Life Sciences Commons^™

A Robust Convnext-Based Framework For Efficient, Generalizable, And Explainable Brain Tumor Classification On Mri, Kirti Pant, Pijush Kanti Dutta Pramanik, Zhongming Zhao

Faculty, Staff and Student Publications

Background: Accurate and dependable brain tumor classification from magnetic resonance imaging (MRI) is essential for clinical decision support, yet remains challenging due to inter-dataset variability, heterogeneous tumor appearances, and limited generalization of many deep learning models. Existing studies often rely on single-dataset evaluation, insufficient statistical validation, or lack interpretability, which restricts their clinical reliability and real-world deployment.

Methods: This study proposes a robust brain tumor classification framework based on the ConvNeXt Base architecture. The model is evaluated across three independent MRI datasets comprising four classes-glioma, meningioma, pituitary tumor, and no tumor. Performance is assessed using class-wise and aggregate metrics, including …

Integrated Proteomics To Understand The Role Of Neuritin-1 (Nrn1) As A Molecular Mediator Of Synaptic Resilience In Alzheimer’S Disease, Derian Pugh

ETDs from 2020-2029

Alzheimer’s disease (AD) is the leading cause of dementia in adults over the age of 65, and currently affects approximately 6.9 million people in the United States. By 2060, the number of people age 65 and older with AD is projected to reach 13.8 million, barring the development of disease-altering therapies to prevent, slow or cure AD. Thus, there is a need for progress in the understanding of AD pathophysiology, as well as in the development of diagnostic and therapeutic interventions. Approximately one-third of individuals without dementia at the time of death are found to harbor high levels of amyloid-beta …

Beyond Neurons: Impact Of Cannabidiol On Glial Cells In Ischemic Stroke, Victória Linden De Rezende, Khiany Mathias, Cinara Ludvig Gonçalves, Rafael Mariano De Bitencourt, Tatiana Barichello, Fabricia Petronilho

Faculty, Staff and Student Publications

Ischemic stroke triggers a complex cascade of events involving inflammation, oxidative stress, and glial cell dysfunction, all of which contribute to neuronal damage and impaired recovery. Glial cells (e.g., astrocytes, microglia, and oligodendrocytes) play key roles in neuroinflammatory responses, making them attractive targets for therapeutic modulation. Cannabidiol, a non-psychoactive phytocannabinoid from Cannabis sativa, exhibits anti-inflammatory, antioxidant, and neuroprotective properties. Preclinical evidence indicates that cannabidiol attenuates glial reactivity, reduces pro-inflammatory signaling, mitigates oxidative stress, and preserves blood-brain and intestinal barrier integrity in stroke models. Moreover, cannabidiol modulates key molecular pathways (e.g., nuclear factor-κB, tumor necrosis factor, and calcium-related signaling), contributing to …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Structures Of Trpv1 Bound By Hyperthermia-Inducing Analgesics, Yu-Hao Gao, Yi-Zhe Huang, Zhao-Xing Li, Xiao-Ying Chen, Chang-Yan Shao, Han-Wen Li, Bin Liu, Fán Yang, Mei-Rong Chen, Mei-Ling Lu, Michael X Zhu, Fan Yang, Yi-Bei Xiao, Ye Yu

Faculty, Staff and Student Publications

TRPV1, a member of the transient receptor potential vanilloid subfamily, mediates nociception and thermoregulation. TRPV1-targeting analgesics frequently induce hyperthermia, underscoring the need for structural insights to guide the development of safer compounds. Here, we determined the structures of rat TRPV1 bound to the clinical candidate analgesics AMG517, AMG9810, and SB366791. AMG517 and AMG9810 are deeply situated within the S3-S4 interface of the vanilloid pocket, where they interact with residues from the S3-S6 helices, as well as the S4-S5 linker. These interactions induce local deformations in the TRP-box and lower S6 helix, accompanied by a modest rotation of the S1-S4 bundle, …

Mechanistic Insights Into The Antimicrobial Effect Of Benzodioxane-Benzamides Against Escherichia Coli, Lorenzo Suigo, Alessia Lanzini, Valentina Straniero, William Margolin

Faculty, Staff and Student Publications

Background/Objectives: The bacterial cell division machinery is emerging as an attractive target for antimicrobial compounds. FtsZ, a highly conserved essential division protein, is the target for a number of small molecules such as benzamides. Recent studies show that benzodioxane-benzamides (BDOBs) are among the most potent inhibitors of FtsZ function in Gram-positive bacteria, although their ability to inhibit Gram-negative FtsZ, in particular Escherichia coli FtsZ, has been more controversial.

Methods: Here, we use genetic and cytological methods to demonstrate that FtsZ of efflux pump-disabled E. coli can be efficiently targeted by BDOBs.

Results: We show that engineered mutants …

Targeting Interleukin-6 Trans-Signaling To Improve Post-Stroke Inflammation: A Precision Immunotherapy Perspective, Kate Mendoza, Dustin T Nguyen, Anjali Chauhan

Faculty, Staff and Student Publications

No abstract provided.

Structures Of Invertebrate Pezo-1 Isoforms With A Compact Architecture And A Dispensable Pore-Distal N-Terminal Blade, Briar Bell, Angela M Jaramillo-Granada, Daniel J Orlin, Wei-Hsiang Weng, Haosheng Wen, Marcos Sotomayor, Alexander T Chesler, Matthew L Baker, Julio F Cordero-Morales, Valeria Vásquez

Faculty, Staff and Student Publications

PIEZO channels are mechanosensitive ion channels conserved from plants to humans, yet structures exist for only a few mammalian orthologs. We define the structural and functional diversity of Caenorhabditis elegans PEZO-1, a single gene with extensive alternative splicing, by determining cryo-electron microscopy structures of three representative isoforms: G (full length), K (lacking the pore-distal N-terminal blade), and L (missing most of the blade). PEZO-1G displays mechanically evoked currents yet adopts a compact, semi-flattened conformation that significantly differs from the mammalian domes. The blades exhibit a three-step slope architecture stabilized by inter-blade latching among transmembrane helical units, yielding a circular, steering-wheel-like …

Assessing Predoctoral Dental Student Interest In Nutrition Education: A Study Across Two Dental Schools, Nadine M. Tassabehji, Xiaoyuan Han, Parvati Iyer Dr., Michelle Brady, Matthew Finkelman, Shafa Nathani, Anna Garrison, Annie Han

Pacific Journal of Health

The mouth is a mirror of overall health. Dentists have a vital role in the diagnosis of oral diseases, prevention, for health promotion. The purposes of our exploratory study were to investigate dental students’ attitudes and perceptions regarding nutrition education and to propose a curriculum checklist for integrating nutrition content into dental curricula.

An optional exploratory survey was distributed at two North American urban dental schools to 351 students, to compare student perspectives regarding implementation of nutrition education. The results were analyzed as a step to improve nutrition education in dental curricula. A validated stepwise checklist was developed to guide …

An Antioxidant Cocktail Of Tert-Butylhydroquinone And A Manganese Porphyrin Induces Toxic Levels Of Oxidative Stress In Cancer Cells, Sandra Tamarin, Hannah Jung, Joseph Lamorte, Laura Biesterveld, Gabriel Piñero, Grace Turchetta, Molly Myers, Rebecca Oberley-Deegan, Aimee Eggler

Student Papers, Posters & Projects

Despite significant advancement in cancer treatments, therapies with minimal toxicity to healthy cells are still limited. One targetable weakness of cancer cells is their sensitivity to oxidative stress. We find that the combination of two antioxidants—the common food additive tert-butylhydroquinone (tBHQ) and a manganese porphyrin in clinical trials, MnTnBuOE-2-PyP5+ (MnBuOE)—increases oxidative stress and causes apoptotic death in several cancer cell lines, but not in mouse primary fibroblasts. Investigating the mechanism of cell death, MnBuOE is observed to catalyze the oxidation of tBHQ, producing the electrophilic quinone tert-butylquinone (tBQ). A critical role for tBQ and its electrophilic character was revealed with …

High Levels Of Circulating Mir-19a-3p In Patients With Metastatic Her2 + Breast Cancer Are Associated With A Favorable Prognosis And Anti-Tumor Immune Responses, Evan N Cohen, Hui Gao, Sanda Tin, Qiong Wu, Cristina Ivan, Naoto T Ueno, Wendy A Woodward, James M Reuben, Simone Anfossi

Faculty, Staff and Student Publications

Background: Trastuzumab, combined with chemotherapy, is the current standard treatment for both metastatic and early-stage HER2-positive (HER2 +) breast cancer. One of the mechanisms of action of trastuzumab is antibody-dependent cellular cytotoxicity (ADCC), which involves engaging FcγRIIIA (CD16) on natural killer (NK) cells. A competent immune system and properly functioning NK cells are crucial for effective ADCC, as they can influence favorable clinical outcomes. Resistance to trastuzumab often develops after about one year. We previously reported that elevated levels of miR-19a-3p in the serum of patients with metastatic HER2 + breast cancer treated with trastuzumab were associated with a favorable …

Clinical Workflow Of Spine Stereotactic Radiotherapy And Radiosurgery: Insights From A Single-Institution Physics Perspective, Dennis Mackin, Gizem Cifter, Yana Zlateva, Jihong Wang, Yao Ding, Muhammad Shafiq Ul Hassan, Zhiheng Wang, Parmeswaran Diagaradjane, Fada Guan, Travis C Salzillo, Shane Krafft, Jing Li, Martin C Tom, Amol J Ghia, Tina Marie Briere

Faculty, Staff and Student Publications

Spine stereotactic radiotherapy and radiosurgery (SSRS) techniques, encompassing both fractionated stereotactic treatments and single-fraction radiosurgery, are widely used for the management of spinal metastases due to their ability to deliver highly conformal radiation while limiting dose to adjacent critical structures. Clinical outcomes following SSRS, including durable local control and acceptable toxicity, have been reported previously in multiple institutional series. In this manuscript, we describe the clinical workflow used to deliver SSRS at a high-volume academic center, with emphasis on the medical physics processes that support routine clinical practice. Key elements of the workflow include patient selection, treatment region-specific immobilization, CT …

Cdk2 Inhibitor Blu-222 Synergizes With Cdk4/6 Inhibitors In Drug Resistant Breast Cancers Through P21/P27 Induction, Linjie Luo, Yan Wang, Tuyen Bui, Xiaoting Jiang, Mei-Kuang Chen, Xiayu Rao, Sepideh Mohammadhosseinpour, Mi Li, Serena Kim, Rachel Y Kim, Saba Kamaliasl, Carmen W Ulizio, Spyros Tsavachidis, Juliana Navarro-Yepes, Nicole M Kettner, Hannah Wingate, Funda Meric-Bernstam, Kelly K Hunt, Jing Wang, Kerrie Faia, Khandan Keyomarsi

Faculty, Staff and Student Publications

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard first-line treatment for hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer, but resistance inevitably develops. In triple-negative breast cancer (TNBC), the efficacy of CDK4/6i remains uncertain. Our study shows that the selective CDK2 inhibitor BLU-222, while effective alone, enhances synergistic activity when combined with CDK4/6i in resistant HR+/HER2- and TNBC models, leading to increased apoptosis and cell cycle arrest. In vivo, combining BLU-222 with palbociclib or ribociclib produced significant antitumor activity across eight resistant models, driving durable tumor regression and prolonged survival. Mechanistically, BLU-222, alone or with palbociclib, upregulated …

The Gene Encoding Ornithine Decarboxylase For Putrescine Biosynthesis Is Essential For The Viability Of Fusobacterium Nucleatum, Shiqi Xu, Bibek G C, Alex Phan, Chenggang Wu

Faculty, Staff and Student Publications

Fusobacterium nucleatum is a Gram-negative anaerobe associated with periodontitis and colorectal cancer. It secretes putrescine, a polyamine that promotes biofilm formation by oral co-colonizers and enhances the proliferation of cancer cells. However, the physiological importance of putrescine for F. nucleatum itself remains unexplored. Here, we show that putrescine biosynthesis, mediated by the ornithine decarboxylase gene oda, is essential for F. nucleatum viability. Deletion of oda was only possible when a functional copy was provided in trans, and CRISPR interference of oda expression resulted in complete growth defects. The essentiality of oda was conserved across multiple subspecies. Supplementation with …

Cdk2 Inhibitor Blu-222 Synergizes With Cdk4/6 Inhibitors In Drug Resistant Breast Cancers Through P21/P27 Induction, Linjie Luo, Yan Wang, Tuyen Bui, Xiaoting Jiang, Mei-Kuang Chen, Xiayu Rao, Sepideh Mohammadhosseinpour, Mi Li, Serena Kim, Rachel Y Kim, Saba Kamaliasl, Carmen W Ulizio, Spyros Tsavachidis, Juliana Navarro-Yepes, Nicole M Kettner, Hannah Wingate, Funda Meric-Bernstam, Kelly K Hunt, Jing Wang, Kerrie Faia, Khandan Keyomarsi

Faculty, Staff and Student Publications

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard first-line treatment for hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer, but resistance inevitably develops. In triple-negative breast cancer (TNBC), the efficacy of CDK4/6i remains uncertain. Our study shows that the selective CDK2 inhibitor BLU-222, while effective alone, enhances synergistic activity when combined with CDK4/6i in resistant HR+/HER2- and TNBC models, leading to increased apoptosis and cell cycle arrest. In vivo, combining BLU-222 with palbociclib or ribociclib produced significant antitumor activity across eight resistant models, driving durable tumor regression and prolonged survival. Mechanistically, BLU-222, alone or with palbociclib, upregulated …

Single-Photon Emission Computed Tomography Functional Liver Imaging To Facilitate Reirradiation For Liver Malignancies: A Phase I Trial, Enoch Chang, Emma B Holliday, Janio Szklaruk, William D Erwin, Ethan B Ludmir, Sonal S Noticewala, Prajnan Das, Albert C Koong, Bruce D Minsky, Grace L Smith, Gabriel O Sawakuchi, Rachael M Martin-Paulpeter, Joshua S Niedzielski, Luis A Perles, Sam Beddar, Veronica S Valino, Joshua L Nguyen, Kanwal P S Raghav, Milind Javle, Ahmed O Kaseb, Arvind N Dasari, Michael J Overman, Christine M Parseghian, Bruno C Odisio, Armeen Mahvash, Joshua D Kuban, Shu-En Shen, Xin S Wang, Aashish C Gupta, Mais M Al Taie, Kristy K Brock, Ching-Wei D Tzeng, Jean-Nicolas Vauthey, Franklin C L Wong, Eugene J Koay

Faculty, Staff and Student Publications

Background & aims: This phase I trial evaluated the safety of hypofractionated liver reirradiation (reRT) with preferential sparing of functional liver identified by technetium-99m sulfur colloid single-photon emission computed tomography (Tc-99m SC SPECT; hereafter SPECT) for patients previously treated with external beam radiotherapy or transarterial radioembolization.

Methods: A 3+3 design evaluated the safety of two escalating SPECT-based functional liver volumetric dose constraints. Dose-limiting toxicities (DLTs), liver segment volumes, and MRI functional liver imaging score, relative liver enhancement, and elastography were assessed.

Results: Thirteen patients were enrolled from 2018 to 2021. Median reRT gross tumor volume was 61 cm3 (range 1-677 …

Disease-Specific And Overall Survival For Patients With Lacrimal Gland Adenoid Cystic Carcinoma In Recent Decades, Bita Esmaeli, Zhouxuan Li, Tracy J Lu, Hila Goldberg, Jing Ning, James Matthew Debnam, Steven Jay Frank, Renata Ferrarotto

Faculty, Staff and Student Publications

Purpose: To evaluate the presenting symptoms, and the overall survival (OS) and disease-specific survival (DSS) in patients with lacrimal gland adenoid cystic carcinoma (LGACC).

Methods: This retrospective single-centre cohort study included all consecutive patients with LGACC treated by the primary author from November 1998 through August 2024. Demographic data, presenting symptoms, the histological subtype of LGACC, type of surgical treatment, adjuvant radiotherapy or chemotherapy, T category at presentation and survival data were reviewed. Correlations between histological subtypes, T-category, type of surgery (eye sparing vs orbital exenteration), and DSS and OS were analysed.

Results: 52 patients had a median age of …

Association Between The 2022 Aha/Acc/Hfsa Heart Failure Staging And Cardiovascular And Kidney Outcomes In Patients With Diabetes And Kidney Disease: A Post Hoc Analysis Of The Scored Randomized Controlled Trial, Ayodele Odutayo, Deepak L Bhatt, Vikas S Sridhar, Michael Szarek, Christopher P Cannon, Lawrence A Leiter, Darren K Mcguire, Julia B Lewis, Renato D Lopes, Benjamin M Scirica, Kausik K Ray, Michael J Davies, Phillip Banks, Manon Girard, Subodh Verma, Jacob A Udell, Bertram Pitt, Ph Gabriel Steg, David Z I Cherney

Faculty, Staff and Student Publications

Background: The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America heart failure (HF) classification incorporates cardiac biomarkers to identify early risk of HF. The HF stages may also guide the prognosis and management of cardiovascular and kidney-related events.

Methods: SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) was a randomized trial in diabetes with kidney disease comparing sotagliflozin versus placebo on cardiovascular death, HF hospitalizations, and urgent HF visits. SCORED participants were grouped by HF stage post hoc. Stage A: no …

Oral Streptococcus And Vitamin B12 Deficiency In E-Cigarette Users: A Microbial–Nutrient–Neurotransmitter Axis Linking To Mood Disturbances, Maryam Sabah Naser, Ali Jabbar Abd Al-Hussain Alkawaz, Ali Abbas Hashim Almusawi, Ali Jalil Obaid, Hasanain Ayed Mohammed Al-Khafaji, Reihaneh Sabbaghzadeh

Karbala International Journal of Modern Science

Background: With the rising popularity of e-cigarettes, questions have emerged regarding their broader influence on oral ecology, nutrient absorption, and psychological health. Disruptions in the oral microbiome may alter vitamin B12 dynamics. This, in turn, may indirectly influence serotonin biosynthesis and mood regulation.

Methods: An observational cross-sectional study involved 150 young adults segregated into groups of 50 each as vapers, smokers, or non-users. Streptococcus sanguinis and vitamin B12 metabolism-related variable statuses methylmalonic acid and holotranscobalamin were quantified in samples, along with inflammatory markers interleukin-6, kynurenine/tryptophan ratio, and serotonin. Statistical techniques, including ANOVA and the Kruskal-Walli’s test, correlation, and serial mediation …

Low Intensity Vibration With Zoledronate Reduces Musculoskeletal Weakness And Adiposity In Estrogen Deprived Female Mice, Gabriel M Pagnotti, Trupti Trivedi, Laura E Wright, Sutha K John, Sreemala Murthy, Ryan R Pattyn, Monte S Willis, Yun She, Sukanya Suresh, Aji F Touray, William R Thompson, Clinton T Rubin, Khalid S Mohammad, Theresa A Guise

Faculty, Staff and Student Publications

Aromatase inhibitors are widely used in the treatment of hormone-sensitive breast cancer, but their suppression of estrogen production accelerates bone loss, increases fracture risk, and negatively impacts muscle and fat metabolism. Here, we demonstrate that daily low intensity vibration, serving as a non-drug mimetic for exercise, protects musculoskeletal health in skeletally immature, female mice under complete estrogen deprivation. Subsequent improvements in vertebral bone density are paralleled by greater and leaner skeletal muscle mass and function alongside reduced fat accretion and circulating metabolites. In mature, estrogen deprived mice, vibration enhances weekly bisphosphonate treatment, improving bone density, cortical thickness, and mechanical resistance …

Genome-Wide Association Study Identifies Novel Variants In Olfactory, Vitamin A, Vitamin B, And Cadherin Pathways Associated With Learning And Memory, Lloyd N. Hopkins, Nesli Avgan, Heidi G. Sutherland, Francesca E. Fernandez, Emma M. Knowles, Larisa M. Haupt, John Blangero, David C. Glahn, David H. K. Shum, Rod A. Lea, Lyn R. Griffiths

Human Genetics Publications

Learning and memory, as fundamental components of human cognition, are heritable traits that are highly variable between individuals and within populations. Investigation into the genetic basis of cognition is a prominent area of research, with genetic associations being previously reported for a wide range of cognitive phenotypes. Here we utilise a genome-wide association study (GWAS) approach to evaluate the contribution of genetic variation to learning and memory phenotypes in a comprehensively phenotyped, well-characterised, healthy, and unrelated cohort of individuals (n = 613). Cognitive phenotypes were assessed using nine comprehensive test batteries consisting of twenty-one cognitive performance assessments including IQ, five …

Simulated Complex Cells Contribute To Object Recognition Through Representational Untangling, Mitchell B Slapik, Harel Z Shouval

Faculty, Staff and Student Publications

The visual system performs a remarkable feat: it takes complex retinal activation patterns and decodes them for object recognition. This operation, termed "representational untangling," organizes neural representations by clustering similar objects together while separating different categories of objects. While representational untangling is usually associated with higher-order visual areas like the inferior temporal cortex, it remains unclear how the early visual system contributes to this process-whether through highly selective neurons or high-dimensional population codes. This article investigates how a computational model of early vision contributes to representational untangling. Using a computational visual hierarchy and two different data sets consisting of numerals …

Genomics Define Malignant Transformation In Myeloma Precursor Conditions, Francesco Maura, P Leif Bergsagel, Bachisio Ziccheddu, Shaji Kumar, Kylee Maclachlan, Andriy Derkach, Juan-Jose Garces, Ross Firestone, Esteban Braggio, Yan Asmann, Michael Durante, Benjamin T Diamond, Marios Papadimitriou, Malin Hultcrantz, Alessio Marella, Giancarlo Castellano, Akihiro Maeda, Marta Lionetti, Antonio Matera, Stefania Pioggia, Matteo Claudio Da Vià, Claudio De Magistris, Daniel Leongamornlert, Danny Deavila, Praneeth Reddy Sudalagunta, Rafael Renatino Canevarolo, Erin M Siegel, Phaedra Agius, Jamie Teer, Andrew Mcpherson, Yusuke Yamashita, Ariosto S Silva, Patrick Blaney, Rachid Baz, Krina K Patel, Peter Campbell, Gareth Morgan, Rafael Fonseca, Ola Landgren, Robert Z Orlowski, Kenneth H Shain, Niccolo Bolli, Saad Usmani, S Vincent Rajkumar

Faculty, Staff and Student Publications

Multiple myeloma (MM) is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). While these precursor conditions are asymptomatic, they are not entirely benign and carry a lifelong risk of progression to MM. Unlike other cancers defined by pathology, malignant transformation from MGUS or SMM to MM has so far relied on demonstration of clinical end-organ damage as morphology and cytogenetics cannot reliably distinguish them. In this study, using genomic data from 374 patients with MGUS or SMM (277 training, 97 validation), to our knowledge, we demonstrate for the first time the ability to identify …

Table Of Contents

Journal of the South Carolina Academy of Science

No abstract provided.

Comprehensive Metabolic Profiling Across Five Lifespan Stages In Murine Hippocampus And Cortex Reveals Sex-Related Variation In Age-Related Cognitive Decline, Xi Long, Wuping Liu, Changhan Chen, Qi Guo, Yidan Wang, Fang Yu, Yujin Zhang, Rodney E Kellems, Yang Xia

Faculty, Staff and Student Publications

This study employs Barnes maze behavioral assessments, untargeted liquid chromatography-mass spectrometry metabolomics, and 13C6-glucose isotopic tracing to systematically investigate cognitive function and metabolic profiles in hippocampal and cortical tissues of male and female mice across five distinct age-ranges. Behavioral analyses reveal significant cognitive decline in both sexes by 16-months-of-age, with females exhibiting more severe impairment by 23-months, demonstrating a sex-related variation. 13C6-glucose tracing analyses reveals that glucose is rapidly and preferentially metabolized toward the Tricarboxylic acid cycle over glycolysis and the pentose phosphate pathway (PPP), with metabolism rates increasing from juvenility to meet developmental demands and maintaining homeostasis into pre-elderly. …

Radionuclide-Stimulated Dynamic Therapy Induces Complementary Immunogenic Necroptosis And Apoptosis Cancer Cell Death Pathways, Christopher Egbulefu, Kvar Black, Xinming Su, Partha Karmakar, Lemoyne Habimana-Griffin, Gail Sudlow, Julie Prior, Ezugo Onejeme, Alex Zheleznyak, Baogang Xu, Yalin Xu, Alison Esser, Matthew Mixdorf, Evan Moss, Brad Manion, Cody Hongsermeier, Nisha Gamadia, Nicole Blasi, Luke Stallings, Chidube Alagbaoso, Nathan Reed, Matthew M Gubin, Chieh-Yu Lin, Robert Schreiber, Katherine Weilbaecher, Samuel Achilefu

Faculty, Staff and Student Publications

Radionuclide-stimulated dynamic therapy (RaST) utilizes Cerenkov-radiating radiopharmaceuticals to activate light-sensitive drugs and materials, generating reactive oxygen species (ROS) that inhibit cancer progression. However, the underlying cell death mechanisms are not fully understood. Using ROS-regenerative nanophotosensitizers coated with a tumor-targeting transferrin-titanocene complex and radiolabeled 2-fluorodeoxyglucose, we found that RaST induced apoptosis and necroptosis, characterized by the activation of RIPK-1, RIPK-3, nuclear factor kappa B, and mixed lineage kinase domain-like pseudokinase, leading to membrane permeabilization, cytokine release, and the expression of immunogenic damage-associated molecular patterns. In immune-deficient breast tumor-bearing mice with adequate stroma and growth factors, RaST did not prevent tumor growth …

Premature Aging In Serious Mental Illness, Breno S Diniz, Gabriel R Fries, Chia-Ling Kuo, Ming Xu, Eric J Lenze

Faculty, Staff and Student Publications

Serious mental illnesses (SMIs), including major depressive disorder, bipolar disorder, and schizophrenia, have long been linked to cognitive decline, multiple chronic medical conditions, and premature mortality. These factors significantly contribute to the severe disability seen in SMIs, extending beyond the severity of psychopathology and indicating a premature aging phenotype associated with these conditions. The mechanisms that underlie the relationship between SMIs and the premature aging phenotype are not well understood, but recent evidence suggests that individuals with SMIs may exhibit accelerated biological aging. In this review, we present a comprehensive analysis of the current literature, demonstrating the potential association of …

Foxo1 Inhibition And Fadd Knockdown Have Opposing Effects On Anticancer Drug-Induced Cytotoxicity And P21 Expression In Osteosarcoma Cells, Danielle Walker, Antanay Hall, Alexis Bonwell, Nancy Gordon, Danielle Robinson, Mario G Hollomon

Faculty, Staff and Student Publications

Forkhead box class O1 (FOXO1) and fas-associated death domain (FADD) regulate cell death pathways and homeostatic processes such as cell cycle progression and apoptosis. FADD phosphorylation promotes nuclear localization of FOXO1, and FOXO1 regulates FADD expression. Therefore, it is plausible that FOXO1 and FADD have synergistic or antagonistic effects on cell cycle regulation and the response to anticancer drug treatment in cancer cells. In the present study, we report that AS1842856-mediated inhibition of FOXO1 reverses anticancer drug-induced cytotoxicity, while FADD knockdown increases anticancer drug-induced cytotoxicity in osteosarcoma (OS). Reversed anticancer drug-induced cytotoxicity was accompanied by G2/M cell cycle arrest and …

Elevated Trna Halves In Olfactory Epithelial Cells Of Patients With Schizophrenia, Justin T. Gumas, Megumi Shigematsu, Karin E. Borgmann-Winter, C. G. Hahn, Yohei Kirino

Computational Medicine Center Faculty Papers

Schizophrenia patients' olfactory epithelial cells contain abundant immune-activating tRNA fragments, linking small RNA biology to inflammation and suggesting avenues for diagnostics.