Genetic Phenomena Commons^™

Resort Enhances Reference-Based Cell Type Deconvolution For Spatial Transcriptomics Through Regional Information Integration, Linhua Wang, Ling Wu, Guantong Qi, Chaozhong Liu, Wanli Wang, Xiang H-F Zhang, Zhandong Liu

Duncan NRI Faculty and Staff Publications

Motivation: Spatial transcriptomics (ST) captures positional gene expression within tissues but lacks single-cell resolution. Reference-based cell type deconvolution methods were developed to understand cell type distributions for ST. However, batch/platform discrepancies between references and ST impact their accuracy.

Results: We present Region-based Cell Sorting (ReSort), which utilizes ST's region-level data to lessen reliance on reference data and alleviate these technical issues. In simulation studies, ReSort enhances reference-based deconvolution methods. Applying ReSort to a mouse breast cancer model highlights macrophages M0 and M2 enrichment in the epithelial clone, revealing insights into epithelial-mesenchymal transition and immune infiltration.

Availability and implementation: Source codes …

Drosophila Models Uncover Substrate Channeling Effects On Phospholipids And Sphingolipids In Peroxisomal Biogenesis Disorders, Michael F Wangler, Yu-Hsin Chao, Mary Roth, Ruth Welti, James A Mcnew

Duncan NRI Faculty and Staff Publications

Peroxisomal Biogenesis Disorders Zellweger Spectrum (PBD-ZSD) disorders are a group of autosomal recessive defects in peroxisome formation that produce a multi-systemic disease presenting at birth or in childhood. Well documented clinical biomarkers such as elevated very long chain fatty acids (VLCFA) are key biochemical diagnostic findings in these conditions. Additional, secondary biochemical alterations such as elevated very long chain lysophosphatidylcholines are allowing newborn screening for peroxisomal disease. In addition, a more widespread impact on metabolism and lipids is increasingly being documented by metabolomic and lipidomic studies. Here we utilize Drosophila models of pex2 and pex16 as well as human plasma …

Recurrent Carotid Paragangliomas In A Syndromic Patient With A Heterozygous Missense Variant In Dna Methyltransferase 3 Alpha, Ryan J German, Blake Vuocolo, Liesbeth Vossaert, Lisa Saba, Robin Fletcher, Matthew L Tedder, Bekim Sadikovic, Jennifer Kerkhof, Michael Wangler, Carlos A Bacino

Duncan NRI Faculty and Staff Publications

We report a 40-year-old African American female with a novel variant in exon 8 of DNA methyltransferase 3 alpha (DNMT3A), (NM_022552.4: c.905G>C, p.G302A) who presented with a history of recurrent carotid paragangliomas, mediastinal mass, intellectual disability, dysarthria, cholelithiasis, diabetes mellitus, hypertension, and dysmorphic features. We interpret this novel variant as likely pathogenic and causative for the patient's syndromic features of Heyn-Sproul-Jackson syndrome. Heyn-Sproul-Jackson syndrome is a condition caused by gain-of-function genetic changes in DNMT3A. Paragangliomas have also been observed in non-syndromic patients with genetic alterations in DNMT3A. We describe a patient with clinical features of Heyn-Sproul-Jackson syndrome such as …

Upregulation Of Delta Opioid Receptor By Meningeal Interleukin-10 Prevents Relapsing Pain, Kufreobong E Inyang, Jaewon Sim, Kimberly B Clark, Matan Geron, Karli Monahan, Christine Evans, Patrick O'Connell, Sophie Laumet, Bo Peng, Jiacheng Ma, Cobi J Heijnen, Robert Dantzer, Grégory Scherrer, Annemieke Kavelaars, Matthew Bernard, Yasser A Aldhamen, Joseph K Folger, Alexis Bavencoffe, Geoffroy Laumet

Faculty, Staff and Student Publications

Chronic pain often includes periods of transient amelioration and even remission that alternate with severe relapsing pain. While most research on chronic pain has focused on pain development and maintenance, there is a critical unmet need to better understand the mechanisms that underlie pain remission and relapse. We found that interleukin (IL)-10, a pain resolving cytokine, is produced by resident macrophages in the spinal meninges during remission from pain and signaled to IL-10 receptor-expressing sensory neurons. Using unbiased RNA-sequencing, we identified that IL-10 upregulated expression and antinociceptive activity of δ-opioid receptor (δOR) in the dorsal root ganglion. Genetic or pharmacological …

Neutrophils Unveiled In Chronic Lymphocytic Leukemia, Sheighlah Mcmanus, Priyanka Khare, Maria Teresa S Bertilaccio

Faculty, Staff and Student Publications

This review explores neutrophils' roles in chronic lymphocytic leukemia (CLL), highlighting their functions within the immune system. While neutrophils are known for fighting infections, their altered behavior in CLL significantly impacts disease progression. This review notes the reduced phagocytic abilities of neutrophils and the increased formation of neutrophil extracellular traps (NETs) in patients with CLL. It also examines the effects of CLL treatments, including chemotherapy, immunotherapy and targeted therapies, on neutrophils' count and function, stressing the need for improved strategies to manage therapy-induced immune dysfunction. This review also provides detailed information about the interactions between neutrophils and other immune elements …

Microbial Imprints On Colorectal Cancer: The Epigenetic Silencing Of Phlpp1 As A Prognostic Nexus, Xiangsheng Huang, Faraz Bishehsari

Faculty, Staff and Student Publications

No abstract provided.

Editorial: Protein Regulation By Lipids, Mikhail V Bogdanov, Elena G Govorunova

Faculty, Staff and Student Publications

No abstract provided.

Protecting Organs-At-Risk In Cancer Therapies Through Temporary Organ Displacement: A Comprehensive Review, Rance B Tino, Michael Li, Amirreza Heshmat, Ayush Suresh, Anasimone Guillaume, Kristy K Brock, Bruno C Odisio, Eugene J Koay

Faculty, Staff and Student Publications

Radiation therapy (RT) and locoregional ablation are cornerstones of modern oncology, yet their therapeutic potential is frequently limited by the challenge of sparing healthy organs-at-risk (OARs) from treatment-related complications. Temporary organ displacement (TOD) techniques directly address this issue by creating a physical separation using 'spacers' during treatment, thereby minimizing collateral damage while enhancing therapeutic precision. The clinical benefits, including improved tumor control, reduced morbidity, and enhanced survival, are documented across malignancies of the head and neck, thorax, abdomen, and pelvis. To create a unified framework for this evolving field, this comprehensive review provides a systematic classification of TOD techniques based …

Digital Twins In Healthcare: A Comprehensive Review And Future Directions, Hamid Khoshfekr Rudsari, Becky Tseng, Hongxu Zhu, Lulu Song, Chunhui Gu, Abhishikta Roy, Ehsan Irajizad, Joseph Butner, James Long, Kim-Anh Do

Faculty, Staff and Student Publications

Digital Twin (DT) technology has emerged as a transformative force in healthcare, offering unprecedented opportunities for personalized medicine, treatment optimization, and disease prevention. This comprehensive review examines the current state of DTs in healthcare, analyzing their implementation across different physiological levels-from cellular to whole-body systems. We systematically review the latest developments, methodologies, and applications while identifying challenges and opportunities. Our analysis encompasses technical frameworks for cardiovascular, neurological, respiratory, metabolic, hepatic, oncological, and cellular DTs, highlighting significant achievements such as population-scale cardiac modeling (3,461 patient cohort), reduced atrial fibrillation recurrence rates through patient-specific cardiac models, improved brain tumor radiotherapy planning, advanced …

Role Of Mir-204 In Controlling Metabolic Functions Of The Subretinal Microglia, Yan Chen, Sarah E Bounds, Neloy Kundu, James Regun Karmoker, Yin Liu, Dongin Kim, Jiyang Cai

Faculty, Staff and Student Publications

Rationale: MicroRNA-204 (miR-204) is one of the most abundant miRNA species in the retinal pigment epithelium (RPE) and RPE-derived extracellular vesicles (EVs). Knockout (KO) of miR-204 leads to dysfunction and degeneration of both the RPE and the retina. In addition to previously reported retinal pathologies, we observed the accumulation of lipid-laden subretinal microglia in miR-204 KO mice. This study aimed to identify potential molecular targets of miR-204 involved in microglia lipid processing and to determine whether RPE-derived EVs can improve the function of miR-204-deficient retinal microglia.

Methods: Lipid accumulation in microglia was detected by staining with LipidTox, a fluorescent dye …

Advancing Alzheimer's Research By Improving Disease Modeling Of Secondary Tauopathy, Ethan R Roy, Wei Cao

Faculty, Staff and Student Publications

Despite decades of mechanistic investigation of Alzheimer's disease (AD), wide gaps exist in disease modeling, particularly the pathobiological arm of tau pathology. Relying on transgenic models expressing mutated forms of tau has contributed much knowledge about primary tauopathy, yet with limited relevance to human AD. To eliminate blind spots for basic and translational research, we review recent developments in this area and discuss key refinements toward next-generation AD-relevant tauopathy modeling.

Combined Inhibition Of Lysine-Specific Demethylase 1 And Kinase Signaling As A Preclinical Treatment Strategy In Glioblastoma, Lea M Stitzlein, Deokhwa Nam, Faith A Hernandez, Kareena H Patel, Alaina Poche, Huaxian Ma, Katie Impelman, Joy Gumin, Heping Wang, Jing Wang, Samantha Gadd, Wafik Zaky, Oren Becher, Richard W Dudley, Frederick F Lang, Gangadhara R Sareddy, Joya Chandra

Faculty, Staff and Student Publications

Background: Lysine-specific demethylase 1 (LSD1) is overexpressed in glioblastoma, contributing to tumor growth and treatment resistance. LSD1 inhibitors have shown preclinical promise but have had limited clinical development for glioblastoma. Given the frequent kinase pathway alterations seen in glioblastoma, the interplay between LSD1 inhibition and kinase signaling pathways was investigated.

Methods: Glioblastoma stem cell (GSC) lines and normal human astrocytes (NHAs) were treated with catalytic LSD1 inhibitors, NCD38 and bomedemstat, and the LSD1 scaffolding inhibitor, seclidemstat alone and in combination with kinase inhibitors, including osimertinib, afatinib, and ulixertinib. The effect on cell viability, proliferation, and neurosphere formation was assessed, and …

International Multicenter Retrospective Study From The Ultra-Rare Sarcoma Working Group On Low-Grade Fibromyxoid Sarcoma, Sclerosing Epithelioid Fibrosarcoma, And Hybrid Forms: Outcome Of Primary Localized Disease, Claudia Giani, Abdulazeez Salawu, Silva Ljevar, Ryan A Denu, Andrea Napolitano, Emanuela Palmerini, Elizabeth A Connolly, Koichi Ogura, Daniel D Wong, Roberto Scanferla, Evan Rosenbaum, Jyoti Bajpai, Zola Chia-Chen Li, Susie Bae, Lorenzo D'Ambrosio, Steve Bialick, Andrew J Wagner, Alexander T J Lee, Hanna Koseła-Paterczyk, Giacomo G Baldi, Antonella Brunello, Yeh Chen Lee, Herbert H Loong, Sosipatros Boikos, Fernando Campos, Carlo M Cicala, Robert G Maki, Nadia Hindi, Costanza Figura, Shahd S Almohsen, Sheyaskumar Patel, Robin L Jones, Toni Ibrahim, Rooshdiya Karim, Akira Kawai, Richard Carey-Smith, Richard Boyle, Silvia M Taverna, Alexander J Lazar, Elizabeth G Demicco, Judith V M G Bovee, Angelo P Dei Tos, Christopher Fletcher, Daniel Baumhoer, Marta Sbaraglia, Inga-Marie Schaefer, Rosalba Miceli, Alessandro Gronchi, Silvia Stacchiotti

Faculty, Staff and Student Publications

The aim of the study was to report the outcome of primary localized low-grade fibromyxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), and hybrid LGFMS/SEF (H-LGFMS/SEF). Patients with primary localized LGFMS, SEF, or H-LGFMS/SEF, surgically treated with curative intent from January 2000 to September 2022, were enrolled from 14 countries and 27 institutions. Pathologic inclusion criteria were predefined by expert pathologists. The primary endpoint was overall survival (OS). Secondary endpoints were crude cumulative incidence (CCI) of local recurrence (LR), CCI of distant metastases (DM), and post-metastases OS (p-OS). Two hundred ninety-four patients (239 LGFMS, 32 SEF, and 23 H-LGFMS/SEF) were identified. …

Histopathologic Progression And Metastatic Relapse Outcomes In Small Cell Neuroendocrine Carcinomas Of The Urinary Tract, Mohammad Jad Moussa, Georges C Tabet, Arlene O Siefker-Radtke, Lianchun Xiao, Nathaniel R Wilson, Jianjun Gao, Christopher J Logothetis, Petros Grivas, Byron Lee, Amishi Y Shah, Pavlos Msaouel, Roger Li, Leticia Campos Clemente, Jianping Zhao, Nizar M Tannir, Ashish M Kamat, Donna E Hansel, Charles C Guo, Matthew T Campbell, Omar Alhalabi

Faculty, Staff and Student Publications

Introduction: Small cell neuroendocrine carcinoma of the urinary tract (SCNEC-URO) has an inferior prognosis compared to conventional urothelial carcinoma (UC). Here, we evaluate the predictors and patterns of relapse after surgery.

Materials and methods: We identified a definitive-surgery cohort (n = 224) from an institutional database of patients with cT1-T4NxM0 SCNEC-URO treated in 1985-2021. Histopathologic review was conducted by independent pathologists. Relapse event was the time-to-event outcome, and relapse probabilities were estimated using a competing risk method with cumulative incidence functions (CIFs). Fine-Gray distribution models assessed covariate associations.

Results: Most patients (161, 71.9%) received neoadjuvant chemotherapy (neoCTX). Ninety two (41%) …

Outcomes Of Patients Treated With Chemotherapy For Breast Cancer During Pregnancy Compared With Nonpregnant Breast Cancer Patients Treated With Systemic Therapy, Helen M Johnson, Juhee Song, Carla L Warneke, Ashley L Martinez, Jennifer K Litton, Oluchi C Oke

Faculty, Staff and Student Publications

Introduction: Prior studies of patients treated for breast cancer during pregnancy (PrBC) report mixed outcomes and are limited by substandard treatment, small cohorts, and short follow-up. This study compared survival outcomes of PrBC patients treated with chemotherapy during pregnancy with nonpregnant patients matched by age, year of diagnosis, stage, and subtype.

Methods: PrBC patients treated from 1989 to 2022 on prospective institutional protocols were eligible. Disease-free survival (DFS), overall survival (OS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method and multivariable Cox proportional hazards regression.

Results: Among 143 PrBC and 285 nonpregnant patients, median follow-up was 11.4 years. …

A Pan-Tumor Review Of The Role Of Poly(Adenosine Diphosphate Ribose) Polymerase Inhibitors, Chadi Hage Chehade, Georges Gebrael, Nicolas Sayegh, Zeynep Irem Ozay, Arshit Narang, Tony Crispino, Talia Golan, Jennifer K Litton, Umang Swami, Kathleen N Moore, Neeraj Agarwal

Faculty, Staff and Student Publications

Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by PARP inhibitors. These agents have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval in ovarian cancer and subsequently in breast, pancreatic, and prostate cancers in different indications. This review offers a comprehensive clinical overview of PARP inhibitor approvals, emphasizing their efficacy across different cancers based on landmark phase 3 clinical …

Outcomes With Bridging Radiation Therapy Prior To Chimeric Antigen Receptor T-Cell Therapy In Patients With Aggressive Large B-Cell Lymphomas, Gohar S Manzar, Chelsea C Pinnix, Stephanie O Dudzinski, Kathryn E Marqueen, Elaine E Cha, Lewis F Nasr, Alison K Yoder, Michael K Rooney, Paolo Strati, Sairah Ahmed, Chijioke Nze, Ranjit Nair, Luis E Fayad, Michael Wang, Loretta J Nastoupil, Jason R Westin, Christopher R Flowers, Sattva S Neelapu, Jillian R Gunther, Bouthaina S Dabaja, Susan Y Wu, Penny Q Fang

Faculty, Staff and Student Publications

Background: Select patients with relapsed/refractory aggressive B cell lymphoma may benefit from bridging radiation (bRT) prior to anti-CD19-directed chimeric antigen receptor T cell therapy (CAR-T). Here, we examined patient and treatment factors associated with outcomes and patterns of failure after bRT and CAR-T.

Methods: We retrospectively reviewed adults with diffuse large B-cell lymphoma (DLBCL) who received bRT prior to axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel between 11/2017-4/2023. Clinical/treatment characteristics, response, and toxicity were extracted. Survival was modeled using Kaplan-Meier or Cox regression models for events distributed over time, or binary logistic regression for disease response. Fisher's Exact Test or Mann-Whitney …

Erratum: Long Non-Coding Rna Uiclm Promotes Colorectal Cancer Liver Metastasis By Acting As A Cerna For Microrna-215 To Regulate Zeb2 Expression: Erratum, Dong-Liang Chen, Yun-Xin Lu, Jia-Xing Zhang, Xiao-Li Wei, Feng Wang, Zhao-Lei Zeng, Zhi-Zhong Pan, Yun-Fei Yuan, Feng-Hua Wang, Helene Pelicano, Paul J Chiao, Peng Huang, Dan Xie, Yu-Hong Li, Huai-Qiang Ju, Rui-Hua Xu

Faculty, Staff and Student Publications

No abstract provided.

Novel Volumetric Modulated Arc Therapy Approach For Lattice Radiation Therapy For Bulky Liver Tumors, Christine V Chung, Saurabh S Nair, Meena S Khan, Callistus I Nguyen, Rachael M Martin-Paulpeter, Ethan B Ludmir, Laurence E Court, Joshua S Niedzielski

Faculty, Staff and Student Publications

Purpose: Lattice radiation therapy (LRT) is a type of spatially fractionated radiation therapy that has emerged as an effective treatment approach for bulky solid tumors. RapidArc Dynamic (RAD) is a novel beam delivery approach that may be advantageous for LRT. The purpose of this in silico study was to evaluate and compare a novel RAD-based LRT approach (RAD-LRT) with conventional volumetric modulated arc therapy (VMAT)-based LRT (VMAT-LRT).

Methods: Twenty patients with bulky liver tumors treated with RT were retrospectively identified. VMAT-LRT and RAD-LRT plans were generated for all patients. Lattice spheres were placed in a standardized hexagonal pattern with alternating …

Relationship Between Trpm4 Rs8104571 Genotype, Circulating Trpm4 And Sur1, And Clinical Outcome Following Traumatic Brain Injury, Joseph D Krocker, Madeline E Cotton, Janet R Ashley, Jacob B Schriner, Baron K Osborn, Yao-Wei Willa Wang, Charles S Cox, Charles E Wade

Faculty, Staff and Student Publications

The variant single nucleotide polymorphism rs8104571 has been associated with poor outcomes following traumatic brain injury (TBI) and is most prevalent in those of African ancestry. This single nucleotide polymorphism (SNP) resides within a gene coding for the TRPM4 protein, which complexes with SUR1 protein to create a transmembrane ion channel and is believed to contribute to cellular swelling and cell death in neurological tissue. Our study evaluates the relationship between circulating TRPM4 and SUR1, rs8104571 genotype, and clinical outcome in TBI patients. Trauma patients with moderate to severe TBI were included in this retrospective study. rs8104571 genotyping and admission …

Mutation Of Conserved Mhc Class I Cytoplasmic Tyrosine Affects Cd8+ T Cell Priming, Effector Function, And Memory Response, Yimo Sun, Yitao Tang, Priscilla Ortiz, Barbara Nassif Rausseo, Barbara Pazdrak, Lama Elzohary, Arjun Katailiha, Amjad Talukder, Cassian Yee, Richard Eric Davis, Gregory Lizée

Faculty, Staff and Student Publications

The cytoplasmic domain of MHC class I (MHC-I) molecules contains a single, highly conserved tyrosine residue (Y320). In previous work, we found that mice expressing a Y320F-mutated form of H-2Kb had reduced capacity to generate Kb-restricted cytotoxic T lymphocyte (CTL) responses following viral infection, due at least in part to defects in endolysosomal trafficking of H-2Kb and antigen cross-presentation by dendritic cells (DCs). In this study, we investigated whether there are additional, post-presentation dependencies on Y320 for T cell priming. We engineered both human- and mouse-derived antigen-presenting cells (APCs) to express either wild-type MHC-I or variants of MHC-I containing Y320F …

Correction: Bronchoalveolar Lavage Cell Percentages As Diagnostic Markers Of Immune Checkpoint Inhibitor Pneumonitis, Mahnoor Mir, Felipe Soto, Pedro Antonio Amezcua Gomez, Rodrigo Del Rio Arroyo, Adarsh Suresh, Amber Su, Qiong Gan, John Stewart, Roberto Adachi, Diwakar D Balachandran, Lara Bashoura, Roberto F Casal, Burton F Dickey, George A Eapen, Scott E Evans, Horiana Grosu, Carlos A Jimenez, Julie Lin, David E Ost, Bruce F Sabath, Vickie R Shannon, Aung Naing, Jianjun Gao, Jia Wu, Karthik Suresh, Saadia A Faiz, Mehmet Altan, Ajay Sheshadri

Faculty, Staff and Student Publications

[This corrects the article DOI: 10.3389/fmed.2025.1582714.].

Case Report: Fia Plus Venetoclax In A Patient On Hemodialysis, Jacob E Herstein, Kayleigh R Marx, J Michael Savoy, Wei Ying Jen, Musa Yilmaz, Nicholas J Short, Ghayas C Issa, Farhad Ravandi, Tapan M Kadia, Naval G Daver, Courtney D Dinardo

Faculty, Staff and Student Publications

The safe and effective delivery of curative cytotoxic chemotherapy for acute myeloid leukemia (AML) in patients receiving intermittent hemodialysis (IHD) for end-stage renal disease (ESRD) remains a clinical challenge; pharmacological and logistical barriers necessitate close interdisciplinary coordination. In this case, we report a 65-year-old female patient with chronic ESRD on IHD and newly diagnosed AML who achieved complete remission (CR) after treatment with fludarabine, idarubicin, and cytarabine plus venetoclax (i.e., FIA + venetoclax).

Autophagy Cargo Profiles In Skeletal Muscle During Starvation And Exercise, Mohd Farhan, Shangze Lyu, Trezze P Nguyen, Dakai Zhang, Hong Liang, Yong Zhou, Yu A An, Jun Wang, Hongyuan Yang, Guangwei Du, Yang Liu

Faculty, Staff and Student Publications

Autophagy is a cellular process to clear unwanted and dysfunctional cellular cargoes, which are sequestered in autophagosomes before their delivery to lysosomes for degradation. Autophagy cargo selection, mediated by cargo receptors, varies across cell types and conditions. Understanding the cargo features is essential for elucidating autophagy's function in specific physiological or pathological contexts. Here, we present a simple and rapid method for isolating LC3B-positive autophagosomes from the tissues of GFP-LC3 transgenic mice, a widely used autophagy reporter model, without relying on the complex ultracentrifugation steps required by traditional methods. When combined with quantitative proteomics, this approach enables efficient in vivo …

Novel Pencil-Beam Scanning Proton Lattice Radiation Therapy For The Treatment Of Bulky Liver Cancer: Dosimetric Comparison With Vmat-Lattice Radiotherapy, Yuting Li, Rachael M Martin-Paulpeter, Christine V Chung, Miguel A Aguilar, Carlos A Matias, Adrian Delgado, Saurabh S Nair, Laurence E Court, Luis Perles, Narayan Sahoo, Ronald X Zhu, Falk Poenisch, David B Flint, Gabriel O Sawakuchi, Sam Beddar, Eugene Koay, Jamie S Baker, Ethan B Ludmir, Joshua S Niedzielski

Faculty, Staff and Student Publications

Background: Spatially fractionated radiotherapy (SFRT) delivered as lattice radiotherapy (LRT) creates high-dose 'vertex' subvolumes (VTVH) embedded within low-dose 'valley' regions (VTVL) to intensify intratumoral dose while minimizing radiation dose and toxicity to organs at risk (OARs). We developed a pencil-beam scanning (PBS) intensity modulated proton therapy (IMPT) LRT planning approach and dosimetrically compared it directly with contemporary photon-based volume modulated arc therapy (VMAT) LRT for liver cancer with bulky tumors.

Methods: Twenty-one retrospective liver cases were replanned in RayStation to a single fraction of 20 Gy to VTVH with explicit VTVL sparing (mean dose < 5Gy). Primary dosimetric endpoints were VTVH D80 and VTVL mean dose (analogous to mean valley dose), with secondary endpoints of VTVH/VTVL ratios (PVDR-like metrics at D80/D90/D100), VTVL D5/D80, GTV D10/D90, and planning risk volume (PRV) 0.03 cm³ hotspots. Statistical analysis consisted of paired tests (t-test or Wilcoxon signed-rank) after assessing data normality (Shapiro-Wilk tests) and using α=0.05 for significance.

Results: Compared with photon VMAT-LRT, IMPT-LRT …

A Prospective Cohort Study On Stereotactic Radiotherapy In The Management Of Dural Recurrence Of Olfactory Neuroblastoma, Christopher D Goodman, Franco Demonte, Theresa P Nguyen, Adam S Garden, Catherine He Wang, Xin A Wang, Kevin Diao, Anna Lee, Jay Reddy, Amy Moreno, Michael Spiotto, Clifton D Fuller, David Rosenthal, Renata Ferrarotto, Shaan M Raza, Shirley Y Su, Andrew Warner, Ehab Hanna, Jack Phan

Faculty, Staff and Student Publications

Background: Treatment for dural recurrence of olfactory neuroblastoma (ONB) is not standardized. We assess the outcomes of stereotactic body radiotherapy (SBRT) in this population.

Methods: ONB patients with dural recurrences treated between 2013 and 2022 on a prospective registry were included. Tumor control, survival, and patient-reported quality of life were analyzed.

Results: Fourteen patients with 32 dural lesions were evaluated. Time to dural recurrence was 58.3 months. Thirty lesions (94%) were treated with SBRT to a median dose of 27 Gy in three fractions. Two patients (3 of 32 lesions; 9%) developed in-field radiographic progression, five patients (38%) experienced progression …

Disulfidptosis And Its Emerging Relevance In Cancer And Immunity, Qidong Li, Shengrong Wu, Li Zhuang, Boyi Gan

Faculty, Staff and Student Publications

Disulfidptosis is a recently identified form of regulated cell death (RCD) triggered by disulfide stress when cystine uptake via solute carrier family 7 member 1 (SLC7A11) overwhelms the cell's reducing capacity. Unlike apoptosis or other "cell suicide" pathways, disulfidptosis likely represents a "cell sabotage" mechanism, defined by aberrant disulfide bonding and catastrophic actin cytoskeleton collapse. In this Perspective, we examine the paradoxical role of SLC7A11 as both a ferroptosis protector and a disulfidptosis trigger, and the mechanistic hallmarks of disulfidptosis. We highlight emerging therapeutic strategies to target disulfidptosis in cancer, including glucose transporter inhibition, redox-targeting agents, and nanomaterial-based approaches, and …

E2f1 Overexpression Reduces Aging-Associated Dna Damage In Cultured Cerebral Endothelial Cells And Improves Cognitive Performance In Aged Mice, Sheelu Monga, Samantha Flores, Maria Pilar Blasco-Conesa, Syed M Rahman, Brian Noh, Pedram Peesh, Bhanu Priya Ganesh, Sean P Marrelli, Louise D Mccullough, Jose Felix Moruno-Manchon

Faculty, Staff and Student Publications

As we age, cerebral endothelial cells (CECs) are less efficient in maintaining genome integrity and accumulate DNA damage. DNA damage in the brain endothelium can lead to the impairment of the blood–brain barrier (BBB), which is a major factor in brain dysfunction and dementia. Thus, identifying factors that regulate DNA repair in the brain endothelium can prevent brain dysfunction associated with aging. E2F1 is a transcription factor that regulates the expression of genes associated with DNA repair, among other functions. We hypothesize that E2F1 is downregulated in the brain vasculature of mice with aging and that E2F1 upregulation can improve …

Keygan: Synthetic Keystroke Data Generation In The Context Of Digital Phenotyping, Alejandro Acien, Aythami Morales, Luca Giancardo, Ruben Vera-Rodriguez, Ashley A Holmes, Julian Fierrez, Teresa Arroyo-Gallego

Faculty, Staff and Student Publications

Objective: This paper aims to introduce and assess KeyGAN, a generative modeling-based keystroke data synthesizer. The synthesizer is designed to generate realistic synthetic keystroke data capturing the nuances of fine motor control and cognitive processes that govern finger-keyboard kinematics, thereby paving the way to support biomarker development for psychomotor impairment due to neurodegeneration.

Methods: KeyGAN is designed with two primary objectives: (i) to ensure high realism in the synthetic distributions of the keystroke features and (ii) to analyze its ability to replicate the subtleties of natural typing for enhancing biomarker development. The quality of synthetic keystroke data produced by KeyGAN …

A Novel Automated Ct Biomarker To Predict Outcomes In Acute Ischemic Stroke: Net Water Uptake, Monica Mallavarapu, Hyun Woo Kim, Ananya Iyyangar, Sergio Salazar-Marioni, Albert J Yoo, Luca Giancardo, Sunil A Sheth, Jerome A Jeevarajan

Faculty, Staff and Student Publications

Background: Recent trials of large core thrombectomy have shown that our traditional understanding of infarct characteristics and reperfusion benefit may be incomplete for patients with acute ischemic stroke (AIS). The Alberta Stroke Program Early CT Score (ASPECTS) has wide inter-rater variability, and modern studies have also shown that reperfusion therapies can benefit some patients regardless of the ASPECTS. Reproducible imaging metrics that account for the degree of hypo-attenuation on non-contrast computed tomography (NCCT) may be better suited to guide treatments. Here, we evaluate Net Water Uptake (NWU), a novel NCCT metric that can be calculated in a rapid and automated …