Digital Commons Network^™

Tumor-Immune-Neural Circuit Disrupts Energy Homeostasis In Cancer Cachexia, Xiuhui Shi, Alex X Arreola, Zhijun Zhou, Jingxuan Yang, Mingyang Liu, Yang Cai, Yu Ren, Hao Yuan, Qun Chen, Xinjie Chen, Xinyu Yang, Yimei Meng, Jingyi Wang, Wenyi Luo, Michael C Rudolph, Rohan Varshney, Kar-Ming Fung, Chao Xu, Wei R Chen, Michael S Bronze, Lei Zheng, Yi-Ping Li, Courtney W Houchen, Yuqing Zhang, Min Li

Faculty, Staff and Student Publications

Cancer-induced cachexia and anorexia are debilitating complications across many cancers, yet effective treatments remain limited due to a poor understanding of the underlying mechanisms. Here, we identify an uncharacterized tumor-immune-neural circuit driving these syndromes, centered on growth and differentiation factor 15 (GDF15). Using genetically engineered mouse models, we find that loss of GDF15 protects against appetite loss, muscle wasting, and fat loss in pancreatic, lung, and skin cancers. Single-cell RNA sequencing reveals macrophages as a major source of GDF15, induced by tumor-derived colony-stimulating factor 1 (CSF1). GDF15 acts via the central nervous system to enhance β-adrenergic signaling in the tumor …

Community Participatory Co-Design And Development Of A Digital Diabetes Prevention Education Program For Hispanic Families With Obesity: Mixed Methods Study, Sandra Mihail, Marbelly Partida, Lizette Villanueva, Debbe Thompson, Teresia M O'Connor, Salma M Musaad, Maria J Redondo, Erica G Soltero

Children’s Nutrition Research Center Staff Publications

Background: Digital health interventions (DHIs) can extend the reach of disease prevention interventions; however, few are evidence-based, theoretically grounded, or developed for high-risk youth and families. Co-design approaches engage end users in the design and development of the DHI, which can lead to increased accessibility and engagement.

Objective: This study aimed to describe the adaptation of an evidence-based diabetes prevention program for remote, digital delivery.

Methods: The adaptation of the in-person intervention was guided by a modified Inclusive Digital Health Intervention Design to Promote Health Equity framework and conducted in collaboration with Hispanic adolescents (n=23) with obesity (BMI ≥95th percentile) …

How Does Pattern Of Bone Healing Affect The Strain Of Plate Implant Via Frequency Detection? A Biomechanical Cadaveric Study, Chavarin Amarase, Chanyaphan Virulsri, Pairat Tangpornprasert, Pisitpong Chancharoen, Saran Tantavisut

Chulalongkorn Medical Journal

Background: Detecting bone union is a crucial process in treating bone fractures to prevent complications, including implant failure and bone nonunion. Nowadays, there are many methods and new innovative devices for detecting bone union through strain measurements, such as strain gauges, fluid level displacement, contrast media, and frequency changes. There is also a trend toward increasing these methods in the future. However, the patterns of bone healing studied with these methods still do not provide a standard for determining the true bone healing process. The aim of this study is to identify the most appropriate bone healing pattern for …

Myokine Sirpα Exacerbates Kidney Disease In Diabetes, Jiao Wu, Elisa Russo, Daniela Verzola, Qingtian Li, Helena Zhang, Bhuvaneswari Krishnan, David Sheikh-Hamad, Zhaoyong Hu, William E Mitch, Sandhya S Thomas

Faculty, Staff and Students Publications

Mechanisms responsible for skeletal muscle kidney crosstalk have not been defined. We have determined that a circulating mediator, signal regulatory protein α (SIRPα), impairs intracellular insulin-mediated functions. To elucidate the effect of myokine SIRPα on diabetic kidney disease (DKD), flox mice and muscle-specific (m-specific) SIRPα-KO mice were subjected to an obesity-induced model of diabetes, high-fat diet (HFD; 60%) or insulin-deficient hyperglycemia model, streptozotocin (STZ), and were subsequently exposed to anti-SIRPα monoclonal antibodies. In the obesity-induced diabetic mice, serum SIRPα increased. Genetic deletion of muscle SIRPα protected against obesity and improved intracellular insulin signaling in muscle and adipose tissue, with reduced …

Human Papillomavirus Vaccine Perceptions Among Noncollege Young Adults And Tiktok Influencers: Qualitative Study, Amelia Burke-Garcia, Dasha Afanaseva, Erin Cutroneo, Kayla Madden, Angela Sustaita-Ruiz, Estefany Rivera Sanchez, Amy Leader

Department of Medical Oncology Faculty Papers

BACKGROUND: Human papillomavirus (HPV) vaccination is a proven and effective tool for preventing several types of cancers, yet vaccination rates among young adults remain suboptimal, particularly among those not enrolled in 4-year colleges. This population can be more difficult to reach due to fewer established institutional touchpoints, limited engagement with campus-based health services, and greater variability in access to preventive care. At the same time, social media has become a dominant source of information for young adults, with TikTok (ByteDance) emerging as one of the most widely used platforms. Approximately 41% of TikTok's users are between the ages of 16 …

The Setd2 L1609p Mutation Found In Leukemia Disrupts Methyltransferase Activity And Reduces Histone H3k36 Trimethylation, Christina Michail, Jérémy Berthelet, Ariel E Mechaly, Linh-Chi Bui, Haopeng Yang, Duo Cai, Amira Al Mahi, Aowei Xie, Valeria Bisio, Valentina Sirri, Jean-Marie Dupret, Fabien Guidez, Ximing Xu, Nicolas Joly, Leslie Regad, Mireille Viguier, Frédérique Deshayes, Nicolas Dulphy, Michael R Green, Ahmed Haouz, Fernando Rodrigues Lima

Faculty, Staff and Student Publications

SETD2 is the primary methyltransferase responsible for generating H3K36me3, an epigenetic mark that is essential for transcriptional regulation and chromatin integrity. SETD2 mutations are frequently observed in various cancers and tend to cluster within its catalytic SET domain. Despite the clinical relevance of SETD2 missense mutations in cancer, their biochemical and structural consequences remain insufficiently characterized. Here, we present the enzymatic and structural characterization of the SETD2 L1609P mutant enzyme identified in leukemia. The L1609 residue is located in the SET domain within a conserved hydrophobic pocket that is involved in substrate H3K36 recognition. Interestingly, site-directed mutagenesis of residues within …

Pain Prevalence And Pain Management At The End Of Life: Regional And Urban-Rural Differences From A National-Representative Survey Of Chinese Older Adults, Yaolin Pei, Xiang Qi, Zexi Zhou, Yifan Lou, Jing Wang, Yang Li, Bei Wu

Faculty, Staff and Student Publications

Background: Effective pain management is essential for improving quality of life at the end of life. However, challenges persist globally, particularly in China, where palliative care remains underdeveloped. This study investigates pain prevalence and the associations between pain severity, place of death, and the quality of pain management among older adults in China, with a focus on regional and urban-rural disparities.

Methods: We used data from the 2014, 2016, 2018, and 2020 waves of the China Longitudinal Aging Social Survey. The final sample included 1,525 older adults who died during the study period. We conducted OLS regression analyses to examine …

Ubiquitination Of Oncogenic Mutant P53 Via Attenuation Of Ribosome Biogenesis Machinery Effectively Inhibits Pancreatic Tumor Growth, Mudassier Ahmad, Sahir Sultan Alvi, Haider Ahsan, Carlos Perez, Andrew Massey, Vivek K Kashyap, Neeraj Chauhan, Emmanuel Anning, Manish K Tripathi, Dae J Kim, Nirakar Sahoo, Tamer Oraby, Murali M Yallapu, Mohammad Moshahid Khan, Manu M Sebastian, Subhash C Chauhan, Bilal B Hafeez

Faculty, Staff and Student Publications

Dysregulated ribosome biogenesis and p53 mutations are known to play oncogenic roles in various cancers, including pancreatic cancer. In this study, we demonstrated the therapeutic potential of BMH-21, a pharmacologic inhibitor of RNA polymerase I, against pancreatic cancer by uncovering a novel molecular mechanism involving RPA194-mediated ubiquitination of mutant p53 without affecting the ubiquitination of wild-type p53. Our key findings are that (i) BMH-21 selectively induces apoptosis and cell growth inhibition of pancreatic cancer cells with no effect on normal human pancreatic ductal epithelial cells; (ii) BMH-21 degrades RPA194; (iii) BMH-21 inhibits recruitment of both RPA194 and RPA135 on rDNA …

Tumor Radiosensitization With Gold Nanoparticles: Evolving Strategies To Improve Tumoral Gold Uptake And Catalyze Future Clinical Translation, Prapannajeet Biswal, Geraldine V Vijay, Gabrielle Krouse, Phuoc Minh Quan Mai, Bhoomika Muruvekere Lakshmisha, Sanaz Keshavarz Shahbaz, Mahdieh Yousefi Taba, Aria Sabbagh, Lydia Wt Cheung, Yuri Mackeyev, Khadijeh Koushki, Sunil Krishnan

Faculty, Staff and Student Publications

Radiation therapy is integral to the treatment regimens of over 50% of cancer patients. However, it is not biologically targeted to just the tumor, leading to adverse effects in peritumoral normal tissue. Selective uptake of gold nanoparticles (AuNPs) by tumors realizes tumor-specific radiosensitization via increased secondary electron release from high atomic number gold atoms. Here, we review AuNP-mediated radiosensitization and outline strategies to optimize tumor-targeted AuNP delivery. Modifying the physicochemical characteristics of AuNPs, including size, shape, charge, and surface chemistry, can increase their ability to evade the reticuloendothelial system (RES) and penetrate the dense tumor stromal architecture, thereby promoting tumor …

The Heart’S Hidden Influencer: Epicardial Adipose Tissue In The Pathogenesis Of Heart Failure, Aobo Li, Avilash Mondal, Jianli Zhao, John Zhang, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

Abstract – Heart failure (HF) is a complex, multifactorial clinical syndrome with diverse etiologies and phenotypic manifestations, affecting millions of people globally. HF is broadly classified into 3 subtypes: HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction. Each subtype exhibits distinct pathophysiological mechanisms, clinical trajectories, and therapeutic responses, posing significant challenges in terms of diagnosis and management. Epicardial adipose tissue (EAT), a metabolically active visceral fat depot situated in close proximity to the myocardium, plays a dual role in physiological and pathological states, offering potential utility as a biomarker and therapeutic …

Nci-Designated Cancer Centers' Policies And Practices With Regard To Alcohol And Cancer: A Call To Lead, Ernest T Hawk, Stephanie L Martch, Meghan Si, Sanjay Shete

Faculty, Staff and Student Publications

Background: Alcohol, a known carcinogen since 1988, increases risk of cancers of the mouth, pharynx, larynx, esophagus, liver, breast, and colorectum. More than one half of US adults consume alcohol whereas about two thirds are unsure whether or unaware that alcohol intake is linked to cancer risk.

Methods: Our objective was to survey awareness, beliefs, intentions, policies, practices, and goals/perceived responsibilities related to establishing/promoting actions to reduce alcohol-related cancer risks from leaders of 72 NCI-Designated Cancer Centers.

Results: Sixty-one percent responded. Forty-three percent either believed in or were uncertain about alcohol's purported health benefits. Nevertheless, 86% considered it part of …

Cd8+ T Cells In The Tumor Microenvironment Modulate The Response To Endocrine Therapy In Breast Cancer, Fabiana Napolitano, Yunguan Wang, Dhivya R Sudhan, Paula I Gonzalez-Ericsson, Luigi Formisano, Nisha Unni, Shahbano Shakeel, James Z Zhu, Khushi Ahuja, Lei Guo, María Rosario Chica-Parrado, Yuki Matsunaga, Pamela Luna, Chang-Ching A Lin, Yasuaki Uemoto, Kyung-Min Lee, Hongli Ma, Nathaniel J Evans, Alberto Servetto, Saurabh Mendiratta, Spencer D Barnes, Roberto Bianco, Yisheng V Fang, Lin Xu, Jeon Lee, Tao Wang, Justin M Balko, Gordon B Mills, Marilyne Labrie, Ariella B Hanker, Carlos L Arteaga

Faculty, Staff and Student Publications

The role of the tumor immune microenvironment (TIME) in modulating responses to antiestrogen therapy in hormone receptor-positive (HR+) breast cancers remains unclear. We analyzed pre- and on-treatment biopsies from patients with HR+ breast cancer treated with letrozole to induce estrogen deprivation (ED). Stromal tumor-infiltrating lymphocytes, assessed by H&E staining, and immune-related gene sets, including IFN-γ signaling genes, measured by RNA-Seq, were increased in ED-resistant tumors. Cyclic immunofluorescence and spatial transcriptomics revealed an abundance of CD8+ T cells and enhanced antigen processing and immune gene signatures in ED-resistant tumors. In this group, the expression of CXCL9, CXCL10, and CXCL11 - chemokine …

Osimertinib Activates A Tgf-Β2-Dependent Secretory Program That Drives Lung Adenocarcinoma Progression, Madhurima Ghosh, Chao Wu, Abhishek Kumar, Monique Nilsson, John V Heymach, Weina Zhao, Jiang Yu, Xin Liu, Na Ding, Shike Wang, Guan-Yu Xiao, Angelo Chen, Kate Grimley, William K Russell, Chad J Creighton, Xiaochao Tan, Jonathan M Kurie

Faculty, Staff and Student Publications

EGFR-mutant lung adenocarcinomas (LUADs) that are vulnerable to the EGFR antagonist osimertinib (Osi) eventually relapse, owing in part to the emergence of drug-tolerant persister (DTP) cells that arise through epigenetic mechanisms. Intratumoral DTP cells can herald a worse clinical outcome, but the way in which DTP cells influence LUAD progression remains unclear. Osi-resistant (OR) cells exhibit typical DTP cell features, including a propensity to undergo senescence and epithelial-mesenchymal transition (EMT), which can activate heightened secretory states. Therefore, we postulated that OR cells influence LUAD progression through paracrine mechanisms. To test this hypothesis, we utilized congenic pairs of EGFR-mutant LUAD cell …

Lysine Demethylase 4a (Kdm4a) Maintains Basal Body Architecture And Protects Against Ciliary Destabilization, Manga Motrapu, Lindsey Hudson, Pratim Chowdhury, Xiaoli Wang, Yuya Nakatani, Sofia Vargas-Hernandez, Sung Y Jung, Menuka Karki, Cheryl Walker, Anna-Karin Gustavsson, Ruhee Dere

Faculty, Staff and Students Publications

Primary cilia are sensory organelles essential for signaling and defects in formation, maintenance or structure underlie diverse ciliopathies. Here, we identify lysine demethylase 4A (KDM4A) as a previously unrecognized mediator of ciliogenesis. Using genetic depletion and pharmacologic inhibition, we show that KDM4A is required for cilia assembly and maintenance. Super-resolution imaging reveals KDM4A localization at the basal body, where it distinctively wraps around the centrioles. We uncover a direct interaction between KDM4A and Rootletin (CROCC), a structural protein mediating centriole cohesion, and demonstrate that KDM4A loss increases inter-centriolar distances, implicating basal body architecture in ciliary failure. Together, these findings define …

Patient, Family And Clinician Priorities For Critical Care Research In Asia And Africa: A James Lind Alliance Priority Setting Partnership Using Modified Delphi And Nominal Group Techniques, Ccaa Priority Setting Partnership Steering Group, Teddy Abonyo, Sumaiya Arfin, Diptesh Aryal, Abi Beane, Martina Borellini, Arjen Dondorp, Emma Donley, Punam Gautam, Tiffany Gooden

Anaesthesiology, East Africa

Background This James Lind Alliance (JLA) Priority Setting Partnership aimed to identify and prioritise unanswered questions important to adult patients, their families and health professionals with lived experience of critical care across Asia and Africa.

Methods Modified Delphi techniques were used to generate suggestions using an online survey. Following verification, literature review and content analysis, these suggestions were iteratively codified into emergent topics. Topics were presented in a second online survey for ranking, prior to an online workshop where nominal group technique was used to identify top priority questions across stakeholder groups. Surveys were disseminated using snowballing techniques.

Findings The …

Total Hip Replacement Eras, Children's Mercy Kansas City

Clinical Pathways

No abstract provided.

“Now That The Baby Is Out, I Can Be Vaccinated”: A Qualitative Study On Covid-19 Vaccine Hesitancy In Pregnant Women In Kilifi, Kenya, Angela Koech, Onesmus Wanje, Grace Mwashigadi, Geoffrey Katana, Richmond Mdindi, Peter Mwangome, Rachel Craik, Marianne Vidler, Mai-Lei Kinshella, Marleen Temmerman

Centre of Excellence in Women and Child Health

COVID-19 vaccines are safe and effective in pregnancy, but vaccine hesitancy limits uptake and effectiveness. This study explored COVID-19 vaccine hesitancy in pregnancy in Kilifi, coastal Kenya, to elicit reasons for vaccine hesitancy and acceptance, and to compile misconceptions around vaccination in pregnancy. Twenty-three in-depth interviews were conducted with pregnant women, mothers who had given birth in the previous 2 years and health workers (community health promoters, nurses, and supervisors). Data were analyzed using thematic template analysis based on the Vaccine Hesitancy Determinants Matrix. Concern about vaccine safety for the unborn baby was a major driver of hesitancy. Many pregnant …

Qualitative Exploration Of Factors Associated With Covid-19 Vaccination Among Pregnant Women In Kenya, Violet Naanyu, Ferdinand Okwaro, Ingrid Gichere, Mandeep Sura, Prachi Singh, Berhaun Fesshaye, Marleen Temmerman

Centre of Excellence in Women and Child Health

The COVID-19 pandemic significantly disrupted societies worldwide, and COVID-19 vaccination has been identified as instrumental in the fight against the pandemic. While studies have examined uptake of COVID-19 vaccination, more research is needed to gain a better understanding of the factors influencing pregnant women’s decisions to get vaccinated. In this study, we used a cross-sectional descriptive qualitative study to explore the attitudes, beliefs, and behaviors related to COVID-19 vaccination during pregnancy in Kenya. A total of 50 in-depth interviews were conducted between October 2023 to March 2024 with a purposively drawn sample of 25 pregnant and 25 postpartum women during …

Can Tanzanian Neurosurgeons Access Tanzanian Neurosurgical Literature? A Systematic Review And Survey Of Neurosurgical Publications, Romani R. Sabas, Julie Woodfield, Chibuikem Anthony Ikwuegbuenyi, Magalie Cadieux, Consolata Shayo, Zarina Shabhay, Happiness Rabiel, Beverly Cheserem, Joel Bwemelo, Drew N. Wright

General Surgery, East Africa

Background and Objectives: Free and open access to research data and findings promotes equity in access to healthcare knowledge and equity in patient care and treatment. To benefit the health care of the population studied, research findings must be accessible to clinicians, academics, and policymakers serving those populations. The aim of this study was to assess the extent of published Tanzanian neurosurgical data and its accessibility to those practicing within the country.

Methods: A systematic review of all published neurosurgical studies from Tanzania was conducted. Authorship, funding, and open-access status were recorded. Tanzanian neurosurgeons were surveyed by telephone or in …

Controlled Antibiotic Release From Emulsion-Loaded Alginate And Fibrin Hydrogels Using Ultrasound, Ziba Ghareh Nazi Fam, Asia Winslow, Mario Fabiilli, Sam Varghese, Brian Oeffinger, Flemming Forsberg, Noreen Hickok, Lauren Delaney

Department of Radiology Faculty Papers

Postoperative infections remain a major complication after spinal fusion surgery, often caused by biofilm-forming bacteria that resist short-term antibiotic prophylaxis. Vancomycin (VAN) is sometimes delivered locally during surgery; however, levels diminish rapidly, leaving patients vulnerable to late-onset infections. We developed a composite hydrogel integrating perfluorohexane-based emulsions within alginate or fibrin matrices to enable both sustained and ultrasound-triggered VAN release. Water-in-oil-in-water emulsions were prepared using fluorosurfactant-stabilized perfluorohexane as the volatile oil phase, then embedded in hydrogels and exposed to ultrasound (2.5 MHz, 5.5 MPa peak negative pressure) to initiate acoustic droplet vaporization for triggered release. Drug release was quantified spectrophotometrically and …

Investigation Of Teratogenic Concerns In The Coronavirus Disease Of 2019 Era, Kate Richardson, Emily C Daykin, Kathleen Shields, S Shahrukh Hashmi, Lorrie Harris-Sagaribay, Molly Daniels, Myla Ashfaq

Faculty, Staff and Student Publications

Background: MotherToBaby (MTB) is a teratogen information service that provides information about exposures during pregnancy and breastfeeding to the public and healthcare providers. During the Coronavirus Disease of 2019 (COVID-19) pandemic, MTB received an influx of queries regarding the teratogenicity of the virus and the vaccine. The purpose of this study was to assess the frequency and type of exposures asked about prior to the onset of the COVID-19 pandemic through March 2022 and to evaluate the demographics of individuals who made inquiries.

Methods: Data from MTB contacts (2018-2022) were accessed through a data-sharing agreement. The data were cleaned and …

Acta2 Pathogenic Variants Activating Heat Shock Factor 1 And Increasing Cholesterol Biosynthesis In Smooth Muscle Cells Predispose To Early Onset Atherosclerosis, Maura L Boerio, Abhijnan Chattopadhyay, Xue-Yan Duan, Aamuktha Karla, Ernesto Calderon Martinez, Amelie Pinard, Andrew K Morse, Darshan Reddy, Sree Dharma, Walter Velasco-Torrez, Julien Marcadier, Siddharth K Prakash, Sherene Shalhub, Julie De Backer, Richmond Jeremy, Shaine A Morris, Anji T Yetman, Alan C Braverman, Dianna M Milewicz

Faculty, Staff and Student Publications

Background: ACTA2 pathogenic variants predispose to thoracic aortic disease, and a subset of variants lead to early onset atherosclerotic cardiovascular disease (ASCVD). The molecular pathway linking misfolded SMA (α-smooth muscle actin) monomers to augmented atherosclerosis-associated smooth muscle cell phenotypic modulation can be modeled in vitro by stably expressing the ACTA2 p.R149C variant in Acta2-/- smooth muscle cells.

Methods: The Montalcino Aortic Consortium patient registry was used to identify cases with ACTA2 pathogenic/likely pathogenic missense variants. These patients were surveyed, and medical records were reviewed, to identify cases with early onset ASCVD. The variants for these cases, as well as …

Presenilin L166p Mutation, A Model Of Familial Alzheimer's Disease, Leads To Early Onset Bone Loss, Vidyani Suryadevara, Connor J Krehbial, Anuradha K Valiya, Melinda Vang, Julian Balanta-Melo, Pierre P Eleniste, Sumana Posritong, Jung Min Hong, Katie Chester, Gabriel M Pagnotti, Teresita Bellido, Monte S Willis, Angela Bruzzaniti

Faculty, Staff and Student Publications

Accelerated bone loss has been reported in the early stages of Alzheimer's disease (AD) as indicated by reduced bone mineral density and increased fracture risk in these patients, compared to healthy individuals. In the present study, we investigated bone loss in mouse models of familial Alzheimer's disease harboring the Presenilin 1 (L166P) knock-in mutation (PSEN1 KI), with or without the human amyloid precursor protein transgene (hAPP Tg+) known to induce brain amyloid pathology by 6 months. Female and not male 12-month PSEN1/hAPP Tg+ mice exhibited reduced whole-body bone mineral density and bone mineral content, compared to sex-matched controls. Consistent with …

Cardiometabolic Indicators Of Cognitive Impairment In The Cameron County Hispanic Cohort, Fadi I Musfee, Seema Agarwal, Vahed Maroufy, Chelsea Liu, Joseph B Mccormick, Susan Fisher-Hoch, Sean I Savitz

Faculty, Staff and Student Publications

Background

Objective

Methods

Decellularized Extracellular Matrix Scaffolds To Engineer The Dormant Landscape Of Microscopic Colorectal Cancer Liver Metastasis, Sabrina N Vandenheuvel, Lucia L Nash, Abigail J Clevenger, Claudia A Collier, Oscar R Benavides, Sanjana Roy, Brinlee Goggans, Aelita Salikhova, Anvitha Tharakesh, Svasti Haricharan, Amber N Stratman, Scott Kopetz, Alex J Walsh, Shreya A Raghavan

Faculty, Staff and Student Publications

Recurrent liver-metastatic colorectal cancer contributes to high mortality. Recurrence occurs when dormant, microscopic residual disease survives initial treatment to escape dormancy. In their dormant, microscopic state within the liver, these metastatic lesions are undetectable by clinical diagnostic imaging until they form overt, chemoresistant metastases. Therefore, understanding the molecular mechanisms underlying dormancy in colorectal cancer liver metastases is a significant knowledge gap, motivating the engineering of nuanced in vitro models of disease. The current work presents an engineered model of liver-metastatic colorectal cancer dormancy. Decellularized extracellular matrix (dECM) scaffolds are used to provide microscopic colorectal cancer cell clusters with a biomimetic, …

Melody: Mediation Analysis In Logistic Regression For High-Dimensional Mediators And A Binary Outcome, Sunyi Chi, Xingyu Li, Peng Wei, Xuelin Huang

Faculty, Staff and Student Publications

Mediation analysis is a pivotal tool for elucidating the indirect effect of an environmental factor or treatment on disease through potentially high‐dimensional omics data, such as gene expression profiles. However, traditional mediation analysis methods tailored for binary outcomes often rely on the rare disease assumption in logistic regression and provide inadequate measures of total mediation effect when multiple mediators have effects in different directions. In this paper, we develop a MEdiation analysis framework in LOgistic regression for high‐Dimensional mediators and a binarY outcome (MELODY). It leverages a second‐moment‐based measure analogous to the ��2 for linear models to quantify the total …

Investigating The Oxygen Dependence Of Flash-Rt Using Electron Paramagnetic Resonance Imaging, Trey Waldrop, Grace Murley, Brett Velasquez, Elise Konradsson, Denae Neill, Luke Connell, Alan Lopez Hernandez, Abagail Delahoussaye, F William Schuler, Jorge De La Cerda, Ziyi Li, Mark D Pagel, Emil Schüler

Faculty, Staff and Student Publications

Purpose: The FLASH effect occurs when radiation given at ultra-high dose rates spares healthy tissue while achieving isoeffective tumor control relative to conventional (CONV) dose rate irradiation. Limited data has implicated oxygen in the FLASH effect. This study investigated the effect of tissue oxygen tension (pO2) on gastrointestinal (GI) FLASH sparing in mice.

Methods: pO2 was quantified in vivo by electron paramagnetic resonance imaging (EPRI)- noninvasive oximetry through spin probe injection and magnetic resonance co-registration- and a phosphorescent quenching microsensor. B6(Cg)-Tyrc-2 J/J female mice were imaged while breathing 10%, 21%, and 95% oxygen. C57BL/6 mice of both sexes underwent microsensor …

Design And Implementation Of An Aapm Volunteer Database For Advancing Global Medical Physics Initiatives., Teh Lin, Minsun Kim, Courtney Morrison, Jiahan Zhang, Kevin Little, Yan-Hong Xin, Michael Woodward, Peter Sandwall, Eun Young Han

Oncology Articles

PURPOSE: The purpose of this study is to assess American Association of Physicists in Medicine (AAPM) members' availability to volunteer, share their expertise, and promote global collaboration in medical physics by partnering with international colleagues who seek support in strengthening their medical physics practice.

METHODS: The questionnaire was administered to AAPM members to assess their willingness to volunteer, preferred engagement modalities, and availability for different types of volunteer activities. The questionnaire was integrated into the AAPM member profile and covered therapy, diagnostic, and nuclear medicine disciplines, capturing participants' visiting preferences and expertise in teaching and training. Respondents were categorized based …

Acute Otitis Media: Antibiotic Length, Children's Mercy Kansas City

Clinical Critically Appraised Topics

No abstract provided.

Ubiquitination Of Oncogenic Mutant P53 Via Attenuation Of Ribosome Biogenesis Machinery Effectively Inhibits Pancreatic Tumor Growth, Mudassier Ahmad, Sahir Sultan Alvi, Haider Ahsan, Carlos Perez, Vivek Kashyap, Neeraj Chauhan, Dae Joon Kim, Nirakar Sahoo, Tamer Oraby, Murali Yallapu, Subhash Chuahan, Bilal Hafeez

School of Medicine Publications

Dysregulated ribosome biogenesis and p53 mutations are known to play oncogenic roles in various cancers, including pancreatic cancer. In this study, we demonstrated the therapeutic potential of BMH-21, a pharmacologic inhibitor of RNA polymerase I, against pancreatic cancer by uncovering a novel molecular mechanism involving RPA194-mediated ubiquitination of mutant p53 without affecting the ubiquitination of wild-type p53. Our key findings are that (i) BMH-21 selectively induces apoptosis and cell growth inhibition of pancreatic cancer cells with no effect on normal human pancreatic ductal epithelial cells; (ii) BMH-21 degrades RPA194; (iii) BMH-21 inhibits recruitment of both RPA194 and RPA135 on rDNA …