line atezolizumab plus bevacizumab (Ate/Bev).

Methods: We included 307 patients with advanced HCC treated with Ate/Bev and classified them into four gross morphological types based on imaging. Multi-omics profiling was conducted on tumor samples. Type IV infiltrative signature was derived and externally validated using five independent HCC cohorts, including IMbrave150.

Results: Infiltrative morphology, encompassing pure and …

Engineering Mutation Clones In Mammalian Cells With Crispr/Cas9, Zijun Huo, Jian Tu, Rachel Shoemaker, Dung-Fang Lee, Ruiying Zhao

Faculty, Staff and Student Publications

CRISPR, Clustered Regularly Interspaced Short Palindromic Repeat, as a powerful genome engineering system, has been widely accepted and employed in gene editing of a vast range of cell types. Compared to zinc finger nucleases (ZFNs) or transcription activator-like effector nucleases (TALENs), CRISPR shows a less complicated process and higher efficiency. With the development of different CRISPR systems, it can be used not only to knock out a gene but also to make precise modifications, activate or repress target genes with epigenetic modifications, and even for genome wide screening. Here we will describe the procedure of generating a stable cell line …

Poly(A) Probe Hcr Rna-Fish Specifically Marks Pyriform Nurse Cells In The Brown Anole Lizard Ovary, Zoe B Griffin, Bonnie K Kircher, Richard R Behringer

Faculty, Staff and Student Publications

Hybridization chain reaction RNA-fluorescent in situ hybridization (HCR RNA-FISH) is a powerful and increasingly used method for visualizing gene expression in cells and tissues. A probe set against polyadenylated RNA (poly(A)) is often used as a positive control for RNA integrity and staining quality. While optimizing this technique in the ovary of the brown anole lizard (Anolis sagrei), we found that the poly(A) probe produced a strikingly specific and intense signal in pyriform cells, a specialized lizard-specific nurse cell type. This staining pattern was found in both whole-mount samples and paraffin sections, suggesting that poly(A) signal intensity can serve as …

Uncertainty-Guided Test-Time Optimization For Personalizing Segmentation Models In Longitudinal Medical Imaging, Jaehee Chun, Austin Castelo, Mckell Woodland, Caleb O'Connor, Mais Al Taie, Mohamed Eltaher, Aashish Gupta, Bilel Daoud, Shanli Ding, Jeddy Bennett, Anirban Maitra, Matthew A Firpo, Kimberly Kirkwood, Eugene J Koay, Kristy K Brock

Faculty, Staff and Student Publications

Background: Accurate and consistent image segmentation across longitudinal scans is essential in many clinical applications, including surveillance, treatment monitoring, and adaptive interventions. While personalized model adaptation using patient-specific prior scans has shown promise, current approaches typically rely on fixed training durations and lack mechanisms to determine optimal stopping points on a per-patient basis, particularly in the absence of validation labels.

Purpose: We propose an uncertainty-guided test-time optimization (TTO) framework that dynamically adjusts the personalization duration for each patient using a validation-free stopping criterion based on predictive uncertainty.

Methods: Our framework personalizes a generalized segmentation model using patient-specific prior imaging and …

Contralateral Breast Cancer After Radiotherapy And Hormone Therapy In Two Cohorts Of Us Breast Cancer Survivors, Lene H S Veiga, Gretchen L Gierach, Susan A Smith, Rebecca M Howell, Matthew M Mille, Monjoy Saha, Rochelle E Curtis, Cody Ramin, Clara Bodelon, Heather Spencer Feigelson, Erin J Aiello Bowles, Diana S M Buist, Sheila Weinmann, Jacqueline B Vo, Choonsik Lee, Amy Berrington De Gonzalez

Faculty, Staff and Student Publications

Background: Radiotherapy increases contralateral breast cancer risk, while hormone therapy reduces it; their combined effects are unclear.

Methods: Data from two US retrospective cohort studies of 5-year breast cancer survivors (stage I-III, ages 20-84), Kaiser Permanente (KP, 1990-2012) and SEER (1990-2013), were analysed. Contralateral breast radiation doses were estimated for the KP cohort. Multivariable Poisson regression estimated relative risks (RRs) and excess relative risks per Gray (ERR/Gy), stratified by hormone therapy use.

Results: KP cohort (n = 9053) included 353 contralateral breast cancer cases (73% ER+); SEER cohort (n = 244,834) included 10,470 cases (72% ER+). Among women with ER+ …

Host Modulation Therapy In Periodontitis: From Established Therapies To Emerging Technologies, Aonjittra Phanrungsuwan, Jiaqi Huang, Neeraja Dharmaraj, Alejandra Cobos Perez, Omid Veiseh, Simon Young, Chun-Teh Lee

Faculty, Staff and Student Publications

Periodontitis is a biofilm-induced chronic inflammatory disease, characterized by gingival inflammation and alveolar bone loss. According to a national survey, approximately half of the U.S. adults are affected by periodontal disease. To effectively prevent and treat periodontitis, it is essential to address its underlying causes. The primary etiological factors include polymicrobial synergy and dysbiosis of the oral microbiota, and a dysregulated immune response. The standard therapeutic approach, mechanical removal of biofilm through debridement, sometimes demonstrates limited efficacy, particularly in cases of severe periodontitis, which may require adjunctive or additional therapy. Emerging evidence indicates that periodontal tissue destruction is initiated by …

Nemolizumab As An Alternative Therapeutic Option For Indolent Systemic Mastocytosis, Sezim Minbaeva, Stephen K Tyring

Faculty, Staff and Student Publications

Indolent systemic mastocytosis (ISM) is a clonal mast cell disorder characterized by recurrent symptoms that can persist despite treatment with antihistamines, leukotriene antagonists, and mast cell stabilizers. Treatment options are limited when symptoms remain refractory, and avapritinib is contraindicated or declined. We describe the case of a 62-year-old female with an 11-year history of ISM who developed worsening pruritus and urticaria despite extensive conservative and biologic therapies, including topical corticosteroids, hydroxyzine, montelukast, omalizumab, and dupilumab. Given her history of stroke, she declined avapritinib. Nemolizumab was initiated with a 60 mg loading dose followed by 30 mg every four weeks. After …

Alternative Polyadenylation Signatures Distinguish Maladaptive Right Ventricular Remodeling In Pulmonary Hypertension: Implications For Rna-Based Diagnostics And Therapeutics, Janani Subramaniam, Venkata Jonnakuti, Scott D Collum, Sandra Martineau, Kai-Lieh Huang, Sandra Breuils-Bonnet, Andrea L Frump, Bindu H Akkanti, Jayeshkumar A Patel, Manish K Patel, Ismael Salas De Armas, Isabella N Lefebvre, Rajko Radovancevic, Elvin Blanco, Eric J Wagner, Igor Gregoric, Sriram Nathan, Biswajit Kar, Steeve Provencher, Sebastien Bonnet, François Potus, Hari Krishna Yalamanchili, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Increased pulmonary vascular pressures due to vascular remodeling, elevated vascular resistance, and vasoconstriction characterize Pulmonary Arterial Hypertension (PAH). The narrowing of the pulmonary arteries and obstruction of blood flow increase the Right Ventricular (RV) afterload, forcing the RV to undergo structural and functional changes. While adaptive remodeling leads to RV compensation by maintaining function, maladaptive remodeling leads to RV decompensation, characterized by worsening function and eventual failure. At present, there is no effective treatment for these patients as therapies for left ventricular failure are ineffectual, and there are no therapies specifically targeting the RV. Therefore, there is a clear need …

Test-Retest Apparent Diffusion Coefficient Reproducibility In Head And Neck Cancer Using A 15-T Mr-Linac, Brigid A Mcdonald, Dina El-Habashy, Renjie He, Sam Mulder, Sarah Mirbahaeddin, Abdallah S R Mohamed, Sara Ahmed, Yao Ding, Jihong Wang, Stephen Y Lai, Alex Dresner, John Christodouleas, Clifton D Fuller

Faculty, Staff and Student Publications

Purpose

To evaluate the reproducibility of apparent diffusion coefficient (ADC) measurements in head and neck squamous cell carcinoma (HNSCC) using a 1.5-T MR-linac (MRI-guided linear accelerator) system.

Materials and Methods

In this retrospective study, conducted between February 2021 and January 2024, patients with HNSCC lesions underwent echo-planar imaging diffusion-weighted MRI on a 1.5-T MR-linac system at two time points before the start of radiation therapy. Mean and median ADC values and volumes were measured for each lesion. Absolute and percent reproducibility coefficients (RCs) were calculated. Linear regression analyses and F tests were performed to determine whether the lesion volume or …

Netrin-1 Promotes Pancreatic Tumorigenesis And Innervation Through Neo1, Hiroki Kobayashi, Yosuke Ochiai, Junya Arai, Masahiro Hata, Feijing Wu, Masaki Sunagawa, Tadashi Iida, Taisuke Baba, Ermanno Malagola, Takayuki Tanaka, Zhengyu Jiang, Ruth A White, Xiaofei Zhi, Jin Qian, Quin T Waterbury, Ruhong Tu, Biyun Zheng, Yi Zeng, Hualong Zheng, Puran Zhang, Shuang Li, Leah B Zamechek, Jonathan S Labella, Takahiro Sugie, Atsushi Enomoto, Holger K Eltzschig, Carmine F Palermo, Iok In Christine Chio, Kenneth P Olive, Timothy C Wang

Faculty, Staff and Student Publications

Nerves can regulate tumorigenesis and cancer progression. However, clarification of the role of axon guidance molecules in tumorigenesis, innervation, and metastasis is required to better understand the tumor-promoting functions of nerves. Using murine KrasG12D-mutant pancreatic organoids, we screened axon guidance molecules and identified netrin-1 upregulation. Netrin-1 was also upregulated in vivo during pancreatic tumorigenesis in humans and mice. Mutant KRAS and β-adrenergic signaling upregulated netrin-1 and its receptor NEO1 in epithelial cells in part through the MAPK pathway. Ex vivo culture of celiac ganglia showed that netrin-1 promoted the axonogenesis of sympathetic neurons through nerve NEO1. In the Pdx1-Cre;LSL-KrasG12D/+ model, …

Speeding Up Interval Estimation For R2-Based Mediation Effect Of High-Dimensional Mediators Via Cross-Fitting, Zhichao Xu, Chunlin Li, Sunyi Chi, Tianzhong Yang, Peng Wei

Faculty, Staff and Student Publications

Mediation analysis is a useful tool in investigating how molecular phenotypes such as gene expression mediate the effect of exposure on health outcomes. However, commonly used mean-based total mediation effect measures may suffer from cancellation of component-wise mediation effects in opposite directions in the presence of high-dimensional omics mediators. To overcome this limitation, we recently proposed a variance-based R-squared total mediation effect measure that relies on the computationally intensive nonparametric bootstrap for confidence interval estimation. In the work described herein, we formulated a more efficient two-stage, cross-fitted estimation procedure for the R2 measure. To avoid potential bias, we performed …

Dcpr: A Deep Learning Framework For Circadian Phase Reconstruction, Xiao Han, Xiaochen Cen, Zhijin Li, Xiaobo Zhou, Zhiwei Ji

Faculty, Staff and Student Publications

Background: The circadian clock is an evolutionarily conserved system that orchestrates 24-h physiological rhythms through transcriptional and translational feedback loops. Mounting evidence suggests a bidirectional relationship between circadian rhythm alteration and disease progression, positioning the circadian clock as a potential therapeutic target. Due to the scarcity of high-resolution temporal omics data, it remains very challenging to elucidate the underlying regulatory mechanisms of the circadian system. As a practical alternative, public untimed transcriptomic datasets offer the potential to infer gene expression oscillations retrospectively. However, existing computational approaches for circadian phase estimation often suffer from limited predictive accuracy, reducing their ability to …

Effects Of Auricular Point Acupressure On Inflammatory Signaling In Chronic Low Back Pain: A Secondary Analysis Of A Randomized Controlled Trial, Nada Lukkahatai, Hongyu Wang, Xinran Huang, Wanqi Chen, Hulin Wu, Jennifer Kawi, Zhiyin Yu, Constance M Johnson, Paul Christo

Faculty, Staff and Student Publications

Objective: Auricular point acupressure (APA) has shown promise for pain relief, but its biological mechanisms remain unclear. This study examined the effects of APA on inflammatory cytokines and explored the relationships between changes in inflammatory markers and clinical outcomes in older adults with chronic low back pain (cLBP).

Method: This secondary analysis utilized plasma samples from a three-arm randomized controlled trial (RCT) (NCT03589703) with 272 participants aged 65 years and older with cLBP. The participants were randomly assigned (1:1:1) to the targeted APA (T-APA), nontargeted APA (NT-APA), or education control (CG) groups for four weeks. Cytokine levels were …

Black Bone Mri Morphometry For Mandibular Cortical Bone Measurement In Head And Neck Cancer Patients: Prospective Method Comparison With Ct, Lisanne V Van Dijk, Juan Ventura, Kareem A Wahid, Lin L Zhu, Brigid A Mcdonald, Sara Ahmed, Keith L Sanders, Sonja M Stieb, Lance Mccoy, Christina S Sharafi, Kathryn E Preston, Natalie A West, Sarah Mirbahaeddin, Dina M El-Habashy, Travis Salzillo, Samuel Mulder, Joly Fahim, Aubryane Dearmas, Mona Arbab, Yao Ding, Jihong Wang, Bastien Rigaud, Anando Sen, Mark Chambers, Katherine A Hutcheson, Kristy K Brock, Abdallah S R Mohamed, Stephen Y Lai, Clifton D Fuller

Faculty, Staff and Student Publications

Objectives: Determine the utility of low-flip angle "black bone" magnetic resonance imaging (MRI) for cortical mandibular bone assessment compared to computed tomography (CT).

Methods: Quantification of cortical mandibular bone width was performed per Hamada et al. at 15 cross-sectional interdentium locations on pretreatment black bone MRI and CT for 15 oropharyngeal cancer patients, with interobserver analyses on a subset of three patients by 11 observers. CT and MRI measurements were compared using Bland-Altman analysis, Lin's concordance, and Deming regression; interobserver variability was assessed with absolute variance and intraclass correlation coefficient (ICC).

Results: Bland Altman and Deming regression analyses showed CT …

Sex Differences In Bile Acid Homeostasis And Excretion Underlie The Disparity In Liver Cancer Incidence Between Males And Females, Megan E Patton, Sherwin Kelekar, Lauren J Taylor, Angela E Dean, Qianying Zuo, Rhishikesh N Thakare, Sung Hwan Lee, Emily C Gentry, Morgan Panitchpakdi, Pieter Dorrestein, Yazen Alnouti, Zeynep Madak-Erdogan, Ju-Seog Lee, Milton J Finegold, Sayeepriyadarshini Anakk

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC), the common liver cancer, exhibits higher incidence in males. Here, we report that mice lacking bile acid (BA) regulators, Farnesoid X Receptor (FXR also termed NR1H4) and Small Heterodimer Partner (SHP also termed NR0B2), recapitulate the sex difference in liver cancer risk. Since few therapeutic options are available, we focused on understanding the intrinsic protection afforded to female livers. Transcriptomic analysis in control and NR1H4 and NR0B2 double knockout livers identified female-specific changes in metabolism, including amino acids, lipids, and steroids. To assess translational relevance, we examined if transcriptomic signatures obtained from this murine HCC model correlate …

Batf2 Is A Glutamine-Responsive Tumour Suppressor Required For Type-I Interferon-Dependent Anti-Tumour Immunity, Wang Gong, Hülya F Taner, Yuesong Wu, Yumin He, Xingwu Zhou, Zaiye Li, Xin Hu, Charisse Ursin, Kala Chand Debnath, Kohei Okuyama, Qiang Hu, Christopher R Donnelly, Felipe Nör, Chamila D Perera, Emily Bellile, Arash Yunesi, Zhiqian Zhai, Mei Zhao, Wanqing Cheng, Zackary R Fitzsimonds, Luke Broses, Jiaqian Li, Shadmehr Demehri, Deepak Nagrath, Gregory T Wolf, Andrew G Sikora, Yanbao Yu, Haitao Wen, Lei Wei, Steven B Chinn, Jeffrey N Myers, Shizuo Akira, Yuying Xie, James J Moon, Yu Leo Lei

Faculty, Staff and Student Publications

Recent evidence highlights the significance of a new type of tumour suppressors, which are not frequently mutated but inhibited by metabolic cues in cancers. Here, we identify BATF2 as a tumour suppressor whose expression is epigenetically silenced by glutamine in Head and Neck Squamous Cell Carcinomas (HNSCC). BATF2 correlates with type-I interferon and Th1 signatures in human HNSCC, with correlation coefficients even stronger than those of the positive control, STING. The phosphorylation of BATF2 at serine 227 promotes the oligomerization of STING. BATF2 deficiency or high glutamine levels result in higher oxygen consumption rates and metabolic profiles unfavorable for …

Context Matching Is Not Reasoning When Performing Generalized Clinical Evaluation Of Generative Language Models, Andrew Wen, Qiuhao Lu, Yu-Neng Chuang, Guanchu Wang, Jiayi Yuan, Jiamu Zhang, Liwei Wang, Sunyang Fu, Kurt D Miller, Heling Jia, Steven D Bedrick, William R Hersh, Kirk E Roberts, Xia Hu, Hongfang Liu

Faculty, Staff and Student Publications

Current discussion surrounding the clinical capabilities of generative language models(GLMs) predominantly centers around multiple-choice question-answer(MCQA) benchmarks derived from clinical licensing examinations. While accepted for human examinees, characteristics unique to GLMs bring into question the validity of such benchmarks. Here, we validate five benchmarks using eight GLMs, ablating for parameter size and reasoning capabilities, validating via prompt permutation three key assumptions that underpin the generalizability of MCQA-based assessments: that knowledge is applied, not memorized, that semantic consistency will lead to consistent answers, and that situations with no answers can be recognized. While large models are more resilient to our perturbations compared …

Context Matching Is Not Reasoning When Performing Generalized Clinical Evaluation Of Generative Language Models, Andrew Wen, Qiuhao Lu, Yu-Neng Chuang, Guanchu Wang, Jiayi Yuan, Jiamu Zhang, Liwei Wang, Sunyang Fu, Kurt D Miller, Heling Jia, Steven D Bedrick, William R Hersh, Kirk E Roberts, Xia Hu, Hongfang Liu

Faculty, Staff and Student Publications

Current discussion surrounding the clinical capabilities of generative language models(GLMs) predominantly centers around multiple-choice question-answer(MCQA) benchmarks derived from clinical licensing examinations. While accepted for human examinees, characteristics unique to GLMs bring into question the validity of such benchmarks. Here, we validate five benchmarks using eight GLMs, ablating for parameter size and reasoning capabilities, validating via prompt permutation three key assumptions that underpin the generalizability of MCQA-based assessments: that knowledge is applied, not memorized, that semantic consistency will lead to consistent answers, and that situations with no answers can be recognized. While large models are more resilient to our perturbations compared …