Medicine and Health Sciences Commons^™

Bard: A Seamless Two-Stage Dose Optimization Design Integrating Backfill And Adaptive Randomization, Yixuan Zhao, Rachael Liu, Jianchang Lin, Ying Yuan

Faculty, Staff and Student Publications

One common approach for dose optimization is a two-stage design, which initially conducts dose escalation to identify the maximum tolerated dose, followed by a randomization stage where patients are assigned to two or more doses to further assess and compare their risk-benefit profiles to identify the optimal dose. A limitation of this approach is its requirement for a relatively large sample size. To address this challenge, we propose a seamless two-stage design, BARD (Backfill and Adaptive Randomization for Dose Optimization), which incorporates two key features to reduce sample size and shorten trial duration. The first feature is the integration of …

Gd3 Synthase Drives Resistance To P53-Induced Apoptosis In Breast Cancer By Modulating Mitochondrial Function, Vivek Anand, Fouad El-Dana, Natalia Baran, Jenny Borgman, Zheng Yin, Hong Zhao, Stephen T Wong, Michael Andreeff, V Lokesh Battula

Faculty, Staff and Student Publications

TP53 mutations are common in breast cancer (BC) and are associated with poor prognosis. GD3 synthase (GD3S/ST8SIA1), a gene associated with breast cancer stem cells, is upregulated in tumors with p53 mutations. However, the functional relationship between GD3S and p53 is unknown. Here, we show that GD3S levels are highest in breast tumors with specific p53 mutations. Functional studies revealed that wild-type (WT) p53 inhibits GD3S expression, whereas mutation in p53 enhances GD3S expression by upregulating GD3S promoter activity. Moreover, we found that GD3S inhibits wild-type p53-induced apoptosis in BC cells, while BC cells harboring gain-of-function p53 mutations are dependent …

Pparγ-Induced Upregulation Of Fatty Acid Metabolism Confers Resistance To Venetoclax And Decitabine Therapy In Aml, Kotoko Yamatani, Tatsuro Watanabe, Kaori Saito, Abdullah Khasawneh, Abhishek Maiti, Zhihong Zeng, Kala Hayes, Shinya Kimura, Courtney D Dinardo, Xiaoping Su, Shuko Nojiri, Yasushi Okazaki, Michael Andreeff, Marina Konopleva, Yoko Tabe

Faculty, Staff and Student Publications

The combination of the B-cell lymphoma 2 (BCL2) inhibitor venetoclax (VEN) and the hypomethylating agent decitabine (DEC; VEN/DEC) constitutes a primary therapeutic strategy for treating older adults with acute myeloid leukemia (AML). However, a notable subset of patients exhibits resistance to VEN/DEC, demonstrating either no disease response or relapse after initial remission. This study aimed to elucidate the molecular mechanisms underlying this resistance through analyses of gene expression and DNA methylation profiles. We conducted comprehensive RNA sequencing analysis and DNA methylation profiling on AML samples from 35 patients undergoing VEN/DEC therapy. The RNA sequencing analysis revealed that several genes related …

Dynamic Long-Term Prediction With Intermediate Event Information: A Flexible Model With Bivariate Time-Varying Coefficients, Yunyi Wang, Wen Li, Ruosha Li, Jing Ning

Faculty, Staff and Student Publications

The integration of time-to-intermediate event data and the evolving characteristics of patients to enhance long-term prediction has garnered significant interest, driven by the wealth of data generated from longitudinal cohorts. In this paper, we propose sequential/dynamic prediction rules by using regression models with time-varying coefficients. We introduce a class of dynamic models that not only incorporates intermediate event information but also leverages information across different landmark times. To address the challenge of right-censoring, we employ an inverse weighting technique in the estimation process. We establish the asymptotic properties of the estimated parameters and conduct extensive simulations to assess the finite …

Single-Cell Proteomic Analysis Reveals Multiple Myeloma Heterogeneity And The Dynamics Of The Tumor Immune Microenvironment In Precursor And Advanced States, Mohamed Kamal, Stephanie N Shishido, Jeremy Mason, Krina Patel, Elisabet E Manasanch, Robert Z Orlowski, Peter Kuhn

Faculty, Staff and Student Publications

Multiple myeloma (MM) is an aggressive hematologic malignancy arising from plasma cell (PC) proliferation in the bone marrow, progressing from its precursor states MGUS and SMM. Despite therapeutic advances, MM remains incurable, underscoring the need for better risk stratification and early detection. Tumor heterogeneity and dynamic immune microenvironment changes drive progression, yet bulk analyses overlook rare subpopulations critical to disease evolution and resistance. This study employed multiplexed targeted proteomics to characterize bone marrow aspirates (BMA) from 22 patients to observe the change in the distribution of PCs and tumor immune microenvironment (TiME) cells across MM disease states and controls. Bone …

De-Escalating Local Therapies Without Compromising Outcomes: Lessons From The Collision Trial, Jessica Albuquerque, Noreen S Siddiqi, Van K Morris, Hop Tran Cao, Iwan Paolucci, Bruno C Odisio

Faculty, Staff and Student Publications

No abstract provided.

Patient, Physician, And Assessor Blinding In Phase Iii Randomized Trials In Oncology: A Meta-Epidemiological Analysis, Gabrielle Brown, Pavlos Msaouel, Avital M Miller, Ramez Kouzy, Timothy A Lin, Joseph Abi Jaoude, Ethan B Ludmir, Alexander D Sherry

Faculty, Staff and Student Publications

Background: Blinding mitigates bias in randomized trials and may be especially crucial for surrogate endpoints, such as progression-free survival (PFS). Here, we characterize utilization of and factors associated with blinding in Phase III oncology trials with PFS primary endpoints.

Methods: Two-arm, superiority-design trials investigating systemic therapy were identified in May 2024 from ClinicalTrials.gov with no date limitation. Trials were required to have a PFS primary endpoint. The study outcomes were the presence of double-blind designs and blinded independent central review (BICR) for the primary endpoint. Ninety-five percent credible intervals for binary outcomes were estimated from beta distributions, and multivariable logistic …

Management Of Aromatase Inhibitor-Associated Bone Loss (Aibl) In Women With Hormone-Sensitive Breast Cancer: An Updated Joint Position Statement Of The Iof, Cabs, Ects, Ieg, Esceo, Ims, And Siog, Peyman Hadji, Matty Aapro, Nasser Al-Dagri, Majed Alokail, Emmanuel Biver, Jean-Jacques Body, Maria Luisa Brandi, Janet Brown, Cyrille Confavreux, Bernard Cortet, Matthew Drake, Peter Ebeling, Erik Fink Eriksen, Ghada El-Hajj Fuleihan, Theresa A Guise, Nick C Harvey, Andreas Kurth, Bente Langdahl, Willem Lems, Radmila Matijevic, Eugene Mccloskey, Rossella Nappi, Santiago Palacios, Georg Pfeiler, Jean-Yves Reginster, René Rizzoli, Daniele Santini, Sansin Tuzun, Catherine Van Poznak, Tobias De Villiers, M Carola Zillikens, Robert Coleman

Faculty, Staff and Student Publications

Background: Women with hormone-responsive breast cancer who receive adjuvant endocrine treatment with aromatase inhibitors (AI) are known to be at higher fracture risk due to a marked increase in bone resorption. In 2017, several interdisciplinary cancer and bone societies involved in the management of women with AI-associated bone loss (AIBL) published a joint position statement comprising evidence-based recommendations and a practical management algorithm for the assessment of fracture risk and optimal treatment of this patient population.

Patients and methods: In order to provide updated recommendations that reflect recent advances in the assessment and management of AIBL since publication of the …

Tert Promoter Mutations And Survival Outcomes In Adult-Type Granulosa Cell Tumors, Allison L Brodsky, Alejandra Flores Legarreta, Bryan M Fellman, Deanna Glassman, Jeffrey How, Veena Vuttaradhi, Anil K Sood, Lois Michelle Ramondetta, David Gershenson, R Tyler Hillman

Faculty, Staff and Student Publications

Objectives: To evaluate survival outcomes among patients with adult-type granulosa cell tumors who have telomerase reverse transcriptase (TERT) promoter mutations.

Methods: This is a retrospective cohort study using the MD Anderson Rare Gynecologic Malignancy Registry. Patients with adult granulosa cell tumors who underwent molecular testing for TERT promoter and FOXL2 c.C402G mutations were included. We used descriptive statistics to compare demographic and clinical variables and estimated progression-free and overall survival with Kaplan-Meier curves. Cox proportional hazards regression and log-rank tests were employed for comparisons, with multivariable analyses adjusting for various factors.

Results: Among 70 patients, 28 (40%) had TERT+ tumors. …

Ppp2r1a Mutations Portend Improved Survival After Cancer Immunotherapy, Yibo Dai, Anne Knisely, Mitsutake Yano, Minghao Dang, Emily M Hinchcliff, Sanghoon Lee, Annalyn Welp, Manoj Chelvanambi, Matthew Lastrapes, Heng Liu, Zhe Yuan, Chen Wang, Hao Nie, Stephanie Jean, Luis J Montaner, Jiakai Hou, Ami Patel, Shrina Patel, Bryan Fellman, Ying Yuan, Baohua Sun, Renganayaki Krishna Pandurengan, Edwin Roger Parra Cuentas, Joseph Celestino, Yan Liu, Jinsong Liu, R Tyler Hillman, Shannon N Westin, Anil K Sood, Pamela T Soliman, Aaron Shafer, Larissa A Meyer, David M Gershenson, David Vining, Dhakshinamoorthy Ganeshan, Karen Lu, Jennifer A Wargo, Weiyi Peng, Rugang Zhang, Linghua Wang, Amir A Jazaeri

Faculty, Staff and Student Publications

Immune checkpoint blockade (ICB) therapy is effective against many cancers, although resistance remains a major issue and new strategies are needed to improve clinical outcomes1-5. Here we studied ICB response in a cohort of patients with ovarian clear cell carcinoma-a cancer type that poses considerable clinical challenges and lacks effective therapies6-8. We observed significantly prolonged overall survival and progression-free survival in patients with tumours with PPP2R1A mutations. Importantly, our findings were validated in additional ICB-treated patient cohorts across multiple cancer types. Translational analyses from tumour biopsies demonstrated enhanced IFNγ signalling, and the presence of tertiary lymphoid structures at the baseline, …

Nature-Inspired Metaheuristics For Optimizing Dose-Finding And Computationally Challenging Clinical Trial Designs, Weng Kee Wong, Yevgen Ryeznik, Oleksandr Sverdlov, Ping-Yang Chen, Xinying Fang, Ray-Bing Chen, Shouhao Zhou, J Jack Lee

Faculty, Staff and Student Publications

Metaheuristics are commonly used in computer science and engineering to solve optimization problems, but their potential applications in clinical trial design have remained largely unexplored. This article provides a brief overview of metaheuristics and reviews their limited use in clinical trial settings. We focus on nature-inspired metaheuristics and apply one of its exemplary algorithms, the particle swarm optimization (PSO) algorithm, to find phase I/II designs that jointly consider toxicity and efficacy. As a specific application, we demonstrate the utility of PSO in designing optimal dose-finding studies to estimate the optimal biological dose (OBD) for a continuation-ratio model with four parameters …

Optimization Of Mhealth Behavioral Interventions For Patients With Chronic Lymphocytic Leukemia: The Health4cll Study, Che Young Lee, Max J Gordon, Melissa M Markofski, Emily C Lavoy, Susan K Peterson, Liang Li, Sara Fares, Miranda Baum, Margaret Pace, Danielle Walsh, Alessandra Ferrajoli, Karen Basen-Engquist

Faculty, Staff and Student Publications

Purpose: This pilot study of a diet and physical activity intervention (HEALTH4CLL) was conducted to reduce fatigue and improve physical function (PF) in patients with chronic lymphocytic leukemia (CLL).

Methods: The HEALTH4CLL study used a randomized factorial design based on the multiphase optimization strategy (MOST). Patients received diet, exercise, and body weight management instructional materials plus a Fitbit and were randomized to undergo one of 16 combinations of 4 evidence-based mHealth intervention strategies over 16 weeks. Patients' fatigue, PF, health-related quality of life, behavior changes, and program satisfaction and retention were assessed. Paired t-tests were used to examine changes in …

Film Measurements Of Kilovoltage X-Ray Percentage Depth Doses For Different Energies And Field Sizes, Tze Yee Lim, Dershan Luo, Jamshid Moradi-Kurdestany, Xin Wang, Ramesh Tailor

Faculty, Staff and Student Publications

Objectives: Kilovoltage x-ray therapy, which includes superficial x-rays and orthovoltage x-rays, is particularly suited for treatments near the skin surface. Radiation dose deposition at depth is typically characterized by percentage depth dose (PDD) curves. However, PDD data are difficult to obtain in kilovoltage x-ray therapy, hence clinics often rely on British Journal of Radiology Supplement 25 (BJR-25) archival data. This study measured PDD for different energies and field sizes on the Xstrahl 300 kilovoltage x-ray therapy unit for comparison with BJR-25 data.

Methods: We irradiated EBT3 film in water using different energy and field size combinations, then, compared the acquired …

Orp2 Regulates Free Cholesterol Accumulation In Hepatocytes During Mash, Jin Wu, Yudi Zhao, Liwen Qiu, Qiaoli Chen, Xiaowei Wang, Jingwen Gu, Yan Liang, Yingjie Zhang, Hong-Yu Wang, Yang Liu, Xiaoqin Wu, Shuai Chen, Feng-Jung Chen, Mingming Gao, Hongyuan Yang

Faculty, Staff and Student Publications

Background: Cholesterol crystals in hepatocytes are known to strongly associate with human metabolic dysfunction-associated steatohepatitis. However, it remains unclear which molecular pathway(s) regulates free cholesterol accumulation and the formation of cholesterol crystals in hepatocytes. In cultured cell lines, oxysterol-binding protein-related protein 2 (ORP2) functions to deliver cholesterol to the plasma membrane from endosomal compartments.

Methods: Here, we generated liver-specific ORP2 knockout (ORP2-LKO) mice and characterized their metabolic phenotypes on chow and high-fat diet.

Results: The ORP2-LKO mice developed much more severe hepatic steatosis than floxed control mice after high-fat diet feeding. They also demonstrated more severe liver inflammation and damage. …

Clinical And Dosimetric Considerations For Yttrium-90 Glass Microspheres Radioembolization Of Intrahepatic Cholangiocarcinoma, Metastatic Colorectal Carcinoma, And Metastatic Neuroendocrine Carcinoma: Recommendations From An International Multidisciplinary Working Group, Marnix Lam, Riad Salem, Beau Toskich, S Cheenu Kappadath, Carlo Chiesa, Kirk Fowers, Paul Haste, Joseph M Herman, Edward Kim, Thomas Leung, Siddharth A Padia, Bruno Sangro, Daniel Y Sze, Etienne Garin

Faculty, Staff and Student Publications

Purpose: The TheraSphere Global Steering Committee reconvened to review clinical data and address knowledge gaps related to treatment and dosimetry in non-HCC indications using Yttrium-90 (90Y) glass microspheres.

Methods: A PubMed search was performed. References were reviewed and adjudicated by the Delphi method. Recommendations were graded according to the degree of recommendation and strength of consensus. Dosimetry focused on a mean dose approach, i.e., aiming for an average dose over either single or multicompartment volumes of interests. Committee discussion and consensus focused on optimal patient selection, disease presentation, liver function, tumour type, tumour vascularity, and curative/palliative treatment intent for intrahepatic …

Evolution Of Esophageal Adenocarcinoma From Precursor Lesion Stem Cells, Wa Xian, Shan Wang, Jingzhong Xie, Yusuke Yamamoto, Melina Khorrami, Yanting Zhang, Raul Caballero Montes, Caycel Desales, Melika Khorrami, Zaal Mory, Ashley Hoffman, Amber Su, Crystal Nguyen, Peter J A Davies, Clifford Stephan, Shuang Pan, Wengen Wu, Yuxin Liu, Jeremy Siegelman, Rebecca E Waters, William A Ross, Shumei Song, Mark Metersky, David G Beer, Christopher P Crum, Alexander J Stewart, Matthew Vincent, Richard Russell, Robert A Izard, Khek Yu Ho, Jack Hung-Sen Lai, William W Bachovchin, Jaffer A Ajani, Frank D Mckeon

Faculty, Staff and Student Publications

Background & aims: Metastatic cancers arise from a decades-long succession of increasingly virulent precursor lesions, each of which represents prospective targets for therapeutic intervention. This evolutionary process has been particularly vivid in esophageal adenocarcinoma (EAC), as this cancer and associated precursor lesions, including Barrett's esophagus (BE), low-grade dysplasia (LGD), and high-grade dysplasia (HGD), coexist in an accessible, 2-dimensional pattern in esophageal mucosa. Given the durability of these precursor lesions, it is likely that they, like EAC, rely on stem cells for their regenerative growth. To assess the role of stem cells in the evolution of EAC, we apply technology that …

Large-Scale Genome-Wide Analyses Of Stuttering, Hannah G Polikowsky, Alyssa C Scartozzi, Douglas M Shaw, Dillon G Pruett, Hung-Hsin Chen, Lauren E Petty, Alexander S Petty, Emily J Lowther, Shu-Hsien Cho, Yao Yu, Sahar Mozaffari, Christy L Avery, Kathleen Mullan Harris, Reyna L Gordon, Janet M Beilby, Kathryn Z Viljoen, Robin M Jones, Chad D Huff, Heather M Highland, Shelly Jo Kraft, Jennifer E Below

Faculty, Staff and Student Publications

Developmental stuttering is a highly heritable, common speech condition characterized by prolongations, blocks and repetitions of speech. Although stuttering is highly heritable and enriched within families, the genetic architecture is largely understudied. We reasoned that there are both shared and distinct genetic variants impacting stuttering risk within sex and ancestry groups. To test this idea, we performed eight primary genome-wide association analyses of self-reported stuttering that were stratified by sex and ancestry, as well as secondary meta-analyses of more than one million individuals (99,776 cases and 1,023,243 controls), identifying 57 unique loci. We validated the genetic risk of self-reported stuttering …

Generation Of Human Induced Pluripotent Stem Cell Lines From An Age-Related Macular Degeneration Patient With Hyperreflective Foci Overlying Drusen (Rfsci002-A) And An Unaffected Sibling (Rfsci001-A), Adnin Ashrafi, Wendy Runyon, Sam Hu, Ritu Kumar, Timothy Catchpole, Ajeet Singh, Rinki Ratnapriya, Karl G Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Age-related macular degeneration (AMD) is a leading cause of vision loss, driven by retinal pigment epithelium (RPE) and photoreceptor degeneration. A key feature is drusen accumulation between the RPE and Bruch's membrane. In intermediate AMD, hyperreflective foci (HRF)-bright intraretinal lesions visible on optical coherence tomography (OCT) imaging-serve as biomarkers of disease progression. To study HRF mechanisms, we generated induced pluripotent stem cell (iPSC) lines from an AMD patient with HRF overlying drusen (RFSC4) and their unaffected sibling (RFSC3). These iPSC models offer a platform to explore disease mechanisms and develop therapies for AMD.

Exploring Behavioural Motivations Of Treatment Refusal In Cancer: A Q-Methodological Approach, Ruby Koyllor A. Gleeson, Nicolas H. Hart, Darren Haywood, Frank D. Baughman

Research outputs 2022 to 2026

Background: Cancer treatment refusal is known to lower survival rates and increase cancer symptoms in individuals with cancer. Behavioural motivations of treatment refusal need to be elucidated for better cancer care. Using Q-methodology, a mixed methods research approach, we explored behavioural motivations of treatment refusal in individuals diagnosed with cancer. Method: Thirty-nine individuals (n = 39; age = 49.2 ± 12.2 years) were recruited from Australia, the UK, and the USA, who had refused cancer treatment within the past decade. Participants completed an online demographic questionnaire and a Q-sort activity which required the organisation and ranking of 44 statements on …

Knowledge And Perceptions Of Modifiable Ischaemic Heart Disease Risk Among Indians: Scoping Review, Kunwar Kaur, Ma'en Zaid Abu-Qamar, Amineh Rashidi, Nilufeur Mckay, Rosemary Saunders

Research outputs 2022 to 2026

Background: Ischaemic heart disease (IHD) causes a significant number of deaths globally. India has the highest IHD burden, with cases up 138% since 1990. Individuals of Indian descent face a greater risk of early IHD and poorer long-term outcomes. Indian people typically develop IHD a decade earlier than other populations, with 52% of IHD-related deaths occurring before the age of 70, compared to 23% in Western populations. Aims: This review aims to synthesise evidence on the Indian population's knowledge and perceptions of modifiable IHD risk factors and identify literature gaps. Methods: Joanna Briggs Institute (JBI) methodology and the Preferred Reporting …

Blood Biomarkers Of Alzheimer's Disease In Australians Habitually Consuming Various Plant-Based Diets, Shaun Eslick, Grace Austin, Jessica J.A. Ferguson, Manohar L. Garg, Christopher Oldmeadow, Ralph N. Martins

Research outputs 2022 to 2026

Background: Evidence suggests that plant-based diets (PBDs) may be protective against neurodegenerative diseases such as Alzheimer's disease (AD). Objective: This study examined associations between blood-based AD biomarkers in individuals 30–75 years without current or diagnosed cardiovascular disease following different PBDs versus regular meat-eating diets (RMEs). Methods: This secondary analysis of the Plant-based Diets study measured Aβ1–42/Aβ1–40, p-tau181, NFL, and GFAP in 237 plasma samples using SIMOA from individuals following vegan, pesco-vegetarian (PVs), lacto-ovo vegetarian (LOVs), semi-vegetarian (SVs), or RME diets. Multivariable regression adjusted for age and sex. Results: Following adjustments for age and sex, plasma Aβ1–42/Aβ1–40ratio was significantly higher in …

Caring For Home Care Workers: Health And Safety Hazards, Harms And Risk Factors, Denise M. Jepsen, Sanetta Henrietta Johanna Du Toit, Toni Robyn Barker, Saul Wodak, Erin Lawn, Tash Freeburn, Josh Rhee, Carmel Laragy, Elizabeth Convery

Research outputs 2022 to 2026

Home care workers support the growing number of older adults or people with disabilities who are living at home in their own private residences. The complex and varied work health and safety (WHS) hazards these workers face on the job include both physical and psychosocial harms. While physical WHS hazards in this sector have been articulated, there is an urgent need to update, understand and address psychosocial risks such as verbal abuse and sexually inappropriate behaviour and bullying, particularly when perpetrated by clients. This study sought to identify the range of WHS hazards and harms that home care workers face …

Exercise Perceptions In People With Metabolic Dysfunction-Associated Steatotic Liver Disease: Insights From A Qualitative Study, Kedar Deshpande, John Olynyk, Oyekoya Ayonrinde, Kazunori Nosaka

Research outputs 2022 to 2026

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver condition associated with lifestyle and metabolic risk factors. While exercise is a beneficial treatment strategy, many patients struggle to implement and perform exercise regularly. It is important for practitioners to know about patient awareness, attitudes, and preferences regarding exercise in the con-text of MASLD. In this study, we examined exercise knowledge, attitudes, and exercise preferences among patients with MASLD to improve their exercise behavior changes. Methods: We conducted a questionnaire and semi-structured inter-view study in adults with MASLD to assess their disease awareness, perspectives on exercise and exercise preferences. …

Nut Intake, Functional Limitations, And Quality Of Life In Older Adults: Findings From Nhanes 2003–2012, Ilili Feyesa, Elena S. George, David Scott, Gavin Abbott, Jeew Hettiarachchi, Robin M. Daly, Jack Dalla Via, Ekavi N. Georgousopoulou, Sze Yen Tan

Research outputs 2022 to 2026

Background: Increased nut consumption has positive effects on physical and cognitive function, but whether these translate into lower functional limitations in older adults is unknown. The aim of this study was to investigate the association between nut intake, functional limitations, the severity of these limitations and health-related quality of life (HRQOL) in older adults. Methods: This cross-sectional study included data from 5807 adults (53.4% female) aged 60 years and older who participated in the US National Health and Nutrition Examination Survey (NHANES) between 2003 and 2012. Nut intake was assessed using two 24-h dietary recalls. Functional limitations were assessed using …

Ocular Changes As Potential Biomarkers For Early Diagnosis Of Alzheimer's Disease, Purna Chandra Poudel, Shaun M. Frost, Shaun Eslick, Hamid R. Sohrabi, Kevin Taddei, Eugene Hone, Ralph N. Martins

Research outputs 2022 to 2026

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. AD diagnosis often involves a thorough assessment, including clinical evaluation, cognitive testing, medical history examination, genetic testing, and biomarker analysis. Currently, the invasive nature and high costs of biomarker testing, such as cerebrospinal fluid analysis and neuroimaging, have limited the early detection and intervention of the disease. Therefore, researchers have explored cheaper and less invasive options, such as ocular imaging. This review discusses the close relationship between the eye and the central nervous system and ocular changes as a potential non-invasive AD biomarker. Ocular changes …

Endogenous Analgesia, Assessed Via Conditioned Pain Modulation, Is Not Different In People With Hip Osteoarthritis Compared To Controls: A Cross-Sectional Study, Myles C. Murphy, Molly Coventry, Ebonie K. Rio, Paola T. Chivers, Benedict Wand, Gordon Waddington, Andrea B. Mosler

Research outputs 2022 to 2026

Background: In people with knee osteoarthritis, measures of pain sensitivity have been demonstrated to relate to both pain severity and treatment outcomes, dependent on the type of pain sensitivity being tested. Objective: Quantify if differences in the pressure pain thresholds (PPT) or conditioned pain modulation (CPM) effect exist between people with hip osteoarthritis and age-matched controls without hip osteoarthritis. Methods: We performed a cross-sectional study across two geographic locations. PPTs at a local (hip) and remote (elbow) site were collected via a manual algometer. CPM was quantified using PPTs immediately prior to, and during ice water immersion of the hand …

Blood-Red And Flaming And True, Kate Gaskin

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Blood-Red and Flaming and True contains poems that explore the immense feelings of love and loss tied to the relationship between parent and child. They chronicle my experience raising a neurodivergent child, as well as undergoing infant loss and navigating a U.S. medical system that is renowned for putting women and people capable of giving birth—especially BIPOC—at greater risk than other countries with similar resources. Through poems that inhabit a variety of forms, I sift through grief and joy while attempting to tap into the sublime state that underlies extreme loss and love. Throughout, I investigate how lyric poetry is …

Determining The Attitudes And Knowledge Related To Sexual Health And Activity Related To Practitioner Action, Kelsey Alt, Callie Honaker, Abby Nichols, Jacob Greenfield, Diana Davis

Graduate Student Scholarship

Background: Research has found that many Occupational Therapy practitioners lack confidence, competence, and fear discussing sexual health and activity with their patients, despite many patients wanting to discuss the topic (Rose & Hughes, 2018). This previous knowledge leads to the purpose of this study, to determine if continuing education on topics related to sexual health and activity increases OTPs’ confidence, competence, and sense of importance in addressing this with patients (Rabathaly & Chattu, 2019). Methods: This study assessed pre- and post-data for each participant'scompleted course survey in the sequence of the continuing education class. All participants were de-identified …

Perioperative Durvalumab Plus Chemotherapy Plus New Agents For Resectable Non-Small-Cell Lung Cancer: The Platform Phase 2 Neocoast-2 Trial, Tina Cascone, Laura Bonanno, Florian Guisier, Amelia Insa, Moishe Liberman, Olivier Bylicki, Lorenzo Livi, Thomas Egenod, Romain Corre, Dong-Wan Kim, Maria Rosario Garcia Campelo, Mariano Provencio Pulla, Byoung Yong Shim, Giulio Metro, Jaafar Bennouna, Agata A Bielska, Alula R Yohannes, Yun He, Adam Dowson, Gozde Kar, Lara Mcgrath, Rakesh Kumar, Italia Grenga, Jonathan Spicer, Patrick M Forde

Faculty, Staff and Student Publications

In the phase II NeoCOAST-2 platform study, 202 patients with untreated, resectable stage IIA–IIIB non-small-cell lung cancer (NSCLC) were randomized to receive neoadjuvant durvalumab plus platinum-doublet chemotherapy with oleclumab, a CD73 inhibitor (Arm 1), or with monalizumab, a NKG2A inhibitor (Arm 2), or neoadjuvant durvalumab plus single-agent platinum chemotherapy with the TROP-2 antibody–drug conjugate (ADC) datopotamab deruxtecan (Arm 4), followed by surgical resection and adjuvant durvalumab with oleclumab or monalizumab (Arms 1 and 2) or durvalumab alone (Arm 4). Primary endpoints were pathological complete response (pCR) rate and safety; secondary endpoints included feasibility of surgery and major pathological response (mPR) …

A Phase 2 Trial Of Cpx-351 Combined With Venetoclax In Relapsed Or Refractory Acute Myeloid Leukemia, Tapan M Kadia, Wei-Ying Jen, Alex Bataller, Alexandre Bazinet, Gautam Borthakur, Elias Jabbour, Wei Qiao, Nicholas J Short, Koichi Takahashi, Ghayas C Issa, Courtney D Dinardo, Guillermo Montalban-Bravo, Naveen Pemmaraju, Andrew Tran, Vanthana Bharathi, Sanam Loghavi, Amin M Alousi, Uday Popat, Naval G Daver, Farhad Ravandi, Hagop M Kantarjian

Faculty, Staff and Student Publications

Outcomes in patients with relapsed/refractory (RR) AML are poor. We sought to investigate if CPX-531 in combination with venetoclax (CPX + VEN) was tolerable and effective in RR AML. This was a single institution phase 1b/2 trial of CPX + VEN. Patients aged ≥ 18 years with RR AML who were fit for intensive chemotherapy were eligible. Prior venetoclax exposure was allowed. The phase 1b portion followed a 3 + 3 design to identify the recommended phase 2 dose (RP2D) for the expansion cohort. At the starting dose level of −1, prolonged myelosuppression was observed, leading to dose level −2 …