Digital Commons Network^™

Electrochemical Strategies For Microrna Quantification Leveraging Amplification And Nanomaterials: A Review, Alexander Hunt, Gymama Slaughter

Center for Bioelectronics Publications

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and have emerged as critical biomarkers in various diseases, including cancer. Their stability in bodily fluids and role as oncogenes or tumor suppressors make them attractive targets for non-invasive diagnostics. However, conventional detection methods, such as Northern blotting, RT-PCR, and microarrays, are limited by low sensitivity, lengthy protocols, and limited specificity. Electrochemical biosensors offer a promising alternative, providing high sensitivity, rapid response times, portability, and cost-effectiveness. These biosensors translate miRNA hybridization events into quantifiable electrochemical signals, often leveraging redox-active labels, mediators, or intercalators. Recent advancements in nanomaterials and signal amplification …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

Metastatic Squamous Cell Carcinoma In A Nonsmoker Presenting With Pathological Humeral Fracture, Nicholas Fuerstenau, Grant Cookson, Smit Jani

South Atlantic Division GME Research Day 2025

No abstract provided.

Maternal Retinoblastoma And Fetal Surveillance During Pregnancy: Is This Hereditary Or Not?, Bethany Bowling, Shea Mcgrinder, Amanda Royek, Reese Groover, Anthony B. Royek

South Atlantic Division GME Research Day 2025

No abstract provided.

Case Series Of Psychiatric Patients With Hypothermia: A Clinical Review, Amy Mackenzie, Brianne Kimmet, James Free, Ubaid Khokhar, Barbara Gracious

South Atlantic Division GME Research Day 2025

No abstract provided.

Developing Chemically Defined Serum-Free Medium For Leukemic Blast And Stem Cell Expansion, Carmen Eva Finley

Dissertations

The relapse and chemotherapy resistance are the major challenges of acute myeloid leukemia (AML) treatment, driven by a rare population of leukemia stem cells (LSCs). LSCs are unique types of cells which evade standard chemotherapies and can regenerate AML post-treatment. Targeting LSC therapy remains limited, in part due to the lack of reliable in vitro AML culture systems to grow LSCs for drug discovery. This study aimed to engineer a chemically defined, serum-free 2D in vitro culture condition that supports either the expansion of leukemic blasts (LBs) or primary human LSCs by optimizing current protocols for hematopoietic stem cells (HSCs) …

Protocol For Development And Validation Of An Early Intervention Device And Its Influence Using Structured Early Physiotherapy (Preemiestep) Intervention On Neuromotor Development In Preterm Infants, Indira D. B. Naidu Boddapati, Sivakumar Gopalakrishnan, Sonia Khurana, Jayashree Purkayastha, Bhaskar Bhatt, Bhamini Krishna Rao

Rehabilitation Sciences Faculty Publications

Early physiotherapy interventions for Moderate to Late Preterm (MLP) infants often lack continuity of care from hospital to home settings. This research aims to develop an Early Intervention (EI) device for home program and determine its influence using STructured Early Physiotherapy (Preemie STEP) intervention in MLP infants. For phase I, qualitative interviews will be conducted with healthcare professionals and parents, to understand user needs on developed prototype. Based on identified needs, an EI device will be developed using a human-centered design approach and iterative design process. In phase II, usability and validity of EI device will be …

Havana Syndrome: A Scientific Review Of An Unresolved Medical Mystery, Aishik Dutta

Digital Journal of Clinical Medicine

Background

Since 2016, U.S. and Canadian officials have reported Anomalous Health Incidents (AHIs), or "Havana Syndrome," characterised by a strange sensory experience followed by chronic neurological, cognitive, and vestibular issues. The cause is intensely debated, with primary hypotheses pointing to either psychosocial factors or a directed-energy weapon, creating a significant medical and geopolitical puzzle.

Methods

This review critically assesses the current evidence by analysing peer-reviewed clinical studies and major institutional reports.

Results

The findings are deeply contradictory. A 2020 NASEM report identified directed, pulsed radiofrequency energy as the most plausible mechanism for a core set of symptoms. Conversely, comprehensive 2024 …

Her2 Alterations Across Solid Tumors: Implications For Comprehensive Testing, Ahmed Ismail, Chimay Jani, Nusrat Jahan, Malla Midhun, Arnab Basu, Garima Gupta, Bassel El-Rayes, Sejong Bae, Tyler Mattox, Cyntanna Hawkins, Rebecca C. Arend, Mehmet Akce, Yanis Boumber, Aakash Desai

Department of Medicine Faculty Publications

Purpose

ERBB2 (HER2) alterations (e.g., overexpression, amplification, and mutations) are known to drive tumor progression. These changes, particularly in non-breast and gastric/gastroesophageal cancers, remain poorly characterized. With pan-tumor approval of HER2-targeted therapies like Trastuzumab deruxetecan (T-DXd), understanding ERBB2 alterations across diverse cancers is crucial.

Methods

HER2 analysis was conducted on 653 solid tumor specimens at the University of Alabama, using immunohistochemistry (IHC), copy number (CN) variation (CNV) assessment, and mutational profiling. The correlation between CN amplification and IHC expression was evaluated using Somers' D ordinal association.

Results

Of the 653 cases, HER2 IHC scores were distributed as 3 + (3.1%), …

Impact Of Aerobic Exercise On Cardiometabolic Health In Patients With Diabesity: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Sameer Badri Al-Mhanna, Barry A. Franklin, John M. Jakicic, Emmanuel Stamatakis, Linda S. Pescatello, Deborah Riebe, Walter R. Thompson, James S. Skinner, Sheri R. Colberg, Jonathan K. Ehrman, George S. Metsios, Norsuhana Omar, Nouf H. Alkhamees, Bodor Bin Sheeha, Abdullah F. Alghannam, Alexios Batrakoulis

Human Movement Studies & Special Education Faculty Publications

Purpose

This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of aerobic exercise on cardiometabolic health-related indices in patients with type 2 diabetes and concurrent overweight/obesity (diabesity).

Methods

PubMed, Web of Science, Scopus, Science Direct, Cochrane Library, and Google Scholar databases were searched from inception to October 2024. The search strategy included the following keywords: diabetes, aerobic exercise, and endurance training. RCTs comparing aerobic exercise training ≥2 weeks in duration to standard treatment were considered eligible. Participants were adults with diabesity.

Results

A total of 1391 middle-aged/older adult patients (55 % females) were included …

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 …

Nutritional Management Of The Child With Chronic Kidney Disease And On Dialysis., Vanessa Shaw, Caroline Anderson, An Desloovere, Larry A. Greenbaum, Lyndsay Harshman, Christina L. Nelms, Pearl Pugh, Nonnie Polderman, José Renken-Terhaerdt, Evelien Snauwaert, Stella Stabouli, Jetta Tuokkola, Johan Vande Walle, Bradley A. Warady, Fabio Paglialonga, Rukshana Shroff

Manuscripts, Articles, Book Chapters and Other Papers

While it is widely accepted that the nutritional management of the infant with chronic kidney disease (CKD) is paramount to achieve normal growth and development, nutritional management is also of importance beyond 1 year of age, particularly in toddlers, to support the delayed infantile stage of growth that may extend to 2-3 years of age. Puberty is also a vulnerable period when nutritional needs are higher to support the expected growth spurt. Inadequate nutritional intake throughout childhood can result in failure to achieve full adult height potential, and there is an increased risk for abnormal neurodevelopment. Conversely, the rising prevalence …

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. …

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 …

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 …

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 …

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 …