Digital Commons Network^™

Application Of Claims-Based Frailty Index To A Structured Electronic Health Record Data, Chan Mi Park, Dae Hyun Kim

Faculty, Staff and Student Publications

Background: The Claims-based Frailty Index (CFI) has been developed and validated using Medicare claims data. However, whether CFI can be applied to structured electronic health record data has not been studied.

Methods: We applied the CFI to a structured electronic health record dataset (Explorys dataset) and a Medicare fee-for-service 5% sample data and compared the prevalence of frailty from each dataset, using the cohort of older adults. Then, we assessed the odds ratio and area under the curve of the frailty predicting adverse clinical outcomes, any hospital or emergency room visit, or any adverse drug events related encounter within 1 …

Sickle Cell Disease Induces Chromatin Introversion And Ferroptosis In Cd8+ T Cells To Suppress Anti-Tumor Immunity, Zilong Zhao, Benxia Hu, Yalan Deng, Melinda Soeung, Jun Yao, Lanxin Bei, Yaohua Zhang, Pengju Gong, Lisa A Huang, Zhou Jiang, Jian Gao, Shuang Peng, Tina K Nguyen, Menuka Karki, Bora Lim, Cassian Yee, Jared K Burks, Qing Zhang, Li Ma, Jianjun Gao, Nizar M Tannir, Leng Han, Dihua Yu, Linghua Wang, Michael A Curran, Maria A Gubbiotti, Giannicola Genovese, Boyi Gan, Wenbo Li, Pavlos Msaouel, Liuqing Yang, Chunru Lin

Faculty, Staff and Student Publications

Understanding how genetic disorders affect CD8+ T cells in the tumor microenvironment is key to improving cancer immunotherapy. Individuals with sickle cell disease (SCD), the most prevalent inherited blood disorder, have a higher risk of developing certain cancers than the general population, but the mechanisms driving this increased risk remain unclear. Our study revealed that SCD altered CD8+ T cell 3D genome architecture, triggering ferroptosis and weakening anti-tumor immunity, thereby promoting tumor growth. Using murine and humanized SCD models, we found that disrupted chromosomal interactions in CD8+ T cells reduced the expression of anti-ferroptotic genes, including SLC7A11 and hydrogen sulfide …

Role Of Interventional Pulmonology In Intensive Care Units: A Scoping Review, Sujith V Cherian

Faculty, Staff and Student Publications

Interventional pulmonology (IP) represents a rapidly growing and developing subspecialty within pulmonary medicine. To the intensivist, given the elaborate undertakings with respect to airway, lung and pleural disease management-IP has shown an increasing presence and remain a major ally in the care of these patients. Thus, an understanding of the different roles that IP could offer to the intensivist is of prime importance in the multi-disciplinary care of the complex patients within the intensive care units, particularly in relation to lung, airway and pleural diseases. This review article will explore the different intersections of IP in critical care and discuss …

Radiotherapy Promotes Cuproptosis And Synergizes With Cuproptosis Inducers To Overcome Tumor Radioresistance, Guang Lei, Mingchuang Sun, Jun Cheng, Rui Ye, Zhengze Lu, Amber Horbath, David Huo, Shengrong Wu, Anagha Alapati, Sadhna Aggarwal, Zhihao Xu, Chao Mao, Yuelong Yan, Jun Yao, Qidong Li, Xiong Chen, Hyemin Lee, Li Zhuang, Dadi Jiang, Apar Pataer, Jack A Roth, Nicholas Navin, Albert C Koong, Mingjian James You, Steven H Lin, Boyi Gan

Faculty, Staff and Student Publications

Cuproptosis is a recently identified form of copper-dependent cell death. Here, we reveal that radiotherapy (RT) induces cuproptosis in cancer cells, independent of apoptosis and ferroptosis, and depletes lipoylated proteins and iron-sulfur (Fe-S) cluster proteins-both hallmarks of cuproptosis-in patient tumors. Mechanistically, RT elevates mitochondrial copper levels by upregulating copper transporter 1 (CTR1) and depleting mitochondrial glutathione, a copper chelator, thereby triggering cuproptosis. Integrated analyses of RNA sequencing (RNA-seq) from radioresistant esophageal cancer cells and single-cell RNA-seq from esophageal tumors of patients unresponsive to RT link radioresistance to the downregulation of BTB and CNC homology 1 (BACH1). This downregulation de-represses the …

Forum Of Esrd Networks: 50 Years Of Collaboration, Innovation, And Education To Promote Equitable And Optimal Kidney-Patient Centered Care, David Henner, Daniel Landry, Donald A Molony, Andrew Howard, Mary Albin, Mary Baliker, Dawn P Edwards, Dee Leduc, Ramin Sam, Preethi Yerram, Kamyar Kalantar-Zadeh

Faculty, Staff and Student Publications

No abstract provided.

Omitting Regional Nodal Irradiation After Response To Neoadjuvant Chemotherapy, Eleftherios P Mamounas, Hanna Bandos, Julia R White, Thomas B Julian, Atif J Khan, Mylin A Torres, Patricia A Ganz, Susan A Mccloskey, Peter C Lucas, Nilendu Gupta, X Allen Li, Beryl Mccormick, Benjamin Smith, Rahul D Tendulkar, Vivek S Kavadi, Koji Matsumoto, Samantha Andrews Seaward, William J Irvin, Jolinta Y Lin, Robert W Mutter, Thierry M Muanza, Jannifer Stromberg, Reshma Jagsi, Anna C Weiss, Walter J Curran, Norman Wolmark

Faculty, Staff and Student Publications

Background: The benefit of regional nodal irradiation in the treatment of breast cancer is well established for patients with pathologically positive axillary nodes, but whether it is also beneficial for patients whose nodes become pathologically tumor free (ypN0) after neoadjuvant chemotherapy remains unclear.

Methods: We evaluated whether regional nodal irradiation improves outcomes in patients with biopsy-proven, node-positive breast cancer who reach ypN0 status after neoadjuvant chemotherapy. Patients with breast cancer with a clinical stage of T1 to T3 (tumor size, ≤2 cm to >5 cm), N1, and M0 (indicating spread to one to three axillary lymph nodes but no distant …

Eph Receptors Activate Myeloid Checkpoint Receptor Lilrb5 To Support Tumor Development, Yubo He, Chengcheng Zhang, Lingxiao Tan, Mi Deng, Xiaoye Liu, Xing Yang, Qi Lou, Meng Fang, Caroline Smith, Samuel John, Wei Xiong, Xin Li, Cheryl Lewis, Jade Homsi, Ankit Gupta, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

Faculty, Staff and Student Publications

Immunosuppressive myeloid cells are critical obstacles to T cell-centered immune checkpoint blockade therapies, which have been successful in treating a fraction of patients with cancer. How tumor cells interact with myeloid cells to regulate immune responses and tumor development is unclear. In this study, we report that certain membrane tyrosine kinase Eph receptors, including EphA7 and EphB1, specifically bind the immune inhibitory receptors leukocyte Ig-like receptor family B 5 (LILRB5) and LILRB2. These Eph receptors induce LILRB5-mediated signaling activation, and LILRB5 also activates Eph receptor signaling. Activation of LILRB5 promoted immunosuppressive marker expression and inhibited activating marker expression on myeloid …

The Present And Future Of Precision Oncology And Tumor-Agnostic Therapeutic Approaches, Nakul M Shah, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Precision oncology has transformed the treatment landscape for patients with advanced solid tumors. Tumor-agnostic therapies, those that have been approved based on genetic mutations or biomarkers across tumor histology types, are important examples of how the implementation of precision oncology can expand therapeutic options for patients, especially those with rare cancer types and treatment-refractory disease. In this review, we first discuss how advances in next-generation sequencing and molecular profiling have enabled the identification of shared actionable alterations. Subsequently, we explore the current landscape of tumor-agnostic therapies that have received approval from the Food and Drug Administration. We discuss the strengths …

Mutant P53 Gain Of Function: Why Many See It, Why Some Do Not, Guillermina Lozano, Carol Prives, Kanaga Sabapathy

Faculty, Staff and Student Publications

Mutations in the TP53 tumor-suppressor gene in human cancer are unique in that 60% to 70% are of the missense variety, resulting in a full-length protein that is often highly expressed in patients' tumors. These missense mutant proteins often exhibit pro-oncogenic activities (referred to as gain of function) in mouse models and human cell lines and correlate with poor cancer prognosis in some cases.

Posterior Predictive Design For Phase I Clinical Trials, Chenqi Fu, Shouhao Zhou, J Jack Lee

Faculty, Staff and Student Publications

Interval-based designs represent cutting-edge adaptive methodologies for phase I clinical trials to identify the maximum tolerated dose (MTD). These designs exhibit robust performance comparable to more intricate, model-based designs, and their pretabulated decision rule enables them to be implemented as simply as the conventional algorithm-based designs. In this paper, we introduce the posterior predictive (PoP) design, a novel interval-based design that leverages advanced Bayesian predictive hypothesis testing techniques for dose escalation and de-escalation. Our work moves beyond the existing model-assisted interval-based designs by achieving global optimality in dose transition. Theoretically, the global optimality ensures that the proposed design can consistently …

Hyaluronan Network Remodeling By Zeb1 And Itih2 Enhances The Motility And Invasiveness Of Cancer Cells, Sieun Lee, Jihye Park, Seongran Cho, Eun Ju Kim, Seonyeong Oh, Sungsoo Park, Dong Hoon Shin, Song Yi Ko, Jonathan M Kurie, Young-Ho Ahn

Faculty, Staff and Student Publications

Hyaluronan (HA) in the extracellular matrix promotes epithelial-mesenchymal transition (EMT) and metastasis; however, the mechanism by which the HA network constructed by cancer cells regulates cancer progression and metastasis in the tumor microenvironment (TME) remains largely unknown. In this study, inter-α-trypsin inhibitor heavy chain 2 (ITIH2), an HA-binding protein, was confirmed to be secreted from mesenchymal-like lung cancer cells when cocultured with cancer-associated fibroblasts. ITIH2 expression is transcriptionally upregulated by the EMT-inducing transcription factor ZEB1, along with HA synthase 2 (HAS2), which positively correlates with ZEB1 expression. Depletion of ITIH2 and HAS2 reduced HA matrix formation and the migration and …

Switching On The Evolutionary Potential Of Pancreatic Cancer: The Tumor Suppressor Functions Of Pbrm1, Luigi Perelli, Giannicola Genovese

Faculty, Staff and Student Publications

Cell plasticity is a hallmark of cancer, enabling tumor cells to acquire multiple phenotypes responsible for tumor progression, metastasis, and therapy resistance. In this issue of the JCI, Kawai and colleagues leveraged genetically engineered mouse models (GEMM) of pancreatic ductal adenocarcinoma (PDAC) to demonstrate that loss of Pbrm1, a member of the SWI/SNF complex, drives dedifferentiation and aggressive tumor features. Pbrm1 loss activated a program of epithelial-to-mesenchymal transition (EMT) and allowed the emergence of poorly differentiated histologies that are commonly associated with high recurrence rate and dismal prognosis. These findings reveal the role of the SWI/SNF complex during PDAC evolution …

Harnessing Electrophiles In Vivo: A Pilot Study In Swine Using A Hydrophobic Radiopaque Formulation Of 2-Propylpentanoyl Chloride, Erik Cressman, Danielle Stolley, Natalie Fowlkes, Edd Felix, Waldemar Priebe, David Fuentes

Faculty, Staff and Student Publications

Manipulating biology through chemistry is older than the discipline of chemistry itself. Traditionally, selectivity of oral or intravenous drugs relied on preferential drug-receptor binding. A novel approach exploiting image-guided techniques to impart spatial selectivity opens up a wide range of new possibilities for study and manipulation of biology. Motivated initially by the poor prognosis for solid tumors such as liver cancer, we demonstrate the use of an extreme form of in vivo chemistry for targeted delivery of 2-propylpentanoyl chloride in a swine model. The ensuing reaction in tissue devitalizes it by multiple mechanisms with lasting effects and, critically, demonstrates very …

Suppression Of Brca1 Facilitates Kidney Regeneration, Kaira A Church, Xunian Zhou, Raghu Kalluri

Faculty, Staff and Student Publications

Maladaptive repair following kidney injury leads to the development of kidney disease. In this issue of JEM, Ajay et al. (https://doi.org/10.1084/jem.20231107) uncover the role of breast cancer susceptibility gene 1 (BRCA1) in cell cycle arrest, DNA damage, and cell senescence, preventing maladaptive repair.

The Promising Use Of An Emergency Department Observation Unit To Manage Patients With Opioid Use Disorder, Thai Tran, Nicholas Imperato, Akiva Dym, Anthony Rosania, Lewis Nelson, Christine Ramdin, Cynthia Santos

Faculty, Staff and Student Publications

Introduction: The opioid epidemic continues to grow, placing a significant strain on Emergency Departments (EDs), resulting in patients presenting daily with opioid-related concerns including intoxication, withdrawal, infections, injury, and death. Consequently, in recent years many EDs, including our own, have utilized Emergency Department Observation Units (EDOU) to not only manage withdrawal and overdose, but also initiate long-term treatment. This study aims to evaluate the outcomes of patients with opioid use disorder (OUD) who were managed in our EDOU.

Methods: This was a retrospective study of patients placed in an EDOU who had the primary diagnosis of OUD in a single …

Predicting Discharge Destination And Length Of Stay After Open Reduction Internal Fixation Of Distal Femur Fractures, Akash A Shah, Brian K Zukotynski, Chohee Kim, Brendan Y Shi, Changhee Lee, Sai K Devana, Alexander Upfill-Brown, Erik N Mayer, Nelson F Soohoo, Christopher Lee

Faculty, Staff and Student Publications

Introduction: Prediction of nonhome discharge after open reduction internal fixation (ORIF) of distal femur fractures may facilitate earlier discharge planning, potentially decreasing costs and improving outcomes. We aim to develop algorithms predicting nonhome discharge and time to discharge after distal femur ORIF and identify features important for model performance.

Methods: This is a retrospective cohort study of adults in the American College of Surgeons National Surgical Quality Improvement Program database who underwent distal femur ORIF between 2010 and 2019. The primary outcome was nonhome discharge, and the secondary outcome was time to nonhome discharge. We developed logistic regression and machine …

Prematurity And Congenial Diaphragmatic Hernia: Revisiting Outcomes In A Contemporary Cohort, Petru I Alexe, Ana Sanchez Torres, Ashley H Ebanks, Enrico Danzer, Krisa Van Meurs, Matthew T Harting, Carmen Mesas Burgos

Faculty, Staff and Student Publications

Objective: To describe outcomes in a contemporary cohort of infants born at gestational age < 34 weeks with congenital diaphragmatic hernia (CDH).

Study design: Data from the multicenter, multinational CDH Study Group (CDHSG) registry on patients born between 1995 and 2022 were analyzed. Variables including prenatal characteristics and therapy, postnatal management, and outcomes to discharge were evaluated. A t test was used for continuous variables, and for categorical variables, the Fisher exact test.

Results: In total, 13 471 patients with CDH were entered into the registry during the study period. 810 (6%) were born at < 34 weeks of gestational age. The survival rate for the preterm cohort was 45%, and 43.5% were not repaired. Survival after surgical repair was 79%, mean age at surgery was 11 days of life, and 65% required patch repair. Extracorporeal life support was used in only 7% of the cases, and 35% survived. In total, 48.9% had an associated anomaly. Oxygen at 30 days of life was required by 76.7%. Very preterm birth (< 32 weeks of gestational age) occurred in 361 patients (2.8%), with a 39.3% survival rate and a high rate of nonrepairs (50.1%). The incidence of birth at < 34 weeks of gestational age for those undergoing fetal tracheal occlusion was 30%.

Conclusions: Survival rates for infants born preterm with CDH remain low and the …

The Association Of Vision And Hearing Impairment On Cognitive Function And Loneliness: Evidence From The Mexican Health And Aging Study, Jessica S West

Faculty, Staff and Student Publications

Objectives: We investigated whether self-reported vision and hearing were associated with cognitive function and loneliness among Mexican adults aged 50 and older.

Methods: Mexican Health and Aging Study data. Vision/hearing status was self-reported (excellent-very good, good, fair-poor). Cognition was measured using nine tasks. Loneliness was measured using the UCLA Loneliness Scale. Analyses controlled for demographic and health characteristics.

Results: Among 12,353 participants (mean age = 67, 58% female), poor vision, but not hearing, was associated with lower global cognition (β = -0.03, p < .05). Poor vision (OR = 1.57, 95% CI = 1.30-1.91) and hearing (OR = 1.35, 95% CI = 1.14-1.61) were associated with higher odds of being lonely after adjusting for demographics and comorbidities, but not when adjusting for limitations in daily activities and depressive symptoms.

Discussion: Poor vision is a potentially modifiable risk factor for lower cognition and loneliness among Mexican adults. …

Early Life Exposure To Fine Particulate Matter And Fine Motor Function, Attentional Function, And Working Memory Among Spanish School-Aged Children, Wei-Jen Chen, Michael Swartz, Elaine Symanski, Antonia Valentin, Carmen Iniguez, Llúcia L González-Safont, Jesús Ibarluzea

Faculty, Staff and Student Publications

Background: Evidence of the association between fine particulate matter (PM2.5) exposure and child neuropsychological function is equivocal. We examined early life PM2.5 exposure in relation to fine motor function, attention, and working memory in early childhood.

Methods: We used data from the Spanish INfancia y Medio Ambiente Project, 2003-2008. Exposure to PM2.5 (μg/m3) was assessed using spatiotemporal land-use random forest models and assigned based on residential address histories. Around age six, children completed the finger tapping test, attentional network test (ANT), and n-back task to evaluate fine motor speed, attention, and working memory, respectively. A total of 1,310 children had …

Understanding Utilization And Prevention Measures Associated With A Caries Risk Assessment In Oral Health Transformation

Faculty, Staff and Student Publications

Objectives: Dental decay is endemic in the United States, underscoring the need to measure the utilization of caries risk management tools to elucidate the effect of prevention interventions in reducing the dental decay rates of individuals. An academic institution partnered with a third-party institute to call attention to the utilization and prevention measures associated with caries risk assessment (CRA) used with children 0-18 years. This environmental scan examined claims across the United States to evaluate the proportion of dental examinations, CRAs, and caries prevention procedures within a calendar year.

Methods: A 12-month deidentified participant list categorized by age, race, sex, …

Factors Associated With Perceived Medication Safety During Transitions Of Care In Patients With Cancer: A Secondary Data Analysis Of A Cross-Sectional Survey

Faculty, Staff and Student Publications

Purpose: This study aimed to investigate perceived medication safety in patients with cancer during transitions of care and identify factors associated with their safety perceptions.

Methods: A secondary data analysis was performed on a cross-sectional survey data of from patients with four types of cancer (i.e., colorectal, lung, prostate, and breast). Perceived medication safety was measured by the sum score of four survey items that assessed patients' feelings about medication safety during transitions of care. Potential associated factors included sociodemographic and clinical factors (i.e., cancer types, taking oral anticancer agents), self-rated health, perceived safety in communicating with clinicians, beliefs about …

Computerized Diagnostic Decision Support Systems-Isabel Pro Versus Chatgpt-4 Part Ii

Faculty, Staff and Student Publications

Objective: Does a Tree-of-Thought prompt and reconsideration of Isabel Pro's differential improve ChatGPT-4's accuracy; does increasing expert panel size improve ChatGPT-4's accuracy; does ChatGPT-4 produce consistent outputs in sequential requests; what is the frequency of fabricated references?

Materials and methods: Isabel Pro, a computerized diagnostic decision support system, and ChatGPT-4, a large language model. Using 201 cases from the New England Journal of Medicine, each system produced a differential diagnosis ranked by likelihood. Statistics were Mean Reciprocal Rank, Recall at Rank, Average Rank, Number of Correct Diagnoses, and Rank Improvement. For reproducibility, the study compared the initial expert panel run …

Exploring Potential Ethnic Bias Among Mmpi-3 Scales In Assessing Personality Psychopathology, Nicole Shumaker, Tessa Long, Andy Torres, Alfonso Mercado, Ryan J Marek, Jaime L Anderson

Faculty, Staff and Student Publications

This study examined statistical bias in the measurement of personality psychopathology in the Latinx population using the Minnesota Multiphasic Personality Inventory-3 (MMPI-3). Data were extracted from two studies that yielded a composite data set of 103 White individuals and 250 Latinx individuals. All participants were administered the MMPI-2-Restructured Form-Extended Battery (MMPI-2-RF-EX) or MMPI-3 and the Personality Inventory for the DSM-5 Short Form (PID-5-SF). First, we conducted correlation analyses between theoretically overlapping scales of the PID-5-SF and the MMPI-3 among White and Latinx individuals. The majority of theoretically associated scales were found to be at least moderately associated in the …

Externally Validated Digital Decision Support Tool For Time-To-Osteoradionecrosis Risk-Stratification Using Right-Censored Multi-Institutional Observational Cohorts, Laia Humbert-Vidan, Serageldin Kamel, Andrew Wentzel, Zaphanlene Kaffey, Moamen Abdelaal, Natalie A West, Guadalupe Canahuate, Xinhua Zhang, Melissa M Chen, Kareem A Wahid, Jillian Rigert, Seyedmohammadhossein Hosseinian, Andrew J Schaefer, Kristy K Brock, Mark Chambers, Adegbenga O Otun, Ruth Aponte-Wesson, Vinod Patel, Andrew Hope, Jack Phan, Adam S Garden, Steven J Frank, William H Morrison, Michael T Spiotto, David Rosenthal, Anna Lee, Renjie He, Mohamed A Naser, Erin Watson, Katherine A Hutcheson, Abdallah S R Mohamed, Vlad C Sandulache, Lisanne V Van Dijk, Amy C Moreno, Teresa Guerrero Urbano, Clifton D Fuller, Stephen Y Lai

Faculty, Staff and Student Publications

Background: Existing studies on osteoradionecrosis of the jaw (ORNJ) have primarily used cross-sectional data, assessing risk factors at a single time point. Determining the time-to-event profile of ORNJ has important implications to monitor oral health in head and neck cancer (HNC) long-term survivors.

Methods: Data were retrospectively obtained for a clinical observational cohort of 1129 patients (198 ORNJ cases) with HNC treated with radiotherapy (RT) at The University of Texas MD Anderson Cancer Center. A Weibull Accelerated Failure Time model was trained on previously identified dosimetric, clinical and demographic predictors. External validation was performed using an independent cohort of 265 …

International Expert-Based Consensus Definition, Classification Criteria, And Minimum Data Elements For Osteoradionecrosis Of The Jaw: An Interdisciplinary Modified Delphi Study, Amy C Moreno, Erin E Watson, Laia Humbert-Vidan, Douglas E Peterson, Lisanne V Van Dijk, Lisa Van Den Bosch, Matthew S Katz, Frank J P Hoebers, Ruth A Aponte Wesson, James E Bates, Paolo Bossi, Adeyinka F Dayo, Mélanie Doré, Eduardo Rodrigues Fregnani, Thomas J Galloway, Daphna Y Gelblum, Issa A Hanna, Christina E Henson, Sudarat Kiat-Amnuay, Anke Korfage, Nancy Y Lee, Carol M Lewis, Charlotte Duch Lynggaard, Antti A Mäkitie, Marco Magalhaes, Yvonne M Mowery, Carles Muñoz-Montplet, Jeffrey N Myers, Ester Orlandi, Jaymit Patel, Jillian M Rigert, Deborah Saunders, Jonathan D Schoenfeld, Ugur Selek, Efsun Somay, Vinita Takiar, Juliette Thariat, Gerda M Verduijn, Alessandro Villa, Nicholas S West, Max J H Witjes, Alex M Won, Mark E Wong, Christopher M K L Yao, Simon W Young, Kamal Al-Eryani, Carly E A Barbon, Doke J M Buurman, François J Dieleman, Theresa M Hofstede, Abdul Ahad Khan, Adegbenga O Otun, John C Robinson, Lauren Hum, Jorgen Johansen, Rajesh Lalla, Alexander Lin, Vinod Patel, Richard J Shaw, Mark S Chambers, Daniel Ma, Mabi Singh, Noam Yarom, Abdallah Sherif Radwan Mohamed, Katherine A Hutcheson, Stephen Y Lai, Clifton David Fuller

Faculty, Staff and Student Publications

Purpose: Osteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy to the head and neck. With >9 published definitions and at least 16 classification systems, the true incidence and severity of ORNJ are obscured by lack of a standard for disease definition and severity assessment, leading to inaccurate estimation of incidence, reporting ambiguity, and likely underdiagnosis worldwide. This study aimed to achieve consensus on an explicit definition and phenotype of ORNJ and related precursor states through data standardization to facilitate effective diagnosis, monitoring, and multidisciplinary management of ORNJ.

Methods and materials: The …

Gsk-3484862, A Dnmt1 Degrader, Promotes Dnmt3b Expression In Lung Cancer Cells, Qin Chen, Swanand Hardikar, Kimie Kondo, Nan Dai, Ivan R Corrêa Jr, Marcos R Estecio, Taiping Chen, Xiaodong Cheng

Faculty, Staff and Student Publications

DNA methylation alterations, including hypermethylation and silencing of tumor suppressor genes, contribute to cancer formation and progression. The FDA-approved nucleoside analogs azacytidine and decitabine are effective demethylating agents for hematologic malignancies but their general use has been limited by their toxicity and ineffectiveness against solid tumors. GSK-3484862, a dicyanopyridine-containing, DNMT1-selective inhibitor and degrader, offers a promising lead for developing novel demethylating therapeutics. Here, we demonstrate that GSK-3484862 treatment upregulates DNMT3B expression in lung cancer cell lines (A549 and NCI-H1299). Disrupting DNMT3B in NCI-H1299 sensitizes these cells to GSK-3484862, enhancing its inhibitory effects on cell viability and growth. GSK-3484862 treatment induces …

Neighborhood Socioeconomic Disadvantage Is Not Associated With Adverse Outcomes Following Elective Spine Surgery In Older Veterans, Andrea L Strayer, Yubo Gao, Michael A Jacobs, Heather Davila, Carly A Jacobs, Leslie R M Hausmann, George Wehby, Daniel E Hall, Mary Vaughan Sarrazin, Katherine E Hadlandsmyth

Faculty, Staff and Student Publications

Background: In the US, over half of all cervical and lumbar arthrodesis spine surgeries are for people ≥60 years of age. The extent to which adverse outcomes vary by social (eg, disadvantaged neighborhoods) and demographic factors have been scarcely investigated in spine surgery. We investigated the association of social, demographic, and clinical factors with complications, 30-day readmission, and 30-day mortality in older Veterans undergoing elective spine surgery.

Methods: Veterans (N=5,277) aged ≥65 years who underwent inpatient elective spine surgery for degenerative disease in the Veterans Affairs Surgical Quality Improvement Program (VASQIP) comprised our retrospective cohort. VASQIP (2013-2019) data were merged …

Fibroblast Dynamics During Mammary Oncogenesis: Senescence, Wnt9a And Beyond, Viktoria Boeker, Raghu Kalluri

Faculty, Staff and Student Publications

Mammary gland fibroblasts are highly plastic and transition through distinct states during development and disease. A new study by Pascual et al (2025) provides a comprehensive single-cell atlas of murine mammary stromal cell hierarchies, revealing dysregulation of progenitor-driven fibroblast lineages in breast cancer and a senescence role of Wnt9a in cancer-associated myofibroblasts.

Outcomes After Palliative Radiation Therapy In Patients With Symptomatic Locoregionally Advanced Breast Cancer, Luisa E Jacomina, David M Swanson, Melissa P Mitchell, Wendy A Woodward, Benjamin D Smith, Chelain R Goodman, Susie X Sun, Timothy A Yap, Funda Meric-Bernstam, Isidora Y Arzu, Elizabeth S Bloom, Pamela J Schlembach, Eric A Strom, Michael C Stauder, Simona F Shaitelman

Faculty, Staff and Student Publications

Purpose: Symptomatic locoregionally advanced breast cancer (SLABC) can cause troublesome pain or wound complications that negatively impact quality of life. Although palliative radiation therapy (RT) can minimize tumor-related symptoms, how best to tailor RT to achieve the most meaningful and durable response is not well defined.

Methods and materials: This is a single institution, multi-site retrospective review of patients with SLABC treated between 2016 and 2023 with palliative RT to symptomatic disease in the breast, chest wall, and/or regional lymph node basins. Overall survival (OS), locoregional control (LC), clinical and radiographic treatment response, overall pain scores, and treatment-related toxicities were …

Association Of Sirt6 Expression With Risk Of Pneumonitis Induced By Radiotherapy In Cancer Patients, Fengyuan Yu, Zheng Gong, Yuan Li, Danial F Naseem, Chen Li, Bingying Zhao, Shanshan Zhang, Rukun Zang, Ailu Wu, Qingxin Han, Shuhui Wu, Hongwei Li, Yipeng Song

Faculty, Staff and Student Publications

Thoracic tumours represent a significant proportion of malignant cancers. While radiotherapy (RT) improves prognosis, it can also lead to side effects such as radiation-induced pneumonitis (RP). Since SIRT6 is involved in DNA repair, energy metabolism and inflammation, this study aims to investigate the expression of SIRT6 in lymphocytes as a potential biomarker and therapeutic target for RP. This study included 170 patients diagnosed with thoracic tumours, all of whom underwent thoracic RT. RP was evaluated and classified as severe RP (SRP) and lower as non-severe RP (NSRP). Analyses were performed using SPSS version 26.0 and the R. Among 170 patients …