Digital Commons Network^™

Ultra-Processed Foods And The Cardiovascular-Kidney-Metabolic Continuum: Integrating Epidemiological, Multi-Omics, And Translational Evidence, Saiful Singar, Amirhossein Ataei Kachouei, Leandro Lantigua-Somoano, David Manley, Anthony Cardinale, Muhammad Zulfiqah Sadikan, Saurabh Kadyan, Donya Shahamati, Lorena Dias, Amber Wood, Cinthia Chavarria, Sara K. Rosenkranz, Neda S. Akhavan

Department of Medicine Faculty Publications

Cardiovascular-kidney-metabolic (CKM) syndrome integrates excess adiposity, metabolic dysfunction, kidney impairment, subclinical cardiovascular diseases, and clinical events along a staged continuum that invites unified prevention and treatment. Ultra-processed foods (UPFs) are a complex, high-prevalence exposure that may influence risk across CKM stages through nutrient profiles, additives, processing-induced compounds, and packaging-related contaminants. This review synthesizes epidemiologic, mechanistic, and translational evidence with attention to exposure definition and analytic rigor. We summarize NOVA-based UPF operationalization across dietary assessment tools, highlighting misclassification of mixed dishes, brand heterogeneity, and energy under-reporting, and we propose further examination of energy-adjusted models, calibration, and harmonized metrics. Observational studies consistently …

Comparison Of Fully Covered Self-Expandable Metal Biliary Stents With Or Without Anchoring Double-Pigtail Plastic Stents: A Systematic Review And Meta-Analysis, Samuel Tanner, Fadi Hawa, Alejandra Vargas, Priyata Dutta, Antonio Facciorusso, Jean M. Chalhoub, Jorge D. Machicado

Department of Medicine Faculty Publications

Background and AIMS

Fully covered self-expandable metal stents (FcSEMSs) have become the mainstay of treatment for a variety of biliary pathologies. However, FcSEMSs have been associated with a greater rate of stent migration than other types of stents. A technique of anchoring double-pigtail plastic stents (DPPSs) has been proposed to minimize migration of biliary FcSEMSs. Herein, we evaluated the efficacy of anchoring DPPSs among patients treated with biliary FcSEMSs.

Methods

We performed a systematic review using PubMed, EMBASE, and Web of Science from database inception through August 2023. Full-text articles comparing FcSEMSs with or without anchoring DPPSs were included. We …

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+ …

Paneugenesis: A Regenerative Systems Hypothesis For Advancing Health Promotion, Craig M. Becker, Leslie Hoglund, Beth Chaney, Joseph G. L. Lee, Michael Stellefson, Alex Davis

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Despite major advances in health promotion science, dominant approaches remain largely prevention-and risk-reduction-oriented. The prevailing orientation creates a substantial opportunity to advance generative, system-design strategies that intentionally produce well-being rather than merely prevent disease. This article proposes paneugenesis as a regenerative systems framework and a testable theoretical model for the intentional creation of net-positive outcomes, thereby extending health promotion beyond its traditional pathogenic emphasis. Paneugenesis integrates systems science, salutogenesis, behavioral science, complexity theory, and quality management principles into a unified four-function process: operationalizing idealized outcomes, identifying key precursors, optimizing processes, and continually plotting progress through feedback mechanisms. The central hypothesis …

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 …

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 …

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 …

Multiparametric Flow Cytometry Immune Profiling Of Pulmonary And Extra-Pulmonary Tuberculosis Reveals Distinct Blood-Based Biomarker Signatures, Kalaiarasan Ellappan, Prakash Babu Narasimhan, Harriet N. Garlant, Seshadri Vasan, Komal Jain, Saka Vinod Kumar, Vishnukanth Govindaraj, Vir Singh Negi, Karen E. Kempsell

Research outputs 2022 to 2026

This study investigated immune cell distributions, cell-specific immune markers, and selected biomarker targets in pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) using multiparametric flow cytometry (MFC). Whole blood was collected from 45 individuals, including healthy controls (HC), EPTB, and PTB patients (n = 15/group). Peripheral blood leukocytes were analysed by MFC to characterize CD4+ and CD8+ T cells, natural killer (NK), invariant NKT (iNKT) and NKT cells, classical (CM), intermediate (IM) and non-classical monocytes (NCM), and activated monocytes (AM). Expression of GBP1, CALCOCO2, IFIT3, SNX10, ARG1, PD-1, and PD-L1 was assessed across these immune subsets. Increased frequencies of NK, NKT, …

Meta-Analysis Of Dna Methylation Aging Signatures In 17 Human Tissues, Macsue Jacques, Kirsten Seale, Sarah Voisin, Anna Lysenko, Robin Grolaux, Bernadette Jones-Freeman, Severine Lamon, Mandhri Abeysooriya, Itamar Levinger, Carlie Bauer, Adam P. Sharples, Aino Heikkinen, Elina Sillanpaa, Miina Ollikainen, Cassandra Smith, James R. Broatch, Navabeh Zarekookandeh, Linn Gillberg, Ida Blom, Jesse R. Poganik, Mahdi Moqri, Vadim N. Gladyshev, Matthew Taper, Cassandra Malecki, Sean Lal, Nathalie Saurat, Steve Horvath, Andrew Teschendorff, Nir Eynon

Research outputs 2022 to 2026

Epigenetic changes, in particular DNA methylation, accumulate with age across different tissues, but whether these changes follow consistent patterns across different organs remains poorly understood. Here we show, through a meta-analysis of more than 15,000 human methylation profiles spanning 17 tissues, that aging produces both conserved and tissue-specific epigenetic signatures. We identify systemic shifts in methylation levels, increases in methylation variability, and growing molecular disorder across tissues. Network analysis revealed tightly connected gene clusters that are not modified by beneficial interventions, alongside a more modifiable cluster linked to NAD⁺ metabolism, supporting NAD⁺ as a potential therapeutic target in …

Gut Microbial Composition And Short-Chain Fatty Acid Metabolism In Cognitively Unimpaired Adults Stratified By Amyloid-Β Status, D. M.Sithara Dissanayaka, Thilini N. Jayasinghe, Hamid R. Sohrabi, Stephanie R. Rainey-Smith, Kevin Taddei, Colin L. Masters, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Short-chain fatty acids (SCFAs) produced by gut microbial fermentation influence host metabolism and neuroinflammatory processes implicated in Alzheimer’s disease (AD). However, the relationship between fecal SCFAs, microbial taxa, and cerebral amyloid-β (Aβ) burden in cognitively unimpaired individuals remains unclear. Fecal SCFAs were quantified using GC-MS, and microbial species were profiled by shotgun metagenomics in 87 participants. Associations between SCFAs, demographics, APOE ε4 status, and Aβ burden were tested using nonparametric statistics and multivariable regression. Microbial–SCFA links were evaluated using Spearman correlations and multivariate ordinations, with mediation analysis exploring potential indirect pathways. Acetate was the predominant SCFA and demonstrated the most …

Application Of The Lancet Commission Criteria For The Diagnosis Of Obesity To A Clinical Trials Population: The Leap Trial, Faith Anne N Heeren, Kathleen R Ruddiman, Courtney Simmons, Brian N White, Byron C Jaeger, Nicholas M Pajewski, Stephanie A Hooker, Deborah B Horn, Katy Martin-Fernandez, Kimberly A Gudzune, Caroline Blackwell Young, Jamy Ard, Kristina Henderson Lewis

Faculty, Staff and Student Publications

Objective: This study aimed to apply The Lancet Diabetes & Endocrinology criteria for diagnosing obesity among clinical trial participants and understand participants' characteristics by obesity status.

Methods: The criteria were operationalized and applied to baseline data from the Long-term Effectiveness of the Anti-obesity medication Phentermine (LEAP) trial (NCT05176626). Excess adiposity, organ and tissue dysfunction, and limitations to daily activities were assessed. We examined differences between participants with "no obesity," "pre-clinical obesity," and "clinical obesity."

Results: Among the 860 participants, 0.8% had no obesity (mean BMI 29.0 kg/m2 [SD 0.6]), 18.7% had pre-clinical obesity (mean BMI 35.2 kg/m2 [SD …

Baseline Characteristics Of Men Undergoing Drug-Coated Balloon Dilation, Urethrotomy, Or Urethroplasty For Urethral Stricture, Melvin Zarghooni, Hoi Doan, Adithya Chandrasekaran, Travis Green, Rodrigo Donalisio Da Silva, Annie Chen

Faculty, Staff and Student Publications

Drug-coated balloon (DCB) dilation, direct vision internal urethrotomy (DVIU), and urethroplasty are used to treat urethral stricture in men. Understanding how patients differ across these procedures, and between those who are and are not retreated, is needed to interpret retreatment outcomes. We described baseline characteristics of men undergoing each procedure, overall and by 12-month retreatment status.

Using Epic Cosmos, a national database of 310 million patients, we identified men with urethral stricture who underwent an index DCB, DVIU, or urethroplasty in 2024-2025, grouped by procedure and 12-month retreatment. We described age, comorbidities, smoking, anticoagulant use, lichen sclerosus, residence, and preoperative …

Physical Activity, Telomere Length, And Cardiometabolic Syndrome In Older Women: The Cardiovascular Health Study, Jeni Page, Melissa Richard, Elizabeth Lyons, Elizabeth Baumler, M Terese Verklan, Michelle C Odden, Elizabeth Lorenzo

Faculty, Staff and Student Publications

Background: Cardiometabolic syndrome (CMS) affects approximately 39% of US women and increases risk for cardiovascular disease, diabetes, and stroke. Telomere length, a biomarker of cellular aging, is associated with CMS and may be influenced by physical activity (PA), potentially mitigating telomere shortening. Black women have higher CMS prevalence compared to white women and may exhibit distinct telomere length dynamics influenced by interactions between CMS and PA.

Methods: Data were drawn from the Cardiovascular Health Study and included black and white women who provided data on PA, CMS risk factors, and telomere length (N = 417). Linear regression models examined the …

When Does Alzheimer's Disease Start? Plasma Aβ42/40 Assays Show Steep Changes At Aβ-Pet Centiloid 15, Mean Age Of 66 Years, Rodrigo Cánovas, Timothy Cox, Vincent Doré, Pierrick Bourgeat, Jurgen Fripp, Azadeh Feizpour, Rosita Shishegar, Christopher J. Fowler, Simon M. Laws, Tenielle Porter, Stephanie Rainey-Smith, Leslie M. Shaw, Randall J. Bateman, Yan Li, Ovod Vitaliy, Michael W. Weiner, John C. Morris, Tammie L.S. Benzinger, Suzanne E. Schindler, Akinori Nakamura, Takeshi Iwatsubo, Takeshi Ikeuchi, Takashi Kato, Paul Maruff, Hamid R. Sohrabi, Christopher C. Rowe, Ralph Martins, Colin L. Masters, James Doecke

Research outputs 2022 to 2026

Objective: Sporadic late-onset Alzheimer's disease (AD) is characterized by a long pre-clinical phase where amyloid-beta (Aβ) and tau begin to accumulate in the brain. The primary objective was to determine the age at which AD starts by finding the average population age when both positron emission tomography (PET) Aβ (Aβ-PET) and plasma Aβ42/40 become abnormal. Methods: Two high performance immunoprecipitation-mass spectrometry (IP-MS) assays (WashU/C2N and Shimadzu) were tested on samples from 1,450 participants who were diagnosed as cognitively unimpaired (CU), mild cognitive impairment (MCI), or AD-dementia across 4 international cohorts. Natural history modeling and trajectory analyses of the combined Aβ-PET …

Insulin Resistance As A Mediator Of Physical Activity's Effects On Beta-Amyloid Accumulation And Tau Phosphorylation: A Scoping Review, Michael G. Slee, Joanne Scotney, Stephanie R. Rainey-Smith, Kirk I. Erickson, Hamid R. Sohrabi, Giuseppe Verdile, Belinda M. Brown

Research outputs 2022 to 2026

Background Type 2 diabetes is associated with increased Alzheimer’s disease risk and brain beta amyloid (Aβ) burden, suggesting an underlying mechanistic relationship between Alzheimer’s disease and type 2 diabetes. Animal studies show exercise reduces levels of brain Aβ and tau, and while human studies are somewhat limited, some studies have reported physical activity is associated with lower brain Aβ and tau levels. Exercise has well established links to reductions in insulin resistance; thus, as physical activity can impact both insulin resistance and Alzheimer’s disease pathology and/or biomarkers, it is reasonable to hypothesise that a mediating relationship may exist. The objective …

Plasma Aβ42/40 Predicts Progression From Aβ-Amyloid Negative To Positive Pet Scans, Azadeh Feizpour, Vincent Doré, Pierrick Bourgeat, James D. Doecke, Rodrigo Canovas, Simon M. Laws, Tenielle Porter, Kun Huang, Christopher Fowler, Ralph N. Martins, Paul Maruff, Hamid R. Sohrabi, Michael W. Weiner, John C. Morris, Tammie L.S. Benzinger, Suzanne E. Schindler, Randall J. Bateman, Yan Li, Ovod Vitaliy, Larry Ward, Jurgen Mejan-Fripp, Colin L. Masters, Victor L. Villemagne, Christopher C. Rowe

Research outputs 2022 to 2026

Background The agreement between plasma Aβ42/40 and Aβ positron emission tomography (PET) is approximately 75 %, with ∼85 % of discrepancies due to positive plasma but negative PET results. It is unclear whether this reflects Aβ changes in plasma before PET-detectable. Objectives To assess the influence of Aβ42/40 positivity on risk of progression to Aβ PET positivity, and feasibility of using plasma Aβ42/40 tests to enrich a primary prevention trial. Design A prospective longitudinal cohort study. Setting Participants of Australian Imaging, Biomarkers and Lifestyle study (AIBL), Alzheimer’s Disease Neuroimaging Initiative (ADNI), and Open Access Series of Imaging Studies 3 (OASIS3). …

Gaze Transition Entropy And Automation Trust In Multitasking Workspace, Yusuke Yamani, Austin Jackson, Tetsuya Sato, Feyishola Ashimi, Michael S. Politowicz, Eric T. Chancey, Makoto Itoh

Psychology Faculty Publications

Safe flight operation requires visual scanning across multiple displays in a cockpit, which collectively represent the state of the aircraft and supporting automation. Trust is a crucial factor that drives human-automation interaction, and recent work has suggested a relationship between an operator's visual attention and automation trust. One index that captures predictability of eye movements between different areas of interest is gaze transition entropy. The current work reanalyzed data from Sato et al., which examined eye movement patterns and trust in automation associated with the system monitoring task of the Multi-Attribute Task Battery. Results showed credible positive correlations between the …

Longitudinal Changes In Plasma Biomarkers Of Immune Activation, Neuronal Inflammation And Injury In Persons With Hiv Initiating Art, Merle Henderson, Peter Dutey-Magni, Carolina Herrera, Wolfgang Stöhr, Alejandro Arenas-Pinto, Owen Swann, Amanda Heslegrave, Henrik Zetterberg, John Tregoning, Sarah Fidler, François Raffi, Andrea Calcagno, Ab Babiker, Alan Winston

CONRAD Publications

Background

Data on changes in biomarkers of brain health, and their associations with cognitive function in adults commencing either dual- or triple-antiretroviral therapy (ART) are sparse.

Methods

Plasma biomarkers (neurofilament light [NfL], glial fibrillary acidic protein [GFAP], sCD14, CXCL10, neopterin and IL-6) were measured at baseline and after 96 weeks on ART in individuals randomized to darunavir/ritonavir and either tenofovir-DF/emtricitabine (triple-ART, n = 119) or raltegravir (dual-ART, n = 119) in NEAT-001/ANRS143. Regression models examined associations of baseline and week-96 biomarker concentrations with HIV clinical parameters, composite cognitive test scores (Standardized neuropsychological test [NPZ], 7-domains) and treatment arm.

Results

In …

Formulation Development Of Topical Inserts Containing Doxycycline And Doxycycline Combined With Tenofovir Alafenamide And Elvitegravir For The Prevention Of Sexually Transmitted Infections, Vivek Agrahari, M. Melissa Peet, Jasmin Monpara, Rijo John, Sriramakamal Jonnalagadda, Pardeep K. Gupta, Meredith R. Clark, Gustavo F. Doncel

CONRAD Publications

Despite advances in oral and injectable HIV prevention options and oral prophylaxis for sexually transmitted infections (STIs) of bacterial origin, there remains a critical need for effective on-demand topical (vaginal and rectal) products for pre- and post-exposure prophylaxis (PrEP and PEP). To fill this gap, we have developed single and first-in-kind multi-active topical inserts for bacterial STIs and HIV/STIs prevention. We have formulated two different inserts, one containing doxycycline (DOX) at 10, 50, and 100 mg doses for bacterial STI prevention, and a multipurpose prevention product (TED insert) that combines DOX (10 mg) with the antiretrovirals tenofovir alafenamide (TAF; 20 …

Micrornas Regulated By Pregnancy Target Antiviral And Cancer Immunity Overlapping With The Hiv Interactome, Paula F. T. Cezar-De-Mello, Jonathan M. Dreyfuss, Pai-Lien Chen, Hidemi Yamamoto, Xiaoming Gao, Hui Pan, Charles Morrison, Gustavo F. Doncel, Robert L. Barbieri, Raina N. Fichorova

CONRAD Publications

Innate immunity predictors of HIV-1 risk and pathogenesis vary with reproductive hormones, pregnancy, and lactation, yet the underlying mechanisms remain unclear. We hypothesized that pregnancy-associated physiological adaptations alter systemic microRNA (miRNA) expression, thereby regulating immunity, pathogenesis and susceptibility to infection. We analyzed 174 serum samples from 88 participants in a longitudinal cohort from Uganda and Zimbabwe across pre-pregnancy (PP), pregnancy (P), and postpartum breastfeeding (BF). Cell-free peripheral blood miRNAs (n = 2083) were profiled using HTG EdgeSeq. Pregnancy-specific miRNAs were identified by intersecting differentially expressed (DE) miRNAs from P vs. PP and P vs. BF comparisons. miRNA targets and pathways …

The Associations Between Sleep Environment Factors And Sleep Health In Individuals Living With Neurological Conditions, Mitchell Turner, Laws, Madeline Griffiths, Travis Cruickshank

Research outputs 2022 to 2026

Objectives: To explore associations between air temperature and light in the sleeping environment and sleep health in individuals with neurological conditions. Methods: The sleep health of 46 individuals with neurological conditions (mean age 51.37 ± 14.24 years; 20 males, 26 females) was measured using the Sleep Health Index (SHI). Air temperature and light data were captured across seven days using a light/temperature data logger positioned next to the participant’s bed. Data recorded during the participants’ sleeping periods (determined using a sleep diary) were analyzed. Linear regression models were used to assess the associations between air temperature and light and sleep …

Beta-Band Modulation Reveals The Cortical Dynamics Of Auditory Statistical Learning In Children, Jarrad A.G Lum, Christine N. Moreau, Li Ann Leow, Welber Marinovic, Sarah J. Lum, Marc F. Joanisse, Laura J. Batterink

Research outputs 2022 to 2026

Children's ability to extract statistical regularities from speech is considered fundamental to lexical, syntactic, and grammatical development. However, the neural oscillatory mechanisms supporting this process in childhood remains poorly understood. While beta-band oscillations have been linked to statistical learning in visual and motor domains, it is unclear whether similar dynamics support auditory statistical learning in children. In this study, we recorded electroencephalography (EEG) from children aged 8–12 years as they listened to a continuous stream of trisyllabic nonwords (e.g., dapiku), where syllable order within each nonword was fixed (high predictability), but transitions between nonwords were variable (low predictability). Beta power …

Exploring The Mechanisms Of Tanshinone Iia In The Treatment Of Intracranial Aneurysm Based On Network Pharmacology And Machine Learning, Wanqi Wang, Lois Balmer, Shaotao Weng

Research outputs 2022 to 2026

Background Intracranial aneurysm (IA) is a cerebrovascular disease with high mortality and limited treatment options. Tanshinone IIA (Tan IIA), a bioactive compound from Salvia miltiorrhiza , has shown vascular protective effects, but its mechanism in the treatment of IA remains unclear. Methods The GSE75436 dataset was used to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was performed to identify disease-related modules. IA targets were obtained from GeneCards and the Comparative Toxicogenomics Database (CTD). Potential targets of Tan IIA were predicted using TCMSP, SwissTargetPrediction, and SymMap. KEGG enrichment analysis was conducted for DEGs, WGCNA modules, disease-related genes, …

Fgf19 As A Colorectal Cancer Serum Biomarker And Fgfr4 As A Mediator Of Anti-Her2 Resistance In Breast Cancer, Jordan Beardsley

Graduate Studies Theses and Dissertations 2026

The fibroblast growth factor 19 (FGF19)-fibroblast growth factor receptor 4 (FGFR4) signaling pathway regulates hepatic metabolism, bile acid (BA) synthesis, and hepatocyte proliferation. This signaling axis also is implicated in promoting tumor progression, therapeutic resistance, and metastasis in certain cancers.

In colorectal cancer (CRC) there is a critical need for non-invasive biomarkers for disease detection and monitoring. We identified FGF19 as a candidate CRC serum marker through meta-transcriptomics and found FGF19 to be expressed and secreted by CRC cell lines. Tumor-derived FGF19 was detectable in mouse serum at levels correlating with tumor volume in a subcutaneous xenograft model. RNA sequencing …

Pioglitazone Uncouples Macrophage Inflammatory Signaling From Epithelial Oxidative Stress During Map Infection Mimicking Crohn’S Disease Treatment, Sabera Akter Bushra

Graduate Studies Theses and Dissertations 2026

Crohn’s disease (CD) is a chronic inflammatory bowel disease characterized by intestinal inflammation, epithelial barrier dysfunction, and abnormal immune signaling. CD pathophysiology is increasingly linked to Mycobacterium avium subspecies paratuberculosis (MAP) infection, which increases chronic macrophage activation and the production of inflammatory mediators that lead to epithelial damage. Among these mediators, CXCL10, TNF-α, and IL-6 contribute in inflammation, while NOX-1 and SERPINE-1 indicate epithelial oxidative stress and damage. Despite the role of macrophage-epithelial interaction in CD, selective pharmaceutical regulation of this axis remains unclear. Pioglitazone, an FDA-approved PPARγ agonist used for type 2 diabetes, is an appealing repurposing candidate, given …

Pilot Study On The Use Of Multimorbidity Index In Patients Receiving Home Parenteral Nutrition, Michael M. Rothkopf, Mohan Pant, Zachary Rothkopf, Rebecca Brown Rdn, Jaime Haselhorst Rdn, Debbie L. Stevenson Rdn, Andrew Depalma Mba, Michael Saracco

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Background

Home parenteral nutrition (HPN) patients often have multiple comorbidities. A validated multimorbidity index (MMI) could help determine resource needs and risks with HPN. We evaluated MMI scoring to determine if it predicted HPN resource use and outcomes.

Methods

We performed a secondary analysis of 60 HPN patients from a previous study based on Cumulative Illness Rating Scale (CIRS) scoring. We examined three variables: PN formula changes, hospitalizations, and hospital length of stay (LOS). Density plots were produced to select a CIRS score cutoff value. Spearman correlations among the three variables of interest were computed. The data were then subjected …

Vitamin D Status During Pregnancy Modulates The Effect Of Pre-Pregnancy Obesity On Gestational Diabetes Mellitus Risk: A Birth Cohort Study, Ali H. Ziyab, Abdullah Al-Taiar, Reem Al-Sabah, Majeda S. Hammoud, Saeed Akhtar

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Objective:

To determine whether gestational vitamin D status modulates the effect of pre-pregnancy obesity on gestational diabetes mellitus (GDM) risk while stratifying by maternal age.

Design:

Birth cohort.

Setting:

A major maternity hospital in Kuwait.

Participants:

Pregnant women in their second/third trimester of gestation were enrolled. Pre-pregnancy body mass index (BMI, kg/m²) was categorized as under/normal weight (< 25.0), overweight (25.0 to < 30.0), and obesity (≥30.0). Gestational 25-hydroxyvitamin D concentrations were categorized as deficiency (< 50 nmol/L) or insufficiency/sufficiency (≥50 nmol/L). GDM status was ascertained according to international guidelines. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated using logistic regression.

Results:

Data from 957 pregnant women were analyzed, with GDM affecting 166 (17.4%) pregnancies. Pre-pregnancy obesity and gestational vitamin D deficiency was ascertained in 275 (28.7%) and 533 (55.7%) pregnant women, respectively. The association between pre-pregnancy obesity and GDM risk differed according …

Deer Antler Tip Cell Culture Supernatant Restores Endothelial Barrier Function And Angiotensin Converting Enzyme 2/Endothelial Nitric Oxide Synthase Nitric Oxide Signaling Impaired By Porphyromonas Gingivalis Lipopolysaccharide, Ming-Shou Hsieh, Ya-Ting Yang, Chin-Sheng Huang, Ting-Yi Renn, Chuen-Kai Wang, Chia-Chen Hsu, Wei Jen Chang, Yu-Sheng Chang

Journal of Dental Sciences

Background/purpose:

Periodontal inflammation contributes to endothelial dysfunction, but effective biologically active strategies for vascular protection remain limited. This study investigated whether deer antler tip cell culture supernatant could rescue Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) induced endothelial injury and restore endothelial homeostasis.

Materials and methods:

Velvet antler tissues from the tip, shaft, and burr regions were examined histologically and used for primary cell isolation. Human umbilical vein endothelial cells were exposed to Pg-LPS or indirectly co-cultured with LPS-stimulated THP-1-derived macrophages. Deer antler tip cell culture supernatant was subsequently applied to these endothelial inflammatory models, and its protective effects were …

Advancing Treatment Of Pleural Infection, Estee Pui Mun Lau

Theses: Doctorates and Masters

Introduction: Pleural infection remains a major clinical concern, with an increasing incidence worldwide. The use of intrapleural tissue plasminogen activator (tPA) with deoxyribonuclease (DNase) therapy represents a major breakthrough as it offers an effective alternative to surgery for patients who fail conventional treatment. However, the optimal dosage of tPA is yet to be established. Indwelling pleural catheter (IPC)-related infections, especially IPC-related pleural infections are a significant concern and a barrier to the uptake of IPC. The development of a long-term preventative strategy is imperative to promote uptake and improve the quality of life of patients, particularly in those who have …

Variability In Documentation Of Neurological And Psychiatric Examinations Among Emergency Department Patients With Behavioral Health-Related Presentations: A Retrospective Study, Heba Mesbah, Payton Kim, Jide Oluwadare, Abdulelah Almanie, Inaara Malick, Nidal Moukaddam

Faculty, Staff and Students Publications

Background: Emergency departments (EDs) serve as a critical safety net for individuals experiencing acute behavioral health crises, a population that faces substantial medical morbidity and well-documented disparities in healthcare delivery. Thorough physical and neuropsychiatric assessment is essential in this setting to identify medical conditions that may mimic or exacerbate psychiatric symptoms. Incomplete documentation of these assessments may reflect gaps in care processes and represent a potential marker of inequity.

Objective: To characterize the completeness of documented neurological and psychiatric examinations among adult ED patients presenting with primary behavioral health-related chief complaints and to assess whether documentation patterns suggest persistent gaps …