Digital Commons Network^™

A New Multiple Imputation Method For High-Dimensional Neuroimaging Data, Tong Lu, Peter Kochunov, Chixiang Chen, Hsin-Hsiung Huang, L Elliot Hong, Shuo Chen

Faculty, Staff and Student Publications

Missing data are a prevalent challenge in neuroimaging, with significant implications for downstream statistical analysis. Neglecting this issue can introduce bias and lead to erroneous inferential conclusions, making it crucial to employ appropriate statistical methods for handling missing data. Although the multiple imputation is a widely used technique, its application in neuroimaging is severely hindered by the high dimensionality of neuroimaging data, and the substantial computational demands. To tackle the critical computational challenges, we propose a novel approach, High dimensional Multiple Imputation (HIMA), based on Bayesian models specifically designed for large-scale neuroimaging datasets. HIMA introduces a new computational strategy to …

Selected Social And Lifestyle Correlates Of Brain Health Markers: The Cross-Cohort Collaboration Consortium, Leslie Grasset, Joshua C Bis, Stefan Frenzel, Daniel Kojis, Jeannette Simino, Amber Yaqub, Alexa Beiser, Claudine Berr, Jan Bressler, Robin Bülow, Charles S Decarli, Alison E Fohner, Laura B Harrington, Catherine Helmer, M Arfan Ikram, Rozenn N Lemaitre, Oscar L Lopez, W T Longstreth, Julia Neitzel, Michelle C Odden, Priya Palta, Carsten O Schmidt, Rajesh Talluri, Meike W Vernooij, Henry Völzke, Trudy Voortman, Quest Whalen, Katharina Wittfeld, Hans J Grabe, Thomas H Mosley, Bruce M Psaty, Frank J Wolters, Sudha Seshadri, Carole Dufouil

Faculty, Staff and Student Publications

Introduction: To investigate the associations of education level, marital status, and physical activity with dementia risk and brain MRI markers.

Methods: Data from six community-based samples from the Cross-Cohort Collaboration Consortium were analyzed. Self-reported education level, marital status, and physical activity at age 60 to 75 years were harmonized. Subsamples of participants with brain MRI markers at time of exposure were selected. Associations with dementia risk and cross-sectional MRI markers were meta-analyzed.

Results: Higher education level was associated with lower dementia risk (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.59; 0.72 vs low level) but not significantly …

Differentiation Stage Predicts Radiosensitivity In Mesenchymal-Like Pancreatic Cancer, Tingshi Su, Xinjian Yu, Mojtaba Hoseini-Ghahfarokhi, David B Flint, Scott J Bright, Joana I D S Antunes, David K J Martinus, Mandira Manandhar, Mariam Ben Kacem, Poliana C Marinello, Eurico J G Pereira, Hua-Sheng Chiu, Uwe Titt, David R Grosshans, Jan Schuemann, Henning Willers, Harald Paganetti, Pavel Sumazin, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Purpose: To derive a genomic classifier to predict radiosensitivity of pancreatic cancer cell lines and patients with pancreatic cancer to allow genomic-guided radiation therapy.

Methods and materials: We collected a comprehensive data set of full clonogenic cell survival curves of 45 pancreatic cancer cell lines irradiated with clinical photon and proton beams. We derived classifiers based on data from human embryonic and fetal pancreas single-cell RNA-sequencing to distinguish between epithelial and mesenchymal cells and to predict pancreas cell-line differentiation stage. Independent testing was done with an embryonic mouse pancreas single-cell RNA-sequencing data set. We then used bulk RNA-seq profiles from …

Fogarty-Funded Research Ethics Education In Latin America And The Caribbean: Progress Despite Ongoing Challenges, Timothy Daly, Ignacio Mastroleo, Luis L García Valiña, Irene Melamed, María Florencia Santi, Theresa J Ochoa, Manuela Fernández Pinto, Paul J Cummins, Bernardo García Camino, Cheryl Macpherson, Elizabeth Heitman, Florencia Luna

Faculty, Staff and Student Publications

Ten years have passed since the last regional assessment of the state of Fogarty International Center-funded research ethics education and challenges facing research ethics in Latin America and the Caribbean basin. Program directors and faculty from four international research ethics education programs met in Spring 2024 to discuss their progress, challenges, and future priorities. The themes that emerged from these discussions were the structural difficulties faced by regional ethicists, the use of pedagogical innovations to mitigate different barriers faced by fellows, and the need to anticipate future challenges for the region including climate change.

Oral Decitabine Cedazuridine With And Without Venetoclax In Higher-Risk Myelodysplastic Syndromes Or Chronic Myelomonocytic Leukemia: A Propensity Score-Matched Study, Alex Bataller, Koji Sasaki, Samuel Urrutia, Guillermo Montalban-Bravo, Alexandre Bazinet, Kelly Chien, Danielle Hammond, Ian M Bouligny, Mahesh Swaminathan, Ghayas Issa, Nicholas Short, Naval Daver, Courtney D Dinardo, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gail J Roboz, Michael Savona, Elizabeth A Griffiths, James Mccloskey, Olatoyosi Odenike, Aram Oganesian, Harold N Keer, Mohammad Azab, Hagop Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Hypomethylating agents (HMA) are indicated in the treatment of higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The combination of hypomethylating agents with venetoclax (Ven) has demonstrated promising results in these diseases, although randomized clinical trials are needed for validation. In this retrospective study, we compared two matched cohorts of patients with MDS or CMML: one receiving oral decitabine-cedazuridine (DEC-C, n = 73) and one receiving DEC-C and Ven (DEC-C-Ven, n = 51), in three contemporary clinical trials. The aim is to determine the impact of the addition of Ven to HMA in MDS and CMML. Individuals were matched …

Walking Interventions And Cognitive Health In Older Adults: A Systematic Review Of Randomized Controlled Trials, Jongwon Lee, Delia West, Christine Pellegrini, Jingkai Wei, Sara Wilcox, Jean Neils-Strunjas, A Caroline Rudisill, Daniela B Friedman, David X Marquez, Jenna Dzwierzynski, Joyce Balls-Berry, Rachelle Gajadhar, Chih-Hsiang Yang

Faculty, Staff and Student Publications

ObjectiveThis systematic review summarizes the effectiveness and the dose of walking interventions on specific cognition domains in older adults, including executive function, memory, attention, processing speed, and global cognition.Data sourcePublished randomized controlled trials in PubMed, Embase, and Web of Science until 10 May 2023.Study Inclusion and Exclusion CriteriaStudies include older adults without Alzheimer's or related dementias, involving a walking intervention and performance-based neuropsychological assessments for executive function, memory, processing speed, attention, or global cognition.Data ExtractionTwo independent research assistants reviewed 8424 studies and included 17 studies.Data SynthesisParticipant demographics, intervention features (type, intensity, time, frequency, duration, format, and context), cognitive assessment tools, …

The Influence Of Tobacco Use, Hazardous Drinking, And Other Risk Factors On Hpv-Associated Oropharyngeal Cancer Risk And Screening Perceptions Among Gay And Bisexual Men: A Cross-Sectional Study, I Niles Zoschke, Sarah L Bennis, Yi Tang, J Michael Wilkerson, Cynthia L Stull, Alan G Nyitray, Samir S Khariwala, C Mark Nichols, B R Simon Rosser, Charlene A Flash, Michael W Ross

Faculty, Staff and Student Publications

Background: Oropharyngeal cancer is the eighth most common cancer among US men and its incidence is sharply rising. Oropharyngeal cancer manifests in two major ways: the classic form is prevalent among people who use alcohol and tobacco heavily, while a growing subset of incident cases is associated with human papillomavirus-16 (HPV) and transmitted via oral sex. Gay and bisexual men appear at higher risk for each etiologic subset of oropharyngeal cancer than heterosexual men. We conducted a cross-sectional study to learn how tobacco use, hazardous drinking, and other key risk factors affect gay and bisexual men's perceptions of oropharyngeal cancer …

Cytosimplex: Visualizing Single-Cell Fates And Transitions On A Simplex, Jialin Liu, Yichen Wang, Chen Li, Yichen Gu, Noriaki Ono, Joshua Welch

Faculty, Staff and Student Publications

Summary: Cells differentiate to their final fates along unique trajectories, often involving multi-potent progenitors that can produce multiple terminally differentiated cell types. Recent developments in single-cell transcriptomic and epigenomic measurement provide tremendous opportunities for mapping these trajectories. The visualization of single-cell data often relies on dimension reduction methods such as UMAP to simplify high-dimensional single-cell data down to an understandable 2D form. However, these dimension reduction methods are not constructed to allow direct interpretation of the reduced dimensions in terms of cell differentiation. To address these limitations, we developed a new approach that places each cell from a single-cell dataset …

Dissemination And Implementation Approach To Increasing Access To Local Pre-Exposure Prophylaxis (Prep) Resources With Black Cisgender Women: Intervention Study With Vlogs Shared On Social Media, Mandy J Hill, Laurenia Mangum, Sandra J Coker, Tristen Sutton, Diane M Santa Maria

Faculty, Staff and Student Publications

Background: Black cisgender women account for only 2% of pre-exposure prophylaxis (PrEP)-eligible people in the United States who use PrEP to prevent HIV. Owing to the low PrEP use, Black cisgender women continue to contract HIV more frequently than women from every other racial group. Intervention efforts that can bridge the link between knowing that PrEP prevents HIV and support with access to PrEP are necessary for Black cisgender women.

Objective: The purposes of the vlogs through the campaign were to share information about ways to prevent HIV using PrEP and fact-based education and provide access to PrEP resources with …

Sitc Strategic Vision: Prevention, Premalignant Immunity, Host And Environmental Factors, Sasha E Stanton, Kristin G Anderson, Tullia C Bruno, Christian M Capitini, Mary L Disis, Jennifer Mcquade, Laszlo Radvanyi, Claire Vanpouille-Box, Jennifer Wargo, Kelly J Baines, Megan M Y Hong, Adnan Rajeh, Raymond H Kim, Phillip Awadalla, Lauren K Hughes, Saman Maleki Vareki

Faculty, Staff and Student Publications

Cancer immunotherapy has improved the survival of a subset of patients by harnessing the power of the immune system to find and destroy malignant cells. The immune system also protects the host by destroying developing premalignant and malignant tumors. Advancing our knowledge of premalignant immunity and immune changes seen in lesions that develop into invasive cancer versus those that regress offers an exciting opportunity to leverage the immune system for immune prevention and immune interception of premalignancy. Understanding the immune environment of premalignant lesions and how chronic inflammation plays a central role in the evolution of premalignancy is essential for …

Association Of Parental Oral Health Knowledge And Self-Efficacy With Early Childhood Caries And Oral Health Quality Of Life In Texas Schoolchildren, Shreela V Sharma, Jeanette E Deason, Mengxi Wang, Alejandra Garcia-Quintana, Ru-Jye Chuang, Kila Johnson, Shalisa Garner, Steven Kelder, Jose-Miguel Yamal

Faculty, Staff and Student Publications

Improving children's oral health is a national priority. Parental knowledge and self-efficacy influence children's health behaviors; however, the relationship between parental oral health-related knowledge, self-efficacy, child oral health-related quality of life (OHQoL), and dental caries remains unclear, especially among low-income, ethnically diverse U.S. families. This study assesses the relationship between parental oral health-related knowledge, self-efficacy, child dental caries, and OHQoL. This cross-sectional seco ndary analysis uses baseline data from a school-based cluster-randomized controlled trial among children (kindergarten-second grade). Dental assessments were conducted using the International Caries Detection and Assessment System (ICDAS) on site in schools at baseline (n = 34 …

Reducing Clinical Trial Eligibility Barriers For Patients With Mds: An Icmds Position Statement, Uma Borate, Kelly Pugh, Allyson Waller, Rina Li Welkie, Ying Huang, Jan Philipp Bewersdorf, Maximilian Stahl, Amy E Dezern, Uwe Platzbecker, Mikkael A Sekeres, Andrew H Wei, Rena J Buckstein, Gail J Roboz, Michael R Savona, Sanam Loghavi, Robert P Hasserjian, Pierre Fenaux, David A Sallman, Christopher S Hourigan, Matteo Giovanni Della Porta, Stephen Nimer, Richard F Little, Valeria Santini, Fabio Efficace, Justin Taylor, Guillermo Garcia-Manero, Olatoyosi Odenike, Tae Kon Kim, Stephanie Halene, Rami S Komrokji, Elizabeth A Griffiths, Peter L Greenberg, Mina L Xu, Zhuoer Xie, Rafael Bejar, Guillermo F Sanz, Mrinal M Patnaik, Maria Figueroa, Hetty E Carraway, Omar Abdel-Wahab, Daniel Starczynowski, Eric Padron, Jacqueline Boultwood, Steven Gore, Naval G Daver, Jane E Churpek, Ravindra Majeti, John M Bennett, Alan F List, Andrew M Brunner, Amer M Zeidan

Faculty, Staff and Student Publications

Excessively restrictive inclusion and exclusion criteria in clinical trials are one of many barriers to clinical trial enrollment for patients with myelodysplastic syndromes/neoplasms (MDSs). Many organizations are developing efforts to increase clinical trial eligibility; yet, several recent publications focused on patients with MDS suggest that many patients with this disease may be excluded from clinical trials unnecessarily. Clinical trial eligibility should reflect the phase of the study and risks of the agent being studied. Phase 3 trials should be less restrictive than early-phase trials to represent the real-world population as closely as possible. We hypothesize that many clinical trials, particularly …

Bh3 Mimetics Augment Cytotoxic T Cell Killing Of Acute Myeloid Leukemia Via Mitochondrial Apoptotic Mechanism, Kapil Saxena, Shao-Hsi Hung, Esther Ryu, Shailbala Singh, Qi Zhang Tatarata, Zhihong Zeng, Zhe Wang, Marina Y Konopleva, Cassian Yee

Faculty, Staff and Student Publications

Adoptive cell therapy (ACT) can address an unmet clinical need for patients with relapsed/refractory acute myeloid leukemia (AML), but its effect is often modest in the setting of high tumor burden. In this study, we postulated that strategies to lower the AML apoptotic threshold will augment T cell killing of AML cells. BH3 mimetics, such as venetoclax, are a clinically approved class of compounds that predispose cells to intrinsic apoptosis by inhibiting anti-apoptotic mitochondrial proteins. We explored the anti-leukemic efficacy of BH3 mimetics combined with WT1-specific CD8+ T cells on AML cell lines and primary samples from patients with a …

Β-Catenin Drives The Foxc2-Mediated Epithelial-Mesenchymal Transition And Acquisition Of Stem Cell Properties, Maria Castaneda, Petra Den Hollander, Steve Werden, Esmeralda Ramirez-Peña, Suhas V Vasaikar, Nick A Kuburich, Claire Gould, Rama Soundararajan, Sendurai A Mani

Faculty, Staff and Student Publications

Background: Aggressive forms of breast cancer, such as triple-negative breast cancer (TNBC), are associated with an increase in cancer cells that exhibit stem cell properties. The activation of the epithelial-mesenchymal transition (EMT) program, mediated by the transcription factor FOXC2, generates these stem-like cells. FOXC2 is linked to poor prognoses across various cancer types and is notably upregulated in TNBC, where it establishes and sustains these stem-like cells within the tumor population.

Methods: Here, we decode the pathways regulating FOXC2 activation using EMT-enriched cell line models. Stemness was assessed using mammosphere assays and mesenchymal markers by western blot. Expression …

Developmental Differentiation Of Mouse Inner Ear Neuron Subpopulations Resolved With A Peripherin-Promoter Reporter Within The Grm8 Locus, Lily J Pearson, Jeremy L Pinyon, Jennie M E Cederholm, Georg Von Jonquieres, Florence Bartlett, Xabier Vázquez-Campos, Fabien Delerue, Lars M Ittner, Gary D Housley

Faculty, Staff and Student Publications

Molecular profiling of inner ear neurons has broadened the classification of the primary afferents that support neural coding for hearing and balance. To extend spatiotemporal characterization of auditory and vestibular neuron diversity, we established a transgenic reporter mouse model (Prphp-mCherry), where elements of the peripherin promoter (Prphp) drive expression of the mCherry fluorescent reporter. Type III intermediate filament protein peripherin expression is a marker for type II spiral ganglion neurons (SGN) that innervate the cochlear outer hair cells, and the small diameter 'bouton' vestibular ganglion neurons (VGN) innervating the type II vestibular hair cells. Using Nanopore genome sequencing, the integration …

Spatial And Seasonal Dynamics Of Mosquito Species In Harris County, Texas, Highlight Risk Of Arbovirus Introduction And Transmission, Morgan Jibowu, Maximea Vigilant, Andre Luis Costa-Da-Silva, Alisa Nelson, Heather T Essigmann, Eric L Brown, Sarah M Gunter

Faculty, Staff and Student Publications

Mosquito-borne diseases pose a significant public health threat, particularly in densely populated urban areas. Climate change, urbanization, and global connectivity have fueled the expansion of mosquitoes and their associated pathogens, increasing the disease burden. Harris County, Texas, is among the most vulnerable regions in the United States for mosquito-borne disease outbreaks, underscoring the critical need for localized insights into mosquito population dynamics to inform vector surveillance and control strategies. This study provides a comprehensive analysis of the population dynamics of mosquito species in Harris County by exploring their species composition, spatial distribution, and seasonal patterns. Our findings reveal the extensive …

Care Guided By Tissue Oxygenation And Haemodynamic Monitoring In Off-Pump Coronary Artery Bypass Grafting (Bottomline-Cs): Assessor Blind, Single Centre, Randomised Controlled Trial, Jiange Han, Wenqian Zhai, Zhenhua Wu, Zhao Zhang, Tao Wang, Min Ren, Ziyue Liu, Daniel I Sessler, Zhigang Guo, Lingzhong Meng

Faculty, Staff and Student Publications

Objective: To assess whether perioperative management guided by near-infrared spectroscopy to determine tissue oxygen saturation and haemodynamic monitoring reduces postoperative complications after off-pump coronary artery bypass grafting.

Design: Assessor blinded, single centre, randomised controlled trial (Bottomline-CS trial).

Setting: A tertiary teaching hospital in China.

Participants: 1960 patients aged 60 years or older who were scheduled for elective off-pump coronary artery bypass grafting.

Interventions: All patients had multisite monitoring of tissue oxygen saturation (bilateral forehead and unilateral forearm brachioradialis) and haemodynamic monitoring. Both groups received usual care, including arterial blood pressure, central venous pressure, electrocardiography, and transoesophageal echocardiography when indicated. Guided …

Treatment Group-Specific Inferences In Phase Iii Randomized Oncology Trials, Alexander D Sherry, Adina H Passy, Joseph Abi Jaoude, Timothy A Lin, Ramez Kouzy, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Background: Estimation of comparative treatment effects between randomized groups is well-supported in randomized trials. By contrast, treatment group-specific inferences are challenging, as patients are selectively chosen for enrollment, and such inferences are formally discouraged by the CONSORT guidelines. The present study is the first-large scale assessment of the proportion of phase III oncology trials that present treatment group-specific inferences.

Methods: Published phase III randomized oncology trials were screened from ClinicalTrials.gov. Treatment group-specific inferences were defined by the presence of 95% CI or standard error for treatment-specific outcomes.

Results: A total of 774 phase III trials enrolling 568,080 patients were included. …

Islet Single-Cell Transcriptomic Profiling During Obesity-Induced Beta Cell Expansion In Female Mice, Peter M Masschelin, Scott A Ochsner, Sean M Hartig, Neil J Mckenna, Aaron R Cox

Faculty, Staff and Student Publications

Targeting beta cell proliferation is an appealing approach to restore glucose control in type 1 diabetes. However, the underlying mechanisms of beta cell proliferation remain incompletely understood, limiting identification of new therapeutic targets. Obesity is a naturally occurring process that potently induces human and rodent beta cell replication, representing an ideal model to study mechanisms of beta cell proliferation. We showed previously acute whole-body

Rare Damaging Ccr2 Variants Are Associated With Lower Lifetime Cardiovascular Risk, Marios K Georgakis, Rainer Malik, Omar El Bounkari, Natalie R Hasbani, Jiang Li, Jennifer E Huffman, Gabrielle Shakt, Reinier W P Tack, Tamara N Kimball, Yaw Asare, Alanna C Morrison, Noah L Tsao, Renae Judy, Braxton D Mitchell, Huichun Xu, May E Montasser, Ron Do, Eimear E Kenny, Ruth J F Loos, James G Terry, John Jeffrey Carr, Joshua C Bis, Bruce M Psaty, W T Longstreth, Kendra A Young, Sharon M Lutz, Michael H Cho, Jai Broome, Alyna T Khan, Fei Fei Wang, Nancy Heard-Costa, Sudha Seshadri, Ramachandran S Vasan, Nicholette D Palmer, Barry I Freedman, Donald W Bowden, Lisa R Yanek, Brian G Kral, Lewis C Becker, Patricia A Peyser, Lawrence F Bielak, Farah Ammous, April P Carson, Michael E Hall, Laura M Raffield, Stephen S Rich, Wendy S Post, Russel P Tracy, Kent D Taylor, Xiuqing Guo, Michael C Mahaney, Joanne E Curran, John Blangero, Shoa L Clarke, Jeffrey W Haessler, Yao Hu, Themistocles L Assimes, Charles Kooperberg, Jürgen Bernhagen, Christopher D Anderson, Scott M Damrauer, Ramin Zand, Jerome I Rotter, Paul S De Vries, Martin Dichgans

Faculty, Staff and Student Publications

BACKGROUND: Previous work has shown a role of CCL2, a key chemokine governing monocyte trafficking, in atherosclerosis. However, it remains unknown whether targeting CCR2, the cognate receptor of CCL2, provides protection against human atherosclerotic cardiovascular disease.

METHODS: Computationally predicted damaging or loss-of-function (REVEL > 0.5) variants within CCR2 were detected in whole-exome-sequencing data from 454,775 UK Biobank participants and tested for association with cardiovascular endpoints in gene-burden tests. Given the key role of CCR2 in monocyte mobilization, variants associated with lower monocyte count were prioritized for experimental validation. The response to CCL2 of human cells transfected with these variants was tested …

Student Expectations And Outcomes In Virtual Vs In-Person Interprofessional Simulations: A Qualitative Analysis, Padmavathy Ramaswamy, Abbey M Bachmann, Tiffany Champagne-Langabeer, Chasisty L Gilder, Samuel E Neher, Jennifer L Swails

Faculty, Staff and Student Publications

Background: Health-related programs frequently integrate interprofessional education (IPE) into their training. The COVID-19 pandemic transitioned many IPE programs online, making it essential to assess student expectations and perceived learning outcomes across virtual simulations and in-person settings.

Methods: This qualitative study compared student expectations and self-reported outcomes across in-person and virtual case scenarios at a Texas health science center. Responses to open-ended questions from two data collection periods were analyzed using inductive coding and thematic analysis.

Results: Students from nursing, medicine, dentistry, public health, and informatics participated in each group. Three major themes emerged from this study: communication, teamwork, and …

Do We Need To Add The Type Of Treatment Planning System, Dose Calculation Grid Size, And Ct Density Curve To Predictive Models?, Reza Reiazi, Surendra Prajapati, Leonardo Che Fru, Dongyeon Lee, Mohammad Salehpour

Faculty, Staff and Student Publications

Background: Generalizability and domain dependency are critical challenges in developing predictive models for healthcare, particularly in medical diagnostics and radiation oncology. Predictive models designed to assess tumor recurrence rely on comprehensive and high-quality datasets, encompassing treatment planning parameters, imaging protocols, and patient-specific data. However, domain dependency, arising from variations in dose calculation algorithms, computed tomography (CT) density conversion curves, imaging modalities, and institutional protocols, can significantly undermine model reliability and clinical utility.

Methods: This study evaluated dose calculation differences in the head and neck cancer treatment plans of 19 patients using two treatment planning systems, Pinnacle 9.10 and RayStation 11, …

Evaluation And Surgical Management Of Pediatric Cutaneous Melanoma And Atypical Spitz And Non-Spitz Melanocytic Tumors (Melanocytomas): A Report From Children's Oncology Group, Michael R Sargen, Raymond L Barnhill, David E Elder, Susan M Swetter, Victor G Prieto, Jennifer S Ko, Armita Bahrami, Pedram Gerami, Arivarasan Karunamurthy, Alberto S Pappo, Lynn M Schuchter, Philip E Leboit, Iwei Yeh, John M Kirkwood, Melinda Jen, Ira J Dunkel, Megan M Durham, Emily R Christison-Lagay, Mary T Austin, Jennifer H Aldrink, Casey Mehrhoff, Elena B Hawryluk, Emily Y Chu, Klaus J Busam, Vernon Sondak, Jane Messina, Susana Puig, Andrew J Colebatch, Carrie C Coughlin, Kristen G Berrebi, Theodore W Laetsch, Sarah G Mitchell, Brittani Seynnaeve

Faculty, Staff and Student Publications

Purpose: The purpose of this study was to develop recommendations for the diagnostic evaluation and surgical management of cutaneous melanoma (CM) and atypical Spitz tumors (AST) and non-Spitz melanocytic tumors (melanocytomas) in pediatric (age 0-10 years) and adolescent (age 11-18 years) patients.

Methods: A Children's Oncology Group-led panel with external, multidisciplinary CM specialists convened to develop recommendations on the basis of available data and expertise.

Results: Thirty-three experts from multiple specialties (cutaneous/medical/surgical oncology, dermatology, and dermatopathology) established recommendations with supporting data from 87 peer-reviewed publications.

Recommendations: (1) Excisional biopsies with 1-3 mm margins should be performed when feasible for clinically …

Dna Damage Response Signatures Are Associated With Frontline Chemotherapy Response And Routes Of Tumor Evolution In Extensive Stage Small Cell Lung Cancer, Benjamin B Morris, Simon Heeke, Yuanxin Xi, Lixia Diao, Qi Wang, Pedro Rocha, Edurne Arriola, Myung Chang Lee, Darren R Tyson, Kyle Concannon, Kavya Ramkumar, C Allison Stewart, Robert J Cardnell, Runsheng Wang, Vito Quaranta, Jing Wang, John V Heymach, Barzin Y Nabet, David S Shames, Carl M Gay, Lauren A Byers

Faculty, Staff and Student Publications

Introduction: A hallmark of small cell lung cancer (SCLC) is its recalcitrance to therapy. While most SCLCs respond to frontline therapy, resistance inevitably develops. Identifying phenotypes potentiating chemoresistance and immune evasion is a crucial unmet need. Previous reports have linked upregulation of the DNA damage response (DDR) machinery to chemoresistance and immune evasion across cancers. However, it is unknown if SCLCs exhibit distinct DDR phenotypes.

Methods: To study SCLC DDR phenotypes, we developed a new DDR gene analysis method and applied it to SCLC clinical samples, in vitro, and in vivo model systems. We then investigated how DDR regulation is …

Do We Need To Add The Type Of Treatment Planning System, Dose Calculation Grid Size, And Ct Density Curve To Predictive Models?, Reza Reiazi, Surendra Prajapati, Leonardo Che Fru, Dongyeon Lee, Mohammad Salehpour

Faculty, Staff and Student Publications

Background: Generalizability and domain dependency are critical challenges in developing predictive models for healthcare, particularly in medical diagnostics and radiation oncology. Predictive models designed to assess tumor recurrence rely on comprehensive and high-quality datasets, encompassing treatment planning parameters, imaging protocols, and patient-specific data. However, domain dependency, arising from variations in dose calculation algorithms, computed tomography (CT) density conversion curves, imaging modalities, and institutional protocols, can significantly undermine model reliability and clinical utility.

Methods: This study evaluated dose calculation differences in the head and neck cancer treatment plans of 19 patients using two treatment planning systems, Pinnacle 9.10 and RayStation 11, …

Improving Dietary Supplement Information Retrieval: Development Of A Retrieval-Augmented Generation System With Large Language Models, Yu Hou, Jeffrey R Bishop, Hongfang Liu, Rui Zhang

Faculty, Staff and Student Publications

Background: Dietary supplements (DSs) are widely used to improve health and nutrition, but challenges related to misinformation, safety, and efficacy persist due to less stringent regulations compared with pharmaceuticals. Accurate and reliable DS information is critical for both consumers and health care providers to make informed decisions.

Objective: This study aimed to enhance DS-related question answering by integrating an advanced retrieval-augmented generation (RAG) system with the integrated Dietary Supplement Knowledgebase 2.0 (iDISK2.0), a dietary supplement knowledge base, to improve accuracy and reliability.

Methods: We developed iDISK2.0 by integrating updated data from authoritative sources, including the Natural Medicines Comprehensive Database, the …

Health System, Community-Based, Or Usual Dementia Care For Persons With Dementia And Caregivers: The D-Care Randomized Clinical Trial, David B Reuben, Thomas M Gill, Alan Stevens, Jeff Williamson, Elena Volpi, Maya Lichtenstein, Lee A Jennings, Rebecca Galloway, Jenny Summapund, Katy Araujo, David Bass, Lisa Weitzman, Zaldy S Tan, Leslie Evertson, Mia Yang, Katherine Currie, Aval-Na'ree S Green, Sybila Godoy, Sitara Abraham, Jordan Reese, Rafael Samper-Ternent, Roxana M Hirst, Pamela Borek, Peter Charpentier, Can Meng, James Dziura, Yunshan Xu, Eleni A Skokos, Zili He, Sherry Aiudi, Peter Peduzzi, Erich J Greene, D-Care Study

Faculty, Staff and Student Publications

Importance: The effectiveness of different approaches to dementia care is unknown.

Objective: To determine the effectiveness of health system-based, community-based dementia care, and usual care for persons with dementia and for caregiver outcomes.

Design, setting, and participants: Randomized clinical trial of community-dwelling persons living with dementia and their caregivers conducted at 4 sites in the US (enrollment June 2019-January 2023; final follow-up, August 2023).

Interventions: Participants were randomized 7:7:1 to health system-based care provided by an advanced practice dementia care specialist (n = 1016); community-based care provided by a social worker, nurse, or licensed therapist care consultant (n = 1016); …

Icos-Expressing Car-T Cells Mediate Durable Eradication Of Triple-Negative Breast Cancer And Metastasis, Shelley Herbrich, Mehdi Chaib, Padmanee Sharma

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) remains one of the most aggressive and therapeutically challenging breast cancer subtypes. In their recent study, Cao et al introduced a B7H3-specific chimeric antigen receptor (CAR)-T cell with constitutive inducible co-stimulator (ICOS) expression (ICOS-B7H3-CAR-T), which demonstrated eradication of TNBC, including metastases, in preclinical models. These CAR-T cells exploit the expression of ICOS ligand on TNBC cells, enhancing antitumor cytotoxicity through ICOS signaling. Compared with conventional B7H3-CAR-T cells, the ICOS-B7H3-CAR-T cells exhibited superior antitumor efficacy, increased cytokine secretion, and prolonged survival in xenograft murine models. This study highlights ICOS as a promising co-stimulatory molecule for improving CAR-T …

Mathematical Modeling To Address Questions In Breast Cancer Screening: An Overview Of The Breast Cancer Models Of The Cancer Intervention And Surveillance Modeling Network, Oguzhan Alagoz, Jennifer L Caswell-Jin, Harry J De Koning, Hui Huang, Xuelin Huang, Sandra J Lee, Yisheng Li, Sylvia K Plevritis, Swarnavo Sarkar, Clyde B Schechter, Natasha K Stout, Amy Trentham-Dietz, Nicolien Van Ravesteyn, Kathryn P Lowry

Faculty, Staff and Student Publications

The National Cancer Institute-funded Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer mathematical models have been increasingly utilized by policymakers to address breast cancer screening policy decisions and influence clinical practice. These well-established and validated models have a successful track record of use in collaborations spanning over 2 decades. While mathematical modeling is a valuable approach to translate short-term screening performance data into long-term breast cancer outcomes, it is inherently complex and requires numerous inputs to approximate the impacts of breast cancer screening. This review article describes the 6 independently developed CISNET breast cancer models, with a particular focus …

Near-Infrared Fluorescence Imaging With An Met-Targeting Probe For Biopsy Site Selection In Patients With Oral Potentially Malignant Disorders, Jingbo Wang, Xuemin Shen, Qifan Ma, Lin Yang, Xiaoyu Zhou, Luting Wang, Junqi Cui, Chunye Zhang, Guojun Li, Neil Gross, Siyi Li, Ruimin Huang, Changyou Zhan, Zhen Cheng, Kun Wang, Jie Tian, Ying Yuan, Xiaofeng Tao

Faculty, Staff and Student Publications

Accurate detection of malignant transformation in oral potentially malignant disorders (OPMDs) is crucial for guiding effective treatment and improving patient management. This study evaluates the potential of MET-binding peptide-indocyanine green (cMBP-ICG), a mesenchymal-epithelial transition factor (MET)-targeted near-infrared fluorescence imaging (NIRFI) probe, for biopsy site selection in OPMDs. Preclinical results demonstrate the superior accuracy of NIRFI-assisted biopsy over conventional oral examination (COE)-based biopsy in detecting high-grade dysplasia (HGD) or squamous cell carcinoma (SCC) and reducing missed detection rates. In a clinical trial with 50 patients, NIRFI-assisted biopsy achieves significantly higher diagnostic accuracy compared to COE-based biopsy (91% vs. 72%, p = …