Digital Commons Network^™

Circulating Tumor Cells In Uveal Melanoma: Multi-Marker Detection And Association With Disease State, Daniel P. De Bruyn, Fabiana Lucia Bassil, Mike Wu, Aaron B. Beasley, Jolanda Vaarwater, Mai N. Van, Jaco Kraan, Robert M. Verdijk, Dion Paridaens, Caroline M. Van Rij, Nicole C. Naus, Annelies De Klein, Elin S. Gray, Erwin Brosens, Emine Kiliç

Research outputs 2022 to 2026

Purpose. Uveal melanoma (UM) is primarily treated with eye-sparing radiotherapy, leaving limited tumor tissue for molecular analysis. Circulating tumor cells (CTCs) may offer a minimally invasive alternative for genomic tumor profiling. This pilot study evaluated the feasibility of a multi-marker CTC capture approach in UM patients at diagnosis, during fractionated stereotactic radiotherapy (fSRT), and at metastatic progression. Methods. Patients with localized or metastatic UM were prospectively enrolled. Peripheral blood samples were collected at baseline, during fSRT, and on detection of metastases. CTCs were captured and enumerated using a multi-marker approach and fluorescence microscopy. Results. A total of 76 patients were …

Rapid Decentralized Prostate Cancer Risk Stratification By Portable Liquid Biopsy Analysis Within A Clinical Biosensor Validation Framework, Kevin M. Koo, Grant Phillips, Sriganesh Srihari, Áine Farrell, Binny Jaradi, Kira J. Fitzpatrick, John W. Yaxley, Hemamali Samaratunga, Paul N. Mainwaring, Ke-Lin Ru, Darren J. Korbie, Scott A. Tomlins, Matthew J. Roberts, Robert A. Gardiner, Matt Trau

Research outputs 2022 to 2026

Clinical liquid biopsy (e.g., blood or urine) specimens, as a minimally invasive source of crucial molecular information, continue to grow in importance for efficacious targeted cancer treatment. Yet, current molecular profiling technologies are still confined to centralized laboratory testing, which escalates testing costs, result turnaround time, and patient anxiety. Crucially, there is also a scarcity of purposeful clinical validation studies to rigorously evaluate emerging liquid biopsy technologies from research settings to facilitate clinical translation. Here, we report liquid biopsy biosensor advancements in achieving rapid, accurate, and decentralized molecular profiling of a clinically accredited prostate cancer (PCa) urinary circulating RNA biomarker …

Feasibility And Preliminary Efficacy Of Integrative Neuromuscular Training For Childhood Cancer Survivors: A Pilot Study, Anna Maria Markarian, U. Newton, Dennis Taaffe, Nicholas G. Gottardo, Santosh Valvi, Carolyn J. Peddle-Mcintyre, Jodie Cochrane Wilkie, Daniel A. Galvão

Research outputs 2022 to 2026

Background: Survivors of childhood acute lymphoblastic leukemia (ALL) often exhibit early deficits in muscle and movement competence, which can compromise long-term health. Integrative neuromuscular training (INT), a multifaceted approach combining fundamental movement activities with strength exercises, may help address these deficits during critical developmental periods. Methods: Eight children treated for ALL (aged 6–12 years) completed a supervised INT intervention (2 sessions/week for 8 weeks). Primary outcomes were feasibility (recruitment, retention, adherence, compliance, and tolerance) and program acceptability. Secondary outcomes included muscle function (isometric midthigh pull [IMTP], countermovement jump, and handgrip strength), dual-energy x-ray absorptiometry (DXA)-derived body composition, peripheral quantitative computed …

Multidimensional Sleep Health And Sleep Environment Factors In Individuals With Cancer Undergoing Outpatient Chemotherapy: An Exploratory Cross-Sectional Analysis, Sam Adams, D. Clay, Arman Hasani, Mitchell Turner, Travis Cruickshank

Research outputs 2022 to 2026

Purpose: Sleep problems are common amongst individuals with cancer receiving chemotherapy and are associated with poorer health outcomes. Considerable research to date has investigated specific sleep domains or symptomology, with little attention given to overall sleep health, which is more closely associated with overall health. This exploratory cross-sectional study aimed to characterize multidimensional sleep health in individuals with cancer reporting sleep complaints whilst undergoing chemotherapy, with exploratory examination of environmental associations. Patients and Methods: Twenty-three participants were included in this exploratory cross-sectional analysis. Participants were diagnosed with cancer within the last 6 months, undergoing outpatient chemotherapy at time of study …

It Was Part Of The Plan, So I Showed Up: An Exploration Of Patient Experiences With An Embedded Exercise Referral Process During Cancer Treatment, Mary A. Kennedy, Jack Dalla Via, Kim Edmunds, Pam Eldridge, Yvonne Zissiadis, Lauren Fortington

Research outputs 2022 to 2026

Introduction: Exercise is a key part of cancer care, yet its integration into routine practice remains limited. This study explored the experiences of people living with and beyond cancer, with an updated, opt-out referral model embedded within a supportive oncology setting, focusing on initial engagement with exercise physiology appointments. Through this model, patients were automatically scheduled for a consultation with an in-house exercise professional during their cancer treatment. Methods: A qualitative descriptive design comprised of two focus groups with 13 participants was employed to explore views across pre-defined elements of the model: referral to exercise, appointments, counselling, and tailoring. Results: …

Cardiovascular–Kidney–Metabolic Syndrome Through The Lens Of Gut‑Derived Uremic Toxins, Chudan Xu, Matthew Snelson, Francine Z. Marques

Research outputs 2022 to 2026

Cardiovascular–Kidney–Metabolic (CKM) syndrome represents a complex, interconnected cluster of cardiovascular disease, chronic kidney disease, and metabolic disorders such as obesity and type 2 diabetes. These conditions share overlapping metabolic, inflammatory, and vascular pathways, with the gut microbiome increasingly recognised as a key contributor and common underlying risk factor. Uremic toxins, traditionally considered waste products of host and microbial metabolism, are now recognised as active mediators of tissue damage across the CKM spectrum, particularly in the context of impaired renal function. Their production and accumulation are amplified by disrupted intestinal barrier integrity, chronic inflammation, and reduced renal clearance, collectively driving systemic …

Emerging Blood-Based Biomarkers For The Detection Of Parenchymal Brain Metastasis: Current Progress And Future Perspectives, Désirée Sexauer, Elin S. Gray, Helen Rizos, Pauline Zaenker, Aaron B. Beasley

Research outputs 2022 to 2026

Parenchymal brain metastases of solid malignancies remain a significant clinical challenge, as they are often detected at later symptomatic stages, which are typically associated with worse prognosis. Delayed detection limits treatment options and contributes to poor outcomes, while early detection is critical for improving patient outcomes and quality of life. In this comprehensive review, we investigated the potential use and challenges of blood-based biomarkers, including circulating tumor cells, cell-free DNA, noncoding RNAs, extracellular vesicles, proteins, and other immune-related biomarkers, for the early detection of parenchymal brain metastasis. The use of blood-based liquid biopsies offers a promising avenue for early detection …

Wnt4 Deficiency Impacts Heart, Diaphragm, And Palate Development: Insights From Human Genetics, Machine Learning, And Mouse Models, Andrés Hernández-García, Bum Jun Kim, David Chitayat, Patrick Shannon, Stephanie Hedges, Maria Al Bandari, Maria J Guillen Sacoto, Emily Anne Bates, Yunus H Ozekin, Victor Faundes, Pamela N Luna, Chad A Shaw, Tara L Rasmussen, Chih-Wei Hsu, Daryl A Scott

Faculty, Staff and Students Publications

WNT4 is a secreted protein that plays a critical role in the regulation of cell fate and embryogenesis. Biallelic variants in WNT4 have been linked to SERKAL syndrome, an autosomal recessive disorder characterized by 46,XX sex reversal and dysgenesis of the kidneys, adrenals, and lungs. SERKAL syndrome has only been described in a single consanguineous kindred with four affected fetuses. Additional features seen in a subset of affected fetuses included ventricular septal defect (VSD), congenital diaphragmatic hernia (CDH), and orofacial clefting (OFC). To determine if these additional features were likely to be caused by WNT4 deficiency, we used machine learning …

Intercornual Distance And Postoperative Reproductive Outcomes In Moderate-To-Severe Intrauterine Adhesions: A Retrospective Cohort Study, Yifu He, Xingping Zhao, Huan Huang, Changfa Shu, Xiaoming Guan, Jia Guo, Dabao Xu

Faculty, Staff and Students Publications

Study question: Does intercornual distance (ICD), as reflected by intrauterine stent size during hysteroscopic adhesiolysis, have an association with reproductive outcomes and provide information for postoperative risk stratification in women with moderate-to-severe intrauterine adhesions?

Summary answer: A smaller ICD was independently associated with a lower likelihood of clinical pregnancy within 1 year of the final hysteroscopy and may offer additional information for postoperative risk stratification in women with moderate-to-severe intrauterine adhesions.

What is known already: Reproductive outcomes following treatment for moderate-to-severe intrauterine adhesions vary considerably. Existing severity classifications offer limited discrimination within this group. The potential association between ICD and …

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 …

Adjuvant Pembrolizumab For Stage Iib Or Iic Melanoma: A Secondary Analysis Of A Randomized Clinical Trial, Sancy A. Leachman, Jason J. Luke, Paolo A. Ascierto, Georgina V. Long, Muhammad Khattak, Piotr Rutkowski, Zhi Jin Xu, Mizuho Fukunaga-Kalabis, Clemens Krepler, Alexander M.M. Eggermont, Dirk Schadendorf

Research outputs 2022 to 2026

Importance Patients with melanoma are at risk of developing subsequent cutaneous malignant neoplasms, and the effect of prior immunotherapy is unknown. Objective To analyze new skin cancers in participants with high-risk stage II melanoma treated with adjuvant pembrolizumab or placebo. Design, Setting, and Participants The multicenter double-blind, phase 3 KEYNOTE-716 randomized clinical trial enrolled 976 participants 12 years or older with completely resected stage IIB or IIC cutaneous melanoma between September 23, 2018, and November 4, 2020. Follow-up was completed on February 16, 2024. This analysis was not prespecified in the trial protocol. Interventions Participants were randomly assigned to receive …

A Collaborative Communities-Of-Practice Methodology For Environmental Design Research: A Case Study Application In Palliative Care, Emil E. Jonescu, Benjamin Farrell, Chamil Erik Ramanayaka, Lori Delaney, Edward Litton, Talia J. Uylaki, Gareth Watts, Bella Brigham, Frances Bellemore, Davinia Seah

Research outputs 2022 to 2026

Environmental design in palliative care settings receives increasing attention, yet methodologies for studying such environments often lack interdisciplinary integration. Traditional research designs may overlook the lived expertise of clinicians and designers. Objectives: This article describes a collaborative, cross-disciplinary communities-of-practice model developed as a methodological framework to enable effective environmental evaluation and design processes in healthcare settings. Its application is illustrated through a case study in a palliative care unit. Methods: A co-designed, multi-methods approach was developed by a team of clinicians, facility managers, and academic researchers. The methodology included a scoping review, site-specific environmental data logging (sound, temperature, lighting), and …

Development Of A Clinical Prediction Model To Guide The Selective Use Of Spect/Ct In Papillary Thyroid Cancer, Liya Zhu, Junik Son, Lu Wang, Haifeng Hou, Byeong Cheol Ahn

Research outputs 2022 to 2026

Background: Radioiodine whole-body scan (WBS) is routinely performed after radioiodine therapy in papillary thyroid cancer (PTC), but its two-dimensional nature limits anatomical localization. The addition of single-photon emission computed tomography/computed tomography (SPECT/CT) improves diagnostic accuracy; however, routine use exposes patients to additional radiation, longer imaging time, and higher costs. This study aimed to establish a predictive model to identify which patients with PTC are more likely to benefit by adding SPECT/CT imaging after WBS, enabling selective rather than routine use. Methods: This retrospective study included 265 patients with pathologically confirmed PTC who underwent postoperative radioiodine therapy followed by WBS and …

Neuron-Enriched Extracellular Vesicle Micrornas Reflect Hormonal Suppression Associated With Oral Contraceptive Use In Young Women, Amulya Chowdhory, Rebekah Frye, Roxann Roberson-Nay

Undergraduate Research Posters

Hormonal contraceptives alter hypothalamic–pituitary–ovarian (HPO) feedback, but their impact on brain-associated molecular communication remains poorly understood. Neuron- enriched extracellular vesicle (nEV) microRNAs (miRNAs), isolated from plasma, provide a minimally invasive window into brain molecular activity. This pilot study examined nEV miRNA expression in young women (ages 18–22) who were either naturally cycling or using a combined monophasic oral contraceptive (OC) pill. To identify hormonally responsive miRNAs, we calculated effect sizes (Cohen’s d) between the two groups and selected those showing large between-group differences (|d| ≥ 0.8). These miRNAs were entered into a principal component analysis (PCA) to reduce dimensionality, and …

Professional Quality Of Life Among Medical Surgical And Telemetry Registered Nurses, William Lim, Emy-Lee Marie Anglo Ricafrente, Jenny Carrillo

Publications 2026-present

No abstract provided.

Oxytocin Dosing During Trial Of Labor After Cesarean To Minimize The Risk Of Uterine Rupture: A Systematic Review And Meta-Analysis, Pierpaolo Nicolì, Moti Gulersen, Jordan Beacham, Hila Hochler, Alessandra Familiari, Anna Locatelli, Cynthia Abraham, Ettore Cicinelli, Amerigo Vitagliano, Vincenzo Berghella

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: Oxytocin remains the mainstay for induction and for the management of labor arrest during trial of labor after cesarean (TOLAC). Therefore, the clinical question should be not whether to use oxytocin, but how to optimize its administration. This meta-analysis aimed to assess which oxytocin protocol, in terms of initial dose, amount of increase, timing to next increase, and maximum dose, may minimize the risk of uterine rupture (UR) during TOLAC.

DATA SOURCES: PubMed, Embase and Clinicaltrials.gov were searched up to September 21, 2024.

STUDY ELIGIBILITY CRITERIA: Randomized and nonrandomized studies evaluating the association between induction and/or augmentation with oxytocin …

Korelasi Kadar Serum Vegf-A Dengan Rasio Albumin-Kreatinin Urin Pada Pasien Penyakit Ginjal Diabetik, Hannie Q. Syaiful, Drajad Priyono, Harnavi Harun, Arina W. Murni, Akmal M. Hanif, Eifel Faheri, Arnelis Arnelis, Vesri Yoga

Jurnal Penyakit Dalam Indonesia

Introduction. Diabetic kidney disease (DKD) is a major microvascular complication of diabetes mellitus, characterized by persistent albuminuria and a progressive decline in glomerular filtration rate (GFR), making it a leading cause of chronic kidney disease (CKD) and end-stage renal disease. Vascular endothelial growth factor-A (VEGF-A) is implicated in the pathogenesis of DKD, being overexpressed in the kidneys and contributing to increased vascular permeability, inflammation, and fibrosis. Albuminuria, an early indicator of renal damage in DKD, is a strong predictor of CKD progression and cardiovascular events. The urine albumin-to-creatinine ratio (UACR) is the recommended test for detecting and monitoring albuminuria. …

Faktor Prediktif Post Dialysis Fatigue Sedang Pada Pasien Yang Menjalani Hemodialisis Reguler, Ivan Virnanda Amu, Maruhum Bonar H Marbun, Pringgodigdo Nugroho, Ikhwan Rinaldi, Hamzah Shatri, Nunuk Mardiana, Rudy Hidayat, Endang Susalit, Evy Yunihastuti, Dyah Purnamasari, Elizabeth Y. Wardoyo

Jurnal Penyakit Dalam Indonesia

Introduction. Fatigue is often found in patients with CKD-HD. Fatigue serves as an indicator of mortality and may be a viable target in a treatment strategy. Current research has not established the determinants of moderate PDF in individuals with CKD who are undergoing HD. Therefore, this study was conducted to prove the predictor factors of moderate PDF.

Methods. A retrospective cohort study in CKD-HD patients at Fatmawati Central General Hospital during the period of November-December 2024. The independent variables of this study are comorbidities, MIS, depression, intradialytic SBPV, dialysis vintage, UFG, IDWG, and anemia status. Primary data from …

Analysis And Numerical Investigation Of A Breast Cancer Treatment Model Incorporating Ketogenic Diet And Immune Boosters Via Optimal Control Theory, Kunnisai Muniroh, Ummu Habibah, Wuryansari Muharini Kusumawinahyu, Nur’Izzati Hamdan

Mathematical Modelling and Numerical Simulation with Applications

This paper develops a mathematical model to investigate breast cancer dynamics by incorporating tumor–immune interactions, ketogenic diet effects, and medical treatment. The model is formulated as a system of nonlinear ordinary differential equations and analyzed within an optimal control framework. Time-dependent control variables are introduced to represent treatment strategies aimed at minimizing tumor progression while reducing therapeutic costs. The model’s well-posedness is established through positivity and boundedness analysis. The necessary conditions for optimality are derived using Pontryagin’s Minimum Principle, resulting in a coupled system of state and adjoint equations. Numerical solutions are obtained using the fourth-order Runge–Kutta method combined with …

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 …

Gut Microbiome Metagenomics In Clinical Practice: Bridging The Gap Between Research And Precision Medicine, Henok Ayalew Tegegne, Tor C Savidge

Faculty, Staff and Students Publications

Gut microbiome metagenomics is emerging as a cornerstone of precision medicine, offering exceptional opportunities for improved diagnostics, risk stratification, and therapeutic development. Advances in high-throughput sequencing have uncovered robust microbial signatures linked to infectious, inflammatory, metabolic, and neoplastic diseases. Clinical applications now include pathogen detection, antimicrobial resistance profiling, microbiota-based therapies, and enterotype-guided patient stratification. However, translation into routine care is hindered by significant barriers including methodological variability, limited functional annotation, lack of bioinformatics standardization, and underrepresentation of global populations. This review synthesizes current translational strategies, emphasizing the need for hypothesis-driven designs, multi-omic integration, longitudinal and multi-center cohorts, and mechanistic validation. …

Nutrition Support Adequacy In Children With Biliary Atresia After Liver Transplant, Nicole Knebusch, Manpreet Virk, Moreshwar S Desai, Marwa Mansour, Stacey Beer, Brittany Pearo, Kelby Fuller, Krupa Mysore, John Goss, Thomas Fogarty, Fernando Stein, Jorge A Coss-Bu

Faculty, Staff and Students Publications

No abstract provided.

Psoriasis Treatments In The Stabilization Of Atherosclerosis: A Systematic Review, Lixin Ji, Sowmya Ravi, Laura Wright, Vi Nguyen, Jose Wiley, Milena Vukelic, Sangkyu Kim

School of Medicine Faculty Publications

This systematic review explores the relationship between achieving minimal disease activity in psoriasis and the progression of atherosclerosis. It investigates how biologic therapies and other treatments impact atherosclerosis markers, offering insights into therapeutic strategies. A comprehensive search of PubMed, Embase, and Web of Science was conducted from January 1, 2000, to April 1, 2023, using terms such as psoriasis, psoriatic arthritis, atherosclerosis, biologic therapy, vascular stiffness, carotid intima-media thickness (CIMT), and coronary computed tomography angiography (CCTA). Eligible studies were those involving human subjects over 18, written in English, that provided quantitative atherosclerosis markers, including CIMT, CCTA, arterial pulse wave velocity …

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 …

Role Of Gut Microbiome In Oncogenesis And Oncotherapies, Renuka Sri Sai Peddireddi, Sai Kiran Kuchana, Rohith Kode, Saketh Khammammettu, Aishwarya Koppanatham, Supriya Mattigiri, Harshavardhan Gobburi, Suresh K. Alahari

School of Graduate Studies Faculty Publications

The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing …

Regenerative And Wellness Medicine: A Boon Or Barrier To Surgical Innovation In Degenerative Spine Care?, Álvaro Dowling, Kai-Uwe Lewandrowski, Morgan P. Lorio, Óscar L. Alves, Rossano Kepler Alvim Fiorelli, Sergio Luis Schmidt, Hansen A. Yuan, Alexander R. Vaccaro

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Regenerative and wellness medicine is rapidly reshaping health care, particularly in the management of degenerative spine conditions. Noninvasive or minimally invasive options such as stem cell therapy, platelet-rich plasma (PRP) injections, and holistic wellness programs are increasingly selected by patients who wish to avoid the risks, costs, and prolonged recovery associated with elective spine surgery.

PURPOSE: This perspective article examines whether regenerative and wellness approaches function primarily as a boon or a barrier to innovation in spine surgery and explores their impact on traditional, insurance-based surgical care models.

METHODS: Using a narrative, opinion-based framework, this article synthesizes current trends …

Loss Of The Maternal Effect Gene Nlrp2 Impairs Embryonic And Extra-Embryonic Development, Revealing A Novel Genetic Cause Of Congenital Anomalies†, Momal Sharif, Zahra Anvar, Imen Chakchouk, Sara H El-Dessouky, Roni Zemet, Eric C Kao, Wessam E Sharaf-Eldin, Ying-Wooi Wan, Zhandong Liu, Pengfei Liu, Michael Jochum, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

Maternal-effect genes (MEGs) play a crucial role in early mammalian development, and their dysfunction can lead to severe embryonic and extra-embryonic abnormalities. NLRP2, a MEG that encodes a subcortical maternal complex (SCMC) protein, has been implicated in preimplantation development, but its role after implantation remains underexplored. In this study, we investigated the developmental consequences of maternal Nlrp2 loss-of-function in a maternal knockout (KO) mouse model at embryonic day 11.5. Embryos derived from Nlrp2-KO females have abnormal yolk sac vasculature, increased embryonic resorption, craniofacial abnormalities, neural tube defects, and congenital heart defects. Placental architecture is disrupted with an altered junctional zone …

A Spatiotemporal Model Of Cxcl10 As A Master Regulator Of Immune Evasion And Metastasis In Osteosarcoma, Benjamin B Gyau, Tsz-Kwong Man

Faculty, Staff and Students Publications

The C-X-C motif chemokine ligand 10 (CXCL10) is implicated in the progression of osteosarcoma (OS), the most aggressive pediatric bone malignancy. However, its role often presents a profound clinical paradox: although high circulating levels are strongly linked to poor prognosis, its canonical function is to recruit anti-tumor immune cells. This review unravels these contrasting roles by proposing a novel spatiotemporal model. We argue that in the early stages, immune-evading OS cells initiate the formation of a pre-metastatic niche (PMN) in the lungs, creating a localized inflammatory environment that becomes the primary source of elevated circulating CXCL10. As the disease progresses, …